bluuebunny/crossref_metadata_2025 huggingface dataset:
The isoperimetric problem in Randers Poincaré disc
Authors: Gangopadhyay Arti Sahu , Gangopadhyay Ranadip , Shah Hemangi Madhusudan , Tiwari Bankteshwar
Published: June 2024

It is known that a simply connected Riemann surface satisfies the isoperimetric equality if and only if it has constant Gaussian curvature. In this paper, we show that the circles centered at origin in the Randers Poincaré disc satisfy the isoperimetric equality with respect to different volume forms however, these Randers metrics do not necessarily have constant (negative) flag curvature. In particular, we show that Osserman’s result [12] of the Riemannian case cannot be extended to the Finsler geometry as such.
Weighted Hesitant Fuzzy Finite Rough Automaton: A Computing Model for Natural Language Processing
Authors: Verma Sunny , Kumari Mausam , Ruhela Shainky , Yadav Vijay Kumar
Published: June 2024

The well-known computing models, classical/fuzzy/rough automata, in spite of their multifarious applications, fail to model those complex real-world systems that contain both vagueness and incomplete information in datasets of real-world complex systems. The computing model, [Formula: see text]-fuzzy rough automata, incorporates both vagueness and incomplete information in datasets of such systems but fails to incorporate the weights of fuzzy attributes. To overcome this issue, we first introduce the concept weighted hesitant fuzzy finite automaton (WHFFA), as a generalized notion of the hesitant [Formula: see text]-fuzzy automaton (HLFA), where weights show that the decision maker has distinct confidence in providing the possible valuation of the membership degree. We used the concept of weighted hesitant fuzzy rough set (WHFRS) as a hybrid concept of hesitant fuzzy rough set (HFRS) and weighted hesitant fuzzy set (WHFS) to introduce a novel computing model weighted hesitant fuzzy finite rough automaton (WHFFRA). The introduced WHFFRA is efficient for dealing with vagueness and incomplete information inherent in our natural languages and in datasets of the real-world complex systems. Finally, we discuss determinization of WHFFRA and demonstrated the application of introduced WHFFRA in decision-making scenarios of medical diagnosis problems.
Effects of Spatial Variation in Relative Density on Seismic Behavior of Saturated Sandy Ground
Authors: Sawatsubashi Masahiro , Ishimaru Makoto , Kobayashi Takaaki , Hiraga Kenji , Nakamura Hideki
Published: June 2024

Proper consideration of variations in soil properties and their effects is necessary to enhance the seismic safety of structures. In this study, the effect of spatial variations in the cyclic resistance ratio on seismic ground behavior was investigated. Initially, dynamic centrifuge model tests were conducted on sandy ground featuring a 20% mixture of weak zones with low relative density and on homogeneous sandy ground with no mixture of weak zones. Subsequently, an effective stress analysis was performed by modeling the distribution of weak zones in the centrifuge model tests. Finally, after confirming the validity of the parameter settings, several analytical models with different weak-zone distributions were generated and numerically analyzed using random field theory. The results indicate that a local mixing of approximately 20% weak zones has only a limited effect on overall ground behavior. However, differences were observed in the rate of increase and dissipation of the excess pore water pressure ratio and in the residual horizontal displacement.
Ambient Vibration-Based Seismic Evaluation of Long-Span Prestressed Concrete Box-Girder Bridges Under Long-Duration, Near-Fault and Far-Fault Ground Motions
Authors: Altunişik Ahmet Can , Sunca Fezayil , Sevim Barış
Published: June 2024

This study investigates the seismic behavior of long-span prestressed concrete box-girder bridges subjected to long-duration (LD) ground motions and spectrally equivalent near-fault (NF) and far-fault (FF) short-duration ground motions. For this purpose, the Kömürhan and Gülburnu Highway Bridges built with the balanced cantilever method using prestressed concrete box-girder were selected. This paper consists of two main sections. First, ambient vibration tests were conducted to identify the modal parameters of the bridges and calibrate the finite element models. Second, using three ground motion sets consisting of 42 acceleration records applied to the orthogonal and vertical directions of the bridges, the structural responses were evaluated and compared. In order to determine the type of ground motion that is critical for this type of bridge, these sets consist of 14 long-duration ground motions, 14 spectrally equivalent near-fault short-duration ground records, and 14 spectrally equivalent far-fault short-duration records. The comparison parameters considered for this study were displacements and internal forces in the piers and decks. The results strive to highlight the extent to which the duration and characteristics of the ground motion sets affect the structural behavior. Results indicate that the mean deck displacements of selected bridges obtained from FF short-duration records were nearly 10.70% and 7.44% less than those obtained from the LD and NF short-duration ground motions. These trends were also observed in the bridge piers. Moreover, increases of up to 17.54% and 26.65% in the mean shear forces of the piers under LD and NF short-duration ground motions were observed compared to those determined from the FF short-duration counterparts. Similar trends were observed in the bending moment values. It was also observed that far-fault short-duration records may have substantial consequences on such structures.
Biomechanical Gait Interventions in Persons with Autism Spectrum Disorder: A Scoping Review
Authors: Luginsland Lauren A. , Haegele Justin A. , Laverdure Patricia A. , Bennett Hunter J.
Published: June 2024

The purpose of this scoping review was to outline the current gait interventions used in biomechanics-based research focused on persons with autism spectrum disorder. A review of articles was conducted using the PRISMA methodology for reporting guidance with an a priori PICO framework. The selected articles were identified, reviewed, evaluated for risk of bias, and used to group biomechanics-based gait interventions that have been implemented in research involving persons with autism spectrum disorder. Titles and abstracts of 573 articles were reviewed; seven articles describing gait interventions met the inclusionary criteria. The interventions reported in the literature were hippotherapy, weighted vests, and exercise programs. Additional orthopedic interventions (serial casting and foot orthoses) were utilized for individuals who primarily walk on their forefoot. Findings from this review reveal changes in spatiotemporal characteristics post-hippotherapy, changes in ground reaction forces and foot pressures after participation in exercise intervention programs, and no change in parameters via weighted vests. For persons with autism spectrum disorder who are forefoot strikers, the use of serial casting and foot orthoses reportedly improved the overall kinematic and spatiotemporal parameters during gait.
AdaptiX - A Transitional XR Framework for Development and Evaluation of Shared Control Applications in Assistive Robotics
Authors: Pascher Max , Goldau Felix Ferdinand , Kronhardt Kirill , Frese Udo , Gerken Jens
Published: June 2024

With the ongoing efforts to empower people with mobility impairments and the increase in technological acceptance by the general public, assistive technologies, such as collaborative robotic arms, are gaining popularity. Yet, their widespread success is limited by usability issues, specifically the disparity between user input and software control along the autonomy continuum. To address this, shared control concepts provide opportunities to combine the targeted increase of user autonomy with a certain level of computer assistance. This paper presents the free and open-source AdaptiX XR framework for developing and evaluating shared control applications in a high-resolution simulation environment. The initial framework consists of a simulated robotic arm with an example scenario in Virtual Reality (VR), multiple standard control interfaces, and a specialized recording/replay system. AdaptiX can easily be extended for specific research needs, allowing Human-Robot Interaction (HRI) researchers to rapidly design and test novel interaction methods, intervention strategies, and multi-modal feedback techniques, without requiring an actual physical robotic arm during the early phases of ideation, prototyping, and evaluation. Also, a Robot Operating System (ROS) integration enables the controlling of a real robotic arm in a PhysicalTwin approach without any simulation-reality gap. Here, we review the capabilities and limitations of AdaptiX in detail and present three bodies of research based on the framework. AdaptiX can be accessed at https://adaptix.robot-research.de.
VR-based Competence Training at Scale: Teaching Clinical Skills in the Context of Virtual Brain Death Examination
Authors: Kockwelp Pascal , Meyerheim Marcel , Valkov Dimitar , Mergen Marvin , Junga Anna , Krüger Antonio , Marschall Bernhard , Holling Markus , Risse Benjamin
Published: June 2024

Teaching medical practical and soft skills in clinical routines is increasingly difficult, and manikin or actor-based simulations have gained popularity in the last decades. These simulations, however, hardly scale with the demand, are commonly insufficient to train crucial clinical competencies, and cannot portray complex visual and dynamic symptomatologies as required in, for example, brain death examinations. In this paper, we explore the requirements and challenges of integrating a large-scale high-throughput VR setup into a real medical curriculum and describe our approaches and implementation. Therefore we extend and evaluate an interactive virtual reality-based simulation for training brain death diagnostics in a virtual intensive care environment, featuring a fully reactive simulated patient. To enable the required scalability we integrated the simulation into a dedicated hardware and software framework, enabling 12 simultaneous VR trainings which are controlled by a centralized server system. Using this setup we continuously collected feedback on the application's usability and realism from hundreds of students to gain first insights into the applicability of large-scale VR-based learning systems in real course designs. After integrating this feedback, we conducted a controlled curricular study in which we compared the virtual brain death simulation with the classical manikin-based training approach. Our results indicate that the immersive learning experience is perceived to be more realistic and engaging and is overall preferred by the students while also providing the same learning effect as the alternatives.
Distributed Computing Column 87
Distributed and Algorithmic Thinking across Domains
Authors: Alistarh Dan
Published: June 2024

Overview. One of the goals of the column is to stimulate and publicise results by the younger generation of Distributed Computing researchers. In this spirit, this month we go into more depth into one of the two theses highlighted by the Doctoral Dissertation Award, by Dr. Siddartha Jayanti. (Unfortunately, the other 2023 recipient, Dr. Dean Leitersdorf, could not contribute this time, due to outside constraints.)

Dr. Siddartha Jayanti's thesis comprises novel results in the scope of distributed and concurrent synchronization. The thesis, and Siddartha's work in general, is remarkable for both its depth and breadth: as you can see in the overview, the work incorporates technical results spanning from multi-processor synchronization to finding equilibria in multiplayer games! Another remarkable aspect is Siddartha's commitment to broadening participation in STEM, specifically to expanding science availability by writing what appears to be the first research paper in the Telugu language. It is also worth noting that Siddartha is part of the second generation of Distributed Computing researchers from his family. (As readers probably know, his father is Prof. Prasad Jayanti.)

The strength and diversity of the 2023 awarded theses, together with the fact that PODC has received a record number of submissions this year, suggest that the future is bright for our area.
Multilevel Interventions Targeting Obesity: State of the Science and Future Directions
Authors: Seguin-Fowler Rebecca A. , Graham Meredith L. , Demment Margaret , Uribe Alexandra L. MacMillan , Rethorst Chad D. , Szeszulski Jacob
Published: June 2024

A seminal report, released in 2001 by the Institute of Medicine, spurred research on the design, implementation, and evaluation of multilevel interventions targeting obesity and related behaviors. By addressing social and environmental factors that support positive health behavior change, interventions that include multiple levels of influence (e.g., individual, social, structural) aim to bolster effectiveness and, ultimately, public health impact. With more than 20 years of multilevel obesity intervention research to draw from, this review was informed by published reviews (n = 51) and identified intervention trials (n = 103), inclusive of all ages and countries, to elucidate key learnings about the state of the science. This review provides a critical appraisal of the scientific literature related to multilevel obesity interventions and includes a description of their effectiveness on adiposity outcomes and prominent characteristics (e.g., population, setting, levels). Key objectives for future research are recommended to advance innovations to improve population health and reduce obesity.
Websites of Note - Summer 2024
Authors: Suroviec Alice H.
Published: June 2024

Websites of Note selected for you by Alice Suroviec
Scoping Review on the Interactive Digital Tools Used for the Physical and Cognitive Stimulation of Healthy Older Adults
Authors: Busser Auriane , Fleury Sylvain , Kadri Abdelmajid , Haj Mahmoud Olfa , Richir Simon
Published: June 2024

As more of our lives are spent using electronic devices, it comes as a natural deduction that those digital tools could be used to maintain people’s health. Gamified exercise or exergames are indeed promising means to motivate the population to get physically active and even cognitively active if paired with the appropriate games. Considering the global concern of an aging population which could benefit from both physical and cognitive stimulation, these tools appear to be an encouraging solution to keep the population healthier over time. This scoping review reports on the digital tools used in publications between January 2015 and December 2023 regarding the physical and cognitive stimulation of healthy elderly people. The search was conducted in PubMed, Web of Science, and ScienceDirect databases. Of the 1579 publications retrieved, a total of 68 publications were analyzed in this review. A wide variety of digital tools were used in the corpus for the combined physical and cognitive stimulation of the elderly. These tools can be categorized into six types of hardware: pressure plates, optical motion capture, inertial motion capture, virtual reality, ergometers, and driving simulators. The apparition of publications using virtual reality and an increase in publications using inertial motion capture in 2020 could be an indicator that digital tools used for cognitive and physical stimulation of the elderly are evolving. Another finding is the wide variety in evaluation tools used to monitor the outcomes of each protocol. A standardization of the testing process might be needed in order to improve comparisons between experiments.
Phylogeny of the Genera with Oromandibular Discs in the Subfamily Labeoninae (Teleostei: Cyprinidae) with Descriptions of Two New Genera
Authors: Li Xu , Zhou Wei , Sun Chao , Yun Xing
Published: June 2024

The aim of this study was to understand the systematic relationships between certain fish genera with oromandibular discs in the Labeoninae. At the same time, this was an opportunity to clarify the taxonomic status of certain species in the generaAgeneiogarra,Garra,Placocheilus, and other taxa distributed in China. Morphological comparison and molecular analysis were used in the study. The results showed that the genera with oromandibular discs had no recent common ancestor and that their oromandibular discs were the result of convergent evolution in different evolutionary lineages. Due to the homogeneity of their habitats, these fish have evolved oromandibular discs with similar appearance and structure. Both morphological and molecular evidence suggests that (1)Placocheilus cryptonemusdistributed in the Nu‐Jiang (the Upper Salween River Basin), Yunnan, China, represent a new genus, here described asPseudoplacocheilus, and (2)Garra micropulvinusoccurring in the Panlong‐He (the upper portion of the Lo River, a branch of the Red River Basin) from Wenshan, Yunnan, represents another new genus, here described asSupradiscus.
An Intelligent System of Predicting Lymph Node Metastasis in Colorectal Cancer Using 3D CT Scans
Authors: Xie Min , Zhang Yi , Li Xinyang , Li Jiayue , Zou Xingyu , Mao Yiji , Zhang Haixian
Published: June 2024

In colorectal cancer (CRC), accurately predicting lymph node metastasis (LNM) contributes to developing appropriate treatment plans and serves as the key to long‐term survival of patients. In the clinical settings, preoperative LNM diagnosis in CRC predominantly depends on computed tomography (CT). Nevertheless, lymph nodes are small in size and difficult to identify on 3D CT scans, and CT‐based diagnosis of metastatic lymph nodes is prone to a significant misdiagnosis rate and lacks consistency across clinicians. Currently, there is no automatic system available for LNM prediction in CRC via 3D CT scans. In addition, existing deep learning‐ (DL‐) based lymph node detection models present low detection accuracy and high false‐positive rates, and most existing DL‐based lymph node metastasis prediction models mainly use tumor area characteristics but fail to adequately utilize lymph node information, thus not yielding satisfactory results. To tackle these issues, we propose an intelligent diagnosis system for this challenging task, mainly including a lymph node detection (LND) model and a lymph node metastasis prediction (LNMP) model. In detail, the LND model utilizes an encoder‐decoder network to detect lymph nodes, and the LNMP model employs an innovative attention‐based multiple instance learning (MIL) network. An instance‐level self‐attention feature enhancement module is designed to extract and augment lymph node features as a bag of instances. Furthermore, a bag‐level MIL prediction module is employed to extract instance features and create a bag representation for the ultimate LNM prediction. As far as we know, the proposed intelligent system represents the pioneering method for addressing this complex clinical challenge. In experiments, our proposed intelligent system achieves the AUC of 75.4% and the accuracy of 73.9%, showcasing a significant enhancement compared to physicians specialising in CRC and highlighting its strong clinical applicability. The accessible code can be found at https://github.com/SCU-MI/IS-LNM.
Nivolumab Reaches Brain Lesions in Patients with Recurrent Glioblastoma and Induces T-cell Activity and Upregulation of Checkpoint Pathways
Authors: Skadborg Signe K. , Maarup Simone , Draghi Arianna , Borch Annie , Hendriksen Sille , Mundt Filip , Pedersen Vilde , Mann Matthias , Christensen Ib J. , Skjøth-Ramussen Jane , Yde Christina W. , Kristensen Bjarne W. , Poulsen Hans S. , Hasselbalch Benedikte , Svane Inge M. , Lassen Ulrik , Hadrup Sine R.
Published: June 2024

Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis. Although immunotherapy is being explored as a potential treatment option for patients with GBM, it is unclear whether systemic immunotherapy can reach and modify the tumor microenvironment in the brain. We evaluated immune characteristics in patients receiving the anti-PD-1 immune checkpoint inhibitor nivolumab 1 week prior to surgery, compared with control patients receiving salvage resection without prior nivolumab treatment. We observed saturating levels of nivolumab bound to intratumorally and tissue-resident T cells in the brain, implicating saturating levels of nivolumab reaching brain tumors. Following nivolumab treatment, significant changes in T-cell activation and proliferation were observed in the tumor-resident T-cell population, and peripheral T cells upregulated chemokine receptors related to brain homing. A strong nivolumab-driven upregulation in compensatory checkpoint inhibition molecules, i.e., TIGIT, LAG-3, TIM-3, and CTLA-4, was observed, potentially counteracting the treatment effect. Finally, tumor-reactive tumor-infiltrating lymphocytes (TIL) were found in a subset of nivolumab-treated patients with prolonged survival, and neoantigen-reactive T cells were identified in both TILs and blood. This indicates a systemic response toward GBM in a subset of patients, which was further boosted by nivolumab, with T-cell responses toward tumor-derived neoantigens. Our study demonstrates that nivolumab does reach the GBM tumor lesion and enhances antitumor T-cell responses both intratumorally and systemically. However, various anti-inflammatory mechanisms mitigate the clinical efficacy of the anti-PD-1 treatment.
Supplementary Figure Legends from Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Eltoukhi Mohamed , Sindhani Mohit , Prunty Megan , Geynisman Daniel M. , Ghatalia Pooja , Valentine Henkel , Calaway Adam , Correa Andres F. , Brown Jason R. , Mishra Kirtishri , Plimack Elizabeth R. , Kutikov Alexander , Ghannoum Mahmoud , Elshaer Mohammed , Retuerto Mauricio , Ponsky Lee , Uzzo Robert G. , Abbosh Philip H.
Published: June 2024

Supplementary Figure Legends
Supplementary Figure 8 from Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Eltoukhi Mohamed , Sindhani Mohit , Prunty Megan , Geynisman Daniel M. , Ghatalia Pooja , Valentine Henkel , Calaway Adam , Correa Andres F. , Brown Jason R. , Mishra Kirtishri , Plimack Elizabeth R. , Kutikov Alexander , Ghannoum Mahmoud , Elshaer Mohammed , Retuerto Mauricio , Ponsky Lee , Uzzo Robert G. , Abbosh Philip H.
Published: June 2024

Supplementary Figure 8: Microbial Composition Differences in Mice Exposed to BBN Versus Water

Water Group:

A: Alpha diversity indices (ACE, Chao1, Shannon) plotted over multiple time points (0, 6, 12, 16-22 weeks), showing variations in microbial diversity in mice given water.

B: Line graph depicting the percentage composition of bacterial families over time.

C: Venn diagram highlighting the unique and shared bacterial operational taxonomic units (OTUs) at different time points.

D: Principal Coordinates Analysis (PCoA) based on weighted UniFrac distances.

E: Bar charts representing the relative abundance of specific taxa, identified as significantly different by LEfSe analysis, across the time points. The bars indicate changes in key microbial taxa that are statistically significant.

BBN Group:

F: Alpha diversity indices (ACE, Chao1, Shannon) for the BBN group.

G: Line graph showing the dynamic changes in the percentage composition of bacterial families over time in the BBN-treated mice.

H: Venn diagram detailing unique and shared bacterial OTUs between the different time points in the BBN group, illustrating the impact of the carcinogen on microbial turnover.

I: PCoA plot for the BBN group, using weighted UniFrac distances to show clustering patterns that differ from the water group.

J: LEfSe analysis bar charts showing the relative abundance of significantly different taxa across time points in the BBN group.
Supplementary Figure 7 from Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Eltoukhi Mohamed , Sindhani Mohit , Prunty Megan , Geynisman Daniel M. , Ghatalia Pooja , Valentine Henkel , Calaway Adam , Correa Andres F. , Brown Jason R. , Mishra Kirtishri , Plimack Elizabeth R. , Kutikov Alexander , Ghannoum Mahmoud , Elshaer Mohammed , Retuerto Mauricio , Ponsky Lee , Uzzo Robert G. , Abbosh Philip H.
Published: June 2024

Supplementary Figure 7: Gut Microbiome Changes in Partners of Bladder Cancer Patients

A: Stacked bar chart representing the relative abundances of key bacterial genera before, during, and after the chemotherapy periods in partners of patients.

B: Principal Coordinates Analysis (PCoA) plot based on weighted UniFrac distances showing the clustering of microbiome samples at different stages of chemotherapy (before, during, after). The ellipses represent the 95% confidence intervals for each group.

C: Violin plots illustrating the distribution of alpha diversity indices (ACE, Chao1, Observed, Pielou, Shannon, Simpson) at three key stages of chemotherapy.

D: Bar graph depicting the percentage representation of selected bacterial genera across the three phases of chemotherapy in partners.

E: Linear Discriminant Analysis (LDA) effect size (LEfSe) plot comparing bacterial taxa before and after chemotherapy, identifying which taxa are statistically significantly different between the two time points.

F: Venn diagram illustrating the unique and shared bacterial taxa found at each phase of chemotherapy.
Supplementary Figure 1 from Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Eltoukhi Mohamed , Sindhani Mohit , Prunty Megan , Geynisman Daniel M. , Ghatalia Pooja , Valentine Henkel , Calaway Adam , Correa Andres F. , Brown Jason R. , Mishra Kirtishri , Plimack Elizabeth R. , Kutikov Alexander , Ghannoum Mahmoud , Elshaer Mohammed , Retuerto Mauricio , Ponsky Lee , Uzzo Robert G. , Abbosh Philip H.
Published: June 2024

Supplementary Figure 1: Overview of Sample Collection and Experimental Setup Diagram outlining the protocols for human fecal sample collection across various time points during chemotherapy in bladder cancer patients, accompanied by the setup of the murine bladder cancer model to study the gut microbiome.
Supplementary Data from Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Eltoukhi Mohamed , Sindhani Mohit , Prunty Megan , Geynisman Daniel M. , Ghatalia Pooja , Valentine Henkel , Calaway Adam , Correa Andres F. , Brown Jason R. , Mishra Kirtishri , Plimack Elizabeth R. , Kutikov Alexander , Ghannoum Mahmoud , Elshaer Mohammed , Retuerto Mauricio , Ponsky Lee , Uzzo Robert G. , Abbosh Philip H.
Published: June 2024

Supplemental Data
FIGURE 1 from Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Eltoukhi Mohamed , Sindhani Mohit , Prunty Megan , Geynisman Daniel M. , Ghatalia Pooja , Valentine Henkel , Calaway Adam , Correa Andres F. , Brown Jason R. , Mishra Kirtishri , Plimack Elizabeth R. , Kutikov Alexander , Ghannoum Mahmoud , Elshaer Mohammed , Retuerto Mauricio , Ponsky Lee , Uzzo Robert G. , Abbosh Philip H.
Published: June 2024

Bladder cancer versus controls microbiome diversity and differences. A, Stacked bar plot displaying the relative abundances of predominant bacterial genera identified in patients with bladder cancer (n = 142) and control individuals (n = 48). B, Distribution of alpha diversity indices across both cohorts, quantified using ACE, Chao1, Observed species, Pielou's evenness, Shannon, and Simpson indices, with error bars denoting variability within each group. C, Overall relative abundances of bacterial general identified by group (bladder cancer vs. control). D, Beta diversity assessed through weighted UniFrac PCoA, highlighting distinct microbial community structures associated with each group. E, LEfSe identifying differentially abundant taxa at various taxonomic levels, supported by a taxonomic cladogram visualized in F.
Data from Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Eltoukhi Mohamed , Sindhani Mohit , Prunty Megan , Geynisman Daniel M. , Ghatalia Pooja , Valentine Henkel , Calaway Adam , Correa Andres F. , Brown Jason R. , Mishra Kirtishri , Plimack Elizabeth R. , Kutikov Alexander , Ghannoum Mahmoud , Elshaer Mohammed , Retuerto Mauricio , Ponsky Lee , Uzzo Robert G. , Abbosh Philip H.
Published: June 2024

Abstract
Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathologic factors on chemotherapy response, the role of the gut microbiome (GM) in bladder cancer chemotherapy response remains poorly understood. This study examines the variance in the GM of patients with bladder cancer compared with healthy adults, and investigates GM compositional differences between patients who respond to chemotherapy versus those who exhibit residual disease.

Our study reveals distinct clustering, effectively separating the bladder cancer and healthy cohorts. However, no significant differences were observed between chemotherapy responders and nonresponders within community subgroups. Machine learning models based on responder status outperformed clinical variables in predicting complete response (AUC 0.88 vs. AUC 0.50), although no single microbial species emerged as a fully reliable biomarker.

The evaluation of short chain fatty acid (SCFA) concentration in blood and stool revealed no correlation with responder status. Still, SCFA analysis showed a higher abundance of Akkermansia (rs = 0.51, P = 0.017) and Clostridia (rs = 0.52, P = 0.018), which correlated with increased levels of detectable fecal isobutyric acid. Higher levels of fecal Lactobacillus (rs = 0.49, P = 0.02) and Enterobacteriaceae (rs = 0.52, P < 0.03) correlated with increased fecal propionic acid.

In conclusion, our study constitutes the first large-scale, multicenter assessment of GM composition, suggesting the potential for a complex microbial signature to predict patients more likely to respond to NAC based on multiple taxa.
Significance:
Our study highlights results that link the composition of the GM to the efficacy of NAC in MIBC. We discovered that patients with higher levels of Bacteroides experienced a worse response to NAC. This microbial signature shows promise as a superior predictor of treatment response over traditional clinical variables. Although preliminary, our findings advocate for larger, more detailed studies to validate these associations.
Epidemiology of Renal Replacement Therapy for Critically Ill Patients across Seven Health Jurisdictions
Authors: Ziegler Jennifer , Morley Katharine , Pilcher David , Bellomo Rinaldo , Soares Marcio , Salluh Jorge I.F. , Borges Lunna P. , Bagshaw Sean M. , Hudson Darren , Christiansen Christian F. , Heide-Jorgensen Uffe , Lone Nazir I. , Buyx Alena , McLennan Stuart , Celi Leo A. , Rush Barret
Published: June 2024

Introduction: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions. Methods: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the USA between 2006 and 2023, depending on data availability of each dataset. Patients with a history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded. Results: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%. Conclusion: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that differences in access to and provision of this therapy are contributing factors.
Neurotrophin-3 Facilitates Stemness Properties and Associates with Poor Survival in Lung Cancer
Authors: Peng Ta-Jung , Chang Wang Chien-Chih , Tang Shye-Jye , Sun Guang-Huan , Sun Kuang-Hui
Published: June 2024

Introduction: Cancer stem cells (CSCs) shape the tumor microenvironment via neuroendocrine signaling and orchestrate drug resistance and metastasis. Cytokine antibody array demonstrated the upregulation of neurotrophin-3 (NT-3) in lung CSCs. This study aims to dissect the role of NT-3 in lung CSCs during tumor innervation. Methods: Western blotting, quantitative reverse transcription-PCR, and flow cytometry were used to determine the expression of the NT-3 axis in lung CSCs. NT-3-knockdown and NT-3-overexpressed cells were derived lung CSCs, followed by examining the stemness gene expression, tumorsphere formation, transwell migration and invasion, drug resistance, soft agar colony formation, and in vivo tumorigenicity. Human lung cancer tissue microarray and bioinformatic databases were used to investigate the clinical relevance of NT-3 in lung cancer. Results: NT-3 and its receptor tropomyosin receptor kinase C (TrkC) were augmented in lung tumorspheres. NT-3 silencing (shNT-3) suppressed the migration and anchorage-independent growth of lung cancer cells. Further, shNT-3 abolished the sphere-forming capability, chemo-drug resistance, invasion, and in vivo tumorigenicity of lung tumorspheres with a decreased expression of CSC markers. Conversely, NT-3 overexpression promoted migration and anchorage-independent growth and fueled tumorsphere formation by upregulating the expression of CSC markers. Lung cancer tissue microarray analysis revealed that NT-3 increased in patients with advanced-stage, lymphatic metastasis and positively correlated with Sox2 expression. Bioinformatic databases confirmed a co-expression of NT-3/TrkC-axis and demonstrated that NT-3, NT-3/TrkC, NT-3/Sox2, and NT-3/CD133 worsen the survival of lung cancer patients. Conclusion: NT-3 conferred the stemness features in lung cancer during tumor innervation, which suggests that NT-3-targeting is feasible in eradicating lung CSCs.
Complementariedades económicas y divergencias locales: el proceso de separación del Reino de Chile y la región mendosanjuanina en la segunda mitad del siglo XVIII
Authors: Sovarzo José
Published: June 2024

This article aims to examine the complexities faced by the economies of Santiago (Kingdom of Chile) and the mendosanjuanina region at the end of the eighteenth century, alongside the intense change existing in the Spanish American territories. The economic complementarities that united both economies were prioritized by local interests that sought to achieve greater autonomy for each of the cities within the monarchical group. Our argument is based on the analysis of the customs notes of Buenos Aires and the documentation generated by the Chilean authorities, the agents of Mendoza, and San Juan in the Spanish Court.
Induction of DEPP1 by HIF Mediates Multiple Hallmarks of Ischemic Cardiomyopathy
Authors: Wyant Gregory A. , Jiang Qinqin , Singh Madhu , Qayyum Shariq , Levrero Clara , Maron Bradley A. , Kaelin William G.
Published: June 2024

BACKGROUND:

HIF (hypoxia inducible factor) regulates many aspects of cardiac function. We and others previously showed that chronic HIF activation in the heart in mouse models phenocopies multiple features of ischemic cardiomyopathy in humans, including mitochondrial loss, lipid accumulation, and systolic cardiac dysfunction. In some settings, HIF also causes the loss of peroxisomes. How, mechanistically, HIF promotes cardiac dysfunction is an open question.

METHODS:

We used mice lacking cardiac pVHL (von Hippel-Lindau protein) to investigate how chronic HIF activation causes multiple features of ischemic cardiomyopathy, such as autophagy induction and lipid accumulation. We performed immunoblot assays, RNA sequencing, mitochondrial and peroxisomal autophagy flux measurements, and live cell imaging on isolated cardiomyocytes. We used CRISPR-Cas9 gene editing in mice to validate a novel mediator of cardiac dysfunction in the setting of chronic HIF activation.

RESULTS:

We identify a previously unknown pathway by which cardiac HIF activation promotes the loss of mitochondria and peroxisomes. We found that DEPP1 (decidual protein induced by progesterone 1) is induced under hypoxia in a HIF-dependent manner and localizes inside mitochondria. DEPP1 is both necessary and sufficient for hypoxia-induced autophagy and triglyceride accumulation in cardiomyocytes ex vivo. DEPP1 loss increases cardiomyocyte survival in the setting of chronic HIF activation ex vivo, and whole-body Depp1 loss decreases cardiac dysfunction in hearts with chronic HIF activation caused by
VHL
loss in vivo.

CONCLUSIONS:

Our findings identify DEPP1 as a key component in the cardiac remodeling that occurs with chronic ischemia.
Deep Learning for Echo Analysis, Tracking, and Evaluation of Mitral Regurgitation (DELINEATE-MR)
Authors: Long Aaron , Haggerty Christopher M. , Finer Joshua , Hartzel Dustin , Jing Linyuan , Keivani Azadeh , Kelsey Christopher , Rocha Daniel , Ruhl Jeffrey , vanMaanen David , Metser Gil , Duffy Eamon , Mawson Thomas , Maurer Mathew , Einstein Andrew J. , Beecy Ashley , Kumaraiah Deepa , Homma Shunichi , Liu Qi , Agarwal Vratika , Lebehn Mark , Leon Martin , Hahn Rebecca , Elias Pierre , Poterucha Timothy J.
Published: June 2024

BACKGROUND:

Artificial intelligence, particularly deep learning (DL), has immense potential to improve the interpretation of transthoracic echocardiography (TTE). Mitral regurgitation (MR) is the most common valvular heart disease and presents unique challenges for DL, including the integration of multiple video-level assessments into a final study-level classification.

METHODS:

A novel DL system was developed to intake complete TTEs, identify color MR Doppler videos, and determine MR severity on a 4-step ordinal scale (none/trace, mild, moderate, and severe) using the reading cardiologist as a reference standard. This DL system was tested in internal and external test sets with performance assessed by agreement with the reading cardiologist, weighted κ, and area under the receiver-operating characteristic curve for binary classification of both moderate or greater and severe MR. In addition to the primary 4-step model, a 6-step MR assessment model was studied with the addition of the intermediate MR classes of mild-moderate and moderate-severe with performance assessed by both exact agreement and ±1 step agreement with the clinical MR interpretation.

RESULTS:

A total of 61 689 TTEs were split into train (n=43 811), validation (n=8891), and internal test (n=8987) sets with an additional external test set of 8208 TTEs. The model had high performance in MR classification in internal (exact accuracy, 82%; κ=0.84; area under the receiver-operating characteristic curve, 0.98 for moderate or greater MR) and external test sets (exact accuracy, 79%; κ=0.80; area under the receiver-operating characteristic curve, 0.98 for moderate or greater MR). Most (63% internal and 66% external) misclassification disagreements were between none/trace and mild MR. MR classification accuracy was slightly higher using multiple TTE views (accuracy, 82%) than with only apical 4-chamber views (accuracy, 80%). In subset analyses, the model was accurate in the classification of both primary and secondary MR with slightly lower performance in cases of eccentric MR. In the analysis of the 6-step classification system, the exact accuracy was 80% and 76% with a ±1 step agreement of 99% and 98% in the internal and external test set, respectively.

CONCLUSIONS:

This end-to-end DL system can intake entire echocardiogram studies to accurately classify MR severity and may be useful in helping clinicians refine MR assessments.
Development and Validation of a Supplementary Grading Scale for Outcomes of Brainstem Cavernous Malformations
Authors: Li Zongze , Lu Junlin , Liu Mingjian , Ma Li , Quan Kai , Zhang Hongfei , Liu Peixi , Shi Yuan , Dong Xuchen , You Chao , Tian Rui , Zhu Wei
Published: June 2024

BACKGROUND:

Surgical risk assessment is intriguing for clinical decision-making of brainstem cavernous malformation (BSCM) treatment. While the BSCM grading scale, encompassing size, developmental venous anomaly, crossing axial midpoint, age, and timing of intervention, is increasingly utilized, the clinical relevance of neurological fluctuation and recurrent hemorrhage has not been incorporated. This study aimed to propose a supplementary grading scale with enhanced predictive efficacy.

METHODS:

Using a retrospective nationwide registry of consecutive patients with BSCMs undergoing surgery in China from March 2011 to May 2023, a new supplementary BSCM grading scale was developed from a derivative cohort of 260 patients and validated in an independent concurrent cohort of 67 patients. The primary outcome was unfavorable neurological function (modified Rankin Scale score >2) at the latest follow-up. The performance of the supplementary grading system was evaluated for discrimination, calibration, and clinical utility and further compared with its original counterpart.

RESULTS:

Over a follow-up of at least 6 months after surgery, the unfavorable outcomes were 31% in the overall cohort (101/327 patients). A preoperative motor deficit (odds ratio, 3.13;
P
=0.001), recurrent hemorrhage (odds ratio, 3.05;
P
<0.001), timing of intervention (odds ratio, 7.08;
P
<0.001), and crossing the axial midpoint (odds ratio, 2.57;
P
=0.006) were associated with the unfavorable outcomes and composed the initial Huashan grading variables. A supplementary BSCM grading system was subsequently developed by incorporating the Huashan grading variables into the original BSCM grading scale. The predictive capability of the supplementary scale was consistently superior to the original counterpart in either the derivative cohort (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.68–0.80] for the supplementary versus 0.68 [95% CI, 0.61–0.74] for the original) or the validation cohort (0.75 [95% CI, 0.62–0.87] versus 0.64 [95% CI, 0.48–0.81]).

CONCLUSIONS:

This study highlights the neurological relevance of BSCM hemorrhage in surgical risk assessment. Via compositing preoperative motor function and recurrent hemorrhages, a supplementary grading scale may improve a dynamic risk assessment for clinical decisions in the management of BSCMs.
Quantile Effects in Discrete Choice with Social Interactions
Authors: Lin Zhongjian
Published: June 2024

This paper provides a method to study quantile effects in discrete choice with social interactions. The method is based on a behavioral social interactions model from quantile preference in decision making and demonstrates peer effects on different quantiles of discrete outcomes. The peer effects parameters are estimated by a nested pseudo score (NPS) approach, which is developed to tackle the computational burden pertaining to the social interactions model. Consistency and asymptotic normality are established for the proposed NPS estimator. We illustrate the finite sample performance of the model and the estimator by Monte Carlo experiments and an application of peer effects among students on exercise decisions, using the National Longitudinal Study of Adolescent Health dataset.
Democracy Doesn't Always Happen Over Night: Regime Change in Stages and Economic Growth
Authors: Boese-Schlosser Vanessa , Eberhardt Markus
Published: June 2024

How substantial are the economic benefits from democratic regime change? We argue that democratisation is often not a discrete event but a two-stage process: autocracies enter into ‘episodes’ of political liberalisation which eventually culminate in regime change or not. To account for this chronology and the implicit counterfactual groups, we introduce a repeated-treatment difference-in-difference implementation capturing non-parallel trends and selection into treatment. We find that modelling regime change in two stages rather than a single event yields stronger long-run growth effects. Among democratizers, experiencing repeated episodes without regime change reduces growth in democracy whereas length of episode does not.
Crusade against Bolshevism
Authors: Bressler Jonas
Published: June 2024

During the Spanish Civil War (1936–1939), many conservatives and fascists in Western Europe supported the Francoist rebels. This paper will outline how conservatives and fascists in Great Britain, France, and Belgium worked together to support the rebellion in Spain. Regarding Great Britain, the pressure group Friends of Nationalist Spain (FNS) will be studied, while for France and Belgium several different groups and individuals will be examined. In all countries, these networks were managed by the Francoist Ambassadors. This paper sheds light on an extensive pro-Francoist network that operated across Western Europe in which conservatives and fascists worked side-by-side. Their cooperation was facilitated by a shared anti-communism and the use of common structures, such as conservative parties. It draws from sources located in archives in Spain, Great Britain, France, and Belgium and includes publications written by the individuals who were involved in this network.
The Duce’s Cheerleaders and the Führer’s Vanguard
Authors: Citrigno Flavia
Published: June 2024

Regimes in the interwar years went to great lengths to educate young girls into their ideology. Fascist Italy had a few years head start—its Accademia fascista di educazione fisica femminile [Fascist Academy of Female Physical Education] was regarded as innovative from likeminded governments of the time, including Nazi Germany, and was the object of visits and attention. This article explores the arc drawn by relationships between Italian and German girl organizations, focusing on encounters between Orvietine and Bund Deutscher Mädel (BDM) members. It focuses on two exemplary moments in the history of the network: the 1937 trip to Berlin by 150 students of the Orvieto Academy, and the one-month observation visit in winter 1941 by Ursel Stein, a rising star of the BDM administration. By analyzing and comparing the dynamics, rituals, and actors of the two occasions the article points out at the different roles given to girl organizations by Nazi Germany and Fascist Italy and raises questions concerning the agency of the members of this women network.