bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker
Authors: Liu Shijin , Wang Penglin , Wang Peize , Zhao Zhan , Zhang Xiaolin , Pan Yunlong , Pan Jinghua
Published: July 2024

Background

Tissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal cancer (CRC) and their advantages remain unclear.

Methods

Clinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry.

Results

In this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of α-SMA+ vessels to the sum of the number of α-SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)-γ, thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN-γ, which resulted in better anti-tumor effects.

Conclusion

We demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.
A randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors
Authors: Vounckx Manon , Tijtgat Jens , Stevens Latoya , Dirven Iris , Ilsen Bart , Vandenbroucke Frederik , Raeymaeckers Steven , Vekens Karolien , Forsyth Ramses , Geeraerts Xenia , Van Riet Ivan , Schwarze Julia Katharina , Tuyaerts Sandra , Decoster Lore , De Ridder Mark , Dufait Ines , Neyns Bart
Published: July 2024

Background

Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB.

Methods

In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS).

Results

Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event.

Conclusion

SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint.

Trial registration number: Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.
LERFNet: an enlarged effective receptive field backbone network for enhancing visual drone detection
Authors: Elsayed Mohamed , Reda Mohamed , Mashaly Ahmed S. , Amein Ahmed S.
Published: July 2024

Recently, the world has witnessed a great increase in drone applications and missions. Drones must be detected quickly, effectively, and precisely when they are being handled illegally. Vision-based anti-drone systems provide an efficient performance compared to radar- and acoustic-based systems. The effectiveness of drone detection is affected by a number of issues, including the drone’s small size, conflicts with other objects, and noisy backgrounds. This paper employs enlarging the effective receptive field (ERF) of feature maps generated from the YOLOv6 backbone. First, RepLKNet is used as the backbone of YOLOv6, which deploys large kernels with depth-wise convolution. Then, to get beyond RepLKNet’s large inference time, a novel LERFNet is implemented. LERFNet uses dilated convolution in addition to large kernels to enlarge the ERF and overcome each other’s problems. The linear spatial-channel attention module (LAM) is used to give more attention to the most informative pixels and high feature channels. LERFNet produces output feature maps with a large ERF and high shape bias to enhance the detection of various drone sizes in complex scenes. The RepLKNet and LERFNet backbones for Tiny-YOLOv6, Tiny-YOLOv6, YOLOv5s, and Tiny-YOLOv7 are compared. In comparison to the aforementioned techniques, the suggested model’s results show a greater balance between accuracy and speed. LERFNet increases the MAP by $$2.8\%$$

2.8
%

, while significantly reducing the GFLOPs and parameter numbers when compared to the original backbone of YOLOv6.
Investigating the spatial propagation patterns of meteorological drought events and underlying mechanisms using complex network theory: A case study of the Yangtze River Basin, China
Authors: Liu Lei , Gao Chao , Zhu Zhanliang , Zhang Silong , Tang Xiongpeng
Published: July 2024

The spatial propagation patterns of meteorological drought events (MDEs) and underlying mechanisms contribute to elucidating and forecasting drought evolution. In this study, gridded MDEs in the Yangtze River Basin (YRB) throughout the entire year, wet season and dry season were extracted from 3-month Standardized Precipitation Evapotranspiration Index (SPEI-3) series. Event synchronization (ES) and complex networks (CN) were employed to construct the MDE synchronization networks and MDE spatial propagation networks for various periods. The former were utilized to identify MDE synchronized subregions where MDEs co-occur and co-evolve in the YRB, while the latter were used to quantify the MDE spatial propagation patterns over both the basin and its subregions. The driving mechanisms behind MDE spatial propagation were further investigated by diagnosing the concomitant drought-inducing climate systems. The findings reveal the presence of four MDE synchronized subregions during the wet season and five subregions during the entire year and dry season. These subregions exhibited distinct spatial propagation patterns of MDEs, aligning with overall findings across the YRB. Notable differences were observed between wet and dry seasons, with various subregions exhibiting distinctive spatial propagation patterns during each season. These patterns are driven by variations in the controlling atmospheric circulation systems, leading to anomalies of wind patterns and moisture distribution, ultimately resulting in deficient moisture supply. The variations of tropical sea surface thermal conditions, influences of the Tibetan Plateau and MDE self-propagation triggered by land–atmosphere feedback are considered as three primary influencing factors for MDE spatial propagation in the YRB.
Cenobamate: real-world data from a retrospective multicenter study
Authors: Lauxmann Stephan , Heuer David , Heckelmann Jan , Fischer Florian P. , Schreiber Melanie , Schriewer Elisabeth , Widman Guido , Weber Yvonne , Lerche Holger , Alber Michael , Schuh-Hofer Sigrid , Wolking Stefan
Published: July 2024

Background

Clinical trials have shown that cenobamate (CNB) is an efficacious and safe anti-seizure medication (ASM) for drug-resistant focal epilepsy. Here, we analyzed one of the largest real-world cohorts, covering the entire spectrum of epilepsy syndromes, the efficacy and safety of CNB, and resulting changes in concomitant ASMs.

Methods

We conducted a retrospective observational study investigating CNB usage in two German tertiary referral centers between October 2020 and June 2023 with follow-up data up to 27 months of treatment. Our primary outcome was treatment response. Secondary outcomes comprised drug response after 12 and 18 months, seizure freedom rates, CNB dosage and retention, adverse drug reactions (ADRs), and changes in concomitant ASMs.

Results

116 patients received CNB for at least two weeks. At 6 months, 98 patients were eligible for evaluation. Thereof 50% (49/98) were responders with no relevant change at 12 and 18 months. Seizure freedom was achieved in 18.4% (18/98) at 6 months, 16.7% (11/66), and 3.0% (1/33) at 12 and 18 months. The number of previous ASMs did not affect the seizure response rate. Overall, CNB was well-tolerated, however, in 7.7% (9/116), ADRs led to treatment discontinuation. The most frequent changes of concomitant ASMs included the discontinuation or reduction of sodium channel inhibitors, clobazam reduction, and perampanel discontinuation, while brivaracetam doses were usually left unchanged.

Conclusions

CNB proved to be a highly effective and generally well-tolerated ASM in patients with severe drug-resistant epilepsy, comprising a broad array of epilepsy syndromes beyond focal epilepsy.
Changes in human skin composition due to intrinsic aging: a histologic and morphometric study
Authors: Arnal-Forné Marta , Molina-García Tamara , Ortega María , Marcos-Garcés Víctor , Molina Pilar , Ferrández-Izquierdo Antonio , Sepulveda Pilar , Bodí Vicente , Ríos-Navarro César , Ruiz-Saurí Amparo
Published: July 2024

Skin represents the main barrier against the external environment, but also plays a role in human relations, as one of the prime determinants of beauty, resulting in a high consumer demand for skincare-related pharmaceutical products. Given the importance of skin aging in both medical and social spheres, the present research aims to characterize microscopic changes in human skin composition due to intrinsic aging (as opposed to aging influenced by external factors) via histological analysis of a photoprotected body region. Samples from 25 autopsies were taken from the periumbilical area and classified into four age groups: group 1 (0–12 years), group 2 (13–25 years), group 3 (26–54 years), and group 4 (≥ 55 years). Different traditional histological (hematoxylin–eosin, Masson’s trichrome, orcein, toluidine, Alcian blue, and Feulgen reaction) and immunohistochemical (CK20, CD1a, Ki67, and CD31) stains were performed. A total of 1879 images photographed with a Leica DM3000 optical microscope were morphometrically analyzed using Image ProPlus 7.0 for further statistical analysis with GraphPad 9.0. Our results showed a reduction in epidermis thickness, interdigitation and mitotic indexes, while melanocyte count was raised. Papillary but not reticular dermis showed increased thickness with aging. Specifically, in the papillary layer mast cells and glycosaminoglycans were expanded, whereas the reticular dermis displayed a diminution in glycosaminoglycans and elastic fibers. Moreover, total cellularity and vascularization of both dermises were diminished with aging. This morphometric analysis of photoprotected areas reveals that intrinsic aging significantly influences human skin composition. This study paves the way for further research into the molecular basis underpinning these alterations, and into potential antiaging strategies.
Relaxin combined with transarterial chemoembolization achieved synergistic effects and inhibited liver cancer metastasis in a rabbit VX2 model
Authors: Wang Fuquan , Zhu Licheng , Xiong Fu , Chai Bin , Wang Jihua , Zhou Guofeng , Cao Yanyan , Zheng Chuansheng
Published: July 2024

Objective

To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE).

Materials and methods

HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment.

Results

RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed.

Conclusion

RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.
Characterising, quantifying, and accessing eruption source parameters of explosive volcanic eruptions for operational simulation of tephra dispersion: a current view and future perspectives
Authors: Engwell Samantha , Mastin Larry G. , Bonadonna Costanza , Barsotti Sara , Deligne Natalia I. , Oladottir Bergrun A.
Published: July 2024

Eruption source parameters (ESPs) are crucial for characterising volcanic eruptions and are essential inputs to numerical models used for hazard assessment. Key ESPs of explosive volcanic eruptions include plume height, mass eruption rate, eruption duration, and grain-size distribution. Some of these ESPs can be directly observed during an eruption, but others are difficult to measure in real-time, or indeed, accurately and precisely quantify afterwards. Estimates of ESPs for eruptions that cannot be observed, for example, due to the remote location of a volcano or poor weather conditions, are often defined using expert judgement and data from past eruptions, both from the volcano of interest and analogue volcanoes farther afield. Analysis of such information is time intensive and difficult, particularly during eruption response. These difficulties have resulted in the production of datasets to aid quick identification of ESPs prior to or during an eruption for use in operational response settings such as those at volcano observatories and Volcanic Ash Advisory Centres. These resources include the Mastin et al. (2009a) ESP dataset and the Catalogue of Icelandic Volcanoes and European Catalogue of Volcanoes aviation tables. Here, we review and compare these resources, which take different approaches to assigning ESPs. We identify future areas for development of these resources, highlighting the need for frequent updates as more knowledge of volcanic activity is gained and as modelling capabilities and requirements change.
Obesity, organ failure, and transplantation: a review of the role of metabolic and bariatric surgery in transplant candidates and recipients
Authors: Ghanem Omar M. , Pita Alejandro , Nazzal Mustafa , Johnson Shaneeta , Diwan Tayyab , Obeid Nabeel R. , Croome Kristopher P. , Lim Robert , Quintini Cristiano , Whitson Bryan A. , Burt Holly Ann , Miller Charles , Kroh Matthew ,   SAGES & ASTS
Published: July 2024

Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.
Pediatric acute kidney injury and adverse health outcomes: using a foundational framework to evaluate a causal link
Authors: Morgan Catherine , Forest Emma , Ulrich Emma , Sutherland Scott
Published: July 2024

Acute kidney injury (AKI) is a major global health problem, expensive to manage, and its associations with negative pediatric health outcomes have been clearly demonstrated. One of the most fundamental questions to consider as we use previous epidemiological information to advance research and care paradigms is the strength of the causal link between pediatric AKI and health outcomes. In this review, we apply the foundational framework of the Bradford Hill criteria to evaluate the extent to which a causal link exists between AKI and the associated adverse outcomes in children. Available data in children support a causal link between AKI and short-term outcomes including mortality, length of stay, and ventilation time. Clarifying the causal nature of longer term associations requires further high-quality observational studies in children, careful consideration of what defines the most meaningful and measurable longer term outcomes after pediatric AKI, and integration of evolving biological data related to mechanisms of disease. Preventing or mitigating AKI should lead to improved outcomes. Demonstrating such reversibility will solidify confidence in the causal relationship, improve child health, and highlight an aspect which is highly relevant to clinicians, scientists, and policy makers.

Graphical abstract
Ant Colony Optimization for solving Directed Chinese Postman Problem
Authors: Sgarro Giacinto Angelo , Santoro Domenico , Grilli Luca
Published: July 2024

The Chinese Postman Problem (CPP) is a well-known optimization problem involving determining the shortest route, modeling the system as an undirected graph, for delivering mail, ensuring all roads are traversed while returning to the post office. The Directed Chinese Postman Problem (DCPP) extends the Chinese Postman Problem (CPP), where the underlying graph representing the system incorporates exclusively directed edges. Similarly to CPP, this problem has plenty of applications in route optimization, interactive system analysis, and circuit design problems. However, due to the added constraint (directionality of edges), DCPP results are more challenging to solve. Although methods to solve it in literature are proposed, typically by using minimum-cost-flow algorithms, the meta-heuristics approaches proposed to deal with it are very limited. In this paper, we propose an innovative meta-heuristic approach to solve DCPP by using an ant colony optimization (ACO) algorithm, i.e., an algorithm that simulates in a simplified way the behavior of some species of ants to solve optimization problems. The efficiency of our ant colony optimization for solving the Directed Chinese Postman Problem (ACO-DCPP) is measured by comparing the ACO outcomes with the results obtained by a recursive algorithm that explores all the possible solutions. Results show that ACO-DCPP is stable and gets the global optimum frequently by using an extremely limited number of solutions explored.
Cai’s herbal tea enhances mitochondrial autophagy of type 1 diabetic mellitus β cells through the AMPK/mTOR pathway and alleviates inflammatory response
Authors: Li Hongchun , Gao Yanfei , Li Mengdi , Dong Yue , Chen Jie , Zhang Bingyue , Li Kaiqiang , Cai Yuqun
Published: July 2024

Background

This study investigates the therapeutic mechanisms of Cai’s Herbal Tea in Type 1 Diabetes Mellitus (T1DM) mice, focusing on its effects on mitochondrial change and autophagy via the AMP-activated protein kinase (AMPK)—mammalian target of rapamycin (mTOR) pathway.

Methods

The composition of Cai’s Herbal Tea was analyzed by Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-Q/TOF-MS). C57BL/6 mice and Min6 pancreatic beta cells were divided into control, diabetic mellitus (DM)/high glucose (HG), and treatment groups (low, medium, and high doses of Cai’s Tea, and Metformin). Key physiological parameters, pancreatic islet health, Min6 cell morphology, viability, and insulin (INS) secretion were assessed. Small Interfering RNA-AMPK (si-AMPK) was utilized to confirm the pathway involvement.

Results

Cai’s Herbal Tea improved body weight, pancreatic islet pathological injury, and INS secretion whereas reduced total triglycerides, fasting blood sugar, and Interferon gamma (INF-γ) in T1DM mice, particularly at higher doses. In Min6 cells, Cai’s Tea mitigated HG-induced damage and proinflammatory response, enhancing cell viability and INS secretion. Notably, it reduced swelling and improved cristae structure in treated groups of mitochondria and promoted autophagy via the AMPK-mTOR pathway, evidenced by increased LC3II/LC3I and P-AMPK/AMPK ratios, and decreased P-mTOR/mTOR and P62 expressions in pancreatic islet β-cells. Furthermore, these effects were converted by si-AMPK interference.

Conclusion

Cai’s Herbal Tea exhibits significant therapeutic efficacy in T1DM mice by improving mitochondrial health and inducing autophagy through the AMPK-mTOR pathway in pancreatic islet β-cells. These findings highlight its potential as a therapeutic approach for T1DM management.
Back-and-Forth (BaF): a new greedy algorithm for geometric path planning of unmanned aerial vehicles
Authors: Aslan Selcuk
Published: July 2024

The autonomous task success of an unmanned aerial vehiclel (UAV) or its military specialization called the unmanned combat aerial vehicle (UCAV) has a direct relationship with the planned path. However, planning a path for a UAV or UCAV system requires solving a challenging problem optimally by considering the different objectives about the enemy threats protecting the battlefield, fuel consumption or battery usage and kinematic constraints on the turning maneuvers. Because of the increasing demands to the UAV systems and game-changing roles played by them, developing new and versatile path planning algorithms become more critical and urgent. In this study, a greedy algorithm named as the Back-and-Forth (BaF) was designed and introduced for solving the path planning problem. The BaF algorithm gets its name from the main strategy where a heuristic approach is responsible to generate two predecessor paths, one of which is calculated from the start point to the target point, while the other is calculated in the reverse direction, and combines the generated paths for utilizing their advantageous line segments when obtaining more safe, short and maneuverable path candidates. The performance of the BaF was investigated over three battlefield scenarios and twelve test cases belonging to them. Moreover, the BaF was integrated into the workflow of a well-known meta-heuristic, artificial bee colony (ABC) algorithm, and detailed experiments were also carried out for evaluating the possible contribution of the BaF on the path planning capabilities of another technique. The results of the experiments showed that the BaF algorithm is able to plan at least promising or generally better paths with the exact consistency than other tested meta-heuristic techniques and runs nine or more times faster as validated through the comparison between the BaF and ABC algorithms. The results of the experiments further proved that the integration of the BaF boosts the performance of the ABC and helps it to outperform all of fifteen competitors for nine of twelve test cases.
Assessing tungsten-based electrodes coated with W and Ce oxides for pH sensing applications
Authors: Díaz-Ballote Luis , Vega-Lizama Elsy Tarly , López Luis Maldonado , González-Gómez William Santiago
Published: July 2024

This study assessed tungsten-based materials with and without dispersed CeO2 for potential use as pH sensors. Specifically, three types of tungsten electrodes were characterized: tungsten electrodes without CeO2 but with native oxide, tungsten electrodes without CeO2 that were oxidized, and a tungsten electrode containing dispersed CeO2 that was oxidized, resulting in a mixture of WO3, CeO2, and Ce2O3. The characterization was performed using SEM/EDAX, X-ray photoelectron spectroscopy (XPS), and electrochemical techniques. The oxide coatings showed higher oxygen contents compared to native tungsten. XPS confirmed the presence of a thick layer of WO3 and cerium oxides. The electrodes exhibited good reproducibility and stability in pH measurements. A linear relationship was found between the open circuit potential and pH, with slopes of 44.9, 40.8, and 46.9 mV pH−1 for native oxide, WO3, and WO3 with CeO2 and Ce2O3, respectively. The latter showed the highest sensitivity and lowest hysteresis. The response times ranged from 14.5–23.5 s and were faster in acidic solutions. Overall, the inexpensive tungsten-based electrodes demonstrated promising capabilities for pH sensing, but in particular ceriated tungsten electrodes.
Analysis of MR–VR tele-operation methods for legged-manipulator robots
Authors: Cruz Ulloa Christyan , Domínguez David , del Cerro Jaime , Barrientos Antonio
Published: July 2024

The development of immersive technologies in recent years has facilitated the control and execution of tasks at a high level of complexity in robotic systems. On the other hand, exploration and manipulation tasks in unknown environments have been one of the main challenges in search and rescue (SAR) robotics. Due to the complexity and uncertainty involved in autonomous manipulation tasks in unstructured environments, these are usually tele-operated initially. This article addresses a comparative study between Mixed Reality (MR—Hololens) and Virtual Reality (VR—HTC-Vive) methods for teleoperating legged-manipulator robots in the context of search and rescue. For this purpose, a teleoperation robotics method was established to address the comparison, developing VR–MR interfaces with the same contextualization and operational functionality for mission management and robot control of a robotic set composed of a quadrupedal robot equipped with a 6 degrees of freedom (6DoF) manipulator, by a user using hand gestures. A set of metrics is proposed for the comparative evaluation of the interfaces considering parameters that allow analyzing operability in the context of the mission (latencies, physical parameters of the equipment, etc.), as well as from the aspect of operator performance (required training, confidence levels, etc.). The experimental phase was conducted using both on-site and remote operations to evaluate and categorize the advantages and disadvantages of each method.
Location and capacity allocation for emergency contact points in large-scale power outages
Authors: Truden Christian , Wankmüller Christian , Zehetner Dominik , Gansterer Margaretha
Published: July 2024

Nowadays, industry and individuals alike are highly dependent on a reliable power supply. A large-scale power outage, commonly known as a “blackout” is caused by natural disasters, cyber attacks, technical failure, or human errors, and can lead to a variety of severe consequences. The far-reaching dynamics of blackouts can even result in the collapse of critical public service infrastructure reliant on electricity (e.g., communication, water supply, medical services, public safety). Particularly, the loss of information and communication infrastructure essential to reporting medical emergencies, and the collapse of the drinking water supply are two critical stressors for the population to cope with. One attempt to tackle this situation is to install temporary emergency contact points (ECPs) into existing infrastructure. These can be approached by the population to communicate with medical personnel and to receive drinking water. Different types of professional personnel, which is a limited resource, are required to run such ECPs. Our study introduces this tactical decision problem. We formulate it as an integer linear program for the optimal spatial allocation of ECPs, such that multiple types of human resources that are required for operating such locations can be efficiently assigned. A comprehensive numerical study, based on data of the City of Vienna, demonstrates how to reduce the walking distance of inhabitants while increasing the efficiency of resource allocation. Matrix pruning based on an enforced limit of the walking distances together with a decomposition approach is utilized to solve the considered instances.
A Hilbert–Mumford criterion for polystability for actions of real reductive Lie groups
Authors: Biliotti Leonardo , Windare Oluwagbenga Joshua
Published: July 2024

We study a Hilbert–Mumford criterion for polystablility associated with an action of a real reductive Lie group G on a real submanifold X of a Kähler manifold Z. Suppose the action of a compact Lie group with Lie algebra

$$\mathfrak {u}$$

u

extends holomorphically to an action of the complexified group

$$U^{\mathbb {C}}$$

U
C

and that the U-action on Z is Hamiltonian. If

$$G\subset U^{\mathbb {C}}$$

G
⊂

U
C

is compatible, there is a corresponding gradient map

$$\mu _\mathfrak {p}: X\rightarrow \mathfrak {p}$$

μ
p

:
X
→
p

, where

$$\mathfrak {g}= \mathfrak {k}\oplus \mathfrak {p}$$

g
=
k
⊕
p

is a Cartan decomposition of the Lie algebra of G. Under some mild restrictions on the G-action on X,  we characterize which G-orbits in X intersect

$$\mu _\mathfrak {p}^{-1}(0)$$

μ

p

-
1

(
0
)

in terms of the maximal weight functions, which we viewed as a collection of maps defined on the boundary at infinity (

$$\partial _\infty G/K$$

∂
∞

G
/
K

) of the symmetric space G/K. We also establish the Hilbert–Mumford criterion for polystability of the action of G on measures.
DoE-Aided Optimization of RP-HPLC Method for Simultaneous Estimation of Amoxicillin and Tinidazole Loaded Mucoadhesive GRDDS Formulation for the Treatment of H. pylori
Authors: Saha Moumita , Gupta Ashutosh , Shetty Shiran , Mutalik Srinivas , Nandakumar K. , Raghu Chandrashekar H. , Dhas Namdev , Moorkoth Sudheer
Published: July 2024

Helicobacter pylori (H. pylori) infection is one of the primary risk factors of peptic ulcer disease worldwide. Treatment of H. pylori with the conventional dosage form is often challenging due to the ineffective reach of the antibiotics to the inner layers of gastric mucosa, where the organism resides. This study developed an eco-friendly, stability-indicating RP-HPLC method to simultaneously estimate amoxicillin and tinidazole from mucoadhesive formulation targeting H. pylori infection. The mucoadhesive GRDDS formulation of antibiotics was developed with a goal of improving bioavailability at the gastric mucosa. The multivariate Box–Behnken design (BBD) was utilized to optimize chromatographic parameters. Independent variable such as ratio of mobile phase, flow rate, pH and injections volume were optimized using DoE, and analyzed using perturbation plots. A desirability of 0.981 was achieved for the optimized variables. The optimized method utilized methanol and phosphate buffer (25:75) at pH 6.3 as the mobile phase in an isocratic elution mode on a Luna ODS C18 column kept at 25 °C as the stationary phase. The method was linear from 0.25 to 20 µg/mL, for both the drugs with R2 values of 0.9993 and 0.9997 for amoxicillin and tinidazole, respectively. This validated RP-HPLC technique demonstrated selectivity in the presence of possible degradation products and excipients present in the mucoadhesive GRDDS beads. The method was used for the determination of entrapment efficiency and in vitro release profile for tinidazole and amoxicillin in the mucoadhesive GRDDS formulation.

Graphical Abstract
Inhibitory immune checkpoints suppress the surveillance of senescent cells promoting their accumulation with aging and in age-related diseases
Authors: Salminen Antero
Published: July 2024

The accumulation of pro-inflammatory senescent cells within tissues is a common hallmark of the aging process and many age-related diseases. This modification has been called the senescence-associated secretory phenotype (SASP) and observed in cultured cells and in cells isolated from aged tissues. Currently, there is a debate whether the accumulation of senescent cells within tissues should be attributed to increased generation of senescent cells or to a defect in their elimination from aging tissues. Emerging studies have revealed that senescent cells display an increased expression of several inhibitory immune checkpoint ligands, especially those of the programmed cell death protein-1 (PD-1) ligand-1 (PD-L1) proteins. It is known that the PD-L1 ligands, especially those of cancer cells, target the PD-1 receptor of cytotoxic CD8+ T and natural killer (NK) cells disturbing their functions, e.g., evoking a decline in their cytotoxic activity and promoting their exhaustion and even apoptosis. An increase in the level of the PD-L1 protein in senescent cells was able to suppress their immune surveillance and inhibit their elimination by cytotoxic CD8+ T and NK cells. Senescent cells are known to express ligands for several inhibitory immune checkpoint receptors, i.e., PD-1, LILRB4, NKG2A, TIM-3, and SIRPα receptors. Here, I will briefly describe those pathways and examine whether these inhibitory checkpoints could be involved in the immune evasion of senescent cells with aging and age-related diseases. It seems plausible that an enhanced inhibitory checkpoint signaling can prevent the elimination of senescent cells from tissues and thus promote the aging process.
Generative Artificial Intelligence as Hypercommons: Ethics of Authorship and Ownership
Authors: Islam Gazi , Greenwood Michelle
Published: July 2024

In this editorial essay, we argue that Generative Artificial Intelligence programs (GenAI) draw on what we term a “hypercommons”, involving collectively produced inputs and labour that are largely invisible or untraceable. We argue that automatizing the exploitation of common inputs, in ways that remix and reconfigure them, can lead to a crisis of academic authorship in which the moral agency involved in scholarly production is increasingly eroded. We discuss the relationship between the hypercommons and authorship in terms of moral agency and the ethics of academic production, speculating on different responses to the crisis of authorship as posed by GenAI.
Metaheuristic algorithms and their applications in wireless sensor networks: review, open issues, and challenges
Authors: Houssein Essam H. , Saad Mohammed R. , Djenouri Youcef , Hu Gang , Ali Abdelmgeid A. , Shaban Hassan
Published: July 2024

Metaheuristic algorithms have wide applicability, particularly in wireless sensor networks (WSNs), due to their superior skill in solving and optimizing many issues in different domains. However, WSNs suffer from several issues, such as deployment, localization, sink node placement, energy efficiency, and clustering. Unfortunately, these issues negatively affect the already limited energy of the WSNs; therefore, the need to employ metaheuristic algorithms is inevitable to alleviate the harm imposed by these issues on the lifespan and performance of the network. Some associated issues regarding WSNs are modelled as single and multi-objective optimization issues. Single-objective issues have one optimal solution, and the other has multiple desirable solutions that compete, the so-called non-dominated solutions. Several optimization strategies based on metaheuristic algorithms are available to address various types of optimization concerns relating to WSN deployment, localization, sink node placement, energy efficiency, and clustering. This review reports and discusses the literature research on single and multi-objective metaheuristics and their evaluation criteria, WSN architectures and definitions, and applications of metaheuristics in WSN deployment, localization, sink node placement, energy efficiency, and clustering. It also proposes definitions for these terms and reports on some ongoing difficulties linked to these topics. Furthermore, this review outlines the open issues, challenge paths, and future trends that can be applied to metaheuristic algorithms (single and multi-objective) and WSN difficulties, as well as the significant efforts that are necessary to improve WSN efficiency.
Owner Guarantees, Observed and Unobserved Risks, and Bank Lending Spreads
Authors: Duarte Fábio Dias , Gama Ana Paula Matias , Gulamhussen Mohamed Azzim
Published: July 2024

In this paper, we examine the influence of owner guarantees on loan rates. Other studies on the influence of business collateral have used survey and credit register data to establish this link. They support it with the pre-lending information theory and post-lending incentive theory and find that the latter predominates the former. Thus, we measure observed and unobserved risks on bank lending spreads negotiated over the counter to show the co-existence of both theories. The main findings and robustness tests show that owner guarantees reduce bank lending spreads for safe but not risky firms, supporting the pre-lending information theory rather than the post-lending incentive theory. These findings underscore the role of owner guarantees in allaying the information problems the bank confronts prior to lending.
Teachers’ pedagogical beliefs in Norwegian school makerspaces
Authors: Høibo Ingrid Holmboe , Seitamaa-Hakkarainen Pirita , Groth Camilla
Published: July 2024

In Norway, makerspaces are emerging as new educational contexts across all school levels. This trend is multifaceted as it is inspired by the global maker movement and supported by local initiatives as well as a national policy to create more opportunities to teach digital competencies. The makerspace concept facilitates this in a concrete and innovative way. Although the maker movement is established, the pedagogical foundations of maker activities in educational settings are still being developed. As the movement meets competent teachers and existing learning cultures, there is the potential to create new pedagogical knowledge and educational practices. This study explored teachers’ values and beliefs regarding maker-centered learning in Norwegian schools through qualitative semi-structured interviews with maker teachers from 18 schools. The results indicate that makerspaces in Norwegian schools are initiated and driven by teachers’ interests in the maker movement, which resonates with their learning beliefs. The individuals in question are mostly natural-science teachers inspired by other makers. The learning culture in Norwegian schools, and that found in the maker movement, coincide in many areas. However, there are some compatibility challenges, such as facilitating open-ended learning processes and initiating learning frameworks that allow students to act and learn based on their motivations and ideas. With guidance from the latest curricula, teachers are encouraged to teach toward learning goals, which have been traditionally achieved with structured and predefined activities. In this goal-directed environment, maker teachers struggle to find room for iterative processes, play, and productive failures.
Integration of Family Navigation into ECHO Autism for Pediatric Primary Care in Underserved Communities
Authors: Mazurek Micah O. , Nevill Rose E. , Orlando Karen , Page Keith , Howard Mya , Davis Beth Ellen
Published: July 2024

Children with autism from underserved communities face complex system-, provider-, and family-level barriers to accessing timely diagnosis and early intervention. The current study evaluated the preliminary effects and feasibility of a new program (ECHO Autism LINKS) that integrated pediatric primary care provider (PCP) training with family navigation (FN) to bridge the gaps between screening, referral, and service access. Three cohorts of PCPs (n = 42) participated in the program, which consisted of 60-minute sessions delivered by Zoom twice per month for 12 months. Each session included didactics, case-based learning, and collaborative discussion with participants and an interdisciplinary team of experts. Family navigators were members of the expert team and provided FN services to families referred by PCP participants. Program attendance and engagement were strong, with 40 cases presented and 258 families referred for FN services, most of whom (83%) needed help accessing and connecting with services, and 13% required ongoing support due to complex needs. PCPs demonstrated significant improvements in self-efficacy in providing best-practice care for children with autism, reported high satisfaction, and observed improved knowledge and practice as a result of the program. The results of this initial pilot provide support for the feasibility, acceptability, and preliminary efficacy of the ECHO Autism LINKS program. The model holds promise in addressing complex barriers to healthcare access by providing both PCPs and families with the knowledge and support they need. Future research is needed to evaluate the efficacy and effectiveness of the program in improving child and family outcomes.
Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis
Authors: Ferré Elise M. N. , Nichols-Vinueza Diana X. , Rosen Lindsey B. , Burbelo Peter D. , Fennelly Kevin P. , Pechacek Joseph , Goldstein Daniel M. , Agharahimi Anahita , Saksena Annapurna , Kleiner David E. , Demirdag Yesim Yilmaz , Rajan Arun , Schrump David S. , Holland Steven M. , Freeman Alexandra F. , Lionakis Michail S.
Published: July 2024

Background

Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome.

Objectives

To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation.

Methods

Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab.

Results

Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12–36 months following treatment initiation.

Conclusion

Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.
Efficient High-Order Space-Angle-Energy Polytopic Discontinuous Galerkin Finite Element Methods for Linear Boltzmann Transport
Authors: Houston Paul , Hubbard Matthew E. , Radley Thomas J. , Sutton Oliver J. , Widdowson Richard S. J.
Published: July 2024

We introduce an hp-version discontinuous Galerkin finite element method (DGFEM) for the linear Boltzmann transport problem. A key feature of this new method is that, while offering arbitrary order convergence rates, it may be implemented in an almost identical form to standard multigroup discrete ordinates methods, meaning that solutions can be computed efficiently with high accuracy and in parallel within existing software. This method provides a unified discretisation of the space, angle, and energy domains of the underlying integro-differential equation and naturally incorporates both local mesh and local polynomial degree variation within each of these computational domains. Moreover, general polytopic elements can be handled by the method, enabling efficient discretisations of problems posed on complicated spatial geometries. We study the stability and hp-version a priori error analysis of the proposed method, by deriving suitable hp-approximation estimates together with a novel inf-sup bound. Numerical experiments highlighting the performance of the method for both polyenergetic and monoenergetic problems are presented.
Digital Physical Activity and Exercise Interventions for People Living with Chronic Kidney Disease: A Systematic Review of Health Outcomes and Feasibility
Authors: Letton Meg E. , Trần Thái Bình , Flower Shanae , Wewege Michael A. , Wang Amanda Ying , Sandler Carolina X , Sen Shaundeep , Arnold Ria
Published: July 2024

Physical activity is essential to interrupt the cycle of deconditioning associated with chronic kidney disease (CKD). However, access to targeted physical activity interventions remain under-supported due to limited funding and specialised staff. Digital interventions may address some of these factors. This systematic review sought to examine the evidence base of digital interventions focused on promoting physical activity or exercise and their effect on health outcomes for people living with CKD. Electronic databases (PubMed, CINAHL, Embase, Cochrane) were searched from 1 January 2000 to 1 December 2023. Interventions (smartphone applications, activity trackers, websites) for adults with CKD (any stage, including transplant) which promoted physical activity or exercise were included. Study quality was assessed, and a narrative synthesis was conducted. Of the 4057 records identified, eight studies (five randomised controlled trials, three single-arm studies) were included, comprising 550 participants. Duration ranged from 12-weeks to 1-year. The findings indicated acceptability and feasibility were high, with small cohort numbers and high risk of bias. There were inconsistent measures of physical activity levels, self-efficacy, body composition, physical function, and psychological outcomes which resulted in no apparent effects of digital interventions on these domains. Data were insufficient for meta-analysis. The evidence for digital interventions to promote physical activity and exercise for people living with CKD is limited. Despite popularity, there is little evidence that current digital interventions yield the effects expected from traditional face-to-face interventions. However, 14 registered trials were identified which may strengthen the evidence-base.