bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal trends in uptake of hormonal long-acting reversible contraception devices throughout the COVID-19 pandemic: an Australian population-based study
Authors: Stevenson Tahlee Blade , Rumbold Alice R , Moore Vivienne , Hall Kelly , Ilomaki Jenni , Mazza Danielle , Bateson Deborah , Grzeskowiak Luke E
Published: May 2024

Background

Little is known about the degree to which the COVID-19 pandemic, and associated restrictions and disruptions to health services, impacted the accessibility of hormonal long-acting reversible contraception (LARC) devices within Australia. Here, we explore longitudinal patterns of dispensing of the contraceptive implant and hormonal intrauterine devices (IUDs) within Australia, before and during the COVID-19 pandemic.

Methods

Population-based cohort study; analysis of 10% random sample of national Pharmaceutical Benefits Scheme dispensing data, for females aged 15–49 years dispensed a hormonal LARC device between February 2017 and November 2021.

Results

Interrupted time-series analysis demonstrated overall that there were no significant differences in monthly dispensing rates of hormonal LARC following the Australian onset of the pandemic in April 2020, with no subsequent change in the trend. However, when stratified by LARC type, a significant increase was evident during the pandemic period (April 2020–November 2021) in the rate of hormonal IUD dispensing per month (0.20 per 10 000 95% CI 0.01 to 0.38)), compared with a decrease for the implant (−0.08 per 10 000 (95% CI −0.16 to 0.01)). Increases in hormonal IUD dispensing during the pandemic were most pronounced for those aged 20–24 years, new users, those without a Commonwealth concession card, and in the State of Victoria.

Conclusions

Within Australia in the defined pandemic period, access to hormonal LARC devices was not negatively impacted. Rather a significant increase in dispensing of hormonal IUDs was evident.
Effectiveness of mindfulness-based interventions on the well-being of healthcare workers: a systematic review and meta-analysis
Authors: Ong Natasha Yixuan , Teo Finn Jing Jie , Ee Jane Zi Ying , Yau Chun En , Thumboo Julian , Tan Hiang Khoon , Ng Qin Xiang
Published: May 2024

Background

Growing evidence attests to the efficacy of mindfulness-based interventions (MBIs), but their effectiveness for healthcare workers remains uncertain.

Aims

To evaluate the evidence for MBIs in improving healthcare workers’ psychological well-being.

Methods

A systematic literature search was conducted on Medline, Embase, Cumulative Index for Nursing and Allied Health Literature, PsycINFO and Cochrane Central Register of Controlled Trials up to 31 August 2022 using the keywords ‘healthcare worker’, ‘doctor’, ‘nurse’, ‘allied health’, ‘mindfulness’, ‘wellness’, ‘workshop’ and ‘program’. Randomised controlled trials with a defined MBI focusing on healthcare workers and quantitative outcome measures related to subjective or psychological well-being were eligible for inclusion. R V.4.0.3 was used for data analysis, with the standardised mean difference as the primary outcome, employing DerSimonian and Laird’s random effects model. Grading of Recommendations, Assessment, Development and Evaluation framework was used to evaluate the quality of evidence. Cochrane’s Risk of Bias 2 tool was used to assess the risk of bias in the included studies.

Results

A total of 27 studies with 2506 participants were included, mostly from the USA, involving various healthcare professions. MBIs such as stress reduction programmes, apps, meditation and training showed small to large effects on anxiety, burnout, stress, depression, psychological distress and job strain outcomes of the participants. Positive effects were also seen in self-compassion, empathy, mindfulness and well-being. However, long-term outcomes (1 month or longer postintervention) varied, and the effects were not consistently sustained.

Conclusions

MBIs offer short-term benefits in reducing stress-related symptoms in healthcare workers. The review also highlights limitations such as intervention heterogeneity, reduced power in specific subgroup analyses and variable study quality.

PROSPERO registration number

CRD42022353340.
Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial
Authors: He Yandong , Huang Xuhong , Li Xiaoxia , Liu Hongwei , Liu Min , Tao Junjia , Shan Yuanzhou , Raza Hafiz Khuram , Liu Yanqiu , Zhong Wenting , Cao Xue-ping , Yang Yuan-yuan , Li Ruimei , Fang Xian-long , Zhang Kang-jian , Zhang Rong , Liu Feng
Published: May 2024

Objective

To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors.

Methods

In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109viral particles (VP)/subject, 5.0×1010VP/subject, and 5.0×1011VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1.

Results

14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%).

Conclusions

The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety.

Trial registration number

NCT05180851.
Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension
Authors: Ørbæk Andersen Mads , Diederichsen Soren Zoga , Svendsen Jesper Hastrup , Carlsen Jørn
Published: May 2024

Background

The treatment of pulmonary hypertension (PH) has improved rapidly in recent decades. There is increasing evidence to support the role of early intervention and treatment in affecting clinical outcomes in PH.

Objectives

To assess treatment effects before and after the escalation of specific PH treatments using continuous heart monitoring with a Reveal LINQ loop recorder.

Methods

Patients were compared before and after treatment escalation. Treatment escalation was defined as an additional pulmonary arterial hypertension (PAH) drug, pulmonary endarterectomy, percutaneous balloon angioplasty or bilateral lung transplantation. Specifically, changes in heart rate variability (HRV), heart rate (HR) and physical activity were assessed.

Results

In this prospective study, 41 patients (27 with PAH and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)) were enrolled. Among them, 15 (36.6%) patients underwent PH treatment escalation. Prior to escalation, patients were monitored for a median of 100 (range: 68–100) days and after therapy escalation for a median duration of 165 (range: 89–308) days. In the escalation group, there was a significant increase in HRV, physical activity indexed by daytime HR and a significant decrease in nighttime HR assessed at baseline and after treatment escalation in both the PAH and CTEPH groups. This was paralleled by significant improvements in WHO functional class, 6-min walking distance and N-terminal pro-b-type natriuretic peptide.

Conclusions

This is the first study to demonstrate an association between specific PH therapies and changes in HRV, HR nighttime and physical activity. This indicates the potential of continuous monitoring in the evaluation of treatment effects in PH.
Intramuscular fat infiltration influences mechanical properties during muscle contraction in older women
Authors: Wang Zimin , Taniguchi Masashi , Saeki Junya , Yagi Masahide , Murota Norihiko , Nakazato Kaede , Niiya Nanami , Ichihashi Noriaki
Published: May 2024

Although evidence suggests that intramuscular fat infiltration may influence muscle strength, the precise mechanisms remain unclear. This study aimed to determine whether intramuscular fat infiltration affects muscle mechanical properties during contraction and whether these mechanical properties mediate the relationship between intramuscular fat infiltration and muscle strength. Seventy-nine healthy older women aged 75.1 ± 6.8 years were included in this study. The echo intensity (EI) of the vastus lateralis (VL) was measured as an intramuscular fat infiltration index using B-mode ultrasonography. Maximum voluntary isometric contraction strength (MVIC) was assessed using a dynamometer. The VL shear elastic modulus (G), a mechanical property index, was measured using ultrasound shear wave elastography under various muscle contraction conditions, at rest and at 15%, 30%, and 45% MVIC (G0, G15, G30, and G45). To evaluate the degree of increase in the shear elastic modulus with increasing muscle contraction intensity, the slope of the regression line (Gslope) between muscle contraction and shear elastic modulus was calculated for each participant. The results showed that EI was significantly associated with G30 and G45 but not with G0 or G15. The EI can significantly explain the inter-individual differences in Gslope. Mediation analysis revealed that the effect of EI on MVIC through Gslope was significant (indirect effect = −0.31, 95% confidence interval (−0.57, −0.12)). These findings suggest that a greater EI is associated with a lower G during muscle contraction. Furthermore, our results show that the relationship between EI and MVIC is mediated by Gslope.
Residual canopy cover provides buffering of near-surface temperatures, but benefits are limited under extreme conditions
Authors: Brackett Amanda E. , Still Christopher J. , Puettmann Klaus J.
Published: May 2024

Increasing summer temperatures and higher probabilities of extreme heat events have led to concerns about tree damage and mortality. However, insufficient attention has been given to conditions leading to heat-related regeneration failures in temperate forests. To address this, managers need to understand how microclimate varies under a range of overstory conditions. We measured air temperatures at 2 cm above-ground underneath a gradient of canopy cover on south-facing slopes in recently thinned Douglas-fir stands in western Oregon, USA. To expand the ecological relevance of these data to impacts on regeneration, we created the stress degree hours (SDH) metric, representing the amount of time—and by how much—temperatures exceeded biologically relevant stress thresholds. Overall, for every 10% increase in canopy cover, maximum temperatures at 2 cm were 1.3 °C lower, the odds of temperatures exceeding stress thresholds for conifer regeneration declined by a multiplicative factor of 0.26, and the total of SDH decreased by 40%. These reductions are large enough to be worthy of attention when managing for tree regeneration. However, data collected during the Pacific Northwest Heat Dome in June 2021 indicate that with various climate change scenarios and heatwave occurrences, temperatures will be unfavorable for regeneration regardless of overstory cover.
Gian-Carlo Wick and neutron physics in the 1930s
Authors: Gould Christopher R. , Sharapov Eduard I.
Published: May 2024

The Italian theorist Gian-Carlo Wick is well known for his work in mathematical physics. Nevertheless, working with Fermi’s group in Rome in the 1930s, he took on several behind-the-scenes roles that resulted in important papers in neutron physics. He clarified Fermi’s methodology for calculating neutron slowing down probabilities; using transport theory, he provided a comprehensive general method for calculating the neutron scattering albedo; and with an insight into the way, neutron scattering could yield information about lattice dynamics, he formulated the first theory of inelastic thermal neutrons scattering in crystalline materials. This work and his contributions are not well known today. We discuss its physical essence, its relevance to neutron physics, and its subsequent impact in later work.
Fast Fourier transforms and fast Wigner and Weyl functions in large quantum systems
Authors: Lei C. , Vourdas A.
Published: May 2024

Two methods for fast Fourier transforms are used in a quantum context. The first method is for systems with dimension of the Hilbert space $$D=d^n$$

D
=

d
n

with d an odd integer, and is inspired by the Cooley-Tukey formalism. The ‘large Fourier transform’ is expressed as a sequence of n ‘small Fourier transforms’ (together with some other transforms) in quantum systems with d-dimensional Hilbert space. Limitations of the method are discussed. In some special cases, the n Fourier transforms can be performed in parallel. The second method is for systems with dimension of the Hilbert space $$D=d_0...d_{n-1}$$

D
=

d
0

.
.
.

d

n
-
1

with $$d_0,...,d_{n-1}$$

d
0

,
.
.
.
,

d

n
-
1

odd integers coprime to each other. It is inspired by the Good formalism, which in turn is based on the Chinese reminder theorem. In this case also the ‘large Fourier transform’ is expressed as a sequence of n ‘small Fourier transforms’ (that involve some constants related to the number theory that describes the formalism). The ‘small Fourier transforms’ can be performed in a classical computer or in a quantum computer (in which case we have the additional well known advantages of quantum Fourier transform circuits). In the case that the small Fourier transforms are performed with a classical computer, complexity arguments for both methods show the reduction in computational time from $$\mathcal{O}(D^2)$$

O
(

D
2

)

to $$\mathcal{O}(D\log D)$$

O
(
D
log
D
)

. The second method is also used for the fast calculation of Wigner and Weyl functions, in quantum systems with large finite dimension of the Hilbert space.
Neural Methods for Data-to-text Generation
Authors: Sharma Mandar , Gogineni Ajay Kumar , Ramakrishnan Naren
Published: May 2024

The neural boom that has sparked natural language processing (NLP) research throughout the last decade has similarly led to significant innovations in data-to-text (D2T) generation. This survey offers a consolidated view into the neural D2T paradigm with a structured examination of the approaches, benchmark datasets, and evaluation protocols. This survey draws boundaries separating D2T from the rest of the natural language generation (NLG) landscape, encompassing an up-to-date synthesis of the literature, and highlighting the stages of technological adoption from within and outside the greater NLG umbrella. With this holistic view, we highlight promising avenues for D2T research that focus not only on the design of linguistically capable systems but also on systems that exhibit fairness and accountability.
Measuring User Experience Inclusivity in Human-AI Interaction via Five User Problem-Solving Styles
Authors: Anderson Andrew , Guevara Jimena Noa , Moussaoui Fatima , Li Tianyi , Vorvoreanu Mihaela , Burnett Margaret
Published: May 2024

Motivations
: Recent research has emerged on generally how to improve AI products’ human-AI interaction (HAI) user experience (UX), but relatively little is known about HAI-UX inclusivity. For example, what kinds of users are supported, and who are left out? What product changes would make it more inclusive?

Objectives
: To help fill this gap, we present an approach to measuring what kinds of diverse users an AI product leaves out and how to act upon that knowledge. To bring actionability to the results, the approach focuses on users’ problem-solving diversity. Thus, our specific objectives were (1) to show how the measure can reveal which participants with diverse problem-solving styles were left behind in a set of AI products and (2) to relate participants’ problem-solving diversity to their demographic diversity, specifically gender and age.

Methods
: We performed 18 experiments, discarding two that failed manipulation checks. Each experiment was a 2

\(\times\)

2 factorial experiment with online participants, comparing two AI products: one deliberately violating 1 of 18 HAI guidelines and the other applying the same guideline. For our first objective, we used our measure to analyze how much each AI product gained/lost HAI-UX inclusivity compared to its counterpart, where inclusivity meant supportiveness to participants with particular problem-solving styles. For our second objective, we analyzed how participants’ problem-solving styles aligned with their gender identities and ages.

Results and Implications
: Participants’ diverse problem-solving styles revealed six types of inclusivity results: (1) the AI products that followed an HAI guideline were almost always more inclusive across diversity of problem-solving styles than the products that did not follow that guideline—but “who” got most of the inclusivity varied widely by guideline and by problem-solving style; (2) when an AI product had risk implications, four variables’ values varied in tandem: participants’ feelings of control, their (lack of) suspicion, their trust in the product, and their certainty while using the product; (3) the more control an AI product offered users, the more inclusive it was; (4) whether an AI product was learning from “my” data or other people’s affected how inclusive that product was; (5) participants’ problem-solving styles skewed differently by gender and age group; and (6) almost all of the results suggested actions that HAI practitioners could take to improve their products’ inclusivity further. Together, these results suggest that a key to improving the demographic inclusivity of an AI product (e.g., across a wide range of genders, ages) can often be obtained by improving the product’s support of diverse problem-solving styles.
A Memory-Disaggregated Radix Tree
Authors: Luo Xuchuan , Zuo Pengfei , Shen Jiacheng , Gu Jiazhen , Wang Xin , Lyu Michael , Zhou Yangfan
Published: May 2024

Disaggregated memory (DM) is an increasingly prevalent architecture with high resource utilization. It separates computing and memory resources into two pools and interconnects them with fast networks. Existing range indexes on DM are based on B+ trees, which suffer from large inherent read and write amplifications. The read and write amplifications rapidly saturate the network bandwidth, resulting in low request throughput and high access latency of B+ trees on DM.

In this article, we propose that the radix tree is more suitable for DM than the B+ tree due to smaller read and write amplifications. However, constructing a radix tree on DM is challenging due to the costly lock-based concurrency control, the bounded memory-side IOPS, and the complicated computing-side cache validation. To address these challenges, we design
SMART
, the first radix tree for disaggregated memory with high performance. Specifically, we leverage (1) a
hybrid concurrency control
scheme including lock-free internal nodes and fine-grained lock-based leaf nodes to reduce lock overhead, (2) a computing-side
read-delegation and write-combining
technique to break through the IOPS upper bound by reducing redundant I/Os, and (3) a simple yet effective
reverse check
mechanism for computing-side cache validation. Experimental results show that SMART achieves 6.1× higher throughput under typical write-intensive workloads and 2.8× higher throughput under read-only workloads in YCSB benchmarks, compared with state-of-the-art B+ trees on DM.
Imprecise perception of hand position during early motor adaptation
Authors: Will Matthias , Stenner Max-Philipp
Published: May 2024

Recent studies indicate that the precision with which people localize their hand limits implicit visuomotor learning. We found that localization precision is not static, but decreases early during learning. This decrease is pronounced when people apply a reaiming strategy to compensate for a visuomotor perturbation and is partly resistant to allocation of attention to the hand. We propose that these dynamics in position sense during learning may influence how implicit and strategy-based motor adaption interact.
A Causal Relationship Between Type 1 Diabetes and Risk of Osteoporosis: A Univariable and Multivariable Mendelian Randomization Study
Authors: Qin Hailin , Yang Kui , Wang Hufei , Jiao Wenyong
Published: May 2024

Objective: This Mendelian randomization (MR) analysis aims to investigate the causal relationship between type 1 diabetes (T1D) and osteoporosis (OP).

Methods: Single nucleotide polymorphisms (SNPs) associated with T1D were selected from the summary statistics of the genome‐wide association study (GWAS) in European ancestry as instrumental variables (IVs) for univariable MR (UVMR) to explore the causal relationship between T1D and OP. Inverse variance weighting (IVW) was the primary method used to assess possible causality between T1D and OP. MR‐PRESSO and MR‐Egger intercepts were used to assess the horizontal pleiotropy of the IVs, and Q tests and the “leave‐one‐out” method were used to test for heterogeneity of MR results. Multivariable MR (MVMR) analysis was used to account for potential confounders such as smoking, obesity, drinking, and serum 25‐hydroxyvitamin D (25OHD) concentrations.

Result: Inverse variance weighted estimates suggest T1D may increase risk of OP (UVMR: OR = 1.06, 95% CI: 1.02–1.10, p = 0.002) (MVMR: OR = 1.50, 95% CI: 1.07–1.90, p < 0.001).

Conclusion: Our findings suggest that T1D can increase the risk of OP.
First Report of Seropositivity to Trypanosoma cruzi in Mexican Afro-Descendants from Guerrero and Oaxaca States
Authors: Espinoza Bertha , Rangel-Flores Hilda , Saucedo-Arteaga Gabriel , Martínez Ignacio , Aguilar-Salinas Carlos A. , Cabrera-Mendoza Brenda , Ponce-Patiño David , Mendoza-Duarter Javier , Martínez-Rangel Carlos Eduardo
Published: May 2024

Mexican Afro-descendant is a population poorly studied in many aspects, between them the infectious diseases that they suffer. This population is mainly found in the country’s Pacific (Oaxaca and Guerrero states) and Atlantic (Veracruz) coast. In these regions, a diversity of triatomine vectors of the Chagas disease is found. Also, all the genotypes of Trypanosoma cruzi DTUs have been reported. That is why the present study aimed to study the presence of antibodies against T. cruzi and cardiac pathology associated with the Chagas disease in the Mexican Afro-descendant population of Guerrero and Oaxaca. ELISA, Western blot, and recombinant antigen’s ELISA were used to evaluate the seropositivity of these communities. Furthermore, an electrocardiographic study and evaluation of risk factors associated with T. cruzi infection in the Oaxaca and Guerrero populations were conducted. 26.77% of the analyzed population was positive for two serological tests. These percentages are higher than the previously reported for the mestizo population in similar studies. Electrocardiographic results showed cardiac disorder associated with the Chagas disease in the population. Also, risk factors were identified associated with the men’s activities in the outdoor working areas.
A Review on the Recent Advances in Battery Development and Energy Storage Technologies
Authors: Njema George G. , Ouma Russel Ben O. , Kibet Joshua K.
Published: May 2024

Energy storage is a more sustainable choice to meet net-zero carbon foot print and decarbonization of the environment in the pursuit of an energy independent future, green energy transition, and uptake. The journey to reduced greenhouse gas emissions, increased grid stability and reliability, and improved green energy access and security are the result of innovation in energy storage systems. Renewable energy sources are fundamentally intermittent, which means they rely on the availability of natural resources like the sun and wind rather than continuously producing energy. Due to its ability to address the inherent intermittency of renewable energy sources, manage peak demand, enhance grid stability and reliability, and make it possible to integrate small-scale renewable energy systems into the grid, energy storage is essential for the continued development of renewable energy sources and the decentralization of energy generation. Accordingly, the development of an effective energy storage system has been prompted by the demand for unlimited supply of energy, primarily through harnessing of solar, chemical, and mechanical energy. Nonetheless, in order to achieve green energy transition and mitigate climate risks resulting from the use of fossil-based fuels, robust energy storage systems are necessary. Herein, the need for better, more effective energy storage devices such as batteries, supercapacitors, and bio-batteries is critically reviewed. Due to their low maintenance needs, supercapacitors are the devices of choice for energy storage in renewable energy producing facilities, most notably in harnessing wind energy. Moreover, supercapacitors possess robust charging and discharging cycles, high power density, low maintenance requirements, extended lifespan, and are environmentally friendly. On the other hand, combining aluminum with nonaqueous charge storage materials such as conductive polymers to make use of each material’s unique capabilities could be crucial for continued development of robust storage batteries. In general, energy density is a key component in battery development, and scientists are constantly developing new methods and technologies to make existing batteries more energy proficient and safe. This will make it possible to design energy storage devices that are more powerful and lighter for a range of applications. When there is an imbalance between supply and demand, energy storage systems (ESS) offer a way of increasing the effectiveness of electrical systems. They also play a central role in enhancing the reliability and excellence of electrical networks that can also be deployed in off-grid localities.
Dual Optical Injection in Semiconductor Lasers with Zero Henry Factor
Authors: Al-Hosiny Najm M.
Published: May 2024

The dynamics of semiconductor lasers subject to dual optical injections are numerically investigated with a zero linewidth enhancement factor. With the aid of stability maps, we show that different chaotic and nonlinear dynamics can be produced (even with zero linewidth enhancement factor) by injecting an additional optical signal. We also study the bifurcation of the system and the carrier dynamics under dual optical injection and a zero linewidth enhancement factor.
Inoculation of Native Arbuscular Mycorrhizae and Bacillus subtilis Can Improve Growth in Vegetable Crops
Authors: Gebreslassie Sara , Jida Mulissa , Puente Mariana Laura , Covacevich Fernanda , Belay Zerihun
Published: May 2024

Arbuscular mycorrhizal fungi (AMF) and some rhizobacteria are known as plant growth‐promoting microorganism (PGPM) as they play significant roles in improving soil fertility structure, plant nutrition, growth, and health. However, little is known about the PGPM potential of AMF and rhizobacteria native to the Rift Valley and highland regions of Ethiopia. Hence, this study aimed to investigate the PGPM effect of single and co‐inoculation of AMF and the Bacillus subtilis ALCR46 strain, on tomato (Lycopersicum esculentum L.), onion (Allium cepa L.), and squash (Cucurbita pepo L.) plants. The experimental setup was a randomized complete block design with three replications of the following treatments: (i) inoculation with a consortium of AMF, (ii) co‐inoculation with a consortium of AMF and the Bacillus subtilis, (iii) inoculation with Rhizophagus clarus, (iv) co‐inoculation with R. clarus and B. subtilis, (v) inoculation with B. subtilis, (vi) plants without inoculation (negative control), and (vii) plants treated with chemical fertilizer (positive control). Plants were maintained in a greenhouse for 60 days, and after harvest, plant growth parameters, percentage of AMF root colonization, and spore number were analyzed. The result shows that the growth of crops significantly increased by co‐inoculation with the consortium of AMF and B. subtilis. AMF spore density and root colonization rate were also increased in co‐inoculated plants. Highest root colonization, spore number, and mycorrhizal dependency were observed in A. cepa. Our results suggest that there is a synergistic effect between the AMF and B. subtilis ALCR46, and between AMF inoculants. However, the application of present findings under field conditions is required to be confirmed by further studies.
Effects of Cranberry Extract (Vaccinium macrocarpon) Supplementation on Lipid Peroxidation and Inflammation in Patients with Chronic Kidney Disease (Stages 3-4): A Randomized Controlled Trial
Authors: de Souza Gouveia Moreira Laís , Resende Teixeira Karla Thaís , Cardozo Ludmila F. M. F. , Alvarenga Livia , Regis Bruna , Sousa de Brito Jessyca , de Oliveira Leal Viviane , Borges Natalia Alvarenga , de Souza da Costa Brum Isabela , Carraro-Eduardo José Carlos , Borini Giovanna B. , Berretta Andresa A. , Ribeiro-Alves Marcelo , Mafra Denise
Published: May 2024

Background. Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD). Objectives. To evaluate cranberry (Vaccinium macrocarpon) supplementation effects on modulation of transcription factors involved in inflammation and oxidative stress in nondialysis (stages 3 and 4) patients with CKD. Design/Participants. A randomized, double-blind, placebo-controlled study was performed with 30 patients to receive capsules containing cranberry extract (1000 mg/day) or placebo (1000 mg/day of corn starch) for two months. Measurements. The mRNA expression of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor-kB (NF-kB) was evaluated in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction. Thiobarbituric acid reactive substances (TBARS) were measured in the plasma to assess oxidative stress. Interleukin-6 (IL-6) plasma levels were assessed by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by immunoturbidimetric method. Results. Twenty-five patients completed the study: 12 in the cranberry group (56.7 ± 7.5 years and body mass index (BMI) of 29.6 ± 5.5 kg/m2) and 13 in the placebo group (58.8 ± 5.1 years and BMI 29.8 ± 5.4 kg/m2). There were no differences in NF-kB or Nrf2 mRNA expressions (p=0.99 and p=0.89) or TBARS, CRP, and IL-6 plasma levels after cranberry supplementation. Conclusions. The cranberry extract administration (1000 mg/day) did not affect Nrf2 and NF-kB mRNA expression, oxidative stress, or inflammatory markers levels in nondialysis CKD patients. This trial is registered with NCT04377919.
Macroalgae as Alkalizing Marine Drugs with a Low Potential Renal Acid Load
Authors: Storz Maximilian Andreas
Published: May 2024

A growing interest in more sustainable and alternative food sources has brought seaweed and macroalgae to the spotlight for the general worldwide cuisine. Algae are often praised for their high nutritional value and are rich in potassium, calcium, and magnesium. Abundant in base precursors, algae are particularly interesting from an acid-base perspective. Their unique biochemical composition suggests a low potential renal acid load (PRAL), which is a commonly used estimate for the amount of acid or base a certain food produces in humans. Here, we analyzed the PRAL value of n = 106 macroalgae. Results suggested a strong alkalizing potential, with a mean PRAL value of −86.76 mEq/100 g. The lowest PRAL values were found for Laminaria ochroleuca (−286.78 mEq/100 g), Gelidium micropterum (−268.46 mEq/100 g), and Palmaria palmata (−259.16 mEq/100 g). We observed a strong inverse relationship of PRAL with algae’s potassium content (Spearman’s rho = −0.79, p<0.001) and a moderate relationship with algae’s calcium content (Spearmen’s rho: −0.34, p<0.001). Our data point at a potential role for several macroalgae as potent alkalizing marine drugs and suggest that a 10 g edible portion of some algae alone could contribute to a substantial PRAL reduction of up to −28.68 mEq. This might be of particular importance for individuals who benefit from a more alkaline diet and warrants further investigation in future studies.
HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T-cell Lymphoma
Authors: Zhu Jiayan , Wang Feng , Wang Lining , Dai Bo , Xu Guilin , Zhao Luyao , Jiang Huimin , Gao Wenhui , Zhang Tingting , Zhao Chenxi , Li Yun-Xuan , Hu Jiong , Li Ke
Published: May 2024

Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Herein, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3 inhibition suppressed lymphoma growth in immunocompetent mice but not in immunodeficient mice. HDAC3 deletion delayed the progression of lymphoma, reduced the lymphoma burden in the thymus, spleen, and lymph nodes, and prolonged the survival of mice bearing N-methyl-N-nitrosourea–induced lymphoma. Furthermore, inhibiting HDAC3 promoted the infiltration and enhanced the function of natural killer (NK) cells. Mechanistically, HDAC3 mediated ATF3 deacetylation, enhancing its transcriptional inhibitory activity. Targeting HDAC3 enhanced CXCL12 secretion through an ATF3-dependent pathway to stimulate NK-cell recruitment and activation. Finally, HDAC3 suppression improved the response of PTCL to conventional chemotherapy. Collectively, this study provides insights into the mechanism by which HDAC3 regulates ATF3 activity and CXCL12 secretion, leading to immune infiltration and lymphoma suppression. Combining HDAC3 inhibitors with chemotherapy may be a promising strategy for treating PTCL.

Significance: Targeting HDAC3 suppresses progression of T-cell lymphoma by activating ATF3 to induce secretion of CXCL12 and promote infiltration of NK cells, providing an immunostimulatory approach for treating T-cell lymphoma patients.
The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention
Authors: Albini Adriana , Noonan Douglas M. , Corradino Paola , Magnoni Francesca , Corso Giovanni
Published: May 2024

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. After this concept was established in the 1970s, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy, prevention, and interception and recently investigated substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, β blockers, renin–angiotensin–aldosterone inhibitors, carnitines, and biguanides, are reviewed.
D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities
Authors: Zhang Jing , Lim Sun Min , Yu Mi Ra , Chen Cheng , Wang Jia , Wang Wenqian , Rui Haopeng , Lu Jingtao , Lu Shun , Mok Tony , Chen Zhi Jian , Cho Byoung Chul
Published: May 2024

First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic “cycling” of KRAS between its guanosine diphosphate (GDP)– and guanosine triphosphate (GTP)–bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report that D3S-001, a next-generation GDP-bound G12C inhibitor with faster target engagement (TE) kinetics, depletes cellular active KRAS G12C at nanomolar concentrations. In the presence of growth factors, such as epithelial growth factor and hepatocyte growth factor, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust antitumor activity preclinically and translated into promising clinical efficacy in an ongoing phase 1 trial (NCT05410145).

Significance: The kinetic study presented in this work unveils, for the first time, that a GDP-bound conformation-selective KRAS G12C inhibitor can potentially deplete cellular active KRAS in the presence of growth factors and offers new insights into the critical features that drive preclinical and clinical efficacy for this class of drugs.
Molecular Landscape and Clinical Implication of CCNE1-amplified Esophagogastric Cancer
Authors: Rustgi Naryan , Wu Sharon , Samec Timothy , Walker Phillip , Xiu Joanne , Lou Emil , Goel Sanjay , Saeed Anwaar , Moy Ryan H.
Published: May 2024

Cyclin E overexpression as a result of CCNE1 amplification is a critical driver of genomic instability in gastric cancer, but its clinical implication is largely unknown. Thus, we integrated genomic, transcriptomic, and immune profiling analysis of 7,083 esophagogastric tumors and investigated the impact of CCNE1 amplification on molecular features and treatment outcomes. We identified CCNE1 amplification in 6.2% of esophageal adenocarcinoma samples, 7.0% of esophagogastric junction carcinoma, 4.2% of gastric adenocarcinoma samples, and 0.8% of esophageal squamous cell carcinoma. Metastatic sites such as lymph node and liver showed an increased frequency of CCNE1 amplification relative to primary tumors. Consistent with a chromosomal instability phenotype, CCNE1 amplification was associated with decreased CDH1 mutation and increased TP53 mutation and ERBB2 amplification. We observed no differences in immune biomarkers such as PD-L1 expression and tumor mutational burden comparing CCNE1-amplified and nonamplified tumors, although CCNE1 amplification was associated with changes in immune populations such as decreased B cells and increased M1 macrophages from transcriptional analysis. Real-world survival analysis demonstrated that patients with CCNE1-amplified gastric cancer had worse survival after trastuzumab for HER2-positive tumors, but better survival after immunotherapy. These data suggest that CCNE1-amplified gastric cancer has a distinct molecular and immune profile with important therapeutic implications, and therefore further investigation of CCNE1 amplification as a predictive biomarker is warranted.

Significance:

Advanced gastric cancer has a relatively dismal outcome with a 5-year overall survival of less than 10%. Furthermore, while comprehensive molecular analyses have established molecular subtypes within gastric cancers, biomarkers of clinical relevance in this cancer type are lacking. Overall, this study demonstrates that CCNE1 amplification is associated with a distinct molecular profile in gastric cancer and may impact response to therapy, including targeted therapy and/or immunotherapy.
B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai
Published: May 2024

Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3–targeting domain in our CAR construct to circumvent the stability issues associated with single-chain variable fragment–based domains. In efforts to expand patient access to CAR T-cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr virus–specific T cells (EBVST), offering a readily available off-the-shelf treatment. B7H3.CAR-armored EBVSTs demonstrated potent in vitro and in vivo activities against multiple B7-H3–positive human tumor cell lines and patient-derived xenograft models. Murine T cells expressing a murine equivalent of our B7H3.CAR exhibited no life-threatening toxicities in immunocompetent mice bearing syngeneic tumors. Further in vitro evaluation revealed that while human T, B, and natural killer cells were unaffected by B7H3.CAR EBVSTs, monocytes were targeted because of upregulation of B7-H3. Such targeting of myeloid cells, which are key mediators of cytokine release syndrome (CRS), contributed to a low incidence of CRS in humanized mice after B7H3.CAR EBVST treatment. Notably, we showed that B7H3.CAR EBVSTs can target B7-H3–expressing myeloid-derived suppressor cells (MDSC), thereby mitigating MDSC-driven immune suppression. In summary, our data demonstrate that our nanobody-based B7H3.CAR EBVSTs are effective as an off-the-shelf therapy for B7-H3–positive solid tumors. These cells also offer an avenue to modulate the immunosuppressive tumor microenvironment, highlighting their promising clinical potential in targeting solid tumors.

Significance:

Clinical application of EBVSTs armored with B7-H3–targeting CARs offer an attractive solution to translate off-the-shelf CAR T cells as therapy for solid tumors.
LYVE-1–expressing Macrophages Modulate the Hyaluronan-containing Extracellular Matrix in the Mammary Stroma and Contribute to Mammary Tumor Growth
Authors: Elfstrum Alexis K. , Rumahorbo Annisa H. , Reese Lyndsay E. , Nelson Emma V. , McCluskey Braedan M. , Schwertfeger Kathryn L.
Published: May 2024

Macrophages represent a heterogeneous myeloid population with diverse functions in normal tissues and tumors. While macrophages expressing the cell surface marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) have been identified in stromal regions of the normal mammary gland and in the peritumoral stroma, their functions within these regions are not well understood. Using a genetic mouse model of LYVE-1+ macrophage depletion, we demonstrate that loss of LYVE-1+ macrophages is associated with altered extracellular matrix remodeling in the normal mammary gland and reduced mammary tumor growth in vivo. In further studies focused on investigating the functions of LYVE-1+ macrophages in the tumor microenvironment, we demonstrate that LYVE-1 expression correlates with an increased ability of macrophages to bind, internalize, and degrade hyaluronan. Consistent with this, we show that depletion of LYVE-1+ macrophages correlates with increased hyaluronan accumulation in both the normal mammary gland and in mammary tumors. Analysis of single-cell RNA sequencing of macrophages isolated from these tumors reveals that depletion of LYVE-1+ macrophages in tumors drives a shift in the majority of the remaining macrophages toward a proinflammatory phenotype, as well as an increase in CD8+ T-cell infiltration. Together, these findings indicate that LYVE-1+ macrophages represent a tumor-promoting anti-inflammatory subset of macrophages that contributes to hyaluronan remodeling in the tumor microenvironment.

Significance:

We have identified a macrophage subset in mouse mammary tumors associated with tumor structural components. When this macrophage subset is absent in tumors, we report a delay in tumor growth and an increase in antitumor immune cells. Understanding the functions of distinct macrophage subsets may allow for improved therapeutic strategies for patients with breast cancer.
Investigating the İmpact of Bariatric Surgery on Macular and Peripapillary Vessel Density in Obese İndividuals Without Metabolic Disease
Authors: Toptan Müslüm , Elkan Hasan
Published: May 2024

Introduction: It is well-established that microvascular structures are affected in obese people with metabolic disease. We aimed to evaluate the effect on microvascular structures by examining macular and peripapillary vessel density with optical coherence tomography angiography (OCTA) after bariatric surgery in obese individuals without metabolic disease. Methods: This prospective study included 96 eyes of 48 obese patients. Body mass index (BMI), macular vessel density in the superficial, intermediate, and deep capillary plexus, and peripapillary vessel density were measured before and 6 months after bariatric surgery. Results: BMI decreased significantly to 43.75±4.4 kg/m2 postoperatively compared to 55.31±5.1 kg/m2 preoperatively (p<0.05). A significant increase was observed in macular vessel density in the deep capillary plexus postoperatively (p<0.01). However, no significant postoperative increase occurred in macular vascular density in the superficial and intermediate capillary plexus (p >0.05). Moreover, there was no change in peripapillary vascular density (p>0.05). Postoperative thickening of the foveal, parafoveal, and perifoveal retinal layers was significant (p < 0.001). No significant correlation was detected between BMI change and macular and peripapillary vessel density changes (p>0.05). Conclusion: An increase in macular vascular density, particularly in the deep capillary plexus, and retinal layer thickness has been observed following bariatric surgery performed on obese individuals without metabolic disease. This increase may indicate that microvascular structures are affected even in the absence of metabolic disease and that microperfusion improves with surgery.