bluuebunny/crossref_metadata_2025 huggingface dataset:
Removal of toxic steroidal glycoalkaloids and bitterness in tomato is controlled by a complex epigenetic and genetic network
Authors: Bai Feng , Wu Mengbo , Huang Wei , Xu Weijie , Wang Yikui , Zhang Yang , Zhong Zhenhui , Hong Yiguo , Pirrello Julien , Bouzayen Mondher , Liu Mingchun
Published: February 2025

The steroidal glycoalkaloids (SGAs) produced in
Solanaceae
crops, including tomato, are antinutritional because of their cellular toxicity and resultant bitter taste to humans. To make fruits palatable, SGA profiles shift from bitter and toxic α-tomatine to nonbitter and nontoxic esculeoside A during the ripening process. However, the mechanisms regulating this conversion remain unclear. In this study, we showed that removal of toxic and bitter SGAs is under the control of DNA demethylation, ethylene, and key transcription factors by forming a feedback loop that governs the expression of key
GLYCOALKALOID METABOLISM
(
GAME
) genes during ripening. Moreover, the ethylene-inducible transcription factors NON-RIPENING, RIPENING INHIBITOR, and FRUITFULL1 coordinately regulate the expression of
GAME31
,
GAME40
,
GAME5
, and the glycoalkaloid transporter gene
GORKY
, whereas jasmonic acid–induced MYC2 modulates the transcription of
GAME36
. Furthermore, DNA demethylation mediated by the
DEMETER
-
LIKE
2 drives SGA detoxification during tomato domestication.
Metal-to-metal charge transfer for stabilizing high-voltage redox in lithium-rich layered oxide cathodes
Authors: Kim Min-Ho , Jang Haeseong , Lee Eunryeol , Seo Jeongwoo , Park Jaehyun , Choi Ahreum , Kim Taewon , Choi Myeongjun , Kim Euna , Jung Yeong Hwa , Kang Seok Ju , Cho Jaephil , Li Yuzhang , Kim Min Gyu , Seo Dong-Hwa , Lee Hyun-Wook
Published: February 2025

Apart from conventional redox chemistries, exploring high-voltage anionic redox processes, such as pure oxygen or high-valent transition metal ion redox, poses challenges due to the instability of O nonbonding or O-dominant energy states. These states are associated with destructive behaviors in layered oxide cathodes, including local structural distortion, cationic disordering, and oxygen gas evolution. In this study, we suppress first-cycle voltage hysteresis and irreversible O
2
evolution in Li-rich oxide cathodes through covalency competition induced by the substitution of electropositive groups. We found that the nonequivalent electron distribution within an asymmetric M
A
-O-M
B
backbone (metal-to-metal charge transfer via oxygen ligands) increases electron density on electronegative transition metal ions, preventing them from reaching unstable oxidation states within an operating voltage range. This phenomenon is observed across diverse transition metal combinations, providing insights into controlling unnecessary oxygen redox activity. Our findings open new avenues for controlling intrinsic redox chemistry and enabling the rational design of high–energy density Li-rich oxide cathodes.
Head-mounted surgical robots are an enabling technology for subretinal injections
Authors: Posselli Nicholas R. , Hwang Eileen S. , Olson Zachary J. , Nagiel Aaron , Bernstein Paul S. , Abbott Jake J.
Published: February 2025

Therapeutic protocols involving subretinal injection, which hold the promise of saving or restoring sight, are challenging for surgeons because they are at the limits of human motor and perceptual abilities. Excessive or insufficient indentation of the injection cannula into the retina or motion of the cannula with respect to the retina can result in retinal trauma or incorrect placement of the therapeutic product. Robotic assistance can potentially enable the surgeon to more precisely position the injection cannula and maintain its position for a prolonged period of time. However, head motion is common among patients undergoing eye surgery, complicating subretinal injections, yet it is often not considered in the evaluation of robotic assistance. No prior study has both included head motion during an evaluation of robotic assistance and demonstrated a significant improvement in the ability to perform subretinal injections compared with the manual approach. In a hybrid ex vivo and in situ study in which an enucleated eye was mounted on a human volunteer, we demonstrate that head-mounting a high-precision teleoperated surgical robot to passively reduce undesirable relative motion between the robot and the eye results in a bleb-formation success rate on moving eyes that is significantly higher than the manual success rates reported in the literature even on stationary enucleated eyes.
It is hard to be a robot in the wild
Authors: Murphy Robin R.
Published: February 2025

The family movie
The Wild Robot
illustrates the rigors of real-world field robotics.
A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma
Authors: Rendo Veronica , Lee Eudocia Q. , Bossi Connor , Khuu Nicholas , Rudek Michelle A. , Pal Sangita , Azazmeh Narmen , Rashid Rumana , Lin Jia-Ren , Cusick Margaret , Reynolds Abigail R. N. , Fassinou Auriole C. R. , Ayoub Georges , Malinowski Seth , Lapinskas Emily , Pisano William , Jeang John , Stopka Sylwia A. , Regan Michael S. , Spetz Johan , Desai Arati , Lieberman Frank , Palanichamy Kamalakannan , Fisher Joy D. , Pelton Kristine , Huang Raymond Y. , Sarosiek Kristopher A. , Nabors Louis B. , Holdhoff Matthias , Danda Neeraja , Strowd Roy , Desideri Serena , Walbert Tobias , Ye Xiaobu , Chakravarti Arnab , Sorger Peter K. , Santagata Sandro , Agar Nathalie Y. R. , Grossman Stuart A. , Alexander Brian M. , Wen Patrick Y. , Ligon Keith L. , Beroukhim Rameen
Published: February 2025

Inhibitors of murine double minute homolog 2 (MDM2) represent a promising therapeutic approach for the treatment of
TP53
wild-type glioblastomas (GBMs), reactivating p53 signaling to induce cancer cell death. We conducted a surgical window-of-opportunity trial (NCT03107780) of the MDM2 inhibitor navtemadlin (KRT-232) in 21 patients with
TP53
wild-type recurrent GBM to determine achievable drug concentrations within tumor tissues and biological mechanisms of response and resistance. Participants received navtemadlin at 120 mg (
n
= 10) or 240 mg (
n
= 11) for 2 days before surgical resection and after surgery until progression or unacceptable toxicity. Both 120 and 240 mg daily dosing achieved a pharmacodynamic impact, but median progression-free survival was 3.1 months. DNA sequencing of three recurrent tumors revealed an absence of
TP53
-inactivating mutations, indicating alternative mechanisms of resistance. To understand the mechanisms of response and resistance associated with navtemadlin, we conducted functional and spatial analyses of human tissue and patient-derived GBM neurosphere models. Navtemadlin induced partial tumor cell death as monotherapy, and combination with temozolomide enhanced apoptosis in GBM neurospheres while sparing normal bone marrow cells in vitro. We also observed up-regulation of oligodendrocyte differentiation genes with navtemadlin treatment and enrichment of oligodendrocyte transcription factor 2 (OLIG2)–positive cells at relapse, suggesting an unexplored mechanism of navtemadlin tolerance in GBM. Overall, these results indicated that clinically achievable doses of navtemadlin exert pharmacodynamic effects on GBM and suggest that combined treatment with temozolomide may be a route to more durable survival benefits.
Large diversity in the O-chain biosynthetic cluster within populations of Pelagibacterales
Authors: Haro-Moreno Jose M. , López-Pérez Mario , Molina-Pardines Carmen , Rodriguez-Valera Francisco
Published: February 2025

Genomic diversity in prokaryotic species is largely due to the existence of extensive pangenomes, allowing different gene complements to be drawn depending on the strain. Here, we have studied the diversity of the O-chain polysaccharide biosynthesis cluster (OBC) in marine bacteria of the Pelagibacterales order as a proxy to measure such genetic diversity in a single population. The study of single-amplified genomes (SAGs) from the whole order found a pattern similar to that of other well-studied microbes, such as the Enterobacteriales or
Alteromonas
, where distinct OBCs represent strains containing different gene pools. We found that most of the OBC sharing happened among individuals of the same clonal frame (>99% average nucleotide identity). Moreover, given the parsimonious way this cluster changes, the diversity of the OBCs can be extrapolated to the size of the population’s pangenome. This assumes that different OBCs correspond to lineages containing unique flexible gene pools, as seen in the aforementioned microbes. Through long-read metagenomics, we could detect 380 different OBCs at a single Mediterranean sampling site. Within a single population (single species and sample) of the endemic Ia.3/VII (gMED) genomospecies, we identified 158 OBCs, of which 130 were unique. These findings suggest that the gene pool within a single population might be substantial (several thousands). While this figure is large, it aligns with the complexity of the dissolved organic matter that these organisms can potentially degrade.

IMPORTANCE

Different strains of the same bacterial species contain very different gene pools. This has been long known by epidemiologists. However, it is unknown what gene pool is present in a single set of environmental conditions, i.e., the same time and place in free-living bacteria. Here, we have leveraged information from SAGs to analyze the diversity of the gene cluster coding for the O-chain polysaccharide, a typical component of the flexible gene pool classically used as a tool to differentiate strains in clinical microbiology. It evolves at a similar rate to the rest of the genome and does not seem to be affected by an arms race with phages. One single species of Pelagibacteriales (gMED) revealed an astounding diversity in one sample studied by long-read metagenomics. Our results point to a large gene pool (local pangenome) present in a single population, which is critical to interpreting the biological meaning of the pangenome,
i.e
., it provides intrapopulation diversity rather than characterizing strains with different distribution in time and/or space.
Unveiling novel features and phylogenomic assessment of indigenous
Priestia megaterium
AB-S79 using comparative genomics
Authors: Adeniji Adetomiwa Ayodele , Chukwuneme Chinenyenwa Fortune , Conceição Emilyn Costa , Ayangbenro Ayansina Segun , Wilkinson Eduan , Maasdorp Elizna , de Oliveira Tulio , Babalola Olubukola Oluranti
Published: February 2025

Priestia megaterium
strain AB-S79 isolated from active gold mine soil previously expressed
in vitro
heavy metal resistance and has a 5.7 Mb genome useful for biotechnological exploitation. This study used web-based bioinformatic resources to analyze
P. megaterium
AB-S79 genomic relatedness, decipher its secondary metabolite biosynthetic gene clusters (BGCs), and better comprehend its taxa. Genes were highly conserved across the 14
P
.
megaterium
genomes examined here. The pangenome reflected a total of 61,397 protein-coding genes, 59,745 homolog protein family hits, and 1,652 singleton protein family hits. There were also 7,735 protein families, including 1,653 singleton families and 6,082 homolog families. OrthoVenn3 comparison of AB-S79 protein sequences with 13 other
P. megaterium
strains, 7 other
Priestia
spp., and 6 other
Bacillus
spp. highlighted AB-S79’s unique genomic and evolutionary trait. antiSMASH identified two key transcription factor binding site regulators in AB-S79’s genome: zinc-responsive repressor (Zur) and antibiotic production activator (AbrC3), plus putative enzymes for the biosynthesis of terpenes and ranthipeptides. AB-S79 also harbors BGCs for two unique siderophores (synechobactins and schizokinens), phosphonate, dienelactone hydrolase family protein, and phenazine biosynthesis protein (phzF), which is significant for this study. Phosphonate particularly showed specificity for the
P. megaterium
sp. validating the effect of gene family expansion and contraction.
P. megaterium
AB-S79 looks to be a viable source for value-added compounds. Thus, this study contributes to the theoretical framework for the systematic metabolic and genetic exploitation of the
P. megaterium
sp., particularly the value-yielding strains.

IMPORTANCE

This study explores microbial natural product discovery using genome mining, focusing on
Priestia megaterium
. Key findings highlight the potential of
P. megaterium
, particularly strain AB-S79, for biotechnological applications. The research shows a limited output of
P. megaterium
genome sequences from Africa, emphasizing the importance of the native strain AB-S79. Additionally, the study underlines the strain’s diverse metabolic capabilities, reinforcing its suitability as a model for microbial cell factories and its foundational role in future biotechnological exploitation.
Supplemental Material: Tracking the spatial and temporal links between late Cenozoic extension and magmatism in the Death Valley region (California, USA)
Authors: Chan Christine F. , et al.
Published: February 2025

Supplemental Text S1: Field descriptions and photos. Figure S1: Cathodoluminescence images of zircon grains. Figure S2: Stacked plots of zircon 206Pb/238U dates. Figure S3: Whole-rock major element oxides versus SiO2 content. Figure S4: Comparison of whole-rock trace element compositions versus SiO2 content. Figure S5: Plots of whole-rock rare earth element ratios and Eu anomaly (Eu/Eu*) versus SiO2 content. Table S1: Chemical abrasion–isotope dilution–thermal ionization mass spectrometry 206Pb/238U zircon dates and zircon trace element concentrations. Table S2: Whole-rock Th/U ratios.
Impact of NICE Guideline NG241 ‘Ovarian Cancer: identifying and managing familial and genetic risk’ on a regional NHS family history and clinical genetics service
Authors: Roe Alexander , Forman Andrea , Lalloo Fiona , McVeigh Terri P , Hanson Helen , Snape Katie
Published: February 2025

Background

NICE Guideline NG241: identifying and managing familial and genetic risk of ovarian cancer (OC) was published by the National Institute for Health and Care Excellence (NICE) in March 2024. NG241 advises germline genetic testing of genes predisposing to OC in unaffected individuals with an OC family history at different mutation likelihood thresholds depending on age and sex, ranging from 2% to 10% likelihood of finding a germline pathogenic variant (GPV). Prior to implementation of NG241, updates to the NHS England National Genomic Test Directory would be required. Clinical genetics services have to consider equity of access to assessment and testing across all familial cancer types, best use of their limited resources and other factors such as complexity of delivery of clinical pathways.

Methods

We analysed data from 8011 patients who provided digital family histories to the South West Thames Centre for Genomics between October 2019 and June 2024.

Results

We estimate 527/782 (68%) females and 28/77 (36%) males would meet test criteria for NICE NG241. We estimate we would reject 2919/5485 (53%) females and 135/1208 (11%) males with the same likelihood of carrying a GPV, but with a breast cancer rather than OC family history. Testing the familial OC cohort at a universal 5% threshold in OC families would detect ~11 carriers for 229 tests compared with ~8 carriers for 278 tests following NG241 criteria.

Conclusion

Our data highlight additional factors needing to be considered before the NICE Guideline NG241 can be implemented by regional genetics services.
Occupational exposure to respirable and inhalable dust and its components in a Nicaraguan sugarcane plantation
Authors: d'Errico Antonio , Peraza Sandra , Weiss Ilana , Martinez William , Monge Esteban Arias , Wouters Inge Maria , Wegman David H , Jakobsson Kristina , Kromhout Hans
Published: February 2025

Objective

To assess personal exposure to respirable and inhalable dust and its components endotoxin, black carbon and crystalline silica among sugarcane workers in Nicaragua.

Methods

Individual exposures to respirable (measurements=98) and inhalable (measurements=36) dust were collected in January and March 2020, with the month of March generally being hotter and less humid. Respirable dust and its components black carbon and crystalline silica, as well as inhalable dust and its component endotoxin, were personally measured. Linear mixed models were used to identify the determinants of occupational dust exposure considering different job tasks and meteorological conditions.

Results

Respirable dust and black carbon concentrations were higher in March among burned cane cutters compared with the other job groups (respirable dust geometric mean (GM)=1.9 mg m−3; black carbon GM=13.7 µg m−3), with considerably lower levels in January (respirable dust GM=0.2 mg m−3; black carbon GM=3.4 µg m−3). Almost all respirable crystalline silica measurements were below the limit of detection, except for four measurements, which ranged from 8 µg m−³ to 15 µg m−³. Seed cutters (GM=3.1 mg m−3) and weeders (GM=2.5 mg m−3) had the highest exposure to inhalable dust, while endotoxin concentrations were higher among seed cutters (GM=100 EU m−3) and burned cane cutters (GM=63 EU m−3) than the other work groups.

Conclusions

Overall, exposure levels to the assessed agents varied across work groups, with higher levels observed among burned cane and seed cutters.
Data and knowledge needs for improving science and policy for peatlands in Canada in a changing world: insights from Global Peatlands Initiative Workshop, June 2023
Authors: Webster Kara L. , Strack Maria , Balliston Nicole , Davies Marissa A. , Hettinga E. Kathryn , Hunter Miranda , Kleinke Kimberly , Schmidt Megan , Barreto Carlos , Bird Melanie , Blann Kristen , Bona Kelly , Cassidy Allison , Connolly John , Davidson Scott J. , Fedorchuk Lee , Garneau Michelle , Harris Lorna , He Hongxing , Howie Sarah , Kirkwood Adam , Pontone Nicholas , Richardson Karen , Sanderson Nicole , Seutin Gilles , Xu Bin , Yin Xiangbo
Published: February 2025

Knowledge and data on the current function, future threats, and benefits of peatlands in Canada are required to support evidence-based decision-making to ensure they continue to provide critical ecosystem services. This is particularly relevant for Canada, given the large expanse of relatively intact peatland area. There is a need, not only to standardize protocols, but also to prioritize types of information and knowledge that can best meet conservation and management goals. This was the challenge posed to the participants of the Global Peatlands Initiative workshop in June 2023 in Quebec City, Quebec, Canada. Participants were composed of researchers using primarily Western science approaches that use peatland data for carbon accounting, policy or sustainable land use, reclamation/restoration, conservation, wildlife, and water resources applications. For seven peatland data categories (hydrometeorological and environmental sensing; peat coring and depth; greenhouse gas monitoring; biodiversity; vegetation, woody debris, and litter; Traditional Knowledge; water quality), three priority measurements were identified and recommendations for their collection were discussed. The key recommendations from the workshop were to (1) create standardized, yet flexible protocols; (2) coordinate field data collection where possible; (3) weave more Traditional Knowledge into understanding of peatlands; (4) create an atlas of existing peatland information; (5) scope opportunities to create a network of peatland “super sites”.
AVITI as an alternative to Illumina for low-cost genome-wide genotyping
Authors: de Ronne Maxime , Boyle Brian , TORKAMANEH Davoud
Published: February 2025

Advancements in sequencing technologies have dramatically transformed genomics research by enabling the analysis of genetic information with unprecedented scale and efficiency. Next-generation sequencing (NGS), renowned for its high-throughput capabilities, has significantly reduced costs and expanded the scope of sequencing applications. Among these, sequencing by synthesis (SBS) on Illumina systems is predominant, favored for its accuracy and cost-effectiveness. However, emerging technologies like Element Biosciences’ sequencing by Avidity (AVITI) are beginning to challenge this dominance. In this study, we sequenced and genotyped a library of 40 cannabis samples using both the AVITI and Illumina NovaSeq systems, observing an 81.2% overlap with 98.9% concordance in genotype calls. AVITI stands out for its flexibility and reduced per-base costs, presenting a viable option particularly for mid-sized laboratories. As the scientific community continues to seek ways to lower genotyping expenses, the combination of the AVITI system with NanoGBS library preparation offers a cost-effective solution adaptable to a wide range of project sizes.
R2T: Instance-optimal Truncation for Differentially Private Query Evaluation with Foreign Keys
Authors: Dong Wei , Fang Juanru , Yi Ke , Tao Yuchao , Machanavajjhala Ashwin
Published: February 2025

Answering SPJA queries under differential privacy (DP), including graph-pattern counting under node-DP as an important special case, has received considerable attention in recent years. The dual challenge of foreign-key constraints and self-joins is particularly tricky to deal with, and no existing DP mechanisms can correctly handle both. For the special case of graph pattern counting under node-DP, the existing mechanisms are correct (that is, satisfy DP), but they do not offer nontrivial utility guarantees or are very complicated and costly. In this paper, we propose the first DP mechanism for answering arbitrary SPJA queries in a database with foreign-key constraints. Meanwhile, it achieves a fairly strong notion of optimality, which can be considered as a small and natural relaxation of instance optimality. Finally, our mechanism is simple enough that it can be easily implemented on top of any RDBMS and an LP solver. Experimental results show that it offers order-of-magnitude improvements in terms of utility over existing techniques, even those specifically designed for graph pattern counting.
Automated Restoration of Portrait Reliefs in the Binyang Central Cave of the Longmen Grottoes
Authors: Chen Qiang , Chen Tian-Ning , Lin Wei-Cheng , Ouyang Zhen-Yu , Wang Xiao-Yi
Published: February 2025

The Longmen Grottoes, a renowned World Heritage site, features a relief carving of the Imperial Couple’s worship scene in the Binyang Central Cave during the reign of Emperor Xuanwu of the Northern Wei Dynasty in China. Portraying the religious activities of the Northern Wei imperial family, these reliefs hold substantial historical and artistic values. However, the reliefs have suffered severe damage because of both natural and human-induced factors. Although initial restoration efforts have taken place in museums, a considerable portion remains irrecoverable, with the facial features of the figures presenting the most formidable challenge for reconstruction. The precise and objective restoration of the missing facial portion in the reliefs is crucial. Although facial three-dimensional reconstruction techniques from a single photograph exist, their stability and accuracy under complex imaging conditions often lack practical requirements. To enhance portrait relief restoration, we propose a method based on the Gaussian process model. Our approach leverages the surviving samples to learn prior shape knowledge, thereby establishing a Gaussian process model. Subsequently, observations from historical photographs and surviving fragments were used as input data to predict the damaged shape. Experimental validation via cross validation confirms the high precision and robustness of the proposed method.
Engaging Youth in Moorish Architectural Heritage through Virtual 3D Experience of the Bardo Palace of Algiers
Authors: Kebir Ahlem , Kacher Sabrina , larabi Mohamed-Chaker , Meneveaux Daniel
Published: February 2025

Digital representations of cultural heritage have many advantages in a wide range of subjects, ranging from archaeological research studies with the possibility to visualize historical assumptions, to virtual restitution dedicated to public release. This article studies the intersection between education, virtual environments modelling, and cultural heritage preservation, with a focus on the Moorish architectural site of the Bardo in Algiers. Our primary objective is to design an accessible, low cost educational tool that employs a Montessori-informed approach to create an engaging learning experience from a virtual 3D restitution. Initially targeting the general public, we aim at attracting and at interesting a younger audience. In this study, we first investigate tools and platforms that can be employed for achieving this objective. We evaluated several platforms with different degrees of immersion, the chosen technology will serve as the foundation for implementing our educational program. The selected platform has been subjected to an evaluation process, consisting of two phases: knowledge assessment and usability testing of digital learning. This article details the process, from acquisition using a standard DSLR camera to the visualization software, including the integration of annotations and questionnaires using Montessori pedagogy as a guideline. Technical aspects are discussed providing usability results. The work has been devised as a virtual learning environment showcasing the 3D reconstruction of the Bardo Palace of Algiers, a renowned historical landmark located in northern Algeria, known for its Moorish architectural style.
Enhancing Recommender Systems: Deep Modality Alignment with Large Multi-Modal Encoders
Authors: Yi Zixuan , Long Zijun , Ounis Iadh , Macdonald Craig , McCreadie Richard
Published: February 2025

In recent years, the rapid growth of online multimedia services, such as e-commerce platforms, has necessitated the development of personalised recommendation approaches that can encode diverse content about each item. Indeed, modern multi-modal recommender systems exploit diverse features obtained from raw images and item descriptions to enhance the recommendation performance. However, the existing multi-modal recommender systems primarily depend on the features extracted individually from different media through pre-trained modality-specific encoders, and exhibit only shallow alignments between different modalities, thereby limiting these systems’ ability to capture the underlying relationships between the modalities. In this paper, we enhance the deep alignment of large multi-modal encoders to address the shallow alignment of modalities in multi-modal recommender systems. These encoders have previously demonstrated state-of-the-art effectiveness in ranking items across various domains. Specifically, we investigate the use of three state-of-the-art large multi-modal encoders — CLIP (dual-stream), VLMo and BEiT-3 (unified) — for recommendation tasks. We explore their benefits for recommendation through using a range of strategies, including the use of pre-trained and fine-tuned encoders, as well as the evaluation of the end-to-end training of these encoders. We show that pre-trained large multi-modal encoders generate more aligned and effective user/item representations compared to existing modality-specific encoders across four existing multi-modal recommendation datasets. Furthermore, we show that fine-tuning these encoders further improves the recommendation performance, with end-to-end training emerging as the most effective paradigm, significantly outperforming both pre-trained and fine-tuned encoders with an improved recommendation performance. We also demonstrate the effectiveness of large multi-modal encoders in facilitating modality alignment by evaluating the contribution of each modality separately. Finally, we show that the dual-stream approach, specifically CLIP, is the most effective architecture for these large multi-modal encoders, outperforming the unified approaches (i.e., VLMo and BEiT3) in terms of effectiveness and efficiency.
Analysis of the Dissolved Surface of NiTi Shape Memory Alloy in Electrochemical Micromachining Process Using Potentiodynamic Polarization and EIS Techniques
Authors: Sethi Abhijeet , Saha Partha
Published: February 2025

Electrochemical micromachining, an unconventional machining method, has emerged as a promising approach for micro-feature fabrication on temperature-sensitive NiTi shape memory alloys. This study investigates NiTi dissolution in neutral aqueous electrolytes (NaCl, NaNO3, NaBr) using potentiodynamic polarization (PDP) techniques, linear sweep voltammetry, and cyclic voltammetry (CV). CV analysis reveals that NiTi dissolution in NaCl and NaNO3 electrolytes is predominantly passive, whereas, in NaBr, it is active, as confirmed by the peak current (Ipk) order: NaCl < NaNO3 < NaBr. Post-CV analysis shows NaNO3 yielding the lowest average surface roughness (

S

a

= 0.072 μm), reflecting uniform dissolution. Surface passivation proves instrumental in enhancing surface roughness, further emphasized by electrochemical impedance spectroscopy techniques like Nyquist and Bode plots, reflecting the dual nature of the oxide layer. X-ray photoelectron spectroscopy reveals the composition of the surface oxide layer, elucidating the role of stable metal complex sodium titanate (Na2TiO3) in facilitating NiTi dissolution in NaNO3. Micro-grooves were attempted using all three electrolytes, but only NaNO3 successfully fabricated them with the lowest surface roughness (

R

a

= 0.86 μm), ensuring a uniform dissolution process.
Abnormal purine metabolism in nasal epithelial cells affects allergic rhinitis by regulating Th17/Treg cells
Authors: Xu Ting , Xia Shitong , Zhang Xingjie , Yuan Yixiao
Published: February 2025

We aimed to explore novel pathogenesis in young AR children, and thus finding novel nasal spray reagents for them, especially under 4 years old. In this study, non-targeted metabolomics analyses were employed to explore the differential metabolites in NALF of AR children. CCK-8 and flow cytometry were employed to assess cell proliferation and apoptosis in HNEpCs. HNEpCs were co-cultured with CD4+T cells, and flow cytometry was employed to detect Th17/Treg cells. RNA sequencing was employed to assess the key pathways in xanthine-treated Jurkat T cells. Finally, both the in vitro and in vivo experiments were employed to assess the effect of DPCPX (Adora1 inhibitor) on ATF4 expression and Th17/Treg cells. Xanthine and uric acid levels were increased in NALF of AR children. XDH, PNP, xanthine/hypoxanthine, and uric acid levels were elevated in Derp1-treated HNEpCs, and si-XDH reversed the reduced cell viability and increased cell apoptosis in Derp1-treated HNEpCs. Both xanthine and Derp1-treated HNEpCs increased Th17/Treg ratio. ERS pathway was affected in xanthine-treated Jurkat T cells, and ATF4 was markedly reduced in xanthine-treated Jurkat T cells. Xanthine exhibited no effect on Adora1 expression, while DPCPX elevated ATF4 expression and reduced Th17/Treg ratio in xanthine-treated Jurkat T cells. The in vitro experiments revealed that DPCPX reduced inflammatory infiltration, Th17/Treg ratio, IL-17, TNF-α, and IL-6 in AR mice. These results demonstrated that xanthine inhibited ATF4 expression via Adora1 to elevate Th17/Treg ratio in nasal cavity, thus participating in AR progression. These findings may provide novel therapeutic interventions for young AR children.
T‐Symmetry in String Geometry Theory
Authors: Sato Matsuo , Tohshima Taiki
Published: February 2025

String geometry theory is one of the candidates of nonperturbative formulation of string theory. In this paper, we have shown that dimensionally reduced string geometry theories have what we call T‐symmetry. In the case of the dimensional reduction in space‐like directions, the T‐symmetry transformation gives the T‐dual transformation between the Type IIA and IIB perturbative vacua. In the case of the dimensional reduction in the direction of string geometry time , the T‐symmetry transformation is independent of the T‐dual transformation and gives a symmetry that cannot be seen in the perturbative string theories.
Exploring the Landscape of Role‐Playing Game Research Through Bibliometric Analysis From 1986 to 2023 Using Scopus Database
Authors: Nguyen Long Thanh , Pham Hiep-Hung , May Amy Yeo Chu , Chin Tay Lee
Published: February 2025

Background: Role‐playing games (RPGs) have long attracted scholars because of their interactive and immersive attributes. The areas of studies on RPGs are various, from computer science to sociology and psychology. Nevertheless, there is a notable absence of comprehensive systematic literature that traces the trends, changes, and developments in RPG research.

Purpose: This paper is aimed at undertaking a systematic review of RPG research by analyzing the Scopus database, covering the period from 1986 to 2023.

Method: The analyzed dataset comprises 1152 documents, filtered through the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) screening method from an initial pool of 2908 data points. This data was subjected to analysis using descriptive statistics and bibliometric techniques to discern trends in RPG research and identify influential documents shaping studies in this domain.

Findings: This research systematically analyzes RPG research, providing insights into growth patterns, global interest, and influential contributors. By synthesizing diverse research strands, the study contributes valuable knowledge for scholars, practitioners, and policymakers as well as guiding future research in RPGs.

Contribution: This research provides valuable insights into the evolving RPG landscape, offering guidance for future research.
Efficacy of Anthelmintics Against Canine Hookworm Infections in the Bono East Region of Ghana
Authors: Ofori Samuel Ayetibo , Amissah-Reynolds Papa Kofi , Gyamfi Opoku , Addo Kofi Agyapong , Nyarko Simon , Agyei Victor , Dwomoh Joshua , Ayemugah Esther
Published: February 2025

Hookworm infections present a major health risk to dogs, especially in areas characterized by warmer climates and poor sanitation. This cross‐sectional study was undertaken to determine the prevalence of hookworm infections and the efficacy of anthelmintic treatments in dogs from the Bono East Region of Ghana. Four hundred and ninety‐one (491) canine stool samples were examined using the McMaster technique to ascertain the prevalence of hookworms. Using in vivo and in vitro techniques, the efficacy of three anthelmintics (albendazole, pyrantel, and niclosamide) was assessed in an experimental control trial involving dogs naturally infected with hookworms. The effects of the drugs on hematological and biochemical parameters were measured within a 14‐day period to assess changes over time. The study found a total prevalence of 54.2% (266), with significantly higher infection rates in puppies (69.8%, 97), hunting dogs (64.1%, 91), and rural dogs (84.2%, 160). Logistic regression identified age, purpose, and settlement type as risk factors for infection. Of the three treatments, niclosamide was the most efficacious, reducing egg counts by 95%, while albendazole was the least efficacious (−69%). In vitro tests confirmed the superior performance of niclosamide, with the lowest IC50 value of 29.19 μg/mL. Hookworm‐infected dogs exhibited anemia, eosinophilia, hypoalbuminemia, and hypoproteinemia. There was significant improvement in the hematobiochemical parameters after treatment, particularly in niclosamide‐treated dogs. Veterinarians can consider niclosamide, especially in resource‐limited settings, due to its affordability. The findings emphasize the importance of regular monitoring and treatment of hookworm infections to improve the overall health and well‐being of dogs in the region. Herein, we report for the first time on reduced efficacy of albendazole and pyrantel against dog‐related hookworms in Ghana.
Active Vibration Isolation Platforms for Wafer Front Opening Unified Pod Transporting Carts Under Raised Floor Irregularities in Industrial Factories
Authors: Lee Chien-Liang , Chen Yung-Tsang , Wang Yen-Po , Chung Lap-Loi , Liu Meng-Chieh , Lu Li-Yen
Published: February 2025

This study was conducted to examine the vibration control performance of the active isolation platform (AIP) implemented on the cart table (CT) of a moving front opening unified pod (FOUP) transporting cart to prevent damage to fragile silicon wafers during transportation across different buildings in semiconductor fabs. Additionally, the equation of motion for the proposed AIP–cart system simulated by a full vehicle model under raised floor irregularities was derived. Moreover, the direct output feedback control algorithm was used to determine the optimal feedback gain matrix for calculating the active control forces of the AIP. Furthermore, the dynamic time histories of the proposed model under raised floor irregularities were analyzed by the discrete–time state–space procedure (SSP), and the numerical simulation results revealed that AIP effectively suppressed the bouncing (or vertical) acceleration with a reduction of > 90% at FOUP locations to 2.37 m/s2 (< 9.81 m/s2 or 1.0 g, the bouncing acceleration threshold) to prevent FOUPs (or fragile silicon wafers) from bouncing away from the CT without AIP, causing damages to the wafers via collisions. Moreover, AIP greatly reduced the pitching angular rotation with a reduction of > 65% to prevent the sliding of FOUP‐stored wafers from the supporting slots inside FOUPs when the FOUP‐transporting cart traversed through a larger bump between the expansion joints. The flexible AIP that demanded less control force (27.08 N) significantly isolated the high‐frequency response transmitted from the CT and effectively enhanced its damping ratio to suppress the resonance low‐frequency response induced by intermittent perforated floor irregularities or bumps. From a practical point of view, the proposed AIP scheme implemented on CT can be adopted for protecting jumping‐ or sliding‐induced collision damages to wafers (or similar fragile products) transported by carts to reduce huge economic losses in industry.
Gli2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating Wnt Ligand and Prostaglandin Signaling
Authors: DeVito Nicholas C. , Nguyen Y-Van , Sturdivant Michael , Plebanek Michael P. , Villarreal Kaylee A. , Yarla Nagendra , Jain Vaibhav , Aksu Michael , Beasley Georgia M. , Theivanthiran Balamayooran , Hanks Brent A.
Published: February 2025

Therapeutic resistance to immune checkpoint blockade has been commonly linked to the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated immune evasion promises to lead to more effective combination therapeutic regimens. Herein, we identified the Hedgehog transcription factor, GLI2, as a key node of tumor-mediated immune evasion and immunotherapy resistance during MT. GLI2 generated an immunotolerant tumor microenvironment through the upregulation of WNT ligand production and increased prostaglandin synthesis. This pathway drove the recruitment, viability, and function of granulocytic myeloid-derived suppressor cells while also impairing type I conventional dendritic cell, CD8+ T cell, and natural killer cell functionality. Pharmacologic inhibition of EP2/EP4 prostaglandin receptor signaling or WNT ligand secretion each reversed a subset of the immunomodulatory effects of GLI2 and prevented primary and adaptive resistance to anti-PD-1 immunotherapy, respectively. A transcriptional GLI2 signature correlated with resistance to anti-PD-1 immunotherapy in stage IV melanoma patients. Together, these findings provide a translational roadmap to direct combination immunotherapies in the clinic.
Spatially resolved, multi-region proteomics for prediction of immunotherapy outcome in deficient mismatch repair metastatic colorectal cancer
Authors: Saberzadeh-Ardestani Bahar , Liu Zhenglong , Stein Mariam I. , Sherman Will A. , Trussoni Christy E. , Abbott Charles W. , Yan Dongyao , Smith Skyler , Shanmugam Kandavel , Graham Rondell P. , Diallo Alos , Levy Joshua J. , Ordog Tamas , Sinicrope Frank A.
Published: February 2025

Purpose. Digital proteomic profiling was performed to identify spatial context in relationship to patient response and survival after anti-PD-1 therapy in metastatic colorectal cancer (CRC). Experimental Design. Primary CRCs with deficient mismatch repair (d-MMR) from patients treated with anti-PD-1 antibodies were analyzed (N=30) using Digital Spatial Profiling (GeoMx® nCounter). At the invasive margin, 71 proteins were profiled in 10 regions of interest /slide that were segmented into 3 compartments labeled with pan-cytokeratin (PanCK; epithelia), CD45 (stromal cells) and SYTO13 (nuclei). In an independent cohort (n=13), DSP data and single cell transcriptomic data were analyzed. Differential protein abundance, after Benjamini-Hochberg correction, was examined by response and progression-free survival (PFS) using multivariable Cox regression. Results. Protein abundance varied significantly between epithelial and stromal compartments. Nonresponders (NR) to anti-PD-1 showed higher fibronectin and smooth muscle actin (SMA) abundance in the epithelial compartment that were associated with significantly shorter PFS (HRadj: 6.49 and 4.52, respectively; p < 0.05). In CD45+ stroma, increased expression of proteins related to T-cells (CD3, CD4), NK cells (CD56), antigen presentation (CD40), immune activation (CD27, ICOS), and apoptosis (GZMA) were found in responders (vs NR) to anti-PD-1; each marker was significantly associated with longer patient PFS (0.02 <HRadj < 0.17; p < 0.05). In a separate cohort, consistent results by compartment were found for fibronectin and CD56. Gene expression data revealed that fibronectin and SMA were primarily derived from cancer-associated fibroblasts. Conclusions. Spatially resolved protein profiles within microenvironments of d-MMR CRCs can influence patient response and survival after anti-PD-1 highlighting their potential clinical significance.
Removal of ticagrelor by hemoadsorption with the HA380 cartridge
Authors: Furukawa Taku , Lankadeva Yugeesh R. , Baldwin Ian C. , Ow Pei Chen Connie , Hood Sally , Daali Youssef , Schneider Antoine , Decosterd Laurent A. , May Clive N. , Bellomo Rinaldo
Published: February 2025

Introduction: Hemoadsorption has emerged as a potential intervention for the removal of ticagrelor. We aimed to evaluate the efficacy of the HA380 hemoadsorption cartridge for this purpose.
Methods: Six healthy adult sheep received 270 mg of ticagrelor via an orogastric tube, followed by hemoadsorption using a HA380 cartridge for a duration of 4 hours. The sorbent-based removal ratio, clearance, and mass removal rate were assessed at multiple time points.
Results: The HA380 cartridge achieved an initial sorbent-based removal ratio of 48.9% (SD 11.8) at 10 minutes, which declined rapidly to 2.66% (SD 18.5) at 120 minutes and 0.48% (SD 17.0) at 240 minutes. Clearance followed a similar trend, starting at 46.1 mL/min (SD 11.4) and decreasing to 0.08 mL/min (SD 16.8) at 240 minutes. The mass removal rate also dropped significantly over time, from 3.74 ng/min (SD 2.54) at 10 minutes to near zero at 120 and 240 minutes.
Conclusion: HA with the HA380 cartridge can achieves an early 50% adsorption level for ticagrelor. If frequently changed, the HA380 cartridge may serve as a potential option for ticagrelor removal, when clinically indicated.
StilOrtiz, bons controles nunca saem de moda
Authors: Faia Valter da Silva , Moura Geany Maria Fugimoto de
Published: February 2025

This is a teaching case for educational purposes related to the topics of management control and performance management systems. It describes the real situation of the company StilOrtiz, a clothing company that operates in a decentralized way through production units. The units have been showing losses in the last months due to unfavorable efficiency rates. This scenario puts in check the skills of Helena Mendonça and Carlos Rodrigues front of the production units. They need to look for solutions and arguments that are good enough to convince Ramiro Ortiz, production director, that changes are required in the unit’s management control and performance system. This case aims to contribute to a practical view of management control theory through an active teaching methodology that puts the student in front of the problem of the company StilOrtiz and encourages them to resolve the case.
Abordagem fisioterapêutica e terapêutica ocupacional integrada: caso de follow-up na Casa da Esperança de Santos
Authors: Buzeto Giovanna Carnelós , Menezes Ilma , Siqueira Paulo Santos de , Santos Maria Lúcia Leal dos
Published: February 2025

A intervenção multidisciplinar para desenvolvimento de componentes motores, cognitivos e sensorial no recém-nascido com malformações congênitas pode favorecer a potencialização do desenvolvimento infantil. Segundo os autores, a literatura científica sugere a combinação de instrumentos padronizados à fomentação de um planejamento que favoreça as atividades orientadas à tarefa para obtenção de resultados. Essas atividades promovem a aquisição de habilidades, de forma direcionada, através do monitoramento e da avaliação de resultados do desempenho motor e cognitivo, que são qualificados por ferramentas capazes de medir a melhora funcional e a participação do paciente em atividade.
Avaliação de descontinuidade de reabilitação em pacientes adultos com paralisia cerebral durante a pandemia
Authors: Hashimoto Mariana Karakida , Kuga Fábio Seiji , Akamine Eduardo Hideyuki , Rocha Eduardo de Melo Carvalho , Gomes Cláudio
Published: February 2025

A pandemia de COVID-19 rapidamente se tornou uma das crises de saúde mais impactantes da história contemporânea. Além das consequências diretas de infecção pelo vírus SARS-CoV-2, essa pandemia trouxe consigo uma série de desafios adicionais para o sistema de saúde global. Diante da rápida transmissão e ausência de tratamento específico ou vacina, medidas para evitar a disseminação da doença precisaram ser tomadas ao redor do mundo. Períodos chamados de “lockdown” foram adotados, restringindo a circulação da população e interrompendo significativamente a rotina de cuidados médicos e de reabilitação, afetando particularmente pacientes com condições crônicas incapacitantes e populações já vulneráveis, como os pacientes com paralisia cerebral.
Estimulação Magnética Transcraniana (EMT) na reabilitação pós-AVC isquêmico: redução de déficit visual mensurada por campimetria visual computadorizada
Authors: Chequer Karen Miranda , Mendes Plínio Duarte
Published: February 2025

Trata-se de relato de caso de paciente do sexo masculino, 47 anos, com histórico de AVC isquêmico em 22/06/2022, que evoluiu com déficit visual agudo completo, alteração do equilíbrio e hemiparesia esquerda. Ressonância Nuclear Magnética (RNM) do Encéfalo demonstrou encefalomalácia acometendo território de artérias cerebrais posteriores, principalmente à direita.
Relação entre gravidade do sentimento de solidão, dor psicológica e impacto na vida diária de mulheres com fibromialgia
Authors: Pinto Junior Alexandre Otilio , Rego Victor Felipe Rodrigues , Sarmento Viviane Porangaba , Chiappetta Lorella Marianne , Melo Neto Valfrido Leão de
Published: February 2025

A fibromialgia é uma doença crônica caracterizada por dor difusa, fadiga e comprometimento cognitivo. A presença de comorbidades psiquiátricas na fibromialgia destaca sua influência na qualidade de vida, piorando o prognóstico da doença. Dentre essas alterações, pode-se destacar o sentimento de solidão e a dor psicológica.
Utilização do ultrassom para aplicação de Toxina Botulínica em paciente com espasticidade pós acidente vascular cerebral
Authors: Fonseca Ana Paula Coutinho , Misk Sheila Cristina da Silva , Cury Ana Carolina , Junqueira Gabriel Fonseca
Published: February 2025

A espasticidade se desenvolve em cerca de 40% dos pacientes pós acidente vascular cerebral (AVC), sendo que 15% desses evoluem com espasticidade grave. A Toxina Botulínica tipo A (BoNT-A) faz parte do tratamento de reabilitação desses pacientes e é indicada para a espasticidade focal de membros superiores e inferiores, em fase subaguda ou crônica.