bluuebunny/crossref_metadata_2025 huggingface dataset:
Necessary and Sufficient Design Conditions for Over-Constrained Cam Mechanisms with Flat-Faced and Roller Follower
Authors: Chen Yen-Nien , Hsu Kuan-Lun
Published: February 2025

Cam, a mechanism usually used to transform a rotary motion into the desired output motion, has been commonly used in modern industry. In practice, various practical methods have been discussed to analyze and synthesize the cam mechanism. However, the mobility of the cam mechanism is seldom mathematically addressed. This paper mathematically discusses the necessary and sufficient design conditions for four kinds of over-constrained cam mechanisms (the one with a translating flat-faced follower, a translating roller follower, an oscillating flat-faced follower, and an oscillating roller follower) to be mobile. For the first two over-constrained cam mechanisms, the relation between the design conditions and the mobility of the cam mechanism is derived by proving that the identical cam contour can be enveloped by the top and bottom follower faces. For the third over-constrained cam mechanism, the relation is derived by transforming the cam contour into a geometric layout associated with an orthoptic curve. For the fourth over-constrained cam mechanism, it is shown that the cam mechanism cannot be theoretically designed due to the variable length of the follower's arm, which does not obey the rigid body assumption. In conclusion, by means of these geometric methods, the first three kinds of cam mechanisms are proved to be mobile if and only if they satisfy the design conditions, and the last cam mechanism is proved to be theoretically infeasible.
Effect of implantation dose on surface gradient structure and properties of magnesium alloy AZ31
Authors: Dou Zhongyu , Wang Xiaomao , An Xueyang , Sun Weisong
Published: February 2025

With an aim to address the issue of poor corrosion resistance in magnesium alloys, we implemented ultrasonic rolling pretreatment on magnesium alloy AZ31, followed subsequently by N-ion implantation treatment. The influences of various implantation doses on the surface structure and friction-corrosion performance of the magnesium alloy were examined. The outcomes disclosed that after N-ion implantation, a new phase Mg3N2 emerged, and the diffraction peak intensity increased as the implantation dose rose. The microhardness of the modified surface layer rose significantly with higher implantation doses due to the formation of nitrides and solid solution strengthening caused by N implantation. The results of the friction wear test showed that the average friction coefficient of the magnesium alloy samples decreased from 0.33 to 0.28 after ion implantation treatment. Notably, the samples with an implantation dose of 5 × 1016 ions/cm2 had the minimum mass loss during wear and demonstrated superior wear resistance, which was in line with the reduced friction coefficients. Electrochemical analysis indicated that increasing the implantation dose enhanced the self-corrosion potential of magnesium alloy samples from −1.39 (for the untreated sample) to −1.19 and significantly decreased the self-corrosion current density due to the diffusion protection provided by Mg3N2 formed on the surface along with the supersaturated nitrogen diffusion effect. These discoveries demonstrate that combining the ion implantation process following ultrasonic rolling pretreatment can further enhance the tribocorrosion resistance of magnesium alloys and serve as a valuable reference for improving the surface properties of these alloys through composite processes.
Structure and tribological evolution of Ta-N layer by controlling the time of microwave plasma nitriding
Authors: Li Jiacheng , Xu Zhigang , Peng Jian , Shen Qiang , Wang Chuanbin
Published: February 2025

To enhance the mechanical properties and wear resistance of the Ta matrix, a Ta-N layer was synthesized on its surface via microwave plasma nitriding (MPN). A systematic investigation was carried out to study the influence of holding time on the phase composition, morphology, mechanical properties, friction behavior, and wear characteristics of the nitriding layers. The results demonstrated that nanocrystalline Ta-N layers with a dense surface and low roughness were successfully fabricated. As the holding time was extended, the thickness of the Ta-N layer increased from 0.87 to 4.23 μm. Specifically, the Ta-N layer formed at 4 h, featuring a nanocrystalline structure, a dense surface, and appropriate thickness, displayed excellent mechanical properties. It had a hardness value of 26.89 GPa, an H/E ratio of 0.109, an H3/E2 value of 0.318 GPa, and an ηw value of 0.634, all of which were significantly higher compared to those of pure Ta. The friction and wear test results indicated that the Ta-N layer showed the best wear resistance when the holding time was 4 h. This was mainly ascribed to the synergy between the dense structure and the formation of nanocrystals. In summary, through MPN treatment, a Ta-N layer with the desired hardness and wear resistance was achieved, providing excellent surface protection for the Ta matrix against wear.
The increasing importance of voice onset time in the perception and production of Zurich German plosives: An ongoing sound change
Authors: Zebe-Sheng Franka , Watter Camille , Schmid Stephan
Published: February 2025

Recent evidence suggests an ongoing sound change in Zurich German, where the primary cue between lenis and fortis plosives is commonly considered to be closure duration, while both plosive types are traditionally unaspirated and phonetically voiceless. There has been a shift toward more lexical items being aspirated by younger speakers, who also are shown to produce generally longer voice onset times (VOTs) in comparison to older speakers. The current study investigates word-medial and word-initial plosives in speech perception and production. Using the apparent-time paradigm, two experiments were conducted with 48 speakers of Zurich German belonging to 2 age groups. Results confirm that younger speakers produce more aspiration in word-initial fortis plosives than older speakers but disconfirm previous findings which found a reduction in closure duration of fortis plosives. Results from the perception experiment reveal that, word-initially, VOT seems to increase in importance and closure duration is not always sufficient in distinguishing between lenis and fortis plosives. Results further highlight the importance of lexical differences, according to which production and perception are either aligned or misaligned. Overall, the current study provides evidence for a sound change affecting word-initial fortis plosives in Zurich German in speech perception and production.
Binaural rendering using higher-order stereophony
Authors: Hollebon Jacob , Maria Fazi Filippo
Published: February 2025

Higher-order stereophony is a new approach for spatial audio reproduction which extends classic two-channel stereophony to higher order soundfield reproduction and generalised multi-channel loudspeaker arrays. Higher order stereophony achieves accurate soundfield reproduction over a line by reproducing the degree m = 0 spherical harmonic soundfield coefficients only. The reproduction line is assumed to align with the interaural axis of a listener. This article addresses the extension of higher order stereophony to binaural reproduction. The technique is shown to exactly reproduce binaural signals when using a rigid sphere head-related transfer function model, and to reorder the energy of more generalised head-related transfer functions into spherical harmonic coefficients with degree index close to 0. To truncation order N, higher order stereophony requires only (N + 1) spherical harmonic coefficients compared to (N + 1)2 with higher order ambisonics, and the two techniques are compared through simulations and a listening test. Higher order stereophony is shown to perform similarly to higher order ambisonics under truncation to the same order, but using a smaller number of soundfield coefficients. For higher virtual source elevations, higher order stereophony performs worse than higher order ambisonics due to its ability to only reproduce axisymmetric head-related transfer functions.
Collaborative non-local topology optimization of gradient acoustic metasurfaces for broadband extreme reflection modulation
Authors: Fu Wen-Xiao , Dong Hao-Wen , Wang Yue-Sheng
Published: February 2025

To control the complex energy flow between neighboring microstructures for realizing the extreme acoustic functionality using a large-scale non-local metamaterial, here this paper shows that a collaborative non-local topology-optimization methodology is developed to construct gradient acoustic metasurfaces with smooth boundaries for the broadband large-angle reflection. An inverse-designed non-local acoustic metasurface is numerically and experimentally validated to support the large reflection angles within the low-frequency broadband range while maintaining high efficiency greater than 98.9%. It is further revealed that the strong non-local energy exchange between the multiple adjacent optimized microstructures can enable arbitrary surface impedances, thus obtaining efficient large-angle anomalous reflection from 52° to 90°. The present collaborative non-local topology-optimization methodology is not only applicable to airborne acoustic waves, but also can be extended to the customization of efficient wave functionalities of elastic and underwater acoustic metasurfaces.
Efficacy, safety, and anti-inflammatory properties of the switch to a doravirine-based regimen among antiretroviral-experienced elderly people living with HIV-1: the DORAGE cohort
Authors: Lazzaro Alessandro , Recchia Gregorio Egidio , Alessi Federica , Santinelli Letizia , Battistini Luigi , Morcos Julieta , Romano Francesco , Bugani Ginevra , Maddaloni Luca , Caruso Sara , D'Amico Marta , Mezzaroma Ivano , Falciano Mario , Fimiani Caterina , Sfara Germana , Leone Maria Gemma , Turriziani Ombretta , Mastroianni Claudio Maria , d’Ettorre Gabriella
Published: February 2025

Doravirine (DOR) is a novel antiretroviral agent with a favorable resistance profile and high tolerability. However, evidence is limited on DOR among elderly people living with HIV (PLWH) and whether it might modulate chronic inflammation. We aimed to investigate the efficacy, safety, and tolerability of DOR as a switching strategy among elderly PLWH and its impact on chronic inflammation in a real-life setting. We recruited a cohort of ART-experienced PLWH undergoing a therapeutic switch to a DOR-based regimen under virologic control (defined as HIV-RNA <200 copies/mL), regardless of the previous ART regimen. The primary objective was the evaluation of the rate of virologic control at 48 weeks post-switch. Secondary objectives included analyzing immune and metabolic outcomes. Plasmatic hs-CRP, IL-6, and D-dimer levels were measured as chronic inflammation markers. Overall, 150 PLWH were screened, and 147 were enrolled into the study. A total of 134 PLWH completed the follow-up. The rate of virological control was 96.1% (122/134;
CIs
: 91.0%–98.7%) in the per-protocol analysis. After 48 weeks from the switch, we recorded significant reductions in serum fasting glycemia (
P
0.019), triglycerides (
P
0.024), and total cholesterol/HDL ratio (
P
0.017); no clinically significant differences were detected in the body weight and BMI, as long as in immune, hepatic, and renal profiles. A significant reduction in IL-6 (
P
0.019) and hs-CRP (
P
0.019) was observed. DOR is an effective and safe treatment choice for elderly PLWH. The intriguing modulatory effect of DOR-based regimens on chronic systemic inflammation deserves further investigation.
The Na
+
-K
+
-ATPase alpha subunit is an entry receptor for white spot syndrome virus
Authors: Zhou Junyi , Zhang Huimin , Wu Gaochun , Zhang Yinghao , Aweya Jude Juventus , Tayyab Muhammad , Zhu Jinghua , Zhang Yueling , Yao Defu
Published: February 2025

White spot syndrome virus (WSSV) is a debilitating viral pathogen that poses a significant threat to the global crustacean farming industry. It has a wide host tropism because it uses several receptors to facilitate its attachment and entry. Thus far, not all the receptors have been identified. Here, we employed a BioID-based screening method to identify the Na
+
-K
+
-ATPase alpha subunit (
Pv
ATP1A) as a potential receptor in
Penaeus vannamei
. Although during the early stages of WSSV infection
, Pv
ATP1A was induced and underwent oligomerization, clustering, and internalization, knockdown of
Pv
ATP1A inhibited viral entry and replication.
Pv
ATP1A interacted with the WSSV envelope protein VP28 through its multiple extracellular regions, whereas synthetic
Pv
ATP1A extracellular region peptides blocked WSSV entry and replication. We showed that
Pv
ATP1A did not affect WSSV attachment but facilitated internalization via caveolin-mediated endocytosis and macropinocytosis. These findings provide a robust receptor screening approach that identified
Pv
ATP1A as an entry receptor for WSSV, presenting a novel target for the development of anti-WSSV therapeutics.

IMPORTANCE

Cell surface receptors are crucial for mediating virus entry into host cells. Identification and characterization of virus receptors are fundamental yet challenging aspects of virology research. In this study, a BioID-based screening method was employed to identify the Na
+
-K
+
-ATPase alpha subunit (
Pv
ATP1A) as a potential receptor for white spot syndrome virus (WSSV) in the shrimp
Penaeus vannamei
. We demonstrated that
Pv
ATP1A interacted with the WSSV envelope protein VP28 via its multiple extracellular regions, thereby promoting viral internalization through caveolin-mediated endocytosis and macropinocytosis. Importantly, compared with previously identified WSSV receptors such as β-integrin, glucose transporter 1 (Glut1), and polymeric immunoglobulin receptor (pIgR),
Pv
ATP1A demonstrated significantly enhanced viral entry, indicating that
Pv
ATP1A is a crucial entry receptor of WSSV. This study not only presents a robust approach for screening virus receptors but also identifies
Pv
ATP1A as a promising target for the development of anti-WSSV therapeutics.
The genome of
Aspergillus niger
strain melanoliber
Authors: Pradeep Pushya , Kolipakala Rakshita Sukruth , Nagarajan Deepesh
Published: February 2025

Aspergillus niger
strain melanoliber was isolated from the coastal region of Mumbai, Maharashtra, India. This strain secretes water-soluble melanin attached to peptides possessing metal-chelation properties. Here, we report the whole-genome sequence of
Aspergillus niger
strain melanoliber. The genome was sequenced using Illumina Novaseq6000 giving a total size of 3.86 Mb.
Draft genome sequencing of a multidrug-resistant and virulent
Escherichia coli
strain isolated from milk of a cow with clinical mastitis
Authors: Arafat Kh. Yeashir , Hasnat Soharth , Siddique Naim , Rahman Md. Morshedur , Homa Syeda Fowzia , Hoque M. Nazmul
Published: February 2025

We present the draft genome of
Escherichia coli
strain MBBL3, a virulent and antimicrobial-resistant pathogen isolated from the milk of a cow suffering from clinical mastitis. The assembled genome spans 4,713,190 base pairs, organized into 115 contigs, and harbors 52 antimicrobial resistance genes (ARGs) alongside 25 virulence factor genes (VFGs).
Isolation and characterization of a protective monoclonal antibody targeting outer membrane protein (OmpA) against tuberculosis
Authors: Li Huoming , Ji Jiahong , Qu Mengjin , Ma Xiuling , Zuo You , Tang Minghui , Zeng Lingyuan , Li Hao
Published: February 2025

Tuberculosis (TB) caused by
Mycobacterium tuberculosis
(Mtb) complex is an important zoonotic infectious disease around the world, and the One Health approach is an essential strategy for TB prevention and control. The abundant surface antigens present on the cell wall of Mtb can induce protective antibodies; however, its full characterization remains incomplete. Previous research has shown that antibodies targeting surface proteins can enhance host defense mechanisms. Therefore, identifying antigens that stimulate the production of protective antibodies is essential. In this study, we focused on a select antigen, outer membrane protein (OmpA), located on the outer membrane of Mtb. By screening for antibodies with protective effects in phagocytosis and intracellular killing
in vitro
, we identified a protective antibody targeting OmpA. We prepared an antibody, designated as 1E1, belonging to the IgG2b isotype, which exhibited high titers of 1:2,048,000. Further research demonstrated that antibody-induced protection was achieved by promoting opsonophagocytosis in a dose-dependent manner, enhancing phagosome-lysosome fusion, and inhibiting mycobacterial intracellular growth. These findings were corroborated
in vivo
, with a reduction in bacterial loads of approximately 0.7 log observed in the preventive group and almost 1.0 log in the therapeutic group of mice treated with the antibodies, compared to the negative control group. Cytotoxicity assays, animal toxicity analyses, and pharmacokinetic evaluations confirmed the safety and sustained effectiveness of the antibody
in vivo
. These findings indicate that OmpA can elicit protective antibodies and may serve as a treatment strategy for drug-resistant TB and a promising antigen for TB vaccine development.

IMPORTANCE

In this study, we identified a protective antibody targeting the outer membrane protein (OmpA) of
Mycobacterium tuberculosis
. This monoclonal antibody (MAb) belongs to the IgG2b isotype and exhibits high titers of 1:2,048,000 to the antigen. The cell infection assays demonstrated that antibody protection was achieved by promoting opsonophagocytosis in a dose-dependent manner, enhancing phagosome-lysosome fusion, and inhibiting mycobacterial intracellular growth
in vitro
and
ex vivo
. Cytotoxicity assays, animal toxicity analyses, and pharmacokinetic evaluations confirmed the safety and sustained effectiveness of the antibody
in vivo
. Furthermore, the mAb 1E1 can reduce the organs' bacterial burdens and pathological damages in the prevention mouse model as well as the treatment models. Above all, in this study, we found a novel mAb named 1E1 with IgG2b isotype targeting OmpA can have protection against tuberculosis (TB) in mice, which may serve as a treatment strategy for drug-resistant TB and a promising antigen for TB vaccine development.
Discrepancies in neglected tropical diseases burden estimates in China: comparative study of real-world data and Global Burden of Disease 2021 data (2004-2020)
Authors: Yang Guo-Jing , Ouyang Han-Qi , Zhao Zi-Yu , Li Wei-Hao , Fall Ibrahima Socé , Djirmay Amadou Garba , Zhou Xiao-Nong
Published: February 2025

Objectives

To assess the discrepancies between real-world data and the Global Burden of Disease (GBD) 2021 estimates for six neglected tropical diseases in China. Additionally, to evaluate the applicability of the GBD model within the Chinese context and to assess the effectiveness of China's historical prevention and control policies for neglected tropical diseases.

Design

Comparative study of real-world data and GBD 2021 (2004-2020).

Main outcome measures

Disability adjusted life years (DALYs).

Methods

DALYs based on reported data for leprosy, echinococcosis, schistosomiasis, visceral leishmaniasis, dengue, and rabies from 2004 to 2020 were compared with the estimated DALYs from the GBD 2021 database. Additionally, we combined and analysed China's historical policies on prevention and control of neglected tropical diseases with real-world DALYs.

Data sources

Reported data were sourced from the Chinese Center for Disease Control and Prevention’s China Public Health Science data centre and related reports. Data for GBD 2021 and GBD 2019 were obtained from GBD databases. These data included all of China’s 31 provinces (including autonomous regions and municipalities) and the Xinjiang Production and Construction Corps.

Results

The total real-world DALYs based on reported data of six neglected tropical diseases decreased from 260 000 person years in 2004 to 19 000 person years in 2020, with a 93% (241 000/260 000 person years) reduction. The 17 year average real-world DALYs from 2004 to 2020 versus the GBD 2021 estimates for the same period were 42
v
500 for leprosy, 960
v
11 000 for echinococcosis, 64 000
v
98 000 for schistosomiasis, 56
v
16 000 for visceral leishmaniasis, 190
v
780 for dengue, and 47 000
v
67 000 for rabies. The ratios of the GBD estimates to the real-world DALYs for the six neglected tropical diseases were 17 for leprosy, 11 for echinococcosis, 1.5 for schistosomiasis, 280 for visceral leishmaniasis, 4.2 for dengue, and 1.4 for rabies.

Conclusions

The findings indicate that reliance solely on global estimates, such as those of the GBD, may not sufficiently capture the dynamics of neglected tropical diseases in China. Integrating local epidemiological data into global health assessments is crucial to develop accurate and effective public health policies. This study highlights the importance of continuously updating and improving data collection and surveillance methods to adapt public health strategies to evolving disease patterns.
Incidence of metabolic and bariatric surgery among US adults with obesity by diabetes status: 2016–2020
Authors: Cheng Yiling J , Bullard Kai McKeever , Hora Israel , Belay Brook , Xu Fang , Holliday Christopher S , Simons-Linares Roberto , Benoit Stephen R
Published: February 2025

Introduction

Metabolic and bariatric surgery (MBS) is an effective intervention to manage diabetes and obesity. The population-based incidence of MBS is unknown.

Objective

To estimate the incidence of MBS among US adults with obesity by diabetes status and selected sociodemographic characteristics.

Research design and methods

This cross-sectional study used data from the 2016–2020 Nationwide Inpatient Sample and Nationwide Ambulatory Surgery Sample to capture MBS procedures. The National Health Interview Survey was used to establish the denominator for incidence calculations. Participants included US non-pregnant adults aged ≥18 years with obesity. The main outcome was incident MBS without previous MBS, defined by International Classification of Diseases, Tenth Revision Procedure Codes, Diagnosis Related Group system codes, and Current Procedural Terminology codes. Adjusted incidence and annual percentage change (2016–2019) were estimated using logistic regression.

Results

Among US adults with obesity, over 900 000 MBS procedures were performed in inpatient and hospital-owned ambulatory surgical centers in the USA during 2016−2020. The age- and sex-adjusted incidence of MBS per 1000 adults was 5.9 (95% CI 5.4 to 6.4) for adults with diabetes and 2.0 (95% CI 1.9 to 2.1) for adults without diabetes. MBS incidence was significantly higher for women and adults with class III obesity regardless of diabetes status. The highest incidence of MBS occurred in the Northeast region. Sleeve gastrectomy was the most common MBS surgical approach.

Conclusions

Incident MBS procedures were nearly threefold higher among adults with obesity and diabetes than those with obesity but without diabetes. Continued monitoring of the trends of MBS and other treatment modalities can inform our understanding of treatment accessibility to guide prevention efforts aimed at reducing obesity and diabetes.
Predicting diabetes self-management education engagement: machine learning algorithms and models
Authors: Jiang Xiangxiang , Lv Gang , Li Minghui , Yuan Jing , Lu Z Kevin
Published: February 2025

Introduction

Diabetes self-management education (DSME) is endorsed by the American Diabetes Association (ADA) as an essential component of diabetes management. However, the utilization of DSME remains limited in the USA. This study aimed to investigate current DSME participation among the older population and to identify comprehensive factors of DSME engagement through employing various machine learning (ML) models based on a US nationally representative survey linked to claims data.

Research design and methods

Data from the Medicare Current Beneficiary Survey were employed, and this study included data on US Medicare beneficiaries with diabetes from 2017 to 2019. Comprehensive variables following the National Institute on Aging Health Disparities Research Framework were employed to ensure a comprehensive evaluation of factors associated with DSME using five common ML approaches.

Results

In our study, 37.94% of participants received DSME after the application of inclusion and exclusion criteria. A total of 95 variables were used and all ML models achieved accuracy scores exceeding 70%. Random forest had better predictive performance, with an accuracy of 85%. Seventy-four of 95 variables were identified as key variables. Racial/ethnic disparities in predictors for DSME were identified in this study.

Conclusions

This study identified comprehensive and critical factors associated with DSME engagement from biological, behavioral, sociocultural, and environmental domains using different ML models, as well as related racial/ethnic disparities. Aligning these findings with the DSME National Standards from the ADA would enhance the guidelines' effectiveness, promoting tailored and equal diabetes management approaches that cater to diverse races/ethnicities.
Enhancing end-of-life care nursing competency: a nursing education quality improvement project in general medical wards
Authors: Lee Chen Na , Lee Guozhang , Aw Fung Chee , Zulkifle Nuraishah Binte , Tan Yih Shan , Amanulla Marianah , Chua Esther Hui Hui , Koh Wei Zhi , Lee Jolin Er Huan , Woong Natalie Liling
Published: February 2025

End-of-life care is a fundamental aspect of nursing that significantly affects patient outcomes and family well-being. Despite its importance, nurses in non-palliative care settings often lack relevant training and confidence to provide high-quality end-of-life care, resulting in suboptimal patient experiences. This paper presents a quality improvement initiative at Singapore General Hospital, the nation’s largest tertiary acute hospital, aimed at addressing this critical gap.

We conducted a targeted educational needs assessment using a modified Palliative Care Quiz that showed a low pass rate of 15% among medical ward nurses. In response, we designed and implemented a structured training programme that integrated lectures with interactive case-based discussions, focusing on practical, real-world applications of end-of-life care. Our findings demonstrate a significant increase in knowledge proficiency, with the pass rate improving to 53% post-intervention. Additionally, nurses reported significant improvements in their confidence and competence across all domains of end-of-life care. Notably, scores for non-pharmacological management increased from 49% to 86%. This domain covered non-pharmacological modalities for managing dyspnoea, secretions, delirium and nausea and vomiting.

These results highlight the effectiveness of targeted educational interventions in equipping nurses with the skills and knowledge to manage the complexities of end-of-life care. Integrating targeted end-of-life training into nursing curricula and institutional practices improves nurses’ confidence and competence and enhances the quality of care for patients and their families facing the end of life. This report is written based on the Standards for Quality Improvement Reporting Excellence guidelines.
In triple-negative breast cancer, fibrotic focus, the mitotic activity index and tumour-infiltrating lymphocytes have independent prognostic value: an observational population-based cohort study with very long follow-up
Authors: Kiraz Umay , Rewcastle Emma , Pettersen Kirsten B , Abono Desmond M , Raghe Sadia H , Gudlaugsson Einar G , Baak Jan P A , Janssen Emilius A M
Published: February 2025

Aims

Triple-negative breast cancer (TNBC) is prognostically and therapeutically heterogeneous. The mitotic activity index (MAI) and fibrotic focus (FF) have been established as predictors in non-TNBC but not in TNBC. Late distant metastases occur in TNBC, but previous studies had short follow-up. High stromal tumour-infiltrating lymphocytes (sTILs) are prognostically favourable, but prognostic sTILs-thresholds are not well assessed. We evaluated prognostic/predictive characteristics in an observational population-based cohort of 231 consecutive TNBC patients with long follow-up.

Methods

MAI, FF, sTILs and other characteristics were analysed with standard receiver operating characteristic curve analysis, percentile-derived prognostic thresholds, univariate and multivariate survival methods. A TNBC index and decision tree were assessed for distant metastasis-free survival.

Results

Long follow-up was decisive: 7% of patients developed late distant metastases. In agreement with the aggressive nature of TNBC, the strongest prognostic MAI-threshold was 5 (p=0.001), lower than that for non-TNBC phenotypes. Lymph-node (LN) status (p=0.0003), FF (p=0.002), MAI5 (p=0.009) and sTILs (threshold 40%, p=0.003) were multivariable based significant and independent prognosticators, but no other characteristics (age, tumour size and grade). LN status was the strongest prognosticator, followed by FF, MAI5 and sTILs40. Subgroup analyses of patients undergoing adjuvant chemotherapy (ACT) showed that only FF and sTILs had significant prognostic value, while LN-positivity and the combination of LN-positivity and MAI≥5 could be a predictive factor for ACT outcome.

Conclusions

LN status, MAI5, FF and sTILs40 are prognostic factors in TNBC patients. In TNBC patients who have undergone ACT, the combination of LN-positivity and MAI5 is predictive for response to treatment.
Cuscuton-like contribution to dark energy evolution
Authors: Bazeia D. , Dantas J. D. , da Costa S. Santos
Published: February 2025

This work deals with the presence of the cuscuton term in the otherwise standard dark energy evolution under the usual FLRW background. We disclose a first-order framework similar to the Hamilton-Jacobi formalism, which helps us to solve the equations of motion and find analytical solutions. We explore several possibilities, concentrating mainly on how the cuscuton-like contribution works to modify cosmic evolution. Some results are of current interest since they describe scenarios capable of changing the evolution, adding or excluding possible distinct phases during the Universe’s expansion history. Additionally, we present interesting constraints on the cuscuton-like contribution for the dark energy evolution using a set of homogeneous geometrical observational probes. Finally, based on the Akaike Information Criterion (AIC), we perform a statistical comparison of the cuscuton-like model with

$$\Lambda $$

Λ

CDM, and find strong support for our model.
Telerobotic Theater of the Oppressed in Israel and Palestine: Becoming Digital Jokers
Authors: Peled Avner , Leinonen Teemu , Hasler Béatrice S.
Published: February 2025

The theatrical and political expression methods of “Theater of the Oppressed” by Augusto Boal were adopted by HCI researchers to facilitate participatory design. However, the potential of technology to expand and enrich these methods, particularly in intergroup settings, is still underexplored. We introduce a novel combination of participatory design, technological education, and theater: a telerobotic theater of the oppressed. We invited activists from Israel and Palestine to learn telerobotic technology and create puppet shows to run simultaneously on both sides of the border. During a weekend workshop, we created and tested the performance in two rooms, simulating Israel and Palestine. We collected, coded, and analyzed qualitative data consisting of semi-structured interviews, videos, photos, and notes. The findings demonstrate how the solution promotes intergroup contact, directly through creative collaboration and indirectly through remote performances. The analysis serves as a guide for adapting Boal’s facilitation method, the joker system, to digital technology.
Cosine Additive Angular Margin Loss for Breast Cancer Classification in Histopathological Images with Small AI Systems
Authors: Alirezazadeh Pendar , Dornaika Fadi , Moujahid Abdelmalik
Published: February 2025

Breast cancer claims thousands of lives annually, emphasizing the need for swift and accurate histopathology image classification to expedite diagnoses. Despite the rapid evolution of Convolutional Neural Networks (CNNs), the conventional softmax loss lacks the robustness required to discern intricate features in breast cancer classification from histopathological images. In response, our study introduces the Cosine Additive Angular Margin Loss (CAAM) to address this limitation and achieve both enhanced intra-class cohesion and distinct inter-class boundaries concurrently. By normalizing weight and feature vectors, we eliminate radial variations before imposing angular and cosine margin constraints on the softmax angle space. This process maximizes the decision margin, resulting in a discriminative feature embedding. Extensive experiments conducted on the BreakHis dataset demonstrate that CAAM consistently outperforms existing methods in breast cancer histopathological image classification. Our findings underscore the efficacy of angular margin-based softmax losses in bolstering the performance of advanced CNN models for breast cancer classification.
LIFE-THREATENING FENTANYL OVERDOSE BEYOND MEDULLARY DEPRESSION IN BREATHING
Authors: JUDENHERC-HAOUZI Annick , Lewis Tristan , Reinhardt Amanda , Haouzi Philippe
Published: February 2025

We sought to determine how the balance between O2 delivery (DO2)and O2 consumption is altered by fentanyl during the initial and the most critical period following a bolus iv injection of high dose fentanyl.

We determined the acute changes in ventilation, gas exchange and hemodynamic - including cardiac function - along with the acid-base and arterial blood gas status - in 27 un-sedated rats, following an intravenous bolus injection of 150 microg/kg fentanyl.

This injection produced an immediate coma and a central apnea, followed by the emergence of a regular and sustained, yet very depressed, breathing pattern ~ 2.5 minutes later. All rats displayed an instantaneous and profound decrease in Q̇c (from 295.7 ± 42.62 to 140.74± 74.96 ml/kg/min (p<0.0001) resulting from an abrupt bradycardia (from 333.3± 20.8 to 112.2± 36.4 b/min, p<0.05) with a transient decreased cardiac contractility, associated with a very severe hypoxemia that persisted throughout the ensuing period of hypoventilation, e.g., PaO2 = 39.0 ± 18.4 mmHg; SaO2= 50.1 ± 26.2%, at 5 min. DO2 was therefore immediately decreased by several folds; and the decrease in Q̇c was even more severely reduced than the drop in oxygenation. Twenty-four rats survived; the three remaining animals presented a rapid cardiac arrest by pulseless electrical activity.

Fentanyl overdose induces an instant decrease in DO2, with a very early drop in Q̇c, out of proportion with the decrease in V̇O2, a protective mechanism produced by hypoxemia. The relevance of these findings to human hypoxic cardiac arrest are discussed.
Domain Knowledge Embedded InSAR‐Based 3D Displacement Monitoring of Urban Buildings
Authors: Du Ya-Nan , Feng De-Cheng , Wu Gang
Published: February 2025

Continuous monitoring of building displacement is crucial for urban structural safety. While traditional methods are costly, Interferometric Synthetic Aperture Radar (InSAR) offers a cost‐effective alternative, providing long‐term displacement data. However, due to the insensitivity of SAR radar to north‐south displacement, using InSAR alone can only measure settlement and east‐west displacement. To address this limitation, this paper presents a three‐dimensional (3D) deformation extraction model. The model embeds domain knowledge to introduce additional constraints, which are then used to establish the relationship between north‐south and east‐west displacement. This relationship allows for the extraction of 3D displacement of buildings from the line of sight (LOS) displacement measured by InSAR. This model was applied to Tower 2 of Yingli International Financial Center (YIFC) in Chongqing, China, and the 3D displacement of the building between 2018 and 2021 was obtained.
Increased interaction between B cells and CD3+ T cells in non-progressors with human papillomavirus-associated oropharyngeal squamous cell carcinoma
Authors: Bartemes Kathleen R. , Moore Raymond M. , Novotny Brenna C. , Pavelko Kevin D. , Sherman Will A. , Rivera Michael , Garcia Joaquin J. , Yin Linda X. , Ma Daniel J. , Moore Eric J. , Van Abel Kathryn M. , Routman David M.
Published: February 2025

Background: Tumor-infiltrating lymphocytes (TILs) are associated with decreased risk of recurrence in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC). The composition and spatial distribution of TILs and tumor-infiltrating immune cells is not well characterized. Methods: Formalin-fixed paraffin-embedded primary and lymph node (LN) tumor tissues from ten progressors (cases) and ten matched non-progressors (controls) were interrogated by imaging mass cytometry. Immune, stromal, and tumor cells were quantified from selected regions of interest (ROIs) using machine learning. Nearest neighbors, cell-cell interactions, and niche analyses were performed. Results: In primary ROIs, immune cell, lymphocyte, T cell, CD8+ T cell, and innate cell prevalence was significantly greater in controls. High prevalence of immune cells, lymphocytes, innate cells, and CD4+ T cells in primary tissues was significantly associated with increased time to event (TTE). Although primary and LN prevalence of T cells, CD4+ T cells, CD8+ T cells, macrophages, and tumor cells were significantly correlated, differences in LNs were neither significant nor associated with TTE. Average distances between T cells and nearest B cells, and between lymphocytes and nearest tumor cells were decreased in control primary tissues. Interactions between B cells and T cells were less organized in primary tissues from cases. A niche predominantly comprising lymphocytes was associated with longer TTE. Conclusion: In HPV(+)OPSCC, immune cell subset prevalence in primary tumors differs with outcome and is associated with TTE. Interactions between B cells and both T cell subsets are associated with longer TTE, underscoring the importance of active intratumoral immune responses in outcomes.
Table S8 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: February 2025

Expression values, Spearman’s correlation coefficient, and GSEA of genes associated with positive or negative correlation with radiographic response to ONC201 treatment.
Table S2 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: February 2025

Individual patients with H3K27M-mutant DMG treated with ONC201.
Table S16 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: February 2025

ONC201 dosage chart for patients younger than 18 years of age.
Table S11 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: February 2025

Volcano plot of differentially expressed genes in DIPG007 cells treated with ONC201 versus vehicle.
Early high postoperative IOP improved the predictability of trabeculectomy in patients with POAG: a retrospective cohort study
Authors: Liu Yao , Shi Huangyang , Gao Xinbo , Huang Wei , Lin Huishan , Tam Weng Ian , Wu Zhuoyi , Zuo Chengguo , Lin Mingkai
Published: February 2025

Introduction: To investigate the effect of different levels of early intraocular pressure (IOP) on long-term outcomes of patients with primary open-angle glaucoma (POAG) who were treated with primary trabeculectomy.
Methods: This was a retrospective cohort study, with a total of 74 patients (90 eyes) with primary open-angle glaucoma (POAG) who were treated with trabeculectomy surgery at a single center from 2021 to 2022. Based on IOP at 1 day after surgery, they were divided into the high IOP group (≥ 15mmHg) and the low IOP group (< 15mmHg). The Student’s t-test and a chi-square test were used to compare the differences between the two groups. The generalized estimating equation (GEE) model compared the included binocular data to adjust for internal correlations between the two eyes of the same subject. The Kaplan–Meier method compared the surgical success rates of the two groups. Besides, to identify the relationship between IOP at different postoperative time points and IOP at 1-year follow-up, the Spearman correlation analysis was established.
Results: A total of 90 eyes (74 patients) with POAG were included in this investigation. After a 1-year follow-up, both the qualified surgical success rates in the high IOP group and the low IOP group were 92.3% and 92.2% respectively, and there was no statistically significant difference between them (P=0.890). The rate of bleb massage in the high IOP group was 82.1% (32 eyes) which was significantly higher than in the low IOP group (19.6%, 10 eyes) (P<0.001). In the Spearman correlation analysis, it was observed that in the high IOP group, the significant correlation with IOP at 1 year emerged at 1 week after surgery (r= 0.496, P=0.002) and a higher correlation at 1 month after surgery (r=0.515, P=0.002). In the low IOP group, the significant correlation with IOP at 1 year emerged at 3 month after surgery (r=0.314, P=0.038) and a higher correlation at 6 month after surgery (r=0.592, P< 0.001).
Conclusion: In the POAG patients with primary trabeculectomy, we demonstrated that compared with the low IOP group, the high IOP group could provide a similar surgical success rate, while requiring a higher frequency of bleb massage. In addition, in the high IOP group, IOP at 1 month after surgery predicted long-term IOP control outcomes.