bluuebunny/crossref_metadata_2025 huggingface dataset:
Scientific Evidence of Prostate Cancer Progression Outcomes in Transgender Females after Hormone Replacement Therapy-Scoping Review Protocol
Authors: McAllister Brenna , Panteah Mylan , Nelson Emily , Petersen Britta , Hoskins Katie , Koshy-Chenthittayil Sherli , Caromile Leslie A.
Published: February 2024

Transgender females undergoing hormone replacement therapy (HRT) as a component of the gender affirmation treatment (GAT) commonly retain their prostate, rendering them susceptible to developing prostate cancer (PC). Currently, patients with localized PC receive endocrine therapy (e.g.,androgen ablation/castration). Once metastatic, patients undergo standard chemotherapy and/or novel treatment. Unfortunately, many fail to respond completely and develop untreatable, drug-resistant tumors consistent with reprogramming of crucial cell signal transduction pathways that promote tumor growth, invasiveness, and survival. There is no consensus among scientists or physicians on how HRT affects PC treatment options or its related signaling pathways, putting patients at risk for delayed diagnosis. This scoping review aims to analyze and collate the current scientific literature on PC progression in transgender females who have undergone HRT and how PC-initiated oncogenic pathways are impacted by HRT. The review’s findings can potentially inform transgender healthcare and research. This scoping review will follow the Population-Concept-Context methodology for Joanna Briggs Institution Scoping Reviews. Relevant peer-reviewed studies will be identified from the following electronic databases: MEDLINE (PubMed), Embase (Elsevier), CINAHL (EBSCO), and Scopus (Elsevier). Sources of unpublished studies/ grey literature to be searched include bioRxiv (Cold Spring Harbor Laboratory), medRxiv (Cold Spring Harbor Laboratory), and MedNar (Deep Web Technologies). The search strings using keywords such as gender-affirmation treatment, transgender females, and prostate cancer will be conducted using Boolean logic. There will be no limitation on language or date of publication.
Immune activation and immune-associated neurotoxicity in Long-COVID: A systematic review and meta-analysis of 82 studies comprising 58 cytokines/chemokines/growth factors
Authors: Almulla Abbas F. , Thipakorn Yanin , Zhou Bo , Vojdani Aristo , Maes Michael
Published: February 2024

Background

Multiple studies have shown that Long COVID (LC) disease is associated with heightened immune activation, as evidenced by elevated levels of inflammatory mediators. However, there is no comprehensive meta-analysis focusing on activation of the immune inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS) along with other immune phenotypes in LC patients.

Objectives

This meta-analysis is designed to explore the IRS and CIRS profiles in LC patients, the individual cytokines, chemokines, growth factors, along with C-reactive protein (CRP) and immune-associated neurotoxicity.

Methods

To gather relevant studies for our research, we conducted a thorough search using databases such as PubMed, Google Scholar, and SciFinder, covering all available literature up to December 20th, 2023.

Results

The current meta-analysis encompassed 82 studies that examined multiple immune profiles, C-reactive protein, and 58 cytokines/chemokines/growth factors in 3836 LC patients versus 4537 normal controls (NC). LC patients showed significant increases in IRS/CIRS ratio (standardized mean difference (SMD:0.156, confidence interval (CI): 0.051;0.261), IRS (SMD: 0.345, CI: 0.222;0.468), M1 macrophage (SMD: 0.421, CI: 0.290;0.551), T helper (Th)1 (SMD: 0.353, CI: 0.189;0.517), Th17 (SMD: 0.492, CI: 0.332;0.651) and immune-associated neurotoxicity (SMD: 0.327 CI: 0.205;0.448). In addition, CRP and 19 different cytokines displayed significantly elevated levels in LC patients compared to NC.

Conclusion

LC disease is characterized by IRS activation and increased immune-associated neurotoxicity.
QCD with an infrared fixed point: The pion sector
Authors: Zwicky Roman
Published: February 2024

The possibility that gauge theories with chiral symmetry breaking below the conformal window exhibit an infrared fixed point is explored. With this assumption three aspects of pion physics are reproduced if the quark mass anomalous dimension at the infrared fixed point is γ*=1. First, by matching the long-distance scalar adjoint correlation function. Second, by perturbing the fixed point by a small quark mass, the mq-dependence of the pion mass is reproduced by renormalization group arguments. Third, consistency of the trace anomaly and the Feynman-Hellmann theorem, for small mq, imply the same result once more. This suggests the following picture for the conformal window; close to its upper boundary γ* is zero and grows as the number of fermions is reduced until its lower boundary γ*=1 is reached, where chiral symmetry breaking sets in. Below, the strongly coupled gauge theory with γ*=1 is infrared dual to the free theory of pions. A possible dilaton sector of the scenario will be addressed in a companion paper.

Published by the American Physical Society
2024
Hunting muonic forces at emulsion detectors
Authors: Ariga Akitaka , Balkin Reuven , Galon Iftah , Kajomovitz Enrique , Soreq Yotam
Published: February 2024

Only two types of Standard Model particles are able to propagate the 480meters separating the ATLAS interaction point and FASER: neutrinos and muons. Furthermore, muons are copiously produced in proton collisions. We propose to use FASERν as a muon fixed target experiment in order to search for new bosonic degrees of freedom coupled predominantly to muons. These muon force carriers are particularly interesting in light of the recent measurement of the muon anomalous magnetic moment. Using a novel analysis technique, we show that even in the current LHC run, FASERν could potentially probe previously unexplored parts of the parameter space. In the high-luminosity phase of the LHC, we find that the improved sensitivity of FASERν2 will probe unexplored parameter space and may be competitive with dedicated search proposals.

Published by the American Physical Society
2024
Octant degeneracy and plots of parameter degeneracy in neutrino oscillations revisited
Authors: Sugama Sho , Yasuda Osamu
Published: February 2024

The three kinds of parameter degeneracy in neutrino oscillation, the intrinsic, sign, and octant degeneracy, form an eight-fold degeneracy. The nature of this eight-fold degeneracy can be visualized on the (sin22θ13, 1/sin2θ23)-plane, through quadratic curves defined by P(νμ→νe)=const and P(ν¯μ→ν¯e)=const, along with a straight line P(νμ→νμ)=const. After θ13 was determined by reactor neutrino experiments, the intrinsic degeneracy in θ13 transforms into an alternative octant degeneracy in θ23, which can potentially be resolved by incorporating the value of P(νμ→νμ). In this paper, we analytically discuss whether this octant parameter degeneracy is resolved or persists in the future long baseline accelerator neutrino experiments, such as T2HK, DUNE, T2HKK, and ESSνSB. It is found that the energy spectra near the first oscillation maximum are effective in resolving the octant degeneracy, whereas those near the second oscillation maximum are not.

Published by the American Physical Society
2024
Second-order gravitational self-force in a highly regular gauge: Covariant and coordinate punctures
Authors: Upton Samuel D.
Published: February 2024

Gravitational self-force theory is the primary way of modeling extreme-mass-ratio inspirals (EMRIs). One difficulty that appears in second-order self-force calculations is the strong divergence at the worldline of the small object, which causes both numerical and analytical issues. Previous work [; ] demonstrated that this could be alleviated within a class of highly regular gauges and presented the metric perturbations in these gauges in a local coordinate form. We build on this previous work by deriving expressions for the highly regular gauge metric perturbations in both fully covariant form and as a generic coordinate expansion. With the metric perturbations in covariant or generic coordinate form, they can easily be expressed in any convenient coordinate system. These results can then be used as input into a puncture scheme in order to solve the field equations describing an EMRI.

Published by the American Physical Society
2024
Advanced implication theory. Symmetry tables
Authors: Pavelcik Frantisek
Published: February 2024

The MIF (multiple implication function) group symmetry was assigned to all 230 space groups. Knowledge of MIF symmetry allows the calculation of an asymmetric unit. A more accurate procedure for calculating MIFs has been developed. Extensive tables of MIF symmetry and asymmetric units were computer generated. The development of implication theory for crystal structure determination seems to have reached completion.
A complex model decomposition algorithm based on 3D frame fields and features
Authors: Zhang Chengpeng , Yu Zhihua , Shi Jimin , Li Yu , Xu Wenqiang , Guo Zheyi , Zhang Hongshi , Zhu Zhongyuan , Qiang Sheng
Published: February 2024

Purpose

Hexahedral meshing is one of the most important steps in performing an accurate simulation using the finite element analysis (FEA). However, the current hexahedral meshing method in the industry is a nonautomatic and inefficient method, i.e. manually decomposing the model into suitable blocks and obtaining the hexahedral mesh from these blocks by mapping or sweeping algorithms. The purpose of this paper is to propose an almost automatic decomposition algorithm based on the 3D frame field and model features to replace the traditional time-consuming and laborious manual decomposition method.

Design/methodology/approach

The proposed algorithm is based on the 3D frame field and features, where features are used to construct feature-cutting surfaces and the 3D frame field is used to construct singular-cutting surfaces. The feature-cutting surfaces constructed from concave features first reduce the complexity of the model and decompose it into some coarse blocks. Then, an improved 3D frame field algorithm is performed on these coarse blocks to extract the singular structure and construct singular-cutting surfaces to further decompose the coarse blocks. In most modeling examples, the proposed algorithm uses both types of cutting surfaces to decompose models fully automatically. In a few examples with special requirements for hexahedral meshes, the algorithm requires manual input of some user-defined cutting surfaces and constructs different singular-cutting surfaces to ensure the effectiveness of the decomposition.

Findings

Benefiting from the feature decomposition and the 3D frame field algorithm, the output blocks of the proposed algorithm have no inner singular structure and are suitable for the mapping or sweeping algorithm. The introduction of internal constraints makes 3D frame field generation more robust in this paper, and it can automatically correct some invalid 3–5 singular structures. In a few examples with special requirements, the proposed algorithm successfully generates valid blocks even though the singular structure of the model is modified by user-defined cutting surfaces.

Originality/value

The proposed algorithm takes the advantage of feature decomposition and the 3D frame field to generate suitable blocks for a mapping or sweeping algorithm, which saves a lot of simulation time and requires less experience. The user-defined cutting surfaces enable the creation of special hexahedral meshes, which was difficult with previous algorithms. An improved 3D frame field generation method is proposed to correct some invalid singular structures and improve the robustness of the previous methods.
Lack of resilience after COVID-19: the role of family firm heterogeneity and behavior. fsQCA versus regression
Authors: Iborra María , López-Muñoz José Fernando , Safón Vicente
Published: February 2024

Purpose

This study analyzes antecedents explaining the lack of resilience in family-owned firms. Our model suggests that family-owned firms’ strategic behaviors and heterogeneity explain a particular crisis outcome: a lack of recovery.

Design/methodology/approach

Our evidence is based on a sample of 842 European family-owned firms. We complement regression analysis results with fuzzy-set qualitative comparative analysis (fsQCA).

Findings

Our results show that lack of resilience is relevant. In fact, in our sample, 60% of family firms (FFs) failed to recover their sales. This evidence supports the role played by exploitation and exploration behavior as well as family heterogeneity in explaining the lack of recovery.

Research limitations/implications

Our results may offer guidance to practitioners and policymakers on the pathways that explain the lack of resilience.

Practical implications

Although it is unlikely that an external crisis such as COVID-19 will occur again to the same extent, other threatening events may occur and impact FFs. Understanding how FFs can avoid non-recovery is crucial: it can inform managers on how to deal with stressful events and provide guidance to economic authorities on how to help FFs around the world avoid non-recovery, which affects the economy.

Originality/value

First, the study contributes to FF research by offering a theoretical explanation for the different effects of FF attributes on non-recovery in the context of a global crisis. Second, it contributes to the literature on organizational resilience by examining explorative and exploitative behaviors as antecedents of FF non-recovery. Third, we show the usefulness of combining fsQCA and regression analysis to understand complex phenomena.
Healthcare entrepreneurship: current trends and future directions
Authors: Lim Weng Marc , Ciasullo Maria Vincenza , Escobar Octavio , Kumar Satish
Published: February 2024

Purpose

The goal of this article is to provide an overview of healthcare entrepreneurship, both in terms of its current trends and future directions.

Design/methodology/approach

The article engages in a systematic review of extant research on healthcare entrepreneurship using the scientific procedures and rationales for systematic literature reviews (SPAR-4-SLR) as the review protocol and bibliometrics or scientometrics analysis as the review method.

Findings

Healthcare entrepreneurship research has fared reasonably well in terms of publication productivity and impact, with diverse contributions coming from authors, institutions and countries, as well as a range of monetary and non-monetary support from funders and journals. The (eight) major themes of healthcare entrepreneurship research revolve around innovation and leadership, disruption and technology, entrepreneurship models, education and empowerment, systems and services, orientations and opportunities, choices and freedom and policy and impact.

Research limitations/implications

The article establishes healthcare entrepreneurship as a promising field of academic research and professional practice that leverages the power of entrepreneurship to advance the state of healthcare.

Originality/value

The article offers a seminal state of the art of healthcare entrepreneurship research.
The influence of CMT-MAG and MAG welding-processes on microstructure and mechanical behaviour of C-Mn E410 structural-steels
Authors: Khajuria Akhil , Misra Anurag , Shiva S.
Published: February 2024

Purpose

An experimental investigation for developing structure-property correlations of hot-rolled E410 steels with different carbon contents, i.e. 0.04wt.%C and 0.17wt.%C metal active gas (MAG) and cold metal transfer (CMT)-MAG weldments was undertaken.

Design/methodology/approach

Mechanical properties and microstructure of MAG and CMT-MAG weldments of two E410 steels with varying content of carbon were compared using standardized mechanical testing procedures, and conventional microscopy.

Findings

0.04wt.%C steel had strained ferritic and cementite sub-structures in blocky shape and large dislocation density, while 0.17wt.%C steel consisted of pearlite and polygonal ductile ferrite. This effected yield strength (YS), and microhardness being larger in 0.04wt.%C steel, %elongation being larger in 0.17wt.%C steel. Weldments of both E410 steels obtained with CMT-MAG performed better than MAG in terms of YS, ultimate tensile strength (UTS), %elongation, and toughness. It was due to low heat input of CMT-MAG that resulted in refinement of weld metal, and subzones of heat affected zone (HAZ).

Originality/value

A substantial improvement in YS (∼9%), %elongation (∼38%), and room temperature impact toughness (∼29%) of 0.04wt.%C E410 steel is achieved with CMT-MAG over MAG welding. Almost ∼10, ∼12.5, and ∼16% increment in YS, %elongation, and toughness of 0.17wt.%C E410 steel is observed with CMT-MAG. Relatively low heat input of CMT-MAG leads to development of fine Widmanstätten and acicular ferrite in weld metal and microstructural refinement in HAZ subzones with nearly similar characteristics of base metal.
Is webcare good for business? A study of the effect of managerial response strategies to online reviews on hotel bookings
Authors: Lopes Ana Isabel , Malthouse Edward C. , Dens Nathalie , De Pelsmacker Patrick
Published: February 2024

Purpose

Engaging in webcare, i.e. responding to online reviews, can positively affect consumer attitudes, intentions and behavior. Research is often scarce or inconsistent regarding the effects of specific webcare strategies on business performance. Therefore, this study tests whether and how several webcare strategies affect hotel bookings.

Design/methodology/approach

We apply machine learning classifiers to secondary data (webcare messages) to classify webcare variables to be included in a regression analysis looking at the effect of these strategies on hotel bookings while controlling for possible confounds such as seasonality and hotel-specific effects.

Findings

The strategies that have a positive effect on bookings are directing reviewers to a private channel, being defensive, offering compensation and having managers sign the response. Webcare strategies to be avoided are apologies, merely asking for more information, inviting customers for another visit and adding informal non-verbal cues. Strategies that do not appear to affect future bookings are expressing gratitude, personalizing and having staff members (rather than managers) sign webcare.

Practical implications

These findings help managers optimize their webcare strategy for better business results and develop automated webcare.

Originality/value

We look into several commonly used and studied webcare strategies that affect actual business outcomes, being that most previous research studies are experimental or look into a very limited set of strategies.
Negative online brand engagement: conceptualisation, scale development and validation
Authors: Dong Xinyu , Veloutsou Cleopatra , Morgan-Thomas Anna
Published: February 2024

Purpose

Negative brand engagement represents a pervasive and persistent feature of interactivity in online contexts. Although existing research suggests that consumer negativity is potentially more impactful or detrimental to brands than its positive counterpart, few studies have examined negative brand-related cognitions, feelings and behaviours. Building on the concept of brand engagement, this study aims to operationalise negative online brand engagement.

Design/methodology/approach

This paper presents the results of nine studies that contributed to the development and validation of the proposed scale. Building on the concept of engagement, Studies 1–3 enhanced the construct conceptualisation and generated items. Study 4 involved validation with an academic expert panel. The process of measure operationalisation and validation with quantitative data was completed in Studies 5–8. Finally, the scale's nomological validity was assessed in Study 9.

Findings

The results confirm the multidimensional nature of negative online brand engagement. The validated instrument encompasses four dimensions (cognition, affection, online constructive behaviour and online destructive behaviour), captured by 17 items.

Originality/value

Progress in understanding and dealing with negative online brand engagement has been hampered by disagreements over conceptualisation and the absence of measures that capture the phenomenon. This work enhances managerial understanding of negativity fostering strategies that protect brand engagement and improve firm performance.
The effects of vitamin D and omega-3 co-supplementation on lipid profile in adults: a systematic review and meta-analysis
Authors: Zamani Mohammad , Sohrabi Zahra , Aghakhani Ladan , Leilami Kimia , Nosratabadi Saeed , Namkhah Zahra , Clark Cain , Haghighat Neda , Asbaghi Omid , Fathi Fatemeh
Published: February 2024

Purpose

Previous research indicates that vitamin D and omega-3 co-supplementation may benefit overall health, but current evidence regarding its effects on lipid profile remains unclear. The present systematic review and meta-analysis aimed to examine the effects of vitamin D and omega-3 co-supplementation on lipid profile (total cholesterol [TC], low-density lipoprotein [LDL], triglyceride [TG] and high-density lipoprotein [HDL]) in adults.

Design/methodology/approach

In this systematic review and meta-analysis, relevant studies were obtained by searching the PubMed, Scopus and Web of Science databases (from inception to January 2022). Weighted mean differences and 95% confidence intervals were estimated via a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods.

Findings

Pooled analysis of six randomized controlled trials (RCTs) revealed that vitamin D and omega-3 co-supplementation yielded significant reductions in TG (p = 0.631). A pooled analysis of five trials indicated a significant association between omega-3 and vitamin D treatment and reductions in TC (p = 0.001) and LDL (p = 0.001). Although, pooled analyses of omega-3 and vitamin D did not significantly affect HDL.

Originality/value

The findings suggest that vitamin D and omega-3 co-supplementation lowers TG, TC and LDL in adults. Future, large-scale, RCTs on various populations are needed to elucidate further beneficial effects of vitamin D and omega-3 co-supplementation on lipid profile and establish guidelines for clinical practice.
The growth of the real estate corporate bond market in Vietnam: the role of investor sentiment
Authors: Nguyen Nhung Thi , Tuan Nguyen An , Nguyen Dinh Trung
Published: February 2024

Purpose

This paper aims to examine the effects of investor sentiment on the development of the real estate corporate bond market in Vietnam.

Design/methodology/approach

The research uses an autoregressive distributed lag (ARDL) model with quarterly data. Additionally, the study employs Google Trends search data (GVSI) related to topics such as “Real Estate” and “Corporate Bond” to construct a sentiment index.

Findings

The empirical outcomes reveal that real estate market sentiment improves the growth of the real estate corporate bond market, while stock market sentiment reduces it. Also, there is evidence of a long-run negative effect of corporate bond market sentiment on the total value of real estate bond issuance. Further empirical research evidences the short-term effect of sentiment and economic factors on corporate bond development in the real estate industry.

Research limitations/implications

Due to difficulties in collecting data, this paper has the limited sample of 54 valid quarterly observations. Moreover, the sentiment index based on Google search volume data only reflects the interest level of investors, not their attitudes.

Practical implications

These results yield important implications for policymakers in respect of strengthening the corporate bond market platform and maintaining stability in macroeconomic and monetary policies in order to promote efficient and sustainable market development.

Social implications

The study offers some suggestions for regulators and governments to improve the real estate corporate bond market.

Originality/value

This is the first quantitative study to examine the effect of sentiment factors on real estate corporate bond development in Vietnam.
“Mining” the herbarium for hyperaccumulators: Discoveries of nickel and zinc (hyper)accumulation in the genus Noccaea (Brassicaceae) through X‐ray fluorescence herbarium scanning
Authors: Jakovljević Ksenija , Mišljenović Tomica , van der Ent Antony , Baker Alan J. M. , Invernón Vanessa R. , Echevarria Guillaume
Published: February 2024

X‐ray fluorescence spectroscopy (XRF) is a relatively new method for non‐destructive elemental analysis of herbarium material that meets the scientific interest in being capable of discovering new hyperaccumulator plant species. Since the genus Noccaea (Brassicaceae family) is known to be one of the most numerous in term of the hyperaccumulator plant species it contains, especially those that hyperaccumulate Ni, the herbarium material available worldwide represents a great resource for expanding our knowledge of their elemental profiles. In this first systematic XRF scanning of herbarium specimens of the genus Noccaea, a total of 794 specimens from the collection of the National Museum of Natural History in Paris (MNHN) were analyzed, and the raw values obtained were corrected using regression formulas against inductively coupled plasma atomic emission spectroscopy data. Hyperaccumulation of Ni was detected in 90 specimens covering 21 taxa, with Ni concentrations reaching up to 48,700 mg kg−1 in Noccaea cappadocica, an ultramaficophyte from Syria. Zinc concentrations above the hyperaccumulation threshold were found in 210 specimens covering 23 taxa, most of which belonged to different subspecies of Noccaea caerulescens, with the highest concentration reaching up to 56,200 mg kg−1 in N. caerulescens subsp. caerulescens. Although the accumulation of Ni and Zn is contrasting in most of the specimens studied, in 10 specimens, predominantly belonging to N. caerulescens, simultaneous hyperaccumulation of Ni and Zn was found. This study also revealed previously unknown hyperaccumulation of Ni in several Noccaea taxa, as well as a simultaneous hyperaccumulation of Ni and Zn that needs to be confirmed by further experimental and field studies.
Sizing mudsnails: Applying superpixels to scale growth detection under ocean warming
Authors: MacNeil Liam , Joly Léa J. , Ito Maysa , Steinmann Anna , Mehler Knut , Scotti Marco
Published: February 2024

The expansion of scientific image data holds great promise to quantify individuals, size distributions and traits. Computer vision tools are especially powerful to automate data mining of images and thus have been applied widely across studies in aquatic and terrestrial ecology. Yet marine benthic communities, especially infauna, remain understudied despite their dominance of marine biomass, biodiversity and playing critical roles in ecosystem functioning.

Here, we disaggregated infauna from sediment cores taken throughout the spring transition (April–June) from a near‐natural mesocosm setup under experimental warming (Ambient, +1.5°C, +3.0°C). Numerically abundant mudsnails were imaged in batches under stereomicroscopy, from which we automatically counted and sized individuals using a superpixel‐based segmentation algorithm. Our segmentation approach was based on clustering superpixels, which naturally partition images by low‐level properties (e.g., colour, shape and edges) and allow instance‐based segmentation to extract all individuals from each image.

We demonstrate high accuracy and precision for counting and sizing individuals, through a procedure that is robust to the number of individuals per image (5–65) and to size ranges spanning an order of magnitude (<750 μm to 7.4 mm). The segmentation routine provided at least a fivefold increase in efficiency compared with manual measurements. Scaling this approach to a larger dataset tallied >40k individuals and revealed overall growth in response to springtime warming.

We illustrate that image processing and segmentation workflows can be built upon existing open‐access R packages, underlining the potential for wider adoption of computer vision tools among ecologists. The image‐based approach also generated reproducible data products that, alongside our scripts, we have made freely available. This work reinforces the need for next‐generation monitoring of benthic communities, especially infauna, which can display differential responses to average warming.
Glasdegib with intensive/nonintensive chemotherapy in Japanese patients with untreated acute myeloid leukemia or high‐risk myelodysplastic syndromes
Authors: Izutsu Koji , Ubukawa Kumi , Morishita Takanobu , Onishi Yasushi , Ishizawa Kenichi , Fujii Yosuke , Kimura Nobuyuki , Yokochi Miyuu , Naoe Tomoki
Published: February 2024

Glasdegib is a potent, selective, oral inhibitor of the hedgehog signaling pathway. In this phase I study, previously untreated Japanese patients with acute myeloid leukemia (AML) or high‐risk myelodysplastic syndromes were treated with glasdegib (100 mg once daily) combinations: low‐dose cytarabine (20 mg twice daily; cohort 1, n = 6; expansion cohort, n = 15); daunorubicin and cytarabine (60 mg/m2 i.v.; cohort 2, n = 6); or azacitidine (100 mg/m2 i.v.; cohort 3, n = 6). Patients, except cohort 2, were ineligible for intensive chemotherapy. The primary end‐point was dose‐limiting toxicity in cohorts 1–3 and disease‐modifying response in the expansion cohort. Disease‐modifying response rate was tested with the null hypothesis of 6.8%, which was set based on the results from the phase II BRIGHT AML 1003 study (NCT01546038). No dose‐limiting toxicities were observed in cohorts 1 or 3; one patient in cohort 2 experienced a dose‐limiting toxicity of grade 3 erythroderma. The most common grade ≥3 treatment‐related adverse events were neutropenia and thrombocytopenia (66.7% each) in cohort 1 and thrombocytopenia (60.0%) in the expansion cohort. In the expansion cohort, the disease‐modifying response rate was 46.7% (90% confidence interval, 24.4–70.0; p < 0.0001), with all patients achieving either a complete response or complete response with incomplete blood count recovery. Median overall survival was 13.9 months. In this study, the primary disease‐modifying response end‐point with glasdegib plus low‐dose cytarabine was met. The study confirms the safety and efficacy of glasdegib plus low‐dose cytarabine in Japanese patients with AML ineligible for intensive chemotherapy.
Synthesis of peiminine derivatives and its effect on A549 lung cancer‐bearing mice
Authors: Jin Xin , Guo Jianpeng , Lan Meng , Li Gao , Zhang Hui
Published: February 2024

To seek an effective anti‐lung cancer drug, a total of 14 derivatives were synthesized and characterized. The anti‐lung cancer effect of peiminine derivatives were evaluated in vitro and in vivo. The results of MTT and cell apoptosis assays showed that in comparison with peiminine and its other derivatives, compound 1c (indole‐3‐acetic acid‐peiminine ester) exhibited the highest activity with an IC50 value of 12.78 ± 0.64 μM. Compound 1c (10 μM) significantly reduced the levels of IL‐6, TNF‐α, and IL‐1β in A549 cells. In addition, the qRT‐PCR results showed that compound 1c (10 μM) reduced the mRNA levels of TNF‐α, mTOR, Bcl‐2, Akt1, PI3K, and p65 and increased those of Bax and caspase‐9. Next, the anti‐lung cancer activity of compound 1c (5 mg/kg) was evaluated in A549‐bearing nude mice. It was revealed that the tumor size and weight were significantly inhibited after treatment with compound 1c. And the levels of IL‐6, TNF‐α, and IL‐1β were decreased in mouse tumors. Finally, the latent mechanism of compound 1c was explored by western blot analysis. It was revealed that compound 1c could decrease the expressions of NF‐κB, Bcl‐2, PI3K, Akt, and mTOR and increase the expressions of Bax and caspase‐9 abundance. In conclusion, compound 1c exhibits an inhibitory effect on lung cancer, which was found to occur via inhibition of the PI3K/AKT/mTOR/NF‐κB signaling pathway, thus representing a potential new lead compound for application in lung cancer therapy.
HSYA prevents IL‐1β‐induced human chondrocyte damage in osteoarthritis by inhibiting NF‐κB activation
Authors: Shen Jiaying , Sheng Qi , Gao Manman , Li Junhong , Zhang Zhen , Wang Fuan , Zhou Zhiyu , Wang Jinping
Published: February 2024

The progression of osteoarthritis (OA) requires the involvement of inflammation, in which chondrocyte damage plays a significant role. Hydroxysafflor yellow A (HSYA), the main active component in the medical and edible dual‐purpose plant safflower, has previously shown anti‐inflammatory effects in various diseases. However, the specific impact of HSYA on OA remains unclear. Here, we investigate the potential role and underlying mechanism of HSYA in chondrocyte damage during the progression of OA. The viability of C28/I2 and iCell‐0092a chondrocytes was measured by CCK8 assay at different concentrations (2.5, 10, 40, and 160 μM). The gene expression of the extracellular matrix was revealed by q‐PCR 24 h after IL‐1β treatment. ROS production and levels of pro‐inflammatory cytokines in C28/I2 cells treated with HSYA were measured by immunoflurescence stating and q‐PCR. The impact of HSYA on the extracellular matrix and inflammation in IL‐1β‐induced OA were detected by western blot, q‐PCR, and immunofluorescence staining. We assessed the effect of HSYA and NF‐κB signaling pathway‐related genes by bioinformatics analysis and conducted molecular docking to assess the interaction of HSYA with a combined protein residue molecule ligand. Western blot was employed to investigate NF‐κB transcription factors in chondrocyte metabolism. HSYA was found to reduce excessive ROS production induced by IL‐1β stimuli, inhibit the expression of matrix metalloproteinase 13, interleukin 6, and tumor necrosis factor‐α, and increase the expression of Type II collagen and SRY‐box transcription factor 9 (p < .05). Mechanistically, HSYA interacted with nuclear factor κB, inhibiting the nuclear translocation and phosphorylation level of NF‐κB p65, and decreasing the phosphorylation and degradation of IκBα (p < .05). In conclusion, HSYA ameliorates inflammation and cartilage damage in OA by inhibiting the NF‐κB pathway, suggesting its potential application as a therapeutic agent for OA treatment.
Stride length and cerebellar regulation: Key features of early gait disorder in cerebral small vessel disease
Authors: Mo Yuting , Ji Biying , Ke Zhihong , Mao Chenglu , Jiang Jialiu , Huang Yanan , Qin Ruomeng , Huang Lili , Yang Dan , Hu Zheqi , Xu Yun
Published: February 2024

Objectives

Gait disorder (GD) is a common problem in cerebral small vessel disease (CSVD). This study aimed to determine (1) the early characteristics of GD in CSVD, (2) cerebellar neuroimaging features related to GD in CSVD, and (3) the association of cognitive impairment with GD.

Methods

In total, 183 subjects were enrolled in this study: patients with CSVD with normal cognitive function (CSVD‐NC) group (64 subjects), patients with CSVD with mild cognitive impairment (CSVD‐MCI) group (66 subjects), and a healthy control (HC) group (53 subjects). The GD patterns were evaluated using the ReadyGo three‐dimensional motion balance testing system. Meanwhile, we analyzed the cerebrum and cerebellum structurally and functionally. Correlation analyses were conducted among gait indicators, neuroimaging features, and neuropsychological tests.

Results

Both the CSVD‐NC and CSVD‐MCI groups had a reduced stride length, cortical atrophy in the left cerebellum VIIIb, and decreased functional connectivity between the left cerebellum VIIIb and left SFGmed compared with the HC group. In the correlation analysis, the gray matter probability of the left cerebellum VIIIb was closely related to stride length in the HC group. In the CSVD‐MCI group, linguistic function, memory, and attention were significantly correlated with gait performance.

Conclusion

Decreased stride length was the earliest characteristic of GD in CSVD. Structural and functional regulation of the left cerebellum VIIIb could play a particularly important role in early GD in CSVD.
Associations between impulsivity and fecal microbiota in individuals abstaining from methamphetamine
Authors: Liu Wen , Liu Linzi , Deng Zijing , Liu Ruina , Ma Tao , Xin Yide , Xie Yu , Zhou Yifang , Tang Yanqing
Published: February 2024

Introduction

Methamphetamine (MA) abuse is a major public problem, and impulsivity is both a prominent risk factor and a consequence of addiction. Hence, clarifying the biological mechanism of impulsivity may facilitate the understanding of addiction to MA. The microbiota–gut–brain axis was suggested to underlie a biological mechanism of impulsivity induced by MA.

Methods

We therefore recruited 62 MA addicts and 50 healthy controls (HCs) to investigate the alterations in impulsivity and fecal microbiota and the associations between them in the MA group. Thereafter, 25 MA abusers who abstained from MA for less than 3 months were followed up for 2 months to investigate the relationship between impulsivity and microbiota as abstinence became longer. 16S rRNA sequencing was conducted for microbiota identification.

Results

Elevated impulsivity and dysbiosis characterized by an increase in opportunistic pathogens and a decrease in probiotics were identified in MA abusers, and both the increased impulsivity and disrupted microbiota tended to recover after longer abstinence from MA. Impulsivity was related to microbiota, and the effect of MA abuse on impulsivity was mediated by microbiota.

Conclusion

Our findings potentially highlighted the importance of abstention and implicated the significant role of the microbiota–gut–brain axis in the interrelationship between microbiota and behaviors, as well as the potential of microbiota as a target for intervention of impulsivity.
Polygalacic acid attenuates cognitive impairment by regulating inflammation through PPARγ/NF‐κB signaling pathway
Authors: Zhao Tan , Jia Jianping
Published: February 2024

Aims

We aimed to explore the role and molecular mechanism of polygalacic acid (PA) extracted from traditional Chinese medicine Polygala tenuifolia in the treatment of Alzheimer's disease (AD).

Methods

The network pharmacology analysis was used to predict the potential targets and pathways of PA. Molecular docking was applied to analyze the combination between PA and core targets. Aβ42 oligomer‐induced AD mice model and microglia were used to detect the effect of PA on the release of pro‐inflammatory mediators and its further mechanism. In addition, a co‐culture system of microglia and neuronal cells was constructed to assess the effect of PA on activating microglia‐mediated neuronal apoptosis.

Results

We predict that PA might regulate inflammation by targeting PPARγ‐mediated pathways by using network pharmacology. In vivo study, PA could attenuate cognitive deficits and inhibit the expression levels of inflammation‐related factors. In vitro study, PA can also decrease the production of activated microglia‐mediated inflammatory cytokines and reduce the apoptosis of N2a neuronal cells. PPARγ inhibitor GW9662 inversed the neuroprotective effect of PA. Both in vivo and in vitro studies showed PA might attenuate the inflammation through the PPARγ/NF‐κB pathway.

Conclusions

PA is expected to provide a valuable candidate for new drug development for AD in the future.
Study on enhancing the union dyeing of cotton/modal blended fabrics with cationic modifier
Authors: Hao Haitao , Chen Xu , Yu Mengyao , Zhu Wenhao , Li Yongqiang
Published: February 2024

Cotton/modal blended fabrics are favoured by the market because not only do they have the advantages of the dimensional stability of cotton and drape wear resistance of modal, they also overcome their shortcomings, displaying a sense of stiffness and smooth feel. However, because of the differences in the physical and chemical properties between each component, the dyeing of blended fabrics with reactive dyes is prone to problems such as low fixation percentage, different dyeing percentages and colour depth. Here, two cationic modifiers, 2,3‐epoxypropyltrimethyl ammonium chloride (GTA) and methaacryloyloxyethyltrimethyl ammonium chloride (DMC), were applied for cationic modification of cotton/modal blended fabrics, and their role in the dyeability and union dyeing of cotton/modal blended fabrics was studied. The results showed that the K/S and fixation percentage of the blended fabric treated with GTA and DMC cationic agents could be significantly improved compared with the control group, and that the colour fastness of the blended fabric can reach grade 4‐5. Compared with GTA, DMC‐modified cotton/modal blended fabric showed better union dyeing properties because of its better diffusion performance in the fibre. The mesoporous volume of the cotton fibre is higher than that of the modal fibre, while the micropore volume is the opposite. Consequently, DMC macromolecules, through free radical graft polymerisation, were more likely to diffuse into cotton fibres with more mesoporous content, increased the interaction force between anionic reactive dye and cotton fibre, and improved the dyeability of the cotton component and the union dyeing performance of the blended fabric.
Superficial acral calcified chondroid mesenchymal neoplasm harboring an FN1::FGFR2 fusion and review of the literature
Authors: Machado Isidro , Damaskou Vasileia , Ioannidis Eleftherios , Jour George , Linos Konstantinos
Published: February 2024

Calcified chondroid mesenchymal neoplasm is a recently recognized bone and soft tissue entity primarily found in the extremities and the temporomandibular joint. This neoplasm is typically driven by the fusion of the FN1 gene with a kinase. In this case report, we provide a detailed account of a rare superficial calcified chondroid mesenchymal neoplasm located on the left big toe, characterized by an FN1::FGFR2 fusion. The tumor exhibited a peripheral collarette and consisted of large intradermal histiocytoid to epithelioid cells with no mitotic activity. These cells displayed fine chromatin and abundant pale eosinophilic cytoplasm, forming a swirling syncytium. They were interspersed with localized areas of glassy chondromyxoid matrix containing randomly mineralized calcific material and isolated osteoclast‐like giant cells. RNA sequencing confirmed the presence of an FN1 (exon 29)::FGFR2 (exon 7) gene fusion. Our report emphasizes the importance for dermatopathologists to consider this entity when evaluating superficial lesions displaying mesenchymal, chondroid, and calcified attributes.
Tumor of follicular infundibulum – reappraisal in a series of 28 patients with critical review of the literature
Authors: Wilk Michael , Zelger Bettina G. , Zelger Bernhard
Published: February 2024

Background and objectives

Tumor of follicular infundibulum (TFI) has been described as a neoplasm – isolated and multiple – and in association with other lesions. Its histopathologic definition is controversial.

Patients and methods

We present a histopathologically analyzed series of 28 patients with TFI features. This has been supplemented by a search in MEDLINE on the literature on this subject. The corresponding figures given in these articles have been discussed and analyzed.

Results

Patients comprised 16 women and twelve men. TFI features were seen in five patients with nevus sebaceous, two trichofolliculomas, one dilated pore Winer, eight viral warts, one dermatofibroma, six seborrheic keratoses, three actinic keratoses, one invasive squamous cell carcinoma, and one basal cell carcinoma in association with a squamous cell carcinoma/actinic keratosis. After study of the literature especially of solitary cases of TFI, we interpret such cases mostly as variants of seborrheic keratoses with variable degree of infundibular, isthmic and/or sebaceous differentiation with or without regression.

Conclusions

We regard TFI as an epithelial growth pattern which may occur in hamartomatous, inflammatory, infectious, reactive, or neoplastic conditions, in most solitary forms likely best classified within the histopathological spectrum of seborrheic keratoses.
Exposure to sign language prior and after cochlear implantation increases language and cognitive skills in deaf children
Authors: Delcenserie A. , Genesee F. , Champoux F.
Published: February 2024

Recent evidence suggests that deaf children with CIs exposed to nonnative sign language from hearing parents can attain age‐appropriate vocabularies in both sign and spoken language. It remains to be explored whether deaf children with CIs who are exposed to early nonnative sign language, but only up to implantation, also benefit from this input and whether these benefits also extend to memory abilities, which are strongly linked to language development. The present study examined the impact of deaf children's early short‐term exposure to nonnative sign input on their spoken language and their phonological memory abilities. Deaf children who had been exposed to nonnative sign input before and after cochlear implantation were compared to deaf children who never had any exposure to sign input as well as to children with typical hearing. The children were between 5;1 and 7;1 years of age at the time of testing and were matched on age, sex, and socioeconomic status. The results suggest that even short‐term exposure to nonnative sign input has positive effects on general language and phonological memory abilities as well as on nonverbal working memory—with total length of exposure to sign input being the best predictor of deaf children's performance on these measures. The present data suggest that even access to early short‐term nonnative visual language input is beneficial for the language and phonological memory abilities of deaf children with cochlear implants, suggesting also that parents should not be discouraged from learning and exposing their child to sign language.

Research Highlights

This is the first study to examine the effects of early short‐term exposure to nonnative sign input on French‐speaking children with cochlear implants’ spoken language and memory abilities.

Early short‐term nonnative exposure to sign input can have positive consequences for the language and phonological memory abilities of deaf children with CIs.

Extended exposure to sign input has some additional and important benefits, allowing children to perform on par with children with typical hearing.
Individuals with cerebral palsy and their families need an evidence‐based quality seal for interventions
Authors: Coughlan, John , Nweke, Nonyelum , Chatelin, Matthieu G. , Kisarale, Dorothy , Maitre, Nathalie L.
Published: February 2024

This letter to the editor is on the invited review by Mayston et al. on pages 564–572 of this issue.