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Purpose – Knowledge state specifies pupils’ mastery level and informs about their strength and weaknesses in the tested domain. This study attempted to diagnose primary pupils’ learning the concept of after through their knowledge states by using Cognitive Diagnostic Assessment (CDA). Methodology – This study employed a survey research design to gauge pupils’ knowledge states for the concept of finding the date after a specific number of days from a given date [abbreviated as the concept of after]. Quantitative data from the pupils’ pattern of response to the items in Cognitive Diagnostic Assessment (CDA) were collected and analyzed. Items in the CDA were designed by three experienced Mathematics Education researchers and content validated by a panel of seven expert primary mathematics teachers. It was then administered to 238 Grade Six pupils from 11 primary schools in Penang, Malaysia. The pupils’ item responses were interpreted into knowledge states and mastery levels. Findings – The overall analysis showed that there were 18 knowledge states diagnosed in the concept of after. This large number of knowledge states indicated the specificity of pupils’ mastery level and thus provided detailed information about their strengths and weaknesses in the concept of after. The findings of this study imply that primary pupils face different levels of difficulty when they are learning the topic of Time. Significance – This method of diagnosing pupils knowledge in terms of mastery level of each attribute tested is different from a conventional diagnostic test which provides only the final score for each pupil. By knowing the pupils knowledge states, teachers can make use of this fine-grained information to enable them to carry out differentiated instructional planning and other remedial work more effectively. Pupils can also use this information to monitor their own learning by maintaining their strengths and overcoming their weaknesses to cope with their own studies.

Calcifying extracellular vesicles (EVs) released from cells within atherosclerotic plaques have received increased attention for their role in mediating vascular calcification, a major predictor of cardiovascular morbidity and mortality. However, little is known about the difference between this pathologic vesicle population and other EVs that contribute to physiological cellular processes. One major challenge that hinders research into these differences is the inability to selectively isolate calcifying EVs from other vesicle populations. In this study, we hypothesized that the formation of mineral within calcifying EVs would increase the density of the vesicles such that they would pellet at a faster rate during ultracentrifugation. We show that after 10 min of ultracentrifugation at 100,000×g, calcifying EVs are depleted from the conditioned media of calcifying coronary artery smooth muscle cells and are enriched in the pelleted portion. We utilized mass spectrometry to establish functional proteomic differences between the calcifying EVs enriched in the 10 min ultracentrifugation compared to other vesicle populations preferentially pelleted by longer ultracentrifugation times. The procedures established in this study will allow us to enrich the vesicle population of interest and perform advanced proteomic analyses to find subtle differences between calcifying EVs and other vesicle populations that may be translated into therapeutic targets for vascular calcification. Finally, we will show that the differences in ultracentrifugation times required to pellet the vesicle populations can also be used to estimate physical differences between the vesicles.

Porphyromonas gingivalis is a gram-negative anaerobic bacterium, a member of the human oral microbiome, and a proposed "keystone" pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation. In this study, we investigate the role of horizontal DNA transfer as an adaptive process to modify behavior, using the major fimbriae as our model system, due to their critical role in mediating interactions with the host environment. We show that P. gingivalis is able to exchange fimbrial allele types I and IV into four distinct strain backgrounds via natural competence. In all recombinants, we detected a complete exchange of the entire fimA allele, and the rate of exchange varies between the different strain backgrounds. In addition, gene exchange within other regions of the fimbrial genetic locus was identified. To measure the biological implications of these allele swaps we compared three genotypes of fimA in an isogenic background, strain ATCC 33277. We demonstrate that exchange of fimbrial allele type results in profound phenotypic changes, including the quantity of fimbriae elaborated, membrane blebbing, auto-aggregation and other virulence-associated phenotypes. Replacement of the type I allele with either the type III or IV allele resulted in increased invasion of gingival fibroblast cells relative to the isogenic parent strain. While genetic variability is known to impact host-microbiome interactions, this is the first study to quantitatively assess the adaptive effect of exchanging genes within the pan genome cloud. This is significant as it presents a potential mechanism by which opportunistic pathogens may acquire the traits necessary to modify host-microbial interactions.

In the last few years, there has been growing interest in employing metamaterials (MTMs) to enhance antenna gain. In this paper we proposed a novel structure of planar folded-line left-handed metamaterial (FL-LHM) and applied it to improve the gain of three 5.8 GHz microstrip antenna types: a circularly polarized patch antenna, an antenna array, and a beam steering antenna. The planar FL-LHM structure was designed based on transmission line analysis. Their scattering parameters were obtained using a numerical model; the negative effective permittivity and permeability were then calculated from these parameters for the assessment of negative refraction index region. The S11 and radiation patterns of three fabricated antennas were measured; these results matched well with the simulation. We observed that the gain was increased up to 3 dBi for all the antennas. In addition, we were also able to maintain the circular polarization as well as the steering of the antenna without changing its dimensions.

To investigate the ability of dynamical seasonal climate predictions for Vietnam, the RegCM4.2 is employed to perform seasonal prediction of 2 m mean (T2m), maximum (Tx), and minimum (Tn) air temperature for the period from January 2012 to November 2013 by downscaling the NCEP Climate Forecast System (CFS) data. For model bias correction, the model and observed climatology is constructed using the CFS reanalysis and observed temperatures over Vietnam for the period 1980–2010, respectively. The RegCM4.2 forecast is run four times per month from the current month up to the next six months. A model ensemble prediction initialized from the current month is computed from the mean of the four runs within the month. The results showed that, without any bias correction (CTL), the RegCM4.2 forecast has very little or no skill in both tercile and value predictions. With bias correction (BAS), model predictions show improved skill. The experiment in which the results from the BAS experiment are further successively adjusted (SUC) with model bias at one-month lead time of the previous run showed further improvement compared to CTL and BAS. Skill scores of the tercile probability forecasts were found to exceed 0.3 for most of the target months.

Pressure depletion and high viscosity of crude oil in oil reservoir are the main challenges in oil recovery process. A potential solution is to employ electromagnetic heating coupled with magnetic fluid injection. The present work delivers a fundamental study on the interaction between magnetic fluid flow with electromagnetic field. The two-dimensional, incompressible flow is solved numerically using mixed finite element method. The velocity fields, temperature and pressure are the variables of interest, to be obtained by solving mass, momentum and energy equations coupled with Maxwell’ equations. The fluid stress arises simultaneously with the external magnetic force which mobilises and increases the temperature of the oil flow. Verification is made against available data obtained from different numerical method reported in literature. The results justify feasibility of the mixed finite element formulation as an alternative for the modelling of the magnetic fluid flow.

Fibroepithelial lesions (FELs) of the breast constitute a heterogeneous group of biphasic tumours with variable morphology and behaviour. The classification of FELs is mainly based on a constellation of diagnostic criteria and intralesional heterogeneity is not uncommon. Therefore, reporting of FELs in a core needle biopsy (CNB) with limited tissue material can be challenging as not all the features may be represented for assessment. Distinction between classic fibroadenoma and representatively sampled phyllodes tumour is generally straightforward. However, cellular fibroadenoma, morphologically heterogeneous benign phyllodes tumour and myoid hamartoma can overlap histologically. Accurate grading of phyllodes tumour is also challenging on CNB and carries significant management implications. In this article, we provide an overview and propose a pragmatic approach to reporting FELs on CNB, particularly for lesions with overlapping features. Guidance using the UK/European 'B' classification of FELs, as well as free text descriptions of the various lesions, is also presented to help further management decision making., (Copyright © 2025. Published by Elsevier Inc.)

Aims: Our study aims to audit and evaluate the accuracy and pitfalls of intraoperative evaluation of frozen sentinel lymph nodes (IOE-FSLN) and resection margins (IOE-FSM) compared to final findings in paraffin sections., Methods: A total of 264 cases underwent intraoperative evaluation, encompassing 688 sentinel lymph nodes (SLNs) and 1186 surgical margins. Frozen section (FS) diagnoses were compared with corresponding permanent sections of FS (PFS). Sensitivity, specificity, false-negative rate, false-positive rate, and concordance rates were assessed. Cases with discrepancies underwent a detailed histological review., Results: The study predominantly comprised cases of invasive breast carcinoma (IBC) (74%). For FSLN reporting, sensitivity was 88.1%, specificity 100%, and FS-PFS concordance 99.0%. FSM reporting showed sensitivity of 85.0%, specificity 99.9%, and concordance 98.4%. Sampling errors accounted for 86% (FSLN) and 88% (FSM) of discrepancies, with interpretive errors present in 1/7 FSLN and in 2/17 FSM cases. The shave margin method demonstrated a higher false-negative rate in FSM reporting. The rate of final positive margins was reduced from 21.3% to 11.4% when IOE-FSM was utilized., Conclusion: IOE-FSLN and IOE-FSM showed high reliability in guiding intraoperative decisions for axillary lymph node dissection and achieving free surgical margins in one-stage surgeries. However, limitations include challenges in distinguishing metastatic carcinoma from benign mimics in FSLN and diagnosing certain features such as IBC with post-treatment changes, invasive lobular carcinoma in FSLN and FSM; IBC rich in tumour-infiltrating lymphocytes, low-grade (DCIS/IBC in FSM) without immunohistochemical studies., (© 2025 John Wiley & Sons Ltd.)

Broken symmetry plays a pivotal role in determining the macroscopic electrical, optical, magnetic, and topological properties of materials. Circular dichroism (CD) has been widely employed to probe broken symmetry in various systems, from small molecules to bulk crystals, but designing CD responses on demand remains a challenge, especially for antiferromagnetic materials. Here we develop a cavity-enhanced CD technique to sensitively probe the magnetic order and broken symmetry in the van der Waals antiferromagnet FePS 3 . By introducing interfacial inversion asymmetry in cavity-coupled FePS 3 crystals, we demonstrate that the induced CD is strongly coupled with the zigzag antiferromagnetic order of FePS 3 and can be tuned both spectrally and in magnitude by varying the cavity length (FePS 3 thickness). Our findings open new avenues for using cavity-modulated CD as a sensitive diagnostic probe to detect weak broken symmetries, particularly at hidden interfaces, and in systems exhibiting hidden spin polarization or strong correlations.

Background: Working from home during the Covid-19 pandemic was perceived differently by men and women working in STEM fields. The aim of this paper is to highlight the unexpected benefits generated by working from home during the pandemic., Methods: Qualitative methodology was used to analyze data, collected via survey. The survey designed and conducted by WiMPBME targeted both males and females working in medical-related STEM fields (physics and engineering) and was answered by 921 individuals from 76 countries across all continents. This report analysed the responses to one open-ended question of the survey, namely: "What is the one positive that you have learnt/experienced as a result of working from home during this pandemic?"., Results: 594 responded to the question of interest. Access to home office was reported by 72.2% of survey participants. Males were more likely than females to report no positives of working from home (62.9%). Females were more likely to cite quality time, physical and mental health as positive factors than males, and to mention children in their responses. The most commonly coded thematic unit for males was remote working, with many males reporting the feasibility of working from home. Increased work productivity, better time management and work organisation were other common themes highlighted by responders irrespective of gender., Conclusion: The findings of the survey show the diversity of perceptions about remote working in STEM fields, while highlighting the importance of considering family dynamics, individual circumstances as well as gender when evaluating varied experiences of STEM professionals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) are linked to breast fibroepithelial tumor development, but their role in solid tumorigenesis is unclear. In this study, we assessed the functional effects of known RARα mutations on retinoic acid signaling using biochemical and cellular assays. All tested mutants exhibited reduced transcriptional activity compared to wild-type RARα and showed a dominant negative effect, a feature associated with developmental defects and tumor formation. X-ray crystallography revealed that the mutants maintained structural integrity, with altered co-activator recruitment explaining the loss of transcriptional function. Transcriptomics and cell growth assays demonstrated that mutant RARα proteins conferred resistance to ligand-induced growth inhibition in phyllodes tumor cells. Although the mutations impair RARα's response to retinoic acid, some mutants could be partially reactivated with synthetic agonists. These findings provide insights into how RARα mutations may contribute to tumorigenesis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Fibromatosis-like metaplastic carcinoma (FLMC) is a rare subtype of metaplastic carcinoma of the breast. Diagnosing this entity poses significant challenges, particularly in core biopsies due to limited sampling and overlap with benign spindle cell lesions such as nodular fasciitis and fibromatosis. We present an example of FLMC in an asymptomatic middle-aged woman. As her breast imaging revealed an irregular lobulated mass, a core biopsy was performed which showed benign breast tissue with fibrosis. However, this was discordant with her imaging findings, hence a subsequent vacuum-assisted biopsy was done which revealed low-grade spindle cell proliferation, consistent with FLMC. This report emphasizes the necessity of a triple assessment and highlights the potential pitfalls in diagnosing FLMC, particularly the risk of misinterpretation due to its histological similarities with benign entities. Understanding these challenges will be crucial to avoid diagnostic delays of this rare breast cancer subtype., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Metaplastic breast cancer (MBC) is a rare and heterogeneous breast cancer subtype, and there are critical gaps in our understanding of its long-term outcomes. This retrospective cohort study aimed to address these gaps by scrutinizing the pathologic and clinical aspects of MBC to enhance clinical decision-making and refine patient care strategies., Methods and Materials: This registry-based retrospective cohort study included women aged ≥21 years diagnosed with MBC or matrix-producing carcinoma. The data were obtained from January 2001 to August 2020 from the Joint Breast Cancer Registry of Singapore Health Services, which included 23,935 patients. Demographic and clinicopathologic characteristics, neoadjuvant chemotherapy responses, and survival outcomes were analyzed. Statistical assessments involved univariate and multivariate Cox proportional hazards models and Kaplan-Meier survival analyses., Results: This study enrolled 170 patients; 87.1% had non-metastatic disease, and 12.9% had metastatic disease. The age of patients at diagnosis ranged from 46 to 65 years (median, 56 years). The cohort's predominant characteristics were triple negative breast cancer (64%), advanced clinical stage (77.6%), node negativity (67.6%), and grade 3 disease (74.1%). In patients receiving neoadjuvant chemotherapy with curative intent treatment (17.6%), neoadjuvant chemotherapy yielded a pathologic complete response of 19.2% and a disease progression rate of 46.2%. Multivariate analysis showed that adjuvant radiation therapy significantly improved overall survival and disease-free survival, with hazard ratios of 0.29 (95% CI, 0.13-0.62; P < .005) and 0.23 (95% CI, 0.10-0.50; P < .005), respectively. Clinical T3 and T4 stages and nodal involvement were associated with poor outcomes. Stable disease after neoadjuvant chemotherapy was associated with poor overall survival and disease-free survival., Conclusions: This study sheds light on the complex landscape of MBC and emphasizes the pivotal role of adjuvant radiation therapy in enhancing patient outcomes. Despite advancements, challenges persist that warrant continued research to refine neoadjuvant chemotherapy strategies and delve into the nuanced factors that influence treatment responses., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Mammography is the mainstay of imaging surveillance after breast cancer (BC) treatment, but false negatives can occur. The objective of the study was to determine the factors that can predict poorer second breast cancer (SBC) mammogram detection of the ipsilateral and contralateral breast separately., Methods: A multicentre retrospective review was performed on female patients with a previous history of treated BC who developed a second breast cancer (SBC) in the ipsilateral (ISBC) or contralateral breast (CSBC) within 10 years from the first BC. SBC cases that occurred between January 2006 and October 2017 were included from the institutional database. The ISBC and CSBC mammogram-occult (MO) rates were correlated with mammographic breast density as well as various clinical, radiological and histological characteristics of the first BC., Results: 274 cases of SBC were evaluated. 39.4 % (108/274) of cases were ISBC and 60.6 % (166/274) were CSBC. 35 (32.4 %) of the ISBCs and 42 (25.3 %) of the CSBCs were MO (p = 0.218). On multivariate analysis, symptomatic first BC (p = 0.041), prevailing dense breast tissue at the time of SBC diagnosis (p = 0.003) and trabecular thickening on surveillance mammograms (p = 0.017) were associated with MO ISBC. MO first BC (p < 0.001) was the only factor found to correlate with MO CSBC., Conclusion: The study found various clinical, radiological and pathological factors associated with mammogram surveillance failure for the ipsilateral and contralateral breast. This information can provide additional guidance in the planning of a personalised surveillance program using adjunct imaging screening., Competing Interests: Declaration of competing interest We have no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ovarian sex cord-stromal tumours (SCSTs) present diagnostic difficulties during frozen section (FS) consultations due to their diverse morphology. This study aimed to evaluate the accuracy of FS evaluation of SCSTs in our institution, as well as to examine the reasons leading to incorrect FS diagnosis. Cases mimicking SCSTs and diagnosed as such during FS were also highlighted. We analysed 121 ovarian SCST cases and their mimics which underwent FS consultations over a 10-year period, to evaluate FS accuracy, reasons for deferrals and discrepancies. FS diagnoses were concordant, deferred and discrepant compared to the final diagnosis in 50 (41.3%), 39 (32.2%) and 32 (26.5%) cases, respectively. Major discrepancies (9/121, 7.4%) were mostly related to the diagnosis of adult granulosa cell tumour (AGCT). A fibromatous AGCT was misinterpreted as fibroma on FS, while a cystic AGCT was called a benign cyst. Conversely, a mesonephric-like adenocarcinoma, a sertoliform endometrioid carcinoma and a thecoma were misinterpreted as AGCT on FS. Another discrepant case was a Krukenberg tumour with prominent fibromatous stroma in which malignant signet ring cells were overlooked and misinterpreted as fibroma. Minor discrepancies were primarily associated with fibroma (21/23, 91.3%), wherein minor but potentially impactful details such as cellular fibroma and mitotically active cellular fibroma were missed due to sampling issues and misinterpretation as leiomyoma. FS evaluation for ovarian SCSTs demonstrated an overall accuracy of 78.5%, 81.0% and 81.8% for benign, uncertain/low malignant potential and malignant categories, respectively. There was no FS-related adverse clinical impact in all cases with available follow-up information (120/121 cases). Intraoperative FS evaluation of ovarian SCSTs is challenging. A small number of cases were misinterpreted, with AGCTs being the primary group where errors occur. Awareness of common diagnostic pitfalls and difficulties, alongside application of a stepwise approach, including (1) obtaining comprehensive clinical information, (2) thorough macroscopic examination and directed sampling, (3) meticulous microscopic examination with consideration of pitfalls and mimics, (4) effective communication with surgeons in difficult cases, and (5) consultation of subspecialty colleagues in challenging cases, will enhance pathologists' reporting accuracy and management of such cases in the future., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Clinical trials have demonstrated conclusively the non-inferiority of breast-conserving surgery followed by breast radiation therapy (BCT) compared with mastectomy for the treatment of early-stage invasive breast cancer (BC). The definition of the required surgical margin to ensure adequate removal of the cancer by BCT to obtain an acceptable low local recurrence (LR) rate remains controversial. Meta-analyses published by Houssami et al. in 2010 and 2014 demonstrated significantly lower LR rates for patients with a negative margin compared with those with positive (ink on tumour) or close (defined as ≤1 mm or ≤2 mm) margins. Neither meta-analysis addressed whether 'no ink on tumour' was adequate to define a negative margin because of a lack of data. Nevertheless, in 2014, the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) with advice from pathologists reviewed these data together and published guidelines recommending that a margin of 'no ink on tumour' was sufficient to define a clear margin in BCT. Subsequently, clinical practice has varied with some national and international bodies endorsing 'no ink on tumour', whilst others have recommended a ≥1 mm margin as acceptable margins for BCT. A more recent meta-analysis conducted by Bundred and colleagues in 2022 did have sufficient data to compare 'no ink on tumour' and 1 mm and concluded that 1 mm rather than 'no ink on tumour', should be used as a minimum negative margin, and recommended that international guidelines be revised. The current review presents a balanced assessment of the evidence relating margin width and local recurrence after BCT. This review concludes that guidelines should consider re-defining a negative margin as ≥1 mm rather than 'no ink on tumour' in the context of BCT, recognising there will be variation to tailor therapy for any individual patient situation to ensure optimal patient care., Competing Interests: Declaration of competing interest None All authors declare that no financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Two-dimensional metal halide perovskites are highly versatile for light-driven applications due to their exceptional variety in material composition, which can be exploited for the tunability of mechanical and optoelectronic properties. The band-edge emission is defined by the structure and composition of both organic and inorganic layers, and electron-phonon coupling plays a crucial role in the recombination dynamics. However, the nature of the electron-phonon coupling and what kind of phonons are involved are still under debate. Here we investigate the emission, reflectance, and phonon response from single two-dimensional lead iodide microcrystals with angle-resolved polarized spectroscopy. We find an intricate dependence of the emission polarization with the vibrational directionality in the materials, which reveals that several bands of low-frequency phonons with nonorthogonal directionality contribute to the band-edge emission. Such complex electron-phonon coupling requires adequate models to predict the thermal broadening of the emission and provides opportunities to design polarization properties.

ConspectusLayered metal halide perovskites represent a natural quantum well system for charge carriers that provides rich physics, and the organic encapsulation of the inorganic metal halide layers not only increases their stability in devices but also provides an immense freedom to design their functionality. Intriguingly, these organic moieties strongly impact the optical, electrical, and mechanical properties, not only through their dielectric, elastic, and chemical properties but also because of induced mechanical distortions in the inorganic lattice. This tunability makes two-dimensional layered perovskites (2DLPs) highly attractive as light emitters. Common consensus is that exciton-phonon coupling plays an important role in radiative recombination. For bulk and some two-dimensional (2D) materials, the band edge emission broadening can be described by the classic models for polar inorganic semiconductors, while for the temperature dependence of the self-trapped exciton emission, an analysis developed for color centers has been successfully applied. For many 2DLPs these approaches do not work because of the complexity of their vibrational spectra. However, their emission is still strongly determined by phonons, and therefore, an adequate understanding of the electron-phonon coupling needs to be developed.With polarized and angle-resolved Raman spectroscopy studies on single 2DLP flakes based on different ammonium molecules as organic cations, in 2020 we revealed very rich phonon spectra in the low-frequency regime. Although the phonon bands at low frequency can generally be attributed to the vibrations of the inorganic lattice, we found very different responses by only changing the type of organic cations. In addition, the intensity of the different phonon modes depended strongly on the angle of the linearly polarized excitation beam with respect to the in-plane axes of the octahedron lattice. In 2022, we mapped this angular dependence of the phonon modes, which allowed identification of the directionality of the different lattice vibrations. By correlating the phonon spectra with the temperature-dependent emission for a set of 2DLPs that featured very different self-trapped exciton (STE) emission, we demonstrated that the exciton relaxation cannot be related to coupling with a single (longitudinal-optical) phonon band and that several phonon bands should be involved in the emission process. To gain insights into the exciton-phonon coupling effects on the band edge emission, we performed both angle-resolved polarized emission and Raman spectroscopy on single 2D lead iodide perovskite microcrystals. These experiments revealed the impact of the organic cations on the linear polarization of the emission and corroborated that multiple phonon bands should be involved in the radiative recombination process. Analysis of the temperature-dependent line width broadening of the band edge emission showed that for many systems, the behavior cannot be described by assuming the involvement of only one phonon mode in the electron-phonon coupling process. Our studies revealed a wealth of highly directional low-frequency phonons in 2DLPs from which several bands are involved in the emission process, which leads to diverse optical and vibrational properties depending on the type of organic cation in the material.

Background and Objectives: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organizations., Methods and Results: The established ICCR process for dataset development was followed. An international expert panel consisting of breast pathologists, a surgeon, and an oncologist prepared a draft set of core and noncore data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalized and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website., Conclusions: This first international dataset for invasive cancer of the breast is intended to promote high-quality, standardized pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve the management of invasive breast cancer patients., (© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Human epidermal growth factor receptor 2 (HER2)-enriched breast cancer benefits significantly from anti-HER2 targeted therapies. This highlights the critical need for precise HER2 immunohistochemistry (IHC) interpretation serving as a triage tool for selecting patients for anti-HER2 regimens. Recently, the emerging eligibility of patients with HER2-low breast cancers for a novel HER2-targeted antibody-drug conjugate (T-DXd) adds challenges to HER2 IHC scoring interpretation, notably in the 0-1+ range, which shows high interobserver and interlaboratory staining platform variability. In this review, we navigate evolving challenges and suggest practical recommendations for HER2 IHC interpretation., (© 2024 John Wiley & Sons Ltd.)

Aims: Ductal carcinoma in situ (DCIS) is recognised by the World Health Organisation (WHO) Classification of Tumours (WCT) as a non-invasive neoplastic epithelial proliferation confined to the mammary ducts and lobules. This report categorises the references cited in the DCIS chapter of the 5th edition of the WCT (Breast Tumours) according to prevailing evidence levels for evidence-based medicine and the Hierarchy of Evidence for Tumour Pathology (HETP), identifying potential gaps that can inform subsequent editions of the WCT for this tumour., Methods and Results: We included all citations from the DCIS chapter of the WCT (Breast Tumours, 5th edition). Each citation was appraised according to its study design and evidence level. We developed our map of cited evidence, which is a graphical matrix of tumour type (column) and tumour descriptors (rows). Spheres were used to represent the evidence, with size and colour corresponding to their number and evidence level respectively. Thirty-six publications were retrieved. The cited literature in the DCIS chapter comprised mainly case series and were regarded as low-level. We found an unequal distribution of citations among tumour descriptors. 'Pathogenesis' and 'prognosis and prediction' contained the most references, while 'clinical features', 'aetiology' and 'diagnostic molecular pathology' had only a single citation each. 'Prognosis and prediction' had the greatest proportion of moderate- and high-levels of evidence., Conclusion: Our findings align with the disposition for observational studies inherent in the field of pathology. Our map is a springboard for future efforts in mapping all available evidence on DCIS, potentially augmenting the editorial process and future editions of WCTs., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer., (© 2024. The Author(s).)

At present, COVID-19 remains a public health concern due to the ongoing evolution of SARS-CoV-2 and its prevalence in particular countries. This paper provides an updated overview of the epidemiology and pathogenesis of COVID-19, with a focus on the emergence of SARS-CoV-2 variants and the phenomenon known as 'long COVID'. Meanwhile, diagnostic and detection advances will be mentioned. Though many inventions have been made to combat the COVID-19 pandemic, some outstanding ones include multiplex RT-PCR, which can be used for accurate diagnosis of SARS-CoV-2 infection. ELISA-based antigen tests also appear to be potential diagnostic tools to be available in the future. This paper also discusses current treatments, vaccination strategies, as well as emerging cell-based therapies for SARS-CoV-2 infection. The ongoing evolution of SARS-CoV-2 underscores the necessity for us to continuously update scientific understanding and treatments for it.

Evidence-based medicine (EBM) can be an unfamiliar territory for those working in tumor pathology research, and there is a great deal of uncertainty about how to undertake an EBM approach to planning and reporting histopathology-based studies. In this article, reviewed and endorsed by the Word Health Organization International Agency for Research on Cancer's International Collaboration for Cancer Classification and Research, we aim to help pathologists and researchers understand the basics of planning an evidence-based tumor pathology research study, as well as our recommendations on how to report the findings from these. We introduce some basic EBM concepts, a framework for research questions, and thoughts on study design and emphasize the concept of reporting standards. There are many study-specific reporting guidelines available, and we provide an overview of these. However, existing reporting guidelines perhaps do not always fit tumor pathology research papers, and hence, here, we collate the key reporting data set together into one generic checklist that we think will simplify the task for pathologists. The article aims to complement our recent hierarchy of evidence for tumor pathology and glossary of evidence (study) types in tumor pathology. Together, these articles should help any researcher get to grips with the basics of EBM for planning and publishing research in tumor pathology, as well as encourage an improved standard of the reports available to us all in the literature., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to measure the preferences for mental health support among health professionals, their willingness to support the mental health of colleagues and associated factors., Method: A descriptive cross-sectional study was performed from August to October 2022 within five hospitals located in Hanoi, Vietnam. A total of 244 health professionals participated in the study. Data on socio-economic status, health and COVID-19-related characteristics, Depression Anxiety Stress Scale (DASS-21); and preferences for mental health support services were collected by using a structured self-reported questionnaire. Multivariate logistic regression models were utilized to identify associated factors with the demand for mental support services., Results: 13.9%, 17.1% and 8.6% reported having at least mild depression, anxiety and stress, respectively. There 13.9% did not seek any mental health support during the COVID-19 pandemic. The most common support included talking with friends (52.9%), family (50.8%), colleagues (47.6%) and using social networks/Internet (43.5%). There 31.1% had been aware of mental health services, but only 18.0% used this service at least once. Regarding preferences, 47.3% had a demand for mental support services, and the most preferred service was providing coping skills (25.9%), followed by skills to support others against mental problems (22.2%). Major sources of support included psychiatrists (34.4%), colleagues (29.1%) and family (27.9%). The main preferred channels for support included telephone/mobile phone (35.7%) and Internet (20.9%). Only 12.3% were willing to provide mental support for colleagues during the pandemic. Age, education, perceived mental health status, ever seeking any mental service, and DASS-21 depression score were associated with demand for mental support services., Conclusion: This study found a lack of awareness of mental health services for health professionals, as well as moderate levels of demand for this service in this population. Raising awareness and developing tailored mental health support services are important to enhancing the mental well-being of health professionals in Vietnam to prepare for the next pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thanh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: The International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations, is an initiative aimed at providing a unified international approach to reporting cancer. ICCR recently published new data sets for the reporting of invasive breast carcinoma, surgically removed lymph nodes for breast tumours and ductal carcinoma in situ, variants of lobular carcinoma in situ and low-grade lesions. The data set in this paper addresses the neoadjuvant setting. The aim is to promote high-quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment that can be used for subsequent management decisions for each patient., Methods: The ICCR convened expert panels of breast pathologists with a representative surgeon and oncologist to critically review and discuss current evidence. Feedback from the international public consultation was critical in the development of this data set., Results: The expert panel concluded that a dedicated data set was required for reporting of breast specimens post-neoadjuvant therapy with inclusion of data elements specific to the neoadjuvant setting as core or non-core elements. This data set proposes a practical approach for handling and reporting breast resection specimens following neoadjuvant therapy. The comments for each data element clarify terminology, discuss available evidence and highlight areas with limited evidence that need further study. This data set overlaps with, and should be used in conjunction with, the data sets for the reporting of invasive breast carcinoma and surgically removed lymph nodes from patients with breast tumours, as appropriate. Key issues specific to the neoadjuvant setting are included in this paper. The entire data set is freely available on the ICCR website., Conclusions: High-quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment are critical for subsequent management decisions for each patient., (© 2024 John Wiley & Sons Ltd.)

Stark effect, the electric-field analogue of magnetic Zeeman effect, is one of the celebrated phenomena in modern physics and appealing for emergent applications in electronics, optoelectronics, as well as quantum technologies. While in condensed matter it has prospered only for excitons, whether other collective excitations can display Stark effect remains elusive. Here, we report the observation of phonon Stark effect in a two-dimensional quantum system of bilayer 2H-MoS 2 . The longitudinal acoustic phonon red-shifts linearly with applied electric fields and can be tuned over ~1 THz, evidencing giant Stark effect of phonons. Together with many-body ab initio calculations, we uncover that the observed phonon Stark effect originates fundamentally from the strong coupling between phonons and interlayer excitons (IXs). In addition, IX-mediated electro-phonon intensity modulation up to ~1200% is discovered for infrared-active phonon A 2u . Our results unveil the exotic phonon Stark effect and effective phonon engineering by IX-mediated mechanism, promising for a plethora of exciting many-body physics and potential technological innovations., (© 2024. The Author(s).)

Background: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties., Methods: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC., Results: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups., Conclusions: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

Purpose: Adenoid cystic carcinoma (ACC) of the trachea is a rare malignancy. We report a patient with ACC who underwent multimodal management including tracheal resection. A systematic review was also conducted on tracheal resection for ACC., Methods: A literature search was conducted on MEDLINE, Embase, and PubMed using the search terms "trachea AND adenoid cystic carcinoma AND (surgery OR resection)" and articles from 2000 to August 2021 were identified. A total of 29 journal articles were included in the review., Results: A total of 403 patients underwent surgery for tracheal ACCs. The mean age was 48.1 years and 54.7% were female. The commonest anatomical location was the lower trachea (46.9%). The mean time from symptom onset to diagnosis was 16.6 months with the commonest symptom being dyspnoea (52%). Fifty-eight percent of the patients had intraluminal growth. Tracheal resection (46.2%) and access via thoracotomy (41.4%) were the commonest procedures described. The mean length of trachea resected was 39.2 mm and the mean tumour size was 31.5 mm. 16.8% of lymph nodes were involved and 73.8% of cases had positive resection margins. The overall complication rate was 1.4-5.4% and the in-hospital mortality rate was 9.8%. The overall survival reported was 61.7% at 5 years and 54.6% at 10 years., Conclusion: Surgical resection followed by adjuvant radiotherapy is the mainstay in the treatment of tracheal ACC, notwithstanding the high rates of involved margins. Achieving tension-free anastomosis should be the first priority given the favourable response of adjuvant therapies in reducing recurrence rate and improving overall survival., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Specific heat capacity is one of the most fundamental thermodynamic properties of materials. In this work, we measured the specific heat capacity of PbSe nanocrystals with diameters ranging from 5 to 23 nm, and its value increases significantly from 0.2 to 0.6 J g -1 °C -1 . We propose a mass assignment model to describe the specific heat capacity of nanocrystals, which divides it into four parts: electron, inner, surface, and ligand. By eliminating the contribution of ligand and electron specific heat capacity, the specific heat capacity of the inorganic core is linearly proportional to its surface-to-volume ratio, showing the size dependence. Based on this linear relationship, surface specific heat capacity accounts for 40-60% of the specific heat capacity of nanocrystals with size decreasing. It can be attributed to the uncoordinated surface atoms, which is evidenced by the appearance of extra surface phonons in Raman spectra and ab initio molecular dynamics (AIMD) simulations.

The nipple can be affected by many malignant and benign entities. A wide variety of diseases including Paget disease, atopic dermatitis and nipple candidiasis can cause eczema-like changes in the nipple. In cases of diagnostic uncertainty, tissue sampling may be indicated. A true eczematous lesion, such as atopic dermatitis, typically shows a spongiotic dermatitis pattern. Paget disease, on the other hand, presents with infiltration of the nipple epidermis by neoplastic cells. The presence of atypical cells scattered in the epidermis in a pagetoid pattern opens up a histopathological differential diagnosis encompassing squamous cell carcinoma in situ and malignant melanoma, among others. Immunohistochemistry is commonly used to render a diagnosis. The objective of this article is to discuss Paget disease and highlight relevant clinical and histopathological differential diagnoses., (Copyright © 2024. Published by Elsevier B.V.)

Metastases to the breast from extramammary sources are extremely rare, with the ovary, primarily high-grade serous carcinoma, being the most common origin. We report a case of breast metastases from advanced stage ovarian mucinous carcinoma in a 48-year-old female- a case hitherto unreported in the literature. The case is noteworthy for its atypical presentation marked by an areolar rash, clinically suggestive of Paget disease of the nipple. This unique clinical scenario, coupled with histopathological examination revealing in-situ -like carcinoma component, posed a diagnostic challenge in discerning the tumour origin. We emphasize the need for heightened awareness among pathologists to avoid misdiagnosing metastatic carcinomas as primary breast tumours, a potential pitfall with significant clinical implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Laokulrath, Lim, Lim, Gudi and Tan.)

Abstract: Overexpression of human epidermal growth factor receptor 2 (HER2) protein in breast cancers carries significant prognostic and therapeutic implications. Anti-HER2 blockade has shown to be a useful adjunct to surgery in treating HER2-positive tumours. Up till today, the HER2 immunohistochemistry (IHC) and in situ hybridisation (ISH) scoring algorithms are geared towards identifying HER2-positive cases. A recently published Phase III clinical trial (DESTINY-Breast04) has demonstrated that an antibody-drug conjugate (trastuzumab-deruxtecan) significantly reduced disease progression and death in patients with metastatic disease with IHC score 1+ or 2+ and without ISH amplification, defining a new category of cases known as HER2 low. At present, IHC scores 0, 1+ and 2+ show significant interobserver variability, and identifying HER2-low breast cancers may pose significant challenges with the current algorithms. More work is needed in this area to better define HER2-low breast cancers, target the appropriate group of patients and assess treatment efficacy., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Two-dimensional materials are expected to play an important role in next-generation electronics and optoelectronic devices. Recently, twisted bilayer graphene and transition metal dichalcogenides have attracted significant attention due to their unique physical properties and potential applications. In this study, we describe the use of optical microscopy to collect the color space of chemical vapor deposition (CVD) of molybdenum disulfide (MoS 2 ) and the application of a semantic segmentation convolutional neural network (CNN) to accurately and rapidly identify thicknesses of MoS 2 flakes. A second CNN model is trained to provide precise predictions on the twist angle of CVD-grown bilayer flakes. This model harnessed a data set comprising over 10,000 synthetic images, encompassing geometries spanning from hexagonal to triangular shapes. Subsequent validation of the deep learning predictions on twist angles was executed through the second harmonic generation and Raman spectroscopy. Our results introduce a scalable methodology for automated inspection of twisted atomically thin CVD-grown bilayers.

In the age of precision medicine, extensive research has investigated tumour biomarkers to predict the behaviour of cancer and/or response to treatment in order to better understand the prognosis and treatment of disease. In breast cancer, significant progress has been made to categorise a common disease into subtypes defined by intrinsic tumour biology, measured by tumour biomarkers. This review encompasses the established biomarkers within breast cancer with the most up-to-date information regarding their understanding and clinical use as predictive and/or prognostic markers of breast cancer., (Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Triple-negative breast cancer (TNBC) has a poor prognosis with limited therapeutic options available for affected patients. Efforts are ongoing to identify surrogate markers for tumor-specific CD8 + T cells that can predict the response to immune checkpoint inhibitor (ICI) therapies, such as programmed cell death protein 1 or programmed cell death ligand-1 blockade. We have previously identified tumor-specific CD39 + CD8 + T cells in non-small cell lung cancer that might help predict patient responses to programmed cell death protein 1 or programmed cell death ligand-1 blockade. Based on this finding, we conducted a comparative interrogation of TNBC in an Asian cohort to evaluate the potential of CD39 as a surrogate marker of tumor-specific CD8 + T cells. Using ICI-treated TNBC mouse models (n = 24), flow cytometric analyses of peripheral blood mononuclear cells and tumor-infiltrating lymphocytes revealed that >99% of tumor-specific CD8 + T cells also expressed CD39. To investigate the relationship between CD39 + CD8 + T-cell density and CD39 expression with disease prognosis, we performed multiplex immunohistochemistry staining on treatment-naive human TNBC tissues (n = 315). We saw that the proportion of CD39 + CD8 + T cells in human TNBC tumors correlated with improved overall survival, as did the densities of other CD39 + immune cell infiltrates, such as CD39 + CD68 + macrophages. Finally, increased CD39 expression on CD8 + T cells was also found to predict the response to ICI therapy (pembrolizumab) in a separate cohort of 11 TNBC patients. These findings support the potential of CD39 + CD8 + T-cell density as a prognostic factor in Asian TNBC patients., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Advancements in cutting-edge molecular profiling techniques, such as next-generation sequencing and bioinformatic analytic tools, have allowed researchers to examine tumour biology in detail and stratify patients based on factors linked with clinical outcome and response to therapy. This manuscript highlights the most relevant prognostic and predictive biomarkers in kidney, bladder, prostate and testicular cancers with recognised impact in clinical practice. In bladder and prostate cancer, new genetic acquisitions concerning the biology of tumours have modified the therapeutic scenario and led to the approval of target directed therapies, increasing the quality of patient care. Thus, it has become of paramount importance to choose adequate molecular tests, i.e., FGFR screening for urothelial cancer and BRCA1-2 alterations for prostate cancer, to guide the treatment plan for patients. While no tissue or blood-based biomarkers are currently used in routine clinical practice for renal cell carcinoma and testicular cancers, the field is quickly expanding. In kidney tumours, gene expression signatures might be the key to identify patients who will respond better to immunotherapy or anti-angiogenic drugs. In testicular germ cell tumours, the use of microRNA has outperformed conventional serum biomarkers in the diagnosis of primary tumours, prediction of chemoresistance, follow-up monitoring, and relapse prediction., (Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Raman scattering provides essential insights into phonons, electronic structures and electron-phonon coupling within solids through the intensity of Raman peaks, which cannot be easily quantified using the classical bond polarizability model. The interlayer bond polarizability model (IBPM) had been developed to understand the Raman intensity of layer-breathing modes (LBMs) in two-dimensional materials. However, the quantitative understanding of the LBM intensity of a van der Waals heterostructure (vdWH) remains challenging. Here, in polynary vdWHs comprising twisted multilayer graphene (tMLG), MoS 2 and hBN, we observed a series of LBMs, whose intensity is markedly dependent on the excitation energy and twist angle of the tMLG constituent. An improved IBPM is proposed to quantitatively understand the Raman intensity of LBMs in the tMLG-based vdWHs, including the emergence or absence of a specific LBM when the excitation energy is resonant with the electronic states of tMLG or MoS 2 constituents. This work underscores the significant potential of the improved IBPM in accurately understanding and predicting the intensity profile of LBM in polynary vdWHs, even for the case of Raman scattering with excitation energies selectively resonant with the electronic states of the corresponding specific constituents.

Peroxiredoxin 3 (PRDX3), a mitochondrial hydrogen peroxide scavenger, is known to be upregulated during tumorigenesis and cancer progression. In this study, we provide evidence for the first time that PRDX3 could regulate cellular signaling pathways associated with Matrix Metalloproteinase-1 (MMP-1) expression and activity in breast cancer progression. We show that shRNA-mediated gene silencing of PRDX3 inhibits cell migration and invasion in two triple-negative breast cancer cell lines. Reciprocal experiments show that PRDX3 overexpression promotes invasion and migration of the cancer cells, processes which are important in the metastatic cascade. Notably, this phenomenon may be attributed to the activation of MMP-1, which is observed to be upregulated by PRDX3 in the breast cancer cells. Moreover, immunohistochemical staining of breast cancer tissues revealed a positive correlation between PRDX3 and MMP-1 expression in both epithelial and stromal parts of the tissues. Further pathway reporter array and luciferase assay demonstrated that activation of ERK signaling is responsible for the transcriptional activation of MMP-1 in PRDX3-overexpressed cells. These findings suggest that PRDX3 could mediate cancer spread via ERK-mediated activation of MMP-1. Targeted inhibition of ERK signaling may be able to inhibit tumor metastasis in triple-negative breast cancer., (© 2024. The Author(s).)