Diagnosis of acinic cell carcinoma of the salivary gland on cytology specimens: Role of NOR-1 (NR4A3) immunohistochemistry.

OBJECTIVES: Acinic cell carcinoma (AcCC) is often a challenging diagnosis on cytology. Recently, NOR-1 (NR4A3) has been demonstrated as a sensitive and specific marker for AcCC. Therefore, we conducted this study to evaluate NOR-1 expression in AcCC cytology specimens and to compare its reactivity in other salivary gland tumours (non-AcCC). METHODS: We retrospectively reviewed our database and selected cytology cases with available cell blocks, including 10 AcCC and 24 non-AcCC tumours (12 benign tumours and 12 malignant tumours). NOR-1 (1:50 dilution; SC393902 [H-7]; Santa Cruz Biotech) immunohistochemistry (IHC) was performed on all cases. RESULTS: All AcCC cases except two (2/10, 80%) showed positive nuclear staining of variable intensity for NOR-1, with the majority of cases (75%) demonstrating at least moderately intense nuclear expression. All non-AcCC cases were negative for NOR-1, demonstrating a specificity of 100%. CONCLUSION: We conclude that NOR-1 IHC is sensitive and very specific on cytology specimens and is able to distinguish AcCC from its mimickers reliably and classify them appropriately for further management.

Analysis of Hemostatic Effect and Safety of Local Spray Treatment With Hemocoagulase Bothrops Atrox for Injection After Resection of Colon Polyps.

Context: Postoperative bleeding after resection of colon polyps (CPs) is an extremely common adverse event with endoscopic treatment. Hemocoagulase Bothrops Atrox (HBA) is a newly discovered hemostatic substance that contains thrombin-like and coagulation kinase-like enzymes. However, research is lacking about its use for the treatment of intestinal polyps. Objective: The study intended to examine the hemostatic efficacy and safety of a local spray treatment with HBA, derived from HBA for injection, after CP resection, to provide a new hemostatic method, support HBA's use, and provide evidence for clinical decision making. Design: The research team performed a randomized controlled study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants: Participants were 200 patients with CP who received treatment at the hospital between December 2020 and December 2022. Intervention: The research team divided participants into two groups with 100 participants each, an intervention group and a control group, using the random number expression method. For hemostasis, the intervention group received a local spray treatment that used HBA for injection, and the control group received metal-clip closure or electrocoagulation. Outcome Measures: The research team measured: (1) the hemostatic efficacy; (2) clinical outcomes-time to hemostasis, hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding; (3) at baseline and at 24h postintervention, the coagulation function-prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB); (4) at baseline and at 24h postintervention, PLT parameters-platelet count (PLT), procalcitonin (PCT), and mean platelet volume (MPV); (5) economic effects-total number of participants with hemostasis, hospital days, and total hospital costs; and (6) adverse reactions. Results: The total hemostatic efficacy for the intervention group was significantly higher than that of the control group (P = .027), and the time to hemostasis was significantly shorter (P < .001) and the hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding were all significantly lower than those of the control group, at P = .009, P = .009, and P = .048, respectively. In addition, the intervention group's postoperative PT, TT, APTT, FIB, and MPV were all significantly lower than those of the control group (all P < .05), while its PLT and PCT were significantly higher than those of the control group (both P < .05). The intervention group's total number of participants with hemostasis, participants with hemostasis, hospital days, and total cost were significantly lower than those of the control group (all P < .05), while no significant difference existed between the groups in the incidence of adverse effects (P > .05). Conclusions: HBA has an excellent hemostatic effect on intestinal polypectomy, with convenient use and high safety. In the future, popularizing the use of HBA in the treatment of intestinal polypectomy can not only effectively guarantee the postoperative safety of patients but also could reduce their economic burden and improve the quality of clinical medical services.

Mechanisms of PKA-Dependent Potentiation of Kv7.5 Channel Activity in Human Airway Smooth Muscle Cells.

ß-adrenergic receptor (ßAR) activation promotes relaxation of both vascular and airway smooth muscle cells (VSMCs and ASMCs, respectively), though the signaling mechanisms have not been fully elucidated. We previously found that the activity of Kv7.5 voltage-activated potassium channels in VSMCs is robustly enhanced by activation of ßARs via a mechanism involving protein kinase A (PKA)-dependent phosphorylation. We also found that enhancement of Kv7 channel activity in ASMCs promotes airway relaxation. Here we provide evidence that Kv7.5 channels are natively expressed in primary cultures of human ASMCs and that they conduct currents which are robustly enhanced in response to activation of the ßAR/cyclic adenosine monophosphate (cAMP)/PKA pathway. MIT Scansite software analysis of putative PKA phosphorylation sites on Kv7.5 identified 8 candidate serine or threonine residues. Each residue was individually mutated to an alanine to prevent its phosphorylation and then tested for responses to ßAR activation or to stimuli that elevate cAMP levels. Only the mutation of serine 53 (S53A), located on the amino terminus of Kv7.5, significantly reduced the increase in Kv7.5 current in response to these stimuli. A phospho-mimic mutation (S53D) exhibited characteristics of ßAR-activated Kv7.5. Serine-to-alanine mutations of 6 putative PKA phosphorylation sites on the Kv7.5 C-terminus, individually or in combination, did not significantly reduce the enhancement of the currents in response to forskolin treatment (to elevate cAMP levels). We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to ßAR activation in vascular and airway smooth muscle cells.

Requirement for Microglia for the Maintenance of Synaptic Function and Integrity in the Mature Retina.

Microglia, the principal resident immune cell of the CNS, exert significant influence on neurons during development and in pathological situations. However, if and how microglia contribute to normal neuronal function in the mature uninjured CNS is not well understood. We used the model of the adult mouse retina, a part of the CNS amenable to structural and functional analysis, to investigate the constitutive role of microglia by depleting microglia from the retina in a sustained manner using genetic methods. We discovered that microglia are not acutely required for the maintenance of adult retinal architecture, the survival of retinal neurons, or the laminar organization of their dendritic and axonal compartments. However, sustained microglial depletion results in the degeneration of photoreceptor synapses in the outer plexiform layer, leading to a progressive functional deterioration in retinal light responses. Our results demonstrate that microglia are constitutively required for the maintenance of synaptic structure in the adult retina and for synaptic transmission underlying normal visual function. Our findings on constitutive microglial function are relevant in understanding microglial contributions to pathology and in the consideration of therapeutic interventions that reduce or perturb constitutive microglial function. SIGNIFICANCE STATEMENT: Microglia, the principal resident immune cell population in the CNS, has been implicated in diseases in the brain and retina. However, how they contribute to the everyday function of the CNS is unclear. Using the model of the adult mouse retina, we examined the constitutive role of microglia by depleting microglia from the retina. We found that in the absence of microglia, retinal neurons did not undergo overt cell death or become structurally disorganized in their processes. However, connections between neurons called synapses begin to break down, leading to a decreased ability of the retina to transmit light responses. Our results indicate that retinal microglia contribute constitutively to the maintenance of synapses underlying healthy vision.

Macroglia-microglia interactions via TSPO signaling regulates microglial activation in the mouse retina.

Chronic retinal inflammation in the form of activated microglia and macrophages are implicated in the etiology of neurodegenerative diseases of the retina, including age-related macular degeneration, diabetic retinopathy, and glaucoma. However, molecular biomarkers and targeted therapies for immune cell activation in these disorders are currently lacking. To address this, we investigated the involvement and role of translocator protein (TSPO), a biomarker of microglial and astrocyte gliosis in brain degeneration, in the context of retinal inflammation. Here, we find that TSPO is acutely and specifically upregulated in retinal microglia in separate mouse models of retinal inflammation and injury. Concomitantly, its endogenous ligand, diazepam-binding inhibitor (DBI), is upregulated in the macroglia of the mouse retina such as astrocytes and Müller cells. In addition, we discover that TSPO-mediated signaling in microglia via DBI-derived ligands negatively regulates features of microglial activation, including reactive oxygen species production, TNF-α expression and secretion, and microglial proliferation. The inducibility and effects of DBI-TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence. Our results indicate that TSPO is a promising molecular marker for imaging inflammatory cell activation in the retina and highlight DBI-TSPO signaling as a potential target for immodulatory therapies.

Genome-wide investigation and transcriptome analysis of the WRKY gene family in Gossypium.

WRKY transcription factors play important roles in various stress responses in diverse plant species. In cotton, this family has not been well studied, especially in relation to fiber development. Here, the genomes and transcriptomes of Gossypium raimondii and Gossypium arboreum were investigated to identify fiber development related WRKY genes. This represents the first comprehensive comparative study of WRKY transcription factors in both diploid A and D cotton species. In total, 112 G. raimondii and 109 G. arboreum WRKY genes were identified. No significant gene structure or domain alterations were detected between the two species, but many SNPs distributed unequally in exon and intron regions. Physical mapping revealed that the WRKY genes in G. arboreum were not located in the corresponding chromosomes of G. raimondii, suggesting great chromosome rearrangement in the diploid cotton genomes. The cotton WRKY genes, especially subgroups I and II, have expanded through multiple whole genome duplications and tandem duplications compared with other plant species. Sequence comparison showed many functionally divergent sites between WRKY subgroups, while the genes within each group are under strong purifying selection. Transcriptome analysis suggested that many WRKY genes participate in specific fiber development processes such as fiber initiation, elongation and maturation with different expression patterns between species. Complex WRKY gene expression such as differential Dt and At allelic gene expression in G. hirsutum and alternative splicing events were also observed in both diploid and tetraploid cottons during fiber development process. In conclusion, this study provides important information on the evolution and function of WRKY gene family in cotton species.

A novel p38 mitogen-activated protein kinase/Elk-1 transcription factor-dependent molecular mechanism underlying abnormal endothelial cell proliferation in plexogenic pulmonary arterial hypertension.

Plexiform lesions (PLs), the hallmark of plexogenic pulmonary arterial hypertension (PAH), contain phenotypically altered, proliferative endothelial cells (ECs). The molecular mechanism that contributes to EC proliferation and formation of PLs is poorly understood. We now show that a decrease in intersectin-1s (ITSN-1s) expression due to granzyme B (GrB) cleavage during inflammation associated with PAH and the high p38/Erk1/2(MAPK) activity ratio caused by the GrB/ITSN cleavage products lead to EC proliferation and selection of a proliferative/plexiform EC phenotype. We used human pulmonary artery ECs of PAH subjects (EC(PAH)), paraffin-embedded and frozen human lung tissue, and animal models of PAH in conjunction with microscopy imaging, biochemical, and molecular biology approaches to demonstrate that GrB cleaves ITSN-1s, a prosurvival protein of lung ECs, and generates two biologically active fragments, an N-terminal fragment (GrB-EH(ITSN)) with EC proliferative potential and a C-terminal product with dominant negative effects on Ras/Erk1/2. The proliferative potential of GrB-EH(ITSN) is mediated via sustained phosphorylation of p38(MAPK) and Elk-1 transcription factor and abolished by chemical inhibition of p38(MAPK). Moreover, lung tissue of PAH animal models and human specimens and EC(PAH) express lower levels of ITSN-1s compared with controls and the GrB-EH(ITSN) cleavage product. Moreover, GrB immunoreactivity is associated with PLs in PAH lungs. The concurrent expression of the two cleavage products results in a high p38/Erk1/2(MAPK) activity ratio, which is critical for EC proliferation. Our findings identify a novel GrB-EH(ITSN)-dependent pathogenic p38(MAPK)/Elk-1 signaling pathway involved in the poorly understood process of PL formation in severe PAH.

Microglia-Müller cell interactions in the retina.

Microglia and Müller cells are cell types that feature prominently in responses to disease and injury in the retina. However, their mutual interactions have not been investigated in detail. Here, we review evidence that indicate that these two cell populations exchange functionally significant signals under uninjured conditions and during retinal inflammation. Under normal conditions, Müller cells constitute a potential source of extracellular ATP that mediates the activity-dependent regulation of microglial dynamic process motility. Following microglial activation in inflammation, microglia can signal to Müller cells, influencing their morphological, molecular, and functional responses. Microglia-Müller cell interactions appear to be a mode of bi-directional communications that help shape the overall injury response in the retina.

[Genome-wide analysis of HSP70 superfamily in Gossypium raimondii and the expression of orthologs in Gossypium hirsutum].

Heat shock 70 (HSP70) proteins are highly conserved molecular chaperones widely existed in the plant kingdom which are involved in cellular protein folding process. In this study, comprehensive evolutionary analyses of the Gossypium raimondii HSP70 gene family members are conducted and 30 HSP70 genes are identified. The gene structure, chromosome distribution, gene duplication and phylogenic evolution of this family are further analyzed. The results reveal that HSP70 family genes can be clustered into several major subgroups based on their sub-cellular locations, and the gene structures are relatively conserved in each subgroup. Both tandem duplications and chromosome segmental duplications are found to contribute to the expansion of HSP70 gene family. Evolutionary analysis of HSP70s in diverse species reveals that the differentiation of HSP70 subgroups occurred before the multi-cell and single-cell differentiation, with the cytoplasmic HSP70s multiple amplified. The expression pattern of HSP70 genes under series of fiber development stages indicates that many HSP70 genes may participate in fiber development processes including fiber initiation and elongation. This study provides the complete profiles of cotton HSP70 family genes for future study on their functions related to the molecular mechanisms of fiber development.

The efficacy of articaine in pain management during endodontic procedures in pediatric patients.

OBJECTIVE: This trial aimed to study the efficacy of articaine in pain management during endodontic procedures in pediatric patients. METHODS: Ninety-eight children who received endodontic painless treatment were collected and randomly divided into the control group and observation group, with 49 cases in each group. The control group received infiltration anesthesia with lidocaine, and the observation group received infiltration anesthesia with articaine. Anesthesia effect, anesthesia onset time, sensory recovery time, duration of anesthesia, pain intensity, blood pressure, heart rate, and adverse reactions were compared. RESULTS: The effective rate of anesthesia in the observation group was higher than that in the control group. The anesthesia onset time and sensory recovery time were shorter, the duration of anesthesia was longer, and the VAS score and facial expression score were lower in the observation group than in the control group. The heart rate of the observation group was lower, and diastolic blood pressure was higher than those of the control group. The total incidence of adverse reactions in the observation group was lower than that in the control group. CONCLUSION: In the treatment of dental pulp diseases in children, the use of articaine can achieve better anesthesia effect and rapid onset of anesthesia and has less impact on the patient's blood pressure and heart rate, but it also can relieve pain and has good safety after the use of medication. It is worthy of clinical application.

Construction of a cold island network for the urban heat island effect mitigation.

The urban heat island (UHI) effect seriously challenges sustainable urban development strategies and livability. Numerous studies have explored the UHI problem from the perspective of isolated blue and green patches, ignoring the overall function of cold island networks. This study aims to explore the construction method of cold island network by integrating scattered cold island resources, rationally guiding urban planning and construction, and providing effective ideas and methods for improving the urban thermal environment. Taking the central city of Fuzhou as an example, the identification of the cold island core source (CICS) was optimized by applying relative land surface temperature (LST), morphological spatial pattern analysis, and landscape connectivity analysis. The combined resistance surface was constructed based on a spatial principal component analysis. Subsequently, the cold island network was constructed by applying circuit theory and identifying the key nodes. The results showed that the central and eastern parts of the study area experienced the most significant UHI effects and there was a tendency for them to cluster. Overall, 48 core sources, 104 corridors, 89 cooling nodes, and 34 heating nodes were identified. The average LST of the CICSs was 28.43 °C, significantly lower than the average LST of the entire study area (31.50 °C), and the 104 cold corridors were classified into three categories according to their importance. Different targeting measures should be adopted for the cooling and heating nodes to maintain the stability of the cold island network and prevent the formation of a heat network. Finally, we suggest a model for urban cold island network construction and explore methods for mitigating issues with UHI to achieve proactive and organized adaptation and mitigation of thermal environmental risks in urban areas, as well as to encourage sustainable urban development.

A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: Evaluation of dermal safety, intra-mammary drug distribution, and biologic effects.

Breast cancer prevention only requires local exposure of the breast to active drug. However, oral preventive agents entail systemic exposure, causing adverse effects that limit acceptance by high-risk women. Drug-delivery through the breast skin is an attractive option, but requires demonstration of dermal safety and drug distribution throughout the breast. We formulated the tamoxifen metabolite (E/Z)-endoxifen for transdermal delivery and tested it in a placebo-controlled, double-blinded Phase I trial with dose escalation from 10 to 20 mg daily. The primary endpoint was dermal toxicity. Thirty-two women planning mastectomy were randomized (2:1) to endoxifen-gel or placebo-gel applied to both breasts for 3-5 weeks. Both doses of endoxifen-gel incurred no dermal or systemic toxicity compared to placebo. All endoxifen-treated breasts contained the drug at each of five sampling locations; the median per-person tissue concentration in the treated participants was 0.6 ng/g (IQR 0.4-1.6), significantly higher (p < 0.001) than the median plasma concentration (0.2 ng/mL, IQR 0.2-0.2). The median ratio of the more potent (Z)-isomer to (E)-isomer at each breast location was 1.50 (IQR 0.96-2.54, p < 0.05). No discernible effects of breast size or adiposity on tissue concentrations were observed. At the endoxifen doses and duration used, and the tissue concentration achieved, we observed a non-significant overall reduction of tumor proliferation (Ki67 LI) and significant downregulation of gene signatures known to promote cancer invasion (FN1, SERPINH1, PLOD2, PDGFA, ITGAV) (p = 0.03). Transdermal endoxifen is an important potential breast cancer prevention agent but formulations with better dermal penetration are needed.

The International System for Reporting Serous Fluid Cytopathology-An Updated Review.

The International System (TIS) for reporting serous fluid cytopathology was published in December 2020 as a joint project by the International Academy of Cytology and the American Society of Cytopathology. The purpose was to standardize the diagnostic criteria and nomenclature used in reporting serous fluid samples, thereby improving the reproducibility of reports and improving communication between pathologists and clinicians. TIS defines a five-tier system consisting of nondiagnostic, negative for malignancy, atypia of uncertain significance, suspicious for malignancy and malignant categories. This review provides an updated summary of the reporting system, risk of malignancy, potential diagnostic pitfalls, and a practical diagnostic approach to serous fluid specimens.

GATA3 expression in primary lung carcinomas: correlation with histopathologic features and TTF-1, napsin A, and p40 expression.

This study assessed the expression of GATA3 in primary lung carcinomas and correlated it with tumor histology and immunostains routinely utilized in the work up of primary lung cancers. Tissue microarrays (TMAs) were constructed from a cohort of 184 non-small cell carcinomas, stained with GATA3, p40, TTF-1, and napsin A, and analyzed semi-quantitatively. All TMA cases with GATA3 expression were further analyzed using corresponding whole slide sections. Positive GATA3 staining was present in 16 cases (9%), including 7 squamous cell carcinomas (SqCCs) (4%), 4 adenocarcinomas (AdCs) (2%), 2 adenosquamous carcinomas (AdSqCs) (1%), 2 large cell carcinomas (LCCs) (1%), and 1 sarcomatoid carcinoma (SC) (<1%). Among tumor histotypes, SqCC was more likely to stain with GATA3 (7/49, 14%), while AdC was less likely (4/111, 4%) (p = 0.04). In GATA3-positive cases, high-level expression was observed in 9 cases (56%), including 5 p40-positive SqCCs (3 were nonkeratinizing), 1 p40-positive AdSqC (negative for TTF-1 and napsin A), and 1 AdC (solid), 1 LCC, and 1 SC, each negative for p40, TTF-1, and napsin A). Low-level GATA3 expression was found in 3 AdCs (1 was lepidic and 2 were acinar predominant), 2 SqCCs (keratinizing), 1 AdSqC, and 1 LCC. These findings indicate that GATA3 expression occurs in a minor but significant proportion of primary non-small cell lung carcinomas, most often involves SqCC, and tends to show increasing levels of expression in more poorly differentiated subtypes. Caution should be exercised when interpreting GATA3 expression, and a panel of immunostains should be utilized when assigning tumor origin.

Application of the International System for Reporting Serous Fluid Cytopathology to pericardial fluid: Root cause analysis of indeterminate diagnoses, cytohistological correlation, and assessment of malignancy risk.

BACKGROUND: This study investigates the utility of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in the categorization of pericardial fluid and assesses the diagnostic performance and risk of malignancy (ROM) for each of the diagnostic categories. METHODS: All pericardial fluid cases at the Yale School of Medicine between January 1, 2017, and December 31, 2020, were reviewed. The diagnoses were reclassified into five categories according to the ISRSFC: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). ROM and performance parameters of each category were calculated. RESULTS: After reclassification, the distribution of 465 pericardial fluid cases in each category was as follows: ND, 19 (4.1%); NFM, 332 (71.4%); AUS, 21 (4.5%); SFM, 11 (2.4%); and MAL, 82 (17.6%). Confirmatory follow-ups were available for 16 ND (66.7%), 299 NFM (90%), 15 AUS (71%), 5 SFM (45.5%), and 30 MAL cases (36.6%). The ROM was 0% for ND, 1.3% for NFM (4 of 332), 20% for AUS (3 of 15), and 100% for both SFM (5 of 5) and MAL (27 of 27). The diagnostic performance was as follows: sensitivity, 87% (27 of 31); specificity, 100% (292 of 292); positive predictive value (PPV), 100% (27 of 27); negative predictive value (NPV), 98.6% (292 of 296); and diagnostic accuracy, 98.8% (319 of 323). CONCLUSIONS: The ISRSFC is a highly useful system for the reporting of pericardial fluid and risk assessment, given that it offers high sensitivity, specificity, PPV, NPV, and diagnostic accuracy. The application of this system may help to better categorize pericardial fluid and facilitate the standardization of cytopathology reporting.

Z-Endoxifen prevents aggressive mammary cancers in mice by inhibiting cell proliferation and creating a tumor suppressive microenvironment.

Aggressive estrogen receptor (ER) positive breast cancer is frequently tamoxifen-resistant; alternative endocrine approaches exist for therapy, but not for prevention, particularly in premenopausal women. We examined the efficacy of the selective ER modulator (Z-endoxifen) as monotherapy and in combination with the selective progesterone receptor modulators (onapristone and ulipristal acetate) in the tamoxifen-insensitive C3(1)/SV40TAg mouse mammary tumorigenesis model. Unlike tamoxifen at human equivalent dose (HED) 101 mg/day, endoxifen at HED 24 mg/day significantly increased latency and reduced tumor growth relative to untreated controls. Ulipristal acetate (UPA) at HED 81 mg/day also significantly increased latency however failed to inhibit tumor growth, while onapristone (HED 98 mg/day) had no tumor prevention efficacy in this model. Addition of UPA to endoxifen did not enhance preventive efficacy over endoxifen alone. The expression of genes associated with cell cycle, cell proliferation and extracellular matrix remodeling was similarly repressed by endoxifen and UPA however only endoxifen significantly downregulated prominent genes associated with poor prognosis (Col11a1, Il17b, Pdgfa, Tnfrsf11a). Our results indicate that endoxifen can prevent breast cancers, even when tamoxifen-resistant, through its role in favorable tissue remodeling and immunomodulation.

Breast Cancer With a HER2 FISH Group 2 Result: Should HER2 Tests be Repeated?

BACKGROUND: Breast cancer with fluorescence in situ hybridization (FISH) group 2 pattern (HER2 <4 and HER2/CEP17 ratio ≥2, a subset of monosomy CEP17) was historically considered HER2-positive, but mostly HER2-negative according to updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines unless 3+ by immunohistochemistry (IHC). Therapeutic relevance of this group remained elusive, therefore we assessed if repeat IHC and FISH can assist final HER2 classification. PATIENT AND METHODS: We retrospectively reviewed HER2 FISH performed at our institution from 2014 to 2018 and identified 23 of 3554 (0.6%) breast cancer cases with at least one-time measurement of HER2 FISH categorized as group 2. Repeat HER2 tests were performed for cases with available alternative tumor samples and compared with initial testing following 2018 ASCO/CAP guidelines. RESULTS: Only 1 of 23 group 2 cases was HER2-positive, 0/18 in primary and 1/5 in metastatic/recurrent tumors. Of 13 primary tumors with repeat HER2 results; 10 (77%) remained HER2-negative; 3 (23%) changed from HER2-negative (group 2 and IHC 2+) to HER2-positive (group 1 and IHC 2+). Among 8 of these 13 patients receiving neoadjuvant systemic therapy containing anti-HER2 agent, 3 (38%) achieved pathologic complete response (pCR). Two of 3 pCR cases were HER2-positive converters on repeat testing. Three pCR cases were ER-negative or -low positive and Ki67 ≥40%, while 5 partial responders were ER-positive and Ki67 <40% (P < .05). CONCLUSION: Breast cancer with HER2 FISH group 2 result may represent heterogeneous populations of tumor cells being originated de novo or preferentially selected secondary to therapy. Repeat HER2 tests on alternative samples may be considered to guide anti-HER2 therapy.

The Clinical Manifestation of p.Asp50Asn Heterozygous Mutation of GJB2 Gene in 3 Members of a Family Is Similar to That of Clouston Syndrome.

Keratitis-ichthyosis-deafness (KID) syndrome has genetic heterogeneity, and the clinical manifestations of some patients may overlap with Clouston syndrome. A 34-year-old female patient came to our department with a complain of "sparse hair, rough skin, photophobia and deafness for more than 30 years." We found that the proband and two other family members (57-year-old mother and 4-year-old daughter) had similar clinical manifestations: systemic hair loss, generalized skin hyperkeratosis, especially in the metacarpophalangeal area. Subungual hyperkeratosis, finger/toenail dystrophy, as well as photophobia and epiphora. According to the investigation, one of the family members also had similar clinical manifestations (grandfather of the proband) and he's died. The other three members of the family had no hearing impairment, and all patients had typical nail dystrophy, hair loss and palmoplantar hyperkeratosis, similar like as seen in Clouston syndrome, so we suspected to diagnose the case as Clouston syndrome. However, after genetic testing, it was found that the proband, his mother and daughter all had p.Asp50Asn heterozygous mutations in the GJB2 gene, and no mutation was detected in GJB6. The modified diagnosis was KID syndrome.

Risk of malignancy assessment of the International System for Reporting Serous Fluid Cytopathology: Experience in a community hospital setting and comparison with other studies.

BACKGROUND: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) was published recently to provide standard reporting terminology for serous fluid. To date, several ISRSFC reclassification studies have reported a wide range of diagnostic category frequency and the associated risk of malignancy (ROM). Herein, the authors applied the ISRSFC to report pleural and peritoneal effusions retrospectively in a community hospital setting. METHODS: With Internal Review Board approval, 446 peritoneal effusion specimens and 299 pleural fluid specimens from 576 patients in three community hospitals over a 12-month period were reviewed and reclassified according to the ISRSFC. RESULTS: After reclassification, in pleural effusions, 18 (5.0%) were nondiagnostic (ND), 273 (76.0%) were negative for malignancy (NFM), 18 (5.0%) were atypia of undetermined significance (AUS), 6 (1.7%) were suspicious for malignancy (SFM), and 44 (12.3%) were malignant (MAL). In peritoneal effusions, after reclassification, 11 (5.5%) were ND, 168 (77.1%) were NFM, 9 (4.1%) were AUS, 2 (0.9%) were SFM, and 27 (12.4%) were MAL. The calculated ROM was 0.0% for ND, 1.8% for NFM, 37.5% for AUS, 83.3% for SFM, and 100.0% for MAL in peritoneal effusions; and the ROM was 8.3% for ND, 1.2% for NFM, 44.4% for AUS, and 100.0% for both SFM and MAL in pleural effusions. Further analysis demonstrated notable heterogeneity among published ISRSFC reclassification studies, although the overall ROMs did not differ significantly from the ISRSFC-determined ROMs (all p values were > .05 for mean ROM comparisons). CONCLUSIONS: The findings suggested the necessity for each laboratory to perform its own ROM analysis based on its statistics for ISRSFC-tiered classification terminology.

Study on the Microclimate Effect of Water Body Layout Factors on Campus Squares.

Quantifying the water layout factors in a campus square helps to lay out water bodies more scientifically and utilize the microclimate effect to alleviate the heat and humidity of campus squares in summer. The West Gate Square of Fujian Agriculture and Forestry University in China has been used as the primary theoretical model, and the landscape pattern index from landscape ecology has been used to quantify the scale, shape, and dispersion of water bodies. Consider the typical weather, the summer solstice, as the experiment time. The relationship between the water body layout factors and cooling effect, the humidification effect, and the wind speed is clarified from both temporal and spatial perspectives. The data were analyzed with ENVI-met and Arcgis software. Then, the optimum campus square water body layout mode was concluded. The results show that: (1) The scale, dispersion, and shape of the water body has a significant effect on the campus temperature and humidity, while the effect on wind speed is not significant. (2) From the cooling and humidifying effect, the ranking of the regulating ability of the water body layout factors is scale > shape > dispersion; the ranking of the influence range is shape > scale > dispersion. (3) When the boundary of the square is determined, the optimum water body layout mode is that the water body area accounts for 36% of the total square area. The shape of the water body is concentrated and not dispersed square. When the water body layout is determined, the optimum layout mode of the boundary is length:width = 1:2.