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The methodology of nanoarchitectonics is to construct functional materials using nanounits such as atoms, molecules, and nanoobjects, just like architecting buildings. Nanoarchitectonics pursues the ultimate concept of materials science through the integration of related fields. In this review paper, under the title of interface-interactive nanoarchitectonics, several examples of structure fabrication and function development at interfaces will be discussed, highlighting the importance of architecting materials with nanoscale considerations. Two sections provide some examples at the solid and liquid surfaces. In solid interfacial environments, molecular structures can be precisely observed and analyzed with theoretical calculations. Solid surfaces are a prime site for nanoarchitectonics at the molecular level. Nanoarchitectonics of solid surfaces has the potential to pave the way for cutting-edge functionality and science based on advanced observation and analysis. Liquid surfaces are more kinetic and dynamic than solid interfaces, and their high fluidity offers many possibilities for structure fabrications by nanoarchitectonics. The latter feature has advantages in terms of freedom of interaction and diversity of components, therefore, liquid surfaces may be more suitable environments for the development of functionalities. The final section then discusses what is needed for the future of material creation in nanoarchitectonics., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Hidradenitis suppurativa patients have an increased risk of developing cancer. This includes not only hematologic malignancies and solid tumors, but also cutaneous squamous cell carcinoma originating within the hidradenitis suppurativa lesions. The development of squamous cell carcinoma is most commonly associated with Caucasian men who smoke and have severe gluteal or perianal lesions of more than 25 years duration. Other factors that have occasionally been associated with hidradenitis suppurativa-related squamous cell carcinoma include treatment with a tumor necrosis factor-alpha inhibitor (such as infliximab and adalimumab), genodermatoses (such as keratitis-ichthyosis-deafness syndrome and Dowling-Degos disease), and paraneoplastic syndromes (such as hypercalcemia, hypercalcemia-leukocytosis, and paraneoplastic neuropathy). The tumor may demonstrate the presence of human papillomavirus; even after treatment, patients have a poor prognosis since cancer metastasis, or recurrence, or both commonly occurs. The potential role of human papillomavirus vaccination for cancer prevention and early treatment of squamous cell carcinoma with targeted therapy (with an epidermal growth factor inhibitor such as cetuximab) and/or checkpoint inhibitor immunotherapy (such as cemiplimab and pembrolizumab) remains to be determined. Rarely, hidradenitis suppurativa lesions have mimicked cutaneous metastases in patients with visceral malignancy by demonstrating an increased uptake of fluorine-18 fluorodeoxyglucose on positron emission tomography and/or computerized tomography scans. Also, both primary cancers (such as cutaneous squamous cell carcinoma and mucinous adenocarcinoma) and breast cancer skin metastases can masquerade as hidradenitis suppurativa lesions. Therefore, when a lesion is located at a current or prior site of hidradenitis suppurativa that is new or rapidly growing and/or does not respond to hidradenitis suppurativa-directed therapy, prompt evaluation to establish or exclude the diagnosis of cancer should be considered., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Acinic cell carcinoma (AciCC) is a rare clinical entity and a salivary gland malignancy. It is associated with wide histological variations in the cytomorphological patterns., Methods: Sixty cases diagnosed as AciCC from 2002 to 2023 were assessed for diverse cytomorphological patterns., Results: The mean age of patients at the time of diagnosis was 44.35±16.8 years ranging from 15 to 81 years. Females comprised 58.3% for a F: M ratio of 1.4:1. Fifty three cases (88.3%) occurred in the parotid gland, two cases in the nasal region (3.3%), and one case each in the soft plate and upper lip (1.7%). The location of the remaining three cases was not specified. The most common presenting complaint was a well-defined facial swelling associated with pain. The average tumor size was 3.8±1.9 cm. The most predominant architectural pattern was solid (83.3%) followed by microcystic (60%), then follicular (41.7%), papillary cystic (14.3%), and tubulocystic (28.6%), and AciCC with de-differentiation/high-grade transformation was reported in three cases (5%). In 83.3% of the cases (50 out of 60), we noticed a mixture of two or more growth patterns. Other degenerative changes included prominent lymphoid stroma, hemorrhage, and cystic change., Conclusion: Awareness and recognition of diverse cytomorphological patterns of AciCC, especially in institutions of a developing country where there is limited availability of highly specific and sensitive immunohistochemical stains or molecular diagnostics, are crucial and essential., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Aga Khan University Ethics Review Committe issued approval 2023-7495-27326. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Suleman et al.)

This article focuses on the area of software development for microcontrollers and details the implementation of modern programming practices and principles in embedded systems and IoT applications. This article explains how we implemented previously unimplemented principles and applied design patterns for quality software design on microcontrollers, which are currently only used for developing applications on the higher layers of the IoT reference model. A custom modular framework for microcontrollers is presented, based on applying SOLID principles and adapting design patterns specific to the microcontrollers' application development needs. The implemented framework enables independent communication between modules and flexible integration of hardware components. It is designed with platform independence in mind, contributing to its wide adaptability and ease of use in diverse development environments. By applying these technological approaches, we can create applications that are not only testable and extensible in terms of application logic but also allow for easy adaptation to changes in these hardware resources. Utilizing these capabilities represents an innovative approach to development for microcontrollers that fundamentally improves the long-term sustainability and scalability of applications.

This study employs response surface methodology and a central composite design (CCD) to optimize hydrothermal treatment (HTT) conditions for the valorization of food waste (FW). Lab-scale pressure reactor-based HTT processes are investigated to detect the effects of temperature (220-340 °C) and resident time (90-260 min) on elemental composition and fatty acid recovery in the hydrothermal liquid. Central to the study is the identification of temperature as the primary factor influencing food waste conversion during the HTT process, showcasing its impact on HTT product yields. The liquid fraction, rich in saturated fatty acids (SFA), demonstrates a temperature-dependent trend, with higher temperatures favoring SFA recovery. Specifically, HTT at 340 °C in 180 min exhibits the highest SFA percentages, reaching up to 52.5 wt%. The study establishes HTT as a promising avenue for nutrient recovery, with the liquid fraction yielding approximately 95% at optimized conditions. Furthermore, statistical analysis using response surface methodology predicts the optimal achievable yields for hydrochar and hydrothermal liquid at 6.15% and 93.85%, respectively, obtained at 320 °C for 200 min., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The conventional building drainage system was constructed based on the theory of two-phase flow involving water and air. However, the drainage system contained a more intricate three-phase flow, encompassing water, air, and solids, which was relatively overlooked in research. This study addressed the impact of solids on pressure fluctuations, air flow rates, and hydraulic jump fullness within the drainage system, considering three factors: the mass factor, cross-section factor, and viscosity. The investigation was conducted within a single-stack system using both experimental methods and CFD simulations. The findings revealed a positive correlation between both positive and negative pressures and above three factors. The mass factor and the cross-section factor had a more significant impact on the negative pressure of the system. The maximum growth rates of negative pressure extremes under different mass and cross-section factors reached 7.72 and 16.52%, respectively. In contrast, the viscosity of fecal sludge had a slightly higher effect on the positive pressure fluctuation of the drainage system, with the maximum growth rate of positive pressure extremes at 3.41%., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY-NC-ND 4.0), which permits copying and redistribution for non-commercial purposes with no derivatives, provided the original work is properly cited (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

We here report the formation of a turbid-gel phase in acrylic cuvettes upon exposure to pure Dimethyl Sulfoxide (DMSO) at room temperature. The observed phenomenon occurred over a 10 h to 14 h incubation in the presence of environmental oxygen. After the turbid gel was removed from the cuvette, it became a white solid exhibiting unique emission behavior. The formation of the turbid-gel phase was accelerated upon exposure to UV 295 LED pulses of light from 6 h to 8 h. Surprisingly, subsequent exposure of the white solid to a few microliters of pure DMSO and vortexing resulted in its transformation into a transparent gel state in just a few minutes, eventually acquiring transparent and liquid properties. Additionally, the white-solid phase can load other molecules, such as Resveratrol and Quercetin, leading to shifts in the respective emission spectra compared with the same molecule in liquid and pure DMSO. These novel findings highlight the interaction between UV photons, oxygen, DMSO and Acrylic, and potentially distort fluorescence spectroscopy experiments., (© 2024 IOP Publishing Ltd.)

Background: Non-predominant or even minimal micropapillary and/or solid (MP/S) subtypes have been reported to exert an unfavorable prognostic influence on surgically resected lung adenocarcinoma (ADC). Currently, there is a lack of evidence to demonstrate that high-grade pathological subtypes, including MP/S components, impact the prognosis of patients with surgically resected lung ADCs with ground-glass opacity (GGO). In this investigation, we explored the prognostic implications of minimal MP/S components in lung ADCs with GGO., Methods: A retrospective cohort study was conducted on 1,004 consecutive patients undergoing curative resection for pathologic stage (p-stage) I lung ADCs featuring GGO on computed tomography (CT) scans between January 2014 and December 2016. Tumors were categorized into MP/S positive (MP/S + ) group and MP/S negative (MP/S - ) group. MP/S + tumors were defined when MP/S subtypes constituted ≥1% of the entire tumor. The prognostic impact of MP/S subtypes was evaluated using Kaplan-Meier analysis, Cox proportional hazard model and restricted cubic spine (RCS) model., Results: A total of 86 (8.6%) cases with MP/S + tumors and 918 (91.4%) cases with MP/S - tumors were identified. The solid component tumor diameter and pathological invasive tumor size of MP/S + tumors were both significantly larger than that of MP/S - tumors (13.0 vs. 4.0 mm, P<0.001, and 18.0 vs. 10.0 mm, P<0.001, respectively). After a median follow-up of 7.3 years, the presence of MP/S components was significantly associated with decreased RFS (5-year RFS, MP/S + 88.3% vs. MP/S - 97.4%; P<0.001; HR =1.02). The presence of a histologic lepidic (Lep) component demonstrated a prognostic advantage in both MP/S - (5-year RFS, MP/S - Lep+ 98.0% vs. MP/S - Lep- 95.3%; P=0.01; HR =0.89) and MP/S + subgroups (5-year RFS, MP/S + Lep+ 93.4% vs. MP/S + Lep- 83.2%; P=0.10; HR =0.84). MP/S + components ≥5% were the only tumor-related factor that independently affected RFS [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.07-2.94] according to multivariate analysis. There was a progressively negative impact of the proportion of MP/S subtypes on RFS as illustrated by RCS model., Conclusions: The presence of MP/S patterns in stage I GGO-featured lung ADCs exhibit significant prognostic value and may have implications for tailored postoperative treatment and surveillance strategies, especially when the proportion exceeds 5% of the entire tumor., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-736/coif). B.Q. serves as an Associate Editor-in-Chief of Translational Lung Cancer Research from September 2023 to August 2024. The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Background: Identification of micropapillary and solid subtypes components in small-sized (≤ 2 cm) lung adenocarcinoma plays a crucial role in determining optimal surgical procedures. This study aims to propose a straightforward prediction method utilizing preoperative available indicators., Methods: From January 2019 to July 2022, 341 consecutive patients with small-sized lung adenocarcinoma who underwent curative resection in thoracic surgery department of Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The patients were divided into two groups based on whether solid or micropapillary components ≥ 5% or not (S/MP5+ and S/MP5-). Univariate analysis and multivariate logistic regression analysis were utilized to identify independent predictors of S/MP5+. Then a nomogram was constructed to intuitively show the results. Finally, the calibration curve with a 1000 bootstrap resampling and the receiver operating characteristic (ROC) curve were depicted to evaluate its performance., Results: According to postoperative pathological results, 79 (23.2%) patients were confirmed as S/MP5+ while 262 (76.8%) patients were S/MP5-. Based on multivariate analysis, maximum diameter (p = 0.010), consolidation tumor ratio (CTR) (p < 0.001) and systemic immune-inflammation index (SII) (p < 0.001) were identified as three independent risk factors and incorporated into the nomogram. The calibration curve showed good concordance between the predicted and actual probability of S/MP5+. Besides, the model showed certain discrimination, with an area under ROC curve of 0.893., Conclusions: The model constructed based on SII is a practical tool to predict high-grade subtypes components of small-sized lung adenocarcinoma preoperatively and contribute to determine the optimal surgical approach., (© 2024. The Author(s).)

Introduction: Although histological subtype in lung adenocarcinoma has been reported as a poor prognostic factor in several studies, its utility has not yet been revealed as an adaptation criterion of postoperative adjuvant chemotherapy., Methods: Four hundred ninety-four lung adenocarcinoma patients were enrolled in this retrospective study. A subanalysis was performed in 420 lung adenocarcinoma patients with pathological stage 0-I disease for risk factors of postoperative recurrence., Results: Maximum standardized uptake value (SUVmax) (p &lt; 0.01), pathological stage ≥II (p &lt; 0.04), and adjuvant chemotherapy (p &lt; 0.01) were risk factors for recurrence in the multivariate analysis, whereas histological subtype was not a significant factor for recurrence at all stages. In the subanalysis, univariate analysis showed that carcinoembryonic antigen expression (p &lt; 0.01), prognostic nutrition index (p = 0.03), SUVmax (p &lt; 0.01), lymphatic invasion (p &lt; 0.01), vascular invasion (p &lt; 0.01), grade 3-4 differentiation (p &lt; 0.01), pathological stage ≥IA3 (p &lt; 0.01), and histological subtype (p = 0.03) were significant risk factors of recurrence. SUVmax (p &lt; 0.01) was the only risk factor for recurrence in the multivariate analysis, whereas histological subtype was not (p = 0.07). Relapse-free survival (RFS) was significantly worse in the micropapillary- and solid-predominant subtype groups than in the other subtypes (p = 0.01). On the other hand, RFS with or without uracil-tegafur as adjuvant chemotherapy in lung micropapillary- or solid-predominant adenocarcinoma patients with pathological stage IA-IB disease was not significantly different., Conclusion: This study suggested that histological subtypes, such as micropapillary- or solid-predominant pattern, are risk factors for recurrence in pathological stage 0-I lung adenocarcinoma and may be necessary adjuvant chemotherapy instead of uracil-tegafur., (© 2023 S. Karger AG, Basel.)

To evaluate the outcomes of robot-assisted partial nephrectomy (RAPN) for solid and cystic renal tumors. We systematically searched the Cochrane Library, PubMed, EMBASE, and Scopus databases up to March 2023. Review Manager 5.4 performed a pooled analysis of the data for random effects. Besides, sensitivity and subgroup analyses to explore heterogeneity, Newcastle-Ottawa scale, and GRADE to evaluate study quality and level of evidence. Five observational studies comprising 1353 patients (Cystic tumor: 183; Solid tumor: 1083) were included in this study. Compared to solid masses, cystic masses were associated with fewer major complications (odds ratio [OR] = 2.2; 95% confidence intervals [CI] = 1.17 to 4.13; p = 0.01). Additionally, no significant differences were observed between the two groups in terms of operative time, warm ischemia time, blood loss, hospital stay, intraoperative complications, postoperative complications, transfusion rate, postoperative estimated glomerular filtration rate (eGFR), eGFR preservation, positive surgical margin (PSM), recurrence, overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS) and trifecta achievement. RAPN can be performed in cystic renal tumors with perioperative, functional, and oncologic outcomes like those achievable in solid tumors. However, our findings need further validation in a large-sample prospective randomized study., Competing Interests: Declaration of competing interest The authors declares that they have no conflict of interest. All participating authors have no declaration of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Supratentorial hemangioblastomas are rare, vascular lesions. The presence of peri-tumoral cysts and edema has meaningful clinical, diagnostic and therapeutic implications. Nevertheless, the pathogenesis of both cyst and edema formation is not fully understood. This study sought to determine if the radiologic phenotype of supratentorial hemangioblastoma is affected by the different cerebral arterial circulations. Review of the English-language literature from 1973 to 2023 yielded 53 cases of parenchymal supratentorial hemangioblastomas eligible for analysis. Patients were divided by the vascular territorial distribution of the lesions: anterior circulation (n = 36) or posterior circulation (n = 17), and the groups were compared for demographic, clinical, radiologic and molecular variables. Univariate analyses yielded a significant difference between the groups in five variables. Cystic changes and "classic" radiological phenotype were associated with hemangioblastomas of the posterior circulation (OR = 0.19, p = 0.045 and OR = 0.287, p = 0.048, respectively), while female gender, significant peritumoral edema and purely solid phenotype were associated with hemangioblastomas of the anterior circulation (OR = 3.384, p = 0.045 and OR = 5.25, p = 0.05 and OR = 14.0, p = 0.015; respectively). On multivariate analysis, solid phenotype and female gender remained significantly associated with the anterior circulation (OR = 36.04, p = 0.014 and OR = 4.45, p = 0.045). The incidence of von-Hippel Lindau disease was higher in the anterior-circulation group. Cystic tumors were present in all females in the posterior-circulation group compared to 43.4% in the anterior-circulation group (OR = 20.714, 95% CI 1.061 to 404.122; p = 0.045). Based on historical cases of supratentorial hemangioblastoma, this study shows that different tumor phenotypes are associated with the different cerebral circulations. Gender was also associated with differences in tumor distribution and radiologic phenotype. These novel data may improve our understanding of unique vascular diseases of the central nervous system., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Odontogenic tumors encompass a heterogeneous group of lesions that range from hamartomatous lesions to malignancy. Considerable variation in histologic presentation can mislead their accurate diagnosis and categorization. Ameloblastoma is generally well understood and is easy to diagnose but there has been a constant change in the classification systems ever since Broca classified odontogenic tumors in the year 1867. Over the years, it has been modified by the World Health Organization with many additions and omissions. This dynamic change is based on the result and conclusions of molecular and genetic studies with the last modification in 2017. Case Report: We present two cases of females aged 32 and 60 years who reported with facial swellings, revealed the presence of distinct histopathological findings and were diagnosed as ameloblastoma with dentinoid or adenoid ameloblastoma. Literature search revealed dearth of distinct forms of ameloblastoma that show the formation of duct like structures and dentinoid. Conclusion: It is interesting to highlight such cases as the biological behavior is still unexplored due to paucity of relevant studies and follow up of patients. Understanding the pathogenesis and the histopathological characteristics of the newer entities will enable the prompt diagnosis, treatment plan and expanding the spectrum of the lesions., Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03534-6., Competing Interests: Conflicts of interest/Competing Interests (include appropriate disclosures)NA., (© Association of Otolaryngologists of India 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.)

Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis.

A growing number of early-stage lung cancers presenting as malignant pulmonary nodules have been diagnosed because of the increased adoption of low-dose spiral computed tomography. But pure solid T1 lung cancer with ≤3 cm in the greatest dimension is not always at an early stage, despite its small size. This type of cancer can be highly aggressive and is associated with pathological involvement, metastasis, postoperative relapse, and even death. However, it is easily misdiagnosed or delay diagnosed in clinics and thus poses a serious threat to human health. The percentage of nodal or extrathoracic metastases has been reported to be >20% in T1 lung cancer. As such, understanding and identifying the aggressive characteristics of pure solid T1 lung cancer is crucial for prevention, diagnosis, and therapeutic strategies, and beneficial to improving the prognosis. With the widespread of lung cancer screening, these highly invasive pure solid T1 lung cancer will become the main advanced lung cancer in future. However, there is limited information regarding precision medicine on how to identify these "early-stage" aggressive lung cancers. To provide clinicians with new insights into early recognition and intervention of the highly invasive pure solid T1 lung cancer, this review summarizes its clinical characteristics, imaging, pathology, gene alterations, immune microenvironment, multi-omics, and current techniques for diagnosis and prediction., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)

Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare sarcoma typically exhibiting myxoid/reticular histology and NR4A3 translocation. However, morphologic variants and the relevance of non-EWSR1::NR4A3 fusions remain underexplored. Three challenging pan-Trk-expressing cases, featuring cellular to solid histology, were subjected to RNA exome sequencing (RES), unveiling different NR4A3-associated fusions. Alongside RES-analyzed cases, fluorescence in situ hybridization was performed to confirm 58 EMCs, with 48 available for pan-Trk immunostaining and KIT sequencing. Except for 1 (2%) NR4A3-rearranged EMC without identifiable partners, 46 (79%), 9 (16%), and 2 (3%) cases harbored EWSR1::NR4A3, TAF15::NR4A3, and TCF12::NR4A3 fusions, respectively. Five EWSR1::NR4A3-positive EMCs occurred in the subcutis (3) and bone (2). Besides 43 classical cases, there were 8 cellular, 4 rhabdoid/anaplastic, 2 solid, and 1 mixed tumor-like variants. Tumor cells were oval/spindle to pleomorphic and formed loose myxoid/reticular to compact sheet-like or fascicular patterns, imparting broad diagnostic considerations. RES showed upregulation of NTRK2/3, KIT, and INSM1. Moderate-to-strong immunoreactivities of pan-Trk, CD117, and INSM1 were present in 35.4%, 52.6%, and 54.6% of EMCs, respectively. KIT p. E554K mutation was detected in 2/48 cases. TAF15::NR4A3 was significantly associated with size >10 cm (78%, P = .025). Size >10 cm, moderate-to-severe nuclear pleomorphism, metastasis at presentation, TAF15::NR4A3 fusion, and the administration of chemotherapy portended shorter univariate disease-specific survival, whereas only size >10 cm (P = .004) and metastasis at presentation (P = .032) remained prognostically independent. Conclusively, EMC may manifest superficial or osseous lesions harboring EWSR1::NR4A3, underrecognized solid or anaplastic histology, and pan-Trk expression, posing tremendous challenges. Most TAF15::NR4A3-positive cases were >10 cm in size, ie, a crucial independent prognosticator, whereas pathogenic KIT mutation rarely occurred., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Solid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated., Methods: We conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center., Results: Along with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy., Conclusions: Compared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy., 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 © 2023 Li, Wang, Wang, Lv, Jin, Yi, Fu, Zhai, Xiao and Mao.)

Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Anoikis refers to apoptosis induced by the loss of contact with the extracellular matrix. Anoikis resistance is essential for metastasis. We have recently shown that it is possible to quantitatively evaluate putative anoikis resistant (AR) subpopulations in colorectal carcinoma (CRC). Abundance of these multi-cell structures is an independent marker of adverse prognosis. Here, we have quantified putative AR subpopulations in lymph node (LN) metastases of CRC and evaluated their prognostic value and relationship with the characteristics of primary tumors. A case series included 137 unselected CRC patients, 54 with LN metastases. Areal densities (structures/mm 2 ) of putative AR structures in primary tumors had been analyzed previously and now were determined from all nodal metastases (n = 183). Areal density of putative AR structures was higher in LN metastases than in primary tumors. Variation of the areal density within different LN metastases of a single patient was lower than between metastases of different patients. Abundance of putative AR structures in LN metastases was associated with shorter cancer specific survival (p = 0.013), and this association was independent of T and N stages. Abundance of putative AR structures in primary tumors and LN metastases had a cumulative adverse effect on prognosis. Enrichment of putative AR subpopulations in LN metastases suggest that in metastasis formation, there is a selection favoring cells capable of forming these structures. Higher intra-case constancy relative to inter-case variation suggests that such selection is stable in metastasis development. Our findings indirectly support the biological validity of our concept of putative AR structures., (© 2022. The Author(s).)

Andrographis paniculata is a well-known Asian medicinal plant with a major phytoconstituent of diterpene lactones, such as andrographolide, 14-deoxyandrographolide, and neoandrographolide. A World Health Organization (WHO) monograph on selected medicinal plants showed that A. paniculata extracts and its major diterpene lactones have promising anti-inflammatory, antidiabetic, antimalarial, anticancer, antifungal, antibacterial, antioxidant, and hypoglycemic activities. However, these active phytochemicals have poor water solubility and bioavailability when delivered in a conventional dosage form. These biological barriers can be mitigated if the extract or isolated compound are delivered as nanoparticles. This review discusses existing studies and marketed products of A. paniculata in solid, liquid, semi-solid, and gaseous dosage forms, either as an extract or isolated pure compounds, as well as their deficits in reaching maximum bioavailability. The pharmaceutics and pharmacological activity of A. paniculata as a nano-delivery system are also discussed.

Background: The histological subtype has been introduced in invasive lung adenocarcinoma. The predominant micropapillary and solid subtypes are categorized as high-grade patterns and provide a worse prognosis. However, the prognostic analysis of high-grade patterns has not previously been fully investigated. Thus, this study aimed to investigate the prognostic role of high-grade patterns in pathological stage I lung adenocarcinoma., Methods: Patients with stage I lung adenocarcinoma and micropapillary or solid components were reviewed. Clinicopathological features and clinical course were compared in these subtypes, and prognostic factors were analyzed in high-grade patterns., Results: The patients were classified into five groups based on the presence of micropapillary or solid subtypes, namely, micropapillary predominant, solid predominant, both nonpredominant subtypes, only minor micropapillary subtype, and only minor solid subtype present. Disease-free interval was significantly different, and the micropapillary predominant group showed worse disease-free interval (p = 0.001). Contrastingly, the solid predominant group showed significantly worse overall survival among high-grade patterns (p = 0.035). The multivariate analysis revealed an association between smoking, micropapillary predominant, blood vessel invasion, and visceral pleural invasion with recurrence and more association between solid predominant and visceral pleural invasion with overall survival., Conclusions: Clinical results were different in stage I high-grade adenocarcinoma. The predominant micropapillary subtype is the independent prognostic factor for recurrence. However, the solid subtype is the significant factor for overall survival. Furthermore, the predominant subtype is the most valuable and independent prognostic factor for predicting recurrence or survival., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Mass lesions in the retroperitoneal space may be primary or secondary. Primary retroperitoneal mass lesions are relatively uncommon as compared to pathology that arises secondarily from retroperitoneal organs. These may be solid or cystic lesions. The overlapping imaging features of various solid primary retroperitoneal tumors make the diagnosis difficult, and hence, histopathology remains the mainstay of diagnosis. This paper provides a brief review of the anatomy of the retroperitoneal space and provides an algorithmic approach based on cross-sectional imaging techniques to narrow down the differential diagnosis of solid primary retroperitoneal masses encountered in the adult population., Competing Interests: Conflicts of Interest None declared., (Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: We aimed to evaluate the impact of micropapillary and/or solid (MPSOL) components on survival and recurrence of patients with resected stage I lung adenocarcinoma (LUAD) according to the extent of surgery and completeness of lymph node assessment (LNA)., Methods: We retrospectively reviewed 1886 consecutive patients who underwent surgical resection for pathologic stage I LUAD between 2009 and 2014. The patients were classified by the presence (≥1%) of MPSOL into the MPSOL(+) (n = 489) and MPSOL(-) (n = 1397) group.We analyzed the outcomes according to the extent of surgery (sublobar resection [SR] vs. lobectomy) and the LNA (complete vs. incomplete). Complete LNA was defined as systematic LN dissection according to European Society of Thoracic Surgeons guideline., Results: In the MPSOL(+) patients, there was no significant difference in adjusted overall survival (OS), recurrence-free survival (RFS), and recurrence pattern between the lobectomy and SR group. Of note, patients with complete LNA had higher adjusted OS and RFS than those with incomplete LNA (aOS, 86.3% vs. 78%, p = 0.002; aRFS, 70% vs 63.1%, p = 0.06). In the MPSOL(-) patients, adjusted RFS of the SR group was better than the lobectomy group (95% vs. 90.5%, p = 0.021), although there was no difference in survival regarding to the LNA. Complete LNA was a favorable prognostic factor for RFS in the MPSOL(+) patients (HR = 0.463, 95% CI: 0.227-0.944, p = 0.034)., Conclusions: In MPSOL(+) patients, complete LN assessment affects the OS and RFS rather than the extent of lung resection. In patients with solid tumor or tumor>2 cm, a complete LN assessment would be required, even if sublobar resection is unavoidable., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: We aimed to develop a prognostic nomogram based on a new classification of combined micropapillary and solid components in pathological stage IA invasive lung adenocarcinoma (LUAD)., Methods: According to the total proportion of solid and micropapillary components (TPSM), the X-tile software was applied to classify patients into the following three groups: TPSM-low (TPSM-L), TPSM-middle (TPSM-M), and TPSM-high (TPSM-H). The postoperative survival was compared among the three groups. The multivariate Cox regression analysis was performed to identify independent prognostic factors for survival. According to these factors, a nomogram model was developed to provide a personalized prognostic evaluation., Results: A total of 595 patients with pathological stage IA invasive LUAD were included in our study. The 5-year disease-free survival and overall survival rates in patients with TPSM-H and TPSM-M were significantly lower than those with TPSM-L. The multivariate Cox regression analysis revealed that the TPSM classification was an independent prognostic factor for survival. According to TPSM classification, we developed a nomogram model which had good calibration and reliable discrimination ability to evaluate survival., Conclusions: The nomogram based on the combination of micropapillary and solid components has good prognostic value in predicting postoperative recurrence and survival of patients with pathological stage IA invasive LUAD., (© 2021 Wiley Periodicals LLC.)

Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension, various congenital diseases, idiopathic diseases, traumas, and other end-organ failure. While organ transplants have been monumental in treatment for these conditions, the ten year survival and long-term outcome for these patients is poor. After receiving the transplant, patients receive a multi-drug regimen of immunosuppressants. These drugs include cyclosporine, mTOR inhibitors, corticosteroids, and antibodies. Polyclonal antibodies, which inhibit the recipient's B lymphocytes, and antibodies targeting host cytokine inhibitors which prevent activation of B cells by T cells. Use of these drugs suppresses the immune system and increases the risk of opportunistic pathogen infections, tumors, and further damage to the transplanted organs and vasculature. Many regulatory mechanisms are present in organs to prevent the development of autoimmune disease, and Tregs are central to these mechanisms. Tregs secrete suppressive cytokines such as IL-10, TGF-B, and IL-35 to suppress T cells. Additionally, Tregs can bind to target cells to induce cell cycle arrest and apoptosis and can inhibit induction of IL-2 mRNA in target T cells. Tregs also interact with CTLA-4 and CD80/CD86 on antigen presenting cells (APCs) to prevent their binding to CD28 present on T cells. Due to their various immunosuppressive capabilities, Tregs are being examined as a possible treatment for patients that receive organ transplants to minimize rejection and prevent the negative outcomes. Several studies in which participants were given Tregs after undergoing organ transplantations were reviewed to determine the efficacy and safety of using Tregs in solid organ transplantation to prevent adverse outcomes., 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 © 2022 Juneja, Kazmi, Mellace and Saidi.)

Purpose: To compare the diagnostic accuracy and safety of computed tomography (CT)-guided core needle biopsy (CNB) between pulmonary ground-glass and solid nodules using propensity score matching (PSM) method and determine the relevant risk factors. Methods: This was a single-center retrospective cohort study using data from 665 patients who underwent CT-guided CNB of pulmonary nodules in our hospital between May 2019 and May 2021, including 39 ground-glass nodules (GGNs) and 626 solid nodules. We used a 1:4 PSM analysis to compared the diagnostic yields and complications rates of CT-guided CNB between 2 groups. Results: After PSM, 170 cases involved in the comparison (34 GGNs vs 136 solid nodules) were randomly matched (1:4) by patient demographics, clinical history, lesion characteristics, and procedure-related factors. There was no statistically significant difference in the diagnostic yields and complications rates between 2 groups. Significant pneumothorax incidence increase was noted at small lesion size, deep lesion location, and traversing interlobar fissure ( P  < .05). Post-biopsy hemorrhage was a protective factor for pneumothorax ( P  < .05). The size/proportion of consolidation of GGN did not influence the diagnostic accuracy and complication incidence ( P  > .05). Conclusions: The accuracy and safety of CT-guided CNB were comparable for ground-glass and solid nodules and the size/proportion of consolidation of GGN may be not a relevant risk factor. The biopsy should avoid traversing interlobar fissure as far as possible. Smaller lesion size and deeper lesion location may lead to higher pneumothorax rate and post-biopsy hemorrhage may be a protective factor for pneumothorax.

Background: Nodularity in thyroid tissue is extremely common. In Mexico, the only openly available treatment for benign cold thyroid nodules that cause compressive or cosmetic symptoms is surgery. This limitation in the availability of non-invasive treatments places an enormous strain on the State's health resources., Objective: To demonstrate the cost-minimization of percutaneous ethanol injection treatment (PEIT) against radiofrequency ablation (RFA) and laser ablation for the treatment of benign solid thyroid nodules., Method: Prospective, comparative, quasi-experimental, longitudinal study with external controls, non-randomized, historical, prolective and open. The significant difference in volume reduction was calculated by paired 2-tailed t-test. Validation was made to prove that the reduction in the final nodule volume was non-inferior to the gold standard. The cost-analysis study was carried out using the Montecarlo method., Results: 15 patients entered the study. The mean volume of the nodules was 14.46 ± 19 cc, with a final mean volume of 5.24 ± 8.44 cc, the average reduction percentage was 63 ± 17%. The cost per procedure was $ 18,807 mx, $ 16,300 mx, $ 9,248 mx and $ 1,615 for RFA, surgery, laser ablation and PEIT, respectively., Conclusions: The results of the study demonstrate the non-inferiority of the ablation of benign solid thyroid nodules with PEIT compared to laser and RFA, at a lower cost., (Copyright: © 2022 Permanyer.)

Purpose: To establish a non-invasive diagnostic model based on convolutional neural networks (CNNs) to distinguish benign from malignant lesions manifesting as a solid, indeterminate solitary pulmonary nodule (SPN) or mass (SPM) on computed tomography (CT)., Method: A total of 459 patients with solid indeterminate SPNs/SPMs on CT were ultimately included in this retrospective study and assigned to the train (n=366), validation (n=46), and test (n=47) sets. Histopathologic analysis was available for each patient. An end-to-end CNN model was proposed to predict the natural history of solid indeterminate SPN/SPMs on CT. Receiver operating characteristic curves were plotted to evaluate the predictive performance of the proposed CNN model. The accuracy, sensitivity, and specificity of diagnoses by radiologists alone were compared with those of diagnoses by radiologists by using the CNN model to assess its clinical utility., Results: For the CNN model, the AUC was 91% (95% confidence interval [CI]: 0.83-0.99) in the test set. The diagnostic accuracy of radiologists with the CNN model was significantly higher than that without the model (89 vs. 66%, P<0.01; 87 vs. 61%, P<0.01; 85 vs. 66%, P=0.03, in the train, validation, and test sets, respectively). In addition, while there was a slight increase in sensitivity, the specificity improved significantly by an average of 42% (the corresponding improvements in the three sets ranged from 43, 33, and 42% to 82, 78, and 84%, respectively; P<0.01 for all)., Conclusion: The CNN model could be a valuable tool in non-invasively differentiating benign from malignant lesions manifesting as solid, indeterminate SPNs/SPMs on CT., 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 © 2021 Sun, Chen, Zhao, Wang, Yang, Wang, Wu and Sun.)

Objectives: Micropapillary (MIP) and solid (SOL) subtypes of early-stage lung adenocarcinomas are associated with lymph node metastasis and local recurrence after limited resection. Preoperative identification of these components may influence the decisions of treatment strategy, additional lymph node evaluation, indication for limited resection, and extent of lymph node dissection. However, conventional biopsy specimens are insufficient for identifying these subtypes, especially MIP components. Cryobiopsy can collect larger tissue samples with fewer crush artifacts than conventional forceps biopsy, which would be helpful for detecting MIP/SOL components. Thus, this study aimed to analyze the feasibility of using cryobiopsy for MIP/SOL subtype detection., Material and Methods: Consecutive patients who underwent surgery for clinical IA lung cancer following a preoperative diagnosis of adenocarcinoma by cryobiopsy at our institution between October 2017 and July 2019 were retrospectively examined. The concordance rate of MIP/SOL subtypes between the specimens obtained by cryobiopsy and surgery was investigated., Results: In total, 115 patients were evaluated. There were 26 (22.6%) and 14 (12.2%) patients with MIP and SOL subtypes, respectively. For concordance of MIP/SOL subtypes, the sensitivity was 65.7% (95% confidence interval [CI]: 57.7-65.7%). For the primary or secondary predominant patterns, a more satisfactory concordance rate of 72.2% (95% CI: 52.6-86.2%) was obtained. On assessing each subtype, high sensitivity was noted in SOL-predominant patterns (85.7%, 95% CI: 56.5%-96.0%) and MIP-secondary predominant patterns (83.3%, 95% CI: 45.8-97.0%). However, SOL-secondary predominant patterns revealed low sensitivity (0%, 95% CI, 0-38.2%). Overall, the MIP subtypes had higher sensitivity than the SOL subtypes (65.4% vs. 50.0%)., Conclusion: Cryobiopsy could be reliable for identifying MIP/SOL components, especially the MIP component, in clinical stage IA adenocarcinomas., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

Inhibin-positive hepatic carcinoma is a rare primary liver neoplasm that resembles sex cord-stromal tumor and thyroid follicular tumors. The term "cholangioblastic variant of intrahepatic cholangiocarcinoma" has been proposed. This study describes the clinicopathologic, immunophenotypic, and molecular features of a small series (n = 6) of this rare tumor. Albumin in situ hybridization (ISH) and capture-based next-generation sequencing (NGS) were also performed. All tumors occurred in young women (mean age 32.5 years, range 19-44 years) as a solitary large mass (mean 15.8 cm, range 6.9-23.5 cm). All tumors showed a highly distinctive morphology with sheets and large nests of tumor cells alternating with tubular and cystic areas imparting a sex cord-like or thyroid follicle-like morphology. Cytologic atypia was mild, and mitotic activity was low. All cases were positive for inhibin, as well as pancytokeratin, CK7, CK19, and albumin ISH. Synaptophysin and chromogranin showed focal or patchy staining, whereas INSM1 was negative. Markers for hepatocellular differentiation, thyroid origin, and sex cord-stromal tumor were negative. There were no recurrent genomic changes based on capture-based NGS of ∼500 cancer genes. Recurrence and/or metastasis was seen in three (50%) cases (follow-up time range for all cases: 5 months to 2 years). In conclusion, this series describes the distinctive morphology, immunophenotypic features, and diffuse albumin staining in six cases of a rare inhibin-positive primary liver carcinoma that runs an aggressive course similar to intrahepatic cholangiocarcinoma. Genomic changes typical of cholangiocarcinoma or hepatocellular carcinoma were not identified, and there were no recurrent genetic abnormalities. We propose the term "solid-tubulocystic variant of intrahepatic cholangiocarcinoma" to reflect the spectrum of morphologic patterns observed in this tumor., (Copyright © 2021. Published by Elsevier Inc.)

Background/aim: Investigation of the influence of different ultra-low dose computed tomography (ULDCT) protocols on the detection of solid and subsolid nodules in a phantom study., Patients and Methods: A chest phantom with pulmonary nodules was scanned with different CT protocols ranging from ultra-low dose settings with spectral shaping to a standard low dose lung cancer screening protocol. Image analysis was performed with different reconstruction algorithms and dedicated computer aided detection (CAD), which was compared to manual readout., Results: The highest sensitivity rates (83%) were achieved for the 90 mAs and 120 mAs protocols when reconstructed with ADMIRE 3 or 5 and manual readout. The only statistically significant difference was found for subsolid nodules with preference of manual readout compared to CAD (p<0.05). Dose levels for the mAs settings ranged from 0.029 to 0.2 mSv., Conclusion: Reliable detectability rates for solid nodules were achieved; CAD software did not prove reliable for subsolid nodules., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The COVID-19 pandemic had a major impact on life in 2020 and 2021. One method of transmission occurs when the causative virus, SARS-CoV-2, contaminates solids. Understanding and controlling the interaction with solids is thus potentially important for limiting the spread of the disease. We review work that describes the prevalence of the virus on common objects, the longevity of the virus on solids, and surface coatings that are designed to inactivate the virus. Engineered coatings have already succeeded in producing a large reduction in viral infectivity from surfaces. We also review work describing inactivation on facemasks and clothing and discuss probable mechanisms of inactivation of the virus at surfaces., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: William Ducker is a part owner of a company that plans to make surface coatings., (© 2021 Elsevier Ltd. All rights reserved.)

Chemically defined media are reconstituted batchwise and stored in hold tanks until use. To avoid large hold tanks and batchwise production of media, we developed continuous on-demand reconstitutions directly from solids consisting of a hopper and a screw conveyor capable of feeding dry powdered media with the required precision ±5% at low dosing rates of 0.171 g min -1 . A commercially available dry powdered cell culture medium was continuously fed over a duration of 12 h into a mixer which was connected to a UV-cell for monitoring and the media were compared to a batchwise production. A comparable amino acid, carbohydrate, and osmolality profile to a batchwise reconstitution could be obtained. Cell cultivation showed comparable performance of batch and continuous reconstitution for two CHO cell lines producing the antibodies adalimumab and trastuzumab on a small and benchtop scale. In-depth analysis of the produced antibodies showed the same glycosylation pattern, other posttranslational profiles such as methionine oxidation and deamidation compared to batchwise reconstitution. Therefore, we conclude a continuous reconstitution of the medium results in the same quality of the product. A continuous on-demand media reconstitution will impact the supply chain and significantly reduce the floor space necessary for preparation and storage., (© 2021 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Solid tumors adopt multiple mechanisms to grow, evade immune responses, and to withstand therapeutic approaches. A major breakthrough in the armamentarium of anti-cancer agents has been the introduction of monoclonal antibodies (mAbs), able to inhibit aberrantly activated pathways and/or to unleash antigen (Ag)-specific immune responses. Nonetheless, mAb-mediated targeted pressure often fails due to escape mechanisms, mainly Ag loss/downregulation, ultimately providing therapy resistance. Hence, in order to target multiple Ag at the same time, and to facilitate cancer-immune cells interactions, bispecific antibodies (bsAbs) have been developed and are being tested in clinical trials, yielding variable safety/efficacy results based on target selection and their structure. While in hematologic cancers the bsAb blinatumomab recently reached the Food and Drug Administration (FDA)-approval for B Cell Acute Lymphoblastic Leukemia, bsAbs use in solid tumors faces considerable challenges, such as target Ag selection, biodistribution, and the presence of an immune-suppressive tumor microenvironment (TME). This review will focus on the state-of-the art, the design, and the exploitation of bsAbs against solid malignancies, delineating their mechanisms of action, major pitfalls, and future directions.

Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1 -deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.

The COVID-19 pandemic has been a disruptive event for cancer patients, especially those with haematological malignancies (HM). They may experience a more severe clinical course due to impaired immune responses. This multi-center retrospective UK audit identified cancer patients who had SARS-CoV-2 infection between 1 March and 10 June 2020 and collected data pertaining to cancer history, COVID-19 presentation and outcomes. In total, 179 patients were identified with a median age of 72 (IQR 61, 81) and follow-up of 44 days (IQR 42, 45). Forty-one percent were female and the overall mortality was 37%. Twenty-nine percent had HM and of these, those treated with chemotherapy in the preceding 28 days to COVID-19 diagnosis had worse outcome compared with solid malignancy (SM): 62% versus 19% died [HR 8.33 (95% CI, 2.56-25), p  < 0.001]. Definite or probable nosocomial SARS-CoV-2 transmission accounted for 16% of cases and was associated with increased risk of death (HR 2.47, 95% CI 1.43-4.29, p  = 0.001). Patients with haematological malignancies and those who acquire nosocomial transmission are at increased risk of death. Therefore, there is an urgent need to reassess shielding advice, reinforce stringent infection control, and ensure regular patient and staff testing to prevent nosocomial transmission.

Pulmonary nodules are the most common incidental finding in the chest, particularly on computed tomographs that include a portion or all of the chest, and may be encountered more frequently with increasing utilization of cross-sectional imaging. Established guidelines address the reporting and management of incidental pulmonary nodules, both solid and subsolid, synthesizing nodule and patient features to distinguish benign nodules from those of potential clinical consequence. Standard nodule assessment is essential for the accurate reporting of nodule size, attenuation, and morphology, all features with varying risk implications and thus management recommendations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aquaculture industry has become increasingly important and is rapidly growing in terms of providing a protein food source for human consumption. With the increase in the global population, demand for aquaculture is high and is estimated to reach 62% of the total global production by 2030. In 2018, it was reported that the demand for aquaculture was 46% of the total production, and with the current positive trends, it may be possible to increase tremendously in the coming years. China is still one of the main players in global aquaculture production. Due to high demand, aquaculture production generates large volumes of effluent, posing a great danger to the environment. Aquaculture effluent comprises solid waste and dissolved constituents, including nutrients and contaminants of emerging concern, thereby bringing detrimental impacts such as eutrophication, chemical toxicity, and food insecurity. Waste can be removed through culture systems, constructed wetlands, biofloc, and other treatment technologies. Some methods have the potential to be applied as zero-waste discharge treatment. Thus, this article analyses the supply and demand for aquaculture products, the best practices adopted in the aquaculture industry, effluent characteristics, current issues, and effluent treatment technology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Wastewater is a pooled sampling instrument that may provide rapid and even early disease signals in the surveillance of COVID-19 disease at the community level, yet the fine-scale temporal dynamics of SARS-CoV-2 RNA in wastewater remains poorly understood. This study tracked the daily dynamics of SARS-CoV-2 RNA in the wastewater from two wastewater treatment plants (WWTPs) in Honolulu during a rapidly expanding COVID-19 outbreak and a responding four-week lockdown that resulted in a rapid decrease of daily clinical COVID-19 new cases. The wastewater SARS-CoV-2 RNA concentration from both WWTPs, as measured by three quantification assays (N1, N2, and E), exhibited both significant inter-day fluctuations (10 1.2 -10 5.1 gene copies or GC/L in wastewater liquid fractions, or 10 1.4 -10 6.2 GC/g in solid fractions) and an overall downward trend over the lockdown period. Strong and significant correlation was observed in measured SARS-CoV-2 RNA concentrations between the solid and liquid wastewater fractions, with the solid fraction containing majority (82.5%-92.5%) of the SARS-CoV-2 RNA mass and the solid-liquid SARS-CoV-2 RNA concentration ratios ranging from 10 3.6 to 10 4.3 mL/g. The measured wastewater SARS-CoV-2 RNA concentration was normalized by three endogenous fecal RNA viruses (F + RNA coliphages Group II and III, and pepper mild mottle virus) to account for variations that may occur during the multi-step wastewater processing and molecular quantification, and the normalized abundance also exhibited similar daily fluctuations and overall downward trend over the sampling period., Competing Interests: Declaration of Competing Interest The authors declare no competing interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: High-grade patterns (micropapillary/solid/complex gland) are associated with a higher recurrence rate and shorter disease-free survival. Thus far, it remains unclear whether the efficacy of first-line anticancer therapy is different from that of the other adenocarcinoma subgroups for patients with high-grade patterns. The study aimed to investigate the association between an adenocarcinoma with high-grade patterns with the outcomes of first-line treatment in patients with lung cancer., Patients and Methods: Patients with a high-grade pattern adenocarcinoma (more than 20% of micropapillary/solid components/complex glandular patterns) were retrospectively analyzed between June 2015 and June 2017. Patients' clinical characteristics and treatment outcomes were compared with those of the remaining control adenocarcinoma subgroups., Results: In total, 239 patients with adenocarcinoma, including 115 (48.1%) high-grade patterns and 124 (51.9%) control groups, were enrolled. Patients' clinical characteristics such as age, sex, smoking status, and stage were similar between the two groups. Among them, 108 patients received first-line chemotherapy, and 131 received epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). In the chemotherapy group, adenocarcinoma of high-grade patterns had a significantly lower objective response rate (ORR; 15.6% vs 36.4%, P=0.045), shorter progression-free survival (PFS; median 4.1 vs 5.4 months, P=0.007) and overall survival (OS, median 19.6 vs 23.8 months, P=0.048) compared with the control group. As for these treated with EGFR-TKIs, a similar ORR (70.7% vs 72.1%, P=0.703), PFS (median 11.3 vs 13.9 months, P=0.065) and OS (median 34.1 vs 29.6%, p=0.575) were observed between these two groups., Conclusion: An adenocarcinoma with high-grade patterns is associated with inferior outcomes to first-line chemotherapy in relapsed lung cancer. Patients who received chemotherapy had a significantly shorter PFS and OS and lower ORR than control subjects, while there was no difference in the EGFR-TKI cohort. This study is the first to report the distribution of adenocarcinoma with high-grade patterns., Competing Interests: The authors report no conflicts of interest or financial interest in this work., (© 2021 Yu et al.)

Background and Aim: Variations in the Chicago 3.0 normative metrics may exist with different postures and with different provocative swallow materials in a healthy Asian population., Method: Eligible healthy Malay volunteers were invited to undergo the high-resolution esophageal manometry (inSIGHT Ultima, Diversatek Healthcare, Milwaukee, WI, USA). In recumbent and standing positions, test swallows were performed using liquid, viscous, and solid materials. Metrics including integrated relaxation pressure 4 s (IRP-4 s, mmHg), distal contractile integral (DCI, mmHg s cm), distal latency (DL, s), and peristaltic break (PB, cm) were reported in median and 95th percentile., Results: Fifty of 57 screened participants were recruited, and 586 saline, 265 viscous, and 261 solid swallows were analyzed. Per-patient wise, in the recumbent position, 95th percentile for IRP-4 s, DCI, DL, and PB were 16.5 mmHg, 2431 mmHg s cm, 8.5 s, and 7.2 cm, respectively. We observed that with each posture, the use of viscous swallows led to changes in DL, but the use of solid swallows led to more changes in the metrics including DCI and length of PB. Compared with a recumbent posture, anupright posture led to lower IRP-4 s and DCI values. Both per-patient analysis and per-swallow analyses yielded almost similar results when comparing the different postures and types of swallows. No major motility disorders were observed in this cohort of asymptomatic population. However, more motility disorders were reported in the upright position., Conclusions: Variations in metrics can be observed in different postures and with different provocative swallow materials in a healthy population. The normative Chicago 3.0 metrics are also determined for the Malay population., (© 2020 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Tumor lysis syndrome, an oncological emergency, is characterized by laboratory parameters such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, as well as renal injury with an elevated creatinine. Tumor lysis syndrome is seen in patients with aggressive malignancies and high tumor burden. More frequently, it occurs in individuals with hematologic malignancies such as high-grade lymphomas (such as Burkitt lymphoma) and leukemia (such as acute lymphocytic leukemia). It also, albeit less commonly, can be seen in patients with widespread solid tumors that are rapidly proliferating and are markedly sensitivity to antineoplastic therapy. Tumor lysis syndrome is usually preceded by cancer-directed therapy; however, the syndrome can present spontaneously prior to the individual receiving malignancy-directed treatment. We reported a man with metastatic salivary duct carcinoma who had cutaneous metastases that presented as carcinoma hemorrhagiectoides. Microscopic examination demonstrated that the metastatic tumor cells had infiltrated and replaced the entire dermis. After the patient received his first dose of antineoplastic therapy, he had an excellent response and the cutaneous metastases developed into ulcers; we hypothesize that most of the dermis, which had been replaced by tumor cells, disappeared as a result of the therapeutic response, and the overlying epidermis became necrotic and shed, leaving an ulcer. His dramatic response to treatment prompted us to propose a new classification of tumor lysis syndrome, which should include the systemic form of the condition as well as the new variant: cutaneous tumor lysis syndrome. We anticipate that, with improvement in targeted therapies, there may be an increase in therapy-associated cutaneous tumor lysis syndrome., Competing Interests: Funded in part by the Joan and Irwin Jacobs Fund and by the National Cancer Institute grant P30 CA016672 (RK)., (Copyright © 2021, Cohen et al.)

Smoothies are a popular breakfast option. However, liquids may evoke weaker satiation than nutritionally comparable semi-solid and solid foods. This study examined consumption of cereal and milk (CM) or a nutritionally comparable fruit smoothie (FS) for breakfast on subsequent dietary behaviours, in a controlled laboratory setting. Twenty-five participants (age 25 ± 6 y) completed three trials, receiving either CM or FS for breakfast. Afterwards, participants remained isolated for 4 h with ad libitum access to foods/beverages. A repeat trial (CM or FS) allowed exploration of normal variability. Post-breakfast energy intake (EI) (CM = 1465(2436) vs. FS = 1787(3190) kJ, Median (IQR), p  = 0.099), time to intake of next food/fluid (meal latency) (CM = 146(97) vs. FS = 180(100) min, p  = 0.127), and subjective hunger, desire to eat, fullness and thirst ratings were similar between conditions ( p's  > 0.05). The mean coefficient of variation for EI and meal latency were 41% and 21%, respectively. Consumption of a FS does not negatively impact acute EI and meal latency.

Background: Posterior fossa hemangioblastomas usually consist of a small solid nodule with a large cyst, while more rarely they present as a large solid mass with a small or absent cyst, which can be surgically challenging. We sought to investigate the potential existence of multiple distinct hemangioblastoma populations using tumor volumetric data as an indicator., Methods: We conducted a retrospective review of surgically treated hemangioblastomas between 2005 and 2019 in our unit, including clinical notes, preoperative magnetic resonance imaging volumetric analysis of the solid component of the tumor, and pathology. Finite Gaussian mixture modeling was applied on the solid component volume dataset to identify potential underlying Gaussian distributions with their associated characteristics. Nonparametric Mann-Whitney U tests were used to investigate significance of differences (P < 0.05) in solid component volume and different variables (Von Hippel-Lindau disease, extent of resection, outcome)., Results: A total of 68 consecutive patients were included. Solid component volumes followed a multimodal distribution (median = 1287 mm 3 , interquartile range of 3428 mm 3 ). The best-fit finite Gaussian mixture modeling model identified 3 statistically significant different (P = 0.001) potential mixture components: X 1 (219 ± 187 mm 3 ) , X 2 (2686 ± 1299 mm 3 ), and X 3 (10,800 ± 5514 mm 3 ). The second-best model detected 2 significantly different (P = 9.99e -08 ) mixture components Y 1 (222 ± 189 mm 3 ) and Y 2 (5391 ± 5094 mm 3 ). A significant difference in solid component volume was found between patients with favorable and unfavorable outcome (P = 0.002)., Conclusions: This study has shown preliminary evidence that large solid hemangioblastomas may constitute a completely distinct population, rather than a variant of one large group of hemangioblastomas., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70 years in the United States. Early immunosuppression and targets for allograft success were measured by incidence and severity of allograft rejection and 1-year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under- and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long-term outcomes during the next era of immunosuppression, which will move from universal protocols to patient-specific optimization., (© 2020 Pharmacotherapy Publications, Inc.)

Background: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA., Methods: We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP-., Results: The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP-; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA., Conclusions: The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed., Key Points: Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma., What This Study Adds: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)