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The article discusses the emergence and evolution of an anti-war movement that gained momentum in 2023, particularly focusing on protests against the Gaza bloodbath and US foreign policy decisions. It highlights the shift in activism among younger generations, critiquing the concept of "woke" culture and its limitations. The text emphasizes the importance of challenging the culture of silence surrounding political issues and calls for a reevaluation of progressive movements in response to global conflicts. [Extracted from the article]

Supplemental Digital Content is Available in the Text.Malignant proliferating pilar tumors (MPPTs) are rare, unique cutaneous adnexal tumors. Sarcomatous transformation in MPPTs is even rarer (4 previous cases reported). Here, we report an extraordinary case of a MPPT with sarcomatous transformation occurring on the scalp of a 63-year-old man with an in-depth molecular profile along with histologic, immunohistochemical, and follow-up data. Shared mutations in the epithelial and sarcomatous components included a loss-of-function TP53mutation. An inactivating TP53mutation was only identified in the epithelial component, and an inactivating CDKN2Amutation was only identified in the sarcomatous component. Copy number variations previously reported in MPPT were also identified, including 6p21.1 loss, 6q arm loss, and 15q21.1-q26.3 gain [epithelial], and 6p22.2-p22.3 loss [sarcoma]. Histologically, the tumor demonstrated juxtaposed areas of proliferating pilar tumor, carcinoma with clear cell change, and sarcomatous areas that did not stain for AE1/AE3, p40, CD34, S100 protein, and smooth muscle actin  by immunohistochemistry. The patient is alive at 2 years without evidence of recurrence or metastasis.

Anaplastic lymphoma kinase(ALK) rearrangements drive most examples of epithelioid fibrous histiocytoma (EFH) and have been reported in an emerging family of receptor tyrosine kinase (RTK) fusion-positive mesenchymal neoplasms, including superficial ones described under the rubric of “superficial ALK-rearranged myxoid spindle cell neoplasm” (SAMS). Here, we describe 35 superficial tumors with SAMS morphology, which occurred in 18 females (51%) and 17 males at a median age at presentation of 39 years (range: 6 to 82 y). Most tumors occurred on the lower extremity (25 tumors; 71%), followed by upper extremity (5; 14%), trunk (3; 9%), and face (2; 6%). Nine tumors were reported to have grown slowly before presentation, including >10 years in 2 cases. Tumors occurred primarily in the dermis (32 tumors; 91%) or subcutis (3; 9%); 8 dermal tumors extended into the subcutis. Median tumor size was 1.3 cm (range: 0.5 to 8.0 cm). Clinical follow-up was available for 12 patients (34%; range: 2 mo to 21 y; median: 2.7 y), none of whom experienced metastasis. One incompletely resected tumor recurred locally at 19 months, and no other patients experienced recurrence. Histologically, tumors were characterized by bland spindle-to-ovoid cells showing whorled growth and myxoid-to-collagenous stroma. Recurrent features included an epidermal collarette (19/30; 63%), perivascular hyalinization (20/35; 57%), amianthoid collagen (14/35; 40%), and metaplastic ossification (2/35; 6%). Immunohistochemistry (IHC) demonstrated expression of ALK (24/31; 77%), CD34 (15/21; 71%), EMA (17/28; 61%), and S-100 (9/32; 28%). Eleven tumors showed hybrid morphologic features between EFH and SAMS; 9 of them (82%) showed cytomorphology typical of EFH but with whorled growth, myxoid stroma, and/or regions of spindle cell morphology. Two hybrid tumors showed sharp transitions between a region characteristic of EFH and a region characteristic of SAMS, with a concomitant sharp transition in EMA, CD34, and S-100 expression by IHC. Sequencing revealed ALKfusions in 15 of 19 tumors: 2 each with fusion partners FLNA, SQSTM1, and VCL, and 1 each with COL1A2, DCTN1, EML4, FXR1, MPRIP, PLEKHH2, PRKAR1A, SPECC1L, and TLN2. Thirteen of 14 ALK-rearranged tumors expressed ALK by IHC. Three tumors negative for ALKfusions instead harbored alternate RTK fusions (NCOA4::RET, TRIM27::RET, and VIM::NTRK3), and 1 tumor was negative for RTK alterations. CDKN2A/Bdeletions were found in 2 tumors with ALKfusions and both tumors with RETfusions. SAMS is on a morphologic and molecular genetic spectrum with EFH, with a similar body site distribution, frequent clinical presentation as an exophytic skin tumor, and invariably benign outcomes; we conclude that SAMS should be considered a histologic variant of EFH. Some morphologically typical examples harbor alternate RETand NTRK3fusions, such that SAMS is not an appropriate designation for this morphologic class; instead, to highlight the clinicopathologic similarities to EFH, we propose the diagnostic term “myxoid spindle cell variant of epithelioid fibrous histiocytoma.”

Purpose of Review: This review examines best practices to ensure patient and clinician safety when performing inpatient dermatology consults. Recent Findings: Inpatient settings may not be optimized for dermatologic procedures and workflows, leading to unique challenges in ensuring patient safety. During consultations, dermatologists should focus on procedural safety in the inpatient setting, communicating clearly with the primary team, and supporting the transition from inpatient to outpatient care. Summary: Best practices emphasize standardization, clear communication, and workflow optimization to minimize safety risks during inpatient dermatology consultations. Dermatologists providing consultations in the inpatient setting should focus on patient and occupational safety during the consultation, particularly biopsies and procedures; optimize workflows for processing of dermatology specimens; and clearly communicate results and management recommendations. During the consultation, dermatologists should establish clear communication with both the primary team and patient to ensure proper implementation of the care plan and timely follow-up after discharge.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach. To develop consensus clinical practice recommendations, we performed a Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), non-transplant hematology/oncology (n = 8), and radiation oncology (n = 5) from across the United States. Consensus required agreement of ≥75% of participants. Sixteen consensus statements were generated on four topics: (1) criteria for referral for consideration for allo-HCT, (2) allo-HCT preparative regimens and procedures (3) disease status at the time of allo-HCT, and (4) multidisciplinary management in the pre- and post-transplant settings. These clinical practice guidelines provide a framework for decision-making regarding allo-HCT for MF/SS and highlight areas for future prospective investigation.

In an era marked by a growing demand for sustainable and high-performance materials, the convergence of additive manufacturing (AM), also known as 3D printing, and the thermal treatment, or pyrolysis, of polymers to form high surface area hierarchically structured carbon materials stands poised to catalyze transformative advancements across a spectrum of electrification and energy storage applications. Designing 3D printed polymers using low-cost resins specifically for conversion to high performance carbon structures via post-printing thermal treatments overcomes the challenges of 3D printing pure carbon directly due to the inability of pure carbon to be polymerized, melted, or sintered under ambient conditions. In this perspective, we outline the current state of AM methods that have been used in combination with pyrolysis to generate 3D carbon structures and highlight promising systems to explore further. As part of this endeavor, we discuss the effects of 3D printed polymer chemistry composition, additives, and pyrolysis conditions on resulting 3D pyrolytic carbon properties. Furthermore, we demonstrate the viability of combining continuous liquid interface production (CLIP) vat photopolymerization with pyrolysis as a promising avenue for producing 3D pyrolytic carbon lattice structures with 15 μm feature resolution, paving way for 3D carbon-based sustainable energy applications.

This article examines the rise of Javier Milei, a political figure in Argentina who has gained popularity among his supporters. Milei is seen as a messianic figure and a folk-hero, particularly in light of the country's increasing hunger and economic stagnation. The article delves into the failures of previous administrations and intellectuals in addressing these issues, and how Milei has capitalized on popular discontent. It also explores the influence of feminism and identity politics on Argentina's political landscape. Overall, the article provides an analysis of the political climate in Argentina and the factors contributing to Milei's rise. The author of the article is a writer who has published political articles in various publications and has also written poetry and performed at poetry festivals. [Extracted from the article]

Irritable bowel syndrome is a gastrointestinal disorder that affects 15%–20% of the US population. Its symptoms can have negative effects on a person's quality of life, and its treatment can be associated with high medical costs. An emerging area of irritable bowel syndrome research concerns the relationship between this condition and the gut microbiome. The purpose of this article is not only to review irritable bowel syndrome, and the role that the microbiome can play in its symptoms, but also to examine new emerging pathways that could blaze the trail for more individualized treatments. If equipped with this knowledge, gastrointestinal nurses and providers of care can be better prepared to help patients with irritable bowel syndrome in order to manage symptoms and improve their quality of life.

IMPORTANCE: In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities. OBJECTIVE: To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts. Median follow-up was 9.5 months (range, 1.2-40.5). EXPOSURES: Cemiplimab or pembrolizumab. MAIN OUTCOMES AND MEASURES: Primary outcomes were radiologic and pathologic response rates. Secondary outcomes were 1-year recurrence-free survival, progression-free survival, disease-specific survival, and overall survival. RESULTS: This cohort study included 27 patients (including 9 patients [33.3%] with a history of lymphoma). Most patients were male (18 of 27 [66.7%]), with a median age of 72 years (range, 53-87 years). Most primary tumors were located on the head/neck (21 of 27 [77.8%]). There were no unexpected delays in surgery. The median number of doses before surgery was 3.5 (range, 1.0-10.0). Five patients (18.5%) ultimately declined to undergo planned surgery due to clinical responses or stability, and 1 (3.7%) did not undergo surgery due to progressive disease. The overall pathologic response rate (pathological complete response [pCR] or major pathological response) was 47.4% (9 of 19), and the overall radiologic response rate (radiologic complete response or partial response) was 50.0% (8 of 16). The pCR rate (7 of 19 [36.8%]) was higher than the radiologic complete response rate (2 of 16 [12.5%]). The pCR rate among patients with cSCC and concomitant lymphoma was 25.0%. The 1-year recurrence-free survival rate was 90.9% (95% CI, 50.8%-98.7%), progression-free survival was 83.3% (95% CI, 27.3%-97.5%), disease-specific survival was 91.7% (95% CI, 53.9%-98.8%), and overall survival was 84.6% (95% CI, 51.2%-95.9%). CONCLUSIONS AND RELEVANCE: The results of this cohort study support the reproducibility of neoadjuvant-intent immunotherapy for cSCC in the clinical setting, including for patients with a history of lymphoma. Outside of clinical trials, it is not infrequent for patients to opt out of surgery for regressing tumors. The inclusion of higher-risk patients and preference for nonsurgical treatment are 2 factors that might explain the numerically lower pathologic response rate in this institutional experience.

This article examines the relationship between the United States and Israel, particularly in light of the recent conflict in Gaza. It raises concerns about why the US seems unable to exert influence over Israeli actions, despite its declining global standing and President Biden's decreasing popularity. The article explores conspiracy theories suggesting that Israel actually controls US policy, criticizing Biden's perceived weakness and performative condemnations of Israeli Prime Minister Netanyahu. It also discusses Biden's history of supporting regime change and disregard for civilian suffering in other countries. The article concludes by suggesting that Biden's attempts at regime change have been unsuccessful, leaving the US weaker and outdated in the eyes of the world. Additionally, the text criticizes Western elites for celebrating the removal of Hamas without considering the loss of civilian lives and argues that the US is being held hostage by Israel's nuclear capabilities. The author suggests that Biden's slow response is influenced by pressure groups, including pro-Israeli lobbyists, and criticizes the failures of his foreign policy and the lack of accountability from progressives. [Extracted from the article]

Particle fabrication has attracted recent attention owing to its diverse applications in bioengineering1,2, drug and vaccine delivery3–5, microfluidics6,7, granular systems8,9, self-assembly5,10,11, microelectronics12,13and abrasives14. Herein we introduce a scalable, high-resolution, 3D printing technique for the fabrication of shape-specific particles based on roll-to-roll continuous liquid interface production (r2rCLIP). We demonstrate r2rCLIP using single-digit, micron-resolution optics in combination with a continuous roll of film (in lieu of a static platform), enabling the rapidly permutable fabrication and harvesting of shape-specific particles from a variety of materials and with complex geometries, including geometries not possible to achieve with advanced mould-based techniques. We demonstrate r2rCLIP production of mouldable and non-mouldable shapes with voxel sizes as small as 2.0 × 2.0 µm2in the print plane and 1.1 ± 0.3 µm unsupported thickness, at speeds of up to 1,000,000 particles per day. Such microscopic particles with permutable, intricate designs enable direct integration within biomedical, analytical and advanced materials applications.

The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cortical hierarchy in five macaque monkeys. The laminar locations of recordings were histologically identified by electrolytic lesions. Across all areas, we found a ubiquitous spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of high-frequency power peaking in layers 2/3 and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Laminar recordings from additional species showed that the spectrolaminar pattern is highly preserved among primates—macaque, marmoset and human—but more dissimilar in mouse. Our results suggest the existence of a canonical layer-based and frequency-based mechanism for cortical computation.

Proliferating pilar tumors are rare neoplasms that differentiate toward the outer sheath near the isthmus and can rarely undergo malignant transformation. We performed histopathologic evaluation on 26 benign proliferating pilar tumor (BPPT) and 17 malignant proliferating pilar tumor (MPPT). Ki-67 and p53 immunostains were performed on 13 BPPT and 10 MPPT. Six MPPT cases were successfully analyzed by a next-generation sequencing platform which surveyed exonic DNA sequences of 447 cancer genes and 191 regions across 60 genes for rearrangement detection. Patient demographics and clinical characteristics were similar between the BPPT and MPPT groups. Follow-up data of 16 of 17 MPPT (median, 25 mo) showed metastasis in 1 MPPT. The histologic features associated with MPPT include size >2.5 cm, adjacent desmoplastic stroma, small nests or cords of atypical epithelium in surrounding stroma, irregular infiltration or borders, abnormal keratinization, large hyperchromatic nuclei, prominent nucleoli, severe cytologic atypia, nuclear pleomorphism, necrosis, and increased mitotic figures. MPPT harbors copy number gains of 15q and losses of 6p and 6q, findings previously reported in BPPT. However, MPPT harbors frequent TP53mutations as molecular markers of progression. Different from cutaneous squamous cell carcinoma, MPPT more frequently demonstrates low tumor mutational burden and typically lacks a UV signature, suggestive of a different etiologic pathway than squamous cell carcinoma. In summary, with a median follow-up of 25 months, this study shows that MPPT is a biologically indolent carcinoma with rare metastasis. Molecular analyses suggest a non–UV-related pathogenesis with frequent TP53aberration.

RNA-guided systems, which use complementarity between a guide RNA and target nucleic acid sequences for recognition of genetic elements, have a central role in biological processes in both prokaryotes and eukaryotes. For example, the prokaryotic CRISPR–Cas systems provide adaptive immunity for bacteria and archaea against foreign genetic elements. Cas effectors such as Cas9 and Cas12 perform guide-RNA-dependent DNA cleavage1. Although a few eukaryotic RNA-guided systems have been studied, including RNA interference2and ribosomal RNA modification3, it remains unclear whether eukaryotes have RNA-guided endonucleases. Recently, a new class of prokaryotic RNA-guided systems (termed OMEGA) was reported4,5. The OMEGA effector TnpB is the putative ancestor of Cas12 and has RNA-guided endonuclease activity4,6. TnpB may also be the ancestor of the eukaryotic transposon-encoded Fanzor (Fz) proteins4,7, raising the possibility that eukaryotes are also equipped with CRISPR–Cas or OMEGA-like programmable RNA-guided endonucleases. Here we report the biochemical characterization of Fz, showing that it is an RNA-guided DNA endonuclease. We also show that Fz can be reprogrammed for human genome engineering applications. Finally, we resolve the structure of Spizellomyces punctatusFz at 2.7 Å using cryogenic electron microscopy, showing the conservation of core regions among Fz, TnpB and Cas12, despite diverse cognate RNA structures. Our results show that Fz is a eukaryotic OMEGA system, demonstrating that RNA-guided endonucleases are present in all three domains of life.

In the study of micro-swimmers, both artificial and biological ones, many-query problems arise naturally. Even with the use of advanced high performance computing (HPC), it is not possible to solve this kind of problems in an acceptable amount of time. Various approximations of the Stokes equation have been considered in the past to ease such computational efforts but they introduce non-negligible errors that can easily make the solution of the problem inaccurate and unreliable. Reduced order modeling solves this issue by taking advantage of a proper subdivision between a computationally expensive offline phase and a fast and efficient online stage. This work presents the coupling of Boundary Element Method (BEM) and Reduced Basis (RB) Reduced Order Modeling (ROM) in two models of practical interest, obtaining accurate and reliable solutions to different many-query problems. Comparisons of standard reduced order modeling approaches in different simulation settings and a comparison to typical approximations to Stokes equations are also shown. Different couplings between a solver based on a HPC boundary element method for micro-motility problems and reduced order models are presented in detail. The methodology is tested on two different models: a robotic-bacterium-like and an Eukaryotic-like swimmer, and in each case two resolution strategies for the swimming problem, the split and monolithic one, are used as starting points for the ROM. An efficient and accurate reconstruction of the performance of interest is achieved in both cases proving the effectiveness of our strategy.

Increases in youth vaping rates and concerns of a new generation of nicotine addicts recently prompted an increase in the federal minimum legal purchase age (MLPA) for tobacco products, including e-cigarettes, to 21 years. This study presents the first regression discontinuity evidence on the effectiveness of e-cigarette MLPA laws. Using data on 12th graders from Monitoring the Future, we obtain robust evidence that federal and state age 18 MLPAs decreased underage e-cigarette use by 15–20 percent and frequent use by 20–40 percent. These findings suggest that the age 21 federal MLPA could meaningfully reduce e-cigarette use among 18- to 20-year-olds.

Cutaneous myiasis is an infection most commonly caused globally by Dermatobia hominus, the human botfly, which is endemic to Central and South America. In North America, the most common cause of cutaneous myiasis is infestation with the larvae of Cuterebra, the North American botfly. The authors describe a 44-year-old man who presented with a 1-month history of intermittent, severe, boring pain along the side of his nose that progressed to swelling and redness along his right inferior orbital rim and lacrimal sac. CT imaging showed a rim-enhancing collection at the right medial canthus with surrounding phlegmonous changes communicating with the skin. Pathologic evaluation revealed curvilinear pigmented material associated with a granulomatous and eosinophil-rich inflammatory infiltrate, consistent with botfly myiasis. This case describes the pathogenesis of the botfly infestation in humans, as well as the clinical, radiographic, and histopathologic features of this rare orbital infection, with an emphasis on its treatment.This report describes a 44-year-old man with botfly myiasis with periorbital involvement and provides an update on the pathophysiology of the infectious agent, as well as the diagnostic and therapeutic modalities for this rare infection.