Compared to conventional inorganic detectors, all-polymer photodetectors (all-PPDs) have attracted significant attention in the field of flexible and wearable electronics owing to their unique mechanical properties. However, their practical applications are often hindered by a narrow spectral response range and limited sensitivity. In this work, we designed and synthesized three polymer acceptors with broad-spectrum absorption capabilities for use in all-PPDs, and systematically investigated the effect of acceptor unit composition on the overall polymer properties. Through comprehensive optical, electrochemical, and computational analyses, we found that the single-acceptor polymer P1-TT exhibits exceptional broadband response characteristics, attributed to the strong intramolecular donor-acceptor (D-A) effect. The photodetector based on P1-TT achieved a remarkable specific detectivity exceeding 1012 Jones across a wide range of 300 to 870 nm under a low bias of -0.1 V, with a peak value of 3.6 × 1013 Jones at 700 nm. Moreover, it demonstrated a low dark current density (5.5 × 10-11 A·cm-2), a wide linear dynamic range (109.0 dB), and a fast response time (rise time/fall time = 2.12/3.59 μs), outperforming many existing acceptor materials. Benefiting from the excellent mechanical properties of the all-polymer blend film, P1-TT can be used to fabricate flexible device, and it also delivered a superior detectivity of 3.3 × 1013 Jones at 700 nm under a bias of -0.1 V. Practical application tests further verified its potential in optical communications, infrared signal detection, and biometric monitoring, demonstrating its promise for use in next-generation flexible optoelectronic systems.

Gastric mucinous adenocarcinoma (GMC) is a rare subtype of gastric cancer characterized by excessive mucus production, aggressive biological behavior, and poor prognosis, with most patients presenting with metastatic disease at initial diagnosis and losing the opportunity for curative resection. Currently, there are no standardized diagnostic and treatment guidelines for metastatic GMC in the conversion therapy setting, and the therapeutic effect of conventional chemotherapy remains unsatisfactory. Herein, we present a 69-year-old male patient diagnosed with HER2-negative, TMB-H advanced GMC, with intraperitoneal and retroperitoneal lymph node metastases. The patient was initially deemed unresectable by the multidisciplinary team (MDT) but opted for conversion therapy due to a strong willingness for treatment and good performance status (ECOG-PS=0). He received 6 cycles of FLOT chemotherapy combined with nivolumab, achieving partial response (PR) per RECIST 1.1. Subsequent laparoscopic distal gastric subtotal resection (D2+ lymphadenectomy) was performed, and postoperative pathology revealed a near pathological complete response (Mandard-TRG1) with no lymph node metastases (0/21), pathologically staged as ypTisN0. Postoperatively, the patient received 4 cycles of XELOX chemotherapy plus nivolumab, followed by consolidative radiotherapy synchronized with capecitabine and nivolumab, and subsequent maintenance therapy with capecitabine and nivolumab until sustained no evidence of disease (NED) was confirmed in January 2023. Regular surveillance, including the latest contrast-enhanced CT in May 2025, showed no recurrence or metastasis, with progression-free survival (PFS) exceeding 5 years. This exceptional and sustained response may be attributed to the synergistic effect of TMB-H and POLD1 mutation, which enhance neoantigen generation and sensitize tumors to immunotherapy. This case highlights the potential of biomarker-driven chemo-immunotherapy combined with MDT-guided multimodal treatment (surgery + adjuvant therapy + consolidative radiotherapy) to achieve curative intent in patients with metastatic GMC, providing valuable insights for personalized treatment strategies in this poor-prognosis population.

The article analyzes the uptick in migration in Latin America and how it is discursively treated as a security issue—a process known as “securitization.” It argues that collective identity becomes the core of “societal security,” and that labeling the migrant population as a “threat” legitimizes exceptional and exclusionary responses. It also engages the debate on the intentional political use of migration flows to exert pressure and international coercion. This is done through a non-systematic narrative review of the literature alongside a trend study that combines, on the one hand, theory and, on the other, technical reports from international organizations. The text likewise shows that digital media in the region frame migration mainly as a threat (crime) or as victimhood (vulnerability), with alarmist headlines that shape public opinion. Consequently, several surveys reveal greater support for restrictive policies, the belief that migrants are a burden, and a growing association between immigration and crime in various countries. However, comparative evidence refutes this link: migrants’ crime rates tend to be equal to or lower than their share of the population. In response, the article concludes by offering a ten-point set (“decalogue”) of concrete tools for formulating regional public policies that guarantee the fundamental rights of migrants.

Charge-localized aza-12-crown based alkalides with exceptional nonlinear optical response

Integrated photonics has emerged as a promising alternative for data communication and computing, ferroelectric BaTiO3 (BTO) stands out for its exceptional electro-optic response among candidate materials. However, direct epitaxial growth of BTO entails a fundamental trade-off: substrates with low refractive index are required for strong optical confinement, yet those with large lattice mismatch degrade film crystalline quality and electro-optic performance. We report a buffer-free, strain-engineered approach to integrate high-performance BTO thin films directly on LaAlO3-Sr2TaAlO6 (LSAT) oxide-insulator substrates. By exploiting a self-buffer layer formed during the initial growth stage, we achieve periodic in-plane strain modulation that stabilizes a polymorphic phase boundary with orthorhombic polar nanoregions, yielding a Pockels coefficient exceeding 358 pm V⁻¹ and a Curie temperature raised to 200 °C. Leveraging this material platform, we demonstrate the first realization of a Mach–Zehnder modulator using epitaxial BTO on LSAT. The device exhibits a half-wave voltage–length product of 0.7 V cm at 1550 nm, which closely matches finite-element simulations, and supports a 6-dB electro-optic bandwidth of 28 GHz. Our results validate BTO on LSAT as a viable photonic platform for scalable, low-voltage and high-speed modulators.

Giant magnetostrictive Tb-Dy-Fe alloys are extensively applied in transducers, actuators, and smart sensors owing to their exceptional magnetostrictive response. Nevertheless, in addition to the fracture failure caused by the inherent brittleness of the Laves intermetallic compound, Tb-Dy-Fe alloys also suffer from severe eddy current losses due to low electrical resistivity, both of which limit the practical application of Tb-Dy-Fe alloys. To further enhance the overall performance of Tb-Dy-Fe alloys and expand their application scope, it has become essential to develop materials that exhibit high magnetostrictive properties, high electrical resistivity and excellent mechanical properties simultaneously. In this work, the effects of Al and Si co-addition on the microstructure and multifunctional properties of directionally solidified Tb0.27Dy0.73(Fe0.9Al0.075Si0.025)1.95 (hereafter TDF-AlSi) alloy were systematically investigated. Microstructural characterization revealed that Al partially substitutes Fe atoms in the matrix phase while promoting Al(Tb,Dy)Fe2 nanocluster, whereas Si preferentially segregated to grain boundary regions forming Tb2Si3 and TbSi1.75 phases. The bending strength of TDF-AlSi alloy was improved from 43 MPa to 65 MPa, an increase of 51.2%, which was attributed to solid solution strengthening by Al and grain boundary reinforcement by Si-rich precipitates. Meanwhile TDF-AlSi alloy exhibits a 2.4 times increase in electrical resistivity (1.619 μΩ·m), resulting in a 49% reduction of total loss at 1000 Hz. The enhancement of electrical resistivity mainly originated from the lattice distortion induced electron scattering by Al substitution and electron impedance at grain boundaries via silicide precipitation. Accompanied by enhancement of mechanical property and electrical resistivity, TDF-AlSi alloy maintained a high magnetostriction strain of 1212 ppm (200 kA/m, 10 MPa pre-compressive stress). The findings of the present study offer valuable theoretical and experimental insights with regard to the optimization of the performance of magnetostrictive Tb-Dy-Fe alloys.

The trial of civilians by military courts in Pakistan constitutes one of the most significant constitutional and human rights controversies in the country’s contemporary legal landscape. Initially introduced as a temporary and exceptional response to terrorism following the 2014 Army Public School attack, military courts were justified on grounds of expediency and national security. However, the gradual expansion and normalization of their jurisdiction over civilians have raised serious concerns regarding their compatibility with constitutional guarantees of fair trial and Pakistan’s international human rights obligations. This paper undertakes a qualitative doctrinal and comparative legal analysis to examine whether military court proceedings align with Article 10A of the Constitution of Pakistan and the fair trial standards enshrined in Article 14 of the International Covenant on Civil and Political Rights (ICCPR). Focusing on the conflicting Supreme Court decisions of October 2023 and May 2025, the study highlights systemic deficiencies in military court proceedings, including the absence of judicial independence, lack of transparency, restricted access to legal representation, and ineffective appellate review. The paper argues that the continued trial of civilians by military courts is constitutionally unsustainable and normatively inconsistent with international human rights law. It concludes by proposing evidence-based legislative and institutional reforms aimed at reconciling national security concerns with constitutional supremacy and fair trial guarantees.

HER2, encoded by the ERBB2 gene, is a receptor tyrosine kinase frequently activated in human cancers via gene amplification, mutation, and/or protein overexpression. In an analysis of 42,415 prospectively analyzed solid tumors, we show that 14.5% of urothelial cancers (n = 295/2,035) have oncogenic or likely oncogenic ERBB2 alterations (6.7% ERBB2 mutation, 6.3% amplification of wildtype ERBB2, and 1.5% concurrent mutation and amplification). Discordance of ERBB2 mutational status between primary and metastatic disease sites is common in patients with urothelial cancer as is discordance of ERBB2 mutational status between patient-derived organoid/xenograft models and the tumors from which they were derived. In patient-derived urothelial cancer models, the HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan is significantly more effective than the HER kinase inhibitor neratinib. In a real-world cohort of patients with urothelial cancer treated with trastuzumab deruxtecan, co-mutation and amplification of ERBB2 is associated with exceptional clinical response. Our data support expanded clinical trials of HER2-targeted ADCs for urothelial cancers with low HER2 expression, the clinical testing of HER2 ADCs with alternative cytotoxic payloads, and the development of functional precision oncology platforms capable of assessing payload sensitivity pre-treatment as a guide to individualized therapy selection.

The crystal phase of metal oxide supports critically governs the gas-sensing performance by modulating metal-support interactions. This study reveals a counterintuitive "reversal effect" induced by Pt modification on the acetone-sensing properties of γ-Fe2O3 and α-Fe2O3. Despite pristine α-Fe2O3 exhibiting a 9.4-fold higher response to acetone than γ-Fe2O3 (179 vs 19), even though the latter possesses a 4-fold larger specific surface area, Pt functionalization dramatically reverses this performance hierarchy. After loading 0.3 wt % Pt, Pt-Fe2O3-γ achieves an exceptional response of 1470 to 100 ppm acetone (77-fold enhancement over pristine γ-Fe2O3), whereas Pt-Fe2O3-α suffers a 9.4-fold reduction. Oxygen temperature-programmed desorption (O2-TPD) and structural characterization demonstrate that this reversal stems from the crystal phase-dependent Pt dispersion: γ-Fe2O3 facilitates atomic dispersion of Pt, optimizing gas adsorption and electron transfer, while α-Fe2O3 promotes Pt nanoparticle aggregation, which impedes charge transport despite enhanced oxygen adsorption. This work elucidates a new mechanism wherein the support crystal phase dictates noble metal dispersion states to control sensing behavior, providing a paradigm for designing phase-engineered sensing materials.

Immunotherapies have significantly transformed the treatment landscape of acute leukemia in adults, most notably in B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab and inotuzumab ozogamicin have become established treatments, enhancing remission rates, measurable residual disease clearance, and overall survival in relapsed/refractory disease, and these agents, are now increasingly incorporated into frontline therapy. Additionally, autologous CD19 chimeric antigen receptor (CAR) T-cell therapy has dramatically improved salvage treatment outcomes, demonstrating exceptional remission rates and durable responses even in heavily pretreated patients. Enhanced understanding of mechanisms underlying disease resistance and relapse is guiding the development of optimized combination and sequential therapeutic approaches. In acute myeloid leukemia (AML), gemtuzumab ozogamicin has shown significant clinical benefits, particularly in molecularly defined subsets. Ongoing research focuses on novel antibody-drug conjugates, immune cell engagers, and advanced cellular therapies, facing challenges primarily in selecting appropriate targets and overcoming the immunosuppressive tumor microenvironment. For T-cell acute lymphoblastic leukemia (T-ALL), therapeutic innovation is confronted with unique challenges due to overlapping antigen expression between malignant, normal, and CAR T-cells. Promising early clinical and preclinical studies are currently evaluating anti-CD38 antibodies and CAR T-cells mostly directed against CD5 and CD7. This review highlights how immunotherapy has reshaped treatment paradigms across acute leukemias, underscoring successful experiences in B-ALL. These insights emphasize the need for continued innovation to overcome existing hurdles in AML and T-ALL, ultimately aiming to enhance patient outcomes and quality of life.

Neoadjuvant chemotherapy plays a critical role for patients eligible for preoperative therapy; especially for those with HER2-positive or triple-negative breast cancer. Advances in systemic therapy have led to increased rates of pathological complete response (pCR), a key indicator of long-term outcomes and a guide for subsequent adjuvant treatments. pCR also serves as a surrogate marker for the approval of new drugs in breast cancer. Neoadjuvant chemotherapy enhances the feasibility of breast-conserving surgery and sentinel lymph node biopsy for patients showing a clinical response. Effective management requires collaboration with a multidisciplinary team—including medical oncologists, surgical oncologists and radiation oncologists—prior to starting treatment. This is to consider therapy sequencing, its results in various treatment options, and appropriate management of breast and axillary nodes for potential de-escalation. Future advancements in personalized therapy involve identifying patients with exceptional responses to neoadjuvant chemotherapy whom may be able to avoid surgery entirely, and developing strategies to tailor neoadjuvant regimens using predictive biomarkers.

Understanding exceptional response: The role of MINDY1 SNP in CDK4/6 inhibitor therapy for ER+, HER2− advanced breast cancer

Recurrent extrahepatic papillary cholangiocarcinoma with CCNE1 amplification, TP53 mutation and CNS involvement a capecitabine exceptional response case report

Cenobamate in pediatric epilepsy and developmental and epileptic encephalopathies: Efficacy, safety, and syndrome-specific considerations.

ABSTRACT Technocratic governments in Italy, often portrayed as caretaker cabinets, have in fact played a pivotal role in reshaping the state. This article systematically analyses the reforms enacted by four technocratic cabinets – those of Carlo Azeglio Ciampi, Lamberto Dini, Mario Monti, and Mario Draghi – between 1993 and 2022. Combining a longitudinal design with in-depth policy analysis, it examines administrative and welfare reforms across three dimensions: domain, scope, and policy orientation. The findings challenge the conventional view of technocracy as an exceptional response to crisis, showing instead that these executives have contributed to recurring patterns of state restructuring. While neoliberal and managerial orientations prevail across all cases, important variations in the scope of reform and in contextual conditions emerge. The analysis avoids deterministic interpretations by situating technocratic agency within the interplay between structural constraints and strategic intervention. Critical junctures – marked by uncertainty and external pressure – are shown to provide opportunities for technocratic actors to implement high-impact reforms with lasting implications. The article concludes that technocracy has become a normalized mode of policy intervention in Italy, particularly effective for advancing politically costly reforms under crisis conditions. These findings have broader implications for understanding the evolution of democratic governance.

Conductive hydrogels are ideal for flexible strain sensors, yet their practical use is often limited by water evaporation, signal hysteresis, and structural instability, which impair linearity, durability, and long-term reliability. To overcome these challenges, we developed a robust multiple-network hydrogel composed of poly(vinyl alcohol) (PVA), polyacrylic acid (PAA), in situ polymerized polyaniline (PANi), and the ionic liquid [EMIM][TFSI]. The resulting composite exhibits an exceptional linear piezoresistive response across its entire working range—from rest to fracture strain of 290%—together with high conductivity (0.68 S/cm), fast response/recovery (0.34 s/0.35 s), and a maximum gauge factor of 2.78. Mechanically robust (tensile strength ≈ 3.7 MPa, modulus ≈ 1.3 MPa), the hydrogel also demonstrates outstanding cyclic durability, withstanding over 12,000 stretching–relaxation cycles, and markedly improved dehydration resistance, retaining about 60% of its mass after 3 days at room temperature. This work provides a holistic material solution for developing high-performance, reliable strain sensors suitable for wearable electronics and soft robotics.

ABSTRACT This study presents, a comprehensive investigation into the failure behavior and parametric optimization of novel 3D‐printed Auxetic Tubular Re‐entrant Structures (ATRS), using an integrated experimental–numerical framework. Compression tests are performed on four ATRS designs featuring different unit cell angles, thicknesses, and widths to confirm simulation accuracy and evaluate mechanical performance. Excellent agreement is observed between experimental and simulation results, capturing both the initial linear response and the nonlinear buckling behavior. The simulations revealed exceptional auxetic responses and showed how geometric parameters govern stress localization and failure initiation. Reduced unit cell widths led to earlier buckling owing to a smaller load‐bearing area and increased soft mode activation, whereas larger angles raised buckling forces but triggered instability sooner. Also, energy absorption capacity rose significantly with increases in unit cell width, angle, and thickness, reaching as much as four times higher in thicker samples. According to Response Surface Methodology (RSM) and Analysis of Variance (ANOVA), thickness and width are the primary parameters influencing buckling force, stiffness, and energy absorption, with thickness having the greatest impact. These findings facilitate accurate predictive modeling of ATRS mechanical behavior driven by geometric design and offer new pathways for designing damage‐tolerant structures with tunable mechanical responses.

Abstract We report two cases of patients with MGMT promoter-methylated glioblastoma who experienced tumor recurrence and demonstrated exceptional responses to temozolomide (TMZ) rechallenge. The first patient received TMZ rechallenge at the time of second recurrence (48 months from original diagnosis). The second patient received TMZ rechallenge at both first and second recurrence (53 and 90 months from original diagnosis). Remarkably, both patients achieved complete radiographic responses after two cycles of TMZ rechallenge, with sustained responses confirmed on follow-up imaging. Both patients are alive and well in complete response, 56 and 95 months from original diagnosis).

Abstract Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults with a median overall survival of less than 20 months despite standard-of-care (SOC) treatment consisting of maximal safe surgical resection, radiation therapy (RT) and temozolomide (TMZ) chemotherapy, with lomustine commonly used at recurrence. Over the past 20 years, the majority of clinical trials have failed to yield significant therapeutic advancements. In spite of this, in many clinical trials, small subsets (~5%) of patients would still exhibit exceptional clinical responses, suggesting that, with more precise selection procedures, more effective therapeutic options could still be offered. While genomic stratification seems insufficient to identify those patients, functional precision oncology (FPO) assays, whereby functional, therapeutic responses are measured in live, ex vivo tumor cells, offers a valuable alternative approach to improve patient selection. Today, the majority of FPO assays rely on cytotoxicity as a readout, limiting insights into the molecular complexity and heterogeneity of GBM. To address this, we created a single-cell therapeutic atlas of GBM by integrating cytotoxicity data from >60 patient-derived cell lines (PDCLs) exposed to the standard of care treatment options (RT, TMZ, RT+TMZ, and lomustine) with single-cell RNA-seq and clinical data. First, by comparing our PDCL single-cell transcriptomic profiles with a large public scRNA-seq dataset from GBM tumors, we found that our cell lines recapitulate the majority of molecular states observed in vivo. Furthermore, cytotoxicity responses in our cell lines were found to correlate with treatment responses observed in patients, underscoring their translational relevance. By subsequently analyzing >280 samples in control and treatment conditions, we created a cellular atlas of >1million single-cell profiles upon treatment. We identified cellular drug response metaprograms that were typically recovered in >5 samples. Additionally, we identified the gene regulatory networks driving these metaprograms and cataloged them based on their dynamics upon perturbation.

MRD-guided ibrutinib plus venetoclax improves outcomes in CLL patients with TP53, ATM, or NOTCH1 aberrations compared to ibrutinib and FCR: Results from the Phase III NCRI FLAIR trial