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\"The Cajun rages on! Join Gambit on a time-tossed trip to the 19th century, and discover how the Thieves' Guild was shaped by Candra...and Mr. Sinister! Back in the present, Remy needs help - and Rogue flies to his aid! Thanks to Gambit's evolving powers, he can finally greet her with a kiss - but as his abilities get more unstable, any thoughts of romance will be short-lived. Gambit's destiny looms as he takes leadership of the Guild - assuming he can survive an Assassination Game against deadly villains like Bullseye, Constrictor, Zaran, Deadpool...and Archangel? And what are X-Cutioner and Ego the Living Planet doing here?! Gambit will finally discover the secret of his mysterious patron, the New Son - but is he hero or villain, and what will Gambit have to sacrifice to triumph?\"--Page [4] of cover.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high‐level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high‐risk prostate cancer to perform dose escalation and improve progression‐free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

The long-term stability of Pt-based catalysts is critical to the reliability of proton exchange membrane fuel cells (PEMFCs), and receives constant attention. However, the current knowledge of Pt oxidation is restricted to unrealistic PEMFC cathode environment or operation, which questions its practical relevance. Herein, Pt oxidation is investigated directly in a PEMFC with stroboscopic operando high energy X-ray scattering. The onset potential for phase transition of the nanoparticles surface from metallic to amorphous electrochemical oxide is observed far below previously reported values, and most importantly, below the open-circuit potential of PEMFC cathode. Such phase transition is shown to impact PEMFC performance and its role on Pt transient dissolution is verified by electrochemical on-line inductively coupled plasma mass spectrometry. By further demonstrating and resolving the limitations of currently employed accelerated stress test protocols in the light of metal-oxide phase transitions kinetics, this picture of Pt oxidation enables new mitigation strategies against PEMFC degradation. The stability of Pt-based catalysts is critical to the reliability of proton exchange membrane fuel cells. Here, the authors use stroboscopic operando high energy X-ray scattering to reveal Pt nanocatalysts experience a metal-oxide phase transition during conventional fuel cell operation.

The mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) pathway is a critical signaling component in the development of obesity-linked insulin resistance and operates a nutrient-sensing negative feedback loop toward the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive. To assess the metabolic effects of chronic inhibition of the mTORC1/S6K1 pathway, rats were treated with rapamycin (2 mg/kg/day) or vehicle for 15 days before metabolic phenotyping. Chronic rapamycin treatment reduced adiposity and fat cell number, which was associated with a coordinated downregulation of genes involved in both lipid uptake and output. Rapamycin treatment also promoted insulin resistance, severe glucose intolerance, and increased gluconeogenesis. The latter was associated with elevated expression of hepatic gluconeogenic master genes, PEPCK and G6Pase, and increased expression of the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) as well as enhanced nuclear recruitment of FoxO1, CRTC2, and CREB. These changes were observed despite normal activation of the insulin receptor substrate/PI 3-kinase/Akt axis in liver of rapamycin-treated rats, as expected from the blockade of the mTORC1/S6K1 negative feedback loop. These findings unravel a novel mechanism by which mTORC1/S6K1 controls gluconeogenesis through modulation of several key transcriptional factors. The robust induction of the gluconeogenic program in liver of rapamycin-treated rats underlies the development of severe glucose intolerance even in the face of preserved hepatic insulin signaling to Akt and despite a modest reduction in adiposity.

Anaplastic thyroid carcinoma (ATC) is a rare and undifferentiated form of thyroid cancer. Its prognosis is poor: the median overall survival (OS) of patients varies from 4 to 10 months after diagnosis. However, a doubling of the OS time may be possible owing to a more systematic use of molecular tests for targeted therapies and integration of fast-track dedicated care pathways for these patients in tertiary centers. The diagnostic confirmation, if needed, requires an urgent biopsy reread by an expert pathologist with additional immunohistochemical and molecular analyses. Therapeutic management, defined in multidisciplinary meetings, respecting the patient’s choice, must start within days following diagnosis. For localized disease diagnosed after primary surgical treatment, adjuvant chemo-radiotherapy is recommended. In the event of locally advanced or metastatic disease, the prognosis is very poor. Treatment should then involve chemotherapy or targeted therapy and decompressive cervical radiotherapy. Here we will review current knowledge on ATC and provide perspectives to improve the management of this deadly disease.

A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2–11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0·79, 95% CI 0·73–0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5–9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56–0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70–0·93) but not adjuvant chemotherapy alone (0·87, 0·68–1·12) or induction chemotherapy alone (0·96, 0·80–1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69–0·81), locoregional control (0·73, 0·64–0·83), distant control (0·67, 0·59–0·75), and cancer mortality (0·76, 0·69–0·84). Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

Trypanosoma brucei, a divergent eukaryote parasite, is responsible for neglected tropical diseases in humans and animals, specifically sleeping sickness or human African trypanosomiasis and nagana. Beyond its scientific significance, a comprehensive understanding of its biology has substantial medical and economical implications. Nuclear pore complexes (NPCs) are large multiprotein channels embedded in the nuclear envelope that regulate nucleocytoplasmic transport. In addition to this critical function, NPCs are involved in essential nuclear processes such as chromosome segregation, transcription, and cytokinesis. This study demonstrates that Myosin-like protein-1 (MLP1) localizes to the nuclear basket of NPCs in T. brucei. Silencing of TbMLP1 by RNA interference in T. brucei procyclic cells resulted in severe growth, significant impairment of messenger RNA export, disorganization of nuclear structure, and marked genomic instability. Flow cytometry and fluorescence in situ hybridization (FISH) analyses revealed abnormal DNA content and a reduction in disomic cells, alongside an increase in monosomic, trisomic, and polysomic cells, indicating intolerable aneuploidy detrimental to cell viability. Together, these findings demonstrate that TbMLP1 links NPC function to multiple key cellular pathways. This research provides new insights into the mechanisms that maintain nuclear architecture, preserve nuclear envelope morphology, ensure genome stability, and faithful chromosome segregation, and support appropriat kinetochore distribution and mitotic spindle organization.

To compare intensive care unit (ICU) nursing workload between spring-summer and winter and to examine factors associated with workload variation across French regions. Critical care nursing workload is high and may fluctuate with seasonal demand and regional ICU bed capacity, challenging fixed-staffing models. Secondary analysis of two nationwide prospective cross-sectional surveys in French ICUs (April-July 2023; January-March 2024). Workload was measured using the Nursing Activities Score (NAS). Outcomes were NAS per patient, NAS per nurse, and NAS per nurse > 100%. ICU-level linear mixed models assessed associations with season and regional ICU bed availability (below, versus, at, or above the national mean), adjusting for ICU characteristics. Forty-three ICUs contributed 2703 nurses and 18,772 patient NAS assessments (8759 NAS per-nurse observations). At the individual level, median NAS per nurse was lower in spring-summer than in winter (124.3% vs. 127.1%; p value = 0.043), whereas NAS per patient was higher in spring-summer (61.3% vs. 59.4%; p < 0.001). The proportion of shifts with NAS per nurse > 100% was higher in winter (69.3% vs. 67.3%; p = 0.044), and the patient-to-nurse ratio was higher (2.06 ± 0.7 vs. 1.96 ± 0.7; p < 0.001). ICUs in regions with fewer ICU beds consistently showed higher NAS per nurse across seasons. In multivariable models, winter (β = 4.5, 95% CI: 2.3-6.7) and residence in under-resourced regions (β = 19.2, 95% CI: 5.9-32.5) were associated with higher NAS per nurse. ICU nursing workload varies by season and regional ICU bed capacity; baseline workload frequently exceeds 100%, limiting surge adaptability and exposing limits of fixed-staffing ratios. Nurse managers may rely on objective and longitudinal workload information to support sustainable decision-making in intensive care. Embedding indicators such as the NAS into staffing policies may facilitate anticipatory planning, reduce reactive staffing responses, and support patient safety and workforce stability.

Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0–2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9–6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84–1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69–1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67–0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1–43·4) after conventional chemoradiotherapy, 34·1% (28·7–39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0–37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3–4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. French Ministry of Health.