Nature Communications最新文献

Radiotherapy-induced oral mucositis (RTOM) is a common side effect of radiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (CCRT). In this phase 3 trial, we aim to evaluate the efficacy and safety of Ulinastatin (UTI) for the prevention and treatment of RTOM in LA-NPC patients (NCT03387774). The primary endpoint is the incidence of grade ≥3 acute RTOM during radiotherapy. Secondary endpoints include cumulative incidence of RTOM, recovery rate, the onset time and duration of grade ≥3 RTOM, oral pain (severe), safety and survival outcomes. 179 eligible patients are randomly assigned to UTI Group (n = 89) or Control group (n = 90). All UTI group patients complete UTI treatment as planned, and both groups complete scheduled CCRT. The incidence of grade 3 RTOM is significantly lower in UTI group compared with control group (25.8% vs 41.1%, P = 0.030). The trial meet its prespecified primary endpoint. No Ulinastatin related adverse events are observed during treatment. The 3-year overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) in UTI group and control group are similar between two groups. In this work, Ulinastatin can effectively reduce the severity of RTOM and oral pain without increasing toxicity and compromising survivals.

Strong interactions preserve an approximate isospin symmetry between up (u) and down (d) quarks, part of the more general flavor symmetry. In the case of K meson production, if this isospin symmetry were exact, it would result in equal numbers of charged (K⁺ and K⁻) and neutral (K⁰ and ({overline{K}}^{0})) mesons produced in collisions of isospin-symmetric atomic nuclei. Here, we report results on the relative abundance of charged over neutral K meson production in argon and scandium nuclei collisions at a center-of-mass energy of 11.9 GeV per nucleon pair. We find that the production of K⁺ and K⁻ mesons at mid-rapidity is (18.4 ± 6.1)% higher than that of the neutral K mesons. Although with large uncertainties, earlier data on nucleus-nucleus collisions in the collision center-of-mass energy range (2.6 , < , sqrt{{s}_{NN}} , < , 200) GeV are consistent with the present result. Using well-established models for hadron production, we demonstrate that known isospin-symmetry breaking effects and the initial nuclei containing more neutrons than protons lead only to a small (few percent) deviation of the charged-to-neutral kaon ratio from unity at high energies. Thus, they cannot explain the measurements. The significance of the flavor-symmetry violation beyond the known effects is 4.7σ when the compilation of world data with uncertainties quoted by the experiments is used. New systematic, high-precision measurements and theoretical efforts are needed to establish the origin of the observed large isospin-symmetry breaking.

The widespread integration of AI algorithms in healthcare has sparked ethical concerns, particularly regarding privacy and fairness. Federated Learning (FL) offers a promising solution to learn from a broad spectrum of patient data without directly accessing individual records, enhancing privacy while facilitating knowledge sharing across distributed data sources. However, healthcare institutions face significant variations in access to crucial computing resources, with resource budgets often linked to demographic and socio-economic factors, exacerbating unfairness in participation. While heterogeneous federated learning methods allow healthcare institutions with varying computational capacities to collaborate, they fail to address the performance gap between resource-limited and resource-rich institutions. As a result, resource-limited institutions may receive suboptimal models, further reinforcing disparities in AI-driven healthcare outcomes. Here, we propose a resource-adaptive framework for collaborative learning that dynamically adjusts to varying computational capacities, ensuring fair participation. Our approach enhances model accuracy, safeguards patient privacy, and promotes equitable access to trustworthy and efficient AI-driven healthcare solutions.

Proton exchange membrane fuel cells show great potential as power source for automobiles, yet are now facing technological challenges of low efficiency in the cathodic oxygen reduction reaction and severe degradation from Nafion ionomers. Herein, we report the design and construction of a core/shell nanoparticle, composing of Pt₃Fe intermetallic nanoparticle as core and atomically-thin porous N-doped carbon layer as shell, to alleviate Nafion ionomer poisoning and local oxygen transport at the interfaces, thereby improving the performance of membrane electrode assemblies. Combining electrochemical, spectroscopic and calculation results verify that the sandwiching carbon layer can effectively prevent surface Pt active sites from poisoning by ionomers. Moreover, this deliberate design facilitates a more homogeneous distribution of ionomers in catalyst layer, and drives a H₂-air fuel cell peak power density up to 1.0 W cm^-2. Due to the configuration-induced strong Fe-N coordination, our unique catalyst efficiently preserves transition metals and consequently delivers a notable fuel cell durability at a constant potential of 0.5 V for 100 h.

Controlling Zinc (Zn) nucleation and subsequent crystal growth are critical for long lifespan aqueous zinc metal batteries. However, the concurrent side reactions and unstable solid-electrolyte interphase (SEI) formations impedes the continuous Zn metal electrodeposition. Herein, induced by a well-designed organic/inorganic dual-phase SEI, we realize ordered zinc electrodeposition of polycrystalline stackings from single-crystal building blocks. The uncommon SEI with appropriate ion transport kinetics and thermodynamic stability protects deposited zinc from side reactions of hydrogen evolution and metal corrosion, enabling rapid and long single crystal Zn nucleation, followed by mitigated crystal growth, and ultimately dense polycrystalline stacking without dendrites. Benefited from the above advantages, the Zn | |Zn symmetric batteries exhibit long lifespan exceeding 5600 h and high depth of discharge of 85.0 %, and the Zn | |I₂ full cell delivers a high capacity of 201.9 mAh g^-1 at -30 ^oC. Furthermore, the practical 0.1 Ah Zn | |I₂ bilayer pouch cell can stably operate for 113 cycles with a high specific energy of 122.1 Wh kg^-1 with a low N/P capacity ratio of 1.5. Our findings advance the understanding of critical roles of SEI on zinc electrodeposition behaviors and provide valuable insights into crystal structure regulation during electrodeposition in other metal batteries.

The health impact of floods has not been well characterized. This study evaluated long-term associations between cause-specific mortality rates and county-level monthly flood days (excluding coastal floods caused by tropical storms) in the post-flood year in the contiguous U.S., using a triply robust approach incorporating propensity score, counterfactual estimation, and confounder adjustment. Death records came from the CDC National Center for Health Statistics (2001-2020) and floods came from the NOAA Storm Events Database (2000-2020). We found that one flood day was associated with 8.3 (95% CI: 2.5 to 14.1) excess all-cause deaths per 10 million individuals, 3.1 due to myocardial infarction, 2.4 due to respiratory diseases, and 5.9 due to external causes. From 2001 to 2020, 22,376 (95% CI: 6,758 to 37,993) all-cause deaths were attributable to floods. Our findings highlight the long-term health risks after floods, and a need for measures to reduce these risks.

Undiagnosed cognitive impairment is a pervasive global issue, often due to subtle nature of early symptoms, necessitating the use of brief cognitive tests for early detection. However, most brief tests are not scalable (requiring trained professionals), and are not designed for lower literacy groups (e.g. in underserved communities). Here, we developed PENSIEVE-AI^TM, a drawing-based digital test that is less dependent on literacy, and can be self-administered in <5 min. In a prospective study involving 1758 community-dwelling individuals aged 65 and older from Singapore (education range = 0–23 years), our deep-learning model showed excellent performance in detecting clinically-adjudicated mild cognitive impairment and dementia (AUC = 93%), comparable to traditional neuropsychological assessments (AUC = 94%, P_comparison = 1.000). Results were consistent even across education subgroups. Being less dependent on literacy, PENSIEVE-AI holds promise for broader deployment in literacy-diverse populations similar to Singapore (e.g. some Asian and lower- and middle-income countries), potentially improving early detection and intervention of cognitive impairment.

Beyond first line, the prognosis of relapsed/refractory (R/R) acute myeloid leukemia (AML) patients is poor with limited treatment options. Bemcentinib is an orally bioavailable, potent, highly selective inhibitor of AXL, a receptor tyrosine kinase associated with poor prognosis, chemotherapy resistance and decreased antitumor immune response. We report bemcentinib monotherapy and bemcentinib+low-dose cytarabine combination therapy arms from the completed BerGenBio-funded open-label Phase 1/2b trial NCT02488408 (www.clinicaltrials.gov), in patients unsuitable for intensive chemotherapy. The primary objective in the monotherapy arm was identification of maximum tolerated dose with secondary objectives to identify dose-limiting toxicities, safety and efficacy, and bemcentinib pharmacokinetic profile. In the combination arm, the primary objective was safety and tolerability, with efficacy and pharmacokinetics as secondary objectives. Safety and tolerability were based on standard clinical laboratory safety tests and Common Terminology Criteria for Adverse Events version 4. Bemcentinib monotherapy (32 R/R, 2 treatment-naïve AML and 2 myelodysplasia patients) was well-tolerated and a loading/maintenance dose of 400/200 mg was selected for combination treatment, comprising 30 R/R and 6 treatment-naïve AML patients. The most common grade 3/4 treatment-related adverse events were cytopenia, febrile neutropenia and asymptomatic QTcF prolongation, with no grade 5 events reported. In conclusion, bemcentinib+low-dose cytarabine was safe and well tolerated.

Brain organoids have been proposed as suitable human brain model candidates for a variety of applications. However, the lack of appropriate maturation limits the transferability of such functional tools. Here, we present a method to facilitate neuronal maturation by integrating astrocyte-secreted factors into hPSC-derived 2D and 3D neural culture systems. We demonstrate that protein- and nutrient-enriched astrocyte-conditioned medium (ACM) accelerates neuronal differentiation with enlarged neuronal layer and the overproduction of deep-layer cortical neurons. We captured the elevated changes in the functional activity of neuronal networks within ACM-treated organoids using comprehensive electrophysiological recordings. Furthermore, astrocyte-secreted cues can induce lipid droplet accumulation in neural cultures, offering protective effects in neural differentiation to withstand cellular stress. Together, these data indicate the potential of astrocyte secretions to promote neural maturation.

Viruses associated with acute febrile illness in Africa cause a spectrum of clinical disease from mild to life-threatening. Routine diagnostic methods are insufficient to identify all viral pathogens in this region. In this study, 1281 febrile Ugandan patients were prospectively recruited as part of the CDC-UVRI Acute Febrile Illness Study and pre-screened for common pathogens. 210/1281 undiagnosed samples, and 20 additional samples from viral outbreaks were subjected to metagenomic sequencing. Viral pathogens were identified in 44/230 (19%), including respiratory, hepatitis, blood-borne, gastrointestinal and vector-borne viruses. Importantly, one case of Crimean-Congo haemorrhagic fever and two cases each of Rift Valley fever, dengue and yellow fever were detected in 7/230 (3%) of cases. Le Dantec virus, last reported in 1969, was also identified in one patient. The presence of high-consequence and (re-)emerging viruses of public health concern highlights the need for enhanced population-based diagnostic surveillance in the African region.