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The Role of NAD+ in Regenerative Medicine

The understanding of the molecular and cellular basis of aging has grown exponentially over recent years, and it is now accepted within the scientific community that aging is a malleable process; just as it can be accelerated, it can also be slowed and even reversed. This has far-reaching implications for our attitude and approach toward aging, presenting the opportunity to enter a new era of cellular regenerative medicine to not only manage the external signs of aging but also to develop therapies that support the body to repair and restore itself back to a state of internal well-being. A wealth of evidence now demonstrates that a decline in cellular nicotinamide adenine dinucleotide (NAD+) is a feature of aging and may play a role in the process. NAD+ plays a pivotal role in cellular metabolism and is a co-substrate for enzymes that play key roles in pathways that modify aging.

Nine-Valent HPV Vaccination and Related Cancers

This retrospective cohort study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. We used the TriNetX platform, a large-scale global database, to evaluate the association of 9v-HPV vaccination for adolescent and young males aged 9 to 26 years with HPV-related cancers, including head and neck, penile, rectal, and anal cancers. TriNetX has stored electronic health records for approximately 190 million patients from 170 health care centers globally as of December 2025.17 Data collected in TriNetX included health care visits, diagnoses, procedures, medications, and laboratory results. In this study, the vaccinated cohort included males aged 9 to 26 years receiving at least one 9v-HPV vaccination with a health examination between January 2016 and December 2024. The unvaccinated cohort included males aged 9 to 26 years who underwent a health examination during the corresponding period but never received any HPV vaccination. Age categorization was based on the current recommendation for HPV vaccination.18 19 Details of the data extraction code and cohort selection flowchart are provided in eTable 1 and eFigure 1 in Supplement 1.

The primary outcome in this study was a composite measure encompassing any diagnosis of the following cancers, as defined by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10): head and neck cancers, penile cancer, esophageal cancer (upper two-thirds only), and anal cancer (eTable 2 in Supplement 1).20 The secondary outcomes included the individual diagnoses of each of the 4 cancers. Data were extracted on February 14, 2026. Outcome follow-up started 180 days after the index date. The index date was defined as the date of the first dose with health examination in the vaccinated group and the date of the first health examination in the unvaccinated group.

The TriNetX platform complied with the Health Insurance Portability and Accountability Act and General Data Protection Regulation.21 Therefore, informed consent was not required because this study utilized only deidentified and aggregated patient data. Although deidentified TriNetX studies generally do not require institutional review board approval,22 this study was reviewed and approved for publication by the institutional review board of Nara Prefecture General Medical Center.

The Role of [18F]FDG PET/CT in Predicting Toxicity in Patients with NHL Treated with CAR-T: A Systematic Review

CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin’s lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([18F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy’s overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [18F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [18F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy.

Intraoperative functional brain mapping for glioma surgery: a comprehensive review of the University of California San Francisco mapping protocol

Intraoperative functional brain mapping is an essential and intricate technique in modern-day glioma surgery. This article is not a review of the literature but of the technical protocol at our institution that has evolved over the recent decades to the current time and is intended to highlight details that enable us to perform maximal safe resection of gliomas.

Prior to surgery, anatomical and functional imaging protocols are obtained to determine the tumor to be resected within its anatomical and functional environment. Preoperative assessments are used to determine which mapping procedures and tasks are most appropriate. Cortical and subcortical motor and language mapping using low and high frequency stimulation paradigms are applied when appropriate during resection. Methods to interpret findings and troubleshoot issues are reviewed herein.

All preoperative imaging including magnetic resonance imaging, magnetoencephalography of functional cortex, and diffusion tensor imaging of subcortical tracts are uploaded into the neuronavigation station and used throughout surgery for guidance. The decision to continue with tumor resection is based on constant feedback from the mapping paradigms as functional pathways are approached in real time. Both awake and asleep anesthesia regimens are utilized depending on the type of testing required to assess and preserve functional areas during tumor resection. Postoperatively, deficits are assessed using MRI along with clinical exam to predict whether they will be temporary or permanent.

Giant skull base collision tumors in NF2-related schwannomatosis: longitudinal outcomes of planned selective resection

Giant skull base collision tumors in neurofibromatosis type 2–related schwannomatosis (NF2-SWN) pose a complex surgical challenge in young patients with lifelong tumor burden. Gross total resection is often impossible without severe neurological morbidity, and data on operative timing and durability are limited. We assessed long-term outcomes of planned, selective resection prioritizing neurological preservation.

We queried a prospective institutional database for NF2-SWN patients undergoing surgery for giant (≥ 4.0 cm) intracranial skull base collision tumors (≥ 2 neoplasms forming one mass) from January 2009 to December 2025. Surgery targeted symptomatic or high-risk components, accepting residual disease. Outcomes included time to reoperation, overall survival, and functional status.

Thirteen patients underwent 31 skull base operations. Mean age at first surgery was 27 years (range 19–42), with mean tumor diameter 5.0 cm (range 4.0–7.7 cm). Most (69%) had prior surgery and/or radiotherapy. Gross total resection was never achieved. Over mean 9.4-year follow-up, Kaplan–Meier analysis demonstrated reoperation-free survival of 61.5% at 5 years (95% CI, 26.6–83.7%), with a median reoperation-free survival of 6.1 years. The mean interval between reoperations was 4.8 years (median, 3.9 years; IQR, 2.7–5.7; range, 0.8–14.6). Overall survival was 100% at 5 years and 88% at 10 years. At last follow-up, median Karnofsky Performance Status was 70.

Molecular basis of human daylight vision

In a new study, the researchers have succeeded for the first time in determining the three-dimensional structure of human cone opsins in their dark state and showing how their molecular architecture enables their rapid activation by light. This provides important new insights into human vision and its evolution and may offer new starting points for the study of eye diseases that currently lack effective treatment. The study published in the journal Science.

Cone opsins are photoreceptor proteins found in the cone cells, which are densely packed in the fovea centralis. This area of the human retina is responsible for sharp vision. We humans have six to seven million cones in each eye. Their receptor proteins are activated by light, triggering a signalling cascade that ultimately produces electrical signals processed by the brain. Because this process is exceptionally fast, cone opsins enable us to track fast-moving objects with our eyes. However, they operate mainly during the day when the light levels are high. In low light, at dusk and at night, their evolutionarily younger relative, the rod opsin in rod cells, takes over this task.

Human colour vision is mediated by three types of cone opsins, each tuned to a different region of the visible spectrum. L cones are most sensitive to red light, M cones to green light, and S cones to blue light. Although there are only three cone types, we see the world in more than just three colours, as our colour perception arises from the interplay of their overlapping spectral sensitivities.

Comparison between molecular and histological IDH-wild-type glioblastoma and extensive subgroup analysis of IDH-wild-type astrocytic tumors without genomic glioblastoma-defining alterations

This study compares clinical characteristics and survival between molecular (MolGBM) and histological IDH-wild-type (IDH-WT) glioblastoma (HistGBM), and further characterizes histological lower-grade IDH-WT astrocytic tumors without genomic GBM-defining alterations.

Adult patients with histologically lower-grade IDH–WT astrocytoma (WHO grade 2–3) and available tumor tissue were included. Tumors were classified according to the 2021 WHO Classification of CNS tumors. Biopsy-only cases were excluded. IDH1 and TERT promoter (TERTp) mutations were analyzed via Sanger and whole-exome sequencing (WES). TERTp-WT tumors underwent WES and subsequent DNA methylation profiling. Clinical, molecular, and outcome data were collected.

The cohort comprised 47 surgically resected histologically lower-grade IDH-WT astrocytic tumors. Thirty-nine fulfilled WHO 2021 criteria for MolGBM, mainly based on TERTp mutation (n = 36), while eight lacked GBM-defining molecular alterations. Compared with HistGBM (n = 54), MolGBM more frequently presented with seizures and showed a lower Ki-67 index. Median overall survival (OS) was 19.8 months in MolGBM and 14.6 months in HistGBM, without a significant difference in univariable analysis (p = 0.11). Patients aged ≥ 60 years showed longer overall survival in the MolGBM group (17.9 vs. 12.3 months; p = 0.0079). In multivariable Cox regression adjusted for age, extent of resection, and completion of the Stupp regimen, MolGBM was independently associated with more favorable OS (HR 0.40, 95% CI 0.24–0.67, p = 0.0005). The eight tumors lacking GBM-defining alterations showed longer survival and marked diagnostic heterogeneity.

An AI model that thinks like we do offers new ways to peer inside the black box

When a standard large language model (LLM) is confronted with a problem, it tries to solve it by matching it to similar information it has seen before, and then give an answer based on those past patterns. But how it decides which information to use and what value it gives to different pieces of information can be somewhat inscrutable from the outside. An EPFL team has created a new large language model that is structured similarly to a human brain, allowing users more control and moving away from “black box” AI.

The LLM MiCRo (Mixture of Cognitive Reasoners) is architecturally divided into four specialized areas that act like different parts of the human brain, allowing users to have more control over how it approaches a question and to better understand how it comes to its answers. The model, which was presented at the International Conference on Learning Representations (ICLR 2026), comes from the NLP Lab, part of the School of Computer and Communication Sciences (IC), and the NeuroAI Lab, part of IC and the School of Life Sciences at EPFL. The paper is posted to the arXiv preprint server.

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