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Precision nutrition must consider cost-effectiveness to deliver benefits to patients 精准营养必须考虑成本效益,为患者带来益处
IF 82.9 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-16 DOI: 10.1038/s41591-026-04231-x
Nicola Guess, Dan Pollard, Alan Brennan, Penny Breeze
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引用次数: 0
A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial 短期致幻剂干预重度抑郁症:IIa期随机安慰剂对照试验
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-16 DOI: 10.1038/s41591-025-04154-z
David Erritzoe, Tommaso Barba, Tiffanie Benway, Zelah Joel, Meghan Good, Marie Layzell, Michelle Baker Jones, Graham Campbell, Ashleigh Murphy-Beiner, Peter Rands, Malcolm Boyce, Helen Topping, Brandon Weiss, Christopher Timmermann, David Nutt, Robin Carhart-Harris, Carol Routledge, Ellen James
Major depressive disorder (MDD) is a leading cause of disability worldwide, yet many patients have inadequate responses to current treatments. Dimethyltryptamine (DMT), a serotonergic psychedelic with rapid onset and short duration, shows promise as a potential antidepressant (AD), although clinical evidence in MDD remains limited. We conducted a phase IIa, double-blind, placebo-controlled, randomized clinical trial to evaluate the efficacy and safety of intravenous DMT (SPL026; DMT fumarate) in adults with moderate-to-severe MDD. Participants received a single 21.5-mg dose of DMT or placebo infused over 10 min, along with supportive psychotherapeutic support, followed by a 2-week assessment. A subsequent open-label phase offered all participants a second DMT dose. The primary outcome was the change in Montgomery–Åsberg Depression Rating Scale (MADRS) at 2 weeks. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS ≤ 10). A total of 34 participants were randomized, 17 to placebo–active and 17 to active–active. At 2 weeks, the DMT group showed a significantly greater reduction in MADRS score than placebo (mean difference = −7.35; 95% CI = −13.62 to −1.08; P = 0.023). In the open-label phase, AD effects persisted up to 3 months, with no significant differences between those who received one versus two doses. Adverse events were mostly mild to moderate, commonly infusion site pain, nausea and transient anxiety. No serious adverse events occurred. A single dose of DMT with psychotherapeutic support produced a rapid, significant reduction in depressive symptoms, sustained up to 3 months. The treatment was well-tolerated and safe. ClinicalTrials.gov registration: NCT04673383 . A single intravenous dose of the psychedelic dimethyltryptamine, combined with psychological support, produces rapid and lasting reductions in depressive symptoms in adults with major depressive disorder.
重度抑郁症(MDD)是世界范围内致残的主要原因,但许多患者对目前的治疗反应不足。二甲基色胺(DMT)是一种起效快、持续时间短的5 -羟色胺能致幻剂,虽然在重度抑郁症中的临床证据仍然有限,但它有望成为潜在的抗抑郁药(AD)。我们进行了一项IIa期、双盲、安慰剂对照、随机临床试验,以评估静脉注射DMT (SPL026;富马酸DMT)治疗中重度重度重度重度重度抑郁症的疗效和安全性。参与者接受单剂量21.5 mg DMT或安慰剂注入超过10分钟,以及支持性心理治疗支持,随后进行为期2周的评估。随后的开放标签阶段为所有参与者提供第二次DMT剂量。主要观察指标为2周时Montgomery -Åsberg抑郁评定量表(MADRS)的变化。次要结局包括缓解(MADRS评分降低≥50%)和缓解(MADRS≤10)。共有34名参与者被随机分配,17名安慰剂组和17名积极组。在2周时,DMT组的MADRS评分明显低于安慰剂组(平均差异= - 7.35;95% CI = - 13.62至- 1.08;P = 0.023)。在开放标签阶段,阿尔茨海默病的影响持续了3个月,在接受一次和两次剂量的患者之间没有显著差异。不良事件多为轻至中度,常见输液部位疼痛、恶心和短暂性焦虑。未发生严重不良事件。在心理治疗支持下,单剂量DMT可迅速显著减轻抑郁症状,持续时间长达3个月。这种治疗耐受性好,而且安全。ClinicalTrials.gov注册:NCT04673383。
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引用次数: 0
Neurodegenerative diseases need more mechanism-informed trials 神经退行性疾病需要更多机制知情的试验
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-16 DOI: 10.1038/s41591-026-04258-0
Recent failures in high-profile clinical trials of neurodegenerative diseases highlight the need to rebalance clinical ambition and biological understanding.
最近一些备受瞩目的神经退行性疾病临床试验的失败,突显了重新平衡临床抱负和生物学理解的必要性。
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引用次数: 0
Embedding equity in clinical research governance. 在临床研究治理中嵌入公平。
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-13 DOI: 10.1038/s41591-026-04232-w
Johanna M C Blom, Ciara Staunton, Sophie Tascedda, Neil Slabbert, Luca Pani, Melodie Labuschaigne
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引用次数: 0
The role of strategy units in guiding research institutions through complexity. 战略单位在指导研究机构应对复杂性中的作用。
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-13 DOI: 10.1038/s41591-026-04218-8
Michela Giulia Bertero, Katrine Sonne-Hansen, Anna-Lynn Wegener, Teresa Sanchis
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引用次数: 0
Climate change could hinder malaria eradication efforts. 气候变化可能会阻碍消灭疟疾的努力。
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-13 DOI: 10.1038/d41591-026-00009-3
Karen O'Leary
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引用次数: 0
Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy 抗pd -1治疗后与HIV储存库衰减相关的先天抗病毒和免疫功能
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-12 DOI: 10.1038/s41591-025-04139-y
Aarthi Talla, Joao L. L. C. Azevedo, Muhammad Bilal Latif, Ana B. Enriquez, Gabriela Pacheco Sanchez, Adam N. Pelletier, Saswat Kumar Bal, Sangeeta Kumari, Viviane Schuch, Khader Ghneim, Ajantha Rhodes, Frank Maldarelli, Robert Yarchoan, Kathryn Lurain, Ramya Ramaswami, Elad Sharon, Bruce W. Hess, Leonard D’Amico, Javier Martinez-Picado, Nicolas Chomont, Sharon R. Lewin, Steven G. Deeks, Steven P. Fling, Martin A. Cheever, Thomas S. Uldrick, Ashish A. Sharma, Rafick-Pierre Sekaly
Antiretroviral therapy (ART) suppresses HIV but does not eliminate the latent viral reservoir, which persists in programmed cell death protein 1 (PD-1)-expressing CD4+ T cells. Anti-PD-1 therapies have reduced the HIV reservoir in people living with HIV (PLWH) and cancer; however, the individuals who benefit and the mechanisms driving reservoir reduction remain unclear. We performed a prespecified exploratory, longitudinal multiomic profiling of 30 PLWH (29 males and one female) with cancer in the phase 1 CITN-12 clinical trial, in which pembrolizumab was evaluated for safety and preliminary antitumor activity. The therapy was generally well tolerated, with most adverse events graded 1–2 and objective antitumor response observed in five participants (one complete response and four partial responses). Within 24 hours of treatment, we observed an expansion of proliferating HIV-specific effector CD8+ T cells and a decline in plasma TGFβ. Furthermore, among the 14 participants tracked to the end of treatment (ranging from 44 to 315 days after therapy initiation), nine display early induction and sustained expression of interferon-stimulated genes (ISGs), antiviral restriction factors and Toll-like receptor (TLR) signaling and a reduction in the HIV reservoir. Mapping these transcriptomic signatures across more than 1,000 public single-cell RNA sequencing datasets reveals that anti-PD-1-induced programs are present in subsets of across subsets of disease states, indicating that some people already display a heightened antiviral state. Together, these findings define immune pathways that help identify PLWH most likely to experience reservoir decay with anti-PD-1 therapy and suggest that sustained ISG activation may contribute to reservoir reduction and prevention of viral rebound upon ART interruption. ClinicalTrials.gov registration: NCT02595866 . A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.
抗逆转录病毒治疗(ART)抑制HIV,但不能消除潜伏病毒库,潜伏病毒库持续存在于表达CD4+ T细胞的程序性细胞死亡蛋白1 (PD-1)中。抗pd -1疗法降低了艾滋病病毒(PLWH)和癌症患者的艾滋病病毒库;然而,哪些个体受益以及导致储层减少的机制仍不清楚。在CITN-12期临床试验中,我们对30名PLWH患者(29名男性和1名女性)进行了预先指定的探索性纵向多组学分析,其中pembrolizumab被评估为安全性和初步抗肿瘤活性。该疗法耐受性良好,大多数不良事件为1-2级,5名参与者观察到客观的抗肿瘤反应(1例完全缓解,4例部分缓解)。在治疗24小时内,我们观察到增殖的hiv特异性效应CD8+ T细胞的扩增和血浆tgf - β的下降。此外,在随访至治疗结束(治疗开始后44至315天)的14名参与者中,有9人表现出干扰素刺激基因(ISGs)、抗病毒限制因子和toll样受体(TLR)信号的早期诱导和持续表达,以及HIV库的减少。将这些转录组特征映射到1000多个公开的单细胞RNA测序数据集中,揭示出抗pd -1诱导的程序存在于疾病状态的亚群中,这表明一些人已经表现出更高的抗病毒状态。总之,这些发现定义了免疫途径,帮助识别抗pd -1治疗最有可能经历储库衰变的PLWH,并表明持续的ISG激活可能有助于储库减少和预防ART中断时病毒反弹。ClinicalTrials.gov注册:NCT02595866。
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引用次数: 0
PD-1 blockade reprograms antiviral immunity and reduces the HIV reservoir PD-1阻断重新编程抗病毒免疫并减少HIV库。
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-12 DOI: 10.1038/s41591-025-04152-1
PD-1 blockade reprograms both innate and adaptive immunity in people living with HIV and cancer, inducing interferon-driven antiviral responses that reduce the HIV reservoir. A pre-existing type I interferon signature predicts reservoir decline, whereas high TGFβ signaling opposes it, defining immune states that influence the outcome of PD-1 therapy.
PD-1阻断可重编程艾滋病毒和癌症患者的先天免疫和适应性免疫,诱导干扰素驱动的抗病毒反应,减少艾滋病毒库。预先存在的I型干扰素信号可以预测储存库的下降,而高tgf - β信号则相反,定义影响PD-1治疗结果的免疫状态。
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引用次数: 0
Microfluidic automation improves oocyte recovery from follicular fluid of patients undergoing in vitro fertilization. 微流控自动化提高体外受精患者卵泡液中卵母细胞的恢复。
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-12 DOI: 10.1038/s41591-026-04207-x
Baris R Mutlu, Sabrina C Civale, Joshua Diettrich, Neha Gupta, Thomas Barber, Mitchel Sayare, Alan S Penzias, Michael M Alper, Thomas L Toth, Ravi Kapur, Mehmet Toner, Denny Sakkas, Emre Ozkumur

Infertility is a global health challenge affecting millions worldwide, and in vitro fertilization (IVF) remains the main treatment option. The increasing demand for IVF necessitates innovations that improve access, efficiency and outcomes. To address this need, we developed a microfluidic device (FIND-Chip) that automates the isolation and denudation of oocytes from follicular fluid (FF), a critical step in IVF workflow. In a clinical study involving 582 patients from four IVF centers, FIND-Chip was utilized to perform automated oocyte recovery from FF and revealed that in more than 50% of the cases functional and mature oocytes are inadvertently discarded under current clinical practice. These undetected oocytes successfully developed into high-quality blastocysts, thereby substantially expanding the embryo pool available for patients' treatment. Notably, an oocyte that was retrieved by FIND-Chip from a clinically screened and discarded FF sample led to a live birth, highlighting the potential of microfluidic automation to enhance IVF success rates.

不孕症是一个全球性的健康挑战,影响着全世界数百万人,体外受精(IVF)仍然是主要的治疗选择。对试管婴儿的需求不断增加,需要创新,以改善获取,效率和结果。为了满足这一需求,我们开发了一种微流体装置(FIND-Chip),可以自动从卵泡液(FF)中分离和剥离卵母细胞,这是试管婴儿(IVF)工作流程中的关键步骤。在一项涉及来自四个IVF中心的582例患者的临床研究中,FIND-Chip被用于从FF中进行自动卵母细胞回收,结果显示,在目前的临床实践中,超过50%的病例中功能和成熟的卵母细胞被无意中丢弃。这些未被发现的卵母细胞成功地发育成高质量的囊胚,从而大大扩大了可供患者治疗的胚胎库。值得注意的是,通过FIND-Chip从临床筛选和丢弃的FF样本中检索到的卵母细胞导致了活产,这突出了微流体自动化提高试管婴儿成功率的潜力。
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引用次数: 0
Lay community health worker-led care with mobile decision support for uncontrolled hypertension: a cluster-randomized trial. 非专业社区卫生工作者主导的护理与移动决策支持对不受控制的高血压:一项集群随机试验。
IF 5 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-12 DOI: 10.1038/s41591-026-04208-w
Felix Gerber, Giuliana Sanchez-Samaniego, Ravi Gupta, Thabo Ishmael Lejone, Thesar Tahirsylaj, Fabian Raeber, Mamakhala Chitja, Malebona Mathulise, Thuso Kabi, Mosoetsi Mokaeane, Malehloa Maphenchane, Manthabiseng Molulela, Makhebe Khomolishoele, Mota Mota, Sesale Masike, Matumaole Bane, Manthati Mofokeng, Mamoronts'ane Pauline Sematle, Retselisitsoe Makabateng, Madavida Mphunyane, Lebohang Sao, Mosa Tlahali, Malitaba Litaba, Dave Brian Basler, Kevin Kindler, Irene Ayakaka, Pauline Grimm, Thilo Burkard, Frédérique Chammartin, Alain Amstutz, Niklaus Daniel Labhardt

Access to hypertension care remains insufficient, particularly in remote rural areas in resource-limited settings. Community health workers (CHWs), lay providers living in the communities they serve, may help close this gap, but the effectiveness and safety of lay CHW-led hypertension care-including independent initiation and titration of medication-remain uncertain. We conducted a 1:1 cluster-randomized trial nested within the Community-Based Chronic Care Lesotho (ComBaCaL) cohort study in 103 rural villages in Lesotho. Following community-based hypertension screening, 547 nonpregnant adults with blood pressure (BP) ≥140/90 mm Hg were enrolled (274 control and 273 intervention). In intervention clusters, lay CHWs independently prescribed and titrated a fixed-dose combination of amlodipine and hydrochlorothiazide, guided by a mobile clinical decision support system. In control clusters, participants were referred to health facilities for standard care. The primary objective was to assess the effectiveness and safety of lay CHW-led care, with the primary outcome defined as BP <140/90 mm Hg at 12 months. In the intention-to-treat analysis (543 participants with 4 exclusions owing to intercurrent pregnancy), BP control was achieved by 156/271 (58%) versus 130/272 (48%) in intervention and control arms, respectively (adjusted odds ratio 1.52, 95% confidence interval 1.01 to 2.29, P = 0.046). A predefined complete case analysis yielded consistent results. No relevant differences in safety outcomes were observed. Among people with uncontrolled hypertension, lay CHW-led, CDSS-supported care was safe and more effective than referral to facility-based professional care. These findings support expanding first-line hypertension management by lay CHWs in remote, resource-limited settings. Clinicaltrials.gov registration: NCT05684055 .

获得高血压护理的机会仍然不足,特别是在资源有限的偏远农村地区。社区卫生工作者(chw),生活在他们服务的社区的非专业提供者,可能有助于缩小这一差距,但非专业chw领导的高血压护理的有效性和安全性-包括独立开始和滴定药物-仍然不确定。我们在莱索托103个乡村的社区慢性护理莱索托(ComBaCaL)队列研究中进行了1:1集群随机试验。在以社区为基础的高血压筛查后,547名血压(BP)≥140/90 mm Hg的未怀孕成人入组(对照组274名,干预组273名)。在干预集群中,在移动临床决策支持系统的指导下,基层chw独立开处方并滴定氨氯地平和氢氯噻嗪的固定剂量组合。在对照组中,参与者被转诊到卫生机构接受标准治疗。主要目的是评估非专业chw主导护理的有效性和安全性,主要结局定义为BP
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Nature Medicine
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