tbuckley/cabot-search huggingface dataset:
Effectiveness of app-based cognitive behavioral therapy for insomnia on preventing major depressive disorder in youth with insomnia and subclinical depression: A randomized clinical trial
Authors: Si-Jing Chen, Jian-Yu Que, Ngan Yin Chan, Le Shi, Shirley Xin Li, Joey Wing Yan Chan, Weizhen Huang, Chris Xie Chen, Chi Ching Tsang, Yuen Lam Ho, Charles M. Morin, Ji-Hui Zhang, Lin Lu, Yun Kwok Wing
Journal: PLoS Medicine (2025)

Background Increasing evidence suggests that insomnia plays an important role in the development of depression, supporting insomnia intervention as a promising approach to prevent depression in youth. This randomized controlled trial evaluated the effectiveness of app-based cognitive behavioral therapy for insomnia (CBT-I) in preventing future onset of major depressive disorder (MDD) in youth. Methods and findings This was a randomized, assessor-blind, parallel group-controlled trial in Chinese youth (aged 15−25 years) with insomnia disorder and subclinical depressive symptoms. Participants were randomly assigned (1:1) to 6-week app-based CBT-I or 6-week app-based health education (HE) delivered through smartphones. Online assessments and telephone clinical interviews were conducted at baseline, post-intervention, 6- and 12-month follow-ups. The primary outcome was time to onset of MDD. The secondary outcomes included depressive symptoms and insomnia at both symptom and disorder levels. Between September 9, 2019, and November 25, 2022, 708 participants (407 females [57%]; mean age, 22.1 years [SD = 1.9]) were randomly allocated to app-based CBT-I group ( n = 354) or app-based HE group ( n = 354). Thirty-seven participants (10%) in the intervention group and 62 participants (18%) in the control group developed new-onset MDD throughout the 12-month follow-up, with a hazard ratio of 0.58 (95% confidence interval 0.38–0.87; p = 0.008). The number needed to treat to prevent MDD at 1 year was 10.9 (6.8–26.6). The app-based CBT-I group has higher remission rates of insomnia disorder than the controls at post-intervention (52% versus 28%; relative risk 1.83 [1.49–2.24]; p &lt; 0.001) and throughout 12-month follow-up. In addition, the CBT-I group reported a greater decrease in depressive (adjusted difference −1.0 [−1.6 to −0.5]; Cohen’s d = 0.53; p &lt; 0.001) and insomnia symptoms (−2.0 [−2.7 to −1.3], d = 0.78; p &lt; 0.001) than the controls at post-intervention and throughout 6-month follow-up. Insomnia was a mediator of intervention effects on depression. No adverse events related to the interventions were reported. Conclusions App-based CBT-I is effective in preventing future onset of major depression and improving insomnia outcomes among youth with insomnia and subclinical depression. These findings highlight the importance of targeting insomnia to prevent the onset of MDD and emphasize the need for wider dissemination of digital CBT-I to promote sleep and mental health in the youth population. Trial registration ClinicalTrials.Gov ( NCT04069247 ).
The Role of Sex and Gender in Acute Kidney Injury - Consensus Statements from the 33rd Acute Disease Quality Initiative
Authors: Danielle E Soranno, Linda Awdishu, Sean M Bagshaw, David Basile, Samira Bell, Azra Bihorac, Joseph Bonventre, Alessandra Brendolan, Rolando Claure-Del Granado, David Collister, Lisa M Curtis, Kristin Dolan, Dana Y Fuhrman, Zahraa Habeeb, Michael P Hutchens, Kianoush B Kashani, Nuttha Lumlertgul, Mignon McCulloch, Shina Menon, Amira Mohamed, Neesh Pannu, Karen Reue, Claudio Ronco, Manisha Sahay, Emily See, Michael Zappitelli, Ravindra Mehta, Marlies Ostermann
Journal: Kidney International (2025)

Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33rd Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed. Recommendations include incorporating sex and gender into research along the bench-to-bedside spectrum, analyzing sex-stratified results, evaluating the effects of sex chromosomes, hormones, and gender on outcomes, considering fluctuations of hormone levels, studying the impact gender may have on access to care, and developing educational tools to inform patients, providers, and stakeholders. This meeting report summarizes what is known about sex and gender along the AKI care continuum and proposes an agenda for translational discovery to elucidate the role of sex and gender in AKI across the lifespan.
Higher Odds of Dupilumab Prescriptions for Black Patients with Atopic Dermatitis: Results of a Retrospective Study Using DataDerm, The Database of The American Academy of Dermatology
Authors: Ramiro Rodriguez, Mindy D Szeto, Jourdan Hydol-Smith, Colin Burnette, Arik Aninos, Toni Kaye, Lisa M Schilling, Robert P Dellavalle
Journal: Journal of the American Academy of Dermatology (2025)
Bioinspired nanofiber dressings with counter-transport of exudate and drug for treating heavily exuding wounds
Authors: Xuening Jin, Yihao Wu, Zizhao Chen, Zheng Chen, Fujin Zhou, Qishu Jin, Shuting Wu, Yanping Feng, Jianfeng Ma, Xiaohui Guo, Jiang Chang, Chen Yang, Botao Song
Journal: Biomaterials (2025)
Nail Unit Melanoma Treated with Mohs Micrographic Surgery: Technique, Local Recurrence Rate, and Surgical Outcomes
Authors: Karla L Valdes Morales, Daniela Frankel, Mara D Trifoi, Stephanie K Lin, Annika M Deitermann, Marissa Lubeck, Joseph F Sobanko, H William Higgins, Cerrene N Giordano, Joanna L Walker, Junqian Zhang, Daniel J Lewis, Benjamin Chang, Jason D Wink, Ines C Lin, Stephen J Kovach, Jeremy R Etzkorn, Christopher J Miller
Journal: Journal of the American Academy of Dermatology (2025)
Biochemical Strategy-Based Hybrid Hydrogel Dressing-Mediated In Situ Synthesis of Selenoproteins for DFU Immunity-Microbiota Homeostasis Regulation
Authors: Xueling Liu, Weidi Wang, Yali Wang, Wenyuan Duan, Chao Liu, Peng Quan, Jiali Xiao, Yunning Zhang, Yu Hao, Liang Fang, Yilin Song, Wenzhou Zhang
Journal: Biomaterials (2025)
Estimating the impact of school closures on the COVID-19 dynamics in 74 countries: A modelling analysis
Authors: Romain Ragonnet, Angus E. Hughes, David S. Shipman, Michael T. Meehan, Alec S. Henderson, Guillaume Briffoteaux, Nouredine Melab, Daniel Tuyttens, Emma S. McBryde, James M. Trauer
Journal: PLoS Medicine (2025)

Background School closures have been a prominent component of the global Coronavirus Disease 2019 (COVID-19) response. However, their effect on viral transmission, COVID-19 mortality and health care system pressure remains incompletely understood, as traditional observational studies fall short in assessing such population-level impacts. Methods and findings We used a mathematical model to simulate the COVID-19 epidemics of 74 countries, incorporating observed data from 2020 to 2022 and historical school closure timelines. We then simulated a counterfactual scenario, assuming that schools remained open throughout the study period. We compared the simulated epidemics in terms of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, deaths, and hospital occupancy pressure. We estimated that school closures achieved moderate to significant burden reductions in most settings over the period 2020 to 2022. They reduced peak hospital occupancy pressure in nearly all countries, with 72 out of 74 countries (97%) showing a positive median estimated effect, and median estimated effect ranging from reducing peak hospital occupancy pressure by 89% in Brazil to increasing it by 19% in Indonesia. The median estimated effect of school closures on COVID-19 deaths ranged from a 73% reduction in Thailand to a 7% increase in the United Kingdom. We estimated that school closures may have increased overall COVID-19 mortality (based on median estimates) in 9 countries (12%), including several European nations and Indonesia. This is attributed to changes in population-level immunity dynamics, leading to a concentration of the epidemic during the Delta variant period, alongside an upward shift in the age distribution of infections. While our estimates were associated with significant uncertainty, our sensitivity analyses exploring the impact of social mixing assumptions revealed robustness in our country-specific conclusions. The main study limitations include the fact that analyses were conducted at the national level, whereas school closure policies often varied by region. Furthermore, some regions, including Africa, were underrepresented due to insufficient data informing the model. Conclusions Our analysis revealed nuanced effects of school closures on COVID-19 dynamics, with reductions in COVID-19 impacts in most countries but negative epidemiological effects in a few others. We identified critical mechanisms for consideration in future policy decisions, highlighting the unpredictable nature of emerging variants and potential shifts in infection demographics associated with school closures.
Targeting allograft inflammatory factor-1 reprograms kidney macrophages to enhance repair
Authors: Irma Husain, Holly Shah, Collin Z. Jordan, Naveen R. Natesh, Olivia K. Fay, Yanting Chen, Jamie R. Privratsky, Hiroki Kitai, Tomokazu Souma, Shyni Varghese, David N. Howell, Edward B. Thorp, Xunrong Luo
Journal: Journal of Clinical Investigation (2025)

The role of macrophages remains incompletely understood in kidney injury and repair. Their plasticity offers an opportunity to polarize them towards mediating injury resolution in both native and transplanted kidneys undergoing ischemia and/or rejection. Here, we show that infiltrating kidney macrophages augmented their AIF-1 expression after injury. Aif1 genetic deletion led to macrophage polarization towards a reparative phenotype while halting the development of kidney fibrosis. The enhanced repair was mediated by higher levels of anti-inflammatory and pro-regenerative markers leading to a reduction in cell death and increase in proliferation of kidney tubular epithelial cells following ischemic reperfusion injury. Adoptive transfer of Aif1-/- macrophages to Aif1+/+ mice conferred protection against ischemia reperfusion injury. Conversely, depletion of macrophages reversed the tissue-reparative effects in Aif1-/- mice. We further demonstrated an increased expression of AIF-1 in human kidney biopsies from native kidneys with acute kidney injury or chronic kidney disease, as well as in biopsies from kidney allografts undergoing acute or chronic rejection. We conclude that AIF-1 is a macrophage marker of renal inflammation, and its targeting uncouples macrophage reparative functions from profibrotic functions. Thus, therapies inhibiting AIF-1 when ischemic injury is inevitable have the potential to reduce the global burden of kidney disease.
Single-cell DNA sequencing reveals pervasive positive selection throughout preleukemic evolution
Authors: Gladys Poon, Aditi Vedi, Mathijs Sanders, Elisa Laurenti, Peter Valk, Jamie R Blundell
Journal: Cell Genomics (2025)

The representation of driver mutations in preleukemic hematopoietic stem cells (pHSCs) provides a window into the somatic evolution that precedes acute myeloid leukemia (AML). Here, we isolate pHSCs from the bone marrow of 16 patients diagnosed with AML and perform single-cell DNA sequencing on thousands of cells to reconstruct phylogenetic trees of the major driver clones in each patient. We develop a computational framework that can infer levels of positive selection operating during preleukemic evolution from the statistical properties of these phylogenetic trees. Combining these data with 67 previously published phylogenetic trees, we find that the highly variable structures of preleukemic trees emerge naturally from a simple model of somatic evolution with pervasive positive selection typically in the range of 9%-24% per year. At these levels of positive selection, we show that the identification of early multiple-mutant clones could be used to identify individuals at risk of future AML.
Glomerular Hyperfiltration and Tubuloglomerular Feedback in Diabetic Kidney Disease
Authors: Rikke Borg, David ZI Cherney
Journal: Journal of the American Society of Nephrology (2025)

1Department of Medicine, Zealand University Hospital, Roskilde, Denmark 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 3University Health Network, University of Toronto, Toronto, Ontario, Canada 4Department of Medicine, Division of Nephrology, Toronto General Hospital, Toronto, Ontario, Canada Correspondence: Dr. Rikke Borg, email: [email protected] See related article, "Acetazolamide Therapy and Kidney Function in Persons with Nonalbuminuric Diabetes Mellitus Type 1," on pages XXX–XXX.
Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli
Authors: Monica Dallmann-Sauer, Vinicius M. Fava, Stephanus T. Malherbe, Candice E. MacDonald, Marianna Orlova, Elouise E. Kroon, Aurélie Cobat, Stéphanie Boisson-Dupuis, Eileen G. Hoal, Laurent Abel, Marlo Möller, Jean-Laurent Casanova, Gerhard Walzl, Nelita Du Plessis, Erwin Schurr
Journal: Journal of Clinical Investigation (2025)

Natural resistance to Mycobacterium tuberculosis (Mtb) infection in some people with HIV (PWH) is unexplained. We performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or ex vivo stimulated with Mtb, for 7 PWH who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters). Alveolar macrophages (AM) from resisters displayed a baseline M1 macrophage phenotype while AM from LTBI did not. Resisters displayed alveolar lymphocytosis, with enrichment of all T cell subpopulations including IFNG-expressing cells. In both groups, mycobactericidal granulysin was expressed almost exclusively by a T cell subtype that co-expressed granzyme B, perforin and NK cell receptors. These poly-cytotoxic T lymphocytes (CTL) over-expressed activating NK cell receptors and were increased in resister BAL. Following challenge with Mtb, only Intraepithelial Lymphocytes-like cells from LTBI participants responded with increased transcription of IFNG. AM from resisters responded with a stronger TNF signature at 6h post-infection while at 24h post-infection AM from LTBI displayed a stronger IFN-γ signature. Conversely, at 24h post-infection only AM from resisters displayed a significant upregulation of MICA transcripts which encode an activating ligand for poly-CTL. These results suggest that poly-CTL and AM mediate the resister phenotype in PWH.
MFGE8 induces anti-PD-1 therapy resistance by promoting extracellular vesicle sorting of PD-L1
Authors: Wenhui Wang, Jiming Chen, Shibo Wang, Xinhai Sun, Jie Yang, Pengfei Yu, Guinv Hu, Jiang Wang, Jing Zhang, Shuya Qiao, Jianli Wang, Gensheng Zhang, Yuzhou He, Huajun Feng, Zhijian Cai
Journal: Cell Reports Medicine (2025)

Anti-PD-1 therapy, effective in patients with various advanced tumors, still encounters the challenge of insensitivity in most patients. Here, we demonstrate that PD-L1 on tumor cell-derived extracellular vesicles (TEVs) is critical for anti-PD-1 therapy resistance. Reducing endogenous and transferring exogenous TEVs abrogates and induces anti-PD-1 therapy resistance, respectively. Notably, PD-L1 is sorted onto TEVs via the endosomal sorting complex required for transport after ubiquitination by UBE4A and gradually upregulated on TEVs with tumor progression. During progression, increased MFGE8 from tumor cells promotes self αv integrin signaling activation, enabling themselves to upregulate UBE4A, thereby increasing PD-L1 on TEVs and enhancing their immunosuppressive abilities. Translationally, anti-MFGE8-neutralizing antibodies effectively downregulate UBE4A and TEV PD-L1, thereby negating anti-PD-1 therapy resistance. Furthermore, serum MFGE8 and PD-L1+ EV levels of tumor patients correlate positively, and high levels of both indicate poor prognosis after anti-PD-1 therapy. Thus, MFGE8 is a promising target for overcoming resistance and predicting responsiveness to anti-PD-1 therapy.
Multicenter Phase 2 Trial of Second-Line Regorafenib in Patients with Unresectable Hepatocellular Carcinoma After Progression on Atezolizumab Plus Bevacizumab (REGONEXT)
Authors: Jaekyung Cheon, Baek-Yeol Ryoo, Hong Jae Chon, Hyung-Don Kim, Min-Hee Ryu, Kyu-Pyo Kim, Beodeul Kang, Richard S. Finn, Stephen Lam Chan, Changhoon Yoo
Journal: Liver Cancer (2025)

Introduction: Atezolizumab-bevacizumab (Atezo-Bev) has become the standard first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). However, data on subsequent treatment after Atezo-Bev failure are lacking. We aimed to investigate the efficacy and safety of regorafenib for uHCC progression after first-line Atezo-Bev. Methods: This investigator-initiated, single-arm, phase 2 trial involved two academic centers in Korea. Eligibility criteria included a diagnosis of HCC, prior treatment with at least 2 cycles of Atezo-Bev, and Child-Pugh A liver function. Eligible patients received regorafenib 160 mg once daily for 3 weeks of every 4-week cycle (i.e., 3 weeks on, 1 week off) until progressive disease or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate, disease control rate according to RECIST v1.1, overall survival (OS), and treatment-related adverse events. Results: Forty patients were enrolled from December 2021 through May 2023. The median follow-up duration was 10.1 months (95% confidence interval [CI], 8.3-12.0). The median PFS was 3.5 months (95% CI, 3.0-3.9). The median OS was 10.5 months (95% CI, 7.1-13.8), and the 6-month OS rate was 65.0%. The objective response rate and disease control rate were 10.0% and 82.5%, respectively. The most common grade 3-4 treatment-related adverse event was thrombocytopenia (5.0%). When stratified according to time to progression on prior Atezo-Bev (first quartile [&lt; 2.3 months] vs. second to fourth quartiles [≥ 2.3 months]), patients with longer time to progression on prior Atezo-Bev had better OS (15.0 vs. 3.6 months, p&lt;0.001), objective response rate (13.3% vs. 0%, p=0.009), and a tendency toward better PFS with regorafenib (3.8 vs. 2.5 months; p=0.054). Conclusions: Second-line regorafenib was effective for treating uHCC progression after first-line Atezo-Bev. The efficacy and safety outcomes from our study were consistent with those observed in the pivotal phase 3 RESORCE trial, which included sorafenib-tolerant/progressed patients.
The Calcium-Sensing Receptor in the Thick Ascending Limb and the Renal Response to Hypercalcemia
Authors: Nina Himmerkus, Catarina Quintanova, Harneet Bhullar, Wouter H. van Megen, Amanda Lima Deluque, Karsten Skjødt, Milos Bogdanovic, Markus Bleich, Todd Alexander, Henrik Dimke
Journal: Journal of the American Society of Nephrology (2025)

Background: The parathyroid calcium-sensing receptor (CASR) controls the release of parathyroid hormone (PTH) in response to changes in serum calcium levels. Activation of the renal CASR increases urinary calcium excretion and is particularly important when CASR-dependent reductions in PTH fail to lower serum calcium. However, the role of the renal CASR in protecting against hypercalcemia and the direct effects of chronic CASR activation on tubular calcium handling remains to be fully elucidated. Methods: Experimental hypercalcemia was induced using the Vitamin D analog (Dihydrotachysterol, DHT) in mice with Ksp -Cre dependent deletion of the Casr ( Ksp - Casr ) in kidney with Cre negative littermates (WT) serving as controls. Urinary and fecal electrolyte determinations, dual-energy x-ray absorptiometry, molecular and biochemical evaluation, and in vitro tubule microperfusion were performed in both sexes. Results: Ksp -Cre-driven Casr deletion strongly reduced CASR abundance in the thick ascending limb (TAL). At baseline, no marked differences were detected in electrolyte handling and tubular permeability characteristics across the TAL. 3 days of DHT administration induced hypercalcemia in both WT and Ksp - Casr mice. However, while WT mice developed hypercalciuria, this response was absent in Ksp - Casr mice. Urinary excretion of magnesium and other electrolytes did not differ between hypercalcemic WT and Ksp - Casr mice. Intestinal electrolyte absorption was comparable between the two groups. Microperfusion of isolated cortical TALs revealed no baseline differences in the transepithelial voltage, resistance, or ion permeabilities. Following hypercalcemia, transepithelial resistance increased and calcium permeability markedly decreased in WT mice, but not in Ksp-Casr mice, with only minor alterations in magnesium permeability and no changes in transepithelial voltage. Conclusions: In hypercalcemic mice, absence of the CASR in TAL prevented the increase in urinary calcium excretion. The CASR specifically regulated the paracellular permeability of the TAL, especially for calcium.
Protective effect of ulinastatin against negative inflammatory response and organ dysfunction in acute aortic dissection surgery: The PANDA trial
Authors: Hong Liu, Si-Chong Qian, Kai Zhu, Yi-Fei Diao, Xiu-Fan Xu, Zhi-Wei Tang, Guo-Liang Fan, Hong-Hua Yue, Jun-Quan Chen, Ji-Nong Yang, Ying-Yuan Zhang, Chao Ma, Xiang Liu, Ying Wu, Zhong Wu, Nan Liu, Ao Li, Bu-Qing Ni, Yong-Feng Shao, Sheng Zhao, Hai-Yang Li, Hong-Jia Zhang
Journal: Cell Reports Medicine (2025)
Sex dimorphism in the mouse bone marrow niche regulates hematopoietic engraftment via sex-specific Kdm5c/Cxcl12 signaling
Authors: Xiaojing Cui, Liming Hou, Bowen Yan, Jinpeng Liu, Cuiping Zhang, Pinpin Sui, Sheng Tong, Larry Luchsinger, Avital Mendelson, Daohong Zhou, Feng-chun Yang, Hui zhong, Ying Liang
Journal: Journal of Clinical Investigation (2025)

The bone marrow (BM) niche is critical in regulating hematopoiesis, and sexual dimorphism and its underlying mechanism in BM niche and its impact on hematopoiesis are not well understood. We show that male mice exhibited a higher abundance of leptin-receptor-expressing mesenchymal stromal cells (LepR-MSCs) compared to female mice. Sex-mismatched co-culture and BM transplantation showed that the male BM niche provided superior support for in vitro colony formation and in vivo hematopoietic engraftment. The co-transplantation of male stromal cells significantly enhanced engraftment in female recipients. Single-cell RNA sequencing revealed that the lower expression of the X-linked lysine H3K4 demethylase, Kdm5c, in male MSCs led to the increased expression of Cxcl12. In MSC-specific Kdm5c knockout mouse model, the reduction of KDM5C in female MSCs enhanced MSC quantity and function, ultimately improving engraftment to the male level. Kdm5c thus plays a role in driving sexual dimorphism in the BM niche and hematopoietic regeneration. Our study unveils a sex-dependent mechanism governing BM niche regulation and its impact on hematopoietic engraftment. The finding offers potential implications for enhancing BM transplantation efficacy in clinical settings by harnessing the resource of male MSCs or targeting Kdm5c.
Finding and Profiling Renal Cells with Spatial Transcriptomics
Authors: Katherine R. Bull
Journal: Journal of the American Society of Nephrology (2025)

1Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK, Oxford Kidney Unit, Oxford University Hospitals Trust, Oxford, UK, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK. aCorresponding author information: [email protected]