tbuckley/cabot-search huggingface dataset:
Neuronal and glial vulnerability of the suprachiasmatic nucleus in tauopathies: evidence from human studies and animal models
Authors: Gowoon Son, Thomas C. Neylan, Lea T. Grinberg
Journal: Molecular Neurodegeneration (2024)

Tauopathies, a group of neurodegenerative diseases that includes Alzheimer's disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm disorders. The circadian rhythm, a recurring 24-hour cycle governing human biological activity, is regulated by the hypothalamic suprachiasmatic nucleus (SCN) and endogenous transcriptional-translational feedback loops. Surprisingly, little attention has been given to investigating tauopathy-driven neuropathology in the SCN and the repercussions of SCN and circadian gene dysfunction in the human brain affected by tauopathies. This review aims to provide an overview of the current literature on the vulnerability of the SCN in tauopathies in humans. Emphasis is placed on elucidating the neuronal and glial changes contributing to the widespread disruption of the molecular circadian clock. Furthermore, this review identifies areas of knowledge requiring further investigation.
Endoscopic ultrasound evaluation of portal cavernoma cholangiopathy and endoscopic management of choledochal variceal rupture during ERCP
Authors: Ana Paula Samy Tanaka Kotinda, Armelle Poujol-Robert, Audrey Payance, Romain Leenhardt, Marine Camus Duboc, Xavier Dray, Ulriikka Chaput
Journal: Endoscopy (2024)

Portal cavernoma cholangiopathy (PCC) is characterized by pathological alterations in the biliary system in patients with extrahepatic portal vein obstruction and portal cavernoma [1]. Choledocholithiasis, found in 17% of these patients, is attributed to biliary stasis related to PCC [2]. The biliary alterations in PCC consist of reversible components, caused by extrinsic compression and varices formation, and fixed components, due to fibrosis secondary to ischemic-inflammatory damage from chronic portal vein thrombosis and portal cavernoma [3] [4]. This case demonstrates the diagnostic utility of endoscopic ultrasound (EUS) in PCC, the endoscopic treatment of stenosis and choledocholithiasis, and the management of hemobilia resulting from biliary varices rupture ([Video 1]).
Endoscopic ultrasound-guided palliative enterocolostomy via lumen-apposing metal stent in the setting of ascites and Roux-en-Y gastric bypass
Authors: Jason DuBroff, Daryl Ramai, John D. Morris
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided enterocolostomy (EUS-EC) has recently been shown to be a novel technique for palliation of malignant, distal, small-bowel obstruction [1]. We present a case in which EUS-EC was successfully created via a lumen-apposing metal stent (LAMS) as an alternative to standard interventions for palliative decompression.
Efficacy of dupilumab in palmoplantar pustulosis treatment highlights the role of Th2 inflammation
Authors: Yu‐Xin Zheng, Xi‐Bei Chen, Zhao‐Yuan Wang, Sui‐Qing Cai, Min Zheng, Li Fang Koh, John E. Common, Xiao‐Yong Man
Journal: Allergy (2024)

Palmoplantar pustulosis is a chronic, recurrent skin disorder characterized by sterile pustules and erythematous scaling on the palms and soles. In our study, dupilumab treatment showed efficacy and safety in PPP patients, potentially resulting from PPP patients' serum Th2 signatures and the similarities between PPP and atopic dermatitis based on serum Olink proteomics. The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
An unusual complication of a ventriculoperitoneal shunt: Endoscopic ultrasound-guided drainage of a giant cerebrospinal fluid pseudocyst
Authors: Jayanta Samanta, Jahnvi Dhar, Pardhu Bharath Neelam, Nitish Sachdeva, Rishav Aggarwal, Antriksh Kumar, Antonio Facciorusso
Journal: Endoscopy (2024)

A 24-year-old man presented with a gradually progressive abdominal distension over 6 months. He received bilateral ventriculoperitoneal shunts 4 years back for tubercular meningitis with multiple revisions since then. At presentation, he had a functioning right ventriculo-pleural shunt and a blocked left ventriculoperitoneal shunt with right double J stent. Examination revealed markings of bilateral shunts in the neck with gross abdominal distension ([Fig. 1]). A contrast-enhanced computed tomography scan of the abdomen revealed a large, encysted collection (16 × 25.6 × 41 cm) displacing the bowel loops peripherally, no free fluid, and a left ventriculoperitoneal shunt entering the collection ([Fig. 2]), also visualized on endoscopic ultrasound (EUS) ([Fig. 3]). The neurosurgery team planned to remove the blocked ventriculoperitoneal shunt only after drainage of the collection to prevent further fluid accumulation. Exploring different treatment options in a multidisciplinary team meeting, the patient opted for EUS-guided drainage.
S1PR1 inhibition induces proapoptotic signaling in T cells and limits humoral responses within lymph nodes
Authors: Dhaval Dixit, Victoria M. Hallisey, Ethan Y.S. Zhu, Martyna Okuniewska, Ken Cadwell, Jerry E. Chipuk, Jordan E. Axelrad, Susan R. Schwab
Journal: Journal of Clinical Investigation (2024)

Effective immunity requires a large, diverse naïve T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we addressed how S1P enables T cell survival, and the implications for patients treated with S1PR1 antagonists. We found that S1PR1 limited apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization were required to prevent this pro-apoptotic cascade. Findings in mice were recapitulated in ulcerative colitis patients treated with the S1PR1 antagonist ozanimod, and the loss of naïve T cells limited B cell responses. Our findings highlighted an effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress, and suggested both limitations and additional uses of this important class of drugs.
Abstract IA010: Molecular archeology of cancer
Authors: Peter Van Loo
Journal: Cancer Research (2024)

Abstract Tumor development is driven by changes to the genome leading to fitness advantages underlying successive clonal expansions. As somatic changes occur across most or all cell cycles, the cancer genome carries an archeological record of its past. Over the past years, we have developed several approaches to mine that archeological record from the cancer genome, which we collectively call 'molecular archeology of cancer'. Using these approaches, we are able to infer the subclonal architecture of tumors and gain key insights into the order and timing of the genomic changes that occurred over their evolutionary history. We have applied these approaches in a large-scale pan-cancer setting, showing that intra-tumor heterogeneity is pervasive across cancers and that the timelines of tumor evolution span multiple years to decades. Key driver events in tumor evolution typically occur early, and copy number gains often accumulate as punctuated bursts, commonly after genome doubling. Late genome doubling is frequent in cancer evolution and is typically followed by an increase in the rate of copy number gains. Genome duplications affect the selection landscape of copy number losses, while only minimally impacting copy number gains. Extending our timing framework to time mutational signatures, we find that, as expected, environmentally associated mutations are associated with early tumor development. We also find evidence of episodic APOBEC mutagenesis across many tumors and clear timing patterns in many mutational processes that have unknown origins. Our approaches increase the evolutionary information that can be obtained from tumor genome sequences and, therefore, improve our understanding of the developmental history of cancer. Citation Format: Peter Van Loo. Molecular archeology of cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA010.
Poor Concordance Between Cancer Antigen-125 and RECIST Assessment for Progression in Patients With Platinum-Sensitive Relapsed Ovarian Cancer on Maintenance Therapy With a Poly(ADP-ribose) Polymerase Inhibitor
Authors: Angelina Tjokrowidjaja, M.L. Friedlander, Jonathan A. Ledermann, Robert L. Coleman, Mansoor R. Mirza, Ursula A. Matulonis, Eric Pujade-Lauraine, Sarah J. Lord, Clare L. Scott, Sandra Goble, Whitney York, Chee K. Lee, Chee Khoon Lee, Benoit You, Xavier Paoletti, Ros Glasspool, Michael Friedlander, Clare Scott, Monsoor Mirza, Eric Pujade Lauraine, Jonathan Ledermann, Yoland Antill, Linda Mileshkin, Josee-Lyne Ethier, Michael Bookman, Charlie Gourley
Journal: Journal of Clinical Oncology (2024)

Cancer antigen-125 (CA-125) is recommended by treatment guidelines and widely used to diagnose ovarian cancer recurrence. The value of CA-125 as a surrogate for disease progression (PD) and its concordance with radiologic progression are unclear, particularly for women with platinum-sensitive relapsed ovarian cancer (PSROC) who have responded to chemotherapy and treated with maintenance poly(ADP-ribose) polymerase inhibitor (PARPi).
CD371-positive pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment
Authors: Barbara Buldini, Elena Varotto, Margarita Maurer-Granofszky, Giuseppe Gaipa, Angela Schumich, Monika Brüggemann, Ester Mejstrikova, Giovanni Cazzaniga, Ondrej Hrusak, Monika Szczepanowski, Pamela Scarparo, Martin Zimmermann, Sabine Strehl, Dagmar Schinnerl, Marketa Zaliova, Leonid Karawajew, Jean-Pierre Bourquin, Tamar Feuerstein, Gunnar Cario, Julia Alten, Anja Möricke, Alessandra Biffi, Rosanna Parasole, Franca Fagioli, Maria Grazia Valsecchi, Andrea Biondi, Franco Locatelli, Andishe Attarbaschi, Martin Schrappe, Valentino Conter, Giuseppe Basso, Michael N. Dworzak
Journal: Blood (2024)
Near‐Infrared Induced miR‐34a Delivery from Nanoparticles in Esophageal Cancer Treatment
Authors: Nick A. Alden, Tyus J. Yeingst, Hanna M. Pfeiffer, Nazmiye Celik, Julien H. Arrizabalaga, Angelica M. Helton, Yiming Liu, Douglas B. Stairs, Adam B. Glick, Neerav Goyal, Daniel J. Hayes
Journal: Advanced Healthcare Materials (2024)

Abstract Current nucleic acid delivery methods have not achieved efficient, non‐toxic delivery of miRNAs with tumor‐specific selectivity. In this study, a new delivery system based on light‐inducible gold–silver–gold, core–shell–shell (CSS) nanoparticles is presented. This system delivers small nucleic acid therapeutics with precise spatiotemporal control, demonstrating the potential for achieving tumor‐specific selectivity and efficient delivery of miRNA mimics. The light‐inducible particles leverage the photothermal heating of metal nanoparticles due to the local surface plasmonic resonance for controlled chemical cleavage and release of the miRNA mimic payload. The CSS morphology and composition result in a plasmonic resonance within the near‐infrared (NIR) region of the light spectrum. Through this method, exogenous miR‐34a‐5p mimics are effectively delivered to human squamous cell carcinoma TE10 cells, leading to apoptosis induction without adverse effects on untransformed keratinocytes in vitro. The CSS nanoparticle delivery system is tested in vivo in Foxn1nu athymic nude mice with bilateral human esophageal TE10 cancer cells xenografts. These experiments reveal that this CSS nanoparticle conjugates, when systemically administered, followed by 850 nm light emitting diode irradiation at the tumor site, 6 h post‐injection, produce a significant and sustained reduction in tumor volume, exceeding 87% in less than 72 h.
A commentary on ‘Prognosis and conditional nomogram of cervical spine fracture in patients with severe spinal cord injury: a multicenter retrospective study’
Authors: WenJian Wang, Desheng Kong, Xiaocong Ju, Feng Chen, Xufeng Yang
Journal: International Journal of Surgery (2024)

Wang, WenJian; Kong, Desheng; Ju, Xiaocong; Chen, Feng; Yang, Xufeng Author Information
Next-generation study databases require FAIR, EHR-integrated, and scalable Electronic Data Capture for medical documentation and decision support
Authors: Martin Dugas, Max Blumenstock, Tobias Dittrich, Urs Eisenmann, Stephan Christoph Feder, Fleur Fritz-Kebede, Lucy J. Kessler, Maximilian Klass, Petra Knaup, Christoph U. Lehmann, Angela Merzweiler, Christian Niklas, Thomas M. Pausch, Nelly Zental, Matthias Ganzinger
Journal: npj Digital Medicine (2024)

Abstract Structured patient data play a key role in all types of clinical research. They are often collected in study databases for research purposes. In order to describe characteristics of a next-generation study database and assess the feasibility of its implementation a proof-of-concept study in a German university hospital was performed. Key characteristics identified include FAIR access to electronic case report forms (eCRF), regulatory compliant Electronic Data Capture (EDC), an EDC with electronic health record (EHR) integration, scalable EDC for medical documentation, patient generated data, and clinical decision support. In a local case study, we then successfully implemented a next-generation study database for 19 EDC systems ( n = 2217 patients) that linked to i.s.h.med (Oracle Cerner) with the local EDC system called OpenEDC. Desiderata of next-generation study databases for patient data were identified from ongoing local clinical study projects in 11 clinical departments at Heidelberg University Hospital, Germany, a major tertiary referral hospital. We compiled and analyzed feature and functionality requests submitted to the OpenEDC team between May 2021 and July 2023. Next-generation study databases are technically and clinically feasible. Further research is needed to evaluate if our approach is feasible in a multi-center setting as well.
Secondary Analysis of the Rate of Second Primary Lung Cancer From Cancer and Leukemia Group B 140503 (Alliance) Trial of Lobar Versus Sublobar Resection for T1aN0 Non–Small-Cell Lung Cancer
Authors: Thomas E. Stinchcombe, Xiaofei Wang, Bryce Damman, Jennifer Mentlick, Rodney Landreneau, Dennis Wigle, David R. Jones, Massimo Conti, Ahmad S. Ashrafi, Moishe Liberman, Marc de Perrot, John D. Mitchell, Robert Keenan, Thomas Bauer, Daniel Miller, Nasser Altorki
Journal: Journal of Clinical Oncology (2024)

JCO
Medicaid Expansion Under the Affordable Care Act and Early Mortality Following Lung Cancer Surgery
Authors: Leticia M. Nogueira, Daniel J. Boffa, Ahmedin Jemal, Xuesong Han, K. Robin Yabroff
Journal: JAMA Network Open (2024)

Importance Medicaid expansion under the Patient Protection and Affordable Care Act is associated with gains in health insurance coverage, earlier stage diagnosis, and improved survival among patients with cancer. Objective To examine the association of Medicaid expansion with changes in early mortality among adults undergoing surgical resection of non–small cell lung cancer (NSCLC), a setting in which access to care is a major determinant of survival. Design, Setting, and Participants This cohort study used the National Cancer Database to identify 14 984 adults 45 to 64 years of age who underwent surgical resection of NSCLC between 2008 and 2019. Analysis was conducted between March 28, 2021, and September 1, 2023. Exposure State of residence Medicaid expansion status. Main Outcomes and Measures Descriptive statistics were used to compare study population characteristics by Medicaid expansion status of patients’ state of residence. Difference-in-differences analyses were used to evaluate the association between Medicaid expansion and postoperative mortality before implementation of the ACA (2008-2013) vs after (2014-2019). Results Among 14 984 adults included, the mean (SD) age was 56.3 (5.1) years, 54.6% were women, and 62.1% lived in Medicaid expansion states. Both 30-day (from 0.97% to 0.26%) and 90-day (from 2.63% to 1.32%) postoperative mortality decreased from before the ACA to after among patients residing in Medicaid expansion states (both P &amp;amp;lt; .001) but not in nonexpansion states (30-day mortality before the ACA, 0.75% vs after the ACA, 0.68%; P = .74; and 90-day mortality before the ACA, 2.43% vs after the ACA, 2.20%; P = .57), leading to a difference-in-differences of −0.64 percentage points (95% CI, −1.19 to −0.08; P = .03) for 30-day mortality and −1.08 percentage points (95% CI, −2.08 to −0.08; P = .03) for 90-day mortality. The difference-in-differences for in-hospital mortality was not significant ( P = .34) between expansion states (1.41% before the ACA to 0.77% after the ACA; 0.63 percentage point decrease; P = .004) and nonexpansion states (1.49% before the ACA to 1.20% after the ACA; 0.30 percentage point decrease; P = .29). Conclusions and Relevance In this cohort study of patients with NSCLC, Medicaid expansion was associated with declines in 30- and 90-day postoperative mortality following hospital discharge. These findings suggest that Medicaid expansion may be an effective strategy for improving access to care and cancer outcomes in this population.
Niche-specific control of tissue function by regulatory T cells—Current challenges and perspectives for targeting metabolic disease
Authors: Maike Becker, Sandra M. Dirschl, Martin G. Scherm, Isabelle Serr, Carolin Daniel
Journal: Cell Metabolism (2024)

Tissue regulatory T cells (Tregs) exert pivotal functions in both immune and metabolic regulation, maintaining local tissue homeostasis, integrity, and function. Accordingly, Tregs play a crucial role in controlling obesity-induced inflammation and supporting efficient muscle function and repair. Depending on the tissue context, Tregs are characterized by unique transcriptomes, growth, and survival factors and T cell receptor (TCR) repertoires. This functional specialization offers the potential to selectively target context-specific Treg populations, tailoring therapeutic strategies to specific niches, thereby minimizing potential side effects. Here, we discuss challenges and perspectives for niche-specific Treg targeting, which holds promise for highly efficient and precise medical interventions to combat metabolic disease.
Revision Carpal Tunnel Release Following Endoscopic Compared With Open Decompression
Authors: Peter C. Ferrin, Bergen K. Sather, Kelsi Krakauer, Timothy P. Schweitzer, Angelo B. Lipira, Ravi F. Sood
Journal: JAMA Network Open (2024)

Importance Carpal tunnel release (CTR) technique may influence the likelihood of revision surgery. Prior studies of revision CTR following endoscopic CTR (ECTR) compared with open CTR (OCTR) have been limited by sample size and duration of follow-up. Objective To estimate the incidence of revision CTR following ECTR compared with OCTR in a national cohort. Design, Setting, and Participants This retrospective cohort study used data from the US Veterans Health Administration. Participants included all adults (age ≥18 years) undergoing at least 1 outpatient CTR from October 1, 1999, to May 20, 2021. Data were analyzed from May 21, 2021, to November 27, 2023. Exposure Index CTR technique. Main Outcomes and Measures The primary outcome was time to revision CTR, defined as repeat ipsilateral CTR during the study period. Secondary outcomes were indications for revision, findings during revision, and additional procedures performed during revision. Results Among 134 851 wrists from 103 455 patients (92 510 [89.4%] male; median [IQR] age, 62 [53-70] years) undergoing at least 1 CTR, 1809 wrists underwent at least 1 revision at a median (IQR) of 2.5 (1.0-3.8) years. In competing-risks analysis, the cumulative incidence of revision was 1.06% (95% CI, 0.99%-1.12%) at 5 years and 1.59% (95% CI, 1.51%-1.67%) at 10 years. ECTR was associated with increased hazard of revision CTR compared with OCTR (adjusted hazard ratio [aHR], 1.56; 95% CI, 1.34-1.81; P &amp;amp;lt; .001). The risk difference for revision CTR associated with ECTR compared with OCTR was 0.57% (95% CI, 0.31%-0.84%) at 5 years (number needed to harm, 176) and 0.72% (95% CI, 0.36%-1.07%) at 10 years (number needed to harm, 139). Regardless of index CTR technique, the most common indication for revision was symptom recurrence (1062 wrists [58.7%]). A reconstituted transverse carpal ligament (TCL) was more common after ECTR compared with OCTR, whereas scarring of the overlying tissues and of the median nerve itself were more common following OCTR. Incomplete transverse-carpal-ligament release was observed in 251 of the wrists undergoing revision CTR (13.94%) and was more common among revisions following ECTR (odds ratio, 1.62; 95% CI, 1.11-2.37; P = .01). Conclusions and Relevance In this cohort study of revision CTR in the Veterans Health Administration, ECTR was associated with increased risk of revision compared with OCTR, but the absolute risk was low regardless of technique. Intraoperative findings at revision varied significantly according to index CTR technique.
Functional magnetic resonance imaging in schizophrenia: current evidence, methodological advances, limitations and future directions
Authors: Aristotle N. Voineskos, Colin Hawco, Nicholas H. Neufeld, Jessica A. Turner, Stephanie H. Ameis, Alan Anticevic, Robert W. Buchanan, Kristin Cadenhead, Paola Dazzan, Erin W. Dickie, Julia Gallucci, Adrienne C. Lahti, Anil K. Malhotra, Dost Öngür, Todd Lencz, Deepak K. Sarpal, Lindsay D. Oliver
Journal: World Psychiatry (2024)

Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case-control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data-driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case-control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.