tbuckley/cabot-search huggingface dataset:
Conotoxins Targeting Voltage-Gated Sodium Ion Channels
Authors: Shengrong Pei, Nan Wang, Zaoli Mei, Dongting Zhangsun, David J. Craik, J. Michael McIntosh, Xiaopeng Zhu, Sulan Luo
Journal: Pharmacological Reviews (2024)

Voltage-gated sodium (Na<sub>V</sub>) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases such as epilepsy, neuropathic pain, psychosis, autism and cardiac arrhythmia. Many venom peptides selectively act on Na<sub>V</sub> channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense, but which are also valuable pharmacological tools for the identification and/or treatment of human diseases. Typically, conotoxins contain two or three disulfide bonds and these internal cross-braces contribute to conotoxins having compact, well-defined structures and high stability. Of the conotoxins containing three disulfide bonds some selectively target mammalian Na<sub>V</sub> channels and can block, stimulate, or modulate these channels. Such conotoxins have great potential to serve as pharmacological tools for studying the functions and characteristics of Na<sub>V</sub> channels or as drug leads for neurological diseases related to Na<sub>V</sub> channels. Accordingly, discovering or designing conotoxins targeting Na<sub>V</sub> channels with high potency and selectivity is important. The amino acid sequences, disulfide bond connectivity, and three-dimensional structures are key factors that affect the biological activity of conotoxins, and targeted synthetic modifications of conotoxins can greatly improve their activity and selectivity. This review examines Na<sub>V</sub> channel-targeted conotoxins, focusing on their structures, activities and designed modifications, with a view towards expanding their applications. <b>Significance Statement</b> Na<sub>V</sub> channels are crucial in various neurological diseases. Some conotoxins selectively target Na<sub>V</sub> channels, causing either blockade or activation, thus enabling their use as pharmacological tools for studying the channels' characteristics and functions. Conotoxins also have promising potential to be developed as drug leads. The disulfide bonds in these peptides are important for stabilizing their structures, thus leading to enhanced specificity and potency. Together, conotoxins targeting Na<sub>V</sub> channels have both immediate research value and promising future application prospects.
177Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors
Authors: Magdalena Mileva, Camille Van Bogaert, Gwennaëlle Marin, Rachele Danieli, Carlos Artigas, Hugo Levillain, Lieveke Ameye, Loubna Taraji-Schiltz, Konstantinos Stathopoulos, Zéna Wimana, Alain Hendlisz, Patrick Flamen, Ioannis Karfis
Journal: Clinical Nuclear Medicine (2024)

The aim of this study was to assess the association among toxicity, dosimetry of organs-at-risk, and disease progression in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177 Lu-DOTATATE.
Renal Transplant Anastomotic Pseudoaneurysm and Stenosis at the Proximal Transplant Renal Artery and Worse Renal Blood Flow After Stent Placement
Authors: Jiaqiong Wang, Yi Li, Jian Q. Yu
Journal: Clinical Nuclear Medicine (2024)

A 60-year-old man with a history of end-stage renal disease received renal transplant and had decreasing renal function 4 months later. Nuclear medicine renal flow and functional study showed severely decreased blood flow and decreased function of the right renal allograft. There was focal increased radiotracer uptake at blood flow phase around the anastomosis of the renal allograft artery and the right external iliac artery. CT angiogram revealed right external iliac artery pseudoaneurysm. Interventional radiology angiography reconfirmed the pseudoaneurysm and revealed stenosis at the proximal transplant renal artery. After stent placement, however, there was worse renal allograft blood flow.
Prostatic Utricle Cysts as a Potential Pitfall in PSMA PET/CT Interpretation
Authors: Bradley J. Girod, Nghi C. Nguyen
Journal: Clinical Nuclear Medicine (2024)

A 60-year-old man with T2aN0M0 prostate cancer underwent intensity-modulated radiotherapy targeting the prostate and seminal vesicles. Experiencing biochemical recurrence after 6 years, 68 Ga-PSMA-11 PET/CT revealed focal radioactivity in the posterior midline of the prostate, identified as a prostatic utricle cyst on subsequent MRI. Similar findings appeared in a previous 18 F-piflufolastat PET/CT, with negative biopsy results. The patient then received intensity-modulated radiotherapy directed to 2 PSMA-avid pelvic nodes and leuprolide acetate, achieving an undetectable PSA in 4 months. This case highlights a potential pitfall in PSMA PET interpretation associated with prostatic utricle cysts.
Diagnostic Accuracy of SPECT for Mild Traumatic Brain Injury
Authors: Alex Koziarz, Frank Koziarz, Rui Shen, Prasaanthan Gopee-Ramanan, Sandra E. Black, Daniel Worsley, Ian Y.M. Chan, David L. Streiner, Katherine A. Zukotynski
Journal: Clinical Nuclear Medicine (2024)

Purpose This study examines the diagnostic accuracy of brain perfusion SPECT for mild traumatic brain injury (mTBI). Patients and Methods A systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO: CRD42023484636). Five databases were searched for studies evaluating brain perfusion SPECT in adult patients with mTBI (GCS 13–15). Study quality was assessed using a modified QUADAS-2 tool. A meta-analysis was performed to pool proportions of hypoperfusion abnormalities across brain lobes. Results Of 4735 records, 22 studies (5 longitudinal [40% high quality], 17 cross-sectional [24% high quality]) were included totaling 800 patients (mean age, 37.4 ± 12.6 years; 36.4% female). Meta-analysis of proportions indicated that the frontal lobe most frequently showed hypoperfusion on brain perfusion SPECT (pooled proportion 40.1% [95% confidence interval, 31.2% to 49.8%], 99/254, I 2 = 54.5%), followed by the temporal lobe (26.1% [95% confidence interval, 19.9% to 33.6%], 68/254, I 2 = 30.7%). Several studies found that hypoperfusion abnormalities were associated with neuropsychological findings. Also, brain perfusion SPECT could detect abnormalities not seen on MRI. Abnormalities in perfusion on brain perfusion SPECT may be more readily detected with a quantitative assessment compared with a visual assessment alone, although there appears to be no consensus on the optimal method for image interpretation. Evidence evaluating the sensitivity and specificity of brain perfusion SPECT for mTBI was limited. Using the GRADE framework, the evidence was rated as low. Conclusions Although perfusion abnormalities can be seen in patients with mTBI, commonly in the frontal and temporal lobes, the findings are nonspecific and may derive from various factors. Ultimately, brain perfusion SPECT provides additional information for mTBI, but the final added value for the detection of mTBI is unknown.
FDG PET in a Patient on a GLP-1 Agonist/Insulin Secretagogue
Authors: Jorge D. Oldan, Paula G. Landman, Jennifer A. Schroeder, Amir H. Khandani, Lilja B. Solnes, Carrie B. Lee, Steven P. Rowe
Journal: Clinical Nuclear Medicine (2024)

With the increase in use of GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy, Rybelsus) in the population, nuclear medicine physicians should be aware of the possibility of nondiagnostic FDG PET scans due to these medications, which work partly by increasing insulin secretion. We demonstrate a case where a patient's use of such a medication presumptively led to muscular and myocardial uptake, complicating scan interpretation considerably. Clinicians should be aware of the presence of these drugs and their potential effect on biodistribution in FDG PET. Further study is needed to best understand the effects of these medications on FDG biodistribution.
Integrated 68Ga-FAPI-04 PET/MR in Pancreatic Cancer
Authors: Zeyu Zhang, Shiwei Guo, Chao Cheng, Kai Cao, Hui Jiang, Gang Jin, Changjing Zuo
Journal: Clinical Nuclear Medicine (2024)

Purpose This study aimed to investigate the value of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer. Patients and Methods This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68 Ga-FAPI PET/MRI from June 2020 to June 2022. The SUV max , SUV mean , SUV peak , uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBR muscle ) and blood (TBR blood ) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3–4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups. Results A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders ( P &lt; 0.05). The SUV max , SUV mean , and TBR muscle were significantly higher in unresectable patients than in resectable ones ( P &lt; 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUV max (AUC = 0.838, P = 0.016), SUV mean (AUC = 0.812, P = 0.026), and TBR muscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response ( P = 0.032) and was an independent predictor of tumor response ( P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability ( P = 0.043). Conclusions This pilot study demonstrates the value of 68 Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.
Left Atrial Appendage Closure Devices May Demonstrate Significant 18F-FDG Uptake in the Absence of Infection
Authors: Harry J. Waring, Kevin M. Bradley
Journal: Clinical Nuclear Medicine (2024)

A 79-year-old man found to have a pulmonary nodule and pleural effusion on CT went on to have an 18 F-FDG PET/CT scan. The lung abnormality did not show FDG uptake and appeared benign. However, PET/CT detected moderately increased FDG uptake associated with a left atrial appendage closure device inserted 11 months prior to the PET/CT. Infection of a left atrial closure device has previously been demonstrated with FDG PET/CT. This case, in the absence of infection, with normal serum inflammatory markers, highlights that left atrial closure devices, in common with other foreign bodies/devices, may demonstrate significant, incidental FDG uptake.
Association of Medicare Advantage Enrollment With Financial Burden of Care
Authors: Sungchul Park, David J. Meyers, Amal N. Trivedi
Journal: Annals of Internal Medicine (2024)

Compared with traditional Medicare (TM), Medicare Advantage (MA) plans typically offer supplemental benefits and lower copayments for in-network services and must include an out-of-pocket spending limit. To examine whether the financial burden of care decreased for persons switching from TM to MA (TM-to-MA switchers) relative to those remaining in TM (TM stayers). Retrospective longitudinal cohort study comparing changes in financial outcomes between TM-to-MA switchers and TM stayers. Population-based. 7054 TM stayers and 1544 TM-to-MA switchers from the Medical Expenditure Panel Survey, 2014 to 2021. Individual health care costs (out-of-pocket spending and cost sharing), financial burden (high and catastrophic), and subjective financial hardship (difficulty paying medical bills, paying medical bills over time, and inability to pay medical bills). Compared with TM stayers, TM-to-MA switchers had small differences in out-of-pocket spending ($168 [95% CI, -$133 to $469]) and proportions of total health expenses paid out of pocket (cost sharing) (0.2 percentage point [CI, -1.3 to 1.7 percentage points]), families with out-of-pocket spending greater than 20% of their income (high financial burden) (0.3 percentage point [CI, -2.5 to 3.0 percentage points]), families reporting out-of-pocket spending greater than 40% of their income (catastrophic financial burden) (0.7 percentage point [CI, -0.1 to 1.6 percentage points]), families reporting paying medical bills over time (-0.2 percentage point [CI, -1.7 to 1.4 percentage points]), families having problems paying medical bills (-0.4 percentage point [CI, -2.7 to 1.8 percentage points]), and families reporting being unable to pay medical bills (0.4 percentage point [CI, -1.3 to 2.0 percentage points]). Inability to account for all medical care and cost needs and variations across MA plans, small baseline differences in out-of-pocket spending, and potential residual confounding. Differences in financial outcomes between beneficiaries who switched from TM to MA and those who stayed with TM were small. Differences in financial burden ranged across outcomes and did not have a consistent pattern. The National Research Foundation of Korea.
Lesbian, Gay, Bisexual, Transgender, Queer, and Other Sexual and Gender Minority Health Disparities: A Position Paper From the American College of Physicians
Authors: Josh Serchen, David R. Hilden, Micah W. Beachy, David Hilden, Micah Beachy, Jan K. Carney, Haidn Foster, Austin Hoeg, Matthew Hollon, Cynthia Jumper, Selvam Joseph Mascarenhas, Ankita Sagar, JennyR. Silberger, Jamar Slocum, Michael Tan, Elham Yousef
Journal: Annals of Internal Medicine (2024)

Lesbian, gay, bisexual, transgender, queer, or other sexual and gender minorities (LGBTQ+) populations in the United States continue to experience disparities in health and health care. Discrimination in both health care and society at large negatively affects LGBTQ+ health. Although progress has been made in addressing health disparities and reducing social inequality for these populations, new challenges have emerged. There is a pressing need for physicians and other health professionals to take a stance against discriminatory policies as renewed federal and state public policy efforts increasingly impose medically unnecessary restrictions on the provision of gender-affirming care. In this position paper, the American College of Physicians (ACP) reaffirms and updates much of its long-standing policy on LGBTQ+ health to strongly support access to evidence-based, clinically indicated gender-affirming care and oppose political efforts to interfere in the patient-physician relationship. Furthermore, ACP opposes institutional and legal restrictions on undergraduate, graduate, and continuing medical education and training on gender-affirming care and LGBTQ+ health issues. This paper also offers policy recommendations to protect the right of all people to participate in public life free from discrimination on the basis of their gender identity or sexual orientation and encourages the deployment of inclusive, nondiscriminatory, and evidence-based blood donation policies for members of LGBTQ+ communities. Underlying these beliefs is a reaffirmed commitment to promoting equitable access to quality care for all people regardless of their sexual orientation and gender identity.
Injectable Therapeutic Hydrogel with H<sub>2</sub>O<sub>2</sub> Self‐supplying and GSH Consumption for Synergistic Chemodynamic/Low‐temperature Photothermal Inhibition of Postoperative Tumor Recurrence and Wound Infection
Authors: Peng Hu, Zhili Jia, Shuang Zhao, Kunpeng Lin, Guoye Yang, Wujie Guo, Shuling Yu, Jianjun Cheng, Guanhua Du, Jiahua Shi
Journal: Advanced Healthcare Materials (2024)

Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H
Pilot Feasibility Study
Authors: Caroline Rousseau, Raphaël Metz, Olivier Kerdraon, Lobna Ouldamer, Florence Boiffard, Karine Renaudeau, Ludovic Ferrer, Johnny Vercouillie, Isabelle Doutriaux-Dumoulin, Alexis Mouton, Maelle Le Thiec, Agnès Morel, Daniela Rusu, Maria-Joao Santiago-Ribeiro, Loïc Campion, Nicolas Arlicot, Françoise Kraeber-Bodéré
Journal: Clinical Nuclear Medicine (2024)

Abstract Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism. Patients and Methods Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted. Results The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%–94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as “above muscular,” “equal to muscular,” and “below muscular” with reference to the muscular background. For the “above muscular” group (2 HAB and 2 MAB), “equal muscular” group (3 HAB, 3 MAB, and 1 LAB), and “below muscular” group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09–5.31), 1.66 (0.93–3.07), and 0.61 (0.43–1.02). Conclusions This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.
Lifetime Medical Spending Attributed to Incident Type 2 Diabetes in Medicare Beneficiaries: A Longitudinal Study Using 1999–2019 National Medicare Claims
Authors: Yixue Shao, Yu Wang, Elizabeth Bigman, Giuseppina Imperatore, Christopher Holliday, Ping Zhang
Journal: Diabetes Care (2024)

To estimate lifetime incremental medical spending attributed to incident type 2 diabetes (T2D) among Medicare beneficiaries by age at diagnosis, sex, and race/ethnicity.
Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation
Authors: Funsho E. Fakuade, Dominik Hubricht, Vanessa Möller, Izzatullo Sobitov, Aiste Liutkute, Yannic Döring, Fitzwilliam Seibertz, Marcus Gerloff, Julius Ryan D. Pronto, Fereshteh Haghighi, Sören Brandenburg, Khaled Alhussini, Nadezda Ignatyeva, Yara Bonhoff, Stefanie Kestel, Aschraf El-Essawi, Ahmad Fawad Jebran, Marius Großmann, Bernhard C. Danner, Hassina Baraki, Constanze Schmidt, Samuel Sossalla, Ingo Kutschka, Constanze Bening, Christoph Maack, Wolfgang A. Linke, Jordi Heijman, Stephan E. Lehnart, George Kensah, Antje Ebert, Fleur E. Mason, Niels Voigt
Journal: Circulation (2024)

Alterations in the buffering of intracellular Ca
Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: An observational cohort study using the OpenSAFELY platform
Authors: Miriam Samuel, Robin Y. Park, Sophie V. Eastwood, Fabiola Eto, Caroline E. Morton, Daniel Stow, Sebastian Bacon, Amir Mehrkar, Jessica Morley, Iain Dillingham, Peter Inglesby, William J. Hulme, Kamlesh Khunti, Rohini Mathur, Jonathan Valabhji, Brian MacKenna, Sarah Finer
Journal: PLoS Medicine (2024)

Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic.
Tension directs cancer cell migration over fiber alignment through energy minimization
Authors: Matthew R. Zanotelli, Joseph P. Miller, Wenjun Wang, Ismael Ortiz, Elise Tahon, Francois Bordeleau, Cynthia A. Reinhart-King
Journal: Biomaterials (2024)

Cell migration during many fundamental biological processes including metastasis requires cells to traverse tissue with heterogeneous mechanical cues that direct migration as well as determine force and energy requirements for motility. However, the influence of discrete structural and mechanical cues on migration remains challenging to determine as they are often coupled. Here, we decouple the pro-invasive cues of collagen fiber alignment and tension to study their individual impact on migration. When presented with both cues, cells preferentially travel in the axis of tension against fiber alignment. Computational and experimental data show applying tension perpendicular to alignment increases potential energy stored within collagen fibers, lowering requirements for cell-induced matrix deformation and energy usage during migration compared to motility in the direction of fiber alignment. Energy minimization directs migration trajectory, and tension can facilitate migration against fiber alignment. These findings provide a conceptual understanding of bioenergetics during migration through a fibrous matrix.