tbuckley/cabot-search huggingface dataset:
Regulatory barriers to US-China collaboration for generative AI development in genomic research
Authors: Zhangyu Wang, Benjamin Gregg, Li Du
Journal: Cell Genomics (2024)

Here, we examine the challenges posed by laws in the United States and China for generative-AI-assisted genomic research collaboration. We recommend renewing the Agreement on Cooperation in Science and Technology to promote responsible principles for sharing human genomic data and to enhance transparency in research. Here, we examine the challenges posed by laws in the United States and China for generative-AI-assisted genomic research collaboration. We recommend renewing the Agreement on Cooperation in Science and Technology to promote responsible principles for sharing human genomic data and to enhance transparency in research.
Compensatory enhancement of input maintains aversive dopaminergic reinforcement in hungry Drosophila
Authors: Eleonora Meschi, Lucille Duquenoy, Nils Otto, Georgia Dempsey, Scott Waddell
Journal: Neuron (2024)

Hungry animals need compensatory mechanisms to maintain flexible brain function, while modulation reconfigures circuits to prioritize resource seeking. In Drosophila, hunger inhibits aversively reinforcing dopaminergic neurons (DANs) to permit the expression of food-seeking memories. Multitasking the reinforcement system for motivation potentially undermines aversive learning. We find that chronic hunger mildly enhances aversive learning and that satiated-baseline and hunger-enhanced learning require endocrine adipokinetic hormone (AKH) signaling. Circulating AKH influences aversive learning via its receptor in four neurons in the ventral brain, two of which are octopaminergic. Connectomics revealed AKH receptor-expressing neurons to be upstream of several classes of ascending neurons, many of which are presynaptic to aversively reinforcing DANs. Octopaminergic modulation of and output from at least one of these ascending pathways is required for shock- and bitter-taste-reinforced aversive learning. We propose that coordinated enhancement of input compensates for hunger-directed inhibition of aversive DANs to preserve reinforcement when required.
Spatially resolved lipidomics shows conditional transfer of lipids produced by Bacteroides thetaiotaomicron into the mouse gut
Authors: Claudia Mirretta Barone, Stacey L. Heaver, Lars Gruber, Fabian Zundel, Dai Long Vu, Ruth E. Ley
Journal: Cell Host & Microbe (2024)

The extent to which bacterial lipids produced by the gut microbiota penetrate host tissues is unclear. Here, we combined mass spectrometry approaches to identify lipids produced by the human gut symbiont Bacteroides thetaiotaomicron (B. theta) and spatially track these bacterial lipids in the mouse colon. We characterize 130 B. theta lipids by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using wild-type and mutant B. theta strains to confidently identify lipid structures and their interconnected pathways in vitro. Of these, 103 B. theta lipids can be detected and spatially mapped in a single MALDI mass spectrometry imaging run. We map unlabeled bacterial lipids across colon sections of germ-free and specific-pathogen-free (SPF) mice and mice mono-colonized with wild-type or sphingolipid-deficient (BTMUT) B. theta. We observe co-localization of bacterially derived phosphatidic acid with host tissues in BTMUT mice, consistent with lipid penetration into host tissues. These results indicate limited and selective transfer of bacterial lipids to the host.
Modulating the immune system towards a functional chronic wound healing: A biomaterials and Nanomedicine perspective
Authors: Kevin Las Heras, Itxaso Garcia-Orue, Fiorenza Rancan, Manoli Igartua, Edorta Santos-Vizcaino, Rosa Maria Hernandez
Journal: Advanced Drug Delivery Reviews (2024)

Chronic non-healing wounds persist as a substantial burden for healthcare systems, influenced by factors such as aging, diabetes, and obesity. In contrast to the traditionally pro-regenerative emphasis of therapies, the recognition of the immune system integral role in wound healing has significantly grown, instigating an approach shift towards immunological processes. Thus, this review explores the wound healing process, highlighting the engagement of the immune system, and delving into the behaviors of innate and adaptive immune cells in chronic wound scenarios. Moreover, the article investigates biomaterial-based strategies for the modulation of the immune system, elucidating how the adjustment of their physicochemical properties or their synergistic combination with other agents such as drugs, proteins or mesenchymal stromal cells can effectively modulate the behaviors of different immune cells. Finally this review explores various strategies based on synthetic and biological nanostructures, including extracellular vesicles, to finely tune the immune system as natural immunomodulators or therapeutic nanocarriers with promising biophysical properties.
Gene therapy for Lafora disease in the Epm2a mouse model
Authors: Luis Zafra-Puerta, Nerea Iglesias-Cabeza, Daniel F Burgos, Miriam Sciaccaluga, Juan González-Fernández, Laura Bellingacci, Jacopo Canonichesi, Gema Sánchez-Martín, Cinzia Costa, Marina P Sánchez, José M Serratosa
Journal: Molecular Therapy (2024)
Neuroglobin overexpression in cerebellar neurons of Harlequin mice improves mitochondrial homeostasis and reduces ataxic behavior
Authors: Hélène Cwerman-Thibault, Vassilissa Malko-Baverel, Gwendoline Le Guilloux, Edward Ratcliffe, Djmila Mouri, Isabel Torres-Cuevas, Ivan Millán, Bruno Saubaméa, Virginie Mignon, Odile Boespflug-Tanguy, Pierre Gressens, Marisol Corral-Debrinski
Journal: Molecular Therapy (2024)

Neuroglobin, a member of the globin superfamily, is abundant in the brain, retina, and cerebellum of mammals and localizes to mitochondria. The protein exhibits neuroprotective capacities by participating in electron transfer, oxygen supply, and protecting against oxidative stress. Our objective was to determine whether neuroglobin overexpression can be used to treat neurological disorders. We chose Harlequin mice, which harbor a retroviral insertion in the first intron of the apoptosis-inducing factor gene resulting in the depletion of the corresponding protein essential for mitochondrial biogenesis. Consequently, Harlequin mice display degeneration of the cerebellum and suffer from progressive blindness and ataxia. Cerebellar ataxia begins in Harlequin mice at the age of 4 months and is characterized by neuronal cell disappearance, bioenergetics failure, and motor and cognitive impairments, which aggravated with aging. Mice aged 2 months received adeno-associated viral vectors harboring the coding sequence of neuroglobin or apoptosis-inducing factor in both cerebellar hemispheres. Six months later, Harlequin mice exhibited substantial improvements in motor and cognitive skills; probably linked to the preservation of respiratory chain function, Purkinje cell numbers and connectivity. Thus, without sharing functional properties with apoptosis-inducing factor, neuroglobin was efficient in reducing ataxia in Harlequin mice.
Evaluation of [18F]fluoroestradiol and ChRERα as a gene expression PET reporter system in rhesus monkey brain
Authors: Bing Li, Palak Wadhwa, Walter Lerchner, Paolo Zanotti-Fregonara, Jeih-San Liow, Xuefeng Yan, Sami S Zoghbi, Sridhar Goud Nerella, Sanjay Telu, Cheryl L Morse, Oscar Solis, Juan L Gomez, Daniel P Holt, Robert F Dannals, Alex C Cummins, Robert B Innis, Victor W Pike, Barry J Richmond, Michael Michaelides, Mark A G Eldridge
Journal: Molecular Therapy (2024)
The novel potential therapeutic target PSMP/MSMP promotes acute kidney injury via CCR2
Authors: Zhanming Song, Weijian Yao, Xuekang Wang, Yaqian Mo, Zhongtian Liu, Qingqing Li, Lei Jiang, Hui Wang, Huiying He, Ning Li, Zhaohuai Zhang, Ping Lv, Yu Zhang, Li Yang, Ying Wang
Journal: Molecular Therapy (2024)
Prediction of recurrence risk in endometrial cancer with multimodal deep learning
Authors: Sarah Volinsky-Fremond, Nanda Horeweg, Sonali Andani, Jurriaan Barkey Wolf, Maxime W. Lafarge, Cor D. de Kroon, Gitte Ørtoft, Estrid Høgdall, Jouke Dijkstra, Jan J. Jobsen, Ludy C. H. W. Lutgens, Melanie E. Powell, Linda R. Mileshkin, Helen Mackay, Alexandra Leary, Dionyssios Katsaros, Hans W. Nijman, Stephanie M. de Boer, Remi A. Nout, Marco de Bruyn, David Church, Vincent T. H. B. M. Smit, Carien L. Creutzberg, Viktor H. Koelzer, Tjalling Bosse
Journal: Nature Medicine (2024)

Abstract Predicting distant recurrence of endometrial cancer (EC) is crucial for personalized adjuvant treatment. The current gold standard of combined pathological and molecular profiling is costly, hampering implementation. Here we developed HECTOR (histopathology-based endometrial cancer tailored outcome risk), a multimodal deep learning prognostic model using hematoxylin and eosin-stained, whole-slide images and tumor stage as input, on 2,072 patients from eight EC cohorts including the PORTEC-1/-2/-3 randomized trials. HECTOR demonstrated C-indices in internal ( n = 353) and two external ( n = 160 and n = 151) test sets of 0.789, 0.828 and 0.815, respectively, outperforming the current gold standard, and identified patients with markedly different outcomes (10-year distant recurrence-free probabilities of 97.0%, 77.7% and 58.1% for HECTOR low-, intermediate- and high-risk groups, respectively, by Kaplan–Meier analysis). HECTOR also predicted adjuvant chemotherapy benefit better than current methods. Morphological and genomic feature extraction identified correlates of HECTOR risk groups, some with therapeutic potential. HECTOR improves on the current gold standard and may help delivery of personalized treatment in EC.
Alzheimer disease–related biomarkers and cancer-related cognitive decline: the Thinking and Living with Cancer study
Authors: Jeanne Mandelblatt, Jeffrey L Dage, Xingtao Zhou, Brent J Small, Tim A Ahles, Jaeil Ahn, Ashley Artese, Traci N Bethea, Elizabeth C Breen, Judith E Carroll, Harvey J Cohen, Martine Extermann, Deena Graham, Isaacs Claudine, Heather S L Jim, Brenna C McDonald, Zev M Nakamura, Sunita K Patel, G William Rebeck, Kelly E Rentscher, James C Root, Kristen A Russ, Danielle B Tometich, R Scott Turner, Kathleen Van Dyk, Wanting Zhai, Li-Wen Huang, Andrew J Saykin
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Purpose We evaluated whether plasma Alzheimer disease (AD)–related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors. Methods We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, β-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant. Results There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P ≤ .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008). Conclusion The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy.
The effectiveness of combined extra-hepatic bile duct resection in radically-resected cases with intrahepatic cholangiocarcinoma: a SEER-based retrospective cohort study and an external validation
Authors: Tian-Run Lv, Jun-Ke Wang, Fu-Yu Li, Hai-Jie Hu
Journal: International Journal of Surgery (2024)

Objective: To evaluate the effectiveness of the combined extrahepatic bile duct resection (EHBDR) in cases with intrahepatic cholangiocarcinoma (IHCC) in terms of clinicopathological features and long-term survival. Methods: Radically resected cases with IHCC from 2000 to 2020 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Comparative analyses were performed between resected IHCC patients who received EHBDR and those without EHBDR. Moreover, an external validation was further performed based on a single-center cohort. Results: A total of 1521 radically resected cases with IHCC (EHBDR: 189) were identified from the SEER database. Comparable age, sex, race, marital status, liver cirrhosis, differentiation status, and adjuvant chemotherapy were acquired between the two groups. EHBDR was associated with a higher incidence of adequate lymphadenectomy ( P &lt;0.001). The incidence of cases with T3–4 or N+ disease was significantly higher in EHBDR group ( P &lt;0.001). Adjuvant radiotherapy was more frequently performed in cases with EHBDR ( P &lt;0.001). EHBDR failed to bring any survival benefit and was associated with a worse prognosis even after matching. Similar findings have also been revealed in the external validation cohort ( n =522, EHBDR: 117). EHBDR was associated with more extended resections, more aggressive tumor biological features, and worse prognosis. In the matched validation cohort, EHBDR was still associated with a higher incidence of early recurrence. Conclusion: EHBDR was an indicator of the advanced stage and failed to bring any survival benefit. It is the tumor stage that really determines the prognosis. More in-depth analyses focusing on different situations of EHBDR with more detailed clinical data are required.
mTORc2 in Distal Convoluted Tubule and Renal K+ Excretion during High Dietary K+ Intake
Authors: Xin-Peng Duan, Jun-Ya Zheng, Shao-Peng Jiang, Ming-Xiao Wang, Chengbiao Zhang, Tanzina Chowdhury, Wen-Hui Wang, Dao-Hong Lin
Journal: Journal of the American Society of Nephrology (2024)

Key Points High K stimulates mechanistic target of rapamycin complex 2 (mTORc2) in the distal convoluted tubule (DCT). Inhibition of mTORc2 decreased the basolateral Kir4.1/Kir5.1 and Na-Cl cotransporter in the DCT. Inhibition of mTORc2 of the DCT compromised kidneys' ability to excrete potassium during high K intake. Background Renal mechanistic target of rapamycin complex 2 (mTORc2) plays a role in regulating renal K + excretion (renal-E K ) and K + homeostasis. Inhibition of renal mTORc2 causes hyperkalemia due to suppressing epithelial Na + channel and renal outer medullary K+ (Kir1.1) in the collecting duct. We now explore whether mTORc2 of distal convoluted tubules (DCTs) regulates basolateral Kir4.1/Kir5.1, Na-Cl cotransporter (NCC), and renal-E K . Methods We used patch-clamp technique to examine basolateral Kir4.1/Kir5.1 in early DCT, immunoblotting, and immunofluorescence to examine NCC expression and in vivo measurement of urinary K + excretion to determine baseline renal-E K in mice treated with an mTORc2 inhibitor and in DCT-specific rapamycin-insensitive companion of mTOR knockout (DCT-RICTOR-KO) mice. Results Inhibition of mTORc2 with AZD8055 abolished high-K + –induced inhibition of Kir4.1/Kir5.1 in DCT, high potassium–induced depolarization of the DCT membrane, and high potassium–induced suppression of phosphorylated Na-Cl cotransporter (pNCC) expression. AZD8055 stimulated the 40-pS inwardly rectifying K + channel (Kir4.1/Kir5.1-heterotetramer) in early DCT in the mice on overnight high potassium intake; this effect was absent in the presence of protein kinase C inhibitors, which also stimulated Kir4.1/Kir5.1. AZD8055 treatment decreased renal-E K in animals on overnight high-potassium diet. Deletion of RICTOR in the DCT increased the Kir4.1/Kir5.1-mediated K + currents, hyperpolarized the DCT membrane, and increased the expression of pWNK4 and pNCC. Renal-E K was lower and plasma K + was higher in DCT-RICTOR-KO mice than corresponding control mice. In addition, overnight high-potassium diet did not inhibit Kir4.1/Kir5.1 activity in the DCT and failed to inhibit the expression of pNCC in DCT-RICTOR-KO mice. Overnight high potassium intake stimulated renal-E K in control mice, but this effect was attenuated in DCT-RICTOR-KO mice. Thus, overnight high potassium intake induced hyperkalemia in DCT-RICTOR-KO mice but not in control mice. Conclusions mTORc2 of the DCT inhibits Kir4.1/Kir5.1 activity and NCC expression and stimulates renal-E K during high potassium intake.
Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial
Authors: Li Wang, Jiacheng Huang, Jiaxing Song, Jie Yang, Linyu Li, Changwei Guo, Qingwu Yang, Wenjie Zi, Fengli Li, Weilin Kong
Journal: International Journal of Surgery (2024)

Background: In the RESCUE BT (endovascular treatment with versus without tirofiban for stroke patients with large vessel occlusion) trial, enrollment in extended time window was based on noncontrast computed tomography. To assess whether perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. Methods: This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6 h window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) within 48 h and 90-day mortality. Results: A total of 652 patients (319 in tirofiban group and 333 in placebo group) who meeting the AHA/ASA guidelines were included in this analysis, with median interquartile ranges (IQR) age of 68 (58–75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1–4) in the tirofiban group, and 3 (IQR, 1–4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% CI: 0.83–1.42). The incidence of sICH [10.1% versus 6.3%; adjusted OR 1.70; (95% CI: 0.95–3.04)] was not significantly different between groups. However, intravenous tirofiban might be associated with lower disability level [adjusted common OR, 1.74 (95% CI: 1.14–2.65); P =0.01] in patients with large artery atherosclerosis. Conclusions: There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. The authors observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.
Most total pancreatectomies for ductal adenocarcinoma potentially can Be replaced by whipple over the splenic artery: a before and after study
Authors: Ting-Chung Kuo, Chien-Huei Wu, Bang-Bin Chen, Young-Jen Lin, Cheng-Maw Ho, Chien-Kai Tseng, Yung-Ming Cheng, Yu-Wen Tien
Journal: International Journal of Surgery (2024)

Introduction: Recently, more and more total pancreatectomy (TP) has been performed for central-located pancreatic ductal cell adenocarcinoma (PDCA), which abuts or involves both gastroduodenal and splenic arteries and demands transaction of both of them for complete resection. Spiked by Warshaw’s procedure (spleen-preserving distal pancreatectomy with excision of splenic vessels), the authors developed a new procedure “Whipple over the splenic artery (WOTSA)” to replace TP by leftward extension of pancreatic parenchyma transaction line and preservation of pancreatic tail and spleen after excision of the splenic artery. This uncontrolled before and after study assesses the safety and efficacy of a new technique “Whipple over the splenic artery (WOTSA)” as a treatment for pancreatectomy for ductal adenocarcinoma (PDAC), which traditionally requires TP for a complete excision. Methods: The study group comprised 40 consecutive patients who underwent WOTSA for PDAC between August 2019 and September 2022. Their clinicopathological characteristics and survival were compared with those of a historical control group comprising 30 consecutive patients who underwent TP between January 2016 and July 2019. Results: None of the 40 patients in the WOTSA group required reoperation due to infarction of the pancreas and/or spleen remnant. Diabetes mellitus (DM) medication after WOTSA were none in 19, oral hypoglycemic agents in 19, and insulin preparations in 2 patients. Compared with TP, patients who underwent WOTSA exhibited similar rates of major operative complications, clear pancreatic parenchyma transaction margin, and a number of harvested positive lymph nodes, but a higher rate of adjuvant chemotherapy completion and a trend toward better median disease-free survival (14 vs. 7.5 months, P =0.023). Conclusions: Compared to TP, WOTSA can be safely performed and have much better postoperative glycemic status without cost of higher operative risk or impaired surgical radicality. These findings indicate that most TPs for PDAC potentially can be replaced by WOTSAs.
The prognostic impact of tumor location in non-muscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing chinese multicenter and SEER registries
Authors: Lilong Liu, Kaiwen Li, Shao-gang Wang, Jianli Wang, Zhipeng Yao, Yu Xie, Zhigang Ji, Zhiwen Chen, Hailong Hu, Haige Chen, Junyi Hu, Yaxin Hou, Zhenghao Liu, Yang Li, Yuhong Ding, Yingchun Kuang, Yang Xun, Jia Hu, Jiaqiao Zhang, Heng Li, Tie Chong, Jianbin Bi, Zhiping Wang, Yinhuai Wang, Peng Zhang, Qiang Wei, Zhaohui Chen, Lei Li, Jian Huang, Zheng Liu, Ke Chen
Journal: International Journal of Surgery (2024)

Most bladder cancers are nonmuscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach.
Author Correction: A systematic review and meta-analysis of artificial intelligence versus clinicians for skin cancer diagnosis
Authors: Maria Paz Salinas, Javiera Sepúlveda, Leonel Hidalgo, Dominga Peirano, Macarena Morel, Pablo Uribe, Veronica Rotemberg, Juan Briones, Domingo Mery, Cristian Navarrete-Dechent
Journal: npj Digital Medicine (2024)
Intracellular Criegee's mechanism-based synergistic ozone therapy mediated by oleogels for cancer treatment
Authors: Jingsong Lu, Rong Zheng, Ziao Shi, Xiaohan Gao, Ying Li, Abdul Fahad, Neema Ufurahi-Pambe, Zeping Jin, Sumei Chen, Wensheng Xie, Zhenhu Guo, Jing Yu, Shenglei Che, Guifeng Zhang, Benhua Xu, Yen Wei, Lingyun Zhao
Journal: Journal of Controlled Release (2024)