tbuckley/cabot-search huggingface dataset:
The role of motivation in clinical presentation, treatment engagement and response in schizophrenia-spectrum disorders: A systematic review
Authors: Helen Thai, Élodie C. Audet, Richard Koestner, Martin Lepage, Gillian A. O'Driscoll
Journal: Clinical Psychology Review (2024)

Schizophrenia, a debilitating psychiatric disorder, has a long-term impact on social and occupational functioning. While negative symptoms, notably amotivation, are recognized as poor prognostic factors, the positive force of patient motivation (autonomous motivation) remains underexplored. This systematic review, guided by Self-Determination Theory (SDT), investigated the impact of motivation on clinical presentation, and treatment engagement and response in schizophrenia-spectrum disorders. Fifty-five independent studies (N = 6897), using 23 different motivation scales, met inclusion criteria. Results were categorized into cross-sectional and longitudinal correlates of autonomous motivation, and the effects of motivational interventions. Cross-sectionally, autonomous motivation was positively associated with social/occupational functioning, and negatively associated with negative and positive symptom severity. In longitudinal studies, baseline autonomous motivation predicted engagement in and response to social/occupational treatments, with mixed results in cognitive interventions. In the 16 randomized controlled trials (RCTs), the most common motivational interventions were individualized goal setting and goal attainment support, followed by increasing sense of competence by challenging defeatist beliefs, and enhancing relatedness by increasing contact time. Motivational interventions consistently increased autonomous motivation, treatment engagement and response. More studies are needed, particularly studies that monitor motivation during treatment: proximal assessments could facilitate the identification of treatment elements that impact motivation and engagement and inform treatment modifications to enhance the patient experience and improve treatment efficacy.
Cutaneous Lupus Erythematosus: Expanding Clinical Trial Eligibility Criteria Based on Quality of Life Data
Authors: Daniella F. Faden, Lillian Xie, Caroline J. Stone, Lais Lopes Almeida Gomes, Ahmed Eldaboush, Cristina Ricco, Rui Feng, Victoria P. Werth
Journal: Journal of the American Academy of Dermatology (2024)
Single-dose of integrated bilayer microneedles for enhanced hypertrophic scar therapy with rapid anti-inflammatory and sustained inhibition of myofibroblasts
Authors: Yihua Xu, Qiong Bian, Yunting Zhang, Yukang Zhang, Dechang Li, Xiaolu Ma, Ruxuan Wang, Weitong Hu, Jingyi Hu, Yuxian Ye, Hangjuan Lin, Tianyuan Zhang, Jianqing Gao
Journal: Biomaterials (2024)
Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche
Authors: Hongjie Xiong, Zhongquan Song, Tingya Wang, Ke Huang, Fangfang Yu, Wenyu Sun, Xiaohui Liu, Liu Liu, Hui Jiang, Xuemei Wang
Journal: Biomaterials (2024)
FDA Approval Summary: Asciminib for Ph+ CML in Chronic Phase Treated with Two or More Tyrosine Kinase Inhibitors and for the T315I Mutation
Authors: Gulsum E. Pamuk, Edwin C.Y. Chow, Alexei C. Ionan, Haiyan Chen, Shwu-Luan Lee, Vicky Hsu, Manuela Grimstein, Nan Zheng, Jielin Sun, Rosane Charlab, Brenda J. Gehrke, Jonathon Vallejo, Lori A. Ehrlich, R. Angelo de Claro, Marc R. Theoret
Journal: Clinical Cancer Research (2024)

Abstract On October 29, 2021, FDA granted accelerated approval to asciminib (SCEMBLIX; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% [95% confidence interval (CI), 30–46] in the asciminib arm versus 16% (95% CI, 8–26) in the bosutinib arm (P value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI, 34–64) in the single-arm CABL001X2101 study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, and increases in creatine kinase, alanine aminotransferase, aspartate aminotransferase, lipase, and amylase. This manuscript describes the basis for approval of these indications.
Clickable nanozyme enhances precise colonization of probiotics for ameliorating inflammatory bowel disease
Authors: Fang Dong, Liangwen Hao, Lin Wang, Ying Huang
Journal: Journal of Controlled Release (2024)

Convincing evidence suggests that aberrant gut microbiota changes play a critical role in the progression and pathogenesis of inflammatory bowel disease (IBD). Probiotic therapeutic interventions targeting the microbiota may provide alternative avenues to treat IBD, but currently available probiotics often suffer from low intestinal colonization and limited targeting capability. Here, we developed azido (N
Editor’s Note: Androgen-Induced Differentiation and Tumorigenicity of Human Prostate Epithelial Cells
Authors: Raanan Berger, Phillip G. Febbo, Pradip K. Majumder, Jean J. Zhao, Shayan Mukherjee, Sabina Signoretti, K. Thirza Campbell, William R. Sellers, Thomas M. Roberts, Massimo Loda, Todd R. Golub, William C. Hahn
Journal: Cancer Research (2024)

The image depicting the LT bands in lanes 3 and 4 in Fig. 1A was incorrectly reused to
Sacituzumab Govitecan Demonstrates Efficacy across Tumor Trop-2 Expression Levels in Patients with Advanced Urothelial Cancer
Authors: Yohann Loriot, Arjun V. Balar, Daniel P. Petrylak, Arash R. Kalebasty, Petros Grivas, Aude Fléchon, Rohit K. Jain, Umang Swami, Manojkumar Bupathi, Philippe Barthélémy, Philippe Beuzeboc, Phillip Palmbos, Christos E. Kyriakopoulos, Damien Pouessel, Cora N. Sternberg, Julia Tonelli, Mitch Sierecki, Marianna Zavodovskaya, Emon Elboudwarej, Lauri Diehl, Juliane M. Jürgensmeier, Scott T. Tagawa
Journal: Clinical Cancer Research (2024)

Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2-directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1-3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression.
Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy
Authors: Kandarp M. Dave, Venugopal R. Venna, Krithika S. Rao, Donna B. Stolz, Bodhi Brady, Victoria A. Quaicoe, Michael E. Maniskas, Ella E. Hildebrand, Dawson Green, Mingxi Chen, Jadranka Milosevic, Si-yang Zheng, Sruti S. Shiva, Louise D. McCullough, Devika S Manickam
Journal: Journal of Controlled Release (2024)
Trajectories of egg sensitization in childhood: Two birth cohorts in Asia and Europe
Authors: Toshinori Nakamura, Taiji Nakano, Angela Simpson, Michihiro Kono, John A. Curtin, Tomoko Kobayashi, Clare S. Murray, Masashi Akiyama, Masahiro Imanishi, Masayuki Mikuriya, Adnan Custovic, Naoki Shimojo
Journal: Allergy (2024)

Abstract Background Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin ( FLG ) gene loss‐of‐function mutations on the natural history of egg sensitization lacks consensus among studies. Objective To evaluate the association between the natural course of egg sensitization and FLG mutations. Methods We used Japanese and the UK birth cohorts (CHIBA and MAAS) to identify the longitudinal patterns of egg sensitization until mid‐school age and examined the relationship between the identified patterns and FLG mutations. Sensitization was assessed using egg white‐specific IgE levels or skin prick tests (SPTs). Egg allergy was confirmed by parental reports and sensitization. Latent class growth analysis identified longitudinal patterns. Results Three similar patterns of egg sensitization (persistent, early‐onset remitting, and no/low grade classes) were identified in both cohorts, with differing prevalence estimates. The proportion of children with egg allergy in the persistent class at 7 or 8 years of age was 23% (CHIBA) and 20% (MAAS). Consistently in both cohorts, FLG mutations were significantly associated only with the persistent class. Children with FLG mutations had an approximately four‐fold increased risk of being in the persistent sensitization class (RRRs: 4.3, 95%C.I. (1.2–16.0), p = .03 in CHIBA; 4.3 (1.3–14.7), p = .02 in MAAS). Conclusion FLG loss‐of‐function mutations are associated with persistent egg sensitization in both Japanese and European ethnicities, and the mutations might be a potential biomarker for identifying the risk of persistent egg sensitization/allergy in early infancy. Future studies should incorporate oral food challenges to confirm this relationship.
Trastuzumab Deruxtecan in Advanced Solid Tumors With Human Epidermal Growth Factor Receptor 2 Amplification Identified by Plasma Cell-Free DNA Testing: A Multicenter, Single-Arm, Phase II Basket Trial
Authors: Masataka Yagisawa, Hiroya Taniguchi, Taroh Satoh, Shigenori Kadowaki, Yu Sunakawa, Tomohiro Nishina, Yoshito Komatsu, Taito Esaki, Daisuke Sakai, Ayako Doi, Takeshi Kajiwara, Hiromi Ono, Masatoshi Asano, Nami Hirano, Justin Odegaard, Satoshi Fujii, Shogo Nomura, Hideaki Bando, Akihiro Sato, Takayuki Yoshino, Yoshiaki Nakamura
Journal: Journal of Clinical Oncology (2024)

PURPOSE HERALD/EPOC1806 was conducted as a multicenter phase II trial assessing trastuzumab deruxtecan (T-DXd) therapy for patients with human epidermal growth factor receptor 2 ( HER2 )–amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing. PATIENTS AND METHODS Patients exhibited advanced solid tumors with HER2 amplification that was identified via next-generation sequencing of cfDNA testing, without the requirement for immunohistochemical HER2 testing. The studied group was administered T-DXd at 5.4 mg/kg once every 3 weeks until onset of disease progression or intolerable toxicity. RESULTS Overall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated HER2 amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma HER2 copy number (CN) of 8.55 (range, 2.4-73.9). Confirmed overall response rate (ORR) by investigator assessment was 56.5% (95% CI, 43.3 to 69.0), thus showing a value beyond the 5% threshold. Responses were evaluated for 13 cancer types, including KRAS -mutant colorectal (1/3), PIK3CA -mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma HER2 CN above versus below the baseline median value did not differ for impact response; however, clearance of HER2 amplification in cfDNA on cycle 2 day 1 had higher response values compared with persistence. Median progression-free survival and response duration were 7.0 (95% CI, 4.9 to 9.7) and 8.8 (95% CI, 5.8 to 11.2) months, respectively, with the majority of complications being mild to moderate. Interstitial lung diseases were identified in 16 (26%) patients, including 14 patients with grade 1 disease, one patient with grade 2 disease, and one patient with grade 3 disease. CONCLUSION T-DXd treatment demonstrated high ORR with durable response in patients with advanced HER2 -amplified solid tumors determined with cfDNA testing.
A low level of tumor necrosis factor α in tumor microenvironment maintains the self-renewal of glioma stem cells by Vasorin-mediated glycolysis
Authors: Yang Zhang, Tianxu Kang, Yuxi Wang, Chao Song, Huan Li, Hailong Mi, Yachao Li, Minhai Dong, Xiaoyu Ma, Hongtao Zhu, Lidong Cheng, Po Zhang, Zhiye Chen, Lin Zhou, Qiulian Wu, Feng Mao, Baofeng Wang, Suojun Zhang, Kai Shu, Feng Wan, Wenchao Zhou, Jeremy N Rich, Jianying Shen, Qungen Xiao, Xingjiang Yu
Journal: Neuro-Oncology (2024)

Self-renewal of glioma stem cells (GSCs) is responsible for glioblastoma (GBM) therapy resistance and recurrence. Tumor necrosis factor α (TNFα) and TNF signaling pathway display an antitumor activity in preclinical models and in tumor patients. However, TNFα exhibits no significance for glioma clinical prognosis based on the Glioma Genome Atlas database. This study aimed to explore whether TNFα of tumor microenvironment maintains self-renewal of GSCs and promotes worse prognosis in glioma patients.
Developmental pluripotency-associated 4 increases aggressiveness of pituitary neuroendocrine tumors by enhancing cell stemness
Authors: Shaista Chaudhary, Ujjal Das, Shaima Jabbar, Omkaram Gangisetty, Bénédicte Rousseau, Simon Hanft, Dipak K Sarkar
Journal: Neuro-Oncology (2024)

Pituitary neuroendocrine tumors, PitNETs, are often aggressive and precipitate in distant metastases that are refractory to current therapies. However, the molecular mechanism in PitNETs' aggressiveness is not well understood. Developmental pluripotency-associated 4 (DPPA4) is known as a stem cell regulatory gene and overexpressed in certain cancers, but its function in the context of PitNETs' aggressiveness is not known. We employed both rat and human models of PitNETs. In the rat pituitary tumor model, we used prenatal-alcohol-exposed (PAE) female Fischer rats which developed aggressive PitNETs following estrogen treatment, while in the human pituitary tumor model, we used aggressively proliferative cells from pituitary tumors of patients undergone surgery. Various molecular, cellular, and epigenetic techniques were used to determine the role of DPPA4 in PitNETs' aggressiveness. We show that DPPA4 is overexpressed in association with increased cell stemness factors in aggressive PitNETs of PAE rats and of human patients. Gene-editing experiments demonstrate that DPPA4 increases the expression of cell stemness and tumor aggressiveness genes and promotes proliferation, colonization, migration, and tumorigenic potential of PitNET cells. ChIP assays and receptor antagonism studies reveal that DPPA4 binds to canonical WINTs promoters and increases directly or indirectly the WNT/β-CATENIN control of cell stemness, tumor growth, and aggressiveness of PitNETs. Epigenetic studies show the involvement of histone methyltransferase in alcohol activation of DPPA4. These findings support a role of DPPA4 in tumor stemness and aggressiveness and provide a preclinical rationale for modulating this stemness regulator for the treatment of PitNETs.
Postzygotic mosaicism of <i>SMARCB1</i> variants in patients with rhabdoid tumors: A not-so-rare condition exposing to successive tumors
Authors: Grégory Thomson, Mathilde Filser, Léa Guerrini-Rousseau, Arnault Tauziede-Espariat, Christine Bourneix, Marion Gauthier-Villars, Fatoumata Simaga, Kévin Beccaria, Cécile Faure-Conter, Aurélien Maureille, Hélène Zattara-Cannoni, Nicolas Andre, Natacha Entz-Werle, Laurence Brugieres, Ludovic Mansuy, Philippe Denizeau, Sophie Julia, Olivier Ingster, Sophie Lejeune, Afane Brahimi, Isabelle Coupier, Valérie Bonadona, Olivier Delattre, Julien Masliah-Planchon, Franck Bourdeaut
Journal: Neuro-Oncology (2024)

Rhabdoid tumors (RT) are aggressive, rare tumors predominantly affecting young children, characterized by biallelic SMARCB1 gene inactivation. While most SMARCB1 alterations are acquired de novo, a third of cases exhibit germline alterations, defining Rhabdoid Tumors Predisposition Syndrome. With the increased sensitivity of next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases are more detectable. This study focuses on exploring SMARCB1 germline alterations, notably mosaicism in blood samples of children with RT and in parents, using a custom NGS panel. A cohort of 280 children and 140 parents with germline analysis was studied. Germline DNA from 111 children with RT and 32 parents were reanalyzed with a custom NGS panel with 1500X average depth targeting the SMARCB1 gene to identify intragenic variants not detected with conventional low-sensitivity methods. Follow-up data was obtained for 77 patients. Nine previously undetected mosaicism cases were identified, totaling 17/280 patients with a mosaic variant (6.1%) in the cohort, with variant allele frequencies between 0.9% and 33%, thus highlighting the prior underestimation of its prevalence. Follow-up data showed that 4 out of 7 survivors with mosaic variants developed distinct novel tumors, 2 sharing SMARCB1 alterations with the initial tumor, emphasizing the potential clinical impact of SMARCB1 mosaicism. The hitherto underestimated rate of SMARCB1 mosaicism in RT underscores the need for optimized genetic counseling and oncological monitoring. The findings have significant medical implications, considering the dire prognosis of RT.
Gene transfer among viruses substantially contributes to gene gain of giant viruses
Authors: Junyi Wu, Lingjie Meng, Morgan Gaïa, Hiroyuki Hikida, Yusuke Okazaki, Hisashi Endo, Hiroyuki Ogata
Journal: Molecular Biology and Evolution (2024)

Abstract The phylum Nucleocytoviricota comprises a diverse group of double-stranded DNA viruses that display a wide range of gene repertoires. Although these gene repertoires determine the characteristics of individual viruses, the evolutionary processes that have shaped the gene repertoires of extant viruses since their common ancestor are poorly characterized. In this study, we aimed to address this gap in knowledge by using amalgamated likelihood estimation, a probabilistic tree reconciliation method that infers evolutionary scenarios by distinguishing origination, gene duplications, virus-to-virus horizontal gene transfer (vHGT), and gene losses. We analyzed over 4,700 gene families from 195 genomes spanning all known viral orders. The evolutionary reconstruction suggests a history of extensive gene gains and losses during the evolution of these viruses, notably with vHGT contributing to gene gains at a comparable level to duplications and originations. The vHGT frequently occurred between phylogenetically closely related viruses, as well as between distantly related viruses with an overlapping host range. We observed a pattern of massive gene duplications that followed vHGTs for gene families that was potentially related to host range control and virus–host arms race. These results suggest that vHGT represents a previously overlooked, yet important, evolutionary force that integrates the evolutionary paths of multiple viruses and affects shaping of Nucleocytoviricota virus gene repertoires.
RNA splicing as a biomarker and phenotypic driver of meningioma DNA-methylation groups
Authors: Nathan K Leclair, Abrar Choudury, William C Chen, Stephen T Magill, Kathleen McCortney, Craig M Horbinski, Zhenhong Chen, Ezequiel Goldschmidt, Charlotte D Eaton, Ketan R Bulsara, Wenya Linda Bi, Akash J Patel, Felix Sahm, David Raleigh, Olga Anczukow
Journal: Neuro-Oncology (2024)

Advances in our understanding of the molecular biology of meningiomas have led to significant gains in the ability to predict patient prognosis and tumor recurrence and to identify novel targets for therapeutic design. Specifically, classification of meningiomas based on DNA methylation has greatly improved our ability to risk stratify patients, however new questions have arisen in terms of the underlying impact these DNA-methylation signatures have on meningioma biology.
Apparently Benign 131I Adrenal Uptake
Authors: Daniela Travaglio Morales, Michael C. Kreissl, Florian Fischer, Alexander Heinzel
Journal: Clinical Nuclear Medicine (2024)

A 60-year-old man suffering from papillary thyroid cancer (pT2 pN0(0/21) cM0) underwent diagnostic 131I whole-body scintigraphy with recombinant thyroid-stimulating hormone for follow-up after thyroidectomy and adjuvant 131I therapy with 4.2 GBq. A focal uptake of radioiodine was found in the right adrenal gland, which had not been seen on the initial posttherapeutic images; therefore, an adrenal metastasis was suspected. However, the diagnostic workup including contrast-enhanced MRI as well as endocrine laboratory tests indicated a benign etiology showcasing a very rare case of false-positive radioiodine uptake in the adrenal gland. The imaging follow-up after 1 year showed no significant changes.
Immunotherapy and Overall Survival Among Patients With Advanced Non–Small Cell Lung Cancer and Obesity
Authors: Yasutaka Ihara, Kenji Sawa, Takumi Imai, Tsubasa Bito, Yuki Shimomura, Ryota Kawai, Ayumi Shintani
Journal: JAMA Network Open (2024)

IMPORTANCE The association between obesity and response to cancer treatment and survival remains unclear, with conflicting findings from various studies. The optimal choice between conventional chemotherapy and immunotherapy for first-line treatment remains uncertain in patients with obesity who potentially have an inadequate therapeutic response to immunotherapy. OBJECTIVE To investigate whether body mass index (BMI) modifies the association of immunotherapy or conventional therapy with overall survival in patients with advanced non–small cell lung cancer (aNSCLC). DESIGN, SETTING, and PARTICIPANTS A retrospective cohort study, using administrative claims data obtained from advanced treatment centers in Japan, was conducted between December 1, 2015, and January 31, 2023. Participants included individuals aged 18 years or older with aNSCLC who received immunotherapy, using immune checkpoint inhibitor (ICI) treatment or conventional chemotherapy. EXPOSURE Immune checkpoint inhibitor therapy as first-line chemotherapy was compared with conventional chemotherapy, identified through patient medical records. MAIN OUTCOMES AND MEASURES The main outcome was overall survival. Survival analysis covered a 3-year follow-up period after the first-line chemotherapy. RESULTS A total of 31 257 patients with aNSCLC were identified. Of these, 12 816 patients received ICI therapy (mean [SD] age, 70.2 [9.1] years; 10 287 [80.3%] men) and 18 441 patients received conventional chemotherapy (mean [SD] age, 70.2 [8.9] years; 14 139 [76.7%] men). Among patients with BMI less than 28, ICI therapy was associated with a significantly lower hazard of mortality (eg, BMI 24: hazard ratio [HR], 0.81; 95% CI, 0.75-0.87) compared with those who underwent conventional chemotherapy. However, no such association was observed among patients with BMI 28 or greater (eg, BMI 28: HR, 0.90; 95% CI, 0.81-1.00). CONCLUSIONS AND RELEVANCE The findings of this retrospective cohort study suggest that BMI modifies the association of ICI therapy compared with conventional chemotherapy with overall survival in patients with aNSCLC. A lack of association between ICI therapy and improved survival in patients with aNSCLC and overweight or obesity compared with conventional chemotherapy was observed. This suggests that ICI therapy may not be the optimal first-line therapy for patients with overweight or obesity and the use of conventional chemotherapy should also be considered in such patients.