tbuckley/cabot-search huggingface dataset:
Cultural adaptation and validation of a Spanish-Language measure of therapist competency working with transgender clients in Colombia
Authors: Sharon G. Horne, Reynel A. Chaparro, Nedim Yel
Journal: International Journal of Transgender Health (2025)

Introduction Transgender people often report negative and harmful experiences accessing and receiving quality mental health care, and mental health professionals rarely receive training in transgender-affirmative practice. This study translated, culturally adapted, and psychometrically assessed a Spanish language version of the Gender Identity Counselor Competency Scale-3 (GICCS-3), a commonly used measure of transgender competency, with a sample of mental health professionals working in Colombia.
Autophagy inhibition alleviates tumor desmoplasia and improves the efficacy of locally and systemically administered liposomal doxorubicin
Authors: Kamalpreet Kaur Sandha, Sukhleen Kaur, Kuhu Sharma, Syed Mudassir Ali, P Ramajayan, Ajay Kumar, Prem N Gupta
Journal: Journal of Controlled Release (2025)
Parkin deficiency promotes colorectal tumorigenesis and progression through RIPK3‐dependent necroptotic inflammation
Authors: Zheming Wu, Huaping Xiao, Jake A Kloeber, Yaobin Ouyang, Ping Yin, Jinzhou Huang, Bin Chen, Shouhai Zhu, Jing Lu, Yiqun Han, Xinyi Tu, Sonja Dragojevic, Kuntian Luo, Adrian T Ting, Meng Welliver, ZhenkunLou Lou
Journal: Cancer Communications (2025)
A prospective, phase II, neoadjuvant study based on chemotherapy sensitivity in HR+/HER2‐ breast cancer‐FINEST study
Authors: Li Chen, Wen‐Ya Wu, Fei Liang, Guang‐Yu Liu, Ke‐Da Yu, Jiong Wu, Gen‐Hong Di, Lei Fan, Zhong‐Hua Wang, Jun‐Jie Li, Zhi‐Ming Shao
Journal: Cancer Communications (2025)

Abstract Background Hormone receptor‐positive (HR+)/humaal growth factor receptor 2‐negative (HER2‐) breast cancer, the most common breast cancer type, has variable prognosis and high recurrence risk. Neoadjuvant therapy is recommended for median‐high risk HR+/HER2‐ patients. This phase II, single‐arm, prospective study aimed to explore appropriate neoadjuvant treatment strategies for HR+/HER2‐ breast cancer patients. Methods Eligible female patients with newly diagnosed, untreated HR+/HER2‐ breast cancer received 2 cycles of nab‐paclitaxel and carboplatin (nabPCb). Magnetic resonance imaging (MRI) was performed to assess tumor responses, and 40% regression of the maximal tumor diameter was deemed chemo‐sensitive. Chemo‐sensitive patients continued nabPCb for 4 more cycles (group A). Chemo‐insensitive patients were randomized to groups B, C, and D at a ratio of 1:3:1 to receive a new chemotherapy for 4 cycles or endocrine‐immune‐based therapy (dalpiciclib, letrozole and adebrelimab, with goserelin if patients were premenopausal) for 4 cycles or to undergo surgery. Peripheral blood and core‐needle biopsy (CNB) samples were collected before treatment, followed by a next‐generation sequencing (NGS) panel detection and similarity network fusion (SNF) typing through digital pathology data. The primary endpoint was the pathological complete response (pCR) rate, and the secondary endpoint was the clinical objective response rate (ORR). Results A total of 121 patients were enrolled (67.8% with stage III disease), with 76, 9, 27, and 9 patients in groups A, B, C and D, respectively. The total pCR rate was 4.1%, and all patients who received pCR were in group A. Group C had a better ORR than Group B (81.5% vs. 66.7%). Exploratory analysis revealed that patients with the SNF4 subtype were the most sensitive to nabPCb (pCR rate of 21.1% vs. 1.8% in group A), whereas patients in group C with the SNF2 subtype were more sensitive to endocrine‐immune‐based therapy (Miller‐Payne grade 4‐5, 45.5% vs. 6.3%). Conclusions Converting to endocrine‐immune‐based therapy improved the ORR, but not the pCR rate in chemo‐insensitive patients. Neoadjuvant chemotherapy and endocrine therapy are not mutually exclusive. The SNF4 subtype of HR+/HER2‐ breast cancer was more chemo‐sensitive, whereas the SNF2 subtype might be more sensitive to immunotherapy.
Adipose ZFP36 protects against diet-induced obesity and insulin resistance
Authors: Yang Hu, Jinghan Hai, Yun Ti, Binghui Kong, Guoqing Yao, Yuan Zhao, Chen Zhang, Xuehui Zheng, Chunmei Zhang, Xiangping Ma, Huaitao Yu, Xiaoning Qin, Pavel Kovarik, Cheng Zhang, Shaozhuang Liu, Wencheng Zhang, Jingyuan Li, Peili Bu
Journal: Metabolism (2025)

Highlights•ZFP36 downregulation in adipose tissues of humans and mice is linked to obesity and metabolic disorders.•Adipose ZFP36 deficiency exacerbates diet-induced obesity and metabolic syndrome in mice.•The expansion of adipocytes contributes to adipose tissue hypoxia, leading to adipose tissue dysfunction in obesity.•ZFP36 attenuates hypertrophy of adipocytes in white adipose tissue via RNF128/Sirt1/lipolysis signaling.AbstractAimsObesity, as a worldwide healthcare problem, has become more prevalent. ZFP36 is a well-known RNA-binding protein and involved in the posttranscriptional regulation of many physiological processes. Whether the adipose ZFP36 plays a role in obesity and insulin resistance remains unclear.MethodsThe expression levels of ZFP36 were analyzed in adipose tissues of obese patients, diet-induced obese mice, ob/ob mice and db/db mice. To determine whether adipose ZFP36 protects against the diet-induced obesity, we generated adipose-specific ZFP36 knockout (ZFP36AKO) mice, which were subjected to high-fat-diet (HFD) for 16 weeks. To explore the specific molecular mechanisms of ZFP36 regulating metabolic disorders, we used gene array assay of control and ZFP36-deficient adipose tissue, and assessed the pathways in vitro and vivo.ResultsWestern blotting and RT-PCR were performed to determine the downregulating level of ZFP36 in adipose tissues of obese patients, diet-induced obese mice, ob/ob mice and db/db mice. Relative to control mice, ZFP36AKO mice were more susceptible to HFD-induced obesity, along with insulin resistance, glucose tolerance, and increased metabolic disorders. The obesity of ZFP36AKO mice was attributed to hypertrophy of adipocytes in white adipose tissue via decreased expression of Perilipin1 (PLIN1), adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL). We discovered that ZFP36 oppositely regulated RNF128 expression by repressing the mRNA stability and translation of RNF128, a negative regulator of SIRT1 expression.ConclusionsThis study suggests that ZFP36 in adipose tissue plays an important role in diet-induced obesity, and identifies a novel molecular signaling pathway of ZFP36/RNF128/Sirt1 involved in obesity.Graphical abstract
The δ-Opioid Receptor: Molecular Pharmacology, Signal Transduction, and the Determination of Drug Efficacy
Authors: Raymond M. Quock, Thomas H. Burkey, Eva Varga, Yoshiaki Hosohata, Keiko Hosohata, Scott M. Cowell, Cheryl A. Slate, Frederick J. Ehlert, William R. Roeske, Henry I. Yamamura
Journal: Pharmacological Reviews (1999)
International Union of Pharmacology. XV. Subtypes of γ-Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Structure and Receptor Function
Authors: E.A. Barnard, P. Skolnick, R.W. Olsen, H. Mohler, W. Sieghart, G. Biggio, C. Braestrup, A.N. Bateson, S.Z. Langer
Journal: Pharmacological Reviews (1998)
D-ribose-5-phosphate inactivates YAP and functions as a metabolic checkpoint
Authors: Cheng-E Tu, Yong-Feng Liu, Hong-Wei Liu, Chun-Mei Jiao, Quentin Liu, Mien-Chie Hung, Peng Li, Xiang-Bo Wan, Xin-Juan Fan, Yun-Long Wang
Journal: Journal of Hematology & Oncology (2025)

Targeting glucose uptake by glucose transporter (GLUT) inhibitors is a therapeutic opportunity, but efforts on GLUT inhibitors have not been successful in the clinic and the underlying mechanism remains unclear. We aim to identify the key metabolic changes responsible for cancer cell survival from glucose limitation and elucidate its mechanism. The level of phosphorylated YAP was analyzed with Western blotting and Phos-tag immunoblotting. Glucose limitation-induced metabolic changes were analyzed using targeted metabolomics (600MRM). The anti-cancer role of metabolite was examined using colony formation assay and APCmin/+ mice. Co-immunoprecipitation, LS-MS, qRT-PCR, and immunofluorescence were performed to explore the underlying mechanisms. We found that D-Ribose-5-phosphate (D5P), a product of the pentose phosphate pathway connecting glucose metabolism and nucleotide metabolism, functions as a metabolic checkpoint to activate YAP under glucose limitation to promote cancer cell survival. Mechanistically, in glucose-deprived cancer cells, D5P is decreased, which facilitates the interaction between MYH9 and LATS1, resulting in MYH9-mediated LATS1 aggregation, degradation, and further YAP activation. Interestingly, activated YAP further promotes purine nucleoside phosphorylase (PNP)-mediated breakdown of purine nucleoside to restore D5P in a feedback manner. Importantly, D5P synergistically enhances the tumor-suppressive effect of GLUT inhibitors and inhibits cancer progression in mice. Our study identifies D5P as a metabolic checkpoint linking glucose limitation stress and YAP activation, indicating that D5P may be a potential anti-cancer metabolite by enhancing glucose limitation sensitivity.
Non canonical c-CBL mutations define a specific phenotype of myeloid neoplasia
Authors: Luca Guarnera, Carmelo Gurnari, Carlos Bravo-Perez, Arda Durmaz, Nakisha D. Williams, Hussein Awada, Naomi Kawashima, Arooj Ahmed, Serhan Unlu, Olisaemeka D. Ogbue, Christopher Haddad, Aashray Mandala, Yasuo Kubota, Juraj Bodo, Genevieve M. Crane, Heesun J. Rogers, Jaroslaw P. Maciejewski, Valeria Visconte
Journal: Leukemia (2025)

CBL proteins are a family of RING finger E3 ubiquitin ligases that regulate proliferative signals via ubiquitination and degradation of tyrosine-phosphorylated signaling proteins, such as KIT, CSF-1, FLT3 and PDGF [1].We previously described c-CBL RING finger mutations in myeloid neoplasia (MN), chiefly myelodysplastic/ myeloproliferative (MDS/MPN) syndromes such as chronic myelomonocytic leukemia [2, 3] and juvenile myelomonocytic leukemia [4].c-CBL mutations are mainly heterozygous, but in some instances homozygous configuration can be found due to somatic uniparental disomy (UPD) affecting 11q chromosome [3].Canonical c-CBL hits [missense (MS) mutations affecting linker and zinc finger domains] impair the ubiquitination function while preserving PI3K/AKT activation, common to RAS pathway, via LYN and KYN-mediated phosphorylation of c-CBL Y700, Y731, Y774.Somatic c-CBL hits have been linked to monocytosis and MPN phenotype [5] and, across MDS and acute myeloid leukemia (AML) phenotypes, these hits cluster with other RAS pathway gene mutations in unsupervised molecular clustering schemes [6,7].Furthermore, outcome studies and prognostic scoring systems assigned a negligible prognostic role to c-CBL mutations in MDS [8] and AML [9], albeit without differentiating the type or mutational configuration.In addition to canonical mutations, c-CBL truncations can be also encountered and, since these lesions could impair not only the ubiquitin-association function, but also the PI3K/AKT activation function (enhanced through MS mutations), we hypothesized that these hits could lead to different, possibly less aggressive clinical phenotypes.To test our theory, we identified several cases of canonical (pathogenic MS mutations occurring in the linker region/zinc finger domains) and truncating c-CBL mutations taking advantage of a large genotyped and clinically annotated cohort (n = 11,543: 7211 AML, 3448 MDS, 575 MPN/MDS; 309 MPN) (Fig. 1A,B, Supplementary Table 1).Clonal hierarchy of c-CBL mutations was assessed using the previously established variant allele frequency (VAF)-based algorithm [10].Pathogenicity of the variants was
Boosting CAR-T cell therapy through vaccine synergy
Authors: Yan-Ruide Li, Zibai Lyu, Xinyuan Shen, Ying Fang, Lili Yang
Journal: Trends in Pharmacological Sciences (2025)

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematological cancers. However, achieving comparable success in solid tumors remains challenging. Factors contributing to these limitations include the scarcity of tumor-specific antigens (TSAs), insufficient CAR-T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Vaccine-based strategies are emerging as potential approaches to address these challenges, enhancing CAR-T cell expansion, persistence, and antitumor efficacy. In this review, we explore diverse vaccine modalities, including mRNA, peptide, viral vector, and dendritic cell (DC)-based vaccines, and their roles in augmenting CAR-T cell responses. Special focus is given to recent clinical advancements combining mRNA-based vaccines with CAR-T therapy for the treatment of genitourinary cancers. In addition, we discuss crucial considerations for optimizing vaccine dosing, scheduling, and delivery to maximize CAR-T synergy, aiming to refine this combination strategy to improve treatment efficacy and safety.
Cost Effectiveness Analysis of Digital Therapeutics for Amblyopia
Authors: Irene Koc, Saghar Bagheri, Rachel K Chau, Sandra Hoyek, Nour Abou Shousha, Golnoush Mahmoudinezhad, Michelle M Falcone, Isdin Oke, David G Hunter, Nimesh A Patel
Journal: Ophthalmology (2025)
Malaysia outbreak survivors retain detectable Nipah antibodies and memory B cells after 25 years
Authors: Hui Ming Ong, Puteri Ainaa S. Ibrahim, Chee Ning Chong, Chong Tin Tan, Jie Ping Schee, Michael Selorm Avumegah, Raúl Gómez Román, Neil George Cherian, Won Fen Wong, Li-Yen Chang
Journal: Journal of Infection (2025)

Highlights•The first report of long-term humoral immunity in 25 Nipah virus survivors from 1998 from Malaysia.•Anti-NiV-F and anti-NiV-G found in 56% and 60% of survivors, respectively.•At least 72% of survivors had detectable neutralizing antibodies.•Six survivors had NiV-specific memory B cells.SummaryObjectiveTo evaluate the long-term humoral immune response to Nipah virus (NiV) in a cohort of 25 survivors after 25 years of post-infection.MethodsA total of 25 survivors of NiV infection from the 1998 outbreak were recruited for sample collection. The serum IgG antibody response to NiV antigens, specifically nucleocapsid (N), fusion glycoprotein (F) and attachment glycoprotein (G) was evaluated using ELISA. Additionally, the samples were tested for neutralizing antibodies and memory B cell responses.ResultsDetection rates of anti-NiV-F and anti-NiV-G were 56% and 60%, respectively, among the survivors at a 1:100 dilution, whereas only 20% were specifically reactive to rNiV-N. Notably, all samples that tested positive for NiV-F and NiV-G at this dilution also exhibited neutralizing antibodies, highlighting the specificity of these assays. Live virus neutralization assay showed that 72% of survivors had detectable neutralizing antibodies, with varying titers, indicating long-lasting immune memory. Furthermore, memory B cell responses specific to NiV-F and NiV-G were observed in six randomly selected survivors, suggesting the presence of enduring immunological memory.ConclusionsThese findings highlight the potential of NiV-F and NiV-G as reliable markers for NiV exposure and underscore the need for continuous surveillance and research. Such efforts are crucial for advancing vaccine development and improving preparedness for future NiV outbreaks.
Immune checkpoint blockade in experimental bacterial infections
Authors: Nicole L. Henriksen, Peter Ø. Jensen, Louise K. Jensen
Journal: Journal of Infection (2025)

Highlights•Immune checkpoint blockade can reduce the bacterial burden of various infections•The efficacy of immune checkpoint blockade in bacterial infections is pathogen dependent•Further research is essential for clinical translation of immune checkpoint blockadeAbstractImmune checkpoint inhibitors designed to reinvigorate immune responses suppressed by cancer cells have revolutionized cancer therapy. Similarities in immune dysregulation between cancer and infectious diseases has prompted investigations into the role of immune checkpoints in infectious diseases, including the therapeutic potential of immune checkpoint blockade and drug repurposing. While most research has centered around viral infections, data for bacterial infections are emerging. This systematic review reports on the in vivo effect of immune checkpoint blockade on bacterial burden and selected immune responses in preclinical studies of bacterial infection, aiming to assess if there could be a rationale for using immunotherapy for bacterial infections. Of the 42 analyzed studies, immune checkpoint blockade reduced the bacterial burden in 60% of studies, had no effect in 28% and increased the bacterial burden in 12%. Findings suggest that the effect of immune checkpoint blockade on bacterial burden is context-dependent and in part relates to the pathogen. Further preclinical research is required to understand how the therapeutic effect of immune checkpoint blockade is mediated in different bacterial infections, and if immune checkpoint blockade can be used as an adjuvant to conventional infection management strategies.
Characteristics, risk factors and clinical impact of penicillin and other antibiotic allergies in adults in the UK General Practice: a population-based cohort study
Authors: Yogini Jani, Boqing Chen, Neil Powell, Philip Howard, Jonathan Sandoe, Rob West, Wallis CY Lau
Journal: Journal of Infection (2025)

ObjectiveTo assess the characteristics, risk factors and clinical impact of penicillin and other antibiotic allergies labels in general practice in the UK.DesignPopulation-based cohort study.SettingPrimary care in the UK, 2000-2018.ParticipantsAdults aged 18-100 years who were registered with their general practice for at least 12 months between 01-Jan-2000 and 31-Dec-2018 and followed until 25-Sep-2019.Main outcome measuresThe main outcomes include the annual prevalence and incidence of penicillin and other antibiotic allergies labels. Multinominal logistic regression was used to examine the characteristics associated with receiving an allergy label to different antibiotics. Cox regression modelling was used to compare the risk of resistant infections (methicillin resistant Staphylococcus aureus [MRSA] and vancomycin resistant enterococci) as well as Clostridioides difficile (C.difficile) infection between patients with and without allergy labels. The monthly proportion of patients who had a penicillin allergy test, either before their allergy label was recorded or within one year, was calculated to assess any impact of NICE penicillin allergy assessment recommendations (Clinical guideline [CG183]) in September 2014.ResultsBoth the prevalence and incidence of penicillin allergy label showed a pattern of initial growth followed by a decline. The prevalence reached a maximum of 8.25% in 2011, and the incidence peaked at 0.46% in 2004. Older age, being female, living in less deprived areas, belonging to a larger general practice, and having co-morbidities were associated with a higher chance of receiving a penicillin or other antibiotic allergy label. Patients with antibiotic allergy labels were more likely to receive alternative broad-spectrum antibiotics and had a higher risk of MRSA and C.difficile infections. The introduction of NICE drug allergy guideline did not alter the proportion of patients undergoing penicillin allergy assessment.ConclusionPenicillin and other antibiotic allergy labels are common and lead to radical change in the antibiotic prescribing practices and are associated with resistant and healthcare associated infections.
Engineered Cell Membrane Vesicles Loaded with Lysosomophilic Drug for Acute Myeloid Leukemia Therapy via Organ-Cell-Organelle Cascade-Targeting
Authors: Fangfang Jin, Xingyu Wei, Yongcan Liu, Lisha Tang, Jun Ren, Jing Yang, Can Lin, Jiayuan Hu, Minghui Sun, Genyou Li, Zihao Yuan, Wen Zhao, Xiaozhong Wang, Zesong Yang, Ling Zhang
Journal: Biomaterials (2025)
Virological characterization of Parvovirus B19 isolated during the atypical 2023-2024 outbreak in France
Authors: Nicolas Veyrenche, Jacques Fourgeaud, Marianne Burgard, Slimane Allali, Julie Toubiana, Yaël Pinhas, Pierre Frange, Tiffany Guilleminot, Neil Derridj, Jérémie F. Cohen, Marianne Leruez-Ville
Journal: Journal of Infection (2025)

A Parvovirus B19 (B19V) outbreak has been reported in Europe in 2023-2024. The aims of this study were 1) to describe the incidence of primary cases from 2012 to 2024 in one French hospital 2) to analyze the genome of 2023 strains 3) to identify virological profiles according to the clinical presentations of B19V infection. The incidence of B19V primary cases was studied through an interrupted time-series analysis. Genomes of 2023 strains were sequenced in the NS1-VP1u region. Blood viral loads, IgG and IgM levels were analyzed in 158 cases according to clinical manifestations with Kruskal-Wallis test and a machine learning approach based on k-nearest neighbors. During the 2023-2024 B19V outbreak, there was an 8-time increase in the incidence of B19V infections compared with pre-pandemic levels (8.25 (95%CI: 5.79-11.76)). The 2023 strains belonged to genotype 1a and were closely related to pre-2019 strains. Blood viral loads were significantly different between clinical presentations (p<0.0001). Machine learning allowed us to classify 68.8% (95% CI: 60.9-75.9) patients into the correct clinical group. The 2023-24 epidemic is probably due to the reemergence of the pre-2019 strain. The virological profiles highlighted in this study could assist in accurately interpreting virology results.
N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis
Authors: Daniel Adon Mapamba, Issa Sabi, Julieth Lalashowi, Elingarami Sauli, Joram Buza, Willyhelmina Olomi, Bariki Mtafya, Michael Kibona, Abhishek Bakhuli, Andrea Rachow, Kavindhran Velen, Michael Hoelscher, Nyanda E Ntinginya, Salome Charalambous, Gavin Churchyard, Robert S. Wallis
Journal: Journal of Infection (2025)

<h2>Abstract</h2><h3>Background</h3> Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed to reduce this burden. N-acetylcysteine (NAC) provides the conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol. We recently reported clinical outcomes of a trial of adjunctive NAC in patients with pulmonary tuberculosis, finding that NAC improved the secondary endpoint of recovery of lung function. Here we report the effects of NAC on biomarkers of oxidation, inflammation, and infection in that trial. <h3>Methods</h3> 140 adults with moderate or far-advanced pulmonary tuberculosis were randomly assigned to standard tuberculosis treatment with or without NAC 1200mg twice daily for months 1-4. Sputum and blood samples were obtained at specified intervals to measure total glutathione, MTB-induced cytokines, haemoglobin, whole blood mycobactericidal activity (WBA), and sputum MTB burden. <h3>Results</h3> NAC treatment rapidly increased total glutathione (P<.0001), but levels did not reach those of healthy volunteers (P<.001). NAC reduced MTB-induced TNF-α (P =.011) without affecting IL-10, and accelerated the recovery of hemoglobin in participants with low values on entry. NAC did not affect killing in <i>ex vivo</i> whole blood culture but did slow the clearance of MTB from sputum (P=0.003). <h3>Conclusion</h3> Adjunctive NAC showed antioxidant and anti-inflammatory effects consistent with the amelioration of immunopathology seen in preclinical models. Two biomarkers of antimicrobial activity showed discordant results; neither demonstrated the enhanced antimicrobial effects seen preclinically. The reduction of oxidative stress and inflammation by NAC may explain its effects on the recovery of lung function post-TB.
Corrigendum to “A bioprinted and scalable model of human tubulo-interstitial kidney fibrosis” [Biomaterials, 316 (2025) 123009]
Authors: Daphne Bouwens, Nazanin Kabgani, Cédric Bergerbit, Hyojin Kim, Susanne Ziegler, Sadaf Ijaz, Ali Abdallah, Tamás Haraszti, Sidrah Maryam, Abdolrahman Omidinia-Anarkoli, Laura De Laporte, Sikander Hayat, Jitske Jansen, Rafael Kramann
Journal: Biomaterials (2025)