tbuckley/cabot-search huggingface dataset:
Identification of novel biomarkers in the early diagnosis of malignant melanoma by untargeted liquid chromatography coupled to high-resolution mass spectrometry-based metabolomics: a pilot study
Authors: Jesús Peña-Martín, María Belén García-Ortega, José Luis Palacios-Ferrer, Caridad Díaz, María Ángel García, Houria Boulaiz, Javier Valdivia, José Miguel Jurado, Francisco M Almazan-Fernandez, Salvador Arias Santiago, Francisca Vicente, Coral del Val, José Pérez del Palacio, Juan Antonio Marchal
Journal: British Journal of Dermatology (2024)

Abstract Background Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge. Objectives To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management. Methods In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM. Results We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample. Conclusions These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.
Reply to “European academy of allergy and clinical immunology, food allergy, anaphylaxis guidelines group. <scp>EAACI</scp> guidelines: Anaphylaxis (2021 update)”
Authors: Blanca Barroso, Alicia Gómez‐López, Diana Betancor, Marcela Valverde‐Monge, Joaquín Sastre
Journal: Allergy (2024)

Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020
Authors: Caroline E Gebhard, Claudia Sütsch, Pimrapat Gebert, Bianca Gysi, Susan Bengs, Atanas Todorov, Manja Deforth, Philipp K Buehler, Alexander Meisel, Reto A Schuepbach, Annelies S Zinkernagel, Silvio D Brugger, Claudio Acevedo, Dimitri Patriki, Benedikt Wiggli, Jürg H Beer, Andrée Friedl, Raphael Twerenbold, Gabriela M Kuster, Hans Pargger, Sarah Tschudin-Sutter, Joerg C Schefold, Thibaud Spinetti, Chiara Henze, Mina Pasqualini, Dominik F Sager, Lilian Mayrhofer, Mirjam Grieder, Janna Tontsch, Fabian C Franzeck, Pedro D Wendel Garcia, Daniel A Hofmaenner, Thomas Scheier, Jan Bartussek, Ahmed Haider, Muriel Grämer, Nidaa Mikail, Alexia Rossi, Núria Zellweger, Petra Opić, Angela Portmann, Roland von Känel, Aju P Pazhenkottil, Michael Messerli, Ronny R Buechel, Philipp A Kaufmann, Valerie Treyer, Martin Siegemund, Ulrike Held, Vera Regitz-Zagrosek, Catherine Gebhard
Journal: Eurosurveillance (2024)

Background Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim We assessed the impact of sex and gender on PASC in a Swiss population. Method Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection. Results Among those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p &lt; 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41–1.79; p &lt; 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03–1.07; p &lt; 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74–1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01–1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03–1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29–2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60–0.97; p = 0.030). Conclusion Specific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.
Early influenza vaccine effectiveness estimates using routinely collected data, Alberta, Canada, 2023/24 season
Authors: Christa Smolarchuk, Carla Ickert, Nathan Zelyas, Jeffrey C Kwong, Sarah A Buchan
Journal: Eurosurveillance (2024)

Timely and precise influenza vaccine effectiveness (VE) estimates are needed to guide public health messaging and impact vaccine uptake immediately. Using routinely collected laboratory, vaccination and health administrative data from Alberta, Canada, we estimated influenza VE against infection for the 2023/24 season on a near real-time basis, to late December, at 61% (95% CI: 58-64) against influenza A(H1N1), 49% (95% CI: 28-63) against influenza A(H3N2) and 75% (95% CI: 58-85) against influenza B.
The MRGPR family of receptors in immunity
Authors: Naina Gour, Xinzhong Dong
Journal: Immunity (2024)

The discovery of Mas-related G protein-coupled receptors (Mrgprs) has opened a compelling chapter in our understanding of immunity and sensory biology. This family of receptors, with their unique expression and diverse ligands, has emerged as key players in inflammatory states and hold the potential to alleviate human diseases. This review will focus on the members of this receptor family expressed on immune cells and how they govern immune and neuro-immune pathways underlying various physiological and pathological states. Immune cell-specific Mrgprs have been shown to control a variety of manifestations, including adverse drug reactions, inflammatory conditions, bacterial immunity, and the sensing of environmental exposures like allergens and irritants.
Intradermal delivery of the antiretroviral drugs cabotegravir and rilpivirine by dissolving microarray patches: Investigation of lymphatic uptake
Authors: Inken K. Ramöller, Fabiana Volpe-Zanutto, Lalitkumar K. Vora, Marco T.A. Abbate, Aaron R.J. Hutton, Peter E. McKenna, Ke Peng, Ismaiel A. Tekko, Akmal Sabri, Emma McAlister, Helen O. McCarthy, Alejandro J. Paredes, Ryan F. Donnelly
Journal: Journal of Controlled Release (2024)

The lymphatic system possesses the main viral replication sites in the body following viral infection. Unfortunately, current antiretroviral agents penetrate the lymph nodes insufficiently when administered orally and, therefore, cannot access the lymphatic system sufficiently to interrupt this viral replication. For this reason, novel drug delivery systems aimed at enhancing the lymphatic uptake of antiretroviral drugs are highly desirable. Dissolving polymeric microarray patches (MAPs) may help to target the lymph intradermally. MAPs are intradermal drug delivery systems used to deliver many types of compounds. The present work describes a novel work investigating the lymphatic uptake of two anti-HIV drugs: cabotegravir (CAB) and rilpivirine (RPV) when delivered intradermally using dissolving MAPs containing nanocrystals of both drugs. Maps were formulated using NCs obtained by solvent-free milling technique. The polymers used to prepare the NCs of both drugs were PVA 10 Kda and PVP 58 Kda. Both NCs were submitted to the lyophilization process and reconstituted with deionized water to form the first layer of drug casting. Backing layers were developed for short application times and effective skin deposition. In vivo biodistribution profiles of RPV and CAB after MAP skin application were investigated and compared with the commercial intramuscular injection using rats. After a single application of RPV MAPs, a higher concentration of RPV was delivered to the axillary lymph nodes (AL) (Cmax 2466 ng/g – Tmax 3 days) when compared with RPV IM injection (18 ng/g - Tmax 1 day), while CAB MAPs delivered slightly lower amounts of drug to the AL (5808 ng/g in 3 days) when compared with CAB IM injection (9225 ng/g in 10 days). However, CAB MAPs delivered 7726 ng/g (Tmax 7 days) to the external lumbar lymph nodes, which was statistically equivalent to IM delivery (Cmax 8282 ng/g - Tmax 7 days). This work provides strong evidence that MAPs were able to enhance the delivery of CAB and RPV to the lymphatic system compared to the IM delivery route.
Anorectal melanoma presenting as a polypoid lesion
Authors: Qi Luo, Liansong Ye, Meiting Liang, Tingfa Peng, Bing Hu, Yi Mou
Journal: Endoscopy (2024)

A 57-year-old woman presented with intermittent painless rectal bleeding for 1 year. Colonoscopy showed a polypoid lesion 2 cm from the anus ([Fig. 1] a). Narrow-band imaging (NBI) revealed the presence of turbulent microvasculature in the surface of the lesion ([Fig. 1] b). Enhanced computed tomography revealed that the rectum was of uneven thickness and showed local enhancement; there were no enlarged lymph nodes.
The definition of treatment resistance in anxiety disorders: a Delphi method‐based consensus guideline
Authors: Katharina Domschke, Patrik D. Seuling, Miriam A. Schiele, Borwin Bandelow, Neeltje M. Batelaan, Wicher A. Bokma, Igor Branchi, Karl Broich, Julius Burkauskas, Simon J.C. Davies, Bernardo Dell'Osso, Harry Fagan, Naomi A. Fineberg, Toshi A. Furukawa, Stefan G. Hofmann, Sean Hood, Nathan T.M. Huneke, Milan Latas, Nicky Lidbetter, Vasilios Masdrakis, R. Hamish McAllister‐Williams, Antonio E. Nardi, Stefano Pallanti, Brenda W.J.H. Penninx, Giampaolo Perna, Steve Pilling, Stefano Pini, Andreas Reif, Soraya Seedat, Gemma Simons, Shrikant Srivastava, Vesta Steibliene˙, Dan J. Stein, Murray B. Stein, Michael van Ameringen, Anton J.L.M. van Balkom, Nic van der Wee, Peter Zwanzger, David S. Baldwin
Journal: World Psychiatry (2024)

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.
Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex
Authors: Chen Xu, Ge Zhang, Xinjian Wang, Xiaozhi Huang, Jiayin Zhang, Shuxian Han, Jinxi Wang, Duane D. Hall, Ruoqing Xu, Feng He, Xing Chang, Fudi Wang, Wenjun Xie, Zhichao Wu, Long-Sheng Song, Peidong Han
Journal: Circulation (2024)

Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear.
Measuring Progress in Precision Oncology
Authors: Peter Horak, Stefan Fröhling
Journal: Cancer Discovery (2024)

Summary: In this issue of Cancer Discovery, Suehnholz and colleagues describe their efforts to quantify the gradual yet steady progress of precision oncology by surveying the regulatory approvals of targeted cancer therapies, and thus the actionability of corresponding molecular alterations in clinical practice, over more than 20 years. Their work also suggests a relationship between the discovery of candidate therapeutic targets through comprehensive tumor profiling and molecularly guided cancer drug development. See related article by Suehnholz et al., p. 49 (5).
Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy
Authors: Gengshen Yin, Liyuan Liu, Ting Yu, Lixiang Yu, Man Feng, Chengjun Zhou, Xiaoying Wang, Guoxin Teng, Zhongbing Ma, Wenzhong Zhou, Chunmiao Ye, Jialin Zhang, Changhua Ji, Linfeng Zhao, Peng Zhou, Yaxun Guo, Xingchen Meng, Qinye Fu, Qiang Zhang, Liang Li, Fei Zhou, Chao Zheng, Yujuan Xiang, Mingming Guo, Yongjiu Wang, Fei Wang, Shuya Huang, Zhigang Yu
Journal: Genome Medicine (2024)

Abstract Background Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. Methods We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. Results The most frequently altered genes were TP53 , TTN , and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C &gt; A transversion mutations in post-treatment tumors ( P = 0.020). NAC significantly decreased the mutation rate ( P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C &gt; T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3 ) and a deleted region at 3p13 (harboring FOXP1 ) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C &gt; T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. Conclusions Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers ( CDKAL1 P409L , ADGRA2 and ADRB3 ) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.
Stemming the tide: the challenges that must be overcome to reverse the great resignation of healthcare staff
Authors: Lucina Rolewicz, Rachel Hutchings, William Palmer, Janet Alexis A. De los Santos
Journal: BMJ (2024)

Global shortages of healthcare staff have been reported for a long time and are a core issue affecting the timely delivery of high quality care.According to the World Health Organisation, there could be a global shortage of 10 million healthcare workers by 2030, highlighting the scale of the staffing challenge. 1educing the demand for healthcare overall, including through the development of coherent public health strategies and improving efficiency in the system, can help limit the impact of staff shortages.But the retention of staff is vital to tackle the backlog of care and manage rising global demand for healthcare. 2 Two recent reports-one from the Institute for Government and one from Women in Global Health-have highlighted the magnitude of the challenge to retain staff and the reasons for poor staff retention, both in UK public services and in healthcare systems around the world. 3 4Because different staff groups working in different regions and countries each have unique sets of challenges, making generalisations about the findings is difficult, but there are some broad and widely reported problems that the global workforce faces.Some of these may be partly due to the shared experience of working through the covid-19 pandemic.
If we build it together, will they use it? A mixed-methods study evaluating the implementation of Prep-to-Play PRO: an injury prevention programme for women’s elite Australian Football
Authors: Andrea M Bruder, Brooke E Patterson, Kay M Crossley, Andrea B Mosler, Melissa J Haberfield, Martin Hägglund, Adam G Culvenor, Sallie M Cowan, Alex Donaldson
Journal: British Journal of Sports Medicine (2024)

Objectives We evaluated the implementation of Prep-to-Play PRO, an injury prevention programme for women’s elite Australian Football League (AFLW). Methods The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) of Prep-to-Play PRO were assessed based on the proportion of AFLW players and/or staff who: were aware of the programme (R), believed it may reduce anterior cruciate ligament injury (E), attempted to implement any/all programme components (A), implemented all intended components as practically as possible (I) and intended future programme implementation (M). Quantitative and qualitative data were triangulated to assess 58 RE-AIM items (evidence of yes/no/unsure/no evidence) and the 5 RE-AIM dimensions (fully achieved=evidence of yes on &gt;50% dimension items, partially achieved=50% of items evidence of yes and 50% unsure or 50% mix of unsure and unanswered, or not met=evidence of yes on &lt;50% dimension items). Results Multiple sources including AFLW training observations (n=7 total), post-implementation surveys (141 players, 25 staff), semistructured interviews (19 players, 13 staff) and internal programme records (9 staff) contributed to the RE-AIM assessment. After the 2019 season, 8 of 10 (80%) AFLW clubs fully met all five RE-AIM dimensions. All 10 clubs participating in the AFLW fully achieved the reach (R) dimension. One club partially achieved the implementation (I) dimension, and one club partially achieved the effectiveness (E) and adoption (A) dimensions. Conclusion The Prep-to-Play PRO injury prevention programme for the AFLW achieved high implementation, possibly due to the programme’s deliberately flexible approach coupled with our pragmatic definition of implementation. Engaging key stakeholders at multiple ecological levels (organisation, coaches, athletes) throughout programme development and implementation likely enhanced programme implementation.
Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab
Authors: Matthew I. Milowsky, Peter H. O'Donnell, Christopher J. Hoimes, Daniel P. Petrylak, Thomas W. Flaig, Helen H. Moon, Terence W. Friedlander, Nataliya Mar, Rana R. McKay, Sandy Srinivas, Gwenaelle Gravis, Chethan Ramamurthy, Manojkumar Bupathi, Sergio Bracarda, Phoebe Wright, Zsolt Hepp, Anne-Sophie Carret, Yao Yu, Ryan Dillon, Ritesh Kataria, Jennifer L. Beaumont, Intan Purnajo, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2024)

Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K.
MOF@COF Nanocapsules Enhance Soft Tissue Sarcoma Treatment: Synergistic Effects of Photodynamic Therapy and PARP Inhibition on Tumor Growth Suppression and Immune Response Activation
Authors: Yi Tai, Zhihao Chen, Tianqi Luo, Bingling Luo, Chuangzhong Deng, Zhenhai Lu, Shijun Wen, Jin Wang
Journal: Advanced Healthcare Materials (2024)

Soft tissue sarcomas (STS) are highly malignant tumors with limited treatment options owing to their heterogeneity and resistance to conventional therapies. Photodynamic therapy (PDT) and poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown potential for STS treatment, with PDT being effective for sarcomas located on the extremities and body surface and PARPi targeting defects in homologous recombination repair. To address the limitations of PDT and harness the potential of PARPi, herein, a novel therapeutic approach for STS treatment combining nanocapsules bearing integrated metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), i.e., MOF@COF, with PDT and PARPi is proposed. Nanocapsules are designed, referred to as ZTN@COF@poloxamer, which contain a Zr-based MOF and tetrakis (4-carbethoxyphenyl) porphyrin as a photosensitizer, are coated with a COF to improve the sensitizing properties, and are loaded with niraparib to inhibit DNA repair. Experiments demonstrate that this new nanocapsules treatment significantly inhibits STS growth, promotes tumor cell apoptosis, exhibits high antitumor activity with minimal side effects, activates the immune response of the tumor, and inhibits lung metastasis in vivo. Therefore, MOF@COF nanocapsules combined with PARPi offer a promising approach for STS treatment, with the potential to enhance the efficacy of PDT and prevent tumor recurrence.
The sense of antisense therapies in ALS
Authors: Sien H. Van Daele, Pegah Masrori, Philip Van Damme, Ludo Van Den Bosch
Journal: Trends in Molecular Medicine (2024)

Treatment of patients with amyotrophic lateral sclerosis (ALS) has entered a new era now that encouraging results about antisense oligonucleotides (ASOs) are becoming available and a first ASO therapy for ALS has been approved by the FDA. Moreover, there is hope not only that ALS can be stopped but also that symptoms can be reversed. Until now, degrading ASOs seemed to be successful mostly for rarer forms of familial ALS. However, the first attempts to correct mis-splicing events in sporadic ALS are underway, as well as a clinical trial examining interference with a genetic modifier. In this review, we discuss the current status of using ASOs in ALS and the possibilities and pitfalls of this therapeutic strategy.