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Objective: To assess the test-retest reliability, internal consistency, and construct validity of the 9-item Tampa Scale for Kinesiophobia in patients with chronic low back pain., Design: Questionnaire validation study., Setting: Study was conducted in an online environment., Participants: We included people aged 18 to 50 years with self-reported low back pain lasting > three months and assessed the Pain-Related Catastrophizing Thoughts Scale and the 9-item Tampa Scale for Kinesiophobia., Main Measures: We used intraclass correlation coefficient, standard error of measurement, minimum detectable change, and Cronbach's alpha to assess the reliability and internal consistency of the 9-item Tampa Scale for Kinesiophobia. We tested correlations between the domains of the 9-item Tampa Scale for Kinesiophobia and the other variables to assess construct validity., Results: A total of 174 participants with chronic low back pain were included in the analysis. No ceiling or floor effect was found. In terms of construct validity, there was a positive correlation between the domains of the 9-item Tampa Scale for Kinesiophobia and the other variables. In the reliability analysis, there was adequate test-retest reliability of the two domains of the 9-item Tampa Scale for Kinesiophobia: intraclass correlation coefficient = 0.99, standard error of measurement = 3.4%, and minimum detectable change = 9.6% for the activity avoidance domain; and intraclass correlation coefficient = 0.99, standard error of measurement = 3.5%, and minimum detectable change = 9.9% for the somatic focus domain. There was acceptable internal consistency (Cronbach's alpha ≥ 0.68) for both domains., Conclusion: The 9-item Tampa Scale for Kinesiophobia has adequate measurement properties in patients with chronic low back pain., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Acute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP., Methods: Liver-targeted lipid nanoparticles (LNP)-mRNA formulations encoding FGF21, APOA1, and a chimeric APOA1-FGF21, were first tested for protein expression and bioavailability in vitro and in mice fed a high-fat diet. Efficacy studies were performed in the caerulein-induced AP (Cer-AP) model, and a new AP model combining ethanol feeding with ethanol binge plus palmitoleic acid administration, the EtOH/POA-AP model. A single dose of the APOA1, FGF21, and APOA1-FGF21 LNP-mRNAs formulations was administered in both models. Serum levels of pancreatic lipase (LIPC), amylase (AMYL), and aspartate aminotransferase (AST), along with pancreatic tissue analyses using two histopathological scores were performed to evaluate treatment effects., Results: In vitro studies demonstrated the translation and secretion of APOA1, FGF21, and APOA1-FGF21 proteins encoded by the LNP-mRNAs. In vivo, LNP-mRNA administration increased serum levels of the respective proteins in metabolically impaired (i.e. high fat diet-fed) mice. In the Cer-AP model, serum markers of pancreatic injury were similarly reduced when mice were treated with APOA1, FGF21, and APOA1-FGF21 LNP-mRNA, and this effect was also observed in the histopathological analyses. The EtOH/POA-AP model was more aggressive than the Cer-AP model. FGF21 and APOA1-FGF21 LNP-mRNAs were protective according to LIPC and AMYL serum levels, while APOA1 LNP-mRNA had little effect. On the other hand, histological improvements were more evident in mice receiving APOA1 LNP-mRNA. In the EtOH/POA-AP model, FGF21 and APOA1-FGF21 LNP-mRNAs reduced serum AST levels, indicating hepatoprotective activity., Discussion: This proof-of-concept study demonstrates the potential of mRNA-based therapies delivering FGF21 and APOA1 in experimental AP. While individual treatments effectively reduced pancreatic injury, the APOA1-FGF21 fusion molecule did not exhibit superior activity. Liver-targeted LNP-mRNA administration may offer a promising approach for treating AP, leveraging endogenous production pathways for therapeutic proteins. Further research is warranted to elucidate the mechanisms underlying their therapeutic efficacy and optimize treatment regimens for clinical translation., Competing Interests: Declarations. Ethics approval and consent to participate: The study received approval from the Ethics Committee for Animal Experimentation of the University of Navarra (protocol #065 − 22). Informed consent: Written informed consent was not applicable. Conflict of interest: Anne-Renee Graham holds stock in and is an employee of Moderna, Inc. The rest of the authors have no conflicts of interest to declare., (© 2025. The Author(s).)

Background: Timely palliative and hospice care, along with advanced care planning, can reduce avoidable high-intensity care and improve quality of life at the end of life (EoL)., Objective: We examined patterns of care at EoL and evaluated predictors of high-intensity care at EoL among adults aged 18-64 with cancer., Methods: Using data from the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database, we examined 1359 patients diagnosed with cancer in 2010-2019, who died of cancer between 2017 and 2019 at 64 years and younger, and who were enrolled in Medicaid or private health insurance in last 30 days before death. We used composite measures for high-intensity and recommended EoL care using claims-based indicators in the last 30 days before death. Multivariable logistic regression was used to examine predictors associated with high-intensity EoL care., Results: About 70.3% of young and middle-aged Hispanic cancer patients received high-intensity EoL care, whereas only 20.6% received recommended EoL care. Patients without recommended EoL care were more likely to receive high-intensity EoL care (aOR=4.23; 95% CI=3.18-5.61). High-intensity EoL care was more likely in female patients (aOR=1.43; 95% CI=1.11-1.85) and patients with hematologic cancers (aOR=1.91; 95% CI=1.13-3.20) and less likely in patients who survived >12 months after cancer diagnosis (aOR=0.55; 95% CI=0.43-0.71)., Conclusions: A high proportion of Hispanic adults with cancer in Puerto Rico receive high-intensity EoL care and have unmet needs at EoL. Tailored interventions can reduce high-intensity EoL care and increase recommended EoL care. Recommended EoL care can ease pain, reduce distress, honor personal preferences, and cut unnecessary medical costs., Competing Interests: The authors declare no conflict of interest.

Objective: Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors., Design: We replicated AIP in non-human primates (NHPs) through selective knockdown of the hepatic PBGD gene and evaluated the safety and therapeutic efficacy of human PBGD (hPBGD) mRNA rescue., Results: Intrahepatic administration of a recombinant adeno-associated viral vector containing short hairpin RNA against endogenous PBGD mRNA resulted in sustained PBGD activity inhibition in liver tissue for up to 7 months postinjection. The administration of porphyrinogenic drugs to NHPs induced hepatic heme synthesis, elevated urinary porphyrin precursors and reproduced acute attack symptoms in patients with AIP, including pain, motor disturbances and increased brain GABAergic activity. The model also recapitulated functional anomalies associated with AIP, such as reduced brain perfusion and cerebral glucose uptake, disturbances in hepatic TCA cycle, one-carbon metabolism, drug biotransformation, lipidomic profile and abnormal mitochondrial respiratory chain activity. Additionally, repeated systemic administrations of hPBGD mRNA in this AIP NHP model restored hepatic PBGD levels and activity, providing successful protection against acute attacks, metabolic changes in the liver and CNS disturbances. This approach demonstrated better efficacy than the current standards of care for AIP., Conclusion: This novel model significantly expands our understanding of AIP at the molecular, biochemical and clinical levels and confirms the safety and translatability of multiple systemic administration of hPBGD mRNA as a potential aetiological AIP treatment., Competing Interests: Competing interests: LJ and PGVM are employees of Moderna Inc. focusing on the development of therapeutic approaches for rare diseases. MAA is Editor of Gut Journal. The rest of the authors have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options and a poor prognosis. The critical role of epigenetic alterations such as changes in DNA methylation, histones modifications, and chromatin remodeling, in pancreatic tumors progression is becoming increasingly recognized. Moreover, in PDAC these aberrant epigenetic mechanisms can also limit therapy efficacy. This study aimed to investigate the expression and prognostic significance of a key epigenetic complex encompassing DNA methyltransferase-1 (DNMT1), the histone methyltransferase G9a, and the scaffold protein UHRF1 in PDAC. We also evaluated the therapeutic potential of an innovative inhibitor targeting these epigenetic effectors., Methods: Immunohistochemical analysis of DNMT1, G9a, and UHRF1 expression was conducted in human PDAC tissue samples. Staining was semi-quantitatively scored, and overexpression was defined as moderate to strong positivity. The prognostic impact was assessed by correlating protein expression with patient survival. The antitumoral effects of the dual DNMT1-G9a inhibitor CM272 were tested in PDAC cell lines, followed by transcriptomic analyses to identify underlying mechanisms. The in vivo antitumoral efficacy of CM272 was evaluated in PDAC xenograft and syngeneic mouse models, both alone and in combination with anti-PD1 immunotherapy., Results: DNMT1, G9a, and UHRF1 were significantly overexpressed in PDAC cells and stroma compared to normal pancreatic tissues. Simultaneous overexpression of the three proteins was associated with significantly reduced survival in resected PDAC patients. CM272 exhibited potent antiproliferative activity in PDAC cell lines, inducing apoptosis and altering key metabolic and cell cycle-related genes. CM272 also enhanced chemotherapy sensitivity and significantly inhibited tumor growth in vivo without detectable toxicity. Combination of CM272 with anti-PD1 therapy further improved antitumor responses and immune cell infiltration, particularly CD4 + and CD8 + T cells., Conclusions: The combined overexpression of DNMT1, G9a, and UHRF1 in PDAC is a strong predictor of poor prognosis. CM272, by targeting this epigenetic complex, shows promising therapeutic potential by inducing apoptosis, reprogramming metabolic pathways, and enhancing immune responses. The combination of CM272 with immunotherapy offers a novel, effective treatment strategy for PDAC., Competing Interests: Declarations. Ethics approval and consent to participate: The collection of PDAC patient samples was performed at two different research institutions while adhering to ethical guidelines and informed consent procedures. The study protocol was reviewed and approved by the local Ethical Committee of the University Hospital of Modena (Comitato Etico dell'Area Vasta Emilia Nord- Protocol Number: 0013043/19—Pratica 299/2019/OSS/AOUMO) and the Clinical Research Ethical Committee of Navarra (Pyto2015/120). All patients provided written informed consent. All animal procedures involving mice were performed in compliance with regulations concerning animals used in scientific research. The animal procedures in the VHIO were approved by the institution's Ethical Committee and the Catalan Regional Government., while the CIMA-University of Navarra approved the project under project approval #R-CP001-15GN. Consent for publication: All authors read this manuscript and approve for publication. Competing interests: The authors declare that they have no competing interest., (© 2025. The Author(s).)

Background: Hepatocellular carcinoma (HCC) genetic/transcriptomic signatures have been widely described. However, its proteomic characterization is incomplete. We performed non-targeted quantitative proteomics of HCC samples and explored its clinical, functional, and molecular consequences., Methods: Non-targeted quantitative proteomics were performed on cytosolic and nuclear fractions of liver samples [HCC vs. non-tumour adjacent tissue (NTAT), n = 42 patients]. Changes were confirmed in 7 in silico HCC cohorts. Functional and molecular implications were evaluated on HCC-derived cell lines after silencing/overexpressing VARS1 and/or MAGI1. VARS1-overexpressing Hep3B cells were used for in vivo studies [Extreme Limiting Dilution Assay (ELDA) and orthotopic tumour formation]. Quantitative proteomics were performed on VARS1-overexpressing HCC cell lines., Results: Quantitative proteomics revealed the dysregulation of the cytosolic and nuclear proteomes in HCC, and defined two proteomic HCC subgroups, the most aggressive associated to the dysregulation of the aminoacyl-tRNA synthetases (ARSs). ARSs dysregulation was corroborated in in silico HCC cohorts and associated to poor prognosis. Patients with ARSs upregulation had genomic/transcriptomic characteristics of the proliferative HCC. Valine tRNA-aminoacyl synthetase (VARS1) was the ARSs most consistently overexpressed and associated to aggressiveness. VARS1 modulation (silencing/overexpression) altered tumour establishment-associated parameters in vitro and/or in vivo. Quantitative proteomics on cells overexpressing VARS1 and rescue experiments identified the downregulation of MAGI1, a tumour suppressor in HCC, as a mediator of VARS1 function., Conclusions: Quantitative proteomics defines two prognosis-related proteomic HCC subgroups. ARSs machinery is dysregulated in the aggressive subgroup, bearing potential as prognostic biomarkers. VARS1 promotes aggressiveness through the modulation of MAGI1, representing a novel targetable vulnerability in HCC., Competing Interests: Declarations. Ethics approval and consent to participate: The Reina Sofia University Hospital Ethics Committee approved the protocol for this study, in agreement to institutional and Good Clinical Practice guidelines (Protocol numbers PI20/01301 and PI23/00652) and the declaration of Helsinki. Informed consent was obtained from all patients or their relatives. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: To develop the Dysmenorrhea-related Impact on Functioning Scale (DIFS) to assess the impact of dysmenorrhea on functioning in cisgender women and transgender men and to evaluate its measurement properties., Methods: Mixed and online design study conducted with adolescents and adult cisgender women and transgender men with dysmenorrhea. We developed the DIFS based on the International Classification of Functioning, Disability, and Health. Content validity was assessed with experts and people with dysmenorrhea. Item Response Theory developed the DIFS total score. Structural validity was assessed by exploratory and confirmatory factor analysis and internal consistency by Cronbach's α and McDonald's Ω. Construct validity and test-retest reliability were assessed by correlation between DIFS and World Health Organization Disability Assessment Schedule and intraclass correlation coefficient, respectively. Measurement error was also assessed., Results: A total of 3335 people participated in the study. The DIFS is a 15-item instrument divided into "Bodily Functions" and "Daily Activities and Social Participation" sections and "Functioning" as a general factor. Internal consistency (α and Ω > 0.7) and test-retest reliability (intraclass correlation coefficient > 0.9) were adequate. No systematic error was found. Correlation was positive and strong between World Health Organization Disability Assessment Schedule and "Functioning" (r = 0.62, P ≤ .05). For the DIFS total score, higher scores indicate a greater impact of dysmenorrhea on functioning, and 44 points is the cutoff point for classifying the person with a significant impact of dysmenorrhea on functioning., Conclusions: DIFS showed excellent measurement properties for assessing the impact of dysmenorrhea on functioning for cisgender women and transgender men., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2025. Published by Elsevier Inc.)

Background: Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified., Objective: We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA., Design: We evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)-an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors-in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms., Results: PRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic CCA. PRMT5-targeting drugs markedly inhibited CCA cell proliferation, synergising with cisplatin and gemcitabine and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodelling and DNA repair, consistently inducing the formation of RNA loops and promoting DNA damage. Treatment with PRMT5-targeting drugs significantly restrained the growth of experimental CCA without adverse effects and concomitantly induced the recruitment of CD4 and CD8 T cells to shrinking tumourous lesions., Conclusion: PRMT5 and MEP50 are frequently upregulated in human CCA, and PRMT5-targeting drugs have significant antitumoural efficacy in clinically relevant CCA models. Our findings support the evaluation of PRMT5 inhibitors in clinical trials, including their combination with cytotoxic and immune therapies., Competing Interests: Competing interests: MAA is editor of Gut. All other authors have no conflict of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The aim of this study is to describe a protocol for evaluating the effects of transcutaneous electrical nerve stimulation (TENS) on pain following breast augmentation surgery. Fifty-four women will be randomly allocated into two groups: active TENS and placebo. Pain will be assessed at rest and during movement, before and immediately after TENS application. Secondary outcomes include pain one-hour post-treatment, respiratory muscle strength, patient satisfaction, and analgesic use in the first four hours post-surgery. The results of this clinical trial could enhance the management of post-operative pain in breast augmentation surgery using non-pharmacological interventions, potentially reducing costs and improving patient experience.Clinical Trial Registration: RBR-96h3k97.

Background: Dysmenorrhea, or menstrual pain, is a subjective experience, and can only be assessed by patient-reported outcomes. These instruments should be reliable, valid and responsive., Aim: To identify and critically appraise the available evidence for the measurement properties of specific patient-reported outcome measures used for dysmenorrhea., Methods: The PRISMA statement was used to report this systematic review. Databases searched were PubMed, SCOPUS, CINAHL, Web of Science, ScienceDirect and Google Scholar (April 2021; updated on February 2023). Original studies with primary data collection, with no restriction on language and publication date that reported psychometric properties of one or more dysmenorrhea-related patient-reported outcome measure. The literature searches, selection of studies, data extraction and assessment of the risk of bias were performed independently by two reviewers and followed the COSMIN guidelines., Results: Thirty studies were analysed in this review, and 19 patient-reported outcome measures were evaluated. The instruments varied in relation to the measured construct and measurement properties (validity, reliability and responsiveness). The methodological quality of the studies and the quality of evidence of the patient-reported outcome measures were variable. Among the 13 studies that reported the development of patient-reported outcome measures, most had inadequate methodological quality, and the overall rating was insufficient or inconsistent., Conclusions: The Dysmenorrhea Symptom Interference (DSI) scale was the only identified patient-reported outcome measure that has the potential to be recommended because of its sufficient rating combined with moderate quality of evidence for content validity. Future studies should further evaluate the measurement properties of the existing patient-reported outcome measures, or develop new patient-reported outcome measures following the COSMIN methodology., Patient or Public Contribution: Not applicable as this is a systematic review., Trial Registration: PROSPERO protocol: CRD42021244410. Registration on April 22, 2021., (© 2024 John Wiley & Sons Ltd.)

Aims: Drug export through ABC proteins hinders cancer response to chemotherapy. Here, we have evaluated the relevance of MRP3 (ABCC3) in cholangiocarcinoma (CCA) as a potential target to overcome drug resistance., Methods: Gene expression was analyzed in silico using the TCGA-CHOL database and experimentally (mRNA and protein) in resected CCA tumors. The effect of manipulating MRP3 function/expression was evaluated in vitro and in vivo., Results: High MRP3 expression at the plasma membrane of human CCA cells was found. MRP3 overexpression in HEK293T cells selectively impaired the cytotoxic effect of etoposide, cisplatin, SN-38, and mitoxantrone. Reduced MRP3 activity with shRNAs or pan-MRP blockers enhanced the sensitivity to these drugs. MRP3 interaction with natural and semisynthetic compounds (≈40,000) was evaluated by virtual drug screening and molecular docking. Two identified potential MRP3 inhibitors (EM-114, EM-188), and sorafenib impaired MRP3 transport activity and enhanced sensitivity of CCA cells to etoposide and cisplatin. The antitumor effect of cisplatin in the mouse xenograft model was enhanced by co-treatment with sorafenib, which was accompanied by a higher intratumor accumulation of cisplatin., Conclusions: Genetic and pharmacological MRP3 inhibition enhances the anti-CCA effect of several drugs, which constitutes a promising strategy to improve the response to chemotherapy in CCA patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jose J.G. Marin reports financial support was provided by Carlos III Health Institute. Jose J.G. Marin reports financial support was provided by Spanish Ministry of Science and Innovation. Jose J.G. Marin reports financial support was provided by Junta de Castilla y León, Consejería de Educación. Jose J.G. Marin reports financial support was provided by Spanish Association Against Cancer Scientific Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Caregiver health literacy (HL) in patients' transition from hospital to home care is an important factor for good results., Methods: This cross-sectional study included 89 patient-informal caregiver dyads in Brazil. Data were collected using a sociodemographic questionnaire and the European Health Literacy Survey Questionnaire short-short form. Data were analyzed using descriptive statistics, univariate analyses, and a binary logistic regression model., Results: The caregivers' average age was 48 ± 13.48 years, and 73.0% of them were female. It was found that 6.7% of the caregivers had inadequate HL, 61.8% had problematic HL, and 31.4% had sufficient HL. Being a healthcare professional was significantly associated with sufficient HL (P = 0.016). Furthermore, healthcare workers had more years of schooling than other caregivers (15.3 ± 4.6 vs. 11.2 ± 4.6; P = 0.013). For every 1-year increase in caregiver age, there was a decrease of 0.041 points on the European Health Literacy Survey Questionnaire short-short form. Being a healthcare professional, increased HL scores by 11.4%., Conclusions: Key findings showed that caregivers with higher HL were typically younger, male, better educated, and more likely to be healthcare professionals. These caregivers managed patients with lower dependence on daily activities, while those with lower HL, mainly females, cared for patients with higher dependence. The study highlights the need for targeted interventions and public policies to enhance HL among caregivers, particularly to improve outcomes for patients with complex needs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Metabolic dysfunction-associated steatohepatitis (MASH) represents a global health threat. MASH pathophysiology involves hepatic lipid accumulation and progression to severe conditions like cirrhosis and, eventually, hepatocellular carcinoma. Fibroblast growth factor (FGF)-19 has emerged as a key regulator of metabolism, offering potential therapeutic avenues for MASH and associated disorders. We evaluated the therapeutic potential of non-mitogenic (NM)-FGF19 mRNA formulated in liver-targeted lipid nanoparticles (NM-FGF19-mRNAs-LNPs) in C57BL/6NTac male mice with diet-induced obesity and MASH (DIO-MASH: 40% kcal fat, 20% kcal fructose, 2% cholesterol). After feeding this diet for 21 weeks, NM-FGF19-mRNAs-LNPs or control (C-mRNA-LNPs) were administered (0.5 mg/kg, i.v.) weekly for another six weeks, in which diet feeding continued. NM-FGF19-mRNAs-LNPs treatment in DIO-MASH mice resulted in reduced body weight, adipose tissue depots, and serum transaminases, along with improved insulin sensitivity. Histological analyses confirmed the reversal of MASH features, including steatosis reduction without worsening fibrosis. NM-FGF19-mRNAs-LNPs reduced total hepatic bile acids (BAs) and changed liver BA composition, markedly influencing cholesterol homeostasis and metabolic pathways as observed in transcriptomic analyses. Extrahepatic effects included the down-regulation of metabolic dysfunction-associated genes in adipose tissue. This study highlights the potential of NM-FGF19-mRNA-LNPs therapy for MASH, addressing both hepatic and systemic metabolic dysregulation. NM-FGF19-mRNA demonstrates efficacy in reducing liver steatosis, improving metabolic parameters, and modulating BA levels and composition. Given the central role played by BA in dietary fat absorption, this effect of NM-FGF19-mRNA may be mechanistically relevant. Our study underscores the high translational potential of mRNA-based therapies in addressing the multifaceted landscape of MASH and associated metabolic perturbations., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Rewiring of cellular metabolism is now fully recognized as a hallmark of cancer. Tumor cells reprogram metabolic pathways to meet the energetic and macromolecular demands to support unrestricted growth and survival under unfavorable conditions. It is becoming apparent that these adaptations underpin most of the traits that define a cancer cell's identity, including the ability to avoid immune surveillance, endure nutrient and oxygen restrictions, detach and migrate from their natural histological niche, and avert human-made aggressions (i.e., therapy). In a recent study, Benichou and collaborators identify carbohydrate-responsive element-binding protein (ChREBP), a master regulator of physiological glucose metabolism, as an oncogene in hepatocellular carcinoma (HCC) development. Upregulation of ChREBP expression results in a self-stimulatory loop interconnecting PI3K/AKT signaling and glucose metabolism to feed fatty acid and nucleotide synthesis supporting tumorigenesis. Importantly, pharmacological inhibition of ChREBP activity quells in vivo HCC tumor growth without causing systemic toxicity. This study identifies novel oncometabolic pathways and open up new avenues to improve the treatment of a deadly tumor., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Antonio Roberto Zamunér,1 Carolina Pieroni Andrade,2 Eduardo Aguilar Arca,3 Mariana Arias Avila41Departamento de Kinesiología, Universidad Católica del Maule, Talca, Maule, Chile; 2Secretaria de Saúde do Município de Guareí, Guareí, São Paulo, Brasil; 3Departamento de Fisioterapia, Universidade do Sagrado Coração, Bauru, São Paulo, Brasil; 4Departamento de Fisioterapia e Programa de Pós-Graduação em Fisioterapia, Universidade Federal de São Carlos, São Carlos, São Paulo, BrasilAbstract: Exercise-related interventions have been recommended as one of the main components in the management of fibromyalgia syndrome (FMS). Water therapy, which combines water’s physical properties and exercise benefits, has proven effective in improving the clinical symptoms of FMS, especially pain, considered the hallmark of this syndrome. However, to our knowledge, the mechanisms underlying water therapy effects on pain are still scarcely explored in the literature. Therefore, this narrative review aimed to present the current perspectives on water therapy and the physiological basis for the mechanisms supporting its use for pain management in patients with FMS. Furthermore, the effects of water therapy on the musculoskeletal, neuromuscular, cardiovascular, respiratory, and neuroendocrine systems and inflammation are also addressed. Taking into account the aspects reviewed herein, water therapy is recommended as a nonpharmacologic therapeutic approach in the management of FMS patients, improving pain, fatigue, and quality of life. Future studies should focus on clarifying whether mechanisms and long-lasting effects are superior to other types of nonpharmacological interventions, as well as the economic and societal impacts that this intervention may present.Keywords: hydrotherapy, exercise, pain management, chronic pain, physical therapy, aquatic therapy

Purpose: Menstrual characteristics can affect a woman's productivity at work and college, but studies in a general population of adult women are scarce. In addition, it is important to know which menstrual symptoms are most associated with presenteeism in women to promote specific health actions. The present study aimed to assess menstrual symptoms associated with presenteeism in adult women., Methods: Online cross-sectional study in which menstrual characteristics, including menstrual flow, age of menarche, menstrual pain and cycle duration were assessed by a self-report questionnaire. The menstrual pain intensity was assessed by Numerical Rating Scale, and the presenteeism, by the Stanford Presenteeism Scale-6 (SPS-6). Women were divided in two groups, with and without presenteeism, based on the SPS-6 cutoff point. Data were analyzed by binary logistic regression and presented as odds ratios (OR)., Results: Among the 430 women who participated in the study, 44.2% were classified as with presenteeism. Women with severe menstrual flow were more likely to have presenteeism (OR = 2.12) compared with women with mild and moderate menstrual flow. The higher menstrual pain intensity the higher the chances of a woman presenting with presenteeism (OR = 1.29)., Conclusions: These menstrual characteristics (intensity of menstrual flow and menstrual pain) seem to affect women's productivity at work and/or college, and should be assessed in research and clinical practice. Thus, public policies on women's health can be carried out based on these results., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Electron Spin Resonance (ESR) experiments in the filled Cei 1-xYbxFe4P12 (x ≲ 0.0023) skutterudite compounds of Th cubic symmetry (Im3) reveal the coexistence of two distinct Yb3+ sites with large difference in their site occupation, hyperfine interaction and temperature dependence of the ESR parameters. These results suggest a scenario where the oversized (Fe 2P3)4-cages of the Ce1-xYb xFe4P12 compounds are occupied with small number of on-center-Yb3+ ions and a distribution of highly occupied off-center-Yb3+ions, rattling at ∼1 GHz and above ∼20 GHz, respectively. © 2010 IOP Publishing Ltd.

Electron-spin-resonance (ESR) measurements performed on the filled skutterudite system Ce1-x Ybx Fe4 P12 (x≲0.003) unequivocally reveal the coexistence of two Yb3+ resonances associated with sites of considerably different occupations and temperature behaviors. Detailed analysis of the ESR data suggests a scenario where the fraction of oversized (Fe2 P3) 4 cages that host Yb ions are filled with a low occupation of on-center Yb3+ sites and a highly occupied T -dependent distribution of off-center Yb3+ sites. Analysis of the Y 171 b3+ (I=1/2) isotope hyperfine splittings reveal that these two sites are associated with a low (∼1 GHz) and a high (≲ 15 GHz) rattling frequency, respectively. Our findings introduce Yb3+ in Th symmetry systems and use the Yb3+ ESR as a sensitive microscopic probe to investigate the Yb3+ ions dynamics. © 2009 The American Physical Society.

Electron-spin-resonance (ESR) measurements performed on the filled skutterudite system Ce1-x Ybx Fe4 P12 (x≲0.003) unequivocally reveal the coexistence of two Yb3+ resonances associated with sites of considerably different occupations and temperature behaviors. Detailed analysis of the ESR data suggests a scenario where the fraction of oversized (Fe2 P3) 4 cages that host Yb ions are filled with a low occupation of on-center Yb3+ sites and a highly occupied T -dependent distribution of off-center Yb3+ sites. Analysis of the Y 171 b3+ (I=1/2) isotope hyperfine splittings reveal that these two sites are associated with a low (∼1 GHz) and a high (≲ 15 GHz) rattling frequency, respectively. Our findings introduce Yb3+ in Th symmetry systems and use the Yb3+ ESR as a sensitive microscopic probe to investigate the Yb3+ ions dynamics. © 2009 The American Physical Society.

Cholangiocarcinomas (CCAs) are a heterogeneous group of malignant tumors that originate from the biliary tract. They are usually diagnosed in advanced stages, leading to a dismal prognosis for affected patients. As CCA often arises as a sporadic cancer in individuals lacking specific risk factors or with heterogeneous backgrounds, and there are no defined high-risk groups, the implementation of effective surveillance programs for CCA is problematic. The identification and validation of new biomarkers useful for risk stratification, diagnosis, prognosis, and prediction of treatment response remains an unmet need for patients with CCA, even though numerous studies have been conducted lately to try to discover and validate CCA biomarkers. In this review, we overview the available information about the different types of biomarkers that have been investigated in recent years using minimally invasive biospecimens (blood, serum/plasma, bile, and urine) and their potential usefulness in diagnosis, prognosis, and risk stratification. It is widely accepted that early detection of CCA will impact patients' outcomes, by improving survival rates, quality of life, and the possibility of less invasive and/or curative treatments; however, challenges to its translation and clinical application for patients with CCA need to be resolved., Competing Interests: Disclosure Statement The authors declare the following competing financial interests: Y.H. served as a consultant on advisory boards from Helio Genomics, Espertiva Therapeutics, Roche Diagnostics, and Elevar Therapeutics; and is a shareholder of Alentis Therapeutics and Espervita Therapeutics. H.K. served as a consultant on advisory boards from Takeda and Bayer., (Copyright © 2024. Published by Elsevier Inc.)

Aim: This study aimed to evaluate adherence to an antibiotic prophylaxis protocol and its impact on incidence of surgical site infection (SSI)., Materials and Method: A prospective observational cohort study was conducted at a teaching hospital in São Paulo, Brazil, from September to November 2015. The population were adults who underwent surgery with surgical antibiotic prophylaxis. The main outcomes measured were incidence of SSI at 30-days postoperatively, protocol adherence and surgical wound complications. STROBE guidelines were followed., Results: Among the 527 participants recruited, a 30-day follow-up was completed by 78.7 % (n = 415). Within this cohort, 57.6 % were females aged over 60 years (36.4 %). The incidence of SSI stood at 9.4 % (n = 39), with dehiscence being the most prevalent complication at 64.1 % (n = 25), followed by increased exudate at 51.3 % (n = 20). Notably, full adherence to the antibiotic prophylaxis protocol was low at 1.7 % (n = 7). The study observed a 60 % increased risk of SSI for every protocol mistake made. Alarmingly, 17.8 % (n = 74) of participants received antibiotic treatment exceeding the stipulated protocol duration. The overall mortality rate stood at 13.5 % (n = 56), with 1 % (n = 4) of these deaths attributed to SSI., Conclusion: There is a pressing global necessity to enhance antibiotic management, as underscored by this study's revelation of low adherence to the antibiotic prophylaxis protocol. This lack of adherence correlated with a notable incidence of SSI and subsequent wound complications. Nearly 20 % of participants received prolonged antibiotic treatment. Adhering strictly to the protocol could substantially impact SSI-related outcomes and enhance global antibiotic management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To evaluate the effectiveness of photobiomodulation (PBM) in conjunction with an aerobic exercise program (AEP) on the level of pain and quality of life of women with fibromyalgia (FM)., Methods: A double-blinded randomized controlled trial in which 51 participants with FM were allocated into 4 groups: control group (CG) (n = 12); active PBM group (APG) (n = 12); AEP and placebo PBM group (EPPG) (n = 13); AEP and active PBM group (EAPG) (n = 14). AEP was performed on an ergometric bicycle; and a PBM (with an increase dosage regime) [20 J, 32 J and 40 J] was applied using a cluster device. Both interventions were performed twice a week for 12 weeks. A mixed generalized model analysis was performed, evaluating the time (initial and final) and group (EAPG, EPPG, APG and CG) interaction. All analyses were based on intent-to-treat for a significance level of p ≤ 0.05., Results: The intra-group analysis demonstrated that all treated groups presented a significant improvement in the level of pain and quality of life comparing the initial and final evaluation (p < 0.05). Values for SF-36 and 6-minute walk test increased significant in intragroup analysis for EPPG comparing the initial and final evaluation. No intergroup differences were observed., Conclusions: Both exercised and PBM irradiated volunteers present improvements in the variables analyzed. However, further studies should be performed, with other PBM parameters to determine the best regime of irradiation to optimize the positive effects of physical exercises in FM patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

In contrast to other types of cancers, there is no available efficient pharmacological treatment to improve the outcomes of patients suffering from major primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation is partly due to the existence in these tumors of many different and synergistic mechanisms of resistance, accounting for the lack of response of these patients, not only to classical chemotherapy but also to more modern pharmacological agents based on the inhibition of tyrosine kinase receptors (TKIs) and the stimulation of the immune response against the tumor using immune checkpoint inhibitors (ICIs). This review summarizes the efforts to develop strategies to overcome this severe limitation, including searching for novel drugs derived from synthetic, semisynthetic, or natural products with vectorial properties against therapeutic targets to increase drug uptake or reduce drug export from cancer cells. Besides, immunotherapy is a promising line of research that is already starting to be implemented in clinical practice. Although less successful than in other cancers, the foreseen future for this strategy in treating liver cancers is considerable. Similarly, the pharmacological inhibition of epigenetic targets is highly promising. Many novel "epidrugs," able to act on "writer," "reader," and "eraser" epigenetic players, are currently being evaluated in preclinical and clinical studies. Finally, gene therapy is a broad field of research in the fight against liver cancer chemoresistance, based on the impressive advances recently achieved in gene manipulation. In sum, although the present is still dismal, there is reason for hope in the non-too-distant future.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Whole-tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly available gene sets or gene signatures have been used to infer functional changes through gene set enrichment methods. However, metabolism-related gene signatures are poorly co-expressed when applied to a biological context. Here, we apply a simple method to infer highly consistent signatures using graph-based statistics. Using the Cancer Genome Atlas Liver Hepatocellular cohort (LIHC), we describe the main metabolic clusters and their relationship with commonly used molecular classes, and with the presence of TP53 or CTNNB1 driver mutations. We find similar results in our validation cohort, the LIRI-JP cohort. We describe how previously described metabolic subtypes could not have therapeutic relevance due to their overall downregulation when compared to non-tumoral liver, and identify N-glycan, mevalonate and sphingolipid biosynthetic pathways as the hallmark of the oncogenic shift of the use of acetyl-coenzyme A in HCC metabolism. Finally, using DepMap data, we demonstrate metabolic vulnerabilities in HCC cell lines., Competing Interests: The authors declare no conflicts of interest.

Aim: Different nonpharmacological strategies are adopted to decrease primary dysmenorrhea (PD)-related pain. The present study aimed to verify women's use of nonpharmacological methods for pain and compare them with evidence from the literature. Materials & methods: A two-step study was conducted, comprising an online survey with 9144 women to assess nonpharmacological strategies for relieving PD-related pain, and a literature review on PubMed of verify the evidence of nonpharmacological methods. Results: Many women reported using heat therapy (61.5%), tea (42.4%) and massage (30.9%) to alleviate menstrual pain. However, the literature on these methods is limited. Conclusion: Several nonpharmacological methods are used by women to relieve PD-related pain and studies with low bias risk are needed to prove their effectiveness.

Background and Aims: Liver regeneration is essential for the preservation of homeostasis and survival. Bile acids (BAs)-mediated signaling is necessary for liver regeneration, but BAs levels need to be carefully controlled to avoid hepatotoxicity. We studied the early response of the BAs-fibroblast growth factor 19 (FGF19) axis in healthy individuals undergoing hepatectomy for living donor liver transplant. We also evaluated BAs synthesis in mice upon partial hepatectomy (PH) and acute inflammation, focusing on the regulation of cytochrome-7A1 (CYP7A1), a key enzyme in BAs synthesis from cholesterol., Methods: Serum was obtained from twelve human liver donors. Mice underwent 2/3-PH or sham-operation. Acute inflammation was induced with bacterial lipopolysaccharide (LPS) in mice fed control or antoxidant-supplemented diets. BAs and 7α-hydroxy-4-cholesten-3-one (C4) levels were measured by HPLC-MS/MS; serum FGF19 by ELISA. Gene expression and protein levels were analyzed by RT-qPCR and western-blot., Results: Serum BAs levels increased after PH. In patients with more pronounced hypercholanemia, FGF19 concentrations transiently rose, while C4 levels (a readout of CYP7A1 activity) dropped 2 h post-resection in all cases. Serum BAs and C4 followed the same pattern in mice 1 h after PH, but C4 levels also dropped in sham-operated and LPS-treated animals, without marked changes in CYP7A1 protein levels. LPS-induced serum C4 decline was attenuated in mice fed an antioxidant-supplemented diet., Conclusions: In human liver regeneration FGF19 upregulation may constitute a protective response from BAs excess during liver regeneration. Our findings suggest the existence of post-translational mechanisms regulating CYP7A1 activity, and therefore BAs synthesis, independent from CYP7A1/Cyp7a1 gene transcription., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Cupping therapy is a widely used technique in Brazilian physical therapy for the treatment of musculoskeletal disorders. However, there is limited scientific evidence to support its effectiveness., Objective: To investigate the profile, training, clinical practice, and scientific updates of Brazilian Physical Therapists who use cupping therapy as a therapeutic resource for musculoskeletal disorders., Methods: A cross-sectional study was conducted through an online questionnaire, including 646 Physical Therapists who use cupping therapy in their practice. All data were analysed descriptively., Results: Cupping therapy is a technique that has been widely adopted in clinical practice by Physical Therapists, particularly among young, female professionals who have recently graduated from private universities. The primary reason for interest in this technique among these Physical Therapists is the high demand from patients. Additionally, it is often used in conjunction with other manual therapeutic techniques. They identified easy access, low cost, and ease of use as the key factors that make cupping therapy an attractive option. However, a lack of high-quality scientific evidence, as described in the literature, was identified as a major barrier to its use., Conclusion: The Physical Therapists included in this study use cupping therapy in their clinical practice, relying heavily on their own experience and the preferences of their patients, rather than utilizing the third pillar of evidence-based practice, which is to rely on the best available evidence. This study suggests that these Physical Therapists are currently implementing a technique without current scientific recommendations for its use in the treatment of musculoskeletal disorders., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study aims to transpose the printed Brazilian Children's Anxiety Questionnaire (CAQ BR) into a 2D digital format, validate it with nurses and hospitalized children, and analyze the association between the printed and 2D digital format versions., Design and Method: This is a descriptive and multicentric study, conducted from 2021 to 2022 on working in pediatric care at two hospitals in Brazil. The nurses analyzed the printed and digital instruments and subsequently applied them to a child and proposed suggestions. A cutoff score of 0.80 on the content validity index was used; items that scored an average lower than the CVI in the study were adequate. Eighty children responded to the questionnaires sequentially according to the randomization table. A 90% agreement rate was used., Results: The digital instrument was validated in content by 51 experts, with a CVI of 0.95. Face validation data for 80 children (mean age = 7.9 years) shows a 90% agreement rate. The intraclass correlation index for the general score was 0.87 and 95% CI (0.79-0.91), which shows good stability of the children's responses in both questionnaires. In addition, 59% (n = 47) of the children reported a preference for the digital questionnaire., Conclusions: The digital CAQ BR can be used as an audiovisual instrument by nurses when implementing the systematization of nursing care in pediatrics., Practical Implications: The digital 2D version was successfully applied and can be used in hospitals to measure children's self-reported anxiety., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The Dysmenorrhea Symptom Interference (DSI) scale is a reliable, valid, and responsive tool to assess the interference of menstrual pain in the physical, mental, and social activities of women., Objective: To translate and cross-culturally adapt the DSI scale into Brazilian-Portuguese (DSI-BrPt) and investigate the measurement properties of this version in on- and off-menses versions., Methods: The original (United States) scale was translated and culturally adapted following existing guidelines. Measurement properties of the DSI-BrPt were investigated in 1387 women with dysmenorrhea. Reliability was analyzed via intraclass correlation coefficients (ICC) and test-retest reliability. Furthermore, structural validity, internal consistency (Cronbach's alpha), cross-cultural validity, construct validity (correlation with WHODAS 2.0 and SPS-6 scores questionnaires), and floor and ceiling effects were determined., Results: No significant adaptations were needed during the translation process of the DSI-BrPt. The values of Cronbach's α were adequate (α ≥0.87) for the unidimensional scale. The test-retest reliability was considered adequate (ICC >0.78) and there was no systematic error for both on-menses and off-menses versions. Moreover, the DSI had a positive and strong correlation with WHODAS 2.0. There were no floor and ceiling effects neither for the total sample, nor among off-menses, or on-menses women., Conclusion: The DSI-BrPt scale has been translated and cross-culturally adapted successfully. The DSI-BrPt scale presented adequate measurement properties. The scale is valid and reliable, and, therefore, an adequate tool for monitoring dysmenorrhea symptoms in Brazilian women during and between menses., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Holding and restraining children during non-urgent clinical procedures continues to be surrounded by uncertainty and mired in controversy. This review aimed to locate, appraise and map the evidence related to health professionals reported and observed practice of holding and restraining children, from birth to 16 years, for clinical procedures. This scoping review, conducted in April 2022, was based on the Joanna Briggs Institute protocol. Screening and full text review resulted in the inclusion of 30 papers. In total, 14 different terms were used to refer to the act of holding or restraining a child for a procedure, in many papers the action of holding was not defined. Professionals report the main factors influencing their decisions to use restraint and/or holding were the age of a child, with younger children being restrained or held most frequently; a child's behaviour; and concerns around a child's safety. Professionals also report that they can perceive pressure from parent/carers to hold or restrain their child and describe how holding practices can be influenced by service and organisational pressures. Health professionals, mainly nurses, continue to report ethical and moral tensions linked to their involvement in the restraint or holding of a child against their will for a clinical procedure. Evidence indicates a need to move practice forward as the issues identified in paediatric practice are long-standing and historical., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of the present study was to investigate the effects of adding Pain Neuroscience Education (PNE) to an aquatic therapy protocol on pain, fibromyalgia (FMS) impact, quality of life and sleep., Materials and Methods: Seventy-five women were randomly allocated into two groups: aquatic exercises (AEG, n  = 36) and aquatic exercises + PNE (PNG, n  = 39). The primary outcome was pain, and the secondary outcomes were FMS impact, quality of life, sleep and pain sensitivity (pressure pain thresholds - PPTs). Participants performed 45-min sessions of aquatic exercises, twice a week, for 12 weeks. PNG also received 4 PNE sessions during this period. Participants were assessed four times: initial (before treatment), after 6 weeks (intermediate) and 12 weeks (final) of treatment and after 12 weeks after the end of treatment (follow-up)., Results: Both groups improved pain after treatment, with no difference between them ( p  > 0.05, partial ƞ 2 0.10). FMS impact and PPTs improved after treatment with no difference between groups, and sleep did not change. Quality of life improved several domains for both groups, with slightly better results for the PNG, with low effect sizes between groups., Conclusions: The present results show that the addition of PNE to an aquatic exercise intervention did not provide larger effects than aquatic exercises alone for people with FMS concerning pain intensity, but provided benefit for health-related quality of life for this population., Trial Registration: ClinicalTrials.gov (NCT03073642, version 2, April 1 st , 2019)., Perspective: The addition of 4 Pain Neuroscience Education sessions to an aquatic exercises protocol did not add benefits for women with fibromyalgia syndrome on pain, fibromyalgia impact, and sleep, but improved quality of life and pain sensitivity.IMPLICATIONS FOR REHABILITATIONAquatic exercises are commonly prescribed, but patient education is crucial for the treatment.The addition of Pain Neuroscience Education to an aquatic exercises protocol did not add benefits for women with fibromyalgia syndrome.The positive changes on quality of life and pain sensitivity that this combination led to had small effect sizes and did not achieve minimal important clinical difference.

Background: Multiple myeloma (MM) survival has increased during the last decades due to the introduction of new therapies. We investigated the intersectionality among age, sex, and race/ethnicity to better understand the pattern of MM incidence, mortality, and survival., Methods: Puerto Rico (PR) Central Cancer Registry and the United States of America (US) Surveillance, Epidemiology, and End Results (SEER) Program databases were used. We analyzed MM incidence and mortality trends from 2001 to 2019 using Joinpoint regression models to calculate annual percent change (APC). Age-standardized rate ratios (SRR) for incidence and mortality were used to compare PR with US SEER racial/ethnic groups during 2015-2019. Five-year survival analyses were also performed stratified by age and sex., Results: Regardless of age and race/ethnicity, males had higher MM incidence and mortality rates than females. PR had a higher increase in incidence rates of MM than other ethnic groups, regardless of sex and age (PR APC = 4.3 among males <65, 3.1 among males ≥65, 6.3 among females <65, and 2.6 among females ≥65 years old). No significant change in mortality APCs (p > 0.05) was observed in PR when stratified by age or sex while other groups showed a decrease. Among males < 65 years, PR had significantly higher incidence rates than non-Hispanic Whites (NHW), and US Hispanics (USH). However, among both males and females ≥ 65 years, PR had significantly lower MM mortality rates than NHW, non-Hispanic Blacks (NHB), USH, and US Overall. In terms of survival, PR showed the lowest 5-year overall survival among males < 65 years (54.6%, 95% CI: 47.2-61.5) and males ≥ 65 years (34.5%, 95% CI: 29.2-39.9) but not among females., Conclusion: The incidence of MM in PR increased significantly over the study period, particularly among younger women. Despite the introduction of new therapies, mortality rates in PR have remained stable while other ethnic groups show significant decreases among all intersections of sex and age., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests related to the content of this work. Dr. Ortiz-Ortiz & Dr. Tortolero-Luna reported receiving grants from the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) during the conduct of the study; and grants from Abbvie Corp. and Merck Co. outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Dysmenorrhea is the pain related to menstruation; to screen for the symptoms, a working ability, location, intensity of days of pain, and dysmenorrhea (WaLIDD) score was created. The purpose of this work was to culturally adapt and assess the measurement properties of the WaLIDD score for dysmenorrhea in Brazilian women., Methods: In this cross-sectional online study, we evaluated women with and without dysmenorrhea. Criterion validity and construct validity were assessed, respectively, by the Receiver Operator Characteristic (ROC) curve and correlations with the bodily pain and social functioning domains of medical outcomes study 36-item short-form health survey (SF-36), self-report of absenteeism and Stanford Presenteeism Scale for presenteeism. Test-retest reliability and measurement errors were assessed, respectively, by intraclass correlation coefficient (ICC) and Bland and Altman Graph., Results: 430 women completed the test, 238 (55.4%) women had dysmenorrhea, and 199 (46.3%) answered the questionnaire twice for the retest. The cutoff points ≥4, ≥5, and ≥5 could discriminate between women with and without dysmenorrhea, absenteeism, and presenteeism related to dysmenorrhea, respectively. Correlations between SF-36 - pain and social functioning domains and WaLIDD score were weak to strong and negative. For WaLIDD total Score, ICC was 0.95 and the limits of agreement were -1.54 and 1.62., Conclusion: WaLIDD score is a short, valid and reliable instrument to screen and predict dysmenorrhea and could predict absenteeism and presenteeism related to dysmenorrhea in Brazilian women., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Introduction: People with chronic conditions and people with colorectal cancer (CRC) may share common risk factors; thus, CRC screening is important for people with chronic conditions. We examined racial and ethnic differences in the use of CRC screening among people with various numbers of chronic conditions., Methods: We included data on adult respondents aged 50 to 75 years from the Behavioral Risk Factor Surveillance System in 2012 through 2020. We categorized counts of 9 conditions as 0, 1, 2, 3, and ≥4. We classified self-reported CRC screening status as up to date or not. We used Poisson models to estimate adjusted prevalence ratios (APRs) among the different counts of chronic conditions in 4 racial and ethnic groups: Hispanic adults with limited English proficiency (LEP), Hispanic adults without LEP, non-Hispanic Black adults, and non-Hispanic White adults., Results: Overall, 66.5% of respondents were up to date with CRC screening. The prevalence of being up to date increased with the number of chronic conditions. We found disparities among racial and ethnic groups. Hispanic respondents with LEP had lower rates than non-Hispanic White adults of being up to date with CRC screening across all counts of chronic conditions (APR for 0 conditions = 0.67; 95% CI, 0.64-0.71; APR for ≥4 conditions = 0.85; 95% CI, 0.79-0.91). Hispanic respondents without LEP with 0, 1, or 2 conditions were less likely than non-Hispanic White respondents to be up to date with CRC screening. We found no significant differences between non-Hispanic Black and non-Hispanic White respondents., Conclusion: We found disparities among Hispanic BRFSS respondents with LEP, who had lower rates than non-Hispanic White respondents of being up to date with CRC screening, regardless of the number of chronic conditions. Tailored interventions are needed to address these disparities and improve screening rates, particularly among Hispanic people.

Background: To date, there are no studies in the literature that define the internal structure of the Tampa Scale for Kinesiophobia (TSK) in patients with chronic neck pain based on factorial analysis. As such, we aimed to verify and identify the best structure of the Brazilian version of the TSK in patients with chronic neck pain., Methods: We included Brazilian participants aged ≥18 years, both sexes, with self-reported neck pain for more than 3 months and pain intensity ≥3 on the Numerical Pain Rating Scale (NPRS). Dimensionality and number of TSK items were assessed using confirmatory factor analysis (CFA). We tested the following internal structures: structure 1 (1 domain and 17 items), structure 2 (1 domain and 11 items), structure 3 (2 domains and 11 items), and structure 4 (2 domains and 9 items). We used the Pain-Related Catastrophizing Thoughts Scale (PCTS) and the NPRS for construct validity. In addition, we assessed test-retest reliability for the seven-day interval using intraclass correlation coefficient (ICC 2,1 ), Cronbach's alpha to assess internal consistency, and ceiling and floor effects., Results: The study sample included of 335 patients. Most were women (77.6%), young adults (~ 34 years), single (48.4%), with complete primary education (57.3%), physically inactive (66.6%), with a mean pain duration of 46 months and a mean pain intensity of ~ 5 points on the NPRS. Redundancy was found in the following items: item 1 with item 2 (modification indices = 21.419) and item 13 with item 15 (modification indices = 13.641). Subsequently, based on these paired analyses, the items with the lowest factor loadings (items 2 and 15) were excluded. As such, TSK structure 4 was composed of two domains ("somatic focus" and "activity avoidance") and 9 items, which showed adequate fit indices and lower AIC and SABIC values. We observed significant values (p < 0.05) with a correlation magnitude greater than 0.142 to 0.657 between the two domains of the TSK-neck and the other instruments (PCTS and NPRS). We found excellent reliability (ICC 2,1  ≥ 0.96) and adequate internal consistency (Cronbach's alpha ≥0.98) of the TSK-neck. Finally, ceiling and floor effects were not observed., Conclusion: The TSK-neck structure with two domains (somatic focus and activity avoidance) and nine items is the most appropriate for patients with chronic neck pain., (© 2024. The Author(s).)

Background: Primary dysmenorrhea (PD) is an etiological cyclic pelvic pain related to the menstrual period; it can negatively impact women's quality of life and productivity. The aim of the present study was to estimate the prevalence of PD and analyze associated symptoms in Brazilian women., Methods: An online cross-sectional study was carried out in Brazil, with a structured questionnaire regarding dysmenorrhea and associated symptoms. PD intensity was measured with the Numerical Rating Scale for Pain and classified as mild (1-3), moderate (4-7) and severe (> 8). The association between qualitative variables was performed using Pearson's Chi-Square Test. The quantification of this association was measured using multinomial logistic regression models, with calculation of Odds Ratio and confidence interval. A significance level of 5% was considered., Results: A total of 10,070 women were included. Most participants classified PD intensity as moderate (40.4%, 41.9% and 49.7%) and severe (21.2%, 24.8% and 28.4%) in the previous month, 3 months and 5 years, respectively. The most common symptoms associated with PD were irritability, abdominal distension sensation, anxiety and feeling more emotional. The increased of the risk (OR > 1.0) for moderate and severe PD-related pain intensity is related to age, nulliparity and presence PD since adolescence., Conclusion: There is a high prevalence of PD among Brazilian women, and the most common symptoms reported were irritability, abdominal distension sensation, anxiety and feeling more emotional., (© 2024. The Author(s).)

Background & Aims: Hepatic fibrosis is characterized by enhanced deposition of extracellular matrix (ECM), which results from the wound healing response to chronic, repeated injury of any etiology. Upon injury, hepatic stellate cells (HSCs) activate and secrete ECM proteins, forming scar tissue, which leads to liver dysfunction. Monocyte-chemoattractant protein-induced protein 1 (MCPIP1) possesses anti-inflammatory activity, and its overexpression reduces liver injury in septic mice. In addition, mice with liver-specific deletion of Zc3h12a develop features of primary biliary cholangitis. In this study, we investigated the role of MCPIP1 in liver fibrosis and HSC activation., Methods: We analyzed MCPIP1 levels in patients' fibrotic livers and hepatic cells isolated from fibrotic murine livers. In vitro experiments were conducted on primary HSCs, cholangiocytes, hepatocytes, and LX-2 cells with MCPIP1 overexpression or silencing., Results: MCPIP1 levels are induced in patients' fibrotic livers compared with their nonfibrotic counterparts. Murine models of fibrosis revealed that its level is increased in HSCs and hepatocytes. Moreover, hepatocytes with Mcpip1 deletion trigger HSC activation via the release of connective tissue growth factor. Overexpression of MCPIP1 in LX-2 cells inhibits their activation through the regulation of TGFB1 expression, and this phenotype is reversed upon MCPIP1 silencing., Conclusions: We demonstrated that MCPIP1 is induced in human fibrotic livers and regulates the activation of HSCs in both autocrine and paracrine manners. Our results indicate that MCPIP1 could have a potential role in the development of liver fibrosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Identifying factors related to persistent human papillomavirus (HPV) infection is essential to reduce the incidence of HPV-related cancers., Objective: To evaluate whether gingival/periodontal inflammation is associated with oral HPV infection., Methods: This cross-sectional study ( n  = 740) uses data from the follow-up visit of the San Juan Overweight Adults Longitudinal Study, which recruited overweight/obese adults aged 40-65 from Puerto Rico. Participants completed a dental examination and two interviews (face-to-face/ACASI) and provided oral rinse samples for HPV detection. Oral inflammation was assessed using two definitions: (1) the number of sites with bleeding on probing (BOP), and (2) the number of teeth with probing pocket depths (PPD) ≥ 4 mm and BOP. Multivariate logistic regression was used to assess the association between oral inflammation and oral HPV., Results: Nearly three-quarters (72%) of participants were female, and 68% had 50 years or older. Participants with HPV had a higher mean number of sites with BOP (15.5 vs. 10.1) and teeth with PPD ≥ 4 mm and BOP (8.5 vs. 3.2) than participants without HPV ( p < 0.05). After adjusting for sex, age, income, and the number of oral sex partners, the odds of having an oral HPV infection increased by 3% (95% confidence interval (CI): 1.00-1.06) for any additional sites with BOP and 5% (95% CI: 1.02-1.09) for any other teeth with PPD ≥ 4 mm and BOP., Conclusions: We found that oral inflammation was associated with oral HPV infection among adults in Puerto Rico. Future studies need to further investigate the underlying mechanisms., Competing Interests: Dr. Ortiz has been a consultant for Merck in the past and participates in an institutional project with Merck. The authors have no other financial relationship or conflict of interest to disclose regarding the publication of this article., (Copyright © 2023 Maira A. Castañeda-Avila et al.)