bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapeutic targeting of aging‐associated isoDGR motif in chronic lung inflammation
Authors: Kalailingam Pazhanichamy , Ngan SoFong Cam , Iyappan Ranjith , Nehchiri Afra , Mohd‐Kahliab Khalilatul‐Hanisah , Lee Benjamin Sian Teck , Sharma Bhargy , Machan Radek , Bo Sint Thida , Chambers Emma S. , Fajardo Val A. , Macpherson Rebecca E. K. , Liu Jian , Klentrou Panagiota , Tsiani Evangelia Litsa , Lim Kah Leong , Su I. Hsin , Gao Yong‐Gui , Richar A. Mark , Kalaria Raj N. , Chen Christopher P. , Balion Cynthia , de Kleijn Dominique , McCarthy Neil E. , Sze Siu Kwan 
Published: January 2025

AbstractAccumulation of damaged biomolecules in body tissues is the primary cause of aging and age‐related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age‐linked lung inflammation. We observed age‐dependent accumulation of the isoDGR motif in human lung tissues, as well as an 8‐fold increase in isoDGR‐damaged proteins in lung fibrotic tissues compared with healthy tissue. This increase was accompanied by marked infiltration of CD68+/CD11b + macrophages, consistent with a role for isoDGR in promoting chronic inflammation. We therefore assessed isoDGR function in mice that were either naturally aged or lacked the isoDGR repair enzyme. IsoDGR‐protein accumulation in mouse lung tissue was strongly correlated with chronic inflammation, pulmonary edema, and hypoxemia. This accumulation also induced mitochondrial and ribosomal dysfunction, in addition to features of cellular senescence, thereby contributing to progressive lung damage over time. Importantly, treatment with anti‐isoDGR antibody was able to reduce these molecular features of disease and significantly reduced lung pathology in vivo.
Recovery and Recurrence From Major Depression in Adolescence and Adulthood
Authors: Desai Boström Adrian E. , Cars Thomas , Hellner Clara , Lundberg Johan 
Published: January 2025

ABSTRACTObjectiveThe study aimed to estimate 5‐year recurrence rates of first‐episode major depressive disorder (MDD) and assess the impact of adolescence on recurrence likelihood after the first episode, compared to adults.MethodsA pre‐registered retrospective cohort study that utilized epidemiological data from the Stockholm MDD Cohort (1997–2018), including all individuals registered with a depression diagnosis in Region Stockholm from 2010 to 2018. This dataset combines longitudinal information from primary and secondary care, socioeconomic data, drug dispensations, psychotherapy sessions, brain stimulation treatments, and inpatient treatment. The study included 9124 individuals (1727 adolescents aged 13–17 and 7397 adults aged 18–40) who experienced their first MDD episode between 2011 and 2012, with at least three months of remission. Propensity score weighting balanced cohorts for biological sex, socioeconomic status, depression severity, psychiatric comorbidities, and treatments.ResultsThe 5‐year recurrence rates were 46.1% for adolescents and 49.0% for adults. The study had over 80% power to detect a minimum absolute difference in recurrence rates of approximately 5.5 percentage points. No significant difference in recurrence likelihood (p = 0.364) or time from remission to recurrence (median 379 days for adolescents, 326 days for adults, p = 0.836) was found between groups. Findings were consistent across bootstrap replicates and sensitivity analyses with extended remission periods.ConclusionsApproximately half of individuals with a first MDD episode experience recurrence within five years. Recurrence rates were higher than expected for adults but consistent with expectations for adolescents. The study underscores the need for relapse prevention from adolescence through adulthood and indicates a similar clinical course of MDD across age groups.
Safety and cost of selective histopathological analysis for detecting cancer in surgical specimens: a systematic review
Authors: Camilos Angelique N. , Bowley Schubert Leo C. , Castro Marcela P. , Nann Silas D. , Edwards Suzanne , Stretton Brandon , Gupta Aashray K. , Kovoor Joshua G. , Marshall‐Webb Matthew , Maddern Guy J. 
Published: January 2025

AbstractBackgroundDue to limited healthcare resources, there is global incentive to maximize efficacy while minimizing patient harm. Given the low rate of cancer diagnoses made via routine histopathological analysis of surgical specimens, a selective approach has been proposed as a viable alternative. This systematic review aimed to evaluate effectiveness of cancer detection and costs with a selective approach.MethodologyThis study was registered with PROSPERO (CRD42022346535) and conducted according to PRISMA 2020 and MOOSE guidelines. Ovid Embase, Ovid MEDLINE and PubMed were searched from earliest result (1973) to 30 July 2022 for studies evaluating selective histopathology for surgical specimens. Screening, risk of bias assessment and data extraction were completed in duplicate. Statistical analysis used a random effects model.ResultsSearches identified 4194 records, with 11 studies included consisting of 26 126 patients. Eight studies analysed patients who underwent cholecystectomy while three analysed patients who underwent appendectomy, vertical laparoscopic sleeve gastrectomy and neurectomy. In total, 295 neoplasms were detected: 196 malignant, 99 benign. Overall mean proportion of malignant neoplasms is 0.01 (95% confidence interval 0.00, 0.01). Weighted mean projected cost savings were calculated in varying formats, ranging from 6891 Euros per year within one hospital, 712 748 Euros per 10 000 patients, to 875 077 Euros per year within one country.ConclusionA selective approach is not associated with a significant proportion of missed cancer diagnoses, and provides considerable cost savings, particularly demonstrated for cholecystectomy samples. Further discussion is required regarding how surgeons will be protected medicolegally without the safety net of routine analysis.
Management of Perianal Fistulizing Crohn's Disease According to Principles of Wound Repair
Authors: McCurdy Jeffrey D. , Hartley Imogen , Behrenbruch Corina , Hart Ailsa , Tozer Phil , Ding Nik S. 
Published: January 2025

ABSTRACTBackgroundPerianal fistulizing Crohn's disease (PFCD) is a challenging and debilitating phenotype of Crohn's disease that can negatively affect quality of life. Studies have begun to uncover the physiologic mechanisms involved in wound repair as it relates to PFCD and how aberrations in these mechanisms may contribute to fistula persistence.AimsTo review the physiologic and pathophysiologic mechanisms of wound repair in PFCD and how specific therapeutic strategies may impact their outcomes.MethodsWe reviewed the latest published literature on wound repair as it relates to PFCD.ResultsWound repair can be categorised into three overlapping biological phases: localised inflammation, cell recruitment/proliferation and tissue remodelling. Each is tightly regulated since insufficient or excessive activation can result in, respectively, chronic wounds and fibrotic tissue, both of which can impair organ function. In PFCD, the outcomes of wound repair include restitution (complete healing), epithelialisation and chronic wounds. Treatment of PFCD should take into consideration the distinct phases of wound repair. Therefore, the ability to differentiate between each phase of wound repair and their outcomes may help physicians deliver the most effective treatment strategy at the most appropriate time.ConclusionsThis review provides a comprehensive overview of the phases of wound repair and specific treatment strategies for each to provide clinicians with a rational framework for managing PFCD.
A Simple Endoscopic Score for Crohn's Disease (SES‐CD) ≥ 7 Predicts Disease Progression
Authors: Peraza Jellyana , Kaper Marco Emilio , Bargas Andre , Kim Iris , Agrawal Manasi , Larsen Lone , Jacobsen Henrik Albaek , Jess Tine , Colombel Jean‐Frederic , Torres Joana , Ungaro Ryan C. , Ananthakrishnan Ashwin N. 
Published: January 2025

ABSTRACTBackgroundUp to 30% of patients with Crohn's disease (CD) will experience a mild disease course. However, there is no consensus definition for mild CD.AimTo examine the Simple Endoscopic Score for Crohn's disease (SES‐CD) thresholds best associated with low likelihood of long‐term disease progression.MethodsWe conducted a multicentre retrospective cohort study at three tertiary care centres in United States and Europe. We analysed data from 177 surgery‐naïve patients with CD who had endoscopic assessment while not on immunosuppressive therapy. The primary outcome was disease progression (systemic steroids, biologic or immunomodulator therapy initiation; new stricturing or penetrating complications; or CD‐related hospitalisation or surgery). Univariable and multivariable Cox proportional hazards modelling identified predictors of the primary outcome at 2 and 5 years following endoscopy.ResultsDisease progression occurred in 23% and 35% of patients at years two and five, respectively. Endoscopic severity at enrolment independently predicted disease progression. Compared to those with an SES‐CD of 0, an SES‐CD ≥ 7 had a greater risk of progression at 2 years (HR 2.50, 95% CI 1.09–5.72) and 5 years (HR 2.89, 95% CI 1.41–5.91). SES‐CD > 7 remained independently predictive of disease progression among the 129 immunosuppression‐naïve patients (HR 5.65, 95% CI 1.49–21.52) and after excluding patients with prior penetrating disease (HR 2.32, 95% CI 1.00–5.45).ConclusionsSES‐CD ≥ 7 predicts disease progression in mild CD. A score ≤ 6 may help identify patients less likely to progress and be part of the definition of mild CD.
Management strategies for patients with chronic lymphocytic leukaemia harbouring complex karyotype
Authors: Serafin Andrea , Ruocco Valeria , Cellini Alessandro , Angotzi Francesco , Bonaldi Laura , Trentin Livio , Visentin Andrea 
Published: January 2025

SummaryChronic lymphocytic leukaemia (CLL) is a heterogeneous disease characterised by the uncontrolled proliferation of mature lymphocytes. A subset of CLL patients harbouring complex karyotype (CK) presents with poor prognosis and limited treatment options. This review aims to discuss the current understanding of such patient subset, including its molecular landscape, diagnostic approaches, treatment modalities and emerging therapies. Furthermore, it outlines strategies for personalised management to improve clinical outcomes in this challenging patient population.
A qualitative exploration of the prospective acceptability of the MiDerm app; a complex digital intervention for adults living with skin conditions
Authors: Hewitt Rachael M. , Dale Carys , Purcell Catherine , Pattinson Rachael , Bundy Chris 
Published: January 2025

AbstractObjectivesSkin conditions carry a substantial psychological burden but support for patients is limited. Digital technology could support patient self‐management; we found preliminary evidence for the effectiveness and acceptability of digital psychological interventions for adults living with skin conditions. We have, therefore, developed a complex digital intervention called MiDerm with patients. This qualitative study explored the prospective acceptability of the complex intervention delivered via a smartphone application (app), and possible barriers and facilitators to use.DesignQualitative research involving a hybrid inductive‐deductive approach. Data collection and analysis were theoretically informed by The Common‐Sense Model of Self‐Regulation, Theoretical Framework of Acceptability and the Capability, Opportunity, Motivation ‐ Behaviour Model.MethodsEight synchronous online group interviews with 43 English‐speaking adults (≥ 18 years) with skin conditions. Data were analysed using Reflexive Thematic Analysis.ResultsThree superordinate themes were generated: (1) Patients' attitudes and concerns about the MiDerm app; (2) Need for personal competence, autonomy and relatedness for effective self‐management; and (3) Physical, psychological and social barriers to app use.ConclusionAdults with skin conditions, mainly those with vitiligo and psoriasis living in the UK, expressed the need for support to self‐manage the psychological aspects of their condition(s). The idea of a new intervention comprised of informational, emotional, behavioural and peer support, delivered via a smartphone app was welcomed and may be especially beneficial for specific patients. Identified barriers must be addressed to maximize engagement and giving users choice, flexibility and control is imperative to this. We have since developed the MiDerm app using these findings.
Serpentinite–Sediment Associations: Provenance Controlled by Competing Extensional–Contractional Tectonic Processes During the Evolution of the Northern Apennines (Eastern Elba Island, Tuscany)
Authors: Jacobs Joachim , Rocchi Sergio , Bach Wolfgang , Masotta Matteo , Rydland Pedersen Leif‐Erik 
Published: January 2025

ABSTRACTOrogenic wedges juxtapose tectonic units that originated far from each other, and tracing these back to their origin is often difficult. We have studied two contrasting serpentinite–sediment associations of the Alpine‐Apennine orogenic wedge of eastern Elba Island with the help of a detrital zircon study of the sediments and a geochemical comparison of the relic phases of their associated serpentinites. We demonstrate that these very likely originated in different branches of the Ligurian Ocean and in contrasting tectonic settings, one during opening of Alpine Tethys and the other during Apenninic contraction‐exhumation. First, the Early Cretaceous Palombini shales are associated with abyssal ocean floor serpentinite–ophicalcites of a Ligurian ophiolite (LO) that originated in the western branch of the Ligurian Ocean during ultraslow spreading. They have an Adria/African zircon provenance, indicating proximity to Adria rather than Corsica‐Europe and the associated serpentinites are highly depleted and relatively little deformed. The second sediment–serpentinite association has a tectonised serpentinite band in contact with highly deformed, Miocene blueschist facies metasediments. Detrital zircons of these metasediments (Acquadolce (AD) and Pseudomacigno) record major Eocene–Oligocene U–Pb zircon age peaks, with an igneous provenance in the western and central Alps respectively. An age peak at ca. 38 Ma links the Pseudomacigno sediments to calc‐alkaline volcanic rocks of the central Adamello massif, whilst an Oligocene age peak at ca. 32 Ma indicates western Alpine sources for the AD Unit. The associated massive, highly tectonised AD serpentinite represents most likely a mantle sliver of subcontinental lithospheric mantle, which together with Oligocene blueschist facies rocks underwent synorogenic Apenninic tectonic extrusion during W‐directed subduction–rollback of the eastern branch of the Ligurian Ocean.
Delivering Results for Canadians: Improving the Contributions of Enabling Functions
Authors: Shepherd Robert P. , Champagne Eric 
Published: January 2025

AbstractImplementing a results‐oriented management system has been a long‐term goal and a challenge for federal public sector organizations in Canada. This article highlights the efforts by the Government of Canada to improve performance measurement, evaluation, and audit (PMEA) functions over time. The article traces administrative reforms since 2000, highlighting the shift from inputs and outputs towards a results‐focused environment aimed at achieving outcomes. However, even after many reforms and goodwill, there remain gaps among the senior policymakers regarding the meaning of “results for Canadians.” The article points out that siloed approaches by function have led to isolated practices and inefficiencies in data sharing and reporting for effectively supporting decision‐making. Although individual functions have improved, implementing a comprehensive results‐focused management architecture continues to pose a significant challenge. The article proposes steps to enhance the effectiveness of PMEA functions, emphasizing the need to integrate functions to enhance public services, decision‐making, and institutional learning.
Comprehensive Genome Profiling‐Initiated Tumor‐Informed Circulating Tumor DNA Monitoring for Patients With Advanced Cancer
Authors: Sasaki Taiga , Hiraki Hayato , Yashima‐Abo Akiko , Nagashima Hiromi , Endo Fumitaka , Yaegashi Mizunori , Miura Shimpei , Obata Keiko , Yanagawa Naoki , Itamochi Hiroaki , Shirota Hidekazu , Iwaya Takeshi , Nishizuka Satoshi S. 
Published: January 2025

ABSTRACTIn Japan, comprehensive genome profiling (CGP) as a companion diagnostic (CDx) has been covered by public insurance since June 2019, but the proportion of patients with cancer who actually received drug therapy based on CGP data is low. In the present study, we attempted to use CGP as a starting point for tumor‐informed circulating tumor DNA (ctDNA) monitoring. We retrospectively validated 219 patients with malignant tumors who underwent CGP at Iwate Medical University Hospital between October 2019 and April 2023 in terms of patient demographics, genetic analysis, drug recommendations, and drug administration rate. The 219 cancer cases analyzed by CGP for 27 target organs, including prostate (n = 27, 12.3%), colorectal (n = 25, 11.4%), lung (n = 19, 8.7%), and other neoplasms (n = 148, 67.6%). Among the cohort, only 14 cases (6.4%) subsequently were able to undertake the recommended action by Molecular Tumor Board. Of patients who underwent ctDNA monitoring based on somatic mutations identified by CGP (n = 11), clinical validity was confirmed in terms of early relapse prediction (n = 5, 45.5%), treatment response evaluation (n = 10, 90.9%), and no relapse/regrowth corroboration (n = 2, 18.2%) whereas 90.9% (n = 10) of patients obtained information with at least one source of the clinical validity. Although the current rate of CGP contributing to a drug recommendation is low, CGP results can be an alternate resource for tumor‐informed longitudinal ctDNA monitoring to provide information concerning early relapse prediction, treatment response evaluation, and no relapse/regrowth corroboration.
Biological Characterization of One Oxadiazole Derivative (5(4‐Hydroxyphenyl)‐2‐(N‐Phenyl Amino)‐1,3,4‐Oxadiazole): In Vitro, In Silico, and Network Pharmacological Approaches
Authors: Duran Tugce , Balikci Irem , Buyukkosucu Busra , Gunes Ibrahim Furkan , Pekgonul Hatice Kubra , Vardar Necati , Yilmaz Mahmut Deniz , Ak Gunes , Zengin Gokhan 
Published: January 2025

ABSTRACTOxadiazole compounds are of great interest because they have a range of biological activities ranging from antioxidants to anticancer agents. Against this background, we wanted to demonstrate the antioxidant, enzyme inhibitory, and anticancer effects of 5(4‐hydroxyphenyl)‐2‐(N‐phenylamino)‐1,3,4‐oxadiazole (Hppo). Antioxidant abilities were measured through free radical scavenging and reducing power tests. Enzyme inhibitory effects were studied by cholinesterases, tyrosinase, amylase, and glucosidase. The anticancer effect was tested on pancreatic cancer cell lines (PANC‐1, CRL‐169) and on HEK293 cell lines. The compound showed significant antioxidant activity (particularly in the CUPRAC (cupric acid‐reducing antioxidant capacity) assay) and enzyme inhibitory properties (particularly glucosidase inhibition). In the anticancer test, the compound showed strong anticancer activity in pancreatic cancer with apoptotic signaling pathways. These results were confirmed by molecular modeling and bioinformatics tools. Thus, our findings can provide novel and versatile compounds for the development of multidirectional drugs in the pharmaceutical industry.
Body Composition, Adipocytokine, and Metabolic Parameters in Men With Congenital Hypogonadotropic Hypogonadism
Authors: Zhang Rui , Mao Jiangfeng , Nie Min , Wang Xi , Xu Tengda , Chen Fengling , Song Ailing , Hu Yingying , Yu Bingqing , Huang Qibin , Sun Bang , Zhang Wei , Zhang Junyi , Lin Songbai , Wu Xueyan 
Published: January 2025

ABSTRACTObjectiveThis study aimed to evaluate the long‐term effects of hormone therapies on the body composition, adipokines and metabolic parameters of adult men with congenital hypogonadotropic hypogonadism (CHH).MethodsSixty‐six patients with CHH and 21 healthy controls were recruited. Patients were divided into untreated (n = 33) and treated (n = 33) groups based on hormone therapy history. Body composition was assessed using dual‐energy X‐ray absorptiometry (DXA), and adipokines and metabolic parameters were measured in all participants.ResultsCompared to the healthy control group, patients in the treated group had lower serum testosterone levels (p < 0.001), increased body fat percentage (BFP) and visceral adipose tissue (VAT) volume, decreased lean soft tissue (LST) and bone mineral content (BMC) (p < 0.05), increased serum leptin levels accompanied by decreased adiponectin (ADP) (p < 0.05), higher HOMA‐IR with lower QUICKI (p < 0.05). Compared to the untreated group, patients in the treated group (therapy duration 4.8 ± 2.3 years) had higher serum testosterone levels (p < 0.001), decreased BFP and VAT volume, increased LST and BMC (p < 0.05), decreased serum leptin levels (p < 0.001), and decreased HOMA‐IR accompanied by increased QUICKI (p < 0.05). Among them, VAT volume, LST, BMC, HOMA‐IR and QUICKI reached healthy control levels (p > 0.05). Multiple stepwise linear regression analysis showed serum testosterone levels were negatively correlated with BFP (β = −0.564, p < 0.001) and VAT volume (β = −0.260, p = 0.045), positively correlated with LST (β = 0.305, p = 0.018) and BMC (β = 0.423, p = 0.001). Serum testosterone levels were independently negatively correlated with leptin levels (β = −0.277, p = 0.004).ConclusionsPatients with untreated CHH had impaired body composition, adipokines and metabolic parameters. While hormone therapies can improve body composition and glucolipid metabolism in patients with CHH, this imperfect treatment does not fully rescue body composition abnormalities when compared to healthy individuals. Abnormal metabolic parameters in patients with CHH are associated with increased fat mass and abnormal serum leptin level. Serum testosterone levels were independently negatively correlated with leptin levels.