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16 pages, 806 KB  
Systematic Review
Evaluating the Outcomes of Vertebral Biopsies Performed in Osteoporotic Vertebral Fractures: A Systematic Review and Meta-Analysis
by Halil Bulut, Chuck Lam, Veer Sheth, Iihan Ali, Christos Tsagkaris, Morgan Jones, Rajesh Botchu, Constantino Errani, Azmi Hamzaoglu and Korhan Ozkan
Osteology 2025, 5(4), 30; https://doi.org/10.3390/osteology5040030 - 11 Oct 2025
Viewed by 142
Abstract
Background/Objectives: Osteoporotic vertebral fractures (OVFs) are common in older adults. While surgery is generally reserved for unstable or painful fractures, some OVFs conceal underlying malignancies, including metastatic and hematologic cancers. This study aimed to determine the pooled prevalence of unsuspected malignancy in patients [...] Read more.
Background/Objectives: Osteoporotic vertebral fractures (OVFs) are common in older adults. While surgery is generally reserved for unstable or painful fractures, some OVFs conceal underlying malignancies, including metastatic and hematologic cancers. This study aimed to determine the pooled prevalence of unsuspected malignancy in patients initially diagnosed with OVFs. Methods: A systematic search of PubMed and Scopus was conducted from inception to September 2025 in accordance with PRISMA guidelines. Eligible studies included adults with presumed OVFs who underwent vertebral biopsy and histopathological evaluation. Prevalence estimates were pooled using a random-effects model, and study quality was assessed with the Newcastle–Ottawa Scale. Results: Thirteen studies involving 3513 patients were included. The pooled prevalence of malignancy was 8.0% (95% CI: 5.4–10.6), comprising metastatic solid tumors (4.9%; 95% CI: 2.3–7.4) and multiple myeloma (2.6%; 95% CI: 1.3–3.9). Malignancy was detected in 2.7% (95% CI: 1.8–4.1) of routine biopsy cohorts versus 36.8% (95% CI: 22.1–54.4) of clinically suspected cases. Diagnostic yield exceeded 45% in patients selected by combined history, imaging, or known malignancy. No biopsy-related complications or procedure-related mortality were reported. Moderate heterogeneity was observed, mainly in suspected cohorts. Conclusions: Vertebral biopsy is a safe and diagnostically valuable procedure in vertebral compression fractures. Its yield ranges from about one in 30 patients in routine settings to nearly one in two in high-risk groups, underscoring the importance of structured patient selection to facilitate timely cancer detection and referral. Full article
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14 pages, 976 KB  
Article
Locoregional Treatment in De Novo Bone-Only Metastatic Breast Cancer: Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a
by Atilla Soran, Berk Göktepe, Berkay Demirors, Ozgur Aytac, Serdar Ozbas, Lutfi Dogan, Didem Can Trablus, Jamila Al-Azhri, Kazım Senol, Shruti Zaveri, Salyna Meas, Umut Demirci, Hasan Karanlik, Aykut Soyder, Ahmet Dag, Ahmet Bilici, Mutlu Dogan, Mehmet Ali Nahit Sendur, Hande Koksal, Mehmet Ali Gulcelik, Neslihan Cabioglu, Levent Yeniay, Zafer Utkan, Nuri Karadurmus, Gul Daglar, Turgay Simsek, Birol Yildiz, Cihan Uras, Mustafa Tukenmez, Cihangir Ozaslan, Niyazi Karaman, Arda Isik, Efe Sezgin, Vahit Ozmen and Anthony Lucciadd Show full author list remove Hide full author list
Curr. Oncol. 2025, 32(10), 556; https://doi.org/10.3390/curroncol32100556 - 3 Oct 2025
Viewed by 307
Abstract
Introduction: The impact of locoregional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (dnBOMBC) is controversial. This study aims to assess the effect of LRT on survival, utilizing international, prospectively acquired data in this cohort of patients. Materials and [...] Read more.
Introduction: The impact of locoregional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (dnBOMBC) is controversial. This study aims to assess the effect of LRT on survival, utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with dnBOMBC were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Further, patients who received LRT were divided into two subgroups: those who received ST after LRT (LRT+ST group) and those who received ST prior to LRT (ST+LRT group). Factors associated with disease progression, including solitary or multiple bone metastases, were analyzed. Results: There was a total of 744 patients with dnBOMBC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32–66, 25–75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs. 55 (44, 66), p = 0.0001]. There were no significant differences in grade, HER2 status, triple-negative status, receipt of hormonal therapy, or intervention to metastatic sites. During follow-up, 58% (n = 217) of patients in the ST group and 32% (n = 120) of patients in the LRT group died (p < 0.001). Local progression was observed in 20% of the patients in the ST group, whereas 9% progressed in the LRT group (p = 0.0001). Systemic progression occurred more in the ST group; 66% (n = 244) compared to 41% (n = 152) of patients in the LRT group (p < 0.001). The hazard of death was 64% lower in the LRT group than in the ST group (HR: 0.36, 95% CI: 0.29–0.45, p < 0.0001). The burden of metastatic disease differed significantly between the two groups, with a higher rate of solitary bone metastases in the LRT group compared to the ST group (50% vs. 24%, p < 0.001). However, the LRT group had better overall survival (OS) for both solitary (HR: 0.38, 95% Cl: 0.26–0.55) and multiple (HR: 0.38, 95% Cl: 0.29–0.51) bone metastasis patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST. Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p < 0.05). Conclusions: Analysis of this large multi-institutional patient cohort provides further evidence that LRT is associated with longer OS and lower locoregional recurrence rates in patients with dnBOMBC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor. Full article
(This article belongs to the Section Breast Cancer)
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20 pages, 1243 KB  
Article
Collaborative Funding Model to Improve Quality of Care for Metastatic Breast Cancer in Europe
by Matti S. Aapro, Jacqueline Waldrop, Oriana Ciani, Amanda Drury, Theresa Wiseman, Marianna Masiero, Joanna Matuszewska, Shani Paluch-Shimon, Gabriella Pravettoni, Franziska Henze, Rachel Wuerstlein, Marzia Zambon, Sofía Simón Robleda, Pietro Presti and Nicola Fenderico
Curr. Oncol. 2025, 32(10), 547; https://doi.org/10.3390/curroncol32100547 - 30 Sep 2025
Viewed by 384
Abstract
Breast cancer (BC) is the most frequently diagnosed malignancy in women. Currently, BC is treated with a holistic and multidisciplinary approach from diagnostic, surgical, radio-oncological, and medical perspectives, and advances including in early detection and treatment methods have led to improved outcomes for [...] Read more.
Breast cancer (BC) is the most frequently diagnosed malignancy in women. Currently, BC is treated with a holistic and multidisciplinary approach from diagnostic, surgical, radio-oncological, and medical perspectives, and advances including in early detection and treatment methods have led to improved outcomes for patients in recent years. Yet, BC remains the second most common cause of cancer-related deaths among women and there is an array of gaps to achieve optimal care. To close gaps in cancer care, here we describe a collaborative Request For Proposals (RFP) framework supporting independent initiatives for metastatic breast cancer (MBC) patients and aiming at improving their quality of care. We set up a collaborative framework between Pfizer and Sharing Progress in Cancer Care (SPCC). Our model is based on an RFP system in which Pfizer and SPCC worked together ensuring the independence of the funded projects. We developed a three-step life cycle RFP. The collaborating framework of the project was based on an RFP with a USD 1.5 million available budget for funding independent grants made available from Pfizer and managed in terms of awareness, selection, and monitoring by SPCC. Our three-step model could be applicable and scalable to quality improvement (QI) initiatives that are devoted to tackling obstacles to reaching optimal care. Through this model, seven projects from five different European countries were supported. These projects covered a range of issues related to the experience of patients with MBC: investigator communication, information, and shared decision-making (SDM) practices across Europe; development, delivery, and evaluation of a scalable online educational program for nurses; assessment of disparities among different minority patient groups; development of solutions to improve compliance or adherence to therapy; an information technology (IT) solution to improve quality of life (QoL) of patients with MBC and an initiative to increase awareness and visibility of MBC patients. Overall, an average of 171 healthcare professionals (HCPs) per project and approximately 228,675 patients per project were impacted. We set up and describe a partnership model among different stakeholders within the healthcare ecosystem―academia, non-profit organizations, oncologists, and pharmaceutical companies―aiming at supporting independent projects to close gaps in the care of patients with MBC. By removing barriers at different layers, these projects contributed to the achievement of optimal care for patients with MBC. Full article
(This article belongs to the Section Breast Cancer)
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12 pages, 1095 KB  
Article
Real-Life Retrospective Turkiye Data of the De-Escalation of ABVD to AVD in Hodgkin Lymphoma: On Behalf of the TSH Turkish Lymphoma Study Group
by Emel Isleyen, Nurcan Alhan, Esra Terzi Demirsoy, Ayfer Geduk, Duygu Nurdan Avci, Mahmut Yeral, Ahmet Burhan Ferhanoglu, Ebru Pekguc, Eren Gunduz, Hava Uskudar Teke, Nihan Alkis, Zafer Serenli Yegen, Fahir Ozkalemkas, Tuba Ersal, Volkan Karakus, Fatma Aykas, Irfan Yavasoglu, Ayse Hilal Eroglu Kucukdiler, Ozan Salim, Gulsum Ozet, Simten Dagdas, Sule Mine Ozturk, Merve Ecem Erdogan Yon, Ozge Soyer Kosemehmetoglu, Emine Merve Savas, Seyma Yildiz, Selami Kocak Toprak, Muhit Ozcan, Guldane Cengiz Seval, Leylagul Kaynar, Sureyya Yigit Kaya, Erman Ozturk, Pinar Tiglioglu, Ahmet Kursat Gunes, Selin Kucukyurt, Cem Selim, Tayfur Toptas, Meral Ulukoylu Menguc, Fatma Arikan, Fatma Keklik Karadag, Hale Bulbul, Aysun Senturk Yikilmaz, Ekin Kircali, Selin Merih Urlu, Deniz Goren, Elif Birtas Atesoglu, Omur Gokmen Sevindik, Fatos Dilan Koseoglu, Taha Ulutan Kars, Atakan Tekinalp, Serkan Guven and Ozgur Mehtapadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(19), 6813; https://doi.org/10.3390/jcm14196813 - 26 Sep 2025
Viewed by 401
Abstract
Background: Classical Hodgkin lymphoma (cHL) demonstrates high survival rates with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine); however, the use of bleomycin is associated with a significant risk of pulmonary toxicity. The Risk-Adapted Treatment of HL (RATHL) trial demonstrated that omitting bleomycin in [...] Read more.
Background: Classical Hodgkin lymphoma (cHL) demonstrates high survival rates with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine); however, the use of bleomycin is associated with a significant risk of pulmonary toxicity. The Risk-Adapted Treatment of HL (RATHL) trial demonstrated that omitting bleomycin in patients with favorable interim Positron Emission Tomography (PET-CT) results did not adversely affect survival outcomes. In this study, we present real-world data from advanced-stage HL patients treated according to the RATHL protocol. Methods: This multicenter, retrospective study included newly diagnosed cHL patients with Ann Arbor stage IIB–IV disease or stage IIA disease with bulky disease or with involvement of three or more sites, enrolled from 29 centers across Türkiye. The analysis focused on patients whose initial treatment was de-escalated from ABVD to AVD (bleomycin was omitted). Data were collected on demographic and clinical prognostic characteristics, interim PET-CT findings (evaluated using the Deauville score), progression-free survival (PFS) and overall survival (OS). Survival outcomes were assessed using Kaplan–Meier analysis. Results: A total of 379 patients were included, with a median age of 34 years (range: 18–78). Following interim PET-CT assessments (After 2 cycles of ABVD), Deauville scores were 1 in 39.8% of patients, 2 in 39.1%, and 3 in 21.1%. Based on these results, bleomycin was omitted immediately after interim PET-CT in 73.9% of patients, after one additional ABVD cycle in 12.1%, and after two additional cycles in 14%. The median follow-up duration was 28 months (range: 6–96). The 3-year PFS and OS rates were 86.0% and 96.1%, respectively. Patients with Deauville scores of 1–2 had a 3-year PFS rate of 87.6%, compared to 79.8% in those with a score of 3 (p = 0.087). Increased age, poor Eastern Cooperative Oncology Group Scale (ECOG) performance status, bulky disease, and higher International Prognostic Scores (IPS) were significantly associated with inferior OS (p < 0.05). There were no significant differences in OS among patients who received 2, 3, or 4 cycles of ABVD. However, among patients treated with 2 cycles of ABVD, both extranodal involvement (p = 0.039) and higher IPS (p = 0.002) were significantly associated with decreased PFS. Conclusions: Our findings demonstrate that PET-guided de-escalation of bleomycin after two cycles of ABVD is feasible, effective, and safe in real-world multicenter practice in Türkiye. The survival outcomes are comparable to those reported in the RATHL study, reinforcing the role of interim PET-CT in guiding individualized therapy. However, patients with high IPS or extranodal involvement may require more tailored management strategies. Full article
(This article belongs to the Special Issue Hematologic Malignancies: Treatment Strategies and Future Challenges)
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19 pages, 2381 KB  
Article
The Longitudinal Influence of Parent–Grandparent Coparenting Relationships on Preschoolers’ Eating Behaviors in Chinese Urban Families: The Mediating Roles of Caregivers’ Feeding Behaviors
by Zhihui Zhao, Fangge Qu, Ruxing Wu, Xiaoxue Wei, Xinyi Song, Chenjun Wu, Jian Wang, Wenzhe Hua and Daqiao Zhu
Nutrients 2025, 17(18), 2961; https://doi.org/10.3390/nu17182961 - 15 Sep 2025
Viewed by 540
Abstract
Background: The early development of children’s eating behaviors is a complex process shaped by dynamic interactions within the family system. While extensive research has focused on parental feeding practices as a primary predictor of children’s eating behaviors, the role of intergenerational coparenting dynamics [...] Read more.
Background: The early development of children’s eating behaviors is a complex process shaped by dynamic interactions within the family system. While extensive research has focused on parental feeding practices as a primary predictor of children’s eating behaviors, the role of intergenerational coparenting dynamics (especially with involved grandparents) is less studied. This study aimed to examines how primary caregivers’ feeding behaviors mediate the relationship between parent–grandparent coparenting dynamics and children’s eating behaviors. Methods: We conducted a longitudinal study among 343 stem families with preschool children. The cross-lagged analysis was applied to examine: the mechanism of parent–grandparent coparenting relationships on preschool children’s eating behaviors and the bidirectional relationship between feeding behaviors and eating behaviors. Results: Our results revealed that coparenting agreement significantly and negatively predicted satiety responsiveness through the mediating role of parental encouragement of healthy eating (β = −0.012, 95% CI [−0.022, −0.001]). Similarly, coparenting support had a significant negatively indirect effect on satiety responsiveness, also partially mediated by parental encouragement of healthy eating (β = −0.012, 95% CI [−0.023, −0.002]). The association between coparenting undermining and satiety responsiveness was mediated by parental encouragement healthy eating (β = −0.612, 95% CI [−0.796, −0.429]). Mutual predictive relationships were observed between preschool children’s satiety responsiveness and parental encouragement of healthy eating (p < 0.05). Conclusions: The study results highlighted the critical role of parent–grandparent coparenting relationships as indirect predictors of preschoolers’ eating behavior through mediator of parental feeding behaviors. Importantly, healthcare providers may be able to offer anticipatory guidance or relevant healthy eating resources to parents and grandparents, who should be recognized as important stakeholders in promoting healthy eating among children. Full article
(This article belongs to the Section Pediatric Nutrition)
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23 pages, 8560 KB  
Article
Methylene Blue Alleviates Inflammatory and Oxidative Lung Injury in a Rat Model of Feces-Induced Peritonitis
by Cengiz Dibekoğlu, Kubilay Kemertaş, Hatice Aygun and Oytun Erbas
Medicina 2025, 61(8), 1456; https://doi.org/10.3390/medicina61081456 - 13 Aug 2025
Cited by 1 | Viewed by 882
Abstract
Background and Objectives: Feces-induced peritonitis (FIP), a clinically relevant model of polymicrobial sepsis, induces systemic inflammation and acute lung injury (ALI). Methylene blue (MB), a phenothiazine-based compound, exhibits vasoregulatory, antioxidant, and anti-inflammatory properties in the context of sepsis. This study aimed to evaluate [...] Read more.
Background and Objectives: Feces-induced peritonitis (FIP), a clinically relevant model of polymicrobial sepsis, induces systemic inflammation and acute lung injury (ALI). Methylene blue (MB), a phenothiazine-based compound, exhibits vasoregulatory, antioxidant, and anti-inflammatory properties in the context of sepsis. This study aimed to evaluate the protective effects of MB on pulmonary injury in a rat model of FIP-induced sepsis. Materials and Methods: Forty male Wistar rats were randomly assigned to four groups: control, FIP, FIP + Saline, and FIP + MB. MB was administered intraperitoneally at a dose of 20 mg/kg, 1 h after FIP induction. At 24 h post-induction, plasma levels of inflammatory markers [interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)], oxidative stress marker [malondialdehyde (MDA)], metabolic indicator [lactic acid], and vascular signaling marker [cyclic guanosine monophosphate (cGMP)] were measured. Lung injury was evaluated through histopathological analysis and thoracic computed tomography (CT)-based Hounsfield unit (HU) quantification, while pulmonary function was assessed via arterial blood gas analysis, including arterial oxygen pressure (PaO2) and carbon dioxide pressure (PaCO2). Results: FIP induction led to significant increases in plasma levels of IL-6, IL-1β, TNF-α, CRP, MDA, cGMP, and lactic acid, accompanied by elevated CT attenuation (HU) values and a marked reduction in arterial PaO2 and PaCO2. MB treatment significantly decreased the levels of IL-6, IL-1β, TNF-α, CRP, MDA, lactic acid, and cGMP, improved PaO2, and attenuated both histopathological lung injury and CT-assessed parenchymal density. No significant differences were observed in PaCO2 among the groups. Conclusions: MB mitigates inflammation, oxidative damage, and pulmonary dysfunction in FIP-induced sepsis. Further studies are warranted to optimize dosing and timing and to evaluate long-term outcomes. Full article
(This article belongs to the Section Infectious Disease)
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13 pages, 1732 KB  
Article
Clinical and Phenotypic Characteristics of Early-Onset Inflammatory Bowel Disease: A Five-Year Observational Study
by Ivan S. Samolygo, Marina A. Manina, Ekaterina A. Yablokova, Pavel A. Stribul, Alexander V. Novikov, Anton S. Antishin, Albina S. Pestova, Alexander S. Tertychnyy, Daniel Munblit and Svetlana I. Erdes
Children 2025, 12(7), 952; https://doi.org/10.3390/children12070952 - 18 Jul 2025
Viewed by 628
Abstract
Background: Inflammatory bowel diseases with an early-onset form (EO-IBDs) make up a special disease group with certain clinical and phenotypic characteristics. This article discusses the features of such early onset in a group of children, based on five years of monitoring a registry [...] Read more.
Background: Inflammatory bowel diseases with an early-onset form (EO-IBDs) make up a special disease group with certain clinical and phenotypic characteristics. This article discusses the features of such early onset in a group of children, based on five years of monitoring a registry of children with IBD from a specialized center. Methods: This retrospective single-center cohort study included pediatric patients diagnosed with EO-IBD between 2019 and 2024. Clinical, laboratory, and endoscopic data were collected from medical records, including fecal calprotectin, inflammatory markers, disease activity indices, and endoscopic severity scores. Localization was classified according to the Paris system, and histological activity was assessed using the IBD-DCA score. Results: There were 20 patients with ulcerative colitis (UC) and 17 with Crohn’s disease (CD). Clinical activity was moderate or high (p = 0.179). UC was more characterized by diarrhea and rectal bleeding. CD was more often accompanied by abdominal pain, weight loss, and fever. In total, 82.4% of patients with CD had an inflammatory form. UC-like intestinal lesion was typical of both nosologies—L3 64.7% and E4 60% forms in CD and UC, respectively. Morphological activity was moderate for both nosologies (p = 0.54). IBD-U was present in 43.2% of patients. The median time after which it was possible to diagnose UC was 24 weeks (IQR 20–48) and 40 weeks (IQR 30–45.5) for CD (p = 0.56). Conclusions: Our study confirms the presence of characteristic signs of EO-IBD development, such as a frequent family history of IBD, high or moderate clinical activity during diagnosis verification, colon damage, and a high frequency of extraintestinal manifestations. Full article
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15 pages, 3716 KB  
Article
Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
by Akiko Hanyuda, Oana A. Zeleznik, Yoshihiko Raita, Danielle E. Haslam, Qi Sun, Kazuno Negishi, Louis R. Pasquale, Jessica Lasky-Su, Janey L. Wiggs and Jae H. Kang
Metabolites 2025, 15(7), 469; https://doi.org/10.3390/metabo15070469 - 9 Jul 2025
Viewed by 989
Abstract
Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS). Methods: We identified [...] Read more.
Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS). Methods: We identified 217 XFG cases and 217 matched controls nested within three prospective health professional cohorts with plasma collected a mean 11.8 years before case identification. Plasma metabolites were analyzed using the targeted NMR Nightingale platform. Conditional logistic models and Metabolite Set Enrichment Analysis were performed. Multiple comparison issues were addressed using the number of effective tests (NEF) and false discovery rate (FDR). Results: Among 235 profiled metabolites, higher glucose was significantly associated with a lower risk of XFG (odds ratio (95%CI) = 0.42 (0.26, 0.7); NEF = 0.03). Among metabolite classes, lipoprotein subclasses and branched-chain amino acids were inversely associated, while relative lipoprotein lipid concentrations were adversely associated (FDR < 0.05). Conclusion: NMR profiling revealed that glucose, branched-chain amino acids, lipoprotein subclasses, and relative lipoprotein lipid concentrations may play important roles in XFG etiology. Full article
(This article belongs to the Special Issue Metabolomics of the Eye and Adnexa)
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16 pages, 1617 KB  
Article
Lens Proteomics Provide Novel Clues for Cataractogenesis: Original Investigation and a Broad Literature Survey
by Banu Cosar, Mustafa Sehvar Nefesoglu, Meric A. Altinoz, Emel Akgun, Betul Sahin, Ahmet Baykal and Mustafa Serteser
J. Clin. Med. 2025, 14(13), 4737; https://doi.org/10.3390/jcm14134737 - 4 Jul 2025
Viewed by 663
Abstract
Background: Previous proteomic studies provided valuable information about cataracts, but unclarified issues, such as sex and ethnicity-associated differences, remain. This study aimed to provide additional data on cataract-related proteins regarding age, sex, and cataract type. Methods: Twenty-six female and seven male [...] Read more.
Background: Previous proteomic studies provided valuable information about cataracts, but unclarified issues, such as sex and ethnicity-associated differences, remain. This study aimed to provide additional data on cataract-related proteins regarding age, sex, and cataract type. Methods: Twenty-six female and seven male Turkish cataract patients were screened for visual acuity and dysfunctional lens index. A nano-LC-MS/MS system and Progenesis QI software v3.0 were used for protein identification and quantification. The remaining data were evaluated with SPSS Version 29.0 software. Results: Proteins that showed age-associated changes were mainly involved in cytoskeletal organization. A glyoxalase enzyme, caveolin 1, and HS90B were lower, and RAB8B and ATP6V1B1 were higher in lenses in women. Proteins with lower levels in cataractous lenses than in transparent lenses included filensin and phakinin, concurrent with previous publications, and LCTL, GDI, HSPB1, and EIF4A2, not reported before. Corticonuclear cataracts constituted the only group showing depletions in putatively protective proteins, while the cortical type was the least influenced. ANXA1 and DNHD1 positively, and TCPD, SEC14L2, and PRPS1 proteins negatively correlated with visual acuity. Conclusions: This study revealed cataract-related proteins concurrent with earlier studies and new ones hitherto unreported. Despite the low number of patients investigated, the results merit further research, as these new proteins are highly likely to be involved in cataractogenesis. Full article
(This article belongs to the Section Ophthalmology)
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24 pages, 9006 KB  
Article
X-Ray Exposure Induces Structural Changes in Human Breast Proteins
by Ren Jie Tuieng, Sarah H. Cartmell, Cliona C. Kirwan, Alexander Eckersley and Michael J. Sherratt
Int. J. Mol. Sci. 2025, 26(12), 5696; https://doi.org/10.3390/ijms26125696 - 13 Jun 2025
Viewed by 918
Abstract
During radiotherapy, X-rays can deliver significant doses of ionising radiation to both cancerous and healthy tissue, often leading to undesirable side effects that compromise patient outcomes. While the cellular effects of such therapeutic X-ray exposures are well studied, the impact on extracellular matrix [...] Read more.
During radiotherapy, X-rays can deliver significant doses of ionising radiation to both cancerous and healthy tissue, often leading to undesirable side effects that compromise patient outcomes. While the cellular effects of such therapeutic X-ray exposures are well studied, the impact on extracellular matrix (ECM) proteins remains poorly understood. This study characterises the response of ECM proteins, including the major tissue components collagen I and fibronectin (FN), to X-ray doses similar to those used in clinical practice (50 Gy, as employed in breast radiotherapy, and 100 Gy), using a combination of gel electrophoresis, biochemical assays, and mass spectrometry-based peptide location fingerprinting (PLF) analysis. In purified protein solutions, 50 Gy X-ray exposure led to the fragmentation of constituent collagen I α chains. Irradiation of purified plasma FN (pFN) induced localised changes in peptide yields (detected by liquid chromatography and tandem mass spectrometry (LC-MS/MS) and PLF) and enhanced its binding to collagen I. In complex environments, such as newly synthesised fibroblast-derived ECM and mature ex vivo breast tissue, X-ray exposure induced peptide yield changes in not only collagen I and FN but also key basement membrane proteins, including collagen IV, laminin, and perlecan. Intracellular proteins associated with gene expression (RPS3, MeCP2), the cytoskeleton (moesin, plectin), and the endoplasmic reticulum (calnexin) were also found to be impacted. These X-ray-induced structural changes may impair the ECM integrity and alter cell–ECM interactions, with potential implications for tissue stiffening, fibrosis, and impaired wound healing in irradiated tissues. Full article
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15 pages, 3055 KB  
Article
Ivermectin Attenuates Methotrexate-Induced Liver Fibrosis by Reducing TGF-β and Syndecan-1 Expression
by Cengiz Dibekoğlu, Kubilay Kemertaş, Hatice Aygun and Oytun Erbaş
Medicina 2025, 61(6), 1036; https://doi.org/10.3390/medicina61061036 - 4 Jun 2025
Cited by 1 | Viewed by 1850
Abstract
Background and Objectives: Methotrexate (MTX) is widely used in clinical settings but is often associated with hepatotoxic side effects, including oxidative stress, inflammation, and fibrosis. Novel therapeutic strategies are needed to mitigate MTX-induced liver injury. This study aimed to evaluate the hepatoprotective effects [...] Read more.
Background and Objectives: Methotrexate (MTX) is widely used in clinical settings but is often associated with hepatotoxic side effects, including oxidative stress, inflammation, and fibrosis. Novel therapeutic strategies are needed to mitigate MTX-induced liver injury. This study aimed to evaluate the hepatoprotective effects of ivermectin in a rat model of MTX-induced hepatotoxicity. Materials and Methods: Thirty male Wistar albino rats were randomly divided into three groups (n = 10 per group): control (saline only), MTX (single intraperitoneal dose of 20 mg/kg MTX), and MTX + ivermectin (20 mg/kg MTX + 0.5 mg/kg/day ivermectin for 10 days). At the end of the experiment, blood and liver tissues were collected for histopathological and biochemical evaluation, including ALT, malondialdehyde (MDA), TGF-β, and syndecan-1 levels. Results: MTX administration significantly increased plasma and hepatic MDA, TGF-β, syndecan-1, and ALT levels, alongside histological evidence of necrosis, fibrosis, and inflammatory infiltration (p < 0.001 vs. control). Ivermectin treatment significantly attenuated these alterations, with reductions in MDA (both plasma and liver), TGF-β, syndecan-1, and ALT levels (p < 0.05–0.001 vs. MTX). Histological scoring also revealed improved liver architecture and decreased necrosis, fibrosis, and leukocyte infiltration. Conclusions: Ivermectin demonstrates a strong hepatoprotective effect against MTX-induced liver injury, likely through antioxidant, anti-inflammatory, antifibrotic, and endothelial-protective mechanisms. These findings support the repurposing potential of ivermectin in mitigating drug-induced hepatic damage. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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31 pages, 2109 KB  
Systematic Review
Cardiometabolic Risk in Chronic Spinal Cord Injury: A Systematic Review with Meta-Analysis and Temporal and Geographical Trends
by Gary J. Farkas, Lizeth J. Caldera, Daniel D. Hodgkiss, Jessica R. Mitchell, Thomas F. Pelaez, Maxwell A. Cusnier, Alex J. Cole, Scott G. Daniel, Matthew T. Farrow, Cameron M. Gee, Eric A. Kincaid-Sharp, Andrew Malcolm Green Logan, David W. McMillan, Tom E. Nightingale, Brieanna Perdue, Pauline Portes, Francis T. Walson, Alyssa M. Volmrich, John M. Reynolds, Mark S. Nash, David R. Gater and Arthur S. Bergadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(9), 2872; https://doi.org/10.3390/jcm14092872 - 22 Apr 2025
Viewed by 1877
Abstract
Objectives: This systematic review with meta-analysis compared cardiometabolic syndrome (CMS) in adults with chronic (≥1 year) spinal cord injury (SCI) to non-SCI individuals (controls) and athletes, analyzing the effect of specific injury characteristics and exploring temporal and geographical trends. Methods: Ovid [...] Read more.
Objectives: This systematic review with meta-analysis compared cardiometabolic syndrome (CMS) in adults with chronic (≥1 year) spinal cord injury (SCI) to non-SCI individuals (controls) and athletes, analyzing the effect of specific injury characteristics and exploring temporal and geographical trends. Methods: Ovid Medline, Embase, Cochrane, CINAHL, Scopus, and Web of Science were searched from inception to September 2024. Adults with chronic SCI were included based on observational and baseline data derived from experimental studies. Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields assessed quality. Weighted means with 95% bootstrapped confidence intervals (CI) were computed for risk stratification. Group differences were assessed using random effects meta-analysis, calculating weighted mean differences with 95% bootstrapped CI. Temporal and geographical trends were evaluated with linear regression based on sample-size-weighted distributions and relevant covariates. Results: Of 31,163 identified records, 471 studies were included (n ≤ 31,782 SCI participants). CMS was present in men with SCI, paraplegia, tetraplegia, and injuries above T6; men with complete SCI (AIS A); and men and women with motor-complete SCI (AIS A–B). Compared to controls, adults with SCI had a lower body mass index (BMI), higher total and visceral fat, and worse lipid and carbohydrate profiles, including increased insulin resistance (IR). Tetraplegia was associated with greater visceral fat, poorer glycemic control, and lower BMI, insulin sensitivity, high-density lipoprotein-cholesterol (HDL-C), and triglycerides than paraplegia. Motor-complete SCI had lower BMI, HDL-C, and fasting glucose than motor-incomplete injuries. Injuries above T6 had lower blood pressure and higher fasting insulin levels than those below T6. Athletes with SCI had a lower BMI, fat mass, and fasting glucose, and higher systolic blood pressure than non-athletes with SCI, but frequently presented with obesity and carbohydrate dysfunction. Temporal analysis revealed increasing obesity trends and improved systolic blood pressure, while other CMS risk factors remained unchanged. We also identified global variations in obesity, lipids, blood pressure, and carbohydrate patterns. Conclusions: With a large sample, we revealed a widespread cardiometabolic burden in chronic SCI, even among athletes. Specifically, obesity, IR, and hypoalphalipoproteinemia worsened with increasing injury severity, alongside rising obesity trends and geographic disparities in risk profiles. These patterns highlight the evolution of what was deemed an epidemic into a global cardiometabolic pandemic. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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25 pages, 2471 KB  
Article
Pain Reduction with Repeated Injections of Botulinum Toxin A in Upper Limb Spasticity: A Longitudinal Analysis from the ULIS-III Study
by Lynne Turner-Stokes, Khan Buchwald, Stephen A. Ashford, Klemens Fheodoroff, Jorge Jacinto, Ajit Narayanan and Richard J. Siegert
Toxins 2025, 17(3), 117; https://doi.org/10.3390/toxins17030117 - 1 Mar 2025
Cited by 1 | Viewed by 1814
Abstract
Pain reduction is a common goal of the treatment of upper limb spasticity with botulinum toxin (BoNT-A). ULIS-III was a large international, observational, longitudinal study (N = 953) conducted in real-life clinical practice over two years. In this secondary post hoc analysis, we [...] Read more.
Pain reduction is a common goal of the treatment of upper limb spasticity with botulinum toxin (BoNT-A). ULIS-III was a large international, observational, longitudinal study (N = 953) conducted in real-life clinical practice over two years. In this secondary post hoc analysis, we examine whether goals for pain reduction were met over repeated injection cycles. We report serial changes in pain severity and explore predictors of pain reduction and injection frequency. Patients were selected if pain reduction was a primary/secondary goal for at least one cycle (n = 438/953). They were assessed at the start and end of each cycle using the goal attainment T-score alongside a self-report of pain severity (range 0–10). Across all cycles, pain-related goals were set for 1189/1838 injections (64.7%) and were achieved in 839 (70.6%). Patients continued to show a significant reduction in pain (p < 0.001) for each injection up to seven cycles, with some cumulative benefit (p < 0.001). Those requiring more frequent injections tended to have higher starting pain scores and a smaller reduction in pain score, but these differences were not significant when other covariates (age, previous injection history, time since onset, severity and distribution of spasticity) were taken into account (p > 0.713). Conclusion: Repeated BoNT-A administration continued to result in a significant reduction in upper limb spasticity-related pain, regardless of patient-related factors. Full article
(This article belongs to the Section Bacterial Toxins)
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10 pages, 503 KB  
Article
The Constancy of Perceived Motion Under Different Spectral Conditions
by Jeffrey Nightingale, James M. Brown and Billy R. Hammond
Vision 2025, 9(1), 15; https://doi.org/10.3390/vision9010015 - 22 Feb 2025
Cited by 1 | Viewed by 790
Abstract
(1) Background: Perceptual constancies are found in numerous categories of visual perception; color, lightness, and size constancy are notable examples where the perception of a visual scene remains constant, even with changing optical conditions. Constancies such as these are essential for survival, as [...] Read more.
(1) Background: Perceptual constancies are found in numerous categories of visual perception; color, lightness, and size constancy are notable examples where the perception of a visual scene remains constant, even with changing optical conditions. Constancies such as these are essential for survival, as they reduce the unpredictability of the world. In this study, we tested the resiliency of motion perception under widely differing spectral conditions. (2) Methods: Sixty healthy subjects (age range 18 to 26) were tested. Motion perception performance and thresholds were assessed using a novel, ecologically valid, psychophysical task implementing modern instruments. A broadband xenon bulb was used as a light source to emulate the spectral characteristics of natural daylight; 3 filter conditions were included to emulate different conditions of environmental light (short-wave, 400 nm–500 nm; medium-wave, 500 nm–600 nm; and long-wave, 600 nm–700 nm). (3) Results: In general, our findings showed that varying the spectral content of the broadband source did not change motion perception performance or thresholds for subjects. (4) Conclusions: These findings indicate that motion perception is highly resistant to changes in optical conditions, such as dramatically different spectral illuminants. This evidence is consistent with motion being considered among the perceptual constancies. Full article
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12 pages, 634 KB  
Article
Post-COVID-19 Condition Prediction in Hospitalised Cancer Patients: A Machine Learning-Based Approach
by Sara Mahvash Mohammadi, Mikhail Rumyantsev, Elina Abdeeva, Dina Baimukhambetova, Polina Bobkova, Yasmin El-Taravi, Maria Pikuza, Anastasia Trefilova, Aleksandr Zolotarev, Margarita Andreeva, Ekaterina Iakovleva, Nikolay Bulanov, Sergey Avdeev, Ekaterina Pazukhina, Alexey Zaikin, Valentina Kapustina, Victor Fomin, Andrey A. Svistunov, Peter Timashev, Nina Avdeenko, Yulia Ivanova, Lyudmila Fedorova, Elena Kondrikova, Irina Turina, Petr Glybochko, Denis Butnaru, Oleg Blyuss, Daniel Munblit and Sechenov StopCOVID Research Teamadd Show full author list remove Hide full author list
Cancers 2025, 17(4), 687; https://doi.org/10.3390/cancers17040687 - 18 Feb 2025
Viewed by 1441
Abstract
Background: The COVID-19 pandemic has led to widespread long-term complications, known as post-COVID conditions (PCC), particularly affecting vulnerable populations such as cancer patients. This study aims to predict the incidence of PCC in hospitalised cancer patients using the data from a longitudinal cohort [...] Read more.
Background: The COVID-19 pandemic has led to widespread long-term complications, known as post-COVID conditions (PCC), particularly affecting vulnerable populations such as cancer patients. This study aims to predict the incidence of PCC in hospitalised cancer patients using the data from a longitudinal cohort study conducted in four major university hospitals in Moscow, Russia. Methods: Clinical data have been collected during the acute phase and follow-ups at 6 and 12 months post-discharge. A total of 49 clinical features were evaluated, and machine learning classifiers including logistic regression, random forest, support vector machine (SVM), k-nearest neighbours (KNN), and neural network were applied to predict PCC. Results: Model performance was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. KNN demonstrated the highest predictive performance, with an AUC of 0.80, sensitivity of 0.73, and specificity of 0.69. Severe COVID-19 and pre-existing comorbidities were significant predictors of PCC. Conclusions: Machine learning models, particularly KNN, showed some promise in predicting PCC in cancer patients, offering the potential for early intervention and personalised care. These findings emphasise the importance of long-term monitoring for cancer patients recovering from COVID-19 to mitigate PCC impact. Full article
(This article belongs to the Collection The Impact of COVID-19 Infection in Cancer)
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