bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of Urinary C-terminal Telopeptide of Type II Collagen and its Correlation with Radiological Grading, Pain, and Function in Patients with Primary Osteoarthritis of the Knee
Authors: Nongmaithem Romi Singh , Lisham Ranjankumar Singh , Jotin Yengkhom , Shahin Kannamthodi Erumbanottil , Obit Jerang 
Published: March 2024

Objective: To estimate the level of urinary C-terminal telopeptide of type II collagen (uCTX-II) as a biomarker of cartilage turnover and to determine its correlation with radiological grading, pain, and functions of patients with knee osteoarthritis (OA). Methods: A descriptive cross-sectional study was conducted between September 2017 and August 2019 on 102 patients suffering from knee OA. Detailed demographic data were collected. uCTX-II level was measured for each patient. Radiological grading, pain and functional assessments were performed using Kellgren-Lawrence (K-L) grading, visual analogue scale (VAS), and Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC). Results: The mean age of 62.3 (6.4) years and most patients (n = 56, 54.9%) were 61–70 years old. Females constituted 80.4% (n = 82). Among the occupations, housewives were more affected (55.9%, n = 57). Out of 102 patients, 32 (31.4%) had VAS pain 4, 25 (24.5%) had 5 and 45 (44.1%) had 6; 9 (8.8%) had K-L score 1, 51 (50%) had 2, 41 (40.2%) had 3 and 1 (1%) had 4; 35(34.3%) had WOMAC score <30, 59 (57.8%) had 30–40, and 8 (7.8%) had >40; 55 ( 53.9%) had uCTX-II level <50 ng/mmole, 25 (24.5%) had between 50 and 200 ng/mmole and 22 (21.6%) had >200 ng/mmole. There was a positive correlation between uCTX-II and WOMAC ( P = .006) and VAS ( P = .042). Conclusion: The present study findings highlighted that higher levels of uCTX-II were associated with higher levels of pain and greater difficulty with daily activities (measured by WOMAC disability score). This suggests that uCTX-II could be a useful biomarker for monitoring cartilage turnover in patients with knee OA and its relationship with pain and functional abilities.
Help-seeking experiences and intimate partner support in vulvodynia: A qualitative exploration
Authors: Lountzi Athina Zoi , Durand Hannah 
Published: March 2024

Background: Vulvodynia is a poorly understood chronic pain condition characterized by persistent and unexplained pain in the vulva. Given the intimate nature of the pain, partners may play an important role in promoting self-management and help-seeking behaviours among women with vulvodynia. Objectives: The current study aimed to explore the role of partner support in pain experiences and help-seeking behaviours among women with vulvodynia. Design: A qualitative interpretive design was used. Methods: Ten women with vulvodynia ( M age = 37.9 years) were interviewed using a semi-structured non-directive topic guide. Data were analysed using reflexive thematic analysis. Results: Three themes around help-seeking experiences were constructed from the data: (1) ‘It’s Been a Battle’ – Failed by the Healthcare System; (2) ‘It’s Just the Vulva’ – Dismissed by Healthcare Professionals; and (3) ‘I Diagnosed Myself’ – The Patient Becomes the Expert. Participants described negative help-seeking experiences characterized by long delays to diagnosis, lack of awareness and understanding from healthcare professionals, minimization of symptoms, and having to advocate for and demand care. A further three themes pertaining to partner support were also developed: (1) ‘That Person to Listen to You’ – Source of Emotional Support; (2) ‘Why Don’t You Try This?’ – Finding Solutions Together; and (3) ‘He Forgets that it’s Still There’ – Vulvodynia is a Foreign Concept. Partners provided emotional support and showed empathy and understanding, and practical support by accompanying women to medical appointments and help with pain management. However, participants felt partners’ understanding of vulvodynia was limited and that this impacted their relationships. Conclusions: Findings highlight a lack of continuity of care and multidisciplinary approach to treatment, with help-seeking experiences being mainly negative in this sample. Increasing public awareness of vulvodynia and improving healthcare access is crucial to improving physical and psychological outcomes for this group. Partners can play an important role in supporting people with vulvodynia; however, other outlets of support should be further explored.
Perceived burden of respiratory physiotherapy in people with cystic fibrosis taking elexacaftor–tezacaftor–ivacaftor combination: a 1-year observational study
Authors: Blardone Chiara , Gambazza Simone , Mariani Alessandra , Galgani Rachele , Brivio Anna , Nobili Rita Maria , Rizza Carmela , Tutino Anna Luisa , Gramegna Andrea , Daccò Valeria , Contarini Martina , Blasi Francesco , Laquintana Dario 
Published: March 2024

Background: To limit the progression of disease, people with cystic fibrosis (pwCF) perform daily respiratory physiotherapy, which is perceived as the most burdensome routine in managing their condition. The elexacaftor–tezacaftor–ivacaftor (ETI) combination has changed respiratory management. Objective: To investigate how the perceived treatment burden changed in 1 year of treatment with ETI. Design: Prospective observational study. Methods: Ad hoc questionnaires for the pwCF and for the caregivers of pwCF < 18 years were administered before the initiation of ETI therapy and then at 6–12 months. The Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the Sinonasal Outcome Test (SNOT-22) were administered to explore disease-related symptoms and social limitations. The International Physical Activity Questionnaire was used to determine levels of physical activity. Mixed-effect models were fitted to explore whether the time engaged in respiratory physiotherapy changed during 1 year. Results: The study included 47/184 pwCF aged 21.4 (5.7) years, who completed 1 year of ETI therapy. At 6 months, time on aerosol therapy was decreased by 2.5 (95% CI −32.9 to 27.8) min/day, time on airway clearance therapies (ACTs) was decreased by 8.8 (95% CI −25.9 to 8.3) min/day, and time for cleaning and disinfecting respiratory equipment was decreased by 10.6 (95% CI −26.5 to 5.3) min/day. At 1 year, gains in time saved were nearly 15 min/day on average. At 1 year, 5/47 (10.6%) pwCF reported that they had discontinued positive expiratory pressure mask. Conclusion: PwCF on ETI may note less time engaged in their daily respiratory physiotherapy routine. Nonetheless, aerosol therapy, ACTs and maintaining respiratory equipment were still perceived as time-consuming daily activities.
The association between gout flares and monosodium urate burden assessed using musculoskeletal ultrasound in patients with gout
Authors: Yang Shaoling , Lin Xiaojing , Gao Yining , Liang Nan , Han Yali , Sun Hang , Qu Shen , Chen Haibing 
Published: March 2024

Background: Ultrasound (US) has a high sensitivity in detecting monosodium urate (MSU) deposition in gout patients. However, the value of US in predicting gout flares has been reported only in a few monocentric studies. Objective: To investigate the association between gout flares in the previous year and US-detected MSU burden using two different US scores. Design: A retrospective study. Methods: Patients with gout were consecutively recruited to undergo musculoskeletal US examinations of their knees, ankles, and feet. The score derived from Outcome Measure in Rheumatology (hereinafter referred to as MSU score) and musculoskeletal US features-based (hereinafter referred to as MSKF score) were used to quantify the MSU burden of gout. Odds ratios for frequent gout flares were calculated. Results: We enrolled 1894 patients with gout (mean age: 45 years; gout duration: 5 years; males: 96.1%), experiencing a median of three flares over the past year. Of these, 428 (22.6%) patients reported frequent (⩾7) gout flares. The MSU and MSKF median scores were 6 and 9, respectively. For each five-point increase in MSU and MSKF score, the odds ratio of frequent gout flares increased 1.13-fold and 1.24-fold, respectively. The area under the curve (AUC) for the MSU and MSKF score was 0.635 [95% confidence interval (CI): 0.604–0.665] and 0.688 (95% CI: 0.659–0.718), respectively, (AUC difference 0.054, p value for AUC difference < 0.001). Conclusion: The MSU and MSKF scores were significantly associated with the number of gout flares in the previous year. The MSKF score outperformed the MSU score in terms of frequent gout flare discrimination.
Significant Clinical Improvement After Arthroscopic Autologous Matrix-Induced Chondrogenesis for Osteochondral Lesions of the Talus: A 5-Year Follow-Up
Authors: Efrima Ben , Barbero Agustin , Maccario Camilla , Indino Cristian , Nocera Chiara , Albagli Assaf , Dahmen Jari , Usuelli Federico Giuseppe 
Published: March 2024

Purpose This study aims to evaluate the clinical outcomes of arthroscopic autologous matrix-induced chondrogenesis (A-AMIC) for osteochondral lesions of the talus (OLT) at 24 months and 60 months of follow-up. The secondary aim was to assess whether age, body mass index (BMI), and lesion surface affect outcomes. Design Sixty-three patients (32 males, 31 females) with a median age of 37 years [interquartile range (IQR): 25-48] were included. Preoperative and postoperative (24 months and 60 months) clinical outcomes were evaluated using a Visual Analog Score (VAS) for pain during walking, the American Orthopaedic Foot and Ankle Society (AOFAS), Short-Form Survey (SF-12), the Halasi, and the University of California, Los Angeles (UCLA) scores. Patients were categorized according to age, BMI, and lesion surface (1-1.5 cm2 and over 1.5 cm2). The effect of each category was evaluated. Results There were significant improvements in the VAS, AOFAS, SF-12, and UCLA, comparing the preoperative scores to the 60-month follow-up scores ( P < 0.001). There were no significant differences in the above-mentioned outcomes between the follow-up periods. Patients older than 33 years had lower SF-12, Halasi, and UCLA scores ( P = 0.005, 0.004, and <0.001, respectively). Overweight patients had lower VAS, SF-12, Halasi, and UCLA scores ( P = 0.006, 0.002, 0.024, and 0.007, respectively). Lesion size was uninfluential. Conclusion A-AMIC yielded clinical improvements at a minimum follow-up of 60 months in patients with symptomatic OLTs, with clinical improvement peaking in the first 2 years, followed by a plateau period. Increased age and BMI were significantly associated with inferior outcomes.
Dynamic shifts in lung cytokine patterns in post-COVID-19 interstitial lung disease patients: a pilot study
Authors: Oatis Daniela , Herman Hildegard , Balta Cornel , Ciceu Alina , Simon-Repolski Erika , Mihu Alin Gabriel , Lepre Caterina Claudia , Russo Marina , Trotta Maria Consiglia , Gravina Antonietta Gerarda , D’Amico Michele , Hermenean Anca 
Published: March 2024

Introduction: The pathogenesis of post-COVID interstitial lung disease, marked by lung tissue scarring and functional decline, remains largely unknown. Objectives: We aimed to elucidate the temporal cytokine/chemokine changes in bronchoalveolar lavage (BAL) from patients with post-COVID interstitial lung disease to uncover potential immune drivers of pulmonary complications. Design: We evaluated 16 females diagnosed with post-COVID interstitial lung disease, originating from moderate to severe cases during the second epidemic wave in the Autumn of 2020, treated at the Pneumology Department of the Arad County Clinical Hospital, Romania. Their inflammatory response over time was compared to a control group. Methods: A total of 48 BAL samples were collected over three intervals (1, 3, and 6 months) and underwent cytology, gene, and protein expression analyses for pro/anti-inflammatory lung cytokines and chemokines using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results: One month after infection, there were significant increases in the levels of IL-6 and IL-8. These levels decreased gradually over the course of 6 months but were still higher than those seen in control. Interferon-gamma and tumor necrosis factor alpha exhibited similar patterns. Persistent elevations were found in IL-10, IL-13, and pro-fibrotic M2 macrophages’ chemokines (CCL13 and CCL18) for 6 months. Furthermore, pronounced neutrophilia was observed at 1 month post-COVID, highlighting persistent inflammation and lung damage. Neutrophil efferocytosis, aiding inflammation resolution and tissue repair, was evident at the 1-month time interval. A notable time-dependent reduction in CD28 was also noticed. Conclusion: Our research provides insight into the immunological processes that may lead to the fibrotic changes noted in the lungs following COVID-19.
Participatory development of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED)
Authors: Novak Jan , Jurkova Katerina , Lojkaskova Anna , Jaklova Andrea , Kuhnova Jitka , Pfeiferova Marketa , Kral Norbert , Janek Michael , Omcirk Dan , Malisova Katerina , Maes Iris , Dyck Delfien Van , Wahlich Charlotte , Ussher Michael , Elavsky Steriani , Cimler Richard , Pelclova Jana , Tufano James J. , Steffl Michal , Seifert Bohumil , Yates Tom , Harris Tess , Vetrovsky Tomas 
Published: March 2024

Abstract
Background
The escalating global prevalence of type 2 diabetes and prediabetes presents a major public health challenge. Physical activity plays a critical role in managing (pre)diabetes; however, adherence to physical activity recommendations remains low. The ENERGISED trial was designed to address these challenges by integrating mHealth tools into the routine practice of general practitioners, aiming for a significant, scalable impact in (pre)diabetes patient care through increased physical activity and reduced sedentary behaviour.

Methods
The mHealth intervention for the ENERGISED trial was developed according to the mHealth development and evaluation framework, which includes the active participation of (pre)diabetes patients. This iterative process encompasses four sequential phases: (a) conceptualisation to identify key aspects of the intervention; (b) formative research including two focus groups with (pre)diabetes patients (n = 14) to tailor the intervention to the needs and preferences of the target population; (c) pre-testing using think-aloud patient interviews (n = 7) to optimise the intervention components; and (d) piloting (n = 10) to refine the intervention to its final form.

Results
The final intervention comprises six types of text messages, each embodying different behaviour change techniques. Some of the messages, such as those providing interim reviews of the patients’ weekly step goal or feedback on their weekly performance, are delivered at fixed times of the week. Others are triggered just in time by specific physical behaviour events as detected by the Fitbit activity tracker: for example, prompts to increase walking pace are triggered after 5 min of continuous walking; and prompts to interrupt sitting following 30 min of uninterrupted sitting. For patients without a smartphone or reliable internet connection, the intervention is adapted to ensure inclusivity. Patients receive on average three to six messages per week for 12 months. During the first six months, the text messaging is supplemented with monthly phone counselling to enable personalisation of the intervention, assistance with technical issues, and enhancement of adherence.

Conclusions
The participatory development of the ENERGISED mHealth intervention, incorporating just-in-time prompts, has the potential to significantly enhance the capacity of general practitioners for personalised behavioural counselling on physical activity in (pre)diabetes patients, with implications for broader applications in primary care.
KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway
Authors: Ye Longwei , Yu Zeqin , He Lin , Yuan Jie , Zhang Xiaodan , Li Lei , Huang Xin , Ma Yanyan , Zhang Lei 
Published: March 2024

Abstract
Background
Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs.

Methods
DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins.

Results
The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation.

Conclusion
KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.
Influence of implant distribution on the biomechanical behaviors of mandibular implant-retained overdentures: a three-dimensional finite element analysis
Authors: Liao Xiaoling , Cao Ruitao , Zhong Juan , Chen Chunxia , Pan Shaoxia 
Published: March 2024

Abstract
Objective
To assess stress distribution in peri-implant bone and attachments of mandibular overdentures retained by small diameter implants, and to explore the impact of implant distribution on denture stability.

Methods
Through three-dimensional Finite Element Analysis (3D FEA), four models were established: three models of a two mandibular implants retained overdenture (IOD) and one model of a conventional complete denture (CD). The three IOD models consisted of one with two implants in the bilateral canine area, another with implants in the bilateral lateral incisor area, and the third with one implant in the canine area, and another in the lateral incisor area. Three types of loads were applied on the overdenture for each model: a 100 N vertical load and a inclined load on the left first molar, and a100N vertical load on the lower incisors. The stress distribution in the peri-implant bone, attachments, and the biomechanical behaviors of the overdentures were analyzed.

Results
Despite different distribution of implants, the maximum stress values in peri-implant bone remained within the physiological threshold for all models across three loading conditions. The dispersed implant distribution design (implant in the canine area) exhibited the highest maximum stress in peri-implant bone (822.8 µe) and the attachments (275 MPa) among the three IOD models. The CD model demonstrated highest peak pressure on mucosa under three loading conditions (0.8188 Mpa). The contact area between the denture and mucosa of the CD model was smaller than that in the IOD models under molar loading, yet it was larger in the CD model compared to the IOD model under anterior loading. However, the contact area between the denture and mucosa under anterior loading in all models was significantly smaller than those under molar loading. The IOD in all three models exhibited significantly less rotational movement than the complete denture. Different implant positions had minimal impact on the rotational movement of the IOD.

Conclusion
IOD with implants in canine area exhibited the highest maximum stress in the peri-implant bone and attachments, and demonstrated increased rotational movement. The maximum principal stress was concentrated around the neck of the small diameter one-piece implant, rather than in the abutment. An overdenture retained by two implants showed better stability than a complete denture.
Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study
Authors: Lu Lifei , Wu Fan , Peng Jieqi , Wu Xiaohui , Hou Xiangqing , Zheng Youlan , Yang Huajing , Deng Zhishan , Dai Cuiqiong , Zhao Ningning , Zhou Kunning , Wan Qi , Tang Gaoying , Cui Jiangyu , Yu Shuqing , Luo Xiangwen , Yang Changli , Chen Shengtang , Ran Pixin , Zhou Yumin 
Published: March 2024

Abstract
Background
The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR.

Methods
Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ − 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ − 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model.

Results
This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up.

Conclusions
The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.