bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patellar Tendon Debridement and Reconstruction With Hamstring Tendon Autografts in the Setting of Severe Patellar Tendinopathy
Authors: Shoemaker Evan P. , Tollefson Luke V. , Slette Erik L. , LaPrade Robert F. 
Published: September 2024

Background: Patellar tendinopathy is a multifactorial condition characterized by micro-degenerative changes in the patellar tendon. This results from repeated stress to the knee extensor mechanism from explosive movement, axial malalignment, and/or abnormal patellar height. Currently, there is no standard surgical procedure for the treatment of severe patellar tendinopathy. Indications: Patellar tendon reconstructions for patellar tendinopathy may be indicated when >50% of the tendon attachment is degenerative and detached from the distal patella and non-operative treatment, like physical therapy, bracing, and injections, have not relieved symptoms. Debridement may not offer long-term viability against augmentation of the patellar tendon with autografts, with a risk of recurrent breakdown of the patellar tendon attachment with resumption of previous activities that initially lead to overload. Technique Description: An anterior incision was made from the superior pole of the patella to the tibial tubercle. Then, dissection was performed medially to harvest the gracilis and semitendinosus tendons. Open harvesters were used, and the hamstring tendons were released proximally, keeping the tibial insertions attached. A horizontal pin was drilled across the tibial tubercle and reamed with a 4.5 mm reamer. A passing stitch was fed through the tunnel. The proximal and distal margins of the patella were localized with spinal needles and a pin was drilled across its midportion, 5 mm deep to the dorsal cortical margin, and then rearmed. Degenerative tissue at the patellar tendon was excised. The gracilis tendon was passed medial to lateral through the tibial tubercle, and a Q-Fix anchor anchored the grafts medially and laterally. The semitendinosus graft was passed medial to lateral through the patella followed by the gracilis tendon lateral to medial. Appropriate reconstruction graft tension was confirmed and grafts were whipstitched together. Results: Clinical outcomes for the debridement of severe patellar tendinopathy report 77% symptomatic relief. With many unable to return to activity, patellar tendon reconstruction can be indicated. Outcomes for reconstructions for severe patellar tendinopathy are not reported. Discussion: Patellar tendon reconstruction with hamstring autografts for the treatment of severe patellar tendinopathy can provide a strong reconstruction graft to allow for the resumption of high-level activities. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Exploring the Potential to Identify Early Development Pre-Atherosclerotic Disease in Pediatric Carotid Arteries
Authors: Evans Kevin D. , Stephens Julie A. , Bradbury Peter , Bloom Isaiah W. , Stigall-Weikle Nicole , Khalsa Amrik Singh , Spees Colleen 
Published: September 2024

Objective: The aim of these analyses was to determine the potential development of increased carotid intima-media thickness (cIMT) and spectral Doppler velocity in a cohort of children who were eligible for federal nutrition support services. Materials and Methods: A secondary data analysis was conducted based on data collected during a larger randomized clinical trial. Data were pulled on 108 children, ages 8 to 11 years, who had both cIMT measures, as well as spectral Doppler data, at the level of measured intimae. Additional data such as vessel geometry, body mass index (BMI), and blood pressure (BP) were added to the analysis to provide additional descriptive data. Results: The posterior cIMT data provided the best visualization and measurements to assess the presence of early risk for atherosclerosis. In this cohort of 8- to 11-year-olds, the median spectral Doppler values did not exceed the published values for these ages, nor did their systolic blood pressure. In this group, 77 (71%) were classified as having a healthy BMI. However, the posterior cIMT data were compared to published measures of pediatric cIMT values and 60 children (55%) exceeded the expected mean thickness of 0.38 mm + 0.04 on the right and 58 (53%) on the left. Conclusion: The use of spectral Doppler to assess the risk of developing atherosclerosis may not be the best diagnostic tool, based on this cohort. The measurement of cIMT has the most promise to proper classify healthy appearing 8- to 11-year-olds, for early signs of diminished cardiovascular health.
Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study
Authors: Chalmers James D. , Shteinberg Michal , Mall Marcus A. , O'Donnell Anne E. , Watz Henrik , Gupta Abhya , Frahm Edith , Eleftheraki Anastasia , Rauch Johanna , Chotirmall Sanjay H. , Armstrong April W. , Eickholz Peter , Hasegawa Naoki , Sauter Wiebke , McShane Pamela J. 
Published: September 2024

BackgroundBronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil-mediated lung damage. This phase II, randomised, double-blind, placebo-controlled trial (AIRLEAF®; clinicaltrials.gov identifierNCT05238675) evaluated efficacy, safety and optimal dosing of BI 1291583, a novel, reversible CatC inhibitor, in adults with bronchiectasis.MethodsIn total, 322 participants were randomised (2:1:1:2) to receive one of three oral doses of BI 1291583 (1 mg/2.5 mg/5 mg) or placebo for 24–48 weeks. A multiple comparison procedure and modelling approach was used to demonstrate a nonflat dose–response curve based on the time to first pulmonary exacerbation up to week 48. In addition, efficacy of individual BI 1291583 doses was evaluated based on the frequency of exacerbations, severe exacerbations (fatal or leading to hospitalisation and/or intravenous antibiotic administration), lung function and quality of life.ResultsA significant dose-dependent benefit of BI 1291583 over placebo was established based on time to first exacerbation (shape: maximum effect curve 1; adjusted p=0.0448). Treatment with BI 1291583 5 mg and 2.5 mg numerically reduced the risk of an exacerbation compared with placebo (hazard ratio (95% CI) 0.71 (0.48 to 1.05) and 0.66 (0.40 to 1.08), respectively; both p>0.05). BI 1291583 2.5 mg showed numerically better efficacy compared with 5 mg across several end-points; 1 mg was similar to placebo. The safety profile of BI 1291583 was similar to placebo.ConclusionTreatment with BI 1291583 resulted in a reduction in the risk of experiencing an exacerbation in adults with bronchiectasis.
IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages
Authors: Lee Sung Woo , Kim Soyoon , Kim Bokyung , Seong Jung Bae , Park Young-Ho , Lee Hong Jun , Choi Dong Kyu , Yeom Eunbyul , Lee Dong-Seok 
Published: September 2024

Abstract
Background
Targeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown.

Methods
In this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified.

Results
IDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial–mesenchymal transition.

Conclusions
Our findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research.
MicroRNAs in metabolism for precision treatment of lung cancer
Authors: Carrà Giovanna , Petiti Jessica , Tolino Federico , Vacca Rita , Orso Francesca 
Published: September 2024

AbstractThe dysregulation of miRNAs in lung cancer has been extensively documented, with specific miRNAs acting as both tumor suppressors and oncogenes, depending on their target genes. Recent research has unveiled the regulatory roles of miRNAs in key metabolic pathways, such as glycolysis, the tricarboxylic acid cycle, fatty acid metabolism, and autophagy, which collectively contribute to the aberrant energy metabolism characteristic of cancer cells. Furthermore, miRNAs are increasingly recognized as critical modulators of the tumor microenvironment, impacting immune response and angiogenesis. This review embarks on a comprehensive journey into the world of miRNAs, unraveling their multifaceted roles, and more notably, their emerging significance in the context of cancer, with a particular focus on lung cancer. As we navigate this extensive terrain, we will explore the fascinating realm of miRNA-mediated metabolic rewiring, a phenomenon that plays a pivotal role in the progression of lung cancer and holds promise in the development of novel therapeutic strategies.
Estimates of eskd risk and timely kidney replacement therapy education
Authors: Haggerty Lauren E. , Rifkin Dena E. , Nguyen Hoang Anh , Abdelmalek Joseph A. , Sweiss Natalie , Miller Lindsay M. , Potok O. Alison 
Published: September 2024

Abstract
Background
Kidney replacement therapy (KRT) needs preparation and its timing is difficult to predict. Nephrologists’ predictions of kidney failure risk tend to be more pessimistic than the Kidney Failure Risk Equation (KFRE) predictions. We aimed to explore how physicians’ risk estimate related to referral to KRT education, vs. the objective calculated KFRE.

Methods
Prospective observational study of data collected in chronic kidney disease (CKD) clinics of the Veterans Affairs Medical Center San Diego and the University of California, San Diego. The study included 257 participants who were aged 18 years or older, English speaking, prevalent CKD clinic patients, with estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 (MDRD equation). The exposure consisted of end stage kidney disease (ESKD) risk predictions. Nephrologists’ kidney failure risk estimations were assessed: “On a scale of 0–100%, without using any estimating equations, give your best estimate of the risk that this patient will need dialysis or a kidney transplant in 2 years.” KFRE was calculated using age, sex, eGFR, serum bicarbonate, albumin, calcium, phosphorus, urine albumin/creatinine ratio. The outcomes were the pattern of referral to KRT education (within 90 days of initial visit) and kidney failure evaluated by chart review. The population was divided into groups either by nephrologists’ predictions or by KFRE. Referral to KRT education was examined by group and sensitivity and specificity were calculated based on whether participants reached kidney failure at 2 years.

Results
A fifth were referred for education by 90 days of enrollment. Low risk patients by both estimates had low referral rates. In those with nephrologists’ predictions ≥ 15% (n = 137), sensitivity was 71% and specificity 76%. In those with KFRE ≥ 15% (n = 55), sensitivity was 85% and specificity 41%.

Conclusions
Although nephrologists tend to overestimate patients’ kidney failure risk, they do not appear to act on this overestimation, as the rates of KRT education referrals are lower than expected when a nephrologist identifies a patient as high risk.

Clinical Trial Number
Not applicable
Family member reported symptom burden, predictors of caregiver burden and treatment effects in a goal-oriented community-based randomized controlled trial in the chronic phase of traumatic brain injury
Authors: Løvstad Marianne , Borgen Ida Maria Henriksen , Hauger Solveig Lægreid , Kleffelgård Ingerid , Brunborg Cathrine , Røe Cecilie , Søberg Helene Lundgaard , Forslund Marit Vindal 
Published: September 2024

Abstract
Background
Family members are often affected by the long-term consequences of traumatic brain injury, but are rarely involved in rehabilitation programs in the chronic phase. We thus do not know what family members´ main concerns are in the chronic phase, what factors are associated with perceived caregiver burden, and whether family members´ health and functioning improves due to rehabilitation efforts received by the patients. This study explored family-members` functioning, predictors of caregiver burden and effect for family members of a goal-oriented intervention in the chronic phase of traumatic brain injury.

Methods
Family members self-reported data measuring their caregiver burden, depression, general health, loneliness, and their evaluation of patient competency in everyday life, patient awareness levels, main problem areas (target outcomes) for the patient related to the brain injury, and demographic data were collected. Regression models were used to explore predictors of caregiver burden, and mixed models analysis was used to explore treatment effects.

Results
In total, 73 family members were included, 39 in the intervention group and 34 in the control group. Moderate to high caregiver burden was reported by 40% of family members, and 16% experienced clinical levels of depression. Family member loneliness and their evaluation of the patient`s level of functional competency explained 57% of the variability in caregiver burden. There were no treatment-related changes in caregiver burden, family member depression or general health. At T2 there was however a significant reduction in how family members rated severity of target outcomes that the family members had nominated at baseline (-0.38, 95% CI, -0.75 to -0.02, p = 0.04), but not for the target outcomes the patients had nominated.

Conclusions
A significant proportion of family members to patients in the chronic phase of TBI continue to experience challenging caregiver burden and emotional symptoms. Both family member-related and patient factors contribute to caregiver burden. Interventions targeting patient complaints do not automatically alleviate family members´ burden. It is important to address social support for family members early after injury, and there is a need for more interventions specifically targeting family members´ needs.

Trial registration
The trial was registered at ClinicalTrials.gov, NCT03545594 on the 4th of June 2018.
Prediction of poststroke independent walking using machine learning: a retrospective study
Authors: Tang Zhiqing , Su Wenlong , Liu Tianhao , Lu Haitao , Liu Ying , Li Hui , Han Kaiyue , Moneruzzaman Md. , Long Junzi , Liao Xingxing , Zhang Xiaonian , Shan Lei , Zhang Hao 
Published: September 2024

Abstract
Background
Accurately predicting the walking independence of stroke patients is important. Our objective was to determine and compare the performance of logistic regression (LR) and three machine learning models (eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Random Forest (RF)) in predicting walking independence at discharge in stroke patients, as well as to explore the variables that predict prognosis.

Methods
778 (80% for the training set and 20% for the test set) stroke patients admitted to China Rehabilitation Research Center between February 2020 and January 2023 were retrospectively included. The training set was used for training models. The test set was used to validate and compare the performance of the four models in terms of area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score.

Results
Among the three ML models, the AUC of the XGBoost model is significantly higher than that of the SVM and RF models (P < 0.001, P = 0.024, respectively). There was no significant difference in the AUCs between the XGBoost model and the LR model (0.891 vs. 0.880, P = 0.560). The XGBoost model demonstrated superior accuracy (87.82% vs. 86.54%), sensitivity (50.00% vs. 39.39%), PPV (73.68% vs. 73.33%), NPV (89.78% vs. 87.94%), and F1 score (59.57% vs. 51.16%), with only slightly lower specificity (96.09% vs. 96.88%). Together, the XGBoost model and the stepwise LR model identified age, FMA-LE at admission, FAC at admission, and lower limb spasticity as key factors influencing independent walking.

Conclusion
Overall, the XGBoost model performed best in predicting independent walking after stroke. The XGBoost and LR models together confirm that age, admission FMA-LE, admission FAC, and lower extremity spasticity are the key factors influencing independent walking in stroke patients at hospital discharge.

Trial registration
Not applicable.
PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study
Authors: Ballé Judith Katharina , Vetter Martina , Kenea Tariku Wakuma , Eber-Schulz Pia , Reibold Christian , Ziegenhorn Hannes-Viktor , Stückrath Kathrin , Wickenhauser Claudia , Addissie Adamu , Santos Pablo , Kantelhardt Eva Johanna , Getachew Sefonias , Bauer Marcus 
Published: September 2024

Abstract
Purpose
Survival rates of breast cancer (BC) patients are particularly low in rural regions in sub-Saharan Africa (SSA) which is due to limited access to therapy. In recent years, gene expression profiling (GEP) of BC showed a strong prognostic value in patients with local tumour surgery and (neo)adjuvant treatment. The aim of this study was to evaluate the impact of intrinsic subtypes on survival of patients in rural Ethiopia without any (neo)adjuvant therapy.

Methods
In total, 113 female patients from Aira Hospital with histologically proven BC and treated only with surgery were included in this study. All samples were analysed by immunohistochemistry (IHC) for estrogen receptor, progesterone receptor, HER2 and Ki67, as well as RNA-expression analysis for PAM50 subtyping.

Results
A positive hormone receptor status was found in 69.0% of the tumours and intrinsic subtyping demonstrated Luminal B to be the most common subtype (34.5%). Follow-up data was available for 79 of 113 patients. Two-year overall survival (OS) was 57.3% and a considerably worse OS was observed in patients with Basal-like BC compared to Luminal A BC. Moreover, advanced tumours showed an increased risk of mortality.

Conclusion
The OS was very low in the patient cohort that received no (neo)adjuvant treatment. Immunohistochemistry and GEP confirmed endocrine-sensitive tumours in more than half of the patients, with a large proportion of Luminal B, HER2-enriched and Basal-like tumours so that adjuvant chemotherapy should be recommended.
Interdisciplinary CBT treatment for patients with odontophobia and dental anxiety related to psychological trauma experiences: a case series
Authors: Westad Yngvill Ane Stokke , Flemmen Gina Løge , Solem Stian , Monsen Trine , Hollingen Henriette , Feuerherm Astrid , Havnen Audun , Hagen Kristen 
Published: September 2024

Abstract
Background
While cognitive-behavioural therapy (CBT) is a well-established treatment for odontophobia, research is sparse regarding its effect on patients with dental anxiety related to psychological trauma experiences. This study aimed to evaluate changes in symptoms and acceptability of interdisciplinary Torture, Abuse, and Dental Anxiety (TADA) team treatment for patients with odontophobia or dental anxiety. We also wanted to describe the sample’s oral health status. The TADA teams offer targeted anxiety treatment and adapted dental treatment using a CBT approach.

Methods
The study used a naturalistic, case series design and included 20 consecutively referred outpatients at a public TADA dental clinic. Pre- and post-treatment assessments included questionnaires related to the degree of dental anxiety, post-traumatic stress, generalized anxiety, and depression. Patients underwent a panoramic X-ray before treatment. Before dental restoration, patients underwent an oral health examination to determine the mucosal and plaque score (MPS) and the total number of decayed, missing, and filled teeth (DMFT). Patients were referred to dentist teams for further dental treatment and rehabilitation (phase 2) after completing CBT in the TADA team (Phase 1). Results from the dental treatment in phase 2 is not included in this study.

Results
All patients completed the CBT treatment. There were significant improvements in symptoms of dental anxiety, post-traumatic stress, and depression and moderate changes in symptoms of generalized anxiety. Dental statuses were heterogeneous in terms of the severity and accumulated dental treatment needs. The TADA population represented the lower socioeconomic range; 15% of patients had higher education levels, and half received social security benefits. All patients were referred to and started adapted dental treatment (phase 2).

Conclusions
TADA treatment approach appears acceptable and potentially beneficial for patients with odontophobia and dental anxiety related to psychological trauma experiences. The findings suggest that further research, including larger controlled studies, is warranted to validate these preliminary outcomes.

Trial registration
The study was approved by the regional ethical committee in Norway (REK-Midt: 488462) and by the Data Protection Board at Møre and Romsdal County Authority.
Current landscape of mRNA technologies and delivery systems for new modality therapeutics
Authors: Lu Ruei-Min , Hsu Hsiang-En , Perez Ser John Lynon P. , Kumari Monika , Chen Guan-Hong , Hong Ming-Hsiang , Lin Yin-Shiou , Liu Ching-Hang , Ko Shih-Han , Concio Christian Angelo P. , Su Yi-Jen , Chang Yi-Han , Li Wen-Shan , Wu Han-Chung 
Published: September 2024

AbstractRealizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases.