bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of the Menstrual Cycle and Training on the Performance of a Perturbed Single-Leg Squatting Task in Female Collegiate Athletes
Authors: Johnson Kristin A. , Shields Richard K. 
Published: June 2024

Background: Anterior cruciate ligament (ACL) injuries often occur when an athlete experiences an unexpected disruption, or perturbation, during sports. ACL injury rates may also be influenced by the menstrual cycle. Purpose: To determine whether training adaptations to knee control and muscle activity during a perturbed single-leg squatting (SLS) task depend on menstrual cycle phase in female athletes. Study Design: Controlled laboratory study. Methods: A total of 21 healthy female collegiate athletes (current or former [<3 years]) who competed in 9 different sports performed an SLS task in which they attempted to match their knee position (user signal) to a target signal. The protocol consisted of a 9-condition pretest, 5 sets of 3 training trials, and a 9-condition posttest. One perturbation was delivered in each condition by altering the resistance of the device. Sagittal knee control (absolute error between the target signal and user signal) was assessed using a potentiometer. Muscle activity during perturbed squat cycles was normalized to maximal activation and to corresponding muscle activity during unperturbed squat cycles (%unperturbed) within the same test condition. Athletes performed the protocol during a distinct menstrual cycle phase (early follicular [EF], late follicular [LF], midluteal [ML]). Two-way mixed analysis of variance was used to determine the effects of the menstrual cycle and training on knee control and muscle activity during task performance. Venous blood was collected for hormonal analysis, and a series of health questionnaires and anthropometric measures were also assessed to determine differences among the menstrual cycle groups. Results: After training, athletes demonstrated better knee control during the perturbed squat cycles (lower absolute error, P < .001) and greater soleus feedback responses to the perturbation (%unperturbed, P = .035). Better knee control was demonstrated in the ML phase versus the EF phase during unperturbed and perturbed squat cycles ( P < .039 for both). Quadriceps activation was greater in the ML phase compared with the EF and LF phases, both immediately before and after the perturbation ( P < .001 for all). Conclusion: Athletes learned to improve knee control during the perturbed performance regardless of menstrual cycle phase. The best knee control and greatest quadriceps activation during the perturbed squatting task was found in the ML phase. Clinical Relevance: These findings may correspond to a lower incidence of ACL injury in the luteal phase and alterations in exercise performance across the menstrual cycle.
The Buford Complex Redefined: A Pathologic Morphology in Sheep's Clothing
Authors: Scott Jasmine A. , Dwek Jerry R. , Cheng Karen Y. , Bryan Tracey P. , Edmonds Eric W. 
Published: June 2024

Background: Considered a normal anatomic variant, the Buford complex has not been studied in children. Hypothesis: A Buford complex is not a normal anatomic variant and would, therefore, be present at a lower rate than that seen in the adult population. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Measurements were recorded from magnetic resonance imaging performed over 13 years in children aged ≤11 years for various pathologies unrelated to glenohumeral instability. Interrater reliability was determined to identify Buford complexes, sublabral foramens and tears, and normal shoulders via 16 preadolescent and adolescent patients with confirmed arthroscopic correlation. The Buford complex and labral foramen rates were then compared with a published rate in adults using a binomial probability test. Results: A total of 122 children (62 girls; mean age, 6.4 years [age range, 2 months-10.9 years]) were evaluated. Interrater reliability was 0.846 (95% CI, 0.56-1) to identify anterosuperior labral variants. The expected sublabral foramen count was 23 children, but only 1 was identified ( P < .001). The expected Buford complex count was 8 children, but none could be identified ( P < .001). Conclusion: The absence of Buford complexes and the significant reduction in sublabral foramen abundance in younger children suggest that these anatomic variants are more likely to be developmental than congenital. The distinct possibility that these previously considered normal variants are truly pathologic findings cannot be ignored. Evidence of a Buford complex could potentially signify an underlying, long-term shoulder instability issue to the treating provider that warrants further investigation or management.
Outcomes After Single-Stage Anatomic Multiligament Knee Reconstruction With Early Range of Motion in Adolescents
Authors: Willimon S. Clifton , Kim Jason , Perkins Crystal A. 
Published: June 2024

Background: Multiligament knee injuries (MLKI), rare in adolescents, are challenging injuries that require complex surgical reconstruction. Historically, nonanatomic reconstructions have been associated with prolonged immobilization and failure to restore normal knee biomechanics, resulting in arthrofibrosis and high rates of graft failure. Purpose: To describe the clinical and patient-reported outcomes (PROs) for adolescent patients treated with single-stage anatomic multiligament knee reconstruction. Study Design: Case series; Level of evidence, 4. Methods: A single-center retrospective study was performed of patients ≤18 years old who underwent reconstruction of MLKIs by a single surgeon between 2014 and 2019 using a single-stage anatomic technique, with protected weightbearing and early range of motion. Complications were defined as infection, arthrofibrosis, deep vein thrombosis (DVT) or pulmonary embolus, and secondary surgery. PROs, including the pediatric version of the International Knee Documentation Committee (Pedi-IKDC) and the Tegner activity score, were obtained at a minimum of 2 years postoperatively. Results: Included were 30 patients (21 male, 9 female; mean age, 15.4 years). The most common ligamentous reconstruction types were anterior cruciate ligament (ACL) + fibular collateral ligament (12 patients; 40%) and ACL + medial collateral ligament (9 patients; 30%). Three patients (10%) had secondary surgeries, including irrigation and debridement of a granuloma, a staged osteochondral allograft transplantation to a lateral femoral condyle impaction fracture, and repair of a medial meniscal tear and lateral femoral condyle fracture associated with new injuries 2 years after ACL + fibular collateral ligament reconstruction. Two patients (7%) developed arthrofibrosis and 1 patient (3%) developed DVT. PRO scores obtained at a mean of 37 months postoperatively included a mean Pedi-IKDC of 87 (range, 52-92) and a median highest Tegner score at any point postoperatively of 9 (range, 5-10). Of the patients who were athletes before their injury, 70% returned to the same or higher level of sport postoperatively. Conclusion: Reconstruction of MLKI in this series of adolescents with single-stage anatomic techniques and early range of motion resulted in low rates of secondary surgery, few complications, and good knee function as well as PRO scores at mean 3-year follow-up.
Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies – insights from the German NeuroTransData registry
Authors: Hong Ja Bin , Israel-Willner Heike , Peikert Andreas , Schanbacher Peter , Tozzi Viola , Köchling Monika , Reuter Uwe , Raffaelli Bianca ,   NTD Study Group
Published: June 2024

Abstract
Background
Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice.

Methods
This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches.

Results
Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group.

Conclusion
Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup.
Differentiation between descending thoracic aortic diseases using machine learning and plasma proteomic signatures
Authors: Momenzadeh Amanda , Kreimer Simion , Guo Dongchuan , Ayres Matthew , Berman Daniel , Chyu Kuang-Yuh , Shah Prediman K. , Milewicz Dianna , Azizzadeh Ali , Meyer Jesse G. , Parker Sarah 
Published: June 2024

Abstract
Background
Descending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection.

Methods
This study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases. Quantitatively similar proteins were clustered based on linkage distance from hierarchical clustering and ML models were trained with uncorrelated protein lists across various linkage distances with hyperparameter optimization using fivefold cross validation. Permutation importance (PI) was used for ranking the most important predictor proteins of ML classification between disease states and the proteins among the top 10 PI protein groups were submitted for pathway analysis.

Results
Of the 1,549 peptides and 198 proteins used in this study, no peptides and only one protein, hemopexin (HPX), were significantly different at an adjusted p < 0.01 between Type B and DTAA cases. The highest performing model on the training set (Support Vector Classifier) and its corresponding linkage distance (0.5) were used for evaluation of the test set, yielding a precision-recall area under the curve of 0.7 to classify between Type B from DTAA cases. The five proteins with the highest PI scores were immunoglobulin heavy variable 6–1 (IGHV6-1), lecithin-cholesterol acyltransferase (LCAT), coagulation factor 12 (F12), HPX, and immunoglobulin heavy variable 4–4 (IGHV4-4). All proteins from the top 10 most important groups generated the following significantly enriched pathways in the plasma of Type B versus DTAA patients: complement activation, humoral immune response, and blood coagulation.

Conclusions
We conclude that ML may be useful in differentiating the plasma proteome of highly similar disease states that would otherwise not be distinguishable using statistics, and, in such cases, ML may enable prioritizing important proteins for model prediction.
Proteomic profiling of extracellular vesicles derived from human serum for the discovery of biomarkers in Avascular necrosis
Authors: Sung Soo-Eun , Lim Ju-Hyeon , Kang Kyung-Ku , Choi Joo-Hee , Lee Sijoon , Sung Minkyoung , Park Wook-Tae , Kim Young-In , Seo Min-Soo , Lee Gun Woo 
Published: June 2024

Abstract
Background
Avascular necrosis (AVN) is a medical condition characterized by the destruction of bone tissue due to a diminished blood supply. When the rate of tissue destruction surpasses the rate of regeneration, effective treatment becomes challenging, leading to escalating pain, arthritis, and bone fragility as the disease advances. A timely diagnosis is imperative to prevent and initiate proactive treatment for osteonecrosis. We explored the potential of differentially expressed proteins in serum-derived extracellular vesicles (EVs) as biomarkers for AVN of the femoral head in humans. We analyzed the genetic material contained in serum-derived exosomes from patients for early diagnosis, treatment, and prognosis of avascular necrosis.

Methods
EVs were isolated from the serum of both patients with AVN and a control group of healthy individuals. Proteomic analyses were conducted to compare the expression patterns of these proteins by proteomic analysis using LC-MS/MS.

Results
Our results show that the levels of IGHV3-23, FN1, VWF, FGB, PRG4, FCGBP, and ZSWIM9 were upregulated in the EVs of patients with AVN compared with those of healthy controls. ELISA results showed that VWF and PRG4 were significantly upregulated in the patients with AVN.

Conclusions
These findings suggest that these EV proteins could serve as promising biomarkers for the early detection and diagnosis of AVN. Early diagnosis is paramount for effective treatment, and the identification of new osteonecrosis biomarkers is essential to facilitate swift diagnosis and proactive intervention. Our study provides novel insights into the identification of AVN-related biomarkers that can enhance clinical management and treatment outcomes.
75 years’ journey of malaria publications in English: what and where?
Authors: Deora Nimita , Kar Sonalika , Pande Veena , Sinha Abhinav 
Published: June 2024

AbstractMalaria has inflicted serious morbidity and mortality across the globe. The major brunt of the disease has been on African, South-East Asian and South American countries. Proportionally, malaria has attracted global research priorities and this is evident from the number of publications related to malaria from across the globe, irrespective of its endemicity. However, formal and exhaustive analyses of these ‘malaria publications’ are rarely reported. The systematic review and secondary data analyses were done to retrieve information on what has been published on malaria, where is it published, and which countries are major contributors to malaria research.The study presents malaria publications from 1945 to 2020 retrieved using three databases: Web of Science™, Embase® and Scopus®. Exported data were examined to determine the number of publications over time, their subject areas, contributions from various countries/organizations, and top publishing journals.The total number of published records on malaria ranged from 90,282 to 112,698 (due to three different databases). Based on the number of publications, USA, UK, France, and India were identified as the top four countries. Malaria Journal, American Journal of Tropical Medicine & Hygiene, and PLoS One were the most preferred journals, whereas the University of London (Institutions other than LSHTM), the National Institute of Health, the London School of Hygiene and Tropical Medicine, and the University of Oxford appeared to be the top contributing organization.A disproportional contribution to malaria research was observed with non-malaria endemic countries making the largest contribution. Databases differed in their output format and needed standardization to make the outputs comparable across databases.
Development of 225Ac-doped biocompatible nanoparticles for targeted alpha therapy
Authors: Toro-González Miguel , Akingbesote Ngozi , Bible Amber , Pal Debjani , Sanders Brian , Ivanov Alexander S. , Jansone-Popova Santa , Popovs Ilja , Benny Paul , Perry Rachel , Davern Sandra 
Published: June 2024

AbstractTargeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.
Graphical Abstract
Improving dermal fibroblast-to-epidermis communications and aging wound repair through extracellular vesicle-mediated delivery of Gstm2 mRNA
Authors: Wu Haiyan , Yao Zuochao , Li Hongkun , Zhang Laihai , Zhao Yuying , Li Yongwei , Wu Yating , Zhang Zhenchun , Xie Jiali , Ding Feixue , Zhu Hongming 
Published: June 2024

AbstractSkin aging is characterized by the disruption of skin homeostasis and impaired skin injury repair. Treatment of aging skin has long been limited by the unclear intervention targets and delivery techniques. Engineering extracellular vesicles (EVs) as an upgraded version of natural EVs holds great potential in regenerative medicine. In this study, we found that the expression of the critical antioxidant and detoxification gene Gstm2 was significantly reduced in aging skin. Thus, we constructed the skin primary fibroblasts-derived EVs encapsulating Gstm2 mRNA (EVsGstm2), and found that EVsGstm2 could significantly improve skin homeostasis and accelerate wound healing in aged mice. Mechanistically, we found that EVsGstm2 alleviated oxidative stress damage of aging dermal fibroblasts by modulating mitochondrial oxidative phosphorylation, and promoted dermal fibroblasts to regulate skin epidermal cell function by paracrine secretion of Nascent Polypeptide-Associated Complex Alpha subunit (NACA). Furthermore, we confirmed that NACA is a novel skin epidermal cell protective molecule that regulates skin epidermal cell turnover through the ROS-ERK-ETS-Cyclin D pathway. Our findings demonstrate the feasibility and efficacy of EVs-mediated delivery of Gstm2 for aged skin treatment and unveil novel roles of GSTM2 and NACA for improving aging skin.
Graphical Abstract
Recent progress of iron-based nanomaterials in gene delivery and tumor gene therapy
Authors: Gong Ya , Hu Xiaoyan , Chen Ming , Wang Jun 
Published: June 2024

AbstractGene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.
Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions
Authors: Cao Lei-Ming , Yu Yi-Fu , Li Zi-Zhan , Zhong Nian-Nian , Wang Guang-Rui , Xiao Yao , Liu Bing , Wu Qiu-Ji , Feng Chun , Bu Lin-Lin 
Published: June 2024

AbstractResearch into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.