bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bee Pollen and Doxorubicin by Synergistic Effects Inhibit the Proliferation of Breast Tumors in 4T1 Tumor-bearing BALB/c Mice: A Biochemical, Immunohistochemical,and Molecular Approach
Authors: Li Jinwen 
Published: October 2023

Objectives This study investigated the effects of BP and doxorubicin (DOX) on 4T1 tumor cells in a mouse model. Materials and Methods After inducing breast tumors, 70 4T1-tumor-bearing BALB/c mice were divided into seven groups ( n = 10/group). The groups were treated with DOX and BP for 35 days. On the 36th day, blood was taken from the heart, and serum was separated to measure levels of cytokines, estrogen, progesterone, testosterone, and nitric oxide. Antioxidant enzyme activities, as well as tissue ferric-reducing antioxidant power (FRAP) and malondialdehyde (MDA) levels, were evaluated. The expression of apoptotic genes and metastasis was measured using real-time polymerase chain reaction (PCR), while the expression of apoptotic proteins was evaluated using Western blotting. Finally, Ki-67 and p-53 were examined using immunohistochemistry to determine apoptosis. Results The study found that BP, with its synergistic effects with DOX, reduced the volume of tumors and increased the expression of apoptotic genes and proteins. In a dose-dependent manner, groups receiving BP and DOX with their synergistic effects reduced the level of estrogen and nitric oxide and also reduced the level of pro-inflammatory cytokines. BP along with DOX increased serum interferon-γ (IFN-γ) levels. Tumor tissue FRAP and thiobarbituric acid reactive substances (TBARS) levels increased in BP-treated groups. Ki-67 and Bcl-2 proliferation markers levels decreased, and p53 levels increased in 4T1-breast tumors. Conclusion The study concluded that BP with its synergistic effects along with DOX has the ability to suppress the growth of tumors and can also inhibit the oxidative damage of DOX.
Exploring Experiences of Pain Management Among Family Caregivers of Community-Dwelling Older Adults With Dementia
Authors: Zhao Hui , Kulbok Pamela A. , Williams Ishan C. , Manning Carol , Logan Jeongok G. , Romo Rafael D. 
Published: October 2023

Background Pain is often underreported and under-treated in older adults with dementia. The role of family caregivers (FCGs) in managing pain for their loved ones with dementia living in community has been significantly burdensome. Surprisingly, research has not delved into the experiences of FCGs’ concerning pain management in this context. Methods A qualitative descriptive study was conducted to gain a deep understanding of FCGs’ experiences in managing pain for their loved ones. Family caregivers participated in semi-structured face-to-face or telephone interviews. Inclusion criterion included being an adult providing care to community-dwelling older adults with dementia. Recruitment stopped upon reaching thematic saturation. Basic demographic characteristics was also collected. Constant comparison analytic method was employed. Results The study included 25 FCGs in central Virginia, spanning ages from 29 to 95. Participants were predominantly white, female, married, and had a minimum high school education. Most of them were adult children (52%) or the spouses (28%) of the care recipients. Four thematic categories emerged around exploring FCGs’ pain management experiences: (1) Values; (2) Barriers; (3) Support; and (4) Adaptation. Each theme included sub-themes. Conclusion Family caregivers follow their values to make decisions in pain management. Barriers existed for effective pain management. Adaptation and support from professional or formal caregivers greatly improved FCGs’ perception of their competence in pain management. The finding underscores the need for further research and the development of interventions aimed at enhancing FCGs’ perception of self-efficacy in this crucial aspect of caregiving.
Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac Events: A Meta-analysis and Scoping Review
Authors: Garcia Michael Cristian , Tsang Kai La , Lohit Simran , Deng Jiawen , Schneider Tyler , Matos Silva Jessyca , Mbuagbaw Lawrence , Holbrook Anne 
Published: October 2023

Objectives: We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ). Data sources: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians. Study selection and data extraction: Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies. Data synthesis: By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I2 = 0%). Relevance to patient care and clinical practice: These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications. Conclusions: Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.
The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer
Authors: Zhao Lamei , Han Dongyan , Zhu Jianghua , Bi Dexi , Ding Tingting , Zhu Xingchen , Huang Dengfeng , Zhang Youhua , Lu Ling , Wu Weijun , Gao Yaohui , Liu Hu , Huang Qiongyi , Wei Qing , Yao Xudong 
Published: October 2023

Background: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC. Methods: Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed. Results: We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC. Conclusion: Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation.
The MoxFo initiative – outcomes: Outcome measures in studies of exercise training in multiple sclerosis; scoping review of reviews and classification according to the ICF framework
Authors: Ramari Cintia , Awadia Zain , Bansi Jens , Casey Blathin , Feys Peter , Pilutti Lara A , Sandroff Brian M , Paul Lorna 
Published: October 2023

Background: The number of published studies of exercise training in multiple sclerosis (MS) has grown exponentially with increasing numbers of outcomes capturing exercise effects. This has complicated the selection of relevant indicators and interpretation of intervention effects. Objectives: The Outcomes subgroup of the MoXFo initiative aimed to (1) identify outcome measures and biomarkers in studies of exercise training in MS; (2) systematically map retrieved outcomes to International Classification of Functioning, Disability and Health (ICF) categories; (3) identify gaps where relevant ICF categories have been omitted. Methods: Electronic databases and registers were searched from 2010 to July 2020 to identify systematic reviews or meta-analyses of controlled trials of exercise training on any outcome in MS. Retrieved outcomes/biomarkers were mapped to the corresponding ICF category. Results: Eighty-one review articles reporting 235 different outcomes were included. The outcomes corresponded to 15 chapters and 45 categories within the ICF. Outcomes mapped primarily to body function (30 categories) and activities and participation (9 categories) components. Few outcomes mapped to body structures (2 categories) or environmental factors (1 category). Conclusion: This sets the stage to develop a resource for researchers/clinicians that will aid in the selection of appropriate outcomes/biomarkers when examining exercise effects in MS.
Foveal triangular fibrocartilage complex pathology: a potentially under-recognized injury
Authors: Welling Benjamin , Kakar Sanjeev 
Published: October 2023

The primary aim of the present study was to present a case series of 24 patients with foveal triangular fibrocartilage complex (TFCC) injuries that were treated with arthroscopically assisted TFCC foveal repair. In total, 19 patients had a stable distal radioulnar joint (DRUJ) and five had an unstable DRUJ. Despite this, all patients were found to have a foveal tear upon DRUJ arthroscopy. Magnetic resonance imaging (MRI) scans detected only eight out of 23 patients with foveal injuries. In addition to their foveal injury, 19 of the 24 patients had additional pathology that required treatment. At a mean follow-up of 18 months, there was a statistically significant improvement in pain, range of motion, grip strength and functional scores. In this study, we demonstrate that having a stable DRUJ upon clinical examination and normal MRI findings does not rule out foveal TFCC injury and a high index of clinical suspicion is needed when managing patients with ulnar sided wrist pain. Level of evidence: IV.
Outcomes and Complications of Surgery for Symptomatic Spinal Metastases; a Comparison Between Patients Aged ≥ 70 and <70
Authors: Tan Jiong Hao Jonathan , Hallinan James Thomas Patrick Decourcy , Ang Shi Wei , Tan Tuan Hao , Tan Hwee Inn Joelle , Tan Le Tian Isaac , Sin Qinxiang Shant , Lee Renick , Hey Hwee Weng Dennis , Chan Yiong Huak , Liu Ka Po Gabriel , Kumar Naresh 
Published: October 2023

Study Design Retrospective cohort study. Objective Physicians may be deterred from operating on elderly patients due to fears of poorer outcomes and complications. We aimed to compare the outcomes of surgical treatment of spinal metastases patients aged ≥70-yrs and <70-yrs Materials and Methods This is a retrospective study of patients surgically treated for metastatic epidural spinal cord compression and spinal instability between January-2005 to December-2021. Follow-up was till death or minimum 1-year post-surgery. Outcomes included post-operative neurological status, ambulatory status, medical and surgical complications. Two Sample t-test/Mann Whitney U test were used for numerical variables and Pearson Chi-Squared or Fishers Exact test for categorical variables. Survival was presented with a Kaplan-Meier curve. P < .05 was significant. Results We identified 412 patients of which 29 (7.1%) patients were excluded due to loss to follow-up and previous surgical treatment. 79 (20.6%) were ≥70-yrs. Age ≥70-yrs patients had poorer ECOG scores ( P = .0017) and Charlson Comorbidity Index ( P < .001). No significant difference in modified Tokuhashi score ( P = .393) was observed with significantly more ≥ prostate ( P < .001) and liver ( P = .029) cancer in ≥70-yrs. Improved or maintained normal neurological function ( P = .934), independent ambulatory status ( P = .171), and survival at 6 months ( P = .119) and 12 months ( P = .659) was not significantly different between both groups. Medical ( P = .528) or surgical ( P = .466) complication rates and readmission rates ( P = .800) were similar. Conclusion ≥70-yrs patients have comparable outcomes to <70-yr old patients with no significant increase in complication rates. Age should not be a determining factor in deciding surgical management of spinal metastases.
Adapting prevention programs for virtual delivery: A case study in adapting a parent-focused child sexual abuse prevention module
Authors: Guastaferro Kate , Melchior Mia , Murphy-Costanzo Alexis , S Sunshine , Neimeyer Alexis , Stewart Sydni , Noll Jennie 
Published: October 2023

Background: Evolving and emerging contexts require interventions to respond and adapt. The COVID-19 pandemic necessitated a quick adaptation from in-person to virtual delivery. Not only were there few programs able to transition to virtual delivery, there was a lack of parent-focused CSA-prevention programs. The current study describes the responsive adaptation of a parent-focused child sexual abuse (CSA) prevention module ( Smart Parents—Safe and Healthy Kids; SPSHK) for virtual delivery. Design and methods: This two-phase study used mixed-methods to inform and pilot test adaptations to the virtual module. In Phase 1, parenting providers with and without experience delivering SPSHK ( N = 110) completed anonymous surveys and a subsample ( n = 27) subsequently participated in brief interviews elaborate on challenges and needed adaptations for virtual platforms. Results: Providers indicated the greatest technological difficulties with parents’ access to technology noting the inability to use a screensharing function. Thus, providers recommended no adaptations for the virtual delivery of SPSHK. In Phase 2, the virtual SPSHK module was piloted with nine parents. Results demonstrated virtual SPSHK was acceptable and feasibly implemented. Pre-posttest assessments indicated increases in parents’ CSA-related awareness and use of protective behaviors. Conclusion: The current study suggests the promise of virtual SPSHK implementation and may act as a blueprint for other parent-focused CSA-prevention programs, but also more general parenting programs, considering virtual delivery.
Midterm Functional Outcomes of Arthroscopically Treated Recalcitrant Osteitis Pubis in Competitive Soccer Players
Authors: Ganal İlker , Çelen Zekeriya Ersin 
Published: October 2023

Background: Outcomes after arthroscopic debridement for isolated osteitis pubis in athletes are unknown, and midterm results following this method have not been established. Purpose/Hypothesis: To evaluate the safety and efficiency of arthroscopic treatment for recalcitrant osteitis pubis in competitive soccer players. It was hypothesized that this treatment modality would yield clinical improvement in functional and patient satisfaction scores compared with preoperative values. Study Design: Case series; Level of evidence 4. Methods: At a single center, 10 consecutive male soccer players (mean age, 23.6 ± 4.4 years; range, 19-32 years) with a mean follow-up period of 72.2 ± 13.4 months (range, 60-97 months) were evaluated. All patients presented with symptomatic osteitis pubis and failed to respond to nonoperative treatment. Arthroscopic pubic symphysiectomy was performed in the supine position, and penile manipulation was performed in all cases to mitigate risks associated with neurovascular structures and the root of the penis. Outcome measurements were time to return to sports, visual analog scale (VAS) for pain, Nirschl Phase Rating Scale (NPRS), Nonarthritic Hip Score (NAHS), modified Harris Hip Score (mHHS), and patient satisfaction. Preoperative and postoperative radiographs were also assessed. Results: The mean time to return to sports was 4.6 ± 1.7 months (range, 3-8 months). The mean VAS pain score decreased from 9.3 ± 0.8 (range, 8-10) to 0.2 ± 0.4 (range, 0-1) ( P = .005). The mean NPRS decreased from 6.6 ± 0.5 (range, 6-7) to 0.3 ± 0.5 (range, 0-1) ( P = .004). The mean NAHS increased from 35.8 ± 16.7 (range, 14-72) to 98.2 ± 2.7 (range, 93-100) ( P = .005). The mean mHHS increased from 47.4 ± 10.6 (range, 27-60) to 98.2 ± 4.5 (range, 86-100) ( p = .005). The mean patient satisfaction was 9.7 ± 0.7 (range, 8-10). Scrotal swelling was observed in 4 patients, which was resolved 36 to 48 hours postoperatively. Conclusion: Arthroscopic treatment of osteitis pubis may be an option for recalcitrant cases when nonoperative treatment fails. However, further studies are needed to determine whether this technique and the outcomes of this study can be reproduced.
MRI Modeling for 3D Printed Fabrication of Nasoalveolar Molding Appliance in Patients With Cleft Lip and Palate
Authors: Wehr Chelsea L. , Lignieres Austin , Obinero Chioma G. , Cepeda Alfredo , Cardenas Antonio , Kurtis Kasper F. , Acharya Bhavini , Bonfante-Mejia Eliana , Riascos-Castaneda Roy , Patel Rajan , Chiquet Brett T. , Greives Matthew R. 
Published: October 2023

Purpose: Present a novel technique for fabrication of nasoalveolar molding (NAM) appliances for neonates with cleft lip and palate (CLP) using magnetic resonance imaging (MRI). Study design: Proof-of-concept study. Setting/Participants: One patient with unilateral CLP was recruited for participation in this study at our institution. Interventions: This study employed 2 different methods for creating a NAM appliance, which is used in patients with CLP to improve anatomic positioning of the orofacial cleft in preparation for primary cheiloplasty. The patient underwent intraoral impression for traditional fabrication of a NAM appliance (PMMA-NAM) and also MRI of the face for digital fabrication of a NAM appliance (CAD-NAM). The 2 appliances were then compared using landmarks for measurements. Primary Outcome: Landmark measurements on NAM appliances; Clinical interchangeability of NAM appliances. Results: There was a statistically significant difference in the external arch width between the CAD-NAM and the PMMA-NAM. All other NAM measurements were statistically similar. Additionally, there was clinical success in the interchangeable fit of both appliances on both models. Conclusions: This technique could potentially eliminate the need for creation of an intraoral impression, as well as the adverse events associated with this, in the fabrication of NAM appliances. Larger studies are necessary to further define the efficacy of this novel approach and generalizability to other patients with CLP.
Reciprocal stabilization of coagulation factor XIII-A and -B subunits is a determinant of plasma FXIII concentration
Authors: Byrnes James R. , Lee Taek , Sharaby Sherif , Campbell Robert A. , Dobson Dre’Von A. , Holle Lori A. , Luo Michelle , Kangro Kadri , Homeister Jonathon W. , Aleman Maria M. , Luyendyk James P. , Kerlin Bryce A. , Dumond Julie B. , Wolberg Alisa S. 
Published: October 2023

Abstract
Transglutaminase factor XIII (FXIII) is essential for hemostasis, wound healing, and pregnancy maintenance. Plasma FXIII is composed of A and B subunit dimers synthesized in cells of hematopoietic origin and hepatocytes, respectively. The subunits associate tightly in circulation as FXIII-A2B2. FXIII-B2 stabilizes the (pro)active site-containing FXIII-A subunits. Interestingly, people with genetic FXIII-A deficiency have decreased FXIII-B2, and therapeutic infusion of recombinant FXIII-A2 (rFXIII-A2) increases FXIII-B2, suggesting FXIII-A regulates FXIII-B secretion, production, and/or clearance. We analyzed humans and mice with genetic FXIII-A deficiency and developed a mouse model of rFXIII-A2 infusion to define mechanisms mediating plasma FXIII-B levels. Like humans with FXIII-A deficiency, mice with genetic FXIII-A deficiency had reduced circulating FXIII-B2, and infusion of FXIII-A2 increased FXIII-B2. FXIII-A-deficient mice had normal hepatic function and did not store FXIII-B in liver, indicating FXIII-A does not mediate FXIII-B secretion. Transcriptional analysis and polysome profiling indicated similar F13b levels and ribosome occupancy in FXIII-A-sufficient and -deficient mice and in FXIII-A-deficient mice infused with rFXIII-A2, indicating FXIII-A does not induce de novo FXIII-B synthesis. Unexpectedly, pharmacokinetic/pharmacodynamic modeling of FXIII-B antigen after rFXIII-A2 infusion in humans and mice suggested FXIII-A2 slows FXIII-B2 loss from plasma. Accordingly, comparison of free FXIII-B2 vs FXIII-A2-complexed FXIII-B2 (FXIII-A2B2) infused into mice revealed faster clearance of free FXIII-B2. These data show FXIII-A2 prevents FXIII-B2 loss from circulation and establish the mechanism underlying FXIII-B2 behavior in FXIII-A deficiency and during rFXIII-A2 therapy. Our findings reveal a unique, reciprocal relationship between independently synthesized subunits that mediate an essential hemostatic protein in circulation. This trial was registered at www.ClinicalTrials.com as #NCT00978380.
Impaired autophagy in the lower airways and lung parenchyma in stable COPD
Authors: Levra Stefano , Rosani Umberto , Gnemmi Isabella , Brun Paola , Leonardi Andrea , Carriero Vitina , Bertolini Francesca , Balbi Bruno , Profita Mirella , Ricciardolo Fabio Luigi Massimo , Di Stefano Antonino 
Published: October 2023

BackgroundThere is increasing evidence of autophagy activation in COPD, but its role is complex and probably regulated through cell type-specific mechanisms. This study aims to investigate the autophagic process at multiple levels within the respiratory system, using different methods to clarify conflicting results reported so far.MethodsThis cross-sectional study was performed on bronchial biopsies and peripheral lung samples obtained from COPD patients (30 and 12 per sample type, respectively) and healthy controls (25 and 22 per sample type, respectively), divided by smoking history. Subjects were matched for age and smoking history. We analysed some of the most important proteins involved in autophagosome formation, such as LC3 and p62, as well as some molecules essential for lysosome function, such as lysosome-associated membrane protein 1 (LAMP1). Immunohistochemistry was used to assess the autophagic process in both sample types. ELISA and transcriptomic analysis were performed on lung samples.ResultsWe found increased autophagic stimulus in smoking subjects, regardless of respiratory function. This was revealed by immunohistochemistry through a significant increase in LC3 (p<0.01) and LAMP1 (p<0.01) in small airway bronchiolar epithelium, alveolar septa and alveolar macrophages. Similar results were obtained in bronchial biopsy epithelium by evaluating LC3B (p<0.05), also increased in homogenate lung tissue using ELISA (p<0.05). Patients with COPD, unlike the others, showed an increase in p62 by ELISA (p<0.05). No differences were found in transcriptomics analysis.ConclusionsDifferent techniques, applied at post-transcriptional level, confirm that cigarette smoke stimulates autophagy at multiple levels inside the respiratory system, and that autophagy failure may characterise COPD.