bluuebunny/crossref_metadata_2025_split huggingface dataset:
Umbilical Cord Mesenchymal Stem Cells‐Derived Exosomes Promote the Repair of Endometrial Injury via the miR‐21‐5p/PTEN/AKT Axis
Authors: Li Ziwei , Ding Hao , Dong Liu , Jiang Xiaohua , Xu Xuan , Yu Zhen , Xing Qiong , Tang Heng , Wei Zhaolian , Wang Jianye 
Published: December 2024

Background: Endometrial injury contributes to the reduction of endometrial receptivity and is widely recognized as a critical factor in implantation failure. Increasing evidence suggests that the therapeutic effects of mesenchymal stem cells (MSCs) mainly depend on their capacity to secrete paracrine factors specifically MSC‐derived exosomes (MSC‐Exos), which are regulated by exosomal miRNA. In this study, we investigated the effects of human umbilical cord MSC‐Exos (hUCMSC‐Exos) on injured endometrium and the potential mechanisms.Methods: To observe the distribution of exosomes in vivo, DIR‐labeled hUCMSC‐Exos were injected into the tail vein of endometrium‐injured mice. The recovery of mice damaged endometrium after exosome treatment was detected by hematoxylin–eosin (HE), TUNEL staining, and immunohistochemistry. Then, western blot measured the expression of Bcl‐2, Bax, and cleaved caspase‐3. The mRNA expression of vascular endothelial growth factor (VEGF) and insulin‐like growth factor‐1 (IGF‐1) was evaluated by quantitative real‐time PCR (qRT‐PCR). Furthermore, miR‐21‐5p was checked in mifepristone‐injured endometrial stromal cells (EndoSC) after the hUCMSC‐Exos addition. The cell viability and apoptosis were analyzed and phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/serine/threonine kinase (AKT) pathway were confirmed with hUCMSC‐Exos transfected the miR‐21‐5p.Results: hUCMSC‐Exos migrated to the damaged endometrium, and the endometrial thickness, the number of glands as well as embryo implantation rate were significantly increased (p < 0.05). hUCMSC‐Exos could inhibit apoptosis in our mouse endometrial injury model. Besides, the expression of Ki67 and cluster of differentiation 31 (CD31) was significantly increased (p < 0.05). The VEGF and IGF‐1 expression was significantly upregulated in the exosome group (p < 0.05). The repair effect of exosomes on damaged cells was further enhanced after transfection with miR‐21‐5p mimics and counteracted after transfection with inhibitors. The repair of damaged cells is related to decreased PTEN level and activated the PI3K/AKT signaling pathway.Conclusion: hUCMSC‐Exos ameliorated the damaged uterus, increased the number of glands and embryo implantation rates, suppressed apoptosis, and improved the cell proliferation in the mouse injured endometrium model. Exosomal miR‐21‐5p positively regulated the repair of endometrial injury and enhances the therapeutic effect of hUCMSC‐Exos by activate the PTEN/AKT signaling pathways.
Potential Synergistic Effect between Niraparib and Statins in Ovarian Cancer Clinical Trials
Authors: Zhang Hailei , Rutkowska Anna , González-Martín Antonio , Mirza Mansoor R. , Monk Bradley J. , Vergote Ignace , Pothuri Bhavana , Graybill Whitney A. Spannuth , Goessel Carsten , Barbash Olena , Bergamini Giovanna , Feng Bin 
Published: December 2024

Abstract
This study investigates the potential clinical synergy between the PARP inhibitor niraparib (Zejula) and concomitant statins, exploring their combined effects on progression-free survival (PFS) in patients with ovarian cancer. We retrospectively analyzed niraparib registrational clinical trials in ovarian cancer to investigate potential interactions between niraparib and statins. In the PRIMA trial, patients receiving niraparib demonstrated improved PFS compared with those on placebo (HR = 0.62; P &lt; 0.001; median PFS 13.8 vs. 8.2 months). The post hoc analysis revealed that patients receiving maintenance niraparib who reported concomitant use of statins exhibited significantly improved PFS compared with those on placebo with concomitant statins (HR = 0.34; P &lt; 0.001; median PFS 18.2 vs. 6.0 months). Notably, the improved efficacy in the two-arm comparison of concomitant statin patients was much better than that in the two-arm comparison of those patients without statin, as reflected in the niraparib–statin interaction (P = 0.005). These findings suggest novel opportunities in oncology for the use of statins in combination therapies with PARP inhibitors and emphasize the need for further investigation.

Significance:
The presented retrospective analysis suggests, to the best of our knowledge for the first time, a potential significant interaction between statins and niraparib in clinical settings. Nevertheless, further investigations are required to gain a better understanding of the potential clinical benefit.
Platelet-Specific Deletion of TGF-β1 Impairs Septic Thrombosis in Mice—Brief Report
Authors: Li Yingying , Jiang Huimin , Li Xinyi , Zhu Hui , Dai Yue , Zhang Jie , Sun Yueyue , Chu Xiang , Ju Wen , Xu Mengdi , Li Zhenyu , Zeng Lingyu , Xu Kailin , Qiao Jianlin 
Published: December 2024

BACKGROUND:
Sepsis is featured as a systemic inflammation and thrombosis induced by infection. TGF-β (transforming growth factor-β) 1 is mainly secreted from platelets and plays a role in immune response and inflammation. Whether platelet-derived TGF-β1 participates in sepsis remains unclear. This study intends to investigate its role in sepsis in mice.

METHODS:
Platelet-specific TGF-β1 knockout mice received cecal ligation and puncture surgery to induce sepsis followed by the analysis of survival time, platelets number, pathology changes of lung and liver, liver function, the recruitment of platelets, neutrophils and monocytes, and neutrophil extracellular traps’ formation. In addition, adoptive transfer of wild-type platelets into platelet-specific TGF-β1 knockout mice was performed to further evaluate the role of TGF-β1 in the pathogenesis of sepsis.

RESULTS:
TGF-β1 level was gradually increased in the lung during the progress of sepsis, and platelets are the major source of the elevated TGF-β1 level in the lung after sepsis. Deficiency of platelet-derived TGF-β1 prolonged the survival of sepsis mice, inhibited the drop of platelet number and bacterial growth, impaired the thrombus formation in the lung and liver, and improved liver function. In addition, platelet TGF-β1 deficiency also decreased the recruitment of neutrophils and monocytes to the lung and impaired neutrophil extracellular trap formation. However, the adoptive transfer of normal platelets to platelet-specific TGF-β1 knockout mice significantly reduced the number of circulating platelets, increased thrombosis in the lung and liver, and promoted the neutrophil extracellular trap formation.

CONCLUSIONS:
Deficiency of platelet-derived TGF-β1 inhibits septic thrombosis and prolongs survival time, indicating that it might be a novel therapeutic target for the treatment of sepsis.
Lacosamide as an Adjunctive Therapy in the Management of Refractory Neonatal Seizures: A Retrospective Study
Authors: Sah Jeetendra Prasad , Javarayee Pradeep , Jain Siddharth , Karia Samir , Karakas Cemal 
Published: December 2024

Objective Neonatal seizures present significant treatment challenges, often requiring adjunctive antiseizure medications. This study aimed to evaluate the efficacy of lacosamide as an adjunctive antiseizure medication in managing refractory neonatal seizures. Methods The study included neonates up to 44 weeks of corrected gestational age who received lacosamide treatment at a level 4 neonatal intensive care unit between January 2015 and December 2023. The collected data encompassed demographic features, birth history, perinatal/postnatal complications, seizure characteristics, and treatment details. The primary outcome was the response to lacosamide, assessed by changes in total seizure burden on electroencephalography (EEG). The cohort characteristics were compared between nonresponders and responders. Results The final analysis was conducted on 18 neonates with available EEG data. Of all patients, 72% showed a favorable response to lacosamide treatment, as evidenced by a reduced seizure burden on EEG. The demographic and clinical characteristics of the neonates varied, including a range of seizure etiologies. Responder and nonresponder groups had no differences in clinical characteristics. Conclusion This study suggests that lacosamide may be an effective adjunctive antiseizure medication in treating refractory neonatal seizures. Further prospective studies are warranted to confirm these findings and explore the long-term outcomes and safety profile of lacosamide in this vulnerable patient group.
Extracorporeal-CPR Versus Conventional-CPR for Adult Patients in Out of Hospital Cardiac Arrest– Systematic Review and Meta-Analysis
Authors: Reddy Swetha , Garcia Samuel , Hostetter Logan J. , Finch Alexander S. , Bellolio Fernanda , Guru Pramod , Gerberi Danielle J. , Smischney Nathan J. 
Published: December 2024

Objective Extracorporeal cardiopulmonary resuscitation (ECPR) utilizes veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in cardiac arrest patients to reduce the risk of mortality and multiorgan dysfunction from systemic hypoperfusion. We aimed to compare clinical outcomes of patients receiving ECPR versus conventional cardiopulmonary resuscitation (CCPR) for refractory cardiac arrest. Data Sources This was a systematic review and meta-analysis. A librarian searched the main databases, Ovid MEDLINE (including epub ahead of print, in-process & other non-indexed citations), Ovid EMBASE and Ovid Cochrane Central Register of Controlled Trials from inception through July 2024. Study Selection We included randomized controlled trials and observational studies that compared the outcomes of ECPR to CCPR in cardiac arrest patients. Primary outcomes were neurological sequelae and survival. Data Extraction We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened articles, extracted data on selected articles and performed risk of bias assessments using ROBINS-I for non-randomized controlled trials and the revised Cochrane risk of bias tool for randomized controlled trials with disagreements settled by a third independent reviewer. Data Synthesis Out of 3458 studies identified and screened, 28 studies including 304,360 cardiac arrest patients met eligibility criteria and were included. Survival at hospital discharge was 20% for ECPR versus 3.3% for CCPR (OR 0.48 [CI 0.27, 0.84]). Favorable neurological outcome at hospital discharge was 11.8% for ECPR versus 1.9% for CCPR (OR 0.41 [CI 0.17, 1.01]). Complications from bleeding were ten times higher in the ECPR group (35.3% vs 3.7%; OR 0.08 [0.03, 0.24]). Conclusions ECPR appeared to be superior to CCPR for improved neurological outcome and survival in cardiac arrest patients, although bleeding was increased. There was large heterogeneity in the included studies and outcomes reported. Future prospective studies may improve the identification of subgroups of patients that will benefit most from ECPR. Systematic review and meta-analysis registration: PROSPERO - CRD42023394128.
Transcellular transport of 18F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis
Authors: Martus Giedre , Siddhuraj Premkumar , Erjefält Jonas S , Kádár András , Lindström Martin , Bergling Karin , Öberg Carl M 
Published: December 2024

Background Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved. Methods Here we sought to elucidate whether diffusion of radiolabeled 18F-deoxyglucose ([18F]-DG) in the opposite direction (plasma → dialysate) is also affected by GLUT inhibition. During GLUT inhibition, such transport may either be increased or unaltered (favors absorption hypothesis) or decreased (favors transcellular hypothesis). Effects on the transport of solutes other than [18F]-DG (or glucose) during GLUT inhibition indicate effects on paracellular transport (between cells) rather than via GLUTs. Results GLUT inhibition using phloretin markedly reduced [18F]-DG diffusion capacity, improved ultrafiltration (UF) rates and enhanced the sodium dip. No other solutes were significantly affected with the exception of urea and bicarbonate. Conclusion The present results indicate that part of glucose is transported via the transcellular route across cells in the peritoneal membrane. Regardless of the channel(s) involved, inhibitors of facilitative GLUTs may be promising agents to improve UF efficacy in patients treated with PD.
A Quality Improvement Initiative to Reduce the Noise Levels in a Tertiary Care Neonatal Intensive Care Unit
Authors: Devaramani Manjunath , Devaranavadagi Ranganatha A. , Nagesh N Karthik 
Published: December 2024

Objective Noise hazard is the issue of most tertiary care due to various paraphernalia and human factors. Recently, our observation has suggested that the new generation of neonatal intensive care unit (NICU) staff and residents are not sensitive to protocols of noise control and maintaining a silent environment in the NICU. Hence, this quality improvement (QI) project was undertaken. Methods The QI team identified the potential sources of noise in the NICU through fishbone analysis in the baseline phase. Noise levels were recorded by a digital sound pressure level meter. Stepwise Plan-Do-Study-Act (PDSA) cycles were conducted over 8 weeks, and the strategies to reduce noise levels targeted behavioural and environmental modification. Further noise levels were assessed for 4 weeks in the post-intervention phase. Results Average noise levels decreased from the baseline 63.3 ± 3.09 dB to 54.3 ± 1.51 dB (14.2% decline) in the post-intervention phase with a highly significant P value (<.0001). The peak noise levels decreased from a baseline 110.6 ± 2.94 dB to 76.9 ± 1.65 dB in the post-intervention phase with a highly significant P value (<.0001). During the day shift, average noise levels decreased from 63.8 to 54.7dB; night shift noise levels decreased from 62.9 to 53.8 dB. Peak noise levels were decreased from 112 and 108.7 dB to 78.1 and 75.7 dB during the day and night shifts, respectively. Conclusion Effective implementation of targeted behavioural and environmental strategies through a stepwise PDSA-driven approach decreased the noise levels in the tertiary care NICU by 14.2% from baseline.
Demographic and clinical characteristics of rural, regional, and metropolitan inpatients during psychiatric inpatient eating disorders treatment
Authors: Seiler Natalie , Ziegeler Benjamin , Stukel Mikayla , Gwee Karen 
Published: December 2024

Objective Eating disorders were previously considered less common in rural/regional areas. However, emerging research suggests that eating disorders may be more prevalent in these populations than initially recognized. We aimed to describe demographic/clinical characteristics of metropolitan compared to rural/regional inpatients during psychiatric inpatient eating disorder treatment at the Eating Disorders Unit (EDU), Austin Health in Melbourne, Australia. Methods Retrospective review of patient files was undertaken for inpatients aged 18–65 years who resided within the Body Image & Eating Disorders Treatment & Recovery Service (BETRS) catchment area and were admitted to EDU between 01/01/21 and 30/10/23. Results Regional/rural patients were on average 2.7 years older and first diagnosed 3.5 years later compared to metropolitan inpatients. These groups showed otherwise similar characteristics in relation to psychiatric/medical history. Conclusion Available and accessible speciality eating disorders services in rural and regional areas are needed for early detection, prevention, and multidisciplinary management.
Association of Clinical, Biomechanical, and Psychosocial Factors with Smile Dynamics in Unilateral Cleft Lip: A Multicenter Observational Study
Authors: Wong Lucinda , Firth Fiona , Fowler Peter , Jack Hannah , Bennani Hamza , Campbell Thomas Noble , Farella Mauro 
Published: December 2024

Objective To investigate the association between clinical, biomechanical, and psychosocial factors and smiling behavior in individuals with treated unilateral cleft lip with or without cleft palate (UCL ± P) compared to non-cleft controls. Design Multicenter observational study in New Zealand. Participants Individuals aged ≥15 ( N = 42) comprised 2 study groups: a UCL ± P group ( N = 21) and a non-cleft control group ( N = 21). Methods Participants viewed an amusing video while their facial expressions were recorded. Smile features were automatically detected via software. A clinical outcome, nasolabial esthetics, was scored using the Asher-McDade system. Perioral biomechanical properties were measured via myotonometry. Smile Esthetics-related Quality of Life (SERQoL), Orofacial Esthetics Scale (OES), and personality (IPIP-NEO-60) questionnaires were completed. Results Smile features and personality traits did not differ between the groups. Participants with UCL ± P exhibited higher stiffness (+44.2%; Cohen's d = 1.6) and tone (+22.6%; Cohen's d = 1.9) at the cleft scar site, and higher decrement (or lower elasticity, +8.5%; Cohen's d = 0.8) adjacent to the scar. Nasolabial esthetics and elasticity of the scar correlated with the duration of smiles and relative smile time (−0.50 < R < −0.44; p < .05). Participants in the UCL ± P group had lower scores for the OES and higher impacts on SERQoL for social contacts and dental self-confidence. Conclusions Adolescents and adults with UCL ± P exhibit similar smile behavior as their cleft-free peers—at least in non-social settings. Nasolabial esthetics and perioral biomechanical properties are associated with propensity to smile. UCL ± P is negatively associated with smile-related quality of life and an individual's perception of their facial appearance.
Removal of aqueous humor and conjunctival compression sutures for a dysesthesic filtering bleb: A surgical technique and case report
Authors: Arias-García Elena , Martinez-Gil Cristina , Bautista-Cortiella Marc , Roig-Ferreruela Gonzalo , Piá-Ludeña Jose Vicente , Lanzagorta-Aresti Aitor 
Published: December 2024

Introduction To present a novel surgical technique for the treatment of a steep-walled filtering bleb following an Ahmed glaucoma valve implant. The primary aim was to alleviate the patient's discomfort and address associated corneal thinning, complications that can arise from this condition. Methods Case report and surgical technique. This case report describes a 29-year-old female who developed a dysesthesic filtering bleb following the implantation of a glaucoma drainage device. The employed surgical technique to address this complication involved the drainage of aqueous from the bleb using a 30-G needle, which effectively reduced its height. Subsequently, a compression suture was applied to maintain an appropriate bleb size. Results With the presented surgical technique, the ultimate control of an overhigh filtering bleb associated to a glaucoma drainage device was possible. Following the procedure, the patient's symptoms and the corneal thinning linked to the bleb's excessive size were successfully managed. Furthermore, the anatomy of the filtering bleb was preserved, and an optimal intraocular pressure outcome was achieved. Conclusions The removal of aqueous and the application of a compression suture are two surgical techniques traditionally used for managing the hypertensive phase of glaucoma drainage devices and for alleviating discomfort from blebs after classical filtering surgery, respectively. In the case presented, the combination of these two techniques effectively reduced the size of an excessively high filtering bleb associated with a glaucoma drainage device. This approach successfully resolved the patient's discomfort and corneal issues related to this complication.
A comparison of postoperative microbiological and histological test results with the indication for revision as listed at the time of surgery in the National Joint Registry: a single-centre cohort study of metal-on-metal total hip replacement and hip resurfacing revision procedures
Authors: Murphy Thomas A , Nandra Rajpal , Berryman Fiona , Whitehouse Michael R , Dunlop David J , Matharu Gulraj S 
Published: December 2024

Introduction: Surgeons allocate an indication(s) for revision surgery on NJR Minimum Data Set forms in the immediate perioperative period, when results from intraoperative histology and microbiology samples are not available. We evaluated to what extent the postoperative diagnostics obtained for patients undergoing metal-on-metal hip arthroplasty (MoMHA) revision surgery align with the indication for revision listed in the NJR. Methods: NJR data for MoMHA revision patients (2004–2015) at a single centre were linked to hospital records of microbiology and histology testing for prosthetic joint infection (PJI) and adverse reaction to metal debris (ARMD). The Musculoskeletal Infection Society and Mirra classifications were used as “gold standards’ to classify PJI and ARMD respectively and to assess the diagnostic accuracy of the clinician selected revision indication recorded on MDS forms. Results: Of 301 cases, 5.6% ( n = 17) and 3.7% ( n = 11) were revised for PJI and ARMD respectively. In a further 6.6% ( n = 20, PJI) and 15.6% ( n = 47, ARMD) the indication for revision selected at the time of surgery did not corroborate with the test results from intraoperative samples. Diagnostic accuracy analysis revealed sensitivity and specificity of indication for surgery at the time of revision for PJI of 35.5% (95% CI, 19.2–54.6) and 97.8% (CI, 54.6–95.2) respectively, and for ARMD of 7.41% (CI, 2.06–17.9) and 97.2% (CI, 94.3–98.9) respectively. Conclusions: We observed that the results of histology and microbiology analyses of intraoperative samples may provide evidence to support alternative diagnoses in 20% of cases. This indicates a need for a change in the work-up of these cases to allow a more accurate prediction of the indication for revision. Alternatively, if there was evidence of a difference in outcome for patients where the indication may be changed when such data becomes available, the feasibility of a facility to add additional information from samples taken intraoperatively when it becomes available should be explored.