bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parent Perspectives of Co-Occupations in Neonatal Intensive Care: A Thematic Review of Barriers and Supports
Authors: Stovall Sydnee G. , George Rylie G. , Lara Madelyn T. , Gainous Kyra O. , Kitchens Riqiea F. , Hilton Claudia L. 
Published: August 2024

Background: Co-occupations within the neonatal intensive care unit (NICU), which include parenting activities, such as bathing, feeding, diapering, comfort care, and bonding for attachment, are consequential for optimal infant development. Objectives: This thematic systematic review examines supports and barriers for facilitating co-occupations between parents and infants in the neonatal setting. Methodology: A search of four databases (MEDLINE, CINAHL, PsycINFO, and PubMed) resulted in 20 studies that met inclusion criteria for data extraction. Results: Family-centered NICU design, good communication between parents and NICU staff, increased physical contact, parent involvement in caregiving, psychological wellness, parent education, peer support, and established parental roles are identified as supports to co-occupational engagement. Identified barriers include physical separation, loss of parental role, restrictions of the NICU environment, medical technology, role strain, psychological burden, lack of knowledge, and poor communication. Implications: Findings suggest that neonatal occupational therapy practitioners can facilitate parent-infant co-occupations by addressing barriers and augmenting existing supports.
Outcomes of ureteroscopy and laser fragmentation using a 60 W MOSES laser: a 3-year prospective study from a University Teaching Hospital
Authors: Jahrreiss Victoria , Ripa Francesco , Somani Bhaskar 
Published: August 2024

Introduction: Modulated optics enhancement system (MOSES) holmium lasers use “pulse modulation” to increase the efficacy of laser lithotripsy. As the clinical evidence on the efficacy of 60 W holmium laser with MOSES technology is scarce, we analyzed the outcomes of patients treated with this laser at our institution. Methods: A total of 96 consecutive patients with urinary stones (72 renal stones and 24 ureteral stones) were treated with the 60 W MOSES laser from 2019 until 2022 and were included in our analysis. Patient data and outcomes were prospectively collected, and analysis was performed regarding patient demographics, stone parameters, as well as stone-free rate, operating time, length of stay, and perioperative and postoperative complications. Results: With a median age of 55 (IQR: 35–69.25) years, the male:female ratio was 53:43. The median stone size was 12 mm (IQR: 7–19), with a mean number of urinary stones of 1.82 (SD ± 1.4). While 36 (35%) patients were pre-stented, a ureteral access sheath was inserted in 36 (37.5%) patients. The median operative time was 44 min (IQR: 22.5–59.5), and 63 (65.5%) patients received postoperative stenting. Perioperative complications (all Clavien ⩽ II complications) were observed in 5 (5.2%) patients (four urinary tract infections and one acute urinary retention), and after the first procedure, 90 (93.8%) patients were stone-free. The median length of hospital stay was 1 day (IQR: 1–1). Conclusion: This study demonstrated that the 60 W MOSES laser was safe and efficient for the treatment of urinary stones with high stone-free rates and a small risk of minor complications. More studies with larger cohorts are necessary in the future to confirm our results.
Treatment patterns and factors associated with discontinuation of monoclonal antibodies
Authors: Alkaabi Muzoon Matar Saleh , Rabbani Syed Arman , Rao Padma GM , Mohamedelhassan Mai Ismail 
Published: August 2024

Background: Biological agents have revolutionized care in specialties such as oncology, immunology, infectious diseases, and genetic disorders, offering targeted actions on specific molecules or select immune cells. Monoclonal antibodies, known for their high specificity and precision, represent one of the most significant and rapidly expanding categories of these agents. Understanding the drug utilization patterns of monoclonal antibodies is crucial to ensure their optimal use, especially given their high cost and potential adverse effects. Methods: This analytical cross-sectional study was conducted in a secondary hospital in the United Arab Emirates. Patients of either gender receiving monoclonal antibodies at the study site were included. Treatment patterns, utilization, and factors associated with the discontinuation of monoclonal antibodies were assessed. Results: Hyperlipidemia (136, 39.1%) was the most common indication for monoclonal antibodies, followed by prophylaxis of respiratory syncytial virus infection in congenital heart disease (104, 29.9%) and osteoporosis (42, 12.1%). Evolocumab was the most commonly prescribed monoclonal antibody (135, 38.8%), followed by palivizumab (104, 29.9%), and dupilumab (38, 10.9%). The majority of monoclonal antibodies demonstrated a prescribed daily dose to defined daily dose ratio of 1.0, reflecting their appropriate utilization. One hundred twenty-nine patients (37.0%) discontinued their treatment during the study. Patient’s level of education (OR: 0.416, 95% CI: 0.183–0.943, p = 0.036), BMI (OR: 2.358, 95% CI: 1.164–4.777, p = 0.017), number of concomitant medications (OR: 2.457, 95% CI: 1.202–5.025, p = 0.014), and treatment duration (OR: 9.180, 95% CI: 4.909–17.165, p < 0.001) were identified as predictors of discontinuation of monoclonal antibodies. Conclusion: This study represents the first comprehensive investigation in the United Arab Emirates focused on treatment patterns, utilization, and discontinuation of monoclonal antibodies among the local population. Monoclonal antibodies were prescribed for the management of a wide range of clinical conditions. The study reports appropriate utilization of most monoclonal antibodies and identifies factors such as patient education level, BMI, concomitant medications, and treatment duration as independent predictors of monoclonal antibody treatment discontinuation.
Facilitating Access to Care for Children With Complex Health Needs Through Low-Barrier Place-Based Intake Processes: Lessons From the RICHER Social Pediatric Model
Authors: So Judy , Sun Sunny , Kim Annie , Nemati Saina , Kim Michelle M. , McIntosh Gwyneth , Pikksalu Kristina , Loock Christine , Carwana Matthew 
Published: August 2024

Introduction/Objectives: Exposure to adverse social determinants of health (SDoH) in childhood is associated with poorer long-term health outcomes. Within structurally marginalized populations, there are disproportionately high rates of developmentally vulnerable children. The RICHER (Responsive, Intersectoral, Child and Community Health, Education and Research) social pediatric model was designed to increase access to care in marginalized neighborhoods. The purpose of this study was to describe the children and youth engaged with the RICHER model of service and characterize the needs of the population. Methods: A retrospective chart review was conducted on children and youth who accessed primary care services through the program between January 1, 2018 and April 30, 2021. Basic descriptive data analysis was done using Stata v15.1. Results: A total of 210 charts were reviewed. The mean age in years at initial assessment was 6.32. Patients most commonly identified their race/ethnicity as Indigenous (33%) and 15% were recent newcomers to Canada. Evidence of at least 1 adverse SDoH was noted in 41% of charts; the most common included material poverty (34%), food insecurity (11%), and child welfare involvement (20%). The median number of diagnoses per patient was 4. The most frequently documented diagnoses were neurodevelopmental disorders (50%) including developmental delay (39%), ADHD (32%), and learning disability (26%). The program referred 72% of patients to general pediatricians and/or other subspecialists; 34% were referred for tertiary neuropsychological assessments and 35% for mental health services. Conclusions: Our data suggests that this low-barrier, place-based primary care RICHER model was able to reach a medically, developmentally, and socially complex population living in disenfranchised urban neighborhoods. Half of the patients identified in our review had neurodevelopmental concerns and a third had mental health concerns, in contrast to an estimated 17% prevalence for mental health, behavioral, or developmental disorders in North American general pediatric aged populations. This highlights the impact adverse SDoH can have on child health and the importance of working with community partners to identify developmentally vulnerable children and support place-based programs in connecting with children who may be missed, overlooked, or disadvantaged through traditional models of care.
The Intra-articular Tendinous Graft Diameter of 10-mm Bone–Patellar Tendon–Bone Autografts in Adolescent Patients: An MRI Analysis of 100 Patients
Authors: Beber Samuel A. , Jones Ruth H. , Cirrincione Peter , Gross Preston W. , Green Daniel W. , Greditzer Harry G. , Heyworth Benton E. , Fabricant Peter D. 
Published: August 2024

Background: Bone–patellar tendon–bone (BPTB) autograft size may be one modifiable predictor of anterior cruciate ligament (ACL) reconstruction postoperative success, as smaller graft diameter has been associated with higher rates of rupture requiring revision. However, measuring the true intra-articular tendinous graft diameter of the soft tissue portion of a BPTB graft with standard intraoperative methods is difficult while keeping the graft intact. Purpose/Hypothesis: The purpose of the study was to use 3-dimensional magnetic resonance imaging (MRI) measurements to determine the cross-sectional area of the soft tissue, tendinous portion of a standard BPTB autograft with 10-mm diameter bone plugs, and, by calculation, the collagen graft size (ie, graft diameter), as would typically be reported in ACL reconstruction studies that consider soft tissue graft size. It was hypothesized that the calculated collagen graft diameter of 10-mm BPTB autografts would be significantly smaller than 10 mm. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 100 patients (10 girls and 10 boys at each age from 13 to 17 years) who underwent a knee MRI at a single academic orthopaedic center without documented extensor mechanism pathology were identified. The central 10-mm width of the patellar tendon that would be harvested for BPTB autograft was measured. The region of interest area tool was then used to measure the cross-sectional area of a 10-mm BPTB graft with subsequent soft tissue autograft diameter calculation. Results: The mean calculated tendinous graft diameter of a 10 mm–wide BPTB graft was 6.3 ± 0.5 mm and was significantly smaller than a 10-mm reference ( P≤ .001). There was no significant association between age and cross-sectional area or graft diameter. Conclusion: Modern 3-dimensional imaging-based measurement techniques demonstrated that the true intra-articular tendinous soft tissue portion of 10-mm BPTB autografts shows substantial variation and is significantly smaller in diameter than the tunnels typically reamed to accommodate the bone plug portions of these grafts. Moreover, as graft size is a predictor of rupture rate, preoperative MRI-based evaluation may be an important tool when considering BPTB autograft for ACL reconstruction. Future comparative clinical research utilizing graft size as a study variable should consider quantifying and utilizing the diameter of the soft tissue component of BPTB autografts.
Knowledge and Associated Factors Towards Sepsis Management Among Nurses Working in the Emergency Department of Public Hospitals in Addis Ababa
Authors: Alaro Michael Geletu , Ashine Taye Mezgebu , Kebede Sofia , Hussien Heyria , Alaro Melaku Geletu , Kechine Tibore Temesgen 
Published: August 2024

Background Sepsis is a major cause of mortality worldwide and an important public health problem. The quality of patient care is negatively impacted when nurses lack adequate knowledge regarding the management of sepsis. On the other hand, little is known regarding Ethiopian nurses’ knowledge of sepsis management. Objective To assess the level of knowledge and the associated factors towards sepsis management among nurses working in emergency departments in public hospitals in Addis Ababa, Ethiopia. Method From March 18 to April 18, 2022, a health facility-based cross-sectional study was conducted. A simple sampling technique (lottery method) was used to select the hospitals. The data was analyzed using SPSS version 25. The study employed logistic regression analysis to examine the association between the independent variables and the level of knowledge. Variables were significantly associated with a level of knowledge if they had a p-value of less than 0.05 and a 95% confidence interval. Result Of the 127 participants, more than half (56.7%) had poor knowledge. Nurses’ knowledge of managing sepsis was significantly associated with not having regular training, a low level of education, and working experience of less than five years. The findings of the multivariable regression analysis revealed that the following variables were associated with a nurse's knowledge of sepsis management: low level of education (AOR = 3.2 (95% CI, 1.16–8.77), lack of training adjusted odd ratio (AOR = 2.5 (95% CI, 1.07–5.93), and less than five years of work experience (AOR = 3.6 (95% CI, 1. 29–9.830). Conclusion The majority of nurses had inadequate knowledge of managing sepsis. On the other hand, the majority of nurses had a favourable attitude toward sepsis management. Lack of prior training, a low level of education, and less than five years of work experience were all significantly associated with nurses’ poor knowledge regarding sepsis management. This study recommends that hospital managers should provide on-the-job and long-term training for nurses working in the emergency department to enhance the level of nurses’ knowledge towards sepsis management at their institutions.
An unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma
Authors: Grillone Katia , Ascrizzi Serena , Cremaschi Paolo , Amato Jussara , Polerà Nicoletta , Croci Ottavio , Rocca Roberta , Riillo Caterina , Conforti Francesco , Graziano Raffaele , Brancaccio Diego , Caracciolo Daniele , Alcaro Stefano , Pagano Bruno , Randazzo Antonio , Tagliaferri Pierosandro , Iorio Francesco , Tassone Pierfrancesco 
Published: August 2024

Abstract
Multiple myeloma (MM) is an incurable malignancy characterized by altered expression of coding and noncoding genes promoting tumor growth and drug resistance. Although the crucial role of long noncoding RNAs (lncRNAs) in MM is clearly established, the function of the noncoding RNAome, which might allow the design of novel therapeutics, is largely unknown. We performed an unbiased CRISPR-Cas9 loss-of-function screen of 671 lncRNAs in MM cells and their bortezomib (BZB)–resistant derivative. To rank functionally and clinically relevant candidates, we designed and used a bioinformatic prioritization pipeline combining functional data from cellular screens with prognostic and transcriptional data from patients with MM. With this approach, we unveiled and prioritized 8 onco-lncRNAs essential for MM cell fitness, associated with high expression and poor prognosis in patients with MM. The previously uncharacterized RP11-350G8.5 emerged as the most promising target, irrespective of BZB resistance. We (1) demonstrated the anti-tumoral effect obtained by RP11-350G8.5 inhibition in vitro and in vivo; (2) highlighted a modulation of the unfolded protein response and the induction of immunogenic cell death triggered by the RP11-350G8.5 knockout, via RNA sequencing and molecular studies; (3) characterized its cytoplasmic homing through RNA fluorescence in situ hybridization; and (4) predicted its 2-dimensional structure and identified 2 G-quadruplex and 3 hairpin-forming regions by biophysical assays, including thioflavin T, 1H nuclear magnetic resonance, and circular dichroism, to pave the way to the development of novel targeted therapeutics. Overall, we provided innovative insights about unexplored lncRNAs in MM and identified RP11-350G8.5 as an oncogenic target for treatment-naïve and BZB-resistant patients with MM.
Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo
Authors: Puy Cristina , Moellmer Samantha A. , Pang Jiaqing , Vu Helen H. , Melrose Alexander R. , Lorentz Christina U. , Tucker Erik I. , Shatzel Joseph J. , Keshari Ravi S. , Lupu Florea , Gailani David , McCarty Owen J. T. 
Published: August 2024

Abstract
Loss of endothelial barrier function contributes to the pathophysiology of many inflammatory diseases. Coagulation factor XI (FXI) plays a regulatory role in inflammation. Although activation of FXI increases vascular permeability in vivo, the mechanism by which FXI or its activated form FXIa disrupts endothelial barrier function is unknown. We investigated the role of FXIa in human umbilical vein endothelial cell (HUVEC) or human aortic endothelial cell (HAEC) permeability. The expression patterns of vascular endothelial (VE)-cadherin and other proteins of interest were examined by western blot or immunofluorescence. Endothelial cell permeability was analyzed by Transwell assay. We demonstrate that FXIa increases endothelial cell permeability by inducing cleavage of the VE-cadherin extracellular domain, releasing a soluble fragment. The activation of a disintegrin and metalloproteinase 10 (ADAM10) mediates the FXIa-dependent cleavage of VE-cadherin, because adding an ADAM10 inhibitor prevented the cleavage of VE-cadherin induced by FXIa. The binding of FXIa with plasminogen activator inhibitor 1 and very low–density lipoprotein receptor on HUVEC or HAEC surfaces activates vascular endothelial growth receptor factor 2 (VEGFR2). The activation of VEGFR2 triggers the mitogen-activated protein kinase (MAPK) signaling pathway and promotes the expression of active ADAM10 on the cell surface. In a pilot experiment using an established baboon model of sepsis, the inhibition of FXI activation significantly decreased the levels of soluble VE-cadherin to preserve barrier function. This study reveals a novel pathway by which FXIa regulates vascular permeability. The effect of FXIa on barrier function may be another way by which FXIa contributes to the development of inflammatory diseases.
Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia
Authors: Zhou Xinyue , Zhang Lixia , Aryal Sajesan , Veasey Virginia , Tajik Amanda , Restelli Cecilia , Moreira Steven , Zhang Pengcheng , Zhang Yanfeng , Hope Kristin J. , Zhou Yang , Cheng Changde , Bhatia Ravi , Lu Rui 
Published: August 2024

Abstract
Menin inhibitors that disrupt the menin-MLL interaction hold promise for treating specific acute myeloid leukemia (AML) subtypes, including those with KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncovered a potential resistance mechanism independent of canonical menin-MLL targets. We show that a group of noncanonical menin targets, which are bivalently cooccupied by active menin and repressive H2AK119ub marks, are typically downregulated after menin inhibition. Loss of polycomb repressive complex 1.1 (PRC1.1) subunits, such as polycomb group ring finger 1 (PCGF1) or BCL6 corepressor (BCOR), leads to menin inhibitor resistance by epigenetic reactivation of these noncanonical targets, including MYC. Genetic and pharmacological inhibition of MYC can resensitize PRC1.1-deficient leukemia cells to menin inhibition. Moreover, we demonstrate that leukemia cells with the loss of PRC1.1 subunits exhibit reduced monocytic gene signatures and are susceptible to BCL2 inhibition, and that combinational treatment with venetoclax overcomes the resistance to menin inhibition in PRC1.1-deficient leukemia cells. These findings highlight the important roles of PRC1.1 and its regulated noncanonical menin targets in modulating the menin inhibitor response and provide potential strategies to treat leukemia with compromised PRC1.1 function.
Targeting CDC42 reduces skeletal degeneration after hematopoietic stem cell transplantation
Authors: Landspersky Theresa , Stein Merle , Saçma Mehmet , Geuder Johanna , Braitsch Krischan , Rivière Jennifer , Hettler Franziska , Romero Marquez Sandra , Vilne Baiba , Hameister Erik , Richter Daniel , Schönhals Emely , Tuckermann Jan , Verbeek Mareike , Herhaus Peter , Hecker Judith S. , Bassermann Florian , Götze Katharina S. , Enard Wolfgang , Geiger Hartmut , Oostendorp Robert A. J. , Schreck Christina 
Published: August 2024

Abstract
Osteopenia and osteoporosis are common long-term complications of the cytotoxic conditioning regimen for hematopoietic stem cell transplantation (HSCT). We examined mesenchymal stem and progenitor cells (MSPCs), which include skeletal progenitors, from mice undergoing HSCT. Such MSPCs showed reduced fibroblastic colony-forming units frequency, increased DNA damage, and enhanced occurrence of cellular senescence, whereas there was a reduced bone volume in animals that underwent HSCT. This reduced MSPC function correlated with elevated activation of the small Rho guanosine triphosphate hydrolase CDC42, disorganized F-actin distribution, mitochondrial abnormalities, and impaired mitophagy in MSPCs. Changes and defects similar to those in mice were also observed in MSPCs from humans undergoing HSCT. A pharmacological treatment that attenuated the elevated activation of CDC42 restored F-actin fiber alignment, mitochondrial function, and mitophagy in MSPCs in vitro. Finally, targeting CDC42 activity in vivo in animals undergoing transplants improved MSPC quality to increase both bone volume and trabecular bone thickness. Our study shows that attenuation of CDC42 activity is sufficient to attenuate reduced function of MSPCs in a BM transplant setting.
Discontinuing hormonal gender reassignment: a nationwide register study
Authors: Kaltiala Riittakerttu , Helminen Mika , Holttinen Timo , Tuisku Katinka 
Published: August 2024

Abstract
Background
With increasing numbers of people seeking medical gender reassignment, the scientific community has become increasingly aware of the issue of detransitioning from social, hormonal or even surgical gender reassignment (GR). This study aimed to assess the proportion of patients who discontinued their established hormonal gender transition and the risk factors for discontinuation.

Methods
A nationwide register-based follow-up was conducted. Data were analysed via cross-tabulations with chi-square statistics and t tests/ANOVAs. Multivariate analyses were performed via Cox regression, which accounts for differences in follow-up times.

Results
Of the 1,359 subjects who had undergone hormonal GR in Finland from 1996 to 2019, 7.9% discontinued their established hormonal treatment during an average follow-up of 8.5 years. The risk for discontinuing hormonal GR was greater among later cohorts. The hazard ratio was 2.7 (95% confidence interval 1.1–6.1) among those who had accessed gender identity services from 2013 to 2019 compared with those who had come to contact from 1996 to 2005. Discontinuing also appeared to be emerging earlier among those who had entered the process in later years.

Conclusions
The risk of discontinuing established medical GR has increased alongside the increase in the number of patients seeking and proceeding to medical GR. The threshold to initiate medical GR may have lowered, resulting in a greater risk of unbalanced treatment decisions.

Trial registration number (TRN)
Not applicable (the paper does not present a clinical trial).