bluuebunny/crossref_metadata_2025_split huggingface dataset:
Questioning approaches to consent in time critical obstetric trials: findings from a mixed-methods study
Authors: Deja Elizabeth , Weeks Andrew , Van Netten Charlotte , Gamble Carrol , Meher Shireen , Gyte Gillian , Lavender Tina , Woolfall Kerry 
Published: February 2024

ObjectiveTrial legislation enables research to be conducted without prior consent (RWPC) in emergency situations, yet this approach has rarely been used in time-critical obstetric trials. This study explored views and experiences of antenatal recruitment and consent and RWPC in an emergency intrapartum randomised clinical trial.DesignEmbedded, mixed-methods study within a trial, involving questionnaires, recorded recruitment discussions, interviews and focus groups in the first 13 months of trial recruitment (December 2020–January 2022).SettingCOPE is a double-blind randomised controlled trial, comparing the effectiveness of carboprost or oxytocin as first-line treatment of postpartum haemorrhage.ParticipantsTwo hundred and eighty-six people (190 women/96 birth partners), linked to 198/380 (52%) COPE recruits participated in the embedded study. Of these, 272 completed a questionnaire (178 women/94 birth partners), 22 were interviewed (19 women/3 birth partners) and 16 consent discussions with 12 women were recorded. Twenty-seven staff took part in three focus groups and nine staff were interviewed.ResultsParticipants recommended that information about the study should be more accessible antenatally for those who wish to be informed. Most women and staff did not think it would be appropriate to seek consent during pregnancy or early labour as it may cause ‘unnecessary panic’ and lead to research waste, as most women would not become eligible. There was support for the use of RWPC as COPE interventions are used in standard clinical practice and viewed as low risk. Women who were approached about the trial while having a postpartum haemorrhage also supported RWPC as they could not recall research discussions.ConclusionsFindings support the use of RWPC for time-critical interventions, and raise questions about the appropriateness of other commonly used consent pathways, including antenatal consent and verbal assent.
Virtual quality improvement collaborative with primary care practices during COVID-19: a case study within a clinically integrated network
Authors: Rohweder Catherine L , Morrison Abigail , Mottus Kathleen , Young Alexa , Caton Lauren , Booth Ronni , Reed Christine , Shea Christopher M , Stover Angela M 
Published: February 2024

IntroductionQuality improvement collaboratives (QICs) are a common approach to facilitate practice change and improve care delivery. Attention to QIC implementation processes and outcomes can inform best practices for designing and delivering collaborative content. In partnership with a clinically integrated network, we evaluated implementation outcomes for a virtual QIC with independent primary care practices delivered during COVID-19.MethodsWe conducted a longitudinal case study evaluation of a virtual QIC in which practices participated in bimonthly online meetings and monthly tailored QI coaching sessions from July 2020 to June 2021. Implementation outcomes included: (1) level of engagement (meeting attendance and poll questions), (2) QI capacity (assessments completed by QI coaches), (3) use of QI tools (plan-do-check-act (PDCA) cycles started and completed) and (4) participant perceptions of acceptability (interviews and surveys).ResultsSeven clinics from five primary care practices participated in the virtual QIC. Of the seven sites, five were community health centres, three were in rural counties and clinic size ranged from 1 to 7 physicians. For engagement, all practices had at least one member attend all online QIC meetings and most (9/11 (82%)) poll respondents reported meeting with their QI coach at least once per month. For QI capacity, practice-level scores showed improvements in foundational, intermediate and advanced QI work. For QI tools used, 26 PDCA cycles were initiated with 9 completed. Most (10/11 (91%)) survey respondents were satisfied with their virtual QIC experience. Twelve interviews revealed additional themes such as challenges in obtaining real-time data and working with multiple electronic medical record systems.DiscussionA virtual QIC conducted with independent primary care practices during COVID-19 resulted in high participation and satisfaction. QI capacity and use of QI tools increased over 1 year. These implementation outcomes suggest that virtual QICs may be an attractive alternative to engage independent practices in QI work.
Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates
Authors: Petersen Mark E. , Brant Michael G. , Lasalle Manuel , Das Samir , Duan Renee , Wong Jodi , Ding Tong , Wu Kaylee J. , Siddappa Dayananda , Fang Chen , Zhang Wen , Wu Alex M. L. , Hirkala-Schaefer Truman , Garnett Graham A. E. , Fung Vincent , Yang Luying , Hernandez Rojas Andrea , Lawn Samuel O. , Barnscher Stuart D. , Rich Jamie R. , Colombo Raffaele 
Published: February 2024

Abstract
In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by the clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present the development of a novel camptothecin ZD06519 (FD1), which has been specifically designed for its application as an ADC payload. A panel of camptothecin analogs with different substituents at the C-7 and C-10 positions of the camptothecin core was prepared and tested in vitro. Selected compounds spanning a range of potency and hydrophilicity were elaborated into drug-linkers, conjugated to trastuzumab, and evaluated in vitro and in vivo. ZD06519 was selected on the basis of its favorable properties as a free molecule and as an antibody conjugate, which include moderate free payload potency (∼1 nmol/L), low hydrophobicity, strong bystander activity, robust plasma stability, and high-monomeric ADC content. When conjugated to different antibodies using a clinically validated MC-GGFG–based linker, ZD06519 demonstrated impressive efficacy in multiple cell line–derived xenograft models and noteworthy tolerability in healthy mice, rats, and non-human primates.
Evaluation of Wintertime Precipitation Estimates and Forecasts in the Mountains of Colorado
Authors: Bytheway Janice L. , Currier William R. , Abel Mimi R. , Mahoney Kelly , Cifelli Rob 
Published: February 2024

Abstract
Wintertime precipitation poses many observational and forecasting challenges, especially in the complex topography of the western United States where radar beam blockage and difficulty siting in situ observations yields more sparse observations than in the eastern United States. Uncertainty in western U.S. winter precipitation is known to be high, so much so that some studies have found model simulated precipitation to produce similar or better large-scale estimates of annual precipitation than gridded observational products during climatologically anomalous years. This study evaluates high-resolution gridded precipitation estimates from Multi-Radar Multi-Sensor (MRMS) and Stage IV as well as forecasts from NOAA’s High-Resolution Rapid Refresh (HRRR) model in the Colorado Rocky Mountains. Gridded precipitation estimates and forecasts are compared with in situ SNOTEL measurements for two seasons of wintertime precipitation. The influence of forecast length, lead time, and model elevation on seasonal precipitation predictions from the HRRR are investigated. Additional comparisons are made with the relatively dense network of observations deployed in Colorado’s East River Watershed during the Study of Precipitation, the Lower Atmosphere and Surface for Hydrometeorology (SPLASH) campaign. Gridded products and forecasts are found to underestimate cold-season precipitation by 25%–65% relative to in situ and aircraft measurements, with longer forecast periods and lead times (6–24 h) having smaller biases (25%–30%) than shorter forecast periods and lead times (55%–65%). The assessment of multiple years of observations indicates that these biases are related more to the data and methods used to create the gridded products and forecasts than to precipitation characteristics.

Significance Statement
In the mountainous western United States, it is very challenging to both observe and forecast wintertime precipitation, yet snowfall plays an important role in providing the region’s annual water supply. This study aims to increase our understanding of the biases in observations and forecasts of snowfall in the Colorado Rocky Mountains, which can in turn impact forecasts of water availability for the ensuing warm season. In this study we find high-resolution gridded precipitation estimates and forecasts to underestimate cold-season precipitation when compared with in situ observing stations, with longer-range forecasts (e.g., daily) being the least biased. These findings were consistent over two years of study and have broad implications for the hydrologic modeling and water management communities.
A Comparative Review of UNCRC and Indian Legislation from the Child Mental Health Perspective
Authors: Srinivasan Shiva Prakash , S Shruthi 
Published: February 2024

Background: The United Nations Convention on the Rights of the Child (UNCRC) is the most comprehensive set of standards promoting and protecting children’s interests. It can be utilized to create appropriate policies and legislation that enshrine the values identified in the UNCRC. In India, children have been considered only in the context of their family and were welfare recipients in the past, but more legislation has been enacted to protect and promote the child’s rights. A comparative review will help identify how the new legislation enacted after India ratified the UNCRC directly or indirectly addressed children’s mental health. Methodology: Legislation enacted after 1992 with the search term “child” was identified in the Indian national portal for legislation. These were compared against specific articles of the UNCRC identified to have a direct or indirect bearing on children’s mental health. Results: The review revealed that only 11 of the 32 legislation enacted after 1992 address different aspects of children’s mental health. Only three refer to the UNCRC in their preamble or content. Six of the 11 legislation addressed Article 24, while Article 32 and Article 34 were addressed in only one legislation each. Notably, most of the legislation is focused on child protection, while very few address the participation component of the guiding principles. Discussion: The UNCRC is a valuable guide to creating a legal framework to support child rights. This review highlights the need to consider children’s mental health as a fundamental right and incorporate the principles into future Indian legislation.
The correlation between high-sensitivity troponin-T and cell-free cardiac DNA in the blood of patients undergoing noncardiac, predominantly vascular surgery
Authors: Alekberli Tural , Ohana Braha Lea , Zemmour Hai , Khader Rudy , Shemer Ruth , Dor Yuval , Landesberg Giora 
Published: February 2024

Objective To present a novel method that uses an epigenetic fingerprint to measure changes in plasma concentrations of cardiac-specific cell-free DNA (CS-cfDNA) as a marker of myocardial cell death. Methods This prospective, analytic, observational comparative study included patients with heart disease or multiple risk factors for heart disease undergoing major noncardiac, mostly vascular surgery, requiring an arterial-line, and at least 24 h hospitalization in the post anaesthesia care unit or critical care unit after surgery. Blood samples were collected at least four times per patient to measure troponin-T (via high-sensitivity troponin-T test) and CS-cfDNA pre- and postoperatively. Results A total of 117 patients were included (group 1, 77 patients [66%] with low preoperative and postoperative troponin-T; group 2, 18 patients [15%] with low preoperative but increased postoperative troponin-T; group 3, 16 patients [14%] with high troponin-T both preoperatively and postoperatively; and group 4, six patients [5%] with elevated preoperative troponin-T that decreased postoperatively). The increase in CS-cfDNA after surgery was statistically significant only in group 2, which correlated with an increase in troponin-T in the same group. Conclusions CS-cfDNA increased early postoperatively, particularly in patients with silent postoperative troponin elevation, and was correlated with an increase in troponin-T. These results may suggest that, in the subgroup of patients with postoperative elevated troponin, cardiomyocyte death indeed occurred.
Detrimental Effects of Chlorhexidine on Articular Cartilage Viability, Matrix, and Mechanics
Authors: Moslehyazdi Maziar , Bielajew Benjamin , Schlechter John A. , Hu Jerry C. , Athanasiou Kyriacos A. , Wang Dean 
Published: February 2024

Background: Chlorhexidine gluconate (CHG) solution is commonly used as an antiseptic irrigation for bacterial decontamination during orthopaedic surgery. Although the chondrotoxicity of CHG on articular cartilage has been reported, the full extent of CHG-related chondrotoxicity and its effects on the extracellular matrix and mechanical properties are unknown. Purpose: To investigate the in vitro effects of a single 1-minute CHG exposure on the viability, biochemical content, and mechanics of native articular cartilage explants. Study Design: Controlled laboratory study. Methods: Articular cartilage explants (6 per group) were harvested from femoral condyles of the porcine stifle and sectioned at tidemark. Explants were bathed in CHG solution (0.05% CHG in sterile water) at varying concentrations (0% control, 0.01% CHG, and 0.05% CHG) for 1 minute, followed by complete phosphate-buffered saline wash and culture in chondrogenic medium. At 7 days after CHG exposure, cell viability, matrix content (collagen and glycosaminoglycan [GAG]), and compressive mechanical properties (creep indentation testing) were assessed. Results: One-minute CHG exposure was chondrotoxic to explants, with both 0.05% CHG (2.6% ± 4.1%) and 0.01% CHG (76.3% ± 8.6%) causing a decrease in chondrocyte viability compared with controls (97.5% ± 0.6%; P < .001 for both). CHG exposure at either concentration had no significant effect on collagen content, while 0.05% CHG exposure led to a significant decrease in mean GAG per wet weight compared with the control group (2.6% ± 1.7% vs 5.2% ± 1.9%; P = .029). There was a corresponding weakening of mechanical properties in explants treated with 0.05% CHG compared with controls, with decreases in mean aggregate modulus (177.8 ± 90.1 kPa vs 280.8 ± 19.8 kPa; P < .029) and shear modulus (102.6 ± 56.5 kPa vs 167.9 ± 16.2 kPa; P < .020). Conclusion: One-minute exposure to CHG for articular cartilage explants led to dose-dependent decreases in chondrocyte viability, GAG content, and compressive mechanical properties. This raises concern for the risk of mechanical failure of the cartilage tissue after CHG exposure. Clinical Relevance: Clinicians should be judicious regarding the use of CHG irrigation at these concentrations in the presence of native articular cartilage.
The Promising 2-Year Performance of the Patient-Reported Outcomes Measurement Information System in Primary Hip Arthroscopy for Femoroacetabular Impingement Syndrome
Authors: Vogel Michael J. , Wright-Chisem Joshua , Alvero Alexander B. , Chan Jimmy J. , Chapman Reagan S. , Nho Shane J. 
Published: February 2024

Background: Minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) thresholds have been previously defined for the Patient-Reported Outcomes Measurement Information System (PROMIS) at 1-year follow-up in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome; however, the MCID and PASS thresholds are yet to be defined for the PROMIS at 2-year follow-up. Purpose: (1) To establish MCID and PASS thresholds for the PROMIS Pain Interference (PROMIS-PI) and PROMIS Physical Function (PROMIS-PF) at 2-year follow-up and (2) to correlate PROMIS scores with hip-specific patient-reported outcome measure (PROM) scores. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Patients undergoing primary hip arthroscopy for femoroacetabular impingement syndrome between August and November 2020 with preoperative and minimum 2-year postoperative data were identified. Collected scores included those for the PROMIS-PI, PROMIS-PF, Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sports Subscale (HOS-SS), International Hip Outcome Tool–12 (iHOT-12), and visual analog scale (VAS) for pain. MCID thresholds were calculated using the distribution-based method and PASS thresholds using the anchor-based method. Pearson correlation coefficients were used to compare scores between PROMs. Results: A total of 65 patients met the criteria for inclusion (72.3% female; mean age, 36.9 ± 13.5 years; mean body mass index, 26.2 ± 6.0). The mean follow-up was 25.3 ± 3.3 months. Significant preoperative to postoperative improvements were observed for all PROMs ( P < .001). MCID thresholds and achievement rates were as follows: HOS-ADL, 10.1 and 75%, respectively; HOS-SS, 13.8 and 79%, respectively; iHOT-12, 14.0 and 67%, respectively; VAS pain, –13.8 and 78%, respectively; PROMIS-PI, –4.7 and 65%, respectively; and PROMIS-PF, 5.8 and 60%, respectively. PASS thresholds and achievement rates were as follows: HOS-ADL, 78.7 and 67%, respectively; HOS-SS, 76.4 and 62%, respectively; iHOT-12, 67.4 and 60%, respectively; VAS pain, 25.5 and 61%, respectively; PROMIS-PI, 57.0 and 65%, respectively; and PROMIS-PF, 45.6 and 58%, respectively. PROMIS-PI scores correlated most strongly with HOS-ADL ( r = −0.836), HOS-SS ( r = −0.767), and iHOT-12 ( r = −0.719) scores and exhibited at least moderate correlations ( r≥−0.595) with the other PROM scores. PROMIS-PF demonstrated moderate correlations with all the other PROM scores ( r≥−0.586). Strong correlations were seen between the hip-specific PROM scores ( r≥−0.745). Conclusion: This study defined 2-year MCID and PASS thresholds for the PROMIS-PI and PROMIS-PF and demonstrated moderate to strong correlations between PROMIS scores and hip-specific PROM scores.
Electroacupuncture attenuates cerebral ischemia/reperfusion injury by regulating oxidative stress, neuronal death and neuroinflammation via stimulation of PPAR-γ
Authors: Cheng Nanfang , Cheng Xinyuan , Tan Feng , Liang Yangui , Xu Lihong , Wang Jian , Tan Jiuqing 
Published: February 2024

Background: Oxidative stress and inflammatory responses play essential roles in cerebral ischemia/reperfusion (I/R) injury. Electroacupuncture (EA) is widely used as a rehabilitation method for stroke in China; however, the underlying mechanism of action remains unclear. Peroxisome proliferator–activated receptor gamma (PPAR-γ) has been reported to impact anti-inflammatory and anti-oxidative effects. Objective: This study investigated the role of PPAR-γ in EA-mediated effects and aimed to illuminate its possible mechanisms in cerebral I/R. Methods: In this study, male Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury were treated with EA at LI11 and ST36 for 30 min daily after MCAO/R for seven consecutive days. The neuroprotective effects of EA were measured by neurobehavioral evaluation, triphenyltetrazolium chloride staining, hematoxylin–eosin staining and transmission electron microscopy. Oxidative stress, inflammatory factors, neural apoptosis and microglial activation were examined by enzyme-linked immunosorbent assay, immunofluorescence and reverse transcriptase polymerase chain reaction. Western blotting was used to assess PPAR-γ-mediated signaling. Results: We found that EA significantly alleviated cerebral I/R-induced infarct volume, decreased neurological scores and inhibited I/R-induced oxidative stress, inflammatory responses and microglial activation. EA also increased PPAR-γ protein expression. Furthermore, the protective effects of EA were reversed by injection of the PPAR-γ antagonist T0070907. Conclusion: EA attenuates cerebral I/R injury by regulating oxidative stress, neuronal death and neuroinflammation via stimulation of PPAR-γ.
Dental caries, tobacco usage and associated risk factor of dental caries in patients visiting a government hospital in Western, Nepal
Authors: Subedi Krishna , Sigdel Bhawana , Khanal Purna Prasad , Sharma Deepa , Chaudhary Ganesh , Singh Ashish Kunwar , Paneru Sunil 
Published: February 2024

Abstract
Background
This study was conducted to assess the prevalence of dental caries, tobacco usage, and associated risk factors for dental caries in patients who visited a government hospital in Western, Nepal.

Methods
This analytical cross-sectional study was conducted from January to April 2022. Patients above 18 years visiting the dental OPD of a government hospital, and who had provided informed consent were enrolled in the study using a convenience sampling technique. As the study also involved an illiterate population, in that case, informed consent was obtained from their respective legal guardian as well. A pretested standardized, close-ended questionnaire was administered by researchers to gather information regarding the associated risk factors and oral hygiene practices. Clinical examination was done for dental caries according to the criteria by the World Health Organization (WHO) using the “DMFT” index (WHO modification 1987). Bivariate and multivariable logistic regression was done and the odds ratio and p-value was calculated. For all tests, statistical significance was set at p < 0.05.

Results
A total of 219 participants completed the study with a mean age of 31.73 ± 12.46. The prevalence of dental caries and tobacco was found to be 80.36% and 5.02% respectively. Participants without health insurance had 2.35 times higher odds of dental caries (95% CI: 1.03–5.36). Not rinsing the mouth after eating sweets was associated with 3.07 times higher odds of dental caries (95% CI: 1.31–7.18). Those who hadn’t visited a dentist in the past 12 months had lower odds (0.42; 95% CI: 0.18–0.94). Eating fresh fruit daily showed statistically higher odds (2.70; 95% CI: 1.04–6.99) of dental caries. Non-tobacco users had higher odds (14.19; 2.55–78.99) of dental caries.

Conclusion
Dental caries is highly prevalent, while tobacco usage is relatively low. Factors associated with dental caries included lack of health insurance coverage, consumption of fruits once daily, recent dental visits within the past year, not rinsing the mouth with water after consuming sweets, and non-tobacco users.
Blood cytopenias as manifestations of inherited metabolic diseases: a narrative review
Authors: Moutapam-Ngamby—Adriaansen Yannick , Maillot François , Labarthe François , Lioger Bertrand 
Published: February 2024

AbstractInherited Metabolic Diseases (IMD) encompass a diverse group of rare genetic conditions that, despite their individual rarity, collectively affect a substantial proportion, estimated at as much as 1 in 784 live births. Among their wide-ranging clinical manifestations, cytopenia stands out as a prominent feature. Consequently, IMD should be considered a potential diagnosis when evaluating patients presenting with cytopenia. However, it is essential to note that the existing scientific literature pertaining to the link between IMD and cytopenia is limited, primarily comprising case reports and case series. This paucity of data may contribute to the inadequate recognition of the association between IMD and cytopenia, potentially leading to underdiagnosis. In this review, we synthesize our findings from a literature analysis along with our clinical expertise to offer a comprehensive insight into the clinical presentation of IMD cases associated with cytopenia. Furthermore, we introduce a structured diagnostic approach underpinned by decision-making algorithms, with the aim of enhancing the early identification and management of IMD-related cytopenia.