bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of MYCN and MAX by PAK family kinases is a novel tumor-suppressor mechanism in neuroblastoma with potential therapeutic implications
Authors: Rozen Esteban J , Wigglesworth Kim , Shohet Jason 
Published: December 2023

AbstractHigh-risk Neuroblastoma (HR-NB) is a very aggressive pediatric cancer, responsible of over 15% of all childhood cancer-associated deaths. Despite very aggressive multimodal interventions, less than 50% of HR-NB patients survive, exhibiting serious long-term sequelae from therapy. Therefore, more efficient, and less toxic interventions are urgently needed. Genomic amplification of the MYCN gene is observed in about 50% of all HR-NB cases, and is the most reliable genomic hallmark associated to a bad prognosis. c-MYC is highly expressed in a significant amount of the remaining (non-MYCN-amplified) HR-NB cases. Here, we investigated an endogenous mechanism mediated by the PAK2 kinase and known to phosphorylate and suppress c-MYC transcriptional activity. We uncovered that PAK2 can also phosphorylate MYCN and its obligate transcriptional partner MAX in two conserved Ser/Thr residues, disrupting MYCN:MAX interaction, transcription, and neuroblastoma cell proliferation. We further provide evidence for a potential mechanism by which PAK kinase activity is blunted in MYCN-amplified neuroblastoma tumors and propose an innovative strategy to circumvent such signaling impairment and potentially suppress HR-NB tumor growth.
Discover overlooked complications after preeclampsia from three real-world medical record datasets of over 100,000 pregnancies
Authors: Zhu Haoming , Yang Xiaotong , Tao Leyang , Xie Wanling , Chang Jui-Hsuan , Wang Zhiping Paul , Langen Elizabeth , Li Ruowang , Gamire Lana X 
Published: December 2023

Structured AbstractImportancePreeclampsia poses a significant threat to women’s long-term health. However, what diseases are affected and at what level they are affected by PE needs a thorough investigation.ObjectiveTo conduct the first large-scale, non-hypothesis-driven study using EHR data from multiple medical centers to comprehensively explore adverse health outcomes after preeclampsiaDesignRetrospective multi-cohort case-control studyParticipantsWe analyzed 3,592 preeclampsia patients and 23,040 non-preeclampsia controls from the University of Michigan Healthcare System. We externally validated the findings using UK Biobank data (443 cases, 14,870 controls) and Cedar Sinai data(2755 cases, 60,305 controls).Main outcomesWe showed that six complications are significantly affected by PE. We demonstrate the effect of race as well as preeclampsia severity on these complications.ResultsPE significantly increases the risk of later hypertension, uncomplicated and complicated diabetes, renal failure and obesity, after careful confounder adjustment. We also identified that hypothyroidism risks are significantly reduced in PE patients, particularly among African Americans. Severe PE affects hypertension, renal failure, uncomplicated diabetes and obesity more than mild PE, as expected. Caucasians are affected more negatively than African Americans by PE on future hypertension, uncomplicated and complicated diabetes and obesity.ConclusionThis study fills a gap in the comprehensive assessment of preeclampsia’s long-term effects using large-scale EHR data and rigorous statistical methods. Our findings emphasize the need for extended monitoring and tailored interventions for women with a history of preeclampsia, by considering pre-existing conditions, preeclampsia severity, and racial differences.Key PointsQuestionWhich complications are more or less likely to occur in patients after preeclampsia (PE), compared to those with normal pregnancies? How do the severity of PE and patient race further affect these complications?FindingsIn a retrospective case-control study on 3 datasets (n = 26,632, n = 15,313, n= 63,060), we identified 5 complications with significantly increased risk due to PE, including hypertension, uncomplicated and complicated diabetes, renal failure and obesity, after careful confounder adjustment. We also identified that hypothyroidism risks are reduced in PE patients, particularly significant among African Americans. Severe PE affects hypertension, renal failure, uncomplicated diabetes and obesity more than mild PE, as expected. Caucasians are affected more negatively than African Americans by PE on future hypertension, uncomplicated and complicated diabetes and obesity.MeaningPatients with a history of PE should be closely monitored and carefully assessed for the risks of developing these complications.
Parkinson’s Families Project: a UK-wide study of early onset and familial Parkinson’s disease
Authors: Towns Clodagh , Fang Zih-Hua , Tan Manuela M. X. , Jasaityte Simona , Schmaderer Theresa M. , Stafford Eleanor J. , Pollard Miriam , Tilney Russel , Hodgson Megan , Wu Lesley , Labrum Robyn , Hehir Jason , Polke James , Lange Lara M. , Schapira Anthony H. V. , Bhatia Kailash P. ,   Parkinson’s Families Project (PFP) Study Group,   Global Parkinson’s Genetics Program (GP2), Singleton Andrew B. , Blauwendraat Cornelis , Klein Christine , Houlden Henry , Wood Nicholas W. , Jarman Paul R. , Morris Huw R. , Real Raquel 
Published: December 2023

ABSTRACTThe Parkinson’s Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson’s disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤ 45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives. We analysed DNA samples with a combination of single nucleotide polymorphism (SNP) array genotyping, multiplex ligation-dependent probe amplification (MLPA), and whole-genome sequencing (WGS). We investigated the association between identified pathogenic mutations and demographic and clinical factors such as age at motor symptom onset, family history, motor symptoms (MDS-UPDRS) and cognitive performance (MoCA). We performed baseline genetic analysis in 718 families, of which 205 had sporadic early-onset PD (sEOPD), 113 had familial early-onset PD (fEOPD), and 400 had late-onset familial PD (fLOPD). 69 (9.6%) of these families carried pathogenic variants in known monogenic PD-related genes. The rate of a molecular diagnosis increased to 28.1% in PD with motor onset ≤ 35 years. We identified pathogenic variants inLRRK2in 4.2% of families, and biallelic pathogenic variants inPRKNin 3.6% of families. We also identified two families withSNCAduplications and three families with a pathogenic repeat expansion inATXN2, as well as single families with pathogenic variants inVCP,PINK1,PNPLA6,PLA2G6,SPG7,GCH1, andRAB32. An additional 73 (10.2%) families were carriers of at least one pathogenic or riskGBA1variant. Most early-onset and familial PD cases do not have a known genetic cause, indicating that there are likely to be further monogenic causes for PD.
“At the end of the day, it is Council’s decision”: Integration of health and equity into urban design and urban planning decisions and policies in Regina Saskatchewan
Authors: Mahani Akram , Lyeo Joonsoo Sean , Fung Agnes , Husack Kelly , Muhajarine Nazeem , Diener Tania , Brown Chelsea 
Published: December 2023

AbstractWhile there is a wealth of literature on the impact of urban design on health, our understanding of the factors that influence integration of health into urban design is limited. With the growing recognition of cities playing a leading role in enhancing health equity and population health outcomes, there is a need to examine the perspectives and experiences of municipal actors around health and equity. To address this gap, we interviewed 30 stakeholders engaged with urban design policy- and decision-making at the City of Regina in Saskatchewan, Canada. We found a lack of shared understanding of health among municipal actors. Our findings identified a number of factors that serve as facilitators and barriers to integrating health and equity in urban design policies. Findings from this case study deepen our understanding of these factors and provide recommendations for developing healthy urban design policies. Our findings underscore the importance of adopting an integrated and holistic approach for healthy and equitable urban design. As urbanisation continues to bring a greater share of the world’s population into urban areas, it is imperative that we deepen our understanding of how municipal governance can be leveraged to create environments that are conducive to the wellbeing of their residents.
Neurocognitive features of mild cognitive impairment and distress symptoms in older adults without major depression
Authors: Nantachai Gallayaporn , Maes Michael , Tran-Chi Vinh-Long , Hemrungrojn Solaphat , Tunvirachaisakul Chavit 
Published: December 2023

AbstractBackgroundTwo distinct symptom dimensions were identified in older adults who did not have major depressive disorder (MDD): a) a dimension associated with mild cognitive dysfunction, and b) a dimension related to distress symptoms of old age (DSOA). It is uncertain whether previous findings regarding the features of amnestic mild cognitive impairment (aMCI) remain valid when patients with MDD are excluded.ObjectivesTo examine, in participants without MDD, the neurocognitive characteristics of aMCI and the objective cognitive characteristics of DSOA. Neurocognition was evaluated utilizing the Cambridge Neurological Test Automated Battery (CANTAB) and memory tests.ResultsThis research demonstrated that CANTAB tests have the capability to differentiate between aMCI and controls. The One Touch Stockings of Cambridge, probability solved on first choice (OTS_PSFC), Rapid Visual Information Processing, A prime, and the Motor Screening Task, mean latency (MOT_ML), were identified as the significant discriminatory CANTAB tests. 37.6% of the variance in the severity of aMCI was predicted by OTS_PSFC, RVP_A’, word list recognition scores, and education. Psychosocial stressors (adverse childhood experiences, negative life events), subjective feelings of cognitive impairment, and RVP, probability of false alarm, account for 40.0% of the DSOA score.DiscussionWhen MDD is ruled out, aMCI is linked to deficits in attention, executive functions, and memory. Psychosocial stressors did not have a statistically significant impact on aMCI or its severity. Enhanced false alarm response bias coupled with heightened psychological stress (including subjective perception of cognitive decline) may contribute to an increase in DSOA among the elderly.Keys word: depression, mild cognitive impairment, adverse childhood experiences, stress, anxiety
SARS-CoV-2 Humoral Immune Responses in Convalescent Individuals Over 12 Months Reveal Severity-Dependent Antibody Dynamics
Authors: Siles Nadia , Schuler Maisey , Maguire Cole , Amengor Dzifa , Nguyen Annalee , Wilen Rebecca , Rogers Jacob , Bazzi Sam , Caslin Blaine , DiPasquale Christopher , Abigania Melissa , Olson Eric , Creaturo Janelle , Hurley Kerin , Triplett Todd A. , Rousseau Justin F. , Strakowski Stephen M. , Wylie Dennis , Maynard Jennifer , Ehrlich Lauren I. R. , Melamed Esther 
Published: December 2023

AbstractBackgroundUnderstanding the kinetics and longevity of antibody responses to SARS-CoV-2 is critical to informing strategies toward reducing Coronavirus disease 2019 (COVID-19) reinfections, and improving vaccination and therapy approaches.MethodsWe evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) of spike in 98 convalescent participants who experienced asymptomatic, mild, moderate or severe COVID-19 disease and in 17 non-vaccinated, non-infected controls, using four different antibody assays. Participants were sampled longitudinally at 1, 3, 6, and 12 months post-SARS-CoV-2 positive PCR test.FindingsIncreasing acute COVID-19 disease severity correlated with higher anti-N and anti-RBD antibody titers throughout 12 months post-infection. Anti-N and anti-RBD titers declined over time in all participants, with the exception of increased anti-RBD titers post-vaccination, and the decay rates were faster in hospitalized compared to non-hospitalized participants. <50% of participants retained anti-N titers above control levels at 12 months, with non-hospitalized participants falling below control levels sooner. Nearly all hospitalized and non-hospitalized participants maintained anti-RBD titers above controls for up to 12 months, suggesting longevity of protection against severe reinfections. Nonetheless, by 6 months, few participants retained >50% of their 1-month anti-N or anti-RBD titers. Vaccine-induced increases in anti-RBD titers were greater in non-hospitalized relative to hospitalized participants. Early convalescent antibody titers correlated with age, but no association was observed between Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or acute steroid treatment and convalescent antibody titers.InterpretationHospitalized participants developed higher anti-SARS-CoV-2 antibody titers relative to non-hospitalized participants, a difference that persisted throughout 12 months, despite the faster decline in titers in hospitalized participants. In both groups, while anti-N titers fell below control levels for at least half of the participants, anti-RBD titers remained above control levels for almost all participants over 12 months, demonstrating generation of long-lived antibody responses known to correlate with protection from severe disease across COVID-19 severities. Overall, our findings contribute to the evolving understanding of COVID-19 antibody dynamics.FundingAustin Public Health, NIAAA, Babson Diagnostics, Dell Medical School Startup.
Bronchoscopy in children with diffuse alveolar hemorrhage under general anesthesia with spontaneous respiration by face mask ventilation: an analysis of thirty-eight procedures
Authors: Yang Ruimin , Wei Qing , Chen Xun , Liu Jing , Li Yan , Liu Jingchen 
Published: December 2023

AbstractPurposeTo improve the management level of general anesthesia during bronchoscopy in the children with diffuse alveolar hemorrhage (DAH).MethodsA retrospective study was conducted in the children with DAH who had performed bronchoscopy under general anesthesia with spontaneous respiration by face mask ventilation initially from June 2021 to June 2022 in our hospital.Results1. Thirty-four children who had underwent 38 bronchoscopy procedures were included. 2. General anesthesia induction was performed by bolus of propofol intravenous in all the procedures. For maintaining anesthesia, 31 procedures (81.6%) received both propofol and remifentanil intravenously infusion and the rest 7 procedures (18.4%) received propofol intravenously infusion only. An intravenous bolus of ketamine or propofol was given as an anesthetic adjuvant in 21 procedures (55.3%). Thirty-five procedures (92.1%) were successfully completed under non-tracheal intubation ventilation, whereas the rest 3 procedures (7.9%) needed change to tracheal intubation ventilation. 3. Respiratory depression was found in 7 procedures (18.4%), laryngospasm was found in 2 procedure (2.6%) and bronchospasm was found in 17 procedures (44.7%). Sixteen procedures (42.1%) developed intraoperative hypoxemia. The incidence of intraoperative hypoxemia in the procedures at the active phage of disease was significantly higher compared to those at the remission phage of the disease (P<0.05). Sixteen procedures (42.1%) developed intraoperative hypercapnia. Two procedures (5.3%) were complicated by severe pulmonary hemorrhage.ConclusionsGeneral anesthesia with spontaneous respiration by face mask ventilation is feasible and relatively safe for the children with DAH undergoing bronchoscopy, whereas the anesthetic protocol still needs to be improved.
Do Networks facilitate innovation, learning and sharing? An evaluation of the Quality-of-Care Network (QCN) in Bangladesh, Ethiopia, Malawi, and Uganda
Authors: Mwandira Kondwani , Lemma Seblewengel , Dube Albert , Akter Kohenour , Tufa Asebe Amenu , Kyamulabi Agnes , Seruwagi Gloria , Nakidde Catherine , Mwaba Kasonde , Djellouli Nehla , Makwenda Charles , Colbourn Tim , Shawar Yusra Ribhi 
Published: December 2023

ABSTRACTThe Quality-of-Care Network (QCN), launched by WHO and partners, links global and national actors across several countries to improve maternal and newborn health. We examine if QCN facilitated learning, sharing and innovations within and between network countries.We evaluated the QCN in Bangladesh, Ethiopia, Malawi and Uganda. We conducted a total 227 qualitative interviews with QCN actors iteratively across a 3-year period from October 2019 to March 2022. We also reviewed all accessible QCN documents.Sharing and learning opportunities were evident through a number of virtual and in-person platforms such as meetings, conferences, webinars, and websites. Conferences and webinars have been hosted on online resource libraries such as the quality-of-care network website. These provided access to materials on strategies and approaches shared by different countries and actors. Innovations were also evident in some countries like Ethiopia. Innovative software applications aimed at boosting the capacity of service providers were developed and these were adopted by countries such as Bangladesh. Locally, there had been strengthening of learning collaborative meetings, coaching and mentorship. Regular meetings such as Stakeholder Coordination Meetings and Learning Collaborative Sessions provided an opportunity for stakeholders to strategize, as well as share and learn approaches within the network.The network has promoted coordination among stakeholders. Similar approaches to sharing and learning such as Learning Collaborative Sessions were evident across the study countries. Innovations were not as apparent across countries and most of the learning and sharing approaches were similar to those from broader, pre-existing maternal health approaches, adopted from an era preceding the QCN. There was evidence that the introduction of the QCN improved the functionality and visibility of learning and sharing platforms.
The role of veterinary diagnostic laboratories during COVID-19 response in the United States
Authors: Clements Nia , Diel Diego G. , Elvinger François , Koretzky Gary , Siler Julie , Warnick Lorin D. 
Published: December 2023

AbstractRobust testing capacity was necessary for public health agencies to respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 19 (COVID-19) pandemic. As the nation faced the need for robust testing capacity, it became necessary to use all possible resources. In many cases, veterinary diagnostic laboratories rose to meet this demand because these facilities routinely perform high throughput diagnostic testing of large animal populations and are typically familiar with pathogens of high pandemic concern. In this study, we evaluated the impact of veterinary diagnostic laboratories in the United States on SARS-CoV-2 testing. Results of surveys, semi-structured interviews, and analysis of publicly available information showed that veterinary diagnostic laboratories had a substantial impact on human health through population-level testing in the COVID-19 response, supporting timely and informed public health interventions. This success was not without significant hurdles, as many participating veterinary diagnostic laboratories experienced restriction in their response due to difficulties obtaining the Clinical Laboratory Improvement Amendments (CLIA) certification required to conduct human diagnostic testing. Our results point out the importance of reducing hurdles before the next major public health emergency to enhance access to testing resources overall and to ultimately improve population health.
Feasibility characteristics of wrist-worn fitness trackers in health status monitoring for post-COVID patients in remote and rural areas
Authors: Wiebe Madeleine , Mackay Marnie , Krishnan Ragur , Tian Julie , Larsson Jake , Modanloo Setayesh , Mcintosh Christiane Job , Sztym Melissa , Elton-Smith Gail , Rose Alyssa , Ho Chester , Greenshaw Andrew , Cao Bo , Chan Andrew , Hayward Jake 
Published: December 2023

AbstractIntroductionCommon, consumer-grade biosensors mounted on fitness trackers and smartwatches can measure an array of biometrics that have potential utility in post-discharge medical monitoring, especially in remote/rural communities. The feasibility characteristics for wrist-worn biosensors are poorly described for post-COVID conditions and rural populations.MethodsWe prospectively recruited patients in rural communities who were enrolled in an at-home rehabilitation program for post-COVID conditions. They were asked to wear a FitBit Charge 2 device and biosensor parameters were analyzed (e.g. heart rate, sleep, and activity). Electronic patient reported outcome measures (E-PROMS) for mental (bi-weekly) and physical (daily) symptoms were collected using SMS text or email (per patient preference). Exit surveys and interviews evaluated the patient experience.ResultsTen patients were observed for an average of 58 days and half (N=5) were monitored for 8 weeks or more. Five patients (50%) had been hospitalized with COVID (mean stay = 41 days) and 4 (36%) had required mechanical ventilation. As baseline, patients had moderate to severe levels of anxiety, depression, and stress; fatigue and shortness of breath were the most prevalent physical symptoms. Four patients (40%) already owned a smartwatch. In total, 575 patient days of patient monitoring occurred across 10 patients. Biosensor data was usable for 91.3% of study hours and surveys were completed 82.1% and 78.7% of the time for physical and mental symptoms, respectively. Positive correlations were observed between stress and resting heart rate (r=0.360, p<0.01), stress and daily steps (r=0.335, p<0.01), and anxiety and daily steps (r=0.289, p<0.01). There was a trend toward negative correlation between sleep time and physical symptom burden (r=-0.211, p=0.05). Patients reported an overall positive experience and identified the potential for wearable devices to improve medical safety and access to care. Concerns around data privacy/security were infrequent.ConclusionsWe report excellent feasibility characteristics for wrist-worn biosensors and e-PROMS as a possible substrate for multi-modal disease tracking in post-COVID conditions. Adapting consumer-grade wearables for medical use and scalable remote patient monitoring holds great potential.