bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic upregulation of Schlafen11 renders &#x2028;WNT- and SHH-activated medulloblastomas sensitive to cisplatin
Authors: Nakata Satoshi , Murai Junko , Okada Masayasu , Takahashi Haruhiko , Findlay Tyler H , Malebranche Kristen , Parthasarathy Akhila , Miyashita Satoshi , Gabdulkhaev Ramil , Benkimoun Ilan , Druillennec Sabine , Chabi Sara , Hawkins Eleanor , Miyahara Hiroaki , Tateishi Kensuke , Yamashita Shinji , Yamada Shiori , Saito Taiki , On Jotaro , Watanabe Jun , Tsukamoto Yoshihiro , Yoshimura Junichi , Oishi Makoto , Nakano Toshimichi , Imamura Masaru , Imai Chihaya , Yamamoto Tetsuya , Takeshima Hideo , Sasaki Atsuo T , Rodriguez Fausto J , Nobusawa Sumihito , Varlet Pascale , Pouponnot Celio , Osuka Satoru , Pommier Yves , Kakita Akiyoshi , Fujii Yukihiko , Raabe Eric H , Eberhart Charles G , Natsumeda Manabu 
Published: October 2022

Abstract

Background
Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma.

Methods
SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo.

Results
High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells.

Conclusions
High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.
Secondhand Smoke Exposure Inside the Home Among Adults in Eight Countries in Sub-Saharan Africa: Global Adult Tobacco Survey, 2012–2018
Authors: Mbulo Lazarous , Palipudi Krishna , Smith Tenecia , Owusu Daniel , Williams Faustine , Dean Anna K , Mamudu Hadii M 
Published: October 2022

AbstractIntroductionSecondhand tobacco smoke (SHS) exposure causes diseases and death in adults and children. Evidence indicates that most SHS exposures occur at home and in the workplace. Therefore, home is a major place where adults and children can be effectively protected from SHS. This study examined the magnitude of SHS exposure at home and associated factors in eight sub-Saharan African countries.Aims and MethodsWe analyzed 2012–2018 Global Adult Tobacco Survey data for Botswana, Cameroon, Ethiopia, Kenya, Nigeria, Senegal, Tanzania, and Uganda. We computed prevalence estimates of self-reported monthly SHS exposure at home reported as anyone smoking inside their home daily, weekly, or monthly. We calculated SHS exposure at home prevalence and applied multivariable logistic regression models to identify related factors.ResultsOverall median prevalence of SHS exposure at home was 13.8% in the eight countries; ranging from 6.6% (95% CI: 5.7%, 7.6%) in Nigeria to 21.6% (95% CI: 19.4%, 24.0%) in Senegal. In multivariable analysis across the countries, SHS exposure at home was associated with living with a smoker, ranging from an adjusted odds ratio (AOR) of 4.6 (95% CI: 3.6, 5.8) in Botswana to 27.6 (95% CI: 20.1, 37.8) in Nigeria. SHS exposure at home was significantly associated with lower education attainment (Kenya and Ethiopia), and lower wealth index (Uganda, Senegal, and Botswana).ConclusionsSHS exposure in homes was associated with the presence of a smoker in the home and lower socioeconomic status.
Female Genital Tuberculosis
Authors: Tzelios Christine , Neuhausser Werner M , Ryley David , Vo Nhi , Hurtado Rocio M , Nathavitharana Ruvandhi R 
Published: October 2022

Abstract
Female genital tuberculosis (FGTB) is an important cause of morbidity and infertility worldwide. Mycobacterium tuberculosis most commonly spreads to the genital tract from a focus elsewhere in the body and affects the bilateral fallopian tubes and/or endometrium. Many patients with FGTB have indolent disease and are only diagnosed after evaluation for infertility. Women may present with menstrual irregularities, lower abdominal or pelvic pain, or abnormal vaginal discharge. Given the low sensitivity of diagnostic tests, various composite reference standards are used to diagnose FGTB, including some combination of endoscopic findings, microbiological or molecular testing, and histopathological evidence in gynecological specimens. Early treatment with a standard regimen of a 2-month intensive phase with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by a 4-month continuation phase with isoniazid and rifampin, is recommended to prevent irreversible organ damage. However, even with treatment, FGTB can lead to infertility or pregnancy-related complications, and stigma is pervasive.
71 Barriers to providing optimal care to children with medical complexity in the emergency department: A physicians' perspective
Authors: Alshammri Fahd , Altamimi Sarah 
Published: October 2022

Abstract

Background
Children with medical complexity (CMC) are a subset of the pediatric population with chronic medical conditions requiring specialized care and high health resource utilization. Due to the nature of their underlying diseases, along with the medical devices that they are reliant on, they account for a large proportion of annual pediatric emergency department (ED) visits in tertiary centres and about one third of the children admitted. ED physicians are often the first to interact with CMC patients and thus the quality of care they provide influences the hospital course of those patients.

Objectives
To determine and explore the barriers that ED physicians face when providing care to CMC in the ED and identify potential areas of improvement in care provided in the ED.

Design/Methods
Semi-structured personal interviews were conducted virtually with 20 pediatric emergency medicine physicians and fellows. Each participant was asked the same set of questions and given extra time to elaborate. Interviews were transcribed verbatim and manual coding was conducted to identify commonalities across the interviews.

Results
We identified four major themes and 12 sub-themes as barriers to optimal care of CMC in the ED. Major themes included time, training, medico-legal concerns, and care plans. The two most commonly identified barriers were time required to care for CMC patients, identified by 90% (n=18) of the participants, and limited exposure during fellowship training, identified by 80% (n=16) of the participants. Only 20% (n=4) identified medico-legal challenges as a unique barrier when managing CMC. All the participants (n=20) emphasized the importance of a care plan, a detailed document given to caregivers of CMC by the primary care team with details about their medical condition, and if not available, 85% (n=17) indicated that it will affect the efficiency and quality of care provided. Even if a care plan is available, 50% (n=10) of the participants would still contact the complex care team for further management recommendations.

Conclusion
Care plan accessibility and time restraint in the ED are major barriers faced by PEM physicians in the ED when caring for CMC. Additional training during fellowship in complex care medicine and providing patients with an updated care plan are two interventions suggested to optimize care of CMC in the ED.
96 Impact and Feasibility of a Pediatric Social Determinants of Health Questionnaire: A Pilot Mixed-Methods Study
Authors: Carwana Matthew , Ricci Taylor , DiCicco Alesia , Ponton Ethan , Duffy Damian , Courtemanche Rebecca , Lau William , Singh Tanjot , Loock Christine 
Published: October 2022

Abstract

Background
Social determinants of health (SDoH)—which are factors such as socioeconomic status (SES), access to transportation, food and housing security, disability and social supports—have been shown to influence up to 50% of health in patients. The project team developed a SDoH Questionnaire which evolved into what is now referred to as BEARS (Barriers to Care, Economic Factors, Adversity, Resiliency, Social Capital). Part of the BEARS Questionnaire includes an optional section for inquiring about Adverse Childhood Experiences (ACEs).

Objectives
The primary purpose of this study was to evaluate the impact and feasibility of the BEARS Questionnaire. Additional objectives were to assess the utility and functionality of the BEARS Questionnaire as a social history-taking tool, including the cumulative ACEs questions, and obtain suggestions for improvement of the tool.

Design/Methods
This was a mixed methods pilot study that consisted of quantitative surveys and qualitative structured interviews with clinicians who had experience using the BEARS Questionnaire. Descriptive statistics were performed on all survey results. Thematic analysis was performed on clinician interviews with recurrent themes being identified through iterative analysis and tagged quotations.

Results
15 clinicians completed the quantitative survey and five took part in a qualitative interview. Study participants included surgeons, pediatricians, speech language pathologists, social workers and nurse clinicians. The BEARS Questionnaire changed clinician practice by increasing the frequency and breadth of social screening in their patients and optimizing care to fit their patients’ social context. Participants described the BEARS as an effective screening tool for SDoH and ACEs that was feasible to implement into their clinic workflow.
Three themes emerged from our interviews: (1) Thorough social history taking highlights family resiliency and improves clinician-patient rapport, (2) Screening for ACEs is acceptable and feasible in a safe clinical environment, and (3) Social screening is feasible in a busy clinical environment and there is room for improvement.

Conclusion
This study highlights the importance of social screening in pediatric patients and their families, and how using a social screening tool allows providers to tailor care for a patients’ social context. The BEARS Questionnaire is feasible to implement within the context of a busy clinic. Finally, despite being a sensitive topic, an ACEs questionnaire can be incorporated when done in a trauma-informed way, and in the context of a longitudinal therapeutic relationship.
Negation in Negationless Intuitionistic Mathematics
Authors: Ferguson Thomas Macaulay 
Published: October 2022

AbstractThe mathematician G.F.C. Griss is known for his program of negationless intuitionistic mathematics. Although Griss’s rejection of negation is regarded as characteristic of his philosophy, this is a consequence of an executability requirement that mental constructions presuppose agents’ executing corresponding mental activity. Restoring Griss’s executability requirement to a central role permits a more subtle characterization of the rejection of negation, according to which D. Nelson’s strong constructible negation is compatible with Griss’s principles. This exposes a ‘holographic’ theory of negation in negationless mathematics, in which a full theory of negation is ‘flattened’ in a putatively negationless setting.
p-Coumaroylation of lignin occurs outside of commelinid monocots in the eudicot genusMorus(mulberry)
Authors: Hellinger Jan , Kim Hoon , Ralph John , Karlen Steven D 
Published: October 2022

AbstractThe presence of p-coumarate (pCA) in plant cell walls is generally considered to be a trait present only in commelinid monocots. Here, we show that this long-held overgeneralizing assumption is incorrect and that mulberry trees (Morus) are eudicot plants that have lignins derived in part from monolignol pCA esters. As in commelinid monocots, the lignin-bound pCA acylates the sidechain γ-hydroxyl of both coniferyl and syringyl units. This discovery expands mulberry’s potential applications to include being a source of p-coumaric acid, a supplier of nutritious berries, a forage crop, a decorative plant, and the main food source for silkworms.
Sympathetic Blocks as a Predictor for Response to Ketamine Infusion in Patients with Complex Regional Pain Syndrome: A Multicenter Study
Authors: Cohen Steven P , Khunsriraksakul Chachrit , Yoo Yongjae , Parker Evan , Samen-Akinsiku Christelle D K , Patel Nirav , Cohen Seffrah J , Yuan Xiaoning , Cheng Jianguo , Moon Jee Youn 
Published: October 2022

Abstract

Background
Ketamine infusions are frequently employed for refractory complex regional pain syndrome (CRPS), but there are limited data on factors associated with treatment response. Sympathetic blocks are also commonly employed in CRPS for diagnostic and therapeutic purposes and generally precede ketamine infusions.

Objectives
We sought to determine whether demographic and clinical factors, and technical and psychophysical characteristics of sympathetic blocks are associated with response to ketamine infusion.

Methods
In this multi-center retrospective study, 71 patients who underwent sympathetic blocks followed by ketamine infusions at 4 hospitals were evaluated. Sympathetically maintained pain (SMP) was defined as ≥ 50% immediate pain relief after sympathetic block and a positive response to ketamine was defined as ≥ 30% pain relief lasting over 3 weeks.

Results
Factors associated with a positive response to ketamine in univariable analysis were the presence of SMP (61.0% success rate vs 26.7% in those with sympathetically independent pain; P = .009) and post-block temperature increase (5.66 ± 4.20 in ketamine responders vs 3.68 ± 3.85 in non-responders; P = .043). No psychiatric factor was associated with ketamine response. In multivariable analysis, SMP (OR 6.54 [95% CI 1.83, 23.44]) and obesity (OR 8.75 [95% 1.45, 52.73]) were associated with a positive ketamine infusion outcome.

Conclusions
The response to sympathetic blocks may predict response to ketamine infusion in CRPS patients, with alleviation of the affective component of pain and predilection to a positive placebo effect being possible explanations.
The Missing Homebuyers: Regional Heterogeneity and Credit Contractions
Authors: Mabille Pierre 
Published: October 2022

Abstract
This paper documents an unprecedented decrease in young homeownership since the Great Recession driven by regions with high house prices. Using a panel of U.S. metro areas, I calibrate an equilibrium spatial macro-finance model with overlapping generations of mobile households. The dynamics of regional housing markets is explained by an aggregate credit contraction with heterogeneous local impacts rather than by local shocks. Lower millennial income and wealth amplify its effect. The impact of subsidies to first-time buyers is dampened, because they fail to stimulate regions that suffer from larger busts. Place-based subsidies achieve larger gains.
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Increased Presynaptic Dopamine Synthesis Capacity Is Associated With Aberrant Dopamine Neuron Activity in the Methylazoxymethanol Acetate Rodent Model Used to Study Schizophrenia-Related Pathologies
Authors: Perez Stephanie M , Elam Hannah B , Lodge Daniel J 
Published: October 2022

AbstractAberrant dopamine system function is thought to contribute to the positive symptoms of schizophrenia. Clinical imaging studies have demonstrated that the largest dopamine abnormality in patients appears to be an increase in presynaptic dopamine activity. Indeed, studies utilizing [18F]DOPA positive emission tomography reliably report increases in presynaptic dopamine bioavailability in patients and may serve as a biomarker for treatment response. The mechanisms contributing to this increased presynaptic activity in human patients is not yet fully understood, which necessitates the use of preclinical models. Dopamine system function can be directly examined in experimental animals using in vivo electrophysiology. One consistent finding from preclinical studies in rodent models used to study schizophrenia-like neuropathology is a 2-fold increase in the number of spontaneously active dopamine neurons in the ventral tegmental area (VTA), termed population activity. We posit that increased striatal dopamine synthesis capacity is attributed to an augmented VTA dopamine neuron population activity. Here, we directly test this hypothesis using [3H]DOPA ex vivo autoradiography, to quantify striatal dopamine synthesis capacity, in the methylazoxymethanol acetate (MAM) model, a validated rodent model displaying neurophysiological and behavioral alterations consistent with schizophrenia-like symptomatologies. Consistent with human imaging studies, dopamine synthesis capacity was significantly increased in dorsal and ventral striatal subregionis, including the caudate putamen and nucleus accumbens, of MAM-treated rats and associated with specific increases in dopamine neuron population activity. Taken together, these data provide a link between mechanistic studies in rodent models and clinical studies of increased presynaptic dopamine function in human subjects.
The missing cost of ecological sleep loss
Authors: Lesku John A , Rattenborg Niels C 
Published: October 2022

AbstractSleep serves many important functions. And yet, emerging studies over the last decade indicate that some species routinely sleep little, or can temporarily restrict their sleep to low levels, seemingly without cost. Taken together, these systems challenge the prevalent view of sleep as an essential state on which waking performance depends. Here, we review diverse case-studies, including elephant matriarchs, post-partum cetaceans, seawater sleeping fur seals, soaring seabirds, birds breeding in the high Arctic, captive cavefish, and sexually aroused fruit flies. We evaluate the likelihood of mechanisms that might allow more sleep than is presently appreciated. But even then, it appears these species are indeed performing well on little sleep. The costs, if any, remain unclear. Either these species have evolved a (yet undescribed) ability to supplant sleep needs, or they endure a (yet undescribed) cost. In both cases, there is urgent need for the study of non-traditional species so we can fully appreciate the extent, causes, and consequences of ecological sleep loss.
Using Pluripotent Stem Cells to Understand Normal and Leukemic Hematopoietic Development
Authors: Bigas Anna , Galán Palma Luis , Kartha Gayathri M , Giorgetti Alessandra 
Published: October 2022

Abstract
Several decades have passed since the generation of the first embryonic stem cell (ESC) lines both in mice and in humans. Since then, stem cell biologists have tried to understand their potential biological and clinical uses for their implementation in regenerative medicine. The hematopoietic field was a pioneer in establishing the potential use for the development of blood cell products and clinical applications; however, early expectations have been truncated by the difficulty in generating bonafide hematopoietic stem cells (HSCs). Despite some progress in understanding the origin of HSCs during embryonic development, the reproduction of this process in vitro is still not possible, but the knowledge acquired in the embryo is slowly being implemented for mouse and human pluripotent stem cells (PSCs). In contrast, ESC-derived hematopoietic cells may recapitulate some leukemic transformation processes when exposed to oncogenic drivers. This would be especially useful to model prenatal leukemia development or other leukemia-predisposing syndromes, which are difficult to study. In this review, we will review the state of the art of the use of PSCs as a model for hematopoietic and leukemia development.
Clinical Nurse Specialist Transition to Practice
Authors: Bloomingdale Rosina , Darmody Julie V. , Ellis Julie L. 
Published: October 2022

Purpose
A quality improvement/evidence-based practice project identified the critical components of clinical nurse specialist (CNS) transition-to-practice (TTP) needs based on the experiences and perceptions of entry-level CNSs (n = 4), experienced CNSs (n = 7), and directors of nursing (n = 6) employed in a tertiary healthcare center. Structured 60- to 90-minute face-to-face discussions were conducted.

Description
As knowledge workers, CNSs are critical to investigating, solving, and transforming some of the most challenging current and future healthcare problems. Lack of standardized CNS TTP may result in variable levels of practice, knowledge, skill attainment, and ability to attain interdisciplinary practice competencies.

Outcomes
Findings included identification of entry-level CNS TTP key components: 16 categories with 8 critical categories identified as imminent needs. Challenges identified included stakeholders' lack of knowledge/understanding of the CNS role and scope; enormous TTP expectations of entry-level CNSs; transdisciplinary relationships and collaboration; leadership culture and collaboration; organizational culture; deliberate practice; and lack of support, resources, and basic needs.

Conclusion
Critical components for advanced deliberate practice within a CNS TTP program include an organizational culture and subculture that understands and values the CNS, along with tiered sustainable support from preceptors, mentors, and support CNSs across the setting and system.
Dynamics of species-rich predator–prey networks and seasonal alternations of keystone species
Authors: Suzuki Sayaka , Baba Yuki G. , Toju Hirokazu 
Published: October 2022

AbstractIn nature, entangled webs of predator–prey interactions constitute the backbones of ecosystems. Uncovering the network architecture of such trophic interactions has been recognized as the essential step for exploring species with great impacts on ecosystem-level phenomena and functions. However, it has remained a major challenge to reveal how species-rich networks of predator–prey interactions are continually reshaped though time in the wild. We here show that dynamics of species-rich predator–prey interactions can be characterized by remarkable network structural changes and alternations of potential keystone species. Based on high-throughput detection of prey DNA from 1,556 spider individuals collected in a grassland ecosystem, we reconstructed dynamics of interaction networks involving, in total, 50 spider species and 974 prey species/strains through eight months. The networks were compartmentalized into modules (groups) of closely interacting predators and prey in some but not all months. As the modules differed in detritus/grazing food chain properties, complex fission-fusion dynamics of below-ground and above-ground energy channels was reconstructed across the seasons. The substantial shifts of network structure entailed alternations of spider species located at the core positions within the entangled webs of interactions. These results indicate that knowledge of dynamically shifting food webs is essential for understanding the temporally-varying roles of keystone species that interlink multiple energy channels.