bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secular variations of magma source compositions in the North Patagonian batholith from the Jurassic to Tertiary: Was mélange melting involved?
Authors: Castro Antonio , Rodriguez Carmen , Fernández Carlos , Aragón Eugenio , Pereira Manuel Francisco , Molina José Francisco 
Published: April 2021

Abstract
This study of Sr-Nd initial isotopic ratios of plutons from the North Patagonian batholith (Argentina and Chile) revealed that a secular evolution spanning 180 m.y., from the Jurassic to Neogene, can be established in terms of magma sources, which in turn are correlated with changes in the tectonic regime. The provenance and composition of end-member components in the source of magmas are represented by the Sr-Nd initial isotopic ratios (87Sr/86Sr and 143Nd/144Nd) of the plutonic rocks. Our results support the interpretation that source composition was determined by incorporation of varied crustal materials and trench sediments via subduction erosion and sediment subduction into a subduction channel mélange. Subsequent melting of subducted mélanges at mantle depths and eventual reaction with the ultramafic mantle are proposed as the main causes of batholith magma generation, which was favored during periods of fast convergence and high obliquity between the involved plates. We propose that a parental diorite (= andesite) precursor arrived at the lower arc crust, where it underwent fractionation to yield the silicic melts (granodiorites and granites) that formed the batholiths. The diorite precursor could have been in turn fractionated from a more mafic melt of basaltic andesite composition, which was formed within the mantle by complete reaction of the bulk mélanges and the peridotite. Our proposal follows model predictions on the formation of mélange diapirs that carry fertile subducted materials into hot regions of the suprasubduction mantle wedge, where mafic parental magmas of batholiths originate. This model not only accounts for the secular geochemical variations of Andean batholiths, but it also avoids a fundamental paradox of the classical basalt model: the absence of ultramafic cumulates in the lower arc crust and in the continental crust in general.
Neonatal amygdala microstructure mediates the relationship between gestational glycemia and offspring adiposity
Authors: Cai Shirong , Aris Izzuddin M , Yuan Wen Lun , Tan Kok Hian , Godfrey Keith M , Gluckman Peter D , Shek Lynette Pei-Chi , Chong Yap-Seng , Yap Fabian , Fortier Marielle V , Meaney Michael J , Lee Yung Seng , Qiu Anqi 
Published: April 2021

IntroductionTo determine if variations in the neonatal amygdala mediate the association between maternal antenatal glycemia and offspring adiposity in early childhood.Research design and methods123 non-obese pregnant women with no pregnancy complications aside from gestational diabetes underwent a 75 g 2-hour oral glucose tolerance test at 26–28 weeks’ gestation. Volume and fractional anisotropy (FA) of the neonatal amygdala (5–17 days old) were measured by MRI. The Body Mass Index (BMI) z-scores and sum of skinfold thickness (subscapular and triceps) of these children were tracked up to 60 months of age (18, 24, 36, 48, 54 and 60 months).ResultsMaternal fasting glucose levels were positively associated with the offspring’s sum of skinfold thickness at age 48 months (β=3.12, 95% CI 0.18 to 6.06 mm) and 60 months (β=4.14, 95% CI 0.46 to 7.82 mm) and BMI z-scores at 48 months (β=0.94, 95% CI 0.03 to 1.85), 54 months (β=0.74, 95% CI 0.12 to 1.36) and 60 months (β=0.74, 95% CI 0.08 to 1.39). Maternal fasting glucose was negatively associated with the offspring’s FA of the right amygdala (β=−0.019, 95% CI −0.036 to −0.003). Right amygdala FA was negatively associated with the sum of skinfold thickness in the offspring at age 48 months (β=−56.95, 95% CI −98.43 to −15.47 mm), 54 months (β=−46.18, 95% CI −88.57 to −3.78 mm), and 60 months (β=−53.69, 95% CI −105.74 to −1.64 mm). The effect sizes mediated by right amygdala FA between fasting glucose and sum of skinfolds were estimated at β=5.14 (95% CI 0.74 to 9.53) mm (p=0.022), β=4.40 (95% CI 0.08 to 8.72) (p=0.049) mm and β=4.56 (95% CI −0.17 to 9.29) mm (p=0.059) at 48, 54 and 60 months, respectively.ConclusionsIn the offspring of non-obese mothers, gestational fasting glucose concentration is negatively associated with neonatal right amygdala FA and positively associated with childhood adiposity. Neonatal right amygdala FA may be a potential mediator between maternal glycemia and childhood adiposity.
Variation in hypoglycemia ascertainment and report in type 2 diabetes observational studies: a meta-epidemiological study
Authors: Rodríguez-Gutiérrez René , Salcido-Montenegro Alejandro , González-González José Gerardo , McCoy Rozalina G 
Published: April 2021

IntroductionObservational studies constitute an important evidence base for hypoglycemia in diabetes management. This requires consistent and reliable ascertainment and reporting methodology, particularly in studies of type 2 diabetes where hypoglycemia risk is heterogeneous. Therefore, we aimed to examine the definitions of hypoglycemia used by observational studies of patients with type 2 diabetes.Research design and methodsWe conducted a meta-epidemiological review of observational studies reporting on hypoglycemia or evaluating glucose-lowering medications in adults with type 2 diabetes. MEDLINE and Google Scholar were searched from January 1970 to May 2018. The definitions of non-severe, severe and nocturnal hypoglycemia were examined.ResultsWe reviewed 243 studies: 47.7% reported on non-severe hypoglycemia, 77.8% on severe hypoglycemia and 16.9% on nocturnal hypoglycemia; 5.8% did not specify. Among 116 studies reporting non-severe hypoglycemia, 18.1% provided no definition, 23.3% used glucose values, 38.8% relied on patient-reported symptoms, 17.2% accepted either glucose values or patient-reported symptoms and 2.6% relied on International Classification of Disease (ICD) codes. Among 189 studies reporting severe hypoglycemia, 11.1% provided no definition, 53.4% required symptoms needing assistance, 3.7% relied on glucose values, 14.8% relied on ICD codes, 2.6% relied on ICD codes or glucose values and 15.9% required both symptoms needing assistance and glucose values. Overall, 38.2% of non-severe and 67.7% of severe hypoglycemia definitions were consistent with the International Hypoglycemia Study Group.ConclusionsThe marked heterogeneity in how hypoglycemia is defined in observational studies may contribute to the inadequate understanding and correction of hypoglycemia risk factors among patients with type 2 diabetes.
Metabolites in the association between early-life famine exposure and type 2 diabetes in adulthood over a 5-year follow-up period
Authors: Wang Yuying , Xia Fangzhen , Wan Heng , Chen Chi , Chen Yi , Zhang Wen , Wang Ningjian , Lu Yingli 
Published: April 2021

IntroductionExposure to malnutrition in early life has been found to significantly elevate type 2 diabetes risk in adulthood. However, the changes in metabolites resulting from malnutrition in early life have not been studied. The aim of this study was to identify metabolites with levels associated with type 2 diabetes resulting from exposure to China’s Great Famine (1959–1962).Research design and methodsParticipants were from SPECT-China 2014 and SPECT-China2 2019, two cross-sectional studies performed at the same site. In total, 2171 subjects participated in SPECT-China and SPECT-China2 simultaneously. The sample size of fetal-exposed (1959–1962) versus non-exposed (1963–1974) individuals was 82 vs 79 in 2014 and 97 vs 94 in 2019. Metabolomic profiling was performed between famine-exposed and non-exposed groups.ResultsAmong the different famine exposure groups, the fetal-exposed group (1959–1962) had the greatest incidence rate (12.5%), with an OR of 2.11 (95% CI 1.01 to 4.44), compared with the non-exposed group (1963–1974). Moreover, compared with those in the non-exposed group (1963–1974), four metabolites (indole-3-carbinol (I3C), phosphatidylcholine (PC) (22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:1(9Z)), pyrimidine, and PC(16:1(9Z)/22:5(4Z,7Z,10Z,13Z,16Z))) showed significantly lower relative intensities in the famine and diabetes groups both in 2014 and 2019. Pyrimidine significantly mediated the association of famine exposure with diabetes, and I3C marginally mediated this association.ConclusionsFamine exposure in the fetal period could increase type 2 diabetes risk in adults, even those in their 60s. I3C and pyrimidine are potential mediators of the effects of famine exposure on diabetes development.
Remote care for mental health: qualitative study with service users, carers and staff during the COVID-19 pandemic
Authors: Liberati Elisa , Richards Natalie , Parker Jennie , Willars Janet , Scott David , Boydell Nicola , Pinfold Vanessa , Martin Graham , Dixon-Woods Mary , Jones Peter 
Published: April 2021

ObjectivesTo explore the experiences of service users, carers and staff seeking or providing secondary mental health services during the COVID-19 pandemic.DesignQualitative interview study, codesigned with mental health service users and carers.MethodsWe conducted semistructured, telephone or online interviews with a purposively constructed sample; a lived experience researcher conducted and analysed interviews with service users. Analysis was based on the constant comparison method.SettingNational Health Service (NHS) secondary mental health services in England between June and August 2020.ParticipantsOf 65 participants, 20 had either accessed or needed to access English secondary mental healthcare during the pandemic; 10 were carers of people with mental health difficulties; 35 were members of staff working in NHS secondary mental health services during the pandemic.ResultsExperiences of remote care were mixed. Some service users valued the convenience of remote methods in the context of maintaining contact with familiar clinicians. Most participants commented that a lack of non-verbal cues and the loss of a therapeutic ‘safe space’ challenged therapeutic relationship building, assessments and identification of deteriorating mental well-being. Some carers felt excluded from remote meetings and concerned that assessments were incomplete without their input. Like service users, remote methods posed challenges for clinicians who reported uncertainty about technical options and a lack of training. All groups expressed concern about intersectionality exacerbating inequalities and the exclusion of some service user groups if alternatives to remote care are lost.ConclusionsThough remote mental healthcare is likely to become increasingly widespread in secondary mental health services, our findings highlight the continued importance of a tailored, personal approach to decision making in this area. Further research should focus on which types of consultations best suit face-to-face interaction, and for whom and why, and which can be provided remotely and by which medium.
Impact and feasibility of a tailor-made patient communication quality improvement programme for hospital-based physiotherapists: a mixed-methods study
Authors: Steenbruggen Rudi A , van Heusden-Scholtalbers Linda AG , Hoogeboom Thomas J , Maas Marjo , Brand Paul , Wees Philip van der 
Published: April 2021

BackgroundIn tailoring a quality improvement programme for hospital-based physiotherapy, the original use of video recordings was replaced by using the tracer methodology.ObjectiveTo examine the impact of a tailor-made quality improvement programme addressing patient communication on the professional development of hospital-based physiotherapists, and to evaluate barriers and facilitators as determinants of feasibility of the programme.MethodsA mixed-methods study was conducted. Participants were clustered in groups per hospital and linked with an equally sized group in a nearby hospital. Within the groups, fixed couples carried out a 2-hour tracer by directly observing each other’s daily work routine. This procedure was repeated 6 months later. Data from feedback forms were analysed quantitatively, and a thematic analysis of transcripts from group interviews was conducted.ResultsFifty hospital-based physiotherapists from 16 hospitals participated. They rated the impact of the programme on professional development, on a scale from 1 (much improvement needed) to 5 (no improvement needed), as 3.99 (SD 0.64) after the first tracer and 4.32 (SD 0.63) 6 months later; a mean improvement of 0.33 (95% CI 0.16 to 0.50). Participants scored, on a scale ranging from 1 to 5 on barriers and facilitators (feasibility), a mean of 3.45 (SD 0.95) on determinants of innovation, 3.47 (SD 0.86) on probability to use and 2.63 (SD 1.07) on the user feedback list. All participants emphasised the added value of the tracer methodology and mentioned effects on self-reflection and awareness most.ConclusionsThe tailor-made quality improvement programme, based on principles of the tracer methodology, was associated with a significant impact on professional development. Barriers and facilitators as determinants of feasibility of the programme showed the programme being feasible.
The Supportive Care sCore (SCC): trigger alert validation study in solid tumours
Authors: Chastenet Mathilde , Laurain Pierre-Antoine , Salleron Julia , Beuzeboc Philippe , Scotté Florian 
Published: April 2021

ObjectivesPatients’ needs are still underestimated during the course of cancer. The development of a simple and accessible screening tool to screen supportive care needs is an innovative approach to improve the cancer care pathway. The Supportive Care sCore (SCC) is a new tool developed to trigger alerts on the main supportive care needs, such as social, nutritional, physical, pain or psychological disorders. We aimed to develop and validate the SCC tool in identifying supportive care needs.MethodsThe SCC, the Edmonton Symptom Assessment System (ESAS) and the EuroQol-5 Dimension (EQ-5D) questionnaire (for quality of life) were distributed to patients with cancer over a week in an ambulatory hospital of an oncology department. Acceptability was measured by assessing the fill rate. Validity of alerts generated by the SCC was assessed by their consistency with the ESAS and EQ-5D scores.ResultsOne hundred patients were included, with an average age of 67.2 years. Acceptability was good with a fill rate of over 90%. For a priori-defined risk groups by SCC with alert or not, the ESAS symptom score and quality of life differed significantly (p<0.05) between groups. We observed higher ESAS symptom scores in the alert group (nutritional alert-appetite: 4 (SD 2.4) vs 0 (SD 2.6), p<0.001; physical alert-fatigue: 4 (SD 1.7) vs 2 (SD 2.2), p<0.001; psychological alert-depressed: 3.5 (SD 2.7) vs 0 (SD 1.5), p<0.001). Quality of life was poorer in each domain of the EQ-5D in the alert group.ConclusionsOur study demonstrates the construct validity of SCC, which holds promise in identifying supportive care needs.
Healthcare system impacts of the 2017 Manchester Arena bombing: evidence from a national trauma registry patient case series and hospital performance data
Authors: Dark Paul , Smith Martin , Ziman Harry , Carley Simon , Lecky Fiona 
Published: April 2021

IntroductionIn response to detonation of an improvised explosive device at the Manchester Arena on 22 May 2017, we aimed to use detailed information about injured patients flowing through hospital healthcare to objectively evaluate the preplanned responses of a regional trauma care system and to show how routinely collected hospital performance data can be used to assess impact on regional healthcare.MethodsData about injury severity, management and outcome for patients presenting to hospitals were collated using England’s major trauma registry for 30 days following hospital attendance. System-wide data about hospital performance were collated by National Health Service England’s North West Utilisation Management Unit and presented as Shewhart charts from 15 April 2017 to 25 June 2017.ResultsDetailed information was obtained on 153 patients (109 adults and 44 children) who attended hospital emergency departments after the incident. Within 6 hours, a network of 11 regional trauma care hospitals received a total of 138 patients (90%). For the whole patient cohort, median Injury Severity Score (ISS) was 1 (IQR 1–10) and median New ISS (NISS) was 2 (IQR 1–14). For the 75 patients (49%) attending a major trauma centre, median ISS was 7.5 (IQR 1–14) and NISS was 10 (IQR 3–22). Limb and torso body regions predominated when injuries were classified as major life threatening (Abbreviated Injury Scale>3). Ninety-three patients (61%) required hospital admission following emergency department management, with 21 (14%) requiring emergency damage control surgery and 24 (16%) requiring critical care. Three fatalities occurred during early resuscitative treatment and 150 (98%) survived to day 30. The increased system-wide hospital admissions and care activity was linked to increases in regional hospital care capacity through cancellations of elective surgery and increased community care. Consequently, there were sustained system-wide hospital service improvements over the following weeks.ConclusionsThe systematic collation of injured patient and healthcare system data has provided an objective evaluation of a regional major incident plan and provided insight into healthcare system resilience. Hospital patient care data indicated that a prerehearsed patient dispersal plan at incident scene was implemented effectively.
Non-invasive assessment of fluid responsiveness to guide fluid therapy in patients with sepsis in the emergency department: a prospective cohort study
Authors: Koopmans Nienke K , Stolmeijer Renate , Sijtsma Ben C , van Beest Paul A , Boerma Christiaan E , Veeger Nic J , ter Avest Ewoud 
Published: April 2021

BackgroundLittle is known about optimal fluid therapy for patients with sepsis without shock who present to the ED. In this study, we aimed to quantify the effect of a fluid challenge on non-invasively measured Cardiac Index (CI) in patients presenting with sepsis without shock.MethodsIn a prospective cohort study, CI, stroke volume (SV) and systemic vascular resistance (SVR) were measured non-invasively in 30 patients presenting with sepsis without shock to the ED of a large teaching hospital in the Netherlands between May 2018 and March 2019 using the ClearSight system. After baseline measurements were performed, a passive leg raise (PLR) was done to simulate a fluid bolus. Measurements were then repeated 30, 60, 90 and 120 s after PLR. Finally, a standardised 500 mL NaCl 0.9% intravenous bolus was administered after which final measurements were done. Fluid responsiveness was defined as >15% increase in CI after a standardised fluid challenge.Measurements and main resultsSeven out of 30 (23%) patients demonstrated a >15% increase in CI after PLR and after a 500 mL fluid bolus. Fluid responders had a higher estimated glomerular filtration rate (eGFR) (64 (44–78) vs 37 (23–47), p=0.009) but otherwise similar patient and treatment characteristics as non-responders. Baseline measurements of cardiac output (CO), CI, SV and SVR were unrelated to PLR fluid responsiveness. The change in CI after PLR was strongly positive correlated to the change in CI after a 500 mL NaCl 0.9% fluid bolus (r=0.88, p<0.001).ConclusionThe results of the present study demonstrate that in patients with sepsis in the absence of shock, three out of four patients do not demonstrate a clinically relevant increase in CI after a standardised fluid challenge. Non-invasive CO monitoring in combination with a PLR test has the potential to identify patients who might benefit from fluid resuscitation and may contribute to a better tailored treatment of these patients.
Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis
Authors: Knitz Michael W , Bickett Thomas E , Darragh Laurel B , Oweida Ayman J , Bhatia Shilpa , Van Court Benjamin , Bhuvane Shiv , Piper Miles , Gadwa Jacob , Mueller Adam C , Nguyen Diemmy , Nangia Varuna , Osborne Douglas G , Bai Xiyuan , Ferrara Sarah E , Boss Mary-Keara , Goodspeed Andrew , Burchill Matthew A , Tamburini Beth A Jirón , Chan Edward D , Pickering Curtis R , Clambey Eric T , Karam Sana D 
Published: April 2021

BackgroundNumerous trials combining radiation therapy (RT) and immunotherapy in head and neck squamous cell carcinoma (HNSCC) are failing. Using preclinical immune cold models of HNSCC resistant to RT-immune checkpoint inhibitors, we investigate therapeutic approaches of overcoming such resistance by examining the differential microenvironmental response to RT.MethodsWe subjected two HPV-negative orthotopic mouse models of HNSCC to combination RT, regulatory T cells (Treg) depletion, and/or CD137 agonism. Tumor growth was measured and intratumorous and lymph node immune populations were compared among treatment groups. Human gene sets, genetically engineered mouse modelsDEREGandBATF3–/–, flow and time-of-flight cytometry, RNA-Seq, Treg adoptive transfer studies, and in vitro experiments were used to further evaluate the role of dendritic cells (DCs) and Tregs in these treatments.ResultsIn MOC2 orthotopic tumors, we find no therapeutic benefit to targeting classically defined immunosuppressive myeloids, which increase with RT. In these radioresistant tumors, supplementing combination RT and Treg depletion with anti-CD137 agonism stimulates CD103+DC activation in tumor-draining lymph nodes as characterized by increases in CD80+and CCR7+DCs, resulting in a CD8 T cell-dependent response. Simultaneously, Tregs are reprogrammed to an effector phenotype demonstrated by increases in interferonγ+, tumor necrosis factorα+, PI3K+, pAKT+and Eomes+populations as well as decreases in CTLA4+and NRP-1+populations. Tumor eradication is observed when RT is increased to an 8 Gy x 5 hypofractionated regimen and combined with anti-CD25+ anti-CD137 treatment. In a human gene set from oral squamous cell carcinoma tumors, high Treg number is associated with earlier recurrence.ConclusionsRegulating Treg functionality and DC activation status within the lymph node is critical for generating a T cell effector response in these highly radioresistant tumors. These findings underscore the plasticity of Tregs and represent a new therapeutic opportunity for reprogramming the tumor microenvironment in HNSCCs resistant to conventional radioimmunotherapy approaches.