bluuebunny/crossref_metadata_2025_split huggingface dataset:
A whole genome approach for discovering the genetic basis of blood group antigens: independent confirmation for P1 and Xga
Authors: Lane William J. , Aguad Maria , Smeland‐Wagman Robin , Vege Sunitha , Mah Helen H. , Joseph Abigail , Blout Carrie L. , Nguyen Tiffany T. , Lebo Matthew S. , Sidhu Manpreet , Lomas‐Francis Christine , Kaufman Richard M. , Green Robert C. , Westhoff Connie M. ,   for the MedSeq Project
Published: December 2018

BACKGROUNDAlthough P1 and Xga are known to be associated with the A4GALT and XG genes, respectively, the genetic basis of antigen expression has been elusive. Recent reports link both P1 and Xga expression with nucleotide changes in the promotor regions and with antigen‐negative phenotypes due to disruption of transcription factor binding.STUDY DESIGN AND METHODSWhole genome sequencing was performed on 113 individuals as part of the MedSeq Project with serologic RBC antigen typing for P1 (n = 77) and Xga (n = 15). Genomic data were analyzed by two approaches, nucleotide frequency correlation and serologic correlation, to find A4GALT and XG changes associated with P1 and Xga expression.RESULTSFor P1, the frequency approach identified 29 possible associated nucleotide changes, and the serologic approach revealed four among them correlating with the P1+/P1– phenotype: chr22:43,115,523_43,115,520AAAG/delAAAG (rs66781836); chr 22:43,114,551C/T (rs8138197); chr22:43,114,020 T/G (rs2143918); and chr22:43,113,793G/T (rs5751348). For Xga, the frequency approach identified 82 possible associated nucleotide changes, and among these the serologic approach revealed one correlating with the Xg(a+)/Xg(a–) phenotype: chrX:2,666,384G/C (rs311103).CONCLUSIONA bioinformatics analysis pipeline was created to identify genetic changes responsible for RBC antigen expression. This study, in progress before the recently published reports, independently confirms the basis for P1 and Xga. Although this enabled molecular typing of these antigens, the Y chromosome PAR1 region interfered with Xga typing in males. This approach could be used to identify and confirm the genetic basis of antigens, potentially replacing the historical approach using family pedigrees as genomic sequencing becomes commonplace.
Massive transfusion of low‐titer cold‐stored O‐positive whole blood in a civilian trauma setting
Authors: Condron Mary , Scanlan Mick , Schreiber Martin 
Published: December 2018

BACKGROUNDBased on the improved outcomes achieved with fresh whole blood in cases of military trauma as well as with 1:1:1 transfusion strategies for massive traumatic hemorrhage in civilian settings, there has been resurgent interest in using whole blood for civilian trauma patients. There have been reports of giving up to 4 units of low‐titer cold‐stored O‐positive to these patients. This is the first modern report of a massive transfusion with unrestricted low‐titer group O whole blood (LTOWB) use in a civilian trauma patient.STUDY DESIGN AND METHODSThis is a case report describing the resuscitation and massive transfusion of LTOWB of a 69‐year‐old man struck by an automobile.RESULTSWhile working to achieve hemorrhage control, the patient received 38 units of LTOWB, 13 units of RBCs, 12 units of fresh frozen plasma, 2 packs of platelets, and 2 units of cryoprecipitate. No evidence of hemolytic reaction was observed. The patient was O positive. Monitoring by thrombelastography revealed adequate clot initiation and propagation, but decreased clot strength (49.6 and 50.2) and a drop in fibrinogen (from 207 to 141) during the resuscitation.CONCLUSIONThis is the first report of a massive transfusion for civilian trauma based on cold‐stored whole blood in the recent era. While this patient suffered a tremendous burden of traumatic injury and his recovery is not yet complete, his LTOWB resuscitation was successful. Frequent monitoring of coagulation status with thrombelastography during utilization of LTOWB is indicated because the efficacy of its components (particularly platelets) is not yet fully understood.
Sleep‐disordered breathing in the Cavalier King Charles spaniel: A case series
Authors: Hinchliffe Tom A. , Liu Nai‐Chieh , Ladlow Jane 
Published: December 2018

AbstractObjectiveTo describe sleep‐disordered breathing (SDB) in the Cavalier King Charles spaniel (CKCS).Study designRetrospective case series.AnimalsFive client‐owned dogs referred for SDB.MethodsMedical records were reviewed including recheck appointments and routine preoperative and postoperative questionnaires. Whole‐body barometric plethysmography was used to categorize SDB.ResultsAll dogs presented with multiple episodes of stertorous breathing, choking, and apnea during sleep. Severe nasal septal deviation, aberrant nasal turbinates, and soft palate elongation and thickening were noted on computed tomography and rhinoscopy of each dog. Whole‐body barometric plethysmography measurements during sleep (in 3 dogs) documented periods of choking, snoring, and apnea. Treatment combined laser turbinectomy, folding flap palatoplasty, tonsillectomy, laryngeal sacculectomy, and cuneiform process resection. All dogs improved in terms of incidence and severity of sleep apnea within 1 week, with 4 of 5 dogs achieving complete resolution.ConclusionThe objective measurements used to characterize SDB in this population of CKCS provided some evidence to support an obstructive cause for this condition, which improved with surgical treatment.Clinical significanceSleep‐disordered breathing in the CKCS is a different clinical presentation of brachycephalic obstructive airway syndrome. Our finding of intranasal abnormalities in these 5 dogs with SDB provides justification for future research into its clinical significance.
Paediatric postdischarge mortality in developing countries: a systematic review
Authors: Nemetchek Brooklyn , English Lacey , Kissoon Niranjan , Ansermino John Mark , Moschovis Peter P , Kabakyenga Jerome , Fowler-Kerry Susan , Kumbakumba Elias , Wiens Matthew O 
Published: December 2018

ObjectivesTo update the current evidence base on paediatric postdischarge mortality (PDM) in developing countries. Secondary objectives included an evaluation of risk factors, timing and location of PDM.DesignSystematic literature review without meta-analysis.Data sourcesSearches of Medline and EMBASE were conducted from October 2012 to July 2017.Eligibility criteriaStudies were included if they were conducted in developing countries and examined paediatric PDM. 1238 articles were screened, yielding 11 eligible studies. These were added to 13 studies identified in a previous systematic review including studies prior to October 2012. In total, 24 studies were included for analysis.Data extraction and synthesisTwo independent reviewers extracted and synthesised data using Microsoft Excel.ResultsStudies were conducted mostly within African countries (19 of 24) and looked at all admissions or specific subsets of admissions. The primary subpopulations included malnutrition, respiratory infections, diarrhoeal diseases, malaria and anaemia. The anaemia and malaria subpopulations had the lowest PDM rates (typically 1%–2%), while those with malnutrition and respiratory infections had the highest (typically 3%–20%). Although there was significant heterogeneity between study populations and follow-up periods, studies consistently found rates of PDM to be similar, or to exceed, in-hospital mortality. Furthermore, over two-thirds of deaths after discharge occurred at home. Highly significant risk factors for PDM across all infectious admissions included HIV status, young age, pneumonia, malnutrition, anthropometric variables, hypoxia, anaemia, leaving hospital against medical advice and previous hospitalisations.ConclusionsPostdischarge mortality rates are often as high as in-hospital mortality, yet remain largely unaddressed. Most children who die following discharge do so at home, suggesting that interventions applied prior to discharge are ideal to addressing this neglected cause of mortality. The development, therefore, of evidence-based, risk-guided, interventions must be a focus to achieve the sustainable development goals.
Hypertension and frailty: a systematic review and meta-analysis
Authors: Vetrano Davide L , Palmer Katie M , Galluzzo Lucia , Giampaoli Simona , Marengoni Alessandra , Bernabei Roberto , Onder Graziano 
Published: December 2018

ObjectiveTo review the association between hypertension and frailty in observational studies.DesignA systematic review of the PubMed, Web of Science and Embase databases was performed. A meta-analysis was performed if at least three studies used the same definition of frailty and a dichotomous definition of hypertension.Setting, participants and measuresStudies providing information on the association between frailty and hypertension in adult persons, regardless of the study setting, study design or definition of hypertension and frailty were included.ResultsAmong the initial 964 articles identified, 27 were included in the review. Four longitudinal studies examined the incidence of frailty according to baseline hypertension status, providing conflicting results. Twenty-three studies assessed the cross-sectional association between frailty and hypertension: 13 of them reported a significantly higher prevalence of frailty in hypertensive participants and 10 found no significant association. The pooled prevalence of hypertension in frail individuals was 72% (95% CI 66% to 79%) and the pooled prevalence of frailty in individuals with hypertension was 14% (95% CI 12% to 17%). Five studies, including a total of 7656 participants, reported estimates for the association between frailty and hypertension (pooled OR 1.33; 95% CI 0.94 to 1.89).ConclusionsFrailty is common in persons with hypertension. Given the possible influence of frailty on the risk–benefit ratio of treatment for hypertension and its high prevalence, it is important to assess the presence of this condition in persons with hypertension.Trial registration numberCRD42017058303.
Qualitative study using interviews and focus groups to explore the current and potential for antimicrobial stewardship in community pharmacy informed by the Theoretical Domains Framework
Authors: Jones Leah Ffion , Owens Rebecca , Sallis Anna , Ashiru-Oredope Diane , Thornley Tracey , Francis Nick A , Butler Chris , McNulty Cliodna A M 
Published: December 2018

ObjectivesCommunity pharmacists and their staff have the potential to contribute to antimicrobial stewardship (AMS). However, their barriers and opportunities are not well understood. The aim was to investigate the experiences and perceptions of community pharmacists and their teams around AMS to inform intervention development.DesignInterviews and focus groups were used to explore the views of pharmacists, pharmacy staff, general practitioners (GPs), members of pharmacy organisations and commissioners. The questioning schedule was developed using the Theoretical Domains Framework which helped inform recommendations to facilitate AMS in community pharmacy.Results8 GPs, 28 pharmacists, 13 pharmacy staff, 6 representatives from pharmacy organisations in England and Wales, and 2 local stakeholders participated.Knowledge and skills both facilitated or hindered provision of self-care and compliance advice by different grades of pharmacy staff. Some staff were not aware of the impact of giving self-care and compliance advice to help control antimicrobial resistance (AMR). The pharmacy environment created barriers to AMS; this included lack of time of well-qualified staff leading to misinformation from underskilled staff to patients about the need for antibiotics or the need to visit the GP, this was exacerbated by lack of space. AMS activities were limited by absent diagnoses on antibiotic prescriptions.Several pharmacy staff felt that undertaking patient examinations, questioning the rationale for antibiotic prescriptions and performing audits would allow them to provide more tailored AMS advice.ConclusionsInterventions are required to overcome a lack of qualified staff, time and space to give patients AMS advice. Staff need to understand how self-care and antibiotic compliance advice can help control AMR. A multifaceted educational intervention including information for staff with feedback about the advice given may help. Indication for a prescription would enable pharmacists to provide more targeted antibiotic advice. Commissioners should consider the pharmacists’ role in examining patients, and giving advice about antibiotic prescriptions.
Concussion assessment in the emergency department: a preliminary study for a quality improvement project
Authors: Mistry Dylan A , Rainer Timothy H 
Published: December 2018

BackgroundIn sport, concussion is assessed using the Sports Concussion Assessment Tool (SCAT) 5 and managed with return to play guidelines. Similar, user-friendly tools are rarely, if ever, used in the emergency department (ED).ObjectivesTo evaluate a modified concussion assessment tool designed for the ED (ED-CAT) in patients presenting with a head injury and to identify variables that predict 30-day reattendance.MethodsA preliminary, prospective, evaluation in a quality improvement project was conducted in one hospital in South Wales. Patients were recruited if they were over 13 years, and either did not have an ED-CT head scan or had a scan with no acute changes. The primary outcome was 30-day reattendance.Results40 patients were recruited, 18 of whom had a CT scan. 37 were discharged on the same day with advice, two discharged the next day and one was admitted. Three (7.5%) patients reattended the department. Predictors of reattendance were headache score (median 3.0 vs 5.0; p<0.05), pressure in head score (2.0 vs 5.0; p<0.05), nausea/vomiting score (1.0 vs 3.0; p<0.05), dizziness score (1.0 vs 4.0; p<0.05), blurred vision score (0 vs 4.0; p<0.01), balance problems score (0 vs 4.0; p<0.05), sensitivity to light and confusion score (0 vs 4.0; p<0.01), orientation score (1. 0 vs 0; p<0.05) and immediate memory score (5.0 vs 4.0; p<0.05).ConclusionsKey symptoms and signs predicted 30-day reattendance. The ED-CAT requires validation and refinement in a larger population to produce a short, practical, user-friendly, relevant tool for ED head injury assessment.
Serum heart-type fatty acid-binding protein decreases and soluble isoform of suppression of tumorigenicity 2 increases significantly by long-term physical activity
Authors: Sponder Michael , Lichtenauer Michael , Wernly Bernhard , Paar Vera , Hoppe Uta , Emich Michael , Fritzer-Szekeres Monika , Litschauer Brigitte , Strametz-Juranek Jeanette 
Published: December 2018

The aim of this prospective study was to investigate the influence of long-term physical activity on biomarkers for myocyte ischemia (heart-type fatty acid-binding protein, H-FABP), matrix remodelling/vascular stress (soluble isoform of suppression of tumorigenicity 2, sST2) and inflammation (soluble urokinase-type plasminogen activator receptor, suPAR). In this prospective observational study 109 subjects were recruited, 98 completed the study. Subjects were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. Twenty-seven subjects with a performance gain <2.9% were excluded. suPAR, H-FABP and sST2 were measured in serum at baseline and after 2, 4 and 8 months by ELISA. We found a significant decrease in H-FABP (1.86 (0.86) to 1.29 (0.98) ng/mL; p<0.01) and a significant increase in sST2 levels (6126 (2759) to 6919 (3720) pg/mL; p=0.045) during the observation period of 8 months while there was no remarkable change in suPAR levels. We interpret the activity-induced decrease in H-FABP as sign of lower subclinical myocardial ischemia and better perfusion, probably due to a more economic metabolization and electrolyte balance. The increase in sST2 might reflect physiological sports-induced vascular stress. As H-FABP and sST2 play an important role in the pathomechanism of ischemic cardiomyopathy (iCMP) further studies should investigate the influence of regular physical activity on these biomarkers in a population of patients with iCMP. Trial registration number NCT02097199.
Differentiating compensatory mechanisms associated with low tolerance to central hypovolemia in women
Authors: Schlotman Taylor Elyse , Akers Kevin S. , Nessen Shawn C. , Convertino Victor A. 
Published: December 2018

Women generally display lower tolerance to acute central hypovolemia than men. The measurement of compensatory reserve (CRM) is a novel metric that provides information about the sum total of all mechanisms that together work to compensate for the relative blood volume deficit. Hemodynamic decompensation occurs with depletion of the CRM (i.e., 0% CRM). In the present study, we hypothesized that the lower tolerance to progressive central hypovolemia reported in women can be explained by a faster reduction rate in CRM compared with men rather than sex differences in absolute integrated compensatory responses. Continuous, noninvasive measures of CRM were collected from 208 healthy volunteers (107 men and 85 women) who underwent progressive stepwise central hypovolemia induced by lower body negative pressure to the point of presyncope. Comparisons revealed shorter ( P < 0.01) times in female participants compared with male participants to reach 30% and 0% CRM. Similarly, the lower body negative pressure level, represented by the cumulative stress index, was less at 30% and 0% CRM in women compared with men ( P < 0.01). Changes in hemodynamic responses and frequency-domain data (oscillations in cerebral blood flow velocity and mean arterial blood pressure) were similar between men and women at 0% CRM ( P > 0.05). We conclude that compensatory responses to central hypovolemia in women were similar to men but were depleted at a faster rate compared with men. The earlier depletion of the compensatory reserve in women appears to be influenced by failure to maintain adequate cerebral oxygen delivery. NEW & NOTEWORTHY We compared hemodynamic and metabolic responses in men and women to experimentally controlled reductions in central blood volume at physiologically equivalent levels of compensatory reserve. We corroborated previous findings that females have lower tolerance to central hypovolemia than males but demonstrated for the first time that compensatory responses are similar. Our findings suggest lower tolerance to central hypovolemia in women results from reaching critical cerebral delivery of oxygen faster than men.
Muscle sympathetic nerve activity and hemodynamic responses to venous distension: does sex play a role?
Authors: Mansur Daniel E. , Campos Monique O. , Mattos João D. , Paiva Adrielle C. S. , Rocha Marcos P. , Videira Rogerio L. R. , Macefield Vaughan G. , Nóbrega Antonio C. L. , Fernandes Igor A. 
Published: December 2018

Peripheral venous distension mechanically stimulates type III/IV sensory fibers in veins and evokes pressor and sympathoexcitatory reflex responses in humans. As young women have reduced venous compliance and impaired sympathetic transduction, we tested the hypothesis that pressor and sympathoexcitatory responses to venous distension may be attenuated in women compared with men. Mean arterial pressure (photoplethysmography), heart rate (HR), stroke volume (SV; Modelflow), cardiac output (CO = HR × SV), muscle sympathetic nerve activity (MSNA), femoral artery blood flow, and femoral artery conductance (Doppler ultrasound) were quantified in eight men (27 ± 4 yr) and nine women (28 ± 4 yr) before [control (CON)], during (INF), and immediately after (post-INF) a local infusion of saline [5% of the total forearm volume (30 ml/min); the infusion time was 2 ± 1 and 1 ± 1 min ( P = 0.0001) for men and women, respectively] through a retrograde catheter inserted into an antecubital vein, to which venous drainage and arterial supply had been occluded. Mean arterial pressure increased during and after infusion in both groups (vs. the CON group, P < 0.05), but women showed a smaller pressor response in the post-INF period (Δ+7.2 ± 2.0 vs. Δ+18.3 ± 3.9 mmHg in men, P = 0.019). MSNA increased and femoral artery conductance decreased similarly in both groups (vs. the CON group, P < 0.05) at post-INF. Although HR changes were similar, increases in SV (Δ+20.4 ± 8.6 vs. Δ+2.6 ± 2.7 ml, P = 0.05) and CO (Δ+0.84 ± 0.17 vs. Δ+0.34 ± 0.10 l/min, P = 0.024) were greater in men compared with women. Therefore, venous distension evokes a smaller pressor response in young women due to attenuated cardiac adjustments rather than reduced venous compliance or sympathetic transduction. NEW & NOTEWORTHY We found that the pressor response to venous distension was attenuated in young women compared with age-matched men. This was due to attenuated cardiac adjustments rather than reduced venous compliance, sympathetic activation, or impaired transduction and vascular control. Collectively, these findings suggest that an attenuated venous distension reflex could be involved in orthostatic intolerance in young women.
Central Nervous System Metastasis in Patients with HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from SystHERs
Authors: Hurvitz Sara A. , O'Shaughnessy Joyce , Mason Ginny , Yardley Denise A. , Jahanzeb Mohammad , Brufsky Adam , Rugo Hope S. , Swain Sandra M. , Kaufman Peter A. , Tripathy Debu , Chu Laura , Li Haocheng , Antao Vincent , Cobleigh Melody 
Published: December 2018

AbstractPurpose:Patients with HER2-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs).Experimental Design:SystHERs (NCT01615068) was a prospective, U.S.-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PRO).Results:Among 977 eligible patients enrolled (2012–2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor–negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis [median overall survival (OS) 30.2 and 38.3 months from MBC diagnosis, respectively] versus no CNS metastasis [median OS not estimable: HR 2.86; 95% confidence interval (CI), 2.05–4.00 and HR 1.94; 95% CI, 1.52–2.49]. Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment.Conclusions:Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.