bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental Coordination of Gamete Differentiation with Programmed Cell Death in Sporulating Yeast
Authors: Eastwood Michael D. , Meneghini Marc D. 
Published: June 2015

ABSTRACT

The gametogenesis program of the budding yeast
Saccharomyces cerevisiae
, also known as sporulation, employs unusual internal meiotic divisions, after which all four meiotic products differentiate within the parental cell. We showed previously that sporulation is typically accompanied by the destruction of discarded immature meiotic products through their exposure to proteases released from the mother cell vacuole, which undergoes an apparent programmed rupture. Here we demonstrate that vacuolar rupture contributes to
de facto
programmed cell death (PCD) of the meiotic mother cell itself. Meiotic mother cell PCD is accompanied by an accumulation of depolarized mitochondria, organelle swelling, altered plasma membrane characteristics, and cytoplasmic clearance. To ensure that the gametes survive the destructive consequences of developing within a cell that is executing PCD, we hypothesized that PCD is restrained from occurring until spores have attained a threshold degree of differentiation. Consistent with this hypothesis, gene deletions that perturb all but the most terminal postmeiotic spore developmental stages are associated with altered PCD. In these mutants, meiotic mother cells exhibit a delay in vacuolar rupture and then appear to undergo an alternative form of PCD associated with catastrophic consequences for the underdeveloped spores. Our findings reveal yeast sporulation as a context of bona fide PCD that is developmentally coordinated with gamete differentiation.
A patient-initiated voluntary online survey of adverse medical events: the perspective of 696 injured patients and families
Authors: Southwick Frederick S , Cranley Nicole M , Hallisy Julia A 
Published: June 2015

BackgroundPreventable medical errors continue to be a major cause of death in the USA and throughout the world. Many patients have written about their experiences on websites and in published books.MethodsAs patients and family members who have experienced medical harm, we have created a nationwide voluntary survey in order to more broadly and systematically capture the perspective of patients and patient families experiencing adverse medical events and have used quantitative and qualitative analysis to summarise the responses of 696 patients and their families.ResultsHarm was most commonly associated with diagnostic and therapeutic errors, followed by surgical or procedural complications, hospital-associated infections and medication errors, and our quantitative results match those of previous provider-initiated patient surveys. Qualitative analysis of 450 narratives revealed a lack of perceived provider and system accountability, deficient and disrespectful communication and a failure of providers to listen as major themes. The consequences of adverse events included death, post-traumatic stress, financial hardship and permanent disability. These conditions and consequences led to a loss of patients’ trust in both the health system and providers. Patients and family members offered suggestions for preventing future adverse events and emphasised the importance of shared decision-making.ConclusionsThis large voluntary survey of medical harm highlights the potential efficacy of patient-initiated surveys for providing meaningful feedback and for guiding improvements in patient care.
Waiting time reduction in intravitreal clinics by optimization of appointment scheduling: balancing demand and supply
Authors: Ugarte Marta 
Published: June 2015

AbstractThis study was designed guided by the Model for Improvement framework to reduce waiting times and visit duration in the intravitreal therapy clinic, while improving patient and staff experience. In our aim to provide good quality, patient-centred care and constantly improve, we optimised the appointment profile and patient flow.We involved a multidisciplinary team (one consultant, junior doctors, staff nurses, technicians, and receptionist), as well as patients and relatives, to try to understand the main delays in the clinic. Process mapping, a fishbone diagram, run charts, together with feedback from patients and staff, provided an insight on the possible roots of the delays experienced by our patients. The results of the inquiry led us to take actions focused on optimising appointment scheduling.After implementing the new scheduling profile (with a gap in the middle of the session), various cycles of plan-do-study-act and a comparative, qualitative study by interviewing 10 patients demonstrated that the waiting times decreased, and patients and staff experience improved.
Mass Cytometric Functional Profiling of Acute Myeloid Leukemia Defines Cell-Cycle and Immunophenotypic Properties That Correlate with Known Responses to Therapy
Authors: Behbehani Gregory K. , Samusik Nikolay , Bjornson Zach B. , Fantl Wendy J. , Medeiros Bruno C. , Nolan Garry P. 
Published: June 2015

Abstract
Acute myeloid leukemia (AML) is characterized by a high relapse rate that has been attributed to the quiescence of leukemia stem cells (LSC), which renders them resistant to chemotherapy. However, this hypothesis is largely supported by indirect evidence and fails to explain the large differences in relapse rates across AML subtypes. To address this, bone marrow aspirates from 41 AML patients and five healthy donors were analyzed by high-dimensional mass cytometry. All patients displayed immunophenotypic and intracellular signaling abnormalities within CD34+CD38lo populations, and several karyotype- and genotype-specific surface marker patterns were identified. The immunophenotypic stem and early progenitor cell populations from patients with clinically favorable core-binding factor AML demonstrated a 5-fold higher fraction of cells in S-phase compared with other AML samples. Conversely, LSCs in less clinically favorable FLT3-ITD AML exhibited dramatic reductions in S-phase fraction. Mass cytometry also allowed direct observation of the in vivo effects of cytotoxic chemotherapy.
Significance: The mechanisms underlying differences in relapse rates across AML subtypes are poorly understood. This study suggests that known chemotherapy sensitivities of common AML subsets are mediated by cell-cycle differences among LSCs and provides a basis for using in vivo functional characterization of AML cells to inform therapy selection. Cancer Discov; 5(9); 988–1003. ©2015 AACR.
See related commentary by Do and Byrd, p. 912.
This article is highlighted in the In This Issue feature, p. 893
APOBEC Enzymes: Mutagenic Fuel for Cancer Evolution and Heterogeneity
Authors: Swanton Charles , McGranahan Nicholas , Starrett Gabriel J. , Harris Reuben S. 
Published: June 2015

Abstract
Deep sequencing technologies are revealing the complexities of cancer evolution, casting light on mutational processes fueling tumor adaptation, immune escape, and treatment resistance. Understanding mechanisms driving cancer diversity is a critical step toward developing strategies to attenuate tumor evolution and adaptation. One emerging mechanism fueling tumor diversity and subclonal evolution is genomic DNA cytosine deamination catalyzed by APOBEC3B and at least one other APOBEC family member. Deregulation of APOBEC3 enzymes causes a general mutator phenotype that manifests as diverse and heterogeneous tumor subclones. Here, we summarize knowledge of the APOBEC DNA deaminase family in cancer, and their role as driving forces for intratumor heterogeneity and a therapeutic target to limit tumor adaptation.
Significance: APOBEC mutational signatures may be enriched in tumor subclones, suggesting APOBEC cytosine deaminases fuel subclonal expansions and intratumor heterogeneity. APOBEC family members might represent a new class of drug target aimed at limiting tumor evolution, adaptation, and drug resistance. Cancer Discov; 5(7); 704–12. ©2015 AACR.
Use of Remote Monitoring Is Associated With Lower Risk of Adverse Outcomes Among Patients With Implanted Cardiac Defibrillators
Authors: Akar Joseph G. , Bao Haikun , Jones Paul W. , Wang Yongfei , Varosy Paul D. , Masoudi Frederick A. , Stein Kenneth M. , Saxon Leslie A. , Normand Sharon-Lise T. , Curtis Jeptha P. 
Published: June 2015

Background—
We examined the association between the use of remote patient monitoring (RPM) of implantable cardioverter defibrillators (ICD) and all-cause mortality and rehospitalization among patients undergoing initial ICD implant.

Methods and Results—

A limited data set was constructed from Boston Scientific ALTITUDE Registry and National Cardiovascular Data Registry ICD Registry between January 2006 and March 2010. Vital status was determined using the Social Security Death Master File. All-cause mortality up to 3 years was compared in patients who used RPM with those who did not use RPM. Time-dependent frailty Cox models quantified the association between RPM use and all-cause mortality. Analyses were repeated in subgroups based on age, sex, race, ICD type, indication, and cardiomyopathy pathogenesis. Similar methodology examined the association between RPM use and all-cause rehospitalization in patients enrolled in Medicare fee-for-service patients ≥65 years. The study cohort (n=37 742, age 67±13, 72% male) had a 3-year mortality of 20.9% (median follow-up 832 days). In multivariable analyses, patients using RPM (n=22 023, 58%) had lower risk of mortality compared with those not using RPM (hazard ratio 0.67, 95% confidence interval 0.64–0.71,
P
<0.0001). The 3-year all-cause rehospitalization rate in the Medicare population (n=15 254) was 69.3% (median follow-up 922 days). Risk of rehospitalization of patients using RPM (n=9150, 60%) was lower than those not using RPM (hazard ratio 0.82, 95% confidence interval 0.80–0.84,
P
<0.0001). Findings were consistent across subgroups.

Conclusions—
Among patients undergoing initial ICD implant, RPM use is associated with significantly lower risk of adverse outcomes.
Elimination of the Negative Component of the Unipolar Atrial Electrogram as an In Vivo Marker of Transmural Lesion Creation
Authors: Bortone Agustín , Brault-Noble Guillaume , Appetiti Anthony , Marijon Eloi 
Published: June 2015

Background—
It has been experimentally shown that elimination of the negative component of the unipolar atrial electrogram (R morphology completion) during radiofrequency applications reflects transmural lesions creation. Subsequently, it has been clinically suggested that such a transmurality can be either irreversible or reversible. The present study is aimed to determine, at the histological level, whether transmural lesions, assessed by R morphology completion, might indeed be reversible in some circumstances or not.

Methods and Results—

In 6 Mongrel hound dogs, superior and inferior vena cavae were isolated and individual lesions were created in the right atrium using radiofrequency energy (30 W/48°C/17 mL/min as presettings and 10
g
of force in average) under CARTO guidance. Five types of lesions were created; R
+
0: termination of ablation at the time of R morphology completion; R
+
5, R
+
10, or R
+
20: extension of ablation for 5, 10, or 20 seconds, respectively, after R morphology achievement; and conventional: radiofrequency applications lasting 30 seconds irrespective of the atrial electrogram modification. All conventional, R
+
5, R
+
10, and R
+
20 lesions were necrotic and transmural, whereas some R
+
0 lesions were not (comprising a part of necrosis and a part of reversible cell damage). Interestingly, surrounding organ injuries were observed after conventional, R
+
10, and R
+
20 radiofrequency applications but were not observed after R
+
0 and R
+
5 applications.

Conclusions—
Elimination of the negative component of the unipolar atrial electrogram reflects, in general, irreversible transmural necrosis creation. In some cases, however, it translates transmural lesion only (with potential reversibility) likely related to transient cell damage creation.
Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest
Authors: Deye Nicolas , Cariou Alain , Girardie Patrick , Pichon Nicolas , Megarbane Bruno , Midez Philippe , Tonnelier Jean-Marie , Boulain Thierry , Outin Hervé , Delahaye Arnaud , Cravoisy Aurélie , Mercat Alain , Blanc Pascal , Santré Charles , Quintard Hervé , Brivet François , Charpentier Julien , Garrigue Delphine , Francois Bruno , Quenot Jean-Pierre , Vincent François , Gueugniaud Pierre-Yves , Mira Jean-Paul , Carli Pierre , Vicaut Eric , Baud Frédéric J. 
Published: June 2015

Background—
Targeted temperature management is recommended after out-of-hospital cardiac arrest. Whether advanced internal cooling is superior to basic external cooling remains unknown. The aim of this multicenter, controlled trial was to evaluate the benefit of endovascular versus basic surface cooling.

Methods and Results—

Inclusion criteria were the following: age of 18 to 79 years, out-of-hospital cardiac arrest related to a presumed cardiac cause, time to return of spontaneous circulation <60 minutes, delay between return of spontaneous circulation and inclusion <240 minutes, and unconscious patient after return of spontaneous circulation and before the start of cooling. Exclusion criteria were terminal disease, pregnancy, known coagulopathy, uncontrolled bleeding, temperature on admission <30°C, in-hospital cardiac arrest, immediate need for extracorporeal life support or hemodialysis. Patients were randomized between 2 cooling strategies: endovascular femoral devices (Icy catheter, Coolgard, Zoll, formerly Alsius; n=203) or basic external cooling using fans, a homemade tent, and ice packs (n=197). The primary end point, that is, favorable outcome evaluated by survival without major neurological damage (Cerebral Performance Categories 1–2) at day 28, was not significantly different between groups (odds ratio, 1.41; 95% confidence interval, 0.93–2.16;
P
=0.107). Improvement in favorable outcome at day 90 in favor of the endovascular group did not reach significance (odds ratio, 1.51; 95% confidence interval, 0.96–2.35;
P
=0.07). Time to target temperature (33°C) was significantly shorter and target hypothermia was more strictly maintained in the endovascular than in the surface group (
P
<0.001). Minor side effects directly related to the cooling method were observed more frequently in the endovascular group (
P
=0.009).

Conclusion—
Despite better hypothermia induction and maintenance, endovascular cooling was not significantly superior to basic external cooling in terms of favorable outcome.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00392639.
Bacterial Laryngotracheitis and Associated Upper Airway Obstruction
Authors: Gross Jennifer H. , Giraldez-Rodriguez Laureano A. , Klein Adam M. 
Published: June 2015

Background: Iatrogenic laryngotracheal stenosis (LTS) continues to be a known complication of indwelling endotracheal tubes (ETTs). It is well established that secondary scar formation caused by inflammation and mucosal injury are the main mechanisms by which stenosis occurs. Additionally, there are reports of bacterial colonization of ETTs and its potential association with tracheal scar formation. We describe 4 cases of patients with history of intubation and/or tracheostomy and presumed LTS that improved with the management of concurrent bacterial laryngotracheitis. Methods: A retrospective case series of 4 subjects initially diagnosed at a tertiary care center with posterior glottic or subglottic stenosis and positive bacterial laryngotracheal cultures was performed. Results: All 4 patients with presumed LTS had culture-proven bacterial growth isolated from the laryngotrachea and were treated with adjunct antibiotics. In the first 3 cases, complete resolution of upper airway obstruction was achieved. The fourth patient had notable improvement in her airway status without the need for additional surgical intervention. Conclusion: This case series suggests that bacterial growth within the airway may play a larger role in adult postintubation airway injury. Those patients presenting with concern for LTS and symptoms suspicious for an ongoing bacterial infection may benefit from adjunct antibiotic therapy.
Acoustic Hearing After Murine Cochlear Implantation
Authors: Kopelovich Jonathan C. , Robinson Barbara K. , Soken Hakan , Verhoeven Kristien J. , Kirk Jonathon R. , Goodman Shawn S. , Hansen Marlan R. 
Published: June 2015

Objectives: To model the contribution of implant material and insertion trauma on loss of acoustic hearing after cochlear implantation in an appropriate animal model. Methods: Sixty-five C57Bl/6J mice underwent unilateral implantation with implant grade materials: 2 implant grade silicones and a third uncoated platinum wire. A sham surgery group was included as a control. Serial auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAEs) were used to discern effects on hearing over 22 weeks. Histologic measurements of damage to the organ of Corti and spiral ganglion were correlated with degree of hearing loss and material type. Results: Organ of Corti damage correlated with rate of hearing loss soon after implantation (0-2 weeks) but not subsequently (2-22 weeks). Organ of Corti damage did not depend on implant type and was present even in sham surgery subjects when hearing was severely damaged. Spiral ganglia appeared unaffected. There was no evidence of an inflammatory or toxic effect of the materials beyond the site of implant insertion. Conclusions: Hearing loss and cochlear damage appear to be related to insertion trauma, with minimal effect on delayed hearing loss caused by different materials. In the C57Bl/6J mouse model, the sensory epithelium appears to be the location of damage after cochlear implantation.
Changing Patterns in Reflux Care
Authors: Gooi Zhen , Ishman Stacey L. , Bock Jonathan M. , Blumin Joel H. , Akst Lee M. 
Published: June 2015

Objectives: To compare patterns of laryngopharyngeal reflux (LPR) diagnosis and management over time by American Broncho-Esophagological Association (ABEA) members. Methods: American Broncho-Esophagological Association members completed an online questionnaire focused on LPR evaluation and management in 2012; responses were compared to a 2002 survey. Results: Four hundred twenty-six members were emailed, of whom 63 (14.8%) responded. In both time periods, throat clearing, heartburn, globus, arytenoid edema, and erythema were considered highly related to LPR. Management in 2012 differed as respondents more commonly treated LPR empirically (82.6% vs 56.3%, P = .036). When adjunctive testing was ordered, dual pH probe were less frequently utilized in 2012 (61.5% vs 78.3%, P = .029). Either esophagogastroduodenoscopy (EGD) or transnasal esophagoscopy (TNE) was used more often in 2012 compared to EGD alone in 2002 (63.8% vs 42.4%, P = .020). Dual pH probe was regarded as the most sensitive and specific evaluation for LPR in both surveys, while the perceived sensitivity/specificity of EGD in 2012 was half that reported in 2002 (28.0% vs 56.3%, P = .003). Conclusion: Attitudes of ABEA members toward empiric treatment and adjunctive tests have changed between 2012 and 2002. While pH probe testing remains the test regarded as most sensitive/specific for evaluation of LPR, empiric management has become more common. Meanwhile, EGD use has increased despite a significant decrease in its perceived sensitivity/specificity.
Evaluation of the effect of clinical validation of out of hours critical laboratory results
Authors: Chandrajay Deepak , Narayanan Deepa , Barth Julian H 
Published: June 2015

Aim The aim of the study was to review the clinical validation process of out of hours critical biochemistry results by a clinical biochemist and its effect on primary care services. Methods A prospective study was conducted of all critical results for primary care patients who were analysed out of hours. The nine-month study period was conducted between June 2013 and February 2014. The data collected include patients’ age, clinical details, critical results and the urgency of result communicated. The patients’ subsequent attendance rate at the emergency department in the local hospital was reviewed. Results A total of 311 out of hours critical results were identified in the laboratory. After clinical validation, 110 (35.4%) results were telephoned urgently and 155 (49.8%) results were deferred to the next day. Forty-six (14.8%) results were not telephoned. Following the urgent result communication, 53/110 (48.2%) patients attended the hospital emergency department within 24 h and 17/110 (15.5%) had their repeat blood test by their general practitioner surgery within 48 h. When the result was telephoned during working hours the next day, only 15/155 (9.7%) attended the hospital acute services within 48 h and 16/155 (10.3%) had repeat blood test at their general practitioner surgery. Conclusion In our practice, the clinical validation of out of hours critical results by a clinical biochemist is associated with a reduction in the number of results telephoned when compared against the critical limits list recommended by the Royal College of Pathologists and may focus out of hours clinical activity on more suitable patients.
Managing the terror of a dangerous world: Political attitudes as predictors of mental health stigma
Authors: DeLuca Joseph S , Yanos Philip T 
Published: June 2015

Background: Previous research has associated self-reported political conservatism to mental health stigma. Although the limitations of self-reported political attitudes are well documented, no study has evaluated this relationship from a more nuanced perspective of sociopolitical identity. Aims: To assess the relationship between political attitudes and mental health stigma (i.e. negative stereotypes and intended social distance), particularly from a standpoint of Right-Wing Authoritarianism (RWA) – a more specific measure of political conservatism. Method: A sample of 505 New York State residents completed an online survey. Results: The results of this study indicated significant relationships between endorsements of self-reported conservatism and RWA to negative stereotypes and social distance in relation to mental illness. Individuals with ‘High RWA’ were more likely to see individuals with mental illness as dangerous and unpredictable, and less willing to want to socially associate with individuals with mental illness. These results remained statistically significant even when controlling for other factors that consistently predict mental health stigma. Negative stereotypes also partially mediated individuals with RWA’s significant relationship to social distance. Conclusion: Characteristics of political conservatives and right-wing authoritarians (e.g. threat-aversion, personal responsibility) are predictive of mental health stigma. Terror Management Theory may also help to explain this phenomenon.