bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacteria Getting into Shape: Genetic Determinants of
E. coli
Morphology
Authors: French Shawn , Côté Jean-Philippe , Stokes Jonathan M. , Truant Ray , Brown Eric D. 
Published: March 2017

ABSTRACT

Perturbation of cellular processes is a prevailing approach to understanding biology. To better understand the complicated biology that defines bacterial shape, a sensitive, high-content platform was developed to detect multiple morphological defect phenotypes using microscopy. We examined morphological phenotypes across the
Escherichia coli
K-12 deletion (Keio) collection at the mid-exponential growth phase, revealing 111 deletions perturbing shape. Interestingly, 64% of these were uncharacterized mutants, illustrating the complex nature of shape maintenance and regulation in bacteria. To understand the roles these genes play in defining morphology, 53 mutants with knockouts resulting in abnormal cell shape were crossed with the Keio collection in high throughput, generating 1,373 synthetic lethal interactions across 1.7 million double deletion mutants. This analysis yielded a highly populated interaction network spanning and linking multiple phenotypes, with a preponderance of interactions involved in transport, oxidation-reduction, and metabolic processes.

IMPORTANCE
Genetic perturbations of cellular functions are a prevailing approach to understanding cell systems, which are increasingly being practiced in very high throughput. Here, we report a high-content microscopy platform tailored to bacteria, which probes the impact of genetic mutation on cell morphology. This has particular utility in revealing elusive and subtle morphological phenotypes associated with blocks in nonessential cellular functions. We report 111 nonessential mutations impacting
E. coli
morphology, with nearly half of those genes being poorly annotated or uncharacterized. Further, these genes appear to be tightly linked to transport or redox processes within the cell. The screening platform is simple and low cost and is broadly applicable to any bacterial genomic library or chemical collection. Indeed, this is a powerful tool in understanding the biology behind bacterial shape.
Impact of the global financial crisis on low birth weight in Portugal: a time-trend analysis
Authors: Kana Musa Abubakar , Correia Sofia , Peleteiro Barbara , Severo Milton , Barros Henrique 
Published: March 2017

BackgroundThe 2007–2008 global financial crisis had adverse consequences on population health of affected European countries. Few contemporary studies have studied its effect on perinatal indicators with long-lasting influence on adult health. Therefore, in this study, we investigated the impact of the 2007–2008 global financial crisis on low birth weight (LBW) in Portugal.MethodsData on 2 045 155 singleton births of 1995–2014 were obtained from Statistics Portugal. Joinpoint regression analysis was performed to identify the years in which changes in LBW trends occurred, and to estimate the annual per cent changes (APC). LBW risk by time period expressed as prevalence ratios were computed using the Poisson regression. Contextual changes in sociodemographic and economic factors were provided by their trends.ResultsThe joinpoint analysis identified 3 distinct periods (2 jointpoints) with different APC in LBW, corresponding to 1995–1999 (APC=4.4; 95% CI 3.2 to 5.6), 2000–2006 (APC=0.1; 95% CI −050 to 0.7) and 2007–2014 (APC=1.6; 95% CI 1.2 to 2.0). For non-Portuguese, it was, respectively, 1995–1999 (APC=1.4; 95% CI −3.9 to 7.0%), 2000–2007 (APC=−4.2; 95% CI −6.4 to −2.0) and 2008–2014 (APC=3.1; 95% CI 0.8 to 5.5). Compared with 1995–1999, all specific maternal characteristics had a 10–15% increase in LBW risk in 2000–2006 and a 20–25% increase in 2007–2014, except among migrants, for which LBW risk remained lower than in 1995–1999 but increased after the crisis. The increasing LBW risk coincides with a deceleration in gross domestic product growth rate, reduction in health expenditure, social protection allocation on family/children support and sickness.ConclusionsThe 2007–2008 global financial crisis was associated with a significant increase in LBW, particularly among infants of non-Portuguese mothers. We recommend strengthening social policies aimed at maternity protection for vulnerable mothers and health system maintenance of social equity in perinatal healthcare.
Statin prescribing for people with severe mental illnesses: a staggered cohort study of ‘real-world’ impacts
Authors: Blackburn R , Osborn D , Walters K , Falcaro M , Nazareth I , Petersen I 
Published: March 2017

ObjectivesTo estimate the ‘real-world effectiveness of statins for primary prevention of cardiovascular disease (CVD) and for lipid modification in people with severe mental illnesses (SMI), including schizophrenia and bipolar disorder.DesignSeries of staggered cohorts. We estimated the effect of statin prescribing on CVD outcomes using a multivariable Poisson regression model or linear regression for cholesterol outcomes.Setting587 general practice (GP) surgeries across the UK reporting data to The Health Improvement Network.ParticipantsAll permanently registered GP patients aged 40–84 years between 2002 and 2012 who had a diagnosis of SMI. Exclusion criteria were pre-existing CVD, statin-contraindicating conditions or a statin prescription within the 24 months prior to the study start.ExposureOne or more statin prescriptions during a 24-month ‘baseline’ period (vs no statin prescription during the same period).Main outcome measuresThe primary outcome was combined first myocardial infarction and stroke. All-cause mortality and total cholesterol concentration were secondary outcomes.ResultsWe identified 2944 statin users and 42 886 statin non-users across the staggered cohorts. Statin prescribing was not associated with significant reduction in CVD events (incident rate ratio 0.89; 95% CI 0.68 to 1.15) or all-cause mortality (0.89; 95% CI 0.78 to 1.02). Statin prescribing was, however, associated with statistically significant reductions in total cholesterol of 1.2 mmol/L (95% CI 1.1 to 1.3) for up to 2 years after adjusting for differences in baseline characteristics. On average, total cholesterol decreased from 6.3 to 4.6 in statin users and 5.4 to 5.3 mmol/L in non-users.ConclusionsWe found that statin prescribing to people with SMI in UK primary care was effective for lipid modification but not CVD events. The latter finding may reflect insufficient power to detect a smaller effect size than that observed in randomised controlled trials of statins in people without SMI.
Does household access to improved water and sanitation in infancy and childhood predict better vocabulary test performance in Ethiopian, Indian, Peruvian and Vietnamese cohort studies?
Authors: Dearden Kirk A , Brennan Alana T , Behrman Jere R , Schott Whitney , Crookston Benjamin T , Humphries Debbie L , Penny Mary E , Fernald Lia C H 
Published: March 2017

ObjectiveTest associations between household water and sanitation (W&S) and children's concurrent and subsequent Peabody Picture Vocabulary Test (PPVT) scores.DesignProspective cohort study.SettingEthiopia, India, Peru, Vietnam.Participants7269 children.Primary outcome measuresPPVT scores at 5 and 8 years. Key exposure variables were related to W&S, and collected at 1, 5 and 8 years, including ‘improved’ water (eg, piped, public tap or standpipe) and ‘improved’ toilets (eg, collection, storage, treatment and recycling of human excreta).ResultsAccess to improved water at 1 year was associated with higher language scores at 5 years (3/4 unadjusted associations) and 8 years (4/4 unadjusted associations). Ethiopian children with access to improved water at 1 year had test scores that were 0.26 SD (95% CI 0.17 to 0.36) higher at 5 years than children without access. Access to improved water at 5 years was associated with higher concurrent PPVT scores (in 3/4 unadjusted associations), but not later scores (in 1/4 unadjusted associations). 5-year-old Peruvian children with access to improved water had better concurrent performance on the PPVT (0.44 SD, 95% CI 0.30 to 0.59) than children without access to improved water. Toilet access at 1 year was also associated with better PPVT scores at 5 years (3/4 unadjusted associations) and sometimes associated with test results at 8 years (2/4 unadjusted associations). Toilet access at 5 years was associated with concurrent PPVT scores (3/4 unadjusted associations). More than half of all associations in unadjusted models (water and toilets) persisted in adjusted models, particularly for toilets in India, Peru and Vietnam.ConclusionsAccess to ‘improved’ water and toilets had independent associations with children's PPVT scores that often persisted with adjustment for covariates. Our findings suggest that effects of W&S may go beyond subacute and acute infections and physical growth to include children's language performance, a critical component of cognitive development.
Successful emergency department interventions that reduce time to antibiotics in febrile pediatric cancer patients
Authors: Spencer Sandra , Nypaver MIchele , Hebert Katherine , Benner Christopher , Stanley Rachel , Cohen Daniel , Rogers Alexander , Goldstick Jason , Mahajan Prashant 
Published: March 2017

Children with cancer and fever are at high risk for sepsis related death. Rapid antibiotic delivery (< 60 minutes) has been shown to reduce mortality.We compared patient outcomes and describe interventions from three separate quality improvement (QI) projects conducted in three United States (US) tertiary care pediatric emergency departments (EDs) with the shared aim to reduce time to antibiotic (TTA) to < 60 minutes in febrile pediatric oncology patients (Temperature > 38.0 C). A secondary objective was to identify interventions amenable to translation to other centers.We conducted a post project analysis of prospectively collected observational data from children < 18 years visiting these EDs during independently conducted QI projects. Comparisons were made pre to post intervention periods within each institution.All interventions were derived independently using QI methods by each institution. Successful as well as unsuccessful interventions were described and common interventions adopted by all sites identified.A total of 1032 ED patient visits were identified from the three projects. Improvement in median TTA delivery (min) pre to post intervention(s) was 118.5–57.0 at site 1, 163.0–97.5 at site 2, and 188.0–111.5 at site 3 (p<.001 all sites). The eight common interventions were 1) Triage application of topical anesthetic 2) Rapid room placement & triage 3) Resuscitation room placement of ill appearing children 4) Close proximity to central line equipment 5) Antibiotic administration before laboratory analyses 6) Consensus clinical practice guideline establishment 7) Family pre-ED education for fever and 8) Staff project updates.This core set of eight low cost, high yield QI interventions were developed independently by the three ED's which led to substantial reduction in time to antibiotic delivery in children with cancer presenting with fever. These interventions may inform future QI initiatives in other settings caring for febrile pediatric oncology patients.
Affording opportunities to discuss deterioration in paediatric palliative care consultations: a conversation analytic study
Authors: Ekberg Stuart , Danby Susan , Herbert Anthony , Bradford Natalie K , Yates Patsy 
Published: March 2017

ObjectiveDiscussing the potential deterioration of a child who has a life-limiting condition has recognised benefits for future care, but can be challenging in a clinical context where uncertain illness trajectories are common. Existing research is restricted to indirect forms of evidence such as self-report data from clinicians and families. This study directly explores how discussions about deterioration are managed within actual paediatric palliative care consultations.Methods9 consultations were video recorded in an Australian paediatric palliative care service. Each consultation involved the same paediatric palliative care specialist. Conversation analysis was used to identify and explore recurrent ways in which discussions about deterioration came to be realised.FindingsThe study identified two communicative practices used by a paediatric palliative care specialist that afforded opportunities to discuss deterioration: (1) soliciting the family's agenda for the consultation; (2) initiating and maintaining topics where discussing deterioration is a relevant possibility. Across these different practices, a common feature was indirect initiation of discussions about deterioration. This approach made such discussions possible, but without mandating or even suggesting that such discussion must occur.ConclusionsThese communicative practices balance the benefit of discussing deterioration against a recognised importance of allowing discussions to be directed by a child's family. This was achieved by creating opportunities for discussing deterioration, without making such discussions necessary.
Do differences in religious affiliation explain high levels of excess mortality in the UK?
Authors: Ralston Kevin , Walsh David , Feng Zhiqiang , Dibben Chris , McCartney Gerry , O'Reilly Dermot 
Published: March 2017

BackgroundHigh levels of mortality not explained by differences in socioeconomic status (SES) have been observed for Scotland and its largest city, Glasgow, compared with elsewhere in the UK. Previous cross-sectional research highlighted potentially relevant differences in social capital, including religious social capital (the benefits of social participation in organised religion). The aim of this study was to use longitudinal data to assess whether religious affiliation (as measured in UK censuses) attenuated the high levels of Scottish excess mortality.MethodsThe study used the Scottish Longitudinal Study (SLS) and the ONS Longitudinal Study of England and Wales. Risk of all-cause mortality (2001–2010) was compared between residents aged 35 and 74 years of Scotland and England and Wales, and between Glasgow and Liverpool/Manchester, using Poisson regression. Models adjusted for age, gender, SES and religious affiliation. Similar country-based analyses were undertaken for suicide.ResultsAfter adjustment for age, gender and SES, all-cause mortality was 9% higher in Scotland than in England and Wales, and 27% higher in Glasgow than in Liverpool or Manchester. Religious affiliation was notably lower across Scotland; but, its inclusion in the models did not attenuate the level of Scottish excess all-cause mortality, and only marginally lowered the differences in risk of suicide.ConclusionsDifferences in religious affiliation do not explain the higher mortality rates in Scotland compared with the rest of the UK. However, it is possible that other aspects of religion such as religiosity or religious participation which were not assessed here may still be important.
Association between income trajectories in childhood and psychiatric disorder: a Swedish population-based study
Authors: Björkenstam Emma , Cheng Siwei , Burström Bo , Pebley Anne R , Björkenstam Charlotte , Kosidou Kyriaki 
Published: March 2017

BackgroundChildhood family income variation is an understudied aspect of households' economic context that may have distinct consequences for children. We identified trajectories of childhood family income over a 12-year period, and examined associations between these trajectories and later psychiatric disorders, among individuals born in Sweden between 1987 and 1991 (n=534 294).MethodsWe used annual income data between the ages of 3–14 years and identified 5 trajectories (2 high-income upward, 1 downward and 2 low-income upward trajectories). Psychiatric disorders in the follow-up period after age 15 were defined from International Classification of Disease (ICD)-codes in a nationwide patient register. Multiadjusted risks for all psychiatric disorders, as well as for specific psychiatric diagnoses, were calculated as HRs with 95% CIs.ResultsOf the 5 identified income trajectories, the constant low and the downward trajectories were particularly associated with later psychiatric disorder. Children with these trajectories had increased risks for psychiatric disorder, including mood, anxiety, psychotic disorders and attention deficit/hyperactivity disorder. The association remained, even after adjusting for important variables including parental psychiatric disorder. In contrast, the relationship was reversed for eating disorders, for which children in higher income trajectories had elevated risks.ConclusionsFindings show that children growing up in a household characterised by low or decreasing family income have an increased risk for psychiatric disorder. Continued work is needed to reduce socioeconomic inequalities in psychiatric disorders. Policies and interventions for psychiatric disorders should consider the socioeconomic background of the family as an important risk or protective factor.
Echo-acoustic flow shapes object representation in spatially complex acoustic scenes
Authors: Greiter Wolfgang , Firzlaff Uwe 
Published: March 2017

Echolocating bats use echoes of their sonar emissions to determine the position and distance of objects or prey. Target distance is represented as a map of echo delay in the auditory cortex (AC) of bats. During a bat’s flight through a natural complex environment, echo streams are reflected from multiple objects along its flight path. Separating such complex streams of echoes or other sounds is a challenge for the auditory system of bats as well as other animals. We investigated the representation of multiple echo streams in the AC of anesthetized bats ( Phyllostomus discolor) and tested the hypothesis that neurons can lock on echoes from specific objects in a complex echo-acoustic pattern while the representation of surrounding objects is suppressed. We combined naturalistic pulse/echo sequences simulating a bat’s flight through a virtual acoustic space with extracellular recordings. Neurons could selectively lock on echoes from one object in complex echo streams originating from two different objects along a virtual flight path. The objects were processed sequentially in the order in which they were approached. Object selection depended on sequential changes of echo delay and amplitude, but not on absolute values. Furthermore, the detailed representation of the object echo delays in the cortical target range map was not fixed but could be dynamically adapted depending on the temporal pattern of sonar emission during target approach within a simulated flight sequence. NEW & NOTEWORTHY Complex signal analysis is a challenging task in sensory processing for all animals, particularly for bats because they use echolocation for navigation in darkness. Recent studies proposed that the bat’s perceptional system might organize complex echo-acoustic information into auditory streams, allowing it to track specific auditory objects during flight. We show that in the auditory cortex of bats, neurons can selectively respond to echo streams from specific objects.
Jab1/Csn5–Thioredoxin Signaling in Relapsed Acute Monocytic Leukemia under Oxidative Stress
Authors: Zhou Fuling , Pan Yunbao , Wei Yongchang , Zhang Ronghua , Bai Gaigai , Shen Qiuju , Meng Shan , Le Xiao-Feng , Andreeff Michael , Claret Francois X. 
Published: March 2017

Abstract
Purpose: High levels of ROS and ineffective antioxidant systems contribute to oxidative stress, which affects the function of hematopoietic cells in acute myeloid leukemia (AML); however, the mechanisms by which ROS lead to malignant transformation in relapsed AML-M5 are not completely understood. We hypothesized that alterations in intracellular ROS would trigger AML-M5 relapse by activating the intrinsic pathway.
Experimental Design: We studied ROS levels and conducted c-Jun activation domain–binding protein-1 (JAB1/COPS5) and thioredoxin (TRX) gene expression analyses with blood samples obtained from 60 matched AML-M5 patients at diagnosis and relapse and conducted mechanism studies of Jab1′s regulation of Trx in leukemia cell lines.
Results: Our data showed that increased production of ROS and a low capacity of antioxidant enzymes were characteristics of AML-M5, both at diagnosis and at relapse. Consistently, increased gene expression levels of TRX and JAB1/COPS5 were associated with low overall survival rates in patients with AML-M5. In addition, stimulating AML-M5 cells with low concentrations of hydrogen peroxide led to increased Jab1 and Trx expression. Consistently, transfection of ectopic Jab1 into leukemia cells increased Trx expression, whereas silencing of Jab1 in leukemia cells reduced Trx expression. Mechanistically, Jab1 interacted with Trx and stabilized Trx protein. Moreover, Jab1 transcriptionally regulated Trx. Furthermore, depletion of Jab1 inhibited leukemia cell growth both in vitro and in vivo.
Conclusions: We identified a novel Jab1–Trx axis that is a key cellular process in the pathobiologic characteristics of AML-M5. Targeting the ROS/Jab1/Trx pathway could be beneficial in the treatment of AML-M5. Clin Cancer Res; 23(15); 4450–61. ©2017 AACR.
NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor–Positive Breast Cancer
Authors: Ma Cynthia X. , Gao Feng , Luo Jingqin , Northfelt Donald W. , Goetz Matthew , Forero Andres , Hoog Jeremy , Naughton Michael , Ademuyiwa Foluso , Suresh Rama , Anderson Karen S. , Margenthaler Julie , Aft Rebecca , Hobday Timothy , Moynihan Timothy , Gillanders William , Cyr Amy , Eberlein Timothy J. , Hieken Tina , Krontiras Helen , Guo Zhanfang , Lee Michelle V. , Spies Nicholas C. , Skidmore Zachary L. , Griffith Obi L. , Griffith Malachi , Thomas Shana , Bumb Caroline , Vij Kiran , Bartlett Cynthia Huang , Koehler Maria , Al-Kateb Hussam , Sanati Souzan , Ellis Matthew J. 
Published: March 2017

Abstract
Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor–positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies.
Experimental Design: Eligible patients with clinical stage II/III ER+/HER2− breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1–21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 &gt; 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%).
Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P &lt; 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression.
Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055–65. ©2017 AACR.