bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of steatosis and inflammation definitions on the performance of NASH tests
Authors: Poynard Thierry , Munteanu Mona , Charlotte Frederic , Perazzo Hugo , Ngo Yen , Deckmyn Olivier , Pais Raluca , Mathurin Philippe , Ratziu Vlad 
Published: December 2017

Background and aim
One of the unmet needs in subjects with metabolic risks is the prediction of metabolic liver disease by noninvasive tests. The construction of performant tests is dependent on the appropriateness of the histological reference definition. The aim of this study was to analyze the limitations of similar European (Fatty Liver Inhibition of Progression) and USA (Clinical-Research-Network) standard definitions and their impact on the construction of tests.

Methods
We hypothesized that a simpler histological definition of non-alcoholo steato-hepatitis (NASH), which does not require the presence of steatosis and the presence of both lobular inflammation and ballooning, should improve the concordance rates with previously validated blood tests. We reviewed the landmark studies in metabolic liver disease, sources of the standard definitions, and we compared the adequacy of these standards to other possible definitions in 1081 subjects with biopsies, by concordance and accuracy rates.

Results
The limitations of standard definitions included the presence of appropriate controls in only 6.6% of landmark studies, an arbitrary definition of steatosis and NASH covering only four (15%) out of 27 possible combinations of features, compared with 18 (67%) for a simplified NASH definition, which did not require steatosis. A total of 39/1081 (3.6%) cases were not identified by standard definition, but were identified by the simplified definition as significant active disease, including 15 cases with significant fibrosis. The simplified definition increased the κ concordance (P<0.0001) between test prediction and histological reference.

Conclusion
A simplified definition of NASH could help in the construction of biomarkers with higher performances.
New therapeutic strategies for high-risk acute myeloid leukemia
Authors: Menghrajani Kamal , Tallman Martin S. 
Published: December 2017

Purpose of review
Treatments for acute myeloid leukemia (AML) had remained essentially unchanged for several years; however, the advent of molecular testing has generated insight into the biology of this disease which is now being translated into clinical practice. New treatment strategies which improve drug delivery and exploit cellular targets are changing the landscape of how we treat this disease.

Recent findings
Induction therapy is in the process of changing for several patient populations. The introduction of CPX-351 offers a novel strategy for treating patients with therapy-related AML or AML with myelodysplasia-related changes; gemtuzumab ozogamicin may become incorporated into standard induction therapy, especially for patients with core-binding factor leukemias; and for older adults, combination therapy with venetoclax may offer a more efficacious strategy than the single-agent regimens previously used. Additionally, targeted therapies are now becoming available for patients with mutations in FMS-like tyrosine kinase 3 (FLT3) or isocitrate dehydrogenase 2 (IDH2), ushering in an era of personalized medicine in the treatment of AML.

Summary
The US Food and Drug Administration approval of several agents in 2017 will change the way AML treatment is approached and will offer both clinicians and patients a new armamentarium with which to treat this disease.
When should patients receive consolidation chemotherapy before allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission?
Authors: Yeshurun Moshe , Wolach Ofir 
Published: December 2017

Purpose of review
Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative therapy for patients with acute myeloid leukemia. Despite the associated graft-versus-leukemia effect, leukemia relapse remains the most common cause of treatment failure after alloHCT. Here, we review the available data on whether there is an advantage in providing pretransplant consolidation chemotherapy prior to alloHCT.

Recent findings
Randomized controlled studies are lacking. Data derive largely from four large retrospective registry studies. These analyses are consistent in demonstrating the lack of any survival benefit for pretransplant consolidation chemotherapy once a patient achieves a complete remission and a donor is readily available. These results are valid across conditioning regimen intensities, donor sources, and doses of cytarabine administered during consolidation.

Summary
Available evidence suggests that patients with acute myeloid leukemia in first complete remission for whom a suitable donor is readily available should not be given pretransplant consolidation before proceeding to alloHCT, regardless of conditioning regimen intensity and that transplantation should be offered promptly at the time remission is achieved without undue delay. Nevertheless, patients for whom a suitable donor is not readily available after achieving first remission, should probably receive ‘bridging’ consolidation chemotherapy while waiting for a donor to be identified in an attempt to decrease the risk of early disease recurrence before transplantation. The role of minimal residual disease and genetic markers in directing consolidation choices are unclear to date.
Have haploidentical transplants replaced umbilical cord transplants for acute leukemias?
Authors: Liu Jia Hau , Kanakry Christopher G. , Luznik Leo 
Published: December 2017

Purpose of review
Haploidentical stem cell transplantation (Haplo SCT) and umbilical cord blood stem cell transplantation (UCB SCT) have emerged over the past two to three decades as viable sources of alternative donor SCT when a human leukocyte antigen matched donor is not available. However, which of these two donor types is optimal for patients with leukemia in need of allografting is unknown.

Recent findings
For patients with acute leukemia, results of UCB SCT have been improved by the use of double umbilical cord units and emerging ex-vivo expansion technologies. However, the costs associated with procuring double cord units and high transplant-related mortality due to delayed immunological reconstitution and infections, particularly in adult patients, remain a problem. Recently, Haplo SCT has become an increasingly utilized alternative donor source. While improvements of ex-vivo T-cell depletion platforms continue, emergence of T-cell-replete platforms, such as the use of post-transplantation cyclophosphamide (PTCy), is increasingly being utilized in treating acute leukemia patients. PTCy-based Haplo SCT is gaining popularity among transplant clinicians due to its relatively easy learning curve, low cost, low incidence of graft-versus-host disease, and favorable survival in acute leukemia patients.

Summary
The clinical question of whether Haplo SCT should replace UCB SCT needs to be answered by ongoing randomized trials. However, the rapidly increasing adoption of Haplo SCT worldwide as the viable alternative for patients without a human leukocyte antigen-matched donor has seemingly addressed the question ahead of scientific judgment.
Sexual Networks of Racially Diverse Young MSM Differ in Racial Homophily But Not Concurrency
Authors: Janulis Patrick , Phillips Gregory , Birkett Michelle , Mustanski Brian 
Published: December 2017

Background:
Substantial racial disparities exist in HIV infection among young men who have sex with men (YMSM). However, evidence suggests black YMSM do not engage in greater levels of risk behavior. Sexual networks may help explain this paradox. This study used egocentric exponential random graph models to examine variation in concurrency (ie, 2 or more simultaneous partners) and homophily (ie, same race/ethnicity partners) across race/ethnicity groups in a diverse sample of YMSM.

Methods:
Data for this study come from a longitudinal cohort study of YMSM. Participants (n = 1012) provided data regarding their sexual contacts during the 6 months before their first study visit. A series of egocentric exponential random graph models examined how providing separate estimates for homophily and concurrency parameters across race/ethnicity improved the fit of these models. Networks were simulated using these parameters to examine how local network characteristics impact risk at the whole network level.

Results:
Results indicated that homophily, but not concurrency, varied across race/ethnicity. Black participants witnessed significantly higher race/ethnicity homophily compared with white and Latino peers. Extrapolating from these models, black individuals were more likely to be in a connected component with an HIV-positive individual and closer to HIV-positive individuals. However, white individuals were more likely to be in large connected components.

Conclusions:
These findings suggest that high racial homophily combined with existing disparities in HIV help perpetuate the spread of HIV among black YMSM. Nonetheless, additional work is required to understand these disparities given that homophily alone cannot sustain them indefinitely.
Is there still a role for vancomycin in skin and soft-tissue infections?
Authors: Savoldi Alessia , Azzini Anna M. , Baur David , Tacconelli Evelina 
Published: December 2017

Purpose of review
Skin and soft-tissue infections (SSIs) are among the commonest infections encountered in clinical practice. Spread of methicillin-resistant Staphylococcus aureus SSIs continues to increase in both health care and community settings and presents a challenge for the best treatment choice. Vancomycin has been the mainstay of SSIs treatment, but recently its use has been questioned because of concerns about its efficacy, tolerability, and unfavorable pharmacokinetic/pharmacodynamic profile. The purpose of this review is to establish the current role for vancomycin in light of the literature published from January 2007 to September 2017 on comparison with both old and new alternatives.

Recent findings
Meta-analyses show better clinical and microbiological outcomes for drugs approved for the treatment of SSI, including those sustained by methicillin-resistant S. aureus, in the last 10 years than for vancomycin. The newer glycopeptides and linezolid decrease the total treatment costs compared with vancomycin, by reducing the length of stay or avoiding the hospitalization.

Summary
Vancomycin is noninferior in efficacy and safety to all comparator drugs, including the newest on the market. However, the SSI treatment evidence base presents several shortcomings limiting the clinical applicability of the results. High-level clinical trials should be performed to obtain results that can be generalized and applied effectively in clinical practice.
A Quality Improvement Initiative to Reduce “Out-of-ICU” Cardiopulmonary Arrests in a Tertiary Care Hospital in India: A 2-Year Learning Experience
Authors: Menon Vidya P. , Prasanna Preetha , Edathadathil Fabia , Balachandran Sabarish , Moni Merlin , Sathyapalan Dipu , Pai Rajesh D. , Singh Sanjeev 
Published: December 2017

Quality Problem or Issue:
To assess impact of medical emergency team (MET) in reducing “out-of-ICU” cardiopulmonary arrests and identify barriers to its optimal utilization.

Initial Assessment:
Frequently observed critical clinical signs and laboratory values of “out-of-ICU” crashes were used to develop Amrita Early Warning Criteria.

Choice of Solution:
A physician-led MET was established to respond to code MET, activated by a primary nurse.

Implementation:
Rates of “out-of-ICU” cardiopulmonary arrests per 1000 admissions were compared in pre-MET (2013-2014) and post-MET periods (2014-2016) along with disposition following MET and mortality. Descriptive statistics and logistic regression were used for comparative analysis.

Evaluation:
For continued quality improvement, a Likert agreement scale questionnaire collated the nurse's feedback on MET. 386 Code MET were recorded with an activation rate of 18.8 per 1000 inpatients for 2014-2016. Common MET triggers were desaturation (53%), seizure (10%), and syncope (9%). Seventy-one percent of activations were attended within 5 minutes, with 45% reported during nurse's night shift hours. Medical emergency team interventions resulted in 59% being shifted to ICU. In the “post-MET” period, “Cold Blue” dose reduced from 6.9 in 2013-2014 to 2.6 (P = .0002) in 2014-2015 and 3.2 (P = .01) in 2015-2016. Ninety-three percent of the Code Blues with prior MET calls were “delayed MET” and 28% of the Code Blues without prior MET activation were “missed MET.” Nurse's feedback revealed that 46% lacked knowledge of correct MET activation process while 31% expressed a fear of reprisal for inappropriate activation.

Lessons Learned:
Although MET intervention was successful in significantly reducing “out-of-ICU” Code Blues, focused training of nurses is required for continued quality improvement.
Thrombin Provokes Degranulation of Platelet α-Granules Leading to the Release of Active Plasminogen Activator Inhibitor-1 (PAI-1)
Authors: Huebner Benjamin R. , Moore Ernest E. , Moore Hunter B. , Stettler Gregory R. , Nunns Geoffrey R. , Lawson Peter , Sauaia Angela , Kelher Marguerite , Banerjee Anirban , Silliman Christopher C. 
Published: December 2017

ABSTRACT

Background:
The balance of fibrinolytic mediators is crucial to the survival of the critically ill patient, with tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) playing significant roles. While elevated levels of PAI-1 are associated with increased morbidity and mortality, the source of this PAI-1 remains elusive. Platelets contain 90% of circulating plasma PAI-1, however, their ability to release active PAI-1 is controversial. We hypothesize platelets contain active PAI-1 in α-granules capable of immediate degranulation when exposed to high concentrations of thrombin.

Methods:

In vitro apheresis platelets were stimulated with thrombin (1 IU/mL, 5 IU/mL) followed by the collection of supernatant (5–120 min). Supernatant and lysate PAI-1 was measured by ELISA. The experiment was repeated in the presence of t-PA followed by measurement of t-PA:PAI-1 complex measurement by ELISA. Finally, healthy whole blood underwent dilution with control and thrombin-treated platelet lysate followed by thrombelastography (TEG) in a t-PA-stimulated TEG.

Results:
Thrombin provoked immediate near-complete degranulation of PAI-1 from α-granules (median 5m 5 IU/mL thrombin 125.1 ng/mL, 1 IU/mL thrombin 114.9 ng/mL, control 9.9 ng/mL). The released PAI-1 rapidly complexed with t-PA, with a 4-fold increase in complex formation in the thrombin-treated supernatant. Conversely, PAI-1 in the control lysate demonstrated a 6-fold increase in complex formation compared with thrombin lysate. Last, control platelet lysate inhibited t-PA-induced fibrinolysis by TEG (median LY30 control 15m 7.9%), while thrombin-treated platelet lysates, after PAI-1 degranulation, were unable to affect the fibrinolysis profile (median LY30 5 IU/mL 28.5%, 1 IU/mL 12.4%).

Conclusion:
Thrombin provokes rapid α-degranulation of active PAI-1, capable of complexing with t-PA and neutralizing t-PA-induced fibrinolysis by TEG.
Critical Illness-Related Corticosteroid Insufficiency in Cardiogenic Shock Patients: Prevalence and Prognostic Role
Authors: Ducrocq Nicolas , Biferi Pascal , Girerd Nicolas , Latar Ichraq , Lemoine Simon , Perez Pierre , Thivilier Carine , Levy Bruno , Kimmoun Antoine 
Published: December 2017

ABSTRACT

Background:
Cardiogenic shock shares with septic shock common hemodynamic features, inflammatory patterns, and most likely similar complications such as critical illness-related corticosteroid insufficiency. The aim of this study was to evaluate the prevalence of critical illness-related corticosteroid insufficiency in cardiogenic shock patients and to secondarily assess its prognostic value on 90-day mortality.

Methods:
A single-center prospective observational study conducted over a 3-year period and including all patients with cardiogenic shock. Main exclusion criteria were patients with prior cardiac arrest, sepsis, ongoing corticosteroid therapy, and etomidate administration. A short corticotropin test was performed in the first 24 h following admission. Serum cortisol levels were measured before (T0) and 60 min (T60) after administration of 250 μg of cosyntropin. Critical illness-related corticosteroid insufficiency was defined according to the 2017 consensus definition (basal total cortisol<10 μg·dL−1 or a delta cortisol T60-T0<9 μg·dL−1) as well as the thresholds published in 2016 in cardiogenic shock patients associated with worst prognosis (basal total cortisol>29 μg·dL−1 and delta cortisol T60-T0<17 μg·dL−1).

Results:
Seventy-nine consecutive patients hospitalized in intensive care for cardiogenic shock met the inclusion criteria. Overall mortality was 43% at day 90. Forty-two percent had critical illness-related corticosteroid insufficiency using the 2017 consensus definition and 32% using the 2016 cardiogenic shock thresholds. Presence of critical illness-related corticosteroid insufficiency was not an independent factor associated with 90-day mortality irrespective of the thresholds used.

Conclusion:
Critical illness-related corticosteroid insufficiency is a frequent occurrence in medical cardiogenic shock. However, in this study, such insufficiency was not associated with prognosis.
Hydrogen Inhalation is Superior to Mild Hypothermia for Improving Neurological Outcome and Survival in a Cardiac Arrest Model of Spontaneously Hypertensive Rat
Authors: Chen Gang , Chen Bihua , Dai Chenxi , Wang Jianjie , Wang Juan , Huang Yuanyuan , Li Yongqin 
Published: December 2017

ABSTRACT

Background:
Postcardiac arrest syndrome is the consequence of whole-body ischemia–reperfusion events that lead to multiple organ failure and eventually to death. Recent animal studies demonstrated that inhalation of hydrogen greatly mitigates postresuscitation myocardial dysfunction and brain injury. However, the influence of underlying heart disease on the efficacy of hydrogen is still unknown. In the present study, we investigated the effects of hydrogen inhalation on neurological outcome and survival in a cardiac arrest model of spontaneously hypertensive rat (SHR).

Methods:
Cardiopulmonary resuscitation was initiated after 4 min of untreated ventricular fibrillation in 40 SHRs. Immediately after successful resuscitation, animals were randomized to be ventilated with 98% oxygen and 2% nitrogen under normothermia (Ctrl), 2% nitrogen under hypothermia (TH), 2% hydrogen under normothermia (H2), or 2% hydrogen under hypothermia (H2+TH) for 2 h. Hypothermia was maintained at 33°C for 2 h. Animals were observed up to 96 h for assessment of survival and neurologic recovery.

Results:
No statistical differences in baseline measurements were observed among groups and all the animals were successfully resuscitated. Compared with Ctrl, serum cardiac troponin T measured at 5 h and myocardial damage score measured at 96 h after resuscitation were markedly reduced in H2, TH, and H2+TH groups. Compared with Ctrl and TH, astroglial protein S100 beta measured during the earlier postresuscitation period, and neurological deficit score and neuronal damage score measured at 96 h were considerably lower in both H2 and H2+TH groups. Ninety-six hours survival rates were significantly higher in the H2 (80.0%) and H2+TH (90.0%) groups than TH (30.0%) and to Ctrl (30.0%).

Conclusions:
Hydrogen inhaling was superior to mild hypothermia for improving neurological outcome and survival in cardiac arrest and resuscitation model of systemic hypertension rats.
Intravaginal Diazepam for the Treatment of Pelvic Floor Hypertonic Disorder: A Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Holland Michael A. , Joyce John S. , Brennaman Lisa M. , Drobnis Erma Z. , Starr Julie A. , Foster Raymond T. 
Published: December 2017

Objectives
Pelvic floor hypertonic disorder is characterized by an involuntary spasm of the levator ani muscles and is associated with several clinical syndromes. Several treatment options have been described; however, treatment efficacy data are limited. The objective of this study was to determine the efficacy of intravaginal diazepam for the treatment of pelvic pain secondary to levator ani muscle spasm in comparison to placebo.

Methods
Adult women with complaints of pelvic pain, who were noted to have levator ani muscle spasm on physical examination, were approached for enrollment in a double-blind, placebo-controlled, randomized clinical trial. Eligible participants were randomized to receive 10-mg diazepam capsules or identical-appearing placebo capsules. The primary outcome was the change in pain scores measured by a 100-mm visual analog scale at 4 weeks. Several validated questionnaires were similarly assessed as secondary outcomes.

Results
In total, 49 women were randomized (25 in the diazepam arm and 24 in the placebo arm). At 4 weeks, 35 women returned for follow-up and had complete data available analysis. There was no difference in visual analog scale scores between the treatment groups after 4 weeks (50 vs 39 mm, for diazepam and placebo, respectively; P = 0.36). There were also no differences noted in the questionnaire scores.

Conclusions
It is unlikely that self-administered intravaginal diazepam suppositories promote an improvement in the 100-mm visual analog scale of 20 mm or more or other substantial symptom improvement in women with pelvic floor hypertonic disorder.
A Near Complete Zonal Map of Mouse Olfactory Receptors
Authors: Tan Longzhi , Xie X. Sunney 
Published: December 2017

AbstractIn the mouse olfactory system, spatially regulated expression of > 1,000 olfactory receptors (ORs) ― a phenomenon termed “zones” ― forms a topological map in the main olfactory epithelium (MOE). However, the zones of most ORs are currently unknown. By sequencing mRNA of 12 isolated MOE pieces, we mapped out zonal information for 1,033 OR genes with an estimated accuracy of 0.3 zones, covering 81% of all intact OR genes and 99.4% of total OR mRNA abundance. Zones tend to vary gradually along chromosomes. We further identified putative non-OR genes that may exhibit zonal expression.
A cloning-free method for CRISPR/Cas9-mediated genome editing in fission yeast
Authors: Zhang Xiao-Ran , He Jia-Bei , Wang Yi-Zheng , Du Li-Lin 
Published: December 2017

ABSTRACTThe CRISPR/Cas9 system, which relies on RNA-guided DNA cleavage to induce site-specific DNA double-strand breaks, is a powerful tool for genome editing. This system has been successfully adapted for the fission yeast Schizosaccharomyces pombe by expressing Cas9 and the single-guide RNA (sgRNA) from a plasmid. In the procedures published to date, the cloning step that introduces a specific sgRNA target sequence into the plasmid is the most tedious and time-consuming. To increase the efficiency of applying the CRISPR/Cas9 system in fission yeast, we here developed a cloning-free procedure that uses gap repair in fission yeast cells to assemble two linear DNA fragments, a gapped Cas9-encoding plasmid and a PCR-amplified sgRNA insert, into a circular plasmid. Both fragments contain only a portion of the ura4 or bsdMX marker so that only the correctly assembled plasmid can confer uracil prototrophy or blasticidin resistance. We show that this gap-repair-based and cloning-free CRISPR/Cas9 procedure permits rapid and efficient point mutation knock-in, endogenous N-terminal tagging, and genomic sequence deletion in fission yeast.