bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Treatment-Resistant and Clozapine-Resistant Schizophrenia: A 12-Year Follow-up Study of First-Episode Schizophrenia-Spectrum Disorders
Authors: Chan Sherry Kit Wa , Chan Hei Yan Veronica , Honer William G , Bastiampillai Tarun , Suen Yi Nam , Yeung Wai Song , Lam Ming , Lee Wing King , Ng Roger Man King , Hui Christy Lai Ming , Chang Wing Chung , Lee Edwin Ho Ming , Chen Eric Yu Hai 
Published: September 2020

Abstract
Studies on the long-term development and early predictors of treatment-resistant schizophrenia (TRS) and clozapine-resistant TRS (CR-TRS) in patients with first-episode schizophrenia-spectrum disorders (FES) are limited and have not considered the impact of early intervention services (EIS). This study aimed to explore the development of TRS and CR-TRS among patients with FES over 12 years of follow-up. Of the 1234 patients with FES, 15% developed TRS. A total of 450 patients with schizophrenia or schizoaffective disorder were included in a nested case-control study (157 TRS and 293 non-TRS). Younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher antipsychotic dose in the first 24 months were associated with earlier TRS. CR-TRS patients, constituting 25% of TRS patients, had a poorer premorbid social adjustment in late adolescence and longer delay before clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. However, TRS patients on clozapine had a lower mortality rate compared with non-TRS patients. EIS did not have a significant impact on the development of TRS, but patients in the EIS group had a shorter delay of clozapine initiation. Results suggested that neurodevelopmental factors, early clinical characteristics, and requirement for higher antipsychotic dose may be associated with TRS development, highlighting multiple pathways leading to this form of illness. Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of TRS and improve patient outcomes.
Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia
Authors: Wolf Robert C , Rashidi Mahmoud , Schmitgen Mike M , Fritze Stefan , Sambataro Fabio , Kubera Katharina M , Hirjak Dusan 
Published: September 2020

Abstract
Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression.
Adintoviruses: a proposed animal-tropic family of midsize eukaryotic linear dsDNA (MELD) viruses
Authors: Starrett Gabriel J , Tisza Michael J , Welch Nicole L , Belford Anna K , Peretti Alberto , Pastrana Diana V , Buck Christopher B 
Published: September 2020

Abstract
Polintons (also known as Mavericks) were initially identified as a widespread class of eukaryotic transposons named for their hallmark type B DNA polymerase and retrovirus-like integrase genes. It has since been recognized that many polintons encode possible capsid proteins and viral genome-packaging ATPases similar to those of a diverse range of double-stranded DNA viruses. This supports the inference that at least some polintons are actually viruses capable of cell-to-cell spread. At present, there are no polinton-associated capsid protein genes annotated in public sequence databases. To rectify this deficiency, we used a data-mining approach to investigate the distribution and gene content of polinton-like elements and related DNA viruses in animal genomic and metagenomic sequence datasets. The results define a discrete family-like clade of viruses with two genus-level divisions. We propose the family name Adintoviridae, connoting similarities to adenovirus virion proteins and the presence of a retrovirus-like integrase gene. Although adintovirus-class PolB sequences were detected in datasets for fungi and various unicellular eukaryotes, sequences resembling adintovirus virion proteins and accessory genes appear to be restricted to animals. Degraded adintovirus sequences are endogenized into the germlines of a wide range of animals, including humans.
New developments in respiratory medicine: a primary immunodeficiency perspective
Authors: Ng Kher , Hurst John R. 
Published: September 2020

Purpose of review
To consider recent developments in respiratory medicine that are of relevance to clinicians caring for adults affected by primary immunodeficiency disorders.

Recent findings
We consider impulse oscillometry, new bronchoscopic techniques for sampling, MRI and PET, the concept of the human airway microbiome, and new treatment approaches for bronchiectasis and interstitial lung disease to better understand the future of respiratory care for people with PID.

Summary
New approaches to the diagnosis and management of respiratory manifestations of PID have been driven by better understanding of the lung in health and disease, progress in imaging and sampling modalities, and new therapeutics.
Learning During and From a Crisis: The Student-Led Development of a COVID-19 Curriculum
Authors: Kochis Michael , Goessling Wolfram 
Published: September 2020

Problem
The speed and scope of the upheaval that COVID-19 inflicted on medical education made innovation a necessity. While medical students wanted high-quality, consolidated educational resources on COVID-19, the medical school faculty who typically produced such resources were increasingly burdened with clinical, administrative, and personal commitments. However, students eager to contribute to the pandemic response were well suited to create these instructional materials for their peers.

Approach
In mid-March 2020, a group of students at Harvard Medical School came together to synthesize the key facts and collate the best existing educational materials about the COVID-19 pandemic into a unified learning resource. The materials were faculty reviewed and shared freely online. The curriculum now contains 8 modules that are updated regularly. Throughout this process, the student authors prioritized accessibility, iterative improvement, and effective pedagogy.

Outcomes
To date, nearly 80,000 users from 132 countries have accessed the curriculum. It has been referenced or incorporated into courses at Harvard Medical School and more than 30 other medical schools across the country. About 40% of all users are from outside the United States, and the materials have been translated into 28 languages. This effort has spurred a number of other educational initiatives led by medical student groups in the United States and abroad.

Next Steps
As understanding of the COVID-19 pandemic is constantly changing, the student authors’ immediate goal is to keep the curriculum up to date in the months to come. They plan to maintain existing partnerships with medical schools and student groups around the world while pursuing new opportunities to expand the curriculum’s reach, provide education, and build community. Students and educators alike should leverage student-driven education efforts to benefit other learners both within and, importantly, beyond their institutions.
A Community Emergency Department Rotation for Pediatric Emergency Medicine Fellows
Authors: Langhan Melissa L. , Woolf Seth , Tiyyagura Gunjan 
Published: September 2020

Objective
There have been increasing job opportunities for pediatric emergency medicine (PEM) specialists within community emergency departments (CEDs), where 90% of children receive emergency care. The majority of training for PEM fellows occurs in academic children's hospitals, which may expose fellows to different resources than CEDs. Our goals were to develop and to evaluate a CED rotation aimed at improving exposure to this care environment for PEM fellows.

Methods
Kern's 6 steps of curriculum development served as our framework to identify the problem, conduct a needs assessment, develop goals and objectives, formulate an educational strategy, and then plan the implementation and evaluation. Discussion and buy-in among trainees and hospital leadership took place during rotation development. Informal and web-based surveys of PEM fellows and CED attendings evaluated the rotation and assessed participants' reactions, changes in knowledge, and changes in behavior.

Results
The CED rotation was piloted at 1 PEM fellowship program over 2 years. Nine PEM fellows participated in the month-long rotation. The majority of participants reported that the rotation goals and objectives were met and that they acquired new skills and rated the CED rotation as good or excellent. Challenges to the CED rotation included lower patient acuity and distance to the CED.

Conclusions
A new CED rotation was developed, piloted, and well received by participants. Given the potential differences in practice between tertiary care children's emergency departments and CEDs, as well as increasing job opportunities in CEDs, program directors should consider incorporating a CED rotation for their PEM fellows.
Patient Outcomes With Febrile Neutropenia Based on Time to Antibiotics in the Emergency Department
Authors: Dessie Almaz S. , Lanning Miranda , Nichols Tristan , Delgado Eva M. , Hart Lisa Sinclair , Agrawal Anurag K. 
Published: September 2020

Objective
Although bacteremia in pediatric oncology patients with febrile neutropenia (FN) is not uncommon, sepsis and mortality are rare. Because of the lack of clinically meaningful decision tools to identify high-risk patients with bacteremia, time to antibiotic administration (TTA) is increasingly considered an important quality and safety measure in the emergency department. Because little evidence exists suggesting that this benchmark is beneficial, we sought to determine whether TTA of 60 minutes or less is associated with improved outcomes.

Methods
We retrospectively reviewed patients presenting to a pediatric emergency department with FN from November 2013 to June 2016. Clinical outcomes including mortality, pediatric intensive care unit admission, imaging, fluid resuscitation of 40 mL/kg or greater in the first 24 hours, and length of stay were compared between TTA of 60 minutes or less and more than 60 minutes.

Results
One hundred seventy-nine episodes of FN were analyzed. The median TTA was 76 minutes (interquartile range, 58–105). The incidence of bacteremia was higher in patients with TTA of more than 60 minutes (12% vs 2%, P = 0.04), but without impact on mortality, pediatric intensive care unit admission, fluid resuscitation, or median length of stay. The median TTA was not different for those who were and were not bacteremic (91 vs 73 minutes, P = 0.11).

Conclusions
Time to antibiotic administration of more than 60 minutes did not increase mortality in pediatric oncology patients with FN. Our study adds to the existing literature that TTA of 60 minutes or less does not seem to improve outcomes in pediatric FN. Further larger studies are required to confirm these findings and determine which features predispose pediatric FN patients to morbidity and mortality.
Cytoreductive Nephrectomy in Patients Presenting With Advanced Disease
Authors: Shapiro Daniel D. , Westerman Mary E. , Karam Jose A. , Wood Christopher G. 
Published: September 2020

Abstract
Determining the appropriate patients for cytoreductive nephrectomy (CN) has evolved with the integration of more effective systemic therapies for patients with metastatic renal cell carcinoma (mRCC). While previously considered to be first-line therapy for mRCC, CN has not demonstrated a significant survival advantage over systemic therapy in more recent randomized trials when compared with targeted therapy. Conversely, multiple observational studies demonstrate a therapeutic benefit for CN. This review synthesizes the current literature regarding patient selection for CN and further evaluates the role of CN in the current era of immune checkpoint inhibitor therapy. With careful patient selection, CN maintains an important role in the management of mRCC patients.
The Immunotherapy Revolution in Kidney Cancer Treatment
Authors: Hasanov Elshad , Gao Jianjun , Tannir Nizar M. 
Published: September 2020

AbstractThe recent discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, including the treatment for renal cell carcinoma (RCC). Following the eras of cytokines and molecularly targeted therapies including vascular endothelial growth factor–directed agents and mammalian target of rapamycin (mTOR) inhibitors, ICIs have become the latest addition to the RCC armamentarium. To understand the scientific rationale behind this revolution in RCC treatment, we have reviewed the fundamental discoveries underlying the transition from old (cytokines) to new (ICIs) immunotherapies. We summarize the pivotal trials (CheckMate 025, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, IMmotion151) of checkpoint inhibitors for clear cell RCC in various treatment settings. With the availability of many different combination therapies and many more currently under investigation, clear cell RCC treatment is becoming more complex. Patient preferences, disease volumes, and adverse event profiles are essential in determining which option is the best for an individual patient. In the future, biomarkers currently under development could guide these treatment decisions.
Advanced Non–Clear Cell Kidney Cancer
Authors: Ornstein Moshe C. , Hutson Thomas E. 
Published: September 2020

AbstractNon–clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of RCC diagnoses. Although broadly labeled as “nccRCC,” they comprised a host of histologies that include papillary, chromophobe, unclassified, and others. Moreover, these histological variants are further subclassified on the basis of genomic profiling, thereby highlighting nccRCC to be anything but a homogenous cohort of RCC. The heterogeneity of nccRCC has proved challenging in developing therapeutics for this population. Although ccRCC therapeutic data have been commonly extrapolated for the treatment of nccRCC, the overall poor outcome of these patients highlights an unmet need. In an era of precision medicine, genomic analysis, and predictive biomarkers, novel approach to drug design and development is necessary to optimize treatment outcomes in nccRCC patients. Herein, we provide an overview of the nccRCC histologies, clinical trial data, and future opportunities for treatment options and development in nccRCC.
Economic Case for Scale-up of the WHO Surgical Safety Checklist at the National Level in Sub-Saharan Africa
Authors: White Michelle C. , Leather Andrew J. M. , Sevdalis Nick , Healey Andy 
Published: September 2020

Objectives:
To evaluate the economic case for nationwide scale-up of the World Health Organization (WHO) Surgical Safety Checklist using cost-effectiveness and benefit-cost analyses.

Background:
The Checklist improves surgical outcomes but the economic case for widespread use remains uncertain. For perioperative quality improvement interventions to compete successfully against other worthwhile health and nonhealth interventions for limited government resources they must demonstrate cost-effectiveness and positive societal benefit.

Methods:
Using data from 3 countries, we estimated the benefits as the total years of life lost (YLL) due to postoperative mortality averted over a 3 year period; converted the benefits to dollar equivalent values using estimates of the economic value of an additional year of life expectancy; estimated total implementation costs; and determined incremental cost-effectiveness ratio (ICER) and benefit-cost ratio (BCR). Costs are reported in international dollars using Word Bank purchasing power parity conversion factors at 2016 price-levels.

Results:
In Benin, Cameroon, and Madagascar ICERs were: $31, $138, and $118 per additional YLL averted; and BCRs were 62, 29, and 9, respectively. Sensitivity analysis demonstrated that the associated mortality reduction and increased usage due to Checklist scale-up would need to deviate approximately 10-fold from published data to change our main interpretations.

Conclusions:
According to WHO criteria, Checklist scale-up is considered “very cost-effective” and for every $ 1 spent the potential return on investment is $9 to $62. These results compare favorably with other health and nonhealth interventions and support the economic argument for investing in Checklist scale-up as part of a national strategy for improving surgical outcomes.
MRI-Diagnosed Tumor Deposits and EMVI Status Have Superior Prognostic Accuracy to Current Clinical TNM Staging in Rectal Cancer
Authors: Lord Amy C. , D’Souza Nigel , Shaw Annabel , Rokan Zena , Moran Brendan , Abulafi Muti , Rasheed Shahnawaz , Chandramohan Anuradha , Corr Alison , Chau Ian , Brown Gina 
Published: September 2020

Summary Background Data:
MRI assessment of rectal cancer not only assesses tumor depth and surgical resectability but also extramural disease which affects prognosis. We have observed that nonnodal tumor nodules (tumor deposits; mrTDs) have a distinct MRI appearance compared to lymph node metastases (mrLNMs).

Objective:
We aimed to assess whether mrTDs and mrLNMs have different prognostic implications and compare these to other known prognostic markers.

Methods:
This was a retrospective cohort study of 233 patients undergoing resection for rectal cancer from January 2007 to October 2015. Data were obtained from electronic records and MRIs blindly rereported. Survival was determined using Kaplan-Meier method. Prognostic markers were evaluated using Cox regression and competing risks analysis. Inter-observer agreement for mrTD was measured using Cohen Kappa.

Results:
On multivariable analysis, baseline mrTD/mrEMVI (extramural venous invasion) status was the only significant MRI factor for adverse survival [hazard ratio (HR) 2.36 (1.54–3.61] for overall survival, 2.37 (1.47–3.80) for disease-free survival (both P < 0.001), superseding T and N categories. mrLNMs were associated with good prognosis (HR 0.50 (0.31–0.80) P = 0.004 for overall survival, 0.60 (0.40–0.90) P = 0.014 for disease-free survival). On multivariable analysis, mrTDs/mrEMVI were strongly associated with distant recurrence (HR 6.53 (2.52–16.91) P ≤ 0.001) whereas T and N category were not. In a subgroup analysis of posttreatment MRIs in postchemoradiotherapy patients, mrTD/mrEMVI status was again the only significant prognostic factor; furthermore those who showed a good treatment response had a prognosis similar to patients who were negative at baseline. Inter-observer agreement for detection of mrTDs was k0.77 and k0.83.

Conclusions:
Current MRI staging predicting T and N status does not adequately predict prognosis. Positive mrTD/mrEMVI status has greater prognostic accuracy and would be superior in determining treatment and follow-up protocols. Chemoradiotherapy may be a highly effective treatment strategy in mrTD/mrEMVI positive patients.
Lipoprotein distribution of Apo CIII glycoforms in healthy men is linked with low TG and increased insulin sensitivity
Authors: Rodríguez Marina , Rehues Pere , Iranzo Víctor , Mora Jorge , Balsells Clara , Guardiola Montse , Ribalta Josep 
Published: September 2020

ABSTRACTGlycosylation of Apo CIII modulates its function in triglyceride metabolism, and some variants are associated with a protective or pro-atherogenic lipid profile. These associations have been studied in whole plasma Apo CIII proteoforms, but the proportion of Apo CIII proteoforms in individual lipoprotein fractions has been rarely evaluated. In the present study, we aim to measure the relative content of Apo CIII proteoforms in each lipoprotein fraction (VLDL, IDL, LDL and HDL) in a group of healthy subjects as a potential biomarker for triglyceride metabolism, cardiovascular risk and diabetes. Lipoprotein fractions were separated by differential ultracentrifugation of plasma samples. The relative concentrations of seven Apo CIII variants were measured by mass spectrometric immunoassay, and the complete lipoprotein profile was determined by NMR. The results showed high interindividual variability in the distribution of Apo CIII proteoforms across the study population but a uniform proportion in all lipoprotein fractions. Two Apo CIII variants, Apo CIII0band Apo CIII1d, were negatively correlated with plasma and VLDL triglycerides regardless of VLDL size and were associated with increased LDL size when transported in LDL particles. Apo CIII0balso showed a negative correlation with lipoprotein-insulin resistance score. Therefore, Apo CIII variants can be reliably measured in lipoprotein fractions, and our results suggest that Apo CIII0band Apo CIII1dhave a protective role in triglyceride metabolism and insulin resistance in healthy individuals.