bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eligibility Criteria and Endpoints in Metastatic Renal Cell Carcinoma Trials
Authors: Wong Sarah E. , Quinn David I. , Bjarnason Georg A. , North Scott A. , Sridhar Srikala S. 
Published: May 2020

Objectives:
Treatments for metastatic renal cell carcinoma (mRCC) are often compared across trials, but trial eligibility criteria and endpoints differ. In an effort to better align trials, the Definition for the Assessment of Time to event Endpoints in CANcer trials (DATECAN) project published recommendations in 2015 to be used in mRCC clinical trial design. We analyzed mRCC trial criteria to determine if DATECAN’s recommendations were followed.

Materials and Methods:
We compared eligibility criteria across 29 phase 3 mRCC trials conducted between 2003 and 2019. We then evaluated endpoints used in 10 phase 3 trials activated between 2015 and 2019 to determine their compliance with DATECAN’s recommendations.

Results:
Among the 29 trials, performance status, renal function, and disease characteristics differed in terms of requirements and measures used. In terms of endpoints, the 10 trials did not entirely follow DATECAN’s recommendations. In total, 7/10 trials’ primary endpoint was progression-free survival (PFS) as recommended; 4/9 trials used PFS as an endpoint but did not publish their definition of PFS, and the 5 that did, included “death from any cause” instead of DATECAN’s recommendation of “death from kidney cancer.”

Conclusions:
Key eligibility criteria were somewhat inconsistent across the phase 3 mRCC trials studied. Endpoints in the newer trials did not align with DATECAN’s recommendations. Not only is greater standardization needed to facilitate meta-analyses and cross-trial comparisons, but as evident from lack of adherence to DATECAN’s recommendations, greater promotion and adoption of recommendations are needed to better harmonize trial design.
A Preliminary Study on the Effect and Mechanism of Breviscapine for Improving Insulin Resistance in HepG2 Cells
Authors: Yan Fangyan , Feng Jibo , Li Weiping , Wu Li , Li Jinping 
Published: May 2020

Abstract:
Insulin resistance (IR) is known to be a critical factor, which can lead to the onset of type 2 diabetes. Traditional Chinese medicine (TCM) has special advantages in treating IR, but the active components and action mechanisms of most TCM remain unclear. Therefore, the elucidation of the potential mechanisms is a major challenge in TCM research. In the study, we tried to elucidate the potential pharmacological efficacy and mechanism of breviacapine for improving IR through network analysis and validate the possible biological target for its quality evaluation. We computationally recognized the active components, potential targets, and the targets closely related to IR by using integrative analysis based on network pharmacology approach. We also established the active components-targets network, protein interactions network and analyzing the biological functions and pathways of targets to evaluate the links between components and pharmacological actions to help explain the action mechanisms of breviscapine. Based on the network analysis, our experimental data preliminarily confirmed that breviscapine could improve IR in HepG2 cells, which may be associated with the dynamic regulation of the PTP1B. This study combined network pharmacology with partial experiment validation to clarify the underlying mechanism of breviscapine in improving IR and thus laid the experimental foundation for the depth exploration of its functional mechanism.
Emerging Dematiaceous and Hyaline Fungi Causing Keratitis in a Tertiary Care Centre From North India
Authors: Ghosh Anup , Kaur Harsimran , Gupta Amit , Singh Shreya , Rudramurthy Shivaprakash Mandya , Gupta Sunita , Chakrabarti Arunaloke 
Published: May 2020

Purpose:
To report rare dematiaceous and hyaline fungal pathogens causing fungal keratitis (FK) at our center and review the published literature in this field.

Methods:
In a retrospective review of FK cases from 2005 to 2011, a total of 14 rare pathogens causing isolated cases of FK of a total of 393 isolates were revived from our collection and reconfirmed by using molecular techniques. The in vitro antifungal susceptibility testing (AFST) was performed against a 6-antifungal drug panel by the CLSI microbroth-dilution method. We reviewed the literature on keratitis due to these rare fungi.

Results:
Two novel fungi, Alternaria tenuissima and Epicoccum nigrum, were reported in addition to 6 dematiaceous (black pigmented) fungi (Acrophialophora fusispora, Chaetomium globosum, Cladophialophora carionii, Nigrospora sphaerica, Papulaspora equi, and Scytalidium lignicola), 5 hyaline (colorless) fungi (Aspergillus tamarii, Fusarium chlamydosporum, Fusarium incarnatum, Fusarium lichenicola, and Fusarium sacchari), and one yeast (Trichosporon asahii). Amphotericin B had good in vitro activity (minimum inhibitory concentration [MIC] ≤1 μg/mL) against most dematiaceous fungi, but not hyaline fungi (MIC ≥1 μg/mL). Natamycin showed variable MIC, itraconazole and voriconazole had good in vitro activity, except in Fusarium species. Alternaria tenuissima and A. fusispora had a very high MIC (≥16 μg/mL) against echinocandins. Literature search revealed 27 FK cases due to F. lichenicola (n = 6), P. equi (n = 5), F. sacchari (n = 4), A. fusispora (n = 3), S. lignicola (n = 2), and others (n = 7), and more than 50% of these were reported from India.

Conclusions:
Plant fungal pathogens with variable antifungal susceptibility are an emerging cause of human keratitis with predominance of dematiaceous fungi. Identification and antifungal susceptibility testing are important for epidemiology and to optimize therapy and improve the patient outcome.
Risk factors for postlaser refractive surgery corneal ectasia
Authors: Jin Sierra X. , Dackowski Evan , Chuck Roy S. 
Published: May 2020

Purpose of review
To summarize newly reported and update previously known risk factors for post laser vision correction (LVC) corneal ectasia.

Recent findings
Advances in corneal topography and tomography have improved detection of preclinical ectasia-related changes. This has allowed for enhanced screening of surgical candidates. There are also known genetic predispositions for corneal ectasia, and recent genetic analyses have revealed various genes and inflammatory biomolecular markers related to corneal biomechanical integrity. Other models of risk assessment such as finite element biomechanical modeling and artificial intelligence tools have shown promise in detecting more subtle risk factors, such as those related to mechanical strain.

Summary
Risk factors for post-LVC corneal ectasia involve both surgery and patient-specific characteristics, such as topographic and tomographic abnormalities, younger age, thinner preoperative corneas, and residual stromal beds, high myopia, and higher percentage tissue altered. Preoperative risk stratification has helped to decrease the incidence of postoperative ectasia, a trend which will likely continue with advancements in analytic tools and better understanding of underlying genetic predispositions.
Characterization of Congenital Toxoplasmosis in Israel
Authors: Kahan Yaara , Avidar Michal , Gottesman Bat-Sheva , Riklis Irena , Dveyrin Zeev , Dalal Ilan , Meir Michal , Glikman Daniel , Bilavsky Efraim , Sherman Gilad , Shehadeh Shereen , Tasher Diana ,   for Israeli Congenital Toxoplasmosis Research Group
Published: May 2020

Background:
Congenital toxoplasmosis (CT) can cause significant neurologic manifestations and other untoward sequelae. Neither the current epidemiology nor the disease severity of CT in Israel is known.

Methods:
Records of CT were collected from the National Toxoplasmosis Reference Laboratory and from 15 medical centers across Israel between 2001 and 2017. Eligible case-patients were fetuses or infants <12 months of age at the time of diagnosis.

Results:
Of the 43 CT cases identified, 24 (55%) were in Jews and the remaining 19 cases were in patients of Arab (non-Bedouin) origin. The overall annual estimated rate of symptomatic CT was calculated as 0.55 per 100,000 live births. One or more severe clinical manifestations were reported in 12 (46%) of the 28 live-born infants and included cerebral calcifications (7 cases), chorioretinitis (4 cases), hydrocephalus (2 cases) and 1 case of death. Sensitivities of blood polymerase chain reaction (PCR), cerebrospinal fluid PCR and IgM antibody tests were 50% each. However, analyzing PCR samples from both sites, together with IgM testing, increased the sensitivity to 93%.

Conclusions:
The relative rate of severe manifestations was higher than in previous European reports. It is possible that the greater disease severity observed in Israel is in part due to the lack of systematic antenatal treatment and screening. Arab (non-Bedouin) infants are at higher risk for contracting CT. Performing serologic and PCR tests simultaneously is essential to improve CT diagnosis. This study demonstrates a need for an educational program to target high-risk populations.
Deoxyuracil in DNA in health and disease
Authors: Chakraborty Joydeep , Stover Patrick J. 
Published: May 2020

Purpose of review
Genome instability has long been implicated as a primary causal factor in cancer and diseases of aging. The genome is constantly under attack from extrinsic and intrinsic damaging agents. Uracil misincorporation in DNA and its repair is an intrinsic factor resulting in genomic instability and DNA mutations. Additionally, the presence of uracil in DNA can modify gene expression by interfering with promoter binding and transcription inhibition or upregulation of apoptotic proteins. In immune cells, uracil in DNA drives beneficial genomic diversity for antigen-driven immunity. This review addresses diseases that are linked to uracil accumulation in DNA, its causes, consequences, and the associated biomarkers of risk factors.

Recent findings
Elevated genomic uracil is associated with megaloblastic anemia, neural tube defects, and retroviral immunity. Current evidence supporting causal mechanisms and nutritional interventions that rescue impaired pathways associated with uracil accumulation in DNA are summarized in this review.

Summary
Nutritional deficiencies in B vitamins can cause uracil misincorporation into DNA leading to genome instability and associated diseases. Nutritional approaches to preventing uracil accumulation in DNA show some promise to address its associated diseases, but additional randomized controlled trials are needed.
Applying the original model for end-stage liver disease score rather than the model for end-stage liver disease-Na score for risk stratification prior to transjugular intrahepatic portosystemic shunt procedures
Authors: Lee Brian T. , Yang Alexander H. , Urban Seth , Kim Ki-Yoon , Ter-Oganesyan Ramon , Yuan Liyun , Han Hyosun H. , Khemichian Saro , Kahn Jeffrey A. , Kim Brian 
Published: May 2020

Objective
The model for end-stage liver disease (MELD) score can be used to predict survival of patients undergoing transjugular intrahepatic portosystemic shunt procedures (TIPS). The effect of hyponatremia on survival resulted in the development of the MELD-Na score. The aim of this study is to compare the prognostic value of MELD and MELD-Na scores in predicting post-TIPS outcomes.

Methods
A retrospective chart review was performed on consecutive patients with cirrhosis who underwent TIPS placement from 2012 to 2017. Indications for TIPS were either refractory ascites or variceal bleeding. Primary outcomes analyzed were death or liver transplantation. Follow-up data were censored at 1 year.

Results
Eighty-three patients underwent TIPS. There was no difference in MELD or MELD-Na score between indication groups. However, the delta MELD (MELD-Na subtracted by MELD score) was higher in those with refractory ascites. There was no difference in outcomes of death or liver transplantation between the MELD and MELD-Na at 1 year. (area under the curve 0.79 vs 0.72, respectively, P = 0.119). In patients with a MELD-Na greater than 18, higher delta MELD was protective (hazard ratio 0.74, P < 0.05).

Conclusions
There was no prognostic difference using either score despite a higher delta MELD in those with refractory ascites. The decision to pursue TIPS should utilize the original MELD score, as the MELD-Na score alone may exclude patients with refractory ascites who may benefit from TIPS.
Uric acid stone disease: lessons from recent human physiologic studies
Authors: Tran Triet Vincent M. , Maalouf Naim M. 
Published: May 2020

Purpose of review
An overly acidic urine resulting in supersaturation of urine with respect to uric acid is the major mechanism responsible for uric acid nephrolithiasis. The present review summarizes findings from recent human physiologic studies examining the pathophysiology and reversibility of low urine pH in uric acid stone formers.

Recent findings
Epidemiologic and metabolic studies have confirmed an increase in the prevalence of uric acid nephrolithiasis and reported its association with several features of the metabolic syndrome including dyslipidemia, hyperglycemia, hepatic steatosis, and greater visceral adiposity. Physiologic studies in uric acid stone formers have identified diet-independent excessive net acid excretion and concomitant reduction in urinary buffering from impaired renal ammoniagenesis as the two causes underlying the greater aciduria. Administration of the insulin sensitizer pioglitazone to uric acid stone formers reduced the acid load presented to the kidney and enhanced ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH.

Summary
Recent human physiologic studies have identified greater acid excretion and reduced urinary buffering by ammonia as two culprits of aciduria in uric acid nephrolithiasis that can be reversed by pioglitazone, raising new questions regarding the origin of the aciduria and opening the door to pathophysiology-based treatment of uric acid stones.
Lessons from rodent gastric bypass model of enteric hyperoxaluria
Authors: Kwenda Elizabeth P. , Rabley Andrew K. , Canales Benjamin K. 
Published: May 2020

Purpose of review
The aim of the article is to review studies on bone health and oxalate metabolism/therapeutics in the obese rodent model of Roux-en-Y gastric bypass (RYGB) and examine pathways to decrease procedural morbidity.

Recent findings
Compared with controls, RYGB rodents have up to 40-fold more fat in their stool (steatorrhea) which positively correlates to increased urinary oxalate. These unabsorbed intestinal fatty acids bind calcium and prevent gut calcium oxalate formation, increasing soluble luminal oxalate availability and absorption (enteric hyperoxaluria). When intraluminal fecal fat exceeded about 175 mg/24 h in our model, more paracellular and transcellular oxalate transport across the distal colon occurred. Increasing dietary calcium and colonization with Oxalobacter formigenes reduced hyperoxaluria, whereas vitamin B6 supplementation did not. RYGB animals, when severely calcium deficient, had bone mineral density loss that could not be rescued with vitamin D supplementation.

Summary
The findings of hyperoxaluria, steatorrhea, and decreased bone mineral density are seen in both human and rodent RYGB. Our model suggests that a low-fat, low-oxalate diet combined with calcium supplementation can decrease urinary oxalate and improve skeletal bone health. Our model is a useful tool to study renal and bone RYGB effects. Studies of longer duration are required to further evaluate mechanisms of disease and durability of therapeutics.
Sense of Coherence and Mortality: A Systematic Review and Meta-Analysis
Authors: Piiroinen Ilkka , Tuomainen Tomi-Pekka , Tolmunen Tommi , Kauhanen Jussi , Kurl Sudhir , Nilsen Charlotta , Suominen Sakari , Välimäki Tarja , Voutilainen Ari 
Published: May 2020

ABSTRACT

Objective
The aim of the study was to investigate the association between sense of coherence (SOC) and all-cause mortality in the general adult population.

Methods
We conducted a systematic review and meta-analysis of prospective cohort studies. We searched eight electronic bibliographic databases for eligible studies. A random effects model and the restricted maximum likelihood method were used to calculate the pooled effect size.

Results
Eight studies were eligible for the meta-analysis. The studies included 48,138 participants, of whom 5307 died during a median follow-up of 14.1 years (range, 8–29.5 years). Their age ranged from 20 to 80 years, and 53% of them were men. In the meta-analysis model of crude values, the risk of all-cause mortality for individuals with a weak SOC (lowest tertile) was 1.30 (95% confidence interval [CI] = 1.09–1.55, p = .003, I
2 = 78.84%) compared with individuals with a strong SOC (highest tertile). In the model adjusted for age, the risk remained almost the same (risk ratio = 1.26, 95% CI = 1.15–1.38, p < .001, I
2 = 69.59%). In the model adjusted for several other risk factors for mortality, the risk was still 1.17 (95% CI = 1.07–1.27, p < .001, I
2 = 57.85%).

Conclusions
This meta-analysis shows that a weak SOC is associated with an increased risk of all-cause mortality in the general adult population. Future studies are needed to further develop assessment tools for SOC with good psychometric properties and to determine the disease processes that mediate the association of SOC with mortality.
Neurological Emergencies in Patients Hospitalized With Nonneurological Illness
Authors: Jeon Sang-Beom , Lee Han-Bin , Koo Yong Seo , Lee Hyunjo , Lee Jung Hwa , Park Bobin , Choi Soh Hyun , Jeong Suyeon , Chang Jun Young , Hong Sang-Bum , Lim Chae-Man , Lee Sang-Ahm 
Published: May 2020

Objective
We aimed to present neurological profiles and clinical outcomes of patients with acute neurological symptoms, which developed during hospitalization with nonneurological illness.

Methods
We organized the neurological alert team (NAT), a neurological rapid response team, to manage in-hospital neurological emergencies. In this registry-based study, we analyzed the clinical profiles and outcomes of patients who were consulted to the NAT. We also compared the 3-month mortality of patients with acute neurological symptoms with that of patients without acute neurological symptoms.

Results
Among the 85,507 adult patients, 591 (0.7%) activated the NAT. The most common reason for NAT activation was stroke symptoms (37.6%), followed by seizures (28.6%), and sudden unresponsiveness (24.0%). The most common diagnosis by the NAT neurologists was metabolic encephalopathy (45.5%), followed by ischemic stroke (21.2%) and seizures or status epilepticus (21.0%). Patients with NAT activation had high rates in mortality before hospital discharge (22.5%) and at 3 months (34.7%), transfer to intensive care units (39.6%), and length of hospital stay (43.1 ± 57.1 days). They also had high prevalence of poor functional status (78.1%) and recurrence of neurological symptoms at 3 months (27.2%). In a Cox proportional hazards model, patients with in-hospital neurological emergencies had a hazard ratio of 13.2 in terms of mortality at 3 months (95% confidence interval, 11.5–15.3; P < 0.001).

Conclusions
Occurrence of acute neurological symptoms during hospital admission was associated with high rate of mortality and poor functional status. These results call for enhanced awareness and hospital-wide strategies for managing in-hospital neurological emergencies.
Sustaining the Gains: A 7-Year Follow-Through of a Hospital-Wide Patient Safety Improvement Project on Hospital-Wide Adverse Event Outcomes and Patient Safety Culture
Authors: Sim Ming Ann , Ti Lian Kah , Mujumdar Sandhya , Chew Sophia Tsong Huey , Penanueva Donna Joy B. , Kumar Bhuvaneshwari Mohan , Ang Sophia Bee Leng 
Published: May 2020

Objectives
Adverse events (AEs) remain a challenge in tertiary healthcare with incidence rates of 4% to 14%, where half are potentially preventable. Reported patient safety strategies rarely involve changing the practices of an entire academic institution and maintaining sustainability. We hypothesize that implementing an effective patient safety strategy (PSS) improves hospital-wide AE rates, cost avoidance, and patient safety culture.

Methods
A 3-stage hospital-wide PSS was implemented from 2012 to 2016, involving a top-down, bottom-up approach in a 1171-bed academic institution. The primary outcome was the incidence, preventability, and severity of hospital-wide AEs, calculated through the Institute of Healthcare Improvement, Global Trigger Tool method (incidence), National Coordinating Council for Medication Error Reporting and Prevention tool (severity), and a preventability decision algorithm (preventability). Secondary outcomes include hospital-wide cost savings and patient safety climate survey results.

Results
A total of 15,120 random chart reviews were performed across 430,868 admissions from 2012 to 2018. Overall, AE rates decreased from 11.6% to 5.4% (R
2 = 0.71, P = 0.017). The incidence of preventable AEs declined from 5.7% to 2.0% (R
2 = 0.80, P = 0.006). The severity of AEs reduced, with the proportion of category G, H, and I AEs decreasing from 8.4% (2012) to 2.6% (2018). A total of 15,960 hospital-wide patient safety climate surveys were administered from 2011 to 2016, demonstrating an improvement in hospital-wide percentage positive patient safety grade from 46.5% pre-PSS to 58.3% post-PSS implementation. This was accompanied by an 82% increase in voluntary event reporting, and cost savings of 20,600 bed-days and U.S. $29.2 million upon completion of stage 3 (2012–2016).

Conclusions
The hospital-wide PSS resulted in significant improvements in the incidence and severity of AEs, healthcare cost savings, and patient safety culture, demonstrating sustainability for 7 years.
Modification of Septal Window to Improve Angled Endoscopic View for Beyond Maxillary Sinus
Authors: Kim Boo-Young , Jeon Jeongbee , Lee Seoungmin 
Published: May 2020

Abstract
Many endoscopic surgeons have showed various techniques on septal window using endoscopic tools. However, each technique has its own merits and faults. In this study, the authors introduce simple and time saving endoscopic window technique by avoiding intranasal suture resulting from simple incision line. The procedure to make septal window is to improve an angled endoscopic view for beyond lateral wall of maxillary sinus with septum preservation. To date, this approach has shown no major or concerning complications and has also showed favorable disease control outcomes while maintaining nasal airway patency and functionality through our experience.