bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-Drug Combinations Can Enhance Toxicity as Shown by Monocyte-Derived Hepatocyte-like Cells From Patients With Idiosyncratic Drug-Induced Liver Injury
Authors: Benesic Andreas , Jalal Kowcee , Gerbes Alexander L
Published: August 2019

Drug-induced liver injury (DILI) is a major cause for acute liver failure and regulatory actions on novel drugs. Individual patient characteristics are the main determinant of idiosyncratic DILI, making idiosyncratic DILI (iDILI) one of the most challenging diagnoses in hepatology. Individual drug-drug interactions might play a role in iDILI. However, the current approaches to iDILI diagnosis are focused on single drugs as causative agents. For the present analysis, 48 patients with acute liver injury who took 2 drugs and who were diagnosed as iDILI were investigated. A novel in vitro test was employed using monocyte-derived hepatocyte-like cells (MH cells) generated from these patients. iDILI diagnosis and causality were evaluated using clinical causality assessment supported by Roussel-Uclaf Causality Assessment Method. In 13 of these 48 patients (27%), combinations of drugs increased toxicity in the MH test when compared with the single drugs. Interestingly, whereas in 24 cases (50%) drug-drug combinations did not enhance toxicity, in 11 cases (23%) only the combinations caused toxicity. The incidence of severe cases fulfilling Hy’s law was higher in patients with positive interactions (57% vs 43%; p = .04), with acute liver failure occurring in 40% versus 8% (p = .01). The most common drug combinations causing increased toxicity were amoxicillin/clavulanate (8 of 9 cases) and diclofenac in combination with steroid hormones (4 of 9 cases). Drug-drug interactions may influence the incidence and/or the severity of idiosyncratic DILI. MH cell testing can identify relevant drug-drug interactions. The data generated by this approach may improve patient safety.

Study identifier

ClinicalTrials.gov NCT 02353455.
The earliest mustelid in North America
Authors: Paterson Ryan , Samuels Joshua X , Rybczynski Natalia , Ryan Michael J , Maddin Hillary C
Published: August 2019

Until now, the pre-Miocene fossil record of mustelids in North America has been restricted to specimens attributable to oligobunine taxa and isolated remains tentatively allocated to the genus Plesictis. In the present study, we report on a nearly complete cranium and a referred dentary of a new genus and species of mustelid. The specimens were recovered from the Turtle Cove and Kimberly Members of the John Day Formation, Oregon, USA.

These excellently preserved specimens more confidently confirm the presence of mustelids in the Early and Late Oligocene (Early and Late Arikareean) of North America. Like the holotype specimen of ‘Plesictis’ julieni, the new species lacks an alisphenoid canal and a postprotocrista on the M1 (synapomorphies of Mustelidae), but retains a dorsally deep suprameatal fossa (a feature occasionally suggested to be unique to Procyonidae). Phylogenetic analyses, applying parsimony and Bayesian inference to combined molecular (five genes totalling 5490 bp) and morphological data, recover this new species of mustelid as sister-species to ‘Plesictis’ julieni. The results of these analyses reveal that the new genus is a close relative of other species of Plesictis and several taxa traditionally allied with Oligobuninae, thereby rendering Oligobuninae paraphyletic. We further discuss the significance of the relatively small size of this new mustelid as it relates to predictions based on increased aridification of the palaeoclimate and the expansion of open habitats in the Oligocene.
Systematics and natural history of mountain reed snakes (genus Macrocalamus; Calamariinae)
Authors: Quah Evan S H , Anuar Shahrul , Grismer Lee L , Wood Perry L , Mohd Nor Siti Azizah
Published: August 2019

The first molecular phylogeny for mountain reed snakes (genus Macrocalamus) based on the mitochondrial gene cytochrome b is not entirely consistent with the previous taxonomy based on morphology and colour pattern. Macrocalamus chanardi is shown to be a species complex composed of three different allopatric lineages distributed across different upland areas in Peninsular Malaysia that are morphologically conserved but genetically distinct. A new and morphologically different species, Macrocalamus emas sp. nov., is described from the Cameron Highlands, Pahang, Peninsular Malaysia. It occurs in sympatry with four other ecologically equivalent species of Macrocalamus and one other species of Collorhabdium. The phylogeographical pattern of sympatric genetically distinct species of Macrocalamus endemic to upland areas is attributed to the fossorial nature of these snakes and the montane forest expansion and retraction resulting from cyclical, glacioeustatically driven climatic processes that have reconstructed the geography of Sundaland continuously over the last 25 Myr.
Association Between the Severity of Dysphagia and Various Parameters of the Cervical Spine; Videofluoroscopic Analysis in Neutral and Retraction Position of the Normal Volunteers
Authors: Hong Jae Taek , Oh Joo Seon , Lee Dong Hoon , Lim Seong Hoon , Kim Joon-Sung
Published: August 2019

Study Design.

Videoflurographic swallowing study in asymptomatic volunteers.

Objective.

The purpose of this study was to investigate the relationship between the severity of dysphagia and various parameters of the subjects.

Summary of Background Data.

Occipitocervical fixation is associated with several potential complications. Malalignment of craniovertebral junction and associated dysphagia have been well described in the literature. However, there has been little attention given to investigate the association between the degree of swallowing dysfunction and various patient's parameters.

Methods.

Thirty-nine healthy asymptomatic volunteers, 18 males and 21 females, were enrolled in this study. Based on videofluorographic swallowing study (VFSS), two scoring systems of swallowing dysfunction (dysphagia rating scale [DRS], dysphagia outcome and severity scale [DOSS]) were measured in neutral and retraction position. Multiple linear regression analysis was performed to evaluate the relationship between the degree of swallowing dysfunction and various factors of the subjects such as radiological and clinical parameters.

Results.

There was statistically significant correlation between DRS and DOSS (r = −0.354, P 
< 0.05). Multiple regression analysis showed that there was a significant association of the dysphagia severity (DRS and DOSS) with the percentile change of the narrowest oropharyngeal diameter (OD) (%dn OD) (r = 0.121, P < 0.01 and r = 0.020, P < 0.01, respectively). Percentile change of OD (neutral and retraction position) was positively associated with the difference of C0–2 angle (r = 1.676, P < 0.01). None of the other variables such as age, sex, C0–1 angle, C1–2 angle, and C2–7 angle were significantly associated with the degree of dysphagia or %dn OD.

Conclusion.

This study demonstrated that the severity of dysphagia is significantly associated with the percentile change of OD and the C0–2 angle has considerable effect on the OD after O-C fusion. Therefore, C0–2 angle could be the most critical radiological parameter not only for predicting the stricture of oropharyngeal space but also for preventing postoperative dysphagia.

Level of Evidence: 4
The Effect of Tobacco Smoking on Adverse Events Following Adult Complex Deformity Surgery
Authors: Wilson Jamie R.F. , Jiang Fan , Badhiwala Jetan H. , Shaffrey Christopher I. , Carreon Leah Y. , Cheung Kenneth M.C. , Dahl Benny T. , Ames Christopher P. , Boachie-Adjei Oheneba , Dekutoski Mark B. , Lewis Stephen J. , Matsuyama Yukihiro , Mehdian Hossein , Pellisé Ferran , Qiu Yong , Schwab Frank J. , Lenke Lawrence G. , Fehlings Michael G.
Published: August 2019

Study Design.

Post-hocanalysis of a prospective, multicenter cohort study.

Objective.

To analyze the impact of smoking on rates of postoperative adverse events (AEs) in patients undergoing high-risk adult spine deformity surgery.

Summary of Background Data.

Smoking is a known predictor of medical complications after adult deformity surgery, but the effect on complications, implant failure and other AEs has not been adequately described in prospective studies.

Methods.

Twenty-six patients with a history of current smoking were identified out of the 272 patients enrolled in the SCOLI-RISK-1 study who underwent complex adult spinal deformity surgery at 15 centers, with 2-year follow-up. The outcomes and incidence of AEs in these patients were compared to the nonsmoking cohort (n = 244) using univariate analysis, with additional multivariate regression to adjust for the effect of patient demographics, complexity of surgery, and other confounders.

Results.

The number of levels and complexity of surgery in both cohorts were comparable. In the univariate analysis, the rates of implant failure were almost double (odds ratio 2.28 [0.75–6.18]) in smoking group (n = 7; 26.9%)) that observed in the nonsmoking group (n = 34; 13.9%), but this was not statistically significant (P = 0.088). Surgery-related excessive bleeding (>4 L) was significantly higher in the smoking group (n = 5vs. n = 9; 19.2%vs. 3.7%; OR 6.22[1.48 – 22.75];P = 0.006). Wound infection rates and respiratory complications were similar in both groups. In the multivariate analysis, the smoking group demonstrated a higher incidence of any surgery-related AEs over 2 years (n = 13vs. n = 95; 50.0%vs. 38.9%; OR 2.12 [0.88–5.09]) (P = 0.094).

Conclusion.

In this secondary analysis of patients from the SCOLI-RISK-1 study, a history of smoking significantly increased the risk of excessive intraoperative bleeding and nonsignificantly increased the rate of implant failure or surgery-related AEs over 2 years. The authors therefore advocate a smoking cessation program in patients undergoing complex adult spine deformity surgery.

Level of Evidence:2
Five-year Reoperation Rates and Causes for Reoperations Following Lumbar Microendoscopic Discectomy and Decompression
Authors: Aihara Takato , Endo Kenji , Sawaji Yasunobu , Suzuki Hidekazu , Urushibara Makoto , Kojima Atsushi , Matsuoka Yuji , Takamatsu Taichiro , Murata Kazuma , Kusakabe Takuya , Maekawa Asato , Yamamoto Kengo
Published: August 2019

Study Design.

Retrospective study of prospectively collected outcome data.

Objective.

The aim of this study was to investigate reoperation cases and determine whether or not the experience period of a single surgeon was associated with the causes of reoperations following lumbar microendoscopic discectomy for disc herniation (MEDH) and microendoscopic decompression for spinal stenosis (MEDS).

Summary of Background Data.

There have been few studies that investigated reoperation cases following MEDH and MEDS.

Methods.

Between June 2005 (first experience of MEDH) and September 2013, the same surgeon had been using MEDH and/or MEDS on 441 consecutive patients. The follow-up rate was 89.3%. The causes and rates of reoperations (RORs) were determined at 5 years after the initial operations. We also investigated the experience period of a single surgeon (EPS, interval between June 2005 and initial operation: median, 37 months).

Results.

The 5-year reoperation rate for all patients combined was 12.4% (49/394). The main causes for reoperations were recurrence of disc herniation (ROR, 7.01%) and increase of postoperative spondylolisthesis and/or instability (ROR, 9/394 = 2.28%); two of the nine cases were caused by excessive decompression, and the EPSs were 11 and 16 months. The other causes for reoperations were postoperative epidural hematoma (ROR, 0.76%; median EPS, 20 months), insufficient decompression (ROR, 0.25%; EPS, 17 months), and residual segmental scoliosis (ROR, 7.69%); two segmental scoliosis cases did not provide relief from sciatica, and therefore L4/5 transforaminal interbody fusions were performed.

Conclusion.

Postoperative epidural hematoma and excessive or insufficient decompression were often observed in the initial series of patients as the causes for reoperations. We think that it is important to be aware of and prevent such potential problems in any initial series of patients, as there are limitations to any surgical indications for the use of microendoscopic decompression for degenerative segmental scoliosis because of original traction and/or kinking of nerve roots.

Level of Evidence: 4
The effects of blood pressure components on cardiovascular events in a Korean hypertensive population according to age and sex
Authors: Kang Eungyu , Lee Seulbi , Ha Eunhee , Oh Hyung Jung , Ryu Dong-Ryeol
Published: August 2019

There is no known study regarding the usefulness of each blood pressure (BP) component based on stratification by age and sex for predicting cardiovascular (CV) events among hypertensive populations without chronic kidney disease (CKD) or diabetes mellitus (DM). This study was performed to investigate the association of BP components and CV events in a Korean hypertensive population according to age and sex. A total of 22,853 Korean hypertensive participants without CKD and DM were stratified into six groups according to age [40–49, 50–59, and 60 years or older] and sex. In each group, multivariate Cox proportional regression analysis was performed to reveal the associations of BP components [systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP)] with CV events. The increase in PP and decrease in DBP were significantly associated with increase of CV events in males, but neither BP component was significantly associated with risk of CV events in females. When subjects were stratified by age and sex, an increase of SBP or PP was significantly related to the increased risk of CV events in 40's male group, and only the elevation of PP was significantly associated with increase in incidence of CV events in 50's male group, while a decrease in DBP was significantly associated with increased risk of CV events in older male group. In addition, there were no the significant associations with the incidence of CV events in MAP, after stratification according to age and sex. In conclusion, this study suggests that, in hypertensive populations, BP management may need to be performed after full consideration of age and sex.
Hospitalization costs of treating colorectal cancer in China
Authors: Yuan Gao-Le , Liang Li-Zhong , Zhang Zhong-Fang , Liang Qi-Lian , Huang Zhen-Yi , Zhang Hui-Jie , Cheng Shao-Ang , Peng Xiao-Xia
Published: August 2019

Background:

The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China.

Methods:

Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank–sum tests (for 2 groups) and the Kruskal–Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer.

Results:

The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ± 13.28 years; male: 59.46%; mean age: 61.80 ± 13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from < 1190.94 to < 1382.50). The mean length of hospital stay was statistically significant difference was found for sexes (P = .039) and insurance status (P < .001). The mean hospitalization costs were < 16,279.58. Mean hospitalization costs were different among the UEBMI, the URBMI and the Unspecified (< 17,114.58, < 15,555.05, and < 17,735.30, respectively; P < .001).

Conclusion:

The study showed that hospitalization costs increase were associated with a small decreasing length of hospital stay and increasing per-day hospitalization costs. Moreover, the proportion of the hospitalization costs reimbursed by insurances increased. For inpatients with UEBMI, it possibly lead to over treatment and the medical expense rise which result in medical resources waste and significant society costs. The rising hospitalization costs may lead to a remarkably increased financial burden in the future in China.
Tubercular hemoptysis in a young liver transplanted patient
Authors: Di Dato Fabiola , Nunziata Francesco , Rosa Margherita , Iorio Raffaele , Spagnuolo Maria Immacolata
Published: August 2019

Rationale:

Liver transplanted patients have excellent survival rates, but infectious complications are a major cause of morbidity and mortality. Diagnosis and treatment of tuberculosis (TB) in liver recipients are very challenging. Specific recommendations for anti-TB treatment in liver transplanted patients are lacking.

Patient concerns and diagnosis:

A 22-year-old male liver transplanted patient because of biliary atresia showed unexpected acute hemoptysis while he was on immunosuppressive therapy with tacrolimus and mycophenolate mofetil. Computed tomography (CT) identified a pulmonary arteriovenous malformation (PAVM) successfully treated with endovascular embolization. A post-embolization thoracic CT revealed pulmonary cavitation and miliary pattern suggesting pulmonary TB causing PAVM. TB diagnosis was confirmed by microbiological assays and genetic amplification techniques.

Intervention:

Anti-TB 4-drug regimen was started. Following the beginning of treatment, liver enzymes increased. In order to clarify if liver cytolysis was due to hepatotoxicity or hepatic rejection linked to the reduction of immunosuppression or a worsening of pre-existing graft hepatitis, a liver biopsy was performed. A mild graft rejection was found so that tacrolimus doses were increased despite the risk of tubercular dissemination.

Outcome:

The patient completed anti-TB therapy in 8 months with resolution of TB disease and stable liver disease.

Lessons:

TB management in liver transplanted patients is challenging and needs to be individualized especially if chronic graft hepatitis is present.
Nutrition management of congenital glucose–galactose malabsorption
Authors: Ma Ming , Long Qi , Chen Fei , Zhang Ting , Lu Mengshan , Wang Weiyan , Chen Lihua
Published: August 2019

Rationale:

Congenital glucose–galactose malabsorption (CGGM) is a rare, autosomal recessive, hereditary disease that usuallypresents in newborns. CGGM manifests as severe diarrhea, hyperosmolar dehydration, and malnutrition. It does not respond to routine treatment and often is life-threatening.

Patient concerns:

We described a Chinese infant girl with refractory diarrhea, who suffered from severe dehydration and malnutrition even if with fluid replacement therapy and fed with several special formulas.

Diagnoses:

The genetic analysis identified CGGM with SLC5A1 mutations. c.1436G > C (p.R479T) was a novel mutation.

Interventions:

The patient was managed by free-glucose and galactose formula, and then special low-carbohydrate dietary therapy.

Outcomes:

The patient improved immediately after starting a free-glucose and galactose formula, and kept healthy with special low-carbohydrate diet. She had been followed up with nutritional management for 20 months.

Lessons:

This report highlights the importance of differential diagnosis of congenital diarrhea and enteropathies. For CGGM, free-glucose and galactose milk powder was the most effective treatment. Low-carbohydrate diet gradually introduced was still a great challenge that requires continuing guidance from child nutritionists and dietitians. Long-term nutrition management was extremely important to ensure the normal growth and development of children.
Adjuvant treatment of coronary heart disease angina pectoris with Chinese patent medicine
Authors: Liu Yijia , Li Zhu , Shen Dandan , Song Yanqi , Huang Mengnan , Xue Xiaoxue , Xie Jing , Jiao Ziyi , Gao Shuming , Xu Yilan , Gao Shan , Wang Xianliang , Xu Qiang , Gao Sheng , Li Chunjie , Li Lin , Niu Kaijun , Yu Chunquan
Published: August 2019

Background:

Patients with coronary heart disease (CHD) angina pectoris are in critical condition, which can cause sudden death, myocardial infarction, and other adverse events, and bring serious burden to families and society. Timely treatment should be given to improve the condition. Western medicine treatment of angina pectoris failed to meet the demand of angina symptom control.

Objective:

It is hoped that the research method with higher evidential value will be adopted to compare the short-term, medium-term, and long-term effects of Chinese patent medicine combined with conventional western medicine and conventional western medicine alone in the treatment of CHD angina pectoris, so as to tap the clinical efficacy advantages of traditional Chinese medicine (TCM) and provide reliable data support for its clinical application.

Methods:

A prospective cohort study was conducted among patients with CHD angina pectoris who were treated with oral Chinese patent medicine and conventional western medicine. The patients were divided into exposed group and nonexposed group according to whether or not the patients with CHD angina pectoris were treated with Chinese patent medicine. The exposed group was treated with TCM combined with conventional western medicine, while the nonexposed group was treated with conventional western medicine alone. Patients need to be hospitalized for 2 weeks as the introduction period and whether to enter the group is determined according to the treatment and medication conditions of the patients. The follow-up time points were 0th, 4th, 12th, 24th, and 48th weeks. The main events and secondary events were used as the evaluation criteria for clinical efficacy of CHD angina pectoris. In the experimental study, we will use strict indicators to detect standard operation procedure for multinomics and bacterial flora detection.

Conclusion:

This study will provide evidence for the clinical efficacy advantages of Chinese patent medicine and reliable support for its clinical application through test data.
Recurrent fever of unknown fungal infection in a low-risk patient
Authors: Guo Tang-meng , Ye Yu , Huang Li-li , Cheng Bei
Published: August 2019

Rationale:

Fungal infectious disease does not usually occur in low-risk patients. Clinicians tend to ignore the role of fungi in the fevers of low-risk patients. If there is not timely control of fungal infections and associated fever, the disease will continue to worsen, resulting in physical dysfunction or death.

Patient concerns:

Recurrent fever continued for 1 month in a young adult.

Diagnoses and interventions:

Non-albicans Candida (NAC) species probably was the main pathogen in this case based on the resolution of fever after capsofungin administration.

Outcomes:

The fever and the associated indicators, including white blood cell count, C-reaction protein, erythrocyte sedimentation rate, and BDG levels, showed improvement quickly. The patient left the hospital successfully after 18 days of caspofungin treatment. There was no recurrent fever at a follow-up of 1 year.

Lessons:

Clinicians should be aware that the incidence of fungal infection is increasing in low-risk patients. The BDG assay is still an effective tool used to diagnose invasive fungal diseases. Caspofungin is an effective drug for the treatment of some unknown fungal infections.
Development of a combined CMV-UL97 C592F and CMV-UL54 T503I resistance mutation during ganciclovir treatment in a kidney transplant recipient
Authors: Karrasch Matthias , Michel Detlef , Schneider Sibylle , Baier Michael , Busch Martin
Published: August 2019

In CMV high-risk kidney transplant recipients (KTR), recommended antiviral human cytomegalovirus (CMV) treatment can lead to nephrotoxicity and antiviral resistance. In this case report, we report the development of a combined CMV-UL97 C592F and CMV UL54 T503I resistance mutation in a high-risk KTR most probably linked to the previous treatment with valganciclovir (valGCV) and ganciclovir (GCV). Routine CMV screening, in addition with testing of CMV immunity and applied stewardship programs for ganciclovir might have been helpful in preventing the development of these mutations in this patient.
Rosai-Dorfman Disease of the Digestive System—Beware Vasculopathy
Authors: Alruwaii Zainab I. , Zhang Yang , Larman Tatianna , Miller James A. , Montgomery Elizabeth A.
Published: August 2019

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferation that occurs in nodal and extranodal sites. Rare examples of the disease involving the digestive system have been described. To characterize the digestive tract manifestations of this disease, 12 specimens from 11 patients with extranodal RDD affecting the digestive organs were analyzed. Hematoxylin and eosin sections and available immunohistochemical stains were reviewed, and the clinical information was obtained from patients’ electronic or submitted records. Eight patients were female and 3 male (median age, 65 y; range, 17 to 76 y). Abdominal pain was the most frequent symptom. Six patients had an associated immunologic or malignant disease. Nine lesions arose in the gastrointestinal tract (1 involving the appendix, 2 right colon, 6 left colon), 2 in the pancreas, and 1 in the liver. Two patients had the coexistent nodal disease, and 1 had bone and soft-tissue involvement. The lesions were generally composed of polygonal to spindle-shaped histiocytes with eosinophilic to clear cytoplasm admixed with lymphoplasmacytic cells. The inflammatory cells formed lymphoid aggregates in 7 cases and included focally scattered or small collections of neutrophils in 6 cases. Fibrosis was variable, and 4 cases had a storiform pattern. Vasculopathy in the form of a thickened capillary wall, medium-sized arterial wall infiltration by lesional and inflammatory cells and phlebitis was seen in 10, 5, and 2 cases, respectively. All cases were reactive for S100-protein. Of the 5 patients with follow-up, 1 developed immunoglobulin A nephropathy and died of renal failure.
Is Disruptive Behavior Inherent to the Surgeon or the Environment? Analysis of 314 Events at a Single Academic Medical Center
Authors: Heslin Martin J. , Singletary Brandon A. , Benos Kaitlin C. , Lee Laura Read , Fry Charles , Lindeman Brenessa
Published: August 2019

Objective:

In 2009, the Joint Commission mandated a process to manage disruptive behavior, as evidence suggests it undermines a culture of safety. This process often reviews only the reporter's side of the story as the truth. In this study, we compared both reporter account (RA) and involved party (IP) responses to determine if disruptive behavior was inherent to the surgeon or the hospital environment and its relationship to patient safety.

Methods:

From 1/1/2015 through 12/31/2017, we prospectively recorded the RA and the IP response. This resulted in 314 reports involving 204 IPs. Four reviewers scored issues, interactions, modifiable stressors, and patient safety. Logistic regression determined factors associated with patient harm. Significance defined as P < 0.05.

Results:

Surgical, medical, and other specialties were IPs 43%, 35%, and 22%, respectively; 73% had only one event. High-intensity environments (OR, ICU, etc.) made up 56% of the total. Perceived unprofessional or lack of communication was present in 70% and 44% of events. A significant direct relationship existed between the stress of the clinical situation and the egregiousness of the behavior (P < 0.0001). Logistic regression revealed that unclear hospital policies, the IP being a surgeon, and urgent competing responsibilities were associated with potential patient harm (P < 0.05).

Conclusions:

Unclear policies and urgent competing responsibilities in the surgical environment create stress, leading to conflict. Single events for the majority suggest the environment as the primary contributor. Tactics to improve stressful environments and clearly communicated policies may be more effective and sustainable than individually targeted interventions in enhancing patient safety.
Fluctuating asymmetry and feather growth bars as biomarkers to assess the habitat quality of shade coffee farming for avian diversity conservation
Authors: Gebremichael Gelaye , Tsegaye Diress , Bunnefeld Nils , Zinner Dietmar , Atickem Anagaw
Published: August 2019

Shade coffee farming has been promoted as a means of combining sustainable coffee production and biodiversity conservation. Supporting this idea, similar levels of diversity and abundance of birds have been found in shade coffee and natural forests. However, diversity and abundance are not always good indicators of habitat quality because there may be a lag before population effects are observed following habitat conversion. Therefore, other indicators of habitat quality should be tested. In this paper, we investigate the use of two biomarkers: fluctuating asymmetry (FA) of tarsus length and rectrix mass, and feather growth bars (average growth bar width) to characterize the habitat quality of shade coffee and natural forests. We predicted higher FA and narrower feather growth bars in shade coffee forest versus natural forest, indicating higher quality in the latter. We measured and compared FA in tarsus length and rectrix mass and average growth bar width in more than 200 individuals of five bird species. The extent of FA in both tarsus length and rectrix mass was not different between the two forest types in any of the five species. Similarly, we found no difference in feather growth between shade coffee and natural forests for any species. Therefore, we conclude our comparison of biomarkers suggests that shade coffee farms and natural forests provide similar habitat quality for the five species we examined.
Influence of chitosan coating and packaging materials on the quality characteristics of fresh-cut cucumber
Authors: Olawuyi Ibukunoluwa Fola , Lee Wonyoung
Published: August 2019

In this study, the influence of chitosan coating and packaging materials on the quality characteristics of fresh-cut cucumber during storage was examined. Fresh cucumber was cut into 10 mm thick slices and then coated with chitosan through immersion in 1% and 2% chitosan solutions while control samples (uncoated) were immersed in distilled water. Coated and uncoated fresh-cut samples were packaged in three different materials: 60 μm low-density polyethylene (LDPE) film, polypropylene tray with 65 μm casted polypropylene (CPP) film and 110 μm composite polyamide-polyethylene (PAPE) film, and then sealed and stored at 5℃ for 12 days. During this storage period, the gas composition, visual quality, weight loss, firmness, total soluble solids, pH, color, and microbial quality of the samples were evaluated periodically. The fresh-cut samples coated with chitosan recorded better quality characteristics compared to those of uncoated samples. This result confirmed the significance of chitosan coating for preserving the quality of fresh-cut fruits. The samples stored in LDPE and CPP packaging materials without chitosan coating showed a decline in quality, while PAPE enhanced the barrier properties of chitosan coating and consequently improved the quality of fresh-cut cucumber during its storage. At the end of the storage period, 2% chitosan-coated and PAPE-packaged fresh-cut cucumber samples showed the best quality characteristics. Hence, we recommend the combined application of chitosan coating with PAPE package for better preserving the quality of fresh-cut cucumber.
Effect of water soaking pretreatment on the quality of glutinous rice cookies
Authors: Chung Hun-Sik , Park Han-Sol , Lee Hyeon-Jeong , Woo Jin-Ho , Moon Kwang-Deog , Youn Kwang-Sup
Published: August 2019

In this study, we aimed to improve the quality of rice cookies by investigating the preparation of the principal ingredient, glutinous rice (Oryza sativa var. glutinosa ‘Dongjin’). The effects of pre-milling water soaking on the quality characteristics of the rice flour and resultant rice cookies were investigated; in particular, the characteristics of cookies made from water-soaked and untreated rice flours were compared. Rice flour, sugar, butter, salt, egg, and baking powder were mixed together to from a dough, which was then cut (thickness 3 mm and diameter 35 mm), baked for 9 min at 170-180℃, cooled, and packaged in plastic bags. In glutinous rice cookies prepared from water-soaked rice flour, the moisture content, water activity, and hue and red-green (h° and -a*) color values were significantly higher but the yield, spread ratio, bulk density, hardness, lightness, yellow-blue and chroma (L*, b* and C*) color values, phenolic compound contents, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity were significantly lower than those prepared from untreated rice flour. These results suggest that the treatment of glutinous rice grain by water soaking before milling affects the quality properties of the resultant cookies, and the pretreatment of glutinous rice results in cookies with a darker color, softer texture, and lower antioxidant ability.
Polyphenolic rich extract from Perilla Frutescens promotes caspase-dependent apoptosis in melanoma cells
Authors: Kwon Soon-Jae , Cho Hyun-Dong , Lee Ju-Hye , Hong Seong-Min , Jeong Il-Yun , Moon Kwang-Deog , Seo Kwon-Il
Published: August 2019

This study aimed to assess the inhibitory potential of Perilla frutescens methanolic extract (PE) and its fractions towards melanoma cells as an herbal medicine. PE (100-400 μg/mL) effectively decreased the viability of the mouse and human melanoma cells (B16 and SK-MEL-2, respectively), whereas, HaCaT human keratinocytes remained un-damaged. It also induced B16 cell apoptosis, as determined by flow cytometry, Hoechst 33258 staining, and DNA fragmentation. Amongst PE fractions, ethyl acetate fraction (PEEF) displayed the most significant anticancer activity in B16 cells. It also exhibited a significant proliferation inhibitory effect on B16 cells as compared to the butanol (PEBF) and water fractions (PEWF). Furthermore, PEEF induced apoptotic cell death, through increased nuclei condensation, DNA fragmentation, and sub-G1 cell cycle arrest. PEEF-induced apoptosis was observed to be involved with the up-regulation of pro-apoptotic caspase-3, -9, Bax, and cleaved PARP, and the down-regulation of anti-apoptotic Bcl-2 protein levels. The total phenolic contents of PEEF were 2.87 and 5.39 times higher than those of PEBF and PEWF. The findings demonstrated that phenolic compound-rich PEEF induced caspase-dependent apoptosis in melanoma cells, and that it could be used as an herbal medicine and functional food material.
An R package for divergence analysis of omics data
Authors: Dinalankara Wikum , Ke Qian , Geman Donald , Marchionni Luigi
Published: August 2019

Given the ever-increasing amount of high-dimensional and complex omics data becoming available, it is increasingly important to discover simple but effective methods of analysis. Divergence analysis transforms each entry of a high-dimensional omics profile into a digitized (binary or ternary) code based on the deviation of the entry from a given baseline population. This is a novel framework that is significantly different from existing omics data analysis methods: it allows digitization of continuous omics data at the univariate or multivariate level, facilitates sample level analysis, and is applicable on many different omics platforms. The divergence package, available on the R platform through the Bioconductor repository collection, provides easy-to-use functions for carrying out this transformation. Here we demonstrate how to use the package with data from the Cancer Genome Atlas.
Sorting motifs target the movement protein of ourmia melon virus to the trans-Golgi network and plasmodesmata
Authors: Ozber Natali , Margaria Paolo , Anderson Charles T. , Turina Massimo , Rosa Cristina
Published: August 2019

Plants have a highly sophisticated endomembrane system targeted by plant viruses for cell-to-cell movement. The movement protein (MP) of ourmia melon virus (OuMV) is delivered to plasmodesmata (PD) and forms tubules to facilitate cell-to-cell movement. Although several functionally important regions for correct subcellular localization of OuMV MP have been identified, little is known about the pathways OuMV MP hijacks to reach the PD. Here, we demonstrate that OuMV MP localizes to the trans-Golgi network (TGN), but not to the multivesicular body/prevacuolar compartment or Golgi, and carries two putative sorting motifs, a tyrosine (Y) and a dileucine (LL) motif, near its N-terminus. Glycine substitutions in these motifs result in loss of OuMV infectivity in Nicotiana benthamiana and Arabidopsis. Live cell imaging of GFP-labeled sorting motif mutants shows that Y motif mutants fail to localize to the TGN, plasma membrane, and PD. Mutations in the LL motif do not impair plasma membrane targeting of MP but affect its ability to associate with callose deposits at the PD. Taken together, these results suggest that both motifs are indispensable for targeting OuMV MP to PD and for efficient systemic infection but show differences in functionality. Co-immunoprecipitation assays coupled with mass spectrometry identified a series of host factors that could interact with the OuMV MP and link the MP with various pathways, in particular vesicle trafficking and membrane lipids. This study provides new insights into the intracellular targeting of MPs and pathways that plant viruses hijack for cell-to-cell movement.
In situgrowth of anammox bacteria in subseafloor sediments
Authors: Zhao Rui , Mogollón José M. , Abby Sophie S. , Schleper Christa , Biddle Jennifer F. , Roerdink Desiree , Thorseth Ingunn H. , Jørgensen Steffen L.
Published: August 2019

The deep biosphere buried in marine sediments was estimated to host an equal number of microbes as found in the above oceans1. It has been debated if these cells are alive and active2, and their per cell energy availability does not seem to allow for net population growth3. Here, we report the growth of anammox bacteria in ∼80,000 year old subsurface sediments indicated by their four orders of magnitude abundance increase in the nitrate-ammonia transition zone (NATZ). Their growth coincides with a local increase in anammox power supply. The genome of the dominant anammox bacterium from the NATZ was reconstructed and showed an increased index of replication confirmingin situactive growth. The genome belongs to a newScalinduaspecies so far exclusively found in marine environments, which has the genetic capacity of urea and cyanate utilization and is enriched in genes allowing it to cope with external environmental stressors, such as energy limitation. Our results suggest that specific microbial groups are not only able to survive over geological timescales, but also thrive in the deep subsurface when encountering favorable conditions.
Genome Report: A highly contiguous reference genome for Northern Bobwhite (Colinus virginianus)
Authors: Salter Jessie F. , Johnson Oscar , Stafford Norman J. , Herrin William F. , Schilling Darren , Cedotal Cody , Brumfield Robb T. , Faircloth Brant C.
Published: August 2019

Northern bobwhites (Colinus virginianus) are small quails in the New World Quail family (Odontophoridae) and are one of the most phenotypically diverse avian species. Despite extensive research on bobwhite ecology, genomic studies investigating the evolution of phenotypic diversity in this species are lacking. Here, we present a new, highly contiguous assembly for bobwhites using tissue samples from a vouchered, wild, female bird collected in Louisiana. Using Dovetail Chicago and HiC libraries with the HiRise assembly pipeline, we produced an 866.8 Mbp assembly including 1,512 scaffolds with a contig N50 of 66.8 Mbp, a scaffold L50 of four, and a BUSCO completeness score of 90.8%. This new assembly greatly improves scaffold lengths and contiguity compared to an existing draft bobwhite genome and provides an important tool for future studies of evolutionary and functional genomics in bobwhites.
MIR3607regulates cerebral cortex development via activation of Wnt/βCat signaling
Authors: Chinnappa Kaviya , Márquez-Galera Ángel , Prieto-Colomina Anna , Nomura Yuki , Cárdenas Adrián , López-Atalaya José P. , Borrell Víctor
Published: August 2019

The evolutionary expansion of the mammalian cerebral cortex is recapitulated during embryonic development in large mammals, but the underlying genetic mechanisms remain mostly unknown. Previous transcriptomic analyses of the developing ferret cortex identify candidate genes related to the expansion of germinal layers and cortex size. Here we focused onMIR3607, a microRNA differentially expressed between germinal layers of the large human and ferret cortex, not expressed in the small mouse cortex. Expression ofMIR3607in mouse embryos at E14.5 leads to increased progenitor cell proliferation. This is reflected in transcriptomic changes, which also reveal increased Wnt/βCatenin signaling. Expression ofMIR3607at E12.5, when progenitor cells expand, causes amplification and severe delamination of apical progenitors, leading to rosette formation. This is rescued by co-expressing Adenomatous Polyposis Coli, inhibitor of canonical Wnt signaling. A similar phenotype is produced in human cerebral organoids. Our findings demonstrate thatMIR3607expands and delaminates apical progenitor cells via activating Wnt/βCatenin, and suggest that a secondary loss of expression in mouse may underlie their reduction in cortex size during recent evolution.
Targeted cell ablation in zebrafish using optogenetic transcriptional control
Authors: Mruk Karen , Ciepla Paulina , Piza Patrick A. , Alnaqib Mohammad A. , Chen James K.
Published: August 2019

Cell ablation is a powerful method for elucidating the contributions of individual cell populations to embryonic development and tissue regeneration. Targeted cell loss in whole organisms has been typically achieved through expression of a cytotoxic or prodrug-activating gene product in the cell type of interest. This approach depends on the availability of tissue-specific promoters, and it does not allow further spatial selectivity within the promoter-defined region(s). To address this limitation, we have developed ablative methods that combine genetically encoded toxins, the tissue specificity afforded bycis-regulatory elements, and the conditionality of optogenetics. Using this integrative approach, we have ablated cells in zebrafish embryos with spatial and temporal precision.
IRG1 and iNOS act redundantly with other interferon gamma-induced factors to restrict intracellular replication ofLegionella pneumophila
Authors: Price Jordan V. , Russo Daniel , Ji Daisy X. , Chavez Roberto , DiPeso Lucian , Lee Angus Yiu-Fai , Coers Jörn , Vance Russell E.
Published: August 2019

Interferon gamma (IFNγ) restricts the intracellular replication of many pathogens, but how IFNγ confers cell-intrinsic pathogen resistance remains unclear. For example, intracellular replication of the bacterial pathogenLegionella pneumophilain macrophages is potently curtailed by IFNγ, but consistent with prior results, no individual genetic deficiency we tested compromised IFNγ-mediated control. Intriguingly, however, we observed that the glycolysis inhibitor 2-deoxyglucose (2DG) partially rescuedL. pneumophilareplication in IFNγ-treated macrophages. 2DG inhibits glycolysis and triggers the unfolded protein response, but unexpectedly, it appears these effects are not responsible for perturbing the antimicrobial activity of IFNγ. Instead, we found that 2DG rescues bacterial replication predominantly by inhibiting the induction of two key antimicrobial factors, inducible nitric oxide synthase (iNOS) and immune responsive gene 1 (IRG1). Using immortalized and primary macrophages deficient in iNOS and IRG1, we confirm that loss of both iNOS and IRG1, but not individual deficiency in each gene, partially reduces IFNγ-mediated restriction ofL. pneumophila. Further, using a combinatorial CRISPR/Cas9 mutagenesis approach, we find that mutation of iNOS and IRG1 in combination with four other genes (CASP11, IRGM1, IRGM3 and NOX2) results in a total loss ofL. pneumophilarestriction by IFNγ in primary bone marrow macrophages. There are few, if any, other examples in which the complete set of cell-intrinsic factors required for IFNγ-mediated restriction of an intracellular bacterial pathogen have been genetically identified. Our results highlight the combinatorial strategy used by hosts to block the exploitation of macrophages by pathogens.

Importance

Legionella pneumophilais one example among many species of pathogenic bacteria that replicate within mammalian macrophages during infection. The immune signaling factor interferon gamma (IFNγ) blocksL. pneumophilareplication in macrophages and is an essential component of the immune response toL. pneumophilaand other intracellular pathogens. However, to date, no study has determined the exact molecular factors induced by IFNγ that are required for its activity. We generated macrophages lacking different combinations of IFNγ-induced genes in an attempt to find a genetic background in which there is a complete loss of IFNγ-mediated restriction ofL. pneumophila. We successfully identified six genes that comprise the totality of the IFNγ-dependent restriction ofL. pneumophilareplication in macrophages. Our results clarify the molecular basis underlying the potent effects of IFNγ and highlight how redundancy downstream of IFNγ is key to prevent exploitation of the macrophage niche by pathogens.
Distinct and shared contributions of diagnosis and symptom domains to cognitive performance in a case-control study of severe mental illness in the Paisa population
Authors: Service Susan K. , Upegui Cristian Vargas , Ramírez Mauricio Castano , Port Allison M. , Moore Tyler M. , Umanes Marfred Munoz , Arango Luis Guillermo Agudelo , Díaz-Zuluaga Ana M. , Espejo Juanita Melo , López María Cecilia , Palacio Juan David , Ruiz Sergio Sánchez , Valencia Johanna , Teshiba Terri , Espinoza Alesandra , Loohuis Loes Olde , De la Hoz Gomez Juan , Brodey Benjamin , Sabatti Chiara , Escobar Javier I. , Reus Victor I. , Jaramillo Carlos Lopez , Gur Ruben C. , Bearden Carrie E. , Freimer Nelson B.
Published: August 2019

Background

Severe mental illness (SMI) diagnoses display overlapping symptomatology and shared genetic risk, motivating trans-diagnostic investigations of disease-relevant quantitative measures. We analyzed relationships between neurocognitive performance, symptom domains, and diagnoses, in a large sample of SMI cases (ascertained agnostic to diagnosis) and healthy controls from a single, homogeneous population.

Methods

2,406 participants (1,689 cases, 717 controls; mean age 39 years, 64% female) were assessed for speed and accuracy using the Penn Computerized Neurocognitive Battery (CNB). Cases carried structured-interview based diagnoses of schizophrenia (SCZ, n=160), bipolar-I (BP-I, n=519), bipolar-II (BP-II, n=204) and major depressive disorder (MDD, n=806). Linear mixed models, using CNB tests as repeated measures, modeled neurocognition as a function of diagnosis, sex, and all interactions. Follow-up analyses, in cases, included symptom factor scores obtained from exploratory factor analysis of symptom data, as main effects.

Findings

BP-I and SCZ displayed nearly identical impairments in accuracy and speed, across cognitive domains. BP-II and MDD performed similarly to controls, with subtle deficits in executive and social cognition. A three-factor model (psychosis, mania, and depression) best represented symptom data. Controlling for diagnosis, premorbid IQ, and disease severity, high lifetime psychosis scores were associated with reduced accuracy and speed across cognitive domains, while high depression scores were associated with increased social cognition accuracy.

Interpretation

Trans-diagnostic investigations demonstrated that neurocognitive function in SMI is characterized by two distinct profiles (BP-I/SCZ and BP-II/MDD), and is associated with specific symptom domains. These results suggest the utility of this design for elucidating SMI causes and trajectories.