bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haplotype-resolved powdery mildew resistance loci reveal the impact of heterozygous structural variation on NLR genes inMuscadinia rotundifolia
Authors: Massonnet Mélanie , Vondras Amanda M , Cochetel Noé , Riaz Summaira , Pap Dániel , Minio Andrea , Figueroa-Balderas Rosa , Walker Michael Andrew , Cantu Dario 
Published: June 2022

AbstractMuscadinia rotundifolia cv. Trayshed is a valuable source of resistance to grape powdery mildew. It carries 2 powdery mildew resistance-associated genetic loci, Run1.2 on chromosome 12 and Run2.2 on chromosome 18. The purpose of this study was to identify candidate resistance genes associated with each haplotype of the 2 loci. Both haplotypes of each resistance-associated locus were identified, phased, and reconstructed. Haplotype phasing allowed the identification of several structural variation events between haplotypes of both loci. Combined with a manual refinement of the gene models, we found that the heterozygous structural variants affected the gene content, with some resulting in duplicated or hemizygous nucleotide-binding leucine-rich repeat genes. Heterozygous structural variations were also found to impact the domain composition of some nucleotide-binding leucine-rich repeat proteins. By comparing the nucleotide-binding leucine-rich repeat proteins at Run1.2 and Run2.2 loci, we discovered that the 2 loci include different numbers and classes of nucleotide-binding leucine-rich repeat genes. To identify powdery mildew resistance-associated genes, we performed a gene expression profiling of the nucleotide-binding leucine-rich repeat genes at Run1.2b and Run2.2 loci with or without powdery mildew present. Several nucleotide-binding leucine-rich repeat genes were constitutively expressed, suggesting a role in powdery mildew resistance. These first complete, haplotype-resolved resistance-associated loci and the candidate nucleotide-binding leucine-rich repeat genes identified by this study are new resources that can aid the development of powdery mildew-resistant grape cultivars.
Impact of drug consumption rooms on non-fatal overdoses, abscesses and emergency department visits in people who inject drugs in France: results from the COSINUS cohort
Authors: Roux P , Jauffret-Roustide M , Donadille C , Briand Madrid L , Denis C , Célérier I , Chauvin C , Hamelin N , Maradan G , Carrieri M P , Protopopescu C , Lalanne L , Auriacombe M ,   the COSINUS Study Group, Auriacombe Marc , Berenger Cyril , Bertoia Gilles , Madrid Laélia Briand , Carrieri Maria Patrizia , Célérier Isabelle , Chauvin Carole , Chevalier Manon , Danion Jean-Marie , de Dinechin Sébastien , Denis Cécile , Grelli Natascia , Gutowski Marie , Hamelin Naomi , Jauffret-Roustide Marie , Kervran Charlotte , Kirchherr Sébastien , Lalanne Laurence , Breton Mireille Le , Maradan Gwenaëlle , Moriceau Sarah , Roux Perrine , Vilotitch Antoine 
Published: June 2022

AbstractBackgroundThe effectiveness of drug consumption rooms (DCRs) for people who inject drugs (PWID) has been demonstrated for HIV and hepatitis C virus risk practices, and access to care for substance use disorders. However, data on other health-related complications are scarce. Using data from the French COSINUS cohort, we investigated the impact of DCR exposure on non-fatal overdoses, abscesses and emergency department (ED) visits, all in the previous 6 months.MethodsCOSINUS is a 12-month prospective cohort study of 665 PWID in France studying DCR effectiveness on health. We collected data from face-to-face interviews at enrolment, and at 6 and 12 months of follow-up. After adjusting for other correlates (P-value &lt; 0.05), the impact of DCR exposure on each outcome was assessed using a two-step Heckman mixed-effects probit model, allowing us to adjust for potential non-randomization bias due to differences between DCR-exposed and DCR-unexposed participants, while taking into account the correlation between repeated measures.ResultsAt enrolment, 21%, 6% and 38% of the 665 participants reported overdoses, abscesses and ED visits, respectively. Multivariable models found that DCR-exposed participants were less likely to report overdoses [adjusted coefficient (95% CI): −0.47 (−0.88; −0.07), P = 0.023], abscesses [−0.74 (−1.11; −0.37), P &lt; 0.001] and ED visits [−0.74 (−1.27; −0.20), P = 0.007].ConclusionThis is the first study to show the positive impact of DCR exposure on abscesses and ED visits, and confirms DCR effectiveness in reducing overdoses, when adjusting for potential non-randomization bias. Our findings strengthen the argument to expand DCR implementation to improve PWID injection environment and health.
Activation and execution of the hepatic integrated stress response by dietary essential amino acid deprivation is amino acid specific
Authors: Jonsson William O. , Mirek Emily T. , Wek Ronald C. , Anthony Tracy G. 
Published: June 2022

AbstractDietary removal of an essential amino acid (EAA) triggers the integrated stress response (ISR) in liver. Herein, we explored the mechanisms that activate the ISR and execute changes in transcription and translation according to the missing EAA. Wild‐type mice and mice lacking general control nonderepressible 2 (Gcn2) were fed an amino acid complete diet or a diet devoid of either leucine or sulfur amino acids (methionine and cysteine). Serum and liver leucine concentrations were significantly reduced within the first 6 h of feeding a diet lacking leucine, corresponding with modest, GCN2‐dependent increases in Atf4 mRNA translation and induction of selected ISR target genes (Fgf21, Slc7a5, Slc7a11). In contrast, dietary removal of the sulfur amino acids lowered serum methionine, but not intracellular methionine, and yet hepatic mRNA abundance of Atf4, Fgf21, Slc7a5, Slc7a11 substantially increased regardless of GCN2 status. Liver tRNA charging levels did not correlate with intracellular EAA concentrations or GCN2 status and remained similar to mice fed a complete diet. Furthermore, loss of Gcn2 increased the occurrence of ribosome collisions in liver and derepressed mechanistic target of rapamycin complex 1 signal transduction, but these changes did not influence execution of the ISR. We conclude that ISR activation is directed by intracellular EAA concentrations, but ISR execution is not. Furthermore, a diet devoid of sulfur amino acids does not require GCN2 for the ISR to execute changes to the transcriptome.
Investigation of the Sectorized Corneal Thickness of Eyes With Corneal Endothelial Dysfunction Using Anterior-Segment Optical Coherence Tomography
Authors: Omoto Takashi , Kim Minjae , Goto Hiroki , Abe Yuito , Ono Takashi , Taketani Yukako , Toyono Tetsuya , Yoshida Junko , Usui Tomohiko , Yamagami Satoru , Aihara Makoto , Miyai Takashi 
Published: June 2022

Purpose:
The aim of this study was to investigate the sectorized corneal thickness of eyes with corneal endothelial dysfunction using anterior-segment optical coherence tomography.

Methods:
We retrospectively collected anterior-segment optical coherence tomography data conducted before endothelial keratoplasty on 53 eyes of 53 patients with corneal endothelial dysfunctions including Fuchs endothelial corneal dystrophy, bullous keratopathy (BK) after trabeculectomy, and BK after laser iridotomy and from 18 normal eyes of 18 subjects. The imaging points were divided into 17 sectors. The mean for each sector was calculated and compared with the corresponding superior/inferior and temporal/nasal sectors.

Results:
In the normal eyes, the superior sectors were thicker than the inferior and the temporal sectors thinner than the nasal. In the diseased eyes, the superior sectors were thicker than the inferior in all subgroups; however, this tendency was no longer observed after the values were divided by the mean for the normal eyes. No significant differences were found on horizontal comparisons; however, after the values were divided by the mean for the normal eyes, the temporal sectors were thicker than the nasal. When comparing the values between the with-hole and the without-hole sides in the BK after laser iridotomy eyes, the sectors on the with-hole side were thicker than the other side.

Conclusions:
Corneal thickness of endothelial dysfunction was thicker in the superior sectors than the inferior but at a similar level to normal eyes. No significant differences were found for horizontal comparisons but, based on comparison with the normal eyes, the temporal sectors were thicker than the nasal.
Structural and Metabolic Imaging after Short-term Use of the Balance Goggles System in Glaucoma Patients: A Pilot Study
Authors: Sun Michelle T. , Beykin Gala , Lee Wen-shin , Sun Yang , Chang Robert , Nunez Mariana , Li Katherine Zhongqiu , Knasel Cara , Rich Collin , Goldberg Jeffrey L. 
Published: June 2022

Precis:
Short-term use of the Balance Goggles System in glaucoma patients was not associated with observable changes in conventional OCT imaging but metabolic imaging using peripapillary flavoprotein fluorescence may represent a useful adjuctive investigation.

Objective:
To determine whether the intraocular pressure (IOP)-lowering effects of the Balance Goggles System (BGS) are accompanied by changes in retinal thickness measured by ocular coherence tomography, retinal vascular density measured by OCT-angiography, or novel peripapillary metabolic profiling using flavoprotein fluorescence (FPF) measured by a fundus camera.

Design:
Prospective comparative case-series.

Subjects:
8 eyes from 8 patients with open-angle glaucoma ranging from mild to severe.

Methods:
In this prospective, single-center, open-label, non-randomized, single-arm study patients received a baseline evaluation including retinal imaging, then one hour of negative pressure application through the BGS, followed by repeat retinal imaging. Participants then used the BGS at home for 1 month and underwent a repeat evaluation at the conclusion of the trial.

Main Outcome Measures:
Changes in nerve fiber layer thickness, OCTA vascular parameters and FPF scores.

Results:
Mean baseline IOP was 18.0±3.1 mmHg and there was no significant change in IOP at follow-up. At 1 month compared to baseline, there was a statistically significant improvement in FPF optic nerve head rim scores (12.7±11.6 to 10.5±7.5; P=0.04). Additionally, there was there was a trend towards an increase in RNFL thickness after 1 month (69.5±14.2 to 72.0±13.7; P=0.1), but there were no statistically significant differences observable with any of the OCTA vascular parameters either at 1 hour or after 1 month.

Conclusions:
There were no significant changes observable using conventional OCT imaging following short-term use of the BGS, although metabolic imaging using FPF may be a useful potential biomarker to complement existing investigations. Additional studies are warranted to further investigate these changes.
The feasibility and safety of stepwise protocol in cardiopulmonary exercise testing-exercise stress echocardiography for subjects with heart failure
Authors: Huang Wei-Ming , Chen Chiao-Nan , Chen Yung-Hsin , Yen Ju-Hsin , Tseng Tzu-Ying , Cheng Hao-Min , Yu Wen-Chung , Chen Chen-Huan , Sung Shih-Hsien 
Published: June 2022

Background:
Exercise stress testing using a ramp protocol has been favored for cardiopulmonary exercise testing (CPX) in patients with heart failure (HF). However, the stepwise protocol for CPX was preferred for its possible combination with exercise stress echocardiography (ESE). We, therefore, investigated the feasibility and safety of using a stepwise protocol for CPX-ESE in patients with HF.

Methods:
Ambulatory outpatients with chronic HF were enrolled for a symptom-limited stepwise bicycle exercise test in the semi-supine position on a cycle ergometer. The test was started at a workload of 30 W and increased by 15 W every 3 minutes until maximal exertion. The echocardiographic and respiratory variables and any complications during the exercise were recorded.

Results:
Among a total of 36 participants (age 61.2 ± 12.4 years; 69.4% men), all subjects achieved anerobic threshold during CPX-ESE and reached 72.3% of the age-predicted peak heart rate. The peak oxygen consumption was 14.7 mL/kg/min, and the peak RER was 1.25. There were no severe adverse complications, and only two minor rhythmic events were reported: nonsustained supraventricular tachycardia and isolated ventricular premature beats. The echocardiographic images acquired at each stage were of good quality in 92.6% of all acquisitions, and the intra-observer and interobserver repeatability was >80%.

Conclusion:
The stepwise protocol, with an initial workload of 30 W, followed by 15 W increments every 3 minutes, was feasible and provided an adequate stress load for patients with HF. This exercise stress modality was safe and well-tolerated.
Endoscopic small bowel balloon dilations in patients with Crohn’s disease: a Danish nationwide cohort study, 1997–2015
Authors: Wewer Mads Damsgaard , Karstensen John Gásdal , Burisch Johan 
Published: June 2022

Objective
Small bowel strictures are a common complication in Crohn’s disease. Endoscopic balloon dilation (EBD) is an emerging therapeutic approach that is minimally invasive and helps to preserve the bowel. The aim of this study was to describe the use of EBD in adult Crohn’s disease patients with small bowel strictures.

Methods
This nationwide cohort comprised individuals ≥18 years old, diagnosed with Crohn’s disease in Denmark between 1 January 1997 and 31 December 2015, according to the National Patient Registry (NPR).

Results
The cohort consisted of 9737 incident Crohn’s disease patients that were followed for a median of 8.2 years [interquartile range (IQR) = 4.1–13.3]. During the observation period, a total of 90 (1%) patients underwent a small bowel-related EBD. After a follow-up period of a median of 3.4 (IQR = 1.8–5.0) years, primary small bowel strictures treated only with one dilation and no subsequent small bowel surgery accounted for 29 (59%) of 49 cases. A median of 7.2 (IQR = 2.4–13.2) months after their first dilation, 13 (27%) of those 49 patients underwent small bowel surgery. Forty-one patients with postsurgical strictures were dilated after a median of 6.5 (IQR = 2.5–10.2) years following small bowel surgery. Postsurgical strictures treated with only one dilation and no further small bowel surgery accounted for 20 (49%) of the 41 cases.

Conclusion
The frequency of EBD in this Danish nationwide cohort was low. During a median follow-up of 5 years after EBD, most patients did not require further surgery. This suggests that EBD is an effective treatment and could be offered to more patients with Crohn’s disease.
Coefficient of Fat Absorption to Measure the Efficacy of Pancreatic Enzyme Replacement Therapy in People With Cystic Fibrosis
Authors: Borowitz Drucy , Aronoff Nell , Cummings Linda C. , Maqbool Asim , Mulberg Andrew E. 
Published: June 2022

Objectives
We sought data on the validity, reliability, responsiveness, and feasibility of the coefficient of fat absorption (CFA) as a measure of pancreatic enzyme replacement therapy (PERT) efficacy in people with cystic fibrosis (pwCF) and reviewed the literature for alternative measures.

Methods
We searched PubMed for the Medical Subject Heading cystic fibrosis and the key words cystic fibrosis, fat absorption, CFA, and fecal fat imbalance; historical articles; and citations in bibliographies.

Results
The lower the CFA, the greater its variability; thus, it is less variable in healthy individuals who have higher CFA than pwCF. In addition, the test-retest values for CFA are more variable in pwCF than the general population. There is no correlation between CFA and body mass index or PERT dose but CFA is related to gastrointestinal signs and symptoms. Research-quality CFA studies are expensive, time consuming, and odious to pwCF and research staff. Sparse stool tests, breath tests, and blood tests of fat absorption have been studied as potential alternatives to CFA to measure PERT efficacy.

Conclusions
Based on the evidence, we conclude that CFA as a measure of the efficacy of PERT is more of a “coal standard” than a gold standard; developing suitable alternatives should be a priority.
The Additional Diagnostic Benefit of Pancreatic Cancer Molecular Profiling After Germline Testing
Authors: Walker Evan J. , Blanco Amie M. , Carnevale Julia , Cinar Pelin , Collisson Eric A. , Tempero Margaret A. , Ko Andrew H. 
Published: June 2022

Objectives
Germline genetic testing is universally recommended for patients with pancreatic cancer to guide therapeutic selection, but tumor molecular profiling (TMP) is not. We aimed to determine the real-world additional diagnostic benefit of TMP after germline testing for detecting therapeutically actionable alterations.

Methods
Medical records and genetic test reports were reviewed for all patients who underwent germline testing and TMP at the University of California San Francisco during January 2016–January 2020. The detection rate of actionable alterations with germline testing alone was compared to that with both germline testing and TMP.

Results
Among 738 eligible patients, 144 (20%) met study criteria. Germline testing detected 10 actionable alterations in 10 patients. Tumor molecular profiling identified 3 new therapeutic targets among these 10 patients and 45 targets in 41 additional patients, increasing the number of patients with actionable findings from 10 (7%) to 51 (35%). Most actionable alterations (35/58, 60%) involved genes associated with the Homologous Recombination DNA Damage Repair pathway.

Conclusions
Tumor molecular profiling after germline testing increased the detection of actionable alterations by 5-fold. Tumor molecular profiling is a necessary complement to germline genetic testing to fully inform therapeutic decision making for all patients with pancreatic cancer.
Combination of Body Mass Index and Fasting Blood Glucose Improved Predictive Value of New-Onset Prediabetes or Diabetes After Acute Pancreatitis
Authors: Guo Shao-Yan , Yang Hai-Yun , Ning Xiao-Yan , Guo Wan-Wei , Chen Xiao-Wu , Xiong Man 
Published: June 2022

Objectives
We sought to evaluate whether combining body mass index (BMI) and fasting blood glucose (FBG) can refine the predictive value of new-onset prediabetes/diabetes after acute pancreatitis (NODAP).

Methods
In this retrospective cohort study, we used Kaplan–Meier analysis to compare differences in the NODAP rate among 492 patients with different BMI or FBG levels, or with the combination of these 2 factors mentioned above.

Results
In all, 153 of 492 (31.1%) eligible patients finally developed NODAP. According to univariate and multivariate analyses, BMI (hazard ratio, 2.075; 95% confidence interval, 1.408–3.060; P < 0.001) and FBG (hazard ratio, 2.544; 95% confidence interval, 1.748–3.710; P < 0.001) were important predictors of the incidence of NODAP. Subsequently, we divided 492 eligible patients into 3 groups according to the median BMI and FBG values, and found that the NODAP rate in the high-risk group was significantly higher than that in the medium-risk group (P = 0.018) or the low-risk group (P < 0.001).

Conclusions
Body mass index and FBG are independent predictors of NODAP. The combination of BMI and FBG can refine the prediction of NODAP and identify candidates for clinical prevention.
The Characteristics and Risk Factors of Asparaginase-Associated Pancreatitis in Pediatric Acute Lymphoblastic Leukemia
Authors: Kuo Shu-Han , Chen Jiann-Shiuh , Cheng Chao-Neng , Lo Hsiao-Yu , Chen Wei-Che , Lai Fu-Ping , Yang Yao-Jong 
Published: June 2022

Objective
This study aimed to elucidate the characteristics and the risk factors for asparaginase-associated pancreatitis (AAP) in pediatric acute lymphoblastic leukemia (ALL) under the Taiwan Pediatric Oncology Group (TPOG)–ALL regimen.

Methods
The study was conducted by reviewing the chart records of 191 patients aged 1 to 18 years treated with TPOG-ALL (2002 and 2013) protocols at the National Cheng Kung University Hospital, Tainan, Taiwan, from 2002 to 2019. The disease incidence, clinical presentations, laboratory data, complications, and outcomes of AAP were investigated.

Results
The incidence of AAP was 4.7%. The incidence was significantly higher in children treated with the TPOG-ALL-2013 (n = 62) than TPOG-ALL-2002 (n = 129) protocol (11.3% vs 1.6%, P = 0.006). Multivariate analysis identified using TPOG-ALL-2013 protocol was an independent risk factor for AAP. Pancreatic necrosis or pseudocysts developed in 7 patients (78%). Notably, 1 AAP case (11%) developed diabetes mellitus and 4 (44%) had chronic pancreatitis during a 1-year observational period. None were mortality.

Conclusions
The incidence of AAP was 4.7% in ALL patients treated with TPOG-ALL protocol. Although a higher cumulative dose of asparaginase in TPOG-ALL-2013 may attribute to the pancreatic toxicity, unidentified factors such as genetic predisposition or other drugs still need further study.
Unexpected Benefits in Single Institution Experience With Successful Implementation of a Standardized Perioperative Protocol in Pediatric Thyroidectomy
Authors: Cossen Kristina , Santore Matthew T. , Prickett Kara K. , Goudy Steven L. , Heiss Kurt F. , Shanker Kanika , Alazraki Adina L. , Patterson Briana C. 
Published: June 2022

Introduction:
To illustrate how quality improvement can produce unexpected positive outcomes.

Methods:
We compared a retrospective review of perioperative management and outcomes of baseline 122 pediatric total thyroidectomies to 121 subsequent total thyroidectomies managed by an Electronic Medical Record protocol in a large, free-standing children’s healthcare system. Process measures included serum calcium measurement 6−12 hours postoperatively; parathyroid hormone measurement 6 hours postoperatively; preoperative iodine for Graves disease, and postoperative prophylactic calcium carbonate administration. In addition, we completed 4 Plan-Do-Study-Act (PDSA) cycles, focusing on implementation, refinement, usage, education, and postoperative calcitriol administration. The primary outcome included transient hypocalcemia during admission.

Results:
All perioperative process measures improved over PDSA cycles. Measurement of postoperative serum calcium increased from 42% at baseline to 100%. Measurement of postoperative PTH increased from 11% to 97%. Preoperative iodine administration for Graves disease surgeries improved from 72% to 94%. Postoperative calcium carbonate administration increased from 36% to 100%. There was a trend toward lower rates of severe hypocalcemia during admission over the subsequent PDSA cycles starting at 11.6% and improving to 3.4%. With the regular review of outcomes, surgical volume consolidated among high-volume providers, associated with a decrease in a permanent hypoparathyroid rate of 20.5% at baseline to 10% by the end of monitoring.

Conclusions:
In standardizing care at 1 large pediatric institution, implementing a focused quality improvement project involving the perioperative management of transient hypocalcemia in total thyroidectomy pediatric patients resulted in additional, unanticipated improvements in patient care.
Pulmonary Artery Angiomatoid Fibrous Histiocytoma Mimicking a Large Pulmonary Embolism
Authors: Haug Logan P. , Zarka Matthew A. , D’Cunha Jonathan , Downey Francis X. , Seetharam Mahesh , Yang Ming 
Published: June 2022

Abstract
A 39-year-old man presented with progressive dyspnea and lower extremity edema. Doppler ultrasound demonstrated bilateral leg partially occluded venous thromboses. A V/Q scan revealed a mismatched perfusion defect involving the entire right middle and lower lobes. Subsequent CT pulmonary angiogram revealed a mass lesion occluding the right interlobar pulmonary artery. Endobronchial ultrasound–guided fine-needle aspiration of the mass was concerning for neoplasm. 18F-FDG PET/CT demonstrated marked hypermetabolism of the mass lesion. Patient underwent transmediastinal right pneumonectomy with histopathologic diagnosis of pulmonary artery angiomatoid fibrous histiocytoma, a rare etiology mimicking large pulmonary artery embolism.