bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal Adjuvant Treatment Approach After Upfront Resection of Pancreatic Cancer
Authors: Moaven Omeed , Clark Clancy J. , Russell Gregory B. , Votanopoulos Konstantinos I. , Howerton Russell , Levine Edward A. , Shen Perry 
Published: January 2020

Objective:
To identify the survival benefit of different adjuvant approaches and factors influencing their efficacy after upfront resection of pancreatic ductal adenocarcinoma (PDAC).

Summary Background Data:
The optimal adjuvant approach for PDAC remains controversial.

Methods:
Patients from the National Cancer Database who underwent upfront PDAC resection from 2010 to 2014 were analyzed to determine clinical outcomes of different adjuvant treatment approaches, stratified according to pathologic characteristics. Factors associated with overall survival were identified with multivariable logistic regression and Cox proportional hazards were used to compare overall survival of different treatment approaches in the whole cohort, and propensity score matched groups.

Results:
We included 16,709 patients who underwent upfront resection of PDAC. On multivariable analysis, tumor size, grade, positive margin, nodal involvement, lymphovascular invasion (LVI), stage, lymph node ratio, not receiving chemotherapy, and/or radiation were predictors for worse survival. In the presence of at least 1 high-risk pathologic feature (nodal or margin involvement or LVI) chemotherapy with subsequent radiation provided the most significant survival benefit (median survivals: 24.8 vs 21.0 mo for adjuvant chemotherapy; HR = 0.81; 95% CI: 0.77–0.86; P < 0.001 in propensity score matching). The addition of radiation to adjuvant chemotherapy did not significantly improve overall survival in those with no high-risk pathologic features (median survivals: 54.6 vs 42.7 mo for adjuvant chemotherapy; HR=0.90; 95% CI: 0.75–1.08; P = 0.25 in propensity score matching).

Conclusions:
In the presence of any high-risk pathologic features (nodal or margin involvement or LVI), adjuvant chemotherapy followed by radiation provides a better survival advantage over chemotherapy alone after upfront resection of PDAC.
Hospital Volume of Antireflux Surgery in Relation to Endoscopic and Surgical Re-interventions
Authors: Markar Sheraz , Santoni Giola , Maret-Ouda John , Artama Miia , Färkkilä Martti , Lynge Elsebeth , Pukkala Eero , Ness-Jensen Eivind , von Euler-Chelpin My , Lagergren Jesper 
Published: January 2020

Objective:
To test the hypothesis that higher hospital volume decreases endoscopic and surgical re-intervention rates after antireflux surgery.

Background:
Antireflux surgery for gastro-esophageal reflux disease is followed by varying rates of re-interventions. Whether hospital volume influences re-intervention rates is uncertain.

Methods:
This population-based cohort study used nationwide data from Denmark, Finland, and Sweden for patients having undergone primary antireflux surgery. Hospitals were divided into tertiles based upon annual volume, that is, 3 equal-sized groups. The outcomes were 30-day surgical re-intervention, endoscopic re-intervention, and secondary antireflux surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for risk of the first outcome occurrence. Incidence rate ratios were calculated to count all outcome occurrences. All risk estimates were adjusted for age, sex, comorbidity, type of antireflux surgery, year of surgery, and country.

Results:
Among 33,060 patients and a median follow-up of 12 years after antireflux surgery, the frequencies of 30-day re-intervention, endoscopic re-intervention, and secondary antireflux surgery were 1.2%, 4.6%, and 7.0%, respectively. When comparing the highest with the lowest tertiles, higher hospital volume did not decrease HRs of 30-day re-intervention (adjusted HR = 1.14, 95% CI 0.73–1.77), endoscopic re-intervention (HR = 1.21, 95% CI 0.96–1.51), or secondary antireflux surgery (HR = 1.28, 95% CI 1.05–1.54), but rather increased point estimates. The incidence rate ratios showed similar patterns.

Conclusions:
Higher hospital volume of primary antireflux surgery may not decrease risk of endoscopic or surgical re-intervention, suggesting that centralization will not decrease rates of postoperative complications or recurrence of gastro-esophageal reflux disease.
Development and Validation of a Deep Learning CT Signature to Predict Survival and Chemotherapy Benefit in Gastric Cancer
Authors: Jiang Yuming , Jin Cheng , Yu Heng , Wu Jia , Chen Chuanli , Yuan Qingyu , Huang Weicai , Hu Yanfeng , Xu Yikai , Zhou Zhiwei , Fisher George A. , Li Guoxin , Li Ruijiang 
Published: January 2020

Objective:
We aimed to develop a deep learning-based signature to predict prognosis and benefit from adjuvant chemotherapy using preoperative computed tomography (CT) images.

Background:
Current staging methods do not accurately predict the risk of disease relapse for patients with gastric cancer.

Methods:
We proposed a novel deep neural network (S-net) to construct a CT signature for predicting disease-free survival (DFS) and overall survival in a training cohort of 457 patients, and independently tested it in an external validation cohort of 1158 patients. An integrated nomogram was constructed to demonstrate the added value of the imaging signature to established clinicopathologic factors for individualized survival prediction. Prediction performance was assessed with respect to discrimination, calibration, and clinical usefulness.

Results:
The DeLIS was associated with DFS and overall survival in the overall validation cohort and among subgroups defined by clinicopathologic variables, and remained an independent prognostic factor in multivariable analysis (P
< 0.001). Integrating the imaging signature and clinicopathologic factors improved prediction performance, with C-indices: 0.792–0.802 versus 0.719–0.724, and net reclassification improvement 10.1%–28.3%. Adjuvant chemotherapy was associated with improved DFS in stage II patients with high-DeLIS [hazard ratio = 0.362 (95% confidence interval 0.149–0.882)] and stage III patients with high- and intermediate-DeLIS [hazard ratio = 0.611 (0.442–0.843); 0.633 (0.433–0.925)]. On the other hand, adjuvant chemotherapy did not affect survival for patients with low-DeLIS, suggesting a predictive effect (P
interaction = 0.048, 0.016 for DFS in stage II and III disease).

Conclusions:
The proposed imaging signature improved prognostic prediction and could help identify patients most likely to benefit from adjuvant chemotherapy in gastric cancer.
The Impact of Intraperitoneal Levobupivacaine on Pain Relief After Laparoscopic Cholecystectomy: A Meta-analysis of Randomized Controlled Studies
Authors: Wei Xuan , Yao Xiaoxiao 
Published: January 2020

Introduction:
The influence of intraperitoneal levobupivacaine on pain relief after laparoscopic cholecystectomy remains controversial. We conducted a systematic review and meta-analysis to explore the impact of intraperitoneal levobupivacaine versus placebo on pain intensity after laparoscopic cholecystectomy.

Materials and Methods:
We searched the PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through March 2019 for randomized controlled trials assessing the effect of intraperitoneal levobupivacaine versus placebo on pain intensity after laparoscopic cholecystectomy. This meta-analysis is performed using the random-effect model.

Results:
Six randomized controlled trials are included in the meta-analysis. Overall, compared with the control group after laparoscopic cholecystectomy, intraperitoneal levobupivacaine is associated with substantially reduced pain scores at 2 hours [standard mean difference (SMD)=−0.70; 95% confidence interval (CI)=−1.04 to −0.37; P<0.0001], 4 hours (SMD=−0.61; 95% CI=−0.90 to −0.32; P<0.0001), and 12 hours postoperatively (SMD=−0.31; 95% CI=−0.60 to −0.03; P=0.03), and analgesic requirement (SMD=−0.83; 95% CI=−1.48 to −0.19; P=0.01), but reveals no obvious impact on pain scores at 24 hours postoperatively (SMD=0.09; 95% CI=−0.64 to 0.83; P=0.80) and the incidence of nausea or vomiting (risk ratio=0.69; 95% CI=0.40-1.20; P=0.19). Total adverse events in the levobupivacaine group seem to be lower than that in the control group (risk ratio=0.57; 95% CI=0.38-0.85; P=0.006).

Conclusion:
Intraperitoneal levobupivacaine provides additional benefits for pain relief after laparoscopic cholecystectomy.
A Novel Method of Nasojejunal Feeding and Gastric Decompression Using a Double Lumen Silicone Tube for Upper Gastrointestinal Obstruction
Authors: Tan Jih H. , Sivadurai Gunasunthari , Tan Henry C.L. , Tan Yun R. , Jahit Shukri , Hans Alexander Mahendran 
Published: January 2020

Background:
Provision of enteral nutrition with jejunal feeding in upper gastrointestinal obstruction is highly recommended. Access to jejunum can be obtained surgically, percutaneously, or endoscopically. Our institution routinely and preferentially utilizes a silicone nasojejunal tube that is inserted past the obstruction endoscopically. We use a custom dual channel tube that allows feeding at the distal tip and another channel 40 cm from the tip that enables decompression proximally. This is a report of our experience with this custom nasojejunal tube.

Methods:
This is a prospective observational study of 201 patients who underwent endoscopic nasojejunal wire-guided feeding tube insertions for obstruction of either the esophagus or the stomach including both benign and malignant pathologies between January 2015 to June 2018 in Hospital Sungai Buloh and Hospital Sultanah Aminah, Malaysia. The indications for tube insertion, insertion technique, and tube-related problems were described.

Results:
The nasojejunal tube was used to establish enteral feeding in patients with obstructing tumors of the distal esophagus in 65 patients (32.3%) and gastric outlet obstruction in 72 patients (35.8%). There were 54 patients (26.9%) who required reinsertion. The most common reason for reinsertion was unintentional dislodgement, where 32 patients (15.9%) followed by tube blockage 20 patients (10.0%). Using our method of advancement under direct vision, we had only 2 cases of malposition due to severely deformed anatomy. We had no incidence of aspiration in this group of patients and overall, the patients tolerated the tube well.

Conclusions:
The novel nasojejunal feeding tube with gastric decompression function is a safe and effective method of delivery of enteral nutrition in patients with upper gastrointestinal obstruction. These tubes if inserted properly are well tolerated with almost no risk of malposition and are tolerated well even for prolonged periods of time until definitive surgery could be performed.
Electroconvulsive Therapy in Veterans Health Administration Hospitals
Authors: Peltzman Talya , Gottlieb Daniel J. , Shiner Brian , Riblet Natalie , Watts Bradley V. 
Published: January 2020

Objectives
The body of large-scale, epidemiological research on electroconvulsive therapy (ECT) in the United States is limited. To address this gap, we assessed demographic, clinical, pharmacological, and mental health treatment history as well as 2-year mortality outcomes associated with ECT use in the largest U.S. health care system.

Methods
Among all patients who sought mental health care at Veterans Health Administration (VHA) hospitals in 2012, we used bivariate analyses to compare patients who did and not receive ECT during 2 years of follow-up. Among the population who received ECT, descriptive statistics were calculated to characterize prior mental health treatment patterns and ECT receipt.

Results
0.11% (N = 1616) of all VHA mental health patients in 2012 (N = 1,457,053) received ECT in 2 years of follow-up. There was significant regional variation in provision of ECT. Those who received ECT were more likely to have diagnoses of major depressive, bipolar, and personality disorders and were significantly more likely to have had a recent mental health inpatient stay (risk ratio, 6.94). Receipt of ECT was not associated with a difference in all-cause mortality (risk ratio, 0.88). Thirty-two percent of those who received ECT had no substantial antidepressant or therapy trial in the year before index mental health encounter.

Conclusions
Use of ECT in the VHA is rare. Patients who receive ECT have a complex and high-risk profile, not necessarily consistent with the most common indications for ECT.
Targeted and passive environmental DNA approaches outperform established methods for detection of quagga mussels,Dreissena rostriformis bugensisin flowing water
Authors: Blackman Rosetta C , Ling Kar Keun Sean , Harper Lynsey R , Shum Peter , Hänfling Bernd , Handley Lori Lawson 
Published: January 2020

AbstractThe early detection of invasive non-native species (INNS) is important for informing management actions. Established monitoring methods require the collection or observation of specimens, which is unlikely at the beginning of an invasion when densities are likely to be low. Environmental DNA (eDNA) analysis is a highly promising technique for the detection of INNS – particularly during the early stages of an invasion.Here, we compared the use of traditional kick-net sampling with two eDNA approaches (targeted detection using both conventional and quantitative PCR, and passive detection via metabarcoding with conserved primers) for detection of quagga mussel,Dreissena rostriformis bugensis;a high priority INNS, along a density gradient on the River Wraysbury, UK.All three molecular tools outperformed traditional sampling in terms of detection. Conventional PCR and qPCR both had 100% detection rate in all samples, and outperformed metabarcoding when the target species was at low densities. Additionally, quagga mussel DNA copy number (qPCR) and relative read count (metabarcoding) were significantly influenced by both mussel density and distance from source population, with distance being the most significant predictor.Synthesis and application. All three molecular approaches were more sensitive than traditional kick-net sampling for the detection of the quagga mussel in flowing water, and both qPCR and metabarcoding enabled estimates of relative abundance. Targeted approaches were more sensitive than metabarcoding, but metabarcoding has the advantage of providing information on the wider community, and consequently impacts of INNS.
Effective psychological treatment for PTSD changes the dynamics of specific large-scale brain networks
Authors: Charquero-Ballester Marina , Kleim Birgit , Vidaurre Diego , Ruff Christian , Stark Eloise , Tuulari Jetro J. , McManners Hugh , Bar-Haim Yair , Bouquillon Linda , Moseley Allison , Williams Steven C. R , Woolrich Mark , Kringelbach Morten L , Ehlers Anke 
Published: January 2020

AbstractVery little is known about the role of effective cognitive therapy in reversing imbalances in brain activity after trauma. We hypothesised that exaggerated threat perception characteristic of post-traumatic stress disorder (PTSD), and subsequent recovery from this disorder, are underpinned by changes in the dynamics of large-scale brain networks. Here, we use a novel data-driven approach with high temporal precision to find recurring brain networks from fMRI data and estimate when these networks become active during exposure to either trauma reminders or neutral pictures. We found that PTSD patients spend less time in two default mode sub-networks in contrast to trauma-exposed healthy controls, and that PTSD symptom severity correlates positively with time spent in the salience network during exposure to trauma reminders. The former are important for different aspects of self-referential processing and the latter for detection of threat. Importantly, the decreased time in the default mode sub-networks is rebalanced after successful cognitive therapy for PTSD. Our results show that remittance of PTSD through trauma-focused cognitive therapy is associated with the successful reinstatement of a healthy balance in self-referential and threat detection brain networks.
Structure-function relation of the developing calyx of Held synapsein vivo
Authors: Sierksma Martijn C. , Slotman Johan A. , Houtsmuller Adriaan B. , Borst J. Gerard G. 
Published: January 2020

AbstractIn adult rodents, a principal neuron in the medial nucleus of the trapezoid (MNTB) is generally contacted by a single, giant axosomatic terminal called the calyx of Held. How this one-on-one relation is established is still unknown, but anatomical evidence suggests that during development principal neurons are innervated by multiple calyces, which may indicate calyceal competition. However,in vivoelectrophysiological recordings from principal neurons indicated that only a single strong synaptic connection forms per cell. To test whether a mismatch exists between synaptic strength and terminal size, we compared the strength of synaptic inputs with the morphology of the synaptic terminals.In vivowhole-cell recordings of the MNTB neurons from newborn Wistar rats of either sex were made while stimulating their afferent axons, allowing us to identify multiple inputs. The strength of the strongest input increased to calyceal levels in a few days across cells, while the strength of the second strongest input was stable. The recorded cells were subsequently immunolabeled for vesicular glutamate transporters (VGluT) to reveal axosomatic terminals with structured-illumination microscopy. Synaptic strength of the strongest input was correlated with the contact area of the largest VGluT cluster at the soma (r= 0.8), and no indication of a mismatch between structure and strength was observed. Together, our data agree with a developmental scheme in which one input strengthens and becomes the calyx of Held, but not with multi-calyceal competition.Key points summaryDuring development the giant, auditory calyx of Held forms a one-to-one connection with a principal neuron of the medial nucleus of the trapezoid body.While anatomical studies described that most of the target cells are temporarily contacted by multiple calyces, multi-calyceal innervation was only sporadically observed inin vivorecordings, suggesting a structure-function discrepancy.We correlated synaptic strength of inputs, identified inin vivorecordings, with post hoc labeling of the recorded neuron and synaptic terminals containing vesicular glutamate transporters (VGluT).During development only one input increased to the level of the calyx of Held synapse, and its strength correlated with the large VGluT cluster contacting the postsynaptic soma.As neither competing strong inputs nor multiple large VGluT clusters on a single cell were observed, our findings did not indicate a structure-function discrepancy.
Origin of the nuclear proteome on the basis of pre-existing nuclear localization signals in prokaryotic proteins
Authors: Lisitsyna Olga M. , Kurnaeva Margarita A. , Arifulin Eugene A. , Shubina Maria Y. , Musinova Yana R. , Mironov Andrey A. , Sheval Eugene V. 
Published: January 2020

AbstractThe origin of the selective nuclear protein import machinery, which consists of nuclear pore complexes and adaptor molecules interacting with the nuclear localization signals (NLSs) of cargo molecules, was one of the most important events in the evolution of the eukaryotic cell. How the proteins were selected for import into the forming nuclei remains an open question. Here, we demonstrate that functional NLSs may be integrated inside nucleotide-binding domains of both eukaryotic and prokaryotic proteins and may co-evolve with these domains. We propose that the pre-existence of NLSs inside prokaryotic proteins dictated, at least partially, the nuclear proteome composition.
p27 regulates the autophagy-lysosomal pathway via the control of Ragulator and mTOR activity in amino acid deprived cells
Authors: Nowosad Ada , Jeannot Pauline , Callot Caroline , Creff Justine , Perchey Renaud T. , Joffre Carine , Codogno Patrice , Manenti Stephane , Besson Arnaud 
Published: January 2020

SummaryAutophagy is a catabolic process whereby cytoplasmic components are degraded within lysosomes, allowing cells to maintain energy homeostasis during nutrient depletion. Several studies have shown that the CDK inhibitor p27Kip1promotes starvation-induced autophagy. However, the underlying mechanism remains unknown. Here, we report that in amino acid deprived cells, p27 controls autophagy via an mTORC1-dependent mechanism. During prolonged amino acid starvation, a fraction of p27 is recruited to lysosomes where it interacts with LAMTOR1, a component of the Ragulator complex required for mTORC1 lysosomal localization and activation. p27 binding to LAMTOR1 prevents Ragulator assembly and function and subsequent mTORC1 activation, thereby promoting autophagy. Conversely, upon amino acid withdrawal, p27−/−cells exhibit elevated mTORC1 signaling, impaired lysosomal activity and autophagy, and resistance to apoptosis. This is associated with sequestration of TFEB in the cytoplasm, preventing the induction of lysosomal genes required for lysosomal function. Silencing of LAMTOR1 or mTOR inhibition restores autophagy and induces apoptosis in p27−/−cells. Together, these results reveal a direct, coordinated regulation between the cell cycle and cell growth machineries.
Representation ofk-mer sets using spectrum-preserving string sets
Authors: Rahman Amatur , Medvedev Paul 
Published: January 2020

AbstractGiven the popularity and elegance ofk-mer based tools, finding a space-efficient way to represent a set ofk-mers is important for improving the scalability of bioinformatics analyses. One popular approach is to convert the set ofk-mers into the more compact set of unitigs. We generalize this approach and formulate it as the problem of finding a smallest spectrum-preserving string set (SPSS) representation. We show that this problem is equivalent to finding a smallest path cover in a compacted de Bruijn graph. Using this reduction, we prove a lower bound on the size of the optimal SPSS and propose a greedy method called UST that results in a smaller representation than unitigs and is nearly optimal with respect to our lower bound. We demonstrate the usefulness of the SPSS formulation with two applications of UST. The first one is a compression algorithm, UST-Compress, which we show can store a set ofk-mers using an order-of-magnitude less disk space than other lossless compression tools. The second one is an exact statick-mer membership index, UST-FM, which we show improves index size by 10-44% compared to other state-of-the-art low memory indices. Our tool is publicly available at:https://github.com/medvedevgroup/UST/.