bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Neoadjuvant Chemotherapy Change the Role of Regional Lymphadenectomy in Pancreatic Cancer Survival?
Authors: Macedo Francis Igor , Picado Omar , Hosein Peter J. , Dudeja Vikas , Franceschi Dido , Mesquita-Neto Jose Wilson , Yakoub Danny , Merchant Nipun B. 
Published: June 2019

Objectives
The objective of this study was to evaluate the role of lymph node (LN) dissection and staging in outcomes of patients with pancreatic adenocarcinoma (PDAC) who underwent neoadjuvant chemotherapy (NAC).

Methods
National Cancer Database was queried for patients with stages I to III PDAC diagnosed between 2004 and 2014. Overall survival (OS) was derived from Kaplan-Meier methods, and Cox-regression model was used to evaluate associations between the number of LN examined, number of positive nodes, and LN ratio with OS.

Results
A total 35,599 patients were included, 3395 (9%) underwent NAC, 19,865 (56%) received adjuvant chemotherapy (AC), and 12,299 (35%) underwent surgery alone. Cox-regression showed superior OS in NAC compared with AC and surgery alone (26 vs 23 vs 14 months, P < 0.001). Minimum number of LN examined affecting OS was 8 LNs in NAC (23.8 vs 26.6 months, P = 0.029), and 12 LNs in AC group (22 vs 23.1 months, P = 0.028). Lymph node ratio cutoff of greater than 0.2 was associated with decreased OS (19.4 vs 24.4 months, P < 0.001).

Conclusions
Neoadjuvant chemotherapy is associated with improved survival in PDAC. Lymph node yield remains a significant prognostic factor after NAC, whereas the minimum number of harvested LNs associated with sufficient staging and survival is decreased.
Perceived Family Impact During Children’s Hospitalization for Treatment of Acute Lymphoblastic Leukemia
Authors: Lyu Qi-yuan , Wong Frances K.Y. , You Li-ming , Li Xian-wen 
Published: June 2019

Background
Improved survival rates of acute lymphoblastic leukemia (ALL) in children are often associated with repeated and prolonged hospitalization, creating an immensely stressful situation for the family.

Objective
The aims of this study were to assess perceived family impact and coping during the child’s hospitalization for ALL treatment and identify potential predictors of perceived family impact.

Interventions/Methods
A total of 212 families with children hospitalized participated. The hospitalization impact and coping scales were used to assess perceived family impact and coping, respectively.

Results
The mean (SD) total score for perceived family impact was 88.11 (22.39); social impact received the highest average score. The mean (SD) total score for family coping was 39.02 (9.84). A significant decrease in family coping was associated with more readmissions. Predictors of perceived family impact were severity of the child’s illness, total days of all admissions, and coping, accounting for 37% of the observed variance.

Conclusions
Families were moderately affected by children’s hospitalizations; social functioning was most affected. Families’ perceived coping effectiveness decreased as the readmissions increased. The higher risk category a child’s diagnosis is, the longer a child’s hospitalization is, and the less perceived coping effectiveness, the higher family perceived impact.

Implications for Practice
The findings provide a direction for the development of family-centered supportive intervention programs. Nurses should be aware that the total days of admission and severity of a child’s illness are significant factors associated with perceived family impact and likely justify special attention. Family coping enhancement interventions could alleviate perceived family impact.
CLINICAL NURSE SPECIALIST PRACTICE INTERVENTIONS FOR SECOND VICTIMS OF ADVERSE PATIENT EVENTS
Authors: Bleazard Mark 
Published: June 2019

Background:
Second-victim impact describes emotional suffering that occurs secondary to an adverse patient event and occurs in approximately half of all healthcare providers. Immediate intervention is needed to reduce consequences including nursing turnover, job absenteeism, repeat adverse events, professional burnout, and posttraumatic stress.

Purpose:
To provide clinical nurse specialists a summary of second-victim impact secondary to adverse patient events, a review of associated negative outcomes, and clinical nurse specialist practice recommendations.

Recommendations:
Clinical nurse specialist nursing interventions include implementation of validated screening tools, identification of healthcare providers at high risk of second-victim impact, recognition of signs of second-victim impact, facilitating supportive clinical debriefings, providing supporting dialogue, and mentorship through stages of recovery and the institutional response. Clinical nurse specialist organization/system interventions to reduce the consequences of second-victim impact include supporting a culture of safety, leading organizational improvement, as well as advocating for education and support for second victims on the national level.

Conclusions:
Clinical nurse specialists have the potential to mitigate the effects of second-victim impact associated with adverse patient events and secondary complications through use of evidence-based practice interventions.
Self-Reported History of Chlamydia or Gonorrhea Testing Among Heterosexual Women at High Risk of HIV Infection, National HIV Behavioral Surveillance, 2013
Authors: Johnson Jones Michelle L. , Kirkcaldy Robert D. , An Qian , Gorwitz Rachel , Bernstein Kyle , Paz-Bailey Gabriela 
Published: June 2019

Background
The US Preventive Services Task Force recommends annual chlamydia and gonorrhea screening for sexually active women <25 and ≥25 years old with associated risk factors. We sought to determine self-reported chlamydia and gonorrhea testing and diagnosis rates in the past 12 months in a community-based sample of heterosexual women at high risk of HIV infection.

Methods
We used National HIV Behavioral Surveillance data from 2013 when surveillance was conducted in heterosexual adults with low social economic status. Our analysis was restricted to 18- to 44-year-old women who answered questions regarding chlamydia/gonorrhea testing and diagnosis in the previous 12 months. We calculated the percentage reporting testing and diagnosis. Poisson regressions with generalized estimating equations clustered on recruitment chain were used to assess factors associated with testing and diagnosis.

Results
Among 18- to 24-year-old women (n = 1017), 61.0% self-reported chlamydia testing and 57.6% gonorrhea testing in the past 12 months. Among 25- to 44-year-old women (n = 2322), 49.0% and 47.0% reported chlamydia and gonorrhea testing, respectively. Among the subset of 25- to 44-year-old women who met screening criteria, 51.2% reported chlamydia testing. Having seen a medical provider and HIV testing (past 12 months) were associated with chlamydia/gonorrhea testing in both age groups. Self-reported chlamydia (18–24 years, 21.4%; 25–44 years, 12.2%) and gonorrhea diagnoses (18–24 years, 8.4%; 25–44 years, 6.6%) were common.

Conclusions
A substantial number of eligible women may not have been screened for chlamydia/gonorrhea. Renewed efforts to facilitate screening may prevent sequelae and support disease control activities.
Surgical Techniques for the Laparoscopic Treatment of Bile Duct Stones in Patients With a History of Upper Abdominal Operations: Retrospective Cohort Study
Authors: Tan Jie-hui , Zhou Lei , Zhang Guo-wei 
Published: June 2019

Purpose:
Few authors have studied applying the laparoscopic approach in patients with previous upper abdominal operations, but no comparison has been made between laparoscopic and open approaches in patients with previous upper abdominal operations. This article aims to introduce surgical techniques and details in treatment to surgeons specialized in minimally invasive surgery.

Materials and Methods:
From January 2010 to January 2018, 460 eligible patients were divided into 3 groups and analyzed retrospectively. Group A: patients with a history of upper abdominal operations who underwent laparoscopy (n=124); group B: patients without a history of upper abdominal operations who underwent laparoscopy (n=140); and group C: patients with a history of upper abdominal operations who underwent an open operation (n=196). Group A was the experimental group; groups B and C served as the control groups.

Results:
No significant difference was found between groups A and B. Significant differences were found between groups A and C in estimated blood loss (258.3±67.2 vs. 424.7±103.7 mL, P<0.001), postoperative hospitalization (5.7±2.3 vs. 10.2±3.1 d, P<0.001), and postoperative complications (16.1% vs. 42.9%, P=0.013). The final rate of stones clearance was 100% in 3 groups. The total rate of stone recurrence was 7.8%.

Conclusions:
Laparoscopy with certain surgical techniques was feasible, effective, and advantageous for patients with previous upper abdominal operations by experienced surgeons. It is necessary for surgeons to have advanced skills and surgical techniques to achieve a successful laparoscopy.
Photovoltaic stimulation efficiently evokes network-mediated activity of retinal ganglion cells
Authors: Chenais Naïg A. L. , Airaghi Leccardi Marta J. I. , Ghezzi Diego 
Published: June 2019

AbstractObjectivePhotovoltaic retinal prostheses theoretically offer the possibility of standalone high-resolution electrical stimulation of the retina. However, in artificial vision, achieving locally selective epiretinal stimulation is particularly challenging, on the grounds of axonal activation and electrical cell coupling.ApproachHere we show that electrical and photovoltaic stimulation of dystrophic retinal circuits with capacitive-like pulses leads to a greater efficiency for indirect network-mediated activation of retinal ganglion cells. In addition, a biophysical model of the inner retina stimulation is proposed to investigate the waveform and duration commitments in the genesis of indirect activity of retinal ganglion cells.Main resultsBoth in-vitro and in-silico approaches suggest that the application of long voltage pulses or gradual voltage changes are more effective to sustainably activate the inner excitatory and inhibitory layers of the retina, thus leading to a reproducible indirect response. The involvement of the inhibitory feedback from amacrine cells in the forming of indirect patterns represents a novel biological tool to locally cluster the response of the retinal ganglion cells.SignificanceThese results demonstrate that recruiting inner retina cells with epiretinal stimulation enables not only to bypass axonal stimulation but also to obtain a more focal activation thanks to the natural lateral inhibition. In this perspective, the use of capacitive-like waveforms generated by photovoltaic prostheses may allow improving the neural response resolution while standing high-frequency stimulation.
Mice with GNAO1 R209H Movement Disorder Variant Display Hyperlocomotion Alleviated by Risperidone
Authors: Larrivee Casandra L. , Feng Huijie , Quinn Josiah A. , Shaw Vincent S. , Leipprandt Jeffrey R. , Demireva Elena Y. , Xie Huirong , Neubig Richard R. 
Published: June 2019

AbstractNeurodevelopmental disorder with involuntary movements (NEDIM, OMIM: 617493) is a severe, early onset neurological condition characterized by a delay in psychomotor development, hypotonia, and hyperkinetic involuntary movements. Heterozygous de novo mutations in the GNAO1 gene cause NEDIM. Gαo, the gene product of GNAO1, is the alpha subunit of Go, a member of the heterotrimeric Gi/o family of G-proteins. Go is found abundantly throughout the brain but the pathophysiological mechanisms linking Gαo functions to clinical manifestations of GNAO1-related disorders are still poorly understood. One of the most common mutant alleles among the GNAO1 encephalopathies is the c.626G>A or p.Arg209His (R209H) mutation. We developed heterozygous knock-in Gnao1+/R209H mutant mice using CRISPR/Cas9 methodology to assess whether a mouse model could replicate aspects of the NEDIM clinical pattern. Mice carrying the R209H mutation exhibited increased locomotor activity and a modest gait abnormality at 8-12 weeks. In contrast to mice carrying other mutations in Gnao1, the Gnao1+/R209H mice did not show enhanced seizure susceptibility. Levels of protein expression in multiple brain regions were unchanged from WT mice but the nucleotide exchange rate of mutant R209H Gαo was 9 times faster than WT. The atypical neuroleptic risperidone has shown efficacy in a patient with the R209H mutation. It also alleviated the hyperlocomotion phenotype observed in our mouse model but suppressed locomotion in WT mice as well. In this study, we show that Gnao1+/R209H mice mirror elements of the patient phenotype and respond to an approved pharmacological agent.
Evaluation of network architecture and data augmentation methods for deep learning in chemogenomics
Authors: Playe Benoit , Stoven Véronique 
Published: June 2019

AbstractAmong virtual screening methods that have been developed to facilitate the drug discovery process, chemogenomics presents the particularity to tackle the question of predicting ligands for proteins, at at scales both in the protein and chemical spaces. Therefore, in addition to to predict drug candidates for a given therapeutic protein target, like more classical ligand-based or receptor-based methods do, chemogenomics can also predict off-targets at the proteome level, and therefore, identify potential side-effects or drug repositioning opportunities. In this study, we study and compare machine-learning and deep learning approaches for chemogenomics, that are applicable to screen large sets of compounds against large sets of druggable proteins. State-of-the-art drug chemogenomics methods rely on expert-based chemical and protein descriptors or similarity measures. The recent development of deep learning approaches enabled to design algorithms that learn numerical abstract representations of molecular graphs and protein sequences in an end-to-end fashion, i.e., so that the learnt features optimise the objective function of the drug-target interaction prediction task. In this paper, we address drug-target interaction prediction at the druggable proteome-level, with what we define as the chemogenomic neuron network. This network consists of a feed-forward neuron network taking as input the combination of molecular and protein representations learnt by molecular graph and protein sequence encoders. We first propose a standard formulation of this chemogenomic neuron network. Then, we compare the performances of the standard chemogenomic network to reference deep learning or shallow (machine-learning without deep learning) methods. In particular, we show that such a representation learning approach is competitive with state-of-the-art chemogenomics with shallow methods, but not ultimately superior. We evaluate the most promising neuron network architectures and data augmentation techniques, such as multi-view and transfer learning, to improve the prediction performance of the chemogenomic network. Our results shed new insights on the design of chemogenomics approaches based on representation learning algorithms. Most importantly, we conclude from our observations that a promising research direction is to integrate heterogeneous sources of data such as various bioactivity datasets, or independently, multiple molecule and protein attribute views, instead of focusing on sophisticated, yet intuitively relevant, encoder’s neuron network architecture.
Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia
Authors: Hong Bo-young , Ideta Takayasu , Igarashi Yuichi , Tan Yuliana , DiSiena Michael , Mo Allen , Birk John W. , Forouhar Faripour , Devers Thomas J. , Weinstock George M. , Rosenberg Daniel W. 
Published: June 2019

AbstractAberrant crypt foci (ACF) are the earliest morphologically identifiable lesion in the colon that can be detected by high-definition chromoendoscopy with contrast dye-spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-associated bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Our study cohort included a total of 16 subjects with no identifiable proximal lesions (either ACF or polyp), 14 subjects with at least 1 ACF but no polyp(s), and 15 subjects with both at least 1 ACF and a synchronous proximal polyp(s) detected at colonoscopy. Bacterial cells adherent to the epithelia of ACF and normal mucosa were visualized by in situ hybridization within confocal sections. Bacterial DNA isolated from biopsies was used to construct PCR amplicon libraries targeting the V4 hypervariable region of the 16S rRNA gene, which were then sequenced on the Illumina platform. ACF showed significantly greater heterogeneity in their bacterial profiles compared to normal mucosa. Interestingly, one of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. The observed dysbiosis is more prominent within the colonic epithelium that also harbors synchronous polyps. Finally using DNA-mass spectrometry to evaluate a panel of colorectal cancer hot-spot mutations present in the ACF, we found that several APC gene mutations (R1450*, R876*, S1465fs*3) were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations (G12V, G12D) were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate (or impede) their progression towards more advanced forms of neoplasia.
Acid Experimental Evolution of the Extremely Halophilic Archaeon Halobacterium sp. NRC-1 Selects Mutations Affecting Arginine Transport and Catabolism
Authors: Kunka Karina S. , Griffith Jessie M. , Holdener Chase , Bischof Katarina M. , Li Haofan , DasSarma Priya , DasSarma Shiladitya , Slonczewski Joan L. 
Published: June 2019

ABSTRACTBackgroundHalobacterium sp. NRC-1 (NRC-1) is an extremely halophilic archaeon that is adapted to multiple stressors such as UV, ionizing radiation and arsenic exposure. We conducted experimental evolution of NRC-1 under acid stress. NRC-1 was serially cultured in CM+ medium modified by four conditions: optimal pH (pH 7.5), acid stress (pH 6.3), iron amendment (600 μM ferrous sulfate, pH 7.5), and acid plus iron (pH 6.3, with 600 μM ferrous sulfate). For each condition, four independent lineages of evolving populations were propagated. After 500 generations, 16 clones were isolated for phenotypic characterization and genomic sequencing.ResultsGenome sequences of all 16 clones revealed 378 mutations, of which 90% were haloarchaeal insertion sequences (ISH) and ISH-mediated large deletions. This proportion of ISH events in NRC-1 was five-fold greater than that reported for comparable evolution of E. coli. One acid-evolved clone had increased fitness compared to the ancestral strain when cultured at low pH. Seven of eight acid-evolved clones had a mutation within or upstream of arcD, which encodes an arginine-ornithine antiporter; no non-acid adapted strains had arcD mutations. Mutations also affected the arcR regulator of arginine catabolism, which protects bacteria from acid stress by release of ammonia. Two acid-adapted strains shared a common mutation in bop, which encodes the bacteriorhodopsin light-driven proton pump. Unrelated to pH, one NRC-1 minichromosome (megaplasmid) pNRC100 had increased copy number, and we observed several mutations that eliminate gas vesicles and arsenic resistance. Thus, in the haloarchaeon NRC-1, as in bacteria, pH adaptation was associated with genes involved in arginine catabolism and proton transport.ConclusionsOur study is among the first to report experimental evolution with multiple resequenced genomes of an archaeon. Haloarchaea are polyextremophiles capable of growth under environmental conditions such as concentrated NaCl and desiccation, but little is known about pH stress. Halobacterium sp. NRC-1 (NRC-1) is considered a model organism for the feasibility of microbial life in iron-rich brine on Mars. Interesting parallels appear between the molecular basis of pH adaptation in NRC-1 and in bacteria, particularly the acid-responsive arginine-ornithine system found in oral streptococci.
TEAD4/YAP1/WWTR1 prevent the premature onset of pluripotency prior to the 16-cell stage
Authors: Frum Tristan , Watts Jennifer , Ralston Amy 
Published: June 2019

AbstractIn the mouse embryo, pluripotent cells arise inside the embryo around the 16-cell stage. During these early stages, Sox2 is the only gene whose expression is known to be induced specifically within inside cells as they are established. To understand how pluripotent cells are created, we investigated the mechanisms regulating the initial activation of Sox2 expression. Surprisingly, Sox2 expression initiated normally in the absence of both Nanog and Oct4, highlighting differences between embryo and stem cell models of pluripotency. However, we observed precocious, ectopic expression of Sox2 prior to the 16-cell stage in the absence of Yap1, Wwtr1, and Tead4. Interestingly, the repression of premature Sox2 expression was sensitive to LATS1/2 activity, even though it normally does not limit TEAD4/YAP1/WWTR1 activity during these early stages. Finally, we present evidence for direct transcriptional repression of Sox2 by YAP1/WWTR1/TEAD4. Taken together, our observations reveal that, while embryos are initially competent to express Sox2 as early as the 4-cell stage, transcriptional repression prevents the premature expression of Sox2, thereby restricting the pluripotency program to the stage when inside cells are first created.