bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted PCR Array Analysis of Genes in Innate Immunity and Glucocorticoid Signaling Pathways in Mice Cochleae Following Acoustic Trauma
Authors: Maeda Yukihide , Kariya Shin , Omichi Ryotaro , Noda Yohei , Sugaya Akiko , Fujimoto Shohei , Nishizaki Kazunori 
Published: July 2018

Aim:
To comprehensively analyze cochlear gene expressions related to innate immunity and glucocorticoid signaling at onset of acute noise-induced hearing loss (NIHL).

Background:
Recent studies suggested innate immunity is involved in the cochlear pathology of NIHL. Glucocorticoids may modulate immune actions in cochleae.

Methods:
Mice were exposed to 120 dB-octave band noise for 2 hours. Twelve hours later, a targeted PCR array analyzed cochlear expressions of 84 key genes in inflammation and immune pathways and 84 genes in the glucocorticoid signaling pathway. Real-time RT-PCR was used to analyze expression of two immune-related genes, Ccl12 and Glycam1, in noise-exposed cochleae with or without dexamethasone.

Result:
In inflammatory and immune gene pathways, 31.0% (26/84 genes) were significantly upregulated (>2-fold change) or downregulated (<0.5-fold change) (p < 0.05) in noise-exposed cochleae compared with controls. Sixteen of these differentially expressed genes (DEGs) encoded chemokines. DEGs included Ccl12, Ccl2, Ccl4, Ccl7, Cxcl1, Cxcl10, and Ptgs2 (upregulated genes), and Ccr7, Cxcr2, Kng1, Ltb, and Tnfsf14 (downregulated genes). In the glucocorticoid signaling pathway, 92.9% (78/84 genes) were unchanged in noise-exposed cochleae without dexamethasone administration. Cochlear expressions of Ccl12 and Glycam1 were significantly upregulated by noise and downregulated by dexamethasone.

Conclusion:
The targeted PCR array demonstrated that several dozen genes involved in innate immunity are actively regulated in cochleae with NIHL. The glucocorticoid signaling pathway was not endogenously regulated at 12 hours post-noise trauma. Systemic dexamethasone downregulated Ccl12 and Glycam1, which are upregulated in noise-exposed cochleae. These data may provide a basis for genomic medicine treatment of acute sensorineural hearing loss.
Readmission Rates and Skilled Nursing Facility Utilization After Major Inpatient Surgery
Authors: Chen Lena M. , Acharya Yubraj , Norton Edward C. , Banerjee Mousumi , Birkmeyer John D. 
Published: July 2018

Background:
There is widespread interest in reducing use of postacute care (ie, care after hospital discharge) following major surgery, provided that such reductions do not worsen quality outcomes such as readmission rates.

Objectives:
To describe the association between changes in skilled nursing facility (SNF) use and changes in readmission rates after surgery.

Research Design:
This was a observational study.

Subjects:
Fee-for-service Medicare beneficiaries undergoing coronary artery bypass grafting (CABG) or total hip replacement (THR) from 2008 to 2013.

Measures:
Primary exposure was risk-adjusted SNF use initiated 0–2 days after hospital discharge, and the primary outcome was risk-adjusted readmission rates from 3 to 30 days after discharge.

Results:
Among 176,994 patients who underwent CABG at 804 hospitals and 233,955 patients who underwent THR at 1220 hospitals, hospital-level SNF utilization increased after CABG (16.4%–19.0%, P=0.001) and THR (40.8%–45.5%, P<0.001), from 2008 to 2013. Hospital readmission rates decreased for CABG (14.7%–12.7%, P<0.001) but did not change for THR (4.9%–4.8%, P=0.55), from 2008 to 2013. However, there was wide variation in hospital-level change in readmission rates. After adjusting for hospital characteristics and baseline readmission rates, there was no statistically significant association between change in SNF use and change in readmission rates (0.017 and 0.011 percentage point increase in SNF use for every one percentage point increase in readmission rates for CABG and THR respectively, P=0.58 and 0.32).

Conclusions:
Changes in use of postacute care after THR and CABG have not been associated with changes in readmission rates.
Defining Multimorbidity in Older Surgical Patients
Authors: Silber Jeffrey H. , Reiter Joseph G. , Rosenbaum Paul R. , Zhao Qingyuan , Small Dylan S. , Niknam Bijan A. , Hill Alexander S. , Hochman Lauren L. , Kelz Rachel R. , Fleisher Lee A. 
Published: July 2018

Background:
There are numerous definitions of multimorbidity (MM). None systematically examines specific comorbidity combinations accounting for multiple testing when exploring large datasets.

Objectives:
Develop and validate a list of all single, double, and triple comorbidity combinations, with each individual qualifying comorbidity set (QCS) more than doubling the odds of mortality versus its reference population. Patients with at least 1 QCS were defined as having MM.

Research Design:
Cohort-based study with a matching validation study.

Subjects:
All fee-for-service Medicare patients between age 65 and 85 without dementia or metastatic solid tumors undergoing general surgery in 2009–2010, and an additional 2011–2013 dataset.

Measures:
30-day all-location mortality.

Results:
There were 576 QCSs (2 singles, 63 doubles, and 511 triples), each set more than doubling the odds of dying. In 2011, 36% of eligible patients had MM. As a group, multimorbid patients (mortality rate=7.0%) had a mortality Mantel-Haenszel odds ratio=1.90 (1.77–2.04) versus a reference that included both multimorbid and nonmultimorbid patients (mortality rate=3.3%), and Mantel-Haenszel odds ratio=3.72 (3.51–3.94) versus only nonmultimorbid patients (mortality rate=1.6%). When matching 3151 pairs of multimorbid patients from low-volume hospitals to similar patients in high-volume hospitals, the mortality rates were 6.7% versus 5.2%, respectively (P=0.006).

Conclusions:
A list of QCSs identified a third of older patients undergoing general surgery that had greatly elevated mortality. These sets can be used to identify vulnerable patients and the specific combinations of comorbidities that make them susceptible to poor outcomes.
Relation Between Memory Impairment and the Fornix Injury in Patients With Mild Traumatic Brain Injury
Authors: Jang Sung Ho , Kim Seong Ho , Do Lee Han 
Published: July 2018

Objective
We investigated the relation between memory impairment and the fornix injury in patients with mild traumatic brain injury, using diffusion tensor tractography.

Design
Eighty-six chronic patients with mild traumatic brain injury and 50 normal control subjects were recruited. Fractional anisotropy and fiber volume were measured for each reconstructed fornix. The patients were classified according to the following three types: type A (47 patients), intact integrity of both fornical crura; type B (27 patients), showed a discontinuation in either fornical crus; and type C (12 patients), discontinuations in both fornical crura. The Memory Assessment Scale was used for evaluation of memory function.

Results
Fractional anisotropy and fiber volume showed weak positive correlations with global memory of Memory Assessment Scale, respectively (r = 0.303, P = 0.006; r = 0.271, P = 0.014). Significant difference in the global memory of Memory Assessment Scale was observed between type A and B and between type A and C without difference between type B and C (P < 0.05).

Conclusion
It seems that the diffusion tensor tractography parameters of the fornix and the integrity of fornical crus can be used as a biomarker for axonal injury of the fornix in patients with mild traumatic brain injury.
Characteristics of Autonomic Activity and Reactivity During Rest and Emotional Processing and Their Clinical Correlations in Somatic Symptom Disorder
Authors: Lee Deokjong , Kim Se Joo , Cheon Jooah , Hwang Eun Hee , Jung Young-chul , Kang Jee In 
Published: July 2018

ABSTRACT

Objective
Altered autonomic nervous system activity is considered to be involved in the pathophysiology of somatic symptom disorder (SSD). This study aimed to investigate whether patients with SSD have disturbed autonomic activity during rest and reactivity to emotional processing and whether altered autonomic nervous system correlates with clinical characteristics and interoceptive accuracy in SSD.

Methods
We recruited 23 patients with SSD and 20 healthy controls. Heart rate variability (HRV) was assessed during recording at rest and during performance of an emotional face dot-probe task. Alpha-amylase responses were also assessed. Patients with SSD completed a self-assessment survey and heart beat perception task, which reflects interoceptive awareness.

Results
Patients with SSD had lower low-frequency HRV, high-frequency HRV, standard deviation of normal to normal R-R intervals (SDNN), and proportion of successive R-R intervals greater than 50 milliseconds (pNN50) at rest (p < .05). The reactivity scores (during-task activity minus resting activity) for SDNN and pNN50 were significantly different between patients with SSD and controls (SDNN: p = .013; pNN50: p = .008). In addition, resting HRV parameters (low-frequency, high-frequency, SDNN, pNN50) correlated with heart beat perception error (p < .01) in patients with SSD. No significant differences in α-amylase activity were found.

Conclusions
Our findings showed that patients with SSD have altered resting-state autonomic activity and reactivity to emotional processing, and the resting-state autonomic activity correlated with their interoceptive awareness. These findings suggest that disturbed interactions between the autonomic nervous, affective, and interoceptive systems may be involved in the pathophysiology of SSD.
Analgesic Use in Dutch Patients With Osteoarthritis
Authors: van den Driest Jacoline J. , Pijnenburg Patrick , Bindels Patrick J. E. , Bierma-Zeinstra Sita M. A. , Schiphof Dieuwke 
Published: July 2018

Objective
The aim of this study was to examine which analgesics are used by patients with osteoarthritis (OA)–related pain and how the analgesics are used in the preceding month. In addition, their beliefs about (pain) medication and the rationale of those declining to use analgesics were explored.

Methods
An online cross-sectional survey was sent to 1521 patients participating in the panel of the Dutch Arthritis Foundation. Descriptive analyses and logistic regression were used to analyze data.

Results
Of the 842 participants (56%) with OA that responded, 70% had generalized OA, 26% had concomitant fibromyalgia, and 34% had another musculoskeletal morbidity. Of all participants, 71% used analgesics, and 34% used more than 1 type. Analgesics were used for more than 14 days in the preceding month by most participants, with paracetamol being used most frequently (51%). Doses used were predominantly lower than the daily defined dose: 58.2% for paracetamol, 31.2% for nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors, and 75.7% for weak opioids. Compared with participants with concomitant fibromyalgia or other musculoskeletal morbidities, participants with OA alone significantly more frequently declined to use analgesics (p < 0.01) and significantly less frequently used 2 or 3 types of analgesics (p < 0.05).

Conclusions
In this population with generalized OA and musculoskeletal comorbidities, medication use was high, and more than 1 type of analgesic was frequently used. Patients with concomitant fibromyalgia or other musculoskeletal morbidities more frequently used 2 or 3 types of analgesics; however, this use was often intermittent and in low doses. Medication use on a daily basis and at higher doses may lead to improved analgesic effect.
Postoperative Complications and Health-related Quality of Life 10 Years After Esophageal Cancer Surgery
Authors: Kauppila Joonas H. , Johar Asif , Lagergren Pernilla 
Published: July 2018

Objective:
To evaluate the impact of postoperative complications on health-related quality of life (HRQOL) up to 10 years after surgery for esophageal cancer.

Background:
The impact of postoperative complications on HRQOL past 5 years is unknown.

Methods:
Some 616 patients undergoing open esophageal cancer surgery between April 2, 2001 and December 31, 2005 in Sweden were enrolled in this population-based, nationwide, and prospective cohort study. Exposure was the occurrence of predefined postoperative complications, and the outcome was HRQOL evaluated by validated European Organization for Research and Treatment of Cancer questionnaires at 6 months, 3, 5, and 10 years after surgery. Linear mixed models, adjusted for longitudinal HRQOL in the general population and confounders, provided mean score differences (MDs) with 95% confidence intervals (CIs) for each HRQOL item and scale in patients with or without postoperative complications.

Results:
At 10 years, 104 (17%) patients were alive and 92 (88%) answered the HRQOL questionnaires. Of these, 37 (40%) had at least 1 predefined postoperative complication. Twelve of the 25 scales and items were significantly worse in patients with postoperative complications 10 years after surgery, for example, physical function (MD −15, 95% CI −24 to −7), fatigue (MD 16, 95% CI 5–26), pain (MD 18, 95% CI 7–30), dyspnea (MD 15, 95% CI 2–27), insomnia (MD 20, 95% CI 8–32), and eating problems (MD 14, 95% CI 3–24) compared to patients without complications.

Conclusions:
Postoperative complications are associated with considerably impaired HRQOL up to 10 years after esophageal cancer surgery.
A transition from SoxB1 to SoxE transcription factors is essential for progression from pluripotent blastula cells to neural crest cells
Authors: Buitrago-Delgado Elsy , Schock Elizabeth N. , Nordin Kara , LaBonne Carole 
Published: July 2018

AbstractThe neural crest is a stem cell population unique to vertebrate embryos that gives rise to derivatives from multiple embryonic germ layers. The molecular underpinnings of potency that govern neural crest potential are highly conserved with that of pluripotent blastula stem cells, suggesting that neural crest cells may have evolved through retention of aspects of the pluripotency gene regulatory network (GRN). A striking difference in the regulatory factors utilized in pluripotent blastula cells and neural crest cells is the deployment of different subfamilies of Sox transcription factors; SoxB1 factors play central roles in the pluripotency of naïve blastula and ES cells, whereas neural crest cells require SoxE function. Here we explore the shared and distinct activities of these factors to shed light on the role that this molecular hand-off of Sox factor activity plays in the genesis of neural crest and the lineages derived from it. Our findings provide evidence that SoxB1 and SoxE factors have both overlapping and distinct activities in regulating pluripotency and lineage restriction in the embryo. We hypothesize that SoxE factors may transiently replace SoxB1 factors to control pluripotency in neural crest cells, and then poise these cells to contribute to glial, chondrogenic and melanocyte lineages at stages when SoxB1 factors promote neuronal progenitor formation.
Selection of an Appropriate Empiric Antibiotic Regimen in Culture-Negative Hematogenous Vertebral Osteomyelitis
Authors: Park Ki-Ho , Kim Dong Youn , Lee Yu-Mi , Lee Mi Suk , Kang Kyung-Chung , Lee Jung Hee , Park Seong Yeon , Moon Chisook , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Bae In-Gyu , Cho Oh-Hyun 
Published: July 2018

AbstractThe aim of this study was to determine which antibiotic combinations are appropriate for culture-negative hematogenous vertebral osteomyelitis (HVO), based on the antibiotic-susceptibility pattern of organisms isolated from cases of culture-proven HVO. We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), aerobic gram-negative bacteria (21.8%), and Streptococcus species (11.7%). Extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Based on the susceptibility results of isolated organisms, levofloxacin plus rifampicin was appropriate in 73.5%, levofloxacin plus clindamycin in 71.2%, and amoxicillin-clavulanate plus ciprofloxacin in 64.5% of cases. These oral combinations were more appropriate for treating community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively) than healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). In conclusion, in a setting with a high prevalence of MRSA HVO, oral antibiotic combinations may be suboptimal for treatment of culture-negative HVO and should be used only in patients with community-acquired HVO. Vancomycin combined with fluoroquinolone or a broad-spectrum cephalosporin was appropriate in most cases of HVO in this study.
Chemical Characterization of Interacting Genes in Few Subnetworks of Alzheimer’s Disease
Authors: Sengupta Antara , Manners Hazel Nicolette , Choudhury Pabitra Pal , Roy Swarup 
Published: July 2018

ABSTRACTA number of genes have been identified as a key player in Alzheimer’s disease (AD). Topological analysis of co-expression network reveals that key genes are mostly central or hub genes. The association between a hub gene and its neighbour genes can be derived easily using relative abundance of their expression levels. However, it is still unexplored fact that whether any hub and its neighbour genes within a sub-network exhibits any kind of proximity with respect to their chemical properties of the DNA sequences or not, that code for a sequence of amino acids.In this work, we try to make a quantitative investigation of the underlying biological facts in DNA sequential and primary protein level in mathematical paradigm. It may gives a holistic view of the interrelationships existing between hub genes and neighbour genes in few selective AD subnetworks. We define a mapping model from physicochemical properties of DNA sequence to chemical characterization of amino acid sequences. We use distribution of chemical groups present in a sequence after decoding into corresponding amino acids to investigate the fact that whether any hub genes are associated closely with its neighbour genes chemically in the subnetworks. Interestingly, our preliminary results confirm the fact the dependent genes that are coexpressed with its hub gene are also having proximity with respect to their amino acid chemical group distributions.CCS Concepts•Applied computing → Computational genomics;
The Genetic Landscape of Diamond-Blackfan Anemia
Authors: Ulirsch Jacob C. , Verboon Jeffrey M. , Kazerounian Shideh , Guo Michael H. , Yuan Daniel , Ludwig Leif S. , Handsaker Robert E. , Abdulhay Nour J. , Fiorini Claudia , Genovese Giulio , Lim Elaine T. , Cheng Aaron , Cummings Beryl B. , Chao Katherine R. , Beggs Alan H. , Genetti Casie A. , Sieff Colin A. , Newburger Peter E. , Niewiadomska Edyta , Matysiak Michal , Vlachos Adrianna , Lipton Jeffrey M. , Atsidaftos Eva , Glader Bertil , Narla Anupama , Gleizes Pierre-Emmanuel , O’Donohue Marie-Françoise , Montel-Lehry Nathalie , Amor David J. , McCarroll Steven A. , O’Donnell-Luria Anne H. , Gupta Namrata , Gabriel Stacey B. , MacArthur Daniel G. , Lander Eric S. , Lek Monkol , Da Costa Lydie , Nathan David. G. , Korostelev Andrei K. , Do Ron , Sankaran Vijay G. , Gazda Hanna T. 
Published: July 2018

ABSTRACTDiamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 1 in 100,000 to 200,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this genetically heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole exome sequencing (WES). Overall, we identified rare and predicted damaging mutations in likely causal genes for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and in one of 19 previously reported genes encoding for a diverse set of ribosomal proteins (RPs). Using WES exon coverage estimates, we were able to identify and validate 31 deletions in DBA associated genes. We also observed an enrichment for extended splice site mutations and validated the diverse effects of these mutations using RNA sequencing in patientderived cell lines. Leveraging the size of our cohort, we observed several robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. In addition to comprehensively identifying mutations in known genes, we further identified rare mutations in 7 previously unreported RP genes that may cause DBA. We also identified several distinct disorders that appear to phenocopy DBA, including 9 individuals with biallelicCECR1mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain > 5% of DBA cases. Overall, this comprehensive report should not only inform clinical practice for DBA patients, but also the design and analysis of future rare variant studies for heterogeneous Mendelian disorders.
Smart bone plates can monitor fracture healing
Authors: Lin Monica C. , Hu Diane , Marmor Meir , Herfat Safa T. , Bahney Chelsea S. , Maharbiz Michel M. 
Published: July 2018

One Sentence SummaryElectrical impedance measurements using microscale sensors implanted in two mouse fracture models tracked longitudinal differences between individual mice with proper healing and mice experiencing poor healing, laying the groundwork for translation to the clinic through integration into fracture fixation implants (i.e. instrumented bone plates).AbstractThere are currently no standardized methods for monitoring fracture healing. While histological studies can clearly identify the tissues found in the four stages of repair, in practice surgeons rely on X-ray, which is only useful at later stages of healing after mineralization has occurred. As electrical impedance spectroscopy (EIS) has previously been used to distinguish tissue types during healing, we hypothesized that microscale sensors embedded in the fracture callus could track the changing tissue with high sensitivity. Using in vivo mouse fracture models, we present the first evidence that microscale instrumented implants provide a route for post-operative fracture monitoring. In this study, we implanted sensors in mouse long bone fractures fixed with either external fixators or bone plates. EIS measurements taken across two electrodes implanted in the fracture gap were able to track longitudinal differences between individual mice with proper healing and mice experiencing poor healing. We additionally present an equivalent circuit model that combines the EIS data in order to classify healing states of fractures. Lastly, we show that EIS measures are strongly correlated with standard µCT measures of healing and that these correlations validate clinically-relevant operating frequencies for implementation of this technique. The data from these two models demonstrate that this technique can be translated to the clinic through integration into current fracture management strategies such as bone plating, providing physicians with quantitative information about the state of a fracture to guide clinical decision-making for patients.