Extracting Inter-Sentence Relations for Associating Biological Context with Events in Biomedical Texts.

We present an analysis of the problem of identifying biological context and associating it with biochemical events described in biomedical texts. This constitutes a non-trivial, inter-sentential relation extraction task. We focus on biological context as descriptions of the species, tissue type, and cell type that are associated with biochemical events. We present a new corpus of open access biomedical texts that have been annotated by biology subject matter experts to highlight context-event relations. Using this corpus, we evaluate several classifiers for context-event association along with a detailed analysis of the impact of a variety of linguistic features on classifier performance. We find that gradient tree boosting performs by far the best, achieving an F1 of 0.865 in a cross-validation study.

Smartphone Apps Targeting Alcohol and Illicit Substance Use: Systematic Search in in Commercial App Stores and Critical Content Analysis.

BACKGROUND: Smartphone apps promise to enhance the reach of evidence-based interventions (cognitive behavior therapy, contingency management and therapeutic education system) for populations with substance use disorders, with minimal disruption to health systems. However, further studies are needed to systematically evaluate smartphone apps targeting alcohol and illicit substances. OBJECTIVE: The aim of this study was to evaluate the functionality, aesthetics, and quality of information of free or low-cost apps claiming to target alcohol, benzodiazepine, cocaine, crack/cocaine, crystal methamphetamine, and heroin use using the validated Mobile App Rating Scale (MARS) and critical content analysis. METHODS: A systematic search of iTunes and Google Play app stores for free or low-cost apps facilitating recovery was conducted in March 2018 and yielded 904 apps using the keywords described in previous studies (eg, recovery, sobriety, sober, alcohol, and heroin). An interdisciplinary team of clinicians, behavioral informatics, and public health reviewers trained in substance use disorders conducted a descriptive analysis of 74 apps categorized as reducing use. In addition to the MARS scale, a descriptive analysis of relevant apps was conducted by the study team to assess for quality indicators emphasized by expert guidelines and review articles. RESULTS: Most apps (n=74) claimed to reduce use or promote abstinence and yielded an overall low median MARS score of 2.82 (0.55) and a wide range of scores (1.64, 4.20). Ratings were also low for engagement (2.75 (0.72)), functionality (3.64 (0.78)), aesthetics (3.03 (0.87)), information (2.82 (0.62)), and satisfaction (1.76 (0.67)) subdomains. Innovative design and content features elicited in the review included initial assessments of substance use following app download, tracking substance use, and related consequences (eg, cost or calorie intake), remote and proximate peer support per geospatial positioning, and allowing users and family members of individuals with substance use disorders to locate 12-step meetings, treatment programs, and mental health services. Few apps integrated evidence-based psychotherapeutic (eg, cognitive behavioral therapy [CBT] or motivational interviewing) and pharmacologic interventions (eg, naloxone or buprenorphine). CONCLUSIONS: Few commercially available apps yielded in our search integrated evidence-based interventions (eg, extended-release naltrexone, buprenorphine, naloxone, Self-Management and Recovery Training recovery, or CBT), and a concerning number of apps promoted harmful drinking and illicit substance use.

Technology preferences to enhance HIV and HCV care among patients with substance use disorders.

We examined technology use patterns (e.g., mobile phone and computer ownership, text messaging, internet access) and preferences for adopting health information technologies to optimize office-based treatment for substance use disorders, HIV, and Hepatitis C virus (HCV) infection. Surveys were administered to patients enrolled in inpatient detoxification program in a publicly-funded tertiary referral center. Most reported mobile phone ownership (86%) and described high rates of mobile phone (3.3) and phone number (2.6) turnover in the preceding year. Internet access was reported on a daily (52%) or weekly basis (22%). Most participants were amenable to receiving text message-based informational content (i.e., medications, support groups, treatment programs) pertaining to substance use disorders (79%), HIV (50%), and HCV care (58%). Respondents reporting less than high school education and past year incarcerated elicited higher favorability in adopting smartphone apps to facilitate peer sharing of HIV-HCV related content. Results suggest high favorability for adopting health information technologies to enhance office-based treatment for substance use disorders, HIV, and HCV, particularly among vulnerable patient sub-groups.

Radioembolization with Yttrium-90 microspheres for patients with unresectable hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is aggressive primary malignancy of the liver that most commonly presents late in the disease course. As a result, the majority of patients are not candidates for curative therapies. Locoregional therapies including Yttrium-90 (Y-90) radioembolization play an important role in management of the vast majority of patients with HCC. METHODS: Patients with unnresectable HCC (n=17) treated with Y-90 radioembolization from 2005 to 2014 were evaluated retrospectively. Data was abstracted from medical records including patient charts, laboratory data, and imaging. Toxicities were recorded using Common Terminology Criteria 3.0. Response was recorded according to modified RECIST (mRECIST) criteria. RESULTS: Seventeen patients received 33 treatments with Y-90 radioembolization. A majority (65%) received TheraSphere with a minority (35%) receiving SIR-Spheres. The median treatment activity delivered was 1.725 gBq (range, 1.4-2.5 gBq). The median treatment dose delivered was 100 Gy (range, 90-120 Gy). The median lung shunt fraction was 2.02% (range, 1.5-4.1%). The most common clinical toxicity among all patients was nausea and vomiting (59%), primarily grade 1 and 2. Other post-treatment findings included abdominal pain (29%), fatigue (53%), and weight loss (18%). One patient developed a grade 5 gastric ulcer after the treatment. A clinical benefit, defined as patients achieving complete response (CR), partial response (PR) or stable disease (SD), was seen in 48% of patients. PR was seen in 24% of cases; progressive disease (PD) was noted in 35%. Patients survived for a median of 8.4 months (range, 1.3 to 21.1 months) after the first radioembolization treatment. Median survival after Y-90 treatment was 8.4 months among patients treated TheraSphere as compared with 7.8 months in patients treated with SIR-Spheres. The mean overall survival from the time of diagnosis was 11.7 months (range, 3.4 to 43.2 months). CONCLUSIONS: For patients with unresectable HCC, Y-90 radioembolization is a safe and well-tolerated procedure. Our experience suggests that a significant percentage of patients achieve clinical benefit including many with PR. Survival after treatment from this single-center, transplant center is in line with prior reports. Prospective, randomized data is required to compare radioembolization with other therapies including chemoembolization and systemic therapy with sorafenib.

Influence on morbidity and mortality of neoadjuvant radiation and chemotherapy among cranial malignancy patients in the postoperative setting.

We sought to assess the impact of neoadjuvant therapy on 30 day mortality and morbidity using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Chemotherapy and radiotherapy are both often indicated for treatment of cranial or systemic malignancy but can have significant adverse effects in the postsurgical setting. Data from 2006 to 2012 were obtained from the national ACS-NSQIP database. A total of 1044 patients were identified who obtained surgery for removal of metastatic brain tumors, of whom 127 received neoadjuvant chemotherapy and 65 neoadjuvant radiotherapy. Our primary outcome was 30 day mortality and secondary outcomes were 30 day surgical and medical morbidities. We selected previously reported preoperative variables to build a univariate and a multivariate model to determine preoperative characteristics most associated with neurosurgical mortality and morbidity. Our study found that neoadjuvant chemotherapy was associated with a 2.4-fold increase in the risk of 30 day mortality compared to the patient cohort who did not receive chemotherapy (p=0.023). Interestingly, there was no statistically significant increase in overall 30 day surgical or medical morbidity for the chemotherapy group. Neoadjuvant radiotherapy was not associated with an increase in 30 day morbidity or mortality. The significant increase in mortality associated with chemotherapy warrants further investigation, particularly to determine how to best personalize neoadjuvant chemotherapy treatment options to improve surgical outcomes. Neoadjuvant radiotherapy may be safer in terms of short-term postoperative morbidity and mortality.

Spontaneous subdural haemorrhage in a patient with scleroderma renal crisis.

A 52-year-old woman with a history of systemic sclerosis presented with new onset seizures and renal failure. The patient's history, laboratory data and pathology supported the diagnosis of scleroderma renal crisis. The patient was also noted to have a subdural haemorrhage (SDH) in the absence of trauma. This is the first report of scleroderma renal crisis associated with a spontaneous SDH.

Acute Respiratory Distress Syndrome in Lemierre's Syndrome.

Lemierre's syndrome is an infectious disease defined by the presence of septic thrombophlebitis with associated embolic phenomenon, most commonly to the lungs. Here we present two cases from a single institution of acute respiratory distress syndrome (ARDS) developing as a result of Lemierre's syndrome in previously healthy young adult men. ARDS can occur as a consequence of pulmonary septic emboli and sepsis, both of which are well-described consequences of Lemierre's syndrome. We describe important diagnostic and management considerations in the care of patients with hypoxemic respiratory failure and Lemierre's syndrome. Essential components of management include prompt antibiotic therapy, lung-protective ventilation strategies, and supportive care.

A protein related to prokaryotic UMP kinases is involved in psaA/B transcript accumulation in Arabidopsis.

Dpt1 (defect in p saA/B transcript accumulation 1) is a novel photosystem (PS) I mutant in Arabidopsis. dpt1 mutants fail to grow photoautotrophically, and are impaired in the accumulation of psaA/B transcripts while the transcript levels for the remaining PSI subunits, for subunits of the PSII, the cyt-b ( 6 )/f-complex, and the ribulose-1,5-bisphosphate carboxylase are comparable to the wild type. In-organello run-on transcription assays demonstrate that the lower psaA/B transcript abundance in dpt1-1 is not caused by the inability to transcribe the psaA/psaB/rps14 operon. psaA/B transcripts in the mutant are associated with polyribosomes and translated. Thus, the mutation affects post-transcriptional processes specific for psaA/B. The dpt1 gene was isolated by map-based cloning. The protein is localized in the stroma of the chloroplast and exhibits striking similarities to UMP kinases of prokaryotic origin. Our results show that the nuclear encoded protein Dpt1 is essential for retaining photosynthetic activity in higher plant chloroplasts and involved in post-transcriptional steps of psaA/B transcript accumulation. We discuss that Dpt1 may be a bifunctional protein that couples the pyrimidine metabolism to the photosynthetic electron transport.

The evolutionarily conserved tetratrico peptide repeat protein pale yellow green7 is required for photosystem I accumulation in Arabidopsis and copurifies with the complex.

Pale yellow green7-1 (pyg7-1) is a photosystem I (PSI)-deficient Arabidopsis (Arabidopsis thaliana) mutant. PSI subunits are synthesized in the mutant, but do not assemble into a stable complex. In contrast, light-harvesting antenna proteins of both photosystems accumulate in the mutant. Deletion of Pyg7 results in severely reduced growth rates, alterations in leaf coloration, and plastid ultrastructure. Pyg7 was isolated by map-based cloning and encodes a tetratrico peptide repeat protein with homology to Ycf37 from Synechocystis. The protein is localized in the chloroplast associated with thylakoid membranes and copurifies with PSI. An independent pyg7 T-DNA insertion line, pyg7-2, exhibits the same phenotype. pyg7 gene expression is light regulated. Comparison of the roles of Ycf37 in cyanobacteria and Pyg7 in higher plants suggests that the ancient protein has altered its function during evolution. Whereas the cyanobacterial protein mediates more efficient PSI accumulation, the higher plant protein is absolutely required for complex assembly or maintenance.

A transcriptional role for C/EBP beta in the neuronal response to axonal injury.

The molecular mechanisms responsible for inducing gene expression following neuronal injury are not well understood. Here, we address this issue by focusing upon C/EBPbeta, a transcription factor implicated in cellular injury and regeneration. We show that C/EBPbeta mRNA is expressed in neurons throughout the mature brain and that levels of both C/EBPbeta mRNA and phosphoprotein are increased in facial motor neurons following axonal injury. To determine the importance of these increases, we examined the regeneration-associated Talpha1 alpha-tubulin gene which contains functional C/EBP binding sites in its promoter. In transgenic mice, expression of a minimal 176 nucleotide Talpha1 alpha-tubulin promoter:nlacZ reporter gene was upregulated in injured facial motor neurons. This injury-induced transcriptional increase was inhibited in C/EBPbeta -/- mice. A similar inhibition was observed in C/EBPbeta -/- mice that carried a larger 1.1-kb promoter Talpha1:nlacZ reporter construct. Moreover, in situ hybridization revealed that the injury-induced upregulation of the endogenous mouse alpha1 alpha-tubulin mRNA, and of a second regeneration-associated mRNA, GAP-43, was inhibited in C/EBPbeta -/- mice. Thus, C/EBPbeta is essential for the neuronal injury response, acting to transcriptionally activate regeneration-associated gene expression.

An essential role for a MEK-C/EBP pathway during growth factor-regulated cortical neurogenesis.

Mammalian neurogenesis is determined by an interplay between intrinsic genetic mechanisms and extrinsic cues such as growth factors. Here we have defined a signaling cascade, a MEK-C/EBP pathway, that is essential for cortical progenitor cells to become postmitotic neurons. Inhibition of MEK or of the C/EBP family of transcription factors inhibits neurogenesis while expression of a C/EBPbeta mutant that is a phosphorylation-mimic at a MEK-Rsk site enhances neurogenesis. C/EBP mediates this positive effect by direct transcriptional activation of neuron-specific genes such as Talpha1 alpha-tubulin. Conversely, inhibition of C/EBP-dependent transcription enhances CNTF-mediated generation of astrocytes from the same progenitor cells. Thus, activation of a MEK-C/EBP pathway enhances neurogenesis and inhibits gliogenesis, thereby providing a mechanism whereby growth factors can selectively bias progenitors to become neurons during development.