bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor-Induced Osteomalacia Caused by a Parotid Basal Cell Adenoma Detected by 68Ga-DOTANOC PET/CT
Authors: He Qiao , Xu Zeqing , Zhang Bing , Hu Wanming , Zhang Xiangsong
Published: April 2018

Tumor-induced osteomalacia is a rare paraneoplastic syndrome, usually caused by small benign mesenchymal tumors. The tumors most arise within the extremities, whereas occurrence within the parotid gland is quite rare. A 54-year-old woman who presented with bone pain and muscle weakness for 2 years was clinically suspected of having tumor-induced osteomalacia. A 68Ga-DOTANOC PET/CT was performed for localization of the causative tumor. The images demonstrated intense radiotracer accumulation in a soft tissue nodule in deep lobe of the right parotid gland. Subsequent surgical resection and pathologic analysis confirmed the diagnosis of parotid basal cell adenoma.
FDG-PET/CT Focal Uptake on an Ocular Prosthesis
Authors: Repetto Alessandra , Igua Carolina , Sopena Pablo , Bello Pilar
Published: April 2018

We present a case of an unexpected focally increased radiotracer uptake in an artificial eye in an FDG-PET/CT scan that was performed on a woman with a history of choroidal melanoma. It is crucial to know the type of prosthesis used and the timing of replacement for a correct interpretation of the findings. Recently, an FDG PET/CT was proposed to monitor the vascularity of the prosthesis instead of gadolinium MRI or of 99mTc bone scintigraphy.
Lateral Recumbent or Prone Positioning for PET of the Urinary Bladder
Authors: ten Broek Marc R.J. , Ausems Peter J. , te Beek Erik T.
Published: April 2018

Evaluation of the urinary bladder on PET with 18F-FDG is hampered by accumulation of activity in the urinary bladder due to physiological excretion of 18F-FDG in urine. We present 2 examples that demonstrate the utility of delayed scanning in lateral recumbent or prone position to improve evaluation of the bladder by differentiating between active bladder wall lesions and intraluminal activity. Changing the body position from a supine to a lateral recumbent or prone position can result in migration of intraluminal activity due to gravitational force, whereas 18F-FDG uptake in bladder wall lesions will show no migration.
Bilateral Adrenal Hyperplasia Due to Adrenocorticotropic Hormone–Secreting Esthesioneuroblastoma on FDG PET and 111In-Pentetreotide Scintigraphy
Authors: Matsusaka Yohji , Nakahara Tadaki , Kurihara Isao , Iwabuchi Yu , Jinzaki Masahiro
Published: April 2018

A 53-year-old woman with metastatic esthesioneuroblastoma was referred for FDG PET/CT imaging. FDG PET/CT showed symmetrical uptake in bilaterally enlarged adrenal glands, in addition to abnormal uptake in bone and lymph node metastases. 111In-pentetreotide scintigraphy was further performed and revealed the lack of adrenal uptake. The patient's serum adrenocorticotropic hormone (ACTH) level was extremely high, suggesting that hyperplastic condition in the adrenal glands due to ACTH stimulation from the metastatic esthesioneuroblastoma was responsible for increased FDG uptake. The combination of FDG PET and 111In-pentetreotide scintigraphy was useful for the pathophysiological evaluation of ACTH-secreting esthesioneuroblastoma.
Added Value of SPECT/CT in the Evaluation of Sacral Fracture in Patients With Lung Cancer
Authors: Zhao Zhen , Zhou Ke , Liu Bin
Published: April 2018

We describe the sacral fractures from 2 lung cancer patients that were confirmed by SPECT/CT. The utilization of SPECT/CT in lung cancer patients can help characterizing the nature of sacral lesions on planar bone scintigraphy.
Imaging of Metastatic Epithelioid Trophoblastic Tumor With 18F-FDG PET/CT
Authors: Patel Tirth , Oldan Jorge
Published: April 2018

Epithelioid trophoblastic tumors are exceptionally rare malignant forms of gestational trophoblastic neoplasia arising from the placenta. We present here a case of a 33-year-old woman with an epithelioid trophoblastic tumor with metastatic disease to the lungs that was initially thought to represent cervical carcinoma. After appropriate diagnosis and treatment, the tumor responded to therapy and was in remission. The cancer recurred 5 years later with new lung metastases. 18F-FDG PET/CT was used for initial tumor staging, to evaluate treatment response, and to help detect the recurrence.
Combined [18F]-Fluoroethylcholine PET/CT and 99mTc–Macroaggregated Albumin SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular Carcinoma
Authors: Hartenbach Markus , Weber Stefan , Pilz Magdalena , Hartenbach Sabrina , Zacherl Mathias J. , Paprottka Philipp M. , Tiling Reinhold , Bartenstein Peter , Hacker Marcus , Haug Alexander R. , Albert Nathalie L.
Published: April 2018

Aim

The aim of this study was to retrospectively analyze the prognostic value of combined 99mTc–macroaggregated albumin (MAA) SPECT/CT and [18F]-fluoroethylcholine (FEC) PET/CT before radioembolization for survival of patients with intermediate-stage hepatocellular carcinoma.

Methods

Twenty-four patients with known hepatocellular carcinoma Barcelona Clinic Liver Cancer stage B were eligible for this analysis. All patients were scheduled for radioembolization and received a pretherapeutic [18F]FEC PET/CT scan as well as 99mTc-MAA SPECT/CT for hepatopulmonary shunting. Laboratory and semiquantitative PET parameters and morphologic and metabolic (intersection) volumes of MAA and FEC were evaluated. Spearman correlation with overall survival, receiver operating curve analyses, univariate and multivariate Cox regression, and Kaplan-Meier-analysis was applied.

Results

All patients (5 female/19 male) are deceased within the observational period. Median survival was 395 days (±51 days; range, 23–1122 days). The percentage of hypervascularized metabolically active tumor volume (vascularized tumor ratio; defined as high MAA and FEC uptake) correlated significantly with survival. Vascularized tumor ratio was a significant predictor in univariate and multivariate analyses (P = 0.026; hazard ratio, 11.65; 95% confidence interval, 1.62–83.73; P = 0.015). Statistical significance was not reached by all other variables in multivariate analysis. Receiver operating curve analysis for 1-year survival revealed an area under the curve of 0.77 (P = 0.024) for vascularized tumor ratio. At a cutoff value of 9%, sensitivity, specificity, and positive and negative prediction were 83%, 67%, and 71% and 80% (P = 0.036). Patients with a higher tumor vascularization had a median survival of 274 ± 80 versus 585 ± 284 days (P = 0.015).

Conclusions

Hepatocellular carcinoma with high vascularization in metabolic active areas as assessed by combined FEC PET/CT and Tc-MAA SPECT/CT represents an unfavorable subgroup with reduced overall survival after radioembolization.
Pedunculated Hepatocellular Carcinoma Mimicking Right Adrenal Tumor on FDG PET/CT
Authors: Dong Aisheng , Zhong Xinping , Wang Yang
Published: April 2018

Pedunculated hepatocellular carcinoma is an unusual form of hepatocellular carcinoma protruding from the liver with or without a pedicle. We present a case of pedunculated hepatocellular carcinoma misdiagnosed as right adrenal tumor on MRI and FDG PET/CT. Intraoperative exploration revealed the mass was attached to the liver, but the right adrenal gland was intact. Laparoscopic biopsy revealed poorly differentiated hepatocellular carcinoma. This case indicates it may be difficult to diagnose pedunculated hepatocellular carcinoma because it is hard to define its origin on imaging. Elevated alpha-fetoprotein level and a history of viral hepatitis may be helpful for the diagnosis.
A Bizarre Bone Scan of Fibrodysplasia Ossificans Progressiva
Authors: Chuang Tzyy-Ling , Ho Kuo-Wei , Wang Yuh-Feng
Published: April 2018

A 27-year-old woman had progressive bony ankylosis over both hands since she was 5 years old. Bony ankylosing over the peripheral joints and spine slowly progressed, and scoliosis surgery was performed at age 14. Recently, she developed difficulty walking, changing position, and opening her mouth. A neurologist was consulted and ruled out the suspicion of narcolepsy. Chest CT showed ankylosing spondylitis. A bone scan showed a bizarre pattern with radiouptake to the left maxilla, bilateral sacroiliac joints, left middle third femur, and soft tissue uptake over bilateral arms, legs, and pelvis. Regional radiograph suggested fibrodysplasia ossificans progressiva.
Loss of PSMA Expression in Non-neuroendocrine Dedifferentiated Acinar Prostate Cancer
Authors: Bronsert Peter , Reichel Kathrin , Ruf Juri
Published: April 2018

The introduction of tracers targeting the prostate-specific membrane antigen (PSMA) has revolutionized PET imaging of acinar prostate adenocarcinoma. In general, an increasing PSMA expression is assumed with increasing dedifferentiation. Whereas loss of PSMA expression has been reported in case of neuroendocrine dedifferentiation, we present a patient with acinar prostate adenocarcinoma with a loss of PSMA expression after chemotherapy on PET/CT and in histological and immunohistochemical analyses. All tissue samples indicated the retention of acinar features but no expression of neuroendocrine markers (NSE, synaptophysin, chromogranin, and CD56), corresponding to nonelevated serum NSE.
Unexpected Vesicoureteral Reflux Into a Nonfunctioning Transplant Kidney on Renal Scintigraphy
Authors: Cruz Adam , Wale Daniel J. , Wong Ka Kit , Arnkoff Brett M. , Viglianti Benjamin L.
Published: April 2018

Vesicoureteral reflux after renal transplantation is associated with increase risk of urinary tract infections, renal scarring, and graft failure. We describe a case of a 46-year-old woman with 2 transplant kidneys, one functioning and another nonfunctioning, presenting with pelvic pain after a bilateral periureteral bulking procedure. Diuretic renography was performed to exclude iatrogenic ureteral obstruction. This showed a normally functioning transplant kidney without obstruction and subsequent vesicoureteral reflux into the collecting system of the nonfunctioning transplant kidney. This inadvertent indirect nuclear cystogram illustrates an unusual imaging presentation of a common disease process requiring further treatment.
Scintigraphic and Sonographic Findings of Subcapsular Cortical Necrosis in a Transplanted Kidney
Authors: Yazici Bulent , Gunay Emrah , Akgün Aysegül , Sen Sait , Ozbek Suha Sureyya
Published: April 2018

Renal transplant scintigraphy, performed in a 23-year-old man who had renal graft from a living donor, showed nearly normal perfusion and moderately low function of the graft. But the margins of the graft were blurred, and it was interestingly appearing enlarged late in the study. Ultrasound demonstrated a hypoechoic rim surrounding the whole kidney. Biopsy revealed necrosis besides normal cortical tissue. Necrosis was thought to be limited to the subcapsular cortical area. It should be considered that these scintigraphic findings could be due to greatly reduced and delayed perfusion of edematous subcapsular necrotic area of the graft even in normal perfusion images.
Mixed Epithelial and Stromal Tumor of the Kidney Mimicking Malignancy on 18F-FDG PET/CT in a Patient With Breast Cancer
Authors: Li Chongjiao , Tian Yueli , Shen Meijuan , Wen Bing , He Yong
Published: April 2018

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare renal tumor composed of solid and cystic components. Mixed epithelial and stromal tumor of the kidney has no pathognomonic imaging feature. It is difficult to distinguish MESTK from other cystic renal neoplasms using current radiological methods. We report a rare case of MESTK that was diagnosed in a 46-year-old woman with breast cancer. 18F-FDG PET/CT and contrast-enhanced CT features of MESTK are presented, which could potentially provide useful information in the differential diagnoses of cystic renal neoplasms.
Peliosis Hepatis Simulating Metastatic Liver Disease on FDG PET/CT
Authors: Levin Daniel , Hod Nir , Anconina Reut , Ezroh Kazap Dina , Shaco-Levy Ruthy , Lantsberg Sophie
Published: April 2018

A 20-year-old man with gastrointestinal symptoms and weight loss underwent FDG PET/CT, which revealed multiple hypermetabolic hepatic lesions concerning for metastatic liver disease. The outcome of liver biopsy was consistent with the diagnosis of peliosis hepatis which is a rare benign disease characterized by multiple blood-filled cystic spaces in the hepatic parenchyma. The findings of peliosis on FDG PET/CT are not well reported in the literature. These interesting images emphasize the importance of including peliosis hepatis in the differential diagnosis of multiple hypermetabolic hepatic lesions on FDG PET/CT, which could simulate malignancy.
Top-Down Systematic Approach to Interpretation of FDG-PET for Dementia
Authors: Sawyer David M. , Kuo Phillip H.
Published: April 2018

Dementia is an important cause of morbidity and mortality worldwide and encompasses a very heterogenous group of disease processes. Positron emission tomography (PET) of the brain using fluorodeoxyglucose (FDG) is a useful modality for differentiating types of dementia. Because FDG does not bind to pathologic proteins, FDG-PET requires that the reader recognize characteristic patterns of glucose hypometabolism to identify pathology. These patterns have been documented in the literature for both primary neurodegenerative disorders and secondary causes of dementia. This article presents an algorithm for organizing these findings and systematically applying them to interpret FDG-PET brain imaging for dementia.
A Smartphone Application to Reduce the Time to Automated External Defibrillator Delivery After a Witnessed Out-of-Hospital Cardiac Arrest
Authors: Hatakeyama Toshihiro , Nishiyama Chika , Shimamoto Tomonari , Kiyohara Kosuke , Kiguchi Takeyuki , Chida Izumi , Izawa Junichi , Matsuyama Tasuku , Kitamura Tetsuhisa , Kawamura Takashi , Iwami Taku
Published: April 2018

Introduction

We developed a new smartphone application to deliver an automated external defibrillator (AED) to out-of-hospital cardiac arrest scene. The aim of this study was to evaluate whether an AED could be delivered earlier with or without an application in a simulated randomized controlled trial.

Methods

Participants, who were asked to work as bystanders, were randomly assigned to either an application group or control group and were asked to bring an AED in both groups. The bystanders in the application group sent a signal notification using the application to two responders, who were stationed within 200 meters of the arrest scene, to carry an AED. The primary outcome was the AED delivery time by either the bystander or his/her responder.

Results

In total, 61 bystanders were eligible and randomized to either the application group (32) or the control group (29). The 52 with time data were available and analyzed. The AED delivery time by either the bystander or his/her responder was significantly shorter in the application group than in the control group [133.6 (44.4) seconds vs. 202.2 (122.2) seconds, P = 0.01].

Conclusions

In this simulation-based trial, AED delivery time was shortened by our newly developed smartphone application for the bystander to ask nearby responders to find and bring an AED to the cardiac arrest scene (UMIN-Clinical Trials Registry 000016506).
Cultural Prototypes and Differences in Simulation Debriefing
Authors: Ulmer Francis F. , Sharara-Chami Rana , Lakissian Zavi , Stocker Martin , Scott Ella , Dieckmann Peter
Published: April 2018

Introduction

Culture is believed to play a role in education, safety, and patient outcome in healthcare. Hofstede’s culture analysis permits a quantitative comparison between countries, along different culture dimensions, including power distance (PD). Power distance index (PDI) is a value reflecting social hierarchy in a country. We sought to explore the relation between PDI and self-reported behavior patterns of debriefers during simulation debriefings. We determined six culture-relevant debriefing characteristics and formulated six hypotheses on how these characteristics correlate with national PDIs.

Methods

Low-PDI countries have a PDI of 50 or less, and high-PDI countries have a PDI of 51 or greater as defined by Hofstede. Interviews with simulation debriefers were used to investigate culture-relevant debriefing characteristics: debriefer/participant talking time, debriefer/participant interaction pattern, debriefer/participant interaction style, debriefer/participant initiative for interactions, debriefing content, and difficulty with which nontechnical skills can be discussed.

Results

During debriefing, in low-PDI countries, debriefers talked less and used more open-ended questions and focused more on nontechnical issues than on medical knowledge and simulation participants initiated most interactions. In low-PDI countries, debriefers felt that participants interacted more with each other and found it easier to address nontechnical skills such as speaking-up.

Conclusions

Our results supported our hypotheses. National culture is related to debriefing practice. There is a clear relation between PDI and debriefer-participant behavior patterns as described by debriefers. The higher the PDI of a country, the more the debriefer determines the course of the debriefing and the more difficult it becomes to address nontechnical skills.
Prospective evaluation of low health literacy and its impact on outcomes in trauma patients
Authors: Swartz Tianyi , Jehan Faisal , Tang Andrew , Gries Lynn , Zeeshan Muhammad , Kulvatunyou Narong , Hamidi Mohammad , O’Keeffe Terence , Joseph Bellal
Published: April 2018

BACKGROUND

Health literacy is an emerging focus of interest in public health and is evolving as an important component of national health policy. Low health literacy (LHL) is associated with poor outcomes. We aimed to identify factors associated with LHL and its relationship with health outcomes in trauma patients.

METHODS

We prospectively enrolled all adult trauma patients (age, > 18 years) in our analysis. Patients were surveyed at discharge and followed up at 4 weeks postdischarge. At discharge, patient’s health literacy was assessed using the Short-Assessment of Health Literacy score. Low health literacy was defined as Short-Assessment of Health Literacy score less than 14. Patients were surveyed regarding their understanding of their injuries, treatment received, discharge instructions, and interaction with the physician. Four weeks postdischarge, all patients were inquired about clinic follow-up details and recovery.

RESULTS

We enrolled 140 patients, of which 70% were white. Mean age was 45 ± 20 years, and median Injury Severity Score was 10 (6–12). Overall, 24% (34) patients had LHL. There was no difference in the Injury Severity Score between LHL and health literate (HL) patients (p = 0.41). The LHL patients were more likely to be Hispanic-white (78% vs. 41%, p = 0.02), had lower socioeconomic status (91% vs. 51%, p = 0.01), uninsured (45% vs. 18%, p = 0.01), and were less likely to have graduated (0% vs. 49%, p = 0.01) compared with the HL patients. At discharge, both groups were satisfied with the time spent by a physician to explain the condition, however, the LHL patients were less likely to recall their injuries (p = 0.03) or how they were treated (p = 0.01). Patients with LHL had lower follow-up rates (p = 0.01) with no difference in the readmission rate (p = 0.71) compared with HL.

CONCLUSION

Every 1 in 4 trauma patients have LHL. Low health literacy is associated with poor understanding of injuries and treatment provided to them, leading to a decrease in compliance with discharge instructions and longer time to recovery. Identifying LHL in high-risk patients and developing appropriate intervention before discharge may help improve outcomes.

LEVEL OF EVIDENCE

Prognostic study, level I.
Meta-analysis of perioperative outcomes of acute laparoscopic versus open repair of perforated gastroduodenal ulcers
Authors: Cirocchi Roberto , Soreide Kjetil , Di Saverio Salomone , Rossi Elena , Arezzo Alberto , Zago Mauro , Abraha Iosief , Vettoretto Nereo , Chiarugi Massimo
Published: April 2018

BACKGROUND

Surgery is the treatment of choice for perforated peptic ulcer disease. The aim of the present review was to compare the perioperative outcomes of acute laparoscopic versus open repair for peptic ulcer disease.

METHODS

A systematic literature search was performed for randomized controlled trials (RCTs) published in PubMed, SCOPUS, and Web of Science.

RESULTS

The search included eight RCTs: 615 patients comparing laparoscopic (307 patients) versus open peptic perforated ulcer repair (308 patients). Only few studies reported the Boey score, the Acute Physiologic Assessment and Chronic Health Evaluation score, and the Mannheim Peritonitis Index. In the RCTs, there is a significant heterogeneity about the gastric or duodenal location of peptic ulcer and perforation size. All trials were with high risk of bias. This meta-analysis reported a significant advantage of laparoscopic repair only for postoperative pain in first 24 hours (−2.08; 95% confidence interval, −2.79 to −1.37) and for postoperative wound infection (risk ratio, 0.39; 95% confidence interval, 0.23–0.66). An equivalence of the other clinical outcomes (postoperative mortality rate, overall reoperation rate, overall leaks of the suture repair, intra-abdominal abscess rate, operative time of postoperative hospital stay, nasogastric aspiration time, and time to return to oral diet) was reported.

CONCLUSION

In this meta-analysis, there were no significant differences in most of the clinical outcomes between the two groups; there was less early postoperative pain and fewer wound infections after laparoscopic repair. The reported equivalence of clinical outcomes is an important finding. These results parallel the results of several other comparisons of open versus laparoscopic general surgery operations—equally efficacious with lower rates of wound infection and improvement in some measures of enhanced speed or comfort in recovery. Notably, the trials included have been published throughout a considerable time span during which several changes have occurred in most health care systems, not least a widespread use of laparoscopy and increase in the laparoscopic skills.

LEVEL OF EVIDENCE

Systematic review and meta-analysis, level III.
Evaluation and management of abdominal stab wounds: A Western Trauma Association critical decisions algorithm
Authors: Martin Matthew J. , Brown Carlos V.R. , Shatz David V. , Alam Hasan B. , Brasel Karen J. , Hauser Carl J. , de Moya Marc , Moore Ernest E. , Rowell Susan E. , Vercruysse Gary A. , Baron Bonny J. , Inaba Kenji
Published: April 2018

This is a recommended management algorithm from the Western Trauma Association addressing the management of adult patients with abdominal stab wounds. Because there is a paucity of published prospective randomized clinical trials that have generated Class I data, these recommendations are based primarily on published observational studies and expert opinion of Western Trauma Association members. The algorithm and accompanying comments represent a safe and sensible approach that can be followed at most trauma centers. We recognize that there will be patient, personnel, institutional, and situational factors that may warrant or require deviation from the recommended algorithm. We encourage institutions to use this as a guideline to develop their own local protocols.
Frailty screening and a frailty pathway decrease length of stay, loss of independence, and 30-day readmission rates in frail geriatric trauma and emergency general surgery patients
Authors: Engelhardt Kathryn E. , Reuter Quentin , Liu Jessica , Bean Jonathan F. , Barnum Joliette , Shapiro Michael B. , Ambre Allison , Dunbar Amanda , Markzon Mara , Reddy Tara N. , Schilling Christine , Posluszny Joseph A.
Published: April 2018

BACKGROUND

Frail geriatric trauma and emergency general surgery (TEGS) patients have longer lengths of stay (LOS), more readmissions, and higher rates of postdischarge institutionalization than their nonfrail counterparts. Despite calls to action by national trauma coalitions, there are few published reports of prospective interventions. The objective of this quality improvement project was to first develop a frailty screening program, and, then, if frail, implement a novel frailty pathway to reduce LOS, 30-day readmissions, and loss of independence.

METHODS

This was a before-after study of a prospective cohort of all geriatric (≥65-years-old) patients admitted to the TEGS service from October 2016 to October 2017. All patients were screened for frailty for 3 months (preintervention) to obtain baseline outcomes. Subsequently, frail patients were entered into our frailty pathway (postintervention). Nonparametric statistical tests were used to assess significant differences in continuous variables; χ2 and Fisher exact tests were used for categorical variables, where appropriate. Both process and outcome measures were evaluated.

RESULTS

Of 239 geriatric TEGS patients screened, 70 (29.3%) were frail. All TEGS geriatric patients were screened within 24 hours of admission. Following frailty pathway implementation, median LOS for frail patients decreased from 9 to 6 days (p = 0.4), readmissions decreased from 36.4% to 10.2% (p = 0.04), and loss of independence decreased by 40%, (100% vs 60%; p = 0.01). Outcomes for nonfrail geriatric patients did not differ between cohorts.

CONCLUSIONS

Screening for frailty followed by implementing a frailty pathway decreased LOS, loss of independence, and 30-day readmission rates for frail geriatric TEGS patients at a single urban academic institution. The pathway required no additional resources; rather, we shifted focus toward frail patients without negatively affecting outcomes in nonfrail geriatric TEGS patients. Implementation of this pathway with larger patient cohorts and in varied settings is needed to confirm a causal relationship between our intervention and improved outcomes.

LEVEL OF EVIDENCE

Therapeutic study, level IV.
External validation of a five-variable clinical prediction rule for identifying children at very low risk for intra-abdominal injury after blunt abdominal trauma
Authors: Arbra Chase A. , Vogel Adam M. , Plumblee Leah , Zhang Jingwen , Mauldin Patrick D. , Dassinger Melvin S. , Russell Robert T. , Blakely Martin L. , Streck Christian J.
Published: April 2018

BACKGROUND

A clinical prediction rule was previously developed by the Pediatric Surgery Research Collaborative (PedSRC) to identify patients at very low risk for intra-abdominal injury (IAI) and intra-abdominal injury receiving an acute intervention (IAI-I) who could safely avoid abdominal computed tomography (CT) scans after blunt abdominal trauma (BAT). Our objective was to externally validate the rule.

METHODS

The public-use dataset was obtained from the Pediatric Emergency Care Applied Research Network (PECARN) Intra-abdominal Injury Study. Patients 16 years of age and younger with chest x-ray, completed abdominal history and physical examination, aspartate aminotransferase (AST), and amylase or lipase collected within 6 hours of arrival were included. We excluded patients who presented greater than 6 hours after injury or missing any of the five clinical prediction variables from the PedSRC prediction rule.

RESULTS

We included 2,435 patients from the PECARN dataset, with a mean age of 9.4 years. There were 235 patients with IAI (9.7%) and 60 patients with IAI-I (2.5%). The clinical prediction rule had a sensitivity of 97.5% for IAI and 100% for IAI-I. In patients with no abnormality in any of the five prediction rule variables, the rule had a negative predictive value of 99.3% for IAI and 100.0% for IAI-I. Of the “very low-risk” patients identified by the rule, 46.8% underwent abdominal CT imaging.

CONCLUSIONS

A highly sensitive clinical prediction rule using history and abdominal physical examination, laboratory values, and chest x-ray was successfully validated using a large public-access dataset of pediatric BAT patients.

LEVEL OF EVIDENCE

Epidemiologic/prognostic study, level III; therapeutic care/management study, level IV.
Functional characterization of sensory neuron membrane proteins (SNMPs)
Authors: Zhang Hui-Jie , Xu Wei , Chen Quan-mei , Sun Le-Na , Anderson Alisha , Xia Qing-You , Papanicolaou Alexie
Published: April 2018

Sensory neuron membrane proteins (SNMPs) play a critical role in the insect olfactory system but there is a deficit of functional studies beyond Drosophila. Here, we provide functional characterisation of insect SNMPs through the use of bioinformatics, genome curation, transcriptome data analysis, phylogeny, expression profiling, and RNAi gene knockdown techniques. We curated 81 genes from 35 insect species and identified a novel lepidopteran SNMP gene family, SNMP3. Phylogenetic analysis shows that lepidopteran SNMP3, but not the previously annotated lepidopteran SNMP2, is the true homologue of the dipteran SNMP2. Digital expression, microarray and qPCR analyses show that the lepidopteran SNMP1 is specifically expressed in adult antennae. SNMP2 is widely expressed in multiple tissues while SNMP3 is specifically expressed in the larval midgut. Microarray analysis suggest SNMP3 may be involved in the silkworm immunity response to virus and bacterial infections. We functionally characterised SNMP1 in the silkworm using RNAi and behavioural assays. Our results suggested that Bombyx mori SNMP1 is a functional orthologue of the Drosophila melanogaster SNMP1 and plays a critical role in pheromone detection. Split-ubiquitin yeast hybridization study shows that BmorSNMP1 has a protein-protein interaction with the BmorOR1 pheromone receptor, and the BmorOrco co-receptor. Concluding, we propose a novel molecular model in which BmorOrco, BmorSNMP1 and BmorOR1 form a heteromer in the detection of the silkworm sex pheromone bombykol.
Rational design of a compact CRISPR-Cas9 activator for AAV-mediated delivery
Authors: Vora Suhani , Cheng Jenny , Xiao Ru , VanDusen Nathan J. , Quintino Luis , Pu William T. , Vandenberghe Luk H. , Chavez Alejandro , Church George
Published: April 2018

Akin to Zinc Finger and Transcription Activator Like Effector based transcriptional modulators, nuclease-null CRISPR-Cas9 provides a groundbreaking programmable DNA binding platform, begetting an arsenal of targetable regulators for transcriptional and epigenetic perturbation, by either directly tethering, or recruiting, transcription enhancing effectors to either component of the Cas9/guide RNA complex. Application of these programmable regulators is now gaining traction for the modulation of disease-causing genes or activation of therapeutic genes, in vivo. Adeno-Associated Virus (AAV) is an optimal delivery vehicle for in vivo delivery of such regulators to adult somatic tissue, due to the efficacy of viral delivery with minimal concerns about immunogenicity or integration. However, present Cas9 activator systems are notably beyond the packaging capacity of a single AAV delivery vector capsid. Here, we engineer a compact CRISPR-Cas9 activator for convenient AAV-mediated delivery. We validate efficacy of the CRISPR-Cas9 transcriptional activation using AAV delivery in several cell lines.
Coordinating the in vivo processes for minicircle production - a novel approach to large scale manufacturing
Authors: Mayrhofer Peter , Jug Hana , Štrancar Aleš , Di Paolo Alexandre , Jost Laurent , Zimmermann Alice , Redl Heinz
Published: April 2018

Safety as well as efficiency issues in connection with bacterial backbone sequences should be carefully considered when designing new DNA vaccines or non-viral gene therapy approaches. Bacterial backbone sequences like antibiotic resistance markers or regulatory bacterial elements constitute biological safety risks and reduce the overall efficiency of the DNA agent. To overcome these problems the minicircle technology has been developed. But, despite all the obvious advantages, minicircles have so far not replaced their problem laden conventional counterpart in gene transfer applications what can be contributed to efficiency issues in large scale manufacturing. In this article we describe the combined efforts of experts in the field of minicircle development, large scale biomanufacturing and downstream process development to provide a new approach. The Recombination Based Plasmid Separation (RBPS) Technology, which has already solved crucial problems associated with minicircle-DNA production, has been developed further for this purpose. A novel parental plasmid exploiting advanced in vivo process coordination for restriction and subsequent degradation of miniplasmid-DNA will be introduced. Furthermore we describe the scale-up of minicircle-DNA production by fermentation in combination with high performance downstream processes including purification by ion exchange and hydrophobic interaction chromatography on monolithic material.
Wanting to like: Motivation influences behavioral and neural responses to social feedback
Authors: Hughes Brent L. , Leong Josiah K. , Shiv Baba , Zaki Jamil
Published: April 2018

Human beings revel in social approval and social connection. For example, individuals want to be liked, and frequently surround themselves with people who provide such positive reinforcement. Past work highlights a “common currency” between social rewards like social approval, and non-social rewards like money. But social and motivational contexts can reshape reward experiences considerably. Here, we examine the boundary conditions that deem social approval subjectively valuable. Participants received feedback about their attractiveness from others. Neural activity in reward-related brain structures (e.g., ventral striatum) increased in response to positive feedback, but only when such feedback came from well-liked targets. These heightened reward responses predicted increases in subsequent attraction to well-liked targets. This work suggests that motivational contexts amplify or diminish the value of social approval in a target-specific manner. The value of social approval is thus defined by the extent to which these experiences bring us closer to people we like.
Pattern-Driven Navigation in 2D Multiscale Visualizations with Scalable Insets
Authors: Lekschas Fritz , Behrisch Michael , Bach Benjamin , Kerpedjiev Peter , Gehlenborg Nils , Pfister Hanspeter
Published: April 2018

We present Scalable Insets, a technique for interactively exploring and navigating large numbers of annotated patterns in multiscale visualizations such as gigapixel images, matrices, or maps. Exploration of many but sparsely-distributed patterns in multiscale visualizations is challenging as visual representations change across zoom levels, context and navigational cues get lost upon zooming, and navigation is time consuming. Our technique visualizes annotated patterns too small to be identifiable at certain zoom levels using insets, i.e., magnified thumbnail views of the annotated patterns. Insets support users in searching, comparing, and contextualizing patterns while reducing the amount of navigation needed. They are dynamically placed either within the viewport or along the boundary of the viewport to offer a compromise between locality and context preservation. Annotated patterns are interactively clustered by location and type. They are visually represented as an aggregated inset to provide scalable exploration within a single viewport. In a controlled user study with 18 participants, we found that Scalable Insets can speed up visual search and improve the accuracy of pattern comparison at the cost of slower frequency estimation compared to a baseline technique. A second study with 6 experts in the field of genomics showed that Scalable Insets is easy to learn and provides first insights into how Scalable Insets can be applied in an open-ended data exploration scenario.
SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides
Authors: Edsinger Eric , Dölen Gül
Published: April 2018

Human and octopus lineages are separated by over 500 million years of evolution, and show divergent anatomical patterns of brain organization. Moreover, while humans exhibit highly complex social behaviors, octopuses are thought to be largely asocial and solitary. Despite these differences, growing evidence suggests that ancient neurotransmitter systems are shared across vertebrate and invertebrate species, and in many cases enable overlapping functions. Here we provide evidence that, as in humans, the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) enhances acute prosocial behaviors in Octopus bimaculoides. This finding is paralleled by the evolutionary conservation of the serotonin transporter (SERT, encoded by the Slc6A4 gene) binding site of MDMA in the O. bimaculoides genome. Taken together, these data provide evidence that the neural mechanisms subserving social behaviors exist in O. bimaculoides, and indicate that the role of serotonergic neurotransmission in regulating social behaviors is evolutionarily conserved.

ONE SENTENCE SUMMARY:

Here we provide evidence that the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) increases acute social approach behaviors in Octopus bimaculoides, a finding that is paralleled by the evolutionary conservation of the SLC6A4 binding site of MDMA.
emeraLD: Rapid Linkage Disequilibrium Estimation with Massive Data Sets
Authors: Quick Corbin , Fuchsberger Christian , Taliun Daniel , Abecasis Gonçalo , Boehnke Michael , Kang Hyun Min
Published: April 2018

Estimating linkage disequilibrium (LD) is essential for a wide range of summary statistics-based association methods for genome-wide association studies (GWAS). Large genetic data sets, e.g. the TOPMed WGS project and UK Biobank, enable more accurate and comprehensive LD estimates, but increase the computational burden of LD estimation. Here, we describe emeraLD (Efficient Methods for Estimation and Random Access of LD), a computational tool that leverages sparsity and haplotype structure to estimate LD orders of magnitude faster than existing tools.

Availability and Implementation

emeraLD is implemented in C++, and is open source under GPLv3. Source code, documentation, an R interface, and utilities for analysis of summary statistics are freely available at http://github.com/statgen/emeraLD

Contact

corbinq@umich.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Epigenetic changes induced by Bacteroides fragilis toxin (BFT)
Authors: Allen Jawara , Hao Stephanie , Sears Cynthia L. , Timp Winston
Published: April 2018

Enterotoxigenic Bacteroides fragilis (ETBF) is a gram negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of mice heterozygous for the adenomatous polyposis coli gene (Apc+/−); tumor formation is dependent on ETBF-secreted Bacteroides fragilis toxin (BFT). Though some of the immediate downstream effects of BFT on colon epithelial cells (CECs) are known, we still do not understand how this potent exotoxin causes changes in CECs that lead to tumor formation and growth. Because of the extensive data connecting alterations in the epigenome with tumor formation, initial experiments attempting to connect BFT-induced tumor formation with methylation in CECs have been performed, but the effect of BFT on other epigenetic processes, such as chromatin structure, remains unexplored. Here, the changes in chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) induced by treatment of HT29/C1 cells with BFT for 24 and 48 hours is examined. Our data show that several genes are differentially expressed after BFT treatment and these changes correlate with changes in chromatin accessibility. Also, sites of increased chromatin accessibility are associated with a lower frequency of common single nucleotide variants (SNVs) in CRC and with a higher frequency of common differentially methylated regions (DMRs) in CRC. These data provide insight into the mechanisms by which BFT induces tumor formation. Further understanding of how BFT impacts nuclear structure and function in vivo is needed.

Importance

Colorectal cancer (CRC) is a major public health concern; there were approximately 135,430 new cases in 2017, and CRC is the second leading cause of cancer-related deaths for both men and women in the US (1). Many factors have been linked to CRC development, the most recent of which is the gut microbiome. Pre-clinical models support that enterotoxigenic Bacteroides fragilis (ETBF), among other bacteria, induce colon carcinogenesis. However, it remains unclear if the virulence determinants of any pro-carcinogenic colon bacterium induce DNA mutations or changes that initiate clonal CEC expansion. Using a reductionist model, we demonstrate that BFT rapidly alters chromatin structure and function consistent with capacity to contribute to CRC pathogenesis.
Metagenomic next-generation sequencing reveals Miamiensis avidus (Ciliophora: Scuticociliatida) in the 2017 epizootic of leopard sharks (Triakis semifasciata) in San Francisco Bay, California
Authors: Retallack Hanna , Okihiro Mark S. , Britton Elliot , Van Sommeran Sean , DeRisi Joseph L.
Published: April 2018

During March to August of 2017, hundreds of leopard sharks (Triakis semifasciata) stranded and died on the shores of San Francisco Bay, California, USA. Similar mass stranding events occurred in 1967 and 2011, yet analysis of these epizootics was incomplete and no etiology was confirmed. Our investigation of the most recent epizootic revealed severe meningoencephalitis in stranded sharks, raising suspicion for infection. On this basis, we pursued a strategy for unbiased pathogen detection using metagenomic next-generation sequencing followed by orthogonal validation and further screening. We show that the ciliated protozoan pathogen, Miamiensis avidus, was present in the central nervous system of leopard (n=12) and other shark species (n=2) that stranded in San Francisco Bay, but absent in leopard sharks caught elsewhere. Whereas this protozoan has previously been implicated in devastating outbreaks in teleost marine fish, our findings represent the first report of a ciliated protozoan infection in wild elasmobranchs. This discovery highlights the benefits of adopting unbiased metagenomic sequencing in the study of wildlife health and disease.
Measuring single neuron visual receptive field sizes by fMRI
Authors: Keliris Georgios A. , Li Qinglin , Papanikolaou Amalia , Logothetis Nikos K. , Smirnakis Stelios M.
Published: April 2018

The non-invasive measurements of neuronal receptive field (RF) properties in-vivo allow a detailed understanding of brain organization as well as its plasticity by longitudinal following of potential changes. Visual RFs measured invasively by electrophysiology in animal models have traditionally provided a great extent of our current knowledge about the visual brain and its disorders. Voxel based estimates of population RF (pRF) by functional magnetic resonance imaging (fMRI) in humans revolutionized the field and have been used extensively in numerous studies. However, current methods cannot estimate single-neuron RF sizes as they reflect large populations of neurons with individual RF scatter. Here, we introduce a new approach to estimate RF size using spatial frequency selectivity to checkerboard patterns. This method allowed us to obtain non-invasive, single-unit, RF estimates in human V1 for the first time. These estimates were significantly smaller compared to prior pRF methods. Further, fMRI and electrophysiological experiments in non-human primates demonstrated an exceptional match validating the approach.
Spotting the path that leads nowhere: Modulation of human theta and alpha oscillations induced by trajectory changes during navigation
Authors: Javadi Amir-Homayoun , Patai Eva Zita , Margois Aaron , Tan Heng-Ru M. , Kumaran Darshan , Nardini Marko , Penny Will , Duzel Emrah , Dayan Peter , Spiers Hugo J.
Published: April 2018

The capacity to take efficient detours and exploit novel shortcuts during navigation is thought to be supported by a cognitive map of the environment. Despite advances in understanding the neural basis of the cognitive map, little is known about the neural dynamics associated with detours and shortcuts. Here, we recorded magnetoencephalography from humans as they navigated a virtual desert island riven by shifting lava flows. The task probed their ability to take efficient detours and shortcuts to remembered goals. We report modulation in event-related fields and theta power as participants identified real shortcuts and differentiated these from false shortcuts that led along suboptimal paths. Additionally, we found that a decrease in alpha power preceded ‘back-tracking’ where participants spontaneously turned back along a previous path. These findings help advance our understanding of the fine-grained temporal dynamics of human brain activity during navigation and support the development of models of brain networks that support navigation.
Generative Modeling of Multi-mapping Reads with mHi-C Advances Analysis of High Throughput Genome-wide Conformation Capture Studies
Authors: Zheng Ye , Ay Ferhat , Keleş Sündüz
Published: April 2018

Abstract Current Hi-C analysis approaches are unable to account for reads that align to multiple locations, and hence underestimate biological signal from repetitive regions of genomes. We developed and validated mHi-C, a multi-read mapping strategy to probabilistically allocate Hi-C multi-reads. mHi-C exhibited superior performance over utilizing only uni-reads and heuristic approaches aimed at rescuing multi-reads on benchmarks. Speciffically, mHi-C increased the sequencing depth by an average of 20% resulting in higher reproducibility of contact matrices and detected interactions across biological replicates. The impact of the multi-reads on the detection of signifficant interactions is influenced marginally by the relative contribution of multi-reads to the sequencing depth compared to uni-reads, cis-to-trans ratio of contacts, and the broad data quality as reflected by the proportion of mappable reads of datasets. Computational experiments highlighted that in Hi-C studies with short read lengths, mHi-C rescued multi-reads can emulate the effect of longer reads,. mHi-c also revealed biologically supported bona fide promoter-enhancer interactions and topologically associating domains involving repetitive genomic regions, thereby unlocking a previously masked portion of the genome for conformation capture studies.