bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriateness of the Use of Magnetic Resonance Imaging in the Diagnosis and Treatment of Wrist Soft Tissue Injury
Authors: Michelotti Brett F. , Mathews Alexandra , Chung Kevin C.
Published: October 2017

Background:

When diagnosing wrist soft tissue injury, the authors hypothesize that magnetic resonance imaging is used injudiciously and is associated with unnecessary cost.

Methods:

A retrospective review was conducted of patients aged 20 to 60 years who underwent magnetic resonance imaging for possible wrist soft tissue injury at a tertiary care center between 2009 and 2014. Treatment recommendation was classified as nonoperative, operative, or equivocal. If the magnetic resonance imaging–directed treatment recommendation differed from the pre-imaging recommendation, it was noted that the imaging influenced patient care (impact study). The cost estimate of an impact study was calculated by dividing the total studies performed by the number of studies that impacted the treatment recommendation and multiplying this value by the institutional wrist magnetic resonance imaging cost ($2246 in 2016).

Results:

One hundred forty patients were included. Magnetic resonance imaging affected treatment recommendation in 28 percent of patients. Independent predictors of impact on treatment recommendation were “question specific injury” (OR, 9.46; 95 percent CI, 3.18 to 28.16; p < 0.001) and “question scapholunate injury” (OR, 2.88; 95 percent CI, 1.21 to 6.88; p = 0.02). The only independent predictor of surgery was ordering physician (hand surgeon) (OR, 3.69; 95 percent CI, 1.34 to 10.13; p = 0.01). The cost of an impact study ordered by a non–hand surgeon versus a hand surgeon was $13,359 versus $6491, respectively.

Conclusions:

The provider must carefully consider the pretest probability of ordering a study that will affect treatment recommendation. Injudicious screening with magnetic resonance imaging ($15,565) incurred a cost nearly seven times the cost of the one imaging scan ($2246) before impacting one treatment recommendation. In the current era of cost containment and bundled payment, diagnostic test probability must be appreciated to guide physician ordering practices.
A Comparison of Functional Outcomes and Therapeutic Costs: Single-Digit Replantation versus Revision Amputation
Authors: Zhu Hongyi , Bao Bingbo , Zheng Xianyou
Published: October 2017

Background:

The functional outcomes and therapeutic costs between digit replantation and revision amputation have remained controversial.

Methods:

A total of 1023 patients with single-digit traumatic amputation or devascularization who underwent successful digit replantation (failure excluded) or revision amputation from January 1, 2013, to January 1, 2016, were included in this study. All cases were subgrouped based on Tamai level of amputation and the injured digit. The clinical outcomes were assessed using the Michigan Hand Outcomes Questionnaire 1 year after the initial operation. The authors also compared the cost of treatment, the duration of hospitalization, and the duration of sick leave between the two treatments.

Results:

Replantation of small (level I to V), ring (level I to III), and long (level I) fingers showed no functional benefit compared with initial revision amputation. In contrast, replantation of thumb (level I to V), index (level I to V), long (level II to V), and ring (level IV to V) fingers had better outcomes. The cost of replantation was higher and the durations of hospitalization and sick leave of replantation were also longer compared with the revision amputation group.

Conclusions:

Single amputated injuries of small (level I to V), ring (level I to III), and long (level I) fingers are a relative contradiction for replantation. Replantation of thumb (level I to V), index (level I to V), long (level II to V), and ring (level IV to V) fingers showed extra benefit compared with revision amputation.
Early Macrophage Infiltration Improves Fat Graft Survival by Inducing Angiogenesis and Hematopoietic Stem Cell Recruitment
Authors: Cai Junrong , Feng Jingwei , Liu Kaiyang , Zhou Shaolong , Lu Feng
Published: October 2017

Background:

Fat grafting is a popular soft-tissue filler method; however, its results are variable and technique-dependent. Macrophages are present in fat grafts and closely associated with tissue regeneration. The authors hypothesized that activation/depletion of early macrophages in transferred fat improves/impairs fat graft survival.

Methods:

Mouse inguinal fat (approximately 150 mg) was transferred autologously. Fat grafting was first performed without other manipulations to obtain baseline information. Then, liposome-encapsulated clodronate and macrophage-colony stimulating factor were used in a mouse fat grafting model for local macrophage depletion or activation. The authors examined the graft stromal vascular fraction by fluorescence-activated cell sorting at 1, 2, 4, and 12 weeks after transplantation in manipulation and control groups. Graft weight, vascularization, and secreted factors were also compared.

Results:

Early depletion of macrophages resulted in incompetent angiogenesis, feeble Sca-1+/CD45+ stem cell recruitment, and eventually a poor retention rate (34 ± 6 mg versus control 84 ± 15 mg; p = 0.006), whereas up-regulated macrophages allowed better angiogenesis and survival (117 ± 12 mg versus control, 84 ± 15 mg; p = 0.043).

Conclusions:

In fat grafting, macrophages and their polarization initiated changes in the levels of dominant secreted factors and influenced blood-derived stem cell infiltration, indicating that macrophages were crucial for tissue revascularization. The macrophage manipulation models described here show that graft macrophage number can profoundly influence graft survival.
Minimally Invasive, Spring-Assisted Correction of Sagittal Suture Synostosis: Technique, Outcome, and Complications in 83 Cases
Authors: van Veelen Marie-Lise C. , Kamst Nathalie , Touw Carolina , Mauff Katya , Versnel Sarah , Dammers Ruben , de Jong T. H. Rob , Prasad Vani , Mathijssen Irene M.
Published: October 2017

Background:

This series describes the results of minimally invasive strip craniotomy with additional spring distraction.

Methods:

Included are the first 83 consecutive patients who underwent this procedure (January 1, 2010, to January 1, 2014). Outcome parameters were collected prospectively and included surgical parameters and complications, the occurrence of papilledema, skull growth, cephalic index, and photographic scores.

Results:

Duration of surgery was 63 minutes, 19 percent required blood transfusion, and complications were minor. Postoperative papilledema occurred in two patients (2.4 percent). Head growth increased after insertion of the springs and declined afterward to 0.7 SD, comparable to earlier cohorts in the authors’ center. The cephalic index increased from 67 before surgery to 74 after surgery and showed a small decrease during the 4-year follow-up. Photographic scores confirmed the initial improvement and showed a trend to further improvement during follow-up.

Conclusions:

In this cohort, spring-assisted, minimally invasive strip craniotomy was safe and effective. Results were similar to those from other techniques but with smaller incisions, shorter interventions, reduced blood loss, and a lower incidence of postoperative papilledema.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Anterior Skull Base and Pericranial Flap Ossification after Frontofacial Monobloc Advancement
Authors: Morice Anne , Paternoster Giovanna , Ostertag Agnès , James Syril , Cohen-Solal Martine , Khonsari Roman H. , Arnaud Eric
Published: October 2017

Background:

Frontofacial monobloc advancement creates a communication between the anterior cranial fossa and nasal cavities. To tackle this issue, transorbital pericranial pedicled flaps are routinely performed in the authors’ center. This study aimed to assess the postoperative ossification of the anterior skull base and pedicled flaps following frontofacial monobloc advancement, and to identify factors influencing this ossification.

Methods:

Measurements of the skull base only and of the ossified pedicled flaps together with the skull base were performed on computed tomographic scans at the nasofrontal and the nasoethmoid frontal junctions. The total thickness of the skull vault was measured and a qualitative defect score for the anterior skull base was computed.

Results:

Twenty-two patients who underwent frontofacial monobloc advancement at a median age of 3.1 years (range, 1.9 to 3.6 years) were included: 14 with Crouzon, five with Pfeiffer, and three with Apert syndrome. One year and 5 years after surgery, the distraction gap was completely ossified in the anterior skull base midline in all patients. Ossified pedicled flaps together with the skull base were thicker in patients than in controls at these two time points (p < 0.005 and p < 0.02). Patients with Pfeiffer syndrome had a significantly thicker skull base only and ossified pedicled flaps together with the skull base thicknesses (p = 0.01 and p = 0.03) and lower defect scores than patients with Crouzon or Apert syndrome (p = 0.03) 1 year postoperatively.

Conclusion:

As ossification of the pedicled flaps and total reossification of the anterior skull base midline were observed in all patients, the authors indicate that performing pedicled flaps in frontofacial monobloc advancement surgery could promote the reossification of the anterior skull base.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Percutaneous Mesh Expansion: A Regenerative Wound Closure Alternative
Authors: Khouri Kimberly S. , Cardoso Eufemiano , Khouri Roger K.
Published: October 2017

Background:

Puncture wounds in the 1-mm range usually heal without scars. Stacking rows of these punctures offers a scarless method to generate tissue by mesh expansion. The authors developed a percutaneous mesh expansion procedure and present their experience for its wound closure application.

Methods:

Over a 6-year period, the authors applied percutaneous mesh expansion to 65 consecutive patients aged 58 to 101 years (mean, 72 years) with 67 full-thickness calvarial defects ranging in size from 2.5 × 3 cm to 7 × 8 cm (mean, 14 cm2) that would have all required flaps for closure. Thirty-six were still anticoagulated, and 20 had prior scalp resections. After tumescent epinephrine anesthesia, the authors temporarily approximate the wound by placing it under strong tension. Using 1.1-mm cutting point needles that selectively sever tissues under tension, the authors inflict rows of staggered alternating punctures over a distance five times the defect width. This results in 20 percent expansion of the meshed area, generating the tissue necessary for defect coverage. When the tension is completely released, closure is performed with simple sutures or staples. The authors avoid overmeshing, especially close to the wound edges, and perform no undermining or additional incisions.

Results:

At 6-week follow-up, all defects were healed with only a straight resection scar. However, of the 10 defects larger than 5 × 5 cm, five had wound healing delay and three required a small skin graft. No other complication was observed.

Conclusions:

Percutaneous mesh expansion is a minimally invasive procedure that harnesses the body’s natural capabilities to regenerate across small gaps. It sums these regenerated gaps in a mesh pattern that expands tissues to close complex wounds without flaps or additional incisions.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Important Details in Performing and Interpreting the Scratch Collapse Test
Authors: Kahn Lorna C. , Yee Andrew , Mackinnon Susan E.
Published: October 2017

The utility of the scratch collapse test has been demonstrated in examination of patients with carpal and cubital tunnel syndromes and long thoracic and peroneal nerve compressions. In the authors’ clinic, this lesser known test plays a key role in peripheral nerve examination where localization of the nerve irritation or injury is not fully understood. Test utility and accuracy in patients with more challenging presentations likely correlate with tester understanding and experience. This article offers a clear outline of all stages of the test to improve interrater reliability. The nuances of test performance are described, including a description of situations where the scratch collapse test is deemed inappropriate. Four clinical scenarios where the scratch collapse test may be useful are included. Corresponding video content is provided to improve performance and interpretation of the scratch collapse test.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Diagnostic, V.
Interruption of the Inferior Vena Cava With Azygos Continuation
Authors: Kuo Chien-Wei , Peng Nan-Jing , Chiu Yu-Li
Published: October 2017

This report describes a 19-year-old man with interruption of the inferior vena cava with azygos continuation. Both radionuclide venography and MRI clearly showed venous return of the lower limbs through prominent collateral systems.
Uncommon Metastasis to the Pancreas From Adenocarcinoma of the Cervix Detected on Surveillance 18F-FDG PET/CT Imaging
Authors: Mahajan Sonia , Pandit-Taskar Neeta
Published: October 2017

18F-FDG PET/CT is a sensitive noninvasive imaging tool for assessment of recurrent disease in patients with carcinoma cervix. Its role in early detection of recurrences especially in asymptomatic patients has been demonstrated well in literature. Metastatic involvement of the pancreas in patients with adenocarcinoma of the cervix is a rare occurrence, reported only few times in literature, and is predominantly documented to be associated with uncommon histopathologies such as neuroendocrine and small cell carcinoma. We report a rare asymptomatic case of adenocarcinoma of the cervix, detected and confirmed to have pancreatic metastasis on surveillance FDG PET/CT imaging.
18F-FAZA PET/CT Hypoxia Imaging of High-Grade Glioma Before and After Radiotherapy
Authors: Mapelli Paola , Zerbetto Flavia , Incerti Elena , Conte Gian Marco , Bettinardi Valentino , Fallanca Federico , Anzalone Nicoletta , Di Muzio Nadia , Gianolli Luigi , Picchio Maria
Published: October 2017

A 57 year-old man underwent MRI with dynamic susceptibility contrast and dynamic contrast-enhanced perfusion for neurological symptoms suggesting the diagnosis of high-grade glioma. A 18F-FAZA PET/CT was performed because of the enrollment in a prospective clinical trial. Subsequent radiotherapy treatment has been planned based on conventional imaging; moreover, a 18F-FAZA PET/CT–guided treatment planning highlighting hypoxic regions has been simulated. After radiotherapy treatment, the man underwent MRI and 18F-FAZA PET/CT, showing partial response.
Myocardial Perfusion SPECT and Cardiac MR Correlative Imaging
Authors: Prosper Ashley E. , Colletti Patrick M.
Published: October 2017

An institutional review board–approved retrospective review of 55 patients who received cardiac MRI within 1 year of myocardial SPECT was performed. Forty-nine demonstrated myocardial infarction by MRI. MRI and SPECT agreed in all but 1 case, where SPECT preceded MRI by 97 days. Three cases are presented here: 2 demonstrating congruent MRI and SPECT changes in a vascular distribution status post infarction and a third with a nonvascular pattern of abnormalities related to left ventricular aneurysm in cardiac sarcoidosis. It is useful to review and correlate myocardial SPECT with available cardiac MRI, especially in patients with matching perfusion defects.
Internal Auditory Canal Tumor as an Incidental Finding on a Choline PET/CT Scan in a Prostate Cancer Patient
Authors: Malamitsi Julia , Efthymiadou Roxanni , Pipikos Theodore , Vlachou Fani , Prassopoulos Vassilis
Published: October 2017

An 84-year-old man with a history of prostate cancer, treated with radiotherapy, presented with an increase in PSA levels. 18F-choline PET/CT showed foci of increased choline uptake in L4 and L5 vertebrae, suggestive of bone metastases and another focus in the right cerebellopontine angle. A brain MRI revealed a focus of intense contrast enhancement in the same region, consistent with an acoustic neuroma.
Prostate-Specific Membrane Antigen in Low-Grade Fibromatosis
Authors: Akbarian Aghdam Ramin , Hakiminejad Masoumeh , Hashemifard Hamidreza , Rakhshan Azadeh , Pirayesh Elahe
Published: October 2017

We report a case of fibromatosis demonstrating prostate-specific membrane antigen (PSMA)–positive scan. A 76-year-old man was under assessment because of rising prostate-specific antigen level. Bone scan showed abnormal soft tissue uptake of 99mTc-MDP adjacent to the right scapula, compatible with a mass in MRI, thereafter. Because of the unavailability of 68Ga-PSMA scan in our department and also high cost in other centers, the patient underwent 177Lu-PSMA for more assessment, which revealed PSMA-avid mass. Pathologic examination confirmed the diagnosis of low-grade fibromatosis. This report demonstrates another false-positive result of PSMA scan and highlights the importance of pathologic examination.
Uterine Metastasis From Gastric Adenocarcinoma Masquerading as Physiologic Endometrial Uptake in FDG PET/CT
Authors: Yao Yutang , Su Minggang , Ou Xiaohong , Shen Yangmei
Published: October 2017

A 44-year-old woman with newly diagnosed gastric adenocarcinoma by gastroscopy underwent 18F-FDG PET/CT to evaluate possible metastasis. The images demonstrated intense activity in the region of uterine corpus, as well as greater gastric curvature. Physiologic uptake of endometrium was initially suspected, given the rarity with which extragenital cancers metastasize to the uterus. Ultimately, the endometrium proved to be mucinous adenocarcinoma of gastric origin based on its shared histological features and compatible immunostaining profile.
Stewart-Treves Syndrome on the Lower Extremity Associated to Idiopathic Chronic Lymphedema Visualized on FDG PET/CT
Authors: Brittain Jane Maestri , Nymark Tine , Hildebrandt Malene Grubbe , Hovgaard Dorrit , Andersen Kim Francis
Published: October 2017

Angiosarcomas are highly malignant and rare tumors of vascular or lymphatic endothelial cell origin with a poor prognosis. Lymphangiosarcoma associated with chronic lymphedema is known as Stewart-Treves syndrome. Stewart-Treves syndrome is primarily described in patients with lymphedema of an upper extremity occurring after breast cancer surgery including radical axillary lymph node dissection and subsequent radiotherapy. It is rarely described in the presence of idiopathic chronic lymphedema of the lower extremities. We present a case of lymphangiosarcoma visualized on 18F-FDG PET/CT, where Stewart-Treves syndrome is secondary to probably a combination of idiopathic chronic lymphedema of the lower extremities and systemic immunosuppressive treatment.
Radioguided Occult Lesion Localization
Authors: Manca Gianpiero , Mazzarri Sara , Rubello Domenico , Tardelli Elisa , Delgado-Bolton Roberto C. , Giammarile Francesco , Roncella Manuela , Volterrani Duccio , Colletti Patrick M.
Published: October 2017

Purpose

Regarding radioguided surgery, the concept of “radioguided occult lesion localization” (ROLL) is based on both preoperative interventional imaging and intraoperative radioguided detection of a clinically occult neoplastic lesion.

Methods

This methodology consists in the direct administration into the lesion of 99mTc–macroaggregated human albumin formed by relatively large particles retained at the injection site, which direct radioguided excisional biopsy.

Results

This modality has expanded from the classic application of ROLL for nonpalpable breast lesions to other tumors, such as solitary pulmonary nodules or recurrences from differentiated thyroid carcinoma. In 2011, in order to improve the classification of different radioguided surgical procedures, ROLL applications were included in the more complete concept of GOSTT (Guided intraOperative Scintigraphic Tumor Targeting). This concept was introduced to include the entire range of basic and advanced radioguided procedures necessary to supply a “road map” for the surgeon.

Conclusions

The terms ROLL and GOSTT have further developed by incorporating novel modalities such as hybrid tracers for simultaneous fluorescence and radioactive signal detection and innovative navigation systems based on mixed-reality protocols.
Atlas of Extraosseous Findings Detected by 18F-NaF PET/CT Bone Scan
Authors: Woodhead Gregory J. , Avery Ryan J. , Kuo Phillip H.
Published: October 2017

18F-NaF PET/CT is an evolving technique that provides high sensitivity for detection of osseous metastases. In addition to detecting pathological osseous lesions, 18F uptake is occasionally detected in extraosseous lesions. However, reporting of extraosseous uptake in the literature is limited, and the increasing use of 18F-NaF PET/CT dictates that interpreting physicians learn to recognize extraosseous findings. An atlas of extraosseous findings detected by 18F-NaF PET/CT is presented, which includes cases under 2 broad categories: nonneoplastic and neoplastic.
Effects on 18F-FDG PET/CT Brain Glucose Metabolism in Rectal Cancer Patients Undergoing Neoadjuvant Chemotherapy
Authors: Machado Alexei M. C. , Fagundes Theara C. , Mafra Arnoldo , Silva Rodrigo G. , Castro Ana Carolina G. , Mamede Marcelo
Published: October 2017

Purpose

Retrospective study of the effects of anticancer treatment on the brain metabolism of patients diagnosed with rectal cancer based on a large and homogeneous sample of 40 paired 18F-FDG PET/CT volumes taken from 20 patients. The results are compared to the ones presented by related works to help elucidating the mechanisms of neurotoxicity associated to a decrease in memory, learning and motor skills.

Patients and Methods

Twenty patients with rectal adenocarcinoma were scanned before and after neoadjuvant chemoradiation based exclusively on 5-fluorouracil and leucovorin. The sample was non-rigidly registered to a common template to allow for the comparison of regional metabolism. Statistical analysis was based on adjusted paired t-tests.

Results

The analysis primarily revealed a statistically significant decrease in the metabolism after neoadjuvant chemotherapy at the hypothalamus, putamen, head of the caudate, globus pallidus, red nucleus, substantia nigra, amygdala, cerebellum and the parahippocampal gyrus. The analysis also revealed smaller regions of increased metabolic activity at the middle temporal gyrus, precuneus of the parietal lobe and cuneus of the occipital lobe.

Conclusions

The regions of decreased metabolism detected in the study are related to memory, learning and voluntary movement which is consistent with previous findings based on clinical studies and neuropsychological tests that report impairments on neurocognitive and motor skills associated to these therapies.
Unilateral Submandibular Gland Atrophy and Sialolithiasis Diagnosed on 99mTc-MIBI SPECT/CT in a Patient With Primary Hyperparathyroidism
Authors: Pattanayak Puskar , Santhanam Prasanna , Javadi Mehrbod Som , Solnes Lilja B. , Rowe Steven P.
Published: October 2017

A variety of sequelae of elevated calcium levels are encountered in patients with underlying primary hyperparathyroidism, including stone formation such as calculi in the urinary tract and sialoliths in the salivary glands and ducts. We present a case of a 54-year-old woman with fatigue, myalgia, and poor concentration who was found to have hypercalcemia (corrected calcium, 11.2 mg/dL) and elevated parathyroid hormone level (112 pg/mL), laboratory values consistent with primary hyperparathyroidism. She underwent evaluation with a99mTc-MIBI parathyroid SPECT scan that included x-ray CT acquisitions for anatomical localization and attenuation correction.
68Ga–Prostate-Specific Membrane Antigen–Avid Tubercular Lesions Mimicking Prostate Cancer Metastasis on Simultaneous Prostate-Specific Membrane Antigen PET/MRI
Authors: Ahuja Aashim , Taneja Sangeeta , Thorat Kiran , Jena Amarnath
Published: October 2017

68Ga–prostate-specific membrane antigen (PSMA) has gained increasing interest as a target molecule in imaging of prostate cancer because of its selective overexpression in local prostate cancer lesions and metastasis. We report a case of a 62-year-old man with raised serum prostate-specific antigen levels who presented for 68Ga-PSMA HBED-CC simultaneous PET/MRI for prostate cancer evaluation. A PSMA-nonavid PI-RADS 5 (Prostate Imaging—Reporting and Data System) lesion was confirmed as adenocarcinoma on histopathology. The PSMA-avid lesions were noted in the calvarium and lung, with the calvarial lesion confirmed to be of tubercular etiology on biopsy, and both lesions subsequently responded to antitubercular treatment.
Multimodal Imaging in Klippel-Trénaunay-Weber Syndrome
Authors: Kim Su Wan , Song Heesung
Published: October 2017

We report the case of a 19-year-old man who presented with a 12-year history of progressive fatigue, feeling hot, excessive sweating, and numbness in the left arm. He had undergone multimodal imaging and was diagnosed as having Klippel-Trénaunay-Weber syndrome (KTWS). This is a rare congenital disease, defined by combinations of nevus flammeus, venous and lymphatic malformation, and hypertrophy of the affected limbs. Lower extremities are affected mostly. Conventional modalities for evaluating KTWS are ultrasonography, CT, MRI, lymphoscintigraphy, and angiography. There are few reports on multimodal imaging of upper extremities of KTWS patients, and this is the first report of an infrared thermography in KTWS.
Value of the Delta Neutrophil Index for Predicting 28-Day Mortality in Patients With Acute Pulmonary Embolism in the Emergency Department
Authors: Kong Taeyoung , Park Yoo Seok , Lee Hye Sun , Kim Sinae , Lee Jong Wook , Yu Gina , Eun Claire , You Je Sung , Chung Hyun Soo , Park Incheol , Chung Sung Phil
Published: October 2017

Purpose:

Acute pulmonary embolism (PE), frequently seen in the emergency department (ED), is a leading cause of cardiovascular morbidity and mortality. The delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes as a component of the systemic inflammatory response syndrome criteria. The pathogenesis of acute PE is significantly associated with inflammation. The aim of the study was to investigate the clinical usefulness of the DNI as a marker of severity in patients with acute PE admitted to the ED.

Methods:

We retrospectively analyzed the data of patients who were diagnosed with acute PE at a single ED, admitted from January 1, 2011 to June 30, 2017. The diagnosis of acute pulmonary embolism was confirmed using clinical, laboratory, and radiological findings. The DNI was determined at presentation. The clinical outcome was all-cause mortality within 28 days of emergency department admission.

Results:

We included 447 patients in this study. The multivariate Cox regression model demonstrated that higher DNI values on ED admission were significantly associated with short-term mortality (hazard ratio, 1.107; 95% confidence interval, 1.042–1.177). The optimal cut-off DNI value, measured on ED admission, was 3.0%; this value was associated with an increased hazard of 28-day mortality following PE (HR, 7.447; 95% CI, 4.183–13.366; P < 0.001)

Conclusion:

The DNI value, obtained as part of the complete blood count analysis, can be easily determined without additional burdens of cost or time. A high DNI is useful as a marker to predict 28-day mortality in patients with acute PE.
Time-dependent competition between habitual and goal-directed response preparation
Authors: Hardwick Robert M , Forrence Alexander D , Krakauer John W , Haith Adrian M
Published: October 2017

Converging evidence indicates that separate goal-directed and habitual systems compete to control behavior1. However, it has proven difficult to reliably induce habitual behavior in human participants2–4. We reasoned that habits may be present in the form of habitually prepared responses, but are overridden by goal-directed processes, preventing their overt expression. Here we show that latent habits can be unmasked by limiting the time participants have to respond to a stimulus. Participants trained for 4 days on a visuomotor association task. By continuously varying the time allowed to prepare responses, we found that the probability of expressing a learned habit followed a stereotyped time course, peaking 300-600ms after stimulus presentation. This time course was captured by a computational model of response preparation in which habitual responses are automatically prepared at short latency, but are replaced by goal-directed responses at longer latency. A more extensive period of practice (20 days) led to increased habit expression by reducing the average time of movement initiation. These findings refine our understanding of habits, and show that practice can influence habitual behavior in distinct ways: by promoting habit formation, and by modulating the likelihood of habit expression.
APC/C-Vihar regulates centrosome activity and stability in theDrosophilagermline
Authors: Braun A. L. , Meghini F. , Villa-Fombuena G. , Guermont M. , Fernandez-Martinez E. , Glover D.M. , Martín-Bermudo M. D. , González-Reyes A. , Kimata Y.
Published: October 2017

A universal feature of metazoan reproduction is the elimination of the maternal centrosomes prior to the end of oogenesis. In animals that have a syncytial cyst stage of oocyte development, includingDrosophilaand mouse, the germline centrosomes undergo a migration to all reside within the oocyte. However, the functional significance of centrosome transport within the female germline and the mechanism orchestrating this event are still a mystery. The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit ubiquitin ligase (E3) that temporally regulates progression of the cell cycle as well as the centrosome cycle. By altering the negative regulation of the cooperating ubiquitin conjugating enzyme (E2), Vihar/Ube2c, we show that temporal control of APC/C activity ensures centrosome stability and migration during earlyDrosophilaoogenesis. When there is perduring APC/C activity, Polo kinase is precociously targeted for destruction, which results in centriole instability and decreased centrosome transport to the oocyte. We show that decreased centrosome transport correlates with a decreased accumulation of pericentriolar material (PCM) proteins on the oocyte nucleus, which results in a weakening of the structural integrity of the egg chamber and loss of oocyte fate – the overall consequence being a reduction in female fertility. Considering the conserved roles of the APC/C and Polo kinase throughout the animal kingdom and the fact that many animals have a syncytial stage of egg development, our results provide insight into the general necessity of gametic centrosome transport for female fertility.
Contact inhibitory Eph signaling suppresses EGF-promoted cell migration by decoupling EGFR activity from vesicular recycling
Authors: Stallaert Wayne , Sabet Ola , Brüggemann Yannick , Baak Lisa , Bastiaens Philippe I.H.
Published: October 2017

The ability of cells to adapt their behavior to growth factors in relation to their environment is an essential aspect of tissue development and homeostasis. Here we show that Eph receptor signaling from cell-cell contacts changes the cellular response to EGFR activation by altering its vesicular trafficking. Eph receptor activation traps EGFR in Rab5-positive early endosomes through an inhibition of Akt-dependent vesicular recycling. By altering the spatial distribution of EGFR activity during EGF stimulation, Eph receptor activation selectively suppresses migratory Akt signaling from the plasma membrane, while preserving proliferative ERK signaling from endosomes. We also show that soluble extracellular signals engaging the G-protein coupled receptor Kiss1 similarly suppress vesicular recycling to alter EGFR signaling. The cellular environment can thus modulate EGFR vesicular trafficking dynamics to generate context-dependent responses to EGF stimulation.

Eph receptor activation generates context-dependent cellular responses to EGFR activation by altering its vesicular trafficking dynamics.
Reconstitution of Helical Soluble α-Synuclein through Transient Interaction with Lipid Interfaces
Authors: Rovere Matteo , Sanderson John B. , Fonseca-Ornelas Luis , Bartels Tim
Published: October 2017

α-synuclein (αSyn) is one of the key players in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies. Its misfolding and subsequent aggregation into intracellular inclusions are the pathological hallmark of these diseases and may also play a central role in the molecular cascade leading to neurodegeneration. In this work, we report the existence of a novel soluble α-helical conformer of αSyn, an archetypal “intrinsically disordered protein” (IDP), obtained through transient interaction with lipid interfaces. We describe how the stability of this conformer is highly dependent on the continuous, dynamic oligomerization of the folded species. The conformational space of αSyn appears to be highly context-dependent, and lipid bilayers might play crucial roles as molecular chaperones for cytosolic species in a cellular environment, as they do in the case of this previously unreported structure.

Significance Statement

Both genetic and histopathologic evidence tie α-synuclein (αSyn) to the pathogenesis of Parkinson’s disease (PD), a widespread neurodegenerative disorder. Lipids play a central role in the dynamics of αSyn in physiology and disease. αSyn undergoes a coil-to-helix transition when binding to lipid vesicles and it is involved in the regulation of synaptic vesicle trafficking. Furthermore, recently discovered α-helical, aggregation-resistant “multimers” of αSyn could constitute a protective conformational pathway. We report the existence of a folded, lipid-unbound αSyn conformer that forms upon transient interaction with lipids and is stabilized by dynamic homooligomerization, suggesting that synaptic activity could modulate resistance towards aggregation. Our results are therefore important both for the molecular pathology of PD and the structural biology of intrinsically disordered proteins.
Decisions are expedited through multiple neural adjustments spanning the sensorimotor hierarchy
Authors: Steinemann Natalie A. , O’Connell Redmond G. , Kelly Simon P.
Published: October 2017

When decision makers prioritize speed over accuracy, neural activity is elevated in brain circuits involved in preparing actions. Such “urgency” signal components, defined by their independence from sensory evidence, are observed even before evidence is presented and can grow dynamically during decision formation. Is urgency applied globally, or are there adjustments of a distinct nature applied at different processing levels? Using a novel multi-level recording paradigm, we show that dynamic urgency impacting cortical action-preparation signals is echoed downstream in electromyographic indices of muscle activation, but does not directly influence upstream cortical levels. A motor-independent representation of cumulative evidence reached lower pre-response levels under conditions of greater motor-level urgency, paralleling a decline in choice accuracy. At the sensory level itself, we find a boost in differential evidence, which is correlated with changes in pupil size and acts to alleviate, rather than contribute to, the overall accuracy cost under speed pressure.
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations inPARP1causing PARP inhibitor resistance
Authors: Pettitt Stephen J. , Krastev Dragomir B. , Brandsma Inger , Drean Amy , Song Feifei , Aleksandrov Radoslav , Harrell Maria I. , Menon Malini , Brough Rachel , Campbell James , Frankum Jessica , Ranes Michael , Pemberton Helen N. , Rafiq Rumana , Fenwick Kerry , Swain Amanda , Guettler Sebastian , Lee Jung-Min , Swisher Elizabeth M. , Stoynov Stoyno , Yusa Kosuke , Ashworth Alan , Lord Christopher J.
Published: October 2017

PARP inhibitors (PARPi) target homologous recombination defective tumour cells via synthetic lethality. Genome-wide and high-density CRISPR-Cas9 “tag, mutate and enrich” mutagenesis screens identified single amino acid mutations in PARP1 that cause profound PARPi-resistance. These included PARP1 mutations outside of the DNA interacting regions of the protein, such as mutations in solvent exposed regions of the catalytic domain and clusters of mutations around points of contact between ZnF, WGR and HD domains. These mutations altered PARP1 trapping, as did a mutation found in a clinical case of PARPi resistance. These genetic studies reinforce the importance of trapped PARP1 as a key cytotoxic DNA lesion and suggest that interactions between non-DNA binding domains of PARP1 influence cytotoxicity. Finally, different mechanisms of PARPi resistance (BRCA1reversion,PARP1,53BP1,REV7mutation) had differing effects on chemotherapy sensitivity, suggesting that the underlying mechanism of PARPi resistance likely influences the success of subsequent therapies.
Cell-specific modulation of nuclear pore complexes controls cell cycle entry during asymmetric division
Authors: Kumar Arun , Sharma Priyanka , Shcheprova Zhanna , Daulny Anne , Sanmartín Trinidad , Matucci Irene , Funaya Charlotta , Beato Miguel , Mendoza Manuel
Published: October 2017

The acquisition of cellular identity is coupled to changes in the nuclear periphery and nuclear pore complexes (NPCs). Whether and how these changes determine cell fate remains unclear. We have uncovered a mechanism regulating NPC acetylation to direct cell fate after asymmetric division in budding yeast. The lysine deacetylase Hos3 associates specifically with daughter cell NPCs during mitosis to delay cell cycle entry (Start). Hos3-dependent deacetylation of nuclear basket and central channel nucleoporins establishes daughter cell-specific nuclear accumulation of the transcriptional repressor Whi5 during anaphase and perinuclear silencing of the CLN2 gene in the following G1 phase. Hos3-dependent coordination of both events restrains Start in daughter but not in mother cells. We propose that deacetylation modulates transport-dependent and - independent functions of NPCs, leading to differential cell cycle progression in mother and daughter cells. Similar mechanisms might regulate NPC functions in specific cell types and/or cell cycle stages in multicellular organisms.
Polygenic risk scores applied to a single cohort reveal pleiotropy among hundreds of human phenotypes
Authors: Socrates Adam , Bond Tom , Karhunen Ville , Auvinen Juha , Rietveld Cornelius A. , Veijola Juha , Jarvelin Marjo-Riitta , O’Reilly Paul F.
Published: October 2017

Background

There is now convincing evidence that pleiotropy across the genome contributes to the correlation between human traits and comorbidity of diseases. The recent availability of genome-wide association study (GWAS) results have made the polygenic risk score (PRS) approach a powerful way to perform genetic prediction and identify genetic overlap among phenotypes.

Methods and findings

Here we use the PRS method to assess evidence for shared genetic aetiology across hundreds of traits within a single epidemiological study – the Northern Finland Birth Cohort 1966 (NFBC1966). We replicate numerous recent findings, such as a genetic association between Alzheimer’s disease and lipid levels, while the depth of phenotyping in the NFBC1966 highlights a range of novel significant genetic associations between traits.

Conclusions

This study illustrates the power in taking a hypothesis-free approach to the study of shared genetic aetiology between human traits and diseases. It also demonstrates the potential of the PRS method to provide important biological insights using only a single well-phenotyped epidemiological study of moderate sample size (~5k), with important advantages over evaluating genetic correlations from GWAS summary statistics only.
The genomics of local adaptation in trees: Are we out of the woods yet?
Authors: Lind Brandon M. , Menon Mitra , Bolte Constance E. , Faske Trevor M. , Eckert Andrew J.
Published: October 2017

There is substantial interest in uncovering the genetic basis of the traits underlying adaptive responses in tree species, as this information will ultimately aid conservation and industrial endeavors across populations, generations, and environments. Fundamentally, the characterization of such genetic bases is within the context of a genetic architecture, which describes the mutlidimensional relationship between genotype and phenotype through the identification of causative variants, their relative location within a genome, expression, pleiotropic effect, environmental influence, and degree of dominance, epistasis, and additivity. Here, we review theory related to polygenic local adaptation and contextualize these expectations with methods often used to uncover the genetic basis of traits important to tree conservation and industry. A broad literature survey suggests that most tree traits generally exhibit considerable heritability, that underlying quantitative genetic variation (QST) is structured more so across populations than neutral expectations (FST) in 69% of comparisons across the literature, and that single-locus associations often exhibit small estimated per-locus effects. Together, these results suggest differential selection across populations often acts on tree phenotypes underlain by polygenic architectures consisting of numerous small to moderate effect loci. Using this synthesis, we highlight the limits of using solely single-locus approaches to describe underlying genetic architectures and close by addressing hurdles and promising alternatives towards such goals, remark upon the current state of tree genomics, and identify future directions for this field. Importantly, we argue, the success of future endeavors should not be predicated on the shortcomings of past studies and will instead be dependent upon the application of theory to empiricism, standardized reporting, centralized open-access databases, and continual input and review of the community’s research.
Awake fMRI Reveals Covert Arousal in Aggressive Dogs Under Social Resource Threat
Authors: Cook Peter , Prichard Ashley , Spivak Mark , Berns Gregory S.
Published: October 2017

Domestic dogs are highly social, and have been shown sensitive not only to the actions of humans and other dogs but to the interactions between them. To examine the canine neurobiological response to observed interactions between a human and another dog, we collected fMRI data from dogs while they watched their owner feed a realistic fake dog or deposit food in a bucket. Given the likelyihood that arousal and affective state may contribute to responses to observed social situations, we examined the relationship between amygdala activation in these two conditions and an independent measure of aggressive temperament from the C-BARQ scale. Dogs rated more aggressive showed significantly higher activation in the fake-dog versus bucket condition. This finding suggests a neurobiological mechanism mediated by the amygdala for dog-directed aggression, especially when their owner interacts with another dog. Such a mechanism may have some parallels to human jealousy. Further, it adds to a growing body of evidence that specific neurobiological responses correlate with canine temperament and can be a predictor of future behavior. We also found evidence that the amygdala response habituates with repeated observed interactions. This suggests value in exposure-based interventions for potentially aggressive dogs.
Single-cell transcriptional dynamics of flavivirus infection
Authors: Zanini Fabio , Pu Szu-Yuan , Bekerman Elena , Einav Shirit , Quake Stephen R.
Published: October 2017

Dengue and Zika viral infections affect millions of people annually and can be complicated by hemorrhage or neurological manifestations, respectively. However, a thorough understanding of the host response to these viruses is lacking, partly because conventional approaches ignore heterogeneity in virus abundance across cells. We present viscRNA-Seq (virus-inclusive single cell RNA-Seq), an approach to probe the host transcriptome together with intracellular viral RNA at the single cell level. We applied viscRNA-Seq to monitor dengue and Zika virus infection in cultured cells and discovered extreme heterogeneity in virus abundance. We exploited this variation to identify host factors that show complex dynamics and a high degree of specificity for either virus, including proteins involved in the endoplasmic reticulum translocon, signal peptide processing, and membrane trafficking. We validated the viscRNA-Seq hits and discovered novel proviral and antiviral factors. viscRNA-Seq is a powerful approach to assess the genome-wide virus-host dynamics at single cell level.
Relevance of host cell surface glycan structure for cell specificity of influenza A virus
Authors: Kastner Markus , Karner Andreas , Zhu Rong , Huang Qiang , Zhang Dandan , Liu Jianping , Geissner Andreas , Sadewasser Anne , Lesch Markus , Wörmann Xenia , Karlas Alexander , Seeberger Peter , Wolff Thorsten , Hinterdorfer Peter , Herrmann Andreas , Sieben Christian
Published: October 2017

Influenza A viruses (IAV) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycan receptors on host cells. HAs receptor specificity towards sialic acid (SA) is well studied and clearly critical for virus infection, but the contribution of the highly complex cellular plasma membrane to the cellular specificity remains elusive. In addition, some studies indicated that other host cell factors such as the epidermal growth factor receptor might contribute to the initial virus-cell contact and further downstream signaling1.

Here we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS) to compare influenza virus receptor specificity with actual host cell binding. Unexpectedly, our study reveals that HAs receptor binding preference does not necessarily reflect virus-cell specificity. We propose SVFS as a tool to elucidate the cell binding preference of IAV thereby including the complex environment of sialylated receptors within the plasma membrane of living cells.