bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Postpartum Visit Attendance with a Scheduled 2- to 3-Week or 6-Week Visit after Delivery
Authors: Chen Melissa J. , Hsia Jennifer K. , Hou Melody Y. , Wilson Machelle D. , Creinin Mitchell D.
Published: November 2018

Objective To evaluate whether scheduling a 2- to 3-week versus 6-week postpartum visit results in higher visit attendance.

Study Design We conducted a secondary analysis of a quasi-experimental before–after study to compare postpartum visit attendance after changing routine scheduling of visits from 6 weeks to 2 to 3 weeks after delivery. Secondary outcomes include patient satisfaction and breastfeeding continuation at 3 and 6 months postpartum. We collected postpartum visit information through a chart review and conducted telephonic interviews at 3 and 6 months postpartum to assess satisfaction with visit timing and breastfeeding status. We performed multivariable analyses to assess predictors of visit attendance.

Results Women scheduled at 2 to 3 weeks postpartum demonstrated higher visit attendance (90.2%; 95% confidence interval [CI]: 86.6–93.9%) compared with 6 weeks (81.6%; 95% CI: 76.3–86.2%; p < 0.01). Predictors for visit attendance include postpartum visit timing, age, education, parity, prior miscarriage, and high-risk index pregnancy in multivariate analysis. Scheduling at 2 to 3 weeks postpartum increased visit completion in women who were younger and had lower educational attainment, high-risk index pregnancy, and no prior miscarriages. We found no differences in patient satisfaction or breastfeeding continuation at 3 and 6 months postpartum related to postpartum visit timing.

Conclusion Scheduling a 2- to 3-week postpartum visit is associated with higher attendance.
Undivided Retromandibular Vein Leading to the Absence of External Jugular Vein
Authors: Rao Y. , Ballal Vaishnavi , Murlimanju B. , Pai Mangala , Tonse Mamatha , Krishnamurthy Ashwin
Published: November 2018

We report a case of undivided retromandibular vein (RV) that was associated with the absence of external jugular vein (EJV). This variation in the jugular venous system was observed on the right side of the neck of a male cadaver. The posterior auricular vein drained into the RV, which joined the facial vein resulting in a common trunk. This common trunk then drained directly into the internal jugular vein (IJV) thus bypassing the whole venous drainage area of the EJV. It is believed that the knowledge about the venous variations, as in the present case, is enlightening to the clinicians. The preoperative evaluation of the venous system is essential to prevent complications like catastrophic bleeding and embolism. The knowledge may guide the emergency physician for a quicker cannulation of the veins.
Double Inferior Vena Cava Associated with Double Suprarenal and Testicular Venous Anomalies: A Rare Case Report
Authors: Khamanarong Kimaporn , Mahiphot Jarupon , Iamsaard Sitthichai
Published: November 2018

Introduction The variant courses of blood vessels are very important in considerations for retroperitoneal surgeries or interventional radiology. The present study attempted to describe a very rare case of double inferior vena cava (IVC) associated with double left suprarenal veins (LSRVs) and double right testicular veins (RTVs) in a Thai male embalmed cadaver.

Material and Methods A 70-year-old Thai male cadaver was systemically dissected and observed for the vascular distributions during gross anatomy teaching for medical students at the anatomy department of the faculty of medicine of the Khon Kaen University.

Results We found that the double IVCs were connected with the transverse interiliac vein. While the upper LSRV is a tributary of the IVC, the lower LSRV is a tributary of the left renal vein. The RTV bifurcates at about the height of the iliac cristae to form the medial and lateral RTVs, which drain into the right IVC at different heights.

Conclusion All these duplications and associated anomalies are assumed to occur during the embryological development. These anomalies are rare, but the knowledge about the possibilities of these anomalies is of great importance during retroperitoneal surgeries, and during interventional radiology.
Use of Mannose-Binding Lectin Gene Polymorphisms and the Serum MBL Level for the Early Detection of Neonatal Sepsis
Authors: Badawy Magda , Saber Doaa , Madani Hanan , Mosallam Dalia
Published: November 2018

Background Mannose-binding lectin (MBL) is a component of innate immunity and is particularly important in neonates, in whom adaptive immunity has not yet completely developed. MBL deficiency and MBL2 gene polymorphisms are associated with an opsonization defect and have been associated with neonatal sepsis.

Aim The aim of our study was to assess serum MBL levels and genotype MBL2 genes to determine whether they can serve as markers for predicting neonatal sepsis in neonatal intensive care units.

Patients and Methods A case-control study was conducted with 114 neonates classified into two groups: the septic group included 64 neonates (41 preterm and 23 full-term infants), and the non-septic control group included 50 neonates (29 preterm and 21 full-term infants). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to genotype MBL2 gene exon 1 (rs1800450) and (rs1800451) SNPs. Enzyme-linked immunosorbent assay (ELISA) was used to measure MBL serum concentrations.

Results The polymorphic genotypes BB and AC at codons 54 and 57, respectively, showed higher frequencies than the wild-type genotype (AA) (14.1% versus 12.9% and 28.1% versus 19.4% respectively) in both groups, and this difference was greater in the septic group than in the non-septic group; however, the differences did not reach statistical significance. The B and C allele frequencies were also higher in the septic group than in the non-septic group, but the differences did not reach statistical significance (p = 0.282 and 0.394, respectively). The serum levels of MBL were significantly lower in the septic group than in the non-septic group (p = 0.028).

Conclusion This study found no association between MBL levels or MBL2 exon 1 genotypes or alleles and neonatal sepsis risk. Further studies with larger sample sizes are needed to determine the role of the MBL2 gene as a risk factor and early predictor of neonatal sepsis.
Diets containing pomegranate polyphenol and soy isoflavone attenuate contact hypersensitivity in mice
Authors: Nagano Takao , Ito Hideyuki
Published: November 2018

Contact hypersensitivity (CHS) is frequently used as an animal model for human allergic contact dermatitis (ACD). Diets of pomegranate polyphenols (PPs) or soy isoflavones (SIs) each alleviated CHS symptoms; however, the effect of diets containing a mixture of PPs and SIs on CHS is unclear. We investigated the CHS-inhibitory effects of diets supplemented with a mixture of PPs and SIs at human physiologically relevant doses. Consuming the mixture of PPs and SIs attenuated ear swelling and reduced infiltration of Gr-1-positive cells. Ear swelling decreased in the PP and SI-treated mice compared to the SI-treated mice. The auricle tissues of the PP and SI-fed mice exhibited decreased production of CXCL2 and MCP-5 compared to the SI- and PP-treated mice, respectively. These results suggest that dietary supplementation with a mixture of PPs and SIs may have ACD-preventive effects and may prove more beneficial than supplementation with PPs or SIs alone.
Is Hindsight Really 20/20?: The Impact of Outcome Information on the Decision-Making Process
Authors: Beltrani Amanda , Reed Amanda L. , Zapf Patricia A. , Otto Randy K.
Published: November 2018

Previous research has reviewed the issue of biasability in forensic evaluation and has anecdotally related different forms of bias to forensic work; however, there is no empirical research that explores hindsight bias in forensic evaluation. Hindsight bias is the tendency for an individual to believe that a specific event, in hindsight, was more predictable than it was (in foresight). Using an international sample of 95 mental health professionals the current study explored the impact of outcome knowledge on the decision-making process in forensic evaluation. Using a 2 (suicide/self-harm v. homicide/other-harm) x 2 (outcome provided v. no outcome provided) between groups design, participants reviewed a hypothetical patient’s hospital chart and then indicated their opinion regarding the risk of harm the patient presented to self or others. Participants provided with outcome information were significantly more likely to indicate that they would have predicted the outcome than those who were not provided with outcome information. In addition, participants with outcome information endorsed higher risk ratings for violence than those who were not provided with outcome information, suggesting that context can impact the way in which information is perceived. Thus, participant’s evaluation of and decision-making about an event, in hindsight, may not meet the objective standard to which forensic mental health professionals aspire. The importance of recognizing and understanding this form of bias and its limitations as well as appropriate techniques to reduce biases and achieve a better quality of work are discussed.
A GIS APPROACH TO IDENTIFYING SERVICE ACCESS DISPARITIES IN RURAL APPALACHIA
Authors: Harris A , Savla T , Borowski S , Vipperman A , Roberto K A , Lancki K , Blieszner R , Knight A L
Published: November 2018

Formal service use can help decrease caregiving burden for family members of persons with dementia; however, barriers related to service use are common. For example, driving distance can be problematic in rural areas with mountainous terrain, as in the Appalachian region of Virginia. The purpose of this study was to examine distance from family homes to services and its association with service use. Thirty-nine caregivers’ residences and 84 service locations were mapped, then driving distance to and distribution of services were analyzed using Service Area Solver and Closest Facility Solver in ArcGIS. Results suggest that services were unevenly distributed based on caregiver location. Specifically, of all services examined, food banks and medical facilities had the most facilities near caregiver locations, whereas adult day services, support groups, and educational programs for caregivers were sparse. Findings are discussed in light of identifying vulnerable caregivers as well as hot-spots for potential interventions.
NAT/NCS2-hound: a webserver for the detection and evolutionary classification of prokaryotic and eukaryotic nucleobase-cation symporters of the NAT/NCS2 family
Authors: Chaliotis A , Vlastaridis P , Ntountoumi C , Botou M , Yalelis V , Lazou P , Tatsaki E , Mossialos D , Frillingos S , Amoutzias G D
Published: November 2018

Nucleobase transporters are important for supplying the cell with purines and/or pyrimidines, for controlling the intracellular pool of nucleotides, and for obtaining exogenous nitrogen/carbon sources for metabolism. Nucleobase transporters are also evaluated as potential targets for antimicrobial therapies, since several pathogenic microorganisms rely on purine/pyrimidine salvage from their hosts. The majority of known nucleobase transporters belong to the evolutionarily conserved and ubiquitous nucleobase-ascorbate transporter/nucleobase-cation symporter-2 (NAT/NCS2) protein family. Based on a large-scale phylogenetic analysis that we performed on thousands of prokaryotic proteomes, we developed a webserver that can detect and distinguish this family of transporters from other homologous families that recognize different substrates. We can further categorize these transporters to certain evolutionary groups with distinct substrate preferences. The webserver scans whole proteomes and graphically displays which proteins are identified as NAT/NCS2, to which evolutionary groups and subgroups they belong to, and which conserved motifs they have. For key subgroups and motifs, the server displays annotated information from published crystal-structures and mutational studies pointing to key functional amino acids that may help experts assess the transport capability of the target sequences. The server is 100% accurate in detecting NAT/NCS2 family members. We also used the server to analyze 9,109 prokaryotic proteomes and identified Clostridia, Bacilli, β- and γ-Proteobacteria, Actinobacteria, and Fusobacteria as the taxa with the largest number of NAT/NCS2 transporters per proteome. An analysis of 120 representative eukaryotic proteomes also demonstrates the server's capability of correctly analyzing this major lineage, with plants emerging as the group with the highest number of NAT/NCS2 members per proteome.
Partial Transcondylar Approach for Ventral Foramen Magnum Neurenteric Cyst: 2-Dimensional Operative Video
Authors: Matsushima Ken , Kohno Michihiro , Izawa Hitoshi , Tanaka Yujiro
Published: November 2018

The anterior foramen magnum area, ventral to the brainstem is one of the most difficult regions to access surgically, and the extent of osseous drilling through the far-lateral or transcondylar approach should be planned in each case based on the tumor extension.
1,2
This video, reproduced after informed consent of the patient, demonstrates a case of a ventral foramen magnum neurenteric cyst surgically treated using the partial transcondylar approach. A 27-yr-old woman presented with gait disturbance, oscillopsia, and transient arm numbness. Neuroimaging revealed a ventral foramen magnum cystic tumor involving the basilar and bilateral vertebral arteries. The tumor extended inferiorly from the middle clivus to the C1 level, and occupied the whole premedullary cistern compressing the bilateral lower cranial nerves. The left partial transcondylar approach was performed with drilling the condylar fossa, superior part of the occipital condyle, C1 posterior arch, and posterior part of the jugular process to achieve the sufficient surgical view from the inferolateral side. The drilling of the occipital condyle was minimized so that the articular facet of the occipital condyle was preserved. The tumor on the bilateral side was completely removed as enabled by the sufficient surgical field without new neurological deficits. Three-dimensional reconstructed images based on the postoperative computed tomography scans demonstrated the appropriate extent of the osseous drilling.
Ventral Precentral Fiber Intersection Area: A Central Hub in the Connectivity of Perisylvian Associative Tracts
Authors: Gayoso Sonia , Perez-Borreda Pedro , Gutierrez Antonio , García-Porrero Juan A , Marco de Lucas Enrique , Martino Juan
Published: November 2018

BACKGROUND

The ventral part of the precentral gyrus is considered one of the most eloquent areas. However, little is known about the white matter organization underlying this functional hub.

OBJECTIVE

To analyze the subcortical anatomy underlying the ventral part of the precentral gyrus, ie, the ventral precentral fiber intersection area (VPFIA).

METHODS

Eight human hemispheres from cadavers were dissected, and 8 healthy hemispheres were studied with diffusion tensor imaging tractography. The tracts that terminate at the ventral part of the precentral gyrus were isolated. In addition, 6 surgical cases with left side gliomas close to the VPFIA were operated awake with intraoperative electrical stimulation mapping.

RESULTS

The connections within the VPFIA are anatomically organized along an anteroposterior axis: the pyramidal pathway terminates at the anterior bank of the precentral gyrus, the intermediate part is occupied by the long segment of the arcuate fasciculus, and the posterior bank is occupied by the anterior segment of the arcuate fasciculus. Stimulation of the VPFIA elicited speech arrest in all cases.

CONCLUSION

The present study shows strong arguments to sustain that the fiber organization of the VPFIA is different from the classical descriptions, bringing new light for understanding the functional role of this area in language. The VPFIA is a critical neural epicenter within the perisylvian network that may represent the final common network for speech production, as it is strategically located between the termination of the dorsal stream and the motor output cortex that directly control speech muscles.
Left Transsylvian-Transinsular Approach for Radiation-Induced Cavernous Malformation: 3-Dimensional Operative Video
Authors: Burkhardt Jan-Karl , Gandhi Sirin , Tabani Halima , Benet Arnau , Lawton Michael T
Published: November 2018

De novo cavernous malformation (CM) formation after radiation therapy for brain tumors is well known, but CM formation adjacent to a radiosurgically treated arteriovenous malformation (AVM) is rare.
1
This video demonstrates the microsurgical resection of a de novo CM adjacent to a previously treated high-grade AVM and clipping of a middle cerebral artery (MCA) aneurysm. A 70-yr-old male with history of radiosurgery for AVM presented with aphasia and confusion. Preoperative angiography showed complete occlusion of the AVM. MRI showed multiple cystic lesions suspicious for radiation-induced necrosis and CM.

IRB approval and patient consent was obtained. A pterional craniotomy was performed with transsylvian exposure of the insula. The radiated feeding arteries were followed to the occluded AVM nidus. A CM was noted deep to this candelabra of the MCA vessels, which were mobilized to access and resect the CM. A small incision was made in this insular cortex underneath the malformation circumferentially freeing it of adhesions. The sclerotic AVM nidus was circumferentially dissected and removed en bloc. Thorough exploration of the resection cavity revealed no residual CM or AVM nidus. Attention was then turned to the M2-MCA bifurcation aneurysm, which was occluded with a straight clip. Postoperative imaging confirmed complete CM resection. The patient recovered from his aphasia.

This case demonstrates the management of a radiation-induced de novo CM following treatment of a high-grade AVM. Radiographic follow-up for radiosurgically treated AVM is needed to rule out long-term complications. Bleeding from a de novo CM mimics bleeding from residual AVM nidus, requiring careful angiographic evaluation.
Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals
Authors: Huhn Andrew S. , Strain Eric C. , Bigelow George E. , Smith Michael T. , Edwards Robert R. , Tompkins D. Andrew
Published: November 2018

EDITOR’S PERSPECTIVE

What We Already Know about This Topic

The prevalence of patients prescribed buprenorphine for treatment of opioid use disorder is increasing

Managing acute pain in buprenorphine-maintained individuals can be challenging

What This Article Tells Us That Is New

Large doses of intravenous hydromorphone can provide analgesia in buprenorphine-maintained individuals

However, the use of hydromorphone for analgesia in buprenorphine-maintained individuals confers greater abuse liability and side effects than does supplemental intravenous buprenorphine

Background

Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone.

Methods

Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events.

Results

A significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting.

Conclusions

In this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.
Contribution of Baroreceptor Function to Pain Perception and Perioperative Outcomes
Authors: Suarez-Roca Heberto , Klinger Rebecca Y. , Podgoreanu Mihai V. , Ji Ru-Rong , Sigurdsson Martin I. , Waldron Nathan , Mathew Joseph P. , Maixner William
Published: November 2018

Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain homeostasis by coordinating physiologic responses to external and internal stimuli. While it is recognized that carotid and cardiopulmonary baroreceptor reflexes modulate autonomic output to mitigate excessive fluctuations in arterial blood pressure and to maintain intravascular volume, increasing evidence suggests that baroreflex pathways also project to key regions of the central nervous system that regulate somatosensory, somatomotor, and central nervous system arousal. In addition to maintaining autonomic homeostasis, baroreceptor activity modulates the perception of pain, as well as neuroimmune, neuroendocrine, and cognitive responses to physical and psychologic stressors. This review summarizes the role that baroreceptor pathways play in modulating acute and chronic pain perception. The contribution of baroreceptor function to postoperative outcomes is also presented. Finally, methods that enhance baroreceptor function, which hold promise in improving postoperative and pain management outcomes, are presented.
Excess Mortality Among Adults Hospitalized With Traumatic Brain Injury in Australia: A Population-Based Matched Cohort Study
Authors: Lystad Reidar P. , Cameron Cate M. , Mitchell Rebecca J.
Published: November 2018

Objective:

To quantify and describe excess mortality attributable to traumatic brain injury (TBI) during the 12 months after hospitalization.

Design:

Population-based matched cohort study using linked hospital and mortality data.

Setting:

Australia.

Participants:

Individuals 18 years and older who were hospitalized with a principal diagnosis of TBI in 2009 (n = 6929) and matched noninjured individuals randomly selected from the electoral roll (n = 6929).

Main Measures:

Survival distributions were compared using a Kaplan-Meier plot with a log-rank test. Mortality rate ratios (MRRs) were computed using Cox proportional hazard regression with and without controlling for demographic characteristics and preexisting health status.

Results:

Individuals with TBI experienced significantly worse survival during the 12 months after hospitalization (χ2 = 640.9, df = 1, P < .001), and were more than 7.5 times more likely to die compared with their noninjured counterparts (adjusted MRR, 7.76; 95% confidence interval, 6.07–9.93). TBI was likely to be a contributory factor in 87% of deaths in the TBI cohort. Excess mortality was higher among males, younger age groups, and those with more severe TBI.

Conclusion:

Excess mortality is high among individuals hospitalized with TBI and most deaths are attributable to the TBI. Increased primary and secondary preventive efforts are warranted to reduce the mortality burden of TBI.
Clinical Magnetic Resonance Imaging of the Knee at 7 T
Authors: Wyss Michael , Manoliu Andrei , Marcon Magda , Spinner Georg , Luechinger Roger , Pruessmann Klaas P. , Andreisek Gustav
Published: November 2018

Purpose

The aim of this study was to evaluate the efficiency and performance of different fat suppression techniques for clinical 7 T knee magnetic resonance imaging including the slice-selective gradient reversal (SSGR) technique.

Materials and Methods

This article is an ethical board–approved prospective study with written informed consent from 8 volunteers (mean, 31 ± 4 years). It included fat phantom and knee magnetic resonance imaging at 3 T (Magnetom Skyra; Siemens Healthcare) and at 7 T (Achieva, Philips Healthcare). At 3 T, an axial proton density-weighted turbo spin echo sequence with spectral adiabatic inversion recovery (SPAIR) was acquired. At 7 T, a series of 5 proton density-weighted turbo spin echo sequences was acquired: (a) without fat suppression, (b) with spectral presaturation with inversion recovery (SPIR), (c) with SPAIR, (d) with SSGR, and (e) with the combination of SSGR + SPIR. Additional noise scans allowed pixelwise calculation of signal-to-noise ratio and contrast-to-noise ratio maps. Quantitative data at 7 T were compared with each other but not to 3 T. Two independent radiologists evaluated overall image quality, homogeneity and grade of fat suppression, and the delineation between 2 adjacent structures. Results were compared using Wilcoxon signed rank and paired sample t tests.

Results

Relative signal-to-noise ratios of fat demonstrated that the SPIR technique reduced the fat signal to 45% ± 5.4%; SPAIR, 18% ± 1.2%; SSGR, 14% ± 1.1%; and SSGR + SPIR, 11% ± 0.3%. Contrast-to-noise ratio showed superior contrast between muscle-fat (P < 0.001) and fluid-fat (P ≤ 0.001) for SSGR and SSGR + SPIR. The radiologists rated the overall image quality higher at 7 T than 3 T. The homogeneity and grade of fat suppression as well as the delineation between 2 different (adjacent) structures were rated best for SSGR + SPIR.

Conclusions

At 7 T, fat saturation for clinical knee imaging using SSGR and the combination of SSGR + SPIR was superior compared with standard methods based on spectrally selective radiofrequency pulses.
Association of MRI T2 Signal Intensity With Desmoid Tumor Progression During Active Observation
Authors: Cassidy Michael R. , Lefkowitz Robert A. , Long Niamh , Qin Li-Xuan , Kirane Amanda , Sbaity Eman , Hameed Meera , Coit Daniel G. , Brennan Murray F. , Singer Samuel , Crago Aimeé M.
Published: November 2018

Objective:

The aim of this study was to identify predictors of desmoid progression during observation.

Summary of Background Data:

Untreated desmoids can grow, remain stable, or regress, but reliable predictors of behavior have not been identified.

Methods:

Primary or recurrent desmoid patients were identified retrospectively from an institutional database. In those managed with active observation who underwent serial magnetic resonance imaging (MRIs) with T2-weighted sequences, baseline tumor size was recorded, and 2 radiologists independently estimated the percentage of tumor volume showing hyperintense T2 signal at baseline. Associations of clinical or radiographic characteristics with progression-free survival (PFS; by RECIST) were evaluated by Cox regression and Kaplan-Meier statistics.

Results:

Among 160 patients with desmoids, 72 were managed with observation, and 37 of these had serial MRI available for review. Among these 37 patients, median age was 35 years and median tumor size was 4.7 cm; all tumors were extra-abdominal (41% in abdominal wall). Although PFS was not associated with size, site, or age, it was strongly associated with hyperintense T2 signal in ≥90% versus <90% of baseline tumor volume (as defined by the “test” radiologist; hazard ratio = 11.3,P= 0.003). For patients in the ≥90% group (n = 20), 1-year PFS was 55%, compared with 94% in the <90% group (n = 17). The percentage of baseline tumor volume with hyperintense T2 signal defined by a validation radiologist correlated with results of the test radiologist (ρ = 0.75).

Conclusion:

The percent tumor volume characterized by hyperintense T2 signal is associated with desmoid progression during observation and may help distinguish patients who would benefit from early intervention from those who may be reliably observed.
Pretransplant Cancer in Kidney Recipients in Relation to Recurrent and De Novo Cancer Incidence Posttransplantation and Implications for Graft and Patient Survival
Authors: Unterrainer Christian , Opelz Gerhard , Döhler Bernd , Süsal Caner
Published: November 2018

Background.

Whether kidney transplant recipients who were treated for a malignant tumor before transplantation are at an increased risk of developing a tumor posttransplantation has not been adequately quantified and characterized.

Methods.

We studied more than 270 000 patients on whom pretransplant and posttransplant malignancy data were reported to the Collaborative Transplant Study. More than 4000 of these patients were treated for pretransplant malignancy. The posttransplant tumor incidence in these patients was compared to that in recipients without a pretransplant tumor. Cox regression, considering multiple confounders, was applied.

Results.

Significant increases in posttransplant tumor incidence with hazard ratio ranging from 2.10 to 5.47 (all P < 0.001) were observed for tumors in the site-specific pretransplant locations, suggesting tumor recurrences. There were also significantly increased de novo tumors in new locations with hazard ratio ranging from 1.28 to 1.89. Pretransplant basal cell carcinoma of the skin and male genital cancer were associated with significantly increased death-censored graft survival, suggesting impaired immune responsiveness against transplanted kidneys. Time interval from pretransplant tumor occurrence to transplantation and posttransplant mammalian target of rapamycin inhibitor treatment was not found to be of significant relevance in this study.

Conclusions.

Patients who experienced a pretransplant tumor are at significant risk of tumor recurrence, regardless of the length of interval between tumor treatment and transplantation. There is also some increased risk for de novo tumors, suggesting impaired immune surveillance. Impaired tumor immunity appears to extend to a lower rate of transplant rejection because patients with pretransplant tumors tended to show improved death-censored graft survival.
Red muscle activity in bluegill sunfishLepomis macrochirusduring forward accelerations
Authors: Schwalbe Margot A. B. , Boden Alexandra L. , Wise Tyler N. , Tytell Eric D.
Published: November 2018

Fishes generate force to swim by activating muscles on either side of their flexible bodies. To accelerate, they must produce higher muscle forces, which leads to higher reaction forces back on their bodies from the environment. If their bodies are too flexible, the forces during acceleration cannot be transmitted effectively to the environment. Here, we investigate whether fish can use their red muscle to stiffen their bodies during acceleration. We used high-speed video, electromyographic recordings, and a new digital inertial measurement unit to quantify body kinematics, red muscle activity, and 3D orientation and centre of mass acceleration during forward accelerations and steady swimming over several speeds. During acceleration, fish co-activated anterior muscle on the left and right side, and activated all muscle sooner and kept it active for a larger fraction of the tail beat cycle. These activity patterns are consistent with our hypothesis that fish use their red muscle to stiffen their bodies during acceleration. We suggest that during impulsive movements, flexible organisms like fishes can use their muscles not only to generate propulsive power but to tune the effective mechanical properties of their bodies, increasing performance during rapid movements and maintaining flexibility for slow, steady movements.
The discovery of three new hare lagoviruses reveals unexplored viral diversity in this genus
Authors: Mahar Jackie E. , Hall Robyn N. , Shi Mang , Mourant Roslyn , Huang Nina , Strive Tanja , Holmes Edward C.
Published: November 2018

Our knowledge of mammalian viruses has been strongly skewed toward those that cause disease in humans and animals. However, recent metagenomic studies indicate that most apparently healthy organisms carry viruses, and that these seemingly benign viruses may comprise the bulk of virus diversity. The bias toward studying viruses associated with overt disease is apparent in the lagoviruses (familyCaliciviridae) that infect rabbits and hares: although most attention has been directed toward the highly pathogenic members of this genus - the rabbit haemorrhagic disease virus and European brown hare syndrome virus - a number of benign lagoviruses have also been identified. To determine whether wild European brown hares in Australia might also carry undetected benign viruses, we used a meta-transcriptomics approach to explore the gut and liver RNA viromes of these invasive animals. This led to the discovery of three new lagoviruses. While one of the three viruses was only detected in a single hare, the other two viruses were detected in 20% of all hares tested. All three viruses were most closely related to other hare lagoviruses, but were highly distinct from both known viruses and each other. We also found evidence for complex recombination events in these viruses, which, combined with their phylogenetic distribution, suggests that there is likely extensive unsampled diversity in this genus. Additional metagenomic studies of hares and other species are clearly needed to fill gaps in the lagovirus phylogeny and hence better understand the evolutionary history of this important group of mammalian viruses.
Comparing DNA, RNA and protein levels for measuring microbial activity in nitrogen-amended soils
Authors: Orellana Luis Humberto , Hatt Janet , Iyer Ramsunder , Chourey Karuna , Hettich Robert L , Spain Jim , Yang Wendy H , Chee-Sanford Joanne , Sanford Robert A , Löffler Frank E , Konstantinidis Konstantinos T
Published: November 2018

Multi-omic techniques can offer a comprehensive overview of microbial communities at the gene, transcript and protein levels. However, to what extent these levels reflect in situ process rates is less clear, especially in highly complex habitats such as soils. Here we performed microcosm incubations using soil from a site with a history of agricultural management. Microcosms, amended with isotopically labelled ammonium and urea to simulate a fertilization event, showed nitrification (up to 4.1 ± 0.87 µg N-NO3-g-1dry soil d-1) and accumulation of N2O after 192 hours of incubation. Nitrification activity (NH4+→NH2OH→NO2-→NO3-) was accompanied by a 6-fold increase in relative expression of the 16S rRNA gene (RNA/DNA) between 10 and 192 hours of incubation for ammonia-oxidizing bacteria (AOB) Nitrosomonas and Nitrosospira. In contrast, ammonia-oxidizing archaea (AOA)and complete ammonia oxidizer (comammox) nitrifiers showed stable gene expression during incubations but were generally more abundant (DNA level) than their Betaproteobacteria AOB counterparts. A strong relationship between nitrification activity and (mostly) betaproteobacterial ammonia monooxygenase (amoA; NH4+→NH2OH) and nitrite oxidoreductase (nxrA; NO2-→NO3-) transcript abundances revealed that mRNA levels quantitatively reflected measured activity and were generally more sensitive than the DNA level in the microcosm incubations. Although peptides related to housekeeping proteins from nitrite-oxidizing microorganisms were detected, their abundance was not significantly correlated with activity, revealing that meta-proteomics provided only a qualitative assessment of activity. Altogether, these findings underscore the strengths and limitations of multi-omic approaches for assessing complex microbial communities and provide the molecular means to assess nitrification processes in soils.
Dynamics of age-related catastrophic mitotic failures and recovery in yeast
Authors: Crane Matthew M. , Russell Adam E. , Schafer Brent J. , Hong Mung Gi , Goings Joslyn E. , Chen Kenneth L. , Blue Ben W. , Kaeberlein Matt
Published: November 2018

Genome instability is a hallmark of aging and contributes to age-related disorders such as progeria, cancer, and Alzheimer’s disease. In particular, nuclear quality control mechanisms and cell cycle checkpoints have generally been studied in young cells and animals where they function optimally, and where genomic instability is low. Here, we use single cell imaging to study the consequences of increased genomic instability during aging, and identify striking age-associated genome missegregation events. During these events the majority of mother cell chromatin, and often both spindle poles, are mistakenly sent to the daughter cell. This breakdown in mitotic fidelity is accompanied by a transient cell cycle arrest that can persist for many hours, as cells engage a retrograde transport mechanism to return chromosomes to the mother cell. The repetitive ribosomal DNA (rDNA) has been previously identified as being highly vulnerable to age-related replication stress and genomic instability, and we present several lines of evidence supporting a model whereby expansion of rDNA during aging results in nucleolar breakdown and competition for limited nucleosomes, thereby increasing risk of catastrophic genome missegregation.
Chromosome-wide evolution and sex determination in a nematode with three sexes
Authors: Tandonnet Sophie , Koutsovoulos Georgios D. , Adams Sally , Cloarec Delphine , Parihar Manish , Blaxter Mark L. , Pires-daSilva Andre
Published: November 2018

The free-living nematode Auanema rhodensis is a rare example of a species with three sexes, in which males, females and hermaphrodites coexist. A. rhodensis males have only one X chromosome (XO), whereas females and hermaphrodites have two (XX). The A. rhodensis X chromosome is unusual: it does not recombine in hermaphrodites and is transmitted from father to son. The mechanism that controls the production of females versus hermaphrodites is unknown but is dependent on maternal and larval environmental factors. Here we report the genome sequence and genetic map of A. rhodensis, placing over 95% of the sequence in seven linkage groups. Comparison of the seven A. rhodensis chromosomes to chromosomal assemblies of Caenorhabditis elegans and three other rhabditine nematodes identified deeply conserved linkage groups we call Nigon units, some of which have been maintained in all species analysed. Others have undergone breakage and fusion, and the A. rhodensis karyotype is the product of a unique set of rearrangements involving three Nigon units. The A. rhodensis X chromosome is much smaller than the autosomes, is less gene dense and is 3 to 4 times more polymorphic, reflecting its unique transmission history. Differential expression analyses comparing females and hermaphrodites, identified several candidate genes, including orthologues of C. elegans gld-1, tra-1 and dmd-10/11, that are potentially involved in the female-hermaphrodite sexual decision.
Memory trace superimposition impairs recall in a mouse model of AD
Authors: Poll Stefanie , Schmid Lena C. , Steffen Julia , Wagner Jens , Schmidt Boris , Jackson Walker S. , Schoch Susanne , Ehninger Dan , Fuhrmann Martin
Published: November 2018

Learning and memory processes depend on the hippocampus and are impaired in Alzheimer’s disease (AD). Active neuronal ensembles form an engram by encoding information during learning. Their reactivation is required for memory recall. However, it remains unresolved whether the engram in CA1 principal neurons is impaired under AD-like conditions. We used two-photon in vivo imaging to visualize the expression of the immediate early gene c-fos within CA1 neurons during contextual fear conditioning and retrieval. Surprisingly, we identified engrams in wild-type mice and in the mouse model of AD indicating intact memory formation. However, under AD-like conditions engrams were superimposed by a high number of newly recruited fosGFP+ neurons during memory recall. This superimposition resembled the network configuration of wild-type mice exposed to a novel context. Artificial superimposition of the memory trace during recall in wild-type mice was sufficient to induce memory impairment. Thus, we propose superimposition of the CA1 memory trace as a mechanism for memory impairment in a mouse model of AD.

Highlights

Decreased fosGFP expression in direct vicinity to amyloid-β plaques

Intact engram in CA1 of APP/PS1 mice

Impurity of the retrieval network in CA1 is sufficient to impair memory recall

Poll et al. present a novel mechanism for memory impairment in a mouse model of AD. The potential memory trace was found intact in the CA1 region of the hippocampus. However, excessive neuronal activity during retrieval, was superimposing the memory trace in a mouse model of AD.
Meiotic MCM proteins promote and inhibit crossovers during meiotic recombination
Authors: Hartmann Michaelyn , Kohl Kathryn P. , Sekelsky Jeff , Hatkevich Talia
Published: November 2018

Crossover formation as a result of meiotic recombination is vital for proper segregation of homologous chromosomes at the end of meiosis I. In many organisms, crossovers are generated through two crossover pathways: Class I and Class II. To ensure accurate crossover formation, meiosis-specific protein complexes regulate the degree in which each pathway is used. One such complex is the mei-MCM complex, which contains MCM (mini-chromosome maintenance) and MCM-like proteins REC (ortholog of Mcm8), MEI-217, and MEI-218, collectively called the mei-MCM complex. The mei-MCM complex genetically promotes Class I crossovers and inhibits Class II crossovers inDrosophila, but it is unclear how individual mei-MCM proteins contribute to crossover regulation. In this study, we perform genetic analyses to understand how specific regions and motifs of mei-MCM proteins contribute to Class I and II crossover formation and distribution. Our analyses show that the long, disordered N-terminus of MEI-218 is dispensable for crossover formation, and that mutations that disrupt REC’s Walker A and B motifs differentially affect Class I and Class II crossover formation. In Rec Walker A mutants, Class I crossovers exhibit no change, but Class II crossovers are increased. However, inrecWalker B mutants, Class I crossovers are severely impaired, and Class II crossovers are increased. These results suggest that REC may form multiple complexes that exhibit differential REC-dependent ATP binding and hydrolyzing requirements. These results provide genetic insight into the mechanisms through which mei-MCM proteins promote Class I crossovers and inhibit Class II crossovers.
Tamoxifen improves glucose tolerance in a delivery, sex, and strain-dependent manner in mice
Authors: Ceasrine Alexis M. , Lin Eugene E. , Lumelsky David N. , Ruiz-Otero Nelmari , Boehm Erica D. , Kuruvilla Rejji
Published: November 2018

Tamoxifen, a selective estrogen receptor modulator, is widely used in mouse models to temporally control gene expression but is also known to affect body composition. Here, we report that tamoxifen has significant and sustained effects on glucose tolerance, independent of effects on insulin sensitivity, in mice. Intraperitoneal, but not oral, tamoxifen delivery improved glucose tolerance in three inbred mouse strains. The extent and persistence of tamoxifen-induced effects were sex- and strain-dependent. These findings highlight the need to revise commonly used tamoxifen-based protocols for gene manipulation in mice by including longer chase periods following injection, oral delivery, and the use of tamoxifen-treated littermate controls.
A New Method to Correct for Habitat Filtering in Microbial Correlation Networks
Authors: Brisson Vanessa , Schmidt Jennifer , Northen Trent R. , Vogel John P. , Gaudin Amélie
Published: November 2018

Amplicon sequencing of 16S, ITS, and 18S regions of microbial genomes is a commonly used first step toward understanding microbial communities of interest for human health, agriculture, and the environment. Correlation network analysis is an emerging tool for investigating the interactions within these microbial communities. However, when data from different habitats (e.g sampling sites, host genotype, etc.) are combined into one analysis, habitat filtering (co-occurrence of microbes due to habitat sampled rather than biological interactions) can induce apparent correlations, resulting in a network dominated by habitat effects and masking correlations of biological interest. We developed an algorithm to correct for habitat filtering effects in microbial correlation network analysis in order to reveal the true underlying microbial correlations. This algorithm was tested on simulated data that was constructed to exhibit habitat filtering. Our algorithm significantly improved correlation detection accuracy for these data compared to Spearman and Pearson correlations. We then used our algorithm to analyze a real data set of 16S-V4 amplicon sequences that was expected to exhibit habitat filtering. Our algorithm was found to effectively reduce habitat effects, enabling the construction of consensus correlation networks from data sets combining multiple related sample habitats.
Chemically-induced Neurite-like Outgrowth Reveals Multicellular Network Function in Patient-derived Glioblastoma Cells
Authors: da Silva Barbara , Polson Euan S. , Droop Alastair , Mathew Ryan K. , Stead Lucy F. , Williams Jennifer , Short Susan C. , Scarcia Margherita , Mavria Georgia , Wurdak Heiko
Published: November 2018

Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of Glioblastoma Multiforme (GBM), the most aggressive type of brain cancer in adults. We show that small molecule inhibition of RHO-associated serine/threonine kinase (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formedde novo-induced cellular network (iNet) ‘webs’, which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range calcium signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet websex vivo, and may thereby accelerate future studies into the biology of GBM cellular networks.
Ribosomal protein imbalance launches a C/EBP-based program to preserve tissue integrity
Authors: Baillon Ludovic
Published: November 2018

Genes encoding ribosomal proteins are expressed at rate limiting levels, rendering their biological function highly sensitive to the copy-number variation that results from genomic instability. Cells with a reduced number of ribosomal protein genes (RPGs) are eliminated, when intermingled with wild type cells, via a process known as cell competition. The mechanisms underlying this phenomenon are poorly understood. Here we report the function of a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1, that is critically required for the elimination of cells with a hemizygous RPG genotype. In such cells,Xrp1is transcriptionally upregulated by an autoregulatory loop and is able to trigger cell elimination. Since genomic instability is likely to cause the loss of a haploinsufficient RPG, we propose a molecular model of how RPGs, together with a C/EBP-dependent transcriptional program, could preserve the genomic integrity of tissues.