bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Increased Patient Load Improve Mortality in Burns?
Authors: Busche Marc Nicolai , Jacobs Denise , Rennekampff Hans-Oliver
Published: March 2019

Introduction

In burn care, as in other medical fields, there is a tendency to increase the required number of patients for center certifications. Does the increase in patient load automatically improve the quality of burn care? What are the benchmark parameters that have been shown to improve burn care?

Methods

To answer these questions, Medline, Cochrane Library, and Livivo were searched from inception through January 2018 for all studies evaluating the influence of treatment parameters on outcomes in different burn care settings.

Results

Fifteen studies were included in this systematic review. In adults, not a single study showed a decreased mortality due to a higher patient load. However, in children, 2 studies demonstrated a further decrease of the already low mortality due to an increase in patient load. In contrast to patient load, benchmark parameters that had a significant influence on the outcome of burn care for adults and children were: single bed isolation, residency programs, American Burn Association certifications of burn centers, speed of wound closure, and standard operating procedures for burn care.

Conclusions

This systematic review demonstrates that a clear correlation between patient load and mortality reduction in adult burn treatment is not supported by the existing literature, requiring future studies. In contrast, all efforts aiming to improve the quality of burn care, such as isolation of burn patients, speed of wound closure, American Burn Association verification and especially standard operating procedures for burn care improve survival and quality of burn care.
A Systematic Review of Sensory Outcomes of Digital Nerve Gap Reconstruction With Autograft, Allograft, and Conduit
Authors: Mauch Jaclyn T. , Bae Alison , Shubinets Valeriy , Lin Ines C.
Published: March 2019

Background

Direct comparison of nerve autograft, conduit, and allograft outcomes in digital nerve injuries is limited. This study aims to compare the outcomes of nerve autografts, allografts, and conduits relative to primary repair (PR) through a systematic review.

Methods

A review of literature related to digital nerve gap repairs was conducted using PubMed/MEDLINE. Included articles were human clinical studies on digital nerve injuries repaired with nerve autograft, allograft, bovine collagen conduit, or PR. Patient characteristics, injury details, and complications were collected. Greater than 6-month outcomes included static 2-point discrimination, the British Medical Research Council Scale, or Semmes-Weinstein.

Results

Four autograft, 4 allograft, 5 conduit, and 7 PR publications were included. Allografts had the most repairs (100%) with static 2-point discrimination less than 15 mm, followed by autografts (88%), conduits (72%), and PR (63%). In British Medical Research Council Scale results, autografts (88%) and allografts (86%) were similar for patients with at least S3+ sensibility, compared to conduit (77%) and PR (39%). For Semmes-Weinstein, autografts demonstrated 93% normal sensation or diminished light touch, compared to allografts (71%), PR (70%), or conduits (46%). Conduits had the highest complication rate (10.9%), followed by autografts (5.7%), allografts (3.0%), and PRs (0.4%).

Conclusions

Although a randomized clinical trial would provide strongest evidence of superiority, this review presents the highest percentage of patients with normal to near normal sensory recovery in allograft and autograft repairs with low rates of complications. Nerve conduit studies reported a higher rate of incomplete recovery of sensation and complications.
Lymphedema Incidence After Axillary Lymph Node Dissection
Authors: Johnson Anna Rose , Kimball Sarah , Epstein Sherise , Recht Abram , Lin Samuel J. , Lee Bernard T. , James Ted A. , Singhal Dhruv
Published: March 2019

Background

Axillary surgery and radiotherapy are important aspects of breast cancer treatment associated with development of lymphedema. Studies demonstrate that Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) may greatly reduce the incidence of lymphedema in high-risk groups. The objective of this study is to summarize the evidence relating lymphedema incidence to axillary lymph node dissection (ALND), regional lymph node radiation (RLNR) therapy, and LYMPHA.

Methods

We performed a literature search to identify studies involving breast cancer patients undergoing ALND with or without RLNR. Our primary outcome was the development of lymphedema. We analyzed the effect of LYMPHA on lymphedema incidence. We chose the DerSimonian and Laird random-effects meta-analytic model owing to the clinical, methodological, and statistical heterogeneity of studies.

Results

Our search strategy yielded 1476 articles. After screening, 19 studies were included. Data were extracted from 3035 patients, 711 of whom had lymphedema. The lymphedema rate was significantly higher when RLNR was administered with ALND compared with ALND alone (P < 0.001). The pooled cumulative incidence of lymphedema was 14.1% in patients undergoing ALND versus 2.1% in those undergoing LYMPHA and ALND (P = 0.029). The pooled cumulative incidence of lymphedema was 33.4% in those undergoing ALND and RLNR versus 10.3% in those undergoing ALND, RLNR, and LYMPHA (P = 0.004).

Conclusion

Axillary lymph node dissection and RLNR are important interventions to obtain regional control for many patients but were found to constitute an increased risk of development of lymphedema. Our findings support that LYMPHA, a preventive surgical technique, may reduce the risk of breast cancer–related lymphedema in high-risk patients.
How Breast Implant Surface Type Is Influenced by Breast Implant-associated Anaplastic Large Cell Lymphoma
Authors: Carr Logan W. , Roberts John , Potochny John D.
Published: March 2019

Introduction

Breast implant selection is multifactorial and must assess risk profiles of the implants. Textured implants are available in an anatomically shaped form and are thought to have lower rates of capsular contracture. However, evidence is mounting that they carry a significantly higher risk of breast implant associated anaplastic large cell lymphoma. Given this relationship, we aimed to assess breast implant preferences and device selection for members of the American Society of Plastic Surgeons (ASPS).

Methods

An online survey of all active members of ASPS was performed. Questions analyzed the surgeons' demographic data as well as implant and tissue expander choices for patients receiving either breast augmentation or reconstruction. Logistic regression models of summarized data were used to assess surgeons' implant choices.

Results

The survey was sent to 5000 members and was completed by 824 for a response rate of 16.5%. Demographic data indicate a homogenous sampling of ASPS members from all geographical areas. A majority of surgeons reported that they perform 21–50 implant cases in the last year (n = 219, 28.5%), followed closely by surgeons performing greater than 100 cases (n = 194, 25.3%) and those placing between 51 and 100 (n = 189, 24.6%). Almost one-half of respondents (n = 361, 46.9%) stated that the majority (>50%) of the implants they placed were for cosmetic purposes. Conversely, 306 (37.9%) respondents stated that the majority of implants they placed were for reconstructive purposes and 102 (13.3%) respondents indicated equal placement of cosmetic and reconstructive implants. There were 40.9% (n = 318) surgeons who continue to use textured implants, whereas 59.1% (n = 460) report using only smooth implants. This data includes 47.7% (n = 363) of respondents who report switching to only smooth implants due to awareness of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

Conclusions

The incidence of BIA-ALCL continues to rise. All known cases have some link to textured implants. With equally efficacious alternatives available with smooth implants, surgeons and patients are altering their implant choices.
The Impact of Taxane-based Chemotherapy on the Lymphatic System
Authors: Johnson Anna Rose , Granoff Melisa D. , Lee Bernard T. , Padera Timothy P. , Bouta Echoe M. , Singhal Dhruv
Published: March 2019

Background

Breast cancer–related lymphedema affects 700,000 breast cancer survivors in the United States. Although taxane-based chemotherapy regimens are commonly used in the treatment of breast cancer, the impact of taxanes on the lymphatic system remains poorly understood. This study aims to examine the influence of taxane-based chemotherapy on lymphatic function in breast cancer patients.

Methods

A retrospective review of a prospectively-maintained database was performed. Consecutive patients with node positive breast cancer who underwent preoperative indocyanine green (ICG) lymphangiograms were identified. Information including patient demographics, baseline measurements, cancer characteristics, and treatment information were retrieved. Preoperative ICG lymphangiography videos were analyzed and lymphatic contractility was quantified for each subject. Multiple regions of interest were selected on each lymphatic channel and signal intensity was recorded for 3 minutes to generate contractility curves. Each lymphatic contraction was identified using a novel, systematic, and algorithmic approach.

Results

Twenty-nine consecutive patients with unilateral node-positive breast cancer were included for analysis. Average patient age was 54.5 (13) years and mean BMI was 26.8 kg/m2 (4). The mean lymphatic contractility of patients who received taxane-based neoadjuvant chemotherapy was 0.7 contractions/minute (c/m) (n = 19) compared to 1.1 c/m in those who received no neoadjuvant therapy (n = 10), (P = 0.11). In subgroup analysis, patients who reported taxane induced neuropathy demonstrated significantly lower lymphatic contractility values than those who were asymptomatic or did not receive any chemotherapy (P = 0.018).

Conclusions

In this study, we used a novel method for quantifying and evaluating lymphatic contractility rates in routine ICG lymphangiograms. Diminished lymphatic contractility was noted in patients who received taxane-based neoadjuvant chemotherapy compared with those who did not. Taxane-based neoadjuvant chemotherapy may adversely affect the lymphatic system in the breast cancer population. A larger patient cohort with longer follow-up time is needed to validate this finding and evaluate any potential association with breast cancer–related lymphedema development.
Comparative Accuracy of Clinical and Formula-Based Estimation of Resection Weight in Reduction Mammoplasty and Implications for Insurance Preapproval and Payment
Authors: Wampler Ariel , Powelson Ian , Matthew Michael K.
Published: March 2019

Introduction

Insurance companies use minimum resection weight, sometimes based on body surface area (Schnur sliding scale), as a criterion for preapproval and ultimately coverage of reduction mammoplasty. The purpose of this study is to compare the accuracy of subjective resection estimates and estimates calculated by published formulae versus measured resection weights, and to explore the impact of these estimates on insurance preauthorization and payment.

Methods

A retrospective chart review of bilateral reduction mammaplasties performed at a single academic medical center by seven plastic surgeons from January 2011 to December 2017 was performed. Patients undergoing oncoplastic reduction, simultaneous additional body-contouring procedures, or lacking complete data were excluded. A total of 762 patients were reviewed. Absolute and relative errors between preoperative estimate and actual resection weights were calculated. A subset of patients with requisite breast measurements (n = 579) was examined to compare formula-based with clinical estimates of resection weights.

Results

Median error was 105 g (14% normalized by resection weight). Frequency of underestimation (40.5%) and overestimation (55.7%) were similar. In 19% (n = 291) of reduced breasts, resection estimate was less than the Schnur requirement. For 5 (2.8%) of these patients, insurers denied coverage explicitly for this reason. Our surgeons' positive predictive value of estimate > Schnur was 86.6%. In 23% (n = 352) of breasts, resection was < Schnur requirement. No insurance claim was denied a posteriori due to resection weight less than Schnur. The formula proposed by Appel et al. produced the most accurate estimates, and is the most likely to produce an estimate < Schnur in nonobese women. Correlations between each surgeon's relative errors and years of faculty experience (r
2 < 0.07) and number of reduced breasts (r
2 = 0.0275) were very weak.

Conclusions

Resection estimate accuracy varies among surgeons and does not appear to be affected by experience. Because insurers use resection estimates to determine preauthorization, this could be problematic, particularly for surgeons tending to underestimate. However, insurers are inconsistent in application of the Schnur requirement once surgery has been preapproved and its validity as a determinant of medical necessity is in question.
Would Plastic Surgeons Choose Breast Conservation Therapy?
Authors: Myers Paige L. , Park Rachel H. , Mitchell Drew C. , Nghiem Bao Tram , Amalfi Ashley N.
Published: March 2019

Background

Breast conservation therapy is defined as partial mastectomy with subsequent radiation therapy and is the treatment for early-stage breast cancer. However, the unwanted risks of radiation must be considered as well as the impact on future breast reconstruction options. The purpose of this study was to assess the preference of plastic surgeons when given the hypothetical diagnosis of breast cancer.

Methods

A survey assessing treatment preference of 3 hypothetical breast cancer diagnosis scenarios was designed and distributed by American Society of Plastic Surgeons via e-mail invite to its members.

Results

The risk of cancer recurrence was the most common reason for treatment preferences of all three choices. However, for ductal carcinoma in situ, unilateral mastectomy with implant-based reconstruction is the preferred option with the second most influential reason of avoiding the risks of radiation therapy. For invasive ductal carcinoma node negative, unilateral mastectomy with implant-based reconstruction was the preferred option also due to risks of radiation therapy and anxiety of future surveillance. For invasive ductal carcinoma node positive, bilateral mastectomy with implant-based reconstruction was the preferred choice because of anxiety of future surveillance and also risks of radiation therapy.

Conclusions

In general, plastic surgeons did not prefer breast conservation therapy for in situ and early-stage breast cancer. Although the most common rationale for total mastectomy was risk of cancer recurrence for all disease severity, risks of radiation therapy are real and play an integral role in the decision-making process. In understanding our own biases, we can help better empathize with patients in consultation for breast reconstruction.
Laparoscopic Anatomic Spiegel Lobectomy With the Extrahepatic Glissonean Approach
Authors: Xiang Shuai , Zhang Yu-xin , Chai Song-shan , Zhang Wan-guang
Published: March 2019

Background:

Laparoscopic Spiegel lobectomy is difficult due to its deep location and being surrounded by gross vessels. Extrahepatic Glissonean pedicle transection method has been proposed by Takasaki during open liver resections. This approach can be successfully performed during laparoscopic anatomic hepatectomy. Here we describe pure laparoscopic Spiegel lobectomy using the extrahepatic Glissonean approach.

Methods:

The patient was a 25-year-old male with a background of hepatitis B. A 1.5 cm×1.7 cm mass was detected in liver Spiegel lobe and highly suspected to be an hepatocellular carcinoma. The liver function was normal (Child-pugh 5), and alpha-fetoprotein was within the normal ranges. Laparoscopic Spiegel lobectomy using extrahepatic Glissonean approach was proposed. The hilar plate was partly detached from liver parenchyma, and 2 Glissonean pedicles of the Spiegel lobe were dissected, clamped and divided. Liver parenchymal transection was performed using the harmonic scalpel.

Results:

The operation time was 196 minutes without Pringle’s maneuver. Estimated blood loss was <50 mL, and no blood transfusion was required. The patient recovered well and was discharged on postoperative day 6. There was no complication. Pathologic findings support the diagnosis of hepatocellular carcinoma.

Conclusions:

Laparoscopic Spiegel lobectomy using the extrahepatic Glissonean approach is safe and feasible.
Assessment of conditioned pain modulation in healthy participants and patients with chronic pain: manifestations and implications for pain progression
Authors: Petersen Kristian K. , McPhee Megan E. , Hoegh Morten S. , Graven-Nielsen Thomas
Published: March 2019

Purpose of review

The purpose of this review is to summarize recent findings on conditioned pain modulation (CPM) in humans with a focus on methodology, factors modulating CPM, and the potential for CPM as a clinical marker for pain progression.

Recent findings

CPM can be evoked by combining different stimulus modalities with good reliability; sequential CPM effects are stable over time with limited carryover effects. Optimism and pain catastrophizing might influence pain inhibition. Further, studies suggest that the CPM effect can be improved by gabapentinoids, transcranial direct current stimulation to cortical structures, and exercise and that long-term opioid use might impair CPM in patients with chronic pain. Clinical evidence suggests that preoperative impaired CPM may predict more severe chronic postoperative pain. The effect of pain duration on CPM impairment has been challenged by recent studies.

As CPM methodology is optimized, studies are revealing factors that can modulate descending pain inhibitory pathways. Understanding underlying mechanisms of CPM will improve the utility of CPM in a clinical setting and potentially lead to personalized treatments for chronic pain patients.
Eco-evolutionary dynamics further weakens mutualistic interaction and coexistence under population decline
Authors: Weinbach Avril , Loeuille Nicolas , Rohr Rudolf P.
Published: March 2019

Abstract

With current environmental changes, evolution can rescue declining populations, but what happens to their interacting species? Mutualistic interactions can help species sustain each other when their environment worsens. However, mutualism is often costly to maintain, and evolution might counter-select it when not profitable enough. We investigate how evolution of mutualism affects the coexistence of two mutualistic species, e.g. a plant-pollinator or plant-fungi system. Specifically, using eco-evolutionary dynamics, we study the evolution of the focal species investment in the mutualistic interaction of a focal species (e.g. plant attractiveness via flower or nectar production for pollinators or carbon exudate for mycorrhizal fungi), and how it is affected by the decline of the partner population with which it is interacting. We assume an allocation trade-off so that investment in the mutualistic interaction reduces the species intrinsic growth rate. First, we investigate how evolution changes species persistence, biomass production, and the intensity of the mutualistic interaction. We show that concave trade-offs allow evolutionary convergence to stable coexistence. We next assume an external disturbance that decreases the partner population by lowering its intrinsic growth rate. Such declines result in the evolution of lower investment of the focal species in the mutualistic interaction, which eventually leads to the extinction of the partner species. With asymmetric mutualism favouring the partner, the evolutionary disappearance of the mutualistic interaction is delayed. Our results suggest that evolution may account for the current collapse of some mutualistic system like plant-pollinator ones, and that restoration attempts should be enforced early enough to prevent potential negative effects driven by evolution.
Evolutionary stability of collateral sensitivity to antibiotics in the model pathogenPseudomonas aeruginosa
Authors: Barbosa Camilo , Roemhild Roderich , Rosenstiel Philip , Schulenburg Hinrich
Published: March 2019

Evolution is at the core of the impending antibiotic crisis. Sustainable therapy must thus account for the adaptive potential of pathogens. One option is to exploit evolutionary trade-offs, like collateral sensitivity, where evolved resistance to one antibiotic causes hypersensitivity to another one. To date, the evolutionary stability and thus clinical utility of this trade-off is unclear. We performed a critical experimental test on this key requirement, using evolution experiments withPseudomonas aeruginosacombined with genomic and genetic analyses, and identified three main outcomes: (i) bacteria commonly failed to counter hypersensitivity and went extinct; (ii) hypersensitivity sometimes converted into multidrug resistance; and (iii) resistance gains occasionally caused re-sensitization to the previous drug, thereby maintaining the trade-off. Drug order affected the evolutionary outcome, most likely due to variation in fitness costs and epistasis among adaptive mutations. Our finding of robust genetic trade-offs and drug-order effects can guide design of evolution-informed antibiotic therapy.
Mammalian olfaction is a high temporal bandwidth sense
Authors: Erskine Andrew , Ackels Tobias , Dasgupta Debanjan , Fukunaga Izumi , Schaefer Andreas T.
Published: March 2019

Odours are transported in turbulent plumes resulting locally in highly fluctuating odour concentration (Celani et al., 2014; Murlis et al., 1992; Mylne and Mason, 1991; Shraiman and Siggia, 2000). Yet, whether mammals can make use of the ensuing temporal structure (Celani et al., 2014; Crimaldi and Koseff, 2001; Murlis et al., 1992; Mylne and Mason, 1991; Schmuker et al., 2016; Vickers, 2000) to extract information about the olfactory environment remains unknown. Here, we use dual-energy photoionisation recording with >300 Hz bandwidth to simultaneously determine odour concentrations of two odours in air. We show that temporal correlation of odour concentrations reliably predicts whether odorants emerge from the same or different sources in normal turbulent environments outside and in laboratory conditions. To replicate natural odour dynamics in a reproducible manner we developed a multichannel odour delivery device allowing presentation of several odours with 10 ms temporal resolution. Integrating this device in an automated operant conditioning system we demonstrate that mice can reliably discriminate the correlation structure of odours at frequencies of up to 40 Hz. Consistent with this finding, output neurons in the olfactory bulb show segregated responses depending on the correlation of odour stimuli with populations of 10s of neurons sufficient to reach behavioural performance. Our work thus demonstrates that mammals can perceive temporal structure in odour stimuli at surprisingly fast timescales. This in turn might be useful for key behavioural challenges (Jacobs, 2012) such as odour source separation (Hopfield, 1991), figure-ground separation (Rokni et al., 2014) or odour localisation (Vergassola et al., 2007; Vickers, 2000).
Transcriptional signatures of invasiveness inMeloidogyne incognitapopulations from sub-Saharan Africa
Authors: Cox Deborah , Reilly Brian , Warnock Neil D. , Dyer Steven , Sturrock Matthew , Cortada Laura , Coyne Danny , Maule Aaron G. , Dalzell Johnathan J.
Published: March 2019

Meloidogyne incognitais an economically important plant parasitic nematode. Here we demonstrate substantial variation in the invasiveness of fourM. incognitapopulations relative to tomato. Infective (J2) stage transcriptomes reveal significant variation in the expression of protein-coding and non-coding RNAs between populations. We identify 33 gene expression markers (GEMs) that correlate with invasiveness, and which map to genes with predicted roles in host-finding and invasion, including neuropeptides, ion channels, GPCRs, cell wall-degrading enzymes and microRNAs. These data demonstrate a surprising diversity in microRNA complements between populations, and identify GEMs for invasiveness ofM. incognitafor the first time.
A low-cost, open-source framework for tracking and behavioural analysis of animals in aquatic ecosystems
Authors: Francisco Fritz A. , Nührenberg Paul , Jordan Alex L.
Published: March 2019

Although methods for tracking animals underwater exist, they frequently involve costly infrastructure investment, or capture and manipulation of animals to affix or implant tags. These practical concerns limit the taxonomic coverage of aquatic movement ecology studies and implementation in areas where high infrastructure investment is impossible. Here we present a method based on deep-learning and structure-from-motion, with which we can accurately determine the 3D location of animals, the structure of the environment in which they are moving. Further behavioural decomposition of the body position and contour of animals subsequently allow quantifying the behavioural states of each interacting animal. This approach can be used with minimal infrastructure and without confining animals to to a fixed area, or capturing and interfering with them in any way. With this approach, we are able to track single individuals (Conger Eel,Conger oceanus), small heterospecific groups (Mullus surmuletus, Diplodus sp.), and schools of animals (Tanganyikan cichlidsLamprologus callipterus) in freshwater and marine systems, and in habitats ranging in environmental complexity. Positional information was highly accurate, with errors as low as 1.67% of body length. Tracking data was embedded in 3D environmental models that could be used to examine collective decision making, obstacle avoidance, and visual connectivity of groups. By analyzing body contour and position, we were also able to use unsupervised classification to quantify the kinematic behavioural states of each animal. The proposed framework allows us to understand animal behaviour in aquatic systems at an unprecedented resolution and a fraction of the cost of established methodologies, with minimal domain expertise at the data acquisition or analysis phase required. Implementing this method, research can be conducted in a wide range of field contexts to collect laboratory standard data, vastly expanding both the taxonomic and environmental coverage of quantitative animal movement analysis with a low-cost, open-source solution.
Behavioural and neural limits in competitive decision making: The roles of outcome, opponency and observation
Authors: Dyson Benjamin James , Steward Ben Albert , Meneghetti Tea , Forder Lewis
Published: March 2019

To understand the boundaries we set for ourselves in terms of environmental responsibility during competition, we examined a neural index of outcome valence (feedback-related negativity; FRN) in relation to earlier indices of visual attention (N1), later indices of motivational significance (P3), and, eventual behaviour. In Experiment 1 (n=36), participants either were (play) or were not (observe) responsible for action selection. In Experiment 2 (n=36), opponents additionally either could (exploitable) or could not (unexploitable) be beaten. Various failures in reinforcement learning expression were revealed including large-scale approximations of random behaviour. Against unexploitable opponents, N1 determined the extent to which negative and positive outcomes were perceived as distinct categories by FRN. Against exploitable opponents, FRN determined the extent to which P3 generated neural gain for future events. Differential activation of the N1 – FRN – P3 processing chain provides a framework for understanding the behavioural dynamism observed during competitive decision making.
Survival of prey growing through gape-limited predators
Authors: Anderson James J.
Published: March 2019

Juvenile to adult survival of fish is modeled by the rate at which prey progressively escape the size distribution of gape-limited predators through growth. The model characterizes adult survival as a function of the mean and standard deviation of the predator population gape sizes, the ratio of mortality and growth rates and a compensatory growth factor. The model fits the survival of adult returns of Chinook salmon and reveals that a 25% increase in either the initial size at ocean entrance or the growth to mortality rate over the first few months of ocean residence can increase adult survival by a factor of 2 to 3. Additionally, the model proposes a rigorous mechanism through which the size distribution of predators determines the effects of juvenile growth on adult survival. Finally, possible contributions of the model framework to fisheries management and predator-prey theory are noted.
Cellular and network mechanisms may generate sparse coding of sequential object encounters in hippocampal-like circuits
Authors: Trinh Anh-Tuan , Clarke Stephen E. , Harvey-Girard Erik , Maler Leonard
Published: March 2019

In mammals, the localization of distinct landmarks is performed by hippocampal neurons that sparsely encode an animal’s location relative to surrounding objects. Similarly, the dorsal lateral pallium (DL) is essential for spatial learning in teleost fish. The DL of weakly electric gymnotiform fish receives sensory inputs from the preglomerular nucleus (PG), which has been hypothesized to encode the temporal sequence of electrosensory or visual landmark/food encounters. Here, we show that DL neurons have a hyperpolarized resting membrane potential combined with a high and dynamic spike threshold that increases following each spike. Current-evoked spikes in DL cells are followed by a strong small-conductance calcium-activated potassium channel (SK) mediated after-hyperpolarizing potential (AHP). Together, these properties prevent high frequency and continuous spiking. The resulting sparseness of discharge and dynamic threshold suggest that DL neurons meet theoretical requirements for generating spatial memory engrams by decoding the landmark/food encounter sequences encoded by PG neurons.
Resting-state functional connectivity modulates the BOLD activation induced by nucleus accumbens stimulation in the swine brain
Authors: Cho Shinho , Hachmann Jan T. , Balzekas Irena , In Myung-Ho , Andres-Beck Lindsey G. , Lee Kendall H. , Min Hoon-Ki , Jo Hang Joon
Published: March 2019

While it is known that the clinical efficacy of deep brain stimulation (DBS) alleviates motor-related symptoms, cognitive and behavioral effects of DBS and its action mechanism on brain circuits are not clearly understood. By combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood-oxygenation-level-dependent (BOLD) signal changes induced by stimulating the nucleus accumbens and how inter-regional resting-state functional connectivity is related with the stimulation DBS effect in a healthy swine model. We found that the pattern of stimulation-induced BOLD activation was diffused across multiple functional networks including the prefrontal, limbic, and thalamic regions, altering inter-regional functional connectivity after stimulation. Furthermore, our results showed that the strength of the DBS effect is closely related to the strength of inter-regional resting-state functional connectivity including stimulation locus and remote brain regions. Our results reveal the impact of nucleus accumbens stimulation on major functional networks, highlighting functional connectivity may mediate the modulation effect of DBS via large-scale brain networks.
Evolution, not transgenerational plasticity, explains the divergence of acorn ant thermal tolerance across an urban-rural temperature cline
Authors: Martin Ryan A. , Chick Lacy D. , Yilmaz Aaron R. , Diamond Sarah E.
Published: March 2019

Disentangling the mechanisms of phenotypic shifts in response to environmental change is critical, and although studies increasingly disentangle phenotypic plasticity from evolutionary change, few explore the potential role for transgenerational plasticity in this context. Here, we evaluate the potential role that transgenerational plasticity plays in phenotypic divergence of acorn ants in response to urbanization. F2 generation worker ants (offspring of lab-born queens) exhibited similar divergence among urban and rural populations as F1 generation worker ants (offspring of field-born queens) indicating that evolutionary differentiation rather than transgenerational plasticity was responsible for shifts towards higher heat tolerance and diminished cold tolerance in urban acorn ants. Hybrid matings between urban and rural populations provided further insight into the genetic architecture of thermal adaptation. Heat tolerance of hybrids more resembled the urban-urban pure type, whereas cold tolerance of hybrids more resembled the rural-rural pure type. As a consequence, thermal tolerance traits in this system appear to be influenced by dominance rather than being purely additive traits, and heat and cold tolerance might be determined by separate genes. Though transgenerational plasticity does not explain divergence of acorn ant thermal tolerance, its role in divergence of other traits and across other urbanization gradients merits further study.
Histological validation of per-bundle water diffusion metrics within a region of fiber crossing following axonal degeneration
Authors: Rojas-Vite Gilberto , Coronado-Leija Ricardo , Narvaez-Delgado Omar , Ramírez-Manzanares Alonso , Marroquín José Luis , Noguez-Imm Ramsés , Aranda Marcos L. , Scherrer Benoit , Larriva-Sahd Jorge , Concha Luis
Published: March 2019

Micro-architectural characteristics of white matter can be inferred through analysis of diffusion-weighted magnetic resonance imaging (dMRI). The diffusion-dependent signal can be analyzed through several methods, with the tensor model being the most frequently used due to its straightforward interpretation and relaxed acquisition parameters. While valuable information can be gained from the tensor-derived metrics in regions of homogeneous tissue organization, this model does not provide reliable microstructural information at crossing fiber regions, which are pervasive throughout human white matter. Several multiple fiber models have been proposed that seem to overcome the limitations of the tensor, with few providing per-bundle dMRI-derived metrics. However, biological interpretations of such metrics are limited by the lack of histological confirmation. To this end, we developed a straightforward biological validation framework. Unilateral retinal ischemia was induced in ten rats, which resulted in axonal (Wallerian) degeneration of the corresponding optic nerve, while the contralateral was left intact; the intact and injured axonal populations meet at the optic chiasm as they cross the midline, generating a fiber crossing region in which each population has different diffusion properties. Five rats served as controls. High-resolutionex vivodMRI was acquired five weeks after experimental procedures. We correlated and compared histology to per-bundle descriptors derived from three novel methodologies for dMRI analysis (constrained spherical deconvolution and two multi-tensor representations). We found a tight correlation between axonal density (as evaluated through automatic segmentation of histological sections) with per-bundle apparent fiber density and fractional anisotropy (derived from dMRI). The multi-fiber methods explored were able to correctly identify the damaged fiber populations in a region of fiber crossings (chiasm). Our results provide validation of metrics that bring substantial and clinically useful information about white-matter tissue at crossing fiber regions. Our proposed validation framework is useful to validate other current and future dMRI methods.
A novel network controllability algorithm to target personalized driver genes for discovering combinational drugs of individual cancer patient
Authors: Guo Wei-Feng , Zhang Shao-Wu , Zeng Tao , Chen Luonan
Published: March 2019

Treating cancer in precision medicine, it is important to identify the personalized combinational drugs under consideration of the individual heterogeneity. Many bioinformatics tools for the personalized driver genes identification have presented promising clues in determining candidate personalized drug targets for the personalized drugs discovery. However, it has not been studied how to fill the gap between personalized driver genes identification and personalized combinational drugs discovery. In this work, we developed a novel algorithm of structure network Controllability-based Personalized driver Genes and combinational Drug identification (CPGD), aiming to mine the personalized driver genes and identify the combinational drugs of an individual cancer patient. On two benchmark cancer datasets, the performance of CPGD for predicting the clinical efficacious combinational drugs is superior to that of other state-of-the-art driver gene-focus algorithms in terms of precision accuracy. In particular, by quantifying and referring the relationships between target genes of pairwise combinatorial drugs and disease module genes on breast cancer data set, CPGD can significantly divide patients into the discriminative high-risk and low-risk groups for risk asessment in combination therapy. In addition, CPGD can further enhance cancer subtyping by providing computationally personalized side effect signatures for individual patients. Collectively, CPGD provided a new and effecient bioinformatics tool from structure network controllability perspective for discovering personalized combinational drugs with personalized side effect consideration, so as to effectively support personalized risk assessement and disease subtyping.

Significance

It is quite challenging to predict personalized combinational drugs rather than patient-cohort‘s drugs based on cancer omics data. In this work, a novel structure network Controllability-based algorithm (CPGD) from feedback vertex sets control perspective was developed, for discovering efficacious combinational drugs of an individual cancer patient by targeting the personalized driver genes. The CPGD contains three methodological advances by exploring more precise mathematical models on high-throughput personalized multi-omics data. The first is that a proper network structure is constructed to characterize the gene regulatory mechanism of an individual patient. The second is that considering the weight information of network edges/relations improves the performance for predicting clinical efficacious combinational drugs compared with other drivers-focus methods. And the third is that proper evaluation metrics for personalized combinational drugs prioritization, personalized risk assessment and disease subtyping are designed when evaluating the performance of CPGD.
Nicotinamide Deficiency in Primary Open-Angle Glaucoma
Authors: Nzoughet Judith Kouassi , de la Barca Juan Manuel Chao , Guehlouz Khadidja , Leruez Stéphanie , Coulbault Laurent , Allouche Stéphane , Bocca Cinzia , Muller Jeanne , Amati-Bonneau Patrizia , Gohier Philippe , Bonneau Dominique , Simard Gilles , Milea Dan , Lenaers Guy , Procaccio Vincent , Reynier Pascal
Published: March 2019

Purpose

To investigate the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG).

Methods

Plasma of 34 POAG individuals were compared to that of 30 age-and sex-matched controls using a semi-quantitative method based on liquid chromatography coupled to high-resolution mass spectrometry. Subsequently, an independent quantitative method, based on liquid chromatography coupled to mass spectrometry, was used to assess nicotinamide concentration in the plasma from the same initial cohort and from a replicative cohort of 20 POAG individuals and 15 controls.

Results

Using the semi-quantitative method, the plasma nicotinamide concentration was significantly lower in the initial cohort of POAG individuals compared to and further confirmed in the same cohort, using the targeted quantitative method, with mean concentrations of 0.14 µM (median: 0.12 µM; range: 0.06-0.28 µM) in the POAG group (−30 %;p= 0.022), and 0.19 µM (median: 0.18 µM; range: 0.08-0.47 µM) in the control group. The quantitative dosage also disclosed a significantly lower plasma nicotinamide concentration (−33 %;p= 0.011) in the replicative cohort with mean concentrations of 0.14 µM (median: 0.14 µM; range: 0.09-0.25 µM) in the POAG group, and 0.19 µM (median: 0.21 µM; range: 0.09-0.26 µM) in the control group.

Conclusions

Glaucoma is associated with lower plasmatic nicotinamide levels, compared to controls, suggesting that nicotinamide supplementation might become a future therapeutic strategy. Further studies are needed, in larger cohorts, to confirm these preliminary findings.
A Bayesian framework for inferring the influence of sequence context on single base modifications
Authors: Ling Guy , Miller Danielle , Nielsen Rasmus , Stern Adi
Published: March 2019

The probability of single base modifications (mutations and DNA/RNA modifications) is expected to be highly influenced by the flanking nucleotides that surround them, known as the sequence context. This phenomenon may be mainly attributed to the enzyme that modifies or mutates the genetic material, since most enzymes tend to have specific sequence contexts that dictate their activity. Thus, identification of context effects may lead to the discovery of additional editing sites or unknown enzymatic factors. Here, we develop a statistical model that allows for the detection and evaluation of the effects of different sequence contexts on mutation rates from deep population sequencing data. This task is computationally challenging, as the complexity of the model increases exponentially as the context size increases. We established our novel Bayesian method based on sparse model selection methods, with the leading assumption that the number of actual sequence contexts that directly influence mutation rates is minuscule compared to the number of possible sequence contexts. We show that our method is highly accurate on simulated data using pentanucleotide contexts, even when accounting for noisy data. We next analyze empirical population sequencing data from polioviruses and detect a significant enrichment in sequence contexts associated with deamination by the cellular deaminases ADAR 1/2. In the current era, where next generation sequencing data is highly abundant, our approach can be used on any population sequencing data to reveal context-dependent base alterations, and may assist in the discovery of novel mutable sites or editing sites.
Lactate potentiates differentiation and expansion of cytotoxic T cells
Authors: Rundqvist Helene , Veliça Pedro , Barbieri Laura , Gameiro Paulo A. , Cunha Pedro P. , Gojkovic Milos , Mijwel Sara , Ahlstedt Emil , Foskolou Iosifina P. , Ruiz-Pérez María Victoria , Arsenian-Henriksson Marie , Ule Jernej , Östman Arne , Johnson Randall S.
Published: March 2019

Exercise has a range of effects on metabolism. In animal models, repeated exertion reduces malignant tumour progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effect of exercise on tumour progression is unclear, as are the cellular actors involved. We show here that exercise-induced reduction in tumour growth is dependent on CD8+ T cells and that lactate, which is produced at high levels during exertion, increases proliferative capacity and cytotoxicity of CD8+ T cells. We found that at elevated levels lactate is used as a fuel during T cell activation. We further found that injection of lactate into animals can reduce malignant tumour growth in a dose-and CD8+ T cell-dependent manner. These data demonstrate that lactate can act to increase the anti-tumour activity of cytotoxic T cells, and in so doing, reduce cancer progression.
Soil protist diversity in the Swiss western Alps is better predicted by topo-climatic than by edaphic variables
Authors: Seppey Christophe V.W. , Broennimann Olivier , Buri Aline , Yashiro Erika , Pinto-Figueroa Eric , Singer David , Blandenier Quentin , Mitchell Edward A.D. , Hirzel Hélène Niculita , Guisan Antoine , Lara Enrique
Published: March 2019

Aim

General trends in spatial patterns of macroscopic organisms diversity can be reasonably well predicted from correlative models, using for instance topo-climatic variables for plants and animals allowing inference over large scales. By contrast, soil microorganisms diversity is generally considered as mostly driven by edaphic variables and, therefore, difficult to extrapolate on a large spatial scale based on predictive models. Here, we compared the power of topo-climatic vs. edaphic variables for predicting the diversity of various soil protist groups at the regional scale.

Location

Swiss western Alps.

Taxa

Full protist community and nine clades belonging to three functional groups: parasites (Apicomplexa, Oomycota, Phytomyxea), phagotrophs (Sarcomonadea, Tubulinea, Spirotrichea) and phototrophs (Chlorophyta, Trebouxiophyceae, Bacillariophyta).

Methods

We extracted soil environmental DNA from 178 sites along a wide range of elevations with a random-stratified sampling design. We defined protist Operational Taxonomic Units assemblages by metabarcoding of the V4 region of the ribosomal RNA small sub-unit gene. We assessed and modelled the diversity (Shannon index) patterns of all selected groups as a function of topo-climatic and edaphic variables using Generalized Additive Models.

Results

The respective significance of topo-climatic and edaphic variables varied among taxonomic and – to a certain extent – functional groups: while many variables explained significantly the diversity of phototrophs this was less the case for parasites. Generally, topo-climatic variables had a better predictive power than edaphic variables, yet predictive power varied among taxonomic and functional groups.

Main conclusions

Topo-climatic variables are, on average, better predictors of protist diversity at the landscape scale than edaphic variables, which opens the way to wide-scale sampling designs avoiding costly and time-consuming laboratory protocols. However, predictors of diversity differ considerably among taxonomic and functional groups; such relationships may be due to direct and/or indirect, e.g. biotic influences. Future prospects include using such spatial models to predict hotspots of diversity or pathogens outbreaks.