bluuebunny/crossref_metadata_2025 huggingface dataset:
Nipple Areola Complex Reconstruction With the “Half-Dome” Technique Following Implant-Based Breast Reconstruction
Authors: Chen Wendy , Fishman Jordan E. , de la Cruz Carolyn
Published: March 2019

Background

No single technique for nipple areola reconstruction best fits every patient and clinical scenario. Many techniques fail to provide long-term projection. One especially challenging cohort are those patients who have undergone bilateral implant-based reconstruction. We developed a modification of the C-V flap reconstruction that increases projection in the bilateral, implant-based reconstruction patient.

Methods

All patients who underwent nipple areola reconstruction following implant-based breast reconstruction and who had at least a 12-month follow-up visit were identified. Nipple projection was measured and compared between the 2 groups.

Results

Forty patients were identified. Twelve patients, 23 nipples, underwent the standard C-V flap reconstruction. Twenty-eight patients, 59 nipples, underwent the half-dome modification. Average nipple projection following the half-dome technique is more than twice that of the C-V flap.

Conclusions

The half-dome technique provides a useful alternative modification of the C-V flap in patients with implant-based reconstruction.
Effect on Facial Growth of the Management of Cleft Lip and Palate
Authors: Farber Scott J. , Maliha Samantha G. , Gonchar Marina N. , Kantar Rami S. , Shetye Pradip R. , Flores Roberto L.
Published: March 2019

Treatment of cleft lip and palate ordinarily requires multiple interventions spanning the time of birth to adulthood. Restriction of facial growth, a common occurrence in affected children, is due to multiple factors. There are multiple surgical and therapeutic options, which may have influence on facial growth in these patients. As restriction to facial development can have significant implications to form, function, and psychological well-being, practitioners should have an appreciation for the effects of the different cleft therapies to facial growth. We have outlined and thoroughly reviewed in chronological order all of the interventions from birth to adulthood necessary in the comprehensive care of the patient with cleft lip and palate, along with the effects they may or may not have on facial growth.
Early Experience With Body Contouring Procedures in Patients With End-Stage Renal Disease Awaiting Renal Transplant
Authors: Xue Yunfeng , Song Ping , Wong Michael S.
Published: March 2019

Introduction

Patients with (end-stage renal disease) ESRD often have many medical comorbidities, posing a higher risk for any surgical procedure. Obese patients are asked to lose weight to become more acceptable renal transplant candidates. Unfortunately, this often results in a panniculus and excess ptotic skin with accompanying functional and aesthetic concerns. We report our early experience in body contouring procedures in patients with ESRD who underwent massive weight loss.

Methods

Three patients with ESRD on the renal transplant waitlist at UC Davis Medical Center opted for elective body contouring procedures before their transplant surgery. All 3 patients were determined by the transplant team to have a high-risk panniculus and were referred to plastic surgery for panniculectomy before renal transplant. Two of the patients had concurrent lower body lift with panniculectomy, and the third patient underwent modified upper body lift with gynecomastia surgery 7 months after the initial panniculectomy.

Results

The mean age of the group was 49 (range = 40–62) years, including 1 male and 2 female patients. The average body mass index of the group was 25.6 (range = 22.8–31.8), and all 3 patients had massive weight loss, with a mean BMI drop of 28.1 (range = 24.2–34.9). Postoperatively, only 1 patient experienced minor wound healing delay, which resolved 3 months after surgery with debridement in clinic and local wound care.

Conclusions

In our early experience, we have seen that body contouring surgery in patients with ESRD awaiting renal transplant has an acceptable and manageable risk profile. By making minor modifications to preoperative, intraoperative, and postoperative routines, body contouring procedures can be safely performed in this patient population and can significantly decrease the functional and aesthetic problems caused by excess skin, resulting in improved body image and quality of life.
Tailored Microform Cleft Lip Repair: Personalizing Small Incisions, Orbicularis Reconstruction, and Rhinoplasty
Authors: He Lin , Yu Xueyuan , Liu Xiangyu , Chen Wendy , Shu Maoguo
Published: March 2019

Background:

In the last decade, many surgeons have reported their perspectives on microform cleft lip repair, including techniques for incision placement and size, philtral reconstruction, and nasal base reconstruction. This interest demonstrates continued controversy in the repair of microform cleft lip.

Methods:

This is a retrospective cohort of patients from 2010 to 2016. The authors included patients with microform cleft lip repaired by our described technique who had both preoperative photographs, as well as photographs taken at >1-year follow-up. Patient outcomes were assessed through anthropometric measurements and also subjectively by 3 senior residents of plastic surgery.

Results:

The inclusion criteria yielded 36 microform cleft lip patients. Most patients were satisfied with their results. Regarding subjective assessment, the scar appearance and symmetry was fairly good. Objective measurements indicated excellent symmetry, with the cleft side achieving 92.58% of the height and measurements of the non-cleft side.

Conclusions:

Our method of combining labial muscle reconstruction through a personalized, small incision effectively corrects microform cleft lip deformity with minimal scar burden.
Direct Three-Dimensional Diagnosis of Ex Vivo Facial Fractures
Authors: Sirin Yigit , Yildirimturk Senem , Horasan Sinan , Guven Koray
Published: March 2019

The aim of the present study is to assess the reliability and accuracy of different 3-dimensional (3D) reconstruction algorithms in detecting undisplaced condylar, zygomatic arc, and orbital rim fractures based on cone-beam computed tomography data set. Twenty sheep heads were used in the present study. Sixty fractured and 60 nonfractured (control) zones were randomly allocated. Three groups consisting of nondisplaced fractures of condyle (CF, n = 20), orbital (OF, n = 20), and zygomatic arc (ZF, n = 20) were created by using a diamond cutting disc. Soft tissues were only dissected and no fractures were generated in the control group (n = 60). The 3D reconstructions were created by using multiplanar reconstruction (MPR), surface rendering (SR), volume rendering (VR), and maximum intensity projection (MIP) algorithms. Final 3D models were examined in Osirix software (Pixmeo SARL, Bernex, Switzerland) by 6 observers. Diagnostic accuracies of each algorithm were statistically compared by receiver operating characteristics (ROC) and area under the ROC curves (AUCs). For the detection of CF, AUC for VR algorithm was found to be statistically larger than that of MIP while AUCs for VR and MIP were larger than those of MPR and SR for OF detection. For the detection of ZF, AUCs for MPR and VR were significantly larger than those of MIP and SR (P < 0.05 for each). Within the limitations of this experimental study, it can be concluded that for maxillofacial surgeons, it is more likely to detect condylar, orbital, and zygomatic fractures by using VR algorithm in 3D reconstruction.
Simultaneous Forehead Lift and Blepharoplasty Techniques in Management of Orbito-Temporal Plexiform Neurofibroma
Authors: Choi Jangyoun , Choi Hyuk Joon , Kang Kyo Joon , Kwon Ho , Shin Jongweon
Published: March 2019

Plexiform neurofibromas are common complications in neurofibromatosis type 1 patients. Currently, surgery is the treatment of choice. However, complete surgical resection is difficult due to the infiltration to the surrounding tissue and the increased vascularity. Plexiform neurofibromas arising in the orbito-temporal area pose a greater challenge due to its critical function and cosmetic importance of the face. Such plexiform neurofibromas, separately designated as orbito-temporal plexiform neurofibromas, show complex symptoms such as severe ptosis, ectropion, lacrimal gland dysfunction, and even vision loss. We present a case of successful correction of upper eyelid entropion and severe eyebrow ptosis in a 48-year-old orbito-temporal plexiform neurofibromas patient with combined forehead lift and blepharoplasty techniques including double fold formation and mass excision.
A New Method for Determining the Level of the Carotid Artery Bifurcation
Authors: Denli Yalvac Emine Seyma , Balak Naci , Atalay Basak , Bademci Mehmet Senel , Kocaaslan Cemal , Oztekin Ahmet , Ankarali Handan , Aydin Ebuzer
Published: March 2019

Exact localization of the bifurcation of the common carotid artery using skin surface landmarks is important for various diagnostic and therapeutic purposes, including emergency cases. Traditional methods have confirmed their accuracy in only a certain percentage of cases and there are inconsistencies among various publications. The cervical computed tomography-angiographic examinations for any diagnostic purpose between June 2017 and December, 2017 in the authors’ hospital were examined. Measurements were performed for (MT-CB) and (MT-SE) distances and the results were recorded [MT = The tip of the mastoid process; CB = common carotid artery bifurcation; SE = sternal extremity of the clavicle]. Cervical computed tomography angiography was found in the records of 91 patients in the 6-month period between June 2017 and December 2017. After exclusion criteria were applied, a total of 116 carotid bifurcation levels on the right and left sides were measured in 58 patients. The mean MT-CB distance was 6.29 ± 0.9 cm (range: 2.9–8.4 cm). The mean distance between MT and SE was 15.3 ± 1.7 cm (range: 9.9–19.0 cm). The (MT-CB): (MT-SE) ratios ranged from 29% to 51% with a mean of 41 ± 4.2% (95% CI: 39.88%–42.10%) and a median of 41.1% (P < 0.05) (Kolmogorov–Smirnov test). The distance ratio values did not change significantly according to age and gender (respectively P = 0.341, P = 0.093). These results show that the CB is usually located at two-fifths of the distance from the mastoid tip to the sternal extremity of the clavicle and closer to the mastoid tip.
The Implementation of a Multidisciplinary Approach for Potential Organ Donors in the Emergency Department
Authors: Witjes Marloes , Kotsopoulos Angela M.M. , Otterspoor Luuk , Herold Ingeborg H.F. , Simons Koen S. , Woittiez Karen , Eijkenboom Jos J.A. , van der Hoeven Johannes G. , Jansen Nichon E. , Farid Abdo Wilson
Published: March 2019

Background.

The aim of this study was to evaluate the implementation process of a multidisciplinary approach for potential organ donors in the emergency department (ED) in order to incorporate organ donation into their end-of-life care plans.

Methods.

A new multidisciplinary approach was implemented in 6 hospitals in The Netherlands between January 2016 and January 2018. The approach was introduced during staff meetings in the ED, intensive care unit (ICU), and neurology department. When patients with a devastating brain injury had a futile prognosis in the ED, without contraindications for organ donation, an ICU admission was considered. Every ICU admission to incorporate organ donation into end-of-life care was systematically evaluated with the involved physicians using a standardized questionnaire.

Results.

In total, 55 potential organ donors were admitted to the ICU to incorporate organ donation into end-of-life care. Twenty-seven families consented to donation and 20 successful organ donations were performed. Twenty-nine percent of the total pool of organ donors in these hospitals were admitted to the ICU for organ donation.

Conclusions.

Patients with a devastating brain injury and futile medical prognosis in the ED are an important proportion of the total number of donors. The implementation of a multidisciplinary approach is feasible and could lead to better identification of potential donors in the ED.
Processing of Local and Global Auditory Deviants in Parkinson Disease: Electrophysiological Evidence for Enhanced Attention Capture
Authors: Heldmann Marcus , Teichmann Sebastian , Al-Khaled Mohamed , Brüggemann Norbert , Münte Thomas F.
Published: March 2019

Objective:

To investigate automatic auditory-change detection in patients with Parkinson disease (pwPD).

Background:

Previous results regarding changes in preattentive processing in pwPD have been inconclusive.

Methods:

We employed a paradigm assessing the preattentive processing of sequences of auditory tones containing deviants at either the local or global level, or at both levels. Twenty pwPD and 20 age-matched healthy controls were exposed to the tone series while they performed a visual task and had their event-related potentials recorded by electroencephalogram.

Results:

Event-related potentials showed a mismatch negativity, which was largest for the double-deviant stimuli, of intermediate amplitude for the local deviant stimuli, and smallest for the global deviant stimuli. The mismatch negativity was of similar size in the patients and controls, with the exception of the double-deviant condition (larger in controls). By contrast, the subsequent positive component was more pronounced for the Parkinson disease group than controls, particularly for the double-deviant condition.

Conclusions:

The larger positivity suggests that pwPD are more prone to distraction than healthy controls, probably because dopaminergic medication shifts the stability-flexibility balance toward cognitive flexibility with increased distractibility.
Detection of antisense protein (ASP) RNA transcripts in individuals infected with human immunodeficiency virus type 1 (HIV-1)
Authors: Mancarella Antonio , Procopio Francesco A. , Achsel Tilmann , De Crignis Elisa , Foley Brian T. , Corradin Giampietro , Bagni Claudia , Pantaleo Giuseppe , Graziosi Cecilia
Published: March 2019

The detection of antisense RNA is hampered by reverse transcription (RT) non-specific priming, due to the ability of RNA secondary structures to prime RT in the absence of specific primers. The detection of antisense RNA by conventional RT-PCR does not allow assessment of the polarity of the initial RNA template, causing the amplification of non-specific cDNAs. In this study we have developed a modified protocol for the detection of human immunodeficiency virus type 1 (HIV-1) antisense protein (ASP) RNA. Using this approach, we have identified ASP transcripts in CD4+ T cells isolated from five HIV-infected individuals, either untreated or under suppressive therapy. We show that ASP RNA can be detected in stimulated CD4+ T cells from both groups of patients, but not in unstimulated cells. We also show that in untreated patients, the patterns of expression of ASP and env are very similar, with the levels of ASP RNA being markedly lower than those of env. Treatment of cells from one viraemic patient with α-amanitin greatly reduces the rate of ASP RNA synthesis, suggesting that it is associated with RNA polymerase II, the central enzyme in the transcription of protein-coding genes. Our data represent the first nucleotide sequences obtained in patients for ASP, demonstrating that its transcription indeed occurs in those HIV-1 lineages in which the ASP open reading frame is present.
Graphical factorial surveys reveal the acceptability of wildlife observation at protected areas
Authors: Cerri Jacopo , Martinelli Elena , Bertolino Sandro
Published: March 2019

Approaching large ungulates at protected areas is dangerous both for visitors and the animals. Nudging interventions can mitigate this issue, but conservationists need to be sure about which factors influence the acceptability of human-wildlife encounters, to design them.

In summer 2018, we recruited a sample of visitors (n = 205) at the Gran Paradiso National Park (Italy). They evaluated the acceptability of 9 digitally modified pictures, depicting a group of visitors observing an alpine ibex (Capra ibex) close to a trail. Pictures were characterized in terms of group size and distance from the ibex.

Observing ibexes was deemed to be acceptable if visitors were further than 25 meters from animals and when groups included less than 3 people. Approaching ibexes at 5 meters was always deemed to be unacceptable. Potential for Conflict Index (PCI) was constant across distance classes and it was generally low.

Our findings indicate that visitors share normative beliefs about the optimal distance and group size, that should characterize encounters with large ungulates, when visiting the park. These normative beliefs are crystallized, because previous encounters with ibexes did not affect the evaluation of each scenario and because the PCI was constant and low. We believe that behavioral interventions aimed at promoting respectful and safe human-ibex interactions can be enforced in areas where this interaction is critical, mostly in form of panels on hiking trails introducing normative pressures on visitors and motivating them to comply with rules.
Acute lymphoblastic leukemia cells image analysis with deep bagging ensemble learning
Authors: Liu Ying , Long Feixiao
Published: March 2019

Acute lymphoblastic leukemia (ALL) is a blood cancer which leads 111,000 depth globally in 2015. Recently, diagnosing ALL often involves the microscopic image analysis with the help of deep learning (DL) techniques. However, as most medical related problems, deficiency training samples and minor visual difference between ALL and normal cells make the image analysis task quite challenging. Herein, an augmented image enhanced bagging ensemble learning with elaborately designed training subsets were proposed to tackle above challenges. The weightedF1-scores of preliminary test set and final test are 0.84 and 0.88 respectively employing our ensemble model predictions and ranked within top 10% in ISBI-2019 Classification of Normal vs. Malignant White Blood Cancer Cells contest. Our results preliminarily show the efficacy and accuracy of employing DL based techniques in ALL cells image analysis.
Heterologous Expression of Human Norovirus GII.4 VP1 Leads to Assembly of T=4 Virus-Like Particles
Authors: Devant Jessica , Hofhaus Götz , Bhella David , Hansman Grant S.
Published: March 2019

Human noroviruses are a leading cause of acute gastroenteritis, yet there are still no vaccines or antivirals available. Expression of the norovirus capsid protein (VP1) in insect cells typically results in the formation of virus-like particles (VLPs) that are morphologically and antigenically comparable to native virions. Previous structural analysis of norovirus VLPs showed that the capsid has a T=3 icosahedral symmetry and is composed of 180 copies of VP1 that are folded into three quasi-equivalent subunits (A, B, and C). In this study, we determined the cryo-EM VLP structures of two GII.4 variants, termed CHDC-1974 and NSW-2012. Surprisingly, we found that greater than 95% of these GII.4 VLPs were larger than virions and 3D reconstruction showed that these VLPs exhibited T=4 icosahedral symmetry. We found that the T=4 VLPs showed several structural differences to the T=3 VLPs. The T=4 particles assemble from 240 copies of VP1 that adopt four quasi-equivalent conformations (A, B, C, and D) that form two distinct dimers, A/B and C/D. The T=4 protruding domains were elevated ∼21-Å off the capsid shell, which was ∼7-Å more than the previously studied GII.10 T=3 VLPs. A small cavity and flap-like structure at the icosahedral twofold axis disrupted the contiguous T=4 shell, a consequence of the D-subunit S-domains having smaller contact interfaces with neighboring dimers. Overall, our findings that old and new GII.4 VP1 sequences assemble T=4 VLPs might have implications for the design of potential future vaccines.

IMPORTANCE

The discovery that the GII.4 VLPs have a T=4 symmetry is of significance, since this represents the first known T=4 calicivirus structure. Interestingly, the GII.4 2012 variant shares 96% amino acid identity with a current GII.4 VLP vaccine candidate sequence, which suggests that this vaccine might also have a T=4 symmetry. Our previous results with these GII.4 VLPs showed functional binding properties to antibodies and Nanobodies that were raised against T=3 (GII.10) VLPs. This suggests that the T=4 VLPs were antigenically comparable to T=3 particles, despite the obvious structural and size differences. On the other hand, these larger T=4 VLPs with novel structural features and possibly new epitopes might elicit antibodies that do not recognize equivalent epitopes on the T=3 VLPs. Further structural and binding studies using a library of GII.4-specific Nanobodies are planned in order to precisely investigate whether new epitopes are formed.
Long-term exposure to daily ethanol injections in DBA2/J and Swiss mice: Lessons for the interpretation of ethanol sensitization
Authors: Didone Vincent , van Ingelgom Théo , Tirelli Ezio , Quertemont Etienne
Published: March 2019

Most mice ethanol sensitization studies focused on neurobiology at the expense of its behavioral characterization. Furthermore, relatively short ethanol exposures (10 to 20 injections) were used in these studies. The first aim of the present study is to better characterize the development and expression of ethanol sensitization after an extended exposure of 45 daily injections. In some previous studies, mice were classified as “respondent” and “resistant” to ethanol sensitization. The second aim of the present study is to test the long-term reliability of such categorizations and the consequences of their use on the interpretation of the ethanol sensitization results.

Swiss and DBA2/j female mice received 45 consecutive daily ethanol administrations (respectively 2.5 and 2.0 g/kg) and their locomotor activity was daily recorded to test the development of ethanol sensitization. At the end of the procedure, a challenge test assessed the inter-group ethanol sensitization.

The results of the present study show that ethanol sensitization continues to develop beyond 20 days to reach maximal levels after about 25 injections in DBA2/j mice and 40 injections in Swiss mice, although the core phase of the development of ethanol sensitization occurred in both strains during the first 20 days. Remarkably, ethanol sensitization after such a long daily ethanol treatment resulted in both an upward shift of the magnitude of ethanol stimulant effects and a prolongation of these effects in time (up to 30 minutes). Mice classified as “resistant to ethanol sensitization” according to previous studies developed very significant levels of ethanol sensitization when tested after 45 ethanol injections and are best described as showing a delayed development of ethanol sensitization. Furthermore, mice classified as respondent or resistant to ethanol sensitization also differ in their acute response to ethanol, such that it is difficult to ascertain whether these classifications are specifically related to the sensitization process.
Implementation of Design of Experiments (DOE) for Optimization of Feeding Strategy and Glyco-Engineering of Trastuzumab Biosimilar
Authors: Mahboudi Rasoul , Samavat Sepideh , Afrah Amir , Khorshidtalab Mehdi , Tehran Arezou Fadaei , Motahari Paria , Iri Sofla Farnoush Jafari , Maleknia Shayan
Published: March 2019

Fed-batch cell culture is the most commonly used process for antibody production in biopharmaceutical industries. Basal media, feed, feeding strategy and glycan structures are always among the most important concerns during process development and optimization. In this study, first, a traditional screening study was performed to identify the top media/feed combinations by evaluating the cell culture performance including cell growth and protein titre. Optimization of the process was also performed using response surface methodology in order to find the most optimum feeding strategy and glucose set point regarding final titre of the recombinant monoclonal antibody being produced in Chinese hamster ovary cell line. The focus of this study is not only on titre, but also on product quality and comparability especially protein glycosylation. The prediction model of product titre as a function of feeding percentage and glucose set point was successfully applied for the second set of experiments that was performed for glycan improvement. Statistical design of experiments was applied to determine the most important factors and their effects on galactosylated and afucosylated glycans. Uridine, manganese, galactose and fucosyltransferase inhibitor were chosen to evaluate if their presence can affect glycans and to obtain their best combination for fed-batch culture supplementation. We determined that 2.5 % daily feeding combined with maintaining the glucose set point on 2.5±0.2 g/L could achieve final titre of 2.5± 0.1 g/L. Galactosylation of antibody was increased about 25% using MnCl2and galactose while afucosylation was increased about 8% in presence of fucosyltransferase inhibitor. Galactose and Mn2+led to a shift from G0F to G1F and presence of Fucosyltransferase inhibitor caused to an increase in G0 compared to its absence. These results demonstrated that supplementation of culture with all these components can provide exact control of antibody galactosylation and fucosylation with minimal impact on culture characteristics and product quality attributes. Subsequently, validation experiments were also carried out in 5L STR bioreactors which showed that similar results could be achieved in bioreactors compared to shake flasks regarding both titre and quality.
Integrated Open-Source Software for Multiscale Electrophysiology
Authors: Nasiotis Konstantinos , Cousineau Martin , Tadel François , Peyrache Adrien , Leahy Richard M. , Pack Christopher C. , Baillet Sylvain
Published: March 2019

The methods for electrophysiology in neuroscience have evolved tremendously over the recent years with a growing emphasis on dense-array signal recordings. Such increased complexity and augmented wealth in the volume of data recorded, have not been accompanied by efforts to streamline and facilitate access to processing methods, which too are susceptible to grow in sophistication. Moreover, unsuccessful attempts to reproduce peer-reviewed publications indicate a problem of transparency in science. This growing problem could be tackled by unrestricted access to methods that promote research transparency and data sharing, ensuring the reproducibility of published results.

Here, we provide a free, extensive, open-source software that provides data-analysis, data-management and multi-modality integration solutions for invasive neurophysiology. Users can perform their entire analysis through a user-friendly environment without the need of programming skills, in a tractable (logged) way. This work contributes to open-science, analysis standardization, transparency and reproducibility in invasive neurophysiology.
Deep representation learning for domain adaptatable classification of infrared spectral imaging data
Authors: Raulf Arne P. , Butke Joshua , Küpper Claus , Großerueschkamp Frederik , Gerwert Klaus , Mosig Axel
Published: March 2019

Motivation

Applying infrared microscopy in the context of tissue diagnostics heavily relies on computationally preprocessing the infrared pixel spectra that constitute an infrared microscopic image. Existing approaches involve physical models, which are non-linear in nature and lead to classifiers that do not generalize well, e.g. across different types of tissue preparation. Furthermore, existing preprocessing approaches involve iterative procedures that are computationally demanding, so that computation time required for preprocessing does not keep pace with recent progress in infrared microscopes which can capture whole-slide images within minutes.

Results

We investigate the application of stacked contractive autoencoders as an unsupervised approach to preprocess infrared microscopic pixel spectra, followed by supervised fine-tuning to obtain neural networks that can reliably resolve tissue structure. To validate the robustness of the resulting classifier, we demonstrate that a network trained on embedded tissue can be transferred to classify fresh frozen tissue. The features obtained from unsupervised pretraining thus generalize across the large spectral differences between embedded and fresh frozen tissue, where under previous approaches seperate classifiers had to be trained from scratch.

Availability

Our implementation can be downloaded fromhttps://github.com/arnrau/SCAE_IR_Spectral_Imaging

Contact

axel.mosig@bph.rub.de
The Arrival of Steppe and Iranian Related Ancestry in the Islands of the Western Mediterranean
Authors: Fernandes Daniel M. , Mittnik Alissa , Olalde Iñigo , Lazaridis Iosif , Cheronet Olivia , Rohland Nadin , Mallick Swapan , Bernardos Rebecca , Broomandkhoshbacht Nasreen , Carlsson Jens , Culleton Brendan J. , Ferry Matthew , Gamarra Beatriz , Lari Martina , Mah Matthew , Michel Megan , Modi Alessandra , Novak Mario , Oppenheimer Jonas , Sirak Kendra A. , Stewardson Kirstin , Vai Stefania , Camarós Edgard , Calò Carla , Catalano Giulio , Cueto Marian , Forgia Vincenza , Lozano Marina , Marini Elisabetta , Micheletti Margherita , Miccichè Roberto M. , Palombo Maria R. , Ramis Damià , Schimmenti Vittoria , Sureda Pau , Teira Luís , Teschler-Nicola Maria , Kennett Douglas J. , Lalueza-Fox Carles , Patterson Nick , Sineo Luca , Caramelli David , Pinhasi Ron , Reich David
Published: March 2019

A series of studies have documented how Steppe pastoralist-related ancestry reached central Europe by at least 2500 BCE, while Iranian farmer-related ancestry was present in Aegean Europe by at least 1900 BCE. However, the spread of these ancestries into the western Mediterranean where they have contributed to many populations living today remains poorly understood. We generated genome-wide ancient DNA from the Balearic Islands, Sicily, and Sardinia, increasing the number of individuals with reported data from these islands from 3 to 52. We obtained data from the oldest skeleton excavated from the Balearic islands (dating to ∼2400 BCE), and show that this individual had substantial Steppe pastoralist-derived ancestry; however, later Balearic individuals had less Steppe heritage reflecting geographic heterogeneity or immigration from groups with more European first farmer-related ancestry. In Sicily, Steppe pastoralist ancestry arrived by ∼2200 BCE and likely came at least in part from Spain as it was associated with Iberian-specific Y chromosomes. In Sicily, Iranian-related ancestry also arrived by the Middle Bronze Age, thus revealing that this ancestry type, which was ubiquitous in the Aegean by this time, also spread further west prior to the classical period of Greek expansion. In Sardinia, we find no evidence of either eastern ancestry type in the Nuragic Bronze Age, but show that Iranian-related ancestry arrived by at least ∼300 BCE and Steppe ancestry arrived by ∼300 CE, joined at that time or later by North African ancestry. These results falsify the view that the people of Sardinia are isolated descendants of Europe’s first farmers. Instead, our results show that the island’s admixture history since the Bronze Age is as complex as that in many other parts of Europe.
Self-reported sleep duration and daytime napping are associated with renal hyperfiltration and microalbuminuria in apparently healthy Chinese population
Authors: Ye Yingnan , Zhang Linxi , Yan Wenhua , Wang Anping , Wang Weiqing , Gao Zhengnan , Tang Xulei , Yan Li , Wan Qin , Luo Zuojie , Qin Guijun , Chen Lulu , Wang Shiqing , Wang Yuxia , Mu Yiming
Published: March 2019

Background

Sleep duration affects health in various way. The objective of this study was to investigate the relationship between sleep duration, daytime napping and kidney function in a middle-aged apparently healthy Chinese population.

Methods

According to self-reported total sleep and daytime napping duration, 33,850 participants aged 38 to 90 years old from 8 regional centers were divided into subgroups. Height, weight, waistline, hipline, blood pressure, biochemical index, FBG, PBG, HbA1c, creatinine and urinary albumin-creatinine ratio (UACR) were measured and recorded in each subject. Microalbuminuria was defined as UACR>=30 mg/g, CKD was defined as eGFR<60 ml/min and hyperfiltration was defined as eGFR>=135 ml/min. Multiple logistic regressions were applied to investigate associations between sleep and kidney function.

Results

Compared to participants with [7-8]h/day sleep, ORs of >9 h/day, (8, 9]h/day and <6h/day sleep for microalbuminuria were 1.317 (1.200-1.446, p<0.001), 1.215 (1.123-1.315, p<0.001) and 1.218 (0.967-1.534, p=0.094). eGFR levels were U-shaped associated with sleep duration among subjects with >=90ml/min eGFR, and N-shaped associated with sleep duration among subjects with <90ml/min eGFR. OR of >9h/day sleep for hyperfiltration was 1.400 (1.123-1.745, p=0.003) among eGFR>=90 ml/min participants. Daytime napping had a negative effect on renal health. Compared to participants did not have napping habit, the ORs of (0, 1]h/day, (1, 1.5]h/day and >1.5h/day daytime napping for microalbuminuria were 1.477 (1.370-1.591, p<0.001), 1.217 (1.056, 1.403, p=0.007) and 1.447 (1.242, 1.687, p<0.001).

Conclusions

Total sleep duration are U-shaped associated with renal health outcomes. Daytime napping had a negative effect on renal health.
Effect of different forage-to-concentrate ratios on the structure of rumen bacteria and its relationship with nutrition levels and real-time methane production in sheep
Authors: Li Runhang , Teng Zhanwei , Lang Chaoli , Zhou Haizhu , Zhong Weiguang , Ban Zhibin , Yan Xiaogang , Yang Huaming , Farouk Mohammed Hamdy , Lou Yujie
Published: March 2019

Emission from ruminants has become the largest source of anthropogenic emission of methane in China. The structure of the rumen flora has a significant effect on methane production. To establish a more accurate prediction model for methane production, the rumen flora should be one of the most important parameters. The objective of the present study was to investigate the relationship among changes in rumen flora, nutrient levels, and methane production in sheep fed with the diets of different forage-to-concentration ratios, as well as to screen for significantly different dominant genera. Nine rumen-cannulated hybrid sheep were separated into three groups and fed three diets with forage-to-concentration ratios of 50:50, 70:30, and 90:10. Three proportions of the diets were fed according to a 3 × 3 incomplete Latin square, design during three periods of 15 d each. The ruminal fluid was collected for real-time qPCR, high-throughput sequencing andin vitrorumen fermentation in a new real-time fermentation system wit. Twenty-two genera were screened, the abundance of which varied linearly with forage-to-concentration ratios and methane production. In addition, during the 12-hourin vitrofermentation, the appearance of peak concentration was delayed by 26-27 min with the different structure of rumen bacteria. The fiber-degrading bacteria were positively correlated with this phenomenon, but starch-degrading and protein-degrading bacteria were negative correlated. These results would facilitate macro-control of rumen microorganisms and better management of diets for improved nutrition in ruminants. In addition, our findings would help in screening bacterial genera that are highly correlated with methane production.
Clinical pattern of antibiotic overuse and misuse in primary healthcare hospitals in the southwest of China
Authors: Yue Chang , Chusri Sarunyou , Sangthong Rassamee , McNeil Edward , Jiaqi Hu , Wei Du , Duan Li , Xingying Fan , Hanni Zhou , Chongsuvivatwong Virasakdi , Lei Tang
Published: March 2019

Purpose

Overuse and misuse of antibiotics are the primary risk factors for antibiotics resistance. Inadequate professional competence of primary care physicians might exacerbate these problems in China. This retrospective study aims to document the clinical pattern of antibiotics use and its overuse and misuse rates in rural primary care institutions, and to evaluate the association between antibiotics use and characteristics of the physicians and their patients.

Methods

Medical records from 16 primary care hospitals in rural areas of Guizhou province, China were obtained from the Health Information System in 2018. Classification of incorrect and/or unnecessary use, escalated use and combined antibiotics use was based on the Guiding Principle of Clinical Use of Antibiotics (2015, China) and the standard of USA Centers for Disease Control and Prevention. Generalized Estimating Equations were employed to determine predictive factors for inappropriate antibiotics use.

Results

A total of 74,648 antibiotics prescriptions were retrieved. Uncomplicated respiratory infection was the most common disease accounting for 58.6% of all prescriptions. The main antibiotic group used was penicillins (51.5%) followed by cephalosporins and macrolides (14% each). Of 57,009 patient visits, only 8.7% of the antibiotic prescriptions were appropriate. Combined, escalated, and incorrect and/or unnecessary antibiotics use was found in 7.8%, 6.2% and 77.3% of patient visits, respectively, of which 28.7% were given intravenously. Antibiotics misuse was significantly more likely among newly employed physicians with lower levels of professional education. Adult patients and those who had public insurance had a higher risk of being prescribed incorrect and/or unnecessary antibiotics.

Conclusion

Overuse of antibiotics for uncomplicated respiratory infection and use of cephalosporins, macrolides and injection antibiotics in primary care are the major problems of clinical practice in rural areas of Guizhou.
The land-use dynamics of potato agrobiodiversity in the highlands of central Peru: a case study of spatial-temporal management across farming landscapes
Authors: Arce Alejandra , de Haan Stef , Juarez Henry , Plasencia Franklin , Burra Dharani , Ccanto Raul , Polreich Severin , Scurrah Maria
Published: March 2019

In the high Andes, environmental and socio-economic drivers are transforming land use and presumably affecting thein situconservation of potato (Solanumspp.). To monitor the use and conservation of intraspecific diversity, systematic and comparative studies across land-use systems are needed. We investigated the spatial-temporal dynamics of potato in two contrasting landscapes of Peru’s central Andes: a highland plateau (Huancavelica) vs. an eastern slope (Pasco). We examined household-level areal allocations, altitudinal distribution, sectoral fallowing practices, and the conservation status for three main cultivar groups: (i) bred varieties, (ii) floury landraces, and (iii) bitter landraces. Mixed methods were used to survey 323 households and the 1,101 potato fields they managed in 2012–2013. We compared the contemporary altitudinal distribution of landraces with 1975–1985 altimeter genebank data from the International Potato Center. We show that intensification occurs in each landscape through adaptations of traditional management practices while maintaining high intraspecific diversity. Access to land and production end use (sale vs. consumption) significantly affected smallholder management and differentiated the landscapes. Total areas in Huancavelica and Pasco were allocated to 82.9% vs. 74.2% floury landraces, 9.2% vs. 25.7% bred varieties, and 7.9% vs. 0.1% bitter landraces. In market-oriented Pasco, fields in sectoral fallows between 3,901 m and 4,116 m above sea level consistently contained the highest levels of landrace diversity. The bulk of diversity in subsistence-oriented Huancavelica occurred between 3,909 m and 4,324 m outside sectoral fallows. Most of the unique landraces documented were scarce across households: 45.4% and 61.7% respectively in Huancavelica and Pasco. Bred varieties showed the widest (1,100 m) and bitter landraces the narrowest (400 m) altitudinal distributions. Potato cultivation has moved upward by an average of 306 m since 1975. Landrace diversity is versatile but unevenly distributed across landscapes. This requires adaptive ways to incentivizein situconservation.
Mitigating Pandemic Risk with Influenza A Virus Field Surveillance at a Swine-Human Interface
Authors: Rambo-Martin Benjamin L. , Keller Matthew W. , Wilson Malania M. , Nolting Jacqueline M. , Anderson Tavis K. , Vincent Amy L. , Bagal Ujwal , Jang Yunho , Neuhaus Elizabeth B. , Davis C. Todd , Bowman Andrew S. , Wentworth David E. , Barnes John R.
Published: March 2019

Working overnight at a large swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, nanopore-sequenced 13 IAV genomes from samples collected, and in real-time, determined that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current pre-pandemic candidate vaccine viruses (CVV). We developed and used a portable IAV sequencing and analysis platform calledMia (Mobile Influenza Analysis)to complete and characterize full-length consensus genomes approximately 18 hours after unpacking the mobile lab. Swine are important animal IAV reservoirs that have given rise to pandemic viruses via zoonotic transmission. Genomic analyses of IAV in swine are critical to understanding pandemic risk of viruses in this reservoir, and characterization of viruses circulating in exhibition swine enables rapid comparison to current seasonal influenza vaccines and CVVs. TheMiasystem rapidly identified three genetically distinct swine IAV lineages from three subtypes: A(H1N1), A(H3N2) and A(H1N2). Additional analysis of the HA protein sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 portion of the hemagglutinin of these viruses and the most closely related pre-2009 CVV. All virus sequences were emailed to colleagues at CDC who initiated development of a synthetically derived CVV designed to provide an optimal antigenic match with the viruses detected in the exhibition. In subsequent months, this virus caused 13 infections in humans, and was the dominant variant virus in the US detected in 2018. Had this virus caused a severe outbreak or pandemic, our proactive surveillance efforts and CVV derivation would have provided an approximate 8 week time advantage for vaccine manufacturing. This is the first report of the use of field-derived nanopore sequencing data to initiate a real-time, actionable public health countermeasure.
Detection of vancomycin-resistant Enterococcus faecium hospital-adapted lineages in municipal wastewater treatment plants indicates widespread distribution and release into the environment
Authors: Gouliouris Theodore , Raven Kathy E. , Moradigaravand Danesh , Ludden Catherine , Coll Francesc , Blane Beth , Naydenova Plamena , Horner Carolyne , Brown Nicholas M. , Corander Jukka , Limmathurotsakul Direk , Parkhill Julian , Peacock Sharon J.
Published: March 2019

Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of healthcare-associated infection. Reservoirs of VREfm are largely assumed to be nosocomial although there is a paucity of data on alternative sources. Here, we describe an integrated epidemiological and genomic analysis of E. faecium associated with bloodstream infection and isolated from wastewater. Treated and untreated wastewater from 20 municipal treatment plants in the East of England, United Kingdom was obtained and cultured to isolate E. faecium, ampicillin-resistant E. faecium (AREfm), and VREfm. VREfm was isolated from all 20 treatment plants and was released into the environment by 17/20 plants, the exceptions using terminal ultraviolet light disinfection. Median log10 counts of AREfm and VREfm in untreated wastewater from 10 plants in direct receipt of hospital sewage were significantly higher than 10 plants that were not. We sequenced and compared the genomes of 423 isolates from wastewater with 187 isolates associated with bloodstream infection at five hospitals in the East of England. Among 481 E. faecium isolates belonging to the hospital-adapted clade, we observed genetic intermixing between wastewater and bloodstream infection, with highly related isolates shared between a major teaching hospital in the East of England and 9/20 plants. We detected 28 antibiotic resistance genes in the hospital-adapted clade, of which 23 were represented in bloodstream, hospital sewage, and municipal wastewater isolates. We conclude that our findings are consistent with widespread distribution of hospital-adapted VREfm beyond acute healthcare settings with extensive release of VREfm into the environment in the East of England.
Acute stress-induced cortisol elevation during memory consolidation enhances pattern separation
Authors: Jiang Alice , Tran Tammy T. , Madison Farrah N. , Bakker Arnold
Published: March 2019

Stress is a potent modulator of brain function and particularly mnemonic processes. While chronic stress is associated with long-term deficits in memory, the effects of acute stress on mnemonic functions are less clear as previous reports have been inconsistent. Some studies suggest that cortisol, a stress hormone that modulates biological changes in response to stress, may enhance memory consolidation and impair memory retrieval. However, other studies report no effect of cortisol on either memory consolidation or retrieval. These discrepancies could be due to differences in the timing and sequencing of the experimental procedures or individual differences in participants’ stress response. In the present study, we examined the effect of increased cortisol levels due to acute stress, induced by the Trier Social Stress Test (TSST), on a pattern separation memory task while differentiating the distinct stages of memory processing and controlling for the effects of diurnal variation. Sixty-nine young adults completed a 2-d study in which subjects either underwent the TSST immediately following the encoding part of the memory task, targeting memory consolidation, or immediately prior to the recognition part of the memory task on the second day, targeting memory retrieval. Control subjects completed the same study procedures but underwent a control version of the TSST that did not induce a stress response. Mnemonic discrimination of highly similar stimuli was enhanced by stress induced during consolidation with better discrimination showing a significant correlation with increased cortisol responses. Stress induced during memory retrieval showed no significant effect on memory performance. These findings suggest that stress induced changes in cortisol differentially affect the consolidation and retrieval stages of memory function.
Exploring the relationship between actions, habits, and automaticity in an action sequence task
Authors: Garr Eric , Delamater Andrew R.
Published: March 2019

It is tempting to equate the automatization of an action sequence with the formation of a habit. However, the term “habit” specifically implies a failure to evaluate future consequences to guide behavior. To test if automatized sequences become habitual, we trained rats on an action sequence task for either 20 or 60 d and then conducted reward devaluation tests. While both groups showed equivalent goal-directed performance of the trained action sequence on a global measure of behavior, sequence initiation and completion times were differentially sensitive to outcome devaluation in moderately and extensively trained rats.