bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: The Amsterdam Symptom and Risk-Based Score Predicts for Acute HIV Infection in Men Who Have Sex With Men in San Diego
Authors: Lin Timothy C. , Dijkstra Maartje , De Bree Godelieve J. , Schim van der Loeff Maarten F. , Hoenigl Martin
Published: July 2018

Objective:

Dijkstra et al recently described a risk- and symptom-based score moderately predictive for HIV seroconversion in the preceding 6–12 months in men who have sex with men (MSM) in Amsterdam. Our objective was to determine whether this “Amsterdam Score” could also predict for acute HIV infection (AHI) in MSM.

Design and Setting:

This study is a case–control analysis of a prospectively enrolled cohort of MSM who voluntarily presented for HIV testing in San Diego. The study sample was composed of MSM who screened HIV antibody-negative and then either tested positive with AHI [HIV nucleic acid test (NAT)-positive] or tested HIV NAT-negative.

Methods:

The Amsterdam Score was calculated for each participant in the study sample. Score performance was assessed using receiver operating characteristic curves and their area under the curve (AUC). An optimal cutoff was determined using the Youden index.

Results:

Seven hundred fifty-seven MSM (110 AHI and 647 HIV NAT-negative) were included in the analysis. AHI and HIV-negative cases were similar in age [median 32 years (interquartile range 26–42) vs 33 (27–45), respectively, P = 0.082]. The Amsterdam Score yielded a receiver operating characteristic curve with an AUC of 0.88 (95% confidence interval: 0.84 to 0.91). An optimal cutoff of ≥1.6 was 78.2% sensitive and 81.0% specific.

Conclusions:

The risk- and symptom-based Amsterdam Score was highly predictive (AUC of 0.88) of AHI in MSM in San Diego. The Amsterdam Score could be used to target NAT utilization in resource-poor settings among MSM who test HIV antibody-negative, although the potential cost-savings must be balanced with the risk of missing AHI diagnoses.
Standardizing Magnetic Resonance Imaging Protocols, Requisitions, and Reports in Multiple Sclerosis: An Update for Radiologist Based on 2017 Magnetic Resonance Imaging in Multiple Sclerosis and 2018 Consortium of Multiple Sclerosis Centers Consensus Guidelines
Authors: Arevalo Octavio , Riascos Roy , Rabiei Pejman , Kamali Arash , Nelson Flavia
Published: July 2018

The advent of magnetic resonance imaging has improved our understanding of the pathophysiology and natural course of multiple sclerosis (MS). The ability of magnetic resonance imaging to show the evolution of MS lesions on sequential scans has brought it to be one of the endpoints in clinical trials for disease-modifying therapies. Based on the most updated consensus guidelines from the American (Consortium of MS Centers) and European (Magnetic Resonance Imaging in MS) boards of experts in MS, this document shows the most relevant landmarks related to imaging findings, diagnostic criteria, indications to obtain a magnetic resonance, scan protocols and sequence options for patients with MS. Although incorporating the knowledge derived from the research arena into the daily clinical practice is always challenging, in this article, the authors provide useful recommendations to improve the information contained in the magnetic resonance report oriented to facilitate communication between radiologists and specialized medical teams involved in MS patients' multidisciplinary care.
Measurement of Vascular Diameter in Computed Tomography Angiography With Reduced Iodine Load: Comparison of Virtual Monochromatic Imaging in Dual-Energy Computed Tomography and Conventional Polychromatic Scan In Vitro
Authors: Sugawara Haruto , Suzuki Shigeru , Katada Yoshiaki , Ishikawa Takuya , Fukui Rika , Yamamoto Yuzo , Abe Osamu
Published: July 2018

Objectives

The aim of this study was to compare accuracy of measurement between virtual monochromatic imaging (VMI) in dual-energy computed tomography and conventional polychromatic 120-kVp computed tomographic scan in vascular models containing various densities of contrast material.

Methods

We evaluated measured diameters of 12 models of vessels of 4 inner diameters containing high, intermediate, and low densities of contrast material using software automation.

Results

Measurement errors with 70-keV VMI were significantly larger than or comparable to errors with 120-kVp scan for all models, and those with 50-keV VMI were significantly smaller than errors with 120-kVp scan for low-density models and larger for high-density models.

Conclusions

Acquisition of images by VMI at low energy facilitates accurate measurement of diameters of poorly enhanced vessels with reduced iodine load but can increase measurement errors in other situations by decreasing spatial resolution, so VMI should be applied carefully to evaluate vessel diameter.
Prospective Serial FDG PET/CT During Treatment of Extrapulmonary Tuberculosis in HIV-Infected Patients
Authors: Martin Charlotte , Castaigne Catherine , Vierasu Irina , Garcia Camilo , Wyndham-Thomas Chloe , de Wit Stéphane
Published: July 2018

Purpose

The aim of this study was to prospectively describe evolution of 18F-FDG uptake of extrapulmonary tuberculosis (TB) throughout the course of TB treatment in HIV patients to evaluate 18F-FDG PET/CT as a monitoring tool of treatment response.

Methods

We performed baseline FDG PET/CT, PET-2 after 2 months, and PET-3 at the end of TB treatment in 18 HIV/TB patients. We correlated evolution of FDG uptake with clinical outcome of patients.

Results

After 2 months of treatment, 78% of the patients had a significant metabolic response. Lymph node (LN) metabolic response was heterogeneous, with 57% of LN sites showing decreased SUVmax and 41% showing unchanged FDG uptake. Organs other than LNs showed more homogeneous response. The FDG PET/CT performed at the end of TB treatment showed a complete response of all infected organs and a drastic response in terms of active LNs in 95% of the patients (SUVmax mean decrease = 85%, median = 100%). A complete metabolic response after TB treatment was seen in only 47% of patients.

Conclusions

In difficult-to-treat entities such as extrapulmonary TB in HIV patients, FDG PET/CT is a potential tool in monitoring TB treatment response and should be explored in larger studies.
Causes of the Removal of High-Density Polyethylene Sheets (Medpor) in Revision Rhinoplasty
Authors: Kim Jae Hoon , Hwang Kun
Published: July 2018

The aim of this study was to identify the causes of complications in rhinoplasties using Medpor. The medical records of 71 patients who had undergoing a reoperation after a rhinoplasty using Medpor were reviewed. From each patient's history, examination records, and operative records, the method of the previous rhinoplasty using Medpor was extracted. The previously inserted Medpor and the septal mucosa covering it were removed during the reoperation and observed in 3 cases. A turned-up or short nose (43.8%) and tip stiffness (25.3%) were significantly more common than other complaints (P < 0.05). The strut type (49.2%) and the septal extension type (43.8%) were significantly more common than the spreader type (P < 0.001). In the reoperation, extension grafts (47.1%) and by tip grafts (39.7%) were significantly more common than other procedures (P < 0.001). Grossly, the specimens were covered with septal mucosa and multiple ball-like granulation tissues (cobblestone appearance) at the “pores” of the Medpor. Microscopically, Medpor was covered with fibrous collagenous tissue, partially bridging through the pores. Inflammatory cells had infiltrated around the polyethylene. The authors classify the patients in the present series as: those with a long columella strut to the anterior nasal spine, those with Medpor inserted onto the membranous septum (septal extension graft or too large), and those with Medpor used as spreader graft covered with nasal mucosa (causing weakness of the nasal septum and thinning or necrosis of the mucosa). Using Medpor as a strut graft seems to be relatively safe if the floating type is used.
Nerve Switch for Reducing Synkinesis After Gracilis Muscle Transfer Innervated Via the Masseter Nerve
Authors: Ota Tomoyuki , Matsumoto Hiroshi , Yamada Kiyoshi , Kimata Yoshihiro
Published: July 2018

Background:

In surgical treatment for longstanding facial paralysis, muscle transplantation is considered a useful and important method. To obtain a spontaneous smile, the use of the facial nerve of the healthy side as a motor source is better, but use of the masseter nerve allows prompt reinnervation and powerful movement. However, in some patients in whom the masseter nerve is used, separating masticatory movement and commissure contraction is difficult. Solutions for such patients have not been determined.

Case History and Discussion:

A 46-year-old female patient presented with longstanding complete facial paralysis after resection of a right acoustic neurinoma. As initial surgery, free gracilis transfer was performed on the cheek, but the patient experienced commissure movement during meals postsurgery. Secondary corrective surgery was performed to detach the motor nerve of the gracilis from the masseter nerve and suture it to the facial nerve of the healthy side via cross-face nerve graft. The symptom improved but partially recurred. Improvement in synkinetic movement can be obtained by performing cross-face nerve grafting and subsequent nerve switch.
Facial Growth Changes Induced by Orthodontic Treatment in Patients With Unilateral Cleft Lip and Palate
Authors: Lacerda Filho Rosa Helena Wanderley , Ramos Tânia Braga , Filho Valdécio Vasconcelos Lacerda , Chaves Ana Maria Barros , Furtado Paulo Germano Cavalcanti , Ozawa Terumi Okada
Published: July 2018

The aim of this study was to investigate the effect of orthodontic treatment on the maxillofacial growth of patients with unilateral cleft lip and palate. The Great Ormond Street, London and Oslo (GOSLON) yardstick was used for a longitudinal evaluation of 24 patients with cleft lip and palate treated at the Cleft Center of the Lauro Wanderley University Hospital, Paraiba State, northeastern Brazil. Dental casts were evaluated by 3 orthodontists and classified according to the GOSLON yardstick. The evaluation was performed at 2 different stages: T1 (before orthodontic treatment) and T2 (follow-up evaluation) after a 6-year mean follow-up interval. The Kappa test was used to evaluate intra- and interexaminer agreement, and paired t-test was used to compare the differences between T1 and T2, with a 99% confidence interval. The average intraexaminer Kappa was 0.979, ranging from 0.971 to 0.990. The interexaminer Kappa value was 0.926 at T1, ranging from 0.885 to 0.964, and 0.896 at T2, ranging from 0.696 to 1.0. The mean GOSLON yardstick found at T1 was 2.5 ± 1.18 with 50% in G1 + G2, 29.18% in G3, and 20.82% in G4 + G5. At T2, the GOSLON average was 1.71 ± 1.12, with 79.18% in G1 + G2, 12.5% in G3, and 8.32% in G4 + G5. A statistically significant difference was found between T1 and T2. The results suggest that orthodontic treatment improves facial growth in patients with unilateral cleft lip and palate.
Craniofacial Microsomia: Orthodontic Surgical Treatment of Growing Patients
Authors: Agurto Veas Pamela , Castellón Zirpel Loreto , Morovic Carmen Gloria
Published: July 2018

Craniofacial microsomia covers a set of morphogenetic anomalies that affect structures arising from the first and second brachial arches. Due to the vast phenotypic variation and complexity of the malformation, a global treatment that is coordinated by a multidisciplinary team is imperative. Herein, the authors describe 3 clinical patients and discuss the different therapies used according to the type of microsomia present. It was concluded that early and integrated treatment, which considers all the affected and potentially affected soft and hard tissue, is needed, and that patients must be monitored until they have finished growing.
Management of nonmetastatic castration-resistant prostate cancer
Authors: Traboulsi Samer L. , Saad Fred
Published: July 2018

Purpose of review

The widespread use of prostate-specific antigen (PSA) resulted in stage migration of prostate cancer where androgen deprivation therapy (ADT) is administered for biochemical recurrence in patients following primary treatment. A proportion of these patients progress to a disease state termed nonmetastatic castration-resistant prostate cancer (nmCRPC), with a rising PSA despite ADT and without evidence of metastases on conventional imaging. We will review the treatment options in nmCRPC, especially in light of recent trials showing significant improvement in metastasis-free survival with newer agents.

Recent findings

Historically, nmCRPC patients were followed-up if PSA doubling-time (PSADT) exceeded 10 months. Treatment options for patients with shorter PSADT included hormonal manipulations that often resulted in transient PSA decline. Denosumab was found to delay the onset of bone metastasis but did not impact survival. Recently, phase 3 trials showed that second-generation antiandrogens resulted in a significant delay in metastasis and a trend toward survival improvement in a select group of nmCRPC patients.

The importance of reducing mortality and morbidity associated with metastasis has led to the acceptance of new primary endpoints in the design of trials for nmCRPC and might result in widespread approval of new agents for this disease state.
A contemporary review about the management of radiation-induced hemorrhagic cystitis
Authors: Dautruche Antoine , Delouya Guila
Published: July 2018

Purpose of review

There are various specific therapeutic intervention available to treat hemorrhagic cystitis, once emergency treatment has been carried out. The lack of prospective studies, because of the relative rarity of this condition, makes it difficult to hierarchize the therapeutic sequence. The present review presents and summarizes the literature published on radiation-induced hemorrhagic cystitis from April 2015, date of a precedent exhaustive review, to March 2018.

Recent findings

During our period of interest, 13 clinical studies and two new clinical trials protocols were published. Most of the clinical studies were retrospective and presented data about hyperbaric oxygen (HBO) therapy, comforting its place as a well tolerated and effective first-line treatment. Other studies reported the outcomes of treatments with alum, formalin, silver nitrate, fulguration with laser or definitive surgery.

Although authors seem to agree that formalin and surgery have their role as effective but potentially morbid last-line treatments, there is no consensus on primary approach to management of radiation-induced hemorrhagic cystitis beyond symptomatic measures. Several treatments have proven excellent response rates and few side effects. The results of on-going prospective studies on mesenchymal stromal cells or tacrolimus instillations are awaited, but the main discriminating factor to choose between treatments remains local availability.
Chikungunya on Kidney Transplant Recipients: Is It the Same?
Authors: Tavares Bruno M. , Fernandes Paula FCBC , Oliveira Cláudia Maria C. , Silva Sônia L. , Mota Márcia U. , Andrade Tacilla HS , Cunha Samuel F. , Girão Evelyne S.
Published: July 2018

Background

Chikungunya virus (CHIKV) infection is an acute febrile illness with polyarthralgia and arthritis. There are few data about CHIKV infection in kidney transplant recipients (KTR). We report the largest case series of CHIKV infection in this population.

Methods

We retrospectively analyzed 32 cases of CHIKV infection in KTR between January 2016 and December 2017 at Hospital Universitário Walter Cantídio of Federal University of Ceará.

Results

All patients had been in endemic areas before the beginning of the symptoms. All presented arthralgia, 15 (46.9%) with joint inflammatory symptoms and 14 (43.8%) evolved to chronic arthralgia. Seven (21.9%) showed acute kidney injury (AKI) by Kidney Disease: Improving Global Outcomes criteria during the acute phase. Acute kidney injury was not related to prednisone use (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.04-2.61, P = 0.3) nor chronic arthralgia (OR, 1.2; 95% CI, 0.2-8.4, P = 0.8) as well as male sex, chronic kidney disease and older than 60 years (OR, 1.7; 95% CI, 0.3-10.3, P = 0.58; OR, 0.4; 95% CI, 0.1-2.7, P = 0.4; and OR, 2.1; 95% CI, 0.3-14.9, P = 0.45, respectively). Hospitalization was associated to AKI (OR, 44.0; 95% CI, 3.8-503.1; P = 0.002), probably due to diarrhea or dehydration. One patient died throughout the study, possibly unassociated with CHIKV infection.

Conclusions

KTR with CHIKV infection have a clinical presentation and evolution similar to those seen in the general population. Kidney function is generally well preserved, with transitory graft dysfunction without negative impact after 3 months from the beginning of the symptoms. Previous costicosteroids use did not relate with AKI or chronic arthralgia.
Procurement Biopsy Findings Versus Kidney Donor Risk Index for Predicting Renal Allograft Survival
Authors: Hall Isaac E. , Parikh Chirag R. , Schröppel Bernd , Weng Francis L. , Jia Yaqi , Thiessen-Philbrook Heather , Reese Peter P. , Doshi Mona D.
Published: July 2018

Background

Efforts to maximize transplantation by matching organ quality to recipient longevity require reliable tools. The US kidney allocation system uses the Kidney Donor Risk Index (KDRI) for this purpose, and many centers additionally rely on donor biopsies. The Leuven score combines donor age with procurement histology (glomerulosclerosis and interstitial fibrosis/tubular atrophy) to predict allograft survival.

Methods

We compared KDRI with Leuven scores for associations with kidney discard, delayed graft function, and allograft function and survival. We used Cox, modified Poisson, and linear regression to calculate risks based on KDRI and (separately) Leuven scores, adjusting for important transplant and recipient variables.

Results

From 890 donors, 1729 kidneys were procured and biopsied. Five hundred eighty-five (34%) kidneys were discarded. Median donor age was 53 years (interquartile range [IQR], 44-61 years). Median KDRI and Leuven scores were 1.56 (IQR, 1.28-1.90) and 59 (IQR, 49-69). Relative risk for discard was 1.21 (95% confidence interval [CI], 1.17-1.24) per 0.2-unit increase in KDRI and 1.38 (1.31-1.46) per 10-unit increase in Leuven score. Adjusted relative risks for delayed graft function were 0.98 (95% CI, 0.94-1.02) and 0.94 (95% CI, 0.90-0.99), adjusted hazard ratios for graft failure were 1.10 (95% CI, 1.04-1.16) and 1.11 (95% CI, 1.02-1.21), and adjusted linear regression coefficients for 3-year estimated glomerular filtration rate were −3.88 (−4.63 to −3.13) and -5.18 (−6.19 to −4.18).

Conclusions

In kidneys clinically selected for procurement biopsy, the Leuven score was more strongly associated with discard but performed similarly to KDRI for predicting transplant outcomes, suggesting the need to reevaluate current procurement biopsy practices. Given modest associations for both tools; however, neither KDRI nor the Leuven score should be used in isolation for individual organ acceptance decisions.
Social relationships and death-related behaviour in aquatic mammals: a systematic review
Authors: Reggente Melissa A. L. V. , Papale Elena , McGinty Niall , Eddy Lavinia , de Lucia Giuseppe Andrea , Bertulli Chiara Giulia
Published: July 2018

Some aquatic mammals appear to care for their dead, whereas others abandon their live offspring when conditions are unfavourable. This incredible variety in behaviours suggests the importance of comparing and contrasting mechanisms driving death-related behaviours among these species. We reviewed 106 cases of aquatic mammals (81 cetaceans and 25 non-cetaceans) reacting to a death event, and extrapolated ‘participant’ (age class,sex,relationshipanddecomposition) and ‘social’ characteristics (escorting,calf dependence,alloparental care,herdinganddispersal patterns) from published and unpublished literature. A multiple correspondence analysis (MCA) was performed to explore the relationships between these characteristics and death-related behaviours, with species clustered based on MCA scores. Results showed that both cetaceans and non-cetaceans react to death but in different ways. Non-cetaceans, characterized by a short maternal investment, were observed to protect the dead (defending it from external attacks), while cetaceans spent much longer with their offspring and display carrying (hauling, spinning, mouthing with the carcass and diving with it) and breathing-related (lifting and sinking the carcass) activities with the dead generally in association with other conspecifics. Our work emphasizes the need of increased documentation of death-related cases around the world to improve our understanding of aquatic mammals and their responses to death.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
The lure of death: suicide and human evolution
Authors: Humphrey Nicholas
Published: July 2018

At some point in evolutionary history, human beings came to understand, as no non-human animals do, that death brings to an end a person's bodily and mental presence in the world. A potentially devastating consequence was that individuals, seeking to escape physical or mental pain, might choose to kill themselves.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
The moral standing of the dead
Authors: Luper Steven
Published: July 2018

In choosing to do certain things, we appear to presuppose that we can act in the interests the dead, and that we have a duty to do so. For example, some of us go to great lengths to carry out their final wishes. Given that the dead no longer exist, however, it seems that nothing can be good or badforthem: they lack prudential interests. In that case, it is hard to see how we could owe them anything. They seem to lack moral standing altogether. In this essay, I will rebut this line of thought. I will claim that in some cases things that happen after people die are indeed good or bad for them. Their interests can still be advanced or hindered, so the dead have moral standing.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Changing relationship between the dead and the living in Japanese prehistory
Authors: Matsumoto Naoko
Published: July 2018

The aim of this paper is to propose a new insight on the changing burial practice by regarding it as a part of the cognitive system for maintaining complex social relationships. Development of concentrated burials and their transformation in Japanese prehistory are examined to present a specific case of the changing relationship between the dead and the living to highlight the significance of the dead in sociocultural evolution. The essential feature of the burial practices observed at Jomon sites is the centrality of the dead and their continuous presence in the kinship system. The mortuary practices discussed in this paper represent a close relationship between the dead and the living in the non-hierarchical complex society, in which the dead were not detached from the society, but kept at its core, as a materialized reference of kin networks.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Speaking of death
Authors: Husband E. Matthew
Published: July 2018

As a human-specific trait, language offers a unique window on human cognition. Grammatical constraints on the ways we speak about events, for instance, have long been thought to reveal the representational formats that our minds impose on the ways that we think about events. In recent research, verbs that name events of death have stood out as key counterexamples to standard theories of the grammatical constraints on possible verbs. The special status of these thanatological verbs raises two important questions: why, given the vast number of verbs in any language, is it that verbs of death hold this special status, and what do they tell us about the restrictions on the representational format for possible verbs? This paper reexamines the evidence coming from verbs of death, confirming that they are counterexamples to standard theories, but that their behaviour suggests a more revealing constraint on our mental representations—that our minds impose strict restrictions on the format of asserted meaning. Thus, the constraints on linguistic representation and the human mind offer a unique perspective on the mental representations of thanatological phenomena.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Gfi1-expressing Paneth cells revert to stem cells following intestinal injury
Authors: Chen Min-Shan , Lo Yuan-Hung , Butkus Joann , Zou Winnie , Tseng Yu-Jung , Jen Hsin-I , Patel Shreena , Groves Andrew , Estes Mary , Sahin Ergun , Frey Mark , Dempsey Peter , Shroyer Noah
Published: July 2018

Background＆Aim

Chemotherapy drugs harm rapidly dividing normal healthy cells such as those lining the gastrointestinal tract, causing morbidity and mortality that complicates medical treatment modalities. Growth Factor-Independent 1 (GFI1) is a zinc finger transcriptional repressor implicated in the differentiation of secretory precursors into Paneth and goblet cells in the intestinal epithelium. We hypothesize that stimulating the reversion of Gfi1+ secretory cells into stem cells will improve intestinal epithelial regeneration and mitigate injury.

Methods

Gfi1 reporter mice (Gfi1cre/+; ROSA26 LSL-YFP) were treated with Doxorubicin, radiation, anti-CD3 antibody, and rotavirus to induce intestinal injury. Mice and intestinal organoids (enteroids) were used to investigate cellular repair mechanisms following injury.

Results

Under homeostatic conditions, Gfi1-lineage cells are Paneth and goblet cells, which were non-proliferative and not part of the stem cell pool. After injury, Gfi1+ secretory cells can re-enter the cell cycle and give rise to all cell lineages of the intestinal epithelium including stem cells. Reversion of Gfi1-lineage cells was observed in other injury model systems, including irradiation and anti-CD3 treatment, but not in ISC-sparing rotavirus infection. Our results also demonstrated that PI3kinase/AKT activation improved cell survival, and elevated WNT signaling increased the efficiency of Gfi1+ cell reversion upon injury.

Conclusions

These findings indicate that Gfi1+ secretory cells display plasticity and reacquire stemness following severe damage. Moreover, PI3kinase/AKT and WNT are key regulators involved in injury-induced regeneration. Our studies identified potential therapeutic intervention strategies to mitigate the adverse effects of chemotherapy-induced damage to normal tissues and improve the overall effectiveness of cancer chemotherapy.
Speed breeding in growth chambers and glasshouses for crop breeding and model plant research
Authors: Ghosh Sreya , Watson Amy , Gonzalez-Navarro Oscar E. , Ramirez-Gonzalez Ricardo H. , Yanes Luis , Mendoza-Suárez Marcela , Simmonds James , Wells Rachel , Rayner Tracey , Green Phon , Hafeez Amber , Hayta Sadiye , Melton Rachel E. , Steed Andrew , Sarkar Abhimanyu , Carter Jeremy , Perkins Lionel , Lord John , Tester Mark , Osbourn Anne , Moscou Matthew J. , Nicholson Paul , Harwood Wendy , Martin Cathie , Domoney Claire , Uauy Cristobal , Hazard Brittany , Wulff Brande B. H. , Hickey Lee T.
Published: July 2018

1.

To meet the challenge of feeding a growing population, breeders and scientists are continuously looking for ways to increase genetic gain in crop breeding. One way this can be achieved is through “speed breeding” (SB), which shortens the breeding cycle and accelerates research studies through rapid generation advancement. The SB method can be carried out in a number of ways, one of which involves extending the duration of a plant’s daily exposure to light (photoperiod) combined with early seed harvest in order to cycle quickly from seed to seed, thereby reducing the generation times for some long-day (LD) or day-neutral crops. Here we present glasshouse and growth chamber-based SB protocols with supporting data from experimentation with several crop species. These protocols describe the growing conditions, including soil media composition, lighting, temperature and spacing, which promote rapid growth of spring and winter bread wheat, durum wheat, barley, oat, various members of the Brassica family, chickpea, pea, grasspea, quinoa and the model grass Brachypodium distachyon. Points of flexibility within the protocols are highlighted, including how plant density can be increased to efficiently scale-up plant numbers for single seed descent (SSD) purposes. Conversely, instructions on how to perform SB on a small-scale by creating a benchtop SB growth cabinet that enables optimization of parameters at a low cost are provided. We also outline the procedure for harvesting and germinating premature wheat, barley and pea seed to reduce generation time. Finally, we provide troubleshooting suggestions to avoid potential pitfalls.
Combinatorial Detection of Conserved Alteration Patterns for Identifying Cancer Subnetworks
Authors: Hodzic Ermin , Shrestha Raunak , Zhu Kaiyuan , Cheng Kuoyuan , Collins Colin C. , Cenk Sahinalp S.
Published: July 2018

Background

Advances in large scale tumor sequencing have lead to an understanding that there are combinations of genomic and transcriptomic alterations speciflc to tumor types, shared across many patients. Unfortunately, computational identiflcation of functionally meaningful shared alteration patterns, impacting gene/protein interaction subnetworks, has proven to be challenging.

Findings

We introduce a novel combinatorial method, cd-CAP, for simultaneous detection of connected subnetworks of an interaction network where genes exhibit conserved alteration patterns across tumor samples. Our method differentiates distinct alteration types associated with each gene (rather than relying on binary information of a gene being altered or not), and simultaneously detects multiple alteration proflle conserved subnetworks.

Conclusions

In a number of The Cancer Genome Atlas (TCGA) data sets, cd-CAP identifled large biologically signiflcant subnetworks with conserved alteration patterns, shared across many tumor samples.
Dynamic plant height QTL revealed in maize through remote sensing phenotyping using a high-throughput unmanned aerial vehicle (UAV)
Authors: Wang Xiaqing , Zhang Ruyang , Han Liang , Yang Hao , Song Wei , Liu Xiaolei , Sun Xuan , Luo Meijie , Chen Kuan , Zhang Yunxia , Yang Guijun , Zhao Yanxin , Zhao Jiuran
Published: July 2018

Plant height is the key factor for plant architecture, biomass and yield in maize (Zea mays). In this study, plant height was investigated using unmanned aerial vehicle high-throughput phenotypic platforms (UAV-HTPPs) for maize diversity inbred lines at four important growth stages. Using an automated pipeline, we extracted accurate plant heights. We found that in temperate regions, from sowing to the jointing period, the growth rate for temperate maize was faster than tropical maize. However, from jointing to flowering stage, tropical maize maintained a vigorous growth state, and finally resulted in a taller plant than temperate lines. Genome-wide association study for temperate, tropical and both groups identified a total of 238 quantitative trait locus (QTLs) for the 16 plant height related traits over four growth periods. And, we found that plant height at different stages were controlled by different genes, for example, PIN1 controlled plant height at the early stage and PIN11 at the flowering stages. In this study, the plant height data collected by the UAV-HTTPs were credible and the genetic mapping power is high, indicating that the application of this UAV-HTTPs into the study of plant height will have great prospects.

Highlight

We used UAV-based sensing platform to investigate plant height over 4 growth stages for different maize populations, and detected numbers of reliable QTLs using GWAS.
Drug-target binding quantitatively predicts optimal antibiotic dose levels
Authors: Clarelli Fabrizio , Palmer Adam , Singh Bhupender , Storflor Merete , Lauksund Silje , Cohen Ted , Abel Sören , zur Wiesch Pia Abel
Published: July 2018

Combatting antibiotic resistance will require both new antibiotics and strategies to preserve the effectiveness of existing drugs. Both approaches would benefit from predicting optimal dosing of antibiotics based on drug-target binding parameters that can be measured early in drug development and that can change when bacteria become resistant. This would avoid the currently frequently employed trial-and-error approaches and might reduce the number of antibiotic candidates that fail late in drug development.

Here, we describe a computational model (COMBAT-COmputational Model of Bacterial Antibiotic Target-binding) that leverages accessible biochemical parameters to quantitatively predict antibiotic dose-response relationships. We validate our model with MICs of a range of quinolone antibiotics in clinical isolates demonstrating that antibiotic efficacy can be predicted from drug-target binding (R2 > 0.9). To further challenge our approach, we do not only predict antibiotic efficacy from biochemical parameters, but also do the reverse: estimate the magnitude of changes in drug-target binding based on antibiotic dose-response curves. We experimentally demonstrate that changes in drug-target binding can be predicted from antibiotic dose-response curves with 92-94 % accuracy by exposing bacteria overexpressing target molecules to ciprofloxacin. To test the generality of COMBAT, we apply it to a different antibiotic class, the beta-lactam ampicillin, and can again predict binding parameters from dose-response curves with 90 % accuracy. We then apply COMBAT to predict antibiotic concentrations that can select for resistance due to novel resistance mutations.

Our goal here is dual: First, we address a fundamental biological question and demonstrate that drug-target binding determines bacterial response to antibiotics, although antibiotic action involves many additional effects downstream of drug-target binding. Second, we create a tool that can help accelerate drug development by predicting optimal dosing and preserve the efficacy of existing antibiotics by predicting optimal treatment for possible resistant mutants.
Predicting the Outcomes of New Short-Course Regimens for Multi-Drug Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modelling
Authors: Doan Tan N , Cao Pengxing , Emeto Theophilus I , McCaw James M , McBryde Emma S
Published: July 2018

Short-course regimens for multi-drug resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug, bedaquiline (BDQ), may have the potential to shorten MDR-TB treatment to less than six months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modelling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modelling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (four months) while still maintaining a very high treatment success rate (100% for daily BDQ for two weeks, or 95% for daily BDQ for one week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes then we anticipate clear cost-savings and a subsequent improvement in the efficiency of national TB programs.
Parallel Evolution in the Emergence of Highly Pathogenic Avian Influenza A Viruses
Authors: Escalera-Zamudio Marina , Golden Michael , Gutiérrez Bernardo , Thézé Julien , Keown Jeremy Russell , Carrique Loic , Bowden Thomas A. , Pybus Oliver G.
Published: July 2018

Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs independently evolve from low-pathogenic ancestors via acquisition of a polybasic cleavage sites (pCS). Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the AIV genome. We combined phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a new statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein function. The mutational panel we present reveals new links between virulence evolution and other viral traits and raises the possibility of predicting aspects of AIV evolution.
The integration of visual and target signals in V4 and IT during visual object search
Authors: Roth Noam , Rust Nicole C.
Published: July 2018

Searching for a specific visual object requires our brain to compare the items in view with a remembered representation of the sought target to determine whether a target match is present. This comparison is thought to be implemented, in part, via the combination of top-down modulations reflecting target identity with feed-forward visual representations. However, it remains unclear whether top-down signals are integrated at a single locus within the ventral visual pathway (e.g. V4) or at multiple stages (e.g. both V4 and inferotemporal cortex, IT). To investigate, we recorded neural responses in V4 and IT as rhesus monkeys performed a task that required them to identify when a target object appeared across variation in position, size and background context. We found non-visual, task-specific signals in both V4 and IT. To evaluate whether V4 was the only locus for the integration of top-down signals, we evaluated several feed-forward accounts of processing from V4 to IT, including a model in which IT preferentially sampled from the best V4 units and a model that allowed for nonlinear IT computation. IT task-specific modulation was not accounted for by any of these feed-forward descriptions, suggesting that during object search, top-down signals are integrated directly within IT.

NEW & NOTEWORTHY

To find specific objects, the brain must integrate top-down, target-specific signals with visual information about objects in view. However, the exact route of this integration in the ventral visual pathway is unclear. In the first study to systematically compare V4 and IT during an invariant object search task, we demonstrate that top-down signals found in IT cannot be described as being inherited from V4, but rather must be integrated directly within IT itself.
Characterisation of morphological differences in well-differentiated nasal epithelial cell cultures from preterm and term infants at birth and one-year
Authors: Groves Helen E. , Guo-Parke Hong , Broadbent Lindsay , Shields Michael D. , Power Ultan F.
Published: July 2018

Background

Innate immune responses of airway epithelium are important defences against respiratory pathogens and allergens. Newborn infants are at greater risk of severe respiratory infections compared to older infants. However, very little is known regarding human neonatal airway epithelium immune responses and whether age-related morphological and/or innate immune changes contribute to the development of airway disease.

Methods

We collected nasal epithelial cells from 41 newborn infants (23 term, 18 preterm) within 5 days of birth. Repeat sampling was achieved for 24 infants (13 term, 11 preterm) at a median age of 12.5 months. Morphologically and physiologically authentic well-differentiated primary paediatric nasal epithelial cell (WD-PNEC) cultures were generated and characterised using light microscopy and immunofluorescence.

Results

WD-PNEC cultures were established for 15/23 (65%) term and 13/18 (72%) preterm samples at birth, and 9/13 (69%) term and 8/11 (73%) preterm samples at one-year. Newborn and infant WD-PNEC cultures demonstrated extensive cilia coverage, mucous production and tight junction integrity. Newborn WD-PNECs took significantly longer to reach full differentiation and were noted to have much greater proportions of goblet cells compared to one-year repeat WD-PNECs. No differences were evident in ciliated/goblet cell proportions between term- and preterm-derived WD-PNECs at birth or one-year old.

Conclusion

WD-PNEC culture generation from newborn infants is feasible and represents a powerful and exciting opportunity to study differential innate immune responses in human airway epithelium very early in life.
Computational metabolomics hints at the relevance of glutamine metabolism in breast cancer
Authors: Trilla-Fuertes Lucía , Gámez-Pozo Angelo , López-Camacho Elena , Prado-Vázquez Guillermo , Zapater-Moros Andrea , López-Vacas Rocío , Arevalillo Jorge M , Díaz-Almirón Mariana , Navarro Hilario , Maín Paloma , Espinosa Enrique , Zamora Pilar , Fresno Vara Juan Ángel
Published: July 2018

Metabolomics has a great potential in the development of new biomarkers in cancer. In this study, metabolomics and gene expression data from breast cancer tumor samples were analyzed, using (1) probabilistic graphical models to define associations using quantitative data without othera prioriinformation; and (2) Flux Balance Analysis and flux activities to characterize differences in metabolic pathways. On the one hand, both analyses highlighted the importance of glutamine in breast cancer. Moreover, cell experiments showed that treating breast cancer cells with drugs targeting glutamine metabolism significantly affects cell viability. On the other hand, these computational methods suggested some hypotheses and have demonstrated their utility in the analysis of metabolomics data and in associating metabolomics with patient’s clinical outcome.
Functional phenomics: An emerging field integrating high-throughput phenotyping, physiology, and bioinformatics
Authors: York Larry M.
Published: July 2018

Highlight

Functional phenomics is an emerging field in plant biology that relies on high-throughput phenotyping, big data analytics, controlled manipulative experiments, and simulation modelling to increase understanding of plant physiology.

The emergence of functional phenomics signifies the rebirth of physiology as a 21st century science through the use of advanced sensing technologies and big data analytics. Functional phenomics highlights the importance of phenotyping beyond only identifying genetic regions because a significant knowledge gap remains in understanding which plant properties will influence ecosystem services beneficial to human welfare. Here, a general approach for the theory and practice of functional phenomics is outlined including exploring the phene concept as a unit of phenotype. The functional phenomics pipeline is proposed as a general method for conceptualizing, measuring, and validating utility of plant phenes. The functional phenomics pipeline begins with ideotype development. Second, a phenotyping platform is developed to maximize the throughput of phene measurements. A mapping population is screened measuring target phenes and indicators of plant performance such as yield and nutrient composition. Traditional forward genetics allows genetic mapping, while functional phenomics links phenes to plant performance. Based on these data, genotypes with contrasting phenotypes can be selected for smaller yet more intensive experiments to understand phene-environment interactions in depth. Simulation modeling can be used to understand the phenotypes and all stages of the pipeline feed back to ideotype and phenotyping platform development.
MSTD: an efficient method for detecting multi-scale topological domains from symmetric and asymmetric 3D genomic maps
Authors: Ye Yusen , Gao Lin , Zhang Shihua
Published: July 2018

The chromosome conformation capture (3C) technique and its variants have been employed to reveal the existence of a hierarchy of structures in three-dimensional (3D) chromosomal architecture, including compartments, topologically associating domains (TADs), sub-TADs and chromatin loops. However, existing methods for domain detection were only designed based on symmetric Hi-C maps, ignoring long-range interaction structures between domains. To this end, we proposed a generic and efficient method to identify multi-scale topological domains (MSTD), including cis- and trans-interacting regions, from a variety of 3D genomic datasets. We first applied MSTD to detect promoter-anchored interaction domains (PADs) from promoter capture Hi-C datasets across 17 primary blood cell types. The boundaries of PADs are significantly enriched with one or the combination of multiple epigenetic factors. Moreover, PADs between functionally similar cell types are significantly conserved in terms of domain regions and expression states. Cell type-specific PADs involve in distinct cell type-specific activities and regulatory events by dynamic interactions within them. We also employed MSTD to define multi-scale domains from typical symmetric Hi-C datasets and illustrated its distinct superiority to the-state-of-art methods in terms of accuracy, flexibility and efficiency.
The phospholamban pentamer interacts with the sarcoplasmic reticulum calcium pump SERCA
Authors: Glaves J. P. , Primeau J. O. , Espinoza-Fonseca L. M. , Lemieux M. J. , Young H. S.
Published: July 2018

The interaction of phospholamban with the sarcoplasmic reticulum calcium pump (SERCA) is a major regulatory axis in cardiac muscle contractility. The prevailing model involves reversible inhibition of SERCA by monomeric phospholamban and storage of phospholamban as an inactive pentamer. However, this paradigm has been challenged by studies demonstrating that phospholamban remains associated with SERCA and that the phospholamban pentamer is required for cardiac contractility. We have previously used two-dimensional crystallization and electron microscopy to study the interaction between SERCA and phospholamban. To further understand this interaction, we compared small helical crystals and large two-dimensional crystals of SERCA in the absence and presence of phospholamban. In both crystal forms, SERCA molecules are organized into identical anti-parallel dimer ribbons. The dimer ribbons pack together with distinct crystal contacts in the helical versus large two-dimensional crystals, which allow phospholamban differential access to potential sites of interaction with SERCA. Nonetheless, we show that a phospholamban oligomer interacts with SERCA in a similar manner in both crystal forms. In the two-dimensional crystals, a phospholamban pentamer interacts with transmembrane segments M3 of SERCA and participates in a crystal contact that bridges neighboring SERCA dimer ribbons. In the helical crystals, an oligomeric form of phospholamban also interacts with M3 of SERCA, though the phospholamban oligomer straddles a SERCA-SERCA crystal contact. We conclude that the pentameric form of phospholamban interacts with SERCA, and that it plays distinct structural and functional roles in SERCA regulation.