bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterialized Posterior Interosseous Nerve Graft for Digital Neuroma
Authors: Foo Anthony , Martin-Playa Patricia , Sebastin Muttath Sandeep J.
Published: June 2019

Painful neuromas are not uncommon following nerve injury, and are especially bothersome in the hand, with severe cases resulting in significant disability. Outcomes of neuroma surgery are unpredictable regardless of technique. It is recognized that optimal soft tissue environment influences nerve healing more than the specific nerve graft technique, and it is in this context, we present a novel technique of transferring a posterior interosseous nerve graft along with vascularized synovial and fat tissue based on a branch of the posterior interosseous artery to provide healthy soft tissue for nerve healing of neuroma in continuity about the hand and digits.
Triquetrum Excision in Radioscapholunate Arthrodesis for Posttraumatic Radiocarpal Osteoarthritis With Ulnar Impaction Syndrome
Authors: Liechti Rémy , Beeres Frank J.P. , Hug Urs
Published: June 2019

Dependent on fracture type, concomitant carpal injuries, and operative treatment, distal radius fractures can lead to symptomatic radiocarpal osteoarthritis. In addition, radial shortening can cause ulnar impaction syndrome. Radiocarpal arthrodesis and ulnar shortening osteotomy are known and frequently applied surgical procedures for each of those pathologies. There are limited data concerning treatment options for a combined disorder. The presented technique in this article demonstrates that radioscapholunate arthrodesis with distal pole scaphoidectomy and total triquetrum excision successfully treats both symptomatic radiocarpal osteoarthritis and ulnar impaction syndrome without further surgery on the ulna.
Using Tongue Depressors as a Technique to Aid Cord Localization During Collagenase Injection For Dupuytren Disease
Authors: Mehdi Syed K. , Yonz Michael C. , Keshtvarz Sara , Kamineni Srinath , Dhawan Vikas
Published: June 2019

Collagenase injections are used as a minimally invasive treatment for Dupuytren contracture of the palm and fingers, with good published success. Most complications are related to injection-site swelling, pain, and ecchymosis. However, the risk of flexor tendon and digital nerve injury can occur when injecting cords that cause proximal interphalangeal joint contractures. In addition, poor localization and incorrect injection of the solution into cords may result in an incomplete correction. We describe a technique to improve visualization and isolation of Dupuytren cords using a tongue depressor.
Fine Particulate Air Pollution and Birthweight: Differences in Associations Along the Birthweight Distribution
Authors: Fong Kelvin C. , Kosheleva Anna , Kloog Itai , Koutrakis Petros , Laden Francine , Coull Brent A. , Schwartz Joel D.
Published: June 2019

Background:

Maternal exposure to fine particulate air pollution (PM2.5) during pregnancy is associated with lower newborn birthweight, which is a risk factor for chronic disease. Existing studies typically report the average association related with PM2.5 increase, which does not offer information about potentially varying associations at different points of the birthweight distribution.

Methods:

We retrieved all birth records in Massachusetts between 2001 and 2013 then restricted our analysis to full-term live singletons (n = 775,768). Using the birthdate, gestational age, and residential address reported at time of birth, we estimated the average maternal PM2.5 exposure during pregnancy of each birth. PM2.5 predictions came from a model that incorporates satellite, land use, and meteorologic data. We applied quantile regression to quantify the association between PM2.5 and birthweight at each decile of birthweight, adjusted for individual and neighborhood covariates. We considered effect modification by indicators of individual and neighborhood socioeconomic status (SES).

Results:

PM2.5 was negatively associated with birthweight. An interquartile range increase in PM2.5 was associated with a 16 g [95% confidence interval (CI) = 13, 19] lower birthweight on average, 19 g (95% CI = 15, 23) lower birthweight at the lowest decile of birthweight, and 14 g (95% CI = 9, 19) lower birthweight at the highest decile. In general, the magnitudes of negative associations were larger at lower deciles. We did not find evidence of effect modification by individual or neighborhood SES.

Conclusions:

In full-term live births, PM2.5 and birthweight were negatively associated with more severe associations at lower quantiles of birthweight.
The glutamate to γ-aminobutyric acid ratio in the posterior insula is associated with pain perception in healthy women but not in women with borderline personality disorder
Authors: Gradinger Tobias , Sack Markus , Cardinale Vita , Thiacourt Margot , Baumgärtner Ulf , Schmahl Christian , Ende Gabriele
Published: June 2019

This study aimed to investigate whether the differences in pain perception between patients with borderline personality disorder (BPD) and healthy subjects (HCs) can be explained by differences in the glutamate/GABA ratio in the posterior insula. In total, 29 BPD patients and 31 HCs were included in the statistical analysis. Mechanical pain sensitivity was experimentally assessed with pinprick stimuli between 32 and 512 mN on a numeric rating scale. The metabolites were measured in the right posterior insula using the MEshcher–GArwood Point-RESolved Spectroscopy sequence for single-voxel magnetic resonance spectroscopy (1H-MRS). The 256- and the 512-mN pinprick stimuli were perceived as significantly less painful by the BPD patient group compared with HCs. No differences were found between groups for the glutamate/GABA ratios. A positive correlation between the glutamate/GABA ratio and the pain intensity ratings to 256- and 512-mN pinpricks could be found in the combined and in the HC group. In the BPD patient group, the correlations between the glutamate/GABA ratio and the pain intensity ratings to 256- and 512-mN pinpricks did not reach significance. In conclusion, the study showed that individual differences in pain perception may in part be explained by the individual glutamate/GABA ratio in the posterior insula. However, this possible mechanism does not explain the differences in pain perception between BPD patients and HCs.
The Price of Immune Responses and the Role of Vitamin D in the Inner Ear
Authors: Büki Béla , Jünger Heinz , Zhang Yan , Lundberg Yunxia Wang
Published: June 2019

Objective:

In this review the authors discuss evidence from the literature concerning vitamin D and temporal bone diseases (benign paroxysmal positional vertigo [BPPV], Menière's disease [MD], vestibular neuritis, idiopathic facial paralysis, idiopathic acute hearing loss). Common features shared by Menière's disease, glaucoma, and the possible influence by vitamin D are briefly discussed.

Data Sources, Study Selection:

Publications from 1970 until recent times have been reviewed according to a keyword search (see above) in PubMed.

Conclusions:

MD, BPPV, vestibular neuritis, idiopathic facial paralysis, idiopathic acute hearing loss may all have several etiological factors, but a common feature of the current theories is that an initial viral infection and a subsequent autoimmune/autoinflammatory reaction might be involved. Additionally, in some of these entities varying degrees of demyelination have been documented. Given the immunomodulatory effect of vitamin D, we postulate that it may play a role in suppressing an eventual postviral autoimmune reaction. This beneficial effect may be enhanced by the antioxidative activity of vitamin D and its potential in stabilizing endothelial cells. The association of vitamin D deficiency with demyelination has already been established in other entities such as multiple sclerosis and experimental autoimmune encephalitis. Mice without vitamin D receptor show degenerative features in inner ear ganglia, hair cells, as well as otoconia. The authors suggest further studies concerning the role of vitamin D deficiency in diseases of the temporal bone. Additionally, the possible presence and degree of demyelination in these entities will have to be elucidated more systematically in the future.
Age Dependent Cost-Effectiveness of Cochlear Implantation in Adults. Is There an Age Related Cut-off?
Authors: Laske Roman D. , Dreyfuss Michael , Stulman Alan , Veraguth Dorothe , Huber Alexander M. , Röösli Christof
Published: June 2019

Objective:

To analyze the impact of age at implantation on the cost-effectiveness of cochlear implantation (CI).

Study Design:

Cost-utility analysis in an adapted Markov model.

Setting:

Adults with profound postlingual hearing loss in a “high income” country.

Intervention:

Unilateral and sequential CI were compared with hearing aids (HA).

Main Outcome Measure:

Incremental cost-effectiveness ratio (ICER), calculated as costs per quality adjusted life year (QALY) gained (in CHF/QALY), for individual age and sex combinations in relation to two different willingness to pay thresholds. 1 CHF (Swiss franc) is equivalent to 1.01 USD.

Results:

When a threshold of 50,000 CHF per QALY is applied, unilateral CI in comparison to HA is cost-effective up to an age of 91 for women and 89 for men. Sequential CI in comparison to HA is cost-effective up to an age of 87 for women and 85 for men. If a more contemporary threshold of 100,000 CHF per QALY is applied, sequential CI in comparison to unilateral CI is cost-effective up to an age of 80 for women and 78 for men.

Conclusions:

Performing both sequential and unilateral CI is cost-effective up to very advanced ages when compared with hearing aids.
Pancreatobiliary Versus Head and Neck Manifestations in Immunoglobulin G4–related Disease
Authors: Mohapatra Sonmoon , Sharma Ayush , Chari Suresh T.
Published: June 2019

Objectives

We compared the clinical profiles and organ manifestations of the commonly encountered immunoglobulin G4–related diseases (IgG4-RDs) on either side of the diaphragm: head and neck (HN) versus pancreatobiliary (PB) in IgG4-RD.

Methods

From the Mayo Clinic, Rochester, database, we identified 53 HN and 88 PB IgG4-RD based on the first affected organ manifestation.

Results

Compared with HN IgG4-RD, subjects with PB IgG4-RD were likely to be older (median, 64.8 vs 50.2 years; P < 0.0001), male (83% vs 60.4%; P = 0.003), and with a shorter duration of follow-up (24.4 vs 48.7 months; P < 0.0001). In HN versus PB-IgG4-RD orbital, lacrimal gland, submandibular, parotid gland, asthma, and sinusitis manifestations were more common (77% vs 4.5%, 21% vs 0%, 32% vs 8%, 13% vs 0%, 36% vs 9%, and 51% vs 6.8%; P < 0.0001, respectively), whereas lung manifestations were similar (13.2% vs 5.6%; P = 0.12). In contrast, in PB versus HN IgG4-RD, pancreas and biliary were more frequent (98.8% vs 15%, 56.8% vs 3.7%; P < 0.0001), whereas renal lesions were similar (12.5% vs 7.5%; P = 0.36).

Conclusion

Pancreatobiliary and HN IgG4-RD have distinct clinical profiles. Proximity matters in other organ involvement in IgG4-RD, and organs involved tend to cluster close to each.
Predicting Successful Catheter Drainage in Patients With Pancreatic Fistula After Pancreatoduodenectomy
Authors: Smits F. Jasmijn , van Santvoort Hjalmar C. , Besselink Marc G. , Boerma Djamila , Busch Olivier R. , van Dam Ronald M. , van Eijck Casper H. , Festen Sebastiaan , van der Harst Erwin , de Hingh Ignace H. , de Jong Koert P. , Borel Rinkes Inne H. , Molenaar I. Quintus
Published: June 2019

Objectives

The objective of this study was to identify predictors for successful minimally invasive catheter drainage (ie, survival without relaparotomy) for pancreatic fistula after pancreatoduodenectomy.

Methods

Included were consecutive patients undergoing catheter drainage as first intervention for pancreatic fistula after pancreatoduodenectomy (2005–2013) in 9 Dutch centers. Possible prognostic factors for successful catheter drainage (ie, survival without relaparotomy) were selected using Akaike information criterion.

Results

Included were 227 patients after 2196 pancreatoduodenectomies. Primary catheter drainage was successful in 175 (77%) of 227 patients. Multivariable logistic regression revealed the following negative prognostic factors for success: male sex (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21–1.00; P = 0.049), higher age (for every 5 years over 50; OR, 0.69; 95% CI, 0.57–0.84; P < 0.001), and respiratory failure at time of catheter drainage (OR, 0.10; 95% CI, 0.03–0.33; P < 0.001). A prognostic model incorporating these factors yielded an area under the curve of 0.76 and demonstrated a success range of 98% to 14%.

Conclusions

Male sex, higher age, and respiratory failure are associated with a low success rate of catheter drainage in patients with pancreatic fistula after pancreatoduodenectomy. These patients might benefit from an intensified postoperative monitoring for early detection and management of pancreatic fistula to prevent respiratory failure.
Low Serum Trypsin Levels Predict Deep Pancreatic Cannulation Failure During Endoscopic Retrograde Cholangiopancreatography in Patients With Symptomatic Obstructive Chronic Pancreatitis
Authors: Faghih Mahya , Boortalary Tina , Jalaly Niloofar Y. , Brewer Gutierrez Olaya I. , Chen Yen-I , Azadi Javad R. , Parsa Nasim , Noë Michaël , Fan Christopher , Kumbhari Vivek , Kalloo Anthony N. , Zaheer Atif , Khashab Mouen A. , Singh Vikesh K.
Published: June 2019

Objectives

Deep pancreatic cannulation (DPC) failure during endoscopic retrograde cholangiopancreatography (ERCP) in patients with chronic pancreatitis (CP) can occur in the presence of ductal obstruction due to strictures and/or stones. There are currently no simple preprocedure clinical or laboratory tests that can predict DPC failure during ERCP.

Methods

All adult patients with definite CP by M-ANNHEIM criteria referred to the pancreatitis clinic between 2010 and 2017 were evaluated. Serum trypsin levels were obtained to assess the morphologic severity of disease and/or exocrine insufficiency. Univariable and multivariable logistic regression analyses were performed to identify factors associated with DPC failure.

Results

There were 346 patients, of whom 100 underwent trypsin measurements and ERCP for symptomatic CP. Deep pancreatic cannulation failure occurred in 32 (32%). There were no significant differences with regard to age, sex, etiology, smoking, and alcohol use. Deep pancreatic cannulation failure was more likely to occur in patients with low trypsin levels (53.1% vs 25%, P = 0.007) compared with those with successful DPC. Low trypsin levels were independently associated with DPC failure in adjusted analysis (odds ratio, 3.7; 95% confidence interval, 1.2–11; P = 0.02).

Conclusions

Low serum trypsin levels independently predict DPC failure during ERCP in patients with symptomatic obstructive CP.
Fecal Occult Blood Tests
Authors: Danesh Valerie , Gisi Brittany , Narayan Maitreyi , Yoder Linda , Zad Omid
Published: June 2019

Purpose/Objectives

The purpose of this program was to deimplement the use of fecal occult blood tests (FOBTs) for hospitalized patients.

Description of the Project/Program

We used a multipronged multidisciplinary approach to deimplement the use of FOBT, including physician-nurse collaborations, data-based poster displays, and a review of test utilization and patient cost throughout all facilities.

Outcome

Despite a downward trend in FOBT orders for hospitalized patients over 3 years, the inappropriate use of FOBT remains a cause of unnecessary delays of diagnostic workups and patient care and excess costs ranging from US $22 000 to $41 000 annually for each hospital.

Conclusion

Clinical nurse specialists can question the empirical origin and patient outcomes associated with clinical practice and are positioned to assess and champion deimplementation processes.
Mycoplasma genitalium Coinfection in Women With Chlamydia trachomatis Infection
Authors: Harrison Sally A. , Olson Kristin M. , Ratliff Amy E. , Xiao Li , Van Der Pol Barbara , Waites Ken B. , Geisler William M.
Published: June 2019

We evaluated the prevalence of Mycoplasma genitalium coinfection in 302 chlamydia-infected women seen at a sexually transmitted disease clinic in Birmingham, AL. M genitalium coinfection was detected in 22 (7.3%). No participant characteristics predicted coinfection. Among coinfected women, M genitalium was detected again in 6 (28.6%) of 21 women returning for a 3-month follow-up visit after azithromycin treatment.
Penile Reinnervation Surgery
Authors: Shauly Orr , Gould Daniel J. , Patel Ketan M.
Published: June 2019

Background

Modern approaches to erectile dysfunction (ED) often entail the use of multimodal medical therapy and surgery; however, with recent advances in microsurgery, new options may exist for patients suffering from ED. This comprehensive review of the literature serves to reevaluate anatomical and physiological principles that mediate erection to improve understanding for reconstructive surgeons hoping to offer new interventions.

Methods

A search strategy for this review was agreed upon by all authors. Articles were divided into 2 categories — primary and secondary. Primary articles were defined as those in which the anatomy of the pelvis and/or perineum was the primary focus of the article, whereas secondary did not directly focus on anatomic considerations. Select historical texts and textbook chapters were also included to provide well established and critical anatomical evidence for this review.

Results

Several approaches may be used to restore nerve function to treat neurogenic and vasculogenic ED. Somatic sensory loss can be treated by either direct neurorrhaphy or neuroplasty in the location of disruption. Microvascular techniques also exist to improve flow or to repair small vessels injured in the pelvis. Classical approaches to impotence include vein stripping to reduce venous outflow or direct vascularization to improve inflow.

Conclusions

Postradical prostatectomy ED has been demonstrated to improve with microsurgical interventions. In the coming years, innovation will continue and collaboration between plastic surgeons and urologists will allow us to tackle this common and difficult problem.
Keratinocyte Cytotoxicity of Peracetic Acid Used as Sterilizing Agent for Implant Scaffolds
Authors: Soto Artur Ferronato , Arthur Rodrigo Alex , Kapczinski Myriam Pereira , Lamers Marcelo Lazzaron , Mengatto Cristiane Machado
Published: June 2019

Peracetic acid (PAA) has been used to sterilize biomaterial scaffolds and allografts before their implantation. Although the antimicrobial effectiveness of PAA is widely known, there are no studies investigating its cytotoxicity on keratinocytes. This study aimed to investigate the cytotoxicity of PAA concentrations on keratinocytes by growing HaCaT cells in culture medium. Different concentrations of PAA (control-untreated, 0.01, 0.1, 1, 10, 100, 200, 400, 800, 1200, 1600, and 2000 ppm) were added to the culture wells and allowed to be in direct contact with cells for up to 24 hours. Cytotoxicity was quantitatively and qualitatively determined by cell viability assay and analysis of morphological changes. Statistical analysis was performed with 1-way analysis of variance and Tukey test at 5% significance. Cells treated with 0.01 and 0.1 ppm followed the same morphological pattern of untreated cells, whereas cells treated with 1.0 ppm presented about 20% of floating cells and dark cytoplasmic granules. More than 50% of the cells treated with 10 and 100 ppm were destroyed, whereas the attached ones showed unclear and interrupted cell membranes. Concentrations of 1 ppm or greater had less than 64.4% of viable cells compared with the control group. This study concluded that exposure of keratinocytes to concentrations of 1 ppm or greater of PAA resulted in strong cytotoxic effects.
New Perspectives in Surgical Marking Since the Advent of Infrared Laser Angiography
Authors: Hammond Jacob B. , Bryant Lyndsey A. , Casey William J. , Rebecca Alanna M.
Published: June 2019

Introduction

This study investigates the utility of common surgical dyes under direct visualization and infrared laser angiography.

Methods

Pigments affecting light within the visual (λ = 400–700 nm) and infrared (λ = 700–1000 nm) spectra were placed on subjects spanning the Fitzpatrick scale. Photometric properties of these pigments were assessed under direct visualization and infrared laser angiography.

Results

Among patients of various Fitzpatrick classifications, black ink pigment and pigment within the violet spectrum (λ = 380–450 nm) were most distinguishable under direct visualization. Colored inks, gentian violet and methylene blue dyes, were not visualized under infrared laser angiography. Black permanent ink appeared under both direct visualization and infrared laser angiography. Indocyanine green suspended in ethyl alcohol and applied to skin as a marking pen appeared clear under direct visualization and was detectable under infrared laser angiography.

Conclusions

Black permanent marking ink allows visualization of surgical markings under infrared laser angiography, whereas gentian violet and methylene blue did not interfere with infrared visualization. Indocyanine green suspended in ethyl alcohol is a contemporary marking pen that may be used to outline anatomical surface landmarks under infrared laser angiography.
Topical Leptospermum Honey in the Management of Aplasia Cutis Congenita in Neonates
Authors: Boyar Vita
Published: June 2019

BACKGROUND:

Aplasia cutis congenita (ACC) is an uncommon, heterogeneous group of disorders characterized by focal or widespread absence of skin from certain parts of the body. Complications range from 20% to 50%; they are potentially life-threatening. There is no consensus on best treatment of ACC. We report on successful closure of aplasia cutis lesions using topical active Leptospermum honey (ALH).

CASES:

This article describes a case of a full-term neonate with a large ACC lesion. A conservative approach was taken in the care of this lesion, in accordance with appropriate wound care principles and the care of this medically fragile neonate. This included applying topical ALH twice a day and covering defects with a secure dressing. All lesions progressed to complete closure. Time to closure was either similar or shorter than published data.

CONCLUSIONS:

Our experience with these cases suggests that topical ALH may be an effective natural treatment option for neonates with ACC. This conservative management led to wound closure without topical or systemic antibiotics or prolonged hospital stay.
The impact of worldwide, national and sub-national severity distributions in Burden of Disease studies: a case study of individual cancer types in Scotland
Authors: Wyper Grant MA , Grant Ian , Fletcher Eilidh , McCartney Gerry , Stockton Diane L
Published: June 2019

Aim

The main aim of this study was to consider the extent to which the use of worldwide severity distributions in Burden of Disease studies are influencing cross-country comparisons, by comparing Global Burden of Disease distributions with nationally derived severity distributions in Scotland for cancer types.

Methods

We obtained individual records from the Scottish Cancer Registry for 21 cancer types and linked these to registered deaths. We estimated prevalent cancer cases for 2016 and assigned each case to sequelae using Global Burden of Disease (GBD) 2016 study definitions. We compared the impact of using severity distributions based on GBD 2016, a Scotland-wide distribution, and a distribution specific to deprivation strata in Scotland, on the weighted-average disability weights for each cancer type in Scotland.

Results

The relative difference in point estimates of weighted-average disability weights based on GBD 2016 worldwide severity distributions compared with Scottish national severity distributions resulted in overestimates in the majority of cancers (17 out of 21 cancer types). The largest overestimates were for gallbladder and biliary tract cancer (70.8%), oesophageal cancer (31.6%) and pancreatic cancer (31.2%). Furthermore, the use of weighted-average disability weights based on Scottish national severity distributions rather than sub-national Scottish severity distributions stratified by deprivation quintile overestimated weighted-average disability weights in the least deprived areas (16 out of 18 cancer types), and underestimated in the most deprived areas (16 out of 18 cancer types).

Conclusion

Our findings illustrate a bias in point estimates of weighted-average disability weights created using worldwide severity distributions. This bias would have led to the misrepresentation of non-fatal estimates of the burden of individual cancers, and underestimated the scale of socioeconomic inequality in this non-fatal burden. This highlights the importance of not interpreting non-fatal estimates of burden of disease too precisely, especially for sub-national estimates and those comparing populations when relying on data inputs from other countries. It is essential to ensure that any estimates are based upon the best available country-specific data at the lowest granularity.
A murine aging cell atlas reveals cell identity and tissue-specific trajectories of aging
Authors: Kimmel Jacob C. , Penland Lolita , Rubinstein Nimrod D. , Hendrickson David G. , Kelley David R. , Rosenthal Adam Z.
Published: June 2019

Background

Aging is a pleiotropic process affecting many aspects of organismal and cellular physiology. Mammalian organisms are composed of a constellation of distinct cell type and state identities residing within different tissue environments. Due to technological limitations, the study of aging has traditionally focused on changes within individual cell types, or the aggregate changes across cell types within a tissue. The influence of cell identity and tissue environment on the trajectory of aging therefore remains unclear.

Results

Here, we perform single cell RNA-seq on >50,000 individual cells across three tissues in young and aged mice. These molecular profiles allow for comparison of aging phenotypes across cell types and tissue environments. We find transcriptional features of aging common across many cell types, as well as features of aging unique to each type. Leveraging matrix factorization and optimal transport methods, we compute a trajectory and magnitude of aging for each cell type. We find that cell type exerts a larger influence on these measures than tissue environment.

Conclusion

In this study, we use single cell RNA-seq to dissect the influence of cell identity and tissue environment on the aging process. Single cell analysis reveals that cell identities age in unique ways, with some common features of aging shared across identities. We find that both cell identities and tissue environments exert influence on the trajectory and magnitude of aging, with cell identity influence predominating. These results suggest that aging manifests with unique directionality and magnitude across the diverse cell identities in mammals.
All-or-none visual categorization in the human brain
Authors: Retter Talia L. , Jiang Fang , Webster Michael A. , Rossion Bruno
Published: June 2019

Whether visual categorization, i.e., specific responses to a certain class of visual events across a wide range of exemplars, is graded or all-or-none in the human brain is largely unknown. We address this issue with an original frequency-sweep paradigm probing the evolution of responses between the minimum and optimal presentation times required to elicit both neural and behavioral face categorization responses. In a first experiment, widely variable natural images of nonface objects are progressively swept from 120 to 3 Hz (8.33 to 333 ms duration) in rapid serial visual presentation sequences; variable face exemplars appear every 1 s, enabling an implicit frequency-tagged face-categorization electroencephalographic (EEG) response at 1 Hz. In a second experiment, faces appear non-periodically throughout such sequences at fixed presentation rates, while participants explicitly categorize faces. Face-categorization activity emerges with stimulus durations as brief as 17 ms for both neural and behavioral measures (17 – 83 ms across individual participants neurally; 33 ms at the group level). The face-categorization response amplitude increases until 83 ms stimulus duration (12 Hz), implying graded categorization responses. However, a strong correlation with behavioral accuracy suggests instead that dilution from missed categorizations, rather than a decreased response to each face stimulus, may be responsible. This is supported in the second experiment by the absence of neural responses to behaviorally uncategorized faces, and equivalent amplitudes of isolated neural responses to only behaviorally categorized faces across presentation rates, consistent with the otherwise stable spatio-temporal signatures of face-categorization responses in both experiments. Overall, these observations provide original evidence that visual categorization of faces, while being widely variable across human observers, occurs in an all-or-none fashion in the human brain.
Lactation curve model with explicit representation of perturbations as a phenotyping tool for dairy livestock precision farming
Authors: Ahmed Ben Abdelkrim , Laurence Puillet , Pierre Gomes , Olivier Martin
Published: June 2019

Background

Understanding the effects of environment on livestock provides valuable information on how farm animals express their production potential, and on their welfare. Ruminants often face perturbations that affect their performance. Evaluating the effect of these perturbations on animal performance could provide metrics to quantify how animals cope with their environment and therefore, better manage them. In dairy systems, milk production records can be used to evaluate perturbations because (1) they are easily accessible, (2) the overall dynamics throughout the lactation process have been widely described, and (3) perturbations often occur and cause milk loss. In this study, a lactation curve model with explicit representation of perturbations was developed.

Methods

The perturbed lactation model is made of two components. The first one describes a theoretical unperturbed lactation curve (unperturbed lactation model), and the second describes deviations from the unperturbed lactation model. The model was fitted on 319 complete lactation data from 181 individual dairy goats allowing for the characterization of individual perturbations in terms of their starting date, intensity, and shape.

Results

The fitting procedure detected a total of 2,354 perturbations with an average of 7.40 perturbations per lactation. Loss of production due to perturbations varied between 2% and 19%. Results show that the number of perturbations is not the major factor explaining the loss in milk yield over the lactation, suggesting that there are different types of animal response to challenging factors.

Conclusions

By incorporating explicit representation of perturbations, the model allowed the characterization of potential milk production, deviations induced by perturbations (loss of milk), and thereby comparison between animals. These indicators are likely to be useful to move from raw data to decision support tools in dairy production.
Cold storage reveals distinct metabolic perturbations in processing and non-processing cultivars of potato
Authors: Datir Sagar S , Yousf Saleem , Sharma Shilpy , Kochle Mohit , Ravikumar Ameeta , Chugh Jeetender
Published: June 2019

Cold-induced sweetening (CIS) causes a great loss to the potato (Solanum tuberosumL.) processing industry wherein selection of potato genotypes using biochemical information through marker-trait associations has found to be advantageous. In the present study, we have performed nuclear magnetic resonance (NMR) spectroscopy-based metabolite profiling on tubers from five potato cultivars (Atlantic, Frito Lay-1533, Kufri Jyoti, Kufri Pukhraj, and PU1) differing in their CIS ability and processing characteristics at harvest and after one month of cold storage at 4°C. A total of 39 water-soluble metabolites were detected using1H NMR. Multivariate statistical analysis indicated significant differences in metabolite profiles between processing and non-processing potato cultivars. Further analysis revealed distinct metabolite perturbations as induced by cold storage in both types of cultivars wherein significantly affected metabolites were categorized mainly as sugars, sugar alcohols, amino acids, and organic acids. Significant metabolic perturbations were used to carry out metabolic pathway analysis that in turn tracked 130 genes encoding enzymes (involved directly and/or indirectly) involved in CIS pathway using potato genome sequence survey data. Based on the metabolite perturbations, the possible relevant metabolite biomarkers, significantly affected metabolic pathways, and key candidate genes responsible for the observed metabolite variation were identified. Overall, studies provided new insights in further manipulation of specific metabolites playing a crucial role in determining the cold-induced ability and processing quality of potato cultivars for improved quality traits.

Highlight

Metabolomic profiling using 1D1H-NMR and bioinformatics analysis of potato cultivars for the identification of metabolites and genes controlling biochemical pathways in cold-stored potato tubers
Integration of vestibular and hindlimb inputs by vestibular nucleus neurons: Multisensory influences on postural control
Authors: Miller Derek M. , Balaban Carey D. , McCall Andrew A.
Published: June 2019

1.

We recently demonstrated in both decerebrate and conscious cat preparations that hindlimb somatosensory inputs converge with vestibular afferent input onto neurons in multiple CNS locations that participate in balance control. While it is known that head position and limb state modulate postural reflexes, presumably through both vestibulospinal and reticulospinal pathways, the combined influence of the two inputs on the activity of neurons in these brainstem regions is unknown. In the present study, we evaluated the responses of vestibular nucleus (VN) neurons to vestibular and hindlimb stimuli delivered separately and together in conscious cats. We hypothesized that VN neuronal firing during activation of vestibular and limb proprioceptive inputs would be well-fit by an additive model. Extracellular single-unit recordings were obtained from neurons in the caudal aspects of the VN. Sinusoidal whole-body rotation in the roll plane was used as the search stimulus. Units responding to the search stimulus were tested for their responses to 10° ramp-and-hold roll body rotation, 10° extension hindlimb movement, and both movements delivered simultaneously. Composite response histograms were fit by a model of low and high pass filtered limb and body position signals using least squares nonlinear regression. We found that VN neuronal activity during combined vestibular and hindlimb proprioceptive stimulation in the conscious cat is well-fit by a simple additive model for signals with similar temporal dynamics. The mean R2 value for goodness of fit across all units was 0.74 ± 0.17. It is likely that VN neurons that exhibit these integrative properties participate in adjusting vestibulospinal outflow in response to limb state.

New and Noteworthy

Vestibular nucleus neurons receive convergent information from hindlimb somatosensory inputs and vestibular inputs. In this study, extracellular single unit recordings of vestibular nucleus neurons during conditions of passively applied limb movement, passive whole-body rotations, and combined stimulation, were well fit by an additive model. The integration of hindlimb somatosensory inputs with vestibular inputs at the first stage of vestibular processing suggests vestibular nucleus neurons account for limb position in determining vestibulospinal responses to postural perturbations.
Linear modeling reveals a predominance ofcis- overtrans- regulatory effects in wild and domesticated barley
Authors: Haas Matthew , Himmelbach Axel , Mascher Martin
Published: June 2019

Barley, like other crops, has experienced a series of genetic changes that have impacted its architecture and growth habit to suit the needs of humans, termed the domestication syndrome. Domestication also resulted in a concomitant bottleneck that reduced sequence diversity in genes and regulatory regions. Little is known about regulatory changes resulting from domestication in barley. We used RNA-seq to examine allele-specific expression (ASE) in hybrids between wild and domesticated barley. Our results show that most genes have conserved regulation. In contrast to studies of allele specific expression in interspecific hybrids, we find almost a complete absence oftranseffects. We also find thatcisregulation is largely stable in response to short-term cold stress. Our study has practical implications for crop improvement using wild relatives. Genes regulated incisare more likely to be expressed in a new genetic background at the same level as in their native background.
Individual-subject functional localization increases univariate activation but not multivariate pattern discriminability in the ‘multiple-demand’ frontoparietal network
Authors: Shashidhara Sneha , Spronkers Floortje S. , Erez Yaara
Published: June 2019

The frontoparietal ‘multiple-demand’ (MD) control network plays a key role in goal-directed behavior. Recent developments of multivoxel pattern analysis (MVPA) for fMRI data allow for more fine-grained investigations into the functionality and properties of brain systems. In particular, MVPA in the MD network was used to gain better understanding of control processes such as attentional effects, adaptive coding, and representation of multiple task-relevant features, but overall low decoding levels have limited its use for this network. A common practice of applying MVPA is by investigating pattern discriminability within a region-of-interest (ROI) using a template mask, thus ensuring that the same brain areas are studied in all participants. This approach offers high sensitivity, but does not take into account differences between individuals in the spatial organization of brain regions. An alternative approach uses independent localizer data for each subject to select the most responsive voxels and define individual ROIs within the boundaries of a group template. Such an approach allows for a refined and targeted localization based on the unique pattern of activity of individual subjects while ensuring that functionally similar brain regions are studied for all subjects. In the current study we tested whether using individual ROIs leads to changes in decodability of task-related neural representations as well as univariate activity across the MD network compared to when using a group template. We used three localizer tasks to separately define subject-specific ROIs: spatial working memory, verbal working memory, and a Stroop task. We then systematically assessed univariate and multivariate results in a separate rule-based criterion task. All the localizer tasks robustly recruited the MD network and evoked highly reliable activity patterns in individual subjects. Consistent with previous studies, we found a clear benefit of the subject-specific ROIs for univariate results from the criterion task, with increased activity in the individual ROIs based on the localizers’ data, compared to the activity observed when using the group template. In contrast, there was no benefit of the subject-specific ROIs for the multivariate results in the form of increased discriminability, as well as no cost of reduced discriminability. Both univariate and multivariate results were similar in the subject-specific ROIs defined by each of the three localizers. Our results provide important empirical evidence for researchers in the field of cognitive control for the use of individual ROIs in the frontoparietal network for both univariate and multivariate analysis of fMRI data, and serve as another step towards standardization and increased comparability across studies.
Predicting transfer RNA gene activity from sequence and genome context
Authors: Thornlow Bryan , Armstrong Joel , Holmes Andrew , Corbett-Detig Russell , Lowe Todd
Published: June 2019

Transfer RNA (tRNA) genes are among the most highly transcribed genes in the genome due to their central role in protein synthesis. However, there is evidence for a broad range of gene expression across tRNA loci. This complexity, combined with difficulty in measuring transcript abundance and high sequence identity across transcripts, has severely limited our collective understanding of tRNA gene expression regulation and evolution. We establish sequence-based correlates to tRNA gene expression and develop a tRNA gene classification method that does not require, but benefits from comparative genomic information, and achieves accuracy comparable to molecular assays. We observe that guanine+cytosine (G+C) content and CpG density surrounding tRNA loci is exceptionally well correlated with tRNA gene activity, supporting a prominent regulatory role of the local genomic context in combination with internal sequence features. We use our tRNA gene activity predictions in conjunction with a comprehensive tRNA gene ortholog set spanning 29 placental mammals to infer the frequency of changes to tRNA gene expression among orthologs. Our method adds an important new dimension to tRNA annotation and will help focus the study of natural tRNA variants. Its simplicity and robustness enables facile application to other clades and timescales, as well as exploration of functional diversification of tRNAs and other large gene families.
Machine-Learning Prediction of Comorbid Substance Use Disorders in ADHD Youth Using Swedish Registry Data
Authors: Zhang-James Yanli , Chen Qi , Kuja-Halkola Ralf , Lichtenstein Paul , Larsson Henrik , Faraone Stephen V
Published: June 2019

Background

Children with attention-deficit/hyperactivity disorder (ADHD) have a high risk for substance use disorders (SUDs). Early identification of at-risk youth would help allocate scarce resources for prevention programs.

Methods

Psychiatric and somatic diagnoses, family history of these disorders, measures of socioeconomic distress and information about birth complications were obtained from the national registers in Sweden for 19,787 children with ADHD born between 1989-1993. We trained 1) cross-sectional machine learning models using data available by age 17 to predict SUD diagnosis between ages 18-19; and 2) a longitudinal model to predict new diagnoses at each age.

Results

The area under the receiver operating characteristic curve (AUC) was 0.73 and 0.71 for the random forest and multilayer perceptron cross-sectional models. A prior diagnosis of SUD was the most important predictor, accounting for 25% of correct predictions. However, after excluding this predictor, our model still significantly predicted the first-time diagnosis of SUD during age 18-19 with an AUC of 0.67. The average of the AUCs from longitudinal models predicting new diagnoses one, two, five and ten years in the future was 0.63.

Conclusions

Significant predictions of at-risk co-morbid SUDs in individuals with ADHD can be achieved using population registry data, even many years prior to the first diagnosis. Longitudinal models can potentially monitor their risks over time. More work is needed to create prediction models based on electronic health records or linked population-registers that are sufficiently accurate for use in the clinic.
Kindlin Assists Talin to Promote Integrin Activation
Authors: Haydari Z. , Shams H. , Jahed Z. , Mofrad M.R.K.
Published: June 2019

Integrin αIIbβ3 is a predominant type of integrin abundantly expressed on the surface of platelets and its activation regulates the process of thrombosis. Talin and kindlin are cytoplasmic proteins that bind to integrin and modulate its affinity for extracellular ligands. While the molecular details of talin-mediated integrin activation are known, the mechanism of kindlin involvement in this process remains elusive. Here, we demonstrate that the interplay between talin and kindlin promotes integrin activation. Our all-atomic molecular dynamics simulations on complete transmembrane and cytoplasmic domains of integrin αIIbβ3, talin1 F2/F3 subdomains, and kindlin2 FERM domain in an explicit lipid-water environment over microsecond timescale, unraveled the role of kindlin as an enhancer of the talin interaction with the membrane proximal region of β–integrin. The cooperation of kindlin with talin results in a complete disruption of salt bridges between R995 on αIIb and D723/E726 on β3. Furthermore, kindlin modifies the molecular mechanisms of inside-out activation by decreasing the crossing angle between transmembrane helices of integrin αIIb-β3, which eventually results in parallelization of integrin dimer. In addition, our control simulation featuring integrin in complex with kindlin reveals that kindlin binding is not sufficient for unclasping the inner membrane and outer membrane interactions of integrin dimer, thus ruling out the possibility of solitary action of kindlin in integrin activation.

Statement of Significance

Using the newly solved crystal structure of kindlin, we investigated, for the first time, the molecular mechanism of kindlin-mediated integrin activation through simultaneous binding of talin and kindlin. We demonstrate in atomist details how kindlin cooperates with talin to promote the activation of integrin αIIb-β3.
The effect of insect cyanoglucosides on predation by domestic chicks
Authors: Cardoso Márcio Zikán
Published: June 2019

Cyanogenic insects release cyanide and other byproducts that are thought to make them unpalatable to would be predators. In fact, aposematic Heliconius butterflies and Zygaena moths are rejected by vertebrate predators. Nevertheless, there have been few studies testing the effect of cyanoglucosides on vertebrate predation. Here I report tests undertook with captive domestic chicks in order to evaluate the effect of two chemically diverse cyanoglucosides, linamarin and prunasin. In insects as well as plants, cyanoglucosides are stored in vacuoles and are enzymatically broken down when the tissue is disrupted as in the case of a predator attack. Linamarin is an aliphatic that releases cyanide and acetone upon breakdown, while prunasin is an aromatic cyanoglucoside that releases cyanide and benzaldehyde. Using concentrations that mimicked the average concentration of a Heliconius butterfly, supplemented by test with higher concentrations, I ran a series of trials with naïve chicks by offering prey laced with chemicals. I categorized prey acceptance and compared the behavior of the predators towards test and control larvae. Prey coated with cyanide and benzaldehyde were significantly rejected by the birds, while acetone did not elicit avoidance behavior. Intact cyanoglucosides apparently were not detected by the predators, presumably because of fast ingestion time or lack of enzymes to breakdown cyanoglucosides. The rejection of cyanide laced prey confirm the protective nature of cyanoglucosides against a vertebrate predator. Additionally, the rejection of the pungent but not toxic benzaldehyde suggests that some species that store aromatic cyanoglucosides could be detected via smell as well by taste. These results provide support for cyanoglucosides as defensive chemicals of aposematic lepidopterans and related arthropods.