bluuebunny/crossref_metadata_2025 huggingface dataset:
High strains near femoral insertion site of the superficial medial collateral ligament of the Knee can explain the clinical failure pattern
Authors: Luyckx Thomas , Verstraete Matthias , De Roo Karel , Van Der Straeten Catherine , Victor Jan
Published: March 2016

The three dimensional (3D) deformation of the superficial medial collateral ligament (sMCL) of the knee might play an important role in the understanding of the biomechanics of sMCL lesions. Therefore, the strain and deformation pattern of the sMCL during the range of motion were recorded in five cadaveric knees with digital image correlation. During knee flexion, the sMCL was found to deform in the three planes. In the sagittal plane, a rotation of the proximal part of the sMCL relative to the distal part occurred with the center of this rotation being the proximal tibial insertion site of the sMCL. This deformation generated high strains near the femoral insertion site of the sMCL. These strains were significantly higher than in the other parts and were maximal at 90° with on average +3.7% of strain and can explain why most lesions in clinical practice are seen in this proximal region. The deformation also has important implications for sMCL reconstruction techniques. Only a perfect anatomic restoration of the insertion sites of the sMCL on both the proximal and distal tibial insertion sites will be able to reproduce the isometry of the sMCL and thus provide the adequate stability throughout the range of motion. The fact that knee motion between 15° and 90° caused minimal strain in the sMCL might suggest that early passive range of motion in physical therapy postoperatively should have little risk of stretching a graft out in the case of an anatomical reconstruction. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2016–2024, 2016.
Articular cartilage calcification of the humeral head is highly prevalent and associated with osteoarthritis in the general population
Authors: Hawellek Thelonius , Hubert Jan , Hischke Sandra , Vettorazzi Eik , Wegscheider Karl , Bertrand Jessica , Pap Thomas , Krause Matthias , Püschel Klaus , Rüther Wolfgang , Niemeier Andreas
Published: March 2016

Articular cartilage calcification is considered a pathological albeit incompletely understood process which is known to be associated with osteoarthritis of the knee and hip. The goal of this study was to determine the prevalence of articular cartilage calcification of the shoulder as a non‐weight‐bearing joint and to analyze the interrelationship of calcification with age and histological severity of shoulder osteoarthritis in the general population. In a cross‐sectional study of 180 humeral heads from 90 donors (n = 49 male, n = 41 female; mean age 62.7 years [20–93]), cartilage calcification of the humeral head was quantified by digital contact radiography (DCR). Histological OA grade (OARSI) was determined and structural equation modeling (SEM) was used to analyze the interrelationship of cartilage calcification, OARSI and age. The prevalence of articular cartilage calcification was 98.9% (95%CI: [93.96%, 99.97%]) and was independent of gender (p = 0.55). Cartilage calcification of one shoulder correlated significantly with that of the contralateral side (r = 0.61, 95%CI: [0.46, 0.73], p < 0.001). SEM demonstrated significant associations between histological OA grade and cartilage calcification (r = 0.55, p = 0.039), between histological OA grade and age (β = 0.59, p < 0.001) but not between age and cartilage calcification (β = 0.24, p = 0.116). In conclusion, the prevalence of shoulder cartilage calcification in the general population is higher than anticipated. The high prevalence, its concomitant bilateral manifestation and the association between the amount of cartilage calcification and OA severity, but not age, suggest that cartilage calcification is a systemically driven process with early onset in life and may be a causative factor in the pathogenesis of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1984–1990, 2016.
rAAV‐mediated combined gene transfer and overexpression of TGF‐β and SOX9 remodels human osteoarthritic articular cartilage
Authors: Tao Ke , Rey‐Rico Ana , Frisch Janina , Venkatesan Jagadeesh K. , Schmitt Gertrud , Madry Henning , Lin Jianhao , Cucchiarini Magali
Published: March 2016

Direct administration of therapeutic candidate gene sequences using the safe and effective recombinant adeno‐associated virus (rAAV) vectors is a promising strategy to stimulate the biologic activities of articular chondrocytes as an adapted tool to treat human osteoarthritic (OA) cartilage. In the present study, we developed a combined gene transfer approach based on the co‐delivery of the pleiotropic transformation growth factor beta (TGF‐β) with the specific transcription factor SOX9 via rAAV to human normal and OA chondrocytes in vitro and cartilage explants in situ in light of the mitogenic and pro‐anabolic properties of these factors. Effective, durable co‐overexpression of TGF‐β and SOX9 significantly enhanced the levels of cell proliferation both in human normal and OA chondrocytes and cartilage explants over an extended period of time (21 days), while stimulating the biosynthesis of key matrix components (proteoglycans, type‐II collagen) compared with control conditions (reporter lacZ gene transfer, absence of vector treatment). Of further note, expression of hypertrophic type‐X collagen significantly decreased following co‐treatment by the candidate vectors. The present findings show the value of combining the transfer and expression of potent candidate factors in human OA cartilage as a means to re‐establish essential features of normal cartilage and counteract the pathological shift of homeostasis. These observations support the concept of developing dual therapeutic rAAV gene transfer strategies as future, adapted tools for the direct treatment of human OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2181–2190, 2016.
Phosphorus forms in forest soil colloids as revealed by liquid‐state 31P‐NMR
Authors: Missong Anna , Bol Roland , Willbold Sabine , Siemens Jan , Klumpp Erwin
Published: March 2016

Nanoparticles and colloids affect the storage and hence the availability of P in forest ecosystems. We investigated the fine colloids present in forest soils and their association with inorganic and organic P. To differentiate between the different P forms, we performed liquid‐state 31P‐nucelar magnetic resonance (31P‐NMR) measurements on forest bulk soil extracts, on colloid extracts and on the electrolyte phase of their soil suspensions. The 31P‐NMR spectra indicated that soil nanoparticles and colloids were more enriched with organic than with inorganic P forms compared to the electrolyte phase. The P concentration was enriched in the colloidal fraction in comparison to the bulk soil and the phosphate diesters were more dominant in the colloidal fraction when compared to the bulk soil. The colloidal P‐diester to P‐monoester ratios were 2 to 3 times higher in the colloidal fraction than in the bulk soil. In contrast, relatively large percentages of inorganic P were found in the electrolyte phase. Supplementary (not shown) Data are available at the JuSER Server (juser.fz‐juelich.de, reference number: FZJ‐2016‐01739) https://juser.fz‐juelich.de/record/283057.
The effect of supplementation with three commercial inactive dry yeasts on the colour, phenolic compounds, polysaccharides and astringency of a model wine solution and red wine
Authors: González‐Royo Elena , Esteruelas Mireia , Kontoudakis Nikolaos , Fort Francesca , Canals Joan Miquel , Zamora Fernando
Published: March 2016

BACKGROUND

Nowadays supplementing red wines with commercial inactive dry yeasts is a widespread practice in winemaking because it leads to better balanced wines through increased mouthfeel and smooth astringency. The aim of this article is to study, in a red wine and in a model wine solution, how supplementation with three commercial inactive dry yeasts affects chemical composition and astringency. This will give us a better understanding of the action mechanism involved.

RESULTS

The results suggest that this action mechanism is related to two different phenomena. The first is that inactive yeasts release polysaccharides and oligosaccharides which can increase mouthfeel and inhibit interactions between salivary protein and tannins. The second is that they have a direct effect on the precipitation or absorption of proanthocyanidins, especially the larger polymers, which have been described as the most astringent.

CONCLUSION

It can be concluded that supplementation with inactive yeasts is indeed a useful tool for smoothing the astringency of red wines. © 2016 Society of Chemical Industry
Preparation and structural characterization of corn starch–aroma compound inclusion complexes
Authors: Zhang Shu , Zhou Yibin , Jin Shanshan , Meng Xin , Yang Liping , Wang Haisong
Published: March 2016

BACKGROUND

Six corn starch inclusion complexes were synthesized using small nonpolar or weak polar aroma compounds (heptanolide, carvone and menthone) and small polar aroma compounds (linalool, heptanol and menthol). The objectives of this study were to (a) investigate the ability of corn starch to form inclusion complexes with these aroma compounds and (b) characterize the structure of the corn starch inclusion complexes.

RESULTS

The resulting inclusion ratios were 75.6, 36.9, 43.8, 91.9, 67.2 and 54.7% for heptanolide, carvone, menthone, linalool, heptanol and menthol respectively. The inclusion complexes had laminated structures with a certain amount of holes or blocky constructions. Compared with gelatinized corn starch, the transition temperatures, peak temperatures and enthalpies of the inclusion complexes were significantly different. The major peak of CO at 1771 cm−1 and significant peak shifts revealed the formation of inclusion complexes. X‐ray diffractometry (XRD) analyses revealed that the crystallinity of corn starch–polar aroma compound inclusion complexes increased. Based on cross‐polarization magic angle spinning 13C nuclear magnetic resonance (CP‐MAS 13C NMR) results, novel peaks and chemical shifts were attributed to the presence of small aroma compounds, thereby confirming the formation of corn starch inclusion complexes.

CONCLUSION

Small nonpolar and polar aroma compounds can be complexed to corn starch. © 2016 Society of Chemical Industry
Screening of the anthocyanin profile and in vitro pancreatic lipase inhibition by anthocyanin‐containing extracts of fruits, vegetables, legumes and cereals
Authors: Fabroni Simona , Ballistreri Gabriele , Amenta Margherita , Romeo Flora V , Rapisarda Paolo
Published: March 2016

BACKGROUND

The phytotherapic treatment of overweight and/or moderate obesity is growing widely, thus there is a great interest towards the phenolic compounds of fruits and vegetables which may inhibit pancreatic lipase enzyme. In this study, we report the chemical composition and in vitro pancreatic lipase inhibitory activity of 13 freeze‐dried anthocyanin‐containing extracts of different Mediterranean plants: fruits (blood orange, pomegranate, blackberry, mulberry and sumac), citrus by‐products (blood orange peel), citrus vegetative tissues (young lemon shoots); vegetables (red cabbage and violet cauliflower), legume seeds (black bean), cereals (black rice), and cereal processing by‐products (black rice hull). Total phenols and anthocyanins were determined. Individual anthocyanins were identified by UHPLC‐PDA‐ESI/MSn.

RESULTS

Results revealed a wide variation in the distribution of anthocyanin compounds. Blood orange and pomegranate juice extracts had the highest total anthocyanin content and exhibited the strongest inhibition of pancreatic lipase in vitro.

CONCLUSION

Inhibitory activity was positively correlated with anthocyanin content. In appropriate formulations, anthocyanin‐containing extracts could find a use as anti‐obesity agents. © 2016 Society of Chemical Industry
Rheological properties and bread quality of frozen yeast‐dough with added wheat fiber
Authors: Adams Vivian , Ragaee Sanaa M , Abdel‐Aal El‐Sayed M
Published: March 2016

BACKGROUND

The rheological characteristics of frozen dough are of great importance in bread‐making quality. The effect of addition of commercial wheat aleurone and bran on rheological properties and final bread quality of frozen dough was studied. Wheat aleurone (A) and bran (B) containing 240 g kg−1 and 200 g kg−1 arabinoxylan (AX), respectively, were incorporated into refined wheat flour at 150 g kg−1 substitution level (composite A and B, respectively). Dough samples of composite A and B in addition to two reference dough samples, refined flour (ref A) and whole wheat flour (ref B) were stored at −18°C for 9 weeks.

RESULT

Frozen stored composite dough samples contained higher amounts of bound water, less freezable water and exhibited fewer modifications in gluten network during frozen storage based on data from differential scanning calorimetry and nuclear magnetic resonance spectroscopy. Bread made from composite frozen dough had higher loaf volume compared to ref A or ref B throughout the storage period.

CONCLUSION

The incorporation of wheat fiber into refined wheat flour produced dough with minimum alterations in its rheological properties during 9 weeks of frozen storage compared to refined and 100% wheat flour dough samples. © 2016 Society of Chemical Industry
Selection of Adequate Species for Degraded Areas by Oil‐Exploitation Industry as a Key Factor for Recovery Forest in the Ecuadorian Amazon
Authors: Villacís Jaime , Armas Cristina , Hang Susana , Casanoves Fernando
Published: March 2016

One of the requirements for the forest restoration of soils disturbed by the oil‐exploitation industry is that saplings be able to endure soil‐adverse conditions. In this study, saplings of 20 species susceptible to be used in reforestation programs were evaluated for their ability to grow on substrates derived from soils disturbed by petroleum extractions in the Ecuadorian Amazon. Seeds of each species were planted in germination trays. Once seedlings reached 5 cm in height they were transplanted to plastic bags with three treatment substrates: two derived from petroleum‐exploitation activity (soils from mud and drill cutting cells and from areas surrounding oil wells) and a control soil. Plant survival rate, stem height, and diameter were measured on a weekly basis until 14 weeks after transplantation, when we harvested the plants and also measured plant biomass and calculated the Dickson quality index for each species. Oil‐exploitation by‐product substrates impaired the performance of many saplings, with the substrate from mud and drill cutting cells being the one that most affected plant performance. Only saplings of five native species in the Amazon basin—Apeiba membranaceae, Cedrelinga cateniformis, Inga densiflora, Myroxylon balsamum, and Pouroma cecropiifolia—exhibited high or similar Dickson quality index values in all soil treatments and performed better than the rest. The use of these five species in remediation of soils disturbed by petroleum extraction in the Amazon basin could prove important because of their high potential to adapt to these disturbed sites. Copyright © 2016 John Wiley & Sons, Ltd.
Optical properties of dissolved organic matter (DOM): Effects of biological and photolytic degradation
Authors: Hansen Angela M. , Kraus Tamara E. C. , Pellerin Brian A. , Fleck Jacob A. , Downing Bryan D. , Bergamaschi Brian A.
Published: March 2016

Advances in spectroscopic techniques have led to an increase in the use of optical properties (absorbance and fluorescence) to assess dissolved organic matter (DOM) composition and infer sources and processing. However, little information is available to assess the impact of biological and photolytic processing on the optical properties of original DOM source materials. Over a 3.5 month laboratory study, we measured changes in commonly used optical properties and indices in DOM leached from peat soil, plants, and algae following biological and photochemical degradation to determine whether they provide unique signatures that can be linked to original DOM source. Changes in individual optical parameters varied by source material and process, with biodegradation and photodegradation often causing values to shift in opposite directions. Although values for different source materials frequently overlapped, multivariate statistical analyses showed that unique optical signatures could be linked to original DOM source material, with 17 optical properties determined by discriminant analysis to be significant (p < 0.05) in distinguishing between DOM source and environmental processing. These results demonstrate that inferring source material from optical properties is possible when parameters are evaluated in combination even after extensive biological and photochemical alteration.
Investigation of subsequent deposit growth on pre‐existing lubricant deposits: a substitutional growth model
Authors: Kouame Sylvain‐Didier B. , Vander Wal Randy L. , Perez Joseph
Published: March 2016

The Penn State Micro‐Oxidation (PSMO) test was used in an inverse manner to pre‐cover metallic pan surfaces with polymeric, transitioning and carbonaceous films. These pre‐coated pans were then used as the initial test specimen/surface upon which fresh lubricant samples were aged. The effects of pre‐deposits of varied ages were gauged against the baseline of a virgin metallic surface to decouple the lubricant‐deposit system towards resolving their effect upon further deposit growth. From such data, a uniform deposition model describing deposit formation and aging was developed. Chemical characterisation of PSMO deposits by Fourier transform infrared‐attenuated total reflectance and energy‐dispersive X‐ray spectroscope analyses provide additional supporting evidence of changes in chemical bonding (alkyl C–H and carbonyl C=O bond stretching vibrations) and composition (C‐ and O‐atom content) as the deposits undergo deoxygenation and dehydrogenation reactions. Across different aged oils and films, the substitution tests show a declining activity towards mass deposition with film age, interpreted as decline in reactivity. Copyright © 2016 John Wiley & Sons, Ltd.
An early look at the Organ Procurement and Transplantation Network explant pathology form data
Authors: Harper Ann M. , Edwards Erick , Washburn W. Kenneth , Heimbach Julie
Published: March 2016

In April 2012, the Organ Procurement and Transplantation Network (OPTN) implemented an online explant pathology form for recipients of liver transplantation who received additional wait‐list priority for their diagnosis of hepatocellular carcinoma (HCC). The purpose of the form was to standardize the data being reported to the OPTN, which had been required since 2002 but were submitted to the OPTN in a variety of formats via facsimile. From April 2012 to December 2014, over 4500 explant forms were submitted, allowing for detailed analysis of the characteristics of the explanted livers. Data from the explant pathology forms were used to assess agreement with pretransplant imaging. Explant data were also used to assess the risk of recurrence. Of those with T2 priority, 55.7% were found to be stage T2 on explant. Extrahepatic spread (odds ratio [OR] = 6.8; P < 0.01), poor tumor differentiation (OR = 2.8; P < 0.01), microvascular invasion (OR = 2.6; P < 0.01), macrovascular invasion (OR = 3.2; P < 0.01), and whether the Milan stage based on the number and size of tumors on the explant form was T4 (OR = 2.4; P < 0.01) were the strongest predictors of recurrence. In conclusion, this analysis confirms earlier findings that showed an incomplete agreement between pretransplant imaging and posttransplant pathology in terms of HCC staging, though the number of patients with both no pretransplant treatment and no tumor in the explant was reduced from 20% to <1%. In addition, several factors were identified (eg, tumor burden, age, sex, region, ablative therapy, alpha‐fetoprotein, Milan stage, vascular invasion, satellite lesions, etc.) that were predictive of HCC recurrence, allowing for more targeted surveillance of high‐risk recipients. Continued evaluation of these data will help shape future guidelines or policy recommendations. Liver Transplantation 22 757–764 2016 AASLD.
On the Riemannian curvature tensor of a real hypersurface in a complex projective space
Authors: Pérez Juan de Dios
Published: March 2016

We consider real hypersurfaces M in complex projective space equipped with both the Levi–Civita and generalized Tanaka–Webster connections and classify them when the covariant derivatives associated with both connections, either in the direction of the structure vector field or any direction of the maximal holomorphic distribution, coincide when applying to the Riemannian curvature tensor of the real hypersurface.
Novel Nonsense Calmodulin‐Binding Transcription Activator 1 Mutation Presenting as a Tremor‐Predominant Phenotype
Authors: Agarwal Shashank , Gilbert Rebecca , Lau Heather A.
Published: March 2016

View Supplementary Video 1

A 25‐year‐old right‐handed male presented with head and bilateral arm and leg tremor. His symptoms began at age 10 years with action tremor of both hands and progressed in severity with time. He had difficulty with social interactions but did not have intellectual disabilities. His past medical history was significant for obsessive compulsive disorder and anxiety, asthma, gastroesophageal reflux disease, and scoliosis; and his family history was significant for tremor in his father and paternal grandfather. Genetic testing was performed and identified a deleterious sequence variation in exon 19 of the calmodulin‐binding transcription activator 1 (CAMTA1) gene. The presence of this sequence variation was confirmed in the patient and in his affected father. The case is novel because of tremor predominance and because the mutation is a sequence variation rather than a deletion or duplication.
Multifocal Motor Neuropathy Presenting as Pseudodystonia
Authors: Garg Nidhi , Heard Robert N.S. , Kiers Lynette , Gerraty Richard , Yiannikas Con
Published: March 2016

View Supplementary Video 1

View Supplementary Video 2

Multifocal motor neuropathy (MMN) is an immune‐mediated neuropathy. Wasting and weakness typically dominate the clinical presentation. We describe four cases presenting with prominent cramping resembling a primary movement disorder. All cases had features of focal motor conduction block on neurophysiological studies. The involuntary movements resolved in all four patients following treatment with intravenous immunoglobulin. The presented cases highlight an unusual presentation of MMN and emphasize that peripheral nerve pathology can present with movement disorders mimicking central nervous system disease. Furthermore, the movement disorder appears particularly sensitive to standard therapy.
The Pathophysiology of Fatigue in Parkinson's Disease and its Pragmatic Management
Authors: Kostić Vladimir S. , Tomić Aleksandra , Ječmenica‐Lukić Milica
Published: March 2016

Background

Fatigue is 1 of the most common and most disabling symptoms among patients with Parkinson's disease (PD) and has a significant impact on their quality of life. Yet the pathophysiology of fatigue is poorly understood, while its treatment is “limited to an empirical approach based on plausible hypotheses.”

Methods

PubMed was searched for articles with the key words “Parkinson's disease” or “parkinsonism” and “fatigue” that were published by or before August 2015. The analysis of articles, which were selected on subjective grounds, was used to review the current knowledge of pathophysiology and treatment outcomes in studies focused on fatigue in PD.

Conclusions

Clinical and experimental findings support the view that fatigue is a primary manifestation of PD. The main hypothesized pathophysiological mechanisms include abnormal basal ganglia (BG)‐cortical mechanisms, particularly frontal loops, and an imbalance between neurotransmitters (e.g., dopamine [DA] and serotonin), along with an altered hypothalamus‐pituitary‐adrenal axis, neuroinflammation, cardiac sympathetic denervation, etc. Pragmatic treatment of fatigue in patients with PD includes various pharmacological (dopaminergic and psychostimulant drugs, antidepressants) and nonpharmacological strategies, although current knowledge suffers from insufficient evidence to support the use of any drug or nondrug therapy.
GNAO1‐Associated Movement Disorder
Authors: Dhamija Radhika , Mink Jonathan W. , Shah Binit B. , Goodkin Howard P.
Published: March 2016

View Supplementary Video 1
Thalamic‐Caudal Zona Incerta Deep Brain Stimulation for Refractory Orthostatic Tremor: A Report of 3 Cases
Authors: Athauda Dilan , Georgiev Dejan , Aviles‐Olmos Iciar , Peters Amy , Day Brian , Brown Peter , Zrinzo Ludvic , Hariz Marwan , Limousin Patricia , Foltynie Thomas
Published: March 2016

Orthostatic tremor (OT) is a rare, disabling movement disorder characterized by the development of a high‐frequency tremor of the lower limbs and feelings of unsteadiness upon standing, which compel the patient to sit down or walk. Medical therapy is often unsatisfactory. Previous reports suggest that deep brain stimulation of the ventral intermediate nucleus of the thalamus may improve clinical outcomes. The authors report 3 patients who had intractable orthostatic tremor treated with bilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus‐caudal zona incerta, resulting in improved and sustained clinical improvements in symptoms, although there were no apparent changes in the underlying tremor frequency or onset.
How Do I Examine Parkinsonian Gait?
Authors: Giladi Nir , Herman Talia
Published: March 2016

Gait disturbances and falls are common among older adults and patients with Parkinson's disease. These symptoms curtail mobility, independence, and quality of life. This video illustrates important aspects of parkinsonian gait and highlights features that should be focused on during the clinical examination. These include walking speed, step length, step width, posture, arm swing, shuffling, foot clearance, turning abilities, and freezing of gait. We emphasize the need to distinguish between continuous and episodic walking difficulties and to incorporate walking while dual tasking into the gait assessment. We also demonstrate how to quantify the Timed up and Go test using a stopwatch and how to carry out other clinical tests that can be used to help to characterize mobility, such as the pull test and tandem stand. We show how to test for and provoke freezing of gait by guiding the patient through a series of demanding walking trajectories, turns, and using dual tasking and other relatively challenging conditions. Finally, the walking pattern of a patient with cautious gait of unknown origin (so‐called high‐level gait disorder) is shown. This case illustrates the contribution of fear of falling and the effects of hand support. In general, the video demonstrates the power of clinical observation and its utility when examining the gait of older adults and patients with Parkinson's disease.
Importance of nonsynonymous OCA2 variants in human eye color prediction
Authors: Andersen Jeppe D. , Pietroni Carlotta , Johansen Peter , Andersen Mikkel M. , Pereira Vania , Børsting Claus , Morling Niels
Published: March 2016

Background

The color of the eyes is one of the most prominent phenotypes in humans and it is often used to describe the appearance of an individual. The intensity of pigmentation in the iris is strongly associated with one single‐nucleotide polymorphism (SNP), rs12913832:A>G that is located in the promotor region of OCA2 (OMIM #611409). Nevertheless, many eye colors cannot be explained by only considering rs12913832:A>G.

Methods

In this study, we searched for additional variants in OCA2 to explain human eye color by sequencing a 500 kbp region, encompassing OCA2 and its promotor region.

Results

We identified three nonsynonymous OCA2 variants as important for eye color, including rs1800407:G>A (p.Arg419Gln) and two variants, rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile), not previously described as important for eye color variation. It was shown that estimated haplotypes consisting of four variants (rs12913832:A>G, rs1800407:G>A (p.Arg419Gln), rs74653330:A>T (p.Ala481Thr), and rs121918166:G>A (p.Val443Ile)) explained 75.6% (adjusted R2 = 0.76) of normal eye color variation, whereas rs12913832:A>G alone explained 68.8% (adjusted R2 = 0.69). Moreover, rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile) had a measurable effect on quantitative skin color (P = 0.008).

Conclusion

Our data showed that rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile) have a measurable effect on normal pigmentation variation.
Identification of genetic variants of LGI1 and RTN4R (NgR1) linked to schizophrenia that are defective in NgR1–LGI1 signaling
Authors: Thomas Rhalena A. , Ambalavanan Amirthagowri , Rouleau Guy A. , Barker Philip A.
Published: March 2016

Background

The protein NgR1 is encoded by RTN4R, a gene linked to schizophrenia. We previously reported NgR1 as receptor for the epilepsy‐linked protein LGI1. NgR1 regulates synapse number and synaptic plasticity, whereas LGI1 antagonizes NgR1 signaling and promotes synapse formation. Impairments in synapse formation are common in neurological disease and we hypothesized that an LGI1–NgR1 signaling pathway may contribute to the development of schizophrenia.

Methods

We screened two unrelated schizophrenic populations for variants in RTN4R and LGI1 using whole exome sequencing and Sanger sequencing. We tested the ability of LGI1 to bind rare coding variants of NgR1 using a cell surface binding assays and the signaling ability of NgR1 using COS7 cell‐spreading assays.

Results

We observed a previously reported rare coding variant in RTN4R (c.1195C>T, pR399W). We report the first LGI1 mutations to be identified in individuals with schizophrenia. Three different LGI1 mutations were found, two missense mutations (c.205G>A, p.V69I) and (c.313G>A, V105M), and an intronic variant (g.897T>C) that likely leads to a protein truncation. We found NgR1R119W and NgR1277C have a reduced ability to bind LGI1 in a cell surface binding assay. COS7 cell‐spreading assays reveal that NgR1 mutants are impaired in their ability to mediate RhoA activation.

Conclusion

Variants in NgR1 and LGI1 may be associated with schizophrenia and variants in NgR1 found in schizophrenic patients have impaired LGI1–NgR1 signaling. Impaired LGI1–NgR1 signaling may contribute to disease progression.
Hybrid Network Model for “Deep Learning” of Chemical Data: Application to Antimicrobial Peptides
Authors: Schneider Petra , Müller Alex T. , Gabernet Gisela , Button Alexander L. , Posselt Gernot , Wessler Silja , Hiss Jan A. , Schneider Gisbert
Published: March 2016

We present a “deep” network architecture for chemical data analysis and classification together with a prospective proof‐of‐concept application. The model features a self‐organizing map (SOM) as the input layer of a feedforward neural network. The SOM converts molecular descriptors to a two‐dimensional image for further processing. We implemented lateral neuron inhibition for contrast enhancement. The model achieved improved classification accuracy and predictive robustness compared to feedforward network classifiers lacking the SOM layer. By nonlinear dimensionality reduction the networks extracted meaningful chemical features from the data and outperformed linear principal component analysis (PCA). The learning machine was trained on the sequence‐length independent recognition of antibacterial peptides and correctly predicted the killing activity of a synthetic test peptide against Staphylococcus aureus in an in vitro experiment.
Cellular and molecular mechanisms involved in placental separation in the bovine: A review
Authors: Attupuram N. M. , Kumaresan A. , Narayanan K. , Kumar H.
Published: March 2016

Retention of fetal membranes (RFM), where the fetal placenta is not expelled within 8–12 hr after calving, lowers bovine productivity and fertility, resulting in significant economic loss to the dairy industry. Several risk factors that predispose an individual to RFM are known, but a unifying pathogenesis remains elusive due to its multifactorial etiology. Fetal membrane separation and expulsion after parturition involves structural and immunological changes of the bovine placentome that are governed predominantly by steroid hormones and the prostaglandin milieu of late pregnancy and parturition. Maturation of the placentome, a gradual and concerted event of late gestation, is likely initiated by the up‐regulation of fetal major histocompatibility complex class I in the interplacentomal region—which increases the apoptosis of binucleate and other trophoblastic cells, the degradation of collagen in the extracellular matrix by matrix metalloproteinases, and an influx of phagocytic leukocytes. Shear force further distorts the crypt architecture of the mature placentomes when they are forced against the fetus during the second stage of labor. Cotyledon dehiscence from the caruncular crypts is completed following fetal expulsion as a result of acute shrinkage of the cotelydonary villi as well as reduced perfusion to the caruncle; the secundinae is expelled by uterine contractions. A better understanding of placentomal maturation, intra‐partum, and immediate postpartum changes of the placentome should help develop strategies for the treatment and prevention of RFM. The present review proposes a model of placentome maturation and separation of fetal membranes in the dairy cow.Mol. Reprod. Dev. 83: 287–297, 2016. © 2016 Wiley Periodicals, Inc.
Sperm conjugation in mammal reproductive function: Different names for the same phenomenon?
Authors: Monclus Maria Angeles , Fornes Miguel Walter
Published: March 2016

In many mammalian and non‐mammalian species, mature sperm interact within the female reproductive tract or inside the epididymal lumen using cohesive forces. This phenomenon, known as “sperm conjugation,” is sometimes confused with sperm agglutination, which is the result of the interaction of epididymal or ejaculate spermatozoa upon release into culture medium. In addition to “agglutination,” the terms “association,” “rouleaux,” or “rosettes” are employed interchangeably to describe the conjugation phenomenon, which inevitably causes confusion due to the non‐unifying nomenclature. This variety of descriptions is likely due to a poor understanding of the molecular mechanisms involved in such conspicuous cell‐cell interaction as well as the different morphologies that result from such interactions among species. Here, we summarize the published data regarding mammalian sperm conjugation, considering the organisms in which sperm interaction was observed; the particular terminology employed; findings regarding the components that enable sperm to adhere; sperm behavior when deposited in the female reproductive tract; and hypotheses formulated to clarify the biological function and, when known, the mechanisms for sperm interaction. We also propose a new classification system for this phenomenon that might clearly unify the criteria used to describe this behavior. Mol. Reprod. Dev. 83: 884–896, 2016 © 2016 Wiley Periodicals, Inc.
Real‐time free‐breathing cardiac imaging with self‐calibrated through‐time radial GRAPPA
Authors: Sayin Ozan , Saybasili Haris , Zviman M. Muz , Griswold Mark , Halperin Henry , Seiberlich Nicole , Herzka Daniel A.
Published: March 2016

Purpose

Real‐time free‐breathing cardiac imaging with highly undersampled radial trajectories has previously been successfully demonstrated using calibrated radial generalized autocalibrating partially parallel acquisition (rGRAPPA). A self‐calibrated approach for rGRAPPA is proposed that removes the need for the calibration prescan.

Methods

To investigate the effect of various parameters on image quality, a comprehensive imaging study on one normal swine was performed. Root mean squared errors (RMSEs) were computed with respect to gold standard acquisitions, and several acquisition/reconstruction strategies were compared. Additionally, the method was tested on 13 human subjects, and RMSEs relative to standard through‐time radial GRAPPA were computed.

Results

Real‐time images with high spatiotemporal resolution were obtained. Image quality was comparable to calibrated through‐time rGRAPPA with endocardial and epicardial borders clearly delineated. In the swine, the average RMSE between self‐calibrated and gold‐standard calibrated images was 5.18 ± 0.84%. In normal human subjects, the average RMSE between self‐calibrated and calibrated through‐time rGRAPPA was 3.79 ± 0.64%. For lower accelerations rates (R = 6‐8) image quality was similar to comparable calibrated scans though RMSE increased for higher degrees of undersampling (R = 12–16).

Conclusion

Highly accelerated real‐time imaging with undersampled radial trajectories without additional calibration data is feasible. Image quality was acceptable for real‐time cardiac MRI applications demanding high speed. Magn Reson Med 77:250–264, 2017. © 2016 Wiley Periodicals, Inc.
Desynchronization of Cartesian k‐space sampling and periodic motion for improved retrospectively self‐gated 3D lung MRI using quasi‐random numbers
Authors: Weick Stefan , Völker Michael , Hemberger Kathrin , Meyer Cord , Ehses Philipp , Polat Bülent , Breuer Felix A. , Blaimer Martin , Fink Christian , Schad Lothar R. , Sauer Otto A. , Flentje Michael , Jakob Peter M.
Published: March 2016

Purpose

To demonstrate that desynchronization between Cartesian k‐space sampling and periodic motion in free‐breathing lung MRI improves the robustness and efficiency of retrospective respiratory self‐gating.

Methods

Desynchronization was accomplished by reordering the phase (ky) and partition (kz) encoding of a three‐dimensional FLASH sequence according to two‐dimensional, quasi‐random (QR) numbers. For retrospective respiratory self‐gating, the k‐space center signal (DC signal) was acquired separately after each encoded k‐space line. QR sampling results in a uniform distribution of k‐space lines after gating. Missing lines resulting from the gating process were reconstructed using iterative GRAPPA. Volunteer measurements were performed to compare quasi‐random with conventional sampling. Patient measurements were performed to demonstrate the feasibility of QR sampling in a clinical setting.

Results

The uniformly sampled k‐space after retrospective gating allows for a more stable iterative GRAPPA reconstruction and improved ghost artifact reduction compared with conventional sampling. It is shown that this stability can either be used to reduce the total scan time or to reconstruct artifact‐free data sets in different respiratory phases, both resulting in an improved efficiency of retrospective respiratory self‐gating.

Conclusion

QR sampling leads to desynchronization between repeated data acquisition and periodic respiratory motion. This results in an improved motion artifact reduction in shorter scan time. Magn Reson Med 77:787–793, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Flexible proton 3DMR spectroscopic imaging of the prostate with low‐power adiabatic pulses for volume selection and spiral readout
Authors: Steinseifer Isabell K. , Philips Bart W.J. , Gagoski Borjan , Weiland Elisabeth , Scheenen Tom W. J. , Heerschap Arend
Published: March 2016

Purpose

Cartesian k‐space sampling in three‐dimensional magnetic resonance spectroscopic imaging (MRSI) of the prostate limits the selection of voxel size and acquisition time. Therefore, large prostates are often scanned at reduced spatial resolutions to stay within clinically acceptable measurement times. Here we present a semilocalized adiabatic selective refocusing (sLASER) sequence with gradient‐modulated offset‐independent adiabatic (GOIA) refocusing pulses and spiral k‐space acquisition (GOIA‐sLASER‐Spiral) for fast prostate MRSI with enhanced resolution and extended matrix sizes.

Methods

MR was performed at 3 tesla with an endorectal receive coil. GOIA‐sLASER‐Spiral at an echo time (TE) of 90 ms was compared to a point‐resolved spectroscopy sequence (PRESS) with weighted, elliptical phase encoding at an TE of 145 ms using simulations and measurements of phantoms and patients (n = 9).

Results

GOIA‐sLASER‐Spiral acquisition allows prostate MR spectra to be obtained in ∼5 min with a quality comparable to those acquired with a common Cartesian PRESS protocol in ∼9 min, or at an enhanced spatial resolution showing more precise tissue allocation of metabolites. Extended field of views (FOVs) and matrix sizes for large prostates are possible without compromising spatial resolution or measurement time.

Conclusion

The flexibility of spiral sampling enables prostate MRSI with a wide range of resolutions and FOVs without undesirable increases in acquisition times, as in Cartesian encoding. This approach is suitable for routine clinical exams of prostate metabolites. Magn Reson Med 77:928–935, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Estimating absolute‐phase maps using ESPIRiT and virtual conjugate coils
Authors: Uecker Martin , Lustig Michael
Published: March 2016

Purpose

To develop an ESPIRiT‐based method to estimate coil sensitivities with image phase as a building block for efficient and robust image reconstruction with phase constraints.

Theory and Methods

ESPIRiT is a new framework for calibration of the coil sensitivities and reconstruction in parallel magnetic resonance imaging. Applying ESPIRiT to a combined set of physical and virtual conjugate coils (VCC‐ESPIRiT) implicitly exploits conjugate symmetry in k‐space similar to VCC‐GRAPPA. Based on this method, a new post‐processing step is proposed for the explicit computation of coil sensitivities that include the absolute phase of the image. The accuracy of the computed maps is directly validated using a test based on projection onto fully sampled coil images and also indirectly in phase‐constrained parallel‐imaging reconstructions.

Results

The proposed method can estimate accurate sensitivities which include low‐resolution image phase. In case of high‐frequency phase variations VCC‐ESPIRiT yields an additional set of maps that indicates the existence of a high‐frequency phase component. Taking this additional set of maps into account can improve the robustness of phase‐constrained parallel imaging.

Conclusion

The extended VCC‐ESPIRiT is a useful tool for phase‐constrained imaging. Magn Reson Med 77:1201–1207, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Optimal experimental design for filter exchange imaging: Apparent exchange rate measurements in the healthy brain and in intracranial tumors
Authors: Lampinen Björn , Szczepankiewicz Filip , van Westen Danielle , Englund Elisabet , C Sundgren Pia , Lätt Jimmy , Ståhlberg Freddy , Nilsson Markus
Published: March 2016

Purpose

Filter exchange imaging (FEXI) is sensitive to the rate of diffusional water exchange, which depends, eg, on the cell membrane permeability. The aim was to optimize and analyze the ability of FEXI to infer differences in the apparent exchange rate (AXR) in the brain between two populations.

Methods

A FEXI protocol was optimized for minimal measurement variance in the AXR. The AXR variance was investigated by test‐retest acquisitions in six brain regions in 18 healthy volunteers. Preoperative FEXI data and postoperative microphotos were obtained in six meningiomas and five astrocytomas.

Results

Protocol optimization reduced the coefficient of variation of AXR by approximately 40%. Test‐retest AXR values were heterogeneous across normal brain regions, from 0.3 ± 0.2 s−1 in the corpus callosum to 1.8 ± 0.3 s−1 in the frontal white matter. According to analysis of statistical power, in all brain regions except one, group differences of 0.3–0.5 s−1 in the AXR can be inferred using 5 to 10 subjects per group. An AXR difference of this magnitude was observed between meningiomas (0.6 ± 0.1 s−1) and astrocytomas (1.0 ± 0.3 s−1).

Conclusions

With the optimized protocol, FEXI has the ability to infer relevant differences in the AXR between two populations for small group sizes. Magn Reson Med 77:1104–1114, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Robust diffusion tensor imaging by spatiotemporal encoding: Principles and in vivo demonstrations
Authors: Solomon Eddy , Liberman Gilad , Nissan Noam , Frydman Lucio
Published: March 2016

Purpose

Evaluate the usefulness of single‐shot and of interleaved spatiotemporally encoded (SPEN) methods to perform diffusion tensor imaging (DTI) under various preclinical and clinical settings.

Methods

A formalism for analyzing SPEN DTI data is presented, tailored to account for the spatially dependent b‐matrix weightings introduced by the sequence's use of swept pulses acting while in the presence of field gradients. Using these b‐matrix calculations, SPEN's ability to deliver DTI measurements was tested on phantoms as well as ex vivo and in vivo. In the latter case, DTI involved scans on mice brains and on human lactating breasts.

Results

For both ex vivo and in vivo investigations, SPEN data proved less sensitive to distortions arising from Bo field inhomogeneities and from eddy currents, than conventional single‐shot alternatives. Further resolution enhancement could be achieved using referenceless methods for interleaved SPEN data acquisitions.

Conclusion

The robustness of SPEN‐based sequences vis‐à‐vis field instabilities and heterogeneities, enables the implementation of DTI experiments with good sensitivity and resolution even in challenging environments in both preclinical and clinical settings. Magn Reson Med 77:1124–1133, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Jacobian weighted temporal total variation for motion compensated compressed sensing reconstruction of dynamic MRI
Authors: Royuela‐del‐Val Javier , Cordero‐Grande Lucilio , Simmross‐Wattenberg Federico , Martín‐Fernández Marcos , Alberola‐López Carlos
Published: March 2016

Purpose

To eliminate the need of spatial intraframe regularization in a recently reported dynamic MRI compressed‐sensing‐based reconstruction method with motion compensation and to increase its performance.

Theory and Methods

We propose a new regularization metric based on the introduction of a spatial weighting measure given by the Jacobian of the estimated deformations. It shows convenient discretization properties and, as a byproduct, it also provides a theoretical support to a result reported by others based on an intuitive design. The method has been applied to the reconstruction of both short and long axis views of the heart of four healthy volunteers. Quantitative image quality metrics as well as straightforward visual assessment are reported.

Results

Short and long axis reconstructions of cardiac cine MRI sequences have shown superior results than previously reported methods both in terms of quantitative metrics and of visual assessment. Fine details are better preserved due to the lack of additional intraframe regularization, with no significant image artifacts even for an acceleration factor of 12.

Conclusions

The proposed Jacobian Weighted temporal Total Variation results in better reconstructions of highly undersampled cardiac cine MRI than previously proposed methods and sets a theoretical ground for forward and backward predictors used elsewhere. Magn Reson Med 77:1208–1215, 2017. © 2016 International Society for Magnetic Resonance in Medicine