bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology
Authors: Gazula Harshvardhan , Tregidgo Henry FJ , Billot Benjamin , Balbastre Yael , Williams-Ramirez Jonathan , Herisse Rogeny , Deden-Binder Lucas J , Casamitjana Adria , Melief Erica J , Latimer Caitlin S , Kilgore Mitchell D , Montine Mark , Robinson Eleanor , Blackburn Emily , Marshall Michael S , Connors Theresa R , Oakley Derek H , Frosch Matthew P , Young Sean I , Van Leemput Koen , Dalca Adrian V , Fischl Bruce , MacDonald Christine L , Keene C Dirk , Hyman Bradley T , Iglesias Juan E
Published: June 2024

We present open-source tools for three-dimensional (3D) analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (1) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (2) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable ﬁnancial resources. We tested our tools on synthetic and real data from two NIH Alzheimer’s Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected diﬀerences between post mortem conﬁrmed Alzheimer’s disease cases and controls. The tools are available in our widespread neuroimaging suite ‘FreeSurfer’ (https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools).
Optimal transport for automatic alignment of untargeted metabolomic data
Authors: Breeur Marie , Stepaniants George , Keski-Rahkonen Pekka , Rigollet Philippe , Viallon Vivian
Published: June 2024

Untargeted metabolomic profiling through liquid chromatography-mass spectrometry (LC-MS) measures a vast array of metabolites within biospecimens, advancing drug development, disease diagnosis, and risk prediction. However, the low throughput of LC-MS poses a major challenge for biomarker discovery, annotation, and experimental comparison, necessitating the merging of multiple datasets. Current data pooling methods encounter practical limitations due to their vulnerability to data variations and hyperparameter dependence. Here, we introduce GromovMatcher, a flexible and user-friendly algorithm that automatically combines LC-MS datasets using optimal transport. By capitalizing on feature intensity correlation structures, GromovMatcher delivers superior alignment accuracy and robustness compared to existing approaches. This algorithm scales to thousands of features requiring minimal hyperparameter tuning. Manually curated datasets for validating alignment algorithms are limited in the field of untargeted metabolomics, and hence we develop a dataset split procedure to generate pairs of validation datasets to test the alignments produced by GromovMatcher and other methods. Applying our method to experimental patient studies of liver and pancreatic cancer, we discover shared metabolic features related to patient alcohol intake, demonstrating how GromovMatcher facilitates the search for biomarkers associated with lifestyle risk factors linked to several cancer types.
SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells
Authors: Zhang Linda , Hsu Joanne I , Braekeleer Etienne D , Chen Chun-Wei , Patel Tajhal D , Martell Alejandra G , Guzman Anna G , Wohlan Katharina , Waldvogel Sarah M , Uryu Hidetaka , Tovy Ayala , Callen Elsa , Murdaugh Rebecca L , Richard Rosemary , Jansen Sandra , Vissers Lisenka , de Vries Bert BA , Nussenzweig Andre , Huang Shixia , Coarfa Cristian , Anastas Jamie , Takahashi Koichi , Vassiliou George , Goodell Margaret A
Published: June 2024

The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase Mg2+/Mn2+-dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacological target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D-mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D-mutant cells. Altogether, our results demonstrate a role for SOD1 in the survival of PPM1D-mutant leukemia cells and highlight a new potential therapeutic strategy against PPM1D-mutant cancers.
Senescence of endplate osteoclasts induces sensory innervation and spinal pain
Authors: Pan Dayu , Benkato Kheiria Gamal , Han Xuequan , Zheng Jinjian , Kumar Vijay , Wan Mei , Zheng Junying , Cao Xu
Published: June 2024

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.
Reliance on self-reports and estimated food composition data in nutrition research introduces signiﬁcant bias that can only be addressed with biomarkers
Authors: Ottaviani Javier I , Sagi-Kiss Virag , Schroeter Hagen , Kuhnle Gunter GC
Published: June 2024

The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally aﬀects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: ﬂavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with signiﬁcant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
Targeting plasmid-encoded proteins that contain immunoglobulin-like domains to combat antimicrobial resistance
Authors: Prieto Alejandro , Miró Lluïsa , Margolles Yago , Bernabeu Manuel , Salguero David , Merino Susana , Tomás Joan , Corbera Juan Alberto , Pérez-Bosque Anna , Hüttener Mário , Fernández Luis Ángel , Juárez Antonio
Published: June 2024

Antimicrobial resistance (AMR) poses a significant threat to human health. Although vaccines have been developed to combat AMR, it has proven challenging to associate specific vaccine antigens with AMR. Bacterial plasmids play a crucial role in the transmission of AMR. Our recent research has identified a group of bacterial plasmids (specifically, IncHI plasmids) that encode large molecular mass proteins containing bacterial immunoglobulin-like domains. These proteins are found on the external surface of the bacterial cells, such as in the flagella or conjugative pili. In this study, we show that these proteins are antigenic and can protect mice from infection caused by an AMR
Salmonella
strain harboring one of these plasmids. Furthermore, we successfully generated nanobodies targeting these proteins, that were shown to interfere with the conjugative transfer of IncHI plasmids. Considering that these proteins are also encoded in other groups of plasmids, such as IncA/C and IncP2, targeting them could be a valuable strategy in combating AMR infections caused by bacteria harboring different groups of AMR plasmids. Since the selected antigens are directly linked to AMR itself, the protective effect extends beyond specific microorganisms to include all those carrying the corresponding resistance plasmids.
Structural analysis of the dynamic ribosome-translocon complex
Authors: Lewis Aaron JO , Zhong Frank , Keenan Robert J , Hegde Ramanujan S
Published: June 2024

The protein translocon at the endoplasmic reticulum comprises the Sec61 translocation channel and numerous accessory factors that collectively facilitate the biogenesis of secretory and membrane proteins. Here, we leveraged recent advances in cryo-electron microscopy (cryo-EM) and structure prediction to derive insights into several novel configurations of the ribosome-translocon complex. We show how a transmembrane domain (TMD) in a looped configuration passes through the Sec61 lateral gate during membrane insertion; how a nascent chain can bind and constrain the conformation of ribosomal protein uL22; and how the translocon-associated protein (TRAP) complex can adjust its position during different stages of protein biogenesis. Most unexpectedly, we find that a large proportion of translocon complexes contains RAMP4 intercalated into Sec61’s lateral gate, widening Sec61’s central pore and contributing to its hydrophilic interior. These structures lead to mechanistic hypotheses for translocon function and highlight a remarkably plastic machinery whose conformations and composition adjust dynamically to its diverse range of substrates.
Assessment of the Epigenomic Landscape in Human Myometrium at Term Pregnancy
Authors: Wu San-Pin , Quiroz Elvis , Wang Tianyuan , Redecke Skylar Montague , Xu Xin , Lin Lin , Anderson Matthew L. , DeMayo Francesco J.
Published: June 2024

The myometrium plays a critical component during pregnancy. It is responsible for the uterus’ structural integrity and force generation at term, Emerging studies in mice indicate a dynamic change of the myometrial epigenome and transcriptome during pregnancy to ready the contractile machinery for parturition. However, the regulatory systems underlying myometrial gene expression patterns throughout gestation remain largely unknown. Here we investigated the human term pregnant nonlabor myometrial biopsies for transcriptome, enhancer histone mark cistrome, and chromatin conformation pattern mapping. More than thirty-thousand putative enhancers with H3K27ac and H3K4me1 double positive marks were identified in the myometrium. Enriched transcription factor binding motifs include known myometrial regulators AP-1, STAT, NFkB, and PGR among others. Putative myometrial super enhancers are mostly colocalized with progesterone receptor occupying sites and preferentially associated with highly expressing genes, suggesting a conserved role of PGR in regulating the myometrial transcriptome between species. In human myometrial specimens, inferred PGR activities are positively correlated with
PLCL2
mRNA levels, supporting that PGR may act through this genomic region to promote
PLCL2
expression. PGR overexpression facilitated
PLCL2
gene expression in myometrial cells Using CRISPR activation the functionality of a PGR putative enhancer 35-kilobases upstream of the contractile-restrictive gene
PLCL2
. In summary, results of this study serve as a resource to study gene regulatory mechanisms in the human myometrium at the term pregnancy stage for further advancing women’s health research.
ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins
Authors: Thayer Mathew , Heskett Michael B , Smith Leslie G , Spellman Paul T , Yates Phillip A
Published: June 2024

ASARs are a family of very-long noncoding RNAs that control replication timing on individual human autosomes, and are essential for chromosome stability. The eight known ASAR lncRNAs remain closely associated with their parent chromosomes. Analysis of RNA-protein interaction data (from ENCODE) revealed numerous RBPs with significant interactions with multiple ASAR lncRNAs, with several hnRNPs as abundant interactors. An ~7 kb domain within the ASAR6-141 lncRNA shows a striking density of RBP interaction sites. Genetic deletion and ectopic integration assays indicate that this ~7 kb RNA binding protein domain contains functional sequences for controlling replication timing of entire chromosomes in cis. shRNA-mediated depletion of 10 different RNA binding proteins, including HNRNPA1, HNRNPC, HNRNPL, HNRNPM, HNRNPU, or HNRNPUL1, results in dissociation of ASAR lncRNAs from their chromosome territories, and disrupts the synchronous replication that occurs on all autosome pairs, recapitulating the effect of individual ASAR knockouts on a genome-wide scale. Our results further demonstrate the role that ASARs play during the temporal order of genome-wide replication, and we propose that ASARs function as essential RNA scaffolds for the assembly of hnRNP complexes that help maintain the structural integrity of each mammalian chromosome.
Tribbles1 is host protective during in vivo mycobacterial infection
Authors: Hammond Ffion R , Lewis Amy , Pollara Gabriele , Tomlinson Gillian S , Noursadeghi Mahdad , Kiss-Toth Endre , Elks Philip M
Published: June 2024

Tuberculosis is a major global health problem and is one of the top 10 causes of death worldwide. There is a pressing need for new treatments that circumvent emerging antibiotic resistance. Mycobacterium tuberculosis parasitises macrophages, reprogramming them to establish a niche in which to proliferate, therefore macrophage manipulation is a potential host-directed therapy if druggable molecular targets could be identified. The pseudokinase Tribbles1 (Trib1) regulates multiple innate immune processes and inflammatory profiles making it a potential drug target in infections. Trib1 controls macrophage function, cytokine production, and macrophage polarisation. Despite wide-ranging effects on leukocyte biology, data exploring the roles of Tribbles in infection in vivo are limited. Here, we identify that human Tribbles1 is expressed in monocytes and is upregulated at the transcript level after stimulation with mycobacterial antigen. To investigate the mechanistic roles of Tribbles in the host response to mycobacteria in vivo, we used a zebrafish Mycobacterium marinum (Mm) infection tuberculosis model. Zebrafish Tribbles family members were characterised and shown to have substantial mRNA and protein sequence homology to their human orthologues. trib1 overexpression was host-protective against Mm infection, reducing burden by approximately 50%. Conversely, trib1 knockdown/knockout exhibited increased infection. Mechanistically, trib1 overexpression significantly increased the levels of proinflammatory factors il-1β and nitric oxide. The host-protective effect of trib1 was found to be dependent on the E3 ubiquitin kinase Cop1. These findings highlight the importance of Trib1 and Cop1 as immune regulators during infection in vivo and suggest that enhancing macrophage TRIB1 levels may provide a tractable therapeutic intervention to improve bacterial infection outcomes in tuberculosis.
Structural features of heteromeric channels composed of CALHM2 and CALHM4 paralogs
Authors: Drożdżyk Katarzyna , Peter Martina , Dutzler Raimund
Published: June 2024

The CALHM proteins constitute a family of large pore channels that contains six closely related paralogs in humans. Two family members, CALHM1 and 3, have been associated with the release of ATP during taste sensation. Both proteins form heteromeric channels that activate at positive potential and decreased extracellular Ca2+ concentration. Although the structures of several family members displayed large oligomeric organizations of different size, their function has in most cases remained elusive. Our previous study has identified the paralogs CALHM2, 4 and, 6 to be highly expressed in the placenta and defined their structural properties as membrane proteins exhibiting features of large pore channels with unknown activation properties (Drożdżyk et al., 2020). Here, we investigated whether these placental paralogs would form heteromers and characterized heteromeric complexes consisting of CALHM2 and CALHM4 subunits using specific binders as fiducial markers. Both proteins assemble with different stoichiometries with the largest population containing CALHM2 as the predominant component. In these oligomers, the subunits segregate and reside in their preferred conformation found in homomeric channels. Our study has thus revealed the properties that govern the formation of CALHM heteromers in a process of potential relevance in a cellular context.
Enteric glia regulate Paneth cell secretion and intestinal microbial ecology
Authors: Prochera Aleksandra , Muppirala Anoohya N , Kuziel Gavin A , Soualhi Salima , Shepherd Amy , Sun Liang , Issac Biju , Rosenberg Harry J , Karim Farah , Perez Kristina , Smith Kyle H , Archibald Tonora H , Rakoff-Nahoum Seth , Hagen Susan J , Rao Meenakshi
Published: June 2024

Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier formation
in vitro
. Whether these interactions are important
in vivo,
however, is unclear because previous studies reached conflicting conclusions [1]. To better define the roles of enteric glia in steady state regulation of the intestinal epithelium, we characterized the glia in closest proximity to epithelial cells and found that the majority express
PLP1
in both mice and humans. To test their functions using an unbiased approach, we genetically depleted PLP1
+
cells in mice and transcriptionally profiled the small and large intestines. Surprisingly, glial loss had minimal effects on transcriptional programs and the few identified changes varied along the gastrointestinal tract. In the ileum, where enteric glia had been considered most essential for epithelial integrity, glial depletion did not drastically alter epithelial gene expression but caused a modest enrichment in signatures of Paneth cells, a secretory cell type important for innate immunity. In the absence of PLP1
+
glia, Paneth cell number was intact, but a subset appeared abnormal with irregular and heterogenous cytoplasmic granules, suggesting a secretory deficit. Consistent with this possibility, ileal explants from glial-depleted mice secreted less functional lysozyme than controls with corresponding effects on fecal microbial composition. Collectively, these data suggest that enteric glia do not exert broad effects on the intestinal epithelium but have an essential role in regulating Paneth cell function and gut microbial ecology.
Poseidon – A framework for archaeogenetic human genotype data management
Authors: Schmid Clemens , Ghalichi Ayshin , Lamnidis Thiseas C. , Mudiyanselage Dhananjaya B. A. , Haak Wolfgang , Schiffels Stephan
Published: June 2024

The study of ancient human genomes, archaeo- or palaeogenetics, has accelerated in the last ten years, with now thousands of new ancient genomes being released each year. Operating at the interface of genetics, anthro-pology and archaeology, this data includes features from all three fields, including rich meta- and context-data, for example regarding spatiotemporal provenience. While archives and standards for genetic sequencing data al-ready exist, no such infrastructure exists for combined genetic and meta-data that could ensure FAIR principles across the field. Here, we present Poseidon, a framework for open and FAIR data handling in archaeogenetics, including a specified package format, software tools, and public, community-maintained online archives. Poseidon emphasises human- and machine-readable data storage, the development of convenient and interoperable command line software, and a high degree of source granularity to elevate the original data publication to the main unit of long-term curation.
Predicting inmate suicidal behavior with an interpretable ensemble machine learning approach in smart prisons
Authors: Akhtar Khayyam , Yaseen Muhammad Usman , Imran Muhammad , Khattak Sohaib Bin Altaf , M. Nasralla Moustafa
Published: June 2024

The convergence of smart technologies and predictive modelling in prisons presents an exciting opportunity to revolutionize the monitoring of inmate behaviour, allowing for the early detection of signs of distress and the effective mitigation of suicide risks. While machine learning algorithms have been extensively employed in predicting suicidal behaviour, a critical aspect that has often been overlooked is the interoperability of these models. Most of the work done on model interpretations for suicide predictions often limits itself to feature reduction and highlighting important contributing features only. To address this research gap, we used Anchor explanations for creating human-readable statements based on simple rules, which, to our knowledge, have never been used before for suicide prediction models. We also overcome the limitation of anchor explanations, which create weak rules on high-dimensionality datasets, by first reducing data features with the help of SHapley Additive exPlanations (SHAP). We further reduce data features through anchor interpretations for the final ensemble model of XGBoost and random forest. Our results indicate significant improvement when compared with state-of-the-art models, having an accuracy and precision of 98.6% and 98.9%, respectively. The F1-score for the best suicide ideation model appeared to be 96.7%.
A quantitative test of the “Ecomorphotype Hypothesis” for fossil true seals (Family Phocidae)
Authors: Rule James Patrick , Burin Gustavo , Park Travis
Published: June 2024

The fossil record of true seals (Family Phocidae) is mostly made up of isolated bones, some of which are type specimens. Previous studies have sought to increase referral of non-overlapping and unrelated fossils to these taxa using the ‘Ecomorphotype Hypothesis’, which stipulates that certain differences in morphology between taxa represent adaptations to differing ecology. On this basis, bulk fossil material could be lumped to a specific ecomorphotype, and then referred to species in that ecomorphotype, even if they are different bones. This qualitative and subjective method has been used often to expand the taxonomy of fossil phocids, but has never been quantitatively tested. We test the proposed ecomorphotypes using morphometric analysis of fossil and extant northern true seal limb bones, specifically principal components analysis and discriminant function analysis. A large amount of morphological overlap between ecomorphotypes, and poor discrimination between them, suggests that the ‘Ecomorphotype Hypothesis’ is not a valid approach. Further, the analysis failed to assign fossils to ecomorphotypes designated in previous studies, with some fossils from the same taxa being designated as different ecomorphotypes. The failure of this approach suggests that all fossils referred using this method should be considered to have unknown taxonomic status. In light of this, and previous findings that phocid limb bones have limited utility as type specimens, we revise the status of named fossil phocid species. We conclude that the majority of named fossil phocid taxa should be considered nomina dubia.
Erratic Rise in Tomato Prices, Status, Issues, Government Initiatives and Policy Suggestions to Manage the prices of Tomato and other Vegetables
Authors: Kumar Vikas
Published: June 2024

Tomatoes, hold a paramount position in both Indian cuisine and the nation's economy. The status of tomato area and production in India and in states show its importance in Indian economy. India is leading tomato producer in the world. In India, MP and Andhra Pradesh are the largest producer of tomato in India. The erratic weather conditions, pest attack and transport bottlenecks have raised the tomato prices in June to August 2023. In this regard, the paper is to analyze the status and issues in erratic rise in tomato prices, government initiatives and Policy suggestions to manage the prices of tomato and other vegetables. In the study, it is found that the number of reasons that has led to rise in prices starting from poor prices received for tomato for rabi crop, rise in temperature in May – June and to high rainfall in July end. Government has then initiated number of needed measures to support both producers and consumers from creating the awareness, purchase of produce from surplus areas and then distribution of produce in high price areas. To prevent the abnormal price situations in tomatoes or other vegetables, there is need of a multi-pronged approach involving both short-term relief and long-term strategies. As a policy suggestion, to combat such crisis in future, a collaborative effort and coordination required among government agencies, weather departments, agricultural experts, extension machinery and farmers themselves is essential.
A Case Study on Seasonal Behaviour of Aphodius elegans Allibert an Endocoprid Dung Beetle
Authors: Tshering Nythri
Published: June 2024

Dung beetles (Scarabaeidae) classified into endocoprid, paracoprid, and telecoprid beetles, are fascinating insects with various behaviors. The study focuses on behaviour of endocoprid beetles Aphodius elegans Allibert, found in Bumdeling, Trashi Yangts Bhutan. The observational and scan sampling methods were employed during the study. These beetles locate dung using antennae and dig inside it, resembling a boat propelled by oars. They are active during warm weather and bury themselves under dung during cold. Beetles defecate semi solid feces after dung foraging. They mimic death as defensive and antipredator behaviour. They prefer moist dung pats for burial and use repeated attempts and strongholds of hindwings to initiate flight. This study substantiates the diverse fascinating behaviors of a less-focused group of insects to gain a deeper understanding of their interactions with ecology.
Dilated Cardiomyopathy in the Cardiology Department of the CHU of Casablanca: A One-Year Observational Study
Authors: B.E Ovaga , H Charif , S Ouarrak , S Zahri , M Haboub , Benouna G , A Drighil , R. Habbal
Published: June 2024

Dilated Cardiomyopathy (DCM) is defined by a left ventricle (LV) with reduced systolic function (<45%) and dilation (LV volume > 90 ml/m²), excluding coronary artery disease or sufficient load conditions to explain it. The etiologies are multiple and increasingly well-known. We conducted a single-centre, retrospective observational study within the cardiology department of the CHU IBN ROCHD in Casablanca, Morocco, over one year. The main objective was to describe the characteristics and particularities of patients followed for DCM. The diagnosis is based only on echocardiography, after exclusion of an ischemic cause, severe valvular disease, and congenital heart disease. During the study, 44 patients were included, with a male predominance of 63.6% versus 36.4%. The average age was 60 ± 16.8 years. The initial presentation of cardiomyopathy showed that 73% of patients were admitted with heart failure (HF). The mean left ventricular ejection fraction (LVEF) was 30.2 ± 7.9%. Among the attributed etiologies, idiopathic DCM was the main cause reported in 59% of cases, followed by systemic lupus erythematosus (14%) and myocarditis (14%). In our sample, treatment was based on HF management, including beta-blockers, renin-angiotensin system blockers, SGLT2 inhibitors, and aldosterone antagonists. Implantation of a defibrillator for primary prevention concerned only one patient (3%) of the 33 patients for whom the theoretical indication was retained.
Preparation of porous polycaprolactone tubular matrix by salt leaching process
Authors: Gupta Bhuvanesh , Patra Shamayita , Ray Alok R.
Published: May 2012

Salt leaching technique has been employed to produce polycaprolactone (PCL) based porous tubular matrix. Salt was dispersed into PCL solution in chloroform and the subsequent leaching of salt was accomplished in water. The effect of salt and polymer concentration on the mechanical properties, porosity and surface characteristics was studied. It was observed that salt concentration has significant influence over crystalline nature of the scaffold. The porous structures became more interconnected as the salt concentration increased. This process yields a tubular porous matrix with maximum porosity of 61%, strength of 1.84 (±0.04) MPa and tensile strain of 120 (±7.94). © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
In situ polymerized nanocomposites of poly(butylene succinate)/Tio2 nanofibers: molecular weight, morphology, and thermal properties
Authors: Zhou Weidong , Xu Tao , Wang Xiaowei , Zhi Erjuan , Liu Jun , Zhang Wei , Ji Junhui
Published: May 2012

In this study, the nanocomposites of poly(butylene succinate) (PBS) and TiO2 nanofibers were first synthesized via in situ polymerization. Molecular weight, morphology, and thermal properties of the nanocomposites were characterized. As the weight percentage of TiO2 nanofibers increased from 0 to 2%, the molecular weight of PBS in the nanocomposites decreased gradually compared with that of pure PBS. In morphology, the nanocomposites were constituted by free PBS and PBS‐grafted TiO2 nanofibers (PBS‐g‐TiO2), which were proved by the Fourier transform infrared, scanning electron microscopy (SEM), and transmission electron microscopy. In addition, the SEM demonstrated the strong interfacial interaction and homogeneous distribution between TiO2 nanofibers and PBS matrix. The thermal properties determined by differential scanning calorimetry and thermogravimetric analysis included the increasing of cold crystallization temperatures, the melting temperatures, and the thermal stability. Besides, the crystallinity and the rate of crystallization of the nanocomposites were enhanced, which were also observed by the X‐ray diffraction. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Moderately high refractive index, low optical dispersion polymers with pendant diamondoids
Authors: Robello Douglas R.
Published: May 2012

Soluble, colorless polymers containing pendant diamondoid moieties (adamantane and diamantane) were synthesized and characterized. The materials exhibited an unusual combination of moderately high refractive index with low optical dispersion. These properties may make the polymers valuable as specialty optical plastics. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
JAK‐2 as a novel mediator of the profibrotic effects of transforming growth factor β in systemic sclerosis
Authors: Dees Clara , Tomcik Michal , Palumbo‐Zerr Katrin , Distler Alfiya , Beyer Christian , Lang Veronika , Horn Angelika , Zerr Pawel , Zwerina Jochen , Gelse Kolja , Distler Oliver , Schett Georg , Distler Jörg H. W.
Published: May 2012

Objective

To investigate whether JAK‐2 contributes to the pathologic activation of fibroblasts in patients with systemic sclerosis (SSc) and to evaluate the antifibrotic potential of JAK‐2 inhibition for the treatment of SSc.

Methods

Activation of JAK‐2 in human skin and in experimental fibrosis was determined by immunohistochemical analysis. JAK‐2 signaling was inhibited by the selective JAK‐2 inhibitor TG101209 or by small interfering RNA. Bleomycin‐induced dermal fibrosis in mice and TSK‐1 mice were used to evaluate the antifibrotic potential of specific JAK‐2 inhibition in vivo.

Results

Increased activation of JAK‐2 was detected in the skin of patients with SSc, particularly in fibroblasts. The activation of JAK‐2 was dependent on transforming growth factor β (TGFβ) and persisted in cultured SSc fibroblasts. Inhibition of JAK‐2 reduced basal collagen synthesis selectively in SSc fibroblasts but not in resting healthy dermal fibroblasts. Moreover, inhibition of JAK‐2 prevented the stimulatory effects of TGFβ on fibroblasts. Treatment with TG101209 not only prevented bleomycin‐induced fibrosis but also effectively reduced skin fibrosis in TSK‐1 mice.

Conclusion

We demonstrated that JAK‐2 is activated in a TGFβ‐dependent manner in SSc. Considering the potent antifibrotic effects of JAK‐2 inhibition, our study might have direct translational implications, because inhibitors of JAK‐2 are currently being evaluated in clinical trials for myeloproliferative disorders and would also be available for evaluation in patients with SSc.
Cannulating LIMA graft using right transradial approach: Two simple and innovative techniques
Authors: Patel Tejas , Shah Sanjay , Patel Tejan
Published: May 2012

Angiography and intervention of a LIMA (left internal mammary artery) graft cannot be performed easily while working through right transradial approach (TRA), because of complexity in anatomical relations of right and left subclavian arteries with arch of aorta. We demonstrate two simple and innovative techniques for the same using right TRA. © 2012 Wiley Periodicals, Inc.
Small‐Sized and Contacting Pt–WC Nanostructures on Graphene as Highly Efficient Anode Catalysts for Direct Methanol Fuel Cells
Authors: Wang Ruihong , Xie Ying , Shi Keying , Wang Jianqiang , Tian Chungui , Shen Peikang , Fu Honggang
Published: May 2012

The synergistic effect between Pt and WC is beneficial for methanol electro‐oxidation, and makes Pt–WC catalyst a promising anode candidate for the direct methanol fuel cell. This paper reports on the design and synthesis of small‐sized and contacting Pt–WC nanostructures on graphene that bring the synergistic effect into full play. Firstly, DFT calculations show the existence of a strong covalent interaction between WC and graphene, which suggests great potential for anchoring WC on graphene with formation of small‐sized, well‐dispersed WC particles. The calculations also reveal that, when Pt attaches to the pre‐existing WC/graphene hybrid, Pt particles preferentially grow on WC rather than graphene. Our experiments confirmed that highly disperse WC nanoparticles (ca. 5 nm) can indeed be anchored on graphene. Also, Pt particles 2–3 nm in size are well dispersed on WC/graphene hybrid and preferentially grow on WC grains, forming contacting Pt–WC nanostructures. These results are consistent with the theoretical findings. X‐ray absorption fine structure spectroscopy further confirms the intimate contact between Pt and WC, and demonstrates that the presence of WC can facilitate the crystallinity of Pt particles. This new Pt–WC/graphene catalyst exhibits a high catalytic efficiency toward methanol oxidation, with a mass activity 1.98 and 4.52 times those of commercial PtRu/C and Pt/C catalysts, respectively.
Nanoscale carriers for targeted delivery of drugs and therapeutic biomolecules
Authors: Kiparissides Costas , Kammona Olga
Published: May 2012

This review highlights the recent developments in the area of nanocarrier‐based targeted delivery systems for both conventional drugs and therapeutic agents of increased complexity. A challenging objective of targeted drug delivery is the development of novel nanocarriers for the delivery of protein/peptide drugs via the oral, pulmonary and nasal administration routes. The nanocarriers need to be biocompatible, biodegradable, non‐toxic and stable in biological media, to protect their payload and deliver it to desired sites within the body, preferentially in a temporally regulated manner, and on the other hand to be manufactured in a simple scalable manner, with relatively low cost. © 2012 Canadian Society for Chemical Engineering
Flow regime transition identification in three phase co‐current bubble columns
Authors: Kumar S. , Srinivasulu N. , Munshi P. , Khanna A.
Published: May 2012

Bubble columns have wide applications in absorption, bio‐reactions, catalytic slurry reactions, coal liquefaction; and are simple to operate, have less operating costs; provide good heat and mass transfer. Experiments have been performed for identifying transition regime in a 15 cm diameter bubble column with liquid phase as water and air as the gas phase. Glass beads of mean diameter 35 µm have been used as solid phase. The superficial gas velocity is in the range 0 ≤ Ug ≤ 16.3 cm/s and superficial liquid velocity in the range of 0 ≤ Ul ≤ 12.26 cm/s. Solid loading up to 9% (w/v) has been used. Pressure signals have been measured using differential pressure transducers (DPTs) at four different axial locations. Classical analysis (Wallis approach and Zuber–Findlay approach), Statistical analysis and Fractal analysis have been used for regime transition identification. Statistical analysis and Fractal analysis have shown almost the same transition points for all the liquid and gas velocities. Effect of solid concentration, liquid velocity and gas velocity over transition regime has also been studied. As the solid concentration is increased it has insignificant effect over transition regime for lower values (<1%), while transition values decrease for higher solid concentration (>1%). © 2012 Canadian Society for Chemical Engineering
A prospective evaluation of the utility of 2‐deoxy‐2‐[18F]fluoro‐D‐glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer
Authors: Smyth Elizabeth , Schöder Heiko , Strong Vivian E. , Capanu Marinela , Kelsen David P. , Coit Daniel G. , Shah Manish A.
Published: May 2012

BACKGROUND:

The aim of this study was to examine prospectively the utility of adding preoperative [18F]fluorodeoxyglucose positron emission tomography (FDG‐PET)/computed tomography (CT) to routine CT, endoscopic ultrasound (EUS), and laparoscopic staging of localized gastric cancer.

METHODS:

Patients with locally advanced gastric/gastroesophageal cancer were screened for 2 institutional review board–approved Memorial Sloan‐Kettering Cancer Center neoadjuvant chemotherapy protocols. Locally advanced disease was defined as T3 or T4, or lymph node–positive, based on EUS and high‐resolution CT scan. All patients underwent both standard FDG‐PET/CT and laparoscopy with cytological examination of washings. The sensitivity and specificity of FDG‐PET/CT for the identification of metastatic disease not seen on CT was determined. An economic model using Medicare/Medicaid reimbursement charges was developed to assess the cost‐effectiveness of these interventions.

RESULTS:

A total of 113 patients were enrolled from 2003 to 2010. All patients were assessed as having locally advanced disease by CT/EUS. FDG uptake in the primary tumor was associated with male sex, proximal tumors, and nondiffuse Lauren's subtype. 31 (27%) patients had occult metastatic disease detected by PET/CT (n = 11, 10%) and/or laparoscopy (n = 21, 19%), with a single overlap. Economic modeling suggests that the addition of FDG‐PET/CT to the standard staging evaluation of patients with locally advanced gastric cancer resulted in an estimated cost savings of ∼US $13,000 per patient.

CONCLUSIONS:

FDG‐PET/CT identifies occult metastatic lesions in approximately 10% of patients with locally advanced gastric cancer. Because of reduced morbidity from fewer futile surgeries and lower patient care costs, PET/CT should be considered as a component of the standard staging algorithm for localized gastric cancer. Cancer 2012. © 2012 American Cancer Society.
Efficient routing for wireless mesh networks using a backup path
Authors: Esmailpour Amir , Nasser Nidal , Dallal Jehad Al
Published: May 2012

Wireless mesh networks (WMNs) have a proven record in providing viable solutions for some of the fundamental issues in wireless networks such as capacity and range limitations. WMN infrastructure includes clusters of mobile ad‐hoc networks connected through a fixed backbone of mesh routers. The mesh network can be constrained severely because of various reasons, which could result in performance degradation such as a drop in throughput or long delays. Solutions to this problem often focus on multipath or multichannel extensions to the existing ad‐hoc routing protocols. In this paper, we propose a novel solution by introducing an alternative path to the mesh backbone that traverses the mobile ad‐hoc networks part of the WMN. The new routing solution allows the mobile nodes (MNs) to establish direct communication among peers without going through the backbone. The proposed alternative ad‐hoc path is used only when the mesh backbone is severely constrained. We also propose, for the first time in WMNs, using MNs with two interfaces, one used in the mesh backbone communication and the other engaged in the ad‐hoc network. A scheme is presented for making the MN aware of link quality measures by providing throughput values to the ad‐hoc on‐demand distance vector protocol. We use piggybacking on route reply messages in ad‐hoc on‐demand distance vector to avoid incurring additional costs. We implemented our solution in an OPNET simulator and evaluated its performance under a variety of conditions. Simulation results show that the alternative ad‐hoc path provides higher throughput and lower delays. Delay analysis show that the throughput improvement does not impose additional costs. Copyright © 2012 John Wiley & Sons, Ltd.
Host adaptations reduce the reproductive success ofVarroa destructorin two distinct European honey bee populations
Authors: Locke Barbara , Conte Yves Le , Crauser Didier , Fries Ingemar
Published: May 2012

Honey bee societies (Apis mellifera), the ectoparasitic miteVarroa destructor, and honey bee viruses that are vectored by the mite, form a complex system of host–parasite interactions. Coevolution by natural selection in this system has been hindered for European honey bee hosts since apicultural practices remove the mite and consequently the selective pressures required for such a process. An increasing mite population means increasing transmission opportunities for viruses that can quickly develop into severe infections, killing a bee colony. Remarkably, a few subpopulations in Europe have survived mite infestation for extended periods of over 10 years without management by beekeepers and offer the possibility to study their natural host–parasite coevolution. Our study shows that two of these “natural” honey bee populations, in Avignon, France and Gotland, Sweden, have in fact evolved resistant traits that reduce the fitness of the mite (measured as the reproductive success), thereby reducing the parasitic load within the colony to evade the development of overt viral infections. Mite reproductive success was reduced by about 30% in both populations. Detailed examinations of mite reproductive parameters suggest these geographically and genetically distinct populations favor different mechanisms of resistance, even though they have experienced similar selection pressures of mite infestation. Compared to unrelated control colonies in the same location, mites in the Avignon population had high levels of infertility while in Gotland there was a higher proportions of mites that delayed initiation of egg‐laying. Possible explanations for the observed rapid coevolution are discussed.
A novel tracking jitter computation method for delay‐locked loops in spread‐spectrum systems
Authors: Groh Ingmar , Gentner Christian , Selva Jesus
Published: May 2012

In spread‐spectrum navigation systems, the positioning error (or tracking accuracy) is determined from the jitter deviation of delay‐locked loops (DLLs). However, jitter simulations are computationally complex, and conventional analytical methods provide only unsatisfactory and incomplete jitter results. Thus, our contribution presents a novel method for the analytical jitter computation by mapping the stochastic differential equation (SDE) of the DLL onto an Ornstein–Uhlenbeck (OU) SDE. Its solution is the well‐known OU random process, which is a time‐variant Gaussian distribution. The expectation value and the variance of the OU random process yield the jitter deviation. Thus, we derive the analytical time‐variant jitter function with its transient response, which was to date unavailable. Contrary to previous jitter computations based on a loop transfer function, our method covers DLLs of any order. We obtain the loop parameters that minimise the jitter deviation analytically without computationally complex simulations. Above all, our method based on OU random processes enables for the first time an efficient joint analytical mean time to lose lock (MTLL) and jitter computation. Therefore, both computationally complex MTLL and jitter simulations become obsolete for many kinds of DLLs.Copyright © 2012 John Wiley & Sons, Ltd.
Cost‐effectiveness analysis of alternative treatments of African gambiense trypanosomiasis in Uganda
Authors: Politi Claudio , Carrin Guy , Evans David , Kuzoe F.A.S. , Cattand P.D.
Published: May 2012

African trypanosomiasis, or sleeping sickness, is a tropical disease caused by trypanosome parasites transmitted by tsetse flies. The focus of this paper is on the cost‐effectiveness of alternative drug treatments for patients in the late stage of the disease. Melarsoprol has been used for many decades. More recently, eflornithine has been developed. It has fewer side effects and improves the overall cure rate. It is much more expensive than melarsoprol, however.

The objective of the present cost‐effectiveness is to identify the costs and benefits that would be involved in switching from melarsoprol to eflornithine in the treatment of late stage sleeping sickness. Benefits are expressed in lives saved as well as in disability adjusted life years (DALYs). The analysis is applied to the case of Uganda. The implications for affordability are also considered, by taking account of how the treatment costs would be shared between the national government, donors and patients.

The baseline results indicate that melarsoprol treatment is associated with an incremental cost per life and DALY saved of $209 and $8, respectively. Each additional life saved by switching from melarsoprol alone to a combination of melarsoprol and eflornithine would cost an extra $1,033 per life saved, and an extra $40.9 per DALY gained. Shifting from this second alternative to treatment of all patients with eflornithine leads to an incremental cost per life saved of $4,444 and an incremental cost of $166.8 per DALY gained.
Confidence intervals for cost/effectiveness ratios
Authors: Wakker Peter , Klaassen Marc P.
Published: May 2012

The reduction of costs is becoming increasingly important in the medical field. The relevant topic of many clinical trials is not effectivenessper se, but rather cost‐effectiveness ratios. Surprisingly, no statistical tools for analyzing cost‐effectiveness ratios have been provided in the medical literature yet. This paper explains the gap in the literature, and provides a first technique for obtaining confidence intervals for cost‐effectiveness ratios. The technique does not use sophisticated tools to achieve maximal optimality, but seeks for tractability and ease of application while still satisfying all formal statistical requirements.