bluuebunny/crossref_metadata_2025 huggingface dataset:
Rule-based modulation of a sensorimotor transformation across cortical areas
Authors: Chang Yi-Ting , Finkel Eric A. , Xu Duo , O’Connor Daniel H.
Published: May 2024

Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes rule information and uses this information to guide behavioral responses to sensory stimuli. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task in which they switched between two rules in different blocks of trials: licking in response to tactile stimuli applied to a whisker while rejecting visual stimuli, or licking to visual stimuli while rejecting the tactile stimuli. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, the single-trial activity of individual neurons distinguished between the two rules both prior to and in response to the tactile stimulus. Variable rule-dependent responses to identical stimuli could in principle occur via appropriate configuration of pre-stimulus preparatory states of a neural population, which would shape the subsequent response. We hypothesized that neural populations in S1, S2, MM and ALM would show preparatory activity states that were set in a rule-dependent manner to cause processing of sensory information according to the current rule. This hypothesis was supported for the motor cortical areas by findings that (1) the current task rule could be decoded from pre-stimulus population activity in ALM and MM; (2) neural subspaces containing the population activity differed between the two rules; and (3) optogenetic disruption of pre-stimulus states within ALM and MM impaired task performance. Our findings indicate that flexible selection of an appropriate action in response to a sensory input can occur via configuration of preparatory states in the motor cortex.Task rules are reflected in preparatory activity in sensory and motor cortices.Neural subspaces for processing tactile signals depend on the current task rule.Motor cortical activity tracks rule switches and is required for flexible rule-guided behavior.
Impaired central pattern generators due to abnormal EPHA4 signaling leads to idiopathic scoliosis
Authors: Wang Lianlei , Zhao Sen , Yang Xinyu , Zheng Pengfei , Wen Wen , Xu Kexin , Cheng Xi , Li Qing , Khanshour Anas M. , Koike Yoshinao , Liu Junjun , Fan Xin , Otomo Nao , Chen Zefu , Li Yaqi , Li Lulu , Xie Haibo , Zhu Panpan , Li Xiaoxin , Niu Yuchen , Wang Shengru , Liu Sen , Yuan Suomao , Terao Chikashi , Li Ziquan , Chen Shaoke , Zhao Xiuli , Liu Pengfei , Posey Jennifer E. , Wu Zhihong , Qiu Guixing ,   DISCO study group (Deciphering Disorders Involving Scoliosis & COmorbidities), Ikegawa Shiro , Lupski James R. , Rios Jonathan J. , Wise Carol A. , Zhang Terry Jianguo , Zhao Chengtian , Wu Nan
Published: May 2024

Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we firstly reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate genes across several large IS cohorts encompassing Chinese, East Asian, and European populations. Consequently, we identified variants in the
EPHA4
gene as compelling candidates for IS. To confirm their pathogenicity, we generated zebrafish mutants of
epha4a
. Remarkably, the zebrafish
epha4a
mutants exhibited pronounced scoliosis during later stages of development, effectively recapitulating the IS phenotype. We observed that the
epha4a
mutants displayed defects in left-right coordination during locomotion, which arose from disorganized neural activation in these mutants. Our subsequent experiments indicated that the disruption of the central pattern generator (CPG) network, characterized by abnormal axon guidance of spinal cord interneurons, contributed to the disorganization observed in the mutants. Moreover, when knocked down
efnb3b
, the ligand for Epha4a, we observed similar CPG defects and disrupted left-right locomotion. These findings strongly suggested that ephrin B3-Epha4 signaling is vital for the proper functioning of CPGs, and defects in this pathway could lead to scoliosis in zebrafish. Furthermore, we identified two cases of IS in
NGEF
, a downstream molecule in the
EPHA4
pathway. Collectively, our data provide compelling evidence that neural patterning impairments and disruptions in CPGs may underlie the pathogenesis of IS.
An Evaluation of the Tumor Microenvironment through CALR, IL1R1, IFNB1, and IFNG to Assess Prognosis and Immunotherapy Response in Bladder Cancer Patients
Authors: Liu Lilong , Liu Zhenghao , Fan Lei , Yao Zhipeng , Hu Junyi , Hou Yaxin , Li Yang , Ding Yuhong , Kuang Yingchun , Chen Ke , Hao Yi , Liu Zheng
Published: May 2024

Immunogenic cell death (ICD) is a type of cell death sparking adaptive immune responses, can reshape the tumor microenvironment (TME). Exploring key ICD-related genes in bladder cancer (BLCA) could enhance personalized treatment. TCGA BLCA patients were divided into two ICD subtypes: ICD-high and ICD-low. High ICD expression linked to increased immune cell infiltration and longer survival, but with potentially suppressed immune function. The high ICD group responded better to PD1-targeted therapy. A risk-scoring model with four ICD-related genes (CALR, IL1R1, IFNB1, IFNG) was validated across TCGA, GEO datasets, and tissue samples, showing higher risk-score correlated with weaker anti-tumor immune function, more tumor-promoting elements, lower immunotherapy response rates, and shorter patient survival.This study connects ICD-related genes to BLCA prognosis and immune infiltration, offering a vital tool for personalized treatment guidance.
Engineered Migrasomes: A Robust, Thermally Stable Vaccination Platform
Authors: Wang Dongju , Wang Haifang , Wan Wei , Zhu Zihui , Sho Takami , Zheng Yi , Zhang Xing , Dou Longyu , Ding Qiang , Yu Li , Liu Zhihua
Published: May 2024

The burgeoning abilities of pathogens and tumor cells to evade immune responses underscore the urgent need for innovative vaccination platforms based on a variety of biological mechanisms. The current logistical challenges associated with cold-chain (i.e. low-temperature) transportation particularly impacts access to vaccines in the global south. We recently discovered organelles called migrasomes, and herein we investigate the potential of migrasomes as an alternative vaccination platform. Their inherent stability and their enrichment with immune-modulating molecules make migrasomes promising candidates, but their low yield presents a hurdle. We address this problem through our engineered migrasome-like vesicles (eMigrasomes), which emulate the biophysical attributes of natural migrasomes with substantially improved yield. We show that eMigrasomes loaded with a model antigen elicit potent antibody responses and maintain stability at room temperature. We demonstrate that eMigrasomes bearing the SARS-CoV-2 Spike protein induce robust humoral protection against the virus. Our study demonstrates the potential of eMigrasome-based vaccines as a unique, robust, and accessible alternative to traditional methods.
Professional Regulation and Change in Times of Crisis: Differing Opportunities Within and Across Ecologies
Authors: Prud'homme Julien , Adams Tracey L. , Bédard Jean-Luc
Published: May 2024

This paper analyses the impact of the COVID-19 pandemic crisis on professional regulatory change in two Canadian provinces, drawing on ecological theory. The dataset, constructed using web-scraping techniques, includes all laws and by-law modifications concerning regulated professions enacted during the first 18 months of the pandemic in Quebec and British Columbia. Data show that the crisis prompted regulatory changes but that the impact and nature of these changes varied depending on the structure of the ecology of professional regulation in each province. Furthermore, crisis-related concerns were more likely to induce or accelerate durable changes if they intersected with pre-existing, ongoing professional projects. Our findings have implications for theorizing crisis-related regulatory change and demonstrate the value of a comparative approach to studying professional ecologies and state-profession interfaces.
Alteration of RNA m6A methylation mediates aberrant RNA binding protein expression and alternative splicing in condyloma acuminatum
Authors: Liu Xiaoyan , Xie Bo , Wang Su , Wu Yinhua , Zhang Yu , Ruan Liming
Published: May 2024

Background

Condyloma acuminatum (CA) is caused by low-risk human papillomavirus, and is characterized by high recurrence after treatment. The RNA modification N6-methyladenosine (m6A) plays an important role during diverse viral infections, including high-risk HPV infection in cervical cancer. However, it is unclear whether low-risk HPV infection changes the RNA m6A methylation in CA.

Methods

High-throughputm6A-sequencing was performed to profile the transcriptome-wide mRNA modifications of CA tissues infected by LR-HPVs and the paired normal tissues from CA patients. We further investigated the regulation of alternative splicing by RNA binding proteins (RBPs) with altered m6A modification and constructed a regulatory network among these RBPs, regulated alternative splicing events (RASEs) and regulated alternative splicing genes (RASGs) in CA.

Results

The results show that the m6A level in CA tissues differed from that in the paired controls. Furthermore, cell cycle- and cell adhesion- associated genes with m6A modification were differentially expressed in CA tissues compared to the paired controls. In particular, seven RNA binding protein genes with specific m6A methylated sites, showed a higher or lower expression at the mRNA level in CA tissues than in the paired normal tissues. In addition, these differentially expressed RNA binding protein genes would regulate the alternative splicing pattern of apoptotic process genes in CA tissue.

Conclusions

Our study reveals a sophisticated m6A modification profile in CA tissue that affects the response of host cells to HPV infection, and provides cues for the further exploration of the roles of m6A and the development of a novel treatment strategy for CA.
Terrestrial wildlife as indicators of microplastic pollution in western Thailand
Authors: Teampanpong Jiraporn , Duengkae Prateep
Published: May 2024

Plastic pollution in terrestrial wildlife represents a new conservation challenge, with research in this area, especially within protected areas (PAs), being scant. This study documents the accumulation of microplastics (MPs) in terrestrial wildlife both inside and outside PAs in western Thailand. Carcasses of road-killed vertebrates in good condition, as well as live tadpoles, were collected to examine their exposure to plastic pollution. The digestive tracts of the vertebrate carcasses and the entire bodies of tadpoles were analyzed for MPs, which were identified if they measured over 50 µm. A total of 136 individuals from 48 vertebrate species were examined. The sample comprised snakes (44.12%), birds (11.03%), lizards (5.15%), tadpoles (32.25%), amphibians (5.88%), and mammals (1.47%). In total, 387 MPs were found in 44 species (91.67%), with an average occurrence of 3.25 ± 3.63 MPs per individual or 0.05 ± 0.08 MPs per gram of body weight. The quantities of MPs significantly varied among the animal groups, both in terms of number per individual (p < 0.05) and number per gram of body weight (p < 0.01). Furthermore, a significant difference in MP quantities was observed between specimens collected inside and outside PAs on an individual basis (p < 0.05), but not on a body weight basis (p = 0.07). Most MPs were fibers (77%), followed by fragments (22.22%), with only a minimal presence of film (0.52%) and foam (0.26%). Of all the MPs identified, 36.84% were confirmed as plastics or fibers made from natural materials, and 31.58% were plastics, including Polyethylene (PE), polyethylene terephthalate (PET), polypropylene (PP), Polyvinylidene chloride (PVDC), and polyester (PES). Additionally, fibers made of cotton, and those containing polyurethane (PU), rayon, PES, and combinations of rayon and PU, were identified. The quantities of MPs were significantly influenced by animal body weight, factors associated with human settlement/activity, and land use types. Our findings highlight the prevalence of plastic pollution in terrestrial vertebrates within Thai PAs. Further toxicological studies are required to establish plastic pollution standards. It is proposed that snakes, obtained from road kills, could serve as a non-invasive method for monitoring plastic pollution, thus acting as an indicator of the pollution threat to species within terrestrial ecosystems. There is an urgent need for the standardization of solid waste management at garbage dump sites in remote areas, especially within PAs. Conservation education focusing on MP occurrence, potential sources, and impacts could enhance awareness, thereby influencing changes in behaviors and attitudes toward plastic waste management at the household level.
Frictional characteristics of EN AW-6082 aluminium alloy sheets used in metal forming
Authors: Slota Ján , Kaščák Ľuboš , Lăzărescu Lucian
Published: May 2024

This article is devoted to testing EN AW-6082 aluminium alloy sheets in friction pair with NC6 (1.2063) tool steel. A special tribometer designed to simulate the friction conditions in sheet metal forming processes was used for friction testing. The research aimed to determine the influence of contact pressure, surface roughness of the tool, and lubrication conditions on the value of the coefficient of friction in the strip drawing test. Three grades of typical petroleum-based lubricants with kinematic viscosities between 21.9 and 97 mm2/s were used in the tests. The surface morphologies of the sheet metal after the friction process were observed using a scanning electron microscope. A tendency for the coefficient of friction to decrease with increasing contact pressure was observed. LHL32 and 75W-85 oils lost their lubricating properties at a certain pressure value and with further increase in pressure, the coefficient of friction value tended to increase. The 10W-40 oil with the highest viscosity reduced the coefficient of friction more intensively than the LHL32 oil.
Effect of Different Levels of Nano Boron and Nano Zinc on Plant Growth and Establishment of Passion Fruit (Passiflora edulis Sims) under Prayagraj Agro-climatic Condition
Authors: Shingade Danish , Topno Samir E. , Bahadur Vijay
Published: May 2024

The experiment was carried out at Department of Horticulture, Naini Agricultural Institute, SHUATS, Prayagraj during the year 2023-24.The experiment was laid out in Randomized Block Design comprising of 10 treatments vizT0 Control, T1 Nano Boron @ 1ppm (Foliar application), T2 Nano Boron @ 2ppm (Foliar application), T3 Nano Boron @ 3ppm (Foliar application), T4 Nano Zinc @ 1ppm (Foliar application), T5 Nano Zinc @ 2ppm (Foliar application), T6 Nano Zinc @ 3ppm (Foliar application), T7 Nano Boron 1ppm + Nano Zinc @ 2ppm (Foliar application), T8 Nano Boron 2ppm + Nano Zinc @ 2ppm (Foliar application), and T9 Nano Boron 3ppm + Nano Zinc @ 2ppm (Foliar application) with three replications. Every replication's treatments were distributed at random.The Observations were recorded as per the Vegetative growth parameters, survival (%) and chlorophyll content (SPAD value). The results reveal that the treatment T9 Nano Boron 3ppm + Nano Zinc @ 3ppm (Foliar application) was found to be the most suitable over all the other treatments in relation to vegetative growth parameters, survival (%) and chlorophyll content (SPAD value). The lowest cost of Cultivation was found in Treatment T1 which was 54,191.588/-
Recent Developments Toward the Application of Iron Aluminides in Fossil Fuel Technologies
Authors: Morris David G. , Muñoz‐Morris Maria A.
Published: November 2010

Iron aluminides are of interest for applications in power generation from fossil fuels because of excellent high temperature oxidation–corrosion resistance in aggressive environments and are potential replacements for high temperature steels. The Fe‐base composition ensures relative cheapness, while the high Al content leads to significant density reduction over commercial steels. Problems of low ductility/toughness at room temperature and poor high temperature (creep) strength, however, have prevented significant commercial use. After studies led by Oak Ridge National Laboratory (USA) from about 1980 to 2000, research has continued in Europe both as pan‐European efforts and as national efforts in countries such as the Czech Republic, France, Germany and Spain. An overview of such recent activities is presented, indicating the research strategies involved, and the progress toward making iron aluminides useful engineering materials. Recent activities have targeted microstructural refinement through novel processing to improve room temperature ductility or attempted alloying additions to improve high temperature strength. Achieving the required properties remains difficult, and has led to developments of iron aluminides as cast components and as coatings.
Birth weight and early socio‐economic disadvantage as predictors of sex hormones and sex hormone binding globulin in men at age 49–51 years
Authors: Pearce Mark S. , Groom Alix , Relton Caroline L. , Peaston Robert T. , Pollard Tessa M. , Francis Roger M.
Published: November 2010

Objectives: A number of associations have been shown between early growth and later sex hormone levels in women, but less is known about this relationship in men. This study investigated lifecourse predictors of sex hormones in men in the Newcastle Thousand Families birth cohort.

Methods: The Newcastle Thousand Families Study is a prospective study initiated in 1947. At age 49‐51 years, 574 study members returned detailed self‐completion questionnaires and 412 attended for clinical examination, including 172 men in whom blood samples were taken. Estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were measured. Free testosterone concentrations were also calculated.

Results: Social class at birth independently predicted FSH and LH, with higher levels with increasing socioeconomic disadvantage. SHBG was higher with increasing standardized birth weight and lower with increasing contemporary body mass index (BMI). BMI also predicted LH, SHBG, and testosterone. None of the variables included within this analysis were significant predictors of estradiol. No other associations were seen with any of the variables included from across the lifecourse.

Conclusions: Our findings suggest that birth weight may be positively associated with SHBG and early socioeconomic status may be related to FSH and LH in men. These novel findings are independent of contemporary BMI. Given the links between sex hormones, SHBG and disease outcomes such as type II diabetes and osteoporosis, it is possible that sex hormones may play a mediating role in the associations between circumstances in early life and later risk of chronic disease. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.
Factors associated with experiences of genetic discrimination among individuals at risk for huntington disease
Authors: Bombard Yvonne , Palin JoAnne , Friedman Jan M. , Veenstra Gerry , Creighton Susan , Paulsen Jane S. , Bottorff Joan L. , Hayden Michael R. ,   The Canadian Respond‐HD Collaborative Research Group
Published: November 2010

The purpose of this study was to identify factors that are associated with experiencing genetic discrimination (GD) among individuals at risk for Huntington disease (HD). Multivariable logistic regression analysis was used to examine factors associated with experiencing GD in data from a cross‐sectional, self‐report survey of 293 individuals at risk for HD. The study sample comprised 167 genetically tested respondents, and 66 who were not tested (80% response rate). Overall, individuals who learn they are at risk for HD at a younger age (OR = 3.1; 95% CI: 1.5–6.2; P = 0.002), are mutation‐positive (OR = 2.8; 95% CI: 1.4–6.0; P = 0.006), or are highly educated (OR = 2.7; 95% CI: 1.4–5.1; P = 0.002) are more likely to experience GD, particularly in insurance, family, and social settings. Further, younger age was associated with discrimination in insurance (OR = 0.97; 95% CI: 0.94–1.00; P = 0.038). This study provides evidence that some people who are at risk for HD were more likely to experience GD than others. Individuals who learned they are at risk for HD at a younger age and those who are mutation‐positive were more likely to experience GD, particularly in insurance, family, and social settings. Younger individuals were more likely to experience discrimination in the insurance setting. Overall, highly educated individuals were also more likely to report discrimination. These results provide direction for clinical and family discussions, counseling practice, and policy aimed at mitigating experiences of GD. © 2010 Wiley‐Liss, Inc.
Great apes use weight as a cue to find hidden food
Authors: Schrauf Cornelia , Call Josep
Published: November 2010

Bonobos (Pan paniscus;n= 5), orangutans (Pongo pygmaeus abelii;n= 6), and a gorilla (Gorilla gorilla gorilla;n= 1) were presented with two opaque cups, one empty and one baited (containing two bananas). Subjects had to independently gain weight information about the contents of the cups to find the hidden food. Six apes attained above chance level within a total of 16 trials. Successful subjects spontaneously adopted the method of successively lifting the cups and thus comparing their weight before making a choice. Prior to testing, these apes had participated in a weight discrimination task. To rule out that a subject's good performance was influenced by previous experience in weight experiments, we ran a second test in which the same task was presented to a group of chimpanzees (Pan troglodytes;n= 9) who were naïve to weight experiments. These subjects also participated in an additional test condition in which the same problem was presented based on learning to associate arbitrary visual stimuli. The results show that experience did not affect performance because the nine naïve subjects were equally able to find the food when the task stimuli held a causal relation (i.e. weight indicates the hidden food). Interestingly, only one of the naïve subjects solved the task when the task elements held an arbitrary relation (i.e. certain visual pattern indicates food). Our results confirm previous findings that apes perform better in problems grounded on causal compared to arbitrary relations. Am. J. Primatol. 73:323–334, 2011. © 2010 Wiley‐Liss, Inc.
Quantitative assessment of interproximal wear facet outlines for the association of isolated molars
Authors: Benazzi Stefano , Fiorenza Luca , Katina Stanislav , Bruner Emiliano , Kullmer Ottmar
Published: November 2010

The determination of the minimum number of individuals can be very challenging, especially in an assemblage of fragmentary bones and isolated teeth. Similarities in tooth morphology, degree of wear, and interproximal wear facets (IPWF) are generally used to associate isolated teeth qualitatively. However, no quantitative method has yet been established for an objective identification and matching of isolated tooth crowns. In this study, we analyze the IPWF morphology of adjacent mandibular molars (17 M1/M2 pairs), applying both qualitative and quantitative methods to test a reproducible approach for crown association. The surfaces of distal (for M1) and mesial (for M2) IPWF were surface‐scanned and digitally selected. Three‐dimensional (3D) and two‐dimensional (2D) outlines of IPWF were analyzed using elliptic Fourier analysis (EFA) and geometric morphometrics methods (GMM). Additionally, teeth were qualitatively associated by visual evaluation of the IPWF outline and by physical matching. Unsatisfactory results with less than 50% of tooth pairs correctly associated were obtained by using both methods, shape analysis (digital approach) and the visual evaluation (qualitative assessment) of the IPWF outline. The physical matching of the crowns showed highly variable accuracy ranging between 53% and 77%. The quantitative form‐space analysis of 2D IPWF outlines provided the best results (82% of correctly associated teeth), but no statistically significant differences were recorded when compared with the manual matching. Since three tooth pairs out of 17 could not be quantitatively associated, we suggest that the quantitative analysis of IPWF should be used only in addition with other approaches.Am J Phys Anthropol, 2011. © 2010 Wiley‐Liss, Inc.
Assessment of Hydroxypropyl Methylcellulose, Propylene Glycol, Polysorbate 80, and Hydroxypropyl‐β‐Cyclodextrin for use in developmental and reproductive toxicology studies
Authors: Enright Brian P. , McIntyre Barry S. , Thackaberry Evan A. , Treinen Kimberley A. , Kopytek Stephan J.
Published: November 2010

BACKGROUND: A series of studies were conducted to assess Polysorbate 80 (PS80), Propylene Glycol (PG), and Hydroxypropyl‐β‐Cyclodextrin (HPβCD), when compared with Hydroxypropyl Methylcellulose (MC) in developmental and reproductive toxicology (DART) studies. METHODS: In the rat fertility study, 20 mg/kg MC, 10 mg/kg PS80, 1,000 mg/kg PG, 500 mg/kg HPβCD or 1,000 mg/kg HPβCD were administered orally before/during mating, and on gestation Day (GD) 0–7, followed by an assessment of embryonic development on GD 14. In the rat and rabbit teratology studies, the doses of MC, PS80, PG, and HPβCD were the same as those in the fertility study. In these teratology studies, pregnant females were dosed during the period of organogenesis, followed by an assessment of fetal external, visceral, and skeletal development. RESULTS: In the rat fertility and rat teratology studies, PS80, PG, and HPβCD did not exhibit toxicity, when compared with MC. Similarly, in the rabbit teratology study, there was no PS80 or PG‐related toxicity, when compared with MC. However, individual rabbits in the 500 and 1,000 mg/kg HPβCD groups exhibited maternal toxicity, which included stool findings, decreased food consumption, and body weight gain. Furthermore, one rabbit each in the 500 and 1,000 mg/kg HPβCD groups exhibited evidence of abortion, which was considered secondary to maternal toxicity. CONCLUSIONS: Although HPβCD was not well tolerated in rabbits at doses of 500 and 1,000 mg/kg, PS80 and PG were comparable to MC and should be considered for use in developmental and reproductive toxicology studies. Birth Defects Res (Part B) 89:504–516,2010. © 2010 Wiley‐Liss, Inc.
Functional anatomy of the mandibular nerve: Consequences of nerve injury and entrapment
Authors: Piagkou Maria , Demesticha Theano , Skandalakis Panayiotis , Johnson Elizabeth O.
Published: November 2010

Various anatomic structures including bone, muscle, or fibrous bands may entrap and potentially compress branches of the mandibular nerve (MN). The infratemporal fossa is a common location for MN compression and one of the most difficult regions of the skull to access surgically. Other potential sites for entrapment of the MN and its branches include, a totally or partially ossified pterygospinous or pterygoalar ligament, a large lamina of the lateral plate of the pterygoid process, the medial fibers of the lower belly of the lateral pterygoid muscle and the inner fibers of the medial pterygoid muscle. The clinical consequences of MN entrapment are dependent upon which branches are compressed. Compression of the MN motor branches can lead to paresis or weakness in the innervated muscles, whereas compression of the sensory branches can provoke neuralgia or paresthesia. Compression of one of the major branches of the MN, the lingual nerve (LN), is associated with numbness, hypoesthesia, or even anesthesia of the tongue, loss of taste in the anterior two thirds of the tongue, anesthesia of the lingual gums, pain, and speech articulation disorders. The aim of this article is to review, the anatomy of the MN and its major branches with relation to their vulnerability to entrapment. Because the LN expresses an increased vulnerability to entrapment neuropathies as a result of its anatomical location, frequent variations, as well as from irregular osseous, fibrous, or muscular irregularities in the region of the infratemporal fossa, particular emphasis is placed on the LN. Clin. Anat. 24:143–150, 2011. © 2010 Wiley‐Liss, Inc.
1‐Cyclohexyl‐4‐(4‐arylcyclohexyl)piperazines: Mixed σ and Human Δ8–Δ7 Sterol Isomerase Ligands with Antiproliferative and P‐Glycoprotein Inhibitory Activity
Authors: Abate Carmen , Niso Mauro , Contino Marialessandra , Colabufo Nicola Antonio , Ferorelli Savina , Perrone Roberto , Berardi Francesco
Published: November 2010

Many new chemotherapeutic agents are under preclinical investigation and, despite efforts to more selectively target cancer cells, limitations such as toxicity and inherent resistance are often encountered. Therefore, alternative strategies are needed to treat cancer and overcome such limitations. We describe novel cyclohexylpiperazine derivatives, designed as mixed affinity ligands for sigma (σ) receptors and human Δ8–Δ7 sterol isomerase (HSI) ligands, which also exhibit P‐glycoprotein (P‐gp) inhibitory activity, with the aim of exploiting the antiproliferative effects mediated by σ and HSI sites while overcoming P‐gp‐mediated resistance. All of the compounds displayed high affinities for σ receptors and HSI sites, P‐gp inhibitory activity, and σ2 receptor agonist antiproliferative activity. Antiproliferative activity was also tested in PC‐3 cells to establish σ1 and HSI contribution. Compound cis‐11, which displayed the best antiproliferative and P‐gp inhibitory activities, was co‐administered with 0.1 μM doxorubicin in MDCK‐MDR1 cells. Compound cis‐11 caused 70 % and 90 % cell death when co‐administered at 30 μM and 50 μm, respectively. When administered alone, cis‐11 resulted in 50 % cell death, demonstrating its single agent antitumor properties in a tumor cell line overexpressing P‐gp.
Motile ciliary microorganisms in peritoneal fluid
Authors: Vila Michael , Thompson Karen , Erdem Guliz
Published: November 2010

We report a patient with chronic renal failure and ciliocytophthoria or “detached ciliary tufts” identified from her peritoneal fluid. The recognition of these rare structures is critical to avoid misdiagnosing a presumed protozoan infection and embarking on further costly investigations and unnecessary treatments. Diagn. Cytopathol. 2011. © 2010 Wiley‐Liss, Inc.
Cytology‐based gene mutation tests to predict response to anti‐epidermal growth factor receptor therapy: A review
Authors: Malapelle Umberto , Bellevicine Claudio , Zeppa Pio , Palombini Lucio , Troncone Giancarlo
Published: November 2010

Recent therapeutic progresses in nonsmall cell lung cancer (NSCLC) and in colorectal cancer (CRC) are based on agents that specifically target the epidermal growth factor receptor (EGFR). To identify the patients most likely to benefit from such therapies, EGFR or KRAS gene mutation tests are mandatory, respectively, in NSCLC and in CRC. In patients with locally advanced or metastatic disease, exploiting cytological samples for these tests avoids not curative surgery. Here, we review the studies that have applied gene mutation assays on cytological samples of NSCLC and CRC to select patients for anti‐EGFR therapy. We argue that the standard of quality of gene mutation tests on cytological samples is closely dependent on the extent of the cytopathologist's involvement. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.
The prevalence of abnormal cervical cytology in women with systemic lupus erythematosus
Authors: AbdullGaffar Badr , AlSaleh Jamal , Hattawi Hussain
Published: November 2010

To compare the frequency of abnormal cervical cytology in women with systemic lupus erythematosus (SLE) with that of healthy women without connective tissue diseases by using ThinPrep® liquid based Pap TestsTM. A retrospective case‐control study over 2 years was conducted. The cases included all women with SLE who had Pap tests during their treatment period. The control group included all women without SLE or other connective tissue diseases (CTDs) that had routine Pap tests in the same period. The age and demographic features were adjusted and matched for both groups. Statistical analysis included Chi‐Square test and Fischer exact test. The SLE group (n= 55) showed significantly (P < 0.05) more abnormal cervical squamous epithelial abnormalities [14 positive cases (25.4%) than the controls (n = 8,175, with 285 positive cases (3.5%)]. Women with SLE had statistically significant higher frequency and prevalence of squamous intraepithelial lesions than women without SLE of similar age and demographic background. The data suggested that women with SLE might benefit from more frequent cervical cytology screening. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.
Decoy cells and malignant cells coexisting in the urine from a transplant recipient with BK virus nephropathy and bladder adenocarcinoma
Authors: Galed‐Placed Ignacio , Valbuena‐Ruvira Luis
Published: November 2010

The search for decoy cells (DC) in urine is widely used as screening for BK virus (BKV) reactivation in transplant recipients. BKV cytopathic effect of DC must not be confused with high‐grade urothelial carcinoma. This report presents a case of coexistence of DC and malignant cells in the urine from a transplant recipient with BKV‐associated nephropathy (BKVN) and bladder adenocarcinoma.

A 38‐year‐old female with type 1 diabetes mellitus and end‐stage renal disease underwent a simultaneous pancreas and kidney transplant. Four years post‐transplantation, BK virus studies were performed for renal dysfunction. Isolated DC and DC in casts were identified in urine. Also, the tests for BKV DNA were positive in serum and renal allograft biopsy. BKVN was treatment‐resistant and the patient returned to hemodialysis. A kidney transplant nephrectomy was performed 2 years later. The next urine cytology showed, in addition to DC, other distinct cells with nuclear atypia highly suggestive of malignancy. Some cells showed both, malignant and DC features. A bladder adenocarcinoma was diagnosed on biopsy and BKV proteins were demonstrated on tumor cells, supporting a possible role for BKV in the oncogenic pathway in this clinical setting.

The presence of DC in the urine from a transplant recipient is the hallmark of BKV activation, but it does not exclude the existence of carcinoma. Furthermore, the presence of highly atypical cells should raise, not eliminate, the possibility of neoplastic transformation of the bladder. Diagn. Cytopathol. 2011. © 2010 Wiley Periodicals, Inc.
Contribution of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring
Authors: Wang J.‐S. , Tu S.‐T. , Lee I.‐T. , Lin S.‐D. , Lin S.‐Y. , Su S.‐L. , Lee W.‐J. , Sheu Wayne H.‐H.
Published: November 2010

Background

Previous studies examining the contributions of fasting glucose (FG) and postprandial glucose (PPG) to glycated haemoglobin ($\hbox{HbA}_{{\rm 1c}}$) have yielded conflicting results. We aimed to clarify the contributions of PPG to hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring.

Methods

Continuous glucose monitoring was conducted in 121 non‐insulin‐using type 2 diabetic outpatients, who were divided into five groups according to quintiles of $\hbox{HbA}_{{\rm 1c}}$ (ranging from 5.7 to 12.7%). Glucose area under the curve (AUC) above a glucose value of 5.5 mmol/L 24 or 4 h after meals was defined as $\hbox{AUC}_{{\rm total}}$. Glucose AUC above FG or preprandial glucose levels was defined as $\hbox{AUC}_{{\rm PPG}}$. The contribution of PPG to hyperglycaemia was calculated as ($\hbox{AUC}_{{\rm PPG}}$/$\hbox{AUC}_{{\rm total}}$) × 100%. The contribution of FG or preprandial glucose was calculated as [($\hbox{AUC}_{{\rm total}} -$ $\hbox{AUC}_{{\rm PPG}}$)/$\hbox{AUC}_{{\rm total}}$] × 100%.

Results

The contribution of PPG to either 24‐h hyperglycaemia or 4‐h hyperglycaemia after meals was significantly higher than FG and preprandial glucose in the lowest quintile of $\hbox{HbA}_{{\rm 1c}}$ (both p < 0.001). However, no difference was observed in the other four quintiles. Peak PPG and glucose excursions were higher after breakfast than those after lunch and dinner (p < 0.01 for all comparisons).

Conclusions

In Asian patients with type 2 diabetes, PPG 24 and 4 h after meals was a predominant contributor to excess hyperglycaemia in well‐controlled patients and was equally important as FG or preprandial glucose in moderately to poorly controlled patients with mean $\hbox{HbA}_{{\rm 1c}}$ up to 10%. Copyright © 2010 John Wiley & Sons, Ltd.
Primer and interviews: Molecular mechanisms of morphological evolution
Authors: Kiefer Julie C.
Published: November 2010

The beauty of the developing embryo, and the awe that it inspires, lure many scientists into the field of developmental biology. What compels cells to divide, migrate, and morph into a being with a complex body plan? Evolutionary developmental biologists hold similar fascinations, with dynamics that take place on a grander timescale. How do phenotypic traits diverge over evolutionary time? This primer illustrates how a deep understanding of the basic principles that underlie developmental biology have changed how scientists think about the evolution of body form. The primer culminates in a conversation with David Stern, PhD, and Michael Shapiro, PhD, who discuss current topics in morphological evolution, why the field should be of interest to classic developmental biologists, and what lies ahead. Developmental Dynamics 239:3497–3505, 2010. © 2010 Wiley‐Liss, Inc.
Tissue‐ and development‐dependent expression of the small GTPase Arf6 in mice
Authors: Akiyama Masahiro , Zhou Miao , Sugimoto Rika , Hongu Tsunaki , Furuya Momoko , Funakoshi Yuji , Kato Mitsuyasu , Hasegawa Hiroshi , Kanaho Yasunori
Published: November 2010

The small GTPase Arf6 is a member of the Arf (ADP‐ribosylation factor) family. Although the function of Arf6 has been heavily studied at the cellular level, its physiological function at the whole animal level is largely unknown. In this study, we examined both the tissue distribution and developmental timing of Arf6 expression in wild type mice to obtain valuable information to speculate on the physiological function of Arf6. Western blot analysis using anti‐Arf6 antibody revealed that Arf6 was ubiquitously expressed with its developmental timing differing in a tissue‐specific manner. These results were supported by Arf6 mRNA in situ hybridization experiments, which showed that Arf6 was highly expressed in the polarized epithelial cells and embryonic mesenchymal cells of most tissues in a temporally dependent manner. Taken in toto, our results suggest that the expression of Arf6 in mouse tissues is precisely regulated in a development‐ and tissue‐dependent manner. Developmental Dynamics 239:3416–3435, 2010. © 2010 Wiley‐Liss, Inc.
Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto's thyroiditis
Authors: Kim Kyung Won , Park Young Joo , Kim Eun Hye , Park So Yeon , Park Do Joong , Ahn Soon‐Hyun , Park Do Joon , Jang Hak C. , Cho Bo Youn
Published: November 2010

Background.

Hashimoto's thyroiditis (HT) and higher levels of thyroid‐stimulating hormone (TSH) have been proposed as risk factors for papillary thyroid cancer (PTC), but this issue is still being debated. The purpose of this study was whether HT was related to the risk of PTC over TSH.

Methods.

We enrolled 1329 patients (1028 with PTC, 52 with follicular thyroid cancer, and 249 with benign disease) of 1490 patients who underwent thyroidectomy.

Results.

The TSH concentration was not different among patients with PTC or benign disease. Our study showed that men (odds ratio [OR] = 1.54; p = .049) and the presence of HT (OR = 2.96; p <.001) increased the risk of PTC. Moreover, HT was associated with multifocal cancer (p = .005) and smaller tumor size (p = .031), but it did not influence the extrathyroidal invasion or nodal metastasis.

Conclusion.

Clinicians who deal with thyroid nodules should pay particular attention to HT because it is a stronger predictor for PTC than other risk factors. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland—A review of current recommendations
Authors: O'Hara James , Ferlito Alfio , Takes Robert P. , Rinaldo Alessandra , Strojan Primož , Shaha Ashok R. , Rodrigo Juan P. , Paleri Vinidh
Published: November 2010

Cutaneous squamous cell carcinoma (SCC) of the head and neck may metastasize in up to 5% of patients, with the parotid lymph nodes the most frequent site for spread. Metastases frequently show delayed presentation after the primary cancer had been treated. The optimum treatment should be surgery followed by adjuvant radiotherapy, with an appropriate parotidectomy, and preservation of the facial nerve if not involved by tumor and treatment to the neck. In a clinically N0 neck, levels I to III should be cleared for facial primaries, levels II to III for anterior scalp and external ear primaries, and levels II to V for posterior scalp primaries. Approximate 5‐year disease‐specific survival (DSS) after treatment was 70% to 75%. Patients with immunosuppression, in particular transplant recipients, are at high risk of developing aggressive metastatic cutaneous SCC. Modifications of the staging systems have demonstrated the prognostic benefits of accurately staging parotid and/or neck nodal disease. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Nonsurgical management of oropharyngeal, laryngeal, and hypopharyngeal cancer: The Fox Chase Cancer Center experience
Authors: Andrews Genevieve , Lango Miriam , Cohen Roger , Feigenberg Steven , Burtness Barbara , Mehra Ranee , Ahmed Sidrah , Nicolaou Nicos , Gaughan John , Ridge John A.
Published: November 2010

Background.

Oropharyngeal, laryngeal, and hypopharyngeal cancer treatment has changed at our institution, but survival outcomes have not been evaluated.

Methods.

We approached the evaluation by a retrospective single‐institution cohort study.

Results.

Review of 180 patient records from 1993 to 2004 revealed that the number of patients with oropharyngeal cancer treated nearly doubled, whereas the number of patients with laryngeal and hypopharyngeal cancers declined (p = .006). Since 2000, concurrent chemotherapeutic regimens rather than radiation alone became the dominant treatment approach, with associated improvements in recurrence‐free and overall survival (p = .009 and p = .006, respectively). Stratification by tumor site, however, revealed the survival of patients with oropharyngeal cancer improved markedly, whereas the survival of patients with laryngeal cancer did not change. In the multivariate analysis, T classification (p = .0001) and chemotherapy use (p = .0001) were associated with improved survival. The recurrence‐free survival of nonsmokers was better than that for former or current smokers (p = .01), but was accounted for by earlier T classification on presentation in the multivariate analysis (p = .0001). The predominant initial site of failure remained at the primary site for oropharyngeal cancer (14 of 17 relapses or 82%), but not laryngeal cancer (3 of 7 relapses or 42%). As a result, an increasing number of patients with recurrent oropharyngeal cancer, and a decreasing number of recurrent laryngeal cancer patients were evaluated for salvage surgery. Patients with oropharyngeal recurrences, however, were less likely to undergo surgery with curative intent (p = .02) and were less likely to achieve locoregional control after disease recurrence.

Conclusions.

The survival of patients with oropharyngeal and hypopharyngeal cancers treated at our institution has improved over the last 15 years, which is likely related to changes in treatment and tumor biology. The improvement was not observed in patients with laryngeal cancer. A subset of patients with oropharyngeal cancer remain subject to local failure and disease‐related death. © 2010 Wiley Periodicals, Inc. Head Neck 33:1433–1440, 2010
Energy partitioning scheme based on self‐consistent method for subsystems: Populational space approach
Authors: De Silva Piotr , Korchowiec Jacek
Published: November 2010

The refinement of the previously proposed energy partitioning scheme, self‐consistent charge and configuration method for subsystems (Korchowiec and Uchimaru, J Chem Phys 2000, 112, 1623), is proposed. Our new realization takes rigorously into account all the interactions between subsystems and guarantees proper symmetry of the intermediate wavefunctions. In addition, the scheme is supplemented with natural orbitals for chemical valence to trace the charge reorganization during polarization and charge transfer steps. The water dimer and ammonia borane are used to illustrate the proposed formalism. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
HB‐EGF synthesis and release induced by cholesterol depletion of human epidermal keratinocytes is controlled by extracellular atp and involves both p38 and ERK1/2 signaling pathways
Authors: Giltaire Séverine , Lambert Sylviane , Poumay Yves
Published: November 2010

The heparin‐binding EGF‐like growth factor (HB‐EGF) is an autocrine/paracrine keratinocyte growth factor, which binds to the epidermal growth factor (EGF) receptor family and plays a critical role during the re‐epithelialization of cutaneous wound by stimulating the keratinocytes proliferation and migration. In this study, cellular stressing condition in autocrine cultures of human keratinocytes was induced by cholesterol depletion using methyl‐beta‐cyclodextrin (MβCD). MβCD treatment induces the expression and the release of HB‐EGF. By analysis of the culture media, large amounts of cellular ATP were measured particularly after 1 h of MβCD treatment. To investigate whether ATP contributes to the expression of HB‐EGF, the nonhydrolyzable ATP analogue, ATP‐γ‐S, was used to mimic the extracellular ATP released. We report that keratinocytes stimulated with ATP‐γ‐S induce HB‐EGF expression and activate EGFR and ERK1/2. Using an antagonist of P2 purinergic receptors, we demonstrate that HB‐EGF synthesis induced by lipid rafts disruption is dependent on ATP interaction with P2 purinergic receptors. Moreover, our data suggest that both MAPKs p38 and ERK1/2 are involved together or independently in the regulation of HB‐EGF gene expression. These findings provide new insight into the signaling pathway by which HB‐EGF is expressed after lipid rafts disruption. In summary, after lipid raft disruption, keratinocytes release large amount of extracellular ATP. ATP induces HB‐EGF synthesis and release by interacting with the P2 purinergic receptor and through p38 and ERK1/2 signaling in response to a challenging environment. A release of ATP acts as an early stress response in keratinocytes. J. Cell. Physiol. 226: 1651–1659, 2011. © 2011 Wiley‐Liss, Inc.