bluuebunny/crossref_metadata_2025 huggingface dataset:
PAX8 Expression Variability in Cerebellar Hemangioblastoma: Case Series and Review of the Literature
Authors: Eichberg Daniel G. , Buttrick Simon , White Kyle , Gultekin Sakir H. , Komotar Ricardo J.
Published: April 2018

Hemangioblastomas are benign tumors of undetermined origin, and account for up to 2.5% of all intracranial tumors. They may occur either sporadically or as a manifestation of von Hippel-Lindau (VHL) syndrome. Central nervous system (CNS) hemangioblastomas are pathologically diagnosed by gross and microscopic morphology, with further support of the diagnosis conferred by a characteristic immunohistochemistry profile including PAX8 negativity. Although renal hemangioblastomas have previously been reported to be PAX8 positive, CNS hemangioblastoma positive PAX8 expression has never been reported. We reviewed 11 cases of cerebellar hemangioblastoma from our institution over a 7-year period (2010 to 2017). Tissue was stained for PAX8 to determine immunohistochemical labeling. Of 11 reviewed cases of cerebellar hemangioblastoma, 7 exhibited PAX8 immunohistochemical expression. A review of the literature found no previously reported cases of positive PAX8 labeling in cerebellar hemangiomas. PAX8 negativity is not as specific for cerebellar hemangioblastoma as previously thought, and caution must be used when relying solely on a panel of PAX2, PAX8, and inhibin A for pathologic diagnosis.
Efficacy of GATA3 Versus BRST2 for the Identification of Metastatic Breast Carcinoma in the Upper GI Tract: Which Performs Better?
Authors: Salagean Diana , Streutker Catherine , Faragalla Hala , Jakate Kiran
Published: April 2018

Distinguishing primary diffuse-type gastric carcinoma (PDGC) versus gastric involvement by metastatic breast carcinoma (mBC), particularly the lobular subtype, is difficult on histology alone. Both can appear morphologically similar. GATA3, a novel transcription factor, is used in certain scenarios as an immunohistochemical marker of breast origin. Our objective was to investigate the efficacy of GATA3 in differentiating PDGC and mBC and how it compares to another breast marker, BRST2. We retrospectively stained 40 cases of PDGC and 10 control cases of mBC from upper gastrointestinal tract specimens for antibodies: GATA3, BRST2, CDX2, and estrogen receptor. Staining of tumor cells was semiquantified with a modified Allred score. GATA3 and BRST2 were positive in 17.5% and 12.5% of PDGC cases, respectively, and in 100% of mBC cases. Allred scores for GATA3 were significantly greater in mBC cases compared with PDGC (P=0.001). Allred scores were not significantly different for BRST2 due to low levels of staining in mBC cases. Although sensitivity and specificity were similar, differences in staining between PDGC and mBC were more decisive for GATA3 versus BRST2 and thus easier to interpret. In addition, 50% of PDGC cases were positive for CDX2 and none for estrogen receptor. Overall, our results show that GATA3 can reliably and correctly identify cases of mBC to the upper gastrointestinal tract. However, because a minority of PDGC were positive for GATA3, it should still be used within an antibody panel to resolve this diagnostic dilemma.
Cooperation of Indian Hedgehog and Vascular Endothelial Growth Factor in Tumor Angiogenesis and Growth in Human Hepatocellular Carcinomas, an Immunohistochemical Study
Authors: Li Yang , Liu Yang , Wang Guangxi , Wang Yuxiang , Guo Limei
Published: April 2018

The Hedgehog pathway was recently shown to be involved in vascular development and neovascularization in human embryogenesis and disease. However, the role of Hedgehog pathway in modulating tumor angiogenesis is still unexplored. In the current study, we investigated the expression of Indian Hedgehog (Ihh) and vascular endothelial cell growth factor (VEGF) in human hepatocellular carcinomas (HCCs) with immunohistochemical staining and compared the immunoreaction data with various clinicopathologic characteristics. Immunoreactivity of Ihh and VEGF proteins was observed in 61.5% (56/91) and 64.5% (59/91) cases of HCC tumor tissues, respectively, which was considerably higher than the adjacent nonmalignant tissues. Ihh protein was observed predominantly in the cytoplasm of the tumor cells with a staining pattern of which was sparse and dot-like, or circular around the cell membrane. VEGF protein was expressed heterogenously in the cytoplasm in tumor cells and was negative in peritumoral areas in all cases. CD34 showed diffuse staining in the tumor parenchyma in most HCC specimens. The association of expression of Ihh and VEGF with tumor size was statistically significant (P<0.05), but there was no significant association with other clinicopathologic parameters. Moreover, there was a significant association of the expressions of Ihh and VEGF proteins in HCC (r=0.6, P<0.0001), and of Ihh and CD34 staining (r=0.261, P=0.012). Our findings suggest that Ihh is involved in the development of HCC. These findings are also consistent with the concept that cooperation of Ihh and VEGF modulate HCC tumor angiogenesis and growth.
Clonal Evolution in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System
Authors: Garcia-Reyero Julia , Martinez Magunacelaya Nerea , Gonzalez Pereña Ainara , Marcos Gonzalez Sara , Teran-Villagra Nuria , Azueta Ainara , Batlle Ana , Gonzalez de Villambrosia Sonia , Revert Arce Jose , Montes-Moreno Santiago
Published: April 2018

Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is an aggressive subtype of DLBCL with characteristic clinicopathologic features. Relapse outside the CNS involving extranodal locations has been found in a fraction of cases (16%). Here we describe a case of DLBCL arising in the CNS that relapsed 18 months after the initial diagnosis in the testis and bilateral adrenal glands. Both tumors showed equivalent morphology, phenotype, cytogenetic features, and clonal relationship. Somatic mutation analysis by next generation sequencing demonstrated MYD88L265P mutation in both tumors and de novo CD79B Y196S mutation exclusive to the relapse. The pattern of mutations suggest that the 2 tumors might have evolved from a common progenitor clone with MYD88L265P being the founder mutation. A meta-analysis of the literature shows a significantly high frequency of concurrent MYD88L265P and CD79B ITAM mutations in primary CNS lymphoma and testicular DLBCL, underscoring the role of B cell receptor and nuclear factor kB activation by somatic mutations in these lymphomas that colonize immune-privileged sites. In summary, here we illustrate that targeted next generation sequencing for the detection of hot spot somatic mutations in relapsed DLBCL is useful to confirm ABC phenotype and discovers relevant information that might influence therapeutic decision.
Identification of “Double Hit” Lymphomas Using Updated WHO Criteria: Insights From Routine MYC Immunohistochemistry in 272 Consecutive Cases of Aggressive B-Cell Lymphomas
Authors: Sakr Hany , Cook James R.
Published: April 2018

Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations (“double hit” lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification. The diagnostic yield of MYC immunohistochemistry (IHC) for the identification of DHL is currently uncertain. MYC IHC was performed in 272 consecutive cases of aggressive B-cell lymphoma, and results correlated with fluorescence in situ hybridization (FISH) for MYC translocations. Among 156 patients with IHC and FISH data, MYC IHC identified MYC translocations with 89% sensitivity, 38% specificity, 92% negative predictive value, and 29% positive predictive value. Three of 15 (20%) of DHL were MYC IHC negative. One case contained a MYC translocation detectable IGH/MYC fusion probes but not MYC break-apart probes. A subset of DHL lack MYC protein expression, and recognition of this subset of cases requires FISH testing. These results provide an appropriate diagnostic algorithm for implementation of 2016 WHO diagnostic criteria.
The Expression of TMEM74 in Liver Cancer and Lung Cancer Correlating With Survival Outcomes
Authors: Sun Yizhe , Deng Jinhai , Xia Peng , Chen Wei , Wang Lu
Published: April 2018

Transmembrane 74 (TMEM74), a transmembrane protein as an autophagy inducer, has been proven to promote tumor cell (including cervical cancer cell line HeLa and hepatic carcinoma cell line HepG2) proliferation by triggering autophagy. To further determine the role of TMEM74 in cancer, we performed immunohistochemical staining on tissue array, and the results showed that TMEM74 exhibited significantly higher expression in several tumor types, especially in hepatocellular carcinoma, lung adenocarcinoma, and squamous carcinoma. Furthermore, higher expression level of TMEM74 in HepG2, A549, and H1299 cell lines were also detected compared with the corresponding normal cell lines, as detected by western blot. Meanwhile, further analysis showed that the levels of TMEM74 expression were closely correlated to survival period of patients—the higher expression of TMEM74 was correlated with shorter survival period. Moreover, the in vitro experiments showed that overexpression of TMEM74 led to accelerated proliferation of A549 and H1299 cells, while knockdown of TMEM74 reversed the outcomes. In conclusion, the results suggested that TMEM74 acts as an oncogene and a potential diagnostic marker and a therapeutic target for liver cancer and lung cancer.
Immunohistochemical Analysis of Endothelial Cells in Vascular Transformation of Lymph Node Sinuses: Vascular or Lymphatic Differentiation?
Authors: Basha Basma M. , Hsi Eric D.
Published: April 2018

Introduction:

Vascular transformation of sinuses (VTS) is an uncommon and benign lesion, defined by conversion of lymph node sinuses into complex, anatomizing and endothelial-lined channels. Despite the name of VTS, which implies a change in differentiation from lymphatic to vascular endothelium, very few studies have systematically examined VTS with modern immunohistochemical markers commonly used in clinical laboratories. It is unclear whether endothelial cells in VTS display pure vascular or lymphatic differentiation, or both.

Design:

A total of 11 cases with a diagnosis of VTS (identified in the tissue archives of the Cleveland Clinic between 1992 and 2015) were reviewed and confirmed. Twenty cases of benign lymph nodes without specific diagnoses were used as control tissues. Immunohistochemical stains were performed on formalin-fixed, paraffin-embedded lymph node tissue using an automated immunohistochemistry platform with antibodies against CD31, CD34, D2-40, and ERG. Positivity in the VTS lesions was defined as distinct expression in the appropriate cell compartment in ≥20% of cells. In control cases, staining was evaluated in both vascular and lymphatic channels—vascular structures were identified by presence of red cells or well-formed vascular walls and lymphatics by anatomic location and absence of vascular features.

Results:

In the VTS lesions, D2-40 expression was absent in the lesional endothelial cells of 5/11 (45%) cases. In the cases lacking D240 expression, uninvolved lymphatic endothelium maintained expression. CD34 expression was also seen in 6/11 (54%), CD31 was seen in 10/11 (90%), and ERG expression was seen in all cases. In all the control cases, D240 expression was exclusively seen in lymphatic endothelial cells and not seen in vascular endothelial cells (eg, vascular channels in the hilum). CD34 was weakly positive in the lymphatic endothelium of only 7/20 (35%) control cases, but expressed in 20/20 (100%) control cases in the vascular endothelium. 20/20 (100%) of control cases showed expression of CD31 and ERG in both vascular and lymphatic endothelium.

Conclusion:

VTS lesional endothelial cells demonstrate patterns of vascular markers that show mixed blood vascular and lymphatic features. There appears to be a degree of alignment toward endothelial differentiation with decreased expression of D2-40 in some cases.
Ovarian Clear Cell Carcinoma: From Morphology to Molecular Biology
Authors: Improta Giuseppina , Pettinato Angela , Høgdall Estrid , Santeusanio Giuseppe , Vatrano Simona , Fraggetta Filippo , Zannoni Gian Franco
Published: April 2018

Ovarian clear cell carcinoma (oCCC) is a distinctive subtype of ovarian carcinoma, with peculiar genetic and environmental risk factors, precursor lesions, molecular events during oncogenesis, patterns of spread, and response to treatment. Because of low response to chemotherapy and poor prognosis in advanced stages, there is growing interest in investigating the molecular pathways involved in oCCC development, in order to individualize novel/molecular targeted therapies. Until now, the main molecular genetic changes associated with oCCC remain to be identified, and, although several molecular changes have been reported in clear cell tumors, most studies have analyzed a limited number of cases; therefore, the true prevalence of those changes is not known. The present review will present the clinicopathologic features of oCCC, from morphology to molecular biology, discussing the diagnostic and treatment challenges of this intriguing ovarian carcinoma.
Human Endometriosis Tissue Microarray Reveals Site-specific Expression of Estrogen Receptors, Progesterone Receptor, and Ki67
Authors: Colón-Caraballo Mariano , García Miosotis , Mendoza Adalberto , Flores Idhaliz
Published: April 2018

Most available therapies for endometriosis are hormone-based and generally broadly used without taking into consideration the ovarian hormone receptor expression status. This contrasts strikingly with the standard of care for other hormone-based conditions such as breast cancer. We therefore aimed to characterize the expression of ovarian steroid hormone receptors for estrogen alpha (ESR1), estrogen beta (ESR2), and progesterone (PGR) in different types of endometriotic lesions and eutopic endometrium from women with endometriosis and controls using a tissue microarray (TMA). Nuclear expression levels of the receptors were analyzed by tissue (ie, ectopic vs. eutopic endometrium) and cell type (ie, glands vs. stroma). Ovarian lesions showed the lowest expression of ESR1 and PGR, and the highest expression of ESR2, whereas the fallopian tube lesions showed high expression of the 3 receptors. Differences among endometria included lower expression of ESR1 and higher expression of ESR2 in stroma of proliferative endometrium from patients versus patients, and a trend towards loss of PGR nuclear positivity in proliferative endometrium from patients. The largest ESR2:ESR1 ratios were observed in ovarian lesions and secretory endometrium. The highest proportion of samples with >10% Ki67 positive nuclei was in glands of fallopian tube (54%) and extrapelvic lesions (75%); 60% of glands of secretory endometrium from patients had >10% Ki67 positivity compared with only 15% in controls. Our results provide a better understanding of endometriosis heterogeneity by revealing lesion type-specific differences and case-by-case variability in the expression of ovarian hormone receptors. This knowledge could potentially predict individual responses to hormone therapies, and set the basis for the application of personalized medicine approaches for women with endometriosis.
Utility of Ber-EP4 and MOC-31 in Basaloid Skin Tumor Detection
Authors: Gill Pavandeep , Naugler Christopher , Abi Daoud Marie S.
Published: April 2018

Ber-EP4 has been the traditional immunostain used for the detection of basaloid skin tumors. Recently, MOC-31 has shown be superior to Ber-EP4 in the detection of basosquamous basal cell carcinoma (BCC) and many centers are now using both Ber-EP4 and MOC-31 antibodies together to detect these lesions. The objective of this study was to compare the utility of using both Ber-EP4 and MOC-31 immunostains in the detection of basaloid skin tumors and to better characterize the previously unknown staining properties of MOC-31 in cutaneous lesions. To do this, 76 basaloid skin tumors stained with both Ber-EP4 and MOC-31 were obtained. Diagnoses included basosquamous BCC, Merkel cell carcinoma, adenoid cystic carcinoma, microcystic adnexal carcinoma, sebaceous carcinoma, trichoepithelioma, trichoblastoma, sebaceous adenoma, sebaceoma, and follicular induction overlying dermatofibroma. The distribution and intensity of Ber-EP4 and MOC-31 staining in these lesions was scored. These scores were analyzed using a truth table, χ2 test, and Pearson correlation tests. The overall mean and SD of the scores were also obtained. Overall, we found Ber-EP4 and MOC-31 to be statistically equivalent immunostains for the diagnosis of basaloid skin tumors. We recommend the use of only one of these antibodies and favor MOC-31 for the detection of basaloid skin tumors. We also describe MOC-31 staining properties in different cutaneous lesions.
Hibernoma Mimicking Atypical Lipomatous Tumor
Authors: Al Hmada Youssef , Schaefer Inga-Marie , Fletcher Christopher D.M.
Published: April 2018

Hibernoma is a benign adipocytic tumor with predilection for subcutaneous tissue of the thigh, upper trunk, and neck of middle-aged adults. 11q13 rearrangement resulting in MEN1/AIP codeletion is characteristic. Hibernomas are composed, in varying proportions, of brown fat cells, mature adipocytes, and microvacuolated lipoblast-like cells. Examples containing predominantly multivacuolated lipoblast-like cells are uncommon and distinction from atypical lipomatous tumor (ALT) is important for clinical management. We herein present the clinicopathologic features of 64 hibernomas histologically mimicking ALT. MDM2 and CDK4 immunohistochemistry as well as MDM2 fluorescence in situ hybridization were performed in a subset of cases. Clinical and follow-up information were obtained from referring pathologists. Thirty-four patients were male and 30 female, with a median age of 43 years (range, 24 to 78 y). The tumors were well circumscribed and mostly deeply located (53/64 cases, 83%) with a median tumor size of 12.9 cm (range, 3.5 to 23 cm) and predilection for the thigh (42/64 cases, 66%). Histologically, large cells with prominent lipoblast-like cytoplasmic fatty vacuoles and small central nuclei were present to a prominent degree in all cases, along with mature univacuolated adipocytes and smaller numbers of large, finely vacuolated cells with eosinophilic granular cytoplasm. Nuclear atypia and mitoses were absent. None of the 39 cases tested showed CDK4 and MDM2 overexpression or MDM2 amplification. Follow-up, available for 16/64 cases (median, 47 mo; range, 1 to 165 mo), revealed no recurrences or metastases. Hibernoma mimicking ALT shows predilection for deep soft tissue, especially in the thigh. These tumors behave in a benign manner and MDM2/CDK4 negativity may be useful in excluding ALT.
Wilms Tumor of the Uterus
Authors: Pinto Andre , Huang Marilyn , Castillo Rosa P. , Schlumbrecht Matthew P.
Published: April 2018

Wilms tumor (WT) is an uncommon malignant neoplasm that occurs predominantly in the kidney of pediatric patients; its extrarenal counterpart is exceedingly rare. We present the case of an adult female diagnosed with uterine WT. Following hysterectomy due to a uterine mass, histopathologic examination demonstrated a triphasic malignancy composed of epithelial, stromal, and blastemal elements. The characteristic morphologic features, which were supported by immunohistochemical analysis, were diagnostic of WT of the uterus. A summary of the main clinicopathologic parameters, along with a review of all previously reported cases, are described.
Clinicopathologic Features and Genetic Alterations of a Primary Osteosarcoma of the Uterine Corpus
Authors: Zheng Gang , Richmond Abby , Liu Chengbao , Berrebi Alexander , Pallavajjala Aparna , Haley Lisa , Stone Rebecca L. , McCarthy Edward , Vang Russell , Xing Deyin
Published: April 2018

Primary osteosarcoma (OS) of the uterus is distinctly rare. We report a case of primary uterine OS with pulmonary metastasis in a 74-yr-old woman. Histopathologic features of the uterine tumor were in keeping with a pure chondroblastic OS composed of neoplastic cells with osteoblastic/chondroblastic differentiation and neoplastic bone formation. Despite treatment with Doxorubicin and Olaratumab and later with palliative radiation therapy, the patient died 7 mo after hysterectomy due to multiple distant metastases. A targeted next-generation sequencing assay based on a 637-gene panel was performed to analyze genetic alterations in this highly aggressive tumor, but no somatic mutations that are amenable to targeted therapy were detected. Rather, a 51-nucleotide deletion mutation including partial exon 2 of mediator complex subunit 12 (MED12), a gene commonly mutated in leiomyoma, breast fibroadenoma and phyllodes tumor, was identified. Given the MED12 mutation in this uterine OS, we propose possible mechanisms that account for the origin and development of this tumor.
Biased agonism: the quest for the analgesic holy grail
Authors: Stanczyk M. Alexander , Kandasamy Ram
Published: April 2018

Opioids alleviate pain, but adverse effects severely limit their usefulness. To solve this problem, biased ligands favoring 1 signaling pathway downstream of the μ-opioid receptor over another are being developed. In the target article, the authors synthesize compounds that preferentially activate G-protein or β-arrestin signaling. They find that increased bias towards G-protein signaling produces better antinociception with minimal side effects in mice models. G-protein–biased opioids may provide a safer treatment strategy.
Magnetic Resonance Imaging in Neurocritically Ill Patients: Who Fails and How?
Authors: Kim Joong-Goo , Ko Myung-Ah , Lee Han-Bin , Jeon Sang-Beom
Published: April 2018

Objectives

Performing magnetic resonance imaging (MRI) in neurocritically ill patients is challenging because it often requires sedation and withholding care in the neurological intensive care unit. This study investigated the incidence of and reasons for failed or complicated MRI (MRI-FC) in such patients.

Methods

A consecutive series of 218 neurocritically ill patients who underwent brain MRI were retrospectively evaluated. Failed or complicated MRI included failure to obtain all ordered sequences, unscheduled sedative administration, decrease in oxygen saturation to less than 90%, hypotension (≥40-mm Hg decrease and/or use of inotropic agents), and cardiac or respiratory arrest.

Results

Failed or complicated MRI occurred in 66 patients (30.3%) and included failure to obtain MRI sequences (n = 13), unscheduled use of sedatives (n = 62), oxygen desaturation (n = 9), and hypotension (n = 6). Cardiac or respiratory arrest did not occur. Use of sedative agents while in intensive care (P < 0.01), high Acute Physiology and Chronic Health Evaluation II score (P = 0.031), and low Glasgow Coma Scale score on admission (P = 0.047) were associated with MRI-FC. Scan times were longer (P = 0.004) and Glasgow Coma Scale (P < 0.001) and Richmond Agitation Sedation Scale (P = 0.003) scores were lower (P = 0.004) after imaging in patients with MRI-FC. Previous use of sedative agents was independently associated with MRI-FC (adjusted odds ratio = 3.57, 95% confidence interval = 1.78 to 7.24, P < 0.001).

Conclusions

Failed or complicated MRI was common and was associated with the use of sedative agents, severity of illness, and lower level of consciousness. Studies to ensure effective and safe performance of MRI in neurocritically ill patients are needed.
Utility of Magnetic Resonance Imaging for Predicting Severity of Sciatic Nerve Injury
Authors: Ahlawat Shivani , Belzberg Allan J. , Fayad Laura M.
Published: April 2018

Objective

This study aimed to investigate the diagnostic accuracy of magnetic resonance (MR) imaging for categorizing sciatic peripheral nerve injury (PNI) as high-grade (Sunderland grades IV–V) or low-grade (Sunderland grades I–III) PNI.

Methods

In this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study, consecutive MR imaging of the pelvis and thighs, performed for the evaluation of traumatic sciatic neuropathy, was reviewed for sciatic nerve signal intensity, size, architectural distortion, bulbous enlargement, perineural fibrosis, discontinuity, and muscle denervation changes. Clinical data, electrodiagnostic testing, and surgical history were used to determine PNI grade (high, low). Descriptive and diagnostic performance statistics were applied.

Results

Of 24 patients, there were 12 high-grade and 12 low-grade PNI. There was no significant difference in signal intensity or size between high-grade and low-grade PNI (1.3 ± 0.5 cm vs 0.9 ± 0.3 cm, P = 0.09). The sensitivity and specificity for the presence of individual features in predicting high-grade injury were 83% and 67% for architectural distortion, 58% and 75% for bulbous enlargement, 50% and 83% for perineural fibrosis, 25% and 100% for discontinuity, and 67% and 75% for skeletal muscle denervation changes, respectively. Overall, the sensitivity and specificity of MR imaging for categorizing sciatic PNI as high grade was 75% and 83%, respectively.

Conclusions

The MR characterization of PNI severity remains challenging. Useful features indicative of high-grade PNI include bulbous enlargement, perineural fibrosis, muscle denervation changes, and nerve discontinuity.
Spectral Detector Computed Tomography Pulmonary Angiography: Improved Diagnostic Assessment and Automated Estimation of Window Settings Angiography of Pulmonary Arteries From Novel Spectral Detector Computed Tomography Provides Improved Image Quality if Settings are Adjusted
Authors: Große Hokamp Nils , Kessner Rivka , Van Hedent Steven , Graner Frank Philipp , Gupta Amit , Gilkeson Robert
Published: April 2018

Objective

This study aimed to evaluate image quality (IQ) of virtual monoenergetic images (VMIs) from novel spectral detector computed tomography angiography of the pulmonary arteries and to identify appropriate window settings for each kiloelectron volt level.

Materials

Forty consecutive patients were included in this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant study.

Signal- and contrast-to-noise ratios were calculated within the pulmonary trunk, and pulmonary/lobar/segmental arteries were calculated. The IQ and diagnostic certainty were rated by 2 radiologists on 5-point scales. In addition, they recorded appropriate window settings (center/width) that were linearly modeled against attenuation within the pulmonary trunk to generate generable results.

Results

Signal- and contrast-to-noise ratios, IQ, and diagnostic certainty are significantly increased in low–kiloelectron volt VMIs (≤60 keV). Interrater agreement was excellent (ĸ = 0.89). We developed 2 linear models (R2: 0.91–0.97 and R2: 0.43–0.91, respectively, P ≤ 0.01), that suggest appropriate window settings.

Conclusions

The VMIs from spectral detector computed tomography improve objective and subjective IQ in angiography of the pulmonary arteries, if window settings are adjusted; they can be automatically estimated using reported linear models.
Technical Pitfall in 68Ga–Prostate Specific Membrane Antigen Imaging
Authors: Hod Nir , Anconina Reut , Levin Daniel , Ezroh Kazap Dina , Lantsberg Sophie
Published: April 2018

As with any new molecular imaging modality, accurate characterization of abnormalities on 68Ga-PSMA PET/CT imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants, and potential sources of false imaging findings. Altered biodistribution can have a significant impact on scan interpretation. Presented here is a rare case in which radiopharmaceutical radiolysis occurred causing excessive free 68Ga-citrate showing as an increased vascular activity. As 68Ga-PSMA PET/CT imaging is a relatively new imaging technique, it is important to be aware of such a potential technical pitfall in clinical practice in order to prevent scan misinterpretation.
123I-FP-CIT SPECT and MRI Findings in a Patient With Parkinsonism After Fenpyroximate Intoxication
Authors: Kim Kyeong Joon , Kim Jong-Min , Bae Yun Jung , Song Yoo Sung , Kim Sang Eun
Published: April 2018

Fenpyroximate is a widely used acaricide. Its main action is to inhibit the mitochondrial respiratory chain. Chronic exposure to fenpyroximate is associated with dopaminergic cell loss and parkinsonism; however, to date, there has not been a reported case of parkinsonism as a result of acute fenpyroximate intoxication. Here, we report a 58-year-old man who developed parkinsonism after deliberate fenpyroximate intoxication, but with normal presynaptic 123I-Ioflupane SPECT image.
Automated Reporting of DXA Studies Using a Custom-Built Computer Program
Authors: England Joseph R. , Colletti Patrick M.
Published: April 2018

Dual-energy x-ray absorptiometry (DXA) scans are a critical population health tool and relatively simple to interpret but can be time consuming to report, often requiring manual transfer of bone mineral density and associated statistics into commercially available dictation systems. We describe here a custom-built computer program for automated reporting of DXA scans using Pydicom, an open-source package built in the Python computer language, and regular expressions to mine DICOM tags for patient information and bone mineral density statistics. This program, easy to emulate by any novice computer programmer, has doubled our efficiency at reporting DXA scans and has eliminated dictation errors.
Health Care–Seeking Characteristics of Women With Pelvic Floor Disorders After Obstetric Anal Sphincter Injury
Authors: Pennycuff Jon F. , Karp Deborah R. , Shinnick Julia , Hudson Catherine O. , Northington Gina M.
Published: April 2018

Objectives

Obstetric anal sphincter injury (OASIS) is a potentially serious complication of vaginal delivery and can lead to both short-term and long-term sequelae. This study sought to identify health care seeking patterns of women who developed pelvic floor symptoms including pelvic pain after OASIS. It also identified demographic and clinical factors associated with seeking subspecialty care from a pelvic floor specialist and demographic and clinical factors associated with seeking care for pelvic pain after OASIS.

Methods

This study is a retrospective cohort study of 69 women who developed pelvic floor disorders after OASIS.

Results

For women diagnosed with a pelvic floor symptom, the mean time to follow-up was 2.4 years, the mean number of visits until diagnosis was 2.2 visits, and 2.9 visits were needed for treatment. The most common diagnoses were pelvic pain, lower urinary tract symptoms including incontinence, and defecatory dysfunction. Twenty-five percent of the cohort received treatment from a pelvic floor specialist. These women were more likely to be older and have urinary incontinence. Women with pain were more likely to be seen by a primary care provider and have longer time to diagnosis.

Conclusions

The study showed that multiple visits were needed to both diagnose and treat pelvic floor disorders (PFD) after OASIS. Pelvic pain was the most common primary PFD after OASIS. There should be a high level of suspicion for pelvic floor disorders, especially pain disorders, in women who have sustained a third- or fourth-degree laceration.
Paediatric multiple sclerosis and other acute demyelinating diseases
Authors: Rostásy Kevin , Bajer-Kornek Barbara
Published: April 2018

Purpose of review

Neuroimmunological diseases encompass a wide spectrum of diseases in children. Apart from the discovery of autoantibodies affecting primarily grey matter structures and the improved clinical characterization of rare entities such as N-methyl D-aspartate receptor-R- encephalitis, important strides have also been made in autoimmune-mediated white matter diseases, including paediatric multiple sclerosis (pedMS) and other acute demyelinating syndromes (ADS) often associated with antibodies (abs) against myelin-oligodendrocyte-glycoprotein (MOG). This review will cover findings of recent studies in pedMS, in the emerging field of non-MS acute demyelinating episodes associated with MOG abs and lastly from new imaging techniques such as diffusion tensor imaging (DTI) revealing new insights in the pathogenesis of ADS in children.

Recent findings

The first prospective randomized clinical pedMS trial assessing the clinical and radiological efficacy of fingolimod versus a standard disease-modifying agent has shown clear superiority of fingolimod. The clinical spectrum of MOG-associated diseases has been characterized in more detail revealing clinical subtypes distinct from pedMS. A recent large European study further showed that MOG-associated diseases do not respond to first-line disease-modifying treatment (DMT) in MS but fare better with B-cell modulating therapies including regular intravenous immunoglobulin (IVIG).

Recent findings strongly indicate that in particular in highly active pedMS characterized by new relapses or accrual of new MRI lesions despite first-line DMT treatment should be escalated. Secondly, several studies have shown that MOG-spectrum diseases include children with monophasic and recurrent subtypes other than MS with different clinical, radiological characteristics and treatment challenges.
B cells in multiple sclerosis
Authors: Sospedra Mireia
Published: April 2018

Purpose of review

Although it is becoming increasingly clear that B cells play important roles in multiple sclerosis (MS) pathogenesis, it is incompletely understood how they contribute. The purpose of this review is to provide an overview of the current knowledge about B cells in MS taking into account MS heterogeneity.

Recent findings

The efficacy of B cell-depleting therapies has provided strong evidence for the involvement of these cells in MS pathogenesis. Although pathogenic antibodies were found in some MS patients, the observation that plasma cells and antibodies remain largely unchanged after B-cell depletion suggests that B cells are involved in MS by other mechanisms than antibody production.

MS is an autoimmune disease, in which T and B cells play a crucial role. B cells can be involved in MS by different mechanisms such as presentation of antigens to T cells, transport of antigens from tissues to secondary lymphoid organs, secretion of pro-inflammatory or anti-inflammatory cytokines and in a subgroup of patients also production of pathogenic antibodies. As several B-cell/antibody-directed therapies are available, it is important to understand how these different functions of B cells and antibodies vary among patients in order to identify which could benefit best from the different therapies.
Textural equilibrium melt geometries around tetrakaidecahedral grains
Authors: Rudge John F.
Published: April 2018

In textural equilibrium, partially molten materials minimize the total surface energy bound up in grain boundaries and grain–melt interfaces. Here, numerical calculations of such textural equilibrium geometries are presented for a space-filling tessellation of grains with a tetrakaidecahedral (truncated octahedral) unit cell. Two parameters determine the nature of the geometries: the porosity and the dihedral angle. A variety of distinct melt topologies occur for different combinations of these two parameters, and the boundaries between different topologies have been determined. For small dihedral angles, wetting of grain boundaries occurs once the porosity has exceeded 11%. An exhaustive account is given of the main properties of the geometries: their energy, pressure, mean curvature, contiguity and areas on cross sections and faces. Their effective permeabilities have been calculated, and demonstrate a transition between a quadratic variation with porosity at low porosities to a cubic variation at high porosities.
Impacts of ocean acidification on sea urchin growth across the juvenile to mature adult life-stage transition is mitigated by warming
Authors: Dworjanyn Symon A. , Byrne Maria
Published: April 2018

Understanding how growth trajectories of calcifying invertebrates are affected by changing climate requires acclimation experiments that follow development across life-history transitions. In a long-term acclimation study, the effects of increased acidification and temperature on survival and growth of the tropical sea urchin
Tripneustes gratilla
from the early juvenile (5 mm test diameter—TD) through the developmental transition to the mature adult (60 mm TD) were investigated. Juveniles were reared in a combination of three temperature and three pH/
p
CO
2
treatments, including treatments commensurate with global change projections. Elevated temperature and
p
CO
2
/pH both affected growth, but there was no interaction between these factors. The urchins grew more slowly at pH 7.6, but not at pH 7.8. Slow growth may be influenced by the inability to compensate coelomic fluid acid–base balance at pH 7.6. Growth was faster at +3 and +6°C compared to that in ambient temperature. Acidification and warming had strong and interactive effects on reproductive potential. Warming increased the gonad index, but acidification decreased it. At pH 7.6 there were virtually no gonads in any urchins regardless of temperature. The
T. gratilla
were larger at maturity under combined near-future warming and acidification scenarios (+3°C/pH 7.8). Although the juveniles grew and survived in near-future warming and acidification conditions, chronic exposure to these stressors from an early stage altered allocation to somatic and gonad growth. In the absence of phenotypic adjustment, the interactive effects of warming and acidification on the benthic life phases of sea urchins may compromise reproductive fitness and population maintenance as global climatic change unfolds.
Human, animal and environmental contributors to antibiotic resistance in low-resource settings: integrating behavioural, epidemiological and One Health approaches
Authors: Rousham Emily K. , Unicomb Leanne , Islam Mohammad Aminul
Published: April 2018

Antibiotic resistance (ABR) is recognized as a One Health challenge because of the rapid emergence and dissemination of resistant bacteria and genes among humans, animals and the environment on a global scale. However, there is a paucity of research assessing ABR contemporaneously in humans, animals and the environment in low-resource settings. This critical review seeks to identify the extent of One Health research on ABR in low- and middle-income countries (LMICs). Existing research has highlighted hotspots for environmental contamination; food-animal production systems that are likely to harbour reservoirs or promote transmission of ABR as well as high and increasing human rates of colonization with ABR commensal bacteria such asEscherichia coli. However, very few studies have integrated all three components of the One Health spectrum to understand the dynamics of transmission and the prevalence of community-acquired resistance in humans and animals. Microbiological, epidemiological and social science research is needed at community and population levels across the One Health spectrum in order to fill the large gaps in knowledge of ABR in low-resource settings.
Propagation of information along the cortical hierarchy as a function of attention while reading and listening to stories
Authors: Regev Mor , Simony Erez , Lee Katherine , Tan Kean Ming , Chen Janice , Hasson Uri
Published: April 2018

How does attention route information from sensory to high-order areas as a function of task, within the relatively fixed topology of the brain? In this study, participants were simultaneously presented with two unrelated stories – one spoken and one written – and asked to attend one while ignoring the other. We used fMRI and a novel inter-subject correlation analysis to track the spread of information along the processing hierarchy as a function of task. Processing the unattended spoken (written) information was confined to auditory (visual) cortices. In contrast, attending to the spoken (written) story enhanced the stimulus-selective responses in early sensory regions and allowed it to spread into higher-order areas. Surprisingly, we found that the story-specific spoken (written) responses for the attended story also reached the opposite secondary visual (auditory) regions. These results demonstrate how attention enhances the processing of attended input and allows it to propagate across brain areas.
Spatiotemporal discrimination in attractor networks with short-term synaptic plasticity
Authors: Shlaer Benjamin , Ballintyn Benjamin , Miller Paul
Published: April 2018

We demonstrate the ability of a randomly connected attractor network with dynamic synapses to discriminate between similar sequences containing multiple stimuli and suggest such networks provide a general basis for neural computations in the brain. The network is based on units representing assemblies of pools of neurons, with preferentially strong recurrent excitatory connections within each unit. Such excitatory feedback to a unit can generate bistability, though in many networks only under conditions of net excitatory input from other units. Weak interactions between units leads to a multiplicity of attractor states, within which information can persist beyond stimulus offset. When a new stimulus arrives, the prior state of the network impacts the encoding of the incoming information, with short-term synaptic depression ensuring an itinerancy between sets of active units. We assess the ability of such a network to encode the identity of sequences of stimuli, so as to provide a template for sequence recall, or decisions based on accumulation of evidence. Across a range of parameters, such networks produce the primacy (better final encoding of the earliest stimuli) and recency (better final encoding of the latest stimuli) observed in human recall data and can retain the information needed to make a binary choice based on total number of presentations of a specific stimulus. Similarities and differences in the final states of the network produced by different sequences lead to predictions of specific errors that could arise when an animal or human subject generalizes from training data, when the training data comprises a subset of the entire stimulus repertoire. We suggest that such networks can provide the robust general purpose computational engines needed for us to solve many cognitive tasks.
Historic collections as a tool for assessing the global pollinator crisis
Authors: Bartomeus I. , Stavert J.R. , Ward D. , Aguado O.
Published: April 2018

There is increasing concern about the decline of pollinators worldwide. However, despite reports that pollinator declines are widespread, data are scarce and often geographically and taxonomically biased. These biases limit robust inference about any potential pollinator crisis. Non-structured and opportunistic historical specimen collection data provide the only source of historical information which can serve as a baseline for identifying pollinator declines. Specimens historically collected and preserved in museums not only provide information on where and when species were collected, but also contain other ecological information such as species interactions and morphological traits. Here, we provide a synthesis of how researchers have used historical data to identify long-term changes in biodiversity, species abundances, morphology and pollination services. Despite recent advances, we show that information on the status and trends of most pollinators is absent, but we highlight opportunities and limitations to progress the assessment of pollinator declines globally. Finally, we demonstrate different approaches to analysing museum collection data using two contrasting case studies from distinct geographical regions (New Zealand and Spain) for which long-term pollinator declines have never been assessed. There is immense potential for museum specimens to play a central role in assessing the extent of the global pollination crisis.
Combining Digital Imaging and Genome Wide Association Mapping to Dissect Uncharacterized Traits in Plant/Pathogen Interactions
Authors: Fordyce Rachel F. , Soltis Nicole E. , Caseys Celine , Gwinner Raoni , Corwin Jason A. , Atwell Susana , Copeland Daniel , Feusier Julie , Subedy Anushriya , Eshbaugh Robert , Kliebenstein Daniel J.
Published: April 2018

Plant resistance to generalist pathogens with broad host ranges, such as Botrytis cinerea, is typically quantitative and highly polygenic. Recent studies have begun to elucidate the molecular genetic basis underpinning plant-pathogen interactions using commonly measured traits including lesion size and/or pathogen biomass. Yet with the advent of digital imaging and phenomics, there are a large number of additional resistance traits available to study quantitative resistance. In this study, we used high-throughput digital imaging analysis to investigate previously uncharacterized visual traits of plant-pathogen interactions related disease resistance using the Arabidopsis thaliana/Botrytis cinerea pathosystem. Using a large collection of 75 visual traits collected from every lesion, we focused on lesion color, lesion shape, and lesion size, to test how these aspects of the interaction are genetically related. Using genome wide association (GWA) mapping in A. thaliana, we show that lesion color and shape are genetically separable traits associated with plant-disease resistance. Using defined mutants in 23 candidate genes from the GWA mapping, we could identify and show that novel loci associated with each different plant-pathogen interaction trait, which expands our understanding of the functional mechanisms driving plant disease resistance.

Digital imaging allows the identification of genes controlling novel lesion traits.
Detecting Differential Variable microRNAs via Model-Based Clustering
Authors: Li Xuan , Fu Yuejiao , Wang Xiaogang , DeMeo Dawn L. , Tantisira Kelan , Weiss Scott , Qiu Weiliang
Published: April 2018

Identifying genomic probes (e.g., DNA methylation marks) is becoming a new approach to detect novel genomic risk factors for complex human diseases. The F test is the standard equal-variance test in Statistics. For high-throughput genomic data, the probe-wise F test has been successfully used to detect biologically relevant DNA methylation marks that have different variances between two groups of subjects (e.g., cases vs. controls). In addition to DNA methylation, microRNA is another mechanism of epigenetics. However, to the best of our knowledge, no studies have identified differentially variable (DV) microRNAs. In this article, we proposed a novel model-based clustering to improve the power of the probe-wise F test to detect DV microRNAs. We imposed special structures on covariance matrices for each cluster of microRNAs based on the prior information about the relationship between variance in cases and variance in controls and about the independence among cases and controls. To the best of our knowledge, the proposed method is the first clustering algorithm that aims to detect DV genomic probes. Simulation studies showed that the proposed method outperformed the probe-wise F test and had certain robustness to the violation of the normality assumption. Based on two real datasets about human hepatocellular carcinoma (HCC), we identified 7 DV-only microRNAs (hsa-miR-1826, hsa-miR-191, hsa-miR-194-star, hsa-miR-222, hsa-miR-502-3p, hsa-miR-93, and hsa-miR-99b) using the proposed method, one (hsa-miR-1826) of which has not yet been reported to relate to HCC in the literature.