bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Radon Equilibrium Factors in Underground Mines, Caves, and Thermal Spas
Authors: Chen Jing , Harley Naomi H.
Published: January 2020

Radon equilibrium factor Feq
is an important factor in radon progeny dose assessment. A review of published measurements of Feq
shows a range of values from 0.1 to 1.0 reported in studies from more than 26 countries measured in 173 underground mines, and 136 show caves, tourist mines, and thermal spas. The average values of F
eq are 0.38 in underground mines and 0.39 for show caves, tourist mines, and thermal spas. The wide range of Feq
in those special workplaces suggests that location-, environment-, and operation-specific values are more appropriate than a recommended average value in the calculation of lung bronchial dose. This is especially important in mines or other typically high radon exposure locations because F
eq can be used for recording an individual’s occupational radon exposure or dose.
FEATURES OF THE MACULAR AND PERIPAPILLARY CHOROID AND CHORIOCAPILLARIS IN EYES WITH NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION
Authors: Nam Ki Tae , Chung Hyun Woo , Jang Sungmin , Kim Seong-Woo , Oh Jaeryung , Yun Cheolmin
Published: January 2020

Purpose:

We investigated macular and peripapillary choroidal thickness (CT) and flow voids in the choriocapillaris in eyes with nonexudative age-related macular degeneration.

Methods:

We retrospectively reviewed the medical records of patients with nonexudative age-related macular degeneration and classified their eyes into three categories: pachydrusen, drusen, and subretinal drusenoid deposit. Mean macular and peripapillary CT and choriocapillaris flow void area were compared among the three groups.

Results:

The three groups included 29, 33, and 33 patients, respectively. The mean macular and peripapillary CT findings were 260.64 ± 75.85 µm and 134.47 ± 46.28 µm for the pachydrusen group; 163.63 ± 64.08 µm and 93.47 ± 39.07 µm for the drusen group; and 95.33 ± 28.87 µm and 56.06 ± 11.64 µm for the subretinal drusenoid deposit group (all, P < 0.001). Mean macular and peripapillary flow void area varied among the subretinal drusenoid deposit group (57.07 ± 6.16% and 55.38 ± 6.65%), drusen group (58.30 ± 6.98% and 49.11 ± 9.11%) and pachydrusen group (50.09 ± 5.77% and 45.47 ± 8.06%) (all P < 0.001).

Conclusion:

The peripapillary CT and flow voids in the choriocapillaris varied according to the features of drusen in nonexudative age-related macular degeneration eyes. Greater flow voids and thinner CT in eyes with subretinal drusenoid deposits may suggest that these eyes have diffuse choroidal abnormalities both in and outside the macula.
Multidisciplinary Diagnostic Reconciliation as a Domain of Hospital Physical Therapist Practice
Authors: Corsino John
Published: January 2020

An axiom repeated in health care is that they eyes are unable to see what the mind does not yet know. As diagnosticians trained to evaluate functional capacity, identify the impairments that produce functional limitations, and synthesize knowledge of pathophysiology and psychosocial context, physical therapists enjoy opportunities to function as clinicians uniquely valuable to their patients. The more information that a therapist possesses about a disease state or movement disorder, the better-informed will be their patient examinations, the more readily will they identify the subtle abnormalities that become persuasive constellations, and the greater will become their capacity to help their patients.
Thrombin generation and thromboelastometry in monitoring the in-vitro reversal of warfarin: a comparison between 3-factor and 4-factor prothrombin complex concentrates
Authors: Spiezia Luca , Rossetto Valeria , Campello Elena , Bulato Cristiana , Radu Claudia M. , Simioni Paolo
Published: January 2020

The efficacy of three-factor prothrombin complex concentrates (PCCs) in the reversal of vitamin K antagonists is still a matter of debate. We compared the ‘in-vitro’ effect of three PCCs (one three-factor and two four-factor) on international normalized ratio (INR), thrombin generation and thromboelastometry of patients at different degrees of anticoagulation with vitamin K antagonist. We tested three concentrations of PCC (0.5, 1 and 1.5 U/ml) in six patients: three (INR 2.0–2.9) and three (INR 3.0–4.0). In this preliminary phase, we determined the lowest effective dose for a target INR less than 1.5 and to normalize endogenous thrombin potential and clotting time in EXTEM assay. In the validation phase, we tested the effect of the newly determined lowest effective PCC dose on samples of 40 (INR 2.0–2.9) and 20 (INR 3.0–4.0) patients. The minimum efficacious dosage to achieve the target INR with three-factor PCC (3-PCC) was 0.5 (INR 2.0–2.9) and 1.5 U/ml (INR 3.0–4.0). Four-factor PCCs (4-PCCs) achieved target INR with the lowest dose (0.5 U/ml) independently of baseline INR. Thrombin generation endogenous thrombin potential and EXTEM clotting time achieved normal values with the lowest dose (0.5 U/ml) of either 3-PCC or 4-PCC independently of baseline INR. Data observed in the preliminary phase were confirmed in the validation phase. 3-PCC appears to be as effective as 4-PCC in reversing oral anticoagulant treatment based on thrombin generation and EXTEM data, but not INR data, at least in the range of INR considered in our study. Further studies are needed to address the clinical implications of our results.
HPV-positive Squamous Cell Carcinoma of the Larynx, Oral Cavity, and Hypopharynx
Authors: Rooper Lisa M. , Windon Melina J. , Hernandez Tahyna , Miles Brett , Ha Patrick K. , Ryan William R. , Van Zante Annemieke , Eisele David W. , D’Souza Gypsyamber , Fakhry Carole , Westra William H.
Published: January 2020

Human papillomavirus (HPV) is a principal driver for most oropharyngeal squamous cell carcinomas (OPSCCs), where it is strongly associated with improved survival. HPV is much less frequently detected in squamous cell carcinomas arising in nonoropharyngeal sites (non-OPSCCs), and its pathogenic role and prognostic value in these tumors is unclear. We evaluated the clinicopathologic features of 52 non-OPSCCs considered HPV-positive based upon p16 immunohistochemistry and direct HPV detection using RNA in situ hybridization (ISH), DNA ISH, or real-time DNA polymerase chain reaction. The HPV-positive non-OPSCCs were from the larynx (n=27), oral cavity (n=21), and hypopharynx (n=4). While most cases (n=34, 65%) showed classic histologic features of HPV-positive OPSCC, including endophytic growth, minimal keratinization, and hyperchromatic nuclei without koilocytic changes, a subset (n=13, 25%) were characterized by exophytic growth, exuberant surface hyperkeratosis and parakeratosis, marked nuclear pleomorphism, and prominent koilocytic atypia. These antithetical features were highly reminiscent of the warty variant of HPV-positive squamous cell carcinoma described in anogenital sites. Compared with tumors without warty features, the warty tumors presented at lower stage and were not associated with lymph node metastasis, local recurrence, or distant spread (4 y disease-free survival of 100% vs. 66%, P=0.069). The presence of transcriptionally active HPV as detected by RNA ISH suggests a pathogenic role for HPV in these nonoropharyngeal sites. While most HPV-positive non-OPSCCs are morphologically similar to their tonsillar counterparts, this study highlights a previously unrecognized warty variant that may be associated with a highly favorable clinical outcome.
Characterization of Novel Injectable Lifting Agents Used in Colonic Polyp Removal
Authors: Pezhouh Maryam K. , Burgart Lawrence J. , Chiu Kenrry , Cohen David A. , Hutchings Danielle A. , Sanderson Schuyler O. , Shirazi Maryam , Stanich Peter P. , VandenBussche Christopher J. , Voltaggio Lysandra , Willhoit Ellen D. , Xue Yue , Arnold Christina A.
Published: January 2020

Colon polypectomy can require an injection of a submucosal lifting agent to fully visualize and completely remove the polyp. To the best of our knowledge, this is the largest morphologic series on the novel lifting agents Eleview and Orise. The study consisted of 1 polypectomy and 8 colon resections from 9 patients: 6 women, 3 men (mean age=64 y); Orise=6, Eleview=3; the median time interval between injection and resection=16 weeks. Pathologic diagnoses of the polyps included tubular adenoma (n=4), tubulovillous adenoma (n=4), and sessile serrated adenoma/polyp (n=1). We report that a histologically processed Orise aliquot from the manufacturer showed similar histology to that seen in the specimens from patients with confirmed Orise injection. The morphology of the agents in the patient specimens changed with time status postinjection: immediate resection of the lifting agent showed basophilic, amorphous, and bubbly-extracellular material with prominent hemorrhage, and resection ∼3 months after lifting agent injection showed prominent hyalinized, pink-amorphous ribbons and globules with a foreign body giant cell reaction and fibrosis. The epicenter of the lifting agents was in the submucosa, and the agents were neither refractile nor polarizable. Because of the morphologic overlap with amyloid, 5 cases were stained with Congo Red, and all cases were negative. In conclusion, awareness of the morphology of these new lifting agents is important for accurate diagnosis and to avoid the diagnostic pitfall of amyloid. These lesions can be definitively distinguished from amyloid by their nonreactivity on a Congo Red and familiarity with their characteristic clinicopathologic presentation.
Lung Transplantation for Bronchopulmonary Dysplasia in Adults
Authors: Liu Natalia , Cummings Oscar W. , Lagstein Amir , Hage Chadi A. , Chan Kevin M. , Zhang Chen
Published: January 2020

Bronchopulmonary dysplasia (BPD) is usually seen in premature infants who require mechanical ventilation and oxygen therapy for acute respiratory distress. Although most patients wean from oxygen therapy by the ages of 2 to 3, rehospitalization for respiratory problems is common in these patients in adulthood. There have been few studies that document the long-term outcomes of BPD survivors and information about the pulmonary function and radiographic findings of adult BPD are limited. Data on pathologic features of adult BPD are scarce. Three adult patients who underwent recent lung transplantation for BPD from 2 institutions were identified. Clinical data including clinical presentation, chest radiographic images, pulmonary function tests, cardiac catheterization, and echocardiography were retrieved from the electronic medical records. Hematoxylin and eosin and selective elastic stained sections of the explant lungs were examined. CD31 immunohistochemical stain is performed on representative sections. All 3 cases had similar clinical and radiologic features including the history of prematurity and long-term mechanical ventilation after birth, hyperexpanded lungs with air trapping and mosaic attenuation on chest computed tomographic scan, severe obstructive changes on pulmonary function test, and pulmonary hypertension. Pathologic examination showed common features including enlarged and simplified alveoli, peribronchial, subpleural, and interlobular septal fibrosis, narrowing/obliteration of the small airways by elastosis and muscular hypertrophy, thickening of venous walls by fibromuscular hyperplasia, and bronchitis/bronchiolitis. Cholesterol granulomas were seen in 2 cases. The common pathologic findings in the lungs explain the clinical and radiologic findings. Future studies are warranted to further characterize the clinical and pathologic features of adult BPD to develop optimal management strategies for these patients.
Head and Neck Mesenchymal Neoplasms With GLI1 Gene Alterations
Authors: Xu Bin , Chang Koping , Folpe Andrew L. , Kao Yu-Chien , Wey Shiuan-Li , Huang Hsuan-Ying , Gill Anthony J. , Rooper Lisa , Bishop Justin A. , Dickson Brendan C. , Lee Jen-Chieh , Antonescu Cristina R.
Published: January 2020

Soft tissue tumors with GLI1 gene fusions or amplifications have been recently described as a unique pathologic entity with an established risk of malignancy. We herein expand these findings by investigating a cohort of 11 head and neck lesions with GLI1 alterations, including 8 from the tongue, for their clinicopathologic and molecular features. The tumors commonly affected males in their 30s (male:female ratio 2.7:1; range: 1 to 65). Tumors showed a multinodular growth pattern, nested architecture separated by a delicate, arborizing vascular network, monotonous round to ovoid nuclei, and clear cytoplasm. Tumor protrusion into vascular spaces was common. Genetic alterations were investigated by fluorescence in situ hybridization and/or targeted RNA sequencing. Seven tumors harbored GLI1 fusions with the following partners: ACTB (n=4), PTCH1 (n=2), or MALAT1 (n=1). The remaining 4 cases showed coamplifications of GLI1 with CDK4 and MDM2 genes. Tumors were commonly positive for S100 protein and CD56. CDK4, MDM2, and STAT6 were positive in GLI1-amplified tumors. Two of 6 patients with available follow-up (1 each with GLI1 amplification and PTCH1-GLI1 fusion) developed distant metastases. Both tumors showed a high mitotic index and tumor necrosis. The head and neck region, particularly tongue, is a common location for GLI1-related mesenchymal tumors. Although a morphologic overlap was noted with the previously reported “pericytoma with t(7,12) translocation,” often occurring in the tongue, our findings expand the original findings, to include a more variable immunophenotype, propensity for late distant metastases, and alternative mechanisms of GLI1 oncogenic activation, such as various GLI1 fusion partners or GLI1 coamplifications with MDM2 and CDK4 genes.
Pulsatile Tinnitus Caused by Internal Jugular Phlebectasia in an Adult
Authors: Meng Zhaoli , Chen Fei , Huo Yao , Sun Haocheng , Zheng Yun
Published: January 2020

Internal jugular phlebectasia is a rare condition. Children with internal jugular phlebectasia are often discovered by their parents when they notice a soft mass in the neck that appears when the child cries, coughs, or breathes deeply. Most internal jugular vein dilatations occur unilaterally on the right side according to the literature reports. To our knowledge, no other internal jugular phlebectasia patients reported pulsatile tinnitus as the major complaint without a soft mass in the neck. The authors reported a female adult patient with left-side internal jugular phlebectasia with pulsatile tinnitus as the major complaint without a soft mass in the neck. Internal jugular phlebectasia was diagnosed by color ultrasound of the internal jugular vein. Pure-tone audiometry, tympanometry, hemoglobin, thyroid function, and magnetic resonance imaging were made to differentiate other diseases that can cause the pulsatile tinnitus. Conservative treatment is recommended in this report. The possibility of internal jugular vein dilatation should be considered when differentiate the possible diseases that caused pulsatile tinnitus.
The Management of Head and Neck Sarcoma
Authors: Han Shengwei , Yin Xiteng , Xu Wenguang , Wang Yufeng , Han Wei
Published: January 2020

Objective:

To describe the incidence, types, features, treatment and outcomes of head and neck sarcoma managed at a treatment center in eastern China.

Methods:

Cases of head and neck soft tissue sarcoma and osteogenic sarcoma treated at the Stomatology Hospital of Nanjing University between 2008 and 2018 were retrospectively analyzed. Patient characteristics, site of lesion, main presenting symptoms, treatment, histology, local recurrence, development of metastatic disease, duration of follow-up and survival rates are described and compared.

Results:

Sixty-three patients were diagnosed with head or neck sarcoma of which 42.9% had soft tissue sarcoma and 57.1% had osteogenic sarcoma. Of soft tissue sarcoma patients, the most frequently observed histologies were fibrosarcoma and malignant fibrous histiocytoma. Of 36 cases of osteogenic sarcoma, osteosarcoma, and fibrosarcoma of bone were most frequent. Mean latency period between initial symptoms and clinical presentation was 4.5 months. Radical resection was performed on 56 patients. For 33 patients, resection and radiotherapy were used and 10 patients received a triple combination of resection, chemotherapy and radiotherapy. Within the observation period, 17 patients died.

Conclusions:

Head and neck sarcomas, although rare, can represent a variety of pathological diagnoses. Surgery remains the main intervention although the data suggest chemotherapy, radical resection and irradiation as treatment. Outcomes are poor with high rates of local recurrence. Positive prognostic factors were tumor-free resection margins and choice of therapy. Due to the rarity of head and neck sarcoma, information remains limited and choice of treatment should be within the focus of clinical multi-center studies.
Evaluation of the Relationship Between Olfactory Fossa Measurements and Nasal Septum Deviation for Endoscopic Sinus Surgery
Authors: Bayrak Seval , Aktuna Belgin Ceren , Orhan Kaan
Published: January 2020

Introduction:

Endoscopic sinus surgeries (ESS) are frequently used in the treatment of optic nerve decompression, other intracranial lesions and sinonasal pathologies. The olfactory fossa can be localized on different levels in relation to the anterior cranial fossa. The aim of the present study was to evaluate the depth and width of the olfactory fossa (OF) in relation to nasal septum deviation (NSD).

Methods:

A total of 225 patient (141 female and 84 male, age range between 15 to 56 years) of cone beam computed tomography (CBCT) data was used in this study. NSD, OF width, OF depth were measured. OF depth which was grouped according to the Keros classification as Type I, II, and III was calculated. All measurements were performed bilaterally except for NSD.

Results:

In the right and left OF depth were found Keros Type I 32 (14.2%) and 30 (13.3%), Keros Type II 171 (76%) and 167 (74.2%), and Keros Type III 22 (9.8%) and 28 (12.4%) respectively. There was no statistically significant found between OF depth and NSD (P > 0.05). The mean angle of the NSD in men and women were 4.36 ± 4.69o in women 4.11 ± 4.36o, respectively. The mean width of the right OF was 2.50 ± 0.64 mm and 2.58 ± 0.72 mm for the left side and there was no statistically significant association between OF width – NSD and OF width – OF depth (P > 0.05).

Conclusion:

The anatomy of the OF should be well established before surgical intervention increase of the length of the lateral lamella is also increases the risk of developing complications such as cerebral damage, hemorrhage, and cerebrospinal fluid fistula during endoscopic sinus surgery. Although there is no significant difference between OF measurement and NSD, with three-dimensional imaging detailed research is required before endoscopic sinus surgical operations.
Intraoral Approach for Surgical Treatment of Psammomatoid Juvenile Ossifying Fibroma
Authors: Diniz Jiordanne Araújo , Siqueira Allancardi dos Santos , Araújo Gabriela Madeira , Faro Tatiane Fonseca , Torres Luiz Henrique Soares , Oliveira e Silva Emanuel Dias de , Laureano Filho José Rodrigues
Published: January 2020

Psammomatoid juvenile ossifying fibroma (PJOF) is a rare benign tumor that usually affects the paranasal sinuses, orbit, and skull. In most cases, extensive incisions are necessary for full access to the tumor site. The aim of this paper is to report a case of extensive PJOF in which an intraoral surgical approach was performed with complete excision of the tumor. A female patient, 18-year old had a deforming volume increase in the region of the left facial middle third with an approximate evolution time of 2 years. She complained of headache, epiphora in the left eye, and total obstruction of the left nostril. Extraoral examination showed facial asymmetry with dystopia, ocular proptosis, and considerable sclera exposition of the left eye. Tomography examination showed a mixed aspect lesion on the left side of the face, well delimited. The intraoral surgical approach was chosen for the excision of the lesion. Under general anesthesia and nasotracheal intubation, total resection was performed, followed by exodontia of the directly involved teeth. In the definitive histopathological examination, the diagnosis was confirmed. The patient is currently with 2 years and 6 months of postoperative follow-up and has good healing of intraoral surgical wounds and stable occlusion. Extraoral examination showed harmonic projection of the facial middle third, but still with excessive exposure of the sclera of the left eye due to the defect in the orbital floor. The surgical treatment of PJOF was possible by intraoral approach, even taking into account the limitations of the access and the complexity of the anatomy of the facial bones involved.
Anterior-Approach Versus Posterior-Approach Levator Advancement Surgery in Aponeurotic Ptosis
Authors: Fazil Korhan , Ozturker Can , Ozturk Karabulut Gamze , Aygit Ebru Demet , Kepez Yildiz Burcin , Taskapili Muhittin , Kaynak Pelin
Published: January 2020

Purpose:

To compare the effectiveness and complications of levator reinsertion in aponeurotic ptosis surgery using anterior and posterior approaches.

Methods:

Seventy-eight (36 females, 42 males) patients with acquired aponeurotic ptosis were evaluated. Pre- and postoperative margin reflex distance, symmetry of height, contour and skin crease, corneal problems, and lagophthalmus were evaluated and compared between the 2 groups. Independent and paired samples t-test, Pearson Chi-square, and Fisher exact test were used to evaluate the results.

Results:

The anterior approach was performed on 43 eyelids and the posterior approach was performed on 35 eyelids. The mean age of the anterior-approach group was 62.1 ± 11 years, and posterior-approach group was 50.1 ± 15.1 years, respectively (P < 0.001). The male-female ratio was 28/15 in the anterior-approach group, and 14/21 in the posterior approach group (P = 0.027). The success rate of the anterior approach was 69.8% and the posterior approach was 57.1% (P = 0.248). The mean margin reflex distance change was statistically significant in both anterior- and posterior-approach techniques (P < 0.001, P < 0.001, respectively). Three (6.9%) patients in the anterior-approach group and 11 (31.4%) in the posterior-approach group required reoperation (P = 0.005). Lagophthalmus rates were similar (3 eyes in the anterior versus 7 eyes in the posterior group, P = 0.103).

Conclusions:

Both anterior- and posterior-approaches are effective and safe techniques for aponeurotic ptosis treatment. The posterior approach seems to be preferred by female and younger patients because there is no undesirable scar formation although it has the disadvantage of higher rates of reoperation.
Genome sequence-based criteria for demarcation and definition of species in the genus Rickettsia
Authors: Diop Awa , El Karkouri Khalid , Raoult Didier , Fournier Pierre-Edouard
Published: January 2020

Over recent years, genomic information has increasingly been used for prokaryotic species definition and classification. Genome sequence-based alternatives to the gold standard DNA–DNA hybridization (DDH) relatedness have been developed, notably average nucleotide identity (ANI), which is one of the most useful measurements for species delineation in the genomic era. However, the strictly intracellar lifestyle, the few measurable phenotypic properties and the low level of genetic heterogeneity made the current standard genomic criteria for bacterial species definition inapplicable toRickettsiaspecies. We evaluated a range of whole genome sequence (WGS)-based taxonomic parameters to develop guidelines for the classification ofRickettsiaisolates at genus and species levels. By comparing the degree of similarity of 74 WGSs from 31Rickettsiaspecies and 61 WGSs from members of three closely related genera also belonging to the orderRickettsiales(Orientia, 11 genomes;Ehrlichia, 22 genomes; andAnaplasma, 28 genomes) using digital DDH (dDDh) and ANI by orthology (OrthoANI) parameters, we demonstrated that WGS-based taxonomic information, which is easy to obtain and use, can serve for reliable classification of isolates within theRickettsiagenus and species. To be classified as a member of the genusRickettsia, a bacterial isolate should exhibit OrthoANI values with anyRickettsiaspecies with a validly published name of ≥83.63 %. To be classified as a newRickettsiaspecies, an isolate should not exhibit more than any of the following degrees of genomic relatedness levels with the most closely related species: >92.30 and >99.19 % for the dDDH and OrthoANI values, respectively. When applied to four rickettsial isolates of uncertain status, the above-described thresholds enabled their classification as new species in one case. Thus, we propose WGS-based guidelines to efficiently delineateRickettsiaspecies, with OrthoANI and dDDH being the most accurate for classification at the genus and species levels, respectively.
Urechidicola croceus gen. nov., sp. nov., a member of the family Flavobacteriaceae
Authors: Shin Su-Kyoung , Yi Hana
Published: January 2020

A Gram-stain-negative, rod-shaped, non-flagellated, non-gliding, aerobic bacterial strain, designated LPB0138T, was isolated from a marine spoon worm (Urechis unicinctus). The strain LPB0138T contains a circular chromosome of 3.43 Mb with a DNA G+C content of 30.4 mol%. The genome includes 2987 protein-coding genes and two copies of rRNA operons. The 16S rRNA gene sequence analysis showed that the isolate occurred within a clade containing only members of the family

Flavobacteriaceae

. The highest sequence similarity was observed with the genus

Lutibacter

(93.0–94.3 %), but the phylogenetic leaf of the new isolate did not belong to any of the genera known in the family

Flavobacteriaceae

. The low sequence similarity and the phylogenetic tree topology implied the novel generic status of the new isolate. The phenotypic properties of the strain LPB0138T also differentiated this isolate from its neighbour genera by showing a distinctive fatty acid composition, unique polar lipids profile, and low DNA G+C content. The LPB0138T strain contained menaquinone 6 as the isoprenoid quinone; iso-C15 : 1 G, iso-C15 : 0, iso-C15 : 0 3-OH, and iso-C17 : 0 3-OH as the major fatty acids; and phosphatidylethanolamine, unidentified aminophospholipids, unidentified aminolipids, and unidentified lipids as the major polar lipids. Based on the polyphasic taxonomic data obtained, the LPB0138T strain is considered to represent a novel species in a novel genus of the family Flavobacteriaceae, for which the name Urechidicola croceus gen. nov., sp. nov. was proposed. The type strain is LPB0138T (=KACC 18889T;=JCM 31563T).
ICTV Virus Taxonomy Profile: Nudiviridae
Authors: Harrison Robert L. , Herniou Elisabeth A. , Bézier Annie , Jehle Johannes A. , Burand John P. , Theilmann David A. , Krell Peter J. , van Oers Monique M. , Nakai Madoka ,   ICTV Report Consortium
Published: January 2020

Members of the family Nudiviridae are large dsDNA viruses with distinctive rod-shaped nucleocapsids and circular genomes of 96–232 kbp. Nudiviruses have been identified from a diverse range of insects and crustaceans and are closely related to baculoviruses. This is a summary of the International Committee on Taxonomy of Viruses Report on the taxonomy of the family Nudiviridae, which is available at ictv.global/report/nudiviridae.
Evaluation of chromogenic selective agar (CHROMagar STEC) for the direct detection of Shiga toxin-producing Escherichia coli from faecal specimens
Authors: Jenkins Claire , Perry Neil T. , Godbole Gauri , Gharbia Saheer
Published: January 2020

Shiga toxin-producing

Escherichia coli

(STEC) are zoonotic pathogens that cause symptoms of severe gastrointestinal disease, including haemolytic uraemic syndrome (HUS), in humans. Currently in England, STEC serotypes other than O157:H7 are not cultured at the local hospital laboratories. The aim of this study was to evaluate the utility of CHROMagar STEC for the direct detection of STEC from faecal specimens in a diagnostic setting, compared to the current reference laboratory method using PCR targeting the Shiga-toxin gene (stx) to test multiple colonies cultured on MacConkey agar. Of the 292 consecutive faecal specimens submitted to the Gastrointestinal Bacterial Reference Unit that tested positive for stx by PCR, STEC could not be cultured on MacConkey agar or CHROMagar STEC from 87/292 (29.8 %). Of the 205 that were cultured, 106 (51.7 %) were detected on both MacConkey agar and CHROMagar STEC and 99 (48.3 %) were detected on MacConkey agar only. All 106 (100 %) isolates that grew on CHROMagar STEC had the ter gene cassette, known to be associated with resistance to tellurite, compared to 13/99 (13.1 %) that were not detected on CHROMagar STEC. CHROMagar STEC supported the growth of 36/40 (90 %) isolates harbouring stx2a or stx2d, the subtypes most frequently associated with progression to HUS. Of the 92 isolates harbouring eae, an important STEC virulence marker, 77 (83.7 %) grew on CHROMagar STEC. CHROMagar STEC is a useful selective media for the rapid, near-patient detection of STEC that have the potential to cause HUS.
Peptides encoded in the Streptococcus mutans RcrRPQ operon are essential for thermotolerance
Authors: Shields Robert C. , Kim Jeong Nam , Ahn Sang-Joon , Burne Robert A.
Published: January 2020

The MarR-like transcriptional regulator and two ABC transporters encoded by the rcrRPQ operon in the dental caries pathogen

Streptococcus mutans

have important regulatory roles related to oxidative stress tolerance, genetic competence and (p)ppGpp metabolism. A unique feature of the rcrRPQ operon, when compared to other bacteria, is the presence of two peptides, designated Pep1 and Pep2, encoded in alternative reading frames at the 3′ end of rcrQ. Here, we show that the rcrRPQ operon, including Pep1 and 2, is essential for

S. mutans

to survive and maintain viability at elevated temperatures. No major changes in the levels of the heat shock proteins DnaK or GroEL that could account for the thermosensitivity of rcrRPQ mutants were observed. By introducing a single amino acid substitution into the comX gene that deletes an internally encoded peptide, XrpA, we found that XrpA is a contributing factor to the thermosensitive phenotype of a ΔrcrR strain. Overexpression of XrpA on a plasmid also caused a significant growth defect at 42 °C. Interestingly, loss of the gene for the RelA/SpoT homologue (RSH) enzyme, relA, restored growth of the ΔrcrR strain at 42 °C. During heat stress and when a stringent response was induced, levels of (p)ppGpp were elevated in the ΔrcrR strain. Deletion of relA in the ΔrcrR strain lowered the basal levels of (p)ppGpp to those observed in wild-type

S. mutans

. Thus, (p)ppGpp pools are dysregulated in ΔrcrR, which likely leads to aberrant control of transcriptional/translational processes and the thermosensitive phenotype. In summary, the genes and peptides encoded in the rcrRPQ operon are critical for thermotolerance, and in some strains these phenotypes are related to altered (p)ppGpp metabolism and increased production of the XrpA peptide.
Biomarker-guided treatment strategies for ovarian cancer identified from a heterogeneous panel of patient-derived tumor xenografts
Authors: Palmer Adam C. , Plana Deborah , Gao Hui , Korn Joshua M , Yang Guizhi , Green John , Zhang Xiamei , Velazquez Roberto , McLaughlin Margaret E , Ruddy David A , Kowal Colleen , Goldovitz Julie , Bullock Caroline , Rivera Stacy , Rakiec Daniel , Elliott GiNell , Fordjour Paul , Meyer Ronald , Loo Alice , Kurth Esther , Engelman Jeffrey A , Bitter Hans , Sellers William R , Sorger Peter K , Williams Juliet A
Published: January 2020

Advanced ovarian cancers are a leading cause of cancer-related death in women. Such cancers are currently treated with surgery and chemotherapy which is often temporarily successful but exhibits a high rate of relapse after which treatment options are few. Here we assess the responses of a panel of patient-derived ovarian cancer xenografts (PDXs) to 19 mono and combination therapies, including small molecules and antibody-drug conjugates. The PDX panel aimed to mimic the heterogeneity of disease observed in patients, and exhibited a distribution of responsiveness to standard of care chemotherapy similar to human clinical data. Three monotherapies and one drug combination were found to be active in different subsets of PDXs. By analyzing gene expression data we identified gene expression biomarkers predictive of responsiveness to each of three novel targeted therapy regimens. While no single treatment had as high a response rate as chemotherapy, nearly 90% of PDXs were eligible for and responded to at least one biomarker-guided treatment, including tumors resistant to standard chemotherapy. Biomarker frequency was similar in human patients, suggesting the possibility of a new therapeutic approach to ovarian cancer and demonstrating the potential power of PDX-based trials in broadening the reach of precision cancer medicine.
Multi-Object Tracking in Heterogeneous environments (MOTHe) for animal video recordings
Authors: Rathore Akanksha , Sharma Ananth , Sharma Nitika , Torney Colin J. , Guttal Vishwesha
Published: January 2020

Video recordings of animals are used for many areas of research such as collective movement, animal space-use, animal censuses and behavioural neuroscience. They provide us with behavioural data at scales and resolutions not possible with manual observations. Many automated methods are being developed to extract data from these high-resolution videos. However, the task of animal detection and tracking for videos taken in natural settings remains challenging due to heterogeneous environments.

We present an open-source end-to-end pipeline calledMulti-Object Tracking in Heterogenous environments (MOTHe), a python-based application that uses a basic convolutional neural network for object detection. MOTHe allows researchers with minimal coding experience to track multiple animals in their natural habitats. It identifies animals even when individuals are stationary or partially camouflaged.

MOTHe has a command-line-based interface with one command for each action, for example, finding animals in an image and tracking each individual. Parameters used by the algorithm are well described in a configuration file along with example values for different types of tracking scenario. MOTHe doesn’t require any sophisticated infrastructure and can be run on basic desktop computing units.

We demonstrate MOTHe on six video clips from two species in their natural habitat - wasp colonies on their nests (up to 12 individuals per colony) and antelope herds in four different types of habitats (up to 156 individuals in a herd). Using MOTHe, we are able to detect and track all individuals in these animal group videos. MOTHe’s computing time on a personal computer with 4 GB RAM and i5 processor is 5 minutes for a 30-second long ultra-HD (4K resolution) video recorded at 30 frames per second.

MOTHe is available as an open-source repository with a detailed user guide and demonstrations at Github (https://github.com/tee-lab/MOTHe).
Functional MRI Investigation on Paradigmatic and Syntagmatic Lexical Semantic Processing
Authors: Ying Songsheng , Ploux Sabine
Published: January 2020

The word embeddings related to paradigmatic and syntagmatic axes are applied in an fMRI encoding experiment to explore human brain’s activity pattern during story listening. This study proposes the construction of paradigmatic and syntagmatic semantic embeddings respectively by transforming WordNet-alike knowledge bases and subtracting paradigmatic information from a statistical word embedding. It evaluates the semantic embeddings by leveraging word-pair proximity ranking tasks and contrasts voxel encoding models trained with the two types of semantic features to reveal the brain’s spatial pattern for semantic processing. Results indicate that in listening comprehension, paradigmatic and syntagmatic semantic operations both recruit inferior (ITG) and middle temporal gyri (MTG), angular gyrus, superior parietal lobule (SPL), inferior frontal gyrus. A non-continuous voxel line is found in MTG with a predominance of paradigmatic processing. The ITG, middle occipital gyrus and the surrounding primary and associative visual areas are more engaged by syntagmatic processing. The comparison of two semantic axes’ brain map does not suggest a neuroanatomical segregation for paradigmatic and syntagmatic processing. The complex yet regular contrast pattern starting from temporal pole, along MTG to SPL necessitates further investigation.
Efficient replacement of long DNA fragments via non-homologous end joining at non-doding regions
Authors: Gu Shan-Ye , Li Jia , Cao Jian-Bin , Bu Ji-Wen , Ren Yong-Gang , Du Wen-Jie , Chen Zhe-Cong , Xu Chu-Fan , Wang Min-Cang , Jiang Lai , Huang Cheng , Du Jiu-Lin
Published: January 2020

Genomic DNA replacement for achieving sophisticated genetic manipulation is implemented currently through homogenous recombination/homology-dependent repair (HR/HDR). Here we report an efficient DNA fragment replacement method that is mediated by non-homologous end joining (NHEJ)-dependent DNA repair at two sites of CRISPR/Cas9-induced double-strand breaks at non-coding genomic regions flanking the exons of targeted genes. We demonstrated this method by generating three conditional alleles and two reporter lines of zebrafish. Functional assays of the conditional alleles proved that the genomic sequence between two insertedloxPsites was deleted by the Cre recombinase, and the phenotype after Cre-induced excision was comparable to previously reported mutants or morphants. Furthermore, combining double-fluorescence expression donor vectors, we showed that the efficiency of this NHEJ-mediated DNA replacement was around 3 times larger than that of HR/HDR-mediated approach. Our method provides a feasible strategy for genomic DNA replacement in zebrafish, which can be applicable for other organisms as well.
Size-Based Dominance Hierarchy In One Of Two Sympatric Cryptic Pacific Skinks (Emoia imparAndEmoia Cyanura)
Authors: Hallsten Mary “Molly”
Published: January 2020

Emoia imparandEmoia cyanuraare two morphologically cryptic Pacific skinks that have different preferred thermal micro-habitats but similar geographic range and overlap. Previously individuals have been noted to display a size-based dominance hierarchy at favored basking sites, though this behavior was not specified between species. I found that only one of the two species,E. impar, naturally presents this size-based dominance hierarchy in areas of high population density. Neither species exhibit the hierarchy in low population density areas. No evidence was found to suggest that the presence of this hierarchy allows one species to exclude the other.
Cancer-associated fibroblast compositions change with breast-cancer progression linking S100A4 and PDPN ratios with clinical outcome
Authors: Friedman Gil , Levi-Galibov Oshrat , David Eyal , Bornstein Chamutal , Giladi Amir , Dadiani Maya , Mayo Avi , Halperin Coral , Pevsner-Fischer Meirav , Lavon Hagar , Nevo Reinat , Stein Yaniv , Ali H. Raza , Caldas Carlos , Nili-Gal-Yam Einav , Alon Uri , Amit Ido , Scherz-Shouval Ruth
Published: January 2020

Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes could improve the precision of cancer treatment. CAFs are usually analyzed at a single time-point using specific markers, and it is therefore unclear whether CAFs display plasticity as tumors evolve. Here, we analyze thousands of CAFs using index and transcriptional single-cell sorting, at several time-points along breast tumor progression in mice, uncovering distinct subpopulations. Strikingly, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immune-regulatory program to wound healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is associated with disease outcome across subtypes, and is particularly correlated with BRCA mutations in triple-negative breast cancer. These findings indicate that the repertoire of CAFs changes over time in breast cancer progression, with direct clinical implications.
Conservation motifs - a novel evolutionary-based classification of proteins
Authors: Beer Hodaya , Sherill-Rofe Dana , Unterman Irene , Bloch Idit , Isseroff Mendel , Stupp Doron , Sharon Elad , Zisman Elad , Tabach Yuval
Published: January 2020

Cross-species protein conservation patterns, as directed by natural selection, are indicative of the interplay between protein function, protein-protein interaction and evolution. Since the beginning of the genomic era, proteins were characterized as either conserved or not conserved. This simple classification became archaic and cursory once data on protein orthologs became available for thousands of species. To enrich the language used to describe protein conservation patterns, and to understand their biological significance, we classified 20,294 human proteins against 1096 species. Analyses of the conservation patterns of human proteins in different eukaryotic clades yielded extremely variable and rich patterns that had never been characterized or studied before. Using mathematical classifications, we defined seven conservation motifs: Steps, Critical, Lately Developed, Plateau, Clade Loss, Trait Loss and Gain, which describe the evolution of human proteins. Overall, our work offers novel terms for conservation patterns and defines a new language intended to comprehensively describe protein evolution. This novel terminology enables the classification of proteins based on evolution, reveals aspects of protein evolution, and improves the understanding of protein functions.
Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling
Authors: Asaro Antonino , Carlo-Spiewok Anne-Sophie , Malik Anna R. , Rothe Michael , Schipke Carola G. , Peters Oliver , Heeren Joerg , Willnow Thomas E.
Published: January 2020

INTRODUCTION

ApoE is a carrier for brain lipids and the most important genetic risk factor for Alzheimer’s disease (AD). ApoE binds the receptor sortilin which mediates uptake of apoE-bound cargo into neurons. The significance of this uptake route for brain lipid homeostasis and AD risk seen with apoE4, but not apoE3, remains unresolved.

METHODS

Combining neurolipidomics in patient specimens with functional studies in mouse models, we interrogated apoE isoform-specific functions for sortilin in brain lipid metabolism and AD.

RESULTS

Sortilin directs uptake and conversion of polyunsaturated fatty acids into endocannabinoids, lipid-based neurotransmitters that act through nuclear receptors to sustain neuroprotective gene expression in the brain. This sortilin function requires apoE3, but is disrupted by binding of apoE4, impairing endocannabinoid signaling and increasing amyloidogenic processing.

DISCUSSION

We uncovered the significance of neuronal apoE receptor sortilin in facilitating neuroprotective actions of brain lipids, and its relevance for AD risk seen with apoE4.
Deletion of MOrpholino Binding Sites (DeMOBS) to Assess Specificity of Morphant Phenotypes
Authors: Cunningham Carlee MacPherson , Bellipanni Gianfranco , Habas Raymond , Balciunas Darius
Published: January 2020

Two complimentary approaches are widely used to study gene function in zebrafish: induction of genetic mutations, usually using targeted nucleases such as CRISPR/Cas9, and suppression of gene expression, typically using Morpholino oligomers. Neither method is perfect. Morpholinos (MOs) sometimes produce off-target or toxicity-related effects that can be mistaken for true phenotypes. Conversely, genetic mutants can be subject to compensation, or may fail to yield a null phenotype due to leakiness. When discrepancy between mutant and morpholino-induced (morphant) phenotypes is observed, experimental validation of such phenotypes becomes very labor intensive. We have developed a simple genetic method to differentiate between genuine morphant phenotypes and those produced due to off-target effects. We speculated that indels within 5’ untranslated regions would be unlikely to have a significant negative effect on gene expression. Mutations induced within a MO target site would result in a Morpholino-refractive allele thus suppressing true MO phenotypes whilst non-specific phenotypes would remain. We tested this hypothesis on one gene with an exclusively zygotic function,tbx5a, and one gene with strong maternal effect,ctnnb2. We found that indels within the Morpholino binding site are indeed able to suppress both zygotic and maternal morphant phenotypes. We also observed that the ability of such indels to suppress Morpholino phenotypes does depend on the size and the location of the deletion. Nonetheless, mutating the morpholino binding sites in both maternal and zygotic genes can ascertain the specificity of morphant phenotypes.
Germ plasm localisation dynamics mark distinct phases of transcriptional and post-transcriptional regulation control in primordial germ cells
Authors: D’Orazio Fabio M. , Balwierz Piotr , Guo Yixuan , Hernández-Rodríguez Benjamín , Jasiulewicz Aleksandra , Vaquerizas Juan M. , Cairns Bradley , Lenhard Boris , Müller Ferenc
Published: January 2020

In many animal models, primordial germ cell (PGC) development depends on maternally-deposited germ plasm to avoid somatic cell fate. Here, we show that PGCs respond to regulatory information from the germ plasm in two distinct phases and mechanisms in zebrafish. We show that PGCs commence zygotic genome activation together with the rest of the embryo with no demonstrable differences in transcriptional and chromatin accessibility levels. Thus, cytoplasmic germ plasm determinants only affect post-transcriptional stabilisation of RNAs to diverge transcriptome from somatic cells, which, unexpectedly, also activate germ cell-specific genes. Perinuclear relocalisation of germ plasm is coupled to dramatic divergence in chromatin opening and transcriptome from somatic cells characterised by PGC-specific chromatin topology. Furthermore, we reveal Tdrd7, regulator of germ plasm localisation, as crucial determinant of germ fate acquisition.
URMAP, an ultra-fast read mapper
Authors: Edgar Robert C.
Published: January 2020

Mapping of reads to reference sequences is an essential step in a wide range of biological studies. The large size of datasets generated with next-generation sequencing technologies motivates the development of fast mapping software. Here, I describe URMAP, a new read mapping algorithm. URMAP is an order of magnitude faster than BWA and Bowtie2 with comparable accuracy on a benchmark test using simulated paired 150nt reads of a well-studied human genome. Software is freely available athttps://drive5.com/urmap.
Ubiquitin Ligase MARCH5 Regulates Apoptosis through Mediation of Stress-Induced and NOXA-Dependent MCL1 Degradation
Authors: Arai Seiji , Chen Sen , Xie Lisha , Balk Steven P.
Published: January 2020

MCL1 has critical antiapoptotic functions and its levels are tightly regulated by ubiquitylation and degradation, but mechanisms that drive this degradation, particularly in solid tumors, remain to be established. We show here in prostate cancer cells that increased NOXA, mediated by activation of an integrated stress response, drives the degradation of MCL1, and identify the mitochondria-associated ubiquitin ligase MARCH5 as the primary mediator of this NOXA-dependent MCL1 degradation. Therapies that enhance MARCH5-mediated MCL1 degradation markedly enhance apoptosis in response to a BH3 mimetic agent targeting BCLXL, which may provide for a broadly effective therapy in solid tumors. Conversely, increased MCL1 in response to MARCH5 loss does not sensitize to BH3 mimetic drugs targeting MCL1, but instead also sensitizes to BCLXL inhibition, revealing a codependence between MARCH5 and MCL1 that may also be exploited in tumors withMARCH5genomic loss.