bluuebunny/crossref_metadata_2025 huggingface dataset:
PSXIV-8 Performance of Nellore bulls fed probiotic (Saccharomyces cerevisiae boulardii CNCM I-1079) during adaptation in feedlot
Authors: Bomfim Lorena Emily L M , Nascimento Kaique S , Couto Victor R Moreira , Arnhold Emmanuel , da R Fernandes Márcia Helena M , Moura Silva Luan O , Mari Lucas José , Santos Mateus Castilho , Gauthier Marine , Chevaux Eric , De Resende Fernandes Juliano José
Published: October 2021

This study aimed to evaluate the effect of probiotic (Saccharomyces cerevisiae boulardii CNCM I-1079) supplementation during feedlot adaptation period on performance of Nellore bulls. One-hundred ninety-eight Nellore bulls were used in a completely randomized block design, divided in 22 pens (9 animals/pen). Treatments were: CON – adaptation diet and finishing diet comprised of basal diet (with 28 ppm of monensin); and SCB – same diets as for the previous treatment with monensin plus probiotic (Saccharomyces cerevisiae boulardii CNCM I-1079, ProTernative® 20; Lallemand Animal Nutrition at a dose of 1.0 x 10e10 cfu/animal/d) supplementation. Supplementation was offered for the first 42 days (21 days in the step-up phase and 21 days in the finishing diet with 900 g concentrate/kg DM), then both treatments were fed the same basal diet for another 76d, reaching 118 days in total. Pen was considered the experimental unit. Growth data were analyzed using the MIXED procedure of SAS with Tukey test at 5% significance level, and a linear regression analysis was performed for the dry matter intake (DMI) data. During the first 42 days, average DMI did not differ; however, bulls fed SCB plateaued the curve of at 9.17 kg DMI/d earlier (39 days, R2 = 0.97) than those fed CON (43 days; R2 = 0.96) diets. Final body weight (509.5 vs. 518.0 kg, P = 0.02), total body weight gain (163.7 vs. 170.3 kg, P = 0.01) and average body weight daily gain (1.366 vs. 1.420 kg, P = 0.01) were greater for SCB-fed bulls. Feed efficiency of SCB-supplemented bulls was 8.05% greater than CON (P = 0.04). Probiotic supplementation with live yeast Saccharomyces cerevisiae boulardii CNCM I-1079 during the first 42 days in feedlot contributes to reaching the plateau of DMI curve earlier and improving overall performance of Nellore bulls during the total period.
Proposal of the energy consumption analysis process for the residential houses using big data analytics technique
Authors: Pak W , Kim Inhan , Choi Jungsik
Published: October 2021

Recently, nations around the world have been implementing various policies to reduce energy consumption by improving “building energy performance” at the governmental level. In addition, “the public data opening system” has been institutionalized so that private companies could reproduce useful information by utilizing public data. However, it is insufficient to improve the energy performance of residential houses by analysing the actual energy consumption of residential houses using public open data. This study proposes a “Big Data Analysis Process for Residential Housing Energy Consumption” by utilizing public open data. This process is organized into four stages as follows: Data Understanding, regarding exploring and collecting architectural data, meteorological data, and energy consumption data; Data Processing, regarding the transforming energy consumption data of residential housing and reference input data to make master data, which is analysis data that have been processed by filtering, refining, and type conversion of the collected data, for the big data analysis; Data Analytics, development of an analysis model for the energy consumption of residential housing applying analysis algorithm; Evaluation, data assessment and application of the analytical model.The purpose of this study is to reproduce green remodeling with useful information: analysing a variety of data open to the private sector using big data analysis techniques. It is expected that the “Big Data Analysis Process for Energy Consumption” will be used to confirm the correlation between the energy consumption of residential houses and the architectural elements, and to effectively derive the energy performance improvement factors for energy saving in buildings.
Varieties and Mechanisms of Common Ownership: A Calibration Exercise for Competition Policy
Authors: Tzanaki Anna
Published: October 2021

Minority shareholdings have been on the regulatory agenda of competition authorities for some time. Recent empirical studies, however, draw attention to a new, thought-provoking theory of harm: common ownership by institutional investors holding small, parallel equity positions in several competing firms within concentrated industries. While critical voices abound, EU and U.S. antitrust agencies closely follow these developments indicating an appetite to act. This article connects the common ownership debate to merger control and explores: i) the aims and scope of legal control as regards partial acquisitions in different jurisdictions; ii) the nature of potential competition effects arising from passive minority shareholding; and iii) the plausibility of common owners’ anticompetitive strategies from a corporate governance perspective.

Drawing a distinction between “concentrated” and “diffuse” common ownership, it sheds light on the different supporting mechanisms and varying harm potential of each variety. “Passive influence” mechanisms characterizing “diffuse” common ownership may not only generate plausible and material competition concerns in given circumstances but present challenges for the effective jurisdictional and remedial design of merger law frameworks. Competition policy should stay current by explicitly recognizing these novel insights in enforcement practice and developing guidelines on how to treat common ownership cases in the future.
Long-term good outcome of the fibrocavitary form of pulmonary Mycobacterium avium complex disease with concomitant abatacept monotherapy in a patient with rheumatoid arthritis
Authors: Banno Shogo , Yamaguchi Etsuro , Iwagaitsu Shiho , Nobata Hironobu , Yamaguchi Makoto , Sugiyama Hirokazu , Kinashi Hiroshi , Katsuno Takayuki , Kubo Akihito , Ito Satoru , Ito Yasuhiko
Published: October 2021

A 53-year-old woman diagnosed with rheumatoid arthritis (RA) demonstrated thick-walled large cavities with consolidation in the left upper lobe on chest computed tomography (CT). Mycobacterium avium was isolated from sputum cultures, and she was diagnosed as having the fibrocavitary (FC) form of pulmonary Mycobacterium avium complex (MAC) disease. Clarithromycin-containing, multidrug, anti-MAC chemotherapy was started immediately. After 7 months, the cavitary lesions improved, and sputum cultures showed negative conversion. Thereafter, abatacept monotherapy was started due to high RA disease activity. Clinical remission of RA has been sustained and cavitary lesions disappeared by concomitant abatacept and anti-MAC therapy for more than 5 years. Immediate initiation of anti-MAC therapy and prior confirmed efficacy are needed for the treatment of the FC form. Abatacept and anti-MAC therapy could be continued, leading to the withdrawal of prednisolone, along with careful observation by strict chest CT evaluation and repeated sputum cultures. Biologics are generally contraindicated for pulmonary MAC disease, particularly the FC form. When there is a pre-existing lung lesion apparently of FC type, abatacept cannot be started without prior anti-MAC chemotherapy. This case suggests that abatacept may be carefully used to avoid progressive joint destruction after FC lesions of pulmonary MAC disease are resolved.
Standardization of rounds on a general paediatric ward: Implementation of a checklist to improve efficiency, quality of rounds, and family satisfaction
Authors: Trahan Camille , Hui Angela Y , Binepal Navneet
Published: October 2021

Objective

The purpose of this study was to develop a standardized rounding tool for use on the general paediatric ward and to determine if its use can improve quality of rounds as well as patient and parent satisfaction.

Methodology

The study used a pre- and post-intervention prospective observational methodology. The intervention consisted of the implementation of a Checklist Rounding Tool (CRT) entitled the ‘Paediatric Inpatient Rounding Checklist (PIRC)’ which outlined items deemed essential to discuss during rounds for all patients admitted to the paediatric ward. The PIRC was created by the research team after reviewing the literature and it was peer reviewed by a panel of expert paediatricians. Performance on rounds based on discussion of checklist items as well as patient and parent satisfaction were evaluated by an external observer both pre- and post-PIRC implementation.

Results

Four of the five less frequently addressed checklist items were discussed significantly more post-intervention. The Rounds Quality Score was significantly improved after checklist implementation, the pre- and post-intervention scores being 8.24 and 9.61/10, respectively (P-value <0.001). Patient and parent satisfaction were rated higher with the use of the checklist. There was no difference in the duration of rounds between the pre- and post-implementation phases.

Conclusion

In summary, utilization of a standardized rounding tool on an inpatient paediatric ward led to improvement in quality of rounds as well as patient and parent satisfaction.
Forty years of problem-oriented policing: A review of progress in England and Wales
Authors: Bullock Karen , Sidebottom Aiden , Armitage Rachel , Ashby Matthew P J , Clemmow Caitlin , Kirby Stuart , Laycock Gloria , Tilley Nick
Published: October 2021

This article analyses and critically reflects on the position of problem-oriented policing within England and Wales. Problem-oriented policing is a framework for improving police effectiveness. Its adoption has consistently been shown to be associated with sizable reductions in a wide range of crimes and public safety issues. However, many studies also find that problem-oriented policing is difficult to embed and sustain within police organisations. This article draws on the experiences and perspectives of 86 informed stakeholders to critically examine the position and practice of problem-oriented policing 40 years after its original formulation by Herman Goldstein in 1979. We argue that despite evidence of renewed interest in problem-oriented policing, the approach is not habitually conducted within police organisations in England and Wales. Where it is conducted, the practice of problem-oriented policing is found to lack discipline, the processes tend not to be faithfully followed, and there are weaknesses at all stages of the process. Implications of the findings for future research and police practice are discussed.
Species as a Heuristic: Reconciling Theory and Practice
Authors: Wells Tom , Carruthers Tom , Muñoz-Rodríguez Pablo , Sumadijaya Alex , Wood John R I , Scotland Robert W
Published: October 2021

Species are crucial to most branches of biological research, yet remain controversial in terms of definition, delimitation, and reality. The difficulty of resolving the “species problem” stems from the tension between their theoretical concept as groups of evolving and highly variable organisms and the practical need for a stable and comparable unit of biology. Here, we suggest that treating species as a heuristic can be consistent with a theoretical definition of what species are and with the practical means by which they are identified and delimited. Specifically, we suggest that theoretically species are heuristic since they comprise clusters of closely related individuals responding in a similar manner to comparable sets of evolutionary and ecological forces, whilst they are practically heuristic because they are identifiable by the congruence of contingent properties indicative of those forces. This reconciliation of the theoretical basis of species with their practical applications in biological research allows for a loose but relatively consistent definition of species based on the strategic analysis and integration of genotypic, phenotypic, and ecotypic data. [Cohesion; heuristic; homeostasis; lineage; species problem.]
Genome Assembly and Transcriptome of Colletotrichum sublineola CsGL1, a New Resource to Study Anthracnose Disease in Sorghum
Authors: Baldrich Patricia , Chaya Timothy , Caplan Jeffrey L. , Meyers Blake C.
Published: October 2021

Colletotrichum species are globally distributed and well known as members of a destructive phytopathogenic genus, causing the anthracnose disease in a wide variety of crops and fruits. Colletotrichum sublineola is the causal agent of the anthracnose disease in sorghum, causing losses of up to 50% in yield. Here, we used PacBio sequencing combined with RNA-seq to generate a chromosome-level assembly and annotation of the Colletotrichum sublineola strain CsGL1.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Population Dynamics, Effective Soil Factors, and LAMP Detection Systems forPhytophthoraSpecies Associated with Kiwifruit Diseases in China
Authors: Li Mingzhu , Guo Qian , Liang Mengyi , Zhao Qing , Lin Tao , Gao Han , Hieno Ayaka , Kageyama Koji , Zhang Xin , Cui Langjun , Yan Yaping , Qiang Yi
Published: October 2021

China has the largest area of kiwifruit production in the world. Pathogens associated with root diseases of kiwi trees have not been investigated extensively. In this research, three Phytophthora species, Phytophthora cactorum, Phytophthora cinnamomi, and Phytophthora lateralis, which are pathogenic to kiwi trees in the main planting areas of China, were studied. The population densities of these species in 128 soil samples from 32 kiwi orchards in 2017 and 2018 were measured using multiplex real-time quantitative PCR based on the ras-related protein gene Ypt1. P. cactorum was the most widely distributed of the three species in orchards of the Zhouzhi and Meixian prefectures. We used redundancy analysis to examine soil factors in the kiwi orchards to understand their effects on the population densities of the Phytophthora species. The redundancy analysis indicated that soil temperature and pH were significantly correlated with the abundance of P. cactorum and P. cinnamomi. In addition, two loop-mediated isothermal amplification detection systems for P. cactorum were developed based on the tigA gene. The color-change detection system proved to be accurate, sensitive, and faster than quantitative PCR. The results of this study, along with the loop-mediated isothermal amplification detection systems, will be of great use in the control of Phytophthora diseases for the production of kiwifruits in China.
Characterization and Pathogenicity ofPythium-Like Species Associated with Root and Collar Rot of Kiwifruit in Turkey
Authors: Türkkan Muharrem , Özer Göksel , Karaca Gürsel , Erper İsmail , Derviş Sibel
Published: October 2021

During the period of June to October in 2018, a widespread decline was observed on kiwifruit vines in the vineyards located in the Altınordu, Fatsa, and Perşembe districts of Ordu province in Turkey. The symptoms were associated with reddish-brown rots expanding from the root to the collar with sparse off-color foliage. Based on the percentage of the total infected samples across 18 vineyards, the most common oomycete species were Globisporangium intermedium (37.1%), Phytopythium vexans (34.3%), Globisporangium sylvaticum (14.3%), Globisporangium heterothallicum (11.4%), and Pythium dissotocum (2.9%). The morphological identification of isolates was confirmed based on partial DNA sequences containing the nuclear rDNA internal transcribed spacer region gene and the mitochondrial cytochrome c oxidase subunit II gene. The optimum growth temperature and the optimum pH values of the five species ranged from 22.98 to 28.25°C and 5.67 to 8.51, respectively. Pathogenicity tests on the seedlings of kiwifruit cv. Hayward revealed significant differences in virulence among isolates. Phytopythium vexans and Globisporangium sylvaticum isolates caused severe root and collar rot resulting in seedling death, while Globisporangium heterothallicum and Globisporangium intermedium isolates had relatively lower virulence. All Globisporangium spp. and Phytopythium vexans isolates significantly decreased plant growth parameters (plant height, shoot and root dry weights, and root length); however, Pythium dissotocum caused very mild symptoms and did not affect these parameters of growth. To our knowledge, this is the first study reporting Globisporangium sylvaticum, Globisporangium heterothallicum, and Globisporangium intermedium causing root and collar rot on kiwifruit not only in Turkey but also in the world.
Genome Sequence Resource of the Causal Agent of Persimmon Anthracnose, Colletotrichum horii Strain SD010 from China
Authors: Wang Jie , Yu Xianmei , Ai Chengxiang , Gao Rui
Published: October 2021

Colletotrichum horii is a main causal agent of persimmon (Diospyros kaki) anthracnose and is distributed widely in persimmon-producing areas of the world. Here, we report the first high-quality draft genome sequence of C. horii strain SD010. This will provide a reference for understanding adaptive evolution of genome structure, genes, and population diversity among members of the C. gloeosporioides species complex, and also help in understanding the mechanisms of host–pathogen interactions and improve management strategies of anthracnose.
TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions
Authors: Giaccherini Matteo , Rizzato Cosmeri , Gentiluomo Manuel , Lupetti Antonella , Flores-Luna Lourdes , Vivas Jorge , Bravo Maria Mercedes , Kasamatsu Elena , Muñoz Nubia , Canzian Federico , Kato Ikuko , Campa Daniele
Published: October 2021

Background

Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori, and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population.

Methods

We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer.

Results

Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 (P = 0.006) and rs1726866 (P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04–2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80–2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction.

Conclusion

In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.
Demographics of Gastroparesis Hospitalizations Through the Age Spectrum Using National Inpatient Databases
Authors: Shahsavari Dariush , Thomas Rachel , Ehrlich Adam C. , Feinstein Laurence H. , Malik Zubair , Parkman Henry P.
Published: October 2021

Goal:

The goal of this study was to characterize the etiology and demographics of hospitalized patients with gastroparesis (Gp) across different age groups.

Background:

Gp is a chronic condition associated with increasing hospitalizations and costs. The gender and etiology distributions of Gp throughout the age spectrum are unknown.

Materials and Methods:

Nationwide Inpatient Sample (NIS) and Kid’s Inpatient Database (KID) were used to identify patients using International Classification of Diseases (ICD)-10 codes for Gp as a primary diagnosis or as secondary diagnosis with the first diagnosis a GI-related symptom.

Results:

There were a total of 15,790 admissions (75.6% female, age: 46.2±18.0 y). After age 6, female admissions percentage increased: ages 2 to 5: 45.0%, ages 6 to 12: 62.8%, ages 13 to 20: 76.7% (P<0.001), with a distinct increase at age 12. Diabetic gastroparesis (DG) was seen in 3995 (25.3%) of all Gp admissions but in only 1.1% of children under the age of 20. Overall, 68% of DG admissions were female, but a higher percentage of DG was seen among male admissions for Gp compared with female admissions for Gp between ages 21 and 64 (38.3% vs. 23%, P<0.001). The most common races were white (63.2%), African American (20.6%), and Hispanic (8.7%). DG was more often present in Native American (61.9%), Hispanic (39.1%), and African American (38.2%) admissions than in white patients (17.8%; P<0.05).

Conclusions:

This study using large inpatient databases shows that the gender, race, and etiology of Gp admissions is age-dependent. The female predominance of Gp admissions is more prominent from the second decade of life. DG, although uncommon in children, is seen more often in nonwhite admissions.
Cirrhosis Inpatients Receive More Opioids and Fewer Nonopioid Analgesics Than Patients Without Cirrhosis
Authors: Rubin Jessica B. , Lai Jennifer C. , Shui Amy M. , Hohmann Samuel F. , Auerbach Andrew
Published: October 2021

Goals/Background:

Pain is common among cirrhosis patients, particularly those hospitalized with acute illness. Managing pain in this population is challenging due to concern for adverse events and lack of guidelines for analgesic use. We sought to characterize analgesic use among inpatients with cirrhosis compared with matched noncirrhosis controls, as well as hospital-level variation in prescribing patterns.

Methods:

We utilized the Vizient Clinical Database, which includes clinical and billing data from hospitalizations at >500 US academic medical centers. We identified cirrhosis patients hospitalized in 2017-2018, and a matched cohort of noncirrhosis patients. Types of analgesic given—acetaminophen (APAP), nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvants (eg, gabapentinoids, antidepressants) were defined from inpatient prescription records. Conditional logistic regression was used to associate cirrhosis diagnosis with analgesic use.

Results:

Of 116,363 cirrhosis inpatients, 83% received at least 1 dose of an analgesic and 58% had regular inpatient analgesic use, rates that were clinically similar to noncirrhosis controls. Cirrhosis inpatients were half as likely to receive APAP (26% vs. 42%, P<0.01) or NSAIDs (3% vs. 7%, P<0.01), but were more likely to receive opioids (59% vs. 54%, P<0.01), particularly decompensated patients (60%). There was notable variation in analgesic prescribing patterns between hospitals, especially among cirrhosis patients.

Conclusions:

Analgesic use was common among inpatients, with similar rates among patients with and without cirrhosis. Cirrhosis patients—particularly decompensated patients—were less likely to receive APAP and NSAIDs and more likely to receive opioid analgesics. Because of lack of evidence-based guidance for management of cirrhosis patients with pain, providers may avoid nonopioid analgesics due to perceived risks and consequently may overutilize opioids in this high-risk population.
Improving Automated Glioma Segmentation in Routine Clinical Use Through Artificial Intelligence-Based Replacement of Missing Sequences With Synthetic Magnetic Resonance Imaging Scans
Authors: Thomas Marie Franziska , Kofler Florian , Grundl Lioba , Finck Tom , Li Hongwei , Zimmer Claus , Menze Björn , Wiestler Benedikt
Published: October 2021

Objectives

Although automated glioma segmentation holds promise for objective assessment of tumor biology and response, its routine clinical use is impaired by missing sequences, for example, due to motion artifacts. The aim of our study was to develop and validate a generative adversarial network for synthesizing missing sequences to allow for a robust automated segmentation.

Materials and Methods

Our model was trained on data from The Cancer Imaging Archive (n = 238 WHO II–IV gliomas) to synthesize either missing FLAIR, T2-weighted, T1-weighted (T1w), or contrast-enhanced T1w images from available sequences, using a novel tumor-targeting loss to improve synthesis of tumor areas. We validated performance in a test set from both the REMBRANDT repository and our local institution (n = 68 WHO II–IV gliomas), using qualitative image appearance metrics, but also segmentation performance with state-of-the-art segmentation models. Segmentation of synthetic images was compared with 2 commonly used strategies for handling missing input data, entering a blank mask or copying an existing sequence.

Results

Across tumor areas and missing sequences, synthetic images generally outperformed both conventional approaches, in particular when FLAIR was missing. Here, for edema and whole tumor segmentation, we improved the Dice score, a common metric for evaluation of segmentation performance, by 12% and 11%, respectively, over the best conventional method. No method was able to reliably replace missing contrast-enhanced T1w images.

Discussion

Replacing missing nonenhanced magnetic resonance sequences via synthetic images significantly improves segmentation quality over most conventional approaches. This model is freely available and facilitates more widespread use of automated segmentation in routine clinical use, where missing sequences are common.
Three-Dimensional H-Scan Ultrasound Imaging of Early Breast Cancer Response to Neoadjuvant Therapy in a Murine Model
Authors: Tai Haowei , Song Jane , Li Junjie , Reddy Shreya , Khairalseed Mawia , Hoyt Kenneth
Published: October 2021

Objectives

Three-dimensional (3D) H-scan is a new ultrasound (US) technique that images the relative size of acoustic scatterers. The goal of this research was to evaluate use of 3D H-scan US imaging for monitoring early breast cancer response to neoadjuvant therapy using a preclinical murine model of breast cancer.

Materials and Methods

Preclinical studies were conducted using luciferase-positive breast cancer–bearing mice (n = 40). Anesthetized animals underwent US imaging at baseline before administration with an apoptosis-inducing drug or a saline control. Image data were acquired using a US scanner equipped with a volumetric transducer following either a shorter- or longer-term protocol. The later included bioluminescent imaging to quantify tumor cell viability. At termination, tumors were excised for ex vivo analysis.

Results

In vivo results showed that 3D H-scan US imaging is considerably more sensitive to tumor changes after apoptosis-inducing drug therapy as compared with traditional B-scan US. Although there was no difference at baseline (P > 0.99), H-scan US results from treated tumors exhibited progressive decreases in image intensity (up to 62.2% by day 3) that had a significant linear correlation with cancer cell nuclear size (R
2 > 0.51, P < 0.001). Results were validated by histological data and a secondary longitudinal study with survival as the primary end point.

Discussion

Experimental results demonstrate that noninvasive 3D H-scan US imaging can detect an early breast tumor response to apoptosis-inducing drug therapy. Local in vivo H-scan US image intensity correlated with cancer cell nuclear size, which is one of the first observable changes of a cancer cell undergoing apoptosis and confirmed using histological techniques. Early imaging results seem to provide prognostic insight on longer-term tumor response. Overall, 3D H-scan US imaging is a promising technique that visualizes the entire tumor and detects breast cancer response at an early stage of therapy.
Assessment of Lung Structure and Regional Function Using 0.55 T MRI in Patients With Lymphangioleiomyomatosis
Authors: Bhattacharya Ipshita , Ramasawmy Rajiv , Javed Ahsan , Lowery Margaret , Henry Jennifer , Mancini Christine , Machado Tania , Jones Amanda , Julien-Williams Patricia , Lederman Robert J. , Balaban Robert S. , Chen Marcus Y. , Moss Joel , Campbell-Washburn Adrienne E.
Published: October 2021

Objectives

Contemporary lower-field magnetic resonance imaging (MRI) may offer advantages for lung imaging by virtue of the improved field homogeneity. The aim of this study was to evaluate the utility of lower-field MRI for combined morphologic imaging and regional lung function assessment. We evaluate low-field MRI in patients with lymphangioleiomyomatosis (LAM), a rare lung disease associated with parenchymal cysts and respiratory failure.

Materials and Methods

We performed lung imaging on a prototype low-field (0.55 T) MRI system in 65 patients with LAM. T2-weighted imaging was used for assessment of lung morphology and to derive cyst scores, the percent of lung parenchyma occupied by cysts. Regional lung function was assessed using oxygen-enhanced MRI with breath-held ultrashort echo time imaging and inhaled 100% oxygen as a T1-shortening MR contrast agent. Measurements of percent signal enhancement from oxygen inhalation and percentage of lung with low oxygen enhancement, indicating functional deficits, were correlated with global pulmonary function test measurements taken within 2 days.

Results

We were able to image cystic abnormalities using T2-weighted MRI in this patient population and calculate cyst score with strong correlation to computed tomography measurements (R = 0.86, P < 0.0001). Oxygen-enhancement maps demonstrated regional deficits in lung function of patients with LAM. Heterogeneity of oxygen enhancement between cysts was observed within individual patients. The percent low-enhancement regions showed modest, but significant, correlation with FEV1 (R = −0.37, P = 0.007), FEV1/FVC (R = −0.33, P = 0.02), and cyst score (R = 0.40, P = 0.02). The measured arterial blood ΔT1 between normoxia and hyperoxia, used as a surrogate for dissolved oxygen in blood, correlated with DLCO (R = −0.28, P = 0.03).

Conclusions

Using high-performance 0.55 T MRI, we were able to perform simultaneous imaging of pulmonary structure and regional function in patients with LAM.
An Unusual Case of Bilateral Ureteric Metastasis on PSMA PET-CT Scan in Carcinoma Prostate
Authors: Dang Shreya , Pereira Melvika , Singh Natasha , Shivdasani Divya , Roy Debdip , Kesariya Jugal , Rungta Rachita
Published: October 2021

The most common locations for metastasis in adenocarcinoma of the prostate gland are lymph nodes, bone, lung, and liver. The involvement of the ureter as a site of metastasis in prostate carcinoma is quite rare in literature. Here we present a case involving bilateral ureters along with bilateral vesicoureteric junctions in a known case of prostate adenocarcinoma.
Excellent Response to Adapted Low-Dose 177Lu-PSMA-617 PSMA Therapy in Renal Compromise Patient
Authors: Usmani Sharjeel , Al Kandari Fareeda , Alrekhais Ibrahim , N. Khalaf Shatha , Ahmed Najeeb
Published: October 2021

Prostate-specific membrane antigen (PSMA)–targeted radioligand therapy with 177Lu-PSMA-617 has shown promising results in patients with metastasized castration-resistant prostate cancer. We report a case of a 74-year-old man with metastatic prostate cancer with comorbidities of diabetes mellitus, hypertension, and chronic kidney disease. In order to minimize radiation burden to kidneys, a lower dose of 4 GBq of 177Lu-PSMA-617 was prescribed instead of the usual 6 to 7 GBq. There was significant decrease in prostate-specific antigen levels and symptoms. Renal profile remained stable. This case highlights that compromised renal function is not a definite contraindication to radionuclide therapy, and doses can be modified based on risk versus benefits.
Aminipila luticellarii sp. nov., an anaerobic bacterium isolated from the pit mud of strong aromatic Chinese liquor, and emended description of the genus Aminipila
Authors: Wei Zhixian , Ma Shichun , Chen Rui , Wu Weidong , Fan Hui , Dai Lirong , Deng Yu
Published: October 2021

A novel mesophilic, aerotolerant anaerobic bacterium, designated JN-18T, was isolated from the pit mud of a strong aromatic Chinese liquor. According to a 16S rRNA gene sequence analysis, it had the highest sequence similarity to

Aminipila butyrica

DSM 103574T (95.69%). The G+C content of its genomic DNA was 43.39 mol%. The cells were Gram-stain-negative, slightly curved rods with flagella. Optimum growth was observed at 37 °C, pH 6.5 and without extra addition of NaCl. Strain JN-18Tutilized amino acids (l-alanine, l-arginine, l-asparagine, l-lysine, l-methionine, l-serine and l-threonine), malate and pyruvate, and used l-arginine and l-lysine to produce acetate, butyrate, H2, and CO2. The major cellular fatty acids of strain JN-18T were C14:0, C16:0 DMA and C18:1 cis-9 DMA. The carbohydrate composition of the cell wall predominantly included galactose, glucose and rhamnose. Based on its phylogenetic, phenotypic, physiological and biochemical characteristics, strain JN-18T was classified as a representative of a novel species within the genus

Aminipila

, for which the name Aminipila luticellarii sp. nov. is proposed. The type strain is JN-18T (=CCAM 412T=JCM 39126T).
Replication and transmission of an influenza A(H3N2) virus harboring the polymerase acidic I38T substitution, in guinea pigs.
Authors: Mhamdi Zeineb , Carbonneau Julie , Venable Marie-Christine , Baz Mariana , Abed Yacine , Boivin Guy
Published: October 2021

The polymerase acidic (PA) I38T substitution is a dominant marker of resistance to baloxavir. We evaluated the impact of I38T on the fitness of a contemporary influenza A(H3N2) virus. Influenza A/Switzerland/9715293/2013 (H3N2) wild-type (WT) virus and its I38T mutant were rescued by reverse genetics. Replication kinetics were compared using ST6GalI-MDCK and A549 cells and infectivity/contact transmissibility were evaluated in guinea pigs. Nasal wash (NW) viral titres were determined by TCID50 ml−1 in ST6GalI-MDCK cells. Competition experiments were performed and the evolution of viral population was assessed by droplet digital RT-PCR. I38T did not alter in vitro replication. I38T induced comparable titres vs the WT in guinea pigs NWs and the two viruses transmitted equally by direct contact. However, a 50 %:50 % mixture inoculum evolved to mean WT/I38T ratios of 71 %:29 % and 66.4 %:33.6 % on days 4 and 6 p.i., respectively. Contemporary influenza A(H3N2)-I38T PA variants may conserve a significant level of viral fitness.
The role of interferon regulatory factor 7 in the pathogenicity and immunogenicity of rabies virus in a mouse model
Authors: Wang Caiqian , Lv Lei , Wu Qiong , Wang Zongmei , Luo Zhaochen , Sui Baokun , Zhou Ming , Fu Zhen F. , Zhao Ling
Published: October 2021

Rabies is a zoonotic disease caused by the rabies virus (RABV). RABV can lead to fatal encephalitis and is still a serious threat in most parts of the world. Interferon regulatory factor 7 (IRF7) is the main transcriptional regulator of type I IFN, and it is crucial for the induction of IFNα/β and the type I IFN-dependent immune response. In this study, we focused on the role of IRF7 in the pathogenicity and immunogenicity of RABV using an IRF7-/- mouse model. The results showed that the absence of IRF7 made mice more susceptible to RABV, because IRF7 restricted the replication of RABV in the early stage of infection. IRF7 deficiency affected the recruitment of plasmacytoid dendritic cells to the draining lymph nodes (dLNs), reduced the production of type I IFN and expression of IFN-stimulated genes. Furthermore, we found that the ability to produce specific RABV-neutralizing antibody was impaired in IRF7-/- mice. Consistently, IRF7 deficiency affected the recruitment of germinal-centre B cells to dLNs, and the generation of plasma cells and RABV-specific antibody secreting cells. Moreover, the absence of IRF7 downregulated the induction of IFN-γ and reduced type 1 T helper cell (Th1)-dependent antibody production. Collectively, our findings demonstrate that IRF7 promotes humoral immune responses and compromises the pathogenicity of RABV in a mouse model.
Epithelial-to-mesenchymal transition lowers the cholesterol pathway, which influences colon tumors differentiation
Authors: Aulas Anaïs , Liberatoscioli Maria Lucia , Finetti Pascal , Cabaud Olivier , Birnbaum David J. , Birnbaum Daniel , Bertucci François , Mamessier Emilie
Published: October 2021

Colorectal cancer (CRC) is the second cause of death worldwide. Up to 70% of CRC patients will metastasize. Identify new biomarkers of progression to prevent/delay disease evolution is urgent. Epithelial-to-mesenchymal transition (EMT) is a major program engaged during metastasis. We aim at identifying a combination of new genes that further identify signs of EMT in cancer tissues. We treated HT-29 cells grown in 3D with an EMT Inducing cocktail, and collect them before during and after treatment. For each condition, pan-transcriptomic analyses were done. Genes that were both induced upon EMT induction and inhibited upon EMT release (mesenchymal-to-epithelial transition or MET) were selected. We identified new genes for EMT-MET programs. These genes were used to build a metagene that, when applied to a database of transcriptomic data from primary colorectal tumors (n= 2,239), had an independent prognosis value. Finally, we submitted this metagene to CMap and identified drugs that might affect EMT-MET programs. Statins, well-known inhibitors of cholesterol synthesis, were among them and effectively delayed MET. These data show that cholesterol and EMT pathways are opposite regulators and impact differently tumor differentiation and outcome.

TRANSLATIONAL RELEVANCE

Metastases are the main cause of death of colorectal cancer (CRC) and the major issue in CRC management. Understanding the chain of events that lead to metastasis occurrence is urgent to identify new biomarkers of progression and/or new potential targets. Epithelial to mesenchymal transition (EMT) is a major player in cancer dissemination that remains non-targetable due to its broad involvement in tissue homeostasis. Here, we used a relevant in vitro dynamic model to identify the pathways triggered during EMT in CRC and how this might improve tumors classification, prognosis and open therapeutic avenue for this deadly disease. The cholesterol pathway surprisingly popped-out from this model and turned out to be a good prognosis factor of disease-free survival for CRC. Altogether, our results showed that an active EMT program lowers the cholesterol pathway, which further influence the differentiation of colon tumor toward the most aggressive subtypes.
Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease
Authors: Wellens Judith , Edmans Matthew , Obolski Uri , McGregor Colleen GC , Simmonds Peter , Turner Marc , Jarvis Lisa , Skelley Donal , Dunachie Susanna , Barnes Eleanor , Eyre David W , Colombel Jean-Frederic , Wong Serre-Yu , Klenerman Paul , Lindsey James O , Satsangi Jack , Thompson Craig P
Published: October 2021

There is substantial interest regarding the perceived risk that immunomodulator and biologic therapy could have on COVID-19 disease severity among patients with inflammatory bowel disease (IBD) and clinicians. In this study, we show that infliximab/thiopurine combination therapy is associated with significantly lower IgA, a range of lower IgG responses as well as impaired neutralising antibody responses, compared to responses observed in healthy individuals. We also demonstrate that whilst IgG responses were significantly reduced in individuals with IBD treated with infliximab or vedolizumab monotherapy compared to healthy controls, there was no significant reduction in IgA and neutralising antibody responses. As neutralising antibody responses correlate with protection, this observation may provide the mechanistic explanation for the observation reported by the SECURE-IBD study that individuals on infliximab/thiopurine combination therapy were at greater risk of severe COVID-19 outcomes than patients on monotherapy.
Can individualized targets for transcranial magnetic stimulation increase treatment effectiveness in psychiatric disorders? A systematic review and meta-analysis
Authors: Zheng Yanbin , Zhang Zhaojie , Yang Bo , Zhou Weiran , Che Xianwei , Dong Guang-Heng
Published: October 2021

Background

Transcranial magnetic stimulation (TMS) techniques have developed in recent years in research and clinical treatment. The identification of targets for TMS treatment is increasingly individualized based on morphology or function; however, whether individualized TMS targets could increase the treatment effectiveness of psychiatric disorders remains controversial.

Methods

A meta-analysis was conducted to explore whether individualized TMS targets are better than standard targets. A total of 3340 studies were identified in a systematic search, and twelve were included in the quantitative review. Among them, eight used a structure-based individualized target selection method, nine were on depression, and four compared unilateral and bilateral stimulant targets.

Results

Meta-analyses showed that: (1) individualized TMS targets increased the effectiveness in treating psychiatric disorders; (2) structural-based TMS targets brought additional treatment effectiveness, and PET-based structural selection methods proved to be valid; (3) there was no significant increase in the treatment effects of individualized targets in EEG-based and task-fMRI-based methods; (4) updated stimulant sequences did not increase the individualized target treatment effect; (5) individualized TMS targets showed increased treatment effectiveness in depression but not in schizophrenia; and (6) bilateral stimuli did not show additional effectiveness compared with unilateral stimuli.

Conclusions

The current findings revealed that individualized TMS targets show additional treatment effectiveness compared to standard targets in treating psychiatric disorders, and structure-based selection methods are effective in identifying TMS targets. The current conclusions provide directions for future TMS research and provide valuable references for clinicians treating psychiatric disorders.
SEIRDQ: A COVID-19 case projection modeling framework using ANN to model quarantine
Authors: Chandra Harish , Margaryan Arman , Meng Xianwei
Published: October 2021

We propose and implement a novel approach to model the evolution of COVID-19 pandemic and predict the daily COVID-19 cases (infected, recovered and dead). Our model builds on the classical SEIR-based framework by adding additional compartments to capture recovered, dead and quarantined cases. Quarantine impacts are modeled using an Artificial Neural Network (ANN), leveraging alternative data sources such as the Google mobility reports. Since our model captures the impact of lockdown policies through the quarantine functions we designed, it is able to model and predict future waves of COVID-19 cases. We also benchmark out-of-sample predictions from our model versus those from other popular COVID-19 case projection models.
Molecular and functional characterization of the mouse intracardiac nervous system
Authors: Lizot Guénaëlle , Pasqualin Côme , Tissot Audrey , Pagès Stephane , Faivre Jean-François , Chatelier Aurélien
Published: October 2021

Background

The intracardiac nervous system (ICNS) refers to clusters of neurons, located within the heart, which participate to the neuronal regulation of cardiac functions and which are involved in the initiation of cardiac arrhythmias. Therefore, deciphering its role in cardiac physiology and physiopathology is mandatory.

Objective

The aim of this study is to provide a phenotypic, electrophysiological and pharmacological characterization of the mouse ICNS, which is still poorly characterized.

Methods

Global cardiac innervation and phenotypic diversity were investigated using immunohistochemistry on cleared murine heart and on tissue sections. Patch clamp technique was used for electrophysiological and pharmacological characterization of isolated mouse intracardiac neurons.

Results

We have identified the expression of seven distinct neuronal markers within mouse ICNS, thus proving the neurochemical diversity of this network. Of note, it was the first time that the existence of neurons expressing the calcium binding protein calbindin, the neuropeptide Y (NPY) and the cocain and amphetamine regulated transcript (CART) peptide, was described in the mouse. Electrophysiological studies also revealed the existence of four different neuronal populations based on their electrical behavior. Finally, we showed that these neurons can be modulated by several neuromodulators.

Conclusion

This study showed that mouse ICNS presents a molecular and functional complexity similar to other species, and is therefore a suitable model to decipher the role of individual neuronal subtypes regarding the modulation of cardiac function and the initiation of cardiac arrhythmias.
Adaptive coding of pain prediction error in the anterior insula
Authors: Hoskin R , Talmi D
Published: October 2021

Background

Understanding the mechanisms behind the influence of expectation and context on pain perception is crucial for improving analgesic treatments. Prediction error (PE) signals how much a noxious stimulus deviates from expectation and is therefore crucial for our understanding of pain perception. It is thought that the brain engages in ‘adaptive coding’ of pain PE, such that sensitivity to unexpected outcomes is modulated by contextual information. While there is behavioural evidence that pain is coded adaptively, and evidence that reward PE signals are coded adaptively, controversy remains regarding the underlying neural mechanism of adaptively-coded pain PEs.

Methods

A cued-pain task was performed by 19 healthy adults while undergoing FMRI scanning. BOLD responses to the task were tested using an axiomatic approach to identify areas that may code pain PE adaptively.

Results

The left dorsal anterior insula demonstrated a pattern of response consistent with adaptively-coded pain PE. Signals from this area were sensitive to both predicted pain magnitudes on the instigation of expectation, and the unexpectedness of pain delivery. Crucially however, the response at pain delivery was consistent with the local context of the pain stimulation, rather than the absolute magnitude of delivered pain, a pattern suggestive of an adaptively-coded PE signal.

Conclusions

The study advances our understanding of the neural basis of pain prediction. Alongside existing evidence that the periaqueductal grey codes pain PE and the posterior insula codes pain magnitude, the results highlight a distinct contribution of the left dorsal anterior insula in the processing of pain.

Significance statement

Although there is behavioural evidence that pain is coded adaptively, the neural mechanisms serving this process are not well understood. This study used functional MRI to provide the first evidence that the left dorsal anterior insula, an area associated with aversive learning, responds to pain in a manner consistent with the adaptive coding of pain prediction error. This study aids our understanding of the neural basis of subjective pain representation, and thus can contribute to the advancement of analgesic treatments.