bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Variants in the Regulatory T cell–Related Pathway and Colorectal Cancer Prognosis
Authors: Neumeyer Sonja , Hua Xinwei , Seibold Petra , Jansen Lina , Benner Axel , Burwinkel Barbara , Halama Niels , Berndt Sonja I. , Phipps Amanda I. , Sakoda Lori C. , Schoen Robert E. , Slattery Martha L. , Chan Andrew T. , Gala Manish , Joshi Amit D. , Ogino Shuji , Song Mingyang , Herpel Esther , Bläker Hendrik , Kloor Matthias , Scherer Dominique , Ulrich Alexis , Ulrich Cornelia M. , Win Aung K. , Figueiredo Jane C. , Hopper John L. , Macrae Finlay , Milne Roger L. , Giles Graham G. , Buchanan Daniel D. , Peters Ulrike , Hoffmeister Michael , Brenner Hermann , Newcomb Polly A. , Chang-Claude Jenny
Published: October 2020

Background:

High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis.

Methods:

In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer–specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated because tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2,047 colorectal cancer patients of the International Survival Analysis in Colorectal Cancer Consortium (ISACC).

Results:

A significant association of the TGFBR3 SNP rs7524066 with more favorable colorectal cancer–specific survival [hazard ratio (HR) per minor allele: 0.83; 95% confidence interval (CI), 0.74–0.94; P value: 0.0033] was replicated in ISACC (HR: 0.82; 95% CI, 0.68–0.98; P value: 0.03). Suggestive evidence for association was found with two IL7 SNPs, rs16906568 and rs7845577. Thirteen SNPs with differential associations with overall survival according to MSI in the discovery analysis were not confirmed.

Conclusions:

Common genetic variation in the Treg pathway implicating genes such as TGFBR3 and IL7 was shown to be associated with prognosis of colorectal cancer patients.

Impact:

The implicated genes warrant further investigation.
Low Subcutaneous Adiposity and Mortality in Esophageal Cancer
Authors: Zhou Margaret J. , Tseng Luke , Guo Xiaotao , Jin Zhezhen , Bentley-Hibbert Stuart , Shen Sherry , Araujo James L. , Spinelli Cathy F. , Altorki Nasser K. , Sonett Joshua R. , Neugut Alfred I. , Abrams Julian A.
Published: October 2020

Background:

Recent data suggest that subcutaneous adiposity represents an independent prognostic marker in cancer. We aimed to determine whether subcutaneous adiposity estimated by the subcutaneous adiposity tissue index (SATI) was associated with mortality in esophageal cancer.

Methods:

We conducted a retrospective analysis of a prospectively enrolled cohort from 2009 to 2015 with esophageal cancer at two major cancer centers. CT scans for initial staging were used to quantify adiposity and skeletal muscle areas. Subjects were categorized as above or below median SATI using sex-specific values. Sarcopenia was defined using previously established skeletal muscle area cutoffs. Cox proportional hazards modeling was performed to determine associations between SATI and all-cause mortality.

Results:

Of the original 167 patients, 78 met inclusion criteria and had CT images available. Mean age was 67 years, 81.8% had adenocarcinoma, and 58.9% had stage 3 or 4 disease. Median follow-up time was 29.5 months. Overall 5-year survival was 38.9% [95% confidence interval (CI), 26.8–50.7]. Lower body mass index, higher Charlson comorbidity score, and more advanced stage were independently associated with low SATI. Patients with low SATI had increased mortality (unadjusted HR 2.23; 95% CI, 1.20–4.12), even when adjusted for sarcopenia or for percent weight loss. In a multivariable model including age, histology, stage, and receipt of curative surgery, the association between low SATI and mortality was attenuated (adjusted HR 1.64; 95% CI, 0.81–3.34).

Conclusions:

Low subcutaneous adiposity as estimated by SATI may be associated with increased mortality in esophageal cancer.

Impact:

Interventions to reduce loss of subcutaneous fat may improve survival in esophageal cancer.
Adiposity and Endometrial Cancer Risk in Postmenopausal Women: A Sequential Causal Mediation Analysis
Authors: Dashti S. Ghazaleh , English Dallas R. , Simpson Julie A. , Karahalios Amalia , Moreno-Betancur Margarita , Biessy Carine , Rinaldi Sabina , Ferrari Pietro , Tjønneland Anne , Halkjær Jytte , Dahm Christina C. , Vistisen Helene Tilma , Menegaux Florence , Perduca Vittorio , Severi Gianluca , Aleksandrova Krasimira , Schulze Matthias B. , Masala Giovanna , Sieri Sabina , Tumino Rosario , Macciotta Alessandra , Panico Salvatore , Hiensch Anouk E. , May Anne M. , Quirós J. Ramón , Agudo Antonio , Sánchez Maria-Jose , Amiano Pilar , Colorado-Yohar Sandra , Ardanaz Eva , Allen Naomi E. , Weiderpass Elisabete , Fortner Renée Turzanski , Christakoudi Sofia , Tsilidis Konstantinos K. , Riboli Elio , Kaaks Rudolf , Gunter Marc J. , Viallon Vivian , Dossus Laure
Published: October 2020

Background:

Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity–endometrial cancer link in postmenopausal women.

Methods:

We used data from a case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis.

Results:

The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5−<25 kg/m2 was 2.51 (95% confidence interval, 1.26–5.02). The ORsNIE were 1.95 (1.01–3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06–1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71–1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88–1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89–1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54–3.09). Waist circumference gave similar results.

Conclusions:

Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight.

Impact:

If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.
Implications of MYC Rearrangements in Newly Diagnosed Multiple Myeloma
Authors: Abdallah Nadine , Baughn Linda B. , Rajkumar S. Vincent , Kapoor Prashant , Gertz Morie A. , Dispenzieri Angela , Lacy Martha Q. , Hayman Suzanne R. , Buadi Francis K. , Dingli David , Go Ronald S. , Hwa Yi L. , Fonder Amie , Hobbs Miriam , Lin Yi , Leung Nelson , Kourelis Taxiarchis , Warsame Rahma , Siddiqui Mustaqeem , Lust John , Kyle Robert A. , Ketterling Rhett , Bergsagel Leif , Greipp Patricia , Kumar Shaji K.
Published: October 2020

Purpose:

Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in patients with newly diagnosed multiple myeloma.

Experimental Design:

This is a retrospective study including 1,342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, who had cytogenetic testing by FISH at diagnosis, including MYC testing using the break apart FISH probe (8q24.1).

Results:

A rearrangement involving MYC was found in 8% of patients and was associated with elevated β2-microglobulin, ≥50% bone marrow plasma cells, IgA multiple myeloma, and the cooccurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)-based or PI + IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared with patients without MYC rearrangement (5.3 vs. 8.0 years, P < 0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5; P = 0.007).

Conclusions:

MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in patients with newly diagnosed multiple myeloma.
Antegrade Blood Flow on 4‐Dimensional Computed Tomography Angiography Predict Stroke Subtype in Patients With Acute Large Artery Occlusion
Authors: Zhang Meixia , Chen Zhicai , Xu Jinjin , Gong Xiaoxian , Shi Feina , Lou Min
Published: October 2020

Background

The purpose of this study was to determine whether the presence of antegrade blood flow was related to stroke subtype in patients with acute intracranial large artery occlusion.

Methods and Results

The prospectively collected data for consecutive patients who had occlusion of the unilateral M1 segment of the middle cerebral artery with or without internal carotid artery and received reperfusion therapy were retrospectively reviewed. Stroke causes were determined according to the Trial of
ORG
10172 in Acute Stroke Treatment standard. We defined antegrade flow as early opacification at the distal interface of the clot with subsequent distal extension on 4‐dimensional computed tomography angiography. A total of 387
large artery occlusion
patients were analyzed (229 men and 158 women; mean age, 71±14 years), including 77 (19.9%) with large artery atherosclerosis (
LAA
), 206 (53.2%) with cardioembolism, and 104 (26.9%) with undetermined causes. Antegrade flow was found in 206 (53.2%) patients, and 181 (46.8%) presented with retrograde flow. The rate of antegrade flow was much higher in patients with
LAA
than in those with cardioembolism (85.7% versus 42.2%,
P
<0.001). Multivariable logistic regression revealed that presence of antegrade flow was significantly associated with cuse of
LAA
after adjusting for confounding factors, when setting cardioembolism as reference (odds ratio, 5.650; 95% confidence interval, 2.451–13.158;
P
<0.001). The sensitivity, specificity, and positive and negative predictive values of the antegrade flow for predicting
LAA
were 43.1%, 91.5%, 85.7%, and 57.8%, respectively.

Conclusions

Using 4‐dimensional computed tomography angiography, antegrade flow can be identified in more than half of acute anterior
large artery occlusion
patients and occurs more frequently in those with
LAA
as the cause of stroke.
HIV Protease Inhibitor Ritonavir Impairs Endothelial Function Via Reduction in Adipose Mass and Endothelial Leptin Receptor‐Dependent Increases in NADPH Oxidase 1 (Nox1), C‐C Chemokine Receptor Type 5 (CCR5), and Inflammation
Authors: Bruder‐Nascimento Thiago , Kress Taylor C. , Kennard Simone , Belin de Chantemèle Eric J.
Published: October 2020

Background

Cardiovascular disease is currently the leading cause of death in patients with human immunodeficiency virus on combination antiretroviral therapy. Although the use of the protease inhibitor ritonavir has been associated with increased prevalence of cardiovascular disease, the underlying mechanisms remain ill‐defined. Herein, we tested the hypothesis that ritonavir‐mediated lipoatrophy causes endothelial dysfunction via reducing endothelial leptin signaling.

Methods and Results

Long‐term (4 weeks) but not short‐term (3 days) treatment with ritonavir reduced body weight, fat mass, and leptin levels and induced endothelial dysfunction in mice. Moreover, ritonavir increased vascular NADPH oxidase 1, aortic H
2
O
2
levels as well as interleukin‐1β, GATA3 (GATA binding protein 3), the macrophage marker (F4/80), and C‐C chemokine receptor type 5 (CCR5) expression. Reactive oxygen species scavenging with tempol restored endothelial function, and both NADPH oxidase 1 and CCR5 deletion in mice protected from ritonavir‐mediated endothelial dysfunction and vascular inflammation. Remarkably, leptin infusion markedly improved endothelial function and significantly reduced vascular NADPH oxidase 1, interleukin‐1β, GATA3, F4/80, and CCR5 levels in ritonavir‐treated animals. Selective deficiency in endothelial leptin receptor abolished the protective effects of leptin infusion on endothelial function. Conversely, selective increases in endothelial leptin signaling with protein tyrosine phosphatase deletion blunted ritonavir‐induced endothelial dysfunction.

Conclusions

All together, these data indicate that ritonavir‐associated endothelial dysfunction is a direct consequence of a reduction in adiposity and leptin secretion, which decreases endothelial leptin signaling and leads to a NADPH oxidase 1–induced, CCR5‐mediated reduction in NO bioavailability. These latter data also introduce leptin deficiency as an additional contributor to cardiovascular disease and leptin as a negative regulator of CCR5 expression, which may provide beneficial avenues for limiting human immunodeficiency virus infection.
Negative Polarity Items in Definite Superlatives
Authors: Bumford Dylan , Sharvit Yael
Published: October 2020

Ordinary superlative descriptions are well-known to provide safe harbor to negative polarity items (NPIs), as in the longest book anyone read. What is less well-known is that relative superlative descriptions also sometimes host NPIs, as in the loudest that anyone sang. We observe that this latter pattern is more general than has been previously described. In fact, relative superlatives can license NPIs outside of their own descriptions. On the one hand, we argue that this provides evidence that the superlative adjectives take sentential rather than nominal scope. But on the other, following insights in Howard 2014, we argue that traditional semantic accounts of scope-taking superlatives do not present the right monotonicity profile to account for the NPIs either. A recent, dynamic take on superlative semantics (Bumford 2017) is shown to do better.
Mating behavior and spermatophore morphology of the whip scorpion Typopeltis dalyi Pocock, 1900 (Uropygi, Thelyphonida)
Authors: Seiter Michael , Moser Marie Christine , Schwaha Thomas
Published: October 2020

Whip scorpions are an enigmatic group of terrestrial raptorial arachnids that show remarkable mating and courtship behavior in which the male forms a complex spermatophore. While whip spiders (Amblypygi) are relatively well-studied, whip scorpions (Uropygi) are poorly known. The two orders form the Pedipalpi, whip scorpions (Uropygi include Thelyphonida and Schizomida) and whip spiders (Amblypygi). Two major groups have been described based on the mode of sperm transfer that differ in the duration and mode of the typical female–male tandem mating dance. Because comprehensive studies are lacking, in this study we add to our knowledge of the reproductive biology of whip scorpions by analyzing the mating behavior and spermatophore morphology of the previously unstudied species Typopeltis dalyi Pocock, 1900. Our observations show that this species belongs to the second group and supports the hypothesis of P. Weygoldt that their mode of sperm transfer appears more effective than that of the first group and that sufficient sperm can be supplied with one mating. The mating behavior and spermatophore morphology in T. dalyi are similar to those of closely related species and add additional characters applicable for species classification and phylogenetic inferences.
A skeletochronological estimation of age structure of a population of the paddy frog, Fejervarya multistriata, from the central east of China
Authors: Zhang Lixia , Sheng Yongsun , Yuan Xiangyu , Zhong Xueting , Chen Xiaohong
Published: October 2020

Age determination is crucial for a full understanding of population dynamics. In this context, we studied the age structure of the paddy frog, Fejervarya multistriata, in a population from the central east of China, using a skeletochronological method. The lines of arrested growth in the phalanges were distinct, and each line was assumed to represent one year of age. Ages ranged between one and four years for adult males and two and four years for adult females. No significant difference was observed in the mean adult age between the sexes. In addition, a significant relationship between age and body size within each sex was detected. Results of ANCOVA analysis suggested a significant difference in body size between sexes when the effect of age was removed. The von-Bertalanffy model showed that females had a larger asymptotic body size than males, and the growth rate of females was higher than that of males. Therefore, the growth rate is a major factor underlying body size patterns in both sexes of F. multistriata in the study population.
Carex ledongensis (Cyperaceae), a new sedge from Hainan Isl. Of South China

Authors: YANG HU-BIAO , LIU GUO-DAO
Published: October 2020

A new species of Carex sect. Mitratae, C. ledongensis, is described and illustrated from Hainan, South China. The new species is similar to C. pseudotristachya but differs from the latter in its leaves much longer than culms, inflorescence with 3 spikes, terminal spike with 1.5 cm long peduncle, lateral spikes bisexual, perigynia fusiform, 6–8 mm long, and nutlets brownish black, 5–6 mm long.
Observations on Pluteaceae in Vietnam. 2. One new record and ten new species of Pluteus

Authors: MALYSHEVA EKATERINA , MALYSHEVA VERA , ALEXANDROVA ALINA , MOROZOVA OLGA
Published: October 2020

Fourteen specimens of Pluteus all collected in tropical forests of Vietnam were studied using morphological and molecular approaches. Pluteus subcervinus, is noted as a new record for Vietnam, and one collection appears to be close to P. velutinus, but not phylogenetically identical. One species of Pluteus from sect. Pluteus with metuloid pleurocystidia and pileipellis as a cutis (P. olivaceofibrillosus), one species from sect. Hispidoderma with non-metuloid cystidia and pileipellis as a hymeniderm (P. pallidosquamulosus), and eight species from sect. Celluloderma with non-metuloid cystidia and pileipellis organized as a cutis, an epithelium or a hymeniderm (P. varius, P. atypicus, P. castaneorugosus, P. flavidus, P. squamulososulcatus, P. podospilloides, P. pygmaeus and P. brunneovelutinus) are proposed as new. Descriptions of their macro- and microscopic features with a discussion of similar taxa are given. Their taxonomic positions were confirmed using DNA data.
Typification and taxonomic re-evaluation of Centaurea crnogorica and C. gjurasinii, two neglected yellow-flowered endemics of the Balkan Peninsula (Centaurea sect. Acrocentron, Asteraceae)

Authors: NOVAKOVIĆ JELICA , MRÁZ PATRIK , STEŠEVIĆ DANIJELA , MARIN PETAR D. , ZLATKOVIĆ BOJAN , LAKUŠIĆ DMITAR , JANAĆKOVIĆ PEDJA
Published: October 2020

In the most recent taxonomic literature, Centaurea crnogorica and C. gjurasinii, two neglected yellow-flowered taxa of C. sect. Acrocentron, have been treated as heterotypic synonyms of C. chrysolepis. Based on morphometric study, and study of type specimens and living plants from the locus classicus of C. gjurasinii and the only known population of C. crnogorica, as well as from several populations of C. chrysolepis from Eastern Serbia, we have found morphological differences among these three taxa. This has allowed us to re-evaluate taxonomic status of both, C. crnogorica and C. gjurasinii, which merit the species rank. The names C. crnogorica and C. gjurasinii are typified, and new expanded descriptions and illustrations are provided. We assessed also their conservation status. Because of their rarity, both taxa being narow endemics of two mountain ranges in Montenegro (the Durmitor Mts. and the Prokletje Mts.) and having small population sizes, C. crnogorica and C. gjurasinii are evaluated as critically endangered at national and global levels.
A new Eugenia (Myrtaceae) from Suriname with ‘six petals’ display

Authors: GIARETTA AUGUSTO , SANO PAULO TAKEO
Published: October 2020

Eugenia has ca. 1,100 species mostly with Neotropical distribution. Morphological circumscription of Eugenia has substantially changed over the last 10 years. Recent studies based on molecular and morphological data support a broad morphological circumscription of Eugenia including species with calyx fused and displaying apparently six petals. This is the case of a species here newly described. A detailed description, illustration, conservation assessment and a distribution map are provided.
Human ferroportin mediates proton-coupled active transport of iron
Authors: Li Shuang , Yang Yihu , Li Weikai
Published: October 2020

As the sole iron exporter in humans, ferroportin controls systemic iron homeostasis through exporting iron into the blood plasma. The molecular mechanism of how ferroportin exports iron under various physiological settings remains unclear. Here we found that purified ferroportin incorporated into liposomes preferentially transports Fe2+ and exhibits lower affinities of transporting other divalent metal ions. The iron transport by ferroportin is facilitated by downhill proton gradients at the same direction. Human ferroportin is also capable of transporting protons, and this activity is tightly coupled to the iron transport. Remarkably, ferroportin can conduct active transport uphill against the iron gradient, with favorable charge potential providing the driving force. Targeted mutagenesis suggests that the iron translocation site is located at the pore region of human ferroportin. Together, our studies enhance the mechanistic understanding by which human ferroportin transports iron and suggest that a combination of electrochemical gradients regulates iron export.
Comparison of outcomes of HCT in blast phase of BCR-ABL1− MPN with de novo AML and with AML following MDS
Authors: Gupta Vikas , Kim Soyoung , Hu Zhen-Huan , Liu Ying , Aljurf Mahmoud , Bacher Ulrike , Beitinjaneh Amer , Cahn Jean-Yves , Cerny Jan , Copelan Edward , Gadalla Shahinaz M. , Gale Robert Peter , Ganguly Siddhartha , George Biju , Gerds Aaron T. , Gergis Usama , Hamilton Betty K. , Hashmi Shahrukh , Hildebrandt Gerhard C. , Kamble Rammurti T. , Kindwall-Keller Tamila , Lazarus Hillard M. , Liesveld Jane L. , Litzow Mark , Maziarz Richard T. , Nishihori Taiga , Olsson Richard F. , Rizzieri David , Savani Bipin N. , Seo Sachiko , Solh Melhem , Szer Jeff , Verdonck Leo F. , Wirk Baldeep , Woolfrey Ann , Yared Jean A. , Alyea Edwin P. , Popat Uday R. , Sobecks Ronald M. , Scott Bart L. , Nakamura Ryotaro , Saber Wael
Published: October 2020

Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1− myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation–based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.
Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis
Authors: Maher Toby M. , Costabel Ulrich , Glassberg Marilyn K. , Kondoh Yasuhiro , Ogura Takashi , Scholand Mary Beth , Kardatzke David , Howard Monet , Olsson Julie , Neighbors Margaret , Belloni Paula , Swigris Jeffrey J.
Published: October 2020

This phase 2, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of lebrikizumab, an interleukin (IL)-13 monoclonal antibody, alone or with background pirfenidone therapy, in patients with idiopathic pulmonary fibrosis (IPF).

Patients with IPF aged ≥40 years with forced vital capacity (FVC) of 40%–100% predicted and diffusing capacity for carbon monoxide of 25%–90% predicted and who were treatment-naïve (cohort A) or receiving pirfenidone (2403 mg·day−1; cohort B) were randomised 1:1 to receive lebrikizumab 250 mg or placebo subcutaneously every 4 weeks. The primary endpoint was annualised rate of FVC % predicted decline over 52 weeks.

In cohort A, 154 patients were randomised to receive lebrikizumab (n=78) or placebo (n=76). In cohort B, 351 patients receiving pirfenidone were randomised to receive lebrikizumab (n=174) or placebo (n=177). Baseline demographics were balanced across treatment arms in both cohorts. The primary endpoint (annualised rate of FVC % predicted decline) was not met in cohort A (lebrikizumabversusplacebo, −5.2%versus−6.2%; p=0.456) or cohort B (lebrikizumabversusplacebo, −5.5%versus−6.0%; p=0.557). In cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio 0.42 (95% CI 0.17–1.04)). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.

Lebrikizumab alone or with pirfenidone was not associated with reduced FVC % predicted decline over 52 weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF.
Crystalline and Electrical Property Improvement of Filtrated, Exfoliated Graphite Sheets by an In-Plane Current and Heating Treatment
Authors: Matsumoto Naoyuki , Oshima Azusa , Yumura Motoo , Hata Kenji , Futaba Don N.
Published: October 2020

We report an approach to fabricate high conductivity graphite sheets based on a heat-and-current treatment of filtrated, exfoliated graphite flakes. This treatment combines heating (~ 900 °C) and in-plane electrical current flow (550 A·cm−2) to improve electrical conductivity through the reduction of crystalline defects. This process was shown to require only a 1-min treatment time, which resulted in a 2.1-fold increase in electrical conductivity (from 1088 ± 72 to 2275 ± 50 S·cm−1). Structural characterization by Raman spectroscopy and X-ray diffraction indicated that the improvement electrical conductivity originated from a 30-fold improvement in the crystallinity (Raman G/D ratio increase from 2.8 to 85.3) with no other observable structural transformations. Significantly, this treatment was found to act uniformly across a macroscopic (10 mm) sheet surface indicating it is on the development of applications, such as electrodes for energy generation and storage and electromagnetic shielding, as well as on the potential for the development of large-scale treatment technologies.
Direct and correlated responses to selection for autumn lambing in sheep
Authors: Asadi-Fozi Masood , Bradford Heather L. , Notter David R.
Published: October 2020

Background

Seasonal reproduction limits productivity, flexibility, and profitability in commercial sheep production. Hormonal and (or) photoperiodic manipulation can be used to control estrous cycles in sheep and reduce limitations that are imposed by the seasonal anestrous but are often impractical or incompatible with the extensive management systems preferred for ruminant livestock. Thus, the current study investigated the use of selection to improve realized fertility (i.e., the proportion of ewes that lambed) following an out-of-season spring joining period (May and June) in a crossbred sheep population.

Results

Over 17 years, estimated breeding values (EBV) for fertility in selected (S) ewes increased by 0.175 (0.01 per year). The mean EBV for fertility of S ewes was greater than that of control ewes by year 10 (P = 0.02), and the fertility of adult (≥ 3 years old) ewes reached 0.88 ± 0.05 by year 17. Lambing began approximately 140 days after the introduction of rams, and 64% of the S ewes that lambed did so in the first 17 days of the potential lambing season, which indicated that most of the S ewes were cycling at the time of ram introduction and were not induced to cycle by the introduction of breeding males (i.e., the so-called “ram effect”). Animals in the S line had modest increases in body weight and scrotal circumference. A modest negative trend in the additive maternal effect on birth weight was observed but was reversed by additional selection on EBV for maternal birth weight. The heritability of litter size in autumn lambing was low (0.04) and could potentially limit the response to selection for this trait.

Conclusions

Selection improved realized ewe fertility in out-of-season mating, with absolute increases of approximately 1% per year in the percentage of joined ewes that lambed in the autumn. Genetic antagonisms with other performance traits were generally small. A modest antagonism with maternal breeding values for birth weight was observed but it could be accommodated by selection on EBV for maternal birth weight. Our results support results of previous studies that indicate that these selected ewes had one of the shortest seasonal anestrous periods reported for temperate sheep breeds and that spring-lambing lactating ewes from the selection line were capable of relatively rapid rebreeding in the spring.
SAPPHIRE: a neural network based classifier for σ70 promoter prediction in Pseudomonas
Authors: Coppens Lucas , Lavigne Rob
Published: October 2020

Background

In silico promoter prediction represents an important challenge in bioinformatics as it provides a first-line approach to identifying regulatory elements to support wet-lab experiments. Historically, available promoter prediction software have focused on sigma factor-associated promoters in the model organismE. coli.As a consequence, traditional promoter predictors yield suboptimal predictions when applied to other prokaryotic genera, such asPseudomonas,a Gram-negative bacterium of crucial medical and biotechnological importance.

Results

We developedSAPPHIRE,a promoter predictor for σ70 promoters inPseudomonas.This promoter prediction relies on an artificial neural network that evaluates sequences on their similarity to the − 35 and − 10 boxes of σ70 promoters found experimentally inP. aeruginosaandP. putida.SAPPHIREcurrently outperforms established predictive software when classifyingPseudomonasσ70 promoters and was built to allow further expansion in the future.

Conclusions

SAPPHIREis the first predictive tool for bacterial σ70 promoters inPseudomonas. SAPPHIRE is free, publicly available and can be accessed online atwww.biosapphire.com. Alternatively, users can download the tool as a Python 3 script for local application from this site.
An enigmatic translocation of the vertebrate primordial eye field
Authors: Loosemore R. G. , Matthaei S. D. , Stanger T. C.
Published: October 2020

The primordial eye field of the vertebrate embryo is a single entity of retinal progenitor cells spanning the anterior neural plate before bifurcating to form bilateral optic vesicles. Here we review fate mapping data from zebrafish suggesting that prior to evagination of the optic vesicles the eye field may undergo a Maypole-plait migration of progenitor cells through the midline influenced by the anteriorly subducting diencephalon. Such an enigmatic translocation of scaffolding progenitors could have evolutionary significance if pointing, by way of homology, to an ancient mechanism for transition of the single eye field in chordates to contralateral eye fields in vertebrates.
Development of a relevant strategy using de novo transcriptome assembly method for transcriptome comparisons between Muscovy and common duck species and their reciprocal inter-specific mule and hinny hybrids fed ad libitum and overfed
Authors: Liu Xi , Hérault Frédéric , Diot Christian , Corre Erwan
Published: October 2020

Background

Common Pekin and Muscovy ducks and their intergeneric hinny and mule hybrids have different abilities for fatty liver production. RNA-Seq analyses from the liver of these different genetic types fed ad libitum or overfed would help to identify genes with different response to overfeeding between them. However RNA-seq analyses from different species and comparison is challenging. The goal of this study was develop a relevant strategy for transcriptome analysis and comparison between different species.

Results

Transcriptomes were first assembled with a reference-based approach. Important mapping biases were observed when heterologous mapping were conducted on common duck reference genome, suggesting that this reference-based strategy was not suited to compare the four different genetic types. De novo transcriptome assemblies were then performed using Trinity and Oases. Assemblies of transcriptomes were not relevant when more than a single genetic type was considered. Finally, single genetic type transcriptomes were assembled with DRAP in a mega-transcriptome. No bias was observed when reads from the different genetic types were mapped on this mega-transcriptome and differences in gene expression between the four genetic types could be identified.

Conclusions

Analyses using both reference-based and de novo transcriptome assemblies point out a good performance of the de novo approach for the analysis of gene expression in different species. It also allowed the identification of differences in responses to overfeeding between Pekin and Muscovy ducks and hinny and mule hybrids.
Database: web application for visualization of the cumulated RNAseq data against the salicylic acid (SA) and methyl jasmonate (MeJA) treatment of Arabidopsis thaliana
Authors: Woo Dong U , Jeon Ho Hwi , Park Halim , Park Jin Hwa , Lee Yejin , Kang Yang Jae
Published: October 2020

Background

Plants have adapted to survive under adverse conditions or exploit favorable conditions in response to their environment as sessile creatures. In a way of plant adaptation, plant hormones have been evolved to efficiently use limited resources. Plant hormones including auxin, jasmonic acid, salicylic acid, and ethylene have been studied to reveal their role in plant adaptation against their environment by phenotypic observation with experimental design such as mutation on hormone receptors and treatment / non-treatment of plant hormones along with other environmental conditions.

With the development of Next Generation Sequencing (NGS) technology, it became possible to score the total gene expression of the sampled plants and estimate the degree of effect of plant hormones in gene expression. This allowed us to infer the signaling pathway through plant hormones, which greatly stimulated the study of functional genomics using mutants. Due to the continued development of NGS technology and analytical techniques, many plant hormone-related studies have produced and accumulated NGS-based data, especially RNAseq data have been stored in the sequence read archive represented by NCBI, EBI, and DDBJ.

Description

Here, hormone treatment RNAseq data of Arabidopsis (Col0), wild-type genotype, were collected with mock, SA, and MeJA treatments. The genes affected by hormones were identified through a machine learning approach. The degree of expression of the affected gene was quantified, visualized in boxplot using d3 (data-driven-document), and the database was built by Django.

Conclusion

Using this database, we created a web application (http://pgl.gnu.ac.kr/hormoneDB/) that lists hormone-related or hormone-affected genes and visualizes the boxplot of the gene expression of selected genes. This web application eventually aids the functional genomics researchers who want to gather the cases of the gene responses by the hormones.
Effectiveness and long-term outcomes of different crossing strategies for the endovascular treatment of iliac artery chronic Total occlusions
Authors: Zhang Huan , Li Xiangtao , Niu Luyuan , Feng Yaping , Luo Xiaoyun , Zhang Changming , Zhang Fuxian
Published: October 2020

Background

The iliac occlusive disease is usually treated with endovascular procedures in recent years. The effectiveness of different crossing approaches for these occlusions is not precisely known. We performed a retrospective study to explore the optimal crossing approach (antegrade versus retrograde) for iliac artery chronic total occlusions (CTOs) and to examine the long-term outcomes.

Materials and methods

We performed a study on 107 patients (116 iliac occlusive lesions, mean age 64.0 ± 11.1, 88 men) who underwent an iliac CTO endovascular intervention attempted with the use of both crossing strategies but were managed with one final crossing approach between August 2012 and August 2018. Baseline data, procedural characteristics, and outcomes were described. A Cox proportional hazard model and Kaplan-Meier method were developed to assess the differences in the two crossing approaches in terms of the 1-year and 5-year primary patency rates, target lesion revascularization (TLR) and major adverse limb events (MALEs).

Results

Common iliac artery (CIA) lesions were more likely to be crossed successfully in the retrograde direction (6.8% for antegrade vs. 20.9% for retrograde, p = 0.005), while lesions in the CIA/ external iliac artery (EIA) were more prone to be crossed successfully in the antegrade direction (58.9% for antegrade vs. 39.5% for retrograde, p = 0.016). There were no significant differences in the crossing approach for EIA lesions between the two groups. The two crossing approaches were associated with similar estimates of 1- and 5-year primary patency, TLR and MALE rates.

Conclusion

The antegrade approach was associated with a higher rate of successful crossing in CIA/EIA CTO lesions, while the CIA-only CTOs were more likely to be crossed successfully with the retrograde approach.
The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods
Authors: Duri Kerina , Gumbo Felicity Z. , Munjoma Privilege T. , Chandiwana Precious , Mhandire Kudakwashe , Ziruma Asaph , Macpherson Andrew , Rusakaniko Simbarashe , Gomo Exnevia , Misselwitz Benjamin , Mazengera Lovemore Ronald ,   the UZ-CHS Birth Cohort Team, Altfeld M. , Bunders M. , Rowland Jones S. , Dandara C. , Mleya V. , Mutambara J. , Kandawasvika G. , Kuona P. , Chimhuya S. , Nyamakura R. , Mtapuri-Zinyowera S. , Chandiwana S. P. , Marashiki C. , Mataramvura H. , Mazengera E. , Taremeredzwa N.
Published: October 2020

Background

Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes.

Methods

Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis,Helicobacter pyloriinfections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis.

Discussion

The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity.

Trial registration

ClinicalTrial.gov Identifier:NCT04087239. Registered 12 September 2019.
Altered expression of the DISC1 gene in peripheral blood of patients with schizophrenia
Authors: Fu Xiaoqian , Zhang Guofu , Liu Yansong , Zhang Ling , Zhang Fuquan , Zhou Conghua
Published: October 2020

Background

Schizophrenia is a severe, heritable, and refractory psychiatric disorder. Several studies have shown that the disrupted in schizophrenia 1 (DISC1) gene is closely associated with schizophrenia by its role in neuronal morphology, synaptic function, brain development, and dopamine homeostasis etc. This study intended to investigate the expression levels of DISC1 gene in schizophrenia patients compared with healthy controls, and the expression variation of DISC1 gene before and after antipsychotic treatment in schizophrenia patients.

Methods

In this study, we compared DISC1 expression levels in blood of 48 healthy controls, and 32 schizophrenia patients before and after 12 weeks of antipsychotic treatment using real-time quantitative PCR (RT-qPCR) analysis.

Results

The expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients before antipsychotic treatment were higher than those in healthy controls (P < 0.01); whereas after antipsychotic treatment, the expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients still remained increased (P < 0.01).

Conclusions

Our study provided further support for the involvement of DISC1 in the development of schizophrenia.
Vaginal delivery in women with COVID-19: report of two cases
Authors: Cao Dongmei , Chen Miaomiao , Peng Min , Yin Heng , Sun Guoqiang
Published: October 2020

Background

During the ongoing global outbreak of COVID-19, pregnant women who are susceptible to COVID-19 should be highly concerned. The issue of vertical transmission and the possibility of neonatal infection is a major concern.

Case presentation

Case 1: A 35-year-old pregnant woman with a gestational age of 37 weeks and 6 days was admitted to our hospital at the point of giving birth. Except for the abnormalities in her chest CT image, she was asymptomatic. She had an uncomplicated spontaneous vaginal delivery, and her infant was discharged home for isolation. Because of the positive result of the maternal swabs for SARS-CoV-2 obtained on the 2nd day after sampling, we transferred the mother to the designated hospital and followed up with her by telephone interviews. Luckily, it was confirmed on February 23 that the newborn did not develop any COVID-19 symptoms after observation for 14 days after birth.

Case 2: Another pregnant woman, with a gestational age of 38 weeks and 2 days, was also admitted to our hospital because of spontaneous labor with cervical dilation of 5 cm. Since she had the typical manifestations of COVID-19, including cough, lymphopenia, and abnormal chest CT images, she was highly suspected of having COVID-19. Based on the experience from case 1, we helped the mother deliver a healthy baby by vaginal delivery. On the 2nd day after delivery, the maternal nasopharyngeal swab result was positive, while the infant’s result was negative.

Conclusion

There is still insufficient evidence supporting maternal-fetal vertical transmission for COVID-19-infected mothers in late pregnancy, and vaginal delivery may not increase the possibility of neonatal infection.
Pregnancy complications among nulliparous and multiparous women with advanced maternal age: a community-based prospective cohort study in China
Authors: Luo Jiayou , Fan Chunli , Luo Miyang , Fang Junqun , Zhou Shujin , Zhang Fenfang
Published: October 2020

Background

This study aimed to evaluate the incidence rates and risks of pregnancy complications among nulliparous and multiparous women with advanced maternal age (AMA, ≥35 years) in China.

Methods

We performed a community-based prospective cohort study of 10,171 pregnant women in selected two sub-districts and 11 towns of Liuyang from 2013 to 2015. All subjects were followed up from the first prenatal care (at ≤12 weeks) to delivery, and risks of pregnancy complications were compared by parity and maternal age groups.

Results

Among nulliparas, women with AMA showed significantly increased risks for gestational hypertension (OR 8.44, 95%CI 1.68–2.88), preeclampsia/eclampsia (OR 9.92, 95%CI 4.87–18.78), premature rupture of membrane (OR 6.84, 95%CI 2.00–17.69), as compared to women in the 20–29-year age group. Among multiparas with AMA, increased risks were found for gestational diabetes mellitus (OR 3.29, 95%CI 1.76–5.94), anemia (OR 1.85, 95%CI 1.25–2.69), polyhydramnios (OR 3.29, 95%CI 1.56–6.64), premature rupture of membrane (OR 5.14, 95%CI 2.12–12.29), and preterm labor (OR 1.89, 95CI 1.42–2.50).

Conclusions

Women with AMA were associated with increased risks of pregnancy complications, and complications with increased risks differed in nulliparas and multiparas. Women with AMA should be identified as a high-risk group in clinical practice.