bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II
Authors: Reinisch Walter , Sandborn William J , Danese Silvio , Hébuterne Xavier , Kłopocka Maria , Tarabar Dino , Vaňásek Tomáš , Greguš Miloš , Hellstern Paul A , Kim Joo Sung , Sparrow Miles P , Gorelick Kenneth J , Hoy Michael , Goetsch Martina , Bliss Caleb , Gupta Charu , Cataldi Fabio , Vermeire Séverine
Published: February 2021

Background and Aims

Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II.

Methods

TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator’s discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed.

Results

Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262].

Conclusions

Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.
Diving into Inflammation: A Pilot Study Exploring the Dynamics of the Immune–Microbiota Axis in Ileal Tissue Layers of Patients with Crohn’s Disease
Authors: Russo Edda , Giudici Francesco , Ricci Federica , Scaringi Stefano , Nannini Giulia , Ficari Ferdinando , Luceri Cristina , Niccolai Elena , Baldi Simone , D’Ambrosio Mario , Ramazzotti Matteo , Amedei Amedeo
Published: February 2021

Background and Aims

The pathogenesis of Crohn’s disease [CD] is still unclear. Disorders in the mucosal immunoregulation and its crosstalk with the microbiota may represent an important component in tissue injury. We aimed to characterize the molecular immune response distribution within the ileal layers and to evaluate the correlated microbiota in pathological/healthy settings comparing first surgery/relapse clinical conditions.

Methods

We enrolled 12 CD patients. A comprehensive analysis of an ileal mucosa, submucosa and serosa broad-spectrum cytokine panel was performed through a multiplex approach. In addition, ileal microbiota composition was assessed through next generation sequencing.

Results

We observed a distinct profile [of IL1-α, IL-1β, IL-4, IL-8, ICAM-1, E-Selectin, P-Selectin, IP-10, IL 6 and IL 18] across the CD vs healthy ileal layers; and a different distribution of IFN- γ, P-Selectin, IL-27 and IL-21 in first surgery vs relapse patients. In addition, the phylum Tenericutes, the family Ruminococcaceae, and the genera Mesoplasma and Mycoplasma were significantly enriched in the pathological setting. Significant microbiota differences were observed between relapse and first surgery patients regarding the class Bacteroidia, and the genera Prevotella, Flavobacterium, Tepidimonas and Escherichia/Shigella. Finally, the abundance of the genus Mycoplasma was positively correlated with IL-18.

Conclusions

We describe a dissimilarity of cytokine distribution and microbiota composition within CD and adjacent healthy ileal tissue layers and between first operation and surgical relapse. Our results give potential insight into the dynamics of the gut microbiota–immune axis in CD patients, leading to detection of new biomarkers.
Thromboembolic complications in transfemoral aortic valve implantation due to aortic wall thrombus and shaggy aorta syndrome
Authors: Haensig Martin , Kuntze Thomas , Gonzalez-Lopez David , Lapp Harald , Lauten Philipp , Owais Tamer
Published: February 2021

OBJECTIVES

Aortic wall thrombus (AWT) can affect suitability to endovascular repair, while its most aggressive entity is better known as shaggy aorta syndrome. Primary objective was to study the procedural and clinical outcome with regard to atherothrombotic AWT in transfemoral aortic valve implantation.

METHODS

In a retrospective, single-centre analysis, a qualitative 0–10 AWT score classification system was used. The most severely affected aortic area in computed tomography angiography cross-section was assessed for the number of affected segments, thrombus type, thickness, area and circumference. Primary endpoints were 30-day mortality, neurologic, renal and pulmonary events and signs of solid organ infarction.

RESULTS

Between November 2017 and September 2019, 604 patients underwent transfemoral transcatheter aortic valve implantation in our institution. Computed tomography-guided analysis revealed AWT in 11.3% and shaggy aorta syndrome in 6 patients (1.0% with 83.3% male). AWT was mainly present in the descending thoracic and abdominal aorta and was associated with acute renal failure (11.8% vs 3.2%, P ≤ 0.001) and a seven-fold increased rate of disabling peri-interventional stroke (4.4% vs 0.6%, P ≤ 0.001). In all patients with disabling peri-interventional stroke a balloon-expandable prosthesis was used (P ≤ 0.001). In case of shaggy aorta, mortality was more than six-fold increased (2.8% vs 16.7%, P = 0.046).

CONCLUSIONS

Severe and irregular thrombus of the descending thoracic and abdominal aorta has been strongly associated with acute respiratory failure and peri-interventional stroke in transfemoral aortic valve implantation, being more likely using balloon-expandable devices. Our results imply important changes with regard to device design and present international transcatheter aortic valve implantation guidelines.
Incidence, determinants and clinical impact of left ventricular function recovery after surgical treatments for ischaemic cardiomyopathy
Authors: Nakae Masaro , Kainuma Satoshi , Toda Koichi , Miyagawa Shigeru , Yoshikawa Yasushi , Hata Hiroki , Yoshioka Daisuke , Kawamura Takuji , Kawamura Ai , Kashiyama Noriyuki , Komukai Sho , Kitamura Tetsuhisa , Hirayama Atsushi , Ueno Takayoshi , Kuratani Toru , Kondoh Haruhiko , Masai Takafumi , Hiraoka Arudo , Sakaguchi Taichi , Yoshitaka Hidenori , Shirakawa Yukitoshi , Takahashi Toshiki , Taniguchi Kazuhiro , Sawa Yoshiki ,   Osaka Cardiovascular Surgery Research (OSCAR) Group
Published: February 2021

OBJECTIVES

This retrospective study aimed to clarify the incidence, determinants and clinical impact of left ventricular (LV) function non-recovery after coronary artery bypass grafting (CABG) in patients with ischaemic cardiomyopathy.

METHODS

A total of 490 patients with ischaemic cardiomyopathy (LV ejection fraction ≤ 40%) undergoing CABG were analysed. Follow-up echocardiography was performed at 1 month, 1 year, and annually thereafter. LV function recovery was defined as ejection fraction (EF) ≥40% at least once during follow-up. LV function non-recovery was defined as EF <40% at any follow-up. The primary and secondary end points were changes in LV function and all-cause mortality, respectively. Clinical follow-up was completed in 461 patients (94.1%; mean follow-up: 64.5 ± 45.5 months).

RESULTS

During follow-up, echocardiographic assessments were performed 1863 times (mean, 3.8 ± 2.4), and 193 patients (39.4%) exhibiting LV function non-recovery were identified. Overall survival was significantly higher in the recovery group (53.9%) than in the non-recovery group (31.4%) at 10 years (P < 0.001). Independent predictors of LV function non-recovery were preoperative LV end-systolic diameter [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04–1.10; P < 0.001] and bilateral internal thoracic artery grafting (OR 0.61, 95% CI 0.39–0.95; P = 0.028). In a multivariable Cox proportional hazards model, LV function non-recovery was significantly associated with all-cause mortality (hazard ratio 2.14, 95% CI 1.60–2.86; P < 0.001).

CONCLUSIONS

Almost 40% of patients with ischaemic cardiomyopathy undergoing CABG did not achieve LV function recovery and were associated with poor prognosis. To achieve LV function recovery, CABG with bilateral internal thoracic artery may be recommended before excessive LV remodelling occurs.

Clinical trial registration number

Institutional review board of Osaka University Hospital, number 16105.
Suture tie-down forces and cyclic contractile forces after an undersized tricuspid annuloplasty using a 3-dimensional rigid ring in an ovine model
Authors: Lim Jae Hong , Shin Heean , Shin Dong Ah , Kim Dae Hyun , Sohn Suk Ho , Choi Jae Woong , Cho Sungkyu , Kim Hee Chan , Hwang Ho Young
Published: February 2021

OBJECTIVES

This study was conducted to measure suture tie-down forces and evaluate cyclic contractile forces (CCFs) in beating hearts after undersized 3-dimensional (3D) rigid-ring tricuspid valve annuloplasty (TAP).

METHODS

Eight force transducers were attached to the 3D rigid TAP ring. Segments 1 to 8 were attached from the mid-septal to anterior-septal commissural area in a counterclockwise order. Two-sizes-down ring TAPs were performed in 6 sheep. Tie-down forces and CCF were recorded and analysed at the 8 annular segments and at 3 levels of peak right ventricular pressure (RVP: 30, 50 and 70 mmHg).

RESULTS

The overall average tie-down forces and CCF were 4.34 ± 2.26 newtons (N) and 0.23 ± 0.09 N, respectively. The CCF at an RVP of 30 mmHg were higher at 3 commissural areas (segments 3, 5 and 8) than at the other segments. The increases in the CCF following changes in the RVP were statistically significant only at the 3 commissural areas (P = 0.012). However, mean CCFs remained low at all annular positions (ranges of average CCF = 0.06–0.46 N).

CONCLUSIONS

The risk of suture dehiscence after down-sized 3D rigid-ring TAP might be minimal because the absolute forces remained low in all annular positions even in the condition of high RVP. However, careful suturing in the septal annular area and commissures is necessary to prevent an annular tear during a down-sized 3D rigid-ring TAP.
Revisiting the genome-wide significance threshold for common variant GWAS
Authors: Chen Zhongsheng , Boehnke Michael , Wen Xiaoquan , Mukherjee Bhramar
Published: February 2021

Over the last decade, GWAS meta-analyses have used a strict P-value threshold of 5 × 10−8 to classify associations as significant. Here, we use our current understanding of frequently studied traits including lipid levels, height, and BMI to revisit this genome-wide significance threshold. We compare the performance of studies using the P = 5 × 10−8 threshold in terms of true and false positive rate to other multiple testing strategies: (1) less stringent P-value thresholds, (2) controlling the FDR with the Benjamini–Hochberg and Benjamini–Yekutieli procedure, and (3) controlling the Bayesian FDR with posterior probabilities. We applied these procedures to re-analyze results from the Global Lipids and GIANT GWAS meta-analysis consortia and supported them with extensive simulation that mimics the empirical data. We observe in simulated studies with sample sizes ∼20,000 and >120,000 that relaxing the P-value threshold to 5 × 10−7 increased discovery at the cost of 18% and 8% of additional loci being false positive results, respectively. FDR and Bayesian FDR are well controlled for both sample sizes with a few exceptions that disappear under a less stringent definition of true positives and the two approaches yield similar results. Our work quantifies the value of using a relaxed P-value threshold in large studies to increase their true positive discovery but also show the excess false positive rates due to such actions in modest-sized studies. These results may guide investigators considering different thresholds in replication studies and downstream work such as gene-set enrichment or pathway analysis. Finally, we demonstrate the viability of FDR-controlling procedures in GWAS.
Toward genetic modification of plant-parasitic nematodes: delivery of macromolecules to adults and expression of exogenous mRNA in second stage juveniles
Authors: Kranse Olaf , Beasley Helen , Adams Sally , Pires-daSilva Andre , Bell Christopher , Lilley Catherine J , Urwin Peter E , Bird David , Miska Eric , Smant Geert , Gheysen Godelieve , Jones John , Viney Mark , Abad Pierre , Maier Thomas R , Baum Thomas J , Siddique Shahid , Williamson Valerie , Akay Alper , Eves-van den Akker Sebastian
Published: February 2021

Plant-parasitic nematodes are a continuing threat to food security, causing an estimated 100 billion USD in crop losses each year. The most problematic are the obligate sedentary endoparasites (primarily root knot nematodes and cyst nematodes). Progress in understanding their biology is held back by a lack of tools for functional genetics: forward genetics is largely restricted to studies of natural variation in populations and reverse genetics is entirely reliant on RNA interference. There is an expectation that the development of functional genetic tools would accelerate the progress of research on plant-parasitic nematodes, and hence the development of novel control solutions. Here, we develop some of the foundational biology required to deliver a functional genetic tool kit in plant-parasitic nematodes. We characterize the gonads of male Heterodera schachtii and Meloidogyne hapla in the context of spermatogenesis. We test and optimize various methods for the delivery, expression, and/or detection of exogenous nucleic acids in plant-parasitic nematodes. We demonstrate that delivery of macromolecules to cyst and root knot nematode male germlines is difficult, but possible. Similarly, we demonstrate the delivery of oligonucleotides to root knot nematode gametes. Finally, we develop a transient expression system in plant-parasitic nematodes by demonstrating the delivery and expression of exogenous mRNA encoding various reporter genes throughout the body of H. schachtii juveniles using lipofectamine-based transfection. We anticipate these developments to be independently useful, will expedite the development of genetic modification tools for plant-parasitic nematodes, and ultimately catalyze research on a group of nematodes that threaten global food security.
Whole-genome assembly of Culex tarsalis
Authors: Main Bradley J , Marcantonio Matteo , Johnston J Spencer , Rasgon Jason L , Brown C Titus , Barker Christopher M
Published: February 2021

The mosquito, Culex tarsalis, is a key vector in the western United States due to its role in transmission of zoonotic arboviruses that affect human health. Extensive research has been conducted on Cx. tarsalis ecology, feeding behavior, vector competence, autogeny, diapause, genetics, and insecticide resistance. Population genetic analyses in the western U.S. have identified at least three genetic clusters that are geographically distinct. However, in-depth genetic studies have been hindered by the lack of a reference genome. In this study, we present the first whole-genome assembly of this mosquito species (CtarK1) based on PacBio HiFi reads from high-molecular-weight DNA extracted from a single male. The CtarK1 assembly is 790 Mb with an N50 of 58 kb, which is 27% larger than Culex quinquefasciatus (578 Mb). This difference appears to be mostly composed of transposable elements. To annotate CtarK1, we used a previously assembled Cx. tarsalis transcriptome and approximately 17,456 protein genes from Cx. quinquefasciatus (N = 17,456). Genome completeness was assessed using the Benchmarking Universal Single-Copy Orthologs (BUSCO) tool, which identified 84.8% of the 2799 Dipteran BUSCO genes. Using a Bayesian phylogeny based on mitochondrial genomes, we place Cx. tarsalis in the context of other mosquito species and estimate the divergence between Cx. tarsalis and Cx. quinquefasciatus to be between 15.8 and 22.2 million years ago (MYA). Important next steps from this work include characterizing the genetic basis of diapause and sex determination in Culex mosquitoes.
Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis
Authors: Taxonera Carlos , Olivares David , Alba Cristina
Published: February 2021

Background

Knowledge of the real-world effectiveness and safety of tofacitinib for ulcerative colitis (UC) is relevant to confirm the benefit observed in clinical trials.

Methods

This systematic review and meta-analysis evaluated the real-world effectiveness of tofacitinib for moderate to severely active UC. The primary outcome was clinical remission evaluated at week 8, weeks 12 to 16, and month 6. Secondary outcomes were response, corticosteroid-free remission, mucosal healing, colectomy, and safety.

Results

Seventeen studies with a total of 1162 patients with UC were included. Remission (11 studies) was achieved in 34.7% of patients at week 8 (95% confidence interval [CI], 24.4%-45.1%), 47% at weeks 12 to 16 (95% CI, 40.3%-53.6%), and 38.3% at month 6 (95% CI, 29.2%-47.5%) at month 6 duplicated. Response was achieved in 62.1%, 64.2%, 50.8%, and 41.8% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Corticosteroid-free remission (5 studies) was achieved in 38.4%, 44.3%, 33.6%, and 31% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Mucosal healing was achieved in 48.3% and 45.3% of patients at week 8 and weeks 12 to 16, respectively. Patients who were biologic-naïve (11.6%) had a significantly higher rate of response at week 8 (1.38; 95% CI, 1.03-1.84). The incidence rates of serious adverse events and herpes zoster was 8.9 and 6.9 per 100 patient-years, respectively.

Conclusions

This meta-analysis of real-world studies confirms the effectiveness of tofacitinib in a highly refractory population of patients with moderate to severely active UC. Tofacitinib showed an acceptable safety profile. These findings were consistent with clinical trials and further support the use of tofacitinib in UC.
Left Demazure–Lusztig Operators on Equivariant (Quantum) Cohomology and K-Theory
Authors: Mihalcea Leonardo C , Naruse Hiroshi , Su Changjian
Published: February 2021

We study the Demazure–Lusztig operators induced by the left multiplication on partial flag manifolds $G/P$. We prove that they generate the Chern–Schwartz–MacPherson classes of Schubert cells (in equivariant cohomology), respectively their motivic Chern classes (in equivariant K-theory), in any partial flag manifold. Along the way, we advertise many properties of the left and right divided difference operators in cohomology and K-theory and their actions on Schubert classes. We apply this to construct left divided difference operators in equivariant quantum cohomology, and equivariant quantum K-theory, generating Schubert classes and satisfying a Leibniz rule compatible with the quantum product.
Predictive Modeling to Study the Treatment-Shortening Potential of Novel Tuberculosis Drug Regimens, Toward Bundling of Preclinical Data
Authors: Mudde Saskia E , Ayoun Alsoud Rami , van der Meijden Aart , Upton Anna M , Lotlikar Manisha U , Simonsson Ulrika S H , Bax Hannelore I , de Steenwinkel Jurriaan E M
Published: February 2021

Background

Given the persistently high global burden of tuberculosis, effective and shorter treatment options are needed. We explored the relationship between relapse and treatment length as well as interregimen differences for 2 novel antituberculosis drug regimens using a mouse model of tuberculosis infection and mathematical modeling.

Methods

Mycobacterium tuberculosis–infected mice were treated for up to 13 weeks with bedaquiline and pretomanid combined with moxifloxacin and pyrazinamide (BPaMZ) or linezolid (BPaL). Cure rates were evaluated 12 weeks after treatment completion. The standard regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) was evaluated as a comparator.

Results

Six weeks of BPaMZ was sufficient to achieve cure in all mice. In contrast, 13 weeks of BPaL and 24 weeks of HRZE did not achieve 100% cure rates. Based on mathematical model predictions, 95% probability of cure was predicted to occur at 1.6, 4.3, and 7.9 months for BPaMZ, BPaL, and HRZE, respectively.

Conclusion

This study provides additional evidence for the treatment-shortening capacity of BPaMZ over BPaL and HRZE. To optimally use preclinical data for predicting clinical outcomes, and to overcome the limitations that hamper such extrapolation, we advocate bundling of available published preclinical data into mathematical models.
Quality Improvement in Critical Value Delivery at a Tertiary Care Center
Authors: Hopkins Mark R , Butcher Monica R , Martin Kevin M , Small Lona R , Sokoll Lori J
Published: February 2021

Background

Prompt notification of critical laboratory values to providers is essential for effective patient care. To improve the delivery of these critical values, a quality improvement project was initiated to determine the obstacles to prompt notification and to identify possible interventions to improve this process.

Methods

Critical value call logs were retrieved, and delivery time, patient location, test name, and call time were abstracted and analyzed. All critical values with delivery times greater than 60 min were reviewed by 2 authors for 1 representative month in both the pre- and postintervention period.

Results

Based on the results of the data review, a modification to the laboratory information system call center color-coded alerts was introduced to address delays attributable to the laboratory. The overall rate of calls greater than 60 min decreased from 3.4% ± 0.8% in the preintervention study period to 1.3 ± 0.3%, postintervention. The average number of values not delivered within 60 min decreased by 64% across all locations, following with an 82% decrease for values originating from inpatient locations, and a 39% decrease for outpatient values.

Conclusions

Low complexity interventions to critical value callback protocols can significantly increase the efficacy of communication between the laboratory and providers.
Ductal Carcinoma In Situ and Progression to Invasive Cancer: A Review of the Evidence
Authors: Heller Samantha L , Plaunova Anastasia , Gao Yiming
Published: February 2021

Ductal carcinoma in situ (DCIS), breast cancer confined to the milk ducts, is a heterogeneous entity. The question of how and when a case of DCIS will extend beyond the ducts to become invasive breast cancer has implications for both patient prognosis and optimal treatment approaches. The natural history of DCIS has been explored through a variety of methods, from mouse models to biopsy specimen reviews to population-based screening data to modeling studies. This article will review the available evidence regarding progression pathways and will also summarize current trials designed to assess DCIS progression.
Detection of Two Biotypes ofLiriomyza chinensis(Diptera: Agromyzidae) in Japan
Authors: Tokumaru Susumu , Uesugi Ryuji , Urairi Chihiro , Toyoshima Shingo , Aoki Yumi , Iwasaki Akeo
Published: February 2021

The larva of stone leek leafminer, Liriomyza chinensis (Kato), is known to infest alternately just below the epidermis and inner surface of hollow cylindrical leaves of allium crops, resulting in the formation of discontinuous linear mines (mine form: discontinuous). However, after the fall of 2016, a novel mine form of the same species (mine form: continuous) was detected in Welsh onion fields of Kyoto Prefecture, Japan. We hypothesized that these mine forms were associated with flies having different genetic backgrounds; hence, we compared the mine forms and the partial mtCOI gene of flies collected from Welsh onion fields from 2018 to 2019. The results demonstrated that the flies that emerged from different mine forms could be classified into two haplogroups, i.e., flies displaying a discontinuous mine form were of haplogroup A, whereas those that displayed continuous mines were of haplotype B. Additionally, using populations of these flies reared in the laboratory, we confirmed that the mine form of the larvae of haplotype A on Welsh onions was discontinuous, whereas that of haplotype B was continuous. We named the population that exhibited a discontinuous mine form as biotype A and the population displaying a continuous mine form as biotype B.
Clinical Interpretation Challenges of Germline-Shared Somatic Variants in Cancer
Authors: Park Kyoung-Jin
Published: February 2021

Objective

To investigate the interpretation differences of germline-shared somatic variants.

Methods

A total of 123,302 COSMIC variants associated with hematologic malignant neoplasms were used. The pathogenicity and actionability of shared variants were analyzed based on the standardized guidelines.

Results

The overall frequency of variants shared in ClinVar/HGMD and COSMIC was 10%. The pathogenicity of 54 shared variants was pathogenic/likely pathogenic (P/LP; n = 30), variants of unknown significance (n = 3), and benign/likely benign (n = 21). In total, 30 P/LP variants were reclassified to tier I/tier II (83%) and tier III (17%) variants.

Conclusions

This is the first study about different clinical interpretations of shared variants based on the current standard guidelines. This study takes a meaningful step in bridging the interpretation gap between the somatic and germline variants.
Biological relevance and therapeutic potential of G-quadruplex structures in the human noncoding transcriptome
Authors: Tassinari Martina , Richter Sara N , Gandellini Paolo
Published: February 2021

Noncoding RNAs are functional transcripts that are not translated into proteins. They represent the largest portion of the human transcriptome and have been shown to regulate gene expression networks in both physiological and pathological cell conditions. Research in this field has made remarkable progress in the comprehension of how aberrations in noncoding RNA drive relevant disease-associated phenotypes; however, the biological role and mechanism of action of several noncoding RNAs still need full understanding. Besides fulfilling its function through sequence-based mechanisms, RNA can form complex secondary and tertiary structures which allow non-canonical interactions with proteins and/or other nucleic acids. In this context, the presence of G-quadruplexes in microRNAs and long noncoding RNAs is increasingly being reported. This evidence suggests a role for RNA G-quadruplexes in controlling microRNA biogenesis and mediating noncoding RNA interaction with biological partners, thus ultimately regulating gene expression. Here, we review the state of the art of G-quadruplexes in the noncoding transcriptome, with their structural and functional characterization. In light of the existence and further possible development of G-quadruplex binders that modulate G-quadruplex conformation and protein interactions, we also discuss the therapeutic potential of G-quadruplexes as targets to interfere with disease-associated noncoding RNAs.
Slow real wage growth during the Industrial Revolution: productivity paradox or pro-rich growth?
Authors: Crafts Nicholas
Published: February 2021

abstract

I examine the implications of technological change for productivity, real wages and factor shares during the industrial revolution using recently available data. This shows that real GDP per worker grew faster than real consumption earnings but labour’s share of national income changed little as real product wages grew at a similar rate to labour productivity in the medium term. The period saw modest total factor productivity growth which limited the growth both of real wages and of labour productivity. Economists looking for an historical example of rapid labour-saving technological progress having a seriously adverse impact on labour’s share must look elsewhere.
Chloroplast proteotoxic stress-induced autophagy is involved in the degradation of chloroplast proteins in Chlamydomonas reinhardtii
Authors: Li Nan , Nakamura Sakuya , Ramundo Silvia , Nishimura Yoshiki , Hagihara Shinya , Izumi Masanori
Published: February 2021

Intraorganellar proteases and cytoplasmic proteolytic systems such as autophagy orchestrate the degradation of organellar proteins to ensure organelle homeostasis in eukaryotic cells. The green alga Chlamydomonas reinhardtii is an ideal unicellular model organism for elucidating the mechanisms maintaining proteostasis in chloroplasts. However, the autophagic pathways targeting the photosynthetic organelles of these algae have not been clearly elucidated. Here, we explored the role of autophagy in chloroplast protein degradation in Chlamydomonas cells. We labeled the chloroplast protein Rubisco small subunit (RBCS) with the yellow fluorescent protein Venus in a Chlamydomonas strain in which expression of the chloroplast gene clpP1, encoding a major catalytic subunit of the chloroplast Clp protease, can be conditionally repressed to selectively perturb chloroplast protein homeostasis. We observed transport of both nucleus-encoded RBCS-Venus fusion protein and chloroplast-encoded Rubisco large subunit (rbcL) from the chloroplast to the vacuoles in response to chloroplast proteotoxic stress induced by clpP1 inhibition. This process was retarded by the addition of autophagy inhibitors. Biochemical detection of lytic cleavage of RBCS-Venus supported the notion that Rubisco is degraded in the vacuoles via autophagy. Electron microscopy revealed vacuolar accumulation of autophagic vesicles and exposed their ultrastructure during repression of clpP1 expression. Treatment with an autophagy activator also induced chloroplast autophagy. These results indicate that autophagy contributes to chloroplast protein degradation in Chlamydomonas cells.
Public Policy Reform and Police Prevention Practice: A Journey Upstream?
Authors: Bland Nick , Calder Amy , Fyfe Nicholas R , Anderson Simon , Mitchell James , Reid Susan
Published: February 2021

This article contributes to a growing body of research on the police reforms in Scotland. It examines the particular place given to prevention in public policy and its impact on police practice. We show how public policy reconfigured the place and purpose of prevention for the police, with a focus on safety, wellbeing, and the prevention of harm. The research draws on qualitative data collected in four areas as part of a 4-year evaluation of the police reforms. We refine a public health typology of prevention and operationalize it empirically for the first time to analyse cases of innovative practice. We distinguish a pattern of prevention practice heavily weighted towards secondary prevention, focused predominantly on issues of crime and disorder. In fewer cases, the police applied primary and tertiary prevention, with a focus on vulnerability and harm. Looking in detail at two cases, we illustrate the importance of collaboration for the police, which created opportunities and brought additional resources and expertise to support new prevention approaches which had a significant impact on effectiveness. The police realized collaborative advantage through common aims, trust-building, and leadership. We do not suggest this demonstrates a transformation in police prevention; it illustrates successful police innovation, and identifies the potential to go further. The implications for policy and practice are to recognize the value to the police of investing in new partnerships. They create opportunities for the police to collaborate, innovate, and focus more sharply on the prevention of harm.
Current algebra, a U(1) gauge theory and the Wess–Zumino–Witten model
Authors: Wadia Spenta R
Published: February 2021

In this note we realise current algebra with anomalous terms in terms of a $U(1)$ gauge theory, in the space of maps $M$ from $S^1$ into a compact Lie group corresponding to the current algebra. The Wilson loop around a closed curve in $M$ is shown to be the Wess–Zumino–Witten term. This discussion enables a simple understanding of the non-Abelian anomaly in the Schrödinger picture.
Individual differences and changes in lifestyle behaviours predict decreased subjective well-being during COVID-19 restrictions in an Australian sample
Authors: Brindal Emily , Ryan Jillian C , Kakoschke Naomi , Golley Sinead , Zajac Ian T , Wiggins Bonnie
Published: February 2021

Background

Due to the coronavirus disease 2019 (COVID-19) pandemic, social distancing practices were introduced to curb infection rates in many countries. The purpose of this study was to assess the effects of these restrictions on behaviours and well-being and whether individual differences predict changes in well-being.

Methods

Australian adults participated in a cross-sectional, online survey during May 2020. The survey captured demographic information; health behaviours; personality traits; life satisfaction and COVID-19-related attitudes, financial concerns, perceived risks and impacts.

Results

In total, 3745 (86.8% of 4313) participants completed all items. Participants were mostly female (85.7%) and 56.4 years (standard deviation [SD] = 12.6) on average. Over 95.0% of the sample indicated they had been social distancing or isolating. Health behaviours and well-being had generally worsened, with social connections being the most negatively affected. Life satisfaction was significantly lower since restrictions. For changes in life satisfaction, extroversion was a risk factor and openness to experience was a protective factor.

Conclusions

Overall, well-being was negatively impacted by the COVID-19 pandemic and associated social distancing particularly in this sample containing mainly older women. In future, it will be crucial to understand why and who may be differentially affected, to encourage behaviours that are protective of well-being.
Betel quid chewing and its prevalence and determinants: data from Myanmar Demographic Health and Survey of 2015–2016
Authors: Aye Yin Min , Hong S A , Thepthien B , Tiraphat S
Published: February 2021

Background

Although betel quid chewing with tobacco use is one of the major behavioral risk factors for chronic diseases, the prevalence is rather on the increase in Myanmar. This study determined prevalence of betel quid chewing at the national and subnational levels and its associations with tobacco and sociodemographic factors.

Methods

This study is a secondary data analysis of Myanmar demographic health survey 2015–2016 with a total of 11 773 women and 4251 men aged 18–49 years. Chi-square tests and multivariable logistic regression tests were performed.

Results

Prevalence of betel quid chewing was 61.8% in men and 19.5% in women and by regions it ranged from 34 to 82.2% and from 5–8 to 52.9%, respectively. The prevalence of the concurrent use with tobacco was 25.8 and 2.3%, respectively. Women with older age, low education and low wealth and occupation and living with spouse were associated with betel quid chewing, while low education, living with spouse and Myanmar speaker were associated with men. Tobacco use was inversely and positively associated with betel quid chewing in men and women, respectively (P-interaction <0.0001).

Conclusion

Implementation of culturally sensitive intervention and policies including effective community awareness campaigns for anti-betel quid chewing is strongly recommended in Myanmar.
Combining jobs and motherhood: is it worse when raising children alone?
Authors: Roxo L , Porto G , Perelman J
Published: February 2021

Background

Paid employment has been shown to benefit childless women’s health, while employed mothers experience poorer health, and more pronounced fatigue. This study measures the association between job characteristics and the health and well-being of employed mothers and the differential susceptibility to job characteristics between coupled and single-parent mothers.

Methods

We used data from the 5th Portuguese National Health Survey from 1649 employed women (aged 25–54) living with a child under 16. We modelled depression (assessed by the Personal Health Questionnaire-8) and self-reported health as a function of job characteristics, adding interaction terms to compare coupled and single-parent mothers, using logistic regressions.

Results

Working part-time was associated with depression (odds ratio (OR) = 3.39, 95% confidence interval (CI) = 3.31–3.48) and less-than-good health (OR = 1.28, 95%CI = 1.26–1.31), compared to working full time. Compared to high-skill jobs, the likelihood for depression among low-skill occupations was lower among coupled mothers (OR = 0.25, 95%CI = 0.24–0.26), and higher among single-parent mothers (OR = 1.75, 95%CI = 1.54–1.99). Unstable jobs were associated with depression among coupled mothers.

Conclusions

Part-time jobs are detrimental for mothers’ mental health, but high-skilled jobs are protective for single-parent mothers. Part-time and unstable jobs are linked to poorer self-reported health among coupled mothers. Results question the gendered arrangements that may face employed coupled mothers.
Mindfulness as key in easing COVID-19 vaccine hesitancy
Authors: Capulong Harvey Gain M
Published: February 2021

The public’s trust in the COVID-19 vaccination program is still a problem, especially in the Philippines. Many have suggested that the government and even healthcare workers should exhaust all their efforts to educate the public about the nature of the vaccines. However, rebuilding public trust is not only a governmental concern, but should also be taken as a personal responsibility. Thus, this paper argues that mindfulness through critical thinking is a necessary key in boosting the vaccination program.
Leadership: towards equitable COVID-19 vaccination
Authors: del Castillo Fides A
Published: February 2021

Transformational leaders can lead the society towards equitable access to COVID-19 vaccination. They prioritize most the public health’s well-being, including the poor and the most vulnerable. Thus, authentic leaders can work through a public health crisis’s maelstrom. Through service and inspiration, the community can help out, collaborate and find solutions to mitigate the ill-effects of the COVID-19 pandemic.
Ivermectin shows clinical benefits in mild to moderate COVID19: a randomized controlled double-blind, dose-response study in Lagos
Authors: Babalola O E , Bode C O , Ajayi A A , Alakaloko F M , Akase I E , Otrofanowei E , Salu O B , Adeyemo W L , Ademuyiwa A O , Omilabu S
Published: February 2021

Introduction

In vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS—CoV-2 viral replication, but questions remained as to in-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19.

Methods

We conducted a translational proof of concept randomized, double blind placebo controlled, dose response and parallel group study of IV efficacy in RT—polymerase chain reaction proven COVID 19 positive patients. Sixty-two patients were randomized to three treatment groups. (A) IV 6 mg regime, (B) IV 12 mg regime (given Q84 h for 2 weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care.

Results

The Days to COVID negativity (DTN) was significantly and dose dependently reduced by IV (P = 0.0066). The DTN for Control were, = 9.1+/–5.2, for A 6.0 +/– 2.9 and for B 4.6 +/–3.2. Two way repeated measures ANOVA of ranked COVID 19 +/– scores at 0, 84, 168 and252h showed a significant IV treatment effect (P = 0.035) and time effect (P < 0.0001). IV also tended to increase SPO2% compared to controls, P = 0.073, 95% CI—0.39 to 2.59 and increased platelet count compared to C (P = 0.037) 95%CI 5.55—162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = –0.52, P = 0.005). No SAE was reported.

Conclusions

12mg IV regime given twice a week may have superior efficacy over 6mg IV given twice a week, and certainly over the non IV arm of the study. IV should be considered for use in clinical management of SARS-COV2, and may find applications in prophylaxis in high risk areas.
The impact of a national research assessment on the publications of sociologists in Italy
Authors: Akbaritabar Aliakbar , Bravo Giangiacomo , Squazzoni Flaminio
Published: February 2021

This article investigates the impact of the second national research assessment (VQR 2004–10), which was performed in 2011 by the Italian National Agency for the Evaluation of Universities and Research Institutes, on publication strategies by sociologists in Italy. We reconstructed all publications from Italian sociologists in Scopus between 2006 and 2015, that is five years before and after the assessment. We also checked academic tenure and promotions during the assessment. Our results showed the potentially distortive effect of institutional signals on publications given that Italian sociologists published more in journals that were considered influential for assessment, some, however, being of doubtful quality. Our findings would suggest that the use of informed peer review and ad hoc journal ranking could stimulate adaptive responses based on strategic journal targeting to ensure publication.
Steering the transition from informal to formal service provision: labor platforms in emerging-market countries
Authors: Weber Clarissa E , Okraku Mark , Mair Johanna , Maurer Indre
Published: February 2021

Services that are especially suited to being offered via online labor platforms, such as cleaning, driving and tutoring, are frequently performed in an informal way, especially in emerging-market countries. The informal economy is thus important for recruiting workers for labor platforms. Platform use, however, requires formal service provision, which workers in the informal economy often resist. Thus, labor platforms have to promote workers’ transition from informal to formal service provision. While recent studies have hinted at labor platforms’ fostering of formal economic activity, we know little about how such intermediation unfolds. We use a process lens and comprehensive qualitative data on labor platforms in Panama and Mexico to study how labor platforms steer workers to formal service provision. Detailing the interactive process of workers transitioning to formal service provision as triggered by labor platforms, we add to platform research and literature on intermediation between informal and formal economic activity.
Hosting Overnight Guests: Gendered Unpaid Work as a Solidarity Mechanism of Migrants in the Process of Urbanization in Turkey
Authors: Uyar Mura Elif S
Published: February 2021

This article addresses overnight guest hosting, which is a widespread solidarity practice among rural-to-urban migrants in Turkey. The fieldwork, based on in-depth interviews with 28 first-generation migrant women, reveals that it was mostly the young migrant women who shouldered hosting tasks as gendered unpaid work, which deepen their time poverty and reinforce their dependence on family. The analysis highlights the links between intersectional disadvantages of young migrant women and poverty, the failure of the welfare state to provide social assistance for migrants, and the familialist character of social policy during the peak years of migration.
Interpretation of the difference in shade tolerance of two subtropical forest tree species of different successional stages at the transcriptome and physiological levels
Authors: Yu Zheng-Chao , Lin Wei , Zheng Xiao-Ting , Cai Min-Ling , Zhang Tai-Jie , Luo Yan-Na , Peng Chang-Lian
Published: February 2021

Differences in plant shade tolerance constitute a major mechanism driving the succession of forest communities in subtropical forests. However, the indirect effects of differences in light requirements on the growth of mid- and late-successional tree species are unclear, and this potential growth effect has not been explained at the transcriptome level. Here, a typical mid-successional dominant tree species, Schima superba Gardn. et Champ, and a typical late-successional dominant tree species, Cryptocarya concinna Hance were used as materials and planted under 100% full light (FL) and 30% FL (low light, LL) to explore the responses of tree species in different successional stages of subtropical forests to different light environments. Transcriptome sequencing was used to analyze the expression changes in genes related to growth and photoprotection under different light environments. The young leaves of S. superba accumulated more malondialdehyde (MDA) and superoxide radicals (${\mathrm{O}}_2^{{{}^{\bullet}}^{-}}$) under LL. A lower hormone content (auxin, cytokinin, gibberellin) in the young leaves, a weaker photosynthetic capacity in the mature leaves and significant downregulation of related gene expression were also found under LL, which resulted in the total biomass of S. superba under LL being lower than that under FL. The young leaves of C. concinna had less MDA and ${\mathrm{O}}_2^{{{}^{\bullet}}^{-}}$, and a higher hormone contents under LL than those under FL. There was no significant difference in photosynthetic capacity between mature leaves in contrasting light environments. Although the biomass of C. concinna under LL was less than that under FL, the height of C. concinna under LL was higher than that under FL, indicating that C. concinna could grow well under the two light environments. Our results describing the acclimatization of light at the physiological, molecular and transcriptome levels are important for a complete understanding of successional mechanisms.
Mycetoma in West Africa
Authors: Oladele Rita Okeoghene , Ly Fatimata , Sow Douduo , Akinkugbe Ayesha O , Ocansey Bright K , Fahal Ahmed H , van de Sande Wendy W J
Published: February 2021

Background

Mycetoma is a neglected disease, which is socioeconomically important, and with the possibility of permanent disability in infected persons if not treated early. This is especially true in resource-limited settings such as West Africa, where there is a lack of facilities and skilled personnel to make a definitive laboratory diagnosis. Countries in West Africa have similar climatic conditions to Sudan. The majority of patients seek medical care very late, when there is already bone involvement, resulting in amputations. This results in poor capture of the true burden of the problem in the literature.

Methods

A review of the literature revealed about 2685 documented cases in West Africa from 1929 to 2020; from 15 out of 16 countries, Senegal accounted for 74.1% (1943) of cases in the subregion.

Results

The majority of lesions were found on the foot; however, other body parts were also reported. Rural dwellers accounted for most cases. Only 547 (20.4%) cases had identified isolates reported. Actinomycetoma accounted for 47.9% of cases, eumycetoma 39.7% and unidentified pathogens 12.4%. Actinomadura pelletieri was the predominant pathogen isolated (21.4%; 117 isolates).

Conclusion

There is a dire need for capacity building, provision of facility and health education to raise awareness of this debilitating disease in West Africa.