bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unmasking hidden genetic, vocal, and size variation in the Masked Flowerpiercer along the Andes supports two species separated by Northern Peruvian Low
Authors: Martínez-Gómez Silvia C , Lara Carlos Esteban , Remsen J V , Brumfield Robb T , Cuervo Andrés M 
Published: June 2023

Abstract
Genetic divergence among isolated populations is not always reflected in phenotypic differentiation. We investigated the genetic and phenotypic differentiation in Diglossa cyanea (Thraupidae; Masked Flowerpiercer), a widely distributed species in the tropical Andes. We found strong evidence for 2 main lineages separated by the Marañón River valley in the Northern Peruvian Low (NPL). These 2 lineages show a deep sequence divergence in mitochondrial DNA (mtDNA; ~6.7% uncorrected p-distance, n = 122), spectral frequency and song structure (with exclusive final whistles in southern populations, n = 88), and wing length (the northern populations are smaller, n = 364). The 2 divergent D. cyanea mitochondrial lineages were not sister to each other, suggesting a possible paraphyly with respect to D. caerulescens (Bluish Flowerpiercer) that remains to be tested with nuclear genomic data. No genetic variation, size difference, or song structure was observed within the extensive range of the southern group (from the NPL to central Bolivia) or within all sampled northern populations (from the NPL to Venezuela). These vocal differences appear to have consequences for song discrimination, and species recognition, according to a previously published playback experiment study. We propose that the southern taxon be elevated to species rank as D. melanopis, a monotypic species (with the proposed name Whistling Masked-Flowerpiercer). In turn, we provide a redefinition of D. cyanea (Warbling Masked-Flowerpiercer), which is now restricted to the northern half of the tropical Andes as a polytypic species with 3 subspecies (tovarensis, obscura, and cyanea). Based on our results, the subspecies dispar should be treated as a junior synonym of cyanea. Our study highlights the need to continue amassing complementary data sets from field observations, experiments, and collection-based assessments to better characterize the evolutionary history, biogeography, bioacoustics, and taxonomy of Neotropical montane birds.
Gibberellins Promote Seed Conditioning by Up-Regulating Strigolactone Receptors in the Parasitic Plant Striga hermonthica
Authors: Yap Jia Xin , Tsuchiya Yuichiro 
Published: June 2023

Abstract
Dormant seeds of the root parasitic plant Striga hermonthica sense strigolactones from host plants as environmental cues for germination. This process is mediated by a diversified member of the strigolactone receptors encoded by HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE2 genes. It is known that warm and moist treatment during seed conditioning gradually makes dormant Striga seeds competent to respond to strigolactones, although the mechanism behind it is poorly understood. In this report, we show that plant hormone gibberellins increase strigolactone competence by up-regulating mRNA expression of the major strigolactone receptors during the conditioning period. This idea was supported by a poor germination phenotype in which gibberellin biosynthesis was depleted by paclobutrazol during conditioning. Moreover, live imaging with a fluorogenic strigolactone mimic, yoshimulactone green W, revealed that paclobutrazol treatment during conditioning caused aberrant dynamics of strigolactone perception after germination. These observations revealed an indirect role of gibberellins in seed germination in Striga, which contrasts with their roles as dominant germination-stimulating hormones in non-parasitic plants. We propose a model of how the role of gibberellins became indirect during the evolution of parasitism in plants. Our work also highlights the potential role for gibberellins in field applications, for instance, in elevating the sensitivity of seeds toward strigolactones in the current suicidal germination approach to alleviate the agricultural threats caused by this parasite in Africa.
The current state of neuropalliative care in developing countries. Where are we now?
Authors: Abdul-Rahman Toufik , Badar Sarah M , Ali Mohammed Ahsan , Kundu Mrinmoy , Ademeta Esther , Awuah Wireko Andrew 
Published: June 2023

Abstract
The need for improved palliative care in developing countries is great. Of 58 million people who die every year, 45 million die in developing countries. An estimated 60% (27 million) of these people in poor nations would benefit from palliative care, and this number is growing as chronic diseases such as cancer rise rapidly. Yet a combination of highly restrictive policies on opioid prescription and a lack of awareness within the medical profession conspire to deprive patients of palliative care. Human rights advocates argue that this neglect is a breach of human rights that is tantamount to torture. This editorial explores the neuropalliative approach and addresses the current state of neuropalliative care in developing countries.
Tofacitinib as monotherapy in cutaneous polyarteritis nodosa: a case series
Authors: Roy Debaditya , Sathyanarayana Vanitha Agrahara , Nagaraju Bhavya , Rao Vijay K R 
Published: June 2023

Abstract

Objective
Cutaneous polyarteritis nodosa (CPAN) is a distinct clinical entity represented by a chronic, relapsing, benign course, with rare systemic involvement. Treatment is with CSs, CYC or other conventional synthetic DMARDs (csDMARDs). In this case series, we aimed to share our varied clinical experience of successfully treating patients with CPAN, with tofacitinib in a refractory/relapsing course or as upfront monotherapy without CSs/csDMARDs.

Methods
We report this retrospective case series managed at our rheumatology centre in Bangalore from 2019 to 2022. Four patients identified as CPAN on biopsy were able to achieve disease-free remission with tofacitinib as part of their treatment, with no relapse on further follow-up. Our patients presented with subcutaneous nodules and cutaneous ulcers. After systemic evaluation, all the patients underwent skin biopsy, which showed fibrinoid necrosis in the vessel walls of the dermis, with a histopathological impression of CPAN. They were initially treated with a conventional approach of CSs with/without csDMARDs. On experiencing a refractory/relapsing course, tofacitinib was tried in all the patients as either CS sparing or upfront monotherapy without concomitant csDMARDs.

Results
Use of tofacitinib resulted in improvement of ulcers and paraesthesia and in gradual healing of skin lesions, albeit with scarring, with no further recurrence or relapse over a follow-up period of 6 months for all the patients. The therapeutic effect of tofacitinib was consistent when used either as CS sparing or as upfront monotherapy, thereby proving the drug to be a promising option that warrants larger trials in future to treat the subset of patients with established CPAN.

Conclusion
Tofacitinib could be used for disease-free remission as monotherapy for CPAN either upfront or as CS sparing, even without concomitant csDMARDs, in those patients who are dependent on CSs or multiple DMARDs.
Bioactive nanoglass regulating the myogenic differentiation and skeletal muscle regeneration
Authors: Winston Dagogo Dorothy , Li Ting , Lei Bo 
Published: June 2023

Abstract
Bioactive glass nanoparticles (BGNs) are widely used in the field of biomedicine, including drug delivery, gene therapy, tumor therapy, bioimaging, molecular markers and tissue engineering. Researchers are interested in using BGNs in bone, heart and skin regeneration. However, there is inadequate information on skeletal muscle tissue engineering, limited information on the biological effects of BGNs on myoblasts, and the role of bioactive glass composite materials on myogenic differentiation is unknown. Herein, we report the effects of BGNs with different compositions (60Si-BGN, 80Si-BGN, 100Si-BGN) on the myogenic differentiation in C2C12 cells and in vivo skeletal tissue regeneration. The results showed that 80Si-BGN could efficiently promote the myogenic differentiation of C1C12 cells, including the myotube formation and myogenic gene expression. The in vivo experiment in a rat skeletal muscle defect model also confirmed that 80Si-BGN could significantly improve the complete regeneration of skeletal muscle tissue during 4 weeks implantation. This work firstly demonstrated evidence that BGN could be the bioactive material in enhancing skeletal muscle regeneration.
The Darwinian Returns to Scale
Authors: Baqaee David Rezza , Farhi Emmanuel , Sangani Kunal 
Published: June 2023

Abstract
How does an increase in market size, say due to globalization, affect welfare? We study this question using a model with monopolistic competition, heterogeneous markups, and fixed costs. We characterize changes in welfare and decompose changes in allocative efficiency into three different effects: (1) reallocations across firms with heterogeneous price elasticities due to intensifying competition, (2) reallocations due to the exit of marginally profitable firms, and (3) reallocations due to changes in firms’ markups. Whereas the second and third effects have ambiguous implications for welfare, the first effect, which we call the Darwinian effect, always increases welfare regardless of the shape of demand curves. We nonparametrically calibrate demand curves with data from Belgian manufacturing firms and quantify our results. We find that mild increasing returns at the microlevel can catalyze large increasing returns at the macrolevel. Between 70 and 90% of increasing returns to scale come from improvements in how a larger market allocates resources. The lion’s share of these gains are due to the Darwinian effect, which increases the aggregate markup and concentrates sales and employment in high-markup firms. This has implications for policy: an entry subsidy, which harnesses Darwinian reallocations, can improve welfare even when there is more entry than in the first best.
Immunosuppressive therapy and humoral response to third mRNA COVID-19 vaccination with a six-month interval in rheumatic disease patients
Authors: Kashiwado Yusuke , Kimoto Yasutaka , Ohshima Shiro , Sawabe Takuya , Irino Kensuke , Nakano Shota , Hiura Junki , Yonekawa Akiko , Wang Qiaolei , Doi Goro , Ayano Masahiro , Mitoma Hiroki , Ono Nobuyuki , Arinobu Yojiro , Niiro Hiroaki , Hotta Taeko , Kang Dongchon , Shimono Nobuyuki , Akashi Koichi , Takeuchi Tsutomu , Horiuchi Takahiko 
Published: June 2023

Abstract

Objectives
To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination.

Methods
This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay.

Results
The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3–6 weeks after the second vaccination and 3–6 weeks after the third vaccination. Seroconversion rates were &lt;90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. Antibody levels after the third vaccination were significantly lower in the groups prescribed TNF inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs in a multivariate analysis adjusting for age, sex, and glucocorticoid dosage. The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus.

Conclusions
Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution.
A possible contribution of the locus coeruleus to arousal enhancement with mild exercise: evidence from pupillometry and neuromelanin imaging
Authors: Yamazaki Yudai , Suwabe Kazuya , Nagano-Saito Atsuko , Saotome Kousaku , Kuwamizu Ryuta , Hiraga Taichi , Torma Ferenc , Suzuki Kenji , Sankai Yoshiyuki , Yassa Michael A , Soya Hideaki 
Published: June 2023

Abstract
Acute mild exercise has been observed to facilitate executive function and memory. A possible underlying mechanism of this is the upregulation of the ascending arousal system, including the catecholaminergic system originating from the locus coeruleus (LC). Prior work indicates that pupil diameter, as an indirect marker of the ascending arousal system, including the LC, increases even with very light-intensity exercise. However, it remains unclear whether the LC directly contributes to exercise-induced pupil-linked arousal. Here, we examined the involvement of the LC in the change in pupil dilation induced by very light-intensity exercise using pupillometry and neuromelanin imaging to assess the LC integrity. A sample of 21 young males performed 10 min of very light-intensity exercise, and we measured changes in the pupil diameters and psychological arousal levels induced by the exercise. Neuromelanin-weighted magnetic resonance imaging scans were also obtained. We observed that pupil diameter and psychological arousal levels increased during very light-intensity exercise, which is consistent with previous findings. Notably, the LC contrast, a marker of LC integrity, predicted the magnitude of pupil dilation and psychological arousal enhancement with exercise. These relationships suggest that the LC-catecholaminergic system is a potential a mechanism for pupil-linked arousal induced by very light-intensity exercise.
Long-Term Effects of an Education Stipend Program on Domestic Violence: Evidence from Bangladesh
Authors: Sara Raisa , Priyanka Sadia 
Published: June 2023

Abstract
Intimate partner violence (IPV) remains a widespread global phenomenon. Among various factors, a low level of education is considered a significant risk factor for experiencing IPV. This paper evaluates whether a secondary school stipend program introduced in 1994 for rural girls affected the long-term prevalence of IPV in Bangladesh. The study exploits two sources of variation in the intensity of program exposure and geographic eligibility and finds that cohorts of rural women eligible for the program experienced significant declines in IPV. Evidence on mechanisms suggests that the program delayed marriage formation and changed partner quality, namely their education and employment, consistent with positive assortative matching resulting from women's improved educational attainment. There are no significant changes in labor market outcomes, decision making within the household, or women's attitude toward the acceptability of domestic violence. Marital matches present a plausible channel through which the program reduces the risk of IPV.
Assessing Acinetobacter baumannii virulence and treatment with a bacteriophage using zebrafish embryos
Authors: Neto Sofia , Vieira Ana , Oliveira Hugo , Espiña Begoña 
Published: June 2023

AbstractAcinetobacter baumannii is the leading bacteria causative of nosocomial infections, with high fatality rates, mostly due to their multi‐resistance to antibiotics. The capsular polysaccharide (k‐type) is a major virulence factor. Bacteriophages are viruses that specifically infect bacteria and have been used to control drug‐resistant bacterial pathogens. In particular, A. baumannii phages can recognize specific capsules, from a diversity of >125 that exist. This high specificity demands the in vivo identification of the most virulent A. baumannii k‐types that need to be targeted by phage therapy. Currently, the zebrafish embryo has particularly attained interest for in vivo infection modeling. In this study, an A. baumannii infection was successfully established, through the bath immersion of tail‐injured zebrafish embryos, to study the virulence of eight capsule types (K1, K2, K9, K32, K38, K44, K45, and K67). The model revealed itself as capable of discerning the most virulent (K2, K9, K32, and K45), middle (K1, K38, and K67), and the less virulent (K44) strains. Additionally, the infection of the most virulent strains was controlled in vivo resorting to the same technique, with previously identified phages (K2, K9, K32, and K45 phages). Phage treatments were able to increase the average survival from 35.2% to up to 74.1% (K32 strain). All the phages performed equally well. Collectively, the results show the potential of the model to not only evaluate virulence of bacteria such as A. baumannii but also assess novel treatments' effectiveness.
FEATURE-BASED CLUSTERING OF LEFT VENTRICULAR STRAIN CURVE FOR RISK STRATIFICATION IN GENERAL POPULATION
Authors: Ntalianis Evangelos , Sabovcik Frantisek , Cauwenberghs Nicholas , Kuznetsova Tatiana 
Published: June 2023

Objective:
Global left ventricular (LV) strain has been identified as an important predictor of adverse cardiovascular (CV) events. However, currently only the peak strain is used from the LV deformation curve, neglecting the temporal information hidden in all phases of heart cycle. Therefore, we employed unsupervised machine learning methods on time-series-derived features from LV strain to identify distinct clinical phenogroups associated with the risk of developing adverse events in the general population.

Design and method:
We prospectively studied 1185 community-dwelling individuals (mean age, 53.2 years; 51.3% women), in whom we acquired clinical and echocardiographic data including LV strain traces at baseline and collected CV events (n = 94) on average 5.2 years later. We utilised Gaussian Mixture Model (GMM) on different features derived from LV strain curve, including slope during systole and diastole, peak strain, slope during late diastole and the duration and height of diastasis (Figure, left panel). We evaluated the clinical significance of the clusters (k) by comparing the clinical characteristics and CV adverse outcome.

Results:
Based on inertia and BIC scores the optimal number of clusters (k) was 4. The first two clusters had differences in heart rate, but had similar low CV risk profiles. Cluster 4 had the worst CV risk factors combination, and higher prevalence of LV remodelling and diastolic dysfunction (i.e. lowest e ‘velocity and highest E/e’) compared to other clusters. Kaplan–Meier showed an increased cumulative incidence risk for all CV events across clusters (Figure, right panel). After adjustment for traditional risk factors, the risk was significantly higher in clusters 3 (HR: 1.35; 95% CI: 1.01-1.82; P = 0.043) and 4 (HR: 1.32; 95% CI: 1.05-1.67; P = 0.017) than in cluster 1, while the risk of adverse events did not reach the significant level in subjects with an abnormal peak LV strain (<17%) (HR 1.12; P = 0.66).

Conclusions:
Unsupervised machine learning algorithm employed on features derived from time series LV strain curves identifies clinically meaningful clusters, and provides important prognostic information over the peak LV strain.
THE EFFECT OF SEMAGLUTIDE ON BLOOD PRESSURE IN PATIENTS WITHOUT DIABETES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kennedy Cormac , Hayes Peter , Salama Sulafa , Hennessy Martina , Fogacci Federica 
Published: June 2023

Objective:
The interplay of hypertension and obesity is well described. Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). The aim of this review is to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes.

Design and method:
This systematic review was performed in line with the 2020 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science. Studies were screened to include randomised controlled trials of semaglutide versus a placebo in adults without diabetes. Continuation of anti-hypertensive treatment was a secondary outcome. Pooled and sensitivity analyses were performed and risk of bias was assessed.

Results:
611 potential studies were found by the search and 6 RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in SBP was -4.83 mmHg (95% CI -5.65 to -4.02) while that for DBP was -2.45 mmHg (95% CI -3.65 to -1.24). Only two studies (STEP 1, 4) reported change in anti-hypertensive medications. In STEP 1, 34.3% of those on anti-hypertensive medications, and receiving the intervention, either decreased or stopped these drugs, versus 16% in the placebo group. Equivalent figures were 25.5% and 11.9% for STEP 4. Critical appraisal revealed all included studies to be of a high methodological quality.

Conclusions:
The magnitude of BP reduction evident following semaglutide treatment in normotensive populations with obesity and without diabetes is clinically significant. The effect of semaglutide in those with obesity and hypertension is yet to be determined. Targeting excess body weight may be a novel therapeutic strategy for patients with difficult to control hypertension.