bluuebunny/crossref_metadata_2025 huggingface dataset:
Legal Comparisons Regarding the Content of Franchise Prospectus in Legal System of United States of America, Australia, Indonesia For Legal Protection of Frait Recipients in Indonesia
Authors: Ginting Rika Githamala
Published: May 2021

The prospectus document is given as a consideration for the franchisee whether they want to participate in operating the franchise or not. Apart from being used as a medium to find out information about franchises, this prospectus is also a form of legal protection for franchisees. Article 7 of the Government Regulation on franchising regulates clauses that must be included in the prospectus. The regulations governing minimal clauses in this prospectus are quite minimal. Compared to the United States, which is the originating country for franchising and Australia, which follows the United States in regulating its franchises, Indonesia is still far behind in the preparation of its prospectus documents. The method used is the legal comparative research method because it is used to compare regulations in a country with other countries. The research results show that each prospectus minimum clause in Indonesia has its own objectives in terms of protecting prospective franchisees and franchisees. There are differences between the clauses that must be listed in the prospectus in the United States, Australia and Indonesia, where there are clauses that are regulated in the United States and Australia which are not regulated in the minimum clause of the prospectus in Indonesia, although there are differences, but there are also clauses that are the same regulated in the three countries, it's just that the explanation of the provisions has differences. Regarding whether Indonesia's prospectus is capable of, Indonesia's minimum clause has not been able to provide protection for franchisees in Indonesia.
Child giving birth to child
Authors: Khan Mahbub Ul Karim
Published: May 2021

Abstract not available

CBMJ 2014 July: Vol. 03 No. 02 P: 01-02
Comparison of Doppler waveform and mean velocity of hepatic vein in cirrhotic patients with healthy subjects and their correlation with severity of cirrhosis
Authors: Islam Mahzabeen , Ahmed Akhter Uddin , Mohiuddin AS
Published: May 2021

This descriptive study was carried out in the Department of Radiology and Imaging, BIRDEM (Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorder) Dhaka during the period of 1st June 2008 to 30th May 2009, to compare the pattern of the Doppler waveform and mean velocity of hepatic vein between healthy subjects and that in cirrhotic patients and to detect possible differences and also to assess the accuracy of the detection of changes in hepatic vein waveform and mean velocity for the diagnosis of liver cirrhosis. A total of 40 cirrhotic patients and 40 healthy subjects were enrolled in this study. Doppler waveform was done in all the patients and the healthy subjects. The mean hepatic vein velocity (MHVV) was 12.22±4.22 cm/sec and 5.17±1.19 cm/sec in case and healthy group respectively. The mean MHVV difference was significantly (p<0.001) higher in case group. 37.5% patient had wave form HV-0 and HV-1 and 25.0% had wave form HV-2 in case group, however, in healthy group all subjects had wave form HV-0 and the difference was statistically significant (p<0.05) between case and healthy. In Child's class A wave form HV-0 was found in 75.0%, HV-1 was 25.0% and HV-2 was not found in case group. In Child's class B wave form HV-0 was found in 21.4%, HV-1 was 71.5% and HV-2 was 7.1%. In Child's class C wave form HV-0 was not found, HV-1 was 10.0% and HV-2 was 90.0%. The and the difference was statistically significant (p<0.05) among the different grading level with wave form. In Child's class A the mean velocity was 9.18±1.81 cm/sec and velocity ranged from 7.5 to 14.2 cm/sec. In Child's class B the mean velocity was 11.26 ±1.81 cm/sec and velocity ranged from 7.5 to 14.2 cm/sec. In Child's class C the mean velocity was 18.44±1.91 cm/sec and velocity ranged from 15.5 to 20.9 cm/sec. The mean velocity was statistically significant (p<0.05) among Child's class A, Child's class B and Child's class C. From the above summary and previous study it is observed that there is a significant difference between Doppler waveform and mean velocity of right hepatic vein in cirrhotic patients and in normal subjects. It can be used as a new parameter in the assessment of liver cirrhosis.

CBMJ 2014 July: Vol. 03 No. 02 P: 23-28
Magnitude of Deaths due to Organophosphorus Compounds Poisoning in Bangladesh-A Study at Dhaka Medical College
Authors: Akber Elias Bin , Forhad Abu Jamil , Chowdhury Mohammad Habibuzzaman , Anam AM Ashraful , Jahan Israt
Published: May 2021

Poisoning with Organophosphorus compounds (OPC) is one of the important leading causes of morbidity and mortality for the countrymen of Bangladesh. OPC poisoning is a common cause of acute poisoning. The study was conducted to evaluate the magnitude of death due to OPC poisoning. This paper presents the study of total 852 cases of poisoning comprising 6.42% of the total 13,300 autopsies done during the period of three years (from 01/01/2009 to 31/12/2011) at Dhaka Medical College Mortuary. Of them, there were 478 cases of OPC poisoning. Most of the victims were from rural areas i.e. 296 cases (61.92%) and 182 cases (38.07%) from urban areas. 274 male victims (57.32%) outnumbered females i.e. 204 cases (42.67%) and the most affected age group was 21-30 years i.e. 214 cases (44.76% ). Farmers were the commonest victim i.e. 270 cases (56.48%) followed by housewives i.e. 105 cases (21.96%). Ingestion was the commonest route of poisoning i.e. 460 cases comprising 96.23% followed by 12 cases of inhalation (2.51%) and others. Suicide dominated the list of manner of death i.e. 466 cases comprising 97.48% followed by accidental i.e. 12 cases (2.51%) of the total 478 cases of OPC poisoning.

CBMJ 2014 July: Vol. 03 No. 02 P: 29-33
Hormonal and Psychobehavioral Predictors of Weight Loss in Response to a Short-Term Weight Reduction Program in Obese Women
Authors: Hainer V , Hlavatá K , Gojová M , Kunešová M , Wagenknecht M , Kopský V , Pařízková J , Hill M , Nedvídková J
Published: May 2021

Among the factors influencing weight loss and maintenance, psychobehavioral, nutritional, metabolic, hormonal and hereditary predictors play an important role. Psychobehavioral factors influence adherence to lifestyle changes and thus weight loss maintenance. The outcome of short-term weight reduction treatment is mainly affected by changes in energy and nutrient intake and physical activity and thus the impact of hormones can possibly be obscured. In order to reveal hormonal determinants of weight loss, a 4-week in-patient comprehensive weight reduction program was introduced in which food intake and physical activity were under the strict control. Women (n = 67, BMI: 32.4+/-4.4 kg; age: 48.7+/-12.2 years) who exhibited stable weight on a 7 MJ/day diet during the first week of weight management were given a hypocaloric diet yielding daily energy deficit 2.5 MJ over the subsequent 3-week period. This treatment resulted in a mean weight loss of 3.80+/-1.64 kg. Correlation analysis revealed that baseline concentrations of several hormones were significantly associated either with a higher (free triiodothyronine, C-peptide, growth hormone, pancreatic polypeptide) or with a lower (insulin-like growth factor-I, cortisol, adiponectin, neuropeptide Y) reduction of anthropometric parameters in response to weight management. In a backward stepwise regression model age, initial BMI together with baseline levels of growth hormone, peptide YY, neuropetide Y and C-reactive protein predicted 49.8 % of the variability in weight loss. Psychobehavioral factors (items of the Eating Inventory, Beck Depression score) did not contribute to weight change induced by a well-controlled short-term weight reduction program.
The Effect of Leptin on Bone - an Evolving Concept of Action
Authors: Cirmanová V , Bayer M , Stárka L , Zajíčková K
Published: May 2021

Leptin, a cytokine-like hormone secreted by adipocytes, is known to regulate food intake but has also emerged as a significant factor in the regulation of bone mass. In humans, states of energy deprivation with low serum leptin have been associated with low bone mass. In mice, leptin deficiency led to increased trabecular bone mass with overall decrease in cortical bone. Leptin regulates bone metabolism indirectly in the hypothalamus thereby activating the sympathetic nervous system (SNS). In addition to the SNS, leptin also interacts with various hypothalamic neuropeptides, such as cocaine- and amphetamine-regulated transcript, neuropeptide Y and/or neuromedin U, which might modulate the effects of leptin on bone. In osteoblasts sympathetic signaling is further gated by the transcriptional factors called molecular clock. As a result, bone loss is accelerated showing that the central effect of leptin seems to be antiosteogenic. Additionally, leptin has a direct anabolic effect within the bone driving the differentiation of bone marrow stem cells into the osteoblastic cell lineage. Besides the interaction between the central and peripheral pathways, the overall effect of leptin on bone might be bimodal depending on leptin serum concentrations. Regulatory pathways triggering osteoblast activity might open new possibilities for anabolic treatment of osteoporosis.
Melatonin Negatively Correlates with C-Peptide after Food Intake
Authors: Stárka L , Dušková M , Rácz B , Šimůnková K , Hill M , Kancheva R
Published: May 2021

Melatonin plays a key role in the circadian timing system. At present, many other functions of melatonin are known. Question remains whether changes in endogenous melatonin may be associated with food intake. Hence, the levels of melatonin, C-peptide and glucose were followed during a daily regimen (16 hours) including standardized food intake using commercial kits. The diurnal profiles of the hormones and serum glucose were evaluated using ANOVA with Period and Subject as independent factors. Pearson's correlations and using a multiple stepwise backward regression model consisting of the time factor as a polynomial, and serum C-peptide and glucose assessed the correlations between melatonin and the remaining parameters. Our results showed a significant negative correlation between melatonin and C-peptide. The profile of melatonin was physiological, decreasing after wake-up, showing minor changes during the daytime and increasing in the evening. As documented, lesser alterations were indicated in the course of the melatonin daytime profile, which may reflect periodic food intake. Food intake is not the primary factor influencing the melatonin course. While previous studies have mostly considered the protective effect of melatonin in diabetic subjects, our study brought the results suggesting food intake as a factor contributing to daytime melatonin variation in humans. However, the physiological role of melatonin association with food intake in daytime remains in question and should be further investigated.
Real time RT-PCR with a newly designed set of primers confirmed the presence of 2b and 2x/d myosin heavy chain mRNAs in the rat slow soleus muscle
Authors: Žurmanová J , Půta F , Stopková R , Soukup T
Published: May 2021

In order to re-evaluate the presence and relative quantity of 2b and 2x/d myosin heavy chain (MyHC) transcripts in rat slow soleus muscle by using real time RT-PCR we have compared the available relevant cDNA sequences and designed a new set of primers having similar melting temperatures, matching separate MyHC exons in the regions of maximal differences in MyHC coding sequences, and containing G or C at the 3 -end. These also yielded PCR products of corresponding length, which is an important requirement for real time RT-PCR quantification. The experiments were performed on 8-month-old inbred female Lewis strain rats used in our current study of regenerating transplanted muscles. The real time RT-PCR measurement confirmed the expression of all four MyHC mRNAs (type 1, 2a, 2x/d and 2b) in both fast extensor digitorum longus and slow soleus muscles, although in the soleus muscle of adult rats, only type 1 and 2a protein isoforms can be usually detected.
Modelling the flow through Sugar Cane
Authors: Breward Chris , Hocking Graeme , Ockendon Hilary , Please Colin , Schwendeman Donald
Published: May 2021

We construct mathematical models for the flow of sugarcane and juice through a sugar diffuser. The models describe how the concentration of sugar in the juice increases during the process. The flow through the sugar cane in the diffuser is analysed. The injection of tracer on one of the jets is studied. The diffusivity of the tracer is different for the direction of flow and across the flow. Our model is able to reproduce the behaviour observed in tracer experiments. A cavitation mechanism is investigated for creating dry regions in voids in the sugar cane. We show that voids occur when the permeability varies with depth in a way to produce regions of negative pressure. Their existence depends on the variation in the permeability through the whole depth but especially on regions of low permeability away from the bottom of the bed.
SÍNDROME DE BURNOUT EN PERSONAL DE ATENCIÓN A URGENCIAS MÉDICAS DURANTE LA PANDEMIA DE COVID-19
Authors:   Hospital Provincial General Docente Riobamba, Valdivieso Maggi Janneth Aracely , Noroña Salcedo Darwin Raúl ,   Universidad Regional Autónoma de los Andes, Vega Falcón Vladimir
Published: May 2021

El Síndrome de Burnout constituye un desorden funcional de la esfera neuropsiquiátrica condicionado por la exposición crónica a situaciones que general elevados niveles de estrés. La situación vivida por los trabajadores que brindaron asistencia médica de urgencia durante la pandemia de COVID-19 es consistente con un nivel de estrés elevado y mantenido. El objetivo de esta investigación fue identificar la presencia de Síndrome de Burnout en el personal de atención a urgencias médicas durante la pandemia de COVID-19. Para esto se realizó una investigación básica, descriptiva y explicativa que incluyó a 135 trabajadores de la salud que prestaron servicios en medicina de urgencia del Hospital provincial General Docente de Riobamba durante la pandemia de COVID-19. La muestra quedó conformada por 101 trabajadores a los cuales se les aplicó un cuestionario para características generales y la Escala de Maslach Burnout Inventory para identificar la presencia del Síndrome de Burnout. Existió un promedio de edad de 47,17 años, con predominio de trabajadoras (57,42%) y de personal de enfermería (38,62%). En el 35,64% de los trabajadores se identificó la presencia de Síndrome de Burnout, siendo más frecuente en las féminas (77,78%) y en el personal de enfermería (58,33%). Se concluye que la situación vivida durante la pandemia de COVID-19 generó elevados niveles de estrés en el personal que brindó servicios de emergencia médica en el Hospital Provincial General Docente de Riobamba. Esta situación repercutió en el aumento de trabajadores de salud con diagnóstico de Síndrome de Burnout.
Profile of Muscle Strength and Physical Performance with the Incidence of Urinary Incontinence in Elderly Women
Authors: Pranjasdhina Jihan Nabila , Widajanti Novira , Dharmanta Rwahita Satyawati
Published: May 2021

Introduction: The 200 million people in the world experience urinary incontinence. In general, with increasing age, the capacity of the bladder decreases. The remaining urine in the bladder tends to increase and irregular contraction of the bladder muscles becomes more frequent. This situation often makes the elderly experience problems with the fulfillment of urine elimination needs, namely urinary incontinence. Efforts to overcome urinary incontinence in the form of bladder training programs are aimed at developing muscle tone and bladder sphincter so that it can function optimally. Objective: Knowing the profile of muscle strength and physical performance with the incidence of urinary incontinence in elderly women. Methods: This research was a retrospective descriptive study based on the results of filling out the questionnaire and evaluating it directly. Based on tabulated data, 38 elderly women were selected as the study sample. Results: There were (42.1%) urinary incontinence on elderly with very poor left hand muscle strength and (50%) urinary incontinence on elderly with very poor right hand muscle strength. In physical performance with urinary incontinence as many as (57.8%) were normal and (42.1%) were poor. Conclusions: Muscle strength and physical performance can be used as a measurement to early detection of the urinary incontinence.

Keywords: urinary incontinence; muscle strength; physical performance; descriptive retrospective study
Characteristics of Acute Kidney Injury in the Intensive Care Unit of Dr. Soetomo General Hospital, Surabaya
Authors: Febriyani Putu Laksmi , Semedi Bambang Pujo , Widodo Widodo
Published: May 2021

Acute Kidney Injury (AKI) is one of the causes of morbidity and mortality among people in both developing and developed countries in the intensive care unit (ICU). In Indonesia, the incidence rate is 0.2% while for the Surabaya, AKI research has not been widely carried out and published. This study aims to determine the characteristics of AKI patients in ICU of Dr. Soetomo hospital covers the data distribution of sociodemographic, risk factors, and mortality. This descriptive study involving 23 inpatients at the ICU with AKI as the sample. Samples were selected using total sampling method. Data were collected from medical records with data collection sheets. The results were then analyzed descriptively and tested bivariate using logistic regression. The results showed that 82.6% of the patients were male with the highest age range of 50-56 years old (30.43%). AKI mortality rate in the intensive care unit was 30.43%. The primary diagnosis was diabetes mellitus (34.78%) and the highest exposure factor was a septic shock (38.70%). Factors associated with AKI mortality were diabetes mellitus (p = 0.000) and exposure to septic shock (p = 0.005).

Keywords: acute kidney injury; intensive care unit
Interphase Chromosomes in Replicative Senescence: Chromosome Positioning as a Senescence Biomarker and the Lack of Nuclear Motor-Driven Chromosome Repositioning in Senescent Cells
Authors: Mehta Ishita S. , Riyahi Kumars , Pereira Rita Torres , Meaburn Karen J. , Figgitt Martin , Kill Ian R. , Eskiw Christopher H. , Bridger Joanna M.
Published: May 2021

This study demonstrates, and confirms, that chromosome territory positioning is altered in primary senescent human dermal fibroblasts (HDFs). The chromosome territory positioning pattern is very similar to that found in HDFs made quiescent either by serum starvation or confluence; but not completely. A few chromosomes are found in different locations. One chromosome in particular stands out, chromosome 10, which is located in an intermediate location in young proliferating HDFs, but is found at the nuclear periphery in quiescent cells and in an opposing location of the nuclear interior in senescent HDFs. We have previously demonstrated that individual chromosome territories can be actively and rapidly relocated, with 15 min, after removal of serum from the culture media. These chromosome relocations require nuclear motor activity through the presence of nuclear myosin 1β (NM1β). We now also demonstrate rapid chromosome movement in HDFs after heat-shock at 42°C. Others have shown that heat shock genes are actively relocated using nuclear motor protein activity via actin or NM1β (Khanna et al., 2014; Pradhan et al., 2020). However, this current study reveals, that in senescent HDFs, chromosomes can no longer be relocated to expected nuclear locations upon these two types of stimuli. This coincides with a entirely different organisation and distribution of NM1β within senescent HDFs.
Luminescent AIE Dots for Anticancer Photodynamic Therapy
Authors: He Zhenyan , Tian Sidan , Gao Yuting , Meng Fanling , Luo Liang
Published: May 2021

Photodynamic therapy (PDT) is an emerging effective strategy for cancer treatment. Compared with conventional cancer therapies, such as surgery, chemotherapy, and radiotherapy, PDT has shown great promise as a next-generation cancer therapeutic strategy owing to its many advantages such as non-invasiveness, negligible observed drug resistance, localized treatment, and fewer side effects. One of the key elements in photodynamic therapy is the photosensitizer (PS) which converts photons into active cytotoxic species, namely, reactive oxygen species (ROS). An ideal PS for photodynamic therapy requires the efficient generation of ROS, high stability against photo bleaching, and robust performance in different environments and concentrations. PSs with aggregation-induced emission (AIE) characteristics have drawn significant attention, in that they can overcome the aggregation- caused quenching effect that is commonly seen in the case of fluorescence dyes and provide excellent performance at high concentrations or in their condensed state. Moreover, organic nanomaterials with AIE characteristics, or AIE dots, have played an increasingly significant role in assisting PDT based on its excellent ROS generation efficiency and simultaneous imaging feature. This review summarizes the recent advances on the molecular design of AIE PSs and AIE dots-based probes, as well as their emerging applications for enhanced anticancer PDT theranostics.
Phagocytosis and Efferocytosis by Resident Macrophages in the Mouse Pancreas
Authors: Parv Kristel , Westerlund Nestori , Merchant Kevin , Komijani Milad , Lindsay Robin S. , Christoffersson Gustaf
Published: May 2021

The tissue microenvironment in the mouse pancreas has been shown to promote very different polarizations of resident macrophages with islet-resident macrophages displaying an inflammatory “M1” profile and macrophages in the exocrine tissue mostly displaying an alternatively activated “M2” profile. The impact of this polarization on tissue homeostasis and diabetes development is unclear. In this study, the ability of pancreas-resident macrophages to phagocyte bacterial and endogenous debris was investigated. Mouse endocrine and exocrine tissues were separated, and tissue-resident macrophages were isolated by magnetic immunolabeling. Isolated macrophages were subjected to flow cytometry for polarization markers and qPCR for phagocytosis-related genes. Functional in vitro investigations included phagocytosis and efferocytosis assays using pH-sensitive fluorescent bacterial particles and dead fluorescent neutrophils, respectively. Intravital confocal imaging of in situ phagocytosis and efferocytosis in the pancreas was used to confirm findings in vivo. Gene expression analysis revealed no significant overall difference in expression of most phagocytosis-related genes in islet-resident vs. exocrine-resident macrophages included in the analysis. In this study, pancreas-resident macrophages were shown to differ in their ability to phagocyte bacterial and endogenous debris depending on their microenvironment. This difference in abilities may be one of the factors polarizing islet-resident macrophages to an inflammatory state since phagocytosis has been found to imprint macrophage heterogeneity. It remains unclear if this difference has any implications in the development of islet dysfunction or autoimmunity.
Effectiveness and Overall Safety of NutropinAq® for Growth Hormone Deficiency and Other Paediatric Growth Hormone Disorders: Completion of the International Cooperative Growth Study, NutropinAq® European Registry (iNCGS)
Authors: Coutant Regis , Bosch Muñoz Jordi , Dumitrescu Cristina Patricia , Schnabel Dirk , Sert Caroline , Perrot Valerie , Dattani Mehul
Published: May 2021

Objective

The International Cooperative Growth Study, NutropinAq®European Registry (iNCGS) (NCT00455728) monitored long-term safety and effectiveness of recombinant human growth hormone (rhGH; NutropinAq®[somatropin]) in paediatric growth disorders.

Methods

Open-label, non-interventional, post-marketing surveillance study recruiting children with growth disorders. Endpoints included gain in height standard deviation score (SDS), adult height, and occurrence of adverse events (AEs).

Results

2792 patients were enrolled. 2082 patients (74.6%) had growth hormone deficiency (GHD), which was isolated idiopathic in 1825 patients (87.7%). Non-GHD diagnoses included Turner syndrome (TS) (n=199), chronic renal insufficiency (CRI) (n=10), other non-GHD (n=498), and missing data for three participants. Improvements from baseline height SDS occurred at all time points to Month 132, and in all subgroups by disease aetiology. At Month 12, mean (95% CI) change in height SDS by aetiology was: idiopathic GHD 0.63 (0.61;0.66), organic GHD 0.71 (0.62;0.80), TS 0.59 (0.53; 0.65), CRI 0.54 (-0.49;1.56), and other non-GHD 0.64 (0.59;0.69). Mean height ( ± SD) at the last visit among the 235 patients with adult or near-adult height recorded was 154.0 cm ( ± 8.0) for girls and 166.7 cm ( ± 8.0) for boys. The most frequent biological and clinical non-serious drug-related AEs were increased insulin-like growth factor concentrations (314 events) and injection site haematoma (99 events). Serious AEs related to rhGH according to investigators were reported (n=30); the most frequent were scoliosis (4 events), epiphysiolysis (3 events), and strabismus (2 events).

Conclusions

There was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.
Plastic Plants: The Role of Water Hyacinths in Plastic Transport in Tropical Rivers
Authors: Schreyers Louise , van Emmerik Tim , Nguyen Thanh Luan , Castrop Evelien , Phung Ngoc-Anh , Kieu-Le Thuy-Chung , Strady Emilie , Biermann Lauren , van der Ploeg Martine
Published: May 2021

Recent studies suggest that water hyacinths can influence the transport of macroplastics in freshwater ecosystems at tropical latitudes. Forming large patches of several meters at the water surface, water hyacinths can entrain and aggregate large amounts of floating debris, including plastic items. Research on this topic is still novel and few studies have quantified the role of the water hyacinths in plastic transport. In this study, we present the findings of a six-week monitoring campaign, combining the use of visual observations and Unmanned Aerial Vehicle imagery in the Saigon river, Vietnam. For the first time, we provide observational evidence that the majority of macroplastic is transported by water hyacinth patches. Over the study period, these fast-growing and free-floating water plants transported 78% of the macroplastics observed. Additionally, we present insights on the spatial distribution of plastic and hyacinths across the river width, and the different characteristics of entrapped items compared with free-floating ones. With this study, we demonstrate the role of water hyacinths as a river plastic aggregator, which is crucial for improving the understanding of plastic transport, and optimizing future monitoring and collection strategies.
Four Species Linked by Three Hybrid Zones: Two Instances of Repeated Hybridization in One Species Group (Genus Liolaemus)
Authors: Grummer Jared A. , Avila Luciano J. , Morando Mariana M. , Leaché Adam D.
Published: May 2021

Hybridization is an evolutionary process that can generate diverse outcomes, such as reinforcing species boundaries, generating new species, or facilitating the introgression of locally-adapted alleles into new genomic backgrounds.Liolaemusis a highly diverse clade of South American lizards with ~260 species and as many as ten new species are described each year. PreviousLiolaemusstudies have detected gene flow and introgression among species using phylogenetic network methods and/or through comparisons of nuclear and mitochondrial DNA patterns, yet no study has systematically studied hybrid zones betweenLiolaemusspecies. Here, we compared three hybrid zones between four species in theLiolaemus fitzingeriigroup of lizards in Central Argentina where two species,L. melanopsandL. xanthoviridis, each hybridize with two other species (L. shehuenandL. fitzingerii). We sampled three transects that were each ~120 km in length and sequenced both mitochondrial and genome-wide SNP data for 267 individuals. In our analyses of nuclear DNA, we also compared bi-allelic SNPs to phased alleles (50 bp RAD loci). Population structure analyses confirmed that boundaries separating species are sharp, and all clines are <65 km wide. Cline center estimates were consistent between SNPs and phased alleles, but cline width estimates were significantly different with the SNPs producing wider estimates. The mitochondrial clines are narrower and shifted 4–20 km southward in comparison to the nuclear clines in all three hybrid zones, indicating that either each of the species has sex-biased dispersal (males northward or females southward), the population densities are unequal, or that the hybrid zones are moving north over time. These comparisons indicate that some patterns of hybridization are similar across hybrid zones (mtDNA clines all narrower and shifted to the south), whereas cline width is variable. Hybridization in theL. fitzingeriigroup is common and geographically localized; further studies are needed to investigate whether hybrid zones act as hard species boundaries or promoters of speciation through processes such as reinforcement. Nonetheless, this study provides insights into both biotic and abiotic mechanisms helping to maintain species boundaries within the specioseLiolaemussystem.
Altered Immune Phenotypes and HLA-DQB1 Gene Variation in Multiple Sclerosis Patients Failing Interferon β Treatment
Authors: Devi-Marulkar Priyanka , Moraes-Cabe Carolina , Campagne Pascal , Corre Béatrice , Meghraoui-Kheddar Aida , Bondet Vincent , Llibre Alba , Duffy Darragh , Maillart Elisabeth , Papeix Caroline , Pellegrini Sandra , Michel Frédérique
Published: May 2021

Background

Interferon beta (IFNβ) has been prescribed as a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) for nearly three decades. However, there is still a lack of treatment response markers that correlate with the clinical outcome of patients.

Aim

To determine a combination of cellular and molecular blood signatures associated with the efficacy of IFNβ treatment using an integrated approach.

Methods

The immune status of 40 RRMS patients, 15 of whom were untreated and 25 that received IFNβ1a treatment (15 responders, 10 non-responders), was investigated by phenotyping regulatory CD4+ T cells and naïve/memory T cell subsets, by measurement of circulating IFNα/β proteins with digital ELISA (Simoa) and analysis of ~600 immune related genes including 159 interferon-stimulated genes (ISGs) with the Nanostring technology. The potential impact of HLA class II gene variation in treatment responsiveness was investigated by genotyping HLA-DRB1, -DRB3,4,5, -DQA1, and -DQB1, using as a control population the Milieu Interieur cohort of 1,000 French healthy donors.

Results

Clinical responders and non-responders displayed similar plasma levels of IFNβ and similar ISG profiles. However, non-responders mainly differed from other subject groups with reduced circulating naïve regulatory T cells, enhanced terminally differentiated effector memory CD4+ TEMRA cells, and altered expression of at least six genes with immunoregulatory function. Moreover, non-responders were enriched for HLA-DQB1 genotypes encoding DQ8 and DQ2 serotypes. Interestingly, these two serotypes are associated with type 1 diabetes and celiac disease. Overall, the immune signatures of non-responders suggest an active disease that is resistant to therapeutic IFNβ, and in which CD4+ T cells, likely restricted by DQ8 and/or DQ2, exert enhanced autoreactive and bystander inflammatory activities.
Infection-Associated Thymic Atrophy
Authors: Luo Mingli , Xu Lingxin , Qian Zhengyu , Sun Xi
Published: May 2021

The thymus is a vital organ of the immune system that plays an essential role in thymocyte development and maturation. Thymic atrophy occurs with age (physiological thymic atrophy) or as a result of viral, bacterial, parasitic or fungal infection (pathological thymic atrophy). Thymic atrophy directly results in loss of thymocytes and/or destruction of the thymic architecture, and indirectly leads to a decrease in naïve T cells and limited T cell receptor diversity. Thus, it is important to recognize the causes and mechanisms that induce thymic atrophy. In this review, we highlight current progress in infection-associated pathogenic thymic atrophy and discuss its possible mechanisms. In addition, we discuss whether extracellular vesicles/exosomes could be potential carriers of pathogenic substances to the thymus, and potential drugs for the treatment of thymic atrophy. Having acknowledged that most current research is limited to serological aspects, we look forward to the possibility of extending future work regarding the impact of neural modulation on thymic atrophy.
A Virus-Specific Immune Rheostat in the Immunome of Patients Recovering From Mild COVID-19
Authors: Yeo Joo Guan , Leong Jing Yao , Tay Shi Huan , Nadua Karen Donceras , Anderson Danielle E. , Lim Amanda Jin Mei , Ng Xiang Wen , Poh Su Li , Guo Dianyan , Yaung Katherine Nay , Kumar Pavanish , Wasser Martin , Hazirah Sharifah Nur , Sutamam Nursyuhadah , Chua Camillus Jian Hui , Qui Martin , Foo Randy , Gamage Akshamal Mihiranga , Yeo Kee Thai , Ramakrishna Lakshmi , Arkachaisri Thaschawee , Young Barnaby E. , Lye David Chien , Wang Lin-Fa , Chong Chia Yin , Tan Natalie Woon Hui , Li Jiahui , Kam Kai-Qian , Ginhoux Florent , Thoon Koh Cheng , Chan Jerry Kok Yen , Yung Chee Fu , Albani Salvatore
Published: May 2021

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (Teff) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (Treg) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ+ memory CD4+ T cells and virus-specific follicular helper T (TFH) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.
Cryoglobulins, Cryofibrinogens, and Cold Agglutinins in Cold Urticaria: Literature Review, Retrospective Patient Analysis, and Observational Study in 49 Patients
Authors: Ginter Katharina , Ahsan Dalia Melina , Bizjak Mojca , Krause Karoline , Maurer Marcus , Altrichter Sabine , Terhorst-Molawi Dorothea
Published: May 2021

Introduction

Cryoproteins, such as cryoglobulins, cryofibrinogens and cold agglutinins, precipitate at low temperatures or agglutinate erythrocytes and dissolve again when warmed. Their pathogenetic and diagnostic importance in cold urticaria (ColdU) is unclear. In this study, we aimed to characterize the prevalence of cryoproteins in patients with ColdU.

Methods

We conducted 3 analyses: i) a systematic review and meta-analysis of published data using an adapted version of the Joanna Briggs Institute’s critical appraisal tool for case series, ii) a retrospective analysis of 293 ColdU patients treated at our Urticaria Center of Reference and Excellence (UCARE) from 2014 to 2019, and iii) a prospective observational study, from July 2019 to July 2020, with 49 ColdU patients as defined by the EAACI/GA2LEN/EDF/UNEV consensus recommendations.

Results

Our systematic review identified 14 relevant studies with a total of 1151 ColdU patients. The meta-analyses showed that 3.0% (19/628), 1.1% (4/357) and 0.7% (2/283) of patients had elevated levels of cryoglobulins, cryofibrinogens and cold agglutinins, respectively. Our retrospective analyses showed that cryoproteins were assessed in 4.1% (12/293) of ColdU patients. None of 9 ColdU patients had cryoglobulins, and one of 5 had cold agglutinins. In our prospective study, none of our patients had detectable cryoglobulins (0/48) or cryofibrinogens (0/48), but 4.3% (2/46) of patients had cold agglutinins (without any known underlying autoimmune or hematological disorder).

Conclusion

Our investigation suggests that only very few ColdU patients exhibit cryoproteins and that the pathogenesis of ColdU is driven by other mechanisms, which remain to be identified and characterized in detail.
Ensuring the Sustainability of Coastal Small-Scale Fisheries at Pitcairn Island (South Pacific) Within a Large Scale No-Take MPA
Authors: Duffy Henry J. , Letessier Tom B. , Koldewey Heather J. , Dawson Terence P. , Irving Robert A.
Published: May 2021

The Pitcairn Islands, located in the central South Pacific, contain near-pristine marine ecosystems which support unique fish assemblages, together with both endemic and threatened species. Pitcairn itself is the only inhabited island in the group and, before this study, the environmental impact of local fisheries was unclear, with little data to inform conservation and management. In 2014–2015 coastal fish populations were assessed using a mixed methods approach: a newly introduced system of fishers’ catch monitoring and Baited Remote Underwater Video Systems (BRUVS). Thirty-nine BRUVS deployments recorded 88 species in total, with small-bodied herbivores (e.g., Kyphosus pacificus) and mesopredators (e.g., Xanthichthys mento) dominating a “bottom heavy” assemblage. Several large pelagic predators were recorded, but reef-associated predators were rare with only one shark observed. Pitcairn’s top predator assemblage was relatively impoverished compared to global “pristine” sites, including other islands within the Pitcairn group. Top predator scarcity may be explained by local artisanal fisheries, which have historically targeted sharks and other large reef carnivores, and these taxa may not have recovered despite subsequent declines in fishing pressure. The dominant small-bodied species may have proliferated as a result of diminished top predator populations. Subsequent to BRUVS sampling, a local fisheries officer post was created to collate catch data from coastal fishers. Regular returns were obtained from over half of the active fishers (representing approximately 80% of catches), with K. pacificus also dominating catches and the small grouper Epinephelus fasciatus frequently targeted. Thirty fish species were represented in the recorded catch over a 12 month period. Results were shared with the local community, providing a basis for the cooperative design of a Fisheries Management Plan. This plan ensured traditional fisheries could continue in a sustainable manner within Coastal Conservation Zones around each of the four Pitcairn Islands, established within the large, no-take Marine Protected Area designated in 2016, covering the entire Pitcairn Exclusive Economic Zone. Monitoring of Pitcairn’s artisanal fisheries should be continued beyond this one-off study in order to inform adjustment of the Fisheries Management Plan, as the ongoing island fishery may still have consequences for long-term sustainability, particularly for pelagic species caught in coastal waters which remain a significant data gap.
Novel Immune Cell Subsets Exhibit Different Associations With Vascular Outcomes in Chronic Kidney Disease Patients—Identifying Potential Biomarkers
Authors: Rodríguez-Carrio Javier , Carrillo-López Natalia , Ulloa Catalina , Martín-Carro Beatriz , Rodríguez-Suárez Carmen , Naves-Díaz Manuel , Sánchez-Álvarez Emilio , Rodríguez-García Minerva , Arcidiacono Maria Vittoria , Fernández-Mariño Belinda , Cannata-Andía Jorge B. , Suárez Ana , Dusso Adriana S.
Published: May 2021

Background and Aims: Alterations in novel immune cell subsets, such as angiogenic T cells (Tang), senescent T cells (CD4+CD28null), and monocyte subsets are associated with impaired vascular homeostasis in several inflammatory conditions. However, mediators underlying vascular deterioration in chronic kidney disease (CKD) are poorly characterized. This study assessed their role in the vascular deterioration of CKD using a broad spectrum of surrogate markers ranging from altered functionality to overt calcification.

Methods: Tang (CD3+CD31+CXCR4+), CD4+CD28null cells, and monocytes [CD14/CD16 subsets and angiotensin-converting enzyme (ACE) expression] were measured in peripheral blood by flow cytometry in 33 CKD stage 5 patients undergoing peritoneal dialysis (CKD5-PD) and 15 healthy controls (HCs). Analyses were replicated in a hemodialysis cohort. Vascular surrogate markers (including adventitial vasa vasorum, pulse wave velocity, intima-media thickness, and vascular calcification) were assessed by appropriate imaging methods.

Results: In CKD5-PD, decreased Tang levels (p < 0.001) were unrelated to clinical features or traditional cardiovascular (CV) risk factors but correlated negatively with troponin T levels (r = −0.550, p = 0.003). Instead, CD4+CD28null frequency was increased (p < 0.001), especially in those with vascular calcifications. Quantitative and qualitative differences were also observed within the monocyte pool, a shift toward CD16+ subsets and ACE expression being found in CKD. Equivalent results were observed in the replication cohort. Each subset associated distinctly with adverse vascular outcomes in univariate and multivariate analyses: while Tang depletion was linked to poor vascular function and subclinical atherosclerosis, increases in CD4+CD28null were associated with overt vascular thickening and calcification. Monocytes were not independently associated with vascular outcomes in CKD patients.

Conclusions: Novel T cell and monocyte subsets are altered in CKD. Altered T-cell subpopulations, but not monocytes, exhibited distinct associations with different vascular outcomes in CKD. Tang are emerging biomarkers of subclinical vascular deterioration in CKD.
Deep Learning-Based Quantification of Visceral Fat Volumes Predicts Posttransplant Diabetes Mellitus in Kidney Transplant Recipients
Authors: Kim Ji Eun , Park Sang Joon , Kim Yong Chul , Min Sang-Il , Ha Jongwon , Kim Yon Su , Yoon Soon Ho , Han Seung Seok
Published: May 2021

Background: Because obesity is associated with the risk of posttransplant diabetes mellitus (PTDM), the precise estimation of visceral fat mass before transplantation may be helpful. Herein, we addressed whether a deep-learning based volumetric fat quantification on pretransplant computed tomographic images predicted the risk of PTDM more precisely than body mass index (BMI).

Methods: We retrospectively included a total of 718 nondiabetic kidney recipients who underwent pretransplant abdominal computed tomography. The 2D (waist) and 3D (waist or abdominal) volumes of visceral, subcutaneous, and total fat masses were automatically quantified using the deep neural network. The predictability of the PTDM risk was estimated using a multivariate Cox model and compared among the fat parameters using the areas under the receiver operating characteristic curves (AUROCs).

Results: PTDM occurred in 179 patients (24.9%) during the median follow-up period of 5 years (interquartile range, 2.5–8.6 years). All the fat parameters predicted the risk of PTDM, but the visceral and total fat volumes from 2D and 3D evaluations had higher AUROC values than BMI did, and the best predictor of PTDM was the 3D abdominal visceral fat volumes [AUROC, 0.688 (0.636–0.741)]. The addition of the 3D abdominal VF volume to the model with clinical risk factors increased the predictability of PTDM, but BMI did not.

Conclusions: A deep-learning based quantification of visceral fat volumes on computed tomographic images better predicts the risk of PTDM after kidney transplantation than BMI.
Rabies Virus-Induced Autophagy Is Dependent on Viral Load in BV2 Cells
Authors: Wang Yang , He Hongling , Li Jiesen , Chen Luman , Luo Jun , Kuang Yanqi , Lv Ziyu , Fan Ruqi , Zhang Boyue , Luo Yongwen , Guo Xiaofeng
Published: May 2021

An increasing number of studies are showing that autophagy plays a vital role in viral replication and escape. Rabies virus (RABV), a typical neurotropic virus, has been proven to induce autophagy in neurons. However, there are no reports indicating that RABV can cause autophagy in other cells of the central nervous system. Thus, we aimed to explore the relationship between autophagy and RABV infection in BV2 cells in this study. Results of viral growth curves showed that the titers of microglial BV2 cells infected with RABV peaked at 12 hours post-infection (hpi) and then decreased continuously over time. However, it was found that the viral genome RNA and structural proteins can express normally in BV2 cells. In addition, Western blotting indicated that RABV infection increased LC3-II and p62 expression in BV2 cells. LC3 punctate increased with RABV infection in BV2 cells after the transfection of fluorescent protein-tagged LC3 plasmids. Moreover, autophagy cargo protein further accumulated with RABV infection in Bafilomycin A1-treated cells. Subsequently, RABV infection inhibited the fusion of autophagosomes with lysosomes by using a tandem fluorescent marker. Furthermore, a higher multiplicity of infection induced stronger autophagy. Thus, RABV can induce autophagy in BV2 cells, and the autophagy is positively associated with the viral load.