bluuebunny/crossref_metadata_2025 huggingface dataset:
Jowiseungki decoction affects diabetic nephropathy in mice through renal injury inhibition as evidenced by network pharmacology and gut microbiota analyses
Authors: Meng Xianglong , Ma Junnan , Kang Seok Yong , Jung Hyo Won , Park Yong-Ki
Published: March 2020

Background

Jowiseungki decoction (JSD) is a prescription commonly used for the treatment of diabetic complications or diabetic nephropathy (DN) in traditional medicine clinics. However, the underlying therapeutic mechanisms of JSD are still unclear.

Methods

Streptozotocin (STZ)-induced DN mice were administered 100 and 500 mg/kg JSD for 4 weeks, and the therapeutic mechanisms and targets of JSD were analyzed by network pharmacology and gut microbiota analyses.

Results

JSD significantly decreased the increase in food and water intake, urine volume, fasting blood glucose, serum glucose and triglyceride levels, and urinary albumin excretion. JSD administration significantly increased the decrease in insulin secretion and creatinine clearance and reduced the structural damage to the kidney tissues. Moreover, JSD administration significantly inhibited the expression of protein kinase C-alpha (PKC-α), transforming growth factor beta-1 (TGF-β1), α-smooth muscle actin (α-SMA), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the kidney tissues of DN mice, while it significantly increased the phosphorylation of insulin receptor substrate 1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). In the network pharmacological analysis, JSD obviously influenced phosphatase binding, protein serine/threonine kinase, and mitogen-activated protein kinase (MAPK)-related signaling pathways. Our data suggest that JSD can improve symptoms in STZ-induced DN mice through the inhibition of kidney dysfunction, in particular, by regulating the PKCα/PI3K/Akt and NF-κB/α-SMA signaling pathways. Gut microbiota analysis can help to discover the pharmaco-mechanisms of the influence of JSD on bacterial diversity and flora structures in DN.

Conclusion

JSD can improve the symptoms of DN, and the underlying mechanism of this effect is renal protection through the inhibition of fibrosis and inflammation. JSD can also change bacterial diversity and community structures in DN.
Ovarian follicular response to oestrous synchronisation and induction of ovulation in Norwegian Red cattle
Authors: Berg Halldor Felde , Heringstad Bjørg , Alm-Kristiansen Anne Hege , Kvale Vilde Granne , Dragset Knut Ingolf , Waldmann Andres , Ropstad Erik , Kommisrud Elisabeth
Published: March 2020

Background

Oestrous synchronisation of cattle has been widely applied to accomplish simultaneous ovulation in animals and facilitate timed artificial insemination. The main aim of this study was to investigate the ovarian follicular growth and ovulatory response to oestrus and ovulation synchronisation in Norwegian Red heifers and cows. Oestrous cycles in 34 heifers and 10 cows from 4 herds were synchronised with two PGF2α analogue treatments 11 days apart, followed by GnRH analogue treatment for induction of ovulation. Thereafter, the ovaries were examined by ultrasonography at 3 h intervals until ovulation.

Results

The luteolytic effect of the PGF2α analogue was verified in 9 of 10 cows by progesterone contents in milk. Maximum physical activity of the cows occurred on average 69 h after PGF2α analogue treatment. An ovulatory response was recorded in 95.5% (42/44) of the animals. A significant difference in follicle size at ovulation was found between 2 of the herds. Animals with medium sized and large follicles and heifers aged > 16 months ovulated earlier than other animals.

Conclusions

The applied sequence of treatments in the study was shown to be effective in synchronizing and inducing ovulation within a relatively narrow time interval in the Norwegian Red heifers and cows, consistent with findings in other cattle breeds.
Regenerative potential of allogeneic adipose tissue-derived mesenchymal cells in canine cutaneous wounds
Authors: Enciso Nathaly , Avedillo Luis , Fermín María Luisa , Fragío Cristina , Tejero Concepción
Published: March 2020

Background

Mesenchymal stem cells (MSCs) have generated a great amount of interest over the past decade as a novel therapeutic treatment for a variety of diseases. Emerging studies have indicated that MSCs could enhance the repair of injured skin in canine cutaneous wounds.

Case presentation

A healthy 2 years old Bodeguero Andaluz dog was presented with multiple skin bite wounds. Antibiotic and anti-inflammatory therapy was administered for 8 days. On day three, 107 allogeneic adipose-derived mesenchymal stem cells (ASCs) were intradermally injected approximately equidistant to the ASCs treated wounds. Control wounds underwent conventional treatment with a topical antibacterial ointment until wound healing and closure. Wounds, skin morphology and healing progress were monitored via serial photographs and histopathology of biopsies obtained at day seven after ASC treatment. Histopathology revealed absence of inflammatory infiltrates and presence of multiple hair follicles in contrast to the non-ASCs treated control wounds indicating that ASC treatment promoted epidermal and dermal regeneration. ASCs were identified by flow cytometry and RT-PCR. The immunomodulatory role of ASCs was evidenced by coculturing peripheral blood mononuclear cells with allogeneic ASCs. Phytohemagglutinin was administered to stimulate lymphocyte proliferation. Cells were harvested and stained with an anticanine CD3-FITC antibody. The ASCs inhibited proliferation of T lymphocytes, which was quantified by reduction of carboxyfluorescein succinimidyl ester intensity using flow cytometry.

Conclusions

Compared with conventional treatment, wounds treated with ASCs showed a higher regenerative capacity with earlier and faster closure in this dog.
Herd-level risk factors for cow and calf on-farm mortality in Estonian dairy herds
Authors: Reimus Kaari , Alvåsen Karin , Emanuelson Ulf , Viltrop Arvo , Mõtus Kerli
Published: March 2020

Background

On-farm mortality (unassisted death and euthanasia) is the unwanted loss of animals, and it comes with negative economic consequences. On-farm mortality rates reflect a herd’s animal welfare status. The objective of this historical longitudinal single cohort study was to identify the associations between herd characteristics, animal housing conditions and management routines and within-herd calf and cow mortality rates in participating Estonian dairy herds. All farmers enrolled in the voluntary production recording system with a herd size of 20 or greater cow-years in 2015–2017 were contacted by mail or telephone between October 2017 and March 2018. The survey included questions about management routines and housing conditions of calves up to 3 months of age and of cows. In total, 214 completed questionnaires were returned, corresponding to a 63.3% response rate. The within-herd mortality rate of calves (aged 21–90 days) and cows (cattle over 24 months of age) in years 2017–2018 were calculated and used as outcome variables. Negative binomial and linear regression models were applied for risk factor analysis in calf and cow datasets, respectively.

Results

The median within-herd mortality rate for calves aged 21 to 90 days was 0.15 per 100 calf-months (quartiles 0.00; 0.36). The median within-herd mortality rate for cattle over 24 months of age was 4.57 per 100 cow-years (quartiles 2.44; 6.86). Factors significantly associated with increased mortality of calves were larger herd size, higher proportion of stillbirths and abortions in a herd, prophylactic administration of vitamins to all calves and housing pre-weaned calves in single pens only compared with housing in both single and group pens. Also, farmers who attended more frequent trainings had higher calf mortality rates. Calving in a group pen or in a tie-stall compared with calving in multiple systems was associated with higher calf mortality rates. Higher cow mortality rates were present in herds that had a higher proportion of stillbirths and on farms where employees handled cows. Housing cows in free-stall barns, grazing cows and more frequent hoof trimming were protective for cow on-farm mortality.

Conclusions

This study identified the importance of housing conditions for on-farm cow and calf mortality rates. Our study results suggest that providing good care might ensure better health and welfare of dairy cows and calves.
Design and testing of a centrifugal fluidic device for populating microarrays of spheroid cancer cell cultures
Authors: Weisler Warren , Miller Samuel , Jernigan Shaphan , Buckner Gregory , Bryant Matthew
Published: March 2020

Background

In current cancer spheroid culturing methods, the transfer and histological processing of specimens grown in 96-well plates is a time consuming process. A centrifugal fluidic device was developed and tested for rapid extraction of spheroids from a 96-well plate and subsequent deposition into a molded agar receiver block. The deposited spheroids must be compact enough to fit into a standard histology cassette while also maintaining a highly planar arrangement. This size and planarity enable histological processing and sectioning of spheroids in a single section. The device attaches directly to a 96-well plate and uses a standard centrifuge to facilitate spheroid transfer. The agar block is then separated from the device and processed.

Results

Testing of the device was conducted using six full 96-well plates of fixed Pa14C pancreatic cancer spheroids. On average, 80% of spheroids were successfully transferred into the agar receiver block. Additionally, the planarity of the deposited spheroids was evaluated using confocal laser scanning microscopy. This revealed that, on average, the optimal section plane bisected individual spheroids within 27% of their mean radius. This shows that spheroids are largely deposited in a planar fashion. For rare cases where spheroids had a normalized distance to the plane greater than 1, the section plane either misses or captures a small cross section of the spheroid volume.

Conclusions

These results indicate that the proposed device is capable of a high capture success rate and high sample planarity, thus demonstrating the capabilities of the device to facilitate rapid histological evaluation of spheroids grown in standard 96-well plates. Planarity figures are likely to be improved by adjusting agar block handling prior to imaging to minimize deformation and better preserve the planarity of deposited spheroids. Additionally, investigation into media additives to reduce spheroid adhesion to 96-well plates would greatly increase the capture success rate of this device.
Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies
Authors: Ettl Johannes , Im Seock-Ah , Ro Jungsil , Masuda Norikazu , Colleoni Marco , Schnell Patrick , Bananis Eustratios , Lu Dongrui R. , Cristofanilli Massimo , Rugo Hope S. , Finn Richard S.
Published: March 2020

Background

Palbociclib improves outcomes for women with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC). Dose reductions are recommended for the management of hematologic toxicities. A previous pooled analysis from the PALOMA clinical trials showed that 36.9% of patients required dose reduction, predominantly during the first 6 months of treatment and with decreasing frequency during subsequent 28-day treatment cycles (C). Previous data have shown that palbociclib dose reductions do not affect efficacy. This pooled, post hoc analysis evaluated the frequency of hematologic adverse events (AEs) before and after palbociclib dose reduction in PALOMA-1, PALOMA-2, and PALOMA-3.

Methods

This analysis evaluated the frequency of hematologic AEs 30 days before dose reduction and during each subsequent treatment from C1 to C6 among patients who required palbociclib dose reduction. Data were pooled from 3 randomized studies. PALOMA-1 was a phase 2, open-label study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or letrozole alone. PALOMA-2 was a phase 3, double-blind study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or placebo plus letrozole. PALOMA-3 was a phase 3, double-blind study of pre/perimenopausal or postmenopausal patients, whose disease progressed on prior endocrine therapy, receiving palbociclib plus fulvestrant or placebo plus fulvestrant.

Results

A total of 311 (35.5%) patients with HR+/HER2− ABC required a palbociclib dose reduction (93.6% due to AEs) from 125 to 100 mg. Mean patient age was 59.9 years, and 46.9% of patients had visceral disease. Median time to dose reduction was 70 days. The majority of dose reductions occurred within 3 months of starting palbociclib treatment. Incidences of all-grade and grades 3/4 hematologic AEs were lower following dose reduction.

Conclusions

A decrease in frequency and severity of hematologic AEs, including febrile neutropenia, following palbociclib dose reduction was observed, supporting the recommended use of dose reduction in AE management.

Trial registration

These studies were sponsored by Pfizer. ClinicalTrials.gov:NCT00721409; registration date July 24, 2008. ClinicalTrials.gov:NCT01740427; registration date December 4, 2012. ClinicalTrials.gov:NCT01942135; registration date September 13, 2013.
The effectiveness of a comprehensive corrective exercises program and subsequent detraining on alignment, muscle activation, and movement pattern in men with upper crossed syndrome: protocol for a parallel-group randomized controlled trial
Authors: Bayattork Mohammad , Seidi Foad , Minoonejad Hooman , Andersen Lars Louis , Page Phil
Published: March 2020

Background

Upper crossed syndrome (UCS) refers to specific altered muscle activation and changed movement patterns along with some postural deviations in the upper quarter of the body. This syndrome might contribute to the dysfunction of the cervicothoracic and glenohumeral joints.

Objectives

The present study will aim to investigate the effectiveness of a comprehensive corrective exercises program (CCEP) and subsequent detraining on alignment, muscle activation and movement pattern in men with UCS.

Methods/design

This is a parallel-group randomized controlled trial. Participants will be 22 men aged 18 to 28 years who are suffering from UCS. Participants in the intervention group will conduct CCEP (three times a week for 8 weeks), followed by 4 weeks of detraining. The control group will do their daily activities. Participants will be randomized (1:1) into the intervention or the control group. The primary outcome will be upper trapezius activations. Secondary outcomes consist of electromyography of middle and lower trapezius and serratus anterior muscles, scapular dyskinesis test, forward head and shoulder angles, thoracic kyphosis angle, and neck flexion pattern test.

Discussion

We propose to evaluate the effectiveness of a randomized controlled trial of a CCEP in men with UCS on their alignment, selected muscle activations, and relevant movement patterns. Results from our trial may provide new insights into the effects of exercise not only on the alignment but also on muscle activation and movement patterns that are important outcomes for people with postural malalignments and, if successful, could assist therapists in evidence-based clinical decision-making.

Trial registration

Iranian Registry of Clinical Trials, IRCT20181004041232N1. Registered on 26 October 2018.
Acupoint combination effect of Shenmen (HT 7) and Sanyinjiao (SP 6) in treating insomnia: study protocol for a randomized controlled trial
Authors: Wu Pei , Cheng Cisong , Song Xiaojun , Yang Ling , Deng Dandan , Du Zhenrong , Chen Xingyu , Zou Tingting , Qiao Ling , Li Na , Zhou Pingping , Du Li , Zhu Yihui
Published: March 2020

Background

Insomnia is a global disease with a high incidence and acupuncture therapy is a well appropriate method to treat insomnia. Shenmen (HT 7) and Sanyinjiao (SP 6) are the acupoints most commonly used to treat insomnia. Although they can obviously relieve the clinical symptoms of insomnia, it is unclear whether they must be used together, whether the combination of two acupoints may have a synergistic or antagonistic effect, and whether there is a primary or secondary relationship between the two points in the treatment of insomnia. Further studies are needed. Therefore, in this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia.

Methods/design

This will be a parallel group randomized controlled trial. The study will recruit 120 patients with insomnia randomly assigned to a control group, an electroacupuncture on HT 7 group, an electroacupuncture on SP 6 group, and an electroacupuncture on HT 7 and SP 6 group. The allocation ratio is 1:1:1:1, with 30 subjects in each group. Meanwhile, ten healthy subjects who meet the study criteria will be recruited as the healthy control group. Patients in the intervention groups will be given ten rounds of electroacupuncture stimulation on the corresponding acupoints for 2 weeks, five times per week, with 2 days of rest between the two treatment courses. Patients in the control group will also receive the same two courses of ten rounds of compensatory acupuncture therapy after a 2-week waiting period for treatment. The major outcome measures of this study include the Sleep Dysfunction Rating Scale, the Insomnia Severity Index, Epworth Sleepiness Scale, the Zung Self-Rating Anxiety Scale, and the Zung Self-Rating Depression Scale, combined with the Measure Your Medical Outcome Profile, to evaluate insomnia and the emotional state of patients with insomnia. The secondary outcome measures include sleep composition monitored by polysomnography and measurements of acetylcholine, serotonin, dopamine, norepinephrine, melatonin, gamma-aminobutyric acid, and metabolic biomarkers in serum.

Discussion

In this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia, which may provide evidence for the clinical application of acupuncture and acupoint selection in the treatment of insomnia.

Trial registration

Chinese Clinical Trial Registry, Chi-CTR-1800017483. Registered on 1 August 2018.
CareConekta: study protocol for a randomized controlled trial of a mobile health intervention to improve engagement in postpartum HIV care in South Africa
Authors: Clouse Kate , Phillips Tamsin K. , Camlin Carol , Noholoza Sandisiwe , Mogoba Phepo , Naidoo Julian , Langford Richard , Weiss Martin , Seebregts Christopher J. , Myer Landon
Published: March 2020

Background

South Africa is home to the world’s largest antiretroviral therapy program but sustaining engagement along the HIV care continuum has proven challenging in the country and throughout the wider region. Population mobility is common in South Africa, but there are important research gaps in describing this mobility and its impact on engagement in HIV care. Postpartum women and their infants in South Africa are known to be at high risk of dropping out of HIV care after delivery and are frequently mobile.

Methods

In 2017, we developed a beta version of a smartphone application (app) - CareConekta - that detects a user’s smartphone location to allow for prospective characterization of mobility. Now we will adapt and test CareConekta to conduct essential formative work on mobility and evaluate an intervention - the CareConekta app plus text notifications and phone calls and/or WhatsApp messages - to facilitate engagement in HIV care during times of mobility. During the 3-year project period, our first objective is to evaluate the feasibility, acceptability, and initial efficacy of using CareConekta as an intervention to improve engagement in HIV care. Our second objective is to characterize mobility among South African women during the peripartum period and its impact on engagement in HIV care. We will enroll 200 eligible pregnant women living with HIV and receiving care at the Gugulethu Midwife Obstetric Unit in Cape Town, South Africa.

Discussion

This work will provide critical information about mobility during the peripartum period and the impact on engagement in HIV care. Simultaneously, we will pilot test an intervention to improve engagement with rigorously assessed outcomes. If successful, CareConekta offers tremendous potential as a research and service tool that can be adapted and evaluated in multiple geographic regions, study contexts, and patient populations.

Trial registration

ClinicalTrials.gov: NCT03836625. Registered on 8 February 2019.
Genomic and transcriptomic analysis of Candida intermedia reveals the genetic determinants for its xylose-converting capacity
Authors: Geijer Cecilia , Faria-Oliveira Fábio , Moreno Antonio D. , Stenberg Simon , Mazurkewich Scott , Olsson Lisbeth
Published: March 2020

Background

An economically viable production of biofuels and biochemicals from lignocellulose requires microorganisms that can readily convert both the cellulosic and hemicellulosic fractions into product. The yeastCandida intermediadisplays a high capacity for uptake and conversion of several lignocellulosic sugars including the abundant pentosed-xylose, an underutilized carbon source since most industrially relevant microorganisms cannot naturally ferment it. Thus,C. intermediaconstitutes an important source of knowledge and genetic information that could be transferred to industrial microorganisms such asSaccharomyces cerevisiaeto improve their capacity to ferment lignocellulose-derived xylose.

Results

To understand the genetic determinants that underlie the metabolic properties ofC. intermedia, we sequenced the genomes of both the in-house-isolated strain CBS 141442 and the reference strain PYCC 4715. De novo genome assembly and subsequent analysis revealedC. intermediato be a haploid species belonging to the CTG clade ofascomycetousyeasts. The two strains have highly similar genome sizes and number of protein-encoding genes, but they differ on the chromosomal level due to numerous translocations of large and small genomic segments. The transcriptional profiles for CBS 141442 grown in medium with either high or low concentrations of glucose and xylose were determined through RNA-sequencing analysis, revealing distinct clusters of co-regulated genes in response to different specific growth rates, carbon sources and osmotic stress. Analysis of the genomic and transcriptomic data also identified multiple xylose reductases, one of which displayed dual NADH/NADPH co-factor specificity that likely plays an important role for co-factor recycling during xylose fermentation.

Conclusions

In the present study, we performed the first genomic and transcriptomic analysis ofC. intermediaand identified several novel genes for conversion of xylose. Together the results provide insights into the mechanisms underlying saccharide utilization inC. intermediaand reveal potential target genes to aid in xylose fermentation inS. cerevisiae.
Safety and effectiveness of peficitinib (ASP015K) in patients with rheumatoid arthritis: interim data (22.7 months mean peficitinib treatment) from a long-term, open-label extension study in Japan, Korea, and Taiwan
Authors: Takeuchi Tsutomu , Tanaka Yoshiya , Tanaka Sakae , Kawakami Atsushi , Song Yeong-Wook , Chen Yi-Hsing , Rokuda Mitsuhiro , Izutsu Hiroyuki , Ushijima Satoshi , Kaneko Yuichiro , Nakashima Yoshihiro , Shiomi Teruaki , Yamada Emi
Published: March 2020

Background

Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety for the treatment of rheumatoid arthritis (RA) in randomized, controlled trials of up to 52 weeks’ duration. However, safety and effectiveness after long-term treatment have not been assessed.

Methods

This was an interim analysis of an ongoing open-label, multicenter extension study in RA patients who completed phase 2b (RAJ1; 12 weeks) and phase 3 (RAJ3 and RAJ4; 52 weeks) peficitinib studies in Asia (mainly Japan). Eligible patients (n = 843) received oral peficitinib once daily (100 mg, or 50 mg for patients transferring from RAJ1). The peficitinib dose could be increased (up to 150 mg) or reduced (to 50 mg) at the discretion of the investigator. Efficacy variables assessed included American College of Rheumatology (ACR) response rates, ACR components, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP).

Results

Results up to May 2018 are summarized. Mean peficitinib duration of exposure was 22.7 months and the maximum dose was 100 mg in most (66.5%) patients. ACR responses were maintained during the extension study, with ACR20/50/70 response rates of 71.6%, 52.1%, and 34.7% at week 0 and 78.9%, 61.4%, and 42.7% at end of treatment, respectively. ACR components and DAS28-CRP showed improvements from baselines of the preceding studies and continued to show improvements during the extension study. Treatment-emergent adverse events (TEAEs) were reported in 757/843 (89.8%) patients, the most common being nasopharyngitis (39.7%) and herpes zoster (11.7%). The majority of TEAEs were severity grade 1/2. Drug-related TEAEs leading to permanent study drug discontinuation occurred in 55/843 (6.5%) patients. Regarding AEs of special interest, the incidence per 100 patient-years of serious infections was 2.3 (95% CI 1.6 – 3.1), herpes zoster-related disease 6.8 (95% CI, 5.6 – 8.3), and malignancies 1.1 (95% CI, 0.7 – 1.8). One death from diffuse large B cell lymphoma during the study and one death from uterine sarcoma after the study were considered probably and possibly related to study drug, respectively.

Conclusions

The effectiveness of peficitinib was maintained or improved during long-term administration and treatment up to 6 years was well tolerated in Asian patients with RA.

Trial registration

ClinicalTrials.gov, NCT01638013, registered retrospectively 11 July 2012.
Identification of molecules associated with response to abatacept in patients with rheumatoid arthritis
Authors: Yokoyama-Kokuryo Waka , Yamazaki Hayato , Takeuchi Tsutomu , Amano Koichi , Kikuchi Jun , Kondo Tsuneo , Nakamura Seiji , Sakai Ryoko , Hirano Fumio , Nanki Toshihiro , Koike Ryuji , Harigai Masayoshi
Published: March 2020

Background

Abatacept (ABA) is a biological disease-modifying antirheumatic drug (bDMARD) for rheumatoid arthritis (RA). The aim of this study was to identify molecules that are associated with therapeutic responses to ABA in patients with RA.

Methods

Peripheral blood was collected using a PAX gene Blood RNA kit from 45 bDMARD-naïve patients with RA at baseline and at 6 months after the initiation of ABA treatment. Gene expression levels of responders (n = 27) and non-responders (n = 8) to ABA treatment among patients with RA at baseline were compared using a microarray. The gene expression levels were confirmed using real-time quantitative polymerase chain reaction (RT-qPCR).

Results

Gene expression analysis revealed that the expression levels of 218 genes were significantly higher and those of 392 genes were significantly lower in the responders compared to the non-responders. Gene ontology analysis of the 218 genes identified “response to type I interferon (IFN)” with 24 type I IFN-related genes. RT-qPCR confirmed that there was a strong correlation between the score calculated using the 24 genes and that using OAS3, MX1, and IFIT3 (type I IFN score) (rho with the type I IFN score 0.981); the type I IFN score was significantly decreased after treatment with ABA in the responders (p < 0.05), but not in the non-responders. The receiver operating characteristic curve analysis of the type I IFN score showed that sensitivity, specificity, and AUC (95% confidence interval) for the responders were 0.82, 1.00, and 0.92 (0.82–1.00), respectively. Further, RT-qPCR demonstrated higher expression levels of BATF2, LAMP3, CD83, CLEC4A, IDO1, IRF7, STAT1, STAT2, and TNFSF10 in the responders, all of which are dendritic cell-related genes or type I IFN-related genes with significant biological implications.

Conclusion

Type I IFN score and expression levels of the nine genes may serve as novel biomarkers associated with a clinical response to ABA in patients with RA.
Histone deacetylase inhibitors induce expression of chromosomally tagged variant-specific surface protein genes in Giardia lamblia
Authors: Orozco Daniel Roberto , Garlapati Srinivas
Published: March 2020

Objective

RNA interference and miRNA mediated mechanisms have been proposed to explain the expression of a specific variant of VSP at a time on the surface of Giardia lamblia. Recently, epigenetic mechanisms involving histone acetylations have been proposed to explain the process of vsp gene switching in Giardia lamblia. However, due to the limited availability of specific antibodies for all the vsp variants present in the genome, it was difficult to monitor vsp gene switching. In this study, we have used an endogenous tagging method to tag specific vsp genes vsp1267 and vsp9B10A with a sequence encoding hemagglutinin (HA) epitope at the 3′end of the coding sequences without altering the 5′ upstream elements. With this method, we have monitored the expression of the tagged vsp genes in cells treated with histone deacetylase inhibitors using RT-PCR.

Results

Our results show that vsp1267-3XHA can be induced by treatment with sodium 4-phenylbutyrate, M344 and splitomicin but not by apicidin and Trichostatin A, while vsp9B10A-3XHA expression can be induced by Trichostatin A and splitomicin but not by sodium 4-phenylbutyrate, M344 and apicidin. The induced expression of these variants was not due to growth inhibition. These results support the role of histone acetylations in vsp expression.
A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum
Authors: Yoo Taesun , Kim Sun-Gyun , Yang Soo Hyun , Kim Hyun , Kim Eunjoon , Kim Soo Young
Published: March 2020

Background

DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory postsynaptic scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated that mutations in the DLG2 promoter region are significantly associated with autism spectrum disorder (ASD). Although DLG2 is well known as a schizophrenia-susceptibility gene, the mechanisms that link DLG2 gene disruption with ASD-like behaviors remain unclear.

Methods

Mice lacking exon 14 of the Dlg2 gene (Dlg2–/– mice) were used to investigate whether Dlg2 deletion leads to ASD-like behavioral abnormalities. To this end, we performed a battery of behavioral tests assessing locomotion, anxiety, sociability, and repetitive behaviors. In situ hybridization was performed to determine expression levels of Dlg2 mRNA in different mouse brain regions during embryonic and postnatal brain development. We also measured excitatory and inhibitory synaptic currents to determine the impacts of Dlg2 deletion on synaptic transmission in the dorsolateral striatum.

Results

Dlg2–/– mice showed hypoactivity in a novel environment. They also exhibited decreased social approach, but normal social novelty recognition, compared with wild-type animals. In addition, Dlg2–/– mice displayed strong self-grooming, both in home cages and novel environments. Dlg2 mRNA levels in the striatum were heightened until postnatal day 7 in mice, implying potential roles of DLG2 in the development of striatal connectivity. In addition, the frequency of excitatory, but not inhibitory, spontaneous postsynaptic currents in the Dlg2–/– dorsolateral striatum was significantly reduced.

Conclusion

These results suggest that homozygous Dlg2 deletion in mice leads to ASD-like behavioral phenotypes, including social deficits and increased repetitive behaviors, as well as reductions in excitatory synaptic input onto dorsolateral spiny projection neurons, implying that the dorsal striatum is one of the brain regions vulnerable to the developmental dysregulation of DLG2.
Quantification of [11C]PBR28 data after systemic lipopolysaccharide challenge
Authors: Woodcock Eric A. , Schain Martin , Cosgrove Kelly P. , Hillmer Ansel T.
Published: March 2020

Background

Lipopolysaccharide (LPS) is a classic immune stimulus. LPS combined with positron emission tomography (PET) 18 kDa translocator protein (TSPO) brain imaging provides a robust human laboratory model to study neuroimmune signaling. To evaluate optimal analysis of these data, this work compared the sensitivity of six quantification approaches.

Methods

[11C]PBR28 data from healthy volunteers (N = 8) were collected before and 3 h after LPS challenge (1.0 ng/kg IV). Quantification approaches included total volume of distribution estimated with two tissue, and two tissue plus irreversible uptake in whole blood, compartment models (2TCM and 2TCM-1k, respectively) and multilinear analysis-1 (MA-1); binding potential estimated with simultaneous estimation (SIME); standardized uptake values (SUV); and SUV ratio (SUVR).

Results

The 2TCM, 2TCM-1k, MA-1, and SIME approaches each yielded substantive effect sizes for LPS effects (partial η2 = 0.56–0.89, ps <. 05), whereas SUV and SUVR did not.

Conclusion

These findings highlight the importance of incorporating AIF measurements to quantify LPS-TSPO studies.
Existence uniqueness and stability of mild solutions for semilinear ψ-Caputo fractional evolution equations
Authors: Suechoei Apassara , Sa Ngiamsunthorn Parinya
Published: March 2020

In this paper, we study the local and global existence, and uniqueness of mild solution to initial value problems for fractional semilinear evolution equations with compact and noncompact semigroup in Banach spaces. In particular, we derive the form of fundamental solution in terms of semigroup induced by resolvent and ψ-function from Caputo fractional derivatives. These results generalize previous work where the classical Caputo fractional derivative is considered. Moreover, we prove the Mittag-Leffler–Ulam–Hyers stability result. Finally, we give examples of time-fractional heat equation to illustrate the result.
Degenerate binomial coefficients and degenerate hypergeometric functions
Authors: Kim Taekyun , Kim Dae San , Lee Hyunseok , Kwon Jongkyum
Published: March 2020

In this paper, we investigate degenerate versions of the generalized pth order Franel numbers which are certain finite sums involving powers of binomial coefficients. In more detail, we introduce degenerate generalized hypergeometric functions and study degenerate hypergeometric numbers of order p. These numbers involve powers of λ-binomial coefficients and λ-falling sequence, and can be represented by means of the degenerate generalized hypergeometric functions. We derive some explicit expressions and combinatorial identities for those numbers. We also consider several related special numbers like λ-hypergeometric numbers of order p and Apostol type λ-hypergeometric numbers of order p, of which the latter reduce in a limiting case to the generalized pth order Franel numbers.
Antibiogram and beta-lactamase genes among cefotaxime resistant E. coli from wastewater treatment plant
Authors: Adegoke Anthony Ayodeji , Madu Chibuzor Ezinne , Aiyegoro Olayinka Ayobami , Stenström Thor Axel , Okoh Anthony Ifeanyi
Published: March 2020

Background

The World Health Organization (WHO) recently classified Enterobacteriaceae resistance to third-generation cephalosporin into the group of pathogens with critical criteria for future research.

Methods

A study to assess the antibiogram and beta-lactamase genes among the cefotaxime resistant E. coli (CREc) from a South African wastewater treatment plant (WWTP) was conducted using standard phenotypic and molecular biology characterization methods.

Results

Approximate total E. coli (TEc) concentration (log10 CFU/mL) ranged between 5.7 and 6.8 among which cefotaxime resistant E. coli were between 1.8 and 4.8 (log10 CFU/mL) for cefotaxime antibiotic concentration of 4 and 8 mg/L in the influent samples. Effluent samples, heavily influenced by the chlorination had only 0.3 log10 CFU/mL of TEc. Fifty-one cefotaxime resistant isolates were selected out of an overall of 75 isolates, and subjected to a new round of testing, with a follow up of 36 and 48 isolates for both colistin and gentamicin, respectively as guided by initial results. Selected CREc exhibited resistance to amoxicillin-clavulanic acid (35.3%; n = 51), colistin sulphate (76.5%; n = 36), ciprofloxacin (47.1%; n = 51), gentamicin (87.5%; n = 48) and intermediate-resistance to meropenem (11.8%; n = 51). Extended spectrum-beta-lactamase genes detected, viz.: blaCTX-M (52.6%; n = 38) and blaTEM (84.2%; n = 38) and concurrent blaCTX-M + blaTEM (36.8%; n = 38), but no blaSHV was detected. Carbapenem resistance genes, blaKPC-2 (15.8%; n = 38), blaOXA-1 (57.9%; n = 38), blaNDM-1 (15.8%; n = 38) were also detected. Approximately, 10.5 - 36.8% (n = 38) co-occurrence of two or more beta-lactamase genes was detected in some isolates. Out of the selected number (n = 30), 7(23.3%) were enterotoxigenic E. coli (ETEC), 14 (46.7%) were Enteroaggregative E. coli (EAEC), but no enteropathogenic E. coli (EPEC) was detected.

Conclusion

Resistance to cefotaxime and the presence of a wide range of beta-lactamase genes exposed the potential risks associated with these pathogens via occupational and domestic exposure during the reuse of treated wastewater.
Prevalence, features and health impacts of eating disorders amongst First-Australian Yiramarang (adolescents) and in comparison with other Australian adolescents
Authors: Burt Adam , Mitchison Deborah , Dale Elizabeth , Bussey Kay , Trompeter Nora , Lonergan Alexandra , Hay Phillipa
Published: March 2020

Background

This study aimed to support previous research conducted with First-Australians (FA) by establishing the prevalence of eating disorders, and their demographic distribution and burden in adolescent First-Australians compared to other-Australians (OA).

Methods

Data were used from the baseline survey of the EveryBODY Study, a longitudinal investigation of eating disorders among Australian adolescents. Of the 5068 participants included, 402 (8%) identified as FA, 4586 (90.5%) identified as OA. Diagnosis of eating disorders was based on the Diagnostic and Statistical Manual version 5. Socioeconomic status and measures of impairment were assessed using validated instruments. Body mass index was calculated based on self-reported weight and height. Statistical analyses used data weighted to the distribution of gender in adolescents in New South Wales in the 2016 Australian Census. Chi-square tests were performed to determine prevalence of eating disorders amongst FA and to compare to OA. ANOVA and logistic regression analyses where conducted to examine the moderation effect of sociodemographic status, measures of impairment and FA status on the distribution of eating disorders.

Results

The prevalence rates for eating disorder diagnoses where similar for FA and OA with the exception of Night eating Syndrome (OSFED-NES), which occurred in 7.14% (95%CI 4.81–10.49) of FA vs. 3.72% (95%CI 3.17–4.36) in OA. The greater prevalence of OSFED-NES in FA was largely explained by poorer psychosocial quality of life amongst FA.

Conclusion

Eating disorders are common amongst First-Australian adolescents and are associated with poor psychosocial quality of life. These findings are consistent with previous research conducted with First-Australian adults. There is a need to screen for eating disorders amongst First-Australian adolescent girls and boys.
No differences in knee kinematics between active and passive flexion-extension movement: an intra-operative kinematic analysis performed during total knee arthroplasty
Authors: Grassi Alberto , Pizza Nicola , Lopomo Nicola Francesco , Marcacci Maurilio , Capozzi Michele , Marcheggiani Muccioli Giulio Maria , Colle Francesca , Zaffagnini Stefano
Published: March 2020

Purpose

The objective of the present study was to acquire and compare by the use of a navigation system the intra-operative flexion-extension movement of the knee performed actively by the patient and passively by the surgeon before and after a total knee arthroplasty (TKA) implantation.

Methods

A cohort of 31 patients with primary knee osteoarthritis (OA), candidate for TKA underwent intra-operative kinematics assessment with a commercial navigation system before and after the definitive implant positioning of a Cruciate Retaining (CR) Mobile Bearing (MB) prostheses. The kinematical data were acquired while surgeon performed the flexion-extension movement (passive ROM - pROM), and while the patient performed it (active ROM - aROM). Differences between pre- and post- implantation and between active and passive motions, were statistically analyzed using paired Student t-tests (p = 0.05).

Results

No statistically significant difference were found between aROM and pROM with paired Student t-test regarding internal-external rotation and anterior-posterior translation of the femoral component with respect to the tibia during flexion-extension movement before and after TKA implant (p > 0.05).

Conclusions

Active muscle contraction seems to not significantly affect TKA kinematics. The ROM performed by the surgeon during operation resemble the movement actively performed by the patient.

The clinical relevance of this study further supports the use of CAS system in performing intra-operative analysis concerning knee biomechanics.
Cold-based glaciation of Pavonis Mons, Mars: evidence for moraine deposition during glacial advance
Authors: Parsons Reid A. , Kanzaki Tomohiro , Hemmi Ryodo , Miyamoto Hideaki
Published: March 2020

The three large volcanoes in the Tharsis region of Mars: Arsia, Pavonis, and Ascraeus Montes all have fan-shaped deposits (FSDs) on their northern or western flanks consisting of a combination of parallel ridges, knobby/hummocky terrain, and a smooth, viscous flow-like unit. The FSDs are hypothesized to have formed in the Amazonian during a period of high spin-axis obliquity which redistributed polar ice to the equatorial Tharsis region resulting in thick (> 2 km), flowing ice deposits. Based on previous ice flow simulations and crater surveys, the ridges are interpreted to be recessional drop moraines formed as debris on the ice sheet surface was transported to the ice margin—forming a long ridge sequence over an extended (∼100 Myr) period of ice sheet retreat. We test this hypothesis using a high-resolution, thermomechanical ice sheet model assuming a lower ice loss rate (~ 0.5 mm/year) than prior work based on new experimental results of ice sublimation below a protective debris layer. Our ice flow simulation results, when combined with topographic observations from a long sequence of ridges located interior of the Pavonis FSD, show that the ridged units were more likely deposited during one or more periods of glacial advance (instead of retreat) when repetitive pulses (approx. 120 kyr periodicity) of ice accumulation during high obliquity produced kinematic waves which advected a large volume of surface debris to the ice margin. If ridge deposition does occur during glacial advance, it could explain the cyclic pattern of ridge spacing and would link the dominant, 120 kyr periodicity in obliquity to the time interval between adjacent ridges. By measuring the spacing between these ridges and applying this timescale, we constrain the velocity of glacial margin to be between 0.2 and 4 cm/Earth year—in close agreement with the numerical simulation. This re-interpretation of the FSD ridged unit suggests that the timescale of FSD formation (and perhaps the duration of the Amazonian high obliquity period) was shorter than previously reported.
Use of communication robots to converse with people suffering from schizophrenia
Authors: Ozeki Tomoe , Mouri Tetsuya , Sugiura Hiroko , Yano Yuu , Miyosawa Kunie
Published: March 2020

Background

Medication is an important approach of treatment for patients with schizophrenia; however, the availability of visiting nurses and other human-related support is limited. This study aims to build a system in which service robots support the treatment of individuals with schizophrenia with medication at home. Moreover, medical staff can seamlessly monitor the status of their patients through the robots using this system. In this study, to develop a support system, interactions between a communication robot and patients were surveyed, with a focus on the patients’ impression of the robot and actual utterance times.

Methods

Communication between a commercially available communication robot and schizophrenic patients was investigated, particularly the participants’ feelings about the robot. In addition, the utterance data between the participants and the robot were extracted and the durations of the conversations were assessed.

Results

The examined interaction mode of a robot (talkative or not talkative) and whether the participant spoke or not (spoke or did not speak) revealed no significant association in all adjectives. A co-occurrence network graph showed differences in the participants’ impressions of the robot depending on how talkative the robot was. That is, when the robot did not initiate conversation often, the patient was more likely to initiate interactions and use longer phrases than when the robot initiated conversation frequently. Conversations also lasted longer when the participant, not the robot, initiated conversation.

Conclusions

People with schizophrenia converse with a robot regardless of whether the robot is talkative or not. Since the content of the conversation was not analyzed qualitatively, it is necessary to carefully examine whether people with schizophrenia can develop partnerships with robots.
Dexterous object manipulation by a multi-fingered robotic hand with visual-tactile fingertip sensors
Authors: Choi Seung-hyun , Tahara Kenji
Published: March 2020

In this paper, a novel visual-tactile sensor is proposed; additionally, an object manipulation method for a multi-fingered robotic hand grasping an object is proposed by detecting a contact position using the visual-tactile sensor. The visual-tactile sensor is composed of a hemispheric fingertip made of soft silicone with a hollow interior and a general USB camera located inside the fingertip to detect the displacement of the many point markers embedded in the silicone. The deformation of each point marker due to a contact force is measured, and a contact position is estimated reliably through a novel method of creating virtual points to determine the point clouds. The aim is to demonstrate both the estimation performance of the new visual-tactile sensor and its usefulness in a grasping and manipulation task. By using the contact position obtained from the proposed sensor and the position of each fingertip obtained from kinematics, the position and orientation of a grasped object are estimated and controlled. The effectiveness of the method is illustrated through numerical simulation and its practical use is demonstrated through grasping and manipulating experiments.