bluuebunny/crossref_metadata_2025 huggingface dataset:
Accumulation of saposin in dystrophic neurites is linked to impaired lysosomal functions in Alzheimer’s disease brains
Authors: Sharoar Md Golam , Palko Sarah , Ge Yingying , Saido Takaomi C. , Yan Riqiang
Published: July 2021

Neuritic plaques in Alzheimer’s disease (AD) brains refer to β-amyloid (Aβ) plaques surrounded by dystrophic neurites (DNs), activated microglia and reactive astrocytes. Most recently, we showed that DNs form sequentially in three layers during plaque growth. Although lysosomal proteins such as LAMP1 are found in DNs, it is not clear how many and how early lysosomal proteins are involved in forming neuritic plaques. To answer this unmet question, we examined APP knock-in (APPNL-G-F), 5xFAD and APP/PS1ΔE9 mouse brains and found that the lysosomal activator proteins saposins (SAPs) and LAMP1 were accumulated to surround Aβ plaques at the earliest stage, namely the 1st layer of DNs. Noticeably, lysosomal hydrolases were not detectable in these early DNs, suggesting that DNs at this early stage likely enrich dysfunctional lysosomes. In old AD mouse brains and in the later stage of human AD brains, SAP-C+-DNs and LAMP1+-DNs were gradually reduced in concomitant with the growth of amyloid plaques. Remarkably, the observed LAMP1 immunoreactivity near plaques in aged AD mouse and human brains were actually associated with disease-associated microglia rather than neuronal sources, likely reflecting more severely impaired lysosomal functions in neurons. Western blot analyses showed increased levels of SAP-C in AD mouse brains, and Aβ oligomers induced elevated levels of SAP-C in cellular assays. The elevated protein levels of SAP-C in AD mouse brains during plaque growth potentially contributed lysosomal membrane leakage and loss of hydrolases. Together, our study indicates that lysosomal functions are impaired by being entrapped in DNs early during plaque growth, and this may viciously facilitate growth of amyloid plaques.
Comparative analysis of the health status of the population in six health zones in South Kivu: a cross-sectional population study using the WHODAS
Authors: Makali Samuel Lwamushi , Malembaka Espoir Bwenge , Lambert Anne-Sophie , Karemere Hermès Bimana , Eboma Christian Molima , Mwembo Albert Tambwe , Ssali Steven Barnes , Balaluka Ghislain Bisimwa , Donnen Phillippe , Macq Jean
Published: July 2021

Background

The eastern Democratic Republic of Congo (DRC) has experienced decades-long armed conflicts which have had a negative impact on population’s health. Most research in public health explores measures that focus on a specific health problem rather than overall population health status. The aim of this study was to assess the health status of the population and its predictors in conflict settings of South Kivu province, using the World Health Organization Disability Assessment Schedule (WHODAS).

Methods

Between May and June 2019, we conducted a community-based cross-sectional survey among 1440 adults in six health zones (HZ), classified according to their level of armed conflict intensity and chronicity in four types (accessible and stable, remote and stable, intermediate and unstable). The data were collected by a questionnaire including socio-demographic data and the WHODAS 2.0 tool with 12 items. The main variable of the study was the WHODAS summary score measuring individual’s health status and synthesize in six domains of disability (household, cognitive, mobility, self-care, social and society). Univariate analysis, correlation and comparison tests as well as hierarchical multiple linear regression were performed.

Results

The median WHODAS score in the accessible and stable (AS), remote and stable (RS), intermediate (I) and unstable (U) HZ was 6.3 (0–28.6); 25 (6.3–41.7); 22.9 (12.5–33.3) and 39.6 (22.9–54.2), respectively. Four of the six WHODAS domain scores (household, cognitive, mobility and society) were the most altered in the UHZs. The RSHZ and IHZ had statistically comparable global WHODAS scores. The stable HZs (accessible and remote) had statistically lower scores than the UHZ on all items. In regression analysis, the factors significantly associated with an overall poor health status (or higher WHODAS score) were advanced age, being woman, being membership of an association; being divorced, separated or widower and living in an unstable HZ.

Conclusions

Armed conflicts have a significantly negative impact on people’s perceived health, particularly in crisis health zones. In this area, we must accentuate actions aiming to strengthen people’s psychosocial well-being.
The capacity-building role of community liaison workers with refugee communities in Victoria, Australia
Authors: Wei Karen , Chopra Prem , Strehlow Susie , Stow Mardi , Kaplan Ida , Szwarc Josef , Minas Harry
Published: July 2021

Background

A range of services within Australia and internationally have been developed that are focused on the engagement of individuals who are of refugee background to work as a liaison between their communities and mental health services. The Community Liaison Worker (CLW) role at the Victorian Foundation for Survivors of Torture (VFST) was developed in 2008 in order to engage in such capacity-building initiatives.

Aims

To review and document the establishment, evolution and current status of the VFST CLW role, and examine the perspectives of CLWs on their role in trauma-informed community capacity-building.

Methods

The study comprised of two stages: a historical case study of the development of the CLW role, and a qualitative research study based on interviews with CLWs in order to identify key themes regarding various aspects of their role and understand the facilitators and barriers to their work of trauma-informed capacity-building with their respective communities.

Results

The CLW role has evolved from the provision of direct services through joint work with Counsellor Advocates at VFST to a broader role that is focused on building the capacity of community members. Thematic analysis of interviews with the seven current CLWs identified the complexity of their dual role as members of their community and employees of VFST, their role in addressing short-term goals to meet community needs, and the long-term objective of empowering their community to become integrated and self-sufficient.

Conclusions

CLWs at VFST demonstrate important work of liaison workers in facilitating trauma-informed capacity-building initiatives that are of benefit to members of their communities and also to service providers.
Kdm3b haploinsufficiency impairs the consolidation of cerebellum-dependent motor memory in mice
Authors: Kim Yong Gyu , Bak Myeong Seong , Kim Ahbin , Kim Yujin , Chae Yun-Cheol , Kim Ye Lee , Chun Yang-Sook , An Joon-Yong , Seo Sang-Beom , Kim Sang Jeong , Lee Yong-Seok
Published: July 2021

Histone modifications are a key mechanism underlying the epigenetic regulation of gene expression, which is critically involved in the consolidation of multiple forms of memory. However, the roles of histone modifications in cerebellum-dependent motor learning and memory are not well understood. To test whether changes in histone methylation are involved in cerebellar learning, we used heterozygousKdm3bknockout (Kdm3b+/−) mice, which show reduced lysine 9 on histone 3 (H3K9) demethylase activity. H3K9 di-methylation is significantly increased selectively in the granule cell layer of the cerebellum ofKdm3b+/−mice. In the cerebellum-dependent optokinetic response (OKR) learning,Kdm3b+/−mice show deficits in memory consolidation, whereas they are normal in basal oculomotor performance and OKR acquisition. In addition, RNA-seq analyses revealed that the expression levels of several plasticity-related genes were altered in the mutant cerebellum. Our study suggests that active regulation of histone methylation is critical for the consolidation of cerebellar motor memory.
Tolerability of a new amino acid-based formula for children with IgE-mediated cow’s milk allergy
Authors: Nocerino Rita , Di Scala Carmen , Coppola Serena , Giglio Veronica , Carucci Laura , Cosenza Linda , Voto Luana , Iannicelli Anna Maria , Luzzetti Anna , Berni Canani Roberto
Published: July 2021

Background

Amino acid-based formula (AAF) is a relevant dietary strategy for paediatric patients affected by cow’s milk allergy (CMA). The present study was designed to evaluate the hypoallergenicity of a new AAF in children with immunoglobulin (Ig)E-mediated CMA.

Methods

According to the criteria provided by the American Academy of Pediatrics Subcommittee on Nutrition and Allergic Diseases, we designed a prospective trial in CMA children (aged 1–36 months) aimed to demonstrate the hypoallergenicity of the new AAF in 90% of subjects with 95% confidence during the double-blind, placebo-controlled challenge (DBPCFC). A skin prick test (SPT) with the new AAF was also performed.

Results

Twenty-nine children [all Caucasian, 55.2% male, mean age (±SD) 16.9 ± 5.7 months] were enrolled. The SPT and the DBPCFC with the new AAF were negative in all study subjects.

Conclusions

The study results support the hypoallergenicity of the new AAF. This formula could be considered an additional dietary option for non-breastfed children affected by CMA.

Trial registration

The trial was registered in the ClinicalTrials.gov Protocol Registration System (ID number: NCT03909113).
Crohn disease-like enterocolitis remission after empagliflozin treatment in a child with glycogen storage disease type Ib: a case report
Authors: Rossi Alessandro , Miele Erasmo , Fecarotta Simona , Veiga-da-Cunha Maria , Martinelli Massimo , Mollica Carmine , D’Armiento Maria , Mozzillo Enza , Strisciuglio Pietro , Derks Terry G. J. , Staiano Annamaria , Parenti Giancarlo
Published: July 2021

Background

Besides major clinical/biochemical features, neutropenia and inflammatory bowel disease (IBD) constitute common complications of Glycogen storage disease type Ib (GSD Ib). However, their management is still challenging. Although previous reports have shown benefit of empagliflozin administration on neutropenia, no follow-up data on bowel (macro/microscopic) morphology are available. We herein present for the first time longitudinal assessment of bowel morphology in a GSD Ib child suffering from Crohn disease-like enterocolitis treated with empagliflozin.

Case presentation

A 14-year-old boy with GSD Ib and severe IBD was (off-label) treated with empagliflozin (20 mg/day) after informed oral and written consent was obtained from the patient’s parents. No adverse events were noted. Clinical symptoms and stool frequency improved within the first week of treatment. Pediatric Crohn disease activity index (PCDAI) normalised within the first month of treatment. Abdomen magnetic resonance imaging (MRI) performed 3 months after treatment initiation showed dramatic decrease in disease activity and length. Similar findings were reported on histology at 5.5 months. At 7.5 months hemoglobin levels normalised and fecal calprotectin almost normalised. Improved neutrophil count, metabolic control and quality of life were also noted. G-CSF dose was decreased by 33% and the patient was partly weaned from tube feeding.

Conclusions

This is the first report presenting extensive gastrointestinal morphology follow-up in a GSD Ib patient receiving empagliflozin. The present case suggests that empagliflozin can be safe and effective in inducing IBD remission in GSD Ib patients and can even postpone surgery. Future studies are required to confirm its effect over time and assess its benefit in various disease stages. The development of an international collaborating networks for systematic data collection is worthy.
Expanding the neurological and behavioral phenotype of White-Sutton syndrome: a case report
Authors: Donnarumma Bernadette , Riccio Maria Pia , Terrone Gaetano , Palma Melania , Strisciuglio Pietro , Scala Iris
Published: July 2021

Background

White-Sutton (WHSUS) is a recently recognized syndrome caused by mutations of the POGZ gene. Approximately 70 patients have been reported to date. Intellectual disability, hypotonia, behavioral abnormalities, autism, and typical facial dysmorphisms are recognized as WHSUS features; however, still few patients receive a comprehensive psychometric, behavioral and neurological examination. In this report, we describe the pediatric, dysmorphological, neurological, psychometric and behavioral phenotype in a new WHSUS patient due to a novel heterozygous POGZ mutation, highlighting the distinctive epileptic phenotype and the cognitive pattern.

Case presentation

The patient, an 8 years-old girl, presented history of hypotonia, motor and speech delay, and distinctive facial features. The diagnosis of WHSUS followed the identification of the de novo variant p.Asp828GlyfsTer36 (c.2482dupG) in the POGZ gene. The patient showed a distinctive neurological phenotype with the occurrence of both paroxysmal not-epileptic events in the first 6 months of age and EEG abnormalities without evidence of clinical seizures after the first year of age. Psychological and behavioral testing highlighted moderate intellectual and communication deficit, mild autism spectrum and visual-motor integration deficit.

Conclusions

This is the first described case of WHSUS with a co-existence of paroxysmal not-epileptic events and abnormal EEG without seizures in the same patient. Together with the available literature data, this observation suggests that paroxysmal not-epileptic events could be more frequent than expected and that this feature belongs to the WHSUS phenotypic spectrum. Autism is a known comorbidity of WHSUS but is still poorly investigated. Specific clinical testing could help detect also mild autistic phenotypes and better define autism prevalence in POGZ-related syndrome. Special attention should be given to symptoms such as stereotypies, social withdrawal, and hyperactivity that, when present, should be considered as possible signs of autism symptoms. The dissection of the neurological and behavioral phenotype is crucial for individualized therapies tailored to patient’s needs.
Alkaline post-incubation improves the saccharification of poplar after hydrogen peroxide–acetic acid pretreatment
Authors: Wen Peiyao , Zhang Ying , Zhu Junjun , Xu Yong , Zhang Junhua
Published: July 2021

Background

Hydrogen peroxide–acetic acid (HPAA) is widely used in pretreatment of lignocellulose because it has a good capability in selective delignification. However, high concentration (more than 60%) of HPAA increases the cost of pretreatment and the risk of explosion. In this work, alkaline post-incubation was employed to decrease the HPAA loading and improve the saccharification of poplar.

Results

Pretreatment with 100% HPAA removed 91.0% lignin and retained 89.9% glucan in poplar. After poplar was pretreated by 100% HPAA at 60 °C for 2 h, the glucan conversion in enzymatic hydrolysis by cellulase increased to 90.1%. Alkaline incubation reduced the total lignin, surface lignin, and acetyl group of HPAA-pretreated poplar. More than 92% acetyl groups of HPAA-pretreated poplar were removed by alkaline incubation with 1.0% NaOH at 50 °C for 1 h. After incubation of 60% HPAA-pretreated poplar with 1.0% NaOH, the glucan conversion enhanced to 95.0%. About 40% HPAA loading in pretreatment was reduced by alkaline incubation without the decrease of glucose yield.

Conclusions

Alkaline post-incubation had strong ability on the deacetylation and delignification of HPAA-pretreated poplar, exhibiting a strong promotion on the enzymatic hydrolysis yield. This report represented alkaline incubation reduced the HPAA loading, improved pretreatment safety, exhibiting excellent potential application in saccharification of poplar.
AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation
Authors: Uğurlu-Çimen Deniz , Odluyurt Deniz , Sevinç Kenan , Özkan-Küçük Nazlı Ezgi , Özçimen Burcu , Demirtaş Deniz , Enüstün Eray , Aztekin Can , Philpott Martin , Oppermann Udo , Özlü Nurhan , Önder Tamer T.
Published: July 2021

Background

The histone H3 lysine 79 (H3K79) methyltransferase DOT1L is a key chromatin-based barrier to somatic cell reprogramming. However, the mechanisms by which DOT1L safeguards cell identity and somatic-specific transcriptional programs remain unknown.

Results

We employed a proteomic approach using proximity-based labeling to identify DOT1L-interacting proteins and investigated their effects on reprogramming. Among DOT1L interactors, suppression of AF10 (MLLT10) via RNA interference or CRISPR/Cas9, significantly increases reprogramming efficiency. In somatic cells and induced pluripotent stem cells (iPSCs) higher order H3K79 methylation is dependent on AF10 expression. In AF10 knock-out cells, re-expression wild-type AF10, but not a DOT1L binding-impaired mutant, rescues overall H3K79 methylation and reduces reprogramming efficiency. Transcriptomic analyses during reprogramming show that AF10 suppression results in downregulation of fibroblast-specific genes and accelerates the activation of pluripotency-associated genes.

Conclusions

Our findings establish AF10 as a novel barrier to reprogramming by regulating H3K79 methylation and thereby sheds light on the mechanism by which cell identity is maintained in somatic cells.
Deepoxy-deoxynivalenol (DOM-1), a derivate of deoxynivalenol (DON), exhibits less toxicity on intestinal barrier function, Campylobacter jejuni colonization and translocation in broiler chickens
Authors: Ruhnau Daniel , Hess Claudia , Doupovec Barbara , Grenier Bertrand , Schatzmayr Dian , Hess Michael , Awad Wageha
Published: July 2021

Background

Intestinal epithelial cells are challenged by mycotoxins and many bacterial pathogens. It was previously shown that the mycotoxin deoxynivalenol (DON) as well as Campylobacter (C.) jejuni have a negative impact on gut integrity. Recently, it was demonstrated that DON increased the load of C. jejuni in the gut and inner organs. Based on this finding, it was hypothesized the DON metabolite (deepoxy-deoxynivalenol, DOM-1) should be able to reduce the negative effects of DON on colonization and translocation of C. jejuni in broilers, since it lacks the epoxide ring, which is responsible for the toxicity of DON.

Methods

A total of 180 broiler chickens were housed in floor pens on wood shavings with feed and water provided ad libitum. Birds were divided into six groups (n = 30 with 5 replicates/group): 1. Control, 2. DOM-1, 3. DON, 4. DOM-1 + C. jejuni, 5. DON + C. jejuni, 6. C. jejuni. At day 14, birds of groups 4, 5 and 6 were orally inoculated via feeding tube (gavage) with 1-ml of a PBS suspension containing 1 × 108 CFU of C. jejuni NCTC 12744. The performance parameters: body weight (BW), body weight gain (BWG), and feed intake of the birds were determined. At 7, 14, and 21 days post infection, samples from liver, spleen, duodenum, jejunum and cecum were aseptically collected and processed for bacteriological investigations. Finally, at each killing time point, segments of duodenum, jejunum and cecum were harvested and prepared for Ussing chamber studies to measure the paracellular mannitol fluxes.

Results

A significant decrease in body weight was observed for chickens receiving the DON diet with or without C. jejuni compared to the other groups. Furthermore, it was found that the co-exposure of birds to DON and C. jejuni resulted in a higher C. jejuni load not only in the gut but also in liver and spleen due to increased paracellular permeability of the duodenum, jejunum and cecum. On the contrary, DOM-1 supplementation in the feed improved the birds’ performance and led to a better feed conversion ratio throughout the trial. Furthermore, DOM-1 did not negatively affect gut permeability and decreased the C. jejuni counts in the intestine and internal organs.

Conclusion

Altogether, the presence of DOM-1 in the feed as a result of the enzymatic biotransformation of DON leads to a lower C. jejuni count in the intestine and better feed conversion ratio. Moreover, this study demonstrates that the detoxification product of DON, DOM-1, does not have negative effects on the gastrointestinal tract and reduces the Campylobacter burden in chickens and also the risk for human infection.
Resting-state EEG datasets of adolescents with mild, minimal, and moderate depression
Authors: Rachamanee Saravut , Wongupparaj Peera
Published: July 2021

Objectives

To measure depressive severity of 85 Thai adolescents by using the the Beck Depression Inventory-II and the Patient Health Questionnaire-9 and to record the resting-state EEG of these participants.

Data description

The current data note provides raw data of behavioral (i.e., group, BDI-II score, and PHQ-9 score) and electrophysiological parameters (i.e., absolute and relative EEG powers over 64 electrode sites) of 30, 27, and 28 participants with minimal, mild, and moderate depression, respectively. These data are especially useful to investigate the behavioral and electrophysiological markers of adolescents with subclinical depression. It can also be utilized in comparative analysis among age groups, and races.
PRDX1 gene-related epi-cblC disease is a common type of inborn error of cobalamin metabolism with mono- or bi-allelic MMACHC epimutations
Authors: Cavicchi Catia , Oussalah Abderrahim , Falliano Silvia , Ferri Lorenzo , Gozzini Alessia , Gasperini Serena , Motta Serena , Rigoldi Miriam , Parenti Giancarlo , Tummolo Albina , Meli Concetta , Menni Francesca , Furlan Francesca , Daniotti Marta , Malvagia Sabrina , la Marca Giancarlo , Chery Céline , Morange Pierre-Emmanuel , Tregouet David , Donati Maria Alice , Guerrini Renzo , Guéant Jean-Louis , Morrone Amelia
Published: July 2021

Background

The role of epigenetics in inborn errors of metabolism (IEMs) is poorly investigated. Epigenetic changes can contribute to clinical heterogeneity of affected patients but could also be underestimated determining factors in the occurrence of IEMs. An epigenetic cause of IEMs has been recently described for the autosomal recessive methylmalonic aciduria and homocystinuria, cblC type (cblC disease), and it has been named epi-cblC. Epi-cblC has been reported in association with compound heterozygosity for a genetic variant and an epimutation at the MMACHC locus, which is secondary to a splicing variant (c.515-1G > T or c.515-2A > T) at the adjacent PRDX1 gene. Both these variants cause aberrant antisense transcription and cis-hypermethylation of the MMACHC gene promotor with subsequent silencing. Until now, only nine epi-cblC patients have been reported.

Methods

We report clinical/biochemical assessment, MMACHC/PRDX1 gene sequencing and genome-wide DNA methylation profiling in 11 cblC patients who had an inconclusive MMACHC gene testing. We also compare clinical phenotype of epi-cblC patients with that of canonical cblC patients.

Results

All patients turned out to have the epi-cblC disease. One patient had a bi-allelic MMACHC epimutation due to the homozygous PRDX1:c.515-1G > T variant transmitted by both parents. We found that the bi-allelic epimutation produces the complete silencing of MMACHC in the patient’s fibroblasts. The remaining ten patients had a mono-allelic MMACHC epimutation, due to the heterozygous PRDX1:c.515-1G > T, in association with a mono-allelic MMACHC genetic variant. Epi-cblC disease has accounted for about 13% of cblC cases diagnosed by newborn screening in the Tuscany and Umbria regions since November 2001. Comparative analysis showed that clinical phenotype of epi-cblC patients is similar to that of canonical cblC patients.

Conclusions

We provide evidence that epi-cblC is an underestimated cause of inborn errors of cobalamin metabolism and describe the first instance of epi-cblC due to a bi-allelic MMACHC epimutation. MMACHC epimutation/PRDX1 mutation analyses should be part of routine genetic testing for all patients presenting with a metabolic phenotype that combines methylmalonic aciduria and homocystinuria.
Nonadditivity in public and inhouse data: implications for drug design
Authors: Gogishvili D. , Nittinger E. , Margreitter C. , Tyrchan C.
Published: July 2021

Numerous ligand-based drug discovery projects are based on structure-activity relationship (SAR) analysis, such as Free-Wilson (FW) or matched molecular pair (MMP) analysis. Intrinsically they assume linearity and additivity of substituent contributions. These techniques are challenged by nonadditivity (NA) in protein–ligand binding where the change of two functional groups in one molecule results in much higher or lower activity than expected from the respective single changes. Identifying nonlinear cases and possible underlying explanations is crucial for a drug design project since it might influence which lead to follow. By systematically analyzing all AstraZeneca (AZ) inhouse compound data and publicly available ChEMBL25 bioactivity data, we show significant NA events in almost every second assay among the inhouse and once in every third assay in public data sets. Furthermore, 9.4% of all compounds of the AZ database and 5.1% from public sources display significant additivity shifts indicating important SAR features or fundamental measurement errors. Using NA data in combination with machine learning showed that nonadditive data is challenging to predict and even the addition of nonadditive data into training did not result in an increase in predictivity. Overall, NA analysis should be applied on a regular basis in many areas of computational chemistry and can further improve rational drug design.
Twitter integration of chemistry software tools
Authors: Yoshikawa Naruki , Kubo Ryuichi , Yamamoto Kazuki Z.
Published: July 2021

Abstract﻿

Social media activity on a research article is considered to be an altmetric, a new measure to estimate research impact. Demonstrating software on Twitter is a powerful way to attract attention from a larger audience. Twitter integration of software can also lower the barriers to trying the tools and make it easier to save and share the output. We present three case studies of Twitter bots for cheminformatics: retrosynthetic analysis, 3D molecule viewer, and 2D chemical structure editor. These bots make software research more accessible to a broader range of people and facilitate the sharing of chemical knowledge, concepts, and ideas.
Tumor protein D52 is upregulated in oral squamous carcinoma cells under hypoxia in a hypoxia-inducible-factor-independent manner and is involved in cell death resistance
Authors: Abe Yuzo , Mukudai Yoshiki , Kurihara Mai , Houri Asami , Chikuda Junichiro , Yaso Atsutoshi , Kato Kosuke , Shimane Toshikazu , Shirota Tatsuo
Published: July 2021

Background

Tumor protein D52 (TPD52) reportedly plays an important role in the proliferation and metastasis of various cancer cells, including oral squamous cell carcinoma (OSCC) cells, and is expressed strongly at the center of the tumor, where the microenvironment is hypoxic. Thus, the present study investigated the roles of TPD52 in the survival and death of OSCC cells under hypoxia, and the relationship with hypoxia-inducible factor (HIF). We examined the expression of TPD52 in OSCC cells under hypoxic conditions and analyzed the effects of HIF on the modulation of TPD52 expression. Finally, the combinational effects of TPD52 knockdown and HIF inhibition were investigated both in vitro and in vivo.

Results

The mRNA and protein levels of TPD52 increased in OSCC cells under hypoxia. However, the increase was independent of HIF transcription. Importantly, the observation was due to upregulation of mRNA stability by binding of mRNA to T-cell intercellular antigen (TIA) 1 and TIA-related protein (TIAR). Simultaneous knockdown of TPD52 and inhibition of HIF significantly reduced cell viability. In addition, the in vivo tumor-xenograft experiments showed that TPD52 acts as an autophagy inhibitor caused by a decrease in p62.

Conclusions

This study showed that the expression of TPD52 increases in OSCC cells under hypoxia in a HIF-independent manner and plays an important role in the proliferation and survival of the cells in concordance with HIF, suggesting that novel cancer therapeutics might be led by TPD52 suppression.
Transpulmonary thermodilution in patients treated with veno-venous extracorporeal membrane oxygenation
Authors: Loosen Gregor , Conrad Alice Marguerite , Hagman Michael , Essert Nils , Thiel Manfred , Luecke Thomas , Krebs Joerg
Published: July 2021

Background

We tested the effect of different blood flow levels in the extracorporeal circuit on the measurements of cardiac stroke volume (SV), global end-diastolic volume index (GEDVI) and extravascular lung water index derived from transpulmonary thermodilution (TPTD) in 20 patients with severe acute respiratory distress syndrome (ARDS) treated with veno-venous extracorporeal membrane oxygenation (ECMO).

Methods

Comparative SV measurements with transesophageal echocardiography and TPTD were performed at least 5 times during the treatment of the patients. The data were interpreted with a Bland–Altman analysis corrected for repeated measurements. The interchangeability between both measurement modalities was calculated and the effects of extracorporeal blood flow on SV measurements with TPTD was analysed with a linear mixed effect model. GEDVI and EVLWI measurements were performed immediately before the termination of the ECMO therapy at a blood flow of 6 l/min, 4 l/min and 2 l/min and after the disconnection of the circuit in 7 patients.

Results

170 pairs of comparative SV measurements were analysed. Average difference between the two modalities (bias) was 0.28 ml with an upper level of agreement of 40 ml and a lower level of agreement of -39 ml within a 95% confidence interval and an overall interchangeability rate between TPTD and Echo of 64%. ECMO blood flow did not influence the mean bias between Echo and TPTD (0.03 ml per l/min of ECMO blood flow; p = 0.992; CI − 6.74 to 6.81). GEDVI measurement was not significantly influenced by the blood flow in the ECMO circuit, whereas EVLWI differed at a blood flow of 6 l/min compared to no ECMO flow (25.9 ± 10.1 vs. 11.0 ± 4.2 ml/kg, p = 0.0035).

Conclusions

Irrespectively of an established ECMO therapy, comparative SV measurements with Echo and TPTD are not interchangeable.

Such caveats also apply to the interpretation of EVLWI, especially with a high blood flow in the extracorporeal circulation. In such situations, the clinician should rely on other methods of evaluation of the amount of lung oedema with the haemodynamic situation, vasopressor support and cumulative fluid balance in mind.

Trial registration: German Clinical Trials Register (DRKS00021050). Registered 03/30/2020

https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017237
Physical layer security transmission scheme based on artificial noise in cooperative SWIPT NOMA system
Authors: Jin Yong , Hu Zhentao , Xie Dongdong , Wu Guodong , Zhou Lin
Published: July 2021

Aiming at high energy consumption and information security problem in the simultaneous wireless information and power transfer (SWIPT) multi-user wiretap network, we propose a user-aided cooperative non-orthogonal multiple access (NOMA) physical layer security transmission scheme to minimize base station (BS) transmitted power in this paper. In this scheme, the user near from BS is adopted as a friendly relay to improve performance of user far from BS. An energy harvesting (EH) technology-based SWIPT is employed at the near user to collect energy which can be used at cooperative stage. Since eavesdropper in the downlink of NOMA system may use successive interference cancellation (SIC) technology to obtain the secrecy information of receiver, to tackle this problem, artificial noise (AN) is used at the BS to enhance security performance of secrecy information. Moreover, semidefinite relaxation (SDR) method and successive convex approximation (SCA) technique are combined to solve the above non-convex problem. Simulation results show that in comparison with other methods, our method can effectively reduce the transmitted power of the BS on the constraints of a certain level of the secrecy rates of two users.
Fast ISP coding mode optimization algorithm based on CU texture complexity for VVC
Authors: Liu Zhi , Dong Mengjun , Guan Xiao Han , Zhang Mengmeng , Wang Ruoyu
Published: July 2021

In lately published video coding standard Versatile Video Coding (VVC/ H.266), the intra sub-partitions (ISP) coding mode is proposed. It is efficient for frames with rich texture, but less efficient for frames that are very flat or constant. In this paper, by comparing and analyzing the rate distortion cost (RD-cost) of coding unit (CU) with different texture features for using and not using ISP(No-ISP) coding mode, it is observed that CUs with simple texture can skip ISP coding mode. Based on this observation, a fast ISP coding mode optimization algorithm based on CU texture complexity is proposed, which aims to determine whether a CU needs to use ISP coding mode in advance by calculating CU texture complexity, so as to reduce the computation complexity of ISP. The experimental results show that under All Intra (AI) configuration, the coding time can be reduced by 7%, while the BD rate only increase by 0.09%.
Efficacy and safety of clinically managed weight loss programs: a systematic review and meta-analysis protocol
Authors: Cachero Katrina , Granger Matthew , Mollard Rebecca C. , Askin Nicole , Okoli George N. , Abou-Setta Ahmed M. , MacKay Dylan
Published: July 2021

Background

Obesity has become a major driver in the burden of chronic diseases. The Canadian Clinical Practice Guidelines recommend a lifestyle intervention for the management and prevention of obesity. This includes behavior modification, dietary counseling, and physical activity. With the market overwhelmed with weight loss programs, the majority are focused on low-calorie diets and general recommendations for exercise. Most are not personalized and are not administered by healthcare professionals. An interdisciplinary team of highly trained healthcare professionals has the ability to provide medically sound and safe advice in all aspects of an individuals’ life, such as lifestyle, sleep, mental health, and behaviors. A clinically managed weight loss program is defined as a team including a dietitian, exercise professional, psychologist, and/or physician or nurse practitioner oversight. With limiting results in the literature regarding clinically managed weight loss programs, it is difficult to conclude whether it may be effective. Therefore, the objective of this systematic review is to assess clinically managed weight loss programs, with a physician or nurse practitioner oversight in comparison with non-clinically managed weight loss programs with no physician oversight or nurse practitioner oversight in adults who are living with overweight or obesity.

Methods

A literature search will be executed by a knowledge synthesis librarian on MEDLINE, Cochrane Central, Embase, PsycINFO, and CINAHL. The data collected will be extracted, stored, and managed in MS Excel 2016. The extraction of the data will include study details, study population details, health team details, intervention details, and outcome details.

Discussion

The prevalence of obesity has been increasing throughout the decades. The results from this systematic review may aid in recommending a more clinically safe weight loss program for those who struggle with overweight or obesity.

Systematic review registration

PROSPERO CRD42020170014
Second-order impulsive differential systems with mixed and several delays
Authors: Santra Shyam Sundar , Ghosh Apurba , Bazighifan Omar , Khedher Khaled Mohamed , Nofal Taher A.
Published: July 2021

In this work, we present new necessary and sufficient conditions for the oscillation of a class of second-order neutral delay impulsive differential equations. Our oscillation results complement, simplify and improve recent results on oscillation theory of this type of nonlinear neutral impulsive differential equations that appear in the literature. An example is provided to illustrate the value of the main results.
Enhanced ceramides production by Lactobacillus rhamnosus IDCC 3201 and its proposed mechanism
Authors: Kim Myun Soo , Lee Minjee , Oh Hanna , Seo Wonsang , Kim Gwang-Seob , Ban O-Hyun , Shin Minhye , Jung Young Hoon , Yang Jungwoo
Published: July 2021

The use of probiotics has been applied for a variety of fields (e.g., immune system, mental health, and heart). In this study, the feasibility of lysates from L. rhamnosus IDCC 3201 for cosmetic ingredients was evaluated. More specifically, enhanced ceramides production in human epidermal keratinocytes by the lysates and its proposed machanism were investigated through in vitro and genome analysis. In results, enhanced spingomyelinase activity and thereby increased ceramides production by the lysates from L. rhamnosus IDCC 3201 was observed. Furthermore, it was found that the existence of glucosylceramdase in L. rhamonsus IDCC 3201 was attributed to enhanced ceramides production. Finally, it was verified that the lysates from L. rhamonsus IDCC 3201 was regarded as safe for its use as cosmetic materials. Thus, these findings have significant implications that might lead to the development of functional and safe cosmetic products from probiotics.
Expanded adipose derived mesenchymal stromal cells are effective in treating chronic insertional patellar tendinopathy: clinical and MRI evaluations of a pilot study
Authors: Khoury Miguel A. , Chamari Karim , Tabben Montassar , Alkhelaifi Khalid , Ricardo Trueba , Damián Couto , D’hooghe Pieter
Published: July 2021

Purpose

Effect of ultrasound guided injections of autologous ASCs in chronic recalcitrant patellar tendinopathy.

Methods

Fourteen patients (16 knees, 12/2 males/females) with chronic, recalcitrant (unsuccessfully treated with nonoperative treatments) insertional PT underwent clinical evaluation and magnetic resonance imaging (MRI) before intervention. Stromal vascular fraction cells (SVF) were expanded by in-vitro culture and characterized by flow cytometry. Players were injected with three bi-weekly injections of ASCs followed by physiotherapy. They underwent serial clinical evaluations during a 12-month period with repeated MRI at 6-month post-injection.

Results

Victorian Institute of sports assessment-patellar tendon questionnaire (VISA-P) scores improved from 43.8 ± 4.9 at baseline to 58.1 ± 7.1, 70.3 ± 7.9 and 78.7 ± 7.5 at 3, 6, and12months follow-up, respectively. (p = 0.0004 comparing each variable with the previous one). Mean Visual analogue pain in sports (VAS-sport) score during practice significantly decreased from 7.4 ± 0.5 at baseline to 5.2 ± 1.5 9 (p = 0.0005), 3.3 ± 1.1 (p = 0.0004) and 1.5 ± 0.7 (P = 0.0004) at 3, 6, and 12 months, respectively. Mean Tegner-scores for patients were 8.0 ± 0.8 before injury and 2.3 ± 0.9 before treatment, thereafter, improving to 4.8 ± 0.8 and 7.2 ± 0.7 at 6- and 12- months, respectively (p = 0.0001). MRI assessed tendon width’ did not change over the first 6 months post-intervention. Significant changes were observed for: tendon thickness (12.8 ± 1.1 to 10.9 ± 0.7, P = 0.0001); tear length (9.3 ± 1.3 to 2.3 ± 0.7, P = 0.0001), tear width (6.3 ± 0.8 to 3.4 ± 0.4, P = 0.0001), and tear thickness (4.6 ± 0.4 to 2.6 ± 0., P = 0.0001) at baseline and 6 months, respectively.

Conclusion

Patients with recalcitrant insertional PT showed significant clinical improvement and structural repair at the patellar insertional tendinopathy after injections of autologous ASCs. Results of this study are promising and open a new biological therapeutic modality to treat PT.
Improving the oral health of older people in care homes (TOPIC): a protocol for a feasibility study
Authors: Tsakos Georgios , Brocklehurst Paul R. , Watson Sinead , Verey Anna , Goulden Nia , Jenkins Alison , Hoare Zoe , Pye Kirstie , Wassall Rebecca R. , Sherriff Andrea , Heilmann Anja , O’Neill Ciaran , Smith Craig J. , Langley Joe , Venturelli Renato , Cairns Peter , Lievesley Nat , Watt Richard G. , Kee Frank , McKenna Gerald
Published: July 2021

Background

Evidence for interventions promoting oral health amongst care home residents is weak. The National Institute for Health and Care Excellence (NICE) guideline NG48 aims to maintain and improve the oral health of care home residents. A co-design process that worked with residents and care home staff to understand how the NG48 guideline could be best implemented in practice has been undertaken to refine a complex intervention. The aim of this study is to assess the feasibility of the intervention to inform a future larger scale definitive trial.

Methods

This is a protocol for a pragmatic cluster randomised controlled trial with a 12-month follow-up that will be undertaken in 12 care homes across two sites (six in London, six in Northern Ireland). Care homes randomised to the intervention arm (n = 6) will receive the complex intervention based on the NG48 guideline, whilst care homes randomised to the control arm (n = 6) will continue with routine practice. The intervention will include a training package for care home staff to promote knowledge and skills in oral health promotion, the use of the Oral Health Assessment Tool on residents by trained care home staff, and a ‘support worker assisted’ daily tooth-brushing regime with toothpaste containing 1500 ppm fluoride. An average of ten residents, aged 65 years or over who have at least one natural tooth, will be recruited in each care home resulting in a recruited sample of 120 participants. Assessments will be undertaken at baseline, 6 months and 12 months, and will include a dental examination and questionnaires on general health and oral health administered by a research assistant. A parallel process evaluation involving semi-structured interviews will be undertaken to explore how the intervention could be embedded in standard practice. Rates of recruitment and retention, and intervention fidelity will also be recorded. A cost-consequence model will determine the relevance of different outcome measures in the decision-making context.

Discussion

The study will provide valuable information for trialists, policymakers, clinicians and care home staff on the feasibility and associated costs of oral health promotion in UK care homes.

Trial registration

ISRCTN10276613. Registered on 17th April 2020. http://www.isrctn.com/ISRCTN10276613.
The development and validation of a prognostic model to PREDICT Relapse of depression in adult patients in primary care: protocol for the PREDICTR study
Authors: Moriarty Andrew S. , Paton Lewis W. , Snell Kym I. E. , Riley Richard D. , Buckman Joshua E. J. , Gilbody Simon , Chew-Graham Carolyn A. , Ali Shehzad , Pilling Stephen , Meader Nick , Phillips Bob , Coventry Peter A. , Delgadillo Jaime , Richards David A. , Salisbury Chris , McMillan Dean
Published: July 2021

Background

Most patients who present with depression are treated in primary care by general practitioners (GPs). Relapse of depression is common (at least 50% of patients treated for depression will relapse after a single episode) and leads to considerable morbidity and decreased quality of life for patients. The majority of patients will relapse within 6 months, and those with a history of relapse are more likely to relapse in the future than those with no such history. GPs see a largely undifferentiated case-mix of patients, and once patients with depression reach remission, there is limited guidance to help GPs stratify patients according to risk of relapse. We aim to develop a prognostic model to predict an individual’s risk of relapse within 6–8 months of entering remission. The long-term objective is to inform the clinical management of depression after the acute phase.

Methods

We will develop a prognostic model using secondary analysis of individual participant data drawn from seven RCTs and one longitudinal cohort study in primary or community care settings. We will use logistic regression to predict the outcome of relapse of depression within 6–8 months. We plan to include the following established relapse predictors in the model: residual depressive symptoms, number of previous depressive episodes, co-morbid anxiety and severity of index episode. We will use a “full model” development approach, including all available predictors. Performance statistics (optimism-adjusted C-statistic, calibration-in-the-large, calibration slope) and calibration plots (with smoothed calibration curves) will be calculated. Generalisability of predictive performance will be assessed through internal-external cross-validation. Clinical utility will be explored through net benefit analysis.

Discussion

We will derive a statistical model to predict relapse of depression in remitted depressed patients in primary care. Assuming the model has sufficient predictive performance, we outline the next steps including independent external validation and further assessment of clinical utility and impact.

Study registration

ClinicalTrials.gov ID: NCT04666662
Small-scale spatial genetic structure of Asarum sieboldii metapopulation in a valley
Authors: Jeong Hyeon Jin , Kim Jae Geun
Published: July 2021

Background

Asarum sieboldii Miq., a species of forest understory vegetation, is an herbaceous perennial belonging to the family Aristolochiaceae. The metapopulation of A. sieboldii is distributed sparsely and has a short seed dispersal distance by ants as their seed distributor. It is known that many flowers of A. sieboldii depend on self-fertilization. Because these characteristics can affect negatively in genetic structure, investigating habitat structure and assessment of genetic structure is needed. A total of 27 individuals in a valley were sampled for measuring genetic diversity, genetic distance, and genetic differentiation by RAPD-PCR.

Results

The habitat areas of A. sieboldii metapopulation were relatively small (3.78~33.60 m2) and population density was very low (five to seven individuals in 20×20 m quadrat). The habitat of A. sieboldii was a very shady (relative light intensity = 0.9%) and mature forest with a high evenness value (J = 0.81~0.99) and a low dominance value (D = 0.19~0.28). The total genetic diversity of A. sieboldii was quite high (h = 0.338, I = 0.506). A total of 33 band loci were observed in five selected primers, and 31 band loci (94%) were polymorphic. However, genetic differentiation along the valley was highly progressed (Gst = 0.548, Nm = 0.412). The average genetic distance between subpopulations was 0.387. The results of AMOVA showed 52.77% of variance occurs among populations, which is evidence of population structuring.

Conclusions

It is expected that a small-scale founder effect had occurred, an individual spread far from the original subpopulation formed a new subpopulation. However, geographical distance between individuals would have been far and genetic flow occurred only within each subpopulation because of the low density of population. This made significant genetic distance between the original and new population by distance. Although genetic diversity of A. sieboldii metapopulation is not as low as concerned, the subpopulation of A. sieboldii can disappear by stochastic events due to small subpopulation size and low density of population. To prevent genetic isolation and to enhance the stable population size, conservative efforts such as increasing the size of each subpopulation or the connection between subpopulations are needed.