bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary patterns and associations with biomarkers of inflammation in adults: a systematic review of observational studies
Authors: Hart Michael J. , Torres Susan J. , McNaughton Sarah A. , Milte Catherine M.
Published: March 2021

Background

Evidence indicates that low-grade inflammation is involved in manychronic diseases of ageing. Modifiable lifestyle factors including dietcan affect low-grade inflammation. Dietary patterns allow assessment of the complex interactions of food nutrients and health and may be associated with inflammatory status.

This systematic review aimed to summarises current evidence from observational studies for associations between dietary patterns and inflammatory biomarkers in the general adult population. This review followed the PRISMA guidelines.

Methods

We conducted a systematic search in Embase, CINAHL Complete, Global Health and MEDLINE complete databases. Search terms included terms for diet (“dietary patterns”, “diet scores”) and inflammation (“inflammation“, “c-reactive protein“, “interleukin“).

Results

The search produced 7161 records. Duplicates were removed leaving 3164 for screening. There were 69 studies included (60 cross-sectional, 9 longitudinal). Papers included studies that were: 1) observational studies; 2) conducted in community-dwelling adults over 18 years of age; 3) assessed dietary patterns; 4) measured specified biomarkers of inflammation and 5) published in English. Dietary patterns were assessed using diet scores (n = 45), data-driven approaches (n = 22), both a data-driven approach and diet score (n = 2). The most frequently assessed biomarkers were CRP (n = 64) and/or IL-6 (n = 22). Cross-sectionally the majority of analyses reported an association between higher diet scores (mostly Mediterranean and anti-inflammatory diet scores) and lower inflammatory markers with 82 significant associations from 133 analyses. Only 22 of 145 cross-sectional analyses using data-driven approaches reported an association between a dietary patterns and lower inflammatory markers; the majority reported no association. Evidence of an association between dietary patterns and inflammatory markers longitudinally is limited, with the majority reporting no association.

Conclusions

Adherence to healthy, Mediterranean and anti-inflammatory dietary scores, appear to be associated with lower inflammatory status cross-sectionally. Future research could focus on longitudinal studies using a potential outcomes approach in the data analysis.

Trial registration

PROSPERO Registration NumberCRD42019114501.
Prenatal exposure to bisphenol A and autistic- and ADHD-related symptoms in children aged 2 and5 years from the Odense Child Cohort
Authors: Hansen Julie Bang , Bilenberg Niels , Timmermann Clara Amalie Gade , Jensen Richard Christian , Frederiksen Hanne , Andersson Anna-Maria , Kyhl Henriette Boye , Jensen Tina Kold
Published: March 2021

Background

Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive.

Objective

To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children.

Method

In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score.

Results

BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03).

Conclusion

Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.
Extracellular vesicles isolated by size-exclusion chromatography present suitability for RNomics analysis in plasma
Authors: Yang Yang , Wang Yaojie , Wei Sisi , Zhou Chaoxi , Yu Jiarui , Wang Guiying , Wang Wenxi , Zhao Lianmei
Published: March 2021

Background

Extracellular vesicles (EVs), known as cell-derived membranous structures harboring a variety of biomolecules, have been widely used in liquid biopsy. Due to the complex biological composition of plasma, plasma RNA omics analysis (RNomics) is easily affected, thus it is necessary to select an optimal strategy from exiting methods according to the performance for intended application.

Methods

In this study, four different strategies for EVs isolation were performed and compared (i.e. ultracentrifugation (UC), size exclusion chromatography (SEC), and two most frequently-used commercially available isolation kit (ExoQuick and exoEasy). We compared the yield, purity, PCR quantification of RNAs, miRNA-seq analyses and mRNA-seq analyses of RNAs from EVs isolated using four methods.

Results

The results showed that the lowest miRNA binding protein AGO2 (Argonaute-2) and the highest EVs-specific miRNA and lncRNA were observed in EVs obtained through SEC, meanwhile the content of the non-specific miRNA was the lowest. Further RNA-Seq data revealed that RNAs obtained via SEC presented more useful reads for both miRNA and mRNA. Furthermore, the mRNA delivered via SEC tended to have a concentration comparable to the ideal FPKM (Fragments Per Kilobase Million) value.

Conclusions

SEC shall be used as an optimal strategy for the isolation of EVs in plasma RNomics analysis.
Sialadenoma papilliferum: clinicopathologic, Immunohistochemical, molecular analyses of new five cases and review of the literature
Authors: Chen Shuai , Peng Jie , Yuan Chuantao , Sun Lin , Zhang Renya , Sun Yan
Published: March 2021

Background

Sialadenoma papilliferum (SP) is an extremely rare benign neoplasm of salivary glands. To explore and define the clinicopathological features of SP, we retrospectively analyzed 89 cases previously reported and five new cases.

Methods

The clinical features, histopathology, immunohistochemistry and molecular analysis of our cases were further performed and the related literatures were reviewed and analyzed.

Results

Combining 89 cases from the literature with our cases, the hard palate was the most common locations for SP. However, two of our cases were rarely located in the esophageal mucosa. Among all cases, the male gender was more affected, with the average age and median age of 61.8 and 62 years, respectively. Conventional histomorphologically, SP was characterized by complex papillary structures with a biphasic growth pattern of exophytic squamous component and endophytic glandular component. The glandular structures were lined by a double layer of epithelium composed of flattened or cuboidal basal cells and a cuboidal or columnar luminal cells formed papillary infoldings into the ductal lumina. Immunohistochemically, the luminal epithelial configurations showed strong expression of CK7 along the luminal cell membrane, while the basal myoepithelia displayed strong nuclear p63 expression. In both the glandular and squamous tumour components showed BRAF V600E-positive immunostaining and BRAF V600E mutation.

Conclusion

For the first time, we have comprehensively aggregated and analyzed 90 cases sialadenoma papilliferum from almost all previous publications, and further explored the clinicopathological features of SP; concordantly, this study demonstrated that SP shows a papillomatous growth pattern with exophytic and endophytic proliferation of ductal epithelium composed of double-layered cells harboring BRAF V600E mutation. Additionly, adequate treatment for SP is surgical excision, with a favorable prognosis in patients.
Extending the phenotypic spectrum of PRPF8, PRPH2, RP1 and RPGR, and the genotypic spectrum of early-onset severe retinal dystrophy
Authors: Georgiou Michalis , Ali Naser , Yang Elizabeth , Grewal Parampal S. , Rotsos Tryfon , Pontikos Nikolas , Robson Anthony G. , Michaelides Michel
Published: March 2021

Purpose

To present the detailed retinal phenotype of patients with Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy (LCA/EOSRD) caused by sequence variants in four genes, either not (n = 1) or very rarely (n = 3) previously associated with the disease.

Methods

Retrospective case series of LCA/EOSRD from four pedigrees. Chart review of clinical notes, multimodal retinal imaging, electrophysiology, and molecular genetic testing at a single tertiary referral center (Moorfields Eye Hospital, London, UK).

Results

The mean age of presentation was 3 months of age, with disease onset in the first year of life in all cases. Molecular genetic testing revealed the following disease-causing variants: PRPF8 (heterozygous c.5804G > A), PRPH2 (homozygous c.620_627delinsTA, novel variant), RP1 (homozygous c.4147_4151delGGATT, novel variant) and RPGR (heterozygous c.1894_1897delGACA). PRPF8, PRPH2, and RP1 variants have very rarely been reported, either as unique cases or case reports, with limited clinical data presented. RPGR variants have not previously been associated with LCA/EOSRD. Clinical history and detailed retinal imaging are presented.

Conclusions

The reported cases extend the phenotypic spectrum of PRPF8-, PRPH2-, RP1-, and RPGR-associated disease, and the genotypic spectrum of LCA/EOSRD. The study highlights the importance of retinal and functional phenotyping, and the importance of specific genetic diagnosis to potential future therapy.
Facioscapulohumeral muscular dystrophy: genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: an update
Authors: Schätzl Teresa , Kaiser Lars , Deigner Hans-Peter
Published: March 2021

Whilst a disease-modifying treatment for Facioscapulohumeral muscular dystrophy (FSHD) does not exist currently, recent advances in complex molecular pathophysiology studies of FSHD have led to possible therapeutic approaches for its targeted treatment. Although the underlying genetics of FSHD have been researched extensively, there remains an incomplete understanding of the pathophysiology of FSHD in relation to the molecules leading toDUX4gene activation and the downstream gene targets ofDUX4that cause its toxic effects. In the context of the local proximity of chromosome 4q to the nuclear envelope, a contraction of the D4Z4 macrosatellite induces lower methylation levels, enabling the ectopic expression ofDUX4. This disrupts numerous signalling pathways that mostly result in cell death, detrimentally affecting skeletal muscle in affected individuals. In this regard different options are currently explored either to suppress the transcription ofDUX4gene, inhibitingDUX4protein from its toxic effects, or to alleviate the symptoms triggered by its numerous targets.
The perception of patient safety in an alternate site of care for elective surgery during the first wave of the novel coronavirus pandemic in the United Kingdom: a survey of 158 patients
Authors: Lee George , Clough Oliver T. , Walker Joseph A. , Anakwe Raymond E.
Published: March 2021

Background

We undertook a prospective qualitative survey to ascertain the perceptions and experience of National Health Service patients in the United Kingdom who underwent planned or elective procedures and surgery at alternate ‘clean’ hospital sites during the coronavirus disease 2019 (COVID-19) pandemic. These alternate ‘clean’ hospital sites were independent hospitals running active staff and patient testing programmes for COVID-19 and which did not admit or treat patients suffering with COVID-19.

Methods

A prospective survey was undertaken to include patients at least 30 days after a planned surgery or procedure conducted at a ‘clean’ alternate hospital site during the COVID-19 pandemic. The study was conducted using structured interviews undertaken by trained assessors. A 20% sample group of patients were randomly selected to participate in this study. Qualitative data related to confidence, safety and perceptions of safety were collected.

Results

Ninety-five patients (60%) reported that they had prior worries or concerns about undergoing an elective procedure during the COVID-19 pandemic. A total of 47 patients (30%) had delayed their surgery at least once because of these concerns. A total of 150 patients (95%) felt that the precautions in place to protect their safety in the setting of an alternate ‘clean’ hospital site were well thought out and proportionate. Patients reported high levels of confidence in the measures undertaken. Separation of patient pathways using the independent sector and patient testing were identified by patients as having the greatest impact on their perception of safety.

Conclusions

Patient confidence will be key to ensuring uptake of planned and elective procedures and surgery during the COVID-19 pandemic. Perceptions of safety will be key to this confidence and efforts to demonstrably enhance safety are well received by patients. In particular, patients felt that a dedicated programme of patient testing and separation of patient pathways provided the greatest levels of confidence in the safety of their treatment.
Microbial lipid production from crude glycerol and hemicellulosic hydrolysate with oleaginous yeasts
Authors: Chmielarz Mikolaj , Blomqvist Johanna , Sampels Sabine , Sandgren Mats , Passoth Volkmar
Published: March 2021

Background

Crude glycerol (CG) and hemicellulose hydrolysate (HH) are low—value side-products of biodiesel transesterification and pulp—and paper industry or lignocellulosic ethanol production, respectively, which can be converted to microbial lipids by oleaginous yeasts. This study aimed to test the ability of oleaginous yeasts to utilise CG and HH and mixtures of them as carbon source.

Results

Eleven out of 27 tested strains of oleaginous yeast species were able to grow in plate tests on CG as sole carbon source. Among them, only one ascomycetous strain, belonging to Lipomyces starkeyi, was identified, the other 10 strains were Rhodotorula spec. When yeasts were cultivated in mixed CG/ HH medium, we observed an activation of glycerol conversion in the Rhodotorula strains, but not in L. starkeyi. Two strains—Rhodotorula toruloides CBS 14 and Rhodotorula glutinis CBS 3044 were further tested in controlled fermentations in bioreactors in different mixtures of CG and HH. The highest measured average biomass and lipid concentration were achieved with R. toruloides in 10% HH medium mixed with 55 g/L CG—19.4 g/L and 10.6 g/L, respectively, with a lipid yield of 0.25 g lipids per consumed g of carbon source. Fatty acid composition was similar to other R. toruloides strains and comparable to that of vegetable oils.

Conclusions

There were big strain differences in the ability to convert CG to lipids, as only few of the tested strains were able to grow. Lipid production rates and yields showed that mixing GC and HH have a stimulating effect on lipid accumulation in R. toruloides and R. glutinis resulting in shortened fermentation time to reach maximum lipid concentration, which provides a new perspective on converting these low-value compounds to microbial lipids.
Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells
Authors: Chu Jia-Qi , Gao Fei Fei , Wu Weiyun , Li Chunchao , Pan Zhaobin , Sun Jinhui , Wang Hao , Huang Cong , Lee Sang Hyuk , Quan Juan-Hua , Lee Young-Ha
Published: March 2021

Background

Toxoplasma gondii is a parasite that primarily infects through the oral route. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) play crucial roles in the immune responses generated during parasitic infection and also drive the inflammatory response against invading parasites. However, little is known about the regulation of NLRs and inflammasome activation in T. gondii-infected human small intestinal epithelial (FHs 74 Int) cells.

Methods

FHs 74 Int cells infected with T. gondii were subsequently evaluated for morphological changes, cytotoxicity, expression profiles of NLRs, inflammasome components, caspase-cleaved interleukins (ILs), and the mechanisms of NLRP3 and NLRP6 inflammasome activation. Immunocytochemistry, lactate dehydrogenase assay, reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR, and western blotting techniques were utilized for analysis.

Results

Under normal and T. gondii-infected conditions, members of the NLRs, inflammasome components and caspase-cleaved ILs were expressed in the FHs Int 74 cells, except for NLRC3, NLRP5, and NLRP9. Among the NLRs, mRNA expression of NOD2, NLRP3, NLRP6, and NAIP1 was significantly increased in T. gondii-infected cells, whereas that of NLRP2, NLRP7, and CIITA mRNAs decreased significantly in a time-dependent manner. In addition, T. gondii infection induced NLRP3, NLRP6 and NLRC4 inflammasome activation and production of IL-1β, IL-18, and IL-33 in FHs 74 Int cells. T. gondii-induced NLRP3 inflammasome activation was strongly associated with the phosphorylation of p38 MAPK; however, JNK1/2 had a weak effect. NLRP6 inflammasome activation was not related to the MAPK pathway in FHs 74 Int cells.

Conclusions

This study highlighted the expression profiles of NLRs and unraveled the underlying mechanisms of NLRP3 inflammasome activation in T. gondii-infected FHs 74 Int cells. These findings may contribute to understanding of the mucosal and innate immune responses induced by the NLRs and inflammasomes during T. gondii infection in FHs 74 Int cells.

Graphical Abstract
Exosomes derived from human placental mesenchymal stem cells enhanced the recovery of spinal cord injury by activating endogenous neurogenesis
Authors: Zhou Wenshu , Silva Marta , Feng Chun , Zhao Shumei , Liu Linlin , Li Shuai , Zhong Jingmei , Zheng Wenhua
Published: March 2021

Background

Spinal cord injury (SCI) is a debilitating medical condition that can result in the irreversible loss of sensorimotor function. Current therapies fail to provide an effective recovery being crucial to develop more effective approaches. Mesenchymal stem cell (MSC) exosomes have been shown to be able to facilitate axonal growth and act as mediators to regulate neurogenesis and neuroprotection, holding great therapeutic potential in SCI conditions. This study aimed to assess the potential of human placental MSC (hpMSC)-derived exosomes on the functional recovery and reactivation of endogenous neurogenesis in an experimental animal model of SCI and to explore the possible mechanisms involved.

Methods

The hpMSC-derived exosomes were extracted and transplanted in an experimental animal model of SCI with complete transection of the thoracic segment. Functional recovery, the expression of neural stem/progenitor cell markers and the occurrence of neurogenesis, was assessed 60 days after the treatment. In vitro, neural stem cells (NSCs) were incubated with the isolated exosomes for 24 h, and the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinases (ERK), and cAMP response element binding (CREB) proteins were assessed by western blot.

Results

Exosomes were successfully isolated and purified from hpMSCs. Intravenous injections of these purified exosomes significantly improved the locomotor activity and bladder dysfunction of SCI animals. Further study of the exosomes’ therapeutic action revealed that hpMSC-derived exosomes promoted the activation of proliferating endogenous neural stem/progenitor cells as denoted by the significant increase of spinal SOX2+GFAP+, PAX6+Nestin+, and SOX1+KI67+ cells. Moreover, animals treated with exosomes exhibited a significative higher neurogenesis, as indicated by the higher percentage of DCX+MAP 2+ neurons. In vitro, hpMSC-derived exosomes promoted the proliferation of NSCs and the increase of the phosphorylated levels of MEK, ERK, and CREB.

Conclusions

This study provides evidence that the use of hpMSC-derived exosomes may constitute a promising therapeutic strategy for the treatment of SCI.
Will mesenchymal stem cells be future directions for treating radiation-induced skin injury?
Authors: Fang Zhuoqun , Chen Penghong , Tang Shijie , Chen Aizhen , Zhang Chaoyu , Peng Guohao , Li Ming , Chen Xiaosong
Published: March 2021

Radiation-induced skin injury (RISI) is one of the common serious side effects of radiotherapy (RT) for patients with malignant tumors. Mesenchymal stem cells (MSCs) are applied to RISI repair in some clinical cases series except some traditional options. Though direct replacement of damaged cells may be achieved through differentiation capacity of MSCs, more recent data indicate that various cytokines and chemokines secreted by MSCs are involved in synergetic therapy of RISI by anti-inflammatory, immunomodulation, antioxidant, revascularization, and anti-apoptotic activity. In this paper, we not only discussed different sources of MSCs on the treatment of RISI both in preclinical studies and clinical trials, but also summarized the applications and mechanisms of MSCs in other related regenerative fields.
ChemProps: A RESTful API enabled database for composite polymer name standardization
Authors: Hu Bingyin , Lin Anqi , Brinson L. Catherine
Published: March 2021

The inconsistency of polymer indexing caused by the lack of uniformity in expression of polymer names is a major challenge for widespread use of polymer related data resources and limits broad application of materials informatics for innovation in broad classes of polymer science and polymeric based materials. The current solution of using a variety of different chemical identifiers has proven insufficient to address the challenge and is not intuitive for researchers. This work proposes a multi-algorithm-based mapping methodology entitled ChemProps that is optimized to solve the polymer indexing issue with easy-to-update design both in depth and in width. RESTful API is enabled for lightweight data exchange and easy integration across data systems. A weight factor is assigned to each algorithm to generate scores for candidate chemical names and optimized to maximize the minimum value of the score difference between the ground truth chemical name and the other candidate chemical names. Ten-fold validation is utilized on the 160 training data points to prevent overfitting issues. The obtained set of weight factors achieves a 100% test accuracy on the 54 test data points. The weight factors will evolve as ChemProps grows. With ChemProps, other polymer databases can remove duplicate entries and enable a more accurate “search by SMILES” function by using ChemProps as a common name-to-SMILES translator through API calls. ChemProps is also an excellent tool for auto-populating polymer properties thanks to its easy-to-update design.
On preservation of binomial operators
Authors: Zhang Chungou , Meng Xiangying , Zhang Jingwen
Published: March 2021

Binomial operators are the most important extension to Bernstein operators, defined by$$ \bigl(L^{Q}_{n} f\bigr) (x)=\frac{1}{b_{n}(1)} \sum ^{n}_{k=0}\binom { n}{k } b_{k}(x)b_{n-k}(1-x)f\biggl( \frac{k}{n}\biggr),\quad f\in C[0, 1], $$(LnQf)(x)=1bn(1)∑k=0n(nk)bk(x)bn−k(1−x)f(kn),f∈C[0,1],where$\{b_{n}\}${bn}is a sequence of binomial polynomials associated to a delta operator Q. In this paper, we discuss the binomial operators$\{L^{Q}_{n} f\}${LnQf}preservation such as smoothness and semi-additivity by the aid of binary representation of the operators, and present several illustrative examples. The results obtained in this paper generalize what are known as the corresponding Bernstein operators.
Approximation by a power series summability method of Kantorovich type Szász operators including Sheffer polynomials
Authors: Loku Valdete , Braha Naim L. , Mansour Toufik , Mursaleen M.
Published: March 2021

The main purpose of this paper is to use a power series summability method to study some approximation properties of Kantorovich type Szász–Mirakyan operators including Sheffer polynomials. We also establish Voronovskaya type result.
Dynamic behaviors for inertial neural networks with reaction-diffusion terms and distributed delays
Authors: Zheng Famei
Published: March 2021

A class of inertial neural networks (INNs) with reaction-diffusion terms and distributed delays is studied. The existence and uniqueness of the equilibrium point for the considered system is obtained by topological degree theory, and a sufficient condition is given to guarantee global exponential stability of the equilibrium point. Finally, an example is given to show the effectiveness of the results in this paper.
Genetic and molecular biology of autism spectrum disorder among Middle East population: a review
Authors: Rahmani Zahra , Fayyazi Bordbar Mohammad Reza , Dibaj Mohsen , Alimardani Maliheh , Moghbeli Meysam
Published: March 2021

Background

Autism spectrum disorder (ASD) is a neurodevelopmental disease, characterized by impaired social communication, executive dysfunction, and abnormal perceptual processing. It is more frequent among males. All of these clinical manifestations are associated with atypical neural development. Various genetic and environmental risk factors are involved in the etiology of autism. Genetic assessment is essential for the early detection and intervention which can improve social communications and reduce abnormal behaviors. Although, there is a noticeable ASD incidence in Middle East countries, there is still a lack of knowledge about the genetic and molecular biology of ASD among this population to introduce efficient diagnostic and prognostic methods.

Main body

In the present review, we have summarized all of the genes which have been associated with ASD progression among Middle East population. We have also categorized the reported genes based on their cell and molecular functions.

Conclusions

This review clarifies the genetic and molecular biology of ASD among Middle East population and paves the way of introducing an efficient population based panel of genetic markers for the early detection and management of ASD in Middle East countries.
Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue
Authors: Miller Lauren V. C. , Mukadam Aamir S. , Durrant Claire S. , Vaysburd Marina J. , Katsinelos Taxiarchis , Tuck Benjamin J. , Sanford Sophie , Sheppard Olivia , Knox Claire , Cheng Shi , James Leo C. , Coleman Michael P. , McEwan William A.
Published: March 2021

A fundamental property of infectious agents is their particulate nature: infectivity arises from independently-acting particles rather than as a result of collective action. Assemblies of the protein tau can exhibit seeding behaviour, potentially underlying the apparent spread of tau aggregation in many neurodegenerative diseases. Here we ask whether tau assemblies share with classical pathogens the characteristic of particulate behaviour. We used organotypic hippocampal slice cultures from P301S tau transgenic mice in order to precisely control the concentration of extracellular tau assemblies in neural tissue. Whilst untreated slices displayed no overt signs of pathology, exposure to recombinant tau assemblies could result in the formation of intraneuronal, hyperphosphorylated tau structures. However, seeding ability of tau assemblies did not titrate in a one-hit manner in neural tissue. The results suggest that seeding behaviour of tau arises at high concentrations, with implications for the interpretation of high-dose intracranial challenge experiments and the possible contribution of seeded aggregation to human disease.
Comparability of teachers’ educational background items in TIMSS: a case from Turkey
Authors: Oz Elif
Published: March 2021

Large-scale international assessment studies such as Trends in International Mathematics and Science Study (TIMSS) or Programme for International Student Assessment (PISA) provide researchers and policy makers the opportunity to conduct secondary analyses to answer questions related to educational outcomes and compare the impact of certain inputs on student outcomes across countries. These comparisons are made under the assumption that the questionnaire items translated to different languages are understood in the same way by its participants. Presenting a case from Turkey, this paper shows that equivalency of questionnaire items is not always achieved. The case explores demographic information related to teacher preparation and the sample is drawn from eighth grade science and mathematics teachers participated in TIMSS 2007, 2011, and 2015 in Turkey. Descriptive analysis of data collected from these teachers and comparisons across subjects and years show that teachers may have misunderstood a question regarding their major, thus limiting potential claims related to teacher preparation in Turkey. Researchers and policy analyst who use secondary data collected by international assessment studies should be aware of such comparability issues in adapted items prior to conducting any secondary analyses.
Influence of dosimetry method on bone lesion absorbed dose estimates in PSMA therapy: application to mCRPC patients receiving Lu-177-PSMA-I&T
Authors: Brosch-Lenz Julia , Uribe Carlos , Gosewisch Astrid , Kaiser Lena , Todica Andrei , Ilhan Harun , Gildehaus Franz Josef , Bartenstein Peter , Rahmim Arman , Celler Anna , Ziegler Sibylle , Böning Guido
Published: March 2021

Background

Patients with metastatic, castration-resistant prostate cancer (mCRPC) present with an increased tumor burden in the skeleton. For these patients, Lutetium-177 (Lu-177) radioligand therapy targeting the prostate-specific membrane antigen (PSMA) has gained increasing interest with promising outcome data. Patient-individualized dosimetry enables improvement of therapy success with the aim of minimizing absorbed dose to organs at risk while maximizing absorbed dose to tumors. Different dosimetric approaches with varying complexity and accuracy exist for this purpose. The Medical Internal Radiation Dose (MIRD) formalism applied to tumors assumes a homogeneous activity distribution in a sphere with unit density for derivation of tumor S values (TSV). Voxel S value (VSV) approaches can account for heterogeneous activities but are simulated for a specific tissue. Full patient-individual Monte Carlo (MC) absorbed dose simulation addresses both, heterogeneous activity and density distributions. Subsequent CT-based density weighting has the potential to overcome the assumption of homogeneous density in the MIRD formalism with TSV and VSV methods, which could be a major limitation for the application in bone metastases with heterogeneous density. The aim of this investigation is a comparison of these methods for bone lesion dosimetry in mCRPC patients receiving Lu-177-PSMA therapy.

Results

In total, 289 bone lesions in 15 mCRPC patients were analyzed. Percentage difference (PD) of average absorbed dose per lesion compared to MC, averaged over all lesions, was + 14 ± 10% (min: − 21%; max: + 56%) for TSVs. With lesion-individual density weighting using Hounsfield Unit (HU)-to-density conversion on the patient’s CT image, PD was reduced to − 8 ± 1% (min: − 10%; max: − 3%). PD on a voxel level for three-dimensional (3D) voxel-wise dosimetry methods, averaged per lesion, revealed large PDs of + 18 ± 11% (min: − 27%; max: + 58%) for a soft tissue VSV approach compared to MC; after voxel-wise density correction, this was reduced to − 5 ± 1% (min: − 12%; max: − 2%).

Conclusion

Patient-individual MC absorbed dose simulation is capable to account for heterogeneous densities in bone lesions. Since the computational effort prevents its routine clinical application, TSV or VSV dosimetry approaches are used. This study showed the necessity of lesion-individual density weighting for TSV or VSV in Lu-177-PSMA therapy bone lesion dosimetry.
If I told you that there is no need for yellow fever vaccine booster would you still come to the travel clinic?: a cross-sectional study
Authors: Alves Iolanda , Teodósio Rosa , Pereira Filomena
Published: March 2021

Background

Yellow Fever (YF) immunization required a single dose vaccine with boosters every 10 years. After International Health Regulation (IHR) amendment annex 7 (July 2016), it was accepted that a single dose confers lifelong immunity. Since pre-travel advice is as important as vaccination when traveling, it is essential to clarify why travelers come to a travel health consultation, with the possibility of IHR amendment having a negative impact on travelers’ health. This study aims to describe travelers’ reasons to come to a pre-travel consultation in Lisbon and if they would return if they wouldn’t need the YF vaccine booster.

Methods

An observational cross-sectional study was conducted during 5 months in the waiting room of Instituto de Higiene e Medicina Tropical travel clinic in Lisbon, Portugal. Travelers were asked about sociodemographic characteristics, destination country, travel duration and reasons to travel in an anonymous self-administered questionnaire.

Results

A total of 1043 travelers agreed to participate in the study. Although 61.0% (627/1028) did not come to the clinic to get the YF vaccine, from those who did, 36.7% (133/362) would not come and 12.9% (47/362) didn’t knew if they would come if the vaccine would not be necessary.

Conclusion

The IHR amendment may have a negative impact on travel clinic attendance and on travelers´ health.
Stretching and shearing contamination analysis for Liutex and other vortex identification methods
Authors: Shrestha Pushpa , Nottage Charles , Yu Yifei , Alvarez Oscar , Liu Chaoqun
Published: March 2021

The newly developed vortex-identification method, Liutex, has provided a new systematic description of the local fluid rotation, which includes scalar, vector, and tensor forms. However, the advantages of Liutex over the other widely used vortex-identification methods such asQ, ∆,λ2, and λcihave not been realized. These traditional methods count on shearing and stretching as a part of vortex strength. But, in the real flow, shearing and stretching do not contribute to fluid rotation. In this paper, the decomposition of the velocity gradient tensor is conducted in the Principal Coordinate for uniqueness. Then the contamination effects of stretching and shearing of the traditional methods are investigated and compared with the Liutex method in terms of mathematical analysis and numerical calculations. The results show that the Liutex method is the only method that is not affected by either stretching or shear, as it represents only the local fluid rigid rotation. These results provide supporting evidence that Liutex is the superior method over others.
Performance of albumin-bilirubin score in prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding
Authors: Elsafty Rehab Elsayed , Elsawy Abdallah Ahmed , Selim Ahmed Fawzy , Taha Atef Mohamed
Published: March 2021

Background

Hepatic encephalopathy exacerbates the morbidity, delays hospital discharge, and increases the rate of readmissions of cirrhotic patients, particularly those are admitted by acute variceal bleeding. We evaluated the performance of albumin-bilirubin score in prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding, in comparison to Child-Pugh and MELD scores. This prospective cohort study was conducted on 250 cirrhotic patients who were consecutively presented by acute variceal bleeding in the period from January to December 2020 at Tanta university emergency hospital. Albumin-bilirubin, Child-Pugh, and MELD scores were measured at admission, and then all patients were followed up for 4 weeks after endoscopic bleeding control for possible occurrence of hepatic encephalopathy

Results

Albumin-bilirubin, Child-Pugh, and MELD scores had significant performances in prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding; in this regard, albumin-bilirubin score had the highest accuracy (AUC 0.858, CI 0.802-0.914, sig 0.000) followed by Child-Pugh score (AUC 0.654, CI 0.574–0.735, sig 0.001) and then MELD score (AUC 0.602, CI 0.519–0.686, sig 0.031). The cumulative incidence of hepatic encephalopathy in cirrhotic patients with albumin-bilirubin grade 3 was found to be significantly more than that present in albumin-bilirubin grade 2; most of these hepatic encephalopathy cases occurred in the first 2 weeks of follow-up period.

Conclusions

Albumin-bilirubin score has a significant performance in risk prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding better than Child-Pugh and MELD scores. Albumin-bilirubin grades could be used as a risk stratifying tool to triage cirrhotic patients who will benefit from early discharge after bleeding control and those patients who will benefit from prophylactic measures for hepatic encephalopathy.
Rosuvastatin cocrystals: an attempt to modulate physicochemical parameters
Authors: Vemuri Venkata Deepthi , Lankalapalli Srinivas
Published: March 2021

Background

The meager physicochemical properties like low solubility and low dissolution rate of rosuvastatin calcium remain as an obstruction for formulation development. In the present work, we explore the evolution of rosuvastatin cocrystal, which may offer the synergetic physico-chemical properties of the drug. Cocrystal crafting depends on two possible intermolecular interactions; heteromeric and the homomeric selection of compounds with complementary functional groups are contemplated as a possible cause of supramolecular synthons in cocrystal formation. Specifically, cocrystals of rosuvastatin with l-asparagine and l-glutamine with molar ratio (1:1) were fabricated by using slow solvent evaporation and slow evaporation techniques. Novel cocrystals of rosuvastatin-asparagine (RSC-C) and rosuvastatin-glutamine (RSC-G) cocrystals obtained by slow solvent evaporation were utilized for preliminary investigation and further scale-up was done by using the solvent evaporation technique.

Results

The novel cocrystals showed a new characteristic of powder X-ray diffraction, thermograms of differential scanning calorimetry, 1H liquid FT-NMR spectra, and scanning electron microscopy. These results signify the establishment of intermolecular interaction within the cocrystals. In both the novel cocrystals, rosuvastatin was determined to be engaged in the hydrogen bond interaction with the complementary functional groups of l-asparagine and l-glutamine. Compared with the pure rosuvastatin, RSC-C and RSC-G cocrystal showed 2.17-fold and 1.60-fold improved solubility respectively. The dissolution test showed that the RSC-C and RSC-G cocrystal exhibited 1.97-fold and 1.94-fold higher dissolution rate than the pure rosuvastatin in pH6.8 phosphate buffer respectively.

Conclusion

Modulation in the chemical environment, improvement in the solubility, and dissolution rate demonstrated the benefit of co-crystallization to improve the physicochemical properties of the drug.

Graphical abstract
A review on the phytochemical and pharmacological properties of Hyptis suaveolens (L.) Poit
Authors: Mishra Pratibha , Sohrab Saima , Mishra Sanjay Kumar
Published: March 2021

Background

Plants are the repository of variable number of valuable secondary metabolites that bears pharmacognostic and pharmacological implications having potentiality to emerge as super drugs in future. In-vivo production of these metabolites is influenced by the biotic and abiotic stresses resulting in continuous accumulation of diverse phytochemicals and their derivatives that can be useful in designing and developing potential drugs for future. The aim of the present study is to review the existence of medicinally important secondary metabolites and possible pharmacological and pharmacognostic importance of under-explored weed plant species Hyptis suaveolens (L.) Poit., to explore the potentiality of the plant for developing and designing the drugs for future.

Main body of the abstract

Hyptis suaveolens belonging to family Lamiaceae is the rich source of medicinally important phytochemicals like essential oils, tannins, saponins, phenols, flavonoids, terpenoids, alkaloids, and sterols. One or many of these compounds have antioxidative, anti-inflammatory, antispasmodic, anti-septic, anti-cancer, anti-ulcer, antimicrobial, antibacterial, antiviral, antifungal, anti-diabetic, anti-fertility, diaphoretics, anticutaneous, anticatarrhal, antirheumatic, anti-ulcer, gastroprotective, immunomodulatory, analgesic, and antiviral activity.

Short conclusion

Hyptis suaveolens contains unique terpenoid metabolites like suaveolic acid, suaveolol, methyl suaveolate, beta-sitosterol, ursolic acid, and phenolic compound like rosamarinic acid, methyl rosamarinate that have potentiality to substitute the traditional drugs as therapeutic agent against the resistant and newly emerged bacterial and viral pathogens. Pentacyclic triterpenoid, ursolic acid have been reported to have effective antiviral response against the SARS-CoV2 responsible for the present COVID-19 pandemic and HIV virus for which no effective vaccines are available till date. Ursolic acid has the ability to modulate the activity of main protease (Mpro) that is essential for processing of SARS-CoV2 replicase-transcriptase machinery needed for viral replication and particle assembly.
Relationship Between Maternal Bone Biomarkers and Fetal Adiposity Through Normal Pregnancy
Authors: Mastorakos George , Maliopoulos Dimosthenis , Kasioni Spyridoula , Bargiota Alexandra , Barber Thomas M , Skevaki Chrysanthi , Papassotiriou Ioannis , Vrachnis Nikos , Farmakides George , Vlahos Nikos F , Kumar Sudhesh , Valsamakis Georgios
Published: March 2021

Purpose

To examine the association of maternal bone markers [sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteocalcin, 25-hydroxyvitamin D3] with fetal intra-abdominal and subcutaneous adipose tissue deposition and birthweight during normal pregnancy.

Methods

One hundred pregnant women (aged 30.4 ± 5.6 years, mean ± SD) with prepregnancy body mass index = 24.1 ± 4.6 kg/m2 were seen prospectively during each trimester. At each visit they were submitted to anthropometric measurements, a fasting blood sampling, a 75-g oral glucose tolerance test, and a fetal ultrasonogram. At birth, neonates had birth weight measurement.

Results

In the second trimester, maternal sclerostin concentrations correlated positively with fetal abdominal circumference and birth weight; maternal sRANKL concentrations correlated positively with fetal abdominal subcutaneous fat thickness, sagittal abdominal diameter, and abdominal circumference. Fetuses born to mothers with greater (>254 ng/mL), compared to fetuses born to mothers with lower (≤254ng/mL), sRANKL concentrations had greater abdominal circumference, sagittal diameter, and abdominal subcutaneous fat thickness. Maternal serum sclerostin concentrations were the best positive predictors of birth weight. In the third trimester maternal sclerostin concentrations correlated positively with fetal sagittal abdominal diameter; maternal sRANKL concentrations positively correlated with fetal abdominal circumference and fetal abdominal sagittal diameter.

Conclusions

Maternal bone markers sclerostin and sRANKL may relate to fetal intra-abdominal adipose tissue deposition through as yet unknown direct or indirect mechanisms, thus contributing to birthweight.
Conducting Real-world Evidence Studies on the Clinical Outcomes of Diabetes Treatments
Authors: Schneeweiss Sebastian , Patorno Elisabetta
Published: March 2021

Real-world evidence (RWE), the understanding of treatment effectiveness in clinical practice generated from longitudinal patient-level data from the routine operation of the healthcare system, is thought to complement evidence on the efficacy of medications from randomized controlled trials (RCTs). RWE studies follow a structured approach. (1) A design layer decides on the study design, which is driven by the study question and refined by a medically informed target population, patient-informed outcomes, and biologically informed effect windows. Imagining the randomized trial we would ideally perform before designing an RWE study in its likeness reduces bias; the new-user active comparator cohort design has proven useful in many RWE studies of diabetes treatments. (2) A measurement layer transforms the longitudinal patient-level data stream into variables that identify the study population, the pre-exposure patient characteristics, the treatment, and the treatment-emergent outcomes. Working with secondary data increases the measurement complexity compared to primary data collection that we find in most RCTs. (3) An analysis layer focuses on the causal treatment effect estimation. Propensity score analyses have gained in popularity to minimize confounding in healthcare database analyses. Well-understood investigator errors, like immortal time bias, adjustment for causal intermediates, or reverse causation, should be avoided. To increase reproducibility of RWE findings, studies require full implementation transparency. This article integrates state-of-the-art knowledge on how to conduct and review RWE studies on diabetes treatments to maximize study validity and ultimately increased confidence in RWE-based decision making.
Binational Gatekeepers
Authors: Braun-Strumfels Lauren
Published: March 2021

While the 1891 and 1893 Immigration Acts established inspection protocols that remained in place for decades, less is known about how US agents initially translated gatekeeping laws into the durable policy directives that had a profound effect on the migration of working-class people. Before the “qualitative” restriction of specific racial, social, and economic conditions transitioned to a period of “quantitative” or enumerated exclusion by the 1920s, the US government had to establish a structure to carry out the work of exclusion, but this early era of qualitative gatekeeping is less understood. Italian encounters with federal agents at Ellis Island show how the 1891 and 1893 laws empowered the administrative state to carry out the work of exclusion shadowed by the banality of bureaucratic decision-making. The records of the short-lived Office of Labor Information and Protection for Italians (1894–99), the only outpost of a foreign government allowed to operate in the main processing building on Ellis Island, offers a rare snapshot of the gatekeeping process in its crucial early years. Given that Italians were the single largest ethnic group to be processed at Ellis Island over its sixty-two-year history and the primary target of inspectors in the station’s first decade, their experiences with bureaucratic exclusion illuminate how the United States moved to systematically control working-class migration.