bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bayesian spatio-temporal analysis of mortality rates in Spain: application to the COVID-19 2020 outbreak
Authors: Saavedra Pedro , Santana Angelo , Bello Luis , Pacheco José-Miguel , Sanjuán Esther
Published: May 2021

Background

The number of deaths attributable to COVID-19 in Spain has been highly controversial since it is problematic to tell apart deaths having COVID as the main cause from those provoked by the aggravation by the viral infection of other underlying health problems. In addition, overburdening of health system led to an increase in mortality due to the scarcity of adequate medical care, at the same time confinement measures could have contributed to the decrease in mortality from certain causes. Our aim is to compare the number of deaths observed in 2020 with the projection for the same period obtained from a sequence of previous years. Thus, this computed mortality excess could be considered as the real impact of the COVID-19 on the mortality rates.

Methods

The population was split into four age groups, namely: (< 50; 50–64; 65–74; 75 and over). For each one, a projection of the death numbers for the year 2020, based on the interval 2008–2020, was estimated using a Bayesian spatio-temporal model. In each one, spatial, sex, and year effects were included. In addition, a specific effect of the year 2020 was added ("outbreak"). Finally, the excess deaths in year 2020 were estimated as the count of observed deaths minus those projected.

Results

The projected death number for 2020 was 426,970 people, the actual count being 499,104; thus, the total excess of deaths was 72,134. However, this increase was very unequally distributed over the Spanish regions.

Conclusion

Bayesian spatio-temporal models have proved to be a useful tool for estimating the impact of COVID-19 on mortality in Spain in 2020, making it possible to assess how the disease has affected different age groups accounting for effects of sex, spatial variation between regions and time trend over the last few years.
Exosomes contribution in COVID-19 patients’ treatment
Authors: Mazini Loubna , Rochette Luc , Malka Gabriel
Published: May 2021

Adipose cell-free derivatives have been recently gaining attention as potential therapeutic agents for various human diseases. In this context, mesenchymal stromal/stem cells (MSCs), adipocyte mesenchymal stem cells (Ad-MSCs) and adipose-derived stem cells (ADSC) possessing potent immunomodulatory activities are proposed as a therapeutic option for the treatment of coronavirus disease 2019 (COVID-19). The COVID-19 represents a global concern of public health caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in which there is not actually any specific therapy. MSCs exert an immunomodulation effect due to the secretion of endogenous factors, such as vascular endothelial growth factor (VEGF), insulin growth factor (IGF), and nerve growth factor (NGF), transforming growth factor (TGF)-β and growth differentiation factor (GDF)-11. Recent reports are promising for further studies and clinical applications of ADSCs and Ad-MSCs in COVID-19 patients. Experimental and clinical studies are exploring the therapeutic potential of both MSCs and derived-exosomes in moderating the morbidity and mortality of COVID-19. In this field, more preclinical and clinical studies are warranted to find an effective treatment for the patients suffering from COVID-19 infection.
The “Intermediate” CD14 + CD16 + monocyte subpopulation plays a role in IVIG responsiveness of children with Kawasaki disease
Authors: Kim Yi Seul , Yang Hyun Jin , Kee Seung-Jung , Choi Insu , Ha Kisoo , Ki Katrina K , Jeong In Seok , Cho Hwa Jin
Published: May 2021

Background

Kawasaki disease (KD) is an acute, self-limited febrile illness of unknown cause. Intravenous immunoglobulin (IVIG)-resistance are related to greater risk for permanent cardiac complications. We aimed to determine the correlation between monocytes and the phenotype of KD in relation to IVIG responsiveness in children.

Materials and methods

The study cohort included 62 patients who were diagnosed with KD, 20 non febrile healthy controls (NFC), and 15 other febrile controls (OFC). In all enrolled patients, blood was taken at least 4 times and laboratory tests were performed. In addition, subtypes of monocytes were characterized via flow cytometry.

Results

The numbers of intermediate monocytes were significantly lower in IVIG-resistant group compared to IVIG-responsive group before IVIG infusion (p < 0.0001). After infusion, intermediate monocytes decreased in the responsive group, while a trend of increase was observed in the resistant group. Only intermediate monocytes were significant in logistic regression with adjusted OR of 0.001 and p value of 0.03.

Conclusions

CD14 + CD16 + intermediate monocyte may play an important role in IVIG responsiveness among KD children. Low starting levels of intermediate monocytes, followed by a dramatic increase post-IVIG infusion during acute phase of KD are associated with IVIG-resistance. Functional studies on intermediate monocyte may help to reveal the pathophysiology.
A missed opportunity: underutilization of inpatient behavioral health services to reduce injection drug use sequelae in Florida
Authors: Coye Austin E. , Jones Mackenzie T. , Bornstein Kasha J. , Tookes Hansel E. , St. Onge Joan E.
Published: May 2021

Background

People who inject drugs (PWID) suffer high morbidity and mortality from injection related infections (IRI). The inpatient setting is an ideal opportunity to treat underlying substance use disorder (SUD), but it is unclear how often this occurs.

Objectives

To quantify the utilization of behavioral health services for PWID during inpatient admissions for IRI.

Methods

Data for all hospital admissions in Florida in FY2017 were obtained from the Agency for Healthcare Administration. Hospitalization for IRI were obtained using a validated ICD-10 algorithm and treatment for substance use disorder was quantified using ICD-10-Procedure Coding System (ICD-10-PCS) codes.

Result

Among the 20,001 IRI admissions, there were 230 patients who received behavioral health services as defined by ICD-10-PCS SAT codes for treatment for SUD.

Conclusions

In a state with a large number of IRI, only a very small portion of admissions received behavioral health services. Increased efforts should be directed to studying referral patterns among physicians and other providers caring for this population and increasing utilization of behavioral health services.
Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review
Authors: Migliorini Filippo , Maffulli Nicola , Spiezia Filippo , Peretti Giuseppe Maria , Tingart Markus , Giorgino Riccardo
Published: May 2021

Background

Biochemical markers of bone turnover (BTMs), such as the bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis.

Methods

All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible.

Results

A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up.

Conclusion

The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis.

Level of evidence

I, systematic review of RCTs
Clinical, genetic and quality-of-life study of a cohort of adult patients with tuberous sclerosis
Authors: De Sautu De Borbón Elena Cristina , Guerra Vales Juan Manuel , Lumbreras Bermejo Carlos , Guerrero Ramos Felix , Buj Padilla María José , González de la Aleja Jesús , Morales Conejo Montserrat
Published: May 2021

Background and objective

Tuberous sclerosis (TS) is a condition whose manifestations in childhood have been extensively described, but whose presentation in adults is less well known. This study describes the clinical and genetic characteristics, therapeutic management and quality of life of a cohort of adult patients with TS. A comparative study of the characteristics of patients diagnosed in childhood and adulthood is also carried out.

Material and methods

This observational, retrospective, cross-sectional study included a large cohort of adult patients (≥ 16 years old) followed for 5 years in a specific rare diseases unit.

Results

Fifty-seven patients with a diagnosis of tuberous sclerosis were included, more than 50% of whom were diagnosed as adults. The mean age of the patients was 42 years (20–86). The central nervous system was the main area affected (97%), followed by the skin (80.7%) and kidneys (73%). The most frequent genetic alteration was a mutation in the TSC2 gene (47.7%). Among patients diagnosed in adulthood, there was less neurological involvement, with less frequency of epileptic seizures (30.8% vs 60.79% of patients diagnosed in childhood) and astrocytomas (3.8% vs 53.6%), less intellectual disability (11.5% vs 71.4%) and less expressiveness of the condition. 42% of patients were treated with mTOR pathway inhibitors, and presence of an angiomyolipoma was the main indication. In a quality-of-life analysis, the means of the summary indices were below the scores of the average Spanish population: (47.42 (SD ± 9.82) on the physical health scale, 45.61 (SD ± 7.99) on the mental health scale) versus 50 (SD ± 10) for the general population.

Conclusions

Up to 50% of adult patients with TS were diagnosed in adulthood, and the condition is less severe with less frequent epileptic seizures and intellectual disability. 42% require treatment with mTOR inhibitors, in most cases due to the presence of AMLs. The quality of life of adult patients with TS is diminished compared to the general population.
Impacts of allopolyploidization and structural variation on intraspecific diversification in Brassica rapa
Authors: Cai Xu , Chang Lichun , Zhang Tingting , Chen Haixu , Zhang Lei , Lin Runmao , Liang Jianli , Wu Jian , Freeling Michael , Wang Xiaowu
Published: May 2021

Background

Despite the prevalence and recurrence of polyploidization in the speciation of flowering plants, its impacts on crop intraspecific genome diversification are largely unknown.Brassica rapais a mesopolyploid species that is domesticated into many subspecies with distinctive morphotypes.

Results

Herein, we report the consequences of the whole-genome triplication (WGT) on intraspecific diversification using a pan-genome analysis of 16 de novo assembled and two reported genomes. Among the genes that derive from WGT, 13.42% of polyploidy-derived genes accumulate more transposable elements and non-synonymous mutations than other genes during individual genome evolution. We denote such genes as being “flexible.” We construct theBrassica rapaancestral genome and observe the continuing influence of the dominant subgenome on intraspecific diversification inB. rapa. The gene flexibility is biased to the more fractionated subgenomes (MFs), in contrast to the more intact gene content of the dominant LF (least fractionated) subgenome. Furthermore, polyploidy-derived flexible syntenic genes are implicated in the response to stimulus and the phytohormone auxin; this may reflect adaptation to the environment. Using an integrated graph-based genome, we investigate the structural variation (SV) landscapes in 524B. rapagenomes. We observe that SVs track morphotype domestication. Four out of 266 candidate genes for Chinese cabbage domestication are speculated to be involved in the leafy head formation.

Conclusions

This pan-genome uncovers the possible contributions of allopolyploidization on intraspecific diversification and the possible and underexplored role of SVs in favorable trait domestication. Collectively, our work serves as a rich resource for genome-basedB. rapaimprovement.
High-fat diet impairs ferroptosis and promotes cancer invasiveness via downregulating tumor suppressor ACSL4 in lung adenocarcinoma
Authors: Zhang Yixiang , Li Songyu , Li Fengzhou , Lv Changsheng , Yang Qing-kai
Published: May 2021

Background

Long-chain acyl-CoA synthetase-4 (ACSL4) is involved in fatty acid metabolism, and aberrant ACSL4 expression could be either tumorigenic or tumor-suppressive in different tumor types. However, the function and clinical significance of ACSL4 in lung adenocarcinoma remain elusive.

Results

ACSL4 was frequently downregulated in lung adenocarcinoma when analyzing both the TCGA database and the validation samples, and the lower ACSL4 expression was correlated with a worse prognosis. Using gene set enrichment analysis, we found that high ACSL4 expression was frequently associated with the oxidative stress pathway, especially ferroptosis-related proteins. In vitro functional studies showed that knockdown of ACSL4 increased tumor survival/invasiveness and inhibited ferroptosis, while ACSL4 overexpression exhibited the opposite effects. Moreover, high-fat treatment could also inhibit erastin-induced ferroptosis by affecting ACSL4 expression. The anti-tumor effects of ferroptosis inducers and the anti-ferroptosis effects of the high-fat diet were further validated using the mouse xenograft model.

Conclusions

ACSL4 plays a tumor-suppressive role in lung adenocarcinoma by suppressing tumor survival/invasiveness and promoting ferroptosis. Our study provided a theoretical reference for the application of ferroptotic inducers and dietary guidance for lung adenocarcinoma patients.
Improvements of the productivity and saccharification efficiency of the cellulolytic β-glucosidase D2-BGL in Pichia pastoris via directed evolution
Authors: Kao Mu-Rong , Yu Su-May , Ho Tuan-H ua David
Published: May 2021

Background

β-Glucosidases are essential for cellulose hydrolysis by catalyzing the final cellulolytic degradation of cello-oligomers and cellobiose to glucose. D2-BGL is a fungal glycoside hydrolase family 3 (GH3) β-glucosidase isolated from Chaetomella raphigera with high substrate affinity, and is an efficient β-glucosidase supplement to Trichoderma reesei cellulase mixtures for the saccharification of lignocellulosic biomass.

Results

We have carried out error-prone PCR to further increase catalytic efficiency of wild-type (WT) D2-BGL. Three mutants, each with substitution of two amino acids on D2-BGL, exhibited increased activity in a preliminary mutant screening in Saccharomyces cerevisiae. Effects of single amino acid replacements on catalysis efficiency and enzyme production have been investigated by subsequent expression in Pichia pastoris. Substitution F256M resulted in enhancing the tolerance to substrate inhibition and specific activity, and substitution D224G resulted in increasing the production of recombinant enzyme. The best D2-BGL mutant generated, Mut M, was constructed by combining beneficial mutations D224G, F256M and Y260D. Expression of Mut M in Pichia pastoris resulted in 2.7-fold higher production of recombinant protein, higher Vmax and greater substrate inhibition tolerance towards cellobiose relative to wild-type enzyme. Surprisingly, Mut M overexpression induced the ER unfolded protein response to a level lower than that with WT D2 overexpression in P. pastoris. When combined with the T. reesei cellulase preparation Celluclast 1.5L, Mut M hydrolyzed acid-pretreated sugarcane bagasse more efficiently than WT D2.

Conclusions

D2-BGL mutant Mut M was generated successfully by following directed evolution approach. Mut M carries three mutations that are not reported in other directed evolution studies of GH3 β-glucosidases, and this mutant exhibited greater tolerance to substrate inhibition and higher Vmax than wild-type enzyme. Besides the enhanced specific activity, Mut M also exhibited a higher protein titer than WT D2 when it was overexpressed in P. pastoris. Our study demonstrates that both catalytic efficiency and productivity of a cellulolytic enzyme can be enhanced via protein engineering.
Polysaccharide utilization loci-driven enzyme discovery reveals BD-FAE: a bifunctional feruloyl and acetyl xylan esterase active on complex natural xylans
Authors: Hameleers Lisanne , Penttinen Leena , Ikonen Martina , Jaillot Léa , Fauré Régis , Terrapon Nicolas , Deuss Peter J. , Hakulinen Nina , Master Emma R. , Jurak Edita
Published: May 2021

Background

Nowadays there is a strong trend towards a circular economy using lignocellulosic biowaste for the production of biofuels and other bio-based products. The use of enzymes at several stages of the production process (e.g., saccharification) can offer a sustainable route due to avoidance of harsh chemicals and high temperatures. For novel enzyme discovery, physically linked gene clusters targeting carbohydrate degradation in bacteria, polysaccharide utilization loci (PULs), are recognized ‘treasure troves’ in the era of exponentially growing numbers of sequenced genomes.

Results

We determined the biochemical properties and structure of a protein of unknown function (PUF) encoded within PULs of metagenomes from beaver droppings and moose rumen enriched on poplar hydrolysate. The corresponding novel bifunctional carbohydrate esterase (CE), now named BD-FAE, displayed feruloyl esterase (FAE) and acetyl esterase activity on simple, synthetic substrates. Whereas acetyl xylan esterase (AcXE) activity was detected on acetylated glucuronoxylan from birchwood, only FAE activity was observed on acetylated and feruloylated xylooligosaccharides from corn fiber. The genomic contexts of 200 homologs of BD-FAE revealed that the 33 closest homologs appear in PULs likely involved in xylan breakdown, while the more distant homologs were found either in alginate-targeting PULs or else outside PUL contexts. Although the BD-FAE structure adopts a typical α/β-hydrolase fold with a catalytic triad (Ser-Asp-His), it is distinct from other biochemically characterized CEs.

Conclusions

The bifunctional CE, BD-FAE, represents a new candidate for biomass processing given its capacity to remove ferulic acid and acetic acid from natural corn and birchwood xylan substrates, respectively. Its detailed biochemical characterization and solved crystal structure add to the toolbox of enzymes for biomass valorization as well as structural information to inform the classification of new CEs.
Data management plan for a community-level study of the hidden burden of cutaneous leishmaniasis in Colombia
Authors: Oviedo Sarmiento Oscar Javier , Castro María del Mar , Lerma Yenifer Orobio , Bernal Leonardo Vargas , Navarro Andrés , Alexander Neal D. E.
Published: May 2021

Objectives

Cutaneous leishmaniasis is a vector-borne parasitic disease whose lasting scars can cause stigmatization and depressive symptoms. It is endemic in remote rural areas and its incidence is under-reported, while the effectiveness, as opposed to efficacy, of its treatments is largely unknown. Here we present the data management plan (DMP) of a project which includes mHealth tools to address these knowledge gaps in Colombia. The objectives of the DMP are to specify the tools and procedures for data collection, data transfer, data entry, creation of analysis dataset, monitoring and archiving.

Results

The DMP includes data from two mobile apps: one implements a clinical prediction rule, and the other is for follow-up and treatment of confirmed cases. A desktop interface integrates these data and facilitates their linkage with other sources which include routine surveillance as well as paper and electronic case report forms. Multiple user and programming interfaces are used, as well as multiple relational and non-relational database engines. This DMP describes the successful integration of heterogeneous data sources and technologies. However the complexity of the project meant that the DMP took longer to develop than expected. We describe lessons learned which could be useful for future mHealth projects.
Giant hamartomatous polyp of the uterine cervix with heterologous mesenchymal tissue in a child: a case report
Authors: Esmat Esmatullah , Malakzai Haider Ali , Haidari Mujtaba , Haidary Ahmed Maseh , Baha Merwaise , Abdul-Ghafar Jamshid
Published: May 2021

Background

Polyps of the uterine cervix are one of the most common benign hyperplastic lesions occurring in the female genital tract that usually arise from the endocervical canal and are believed to be the result of reactive changes due to long-standing chronic inflammation, multiparty, and foreign bodies. Cervical polyps are usually small in size (less than 4 cm) that are commonly found in adult women; however, a few cases of giant polyps and the rare occurrence of these lesions in children have also been reported. Heterotopias and malignant transformation in cervical polyps are considered to be very rare.

Case presentation

We present the case of a 10-year-old Afghan girl with a giant pedunculated mass protruding out of the uterine cervix that was accompanied by abdominal pain and mass sensation. The mass was completely excised by surgical intervention and the specimen was submitted for histopathological evaluation. Upon gross and microscopic examination, the characteristic findings of a hamartomatous polyp with heterologous mesenchymal tissue in the form of mature cartilage were seen. To the best of our knowledge, this is the first case of a giant (17.5 cm) hamartomatous polyp of the uterine cervix in this age group.

Conclusion

Giant hamartomatous cervical polyps rarely occur in patients below 10 years of age. The majority of these lesions are benign; however, a few cases with malignant transformation are also reported, which demands elaborate investigations into the etiopathogenesis and nature of the lesions.
Impact of dexamethasone on the incidence of ventilator-associated pneumonia and blood stream infections in COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective study
Authors: Gragueb-Chatti Ines , Lopez Alexandre , Hamidi Dany , Guervilly Christophe , Loundou Anderson , Daviet Florence , Cassir Nadim , Papazian Laurent , Forel Jean-Marie , Leone Marc , Dellamonica Jean , Hraiech Sami
Published: May 2021

Background

Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality.

Results

Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA−) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0–21) vs. 0 (0–11) days; p = 0.009) and a reduced ICU length of stay (20 (11–44) vs. 32 (17–46) days; p = 0.01). Mortality did not differ between groups.

Conclusions

In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.
Nitrogen uptake strategies of mature conifers in Northeastern China, illustrated by the 15N natural abundance method
Authors: Zhou Xulun , Wang Ang , Hobbie Erik A. , Zhu Feifei , Wang Xueyan , Li Yinghua , Fang Yunting
Published: May 2021

Background

Conifers partition different N forms from soil, including ammonium, nitrate, and dissolved organic N (DON), to sustain plant growth. Previous studies focused on inorganic N sources and specific amino acid forms using 15N labelling, but knowledge of the contribution of DON to mature conifers’ N uptake is still scarce. Here, we quantified the contribution of different N forms (DON vs. NH4+ vs. NO3−) to total N uptake, based on 15N natural abundance of plant and soil available N, in four mature conifers (Pinus koraiensis, Pinus sylvestris, Picea koraiensis, and Larix olgensis).

Results

DON contributed 31%, 29%, 28%, and 24% to total N uptake by Larix olgensis, Picea koraiensis, Pinus koraiensis, and Pinus sylvestris, respectively, whereas nitrate contributed 42 to 52% and ammonium contributed 19 to 29% of total N uptake for these four coniferous species.

Conclusions

Our results suggested that all four conifers could take up a relatively large proportion of nitrate, while DON was also an important N source for the four conifers. Given that DON was the dominant N form in study soil, such uptake pattern of conifers could be an adaptive strategy for plants to compete for the limited available N sources from soil so as to promote conifer growth and maintain species coexistence.
Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches
Authors: Shakya Sajina , Gromovsky Anthony D. , Hale James S. , Knudsen Arnon M. , Prager Briana , Wallace Lisa C. , Penalva Luiz O. F. , Brown H. Alex , Kristensen Bjarne W. , Rich Jeremy N. , Lathia Justin D. , Brown J. Mark , Hubert Christopher G.
Published: May 2021

Glioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.
Estimation of renal perfusion based on measurement of rubidium-82 clearance by PET/CT scanning in healthy subjects
Authors: Langaa Stine Sundgaard , Lauridsen Thomas Guldager , Mose Frank Holden , Fynbo Claire Anne , Theil Jørn , Bech Jesper Nørgaard
Published: May 2021

Background

Changes in renal blood flow (RBF) may play a pathophysiological role in hypertension and kidney disease. However, RBF determination in humans has proven difficult. We aimed to confirm the feasibility of RBF estimation based on positron emission tomography/computed tomography (PET/CT) and rubidium-82 (82Rb) using the abdominal aorta as input function in a 1-tissue compartment model.

Methods

Eighteen healthy subjects underwent two dynamic 82Rb PET/CT scans in two different fields of view (FOV). FOV-A included the left ventricular blood pool (LVBP), the abdominal aorta (AA) and the majority of the kidneys. FOV-B included AA and the kidneys in their entirety. In FOV-A, an input function was derived from LVBP and from AA, in FOV-B from AA. One-tissue compartmental modelling was performed using tissue time activity curves generated from volumes of interest (VOI) contouring the kidneys, where the renal clearance of 82Rb is represented by the K1 kinetic parameter. Total clearance for both kidneys was calculated by multiplying the K1 values with the volume of VOIs used for analysis. Intra-assay coefficients of variation and inter-observer variation were calculated.

Results

For both kidneys, K1 values derived from AA did not differ significantly from values obtained from LVBP, neither were significant differences seen between AA in FOV-A and AA in FOV-B, nor between the right and left kidneys. For both kidneys, the intra-assay coefficients of variation were low (~ 5%) for both input functions. The measured K1 of 2.80 ml/min/cm3 translates to a total clearance for both kidneys of 766 ml/min/1.73 m2.

Conclusion

Measurement of renal perfusion based on PET/CT and 82Rb using AA as input function in a 1-tissue compartment model is feasible in a single FOV. Based on previous studies showing 82Rb to be primarily present in plasma, the measured K1 clearance values are most likely representative of effective renal plasma flow (ERPF) rather than estimated RBF values, but as the accurate calculation of total clearance/flow is very much dependent on the analysed volume, a standardised definition for the employed renal volumes is needed to allow for proper comparison with standard ERPF and RBF reference methods.
Review of menopausal palpitations measures
Authors: Sheng Ying , Carpenter Janet S. , Elomba Charles D. , Alwine Jennifer S. , Yue Min , Pike Caitlin A. , Chen Chen X. , Tisdale James E.
Published: May 2021

Palpitations are reported commonly by women around the time of menopause as skipped, missed, irregular, and/or exaggerated heartbeats or heart pounding. However, much less is known about palpitations than other menopausal symptoms such as vasomotor symptoms. The objective of this review was to integrate evidence on menopausal palpitations measures. Keyword searching was done in PubMed, CINAHL, and PsycINFO for English-language, descriptive articles containing data on menopause and palpitations and meeting other pre-specified inclusion criteria. Of 670 articles, 110 met inclusion criteria and were included in the review. Results showed that 11 different measures were used across articles, with variability within and between measures. Inconsistencies in the wording of measurement items, recall periods, and response options were observed even when standardized measures were used. Most measures were limited to assessing symptom presence and severity. Findings suggest that efforts should be undertaken to (1) standardize conceptual and operational definitions of menopausal palpitations and (2) develop a patient-friendly, conceptually clear, psychometrically sound measure of menopausal palpitations.
Influence of low-level laser therapy on implant stability in implants placed in healed sites: a randomized controlled trial
Authors: Kinalski Mateus de Azevedo , Agostini Bernardo Antonio , Bergoli Cesar Dalmolin , dos Santos Mateus Bertolini Fernandes
Published: May 2021

Background

The present study aims to assess the influence of low-level laser therapy (LLLT) on stability in implants placed in healed sites.

Material and methods

The present study followed the SPIRIT statement and is reported according to CONSORT. Patients were randomly allocated to LLLT or control groups. LLLT consisted in the application of 808-nm GaAlA laser applied before the preparation of the implant bed and after suturing (80 seconds; 11J/cm2). Implant stability quotient (ISQ) and the distance between the implant platform to the alveolar bone crest (millimeters) were assessed at implant placement (T0) and the abutment selection phase (4–6 months, Ta).

Results

A total of 64 implants were placed in 33 patients. The insertion torque ranged from 10 to 70 N.cm (mean 43.23; SD ±16.82). The T0 ISQ ranged from 18 to 95.5 (mean 61.7; SD ±18.23) and the crestal bone radiographic distance was 2.03 mm (SD±1.27). At Ta, the ISQ ranged from 39 to 90 (mean 64.2; SD±9.84), and the mean crestal bone radiographic loss was 1.70mm (SD±1.65). However, no differences were observed when LLLT and control groups were compared with ISQ difference (Ta–T0; p=0.598) or radiographical peri-implant alterations (p=0.531).

Conclusion

LLLT did not influence the implant stability in implants placed in healed sites compared to a control group.

Trial registration

ReBEC, RBR-35TNJ7. Registered May 23, 2018
Men’s involvement in family planning service utilization among married men in Kondala district, western Ethiopia: a community-based comparative cross-sectional study
Authors: Assefa Lemessa , Shasho Zemenu , Kasaye Habtamu Kebebe , Tesa Edao , Turi Ebisa , Fekadu Ginenus
Published: May 2021

Background

Men involvement is one of the important factors in family planning (FP) service utilization. Their limitation in the family planning program causes a decrease in service utilization as well as the discontinuation of the method which eventually leads to failure of the program. Family planning uptake is low but there is no enough study conducted on the parameters of husband involvement in Ethiopia. Hence, this study focused to assess men’s involvement in family planning service utilization in Kondala district, western Ethiopia.

Methods

Community based comparative cross-sectional study design was employed in urban and rural kebeles of kondala district using quantitative and qualitative data collection tools. The multi-stage sampling method was employed to select 370 participants from each of the four urban and eight rural kebeles. Logistic regression analysis was used to identify variables that affect husbands’ involvement in FP service utilization. Statistical significance was declared at p-value of < 0.05 with 95% confidence interval (CI) and strength of association was reported by odds ratio (OR).

Results

The study showed that 203(55.6%) men from urban and 178(48.8%) from rural were involved in FP service utilization. The median age of the respondents was 36+ 8.5 years (IQR: 27.5–44.5) in urban and 35 years (IQR: 25–45) in rural parts. Respondents who had four and above current children (AOR = 3.25, 95%CI = 1.51–7.02) in urban and (AOR = 4.20, 95%CI = 1.80–9.79) in rural were positively associated with men’s involvement in FP service utilization. In the urban setting, being government employee (AOR = 2.58, 95%CI = 1.25–5.33), wishing less than two children (AOR = 3.08, 95%CI = 1.80–5.24) and having a better attitude towards FP methods (AOR = 1.86, 95%CI = 1.16–2.99) were positively associated with FP service utilization. While good educational background (AOR = 2.13, 95%CI = 1.02–4.44), short distance from home to health facility (AOR = 2.29, 95%CI = 1.24–4.19) and having better knowledge (AOR = 4.49, 95%CI = 2.72–7.38) were positively associated with men involvement in FP service utilization in the rural area.

Conclusion

Low involvement of men in family planning service utilization was reported in both settings. Factors associated with husbands’ involvement were varied between the two setups, except for the current number of children. Future FP program should incorporate infrastructure associated with the health facility, knowledge, and attitudinal factors.
Metastatic colorectal carcinoma to the right atrium: a case report and review of the literature
Authors: Sarfraz Humaira , Arain Abeer , Divatia Mukul K. , Schwartz Mary R. , Heyne Kirk E.
Published: May 2021

Background

Cardiac metastasis due to colon cancer is extraordinarily uncommon. Given the rarity of diagnosis, there is paucity of evidence and hence, no established guidelines for evaluation or clinical management strategy.

Clinical presentation

We present the case of a 59 year old male with a previously treated colonic carcinoma who presented with new onset exertional dyspnea. He was noted to be having a right atrial mass on an echocardiogram performed at his cardiologist’s office. Further workup with CT angiogram of the chest confirmed a right atrial mass measuring 4.0 cm. Serum CEA was normal. Biopsies of the right atrial mass demonstrated metastatic moderately differentiated colonic adenocarcinoma. Mismatch repair protein expression analysis by immunohistochemistry showed no loss of MLH1, MSH2, MSH6 or PMS2 expression. Next generation sequencing for RAS and BRAF mutations was negative. Patient received treatment with FOLFIRINOX/ bevacizumab with noted reduction in size of mass.

Conclusion

To the best of our knowledge, this is the first report of next generation sequencing results available on a biopsy of metastatic colorectal cancer to the heart with the largest literature review of 31 reported cases of metastatic colorectal cancer to the heart. It will help direct clinical management and also adds evidence to the potential efficacy of treatment of this rare aggressive disease with chemotherapy in combination with VEGF inhibitors.
High sodium food consumption pattern among Malaysian population
Authors: Ahmad Mohamad Hasnan , Man Cheong Siew , Othman Fatimah , He Feng J. , Salleh Ruhaya , Noor Noor Safiza Mohammad , Kozil Wan Nur Khairunnisa Wan , MacGregor Graham , Aris Tahir
Published: May 2021

Background

Sodium is an essential mineral needed by the human body that must be obtained from food. An excess intake, however, can lead to many diseases. As food is the main source of sodium, this study aims to provide information on high sodium food consumption patterns in the Malaysian adult population.

Methods

The Malaysian Community Salt Study (MyCoSS) was a nationwide cross-sectional study, conducted between October 2017 and March 2018. A multistage complex sample was applied to select a nationally representative sample of respondents aged 18 years and above. Face to face interview by a validated Food Frequency Questionnaire (FFQ) comprising 104 food items was used to gain information on high sodium food consumption patterns.

Results

A total of 1047 respondents were involved in this study, with 1032 (98.6%) answering the FFQ. From the number, 54.1% exceed the recommendation of sodium intake <2000mg/day by FFQ assessment. The results also demonstrated that fried vegetables (86.4%) were the most common high sodium food consumed, followed by bread (85.9%) and omelet (80.3%). In urban areas, bread was the most common while fried vegetables took the lead in rural areas. By sex, bread was most commonly eaten by males and fried vegetables by females. The results also found that kolok mee/kampua mee contributed the highest sodium, 256.5mg/day in 9.0% adult population, followed by soy sauce 248.1mg/day in 33.2% adult population, and curry noodles 164.2mg/day in 18.5% adult population.

Conclusion

Fried vegetables, bread, and soy sauce were the main source of sodium consumption among adult. Reducing the amount of sodium added to these foods should be the top priority to reduce population sodium intake and thereby prevent sodium-related diseases in Malaysia.
Knowledge, perception, and practice related to sodium intake among Malaysian adults: findings from the Malaysian Community Salt Study (MyCoSS)
Authors: Cheong Siew Man , Ambak Rashidah , Othman Fatimah , He Feng J. , Salleh Ruhaya , Mohd Sallehudin Syafinaz , Palaniveloo Lalitha , Ganapathy Shubash Shander
Published: May 2021

Background

Excessive intake of sodium is a major public health concern. Information on knowledge, perception, and practice (KPP) related to sodium intake in Malaysia is important for the development of an effective salt reduction strategy. This study aimed to investigate the KPP related to sodium intake among Malaysian adults and to determine associations between KPP and dietary sodium intake.

Methods

Data were obtained from Malaysian Community Salt Survey (MyCoSS) which is a nationally representative survey with proportionate stratified cluster sampling design. A pre-tested face-to-face questionnaire was used to collect information on socio-demographic background, and questions from the World Health Organization/Pan American Health Organization were adapted to assess the KPP related to sodium intake. Dietary sodium intake was determined using single 24-h urinary sodium excretion. Respondents were categorized into two categories: normal dietary sodium intake (< 2000 mg) and excessive dietary sodium intake (≥ 2000 mg). Out of 1440 respondents that were selected to participate, 1047 respondents completed the questionnaire and 798 of them provided valid urine samples. Factors associated with excessive dietary sodium intake were analyzed using complex sample logistic regression analysis.

Results

Majority of the respondents knew that excessive sodium intake could cause health problems (86.2%) and more than half of them (61.8%) perceived that they consume just the right amount of sodium. Overall, complex sample logistic regression analysis revealed that excessive dietary sodium intake was not significantly associated with KPP related to sodium intake among respondents (P > 0.05).

Conclusion

The absence of significant associations between KPP and excessive dietary sodium intake suggests that salt reduction strategies should focus on sodium reduction education includes measuring actual dietary sodium intake and educating the public about the source of sodium. In addition, the relationship between the authority and food industry in food reformulation needs to be strengthened for effective dietary sodium reduction in Malaysia.
Risk factors related with high sodium intake among Malaysian adults: findings from the Malaysian Community Salt Survey (MyCoSS) 2017–2018
Authors: Abdul Aziz Nur Shahida , Ambak Rashidah , Othman Fatimah , He Feng J. , Yusof Muslimah , Paiwai Faizah , Abdul Ghaffar Suhaila , Mohd Yusof Muhammad Fadhli , Cheong Siew Man , MacGregor Graham , Aris Tahir
Published: May 2021

Background

High sodium intake was an established risk factor for stroke and cardiovascular diseases. The objective of this study was to investigate factors associated with high sodium intake based on 24-h urinary sodium excretion from the MyCoSS study.

Methods

The cross-sectional survey was conducted among adults aged 18 years and above in Malaysia. A multi-stage stratified sampling was used to represent nationally. Twenty-four-hour urine was collected from a total of 900 respondents. Indirect ion-selective electrode (ISE) method was used to measure sodium intake. Descriptive and logistic regression analysis was applied to determine factors associated with high sodium intake based on 24-h urinary sodium excretion.

Results

A total of 798 respondents (76% response rate) completed the 24-h urine collection process. Logistic regression revealed that high sodium intake associated with obese [aOR 2.611 (95% CI 1.519, 4.488)], male [aOR 2.436 (95% CI 1.473, 4.030)], having a waist circumference of > 90cm for adult males [aOR 2.260 ( 95% CI 1.020, 5.009) and >80cm for adult females [aOR 1.210 (95% CI 0.556, 2.631)], being a young adult [aOR 1.977 (95% CI 1.094, 3.574)], and living in urban areas [aOR 1.701 (95% CI 1.094, 2.645)].

Conclusion

Adults who are obese, have a large waist circumference, of male gender, living in urban areas, and belonging to the young adult age group were found to have higher sodium intake than other demographic groups. Hence, reduction of salt consumption among these high-risk groups should be emphasised to reduce the risk of cardiovascular diseases.
The prevalence of hypertension among Malaysian adults and its associated risk factors: data from Malaysian Community Salt Study (MyCoSS)
Authors: Zaki Nor Azian Mohd , Ambak Rashidah , Othman Fatimah , Wong Norazizah Ibrahim , Man Cheong Siew , Morad Mohamad Faizul Azham , He Feng J. , MacGregor Graham , Palaniveloo Lalitha , Baharudin Azli
Published: May 2021

Background

Hypertension is one of the most common risk factors for cardiovascular disease and leading cause of mortality globally. The aims of this study were to assess the prevalence of hypertension and its associated risk factors among Malaysian population using data from the Malaysian Community Salt Study (MyCoSS).

Methods

This study was a cross-sectional study using multi-stage stratified sampling method. Data collection was carried out via face-to-face interview at the respondent’s home from October 2017 until March 2018. A total of 1047 respondents aged 18 years and above completed the questionnaires and blood pressure measurement. A person who reported diagnosis of hypertension by a physician and had systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on three readings was categorised as hypertensive. Risk factors of hypertension were analysed using multiple logistic regression.

Results

The prevalence of hypertension in the present study was 49.39% (95% CI 44.27–54.51). There was no statistically significant difference in gender. Age, household income, BMI, and diabetes were significantly associated with hypertension. Hypertension found had inverse association with the level of education. Age was the strongest predictor of hypertension (35–44 years old; OR=2.39, 95% CI=1.39–4.09, 45–54 years old; OR=5.50, 95% CI=3.23–9.38, 55–64 years old OR=13.56, 95% CI=7.77–23.64 and 65 years old and above; OR=25.28, 95% CI=13.33–48.66). Those who had higher BMI more likely to be hypertensive as compared to respondents with normal weight (overweight, OR=1.84; 95% CI=1.18–2.86; obese, OR=4.29% CI=2.56–7.29).

Conclusion

The findings showed that hypertension is prevalent among adults in Malaysia. Those with older age, higher BMI, and diabetes are more likely to have hypertension. Efforts regarding lifestyle modification and education could be important in hypertension management and prevention.