bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired ribosome biogenesis checkpoint activation induces p53-dependent MCL-1 degradation and MYC-driven lymphoma death
Authors: Domostegui Ana , Peddigari Suresh , Mercer Carol A. , Iannizzotto Flavia , Rodriguez Marta L. , Garcia-Cajide Marta , Amador Virginia , Diepstraten Sarah T. , Kelly Gemma L. , Salazar Ramón , Kozma Sara C. , Kusnadi Eric P. , Kang Jian , Gentilella Antonio , Pearson Richard B. , Thomas George , Pelletier Joffrey
Published: January 2021

MYC-driven B-cell lymphomas are addicted to increased levels of ribosome biogenesis (RiBi), offering the potential for therapeutic intervention. However, it is unclear whether inhibition of RiBi suppresses lymphomagenesis by decreasing translational capacity and/or by p53 activation mediated by the impaired RiBi checkpoint (IRBC). Here we generated Eμ-Myc lymphoma cells expressing inducible short hairpin RNAs to either ribosomal protein L7a (RPL7a) or RPL11, the latter an essential component of the IRBC. The loss of either protein reduced RiBi, protein synthesis, and cell proliferation to similar extents. However, only RPL7a depletion induced p53-mediated apoptosis through the selective proteasomal degradation of antiapoptotic MCL-1, indicating the critical role of the IRBC in this mechanism. Strikingly, low concentrations of the US Food and Drug Administration–approved anticancer RNA polymerase I inhibitor Actinomycin D (ActD) dramatically prolonged the survival of mice harboring Trp53+/+;Eμ-Myc but not Trp53–/–;Eμ-Myc lymphomas, which provides a rationale for treating MYC-driven B-cell lymphomas with ActD. Importantly, the molecular effects of ActD on Eμ-Myc cells were recapitulated in human B-cell lymphoma cell lines, highlighting the potential for ActD as a therapeutic avenue for p53 wild-type lymphoma.
ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease
Authors: Connell Nathan T. , Flood Veronica H. , Brignardello-Petersen Romina , Abdul-Kadir Rezan , Arapshian Alice , Couper Susie , Grow Jean M. , Kouides Peter , Laffan Michael , Lavin Michelle , Leebeek Frank W. G. , O’Brien Sarah H. , Ozelo Margareth C. , Tosetto Alberto , Weyand Angela C. , James Paula D. , Kalot Mohamad A. , Husainat Nedaa , Mustafa Reem A.
Published: January 2021

Background:

von Willebrand disease (VWD) is a common inherited bleeding disorder. Significant variability exists in management options offered to patients.

Objective:

These evidence-based guidelines from the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and health care professionals in their decisions about management of VWD.

Methods:

ASH, ISTH, NHF, and WFH formed a multidisciplinary guideline panel. Three patient representatives were included. The panel was balanced to minimize potential bias from conflicts of interest. The University of Kansas Outcomes and Implementation Research Unit and the McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing and updating systematic evidence reviews (through November 2019). The panel prioritized clinical questions and outcomes according to their importance to clinicians and patients. The panel used the GRADE approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.

Results:

The panel agreed on 12 recommendations and outlined future research priorities.

Conclusions:

These guidelines make key recommendations regarding prophylaxis for frequent recurrent bleeding, desmopressin trials to determine therapy, use of antiplatelet agents and anticoagulant therapy, target VWF and factor VIII activity levels for major surgery, strategies to reduce bleeding during minor surgery or invasive procedures, management options for heavy menstrual bleeding, management of VWD in the context of neuraxial anesthesia during labor and delivery, and management in the postpartum setting.
Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: a randomised clinical trial
Authors: Wittermans Esther , Vestjens Stefan M.T. , Spoorenberg Simone M.C. , Blok Willem L. , Grutters Jan C. , Janssen Rob , Rijkers Ger T. , Smeenk Frank W.J.M. , Voorn G. Paul , van de Garde Ewoudt M.W. , Bos Willem Jan W. ,   the Santeon-CAP Study Group
Published: January 2021

Background

Adjunctive intravenous corticosteroid treatment has been shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent.

Methods

In this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I–III and IV–V). The primary outcome was LOS.

Results

Between December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days, 95% CI 4.0–5.0 days) than in the placebo group (5.0 days, 95% CI 4.6–5.4 days; p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. The secondary ICU admission rate was lower in the dexamethasone arm (5 (3%)versus14 (7%); p=0.030); 30-day mortality did not differ between groups. In the dexamethasone group the rate of hospital readmission tended to be higher (20 (10%)versus9 (5%); p=0.051) and hyperglycaemia (14 (7%)versus1 (1%); p=0.001) was more prevalent.

Conclusion

Oral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk–benefit ratio is optimal.
Unsupervised phenotypic clustering for determining clinical status in children with cystic fibrosis
Authors: Filipow Nicole , Davies Gwyneth , Main Eleanor , Sebire Neil J. , Wallis Colin , Ratjen Felix , Stanojevic Sanja
Published: January 2021

Background

Cystic fibrosis (CF) is a multisystem disease in which the assessment of disease severity based on lung function alone may not be appropriate. The aim of the study was to develop a comprehensive machine-learning algorithm to assess clinical status independent of lung function in children.

Methods

A comprehensive prospectively collected clinical database (Toronto, Canada) was used to apply unsupervised cluster analysis. The defined clusters were then compared by current and future lung function, risk of future hospitalisation, and risk of future pulmonary exacerbation treated with oral antibiotics. A k-nearest-neighbours (KNN) algorithm was used to prospectively assign clusters. The methods were validated in a paediatric clinical CF dataset from Great Ormond Street Hospital (GOSH).

Results

The optimal cluster model identified four (A–D) phenotypic clusters based on 12 200 encounters from 530 individuals. Two clusters (A and B) consistent with mild disease were identified with high forced expiratory volume in 1 s (FEV1), and low risk of both hospitalisation and pulmonary exacerbation treated with oral antibiotics. Two clusters (C and D) consistent with severe disease were also identified with low FEV1. Cluster D had the shortest time to both hospitalisation and pulmonary exacerbation treated with oral antibiotics. The outcomes were consistent in 3124 encounters from 171 children at GOSH. The KNN cluster allocation error rate was low, at 2.5% (Toronto) and 3.5% (GOSH).

Conclusion

Machine learning derived phenotypic clusters can predict disease severity independent of lung function and could be used in conjunction with functional measures to predict future disease trajectories in CF patients.
Risk factors associated with the development of interstitial lung abnormalities
Authors: Buendía-Roldán Ivette , Fernandez Rosario , Mejía Mayra , Juarez Fortunato , Ramirez-Martinez Gustavo , Montes Eduardo , Pruneda Ana Karem S. , Martinez-Espinosa Karen , Alarcon-Dionet Aime , Herrera Iliana , Becerril Carina , Chavez-Galan Leslie , Preciado Mario , Pardo Annie , Selman Moisés
Published: January 2021

Background

Around 8–10% of individuals over 50 years of age present interstitial lung abnormalities (ILAs), but their risk factors are uncertain.

Methods

From 817 individuals recruited in our lung ageing programme at the Mexican National Institute of Respiratory Diseases, 80 (9.7%) showed ILAs and were compared with 564 individuals of the same cohort with normal high-resolution computed tomography to evaluate demographic and functional differences, and with 80 individuals randomly selected from the same cohort for biomarkers. We evaluatedMUC5Bvariant rs35705950, telomere length, and serum levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, interleukin (IL)-6, surfactant protein (SP)-D, α-Klotho and resistin.

Results

Individuals with ILAs were usually males (p<0.005), older than controls (p<0.0001), smokers (p=0.01), with a greater frequency ofMUC5Brs35705950 (OR 3.5, 95% CI 1.3–9.4; p=0.01), and reduced diffusing capacity of the lung for carbon monoxide and oxygen saturation. Resistin, IL-6, SP-D, MMP-1, MMP-7 and MMP-13 were significantly increased in individuals with ILAs. Resistin (12±5versus9±4 ng·mL−1; p=0.0005) and MMP-13 (357±143versus298±116 pg·mL−1; p=0.004) were the most increased biomarkers. On follow-up (24±18 months), 18 individuals showed progression which was associated with gastro-oesophageal reflux disease (OR 4.1, 95% CI 1.2–12.9; p=0.02) and in females with diabetes mellitus (OR 5.3, 95% CI 1.0–27.4; p=0.01).

Conclusions

Around 10% of respiratory asymptomatic individuals enrolled in our lung ageing programme show ILAs. Increased serum concentrations of pro-inflammatory molecules and MMPs are associated with ILAs.
Targeted therapy in eosinophilic chronic obstructive pulmonary disease
Authors: Fieldes Mathieu , Bourguignon Chloé , Assou Said , Nasri Amel , Fort Aurélie , Vachier Isabelle , De Vos John , Ahmed Engi , Bourdin Arnaud
Published: January 2021

Chronic obstructive pulmonary disease (COPD) is a common and preventable airway disease causing significant worldwide mortality and morbidity. Lifetime exposure to tobacco smoking and environmental particles are the two major risk factors. Over recent decades, COPD has become a growing public health problem with an increase in incidence. COPD is defined by airflow limitation due to airway inflammation and small airway remodelling coupled to parenchymal lung destruction. Most patients exhibit neutrophil-predominant airway inflammation combined with an increase in macrophages and CD8+T-cells. Asthma is a heterogeneous chronic inflammatory airway disease. The most studied subtype is type 2 (T2) high eosinophilic asthma, for which there are an increasing number of biologic agents developed. However, both asthma and COPD are complex and share common pathophysiological mechanisms. They are known as overlapping syndromes as approximately 40% of patients with COPD present an eosinophilic airway inflammation. Several studies suggest a putative role of eosinophilia in lung function decline and COPD exacerbation. Recently, pharmacological agents targeting eosinophilic traits in uncontrolled eosinophilic asthma, especially monoclonal antibodies directed against interleukins (IL-5, IL-4, IL-13) or their receptors, have shown promising results. This review examines data on the rationale for such biological agents and assesses efficacy in T2-endotype COPD patients.
Telomere shortening and DNA damage in culprit cells of different types of progressive fibrosing interstitial lung disease
Authors: van Batenburg Aernoud A. , Kazemier Karin M. , van Oosterhout Matthijs F.M. , van der Vis Joanne J. , Grutters Jan C. , Goldschmeding Roel , van Moorsel Coline H.M.
Published: January 2021

Pulmonary fibrosis is strongly associated with telomere shortening and increased DNA damage. Key cells in the pathogenesis involve alveolar type 2 (AT2) cells, club cells and myofibroblasts; however, to what extent these cells are affected by telomere shortening and DNA damage is not yet known. We sought to determine the degree of, and correlation between, telomere shortening and DNA damage in different cell types involved in the pathogenesis of progressive fibrosing interstitial lung disease. Telomere length and DNA damage were quantified, using combined fluorescencein situhybridisation and immunofluorescence staining techniques, in AT2 cells, club cells and myofibroblasts of controls and patients with pulmonary fibrosis and a telomerase reverse transcriptase mutation (TERT-PF), idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). In IPF and TERT-PF lungs, AT2 cells contained shorter telomeres and expressed higher DNA damage signals than club cells and myofibroblasts. In fHP lungs, club cells contained highly elevated levels of DNA damage, while telomeres were not obviously short.In vitro, we found significantly shorter telomeres and higher DNA damage levels only in AT2 surrogate cell lines treated with telomerase inhibitor BIBR1532. Our study demonstrated that in IPF and TERT-PF lungs, telomere shortening and accumulation of DNA damage primarily affects AT2 cells, further supporting the importance of AT2 cells in these diseases, while in fHP the particularly high telomere-independent DNA damage signals in club cells underscores its bronchiolocentric pathogenesis. These findings suggest that cell type-specific telomere shortening and DNA damage may help to discriminate between different drivers of fibrogenesis.
Long-term adherence to inhaled corticosteroids and asthma control in adult-onset asthma
Authors: Vähätalo Iida , Kankaanranta Hannu , Tuomisto Leena E. , Niemelä Onni , Lehtimäki Lauri , Ilmarinen Pinja
Published: January 2021

Background

In short-term studies, poor adherence to inhaled corticosteroids (ICS) has been associated with worse asthma control, but the association of long-term adherence and disease control remains unclear.

Objective

To assess the relationship between 12-year adherence to ICS and asthma control in patients with adult-onset asthma.

Methods

As part of the Seinäjoki Adult Asthma Study, 181 patients with clinically confirmed new-onset adult asthma and regular ICS medication were followed-up for 12 years. Adherence (%) to ICS was assessed individually ((µg dispensed/µg prescribed)×100) during the follow-up. Asthma control was evaluated after 12 years of treatment according to the Global Initiative for Asthma 2010 guideline.

Results

Asthma was controlled in 31% and not controlled (partly controlled or uncontrolled) in 69% of the patients. Patients with not-controlled asthma were more often male, older, nonatopic and used higher doses of ICS than those with controlled disease. The mean±sd12-year adherence to ICS was 63±38% in patients with controlled asthma and 76±40% in patients with not-controlled disease (p=0.042). Among patients with not-controlled asthma, those with lower 12-year adherence (<80%) had more rapid decline in forced expiratory volume in 1 s (−47 mL·year−1) compared to patients with better adherence (≥80%) (−40 mL·year−1) (p=0.024). In contrast, this relationship was not seen in patients with controlled asthma.

Conclusions

In adult-onset asthma, patients with not-controlled disease showed better 12-year adherence to ICS treatment than those with controlled asthma. In not-controlled disease, adherence <80% was associated with more rapid lung function decline, underscoring the importance of early recognition of such patients in routine clinical practice.
The Fungal Effector Avr-Pita Suppresses Innate Immunity by Increasing COX Activity in Rice Mitochondria
Authors: Han Jingluan , Wang Xiaoyu , Wang Fengpin , Zhao Zhe , Li Gousi , Zhu Xiaoyuan , Su Jing , Chen Letian
Published: January 2021

Background

Avr-Pita was the first effector identified in the blast fungus (Magnaporthe oryzae)–rice (Oryza sativa) pathosystem. However, the molecular mechanism underlying its effects on the host plant has remained a long-standing mystery.

Results

Here, we report that ectopically expressingAvr-Pitain rice enhances susceptibility toM. oryzaeand suppresses pathogen-associated molecular pattern (PAMP)-triggered defense responses. Avr-Pita targets the host mitochondria and interacts with the cytochromecoxidase (COX) assembly protein OsCOX11, a key regulator of mitochondrial reactive oxygen species (ROS) metabolism in rice. OverexpressingAvr-PitaorOsCOX11increased COX activity and decreased ROS accumulation triggered by the fungal PAMP chitin.OsCOX11-overexpressing plants showed increased susceptibility toM. oryzae, whereasOsCOX11-knockdown plants showed resistance toM. oryzae.

Conclusions

Taken together, these findings suggest that the fungal pathogenM. oryzaedelivers the effector Avr-Pita to the host plant, where it enhances COX activity thus decreasing ROS accumulation. Therefore, this effector suppresses host innate immunity by perturbing ROS metabolism in the mitochondria.
Alternative Polyadenylation in response to temperature stress contributes to gene regulation in Populus trichocarpa
Authors: Yan Chao , Wang Yupeng , Lyu Tao , Hu Zhikang , Ye Ning , Liu Weixin , Li Jiyuan , Yao Xiaohua , Yin Hengfu
Published: January 2021

Background

Genome-wide change of polyadenylation (polyA) sites (also known as alternative polyadenylation, APA) is emerging as an important strategy of gene regulation in response to stress in plants. But little is known in woody perennials that are persistently dealing with multiple abiotic stresses.

Results

Here, we performed a genome-wide profiling of polyadenylation sites under heat and cold treatments in Populus trichocarpa. Through a comprehensive analysis of polyA tail sequences, we identified 25,919 polyA-site clusters (PACs), and revealed 3429 and 3139 genes shifted polyA sites under heat and cold stresses respectively. We found that a small proportion of genes possessed APA that affected the open reading frames; and some shifts were commonly identified. Functional analysis of genes displaying shifted polyA tails suggested that pathways related to RNA metabolism were linked to regulate the APA events under both heat and cold stresses. Interestingly, we found that the heat stress induced a significantly more antisense PACs comparing to cold and control conditions. Furthermore, we showed that a unique cis-element (AAAAAA) was predominately enriched downstream of PACs in P. trichocarpa genes; and this sequence signal was only absent in shifted PACs under the heat condition, indicating a distinct APA mechanism responsive to heat tolerance.

Conclusions

This work provides a comprehensive picture of global polyadenylation patterns in response to temperatures stresses in trees. We show that the frequent change of polyA tail is a potential mechanism of gene regulation responsive to stress, which are associated with distinctive sequence signatures.
Genome evolution during bread wheat formation unveiled by the distribution dynamics of SSR sequences on chromosomes using FISH
Authors: Zhang Yingxin , Fan Chengming , Chen Yuhong , Wang Richard R.-C. , Zhang Xiangqi , Han Fangpu , Hu Zanmin
Published: January 2021

Background

During the bread wheat speciation by polyploidization, a series of genome rearrangement and sequence recombination occurred. Simple sequence repeat (SSR) sequences, predominately located in heterochromatic regions of chromosomes, are the effective marker for tracing the genomic DNA sequence variations. However, to date the distribution dynamics of SSRs on chromosomes of bread wheat and its donors, including diploid and tetraploid Triticum urartu, Aegilops speltoides, Aegilops tauschii, Triticum turgidum ssp. dicocoides, reflecting the genome evolution events during bread wheat formation had not been comprehensively investigated.

Results

The genome evolution was studied by comprehensively comparing the distribution patterns of (AAC)n, (AAG)n, (AGC)n and (AG)n in bread wheat Triticum aestivum var. Chinese Spring and its progenitors T. urartu, A. speltoides, Ae. tauschii, wild tetroploid emmer wheat T. dicocoides, and cultivated emmer wheat T. dicoccum. Results indicated that there are specific distribution patterns in different chromosomes from different species for each SSRs. They provided efficient visible markers for identification of some individual chromosomes and SSR sequence evolution tracing from the diploid progenitors to hexaploid wheat. During wheat speciation, the SSR sequence expansion occurred predominately in the centromeric and pericentromeric regions of B genome chromosomes accompanied by little expansion and elimination on other chromosomes. This result indicated that the B genome might be more sensitive to the “genome shock” and more changeable during wheat polyplodization.

Conclusions

During the bread wheat evolution, SSRs including (AAC)n, (AAG)n, (AGC)n and (AG)n in B genome displayed the greatest changes (sequence expansion) especially in centromeric and pericentromeric regions during the polyploidization from Ae. speltoides S genome, the most likely donor of B genome. This work would enable a better understanding of the wheat genome formation and evolution and reinforce the viewpoint that B genome was originated from S genome.
Proteome-wide and lysine crotonylation profiling reveals the importance of crotonylation in chrysanthemum (Dendranthema grandiforum) under low-temperature
Authors: Lin Ping , Bai Hui-ru , He Ling , Huang Qiu-xiang , Zeng Qin-han , Pan Yuan-zhi , Jiang Bei-bei , Zhang Fan , Zhang Lei , Liu Qing-Lin
Published: January 2021

Background

Low-temperature severely affects the growth and development of chrysanthemum which is one kind of ornamental plant well-known and widely used in the world. Lysine crotonylation is a recently identified post-translational modification (PTM) with multiple cellular functions. However, lysine crotonylation under low-temperature stress has not been studied.

Results

Proteome-wide and lysine crotonylation of chrysanthemum at low-temperature was analyzed using TMT (Tandem Mass Tag) labeling, sensitive immuno-precipitation, and high-resolution LC-MS/MS. The results showed that 2017 crotonylation sites were identified in 1199 proteins. Treatment at 4 °C for 24 h and − 4 °C for 4 h resulted in 393 upregulated proteins and 500 downregulated proteins (1.2-fold threshold andP < 0.05). Analysis of biological information showed that lysine crotonylation was involved in photosynthesis, ribosomes, and antioxidant systems. The crotonylated proteins and motifs in chrysanthemum were compared with other plants to obtain orthologous proteins and conserved motifs. To further understand how lysine crotonylation at K136 affected APX (ascorbate peroxidase), we performed a site-directed mutation at K136 in APX. Site-directed crotonylation showed that lysine decrotonylation at K136 reduced APX activity, and lysine complete crotonylation at K136 increased APX activity.

Conclusion

In summary, our study comparatively analyzed proteome-wide and crotonylation in chrysanthemum under low-temperature stress and provided insights into the mechanisms of crotonylation in positively regulated APX activity to reduce the oxidative damage caused by low-temperature stress. These data provided an important basis for studying crotonylation to regulate antioxidant enzyme activity in response to low-temperature stress and a new research ideas for chilling-tolerance and freezing-tolerance chrysanthemum molecular breeding.
The sniffing bead system, an olfactory dysfunction screening tool for geriatric subjects: a cross-sectional study
Authors: Min Hyun Jin , Kim Sun Mi , Han Doug Hyun , Kim Kyung Soo
Published: January 2021

Background

This study aimed to develop a simple and one-off olfactory screening test, the sniffing bead system, for general clinical use in older adults.

Methods

In this cross-sectional study, geriatric subjects (aged > 50 years) who underwent neurocognitive and olfactory function tests were included. Overall, 137 subjects were enrolled, and the study was conducted at Chung-Ang University, Seoul, Korea. Olfactory function was measured by obtaining the scores of the sniffing bead system using 2-phenylethyl alcohol, n-butanol, and the YSK olfactory function test. Time taken for each olfactory function test was also measured.

Results

The score of the 2-phenylethyl alcohol sniffing bead test was 2.58 ± 1.52, which was significantly associated with the YSK_threshold (2.41 ± 1.79) (p < 0.001, Pearson’s correlation coefficient = 0.429), YSK_identification (8.93 ± 3.25) (p = 0.014, Pearson’s correlation coefficient = 0.208) and YSK_threshold-discrimination-identification (17.46 ± 5.49) (p < 0.001, Pearson’s correlation coefficient = 0.316) test scores. In the normal cognitive function group, YSK_threshold (p < 0.001, Pearson’s correlation coefficient = 0.479), YSK_identification (p = 0.003, Pearson’s correlation coefficient = 0.316), and YSK_threshold-discrimination-identification (p < 0.001, Pearson’s correlation coefficient = 0.429) were significantly correlated with the scores of the 2-phenylethyl alcohol sniffing bead system. In the impaired cognitive function group, the YSK_threshold (p = 0.002, Pearson’s correlation coefficient = 0.415) and YSK_ threshold-discrimination-identification (p = 0.004, Pearson’s correlation coefficient = 0.385) were significantly correlated with the scores of the 2-phenylethyl alcohol sniffing bead system. Time taken for the 2-phenylethyl alcohol sniffing bead system was 5.00 ± 1.51 min, which was significantly lower than that for the YSK_threshold-discrimination-identification (20.43 ± 5.29 min) (p < 0.001). The scores of the 2-phenylethyl alcohol sniffing bead system were significantly correlated with those of the n-butanol sniffing bead system (3.50 ± 1.21) (p < 0.001, Pearson’s correlation coefficient = 0.315).

Conclusions

This sniffing bead system was specifically designed for screening olfactory function in older adults, and it may allow for the rapid and accurate assessment of olfactory dysfunction.
Medication adherence support of an in-home electronic medication dispensing system for individuals living with chronic conditions: a pilot randomized controlled trial
Authors: Arain Mubashir Aslam , Ahmad Armghan , Chiu Venus , Kembel Lorena
Published: January 2021

Background

Medication adherence is challenging for older adults due to factors such as the number of medications, dosing schedule, and the duration of drug therapy. The objective of this study was to examine the effectiveness of an in-home electronic medication dispensing system (MDS) on improving medication adherence and health perception in older adults with chronic conditions.

Methods

A pilot Randomized Controlled Trial (RCT) was conducted using a two-arm parallel assignment model. The intervention group used an MDS as their medication management method. The control group continued to use their current methods of medication management. Block randomization was used to assign participants into the intervention or control group. The inclusion criteria included 1) English speaking 2) age 50 and over 3) diagnosed with one or more chronic condition(s) 4) currently taking five or more oral medications 5) City of Calgary resident. Participants were recruited from a primary care clinic in Alberta, Canada. The study was open-label where knowledge about group assigned to participants after randomization was not withheld. Medication adherence was captured over a continuous, six-month period and analyzed using Intention-to-Treat (ITT) analysis.

Results

A total of 91 participants were assessed for eligibility and 50 were randomized into the two groups. The number of participants analyzed for ITT was 23 and 25 in the intervention and control group, respectively. Most of the demographic characteristics were comparable in the two groups except the mean age of the intervention group, which was higher compared to the control group (63.96 ± 7.86 versus 59.52 ± 5.93, p-value = 0.03). The average recorded adherence over 26 weeks was significantly higher in the intervention group than the control group (98.35% ± 2.15% versus 91.17% ± 9.76%, p < 0.01). The self-rated medication adherence in the intervention group also showed a significant increase from baseline to 6-month (Z=-2.65, p < 0.01). The control group showed a non-significant increase (Z=-1.79, p = 0.07).

Conclusion

The MDS can be an effective, long-term solution to medication non-adherence in older adults experiencing chronic conditions and taking multiple medications. The technology induces better consistency and improvement in medication taking behaviour than simple, non-technological intervention.

Trial registration

Registered with ClinicalTrials.gov on April 09, 2020 with identifier NCT04339296.
Incidence, characteristics and clinical relevance of acute stroke in old patients hospitalized with COVID-19
Authors: Mendes Aline , Herrmann François R. , Genton Laurence , Serratrice Christine , Carrera Emmanuel , Vargas Maria Isabel , Gold Gabriel , Graf Christophe E. , Zekry Dina , Scheffler Max
Published: January 2021

Background

Stroke in the course of coronavirus disease (COVID-19) has been shown to be associated with more severe respiratory symptoms and higher mortality, but little knowledge in this regard exists on older populations. We aimed to investigate the incidence, characteristics, and prognosis of acute stroke in geriatric patients hospitalized with COVID-19.

Methods

A monocentric cross-sectional retrospective study of 265 older patients hospitalized with COVID-19 on acute geriatric wards. 11/265 presented a stroke episode during hospitalization. Mortality rates and two-group comparisons (stroke vs non-stroke patients) were calculated and significant variables added in logistic regression models to investigate stroke risk factors.

Results

Combined ischemic and hemorrhagic stroke incidence was 4.15%. 72.7% of events occurred during acute care. Strokes presented with altered state of consciousness and/or delirium in 81.8%, followed by a focal neurological deficit in 45.5%. Ischemic stroke was more frequently unilateral (88.8%) and localized in the middle cerebral artery territory (55.5%). Smoking and a history of previous stroke increased by more than seven (OR 7.44; 95% CI 1.75–31.64; p = 0.007) and five times (OR 5.19; 95% CI 1.50–17.92; p = 0.009), respectively, the risk of stroke. Each additional point in body mass index (BMI) reduced the risk of stroke by 14% (OR 0.86; 95% CI 0.74–0.98; p = 0.03). In-hospital mortality (32.1% vs. 27.3%; p > 0.999) and institutionalization at discharge (36.4% vs. 21.1%; p = 0.258) were similar between patients with and without stroke.

Conclusion

Incident stroke complicating COVID-19 in old patients was associated with active smoking, previous history of stroke, and low BMI. Acute stroke did not influence early mortality or institutionalization rate at discharge.
Predictors of caregiver burden in aged caregivers of demented older patients
Authors: Tsai Chia-Fen , Hwang Wei-Shen , Lee Jun-Jun , Wang Wen-Fu , Huang Ling-Chun , Huang Li-Kai , Lee Wei-Ju , Sung Pi-Shan , Liu Yi-Chien , Hsu Chih-Cheng , Fuh Jong-Ling
Published: January 2021

Background

Dementia in the oldest-old is projected to increase exponentially as is the burden of their caregivers who may experience unique challenges and suffering. Thus, we aim to investigate which factors are associated with older caregivers’ burden in caring demented outpatients in a multicenter cohort.

Methods

Patients and their caregivers, both aged ≧65 years, in the National Dementia Registry Study in Taiwan (T-NDRS) were included in this study. Caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The correlations between the ZBI scores and characteristics of caregivers and patients, including severity of dementia, physical comorbidities, instrumental activities of daily living (IADL), neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI), and family monthly income, were analyzed.

Results

We recruited 328 aged informal caregiver-patient dyads. The mean age of caregivers was 73.7 ± 7.0 years, with female predominance (66.8%), and the mean age of patients was 78.8 ± 6.9 years, with male predominance (61.0%). Multivariable linear regression showed that IADLs (β = 0.83, p < 0.001) and NPI subscores of apathy (β = 3.83, p < 0.001)and irritability (β = 4.25, p < 0.001) were positively associated with ZBI scores. The highest family monthly income (β = − 10.92, p = 0.001) and caregiver age (β = − 0.41, p = 0.001) were negatively correlated with ZBI scores.

Conclusions

Older caregivers of older demented patients experience a higher care burden when patients had greater impaired functional autonomy and the presence of NPI symptoms of apathy and irritability. Our findings provide the direction to identify risky older caregivers, and we should pay more attention to and provide support for these exhausted caregivers.
Development of an engineered peptide antagonist against periostin to overcome doxorubicin resistance in breast cancer
Authors: Oo Khine Kyaw , Kamolhan Thanpawee , Soni Anish , Thongchot Suyanee , Mitrpant Chalermchai , O-charoenrat Pornchai , Thuwajit Chanitra , Thuwajit Peti
Published: January 2021

Background

Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PN peptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells.

Methods

A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PN peptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data.

Results

The results showed that a candidate anti-PN peptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PN peptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PN peptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data.

Conclusions

This finding supports that anti-PN peptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.
A review of new hormonal therapies for prostate cancer in black men: is there enough data?
Authors: Meunier Matthias E. , Blanchet Pascal , Neuzillet Yann , Lebret Thierry , Brureau Laurent
Published: January 2021

Background

Prostate cancer among black men is known to have specific molecular characteristics, especially the androgen receptor or enzymes related to the androgen metabolism. These targets are keys to the action of new hormonal therapies. Nevertheless, literature has a lack of data regarding black men. We aimed to gather the available literature data on new hormonal therapies among black populations.

Methods

We conducted a literature review from the PubMed / MEDLINE database until October 2020. All clinical studies of new hormonal therapies and black populations, regardless of methodology, were included.

Results

Four studies provided data on new hormonal therapies in black populations. Three studies reported a PSA decline in black patients treated with Abiraterone, higher in black men than in white men. Overall survival also appears to be higher in black patients treated with Abiraterone only or first.

Conclusion

Few articles have evaluated the effectiveness and safety of use of these treatments among black populations. The first results seem to show that Abiraterone can provide a benefit in overall survival in black populations. Prospective studies are needed to answer these questions in the future.
Combined prognostic value of the SUVmax derived from FDG-PET and the lymphocyte-monocyte ratio in patients with stage IIIB-IV non-small cell lung cancer receiving chemotherapy
Authors: Zhao Kewei , Wang Chunsheng , Shi Fang , Huang Yong , Ma Li , Li Minghuan , Song Yipeng
Published: January 2021

Background

We evaluated the prognostic potential of tumor 18F-fluorodeoxyglucose (FDG) uptake derived from positron emission tomography (PET) and known inflammatory hematological markers, both individually and in combination, for chemosensitivity and survival in patients with stage IIIB-IV non-small cell lung cancer (NSCLC) receiving first-line chemotherapy.

Methods

A total of 149 patients with stage IIIB and IV NSCLC (based on TNM 7th edition) were retrospectively reviewed. Maximum standardized uptake value (SUVmax) were used to quantitatively assess FDG uptake. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were selected as hematological markers. Receiver operating characteristic (ROC) curves were constructed for the determination of optimal cut-off values to predict chemotherapeutic response.

Results

Patients with SUVmax > 11.6 or LMR ≤3.73 exhibited a significantly lower objective response rate (ORR) to chemotherapy (p < 0.001 and p < 0.001). Through multivariable logistic regression analysis, both the SUVmax and LMR were identified as independent predictive factors for chemotherapeutic response (p = 0.001 and p < 0.001). Furthermore, a multivariable Cox proportional hazard model identified a high SUVmax (> 11.6) and low LMR (≤3.73) as independent predictors of poor PFS (p < 0.001 and p = 0.025) and OS (p < 0.001 and p = 0.032). A novel score system was constructed based on the SUVmax and LMR (SUV_LMR score), and patients were stratified into three subgroups. The patients with a score of 0 had a significantly higher ORR (88.9%) than did those with a score of 1 (59.6%) and score of 2 (25.0%) (p < 0.001). Moreover, multivariable Cox analysis further identified the SUV_LMR score as an independent prognostic factor for PFS (p < 0.001) and OS (p < 0.001).

Conclusions

Pre-treatment SUVmax and LMR were not only predictive factors for chemotherapeutic response but also independent prognostic factors of survival in stage IIIB-IV NSCLC. Moreover, the SUV_LMR score, which is based on primary tumor metabolic activity and the systemic inflammatory response, might provide a promising tool to predict chemosensitivity, recurrence and survival of advanced NSCLC.
Tumor infiltrating neutrophil might play a major role in predicting the clinical outcome of breast cancer patients treated with neoadjuvant chemotherapy
Authors: Geng Sheng-Kai , Fu Shao-Mei , Ma Shi-Hong , Fu Yi-Peng , Zhang Hong-Wei
Published: January 2021

Background

This study was aimed to explore the predictive ability of tumor infiltrating neutrophil (TIN) in patients with breast cancer treated with neoadjuvant chemotherapy (NACT). Furthermore, the significance of TIN’s dynamic change before and after NACT was investigated.

Methods

Between January 2004 and December 2017, a total of 133 patients with breast cancer who underwent NACT before surgery were enrolled in this retrospective cohort. Eighty-nine of them were able to get the core needle biopsy (CNB) samples and all the pathological samples after surgery were available. TIN was detected by immunohistochemical staining of CD66b. The optimal cut-off value was determined via receiver operating characteristic (ROC) curve analysis. The association of clinicopathologic characteristics and chemotherapy efficiency was analyzed using X2 test or Fisher’s exact test or t-test as appropriate, and the prognostic significances were assessed by univariate and multivariate analyses.

Results

Patients with higher TIN after NACT were confirmed to be significantly associated with worse prognosis (P = 0.002). After stratifying patients into two groups, high difference group was prone to have better chemotherapy efficiency (P < 0.001) and clinical outcome in both univariate (P = 0.002) and multivariate analyses (P = 0.003).

Conclusions

In this study, higher TIN after NACT was confirmed to be associated with breast cancer patients’ worse chemotherapy efficiency and shorter disease-free survival (DFS). Furthermore, the TIN’s dynamic change before and after NACT was firstly proved to be a more accurate predictive marker compared with TIN after NACT.
A retrospective survey of strabismus surgery in a tertiary eye center in northern China, 2014–2019
Authors: Wan Xiaomei , Wan Luqin , Jiang Mingming , Ding Yichao , Wang Yuan , Zhang Jing
Published: January 2021

Background

To evaluate the distribution pattern and changes of strabismus surgery in northern China.

Methods

The records of strabismus patients at Qingdao Eye Hospital from January 2014 to December 2019 were reviewed retrospectively. The characteristics analyzed included gender, regional distribution, constituent ratio of age and type of strabismus. Changes during the periods 2014–2016 and 2017–2019 were compared and analyzed.

Results

A total of 5746 strabismus patients were recruited. The number of strabismus patients was relatively stable each year from 2014 to 2016 but gradually increased each year from 2017 to 2019. Of these, 51.7% (2968/5746) were male, and 48.3% (2778/5746) were female. The majority (89.8%, 5159/5746) of the patients were from Shandong Province. The statistical results of the constituent ratio of age showed that 32.4% (1860/5746) were 7–12 years old (primary school level). Patients under 12 years of age (preschool and primary school level) accounted for 60.0% (3447/5746) of all the patients. In terms of the types of strabismus, exotropia accounted for 63.5% (3650/5746), followed by esotropia and vertical rotational strabismus at 13.2% (758/5746) and 9.7% (555/5746), respectively. Intermittent exotropia was the most common type among the exotropia patients, accounting for 71.3% (2604/3650). Among the patients with intermittent exotropia, 62.5% (1627/2604) were children aged 4–12 years, and the basic type of intermittent exotropia was the main type. Four percent (231/5746) of the patients, of which adult patients comprised the main population, required reoperation.

Conclusions

Patients with strabismus at primary school level comprised the largest group of strabismus patients in north China. Exotropia was the most common type of strabismus, and intermittent exotropia was the most common type of exotropia. The rate of exotropia to esotropia was 5:1.
Can adopting skin cancer preventive behaviors among seafarers be increased via a theory-based mobile phone-based text message intervention? A randomized clinical trial
Authors: Heydari Esmat , Dehdari Tahereh , Solhi Mahnaz
Published: January 2021

Background

One of the main occupational hazards for seafarers is the long exposure to sunlight. This study aimed to determine the efficacy of a mobile phone-based text message intervention in adopting skin cancer preventive behaviors among a sample of seafarers in Genaveh port located in Bushehr province, Iran.

Methods

In this randomized controlled trial, 136 seafarers were randomly selected and assigned to the intervention (n = 68) or a control groups (n = 68). As a theoretical basis, we followed the Protection Motivation Theory (PMT) variables to develop the text messages. The data related to PMT variables and skin cancer preventive behaviors were collected through a questionnaire. Forty-five text messages were designed, pre-tested and sent to the seafarers’ phones in the intervention group in 45 days. Both groups were followed up 1 month after the intervention. Data collected in the two stages were analyzed using paired-samples t-test, ANCOVA, and Chi-square tests.

Results

Following the intervention, the mean scores of adopting skin cancer preventive behaviors (p = 0.001), perceived self-efficacy (p = 0.01), protection motivation (p = 0.02), and fear (p = 0.001) were significantly higher in the intervention group than the control group. There was significant reduction in the response costs (p = 0.05) and perceived rewards (p = 0.01) scores in the intervention group compared with the control group after the intervention. However, there were no significant differences in the perceived vulnerability (p = 0.14), perceived severity (p = 0.09), and response efficacy (p = 0.64) between the two groups after the intervention.

Conclusions

The results of the study indicated the effectiveness of mobile phone-based text message intervention for increasing skin cancer preventive behaviors in Iranian seafarers.

Trial registration

Iranian Registry for Clinical Trial (the link to trial: https://www.irct.ir/trial/7572). Registered 16 July, 2016. Prospectively registered.
Total spine magnetic resonance imaging for detection of multifocal infection in pyogenic spondylodiscitis: a retrospective observational study
Authors: Henkelmann Jeanette , Denecke Timm , Pieroh Philipp , Einhorn Stephanie , von der Hoeh Nicolas H. , Heyde Christoph-Eckhard , Voelker Anna
Published: January 2021

Background

Due to the unspecific symptoms of spondylodiscitis (SpD), an early radiological examination is necessary. However, controversially discussed is the need for magnetic resonance imaging of the entire spine to exclude multisegmental infections and to determine the required surgical interventions. The aims of this study were to assess the incidence of multilevel non-contiguous pyogenic SpD and compare comorbidities, pain symptoms, and subsequent surgical strategies between unifocal (uSpD) and multifocal (mSpD) SpD.

Methods

We retrospectively evaluated the data of patients with confirmed, surgically treated, pyogenic SpD who had received a total spine MRI in a single spine center between 2016 and 2018. MRI findings were classified according to Pola-classification and demographics, duration of clinical symptoms (pain and neurology) and Charlson Comorbidity-Index (CCI) results were compared between uSpD und mSpD groups. Surgical therapy was evaluated in patients with mSpD.

Results

uSpD was detected by MRI in 69 of 79 patients (87%). Of these, mSpD was detected in 10 patients (13%) with 21 infected segments (cervical and/ or thoracic and/ or lumbar region). Age and CCI were similar between uSpD and mSpD and 24 of all SpD regions were clinically unapparent. All patients with uSpD were treated operatively. In seven patients with mSpD, all infected levels of the spine were treated surgically in a one-stage procedure; one patient had a two-stage procedure and one patient had surgery at the lumbar spine, and an additional infected segment of the upper thoracic spine was treated conservatively. One patient died before a planned two-stage procedure was performed.

Conclusions

Due to mSpD being found in approximately 13% of SpD cases, and considering the risk of overlooking an mSpD case, MRI imaging of the total spine is recommended. The detection of multiple infection levels can have an impact on the therapeutic strategy chosen.