bluuebunny/crossref_metadata_2025 huggingface dataset:
Game-Assisted Social Activism: Game Literacy in Hong Kong’s Anti-Extradition Movement
Authors: Lin Holin , Sun Chuen-Tsai
Published: January 2022

This paper describes the appropriation of video game culture for discursive use during the 2019–20 Hong Kong anti-extradition movement, with participants relying on game argot for mass protest communication and mobilization purposes, and employing game frameworks (especially from MMORPGs) for organizing protest actions. Data from online forums are used to present examples of video game rhetoric and narratives in protest-related online discourses, to speculate on their symbolic meanings, and to examine ways that borrowed aspects of game culture influenced movement activities. After describing ways that game culture spilled over into social movements, we highlight examples of gaming literacy during dynamic protest situations. Our evidence indicates that the combination of game culture and online gaming literacy strengthened activist toolkits and intensified the “be water” nature of a social movement that many describe as leaderless.
M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands
Authors: Hason Martina , Mikulasova Tereza , Machonova Olga , Pombinho Antonio , van Ham Tjakko J. , Irion Uwe , Nüsslein-Volhard Christiane , Bartunek Petr , Svoboda Ondrej
Published: January 2022

Macrophage colony-stimulating factor receptor (M-CSFR/CSF1R) signaling is crucial for the differentiation, proliferation, and survival of myeloid cells. The CSF1R pathway is a promising therapeutic target in many human diseases, including neurological disorders and cancer. Zebrafish are commonly used for human disease modeling and preclinical therapeutic screening. Therefore, it is necessary to understand the proper function of cytokine signaling in zebrafish to reliably model human-related diseases. Here, we investigate the roles of zebrafish Csf1rs and their ligands (Csf1a, Csf1b, and Il34) in embryonic and adult myelopoiesis. The proliferative effect of exogenous Csf1a on embryonic macrophages is connected to both receptors, Csf1ra and Csf1rb, however there is no evident effect of Csf1b in zebrafish embryonic myelopoiesis. Furthermore, we uncover an unknown role of Csf1rb in zebrafish granulopoiesis. Deregulation of Csf1rb signaling leads to failure in myeloid differentiation, resulting in neutropenia throughout the whole lifespan. Surprisingly, Il34 signaling through Csf1rb seems to be of high importance as both csf1rbΔ4bp-deficient and il34Δ5bp-deficient zebrafish larvae lack granulocytes. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests that csf1rb is expressed mainly by blood and myeloid progenitors, and the expression of csf1ra and csf1rb is nonoverlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis.
Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis
Authors: Locatelli Franco , Zugmaier Gerhard , Mergen Noemi , Bader Peter , Jeha Sima , Schlegel Paul-Gerhardt , Bourquin Jean-Pierre , Handgretinger Rupert , Brethon Benoit , Rössig Claudia , Kormany William N. , Viswagnachar Puneeth , Chen-Santel Christiane
Published: January 2022

The safety and efficacy of blinatumomab, a CD3/CD19-directed bispecific molecule, were examined in an open-label, single-arm, expanded access study (RIALTO). Children (>28 days and <18 years) with CD19+ relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) received up to 5 cycles of blinatumomab by continuous infusion (cycle: 4 weeks on/2 weeks off). The primary end point was incidence of adverse events. Secondary end points included complete response (CR) and measurable residual disease (MRD) response within the first 2 cycles and relapse-free survival (RFS), overall survival (OS), and allogeneic hematopoietic stem cell transplant (alloHSCT) after treatment. At final data cutoff (10 January 2020), 110 patients were enrolled (median age, 8.5 years; 88% had ≥5% baseline blasts). A low incidence of grade 3 or 4 cytokine release syndrome (n = 2; 1.8%) and neurologic events (n = 4; 3.6%) was reported; no blinatumomab-related fatal adverse events were recorded. The probability of response was not affected by the presence of cytogenetic/molecular abnormalities. Median OS was 14.6 months (95% confidence interval [CI]: 11.0-not estimable) and was significantly better for MRD responders vs MRD nonresponders (not estimable vs 9.3; hazard ratio, 0.18; 95% CI: 0.08-0.39). Of patients achieving CR after 2 cycles, 73.5% (95% CI: 61.4%-83.5%) proceeded to alloHSCT. One-year OS probability was higher for patients who received alloHSCT vs without alloHSCT after blinatumomab (87% vs 29%). These findings support the use of blinatumomab as a safe and efficacious treatment of pediatric R/R B-ALL. This trial was registered at www.clinicaltrials.gov as #NCT02187354.
The role of polyphenols in overcoming cancer drug resistance: a comprehensive review
Authors: Maleki Dana Parisa , Sadoughi Fatemeh , Asemi Zatollah , Yousefi Bahman
Published: January 2022

Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).
Evaluation of the phenotypic and genomic background of variability based on litter size of Large White pigs
Authors: Sell-Kubiak Ewa , Knol Egbert F. , Lopes Marcos
Published: January 2022

Background

The genetic background of trait variability has captured the interest of ecologists and animal breeders because the genes that control it could be involved in buffering various environmental effects. Phenotypic variability of a given trait can be assessed by studying the heterogeneity of the residual variance, and the quantitative trait loci (QTL) that are involved in the control of this variability are described as variance QTL (vQTL). This study focuses on litter size (total number born, TNB) and its variability in a Large White pig population. The variability of TNB was evaluated either using a simple method, i.e. analysis of the log-transformed variance of residuals (LnVar), or the more complex double hierarchical generalized linear model (DHGLM). We also performed a single-SNP (single nucleotide polymorphism) genome-wide association study (GWAS). To our knowledge, this is only the second study that reports vQTL for litter size in pigs and the first one that shows GWAS results when using two methods to evaluate variability of TNB: LnVar and DHGLM.

Results

Based on LnVar, three candidate vQTL regions were detected, on Sus scrofa chromosomes (SSC) 1, 7, and 18, which comprised 18 SNPs. Based on the DHGLM, three candidate vQTL regions were detected, i.e. two on SSC7 and one on SSC11, which comprised 32 SNPs. Only one candidate vQTL region overlapped between the two methods, on SSC7, which also contained the most significant SNP. Within this vQTL region, two candidate genes were identified, ADGRF1, which is involved in neurodevelopment of the brain, and ADGRF5, which is involved in the function of the respiratory system and in vascularization. The correlation between estimated breeding values based on the two methods was 0.86. Three-fold cross-validation indicated that DHGLM yielded EBV that were much more accurate and had better prediction of missing observations than LnVar.

Conclusions

The results indicated that the LnVar and DHGLM methods resulted in genetically different traits. Based on their validation, we recommend the use of DHGLM over the simpler method of log-transformed variance of residuals. These conclusions can be useful for future studies on the evaluation of the variability of any trait in any species.
MicroRNA biogenesis and activity in plant cell dedifferentiation stimulated by cell wall removal
Authors: Dełeńko Konrad , Nuc Przemysław , Kubiak Dawid , Bielewicz Dawid , Dolata Jakub , Niedojadło Katarzyna , Górka Sylwia , Jarmołowski Artur , Szweykowska-Kulińska Zofia , Niedojadło Janusz
Published: January 2022

Background

Despite the frequent use of protoplast-to-plant system in in vitro cultures of plants, the molecular mechanisms regulating the first and most limiting stages of this process, i.e., protoplast dedifferentiation and the first divisions leading to the formation of a microcallus, have not been elucidated.

Results

In this study, we investigated the function of miRNAs in the dedifferentiation of A. thaliana mesophyll cells in a process stimulated by the enzymatic removal of the cell wall. Leaf cells, protoplasts and CDPs (cells derived from protoplasts) cultured for 24, 72 and 120 h (first cell division). In protoplasts, a strong decrease in the amount of AGO1 in both the nucleus and the cytoplasm, as well as dicing bodies (DBs), which are considered to be sites of miRNA biogenesis, was shown. However during CDPs division, the amounts of AGO1 and DBs strongly increased. MicroRNA transcriptome studies demonstrated that lower amount of differentially expressed miRNAs are present in protoplasts than in CDPs cultured for 120 h. Then analysis of differentially expressed miRNAs, selected pri-miRNA and mRNA targets were performed.

Conclusion

This result indicates that miRNA function is not a major regulation of gene expression in the initial but in later steps of dedifferentiation during CDPs divisions. miRNAs participate in organogenesis, oxidative stress, nutrient deficiencies and cell cycle regulation in protoplasts and CDPs. The important role played by miRNAs in the process of dedifferentiation of mesophyll cells was confirmed by the increased mortality and reduced cell division of CDPs derived from mutants with defective miRNA biogenesis and miR319b expression.
tRNA-derived fragments from wheat are potentially involved in susceptibility to Fusarium head blight
Authors: Sun Zhengxi , Hu Yi , Zhou Yilei , Jiang Ning , Hu Sijia , Li Lei , Li Tao
Published: January 2022

Background

Fusarium head blight (FHB) caused by Fusarium graminearum is a devastating fungal disease of wheat. The mechanism underlying F. graminearum-wheat interaction remains largely unknown. tRNA-derived fragments (tRFs) are RNase-dependent small RNAs derived from tRNAs, and they have not been reported in wheat yet, and whether tRFs are involved in wheat-F. graminearum interactions remains unknown.

Results

Herein, small RNAs from the spikelets inoculated with F. graminearum and mock from an FHB-susceptible variety Chinese Spring (CS) and an FHB-resistant variety Sumai3 (SM) were sequenced respectively. A total of 1249 putative tRFs were identified, in which 15 tRFs was CS-specific and 12 SM-specific. Compared with mock inoculation, 39 tRFs were significantly up-regulated across both wheat varieties after F. graminearum challenge and only nine tRFs were significantly down-regulated. tRFGlu, tRFLys and tRFThr were dramatically induced by F. graminearum infection, with significantly higher fold changes in CS than those in SM. The expression patterns of the three highly induced tRFs were further validated by stem-loop qRT-PCR. The accumulation of tRFs were closely related to ribonucleases T2 family members, which were induced by F. graminearum challenge. The tRFs’ targets in host were predicted and were validated by RNA sequencing.

Conclusion

Integrative analysis of the differentially expressed tRFs and their candidate targets indicated that tRFGlu, tRFLys and tRFThr might negatively regulate wheat resistance to FHB. Our results unvealed the potential roles of tRFs in wheat-F. graminearum interactions.
Endophytic fungus Pseudodidymocyrtis lobariellae KL27 promotes taxol biosynthesis and accumulation in Taxus chinensis
Authors: Cao Xiaoying , Xu Lingxia , Wang Jingyi , Dong Mengmeng , Xu Chunyan , Kai Guoyin , Wan Wen , Jiang Jihong
Published: January 2022

Background

Taxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants.

Results

Here, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs.

Conclusions

Our results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.
CRISPR-Cas9-mediated mutagenesis of the SlSRM1-like gene leads to abnormal leaf development in tomatoes
Authors: Tang Yao , Li Huijia , Liu Chunxin , He Yuqing , Wang Hexuan , Zhao Tingting , Xu Xiangyang , Li Jingfu , Yang Huanhuan , Jiang Jingbin
Published: January 2022

Background

Leaves, which are the most important organs of plants, can not only fix carbon sources through photosynthesis, but also absorb nutrients through transpiration. Leaf development directly determines the growth, flowering and fruiting of plants. There are many factors that affect leaf development, such as the growth environment, gene expression, and hormone synthesis. In this study, tomatoes were used to study the role of the transcription factor Solanum lycopersicum salt-related MYB1-like (SlSRM1-like) in the development of tomato leaves.

Results

Loss-of-function of the SlSRM1-like gene mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) resulted in abnormal tomato leaf morphology, including thinner leaves, wrinkled edges, raised veins, disordered edge veins, and left and right asymmetry. An analysis of the transcription levels of genes related to leaf development revealed that the expression of these genes was significantly altered in the SlSRM1-like mutants (SlSRM1-like-Ms). Moreover, the SlSRM1-like gene was expressed at higher transcription levels in young tissues than in old tissues, and its expression was also induced in response to auxin. In addition, the transcription levels of genes related to the auxin pathway, which regulates tomato growth and development, were severely affected in the SlSRM1-like-Ms. Therefore, it is hypothesized that the SlSRM1-like gene functions in the regulation of tomato leaf development through the auxin-related pathway.

Conclusions

In this study, we successfully knocked out the SlSRM1-like gene in the tomato variety Ailsa Craig using CRISPR technology and found that knockout of the SlSRM1-like gene resulted in abnormal development of tomato leaves. Further research indicated that SlSRM1-like regulated tomato leaf development through auxin-related pathways. The results provide an important reference for the functional study of other SRM1-like genes in plants and provide new insights into the regulation of leaf development in tomato and other plants.
The composite risk index based on frailty predicts postoperative complications in older patients recovering from elective digestive tract surgery: a retrospective cohort study
Authors: Li Chun-Qing , Zhang Chen , Yu Fan , Li Xue-Ying , Wang Dong-Xin
Published: January 2022

Background

Limitations exist in available studies investigating effect of preoperative frailty on postoperative outcomes. This study was designed to analyze the association between composite risk index, an accumulation of preoperative frailty deficits, and the risk of postoperative complications in older patients recovering from elective digestive tract surgery.

Methods

This was a retrospective cohort study. Baseline and perioperative data of older patients (age ≥ 65 years) who underwent elective digestive tract surgery from January 1, 2017 to December 31, 2018 were collected. The severity of frailty was assessed with the composite risk index, a composite of frailty deficits including modified frailty index. The primary endpoint was the occurrence of postoperative complications during hospital stay. The association between the composite risk index and the risk of postoperative complications was assessed with a multivariable logistic regression model.

Results

A total of 923 patients were included. Of these, 27.8% (257) developed postoperative complications. Four frailty deficits, i.e., modified frailty index ≥0.27, malnutrition, hemoglobin < 90 g/L, and albumin ≤30 g/L, were combined to generate a composite risk index. Multivariable analysis showed that, when compared with patients with composite risk index of 0, the odds ratios (95% confidence intervals) were 2.408 (1.714–3.383, P <  0.001) for those with a composite risk index of 1, 3.235 (1.985–5.272, P <  0.001) for those with a composite risk index of 2, and 9.227 (3.568–23.86, P <  0.001) for those with composite risk index of 3 or above. The area under receiver-operator characteristic curve to predict postoperative complications was 0.653 (95% confidence interval 0.613–0.694, P <  0.001) for composite risk index compared with 0.622 (0.581–0.663, P <  0.001) for modified frailty index.

Conclusion

For older patients following elective digestive tract surgery, high preoperative composite risk index, a combination of frailty deficits, was independently associated with an increased risk of postoperative complications.
The association of zonulin-related proteins with prevalent and incident inflammatory bowel disease
Authors: Wang Xiao , Memon Ashfaque A. , Palmér Karolina , Hedelius Anna , Sundquist Jan , Sundquist Kristina
Published: January 2022

Background

Current evidence regarding the association of serum zonulin-related proteins (ZRP) levels with prevalent inflammatory bowel disease (IBD) is contradictory. Moreover, the association with the subsequent risk of incident IBD is still unexplored. This study aimed to investigate the association of serum ZRP levels with both prevalent and incident IBD.

Method

The study included a total of 130 women (51–61 years) from the Women’s Health in Lund Area (WHILA) study, which included 18 prevalent IBD (diagnosed before baseline) and 47 incident IBD diagnosed during the 17 years (median) follow-up and age- and sampling time-matched controls. Serum ZRP was tested in all participants by ELISA.

Results

The serum ZRP levels were significantly higher in prevalent IBD compared to their matched controls (63.2 ng/ml vs 57.0 ng/ml, p = 0.02), however, no evidence of a difference in ZRP levels was found between the women who developed IBD during the follow-up period and their matched controls (61.2 ng/ml vs 59.7 ng/ml, p = 0.34). Using linear mixed models, we found that the association between serum ZRP levels and prevalent IBD (β = 6.2, p = 0.01), remained after adjusting for potential confounders. Conditional logistic regression models showed no evidence of an association between ZRP level and incident IBD (OR 1.03, p = 0.34).

Conclusion

Higher serum ZRP levels were associated with prevalent IBD, but not with incident IBD in our study samples.
Brain CT can predict low lean mass in the elderly with cognitive impairment: a community-dwelling study
Authors: Chen Yun-Ting , Yu Chiun-Chieh , Lin Yu-Ching , Chan Shan-Ho , Lin Yi-Yun , Chen Nai-Ching , Lin Wei-Che
Published: January 2022

Background

The coexistence of sarcopenia and dementia in aging populations is not uncommon, and they may share common risk factors and pathophysiological pathways. This study aimed to evaluate the relationship between brain atrophy and low lean mass in the elderly with impaired cognitive function.

Methods

This cross-sectional study included 168 elderly patients who visited the multi-disciplinary dementia outpatient clinic at Kaohsiung Chang Gung Memorial Hospital for memory issues, between 2017 and 2019. The body composition was assessed by dual energy X-ray absorptiometry (DEXA) and CT based skeletal muscle index including L3 skeletal muscle index (L3SMI) and masseter muscle mass index (MSMI). The brain atrophy assessment was measured by CT based visual rating scale. Possible predictors of low lean mass in the elderly with cognitive impairement were identified by binary logistic regression. ROC curves were generated from binary logistic regression.

Results

Among the 81 participants, 43 (53%) remained at a normal appendicular skeletal muscle index (ASMI), whereas 38 (47%) showed low ASMI. Compared with the normal ASMI group, subjects with low ASMI exhibited significantly lower BMI, L3SMI, and MSMI (all p < 0.05), and showed significant brain atrophy as assessed by visual rating scale (p < 0.001). The accuracy of predictive models for low ASMI in the elderly with cognitive impairment were 0.875, (Area under curve (AUC) = 0.926, 95% confidence interval [CI] 0.844–0.972) in model 1 (combination of BMI, GCA and L3SMI) and 0.885, (Area under curve (AUC) = 0.931, [CI] 0.857–0.979) in model 2 (combination of BMI, GCA and MSMI).

Conclusions

Global cortical atrophy and body mass index combined with either L3 skeletal muscle index or masseter skeletal muscle index can predict low lean mass in the elderly with cognitive impairment.
The predictive utility of functional status at discharge: a population-level cohort analysis
Authors: Junek Mats L. , Jones Aaron , Heckman George , Demers Catherine , Griffith Lauren E. , Costa Andrew P.
Published: January 2022

Background

Functional status is a patient-important, patient-centered measurement. The utility of functional status measures to inform post-discharge patient needs is unknown. We sought to examine the utility of routinely collected functional status measures gathered from older hospitalized patients to predict a panel of post-discharge outcomes.

Methods

In this population-based retrospective cohort study, Adults 65+ discharged from an acute hospitalization between 4 November 2008 and 18 March 2016 in Ontario, Canada and received an assessment of functional status at discharge using the Health Outcomes for Better Information and Care tool were included. Multivariable regression analysis was used to determine the relationship between functional status and emergency department (ED) re-presentation, hospital readmission, long term care facility (LTCF) admission or wait listing (‘LTCF readiness’), and death at 180 days from discharge.

Results

A total of 80 020 discharges were included. 38 928 (48.6%) re-presented to the ED, 24 222 (30.3%) were re-admitted, 5 037 (6.3%) were LTCF ready, and 9 047 (11.3%) died at 180 days. Beyond age, diminished functional status at discharge was the factor most associated with LTCF readiness (adjusted Odds Ratio [OR] 4.11 for those who are completely dependent for activities of daily living compared to those who are independent; 95% Confidence Interval [CI]: 3.70-4.57) and death (OR 3.99; 95% CI: 3.67-4.35). Functional status also had a graded relationship with each outcome and improved the discriminability of the models predicting death and LTCF readiness (p<0.01) but not ED re-presentation or hospital re-admission.

Conclusion

Routinely collected functional status at discharge meaningfully improves the prediction of long term care home readiness and death. The routine assessment of functional status can inform post-discharge care and planning for older adults.
Frailty assessment and acute frailty service provision in the UK: results of a national ‘day of care’ survey
Authors: Knight Thomas , Atkin Catherine , Martin Finbarr C , Subbe Chris , Holland Mark , Cooksley Tim , Lasserson Daniel
Published: January 2022

Background

The incorporation of acute frailty services into the acute care pathway is increasingly common. The prevalence and impact of acute frailty services in the UK are currently unclear.

Methods

The Society for Acute Medicine Benchmarking Audit (SAMBA) is a day of care survey undertaken annually within the UK. SAMBA 2019 (SAMBA19) took place on Thursday 27th June 2019. A questionnaire was used to collect hospital and patient-level data on the structure and organisation of acute care delivery. SAMBA19 sought to establish the frequency of frailty assessment tool use and describe acute frailty services nationally. Hospitals were classified based on the presence of acute frailty services and metrics of performance compared.

Results

A total of 3218 patients aged ≥70 admitted to 129 hospitals were recorded in SAMBA19. The use of frailty assessment tools was reported in 80 (62.0%) hospitals. The proportion of patients assessed for the presence of frailty in individual hospitals ranged from 2.2 to 100%. Bedded Acute Frailty Units were reported in 65 (50.3%) hospitals. There was significant variation in admission rates between hospitals. This was not explained by the presence of a frailty screening policy or presence of a dedicated frailty unit.

Conclusion

Two fifths of participating UK hospitals did not have a routine frailty screening policy: where this existed, rates of assessment for frailty were variable and most at-risk patients were not assessed. Responses to positive results were poorly defined. The provision of acute frailty services is variable throughout the UK. Improvement is needed for the aspirations of national policy to be fully realised.
Associations between lifestyle factors and multidimensional frailty: a cross-sectional study among community-dwelling older people
Authors: van Assen Marcel A. L. M. , Helmink Judith H. M. , Gobbens Robbert J. J.
Published: January 2022

Background

Multidimensional frailty, including physical, psychological, and social components, is associated to disability, lower quality of life, increased healthcare utilization, and mortality. In order to prevent or delay frailty, more knowledge of its determinants is necessary; one of these determinants is lifestyle. The aim of this study is to determine the association between lifestyle factors smoking, alcohol use, nutrition, physical activity, and multidimensional frailty.

Methods

This cross-sectional study was conducted in two samples comprising in total 45,336 Dutch community-dwelling individuals aged 65 years or older. These samples completed a questionnaire including questions about smoking, alcohol use, physical activity, sociodemographic factors (both samples), and nutrition (one sample). Multidimensional frailty was assessed with the Tilburg Frailty Indicator (TFI).

Results

Higher alcohol consumption, physical activity, healthy nutrition, and less smoking were associated with less total, physical, psychological and social frailty after controlling for effects of other lifestyle factors and sociodemographic characteristics of the participants (age, gender, marital status, education, income). Effects of physical activity on total and physical frailty were up to considerable, whereas the effects of other lifestyle factors on frailty were small.

Conclusions

The four lifestyle factors were not only associated with physical frailty but also with psychological and social frailty. The different associations of frailty domains with lifestyle factors emphasize the importance of assessing frailty broadly and thus to pay attention to the multidimensional nature of this concept. The findings offer healthcare professionals starting points for interventions with the purpose to prevent or delay the onset of frailty, so community-dwelling older people have the possibility to aging in place accompanied by a good quality of life.
Determinants of trajectories of fatigability and mobility among older medical patients during and after hospitalization; an explorative study
Authors: Feenstra Marlies , van Munster Barbara C. , Smidt Nynke , de Rooij Sophia E.
Published: January 2022

Background

Fatigability is an important marker of functional decline in community dwelling older people, yet its relationship with functional decline after hospitalization is unclear. The objectives of this study were to identify trajectories of fatigability and mobility over time and to examine the association between demographic and clinical characteristics and these trajectories in medical patients aged 70 years and older admitted to a Dutch tertiary care teaching hospital.

Methods

In this prospective cohort study with baseline (in-hospital), discharge, three-, and six-months post discharge follow-up measurements, fatigability was assessed by the physical subscale of the Pittsburgh Fatigability Scale (PFS). Mobility was assessed by the De Morton Mobility Index (DEMMI). Group-based trajectory modeling was used to identify joint trajectories of fatigability and mobility. Covariates included demographic (age, sex, living situation, education) and clinical characteristics (functional status, frailty status, depression, comorbidity, length of hospital stay).

Results

Among 44 patients, three distinct fatigability trajectories and two mobility trajectories were identified over the course from hospital admission up to six months after discharge. Subsequently, three joint trajectories were identified, including low fatigability and high mobility (11%), improving fatigability and high mobility (52%), and high fatigability and low mobility (36%). Controlling for baseline functional status, patients with a lower comorbidity score (OR: 0.27, 95%CI 0.10; 0.74) and higher frailty status (OR: 1.36, 95%CI: 1.07; 1.74) were more likely to be a member of the high fatigability and low mobility trajectories.

Conclusions

From hospital admission up to six months after discharge, three distinct trajectories of fatigability and mobility were identified among older medical patients. Our results should be interpreted with caution due to the small sample size, but may inspire other researchers to determine the value of fatigability assessment in identifying older medical patients at risk for developing mobility problems.
An autopsied case report of spastic paraplegia with thin corpus callosum carrying a novel mutation in the SPG11 gene: widespread degeneration with eosinophilic inclusions
Authors: Hayakawa Mika , Matsubara Tomoyasu , Mochizuki Yoko , Takeuchi Chisen , Minamitani Motoyuki , Imai Masayuki , Kosaki Kenjiro , Arai Tomio , Murayama Shigeo
Published: January 2022

Background

The detailed neuropathological features of patients with autosomal recessive hereditary spastic paraplegia with a thin corpus callosum (TCC) and SPG11 mutations are poorly understood, as only a few autopsies have been reported. Herein, we describe the clinicopathological findings of a patient with this disease who received long-term care at our medical facility.

Case presentation

A Japanese man exhibited a mild developmental delay in early childhood and intellectual disability, followed by the appearance of a spastic gait by age 13. At the age of 25 years, he became bedridden and needed a ventilator. Genetic analysis revealed a homozygous splice site variant in the SPG11 gene (c. 4162–2A > G) after the provision of genetic counselling and acquisition of informed consent from his parents. He died of pneumonia at the age of 44. His brain weighed 967 g and was characterized by a TCC, and his spinal cord was flattened. Microscopically, degeneration was observed in the posterior spinocerebellar tract, the gracile fasciculus, and the posterior column in addition to the corticospinal tract. Marked neuronal loss and gliosis were observed in the anterior horn, Clarke’s column, and hypoglossal and facial nuclei. Various types of neurons, in addition to motor neurons, showed coarse eosinophilic granules that were immunoreactive for p62. The loss of pigmented neurons with gliosis was apparent in both the substantia nigra and locus coeruleus. Lateral geniculate body degeneration was a characteristic feature of this patient. Furthermore, peripheral Lewy body-related α-synucleinopathy and scattered α-synuclein–immunoreactive neurites in the locus coeruleus and reticular formation of the brainstem were observed.

Conclusions

In patients with hereditary spastic paraplegia with SPG11 mutations, a variety of clinical phenotypes develop due to widespread lesions containing p62-immunoreactive neuronal cytoplasmic inclusions. We herein report the lateral geniculate body as another degenerative site related to SPG11-related pathologies that should be studied in future investigations.
What is the added value of CT-angiography in patients with transient ischemic attack?
Authors: Maier Ilko L. , Herpertz Gerrit U. , Bähr Mathias , Psychogios Marios-Nikos , Liman Jan
Published: January 2022

Background

Transient ischemic attack (TIA) is an important predictor for a pending stroke. Guidelines recommend a workup for TIA-patients similar to that of stroke patients, including an assessment of the extra- and intracranial arteries for vascular pathologies with direct therapeutic implications via computed tomography angiography (CTA). Aim of our study was a systematic analysis of TIA-patients receiving early CTA-imaging and to evaluate the predictive value of TIA-scores and clinical characteristics for ipsilateral vascular pathologies and the need of an invasive treatment.

Methods

We analysed clinical and imaging data from TIA patients being admitted to a tertiary university hospital between September 2015 and March 2018. Following subgroups were identified: 1) no- or low-grade vascular pathology 2) ipsilateral high-risk vascular pathology and 3) high-risk findings that needed invasive, surgical or interventional treatment. We investigated established TIA-scores (ABCD2-, the ABCD3- and the SPI-II score) and various clinical characteristics as predictive factors for ipsilateral vascular pathologies and the need for invasive treatment.

Results

Of 812 patients, 531 (65.4%) underwent initial CTA in the emergency department. In 121 (22.8%) patients, ipsilateral vascular pathologies were identified, of which 36 (6.7%) needed invasive treatment. The ABCD2-, ABCD3- and SPI-II-scores were not predictive for ipsilateral vascular pathologies or the need for invasive treatment. We identified male sex (OR 1.579, 95%CI 1.049–2.377,p = 0.029), a short duration of symptoms (OR 0.692, 95% CI 0.542–0.884,p = 0.003), arterial hypertension (OR 1.718, 95%CI 0.951–3.104,p = 0.073) and coronary heart disease (OR 1.916, 95%CI 1.184–3.101,p = 0.008) as predictors for ipsilateral vascular pathologies. As predictors for the need of invasive treatment, a short duration of symptoms (OR 0.565, 95%CI 0.378–0.846,p = 0.006), arterial hypertension (OR 2.612, 95%OR 0.895–7.621,p = 0.079) and hyperlipidaemia (OR 5.681, 95%CI 0.766–42.117,p = 0.089) as well as the absence of atrial fibrillation (OR 0.274, OR 0.082–0.917,p = 0.036) were identified.

Conclusion

More than every fifth TIA-patient had relevant vascular findings revealed by acute CTA. TIA-scores were not predictive for these findings. Patients with a short duration of symptoms and a vascular risk profile including coronary heart disease, arterial hypertension and hyperlipidaemia most likely might benefit from early CTA to streamline further diagnostics and therapy.
A novel ferroptosis-related gene signature associated with cell cycle for prognosis prediction in patients with clear cell renal cell carcinoma
Authors: Chen Siteng , Zhang Encheng , Guo Tuanjie , Shao Jialiang , Wang Tao , Zhang Ning , Wang Xiang , Zheng Junhua
Published: January 2022

Background

It is of great urgency to explore useful prognostic markers for patients with clear cell renal cell carcinoma (ccRCC). Prognostic models based on ferroptosis-related gene (FRG) in ccRCC is poorly reported for now.

Methods

Comprehensive analysis of 22 FRGs were performed in 629 ccRCC samples from two independent patient cohorts. We carried out least absolute shrinkage and selection operator analysis to screen out prognosis-related FRGs and constructed prognosis model for patients with ccRCC. Weighted gene co-expression network analysis was also carried out for potential functional enrichment analysis.

Results

Based on the TCGA cohort, a total of 11 prognosis-associated FRGs were selected for the construction of the prognosis model. Significantly differential overall survival (hazard ratio = 3.61, 95% CI: 2.68–4.87, p < 0.0001) was observed between patients with high and low FRG score in the TCGA cohort, which was further verified in the CPTAC cohort with hazard ratio value of 5.13 (95% CI: 1.65–15.90, p = 0.019). Subgroup survival analysis revealed that our FRG score could significantly distinguish patients with high survival risk among different tumor stages and different tumor grades. Functional enrichment analysis illustrated that the process of cell cycle, including cell cycle-mitotic pathway, cytokinesis pathway and nuclear division pathway, might be involved in the regulation of ccRCC through ferroptosis.

Conclusions

We developed and verified a FRG signature for the prognosis prediction of patients with ccRCC, which could act as a risk factor and help to update the tumor staging system when integrated with clinicopathological characteristics. Cell cycle-related pathways might be involved in the regulation of ccRCC through ferroptosis.
Monitoring of post-transplant MLL-PTD as minimal residual disease can predict relapse after allogeneic HSCT in patients with acute myeloid leukemia and myelodysplastic syndrome
Authors: Kong Jun , Gao Meng-Ge , Qin Ya-Zhen , Wang Yu , Yan Chen-Hua , Sun Yu-Qian , Chang Ying-Jun , Xu Lan-Ping , Zhang Xiao-Hui , Liu Kai-Yan , Huang Xiao-Jun , Zhao Xiao-Su
Published: January 2022

Background

The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation.

Methods

We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People’s Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study.

Results

The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis.

Conclusions

Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.
Prognostic effect of lncRNA SNHG7 on cancer outcome: a meta and bioinformatic analysis
Authors: Zhang Yunyuan , Tian Qingwu , Huang Shifeng , Wang Qing , Wu Hongmei , Dong Qian , Chen Xian
Published: January 2022

Background

New evidence from clinical and fundamental researches suggests that SNHG7 is involved in the occurrence and development of carcinomas. And the increased levels of SNHG7 are associated with poor prognosis in various kinds of tumors. However, the small sample size was the limitation for the prognostic value of SNHG7 in clinical application. The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of SNHG7 in various cancers.

Methods

Articles related to the SNHG7 as a prognostic biomarker for cancer patients, were comprehensive searched in several electronic databases. The enrolled articles were qualified via the preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology checklists. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was further used to validate our results.

Results

We analyzed 2418 cancer patients that met the specified criteria. The present research indicated that an elevated SNHG7 expression level was significantly associated with unfavorable overall survival (OS) (HR = 2.45, 95% CI: 2.12–2.85, p <0.001). Subgroup analysis showed that high expression levels of SNHG7 were also significantly associated with unfavorable OS in digestive system cancer (HR = 2.31, 95% CI: 1.90–2.80, p <0.001) and non-digestive system cancer (HR = 2.67, 95% CI: 2.12–3.37, p <0.001). Additionally, increased SNHG7 expression was found to be associated with tumor stage and progression (III/IV vs. I/II: HR = 1.76, 95% CI: 1.57–1.98, p <0.001). Furthermore, elevated SNHG7 expression significantly predicted lymph node metastasis (LNM) (HR = 1.98, 95% CI: 1.74–2.26, p <0.001) and distant metastasis (DM) (HR = 2.49, 95% CI: 1.88–3.30, p <0.001) respectively. No significant heterogeneity was observed among these studies. SNHG7 was significantly upregulated in four cancers and the elevated expression of SNHG7 predicted shorter OS in four cancers, worse DFS in five malignancies and worse PFI in five carcinomas based on the validation using the GEPIA on-line analysis tool.

Conclusions

The present analysis suggests that elevated SNHG7 is significantly associated with unfavorable OS, tumor progression, LNM and DM in various carcinomas, and may be served as a promising biomarker to guide therapy for cancer patients.
Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors
Authors: Hajj Aline , Chamoun Rami , Salameh Pascale , Khoury Rita , Hachem Roula , Sacre Hala , Chahine Georges , Kattan Joseph , Rabbaa Khabbaz Lydia
Published: January 2022

Background

Cancer-related fatigue (CRF) is one of the most common and distressing complaints reported by cancer patients during chemotherapy considerably impacting all aspects of a patient’s life (physical, psychosocial, professional, and socioeconomic). The aim of this study was to assess the severity of cancer-related fatigue in a group of breast cancer patients undergoing chemotherapy and explore the association between fatigue scores and sociodemographic, clinical, biological, psychiatric, and genetic factors.

Methods

A cross-sectional pilot study carried out at the oncology outpatient unit of Hôtel-Dieu de France University Hospital recruited 67 breast cancer patients undergoing chemotherapy between November 2017 and June 2019 to evaluate fatigue using the EORTC QLQ-C30 scale (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire). Genotyping for seven gene polymorphisms (COMT, DRD2, OPRM1, CLOCK, PER2, CRY2, ABCB1) was performed using the Lightcycler® (Roche).

Results

The prevalence of fatigue was 46.3%. Multivariable analysis taking the fatigue score as the dependent variable showed that a higher number of cycles and a lower hemoglobin level were significantly associated with higher odds of exhibiting fatigue. Moreover, having at least one C allele for DRD2 SNP (vs. TT) was significantly associated with a 4.09 higher odds of expressing fatigue compared to TT patients. Finally, patients with at least one C allele for CLOCK SNP tended to display higher fatigue levels than TT patients.

Conclusions

Our study showed that anemic breast cancer patients with a high number of chemotherapy cycles and those carrying at least one C allele for DRD2 and CLOCK SNPs are at greater risk of exhibiting fatigue. Since no previous research has reported such genetic results, future studies are necessary to confirm our findings.