bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric properties of the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) among Hong Kong Chinese childhood cancer survivors
Authors: Ho K. Y. , Lam Katherine K. W. , Xia W. , Chung J. O. K. , Cheung Ankie T. , Ho Laurie L. K. , Chiu S. Y. , Chan Godfrey C. F. , Li William H. C.
Published: July 2021

Background

Sleep disruption is a prevalent symptom reported by survivors of childhood cancer. However, there is no validated instrument for assessing this symptom in this population group. To bridge the literature gap, this study translated and adapted the Pittsburgh Sleep Quality Index (PSQI) for Hong Kong Chinese cancer survivors and examined its psychometric properties and factor structure.

Methods

A convenience sample of 402 Hong Kong Chinese childhood cancer survivors aged 6–18 years were asked to complete the Chinese version of the PSQI, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Fatigue Scale-Child (FS-C)/Fatigue Scale-Adolescent (FS-A), and Pediatric Quality of Life Inventory (PedsQL). To assess known-group validity, 50 pediatric cancer patients and 50 healthy counterparts were recruited. A sample of 40 children were invited to respond by phone to the PSQI 2 weeks later to assess test–retest reliability. A cutoff score for the translated PSQI used with the survivors was determined using receiver operating characteristic analysis.

Results

The Chinese version of the PSQI had a Cronbach alpha of 0.71, with an intraclass correlation coefficient of 0.90. Childhood cancer survivors showed significantly lower mean PSQI scores than children with cancer, and significantly higher mean scores than healthy counterparts. This reflected that childhood cancer survivors had a better sleep quality than children with cancer, but a poorer sleep quality than healthy counterparts. We observed positive correlations between PSQI and CES-DC scores and between PSQI and FS-A/FS-C scores, but a negative correlation between PSQI and PedsQL scores. The results supported that the Chinese version of the PSQI showed convergent validity. Confirmatory factor analysis showed that the translated PSQI data best fit a three-factor model. The best cutoff score to detect insomnia was 5, with a sensitivity of 0.81 and specificity of 0.70.

Conclusion

The Chinese version of the PSQI is a reliable and valid instrument to assess subjective sleep quality among Hong Kong Chinese childhood cancer survivors. The validated PSQI could be used in clinical settings to provide early assessments for sleep disruption. Appropriate interventions can therefore be provided to minimize its associated long-term healthcare cost.

Trial registration This study was registered in ClinicalTrials.gov with the reference number NCT03858218.
A comparative study of perioperative and survival outcomes of robot-assisted radical cystectomy in patients over 80 and under 80 years old
Authors: Xie Shangxun , Zhao Zihan , Feng Baofu , Zhang Shiwei , Zhang Gutian , Li Xiaogong , Guo Hongqian , Yang Rong
Published: July 2021

Background

Radical cystectomy (RC) is the standard treatment for bladder cancer, but the safety and efficacy of this treatment for elderly people need to be considered. We compare perioperative data and survival outcomes between elderly (≥80 years) and younger (<80 years) patients undergoing robot-assisted radical cystectomy (RARC).

Methods

We reviewed demographic, perioperative clinical and follow-up data of 190 consecutive patients with urothelial carcinoma of bladder who received RARC from May 2015 to December 2018 in Nanjing Drum Tower Hospital. The patients were divided into 2 groups by age: ≥80 years and <80 years. Perioperative outcomes were compared between 2 groups. Logistic regression method was used to analyze the factors that may affect preoperative complications. Cox regression model was employed to analyze the factors affecting 3-year overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS).

Results

Of the 190 patients, 44 (23.2%) were octogenarians. The elderly patients did not statistically differ from younger patients in most of the demographic, perioperative, and pathological information. American Society of Anesthesiologists (ASA) score (p=0.045) and Charlson comorbidity index (CCI) (p=0.035) could predict high-grade and any grade complications, respectively. Positive lymph node and pT≥3 were main factors affecting OS, RFS, and CSS. ASA score (p=0.048) and CCI (p=0.003) could predict OS and RFS, respectively. Elderly group had worse OS (p=0.007) and CSS (p=0.027) but similar RFS (p=0.147) compared with younger group.

Conclusion

The elderly who received RARC had similar risk of perioperative complications and RFS compared with younger patients. RARC could be an alternative treatment for selected octogenarians.
Heart failure with preserved ejection fraction based on aging and comorbidities
Authors: Lin Ying , Fu Shihui , Yao Yao , Li Yulong , Zhao Yali , Luo Leiming
Published: July 2021

Heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of hospitalizations and mortality when diagnosed at the age of ≥ 65 years. HFpEF represents multifactorial and multisystemic syndrome and has different pathophysiology and phenotypes. Its diagnosis is difficult to be established based on left ventricular ejection fraction and may benefit from individually tailored approaches, underlying age-related changes and frequent comorbidities. Compared with the rapid development in the treatment of heart failure with reduced ejection fraction, HFpEF presents a great challenge and needs to be addressed considering the failure of HF drugs to improve its outcomes. Further extensive studies on the relationships between HFpEF, aging, and comorbidities in carefully phenotyped HFpEF subgroups may help understand the biology, diagnosis, and treatment of HFpEF. The current review summarized the diagnostic and therapeutic development of HFpEF based on the complex relationships between aging, comorbidities, and HFpEF.
Establishment, validation and evaluation of predictive model for early relapse after R0 resection in hepatocellular carcinoma patients with microvascular invasion
Authors: Zhang Kai , Tao Changcheng , Siqin Tana , Wu Jianxiong , Rong Weiqi
Published: July 2021

Backgrounds

This is the first study to build and evaluate a predictive model for early relapse after R0 resection in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).

Methods

The consecutive HCC patients with MVI who underwent hepatectomy in Cancer Hospital of Chinese Academy of Medical Science from Jan 2014 to June 2019 were retrospectively enrolled and randomly allocated into a derivation (N = 286) and validation cohort (N = 120) in a ratio of 7:3. Cox regression and Logistic regression analyses were performed and a predictive model for postoperative early-relapse were developed.

Results

A total of 406 HCC patients with MVI were included in our work. Preoperative blood alpha-fetoprotein (AFP) level, hepatitis B e antigen (HBeAg) status, MVI classification, largest tumor diameter, the status of serosal invasion, number of tumors, and the status of satellite nodules were incorporated to construct a model. The concordance index (C-index) was 0.737 and 0.736 in the derivation and validation cohort, respectively. The calibration curves showed a good agreement between actual observation and nomogram prediction. The C-index of the nomogram was obviously higher than those of the two traditional HCC staging systems.

Conclusion

We have developed and validated a prediction model for postoperative early-relapse in HCC patient with MVI after R0 resection.
Group 2 innate lymphoid cells are numerically and functionally deficient in the triple transgenic mouse model of Alzheimer’s disease
Authors: Fung Ivan Ting Hin , Zhang Yuanyue , Shin Damian S. , Sankar Poornima , Sun Xiangwan , D’Souza Shanti S. , Song Renjie , Kuentzel Marcy L. , Chittur Sridar V. , Zuloaga Kristen L. , Yang Qi
Published: July 2021

Background

The immune pathways in Alzheimer’s disease (AD) remain incompletely understood. Our recent study indicates that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the brain barriers of aged mice and that their activation alleviates aging-associated cognitive decline. The regulation and function of ILC2 in AD, however, remain unknown.

Methods

In this study, we examined the numbers and functional capability of ILC2 from the triple transgenic AD mice (3xTg-AD) and control wild-type mice. We investigated the effects of treatment with IL-5, a cytokine produced by ILC2, on the cognitive function of 3xTg-AD mice.

Results

We demonstrate that brain-associated ILC2 are numerically and functionally defective in the triple transgenic AD mouse model (3xTg-AD). The numbers of brain-associated ILC2 were greatly reduced in 7-month-old 3xTg-AD mice of both sexes, compared to those in age- and sex-matched control wild-type mice. The remaining ILC2 in 3xTg-AD mice failed to efficiently produce the type 2 cytokine IL-5 but gained the capability to express a number of proinflammatory genes. Administration of IL-5, a cytokine produced by ILC2, transiently improved spatial recognition and learning in 3xTg-AD mice.

Conclusion

Our results collectively indicate that numerical and functional deficiency of ILC2 might contribute to the cognitive impairment of 3xTg-AD mice.
Advances in HBV infection and replication systems in vitro
Authors: Xu Ruirui , Hu Pingping , Li Yuwen , Tian Anran , Li Jun , Zhu Chuanlong
Published: July 2021

Background

Hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family that has limited tissue and species specificity. Due to the persistence of HBV covalently closed circular DNA (cccDNA) in host cells after HBV infection, current antiviral drugs cannot eradicate HBV. Therefore, the development of an active cell culture system supporting HBV infection has become the key to studying HBV and developing effective therapeutic drugs.

Main body

This review summarizes the significant research achievements in HBV cell culture systems in vitro, including embryonic hepatocytes and primary hepatocytes, which support the virus infection process most similar to that in the body and various liver tumor cells. The discovery of the bile-acid pump sodium-taurocholate co-transporting polypeptide (NTCP) as the receptor of HBV has advanced our understanding of HBV biology. Subsequently, various liver cancer cells overexpressing NTCP that support HBV infection have been established, opening a new door for studying HBV infection. The fact that induced pluripotent stem cells that differentiate into hepatocyte-like cells support HBV infection provides a novel idea for the establishment of an HBV cell culture system.

Conclusion

Because of the host and tissue specificity of HBV, a suitable in vitro HBV infection system is critical for the study of HBV pathogenesis. Nevertheless, recent advances regarding HBV infection in vitro offer hope for better studying the biological characteristics of HBV, the pathogenesis of hepatitis B, the screening of anti-HBV drugs and the mechanism of carcinogenesis.
Association between frequency of spicy food consumption and hypertension: a cross-sectional study in Zhejiang Province, China
Authors: Wang Hao , Chen Lingli , Shen Dun , Cao Yuan , Zhang Xiaoyi , Xie Kaixu , Wang Chunmei , Zhu Shuiqing , Pei Pei , Guo Yu , Bragg Fiona , Yu Min , Chen Zhengming , Li Liming
Published: July 2021

Background

Hypertension is a known risk factor for multiple chronic diseases. Existing literature on the association between frequency of spicy food consumption and hypertension shows mixed findings.

Methods

The analyses are based on the Tongxiang baseline dataset of the China Kadoorie Biobank prospective study, including data from electronic questionnaires, physical measurements and blood sample collection. A total of 53,916 participants aged 30–79 years were included in the final analysis. Multivariable logistic regression was used to estimate the association of spicy food consumption with hypertension, and multiple linear regression was performed to explore the association of spicy food consumption with systolic and diastolic blood pressure.

Results

Of the 53,916 participants, 23,921 had prevalent hypertension. 12.3% of participants reported consuming spicy food weekly. Among female participants, after adjusting for socio-demographic status, lifestyle factors, BMI, waist circumference, sleep duration and snoring, when compared with females who never consumed spicy food, the odds ratios (95% CI) for hypertension were 1.02 (0.96–1.08), 0.90 (0.79–1.01), and 0.88 (0.78–0.99), respectively, for females who consumed spicy food less than once weekly, 1–2 times weekly, and ≥ 3 times weekly (Ptrend = 0.04). The corresponding odds ratios for males were 1.02 (0.95–1.09), 1.07 (0.95–1.20), and 0.91 (0.81–1.01), respectively (Ptrend = 0.39). Among current alcohol drinkers, compared to participants who never consumed spicy food, the odds ratio (95% CI) for hypertension among participants consuming spicy food daily was 0.98 (0.80–1.20). The corresponding figure for non-current drinkers was 0.72 (0.62–0.84). The association was stronger among non-current alcohol drinkers than among current drinkers (Pheterogeneity = 0.02).

Conclusions

Frequency of spicy food consumption is inversely associated with hypertension in females, but not in males.
Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Authors: Chu Xiaojing , Jaeger Martin , Beumer Joep , Bakker Olivier B. , Aguirre-Gamboa Raul , Oosting Marije , Smeekens Sanne P. , Moorlag Simone , Mourits Vera P. , Koeken Valerie A. C. M. , de Bree Charlotte , Jansen Trees , Mathews Ian T. , Dao Khoi , Najhawan Mahan , Watrous Jeramie D. , Joosten Irma , Sharma Sonia , Koenen Hans J. P. M. , Withoff Sebo , Jonkers Iris H. , Netea-Maier Romana T. , Xavier Ramnik J. , Franke Lude , Xu Cheng-Jian , Joosten Leo A. B. , Sanna Serena , Jain Mohit , Kumar Vinod , Clevers Hans , Wijmenga Cisca , Netea Mihai G. , Li Yang
Published: July 2021

Background

Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors.

Result

We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target.

Conclusion

This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets.
Efficacy of i-PRF in regenerative endodontics therapy for mature permanent teeth with pulp necrosis: study protocol for a multicentre randomised controlled trial
Authors: Liang Yuee , Ma Rongyang , Chen Lijuan , Dai Xingzhu , Zuo Shiya , Jiang Weiyi , Hu Naiming , Deng Zilong , Zhao Wanghong
Published: July 2021

Background

Dental pulp necrosis, a common health problem, is traditionally treated with root canal therapy; however, it fails in restoring the vitality of damaged pulp. Most studies regarding regenerative endodontic therapy (RET) are limited to the treatment of immature necrotic teeth. Given that injectable platelet-rich fibrin (i-PRF) has shown great potential in regenerative medicine as a novel platelet concentration, this study is designed to explore whether i-PRF can serve as a biological scaffold, extending the indications for RET and improving the clinical feasibility of RET in mature permanent teeth with pulp necrosis.

Methods

This is a randomised, double-blind, controlled, multicentre clinical trial designed to evaluate the clinical feasibility of RET for mature permanent teeth with pulp necrosis and to compare the efficacy of i-PRF and blood clots as scaffolds in RET. A total of 346 patients will be recruited from three centres and randomised at an allocation ratio of 1:1 to receive RET with either a blood clot or i-PRF. The changes in subjective symptoms, clinical examinations, and imaging examinations will be tracked longitudinally for a period of 24 months. The primary outcome is the success rate of RET after 24 months. The secondary outcome is the change in pulp vitality measured via thermal and electric pulp tests. In addition, the incidence of adverse events such as discolouration, reinfection, and root resorption will be recorded for a safety evaluation.

Discussion

This study will evaluate the clinical feasibility of RET in mature permanent teeth with pulp necrosis, providing information regarding the efficacy, benefits, and safety of RET with i-PRF. These results may contribute to changes in the treatment of pulp necrosis in mature permanent teeth and reveal the potential of i-PRF as a novel biological scaffold for RET.

Trial registration

ClinicalTrials.govNCT04313010. Registered on 19 March 2020
Stress tolerance enhancement via SPT15 base editing in Saccharomyces cerevisiae
Authors: Liu Yanfang , Lin Yuping , Guo Yufeng , Wu Fengli , Zhang Yuanyuan , Qi Xianni , Wang Zhen , Wang Qinhong
Published: July 2021

Background

Saccharomyces cerevisiaeis widely used in traditional brewing and modern fermentation industries to produce biofuels, chemicals and other bioproducts, but challenged by various harsh industrial conditions, such as hyperosmotic, thermal and ethanol stresses. Thus, its stress tolerance enhancement has been attracting broad interests. Recently, CRISPR/Cas-based genome editing technology offers unprecedented tools to explore genetic modifications and performance improvement ofS. cerevisiae.

Results

Here, we presented that the Target-AID (activation-induced cytidine deaminase) base editor of enabling C-to-T substitutions could be harnessed to generate in situ nucleotide changes on theS. cerevisiaegenome, thereby introducing protein point mutations in cells. The general transcription factor geneSPT15was targeted, and total 36 mutants with diversified stress tolerances were obtained. Among them, the 18 tolerant mutants against hyperosmotic, thermal and ethanol stresses showed more than 1.5-fold increases of fermentation capacities. These mutations were mainly enriched at the N-terminal region and the convex surface of the saddle-shaped structure of Spt15. Comparative transcriptome analysis of three most stress-tolerant (A140G, P169A and R238K) and two most stress-sensitive (S118L and L214V) mutants revealed common and distinctive impacted global transcription reprogramming and transcriptional regulatory hubs in response to stresses, and these five amino acid changes had different effects on the interactions of Spt15 with DNA and other proteins in the RNA Polymerase II transcription machinery according to protein structure alignment analysis.

Conclusions

Taken together, our results demonstrated that the Target-AID base editor provided a powerful tool for targeted in situ mutagenesis inS. cerevisiaeand more potential targets of Spt15 residues for enhancing yeast stress tolerance.
Phenotypic plasticity, canalisation and developmental stability of Triatoma infestans wings: effects of a sublethal application of a pyrethroid insecticide
Authors: Nattero Julieta , Mougabure-Cueto Gastón , Debat Vincent , Gürtler Ricardo E.
Published: July 2021

Background

Triatomine control campaigns have traditionally consisted of spraying the inside of houses with pyrethroid insecticides. However, exposure to sublethal insecticide doses after the initial application is a common occurrence and may have phenotypic consequences for survivors. Here, using Triatoma infestans (the main vector of Chagas disease in the Southern Cone of South America) as a model species, we quantified the effects of exposure to a sublethal dose of pyrethroid insecticide on wing morphology. We tested if the treatment (i) induced a plastic effect (change in the character mean); (ii) altered environmental canalisation (higher individual variation within genotypes); (iii) altered genetic canalisation (higher variation among genotypes); and (iv) altered developmental stability (higher fluctuating asymmetry [FA]).

Methods

Each of 25 full-sib families known to be susceptible to pyrethroid insecticides were split in two groups: one to be treated with a sublethal dose of deltamethrin (insecticide-treated group) and the other to be treated with pure acetone (control group). Wings of the emerging adults were used in a landmark-based geometric morphometry analysis to extract size and shape measurements. Average differences among treatments were measured. Levels of variation among families, among individuals within families and among sides within individuals were computed and compared among treatments.

Results

Wing size and shape were affected by a sublethal dose of deltamethrin. The treated insects had larger wings and a more variable wing size and shape than control insects. For both wing size and shape, genetic variation was higher in treated individuals. Individual variations and variations in FA were also greater in deltamethrin-treated insects than in control ones for all full-sib families; however, the patterns of shape variation associated with genetic variation, individual variation and FA were different.

Conclusions

Insects exposed to a sublethal dose of deltamethrin presented larger, less symmetrical and less canalised wings. The insecticide treatment jointly impaired developmental stability and genetic and environmental canalisation. The divergent patterns of shape variation suggest that the related developmental buffering processes differed at least partially. The morphological modifications induced by a single sublethal exposure to pyrethroids early in life may impinge on subsequent flight performance and consequently affect the dynamics of house invasion and reinfestation, and the effectiveness of triatomine control operations.

Graphical Abstract
Influence of glucocorticoid treatment on trabecular bone score and bone remodeling regulators in early rheumatoid arthritis
Authors: Corrado Addolorata , Rotondo Cinzia , Mele Angiola , Cici Daniela , Maruotti Nicola , Sanpaolo Eliana , Colia Ripalta , Cantatore Francesco Paolo
Published: July 2021

Background

Glucocorticoids (GC) modulate several regulators involved in the pathogenesis of bone changes in rheumatoid arthritis (RA). Trabecular bone score (TBS) allows the indirect assessment of bone quality. The aim of this study was to investigate the effects of GC on TBS and serum levels of bone turnover regulators in patients with recent-onset RA.

Materials and methods

Forty-seven subjects with recent-onset RA (< 6 months) were classified in two groups, low (lGC) and high (hGC) glucocorticoids, according to glucocorticoid dose regimens. Bone mineral density (BMD), TBS, and circulating Dickkopf-1 (Dkk1), sclerostin, osteoprotegerin (OPG), and RANK-L were evaluated at baseline and 6 and 12 months.

Results

BMD significantly declined after 12 months with no significant difference between the lGC and hGC group, whereas TBS decreased in the hGC group only. Circulating OPG decreased during the follow-up period, the reduction being significantly greater in hGC group; conversely, sclerostin and RANK-L serum increased, in a significantly greater extent in the hGC group. TBS inversely correlated with sclerostin, RANK-L, and Dkk1 circulating levels whereas directly correlated with OPG circulating levels. GC cumulative dose showed an inverse relationship with BMD in both the hGC and lGC groups; TBS values showed an inverse relationship with GC cumulative dose in the hGC group only. GC cumulative dose was associated to higher sclerostin and lower OPG serum levels. TBS did not correlate with disease activity whereas BMD was inversely related to disease activity.

Conclusions

In early RA, GC exposure contributes to the reduction of BMD and affects bone quality depending on dose regimens. TBS could be a useful tool to evaluate the negative effect of GC on bone microarchitecture.

Trial registration

This study was ancillary to a parallel-group observational prospective study which was approved by the medical local ethics committee (protocol number DDG 334/19-06-2019).
Oxidative phenotype induced by aerobic physical training prevents the obesity-linked insulin resistance without changes in gastrocnemius muscle ACE2-Angiotensin(1-7)-Mas axis
Authors: Vecchiatto Bruno , da Silva Rafael C. , Higa Talita S. , Muller Cynthia R. , Américo Anna Laura V. , Fortunato-Lima Vanessa C. , Ferreira Marília M. , Martucci Luiz Felipe , Fonseca-Alaniz Miriam H. , Evangelista Fabiana S.
Published: July 2021

Background

We investigate the effect of aerobic physical training (APT) on muscle morphofunctional markers and Angiotensin Converting Enzyme 2/Angiotensin 1-7/Mas receptor (ACE2/Ang 1-7/Mas) axis in an obesity-linked insulin resistance (IR) animal model induced by cafeteria diet (CAF).

Methods

Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR (chow diet, trained; n = 10), CAF-SED (n = 10) and CAF-TR (n = 10). APT consisted in running sessions of 60 min at 60% of maximal speed, 5 days per week for 8 weeks.

Results

Trained groups had lower body weight and adiposity compared with sedentary groups. CAF-TR improved the glucose and insulin tolerance tests compared with CAF-SED group (AUC = 28.896 ± 1589 vs. 35.200 ± 1076 mg dL−1120 min−1; kITT = 4.1 ± 0.27 vs. 2.5 ± 0.28% min−1, respectively). CHOW-TR and CAF-TR groups increased exercise tolerance, running intensity at which VO2max was reached, the expression of p-AMPK, p-ACC and PGC1-α proteins compared with CHOW-SED and CAF-SED. Mithocondrial protein expression of Mfn1, Mfn2 and Drp1 did not change. Lipid deposition reduced in CAF-TR compared with CAF-SED group (3.71 vs. 5.53%/area), but fiber typing, glycogen content, ACE2 activity, Ang 1-7 concentration and Mas receptor expression did not change.

Conclusions

The APT prevents obesity-linked IR by modifying the skeletal muscle phenotype to one more oxidative independent of changes in the muscle ACE2/Ang 1-7/Mas axis.
Applicability of human-specific STR systems, GlobalFiler™ PCR Amplification Kit, Investigator 24plex QS Kit, and PowerPlex® Fusion 6C in chimpanzee (Pan troglodytes)
Authors: Singh Abhishek , Sahajpal Vivek , Thakur Mukesh , Sharma Lalit Kumar , Chandra Kailash , Bhandari Deepika , Sharma Arun
Published: July 2021

Objectives

Human identification systems based on STRs are widely used in human population genetics and forensic analysis. This study aimed to validate the cross-reactivity of three widely known human-specific STR identification systems i.e. GlobalFiler™ PCR Amplification Kit, Investigator 24plex QS Kit, and PowerPlex® Fusion 6C in chimpanzee.

Results

The present study revealed the successful amplification of 18 loci using GlobalFiler™ PCR Amplification Kit, 18 loci using Investigator 24plex QS Kit, and 20 loci using PowerPlex® Fusion 6C system. The marker Amelogenin (AMEL) showed differential allele size between male and female revealing the gender identity of chimpanzees and thus validates their application concerning forensic examination, population estimation, and genetic analysis.
Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance
Authors: Keyvani-Ghamsari Saeedeh , Khorsandi Khatereh , Rasul Azhar , Zaman Muhammad Khatir
Published: July 2021

At present, after extensive studies in the field of cancer, cancer stem cells (CSCs) have been proposed as a major factor in tumor initiation, progression, metastasis, and recurrence. CSCs are a subpopulation of bulk tumors, with stem cell-like properties and tumorigenic capabilities, having the abilities of self-renewal and differentiation, thereby being able to generate heterogeneous lineages of cancer cells and lead to resistance toward anti-tumor treatments. Highly resistant to conventional chemo- and radiotherapy, CSCs have heterogeneity and can migrate to different organs and metastasize. Recent studies have demonstrated that the population of CSCs and the progression of cancer are increased by the deregulation of different epigenetic pathways having effects on gene expression patterns and key pathways connected with cell proliferation and survival. Further, epigenetic modifications (DNA methylation, histone modifications, and RNA methylations) have been revealed to be key drivers in the formation and maintenance of CSCs. Hence, identifying CSCs and targeting epigenetic pathways therein can offer new insights into the treatment of cancer. In the present review, recent studies are addressed in terms of the characteristics of CSCs, the resistance thereof, and the factors influencing the development thereof, with an emphasis on different types of epigenetic changes in genes and main signaling pathways involved therein. Finally, targeted therapy for CSCs by epigenetic drugs is referred to, which is a new approach in overcoming resistance and recurrence of cancer.
Gain of CXCR7 function with mesenchymal stem cell therapy ameliorates experimental arthritis via enhancing tissue regeneration and immunomodulation
Authors: Wei Sung-Tai , Huang Yen-Chih , Chiang Jung-Ying , Lin Chia-Ching , Lin Yu-Jung , Shyu Woei-Cherng , Chen Hui-Chen , Hsieh Chia-Hung
Published: July 2021

Background

The major barriers to mesenchymal stem cell (MSC) therapy in rheumatoid arthritis (RA) are a low extent of tissue regeneration and insufficient immunomodulation after cell transplantation. In addition, the role of C-X-C chemokine receptor type 7 (CXCR7) and its mechanism of action in MSC-mediated osteogenic or chondrogenic differentiation and immunomodulation are unclear.

Methods

Gain of CXCR7 function on human MSCs was carried out by lentiviral vector-mediated CXCR7 overexpression or CXCR7 agonist, TC14012. These cells were determined the role and potential mechanisms for CXCR7-regulated MSC differentiation and immunomodulation using cellular and molecular assays. The therapeutic benefits in RA were investigated in rats with collagen-induced arthritis (CIA).

Results

CXCR7 was upregulated in MSCs during the induction of osteogenic or chondrogenic differentiation. Blockage of CXCR7 function inhibited osteogenic or chondrogenic differentiation of MSCs whereas gain of CXCR7 function had the opposite effects. Besides, MSCs with CXCR7 gain-of-function facilitated macrophage apoptosis and regulatory T cell differentiation in a co-culture system. Gain of CXCR7 function also promoted the production of anti-inflammatory soluble factors. A gene expression profiling assay and signaling reporter assays revealed that CXCR7 could regulate several candidate genes related to the PPAR, WNT, Hedgehog or Notch pathways, and their signaling activities, which are known to control cell differentiation and immunomodulation. Finally, MSCs with CXCR7 gain-of-function significantly reduced the articular index scores, ankle circumference, radiographic scores, histologic scores, and inflammation in rats with CIA compared with control MSCs.

Conclusions

CXCR7 promotes the osteogenic and chondrogenic differentiation of MSCs and MSC-mediated immunomodulation by regulating several signaling pathways and anti-inflammatory soluble factors. MSCs with CXCR7 gain-of-function significantly ameliorate arthritic symptoms in a CIA model.
Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release
Authors: Zhou Lin , Zhang Tong , Shao Wei , Lu Ruohan , Wang Lin , Liu Haisheng , Jiang Bin , Li Shiqin , Zhuo Huiqin , Wang Suheng , Li Qinxi , Huang Caihua , Lin Donghai
Published: July 2021

Background

Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia.

Methods

The CT26 and LLC tumor cells were subcutaneously injected into mice to induce colon cancer cachexia and lung cancer cachexia, respectively. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 model and the LLC model were separately characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius.

Results

The CT26 and LLC cachexia models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue, and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. Both the CT26 and LLC cachexia mice showed increased plasma exosome densities which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis, and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius.

Conclusions

Amiloride ameliorates cachectic muscle wasting and alleviates cancer cachexia progression through inhibiting tumor-derived exosome release. Our results are beneficial to understanding the underlying molecular mechanisms, shedding light on the potentials of amiloride in cachexia therapy.
Efficacy of chest X-ray in the diagnosis of COVID-19 pneumonia: comparison with computed tomography through a simplified scoring system designed for triage
Authors: Çinkooğlu Akın , Bayraktaroğlu Selen , Ceylan Naim , Savaş Recep
Published: July 2021

Background

There is no consensus on the imaging modality to be used in the diagnosis and management of Coronavirus disease 2019 (COVID-19) pneumonia. The purpose of this study was to make a comparison between computed tomography (CT) and chest X-ray (CXR) through a scoring system that can be beneficial to the clinicians in making the triage of patients diagnosed with COVID-19 pneumonia at their initial presentation to the hospital.

Results

Patients with a negative CXR (30.1%) had significantly lower computed tomography score (CTS) (p < 0.001). Among the lung zones where the only infiltration pattern was ground glass opacity (GGO) on CT images, the ratio of abnormality seen on CXRs was 21.6%. The cut-off value of X-ray score (XRS) to distinguish the patients who needed intensive care at follow-up (n = 12) was 6 (AUC = 0.933, 95% CI = 0.886–0.979, 100% sensitivity, 81% specificity).

Conclusions

Computed tomography is more effective in the diagnosis of COVID-19 pneumonia at the initial presentation due to the ease detection of GGOs. However, a baseline CXR taken after admission to the hospital can be valuable in predicting patients to be monitored in the intensive care units.
Pulmonary mucormycosis presenting as central bronchopleural fistula—a case report with review of literature
Authors: Padmanaban Elamparidhi , Kannan Preethi , Amirthalingam Umamageswari , Pitchumani Sudhakar , Rekha Padma
Published: July 2021

Background

Bronchopleural fistula (BFF) is a fistulous communication between the trachea or bronchus and the pleural space. Central type of bronchopleural fistula is usually post-surgical. Infective cause for central bronchopleural fistula is rare. This case report encompasses an infective cause of central bronchopleural fistula, mucormycosis. Pulmonary mucormycosis is a rapidly progressive condition with high mortality. A high index of suspicion and timely intervention is required to alleviate fatal outcome. The present case is discussed in detail about the clinical presentation and diagnostic imaging of pulmonary mucormycosis presenting with central bronchopleural fistula.

Case presentation

Thirty-five years old diabetic male, presented with fever, productive cough, mild haemoptysis and chest pain for 10 days duration. The patient was pale on general examination and had decreased breath sound in the right suprascapular and interscapular areas with coarse crackles in the right infrascapular and infra-axillary areas. The laboratory investigations were unremarkable except for anaemia and raised blood glucose level. Sputum examination on potassium hydroxide (KOH) mount showed broad aseptate hyphae. There was a loculated right hydropneumothorax with collapsed lung in chest radiograph. Multi-detector computed tomography of the thorax revealed central type of bronchopleural fistula with the right main bronchus, consolidation of the middle lobe and superior segment of the right lower lobe with multiple internal thick-walled cavities. Right pneumonectomy was performed as the patient did not improve on medical management and showed worsening of symptoms. Histopathological examination was suggestive of mucormycosis.

Conclusion

Central bronchopleural fistula due to an infective aetiology is uncommon. However, mucormycosis should be considered as a differential diagnosis in cases of central bronchopleural fistula with the destroyed lung, especially in diabetic individuals. Hence, a high index of suspicion is necessary for early diagnosis and management as mucormycosis is a rapidly progressive disease with delay in treatment leading to high mortality.
COVID-19 Pandemic and Its Gendered Impact on Indian Physicians
Authors: Jiwnani Sabita , Ranganathan Priya , Tiwari Virendra , Ashok Apurva , Niyogi Devayani , Karimundackal George , Pramesh C. S.
Published: July 2021

PURPOSE

The 2018 WHO health workforce report analyzing gender equity in 104 countries reported that although women constituted 70% of the workers, they were less likely to be employed full-time and faced a 28% gender pay gap. The ongoing COVID-19 pandemic has affected professional as well as personal lives of physicians. We conducted a survey among Indian physicians to understand this impact.

METHODS

A 31-point anonymized survey to evaluate the impact of the COVID-19 pandemic and resultant lockdown on physicians' domestic responsibilities was disseminated via e-mail and text messaging applications. Our aim was to evaluate whether the impact was gender-based and to look for differences in aspects of domestic work, childcare, and professional commitments.

RESULTS

We obtained 1,041 responses, of which 643 identified themselves as men and 393 as women. An increase in the domestic responsibilities during the lockdown was confirmed by 90% of the women compared with 82% men. More women than men were solely responsible for domestic chores (38.7% v 23.7%), managed their children's education (74% v 31%), and felt an adverse impact of the pandemic on their professional work (60.8% v 42.6%). Fewer women's spouses (57/359) than men's (174/594, P = .00001) were forced to take leave or work reduced hours, and double the proportion of women (3.5% v 1.5%) had to quit their jobs to manage responsibilities at home.

CONCLUSION

As the COVID-19 pandemic and the lockdown measures threw newer challenges, more women physicians than men (81% v 63%) shouldered the burden of increased domestic work and childcare. This survey highlights the need to re-examine the specific challenges faced by women physicians and identify means to support and empower them.
Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001
Authors: Vrooman Lynda M. , Blonquist Traci M. , Stevenson Kristen E. , Supko Jeffrey G. , Hunt Sarah K. , Cronholm Sarah M. , Koch Victoria , Kay-Green Samantha , Athale Uma H. , Clavell Luis A. , Cole Peter D. , Harris Marian H. , Kelly Kara M. , Laverdiere Caroline , Leclerc Jean-Marie , Michon Bruno , Place Andrew E. , Schorin Marshall A. , Welch Jennifer J. G. , Neuberg Donna S. , Sallan Stephen E. , Silverman Lewis B.
Published: July 2021

PURPOSE

Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia (ALL) Consortium Protocol 11-001 assessed efficacy and toxicity of calaspargase pegol (calaspargase), a novel pegylated asparaginase formulation with longer half-life, compared with the standard formulation pegaspargase.

METHODS

Patients age 1 to ≤ 21 years with newly diagnosed ALL or lymphoblastic lymphoma were randomly assigned to intravenous pegaspargase or calaspargase, 2,500 IU/m2/dose. Patients received one induction dose. Beginning week 7, pegaspargase was administered every 2 week for 15 doses and calaspargase every 3 week for 10 doses (30 weeks). Serum asparaginase activity (SAA) (≥ 0.1 IU/mL considered therapeutic) was assessed 4, 11, 18, and 25 days after the induction dose and before each postinduction dose.

RESULTS

Between 2012 and 2015, 239 eligible patients enrolled (230 ALL, nine lymphoblastic lymphoma); 120 were assigned to pegaspargase and 119 to calaspargase. After the induction dose, SAA was ≥ 0.1 IU/mL in ≥ 95% of patients on both arms 18 days after dosing. At day 25, more patients had SAA ≥ 0.1 IU/mL with calaspargase (88% v 17%; P ˂ .001). Postinduction, median nadir SAAs were similar (≥ 1.0 IU/mL) for both arms. Of 230 evaluable patients, 99% of pegaspargase and 95% of calaspargase patients achieved complete remission ( P = .12), with no difference in frequency of high end-induction minimal residual disease among evaluable patients with B acute lymphoblastic leukemia (B-ALL). There were no differences in frequencies of asparaginase allergy, pancreatitis, thrombosis, or hyperbilirubinemia. With 5.3 years median follow-up, 5-year event-free survival for pegaspargase was 84.9% (SE ± 3.4%) and 88.1% (± SE 3.0%) for calaspargase ( P = .65).

CONCLUSION

Every 3-week calaspargase had similar nadir SAA, toxicity, and survival outcomes compared with every 2-week pegaspargase. The high nadir SAA observed for both preparations suggest dosing strategies can be further optimized.
Technological Progress and Health Convergence: The Case of Penicillin in Postwar Italy
Authors: Alsan Marcella , Atella Vincenzo , Bhattacharya Jay , Conti Valentina , Mejía-Guevara Iván , Miller Grant
Published: July 2021

Throughout history, technological progress has transformed population health, but the distributional effects of these gains are unclear. New substitutes for older, more expensive health technologies can produce convergence in population health outcomes but may also be prone to elite capture and thus divergence. We study the case of penicillin using detailed historical mortality statistics and exploiting its abruptly timed introduction in Italy after WWII. We find that penicillin reduced both the mean and standard deviation of infectious disease mortality, leading to substantial convergence across disparate regions of Italy. Our results do not appear to be driven by competing risks or confounded by mortality patterns associated with WWII.
A polarized nucleus-cytoskeleton-ECM connection in migrating cardioblasts controls heart tube formation in Drosophila
Authors: Dondi Cristiana , Bertin Benjamin , Da Ponte Jean-Philippe , Wojtowicz Inga , Jagla Krzysztof , Junion Guillaume
Published: July 2021

The formation of the cardiac tube is a remarkable example of complex morphogenetic processes conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts (CBs) prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. Here, we have identified CAP and MSP300 as novel actors involved during CB migration. They both exhibit highly similar temporal and spatial expression patterns in Drosophila migrating cardiac cells, and are necessary for the correct number and alignment of CBs, a prerequisite for the coordination of their collective migration. Our data suggest that CAP and MSP300 are part of a protein complex linking focal adhesion sites to nuclei via the actin cytoskeleton that maintains post-mitotic state and correct alignment of CBs.
Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells
Authors: Jarysta Amandine , Tarchini Basile
Published: July 2021

Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of actin-based stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here, we report a role for multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis in mouse. We show that MPDZ is enriched at the hair cell apical membrane along with MAGUK p55 subfamily member 5 (MPP5/PALS1) and the Crumbs protein CRB3. MPDZ is required there to maintain the proper segregation of apical blueprint proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia placement in Mpdz mutant hair cells, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.
The evolution of autophagy proteins – diversification in eukaryotes and potential ancestors in prokaryotes
Authors: Zhang Sidi , Hama Yutaro , Mizushima Noboru
Published: July 2021

Autophagy is a degradative pathway for cytoplasmic constituents, and is conserved across eukaryotes. Autophagy-related (ATG) genes have undergone extensive multiplications and losses in different eukaryotic lineages, resulting in functional diversification and specialization. Notably, even though bacteria and archaea do not possess an autophagy pathway, they do harbor some remote homologs of Atg proteins, suggesting that preexisting proteins were recruited when the autophagy pathway developed during eukaryogenesis. In this Review, we summarize our current knowledge on the distribution of Atg proteins within eukaryotes and outline the major multiplication and loss events within the eukaryotic tree. We also discuss the potential prokaryotic homologs of Atg proteins identified to date, emphasizing the evolutionary relationships and functional differences between prokaryotic and eukaryotic proteins.