bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of ROS and cell cycle arrest in the genotoxicity induced by gold nanorod core/silver shell nanostructure
Authors: Wang Dan , Dan Mo , Ji Yinglu , Wu Xiaochun , Wang Xue , Wen Hairuo
Published: December 2020

To understand the genotoxicity induced in the liver by silver nanoparticles (AgNPs) and silver ions, an engineered gold nanorod core/silver shell nanostructure (Au@Ag NR) and humanized hepatocyte HepaRG cells were used in this study. The involvement of oxidative stress and cell cycle arrest in the DNA and chromosome damage induced by 0.4–20 µg mL−1 Au@Ag NR were investigated by comet assay, γ-H2AX assay and micronucleus test. Further, the distribution of Au@Ag NR was analyzed. Our results demonstrated that both Ag+ and Au@Ag NR led to DNA cleavage and chromosome damage (clastogenicity) in HepaRG cells and that the Au@Ag NR retained in the nucleus may further release Ag+, aggravating the damages, which are mainly caused by cell cycle arrest and ROS formation. The results reveal the correlation between the intracellular accumulation, Ag+ ion release and the potential genotoxicity of AgNPs.
Identification of Novel Alleles of the Rice Blast-Resistance Gene Pi9 through Sequence-Based Allele Mining
Authors: Zhou Ying , Lei Fang , Wang Qiong , He Weicong , Yuan Bin , Yuan Wenya
Published: December 2020

Background

As rice (Oryza sativa) is the staple food of more than half the world’s population, rice production contributes greatly to global food security. Rice blast caused by the fungus Magnaporthe oryzae (M. oryzae) is a devastating disease that affects rice yields and grain quality, resulting in substantial economic losses annually. Because the fungus evolves rapidly, the resistance conferred by most the single blast-resistance genes is broken after a few years of intensive agricultural use. Therefore, effective resistance breeding in rice requires continual enrichment of the reservoir of resistance genes, alleles, or QTLs. Seed banks represent a rich source of genetic diversity; however, they have not been extensively used to identify novel genes and alleles.

Results

We carried out a large-scale screen for novel blast-resistance alleles in 1883 rice varieties from major rice-producing areas across China. Of these, 361 varieties showed at least moderate resistance to natural infection by rice blast at rice blast nurseries in Enshi and Yichang, Hubei Province. We used sequence-based allele mining to amplify and sequence the allelic variants of the major rice blast-resistance genes at the Pi2/Pi9 locus of chromosome 6 from the 361 blast-resistant varieties, and the full-length coding region of this gene could be amplified from 107 varieties. Thirteen novel Pi9 alleles (named Pi9-Type1 to Pi9-Type13) were identified in these 107 varieties based on comparison to the Pi9 referenced sequence. Based on the sequencing results, the Pi2/Pi9 locus of the 107 varieties was divided into 15 genotypes (including three different genotypes of Pi9-Type5). Fifteen varieties, each representing one genotype, were evaluated for resistance to 34 M. oryzae isolates. The alleles from seven varieties with the highest resistance and widest resistance spectra were selected for transformation into the susceptible variety J23B to construct near-isogenic lines (NILs). These NILs showed resistance in a field test in Enshi and Yichang, indicating that the seven novel rice blast-resistance tandem-repeat regions at the Pi2/Pi9 locus of chromosome 6 could potentially serve as a genetic resource for molecular breeding of resistance to rice blast.

Conclusions

The thirteen novel Pi9 alleles identified in this study expand the list of available of blast-resistance alleles. Seven tandem-repeat regions of the Pi2/Pi9 locus from different donors were characterized as broad-spectrum rice blast-resistance fragments; these donors enrich the genetic resources available for rice blast-resistance breeding programs.
Different classes of small RNAs are essential for head regeneration in the planarian Dugesia japonica
Authors: Cao Zhonghong , Rosenkranz David , Wu Suge , Liu Hongjin , Pang Qiuxiang , Zhang Xiufang , Liu Baohua , Zhao Bosheng
Published: December 2020

Background

Planarians reliably regenerate all body parts after injury, including a fully functional head and central nervous system. But until now, the expression dynamics and functional role of miRNAs and other small RNAs during the process of head regeneration are not well understood. Furthermore, little is known about the evolutionary conservation of the relevant small RNAs pathways, rendering it difficult to assess whether insights from planarians will apply to other taxa.

Results

In this study, we applied high throughput sequencing to identify miRNAs, tRNA fragments and piRNAs that are dynamically expressed during head regeneration in Dugesia japonica. We further show that knockdown of selected small RNAs, including three novel Dugesia-specific miRNAs, during head regeneration induces severe defects including abnormally small-sized eyes, cyclopia and complete absence of eyes.

Conclusions

Our findings suggest that a complex pool of small RNAs takes part in the process of head regeneration in Dugesia japonica and provide novel insights into global small RNA expression profiles and expression changes in response to head amputation. Our study reveals the evolutionary conserved role of miR-124 and brings further promising candidate small RNAs into play that might unveil new avenues for inducing restorative programs in non-regenerative organisms via small RNA mimics based therapies.
Bioinformatic analysis and functional predictions of selected regeneration-associated transcripts expressed by zebrafish microglia
Authors: Issaka Salia Ousseini , Mitchell Diana M.
Published: December 2020

Background

Unlike mammals, zebrafish have a remarkable capacity to regenerate a variety of tissues, including central nervous system tissue. The function of macrophages in tissue regeneration is of great interest, as macrophages respond and participate in the landscape of events that occur following tissue injury in all vertebrate species examined. Understanding macrophage populations in regenerating tissue (such as in zebrafish) may inform strategies that aim to regenerate tissue in humans. We recently published an RNA-seq experiment that identified genes enriched in microglia/macrophages in regenerating zebrafish retinas. Interestingly, a small number of transcripts differentially expressed by retinal microglia/macrophages during retinal regeneration did not have predicted orthologs in human or mouse. We reasoned that at least some of these genes could be functionally important for tissue regeneration, but most of these genes have not been studied experimentally and their functions are largely unknown. To reveal their possible functions, we performed a variety of bioinformatic analyses aimed at identifying the presence of functional protein domains as well as orthologous relationships to other species.

Results

Our analyses identified putative functional domains in predicted proteins for a number of selected genes. For example, we confidently predict kinase function for one gene, cytokine/chemokine function for another, and carbohydrate enzymatic function for a third. Predicted orthologs were identified for some, but not all, genes in species with described regenerative capacity, and functional domains were consistent with identified orthologs. Comparison to other published gene expression datasets suggest that at least some of these genes could be important in regenerative responses in zebrafish and not necessarily in response to microbial infection.

Conclusions

This work reveals previously undescribed putative function of several genes implicated in regulating tissue regeneration. This will inform future work to experimentally determine the function of these genes in vivo, and how these genes may be involved in microglia/macrophage roles in tissue regeneration.
New view on the organization and evolution of Palaeognathae mitogenomes poses the question on the ancestral gene rearrangement in Aves
Authors: Urantówka Adam Dawid , Kroczak Aleksandra , Mackiewicz Paweł
Published: December 2020

Background

Bird mitogenomes differ from other vertebrates in gene rearrangement. The most common avian gene order, identified first inGallus gallus, is considered ancestral for all Aves. However, other rearrangements including a duplicated control region and neighboring genes have been reported in many representatives of avian orders. The repeated regions can be easily overlooked due to inappropriate DNA amplification or genome sequencing. This raises a question about the actual prevalence of mitogenomic duplications and the validity of the current view on the avian mitogenome evolution. In this context, Palaeognathae is especially interesting because is sister to all other living birds, i.e. Neognathae. So far, a unique duplicated region has been found in one palaeognath mitogenome, that ofEudromia elegans.

Results

Therefore, we applied an appropriate PCR strategy to look for omitted duplications in other palaeognaths. The analyses revealed the duplicated control regions with adjacent genes inCrypturellus, RheaandStruthioas well asND6pseudogene in three moas. The copies are very similar and were subjected to concerted evolution. Mapping the presence and absence of duplication onto the Palaeognathae phylogeny indicates that the duplication was an ancestral state for this avian group. This feature was inherited by early diverged lineages and lost two times in others. Comparison of incongruent phylogenetic trees based on mitochondrial and nuclear sequences showed that two variants of mitogenomes could exist in the evolution of palaeognaths. Data collected for other avian mitogenomes revealed that the last common ancestor of all birds and early diverging lineages of Neoaves could also possess the mitogenomic duplication.

Conclusions

The duplicated control regions with adjacent genes are more common in avian mitochondrial genomes than it was previously thought. These two regions could increase effectiveness of replication and transcription as well as the number of replicating mitogenomes per organelle. In consequence, energy production by mitochondria may be also more efficient. However, further physiological and molecular analyses are necessary to assess the potential selective advantages of the mitogenome duplications.
Linkage mapping and QTL analysis of flowering time using ddRAD sequencing with genotype error correction in Brassica napus
Authors: Scheben Armin , Severn-Ellis Anita A. , Patel Dhwani , Pradhan Aneeta , Rae Stephen J. , Batley Jacqueline , Edwards David
Published: December 2020

Background

Brassica napusis an important oilseed crop cultivated worldwide. During domestication and breeding ofB. napus, flowering time has been a target of selection because of its substantial impact on yield. Here we use double digest restriction-site associated DNA sequencing (ddRAD) to investigate the genetic basis of flowering inB. napus. An F2mapping population was derived from a cross between an early-flowering spring type and a late-flowering winter type.

Results

Flowering time in the mapping population differed by up to 25 days between individuals. High genotype error rates persisted after initial quality controls, as suggested by a genotype discordance of ~ 12% between biological sequencing replicates. After genotype error correction, a linkage map spanning 3981.31 cM and compromising 14,630 single nucleotide polymorphisms (SNPs) was constructed. A quantitative trait locus (QTL) on chromosome C2 was detected, covering eight flowering time genes includingFLC.

Conclusions

These findings demonstrate the effectiveness of the ddRAD approach to sample theB. napusgenome. Our results also suggest that ddRAD genotype error rates can be higher than expected in F2populations. Quality filtering and genotype correction and imputation can substantially reduce these error rates and allow effective linkage mapping and QTL analysis.
Prior exposure of Arabidopsis seedlings to mechanical stress heightens jasmonic acid-mediated defense against necrotrophic pathogens
Authors: Brenya Eric , Chen Zhong-Hua , Tissue David , Papanicolaou Alexie , Cazzonelli Christopher Ian
Published: December 2020

Background

Prolonged mechanical stress (MS) causes thigmomorphogenesis, a stress acclimation response associated with increased disease resistance. What remains unclear is if; 1) plants pre-exposed to a short period of repetitive MS can prime defence responses upon subsequent challenge with necrotrophic pathogens, 2) MS mediates plant immunity via jasmonic acid (JA) signalling, and 3) a short period of repetitive MS can cause long-term changes in gene expression resembling a stress-induced memory. To address these points, 10-days old juvenileArabidopsisseedlings were mechanically stressed for 7-days using a soft brush and subsequently challenged with the necrotrophic pathogens,Alternaria brassicicola,andBotrytis cinerea. Here we assessed how MS impacted structural cell wall appositions, disease symptoms and altered gene expression in response to infection.

Results

The MS-treated plants exhibited enhanced cell wall appositions and jasmonic acid (JA) accumulation that correlated with a reduction in disease progression compared to unstressed plants. The expression of genes involved in JA signalling, callose deposition, peroxidase and phytoalexin biosynthesis and reactive oxygen species detoxification were hyper-induced 4-days post-infection in MS-treated plants. The loss-of-function in JA signalling mediated by the JA-insensitivecoronatine-insensitive 1(coi1) mutant impaired the hyper-induction of defense gene expression and promoted pathogen proliferation in MS-treated plants subject to infection. The basal expression level ofPATHOGENESIS-RELATED GENE 1andPLANT DEFENSIN 1.2defense marker genes were constitutively upregulated in rosette leaves for 5-days post-MS, as well as in naïve cauline leaves that differentiated from the inflorescence meristem well after ceasing MS.

Conclusion

This study reveals that exposure of juvenileArabidopsisplants to a short repetitive period of MS can alter gene expression and prime plant resistance upon subsequent challenge with necrotrophic pathogens via the JA-mediatedCOI1signalling pathway. MS may facilitate a stress-induced memory to modulate the plant’s response to future stress encounters. These data advance our understanding of how MS primes plant immunity against necrotrophic pathogens and how that could be utilised in sustainable agricultural practices.
Nothing wrong about change: the adequate choice of the dependent variable and design in prediction of cognitive training success
Authors: Mattes André , Roheger Mandy
Published: December 2020

Background

Even though investigating predictors of intervention success (e.g Cognitive Training, CT) is gaining more and more interest in the light of an individualized medicine, results on specific predictors of intervention success in the overall field are mixed and inconsistent due to different and sometimes inappropriate statistical methods used. Therefore, the present paper gives a guidance on the appropriate use of multiple regression analyses to identify predictors of CT and similar non-pharmacological interventions.

Methods

We simulated data based on a predefined true model and ran a series of different analyses to evaluate their performance in retrieving the true model coefficients. The true model consisted of a 2 (between: experimental vs. control group) × 2 (within: pre- vs. post-treatment) design with two continuous predictors, one of which predicted the success in the intervention group and the other did not. In analyzing the data, we considered four commonly used dependent variables (post-test score, absolute change score, relative change score, residual score), five regression models, eight sample sizes, and four levels of reliability.

Results

Our results indicated that a regression model including the investigated predictor, Group (experimental vs. control), pre-test score, and the interaction between the investigated predictor and the Group as predictors, and the absolute change score as the dependent variable seemed most convenient for the given experimental design. Although the pre-test score should be included as a predictor in the regression model for reasons of statistical power, its coefficient should not be interpreted because even if there is no true relationship, a negative and statistically significant regression coefficient commonly emerges.

Conclusion

Employing simulation methods, theoretical reasoning, and mathematical derivations, we were able to derive recommendations regarding the analysis of data in one of the most prevalent experimental designs in research on CT and external predictors of CT success. These insights can contribute to the application of considered data analyses in future studies and facilitate cumulative knowledge gain.
Extraction of intra-biliary hepatocellular carcinoma by endoscopic retrograde cholangiopancreatography
Authors: Koo Chieh Sian , Ho Khek Yu , Pang Yin Huei , Huang Daniel Q.
Published: December 2020

Background

Hepatocellular carcinoma with biliary ductal invasion is rare and associated with a significantly lower survival rate.

Case presentation

We present an unusual case of a patient with hepatocellular carcinoma and biliary invasion, who had his diagnosis confirmed by histological analysis from tissue extracted by endoscopic retrograde cholangiopancreatography. An 87-year-old male presented with a 1-day history of right upper quadrant pain and jaundice. His past medical history included recurrent gallstone cholangitis and a previous cholecystectomy. An abdominal CT demonstrated a dilated intrahepatic biliary tree with left proximal intrahepatic hyperdensities, as well as a 3 cm hepatocellular carcinoma. He was initially suspected to have concurrent gallstone cholangitis and a newly diagnosed hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography and balloon trawling of the intraductal lesions extracted necrotic tumour-like tissue which was histologically consistent with hepatocellular carcinoma. The extraction of the intra-biliary portion of HCC resulted in complete resolution of his jaundice, enabling further treatment with nivolumab, which would not have been possible if the obstruction was not cleared. The patient is currently well and has completed his 6th cycle of nivolumab.

Conclusion

Obstructive jaundice is an uncommon presentation for patients with HCC. it is key for clinicians to be aware of the possibility of intrabiliary invasion in order obtain an early diagnosis and to reduce any delay in treatment.
‘I wanted to talk about it, but I couldn’t’, an H70 focus group study about experiencing depression in early late life
Authors: Rydberg Sterner Therese , Dahlin-Ivanoff Synneve , Gudmundsson Pia , Wiktorsson Stefan , Hed Sara , Falk Hanna , Skoog Ingmar , Waern Margda
Published: December 2020

Background

Knowledge about experiences of depression among younger-old adults from the general population is limited. The aim was to explore experiences of depression in early late life.

Methods

Sixteen participants in the population-based Gothenburg H70 Birth Cohort Studies (12 women and 4 men) who had reported a history of depression between ages 60–70 took part in focus group discussions (n = 4). Data were analyzed using focus group methodology.

Results

The analysis resulted in the overall theme ‘I wanted to talk about it, but I couldn’t’. The participants expressed unmet needs of communication about depression with family, friends, and healthcare staff. Participants wanted to know more about the causes and effects of depression, available treatment options and how to avoid recurrence. Lack of knowledge was a source of frustration; trust in health care providers was diminished. Being retired meant that opportunities for communication with co-workers were no longer available, and this made it harder to break negative thought and behavioral patterns. Being depressed meant losing one’s normal self, and participants were grieving this. Thoughts of death and suicide were experienced in solitude; knowing that there was an escape could generate a feeling of comfort and control.

Conclusions

Younger-old adults have expressed a need to talk about their experiences of depression. They would like to know more about available treatments, potential side effects, and how to avoid recurrence. Care providers also need to be aware there is a need for an existential dialogue about death.
Barriers to access and utilisation of HIV/STIs prevention and care services among trans-women sex workers in the greater Kampala metropolitan area, Uganda
Authors: Ssekamatte Tonny , Isunju John Bosco , Naume Muyanga , Buregyeya Esther , Mugambe Richard K. , Wanyenze Rhoda K. , Bukenya Justine N.
Published: December 2020

Background

Trans-women sex workers bear the greatest brunt of HIV and other sexually transmitted infections (STI). Trans-women are 49 times more at risk of HIV infections compared to the general population. However, they remain underserved and continue to grapple with access to and utilisation of HIV/STI prevention services. This study explored barriers to access and utilisation of HIV/STI prevention services and associated coping mechanisms.

Methods

This exploratory qualitative study was conducted among trans-women sex workers in the Greater Kampala Metropolitan area, Uganda. A total of 22 in-depth interviews, 6 key informant interviews and 9 focus group discussions were conducted to obtain data on barriers to access and utilisation of HIV and other STI prevention and care services, and coping strategies of trans-women sex workers. Data were analysed through thematic analysis using a hybrid of inductive and deductive approaches.

Results

Individual level barriers to access and utilisation of HIV/STI prevention and care services included internalised stigma and low socio-economic status. Healthcare system barriers included social exclusion and lack of recognition by other key population groups; stigmatisation by some healthcare providers; breach of confidentiality by some healthcare providers; limited hours of operation of some key population-friendly healthcare facilities; discrimination by straight patients and healthcare providers; stockout of STI drugs; inadequate access to well-equipped treatment centres and high cost of drugs. At community level, transphobia hindered access and utilisation of HIV/STI prevention and care services. The coping strategies included use of substitutes such as lotions, avocado or yoghurt to cope with a lack of lubricants. Herbs were used as substitutes for STI drugs, while psychoactive substances were used to cope with stigma and discrimination, and changing the dress code to hide their preferred gender identity.

Conclusions

Individual, community and healthcare system barriers hindered access and utilisation of HIV/STI prevention and care services among the trans-women sex workers. There is a need to create an enabling environment in order to enhance access to and utilisation of HIV/STI prevention and care services for trans-women sex workers through sensitisation of healthcare providers, other key population groups and the community at large on the transgender identity.
The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis
Authors: Ramos Rosa , Chazot Charles , Ferreira Anibal , Di Benedetto Attilio , Gurevich Konstantin , Feuersenger Astrid , Wolf Melanie , Arens Hans-Jürgen , Walpen Sebastian , Stuard Stefano
Published: December 2020

Background

The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients.

Methods

De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1−Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH).

Results

1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77–1.69 mmol/L during Q1–Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2–62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0–5.3 pills/day during Q1–Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1–2.8 pills/day).

Conclusion

In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.
Clinicopathological characteristics, treatment and prognosis of head & neck small cell carcinoma: a SEER population-based study
Authors: Yu Chen-xi , Yibulayin Feiluore , Feng Lei , Wang Meng , Lu Meng-meng , Luo Yuan , Liu Hui , Yang Zhi-cheng , Wushou Alimujiang
Published: December 2020

Background

To investigate the clinicopathological characteristics of head and neck small cell carcinoma (H&NSmCC) and identify prognostic factors on the basis of the Surveillance, Epidemiology and End Results (SEER) database.

Methods

Total of 789 primary cases from 1973 to 2016 were included. Univariate and multivariate analyses were performed to identify independent prognostic indicators. An H&NSmCC-specific nomogram was constructed and compared with the AJCC staging system by calculating the time-dependent area under the curve (AUC) of the receiver operating characteristic (ROC) curves.

Results

The incidence of H&NSmCC peaked during the period of 50 to 70 years old, and the most frequent location was the salivary gland. The 5-year disease specific survival (DSS) was 27%. In the multivariate survival analysis, AJCC III + IV stage [HR = 2.5, P = 0.03, I + II stage as Ref], positive N stage [HR = 1.67, P = 0.05, negative N stage as Ref], positive M stage [HR = 4.12, P = 0.000, negative M stage as Ref] and without chemotherapy [HR = 0.56, P = 0.023, received chemotherapy as Ref] were independently associated with DSS. The H&NSmCC-specific nomogram was built based on the independent prognostic indicators. The nomogram demonstrated better predictive capacity than the AJCC staging system for 5-year DSS [(AUC: 0.75 vs 0.634; Harrell’s C-index (95% CI): 0.7(0.66–0.74) vs 0.59(0.55–0.62), P < 0.05].

Conclusion

N stage, M stage, AJCC stage and chemotherapy were independent prognostic indicators included in the prognostic nomogram model, which can better predict the survival of H&NSmCC than the AJCC staging system.
Cancer patient management strategy in a Cancer Center of Zhejiang, China during the COVID-19 pandemic
Authors: Xu Songxiao , Cheng Xiangdong , Pan Zhiwen , Song Qian , Wang Yihong , Xiong Juan , Chen Yongyi , Fan Fan , Zhu Jing , Wu Wanying , Deng Xueying , Yu Yanpin , Xu Xiaohong , Chen Wenhu , Zhu Tao , Yu Yang , Liu Kaizhong , Shao Guoliang , Chen Ming , Yu Enyan
Published: December 2020

Background

Due to the increased risk of viral infection and the severe shortage of medical resources during the pandemic of COVID-19, most hospitals in the epidemic areas significantly reduced non-emergency admissions and services, if not closed. As a result, it has been difficult to treat cancer patients on time, which adversely affects their prognosis. To address this problem, cancer centers must develop a strategic plan to manage both inpatients and outpatients during the pandemic, provide them with the necessary treatment, and at the same time prevent the spread of the virus among patients, visitors and medical staff.

Methods

Based upon the epidemic situation in Zhejiang Province, China, the number of running non-emergency medical wards in the Zhejiang Cancer Hospital was gradually increased in a controlled manner. All staff of the hospital received COVID-19 preventive training and was provided with three different levels of protection according to the risks of their services. Only patients without a known history of SARS-CoV-2 contact were eligible to schedule an appointment. Body temperature was measured on all patients upon their arrival at the hospital. Chest CT image, blood cell counting and travel/contact history were investigated in patients with fever. Respiratory tract samples, such as sputum and throat swabs, from all patients, including those clinically suspected of SARS-CoV-2 infection, were collected for nucleic acid detection of SARS-CoV-2 before treatment.

Results

A total of 3697 inpatients and 416 outpatients seeking cancer treatment were enrolled from February 1 to April 3, 2020, in compliance with the hospital’s infection-control interventions. The clinicopathological parameters of the patients were summarized herein. 4237 samples from 4101 patients produced negative RNA testing results. Four clinically suspected patients all presented negative RNA test results and were excluded from the SARS-CoV-2 infection through follow-up retesting and monitoring. Seven patients with only N-gene positive results were retested, followed by CT scan and SARS-CoV-2 contact history investigation. All of them were finally diagnosed as non-infected patients. There was one outpatient who was confirmed positive by virus RNA test and then followed up. She might be an asymptomatic laboratory-confirmed case. During the study period, there was no SARS-CoV-2 infection among staff, patients and escorts of patients in the Zhejiang Cancer Hospital.

Conclusion

This study suggested our infection-control interventions, including viral nucleic acid test, could be used as a reliable method to screen cancer patients in the area with moderate COVID-19 prevalence. Cancer may not be a high-risk factor of SARS-CoV-2 infection.
Modified nodal stage of esophageal cancer based on the evaluation of the hazard rate of the negative and positive lymph node
Authors: Zhang Jinling , Li Hongyan , Zhou Liangjian , Yu Lianling , Che Fengyuan , Heng Xueyuan
Published: December 2020

Background

The study aimed to propose a modified N stage of esophageal cancer (EC) on the basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.

Method

Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.

Results

The numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. The log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of patients in the training population. The difference of all the patients using the modified N stage method were more significant than AJCC N stage. The result of ROC analysis indicated that the modified N stage could represent the N stage of EC more accurately.

Conclusion

The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.
Immune-related protein signature in serum stratify relapsed mantle cell lymphoma patients based on risk
Authors: Lokhande Lavanya , Kuci Emruli Venera , Kolstad Arne , Hutchings Martin , Räty Riikka , Jerkeman Mats , Ek Sara
Published: December 2020

Background

Response to modern treatment strategies, which combine cytotoxic compounds with immune stimulatory agents and targeted treatment is highly variable among MCL patients. Thus, providing prognostic and predictive markers for risk adapted therapy is warranted and molecular information that can help in patient stratification is a necessity. In relapsed MCL, biopsies are rarely available and molecular information from tumor tissue is often lacking. Today, the main tool to access risk is the MCL international prognostic index (MIPI), which does not include detailed biological information of relevance for different treatment options. To enable continuous monitoring of patients, non-invasive companion diagnostic tools are needed which can further reduce cost and patient distress and enable efficient measurements of biological markers.

Methods

We have assessed if serum-based protein profiling can identify immune related proteins that stratify relapsed MCL patients based on risk. Overall, 371 scFv targeting 158 proteins were assessed using an antibody microarray platform. We profiled patients (n = 44) who had been treated within the MCL6-Philemon trial combining targeted and immune-modulatory treatment.

Results

The downstream processing led to the identification of the relapsed immune signature (RIS) consisting of 11 proteins with potential to stratify patients with long and short overall survival (OS). Moreover, in this population, MIPI alone failed to separate high, intermediate and low risk patients, but a combined index based on MIPI together with RIS, MIPIris, showed improved performance and significantly stratified all three risk groups based on OS.

Conclusions

Our results show that addition of biological parameters to previous prognostic indices improves patient stratification among patients treated with BTK inhibitor triplet combination, particularly, in the identification of an extreme high risk group.
Distinct mutation profiles between primary bladder cancer and circulating tumor cells warrant the use of circulating tumors cells as cellular resource for mutation follow-up
Authors: Kim Tae-Min , Yoo Jin-seon , Moon Hyong Woo , Hur Kyung Jae , Choi Jin Bong , Hong Sung-Hoo , Lee Ji Youl , Ha U-Syn
Published: December 2020

Background

While circulating tumor cells may serve as minimally invasive cancer markers for bladder cancers, the relationship between primary bladder cancers and circulating tumor cells in terms of somatic mutations is largely unknown. Genome sequencing of bladder tumor and circulating tumor cells is highlighted to identify the somatic mutations of primary bladder cancer.

Methods

Bladder cancer tissue was collected by transurethral resection of the bladder and preserved by snap-freezing. Circulating tumor cells were Isolated from the blood obtained before treatment. We performed whole exome sequencing of 20 matched pairs of primary bladder cancers and circulating tumor cells to identify and compare somatic mutations of these two different genomic resources.

Results

We observed that mutation abundances of primary bladder cancers and circulating tumor cells were highly variable. The mutation abundance was not significantly correlated between matched pairs. Of note, the mutation concordance between two resources was only 3–24% across 20 pairs examined, suggesting that the circulating tumor cell genomes of bladder cancer patients might be genetically distinct from primary bladder cancers. A relative enrichment of mutations belonging to APOBEC-related signature and a depletion of C-to-G transversions were observed for primary- and circulating tumor cells specific mutations, respectively, suggesting that distinct mutation forces might have been operative in respective lesions during carcinogenesis.

Conclusions

The observed discrepancy of mutation abundance and low concordance level of mutations between genomes of primary bladder cancers and circulating tumor cells should be taken into account when evaluating clinical utility of circulating tumor cells for treatments and follow-up of bladder cancers.

Trial registration

Patients were selected and registered retrospectively, and medical records were evaluated.
Development and validation of the tool for the evaluation of the behavioral factors affecting the prevalence of musculoskeletal disorders in Iranian students
Authors: Nazari Mahin , Beigi Rokhsareh , Salesi Mahmood , Cousins Rosanna , Mokarami Hamidreza
Published: December 2020

Background

This study was conducted with the aim of developing a standard and valid questionnaire to evaluate the behavioral factors affecting musculoskeletal disorders among adolescent students based on the educational and ecological diagnosis phase of the PRECEDE model.

Methods

Based on the PRECEDE model and by using available resources and a panel of experts, a reservoir of items was proposed. The content validity of the questions was measured using content validity ratio (CVR) and content validity index (CVI). 400 Iranian first-year female high school students completed the questionnaire. The construct validity was assessed using confirmatory factor analysis (CFA). The reliability of the questionnaire was evaluated using Cronbach’s alpha coefficient.

Results

The age range of study students was 13.69 ± 0.86 years. The final developed questionnaire included 25 items in three dimensions: knowledge (9 items), attitude (10 items) and enabling factors (6 items). The mean scores of CVI and CVR were 0.97 and 0.92, respectively. The results of CFA confirmed the three-factor structure of the questionnaire. The Cronbach’s alpha coefficients of the dimensions of knowledge, attitude and enabling factors were 0.65, 0.80 and 0.71, respectively.

Conclusions

The present questionnaire had appropriate psychometric properties and could be used as a valid tool in evaluating the factors affecting the development of musculoskeletal disorders among adolescent students.
The effectiveness of parent training for children with autism spectrum disorder: a systematic review and meta-analyses
Authors: Deb Shoumitro , Retzer Ameeta , Roy Meera , Acharya Rupali , Limbu Bharati , Roy Ashok
Published: December 2020

Background

Various parent training interventions have been shown to have some effect on the symptoms of children with autism. We carried out a systematic review and meta-analyses to assess effectiveness of parental training for children with autism on their symptoms and parental stress.

Methods

Four electronic databases, CINAHL, EMBASE, MEDLINE and PsycINFO were searched until March 2020 for relevant literature. Two reviewers independently screened bibliographies using an eligibility checklist and extracted data using a structured proforma. We have also carried out meta-analyses when data were available for pooling.

Results

Seventeen papers from 15 studies were included for data analysis. Fifteen papers showed a positive treatment effect when compared with the control group, although not always significant. Meta-analysis based on pooled data from only two studies in each respective intervention, showed small to moderate treatment effects for three interventions, DIR/Floortime, Pivotal Response and Parent focused training respectively.

Conclusions

As in previous systematic reviews there was a mild to moderate treatment effects of three specific types of interventions respectively. However, it was difficult to draw any definitive conclusion about the effectiveness and generalisability of any intervention because of the wide variation in the interventions, control groups, outcome measures, small sample size, small number of studies in meta-analysis, overlap between the intervention and control procedures used in the included studies. There is an urgent need for experts in various international centres to jointly standardise a parent training intervention for children with autism and carry out a large scale RCT to assess its clinical and economic effectiveness.

Research Registry Unique Identifying Number: reviewregistry915.
The impact of the livelihoods and income fortification and socio-civic transformation project on the quality of life, wellbeing, self-esteem, and quality of neighbourhood social environment among the youth in slum areas of in Kampala, Uganda
Authors: Renzaho Andre M. N. , Doh Daniel , Mahumud Rashidul A. , Galukande Moses , Kamara Joseph K.
Published: December 2020

Background

Various interventions to improve the quality of life (QoL) among slum dwellers across sub Saharan Africa have been implemented. However, the interventions impacts remain less understood. We assessed the impact of the Urban Program on Livelihoods and Income Fortification and Socio-civic Transformation (UPLIFT) project on QoL, psychological wellbeing, self-esteem, and the quality of neighbourhood social environment of young people aged 13–25 years in slum areas of Makindye and Nakawa Divisions in Kampala, Uganda.

Methods

The study was designed as a mixed method evaluation using repeated cross-sectional survey and grounded theory in both the intervention and comparison communities. The intervention effect was estimated using the difference-in-differences Kernel propensity-score matching technique, with bootstrapping. The “rcs” option was used given that data were from repeated cross-sectional surveys. A thematic analysis was adopted for the qualitative data to triangulate and complement the quantitative data.

Results

The UPLIFT project led to an improvement in QoL, psychological wellbeing, and self-esteem of young people. In terms of QoL, the project led to a six-percentage point increase in quality of living conditions scores (where higher scores reflect better living conditions; lower ones, worse living conditions). However, a negative effect was observed for personal independence whilst the project did not have any impact on social relations. In terms of self-esteem and psychological wellbeing, the project led to a 4.6-point increase in self-esteem scores, a 5.4-point increase in self-acceptance scores, a 5.3- point increase in purpose in life scores, a 5.7 - point increase in personal growth, and a 10.7-point increase in autonomy scores. However, the project had a negative effect on personal independence; and had no impact on environmental mastery and the quality of neighbourhood social environment.

Conclusion

Functional community-owned assets accumulation and capacity building initiatives for young people in slum areas improved their psychological wellbeing and quality of life. However, such initiatives do not appear to address social relationships and personal independence of young people in slum areas.
Proximate, intermediate, and distal predictors of under-five mortality in Chad: analysis of the 2014–15 Chad demographic and health survey data
Authors: Ahinkorah Bright Opoku , Seidu Abdul-Aziz , Budu Eugene , Armah-Ansah Ebenezer Kwesi , Agbaglo Ebenezer , Adu Collins , Hagan John Elvis , Yaya Sanni
Published: December 2020

Background

Under-five mortality in Chad reached a minimum value of 119 deaths per 1000 live births in 2018, compared with a maximum of 250 in 1972. Despite this decline in the  mortality trend, for every six children in Chad, one dies before the age of five. This study, therefore, investigated the proximate, intermediate, and distal determinants of under-five mortality in Chad.

Methods

We used data from the 2014–15 Chad's Demographic and Health Survey. Data of 7782 children below 5 years were used for the study. Both descriptive and multivariable hierarchical logistic regression analyses were performed. Statistical significance was declared at p < 0.05.

Results

Under-five mortality was found to be 130 deaths per 1000 live births in Chad, with variations across the various population sub-groups. For distal predictors, the likelihood of death was higher in children born in the FChari Baguirmi region (AOR = 3.83, 95% CI: 1.81–8.14). Children whose mothers belonged to the Baguirmi/Barma ethnic group (AOR = 8.04, 95% CI: 1.75–36.99) were more likely to die before the age of five. On the contrary, the likelihood of under-five mortality was low among children born in rural areas (AOR = 0.73, 95% CI: 0.55–0.97). With the intermediate predictors, the likelihood of under-five deaths was higher among children whose mothers had no formal education (AOR = 1.72, 95% CI: 1.06–2.77). Regarding the proximate predictors, the odds of under-five deaths was higher among male children (AOR = 1.03, 95% CI: 1.05–1.63) and first rank children (AOR = 1.58, 95% CI: 1.13–2.21).

Conclusion

The study found that the determinants of under-five mortality in Chad are region of residence, place of residence, ethnicity, education, sex of child, and birth rank. These findings show that both socio-economic and proximate factors explain the disparities in under-five mortality in Chad. The identification of these factors can be pivotal towards the design of evidence-based interventions intended to improve child survival. Therefore, improving maternal education while refocusing and re-packaging existing strategies to target selected sub-regional populations with high under-five mortality is urgently required.