Simultaneous de novo calling and phasing of genetic variants at chromosome-scale using NanoStrand-seq.

The successful accomplishment of the first telomere-to-telomere human genome assembly, T2T-CHM13, marked a milestone in achieving completeness of the human reference genome. The upcoming era of genome study will focus on fully phased diploid genome assembly, with an emphasis on genetic differences between individual haplotypes. Most existing sequencing approaches only achieved localized haplotype phasing and relied on additional pedigree information for further whole-chromosome scale phasing. The short-read-based Strand-seq method is able to directly phase single nucleotide polymorphisms (SNPs) at whole-chromosome scale but falls short when it comes to phasing structural variations (SVs). To shed light on this issue, we developed a Nanopore sequencing platform-based Strand-seq approach, which we named NanoStrand-seq. This method allowed for de novo SNP calling with high precision (99.52%) and acheived a superior phasing accuracy (0.02% Hamming error rate) at whole-chromosome scale, a level of performance comparable to Strand-seq for haplotype phasing of the GM12878 genome. Importantly, we demonstrated that NanoStrand-seq can efficiently resolve the MHC locus, a highly polymorphic genomic region. Moreover, NanoStrand-seq enabled independent direct calling and phasing of deletions and insertions at whole-chromosome level; when applied to long genomic regions of SNP homozygosity, it outperformed the strategy that combined Strand-seq with bulk long-read sequencing. Finally, we showed that, like Strand-seq, NanoStrand-seq was also applicable to primary cultured cells. Together, here we provided a novel methodology that enabled interrogation of a full spectrum of haplotype-resolved SNPs and SVs at whole-chromosome scale, with broad applications for species with diploid or even potentially polypoid genomes.

Factors associated with perceived cognitive function in breast cancer patients treated with chemotherapy: A multicenter cross-sectional study.

PURPOSE: This study aimed to investigate the factors associated with perceived cognitive function among breast cancer patients treated with chemotherapy in China. METHODS: The study was a multicenter cross-sectional design. Data were collected from 10 public hospitals in China between April 2022 and February 2023. A total of 741 participants completed questionnaires assessing sociodemographic and medical characteristics, perceived cognitive function, sleep quality, fatigue, anxiety, and depression. Hierarchical multiple regression analysis was used to assess the determinants of cognitive function. RESULTS: The hierarchical multiple regression model accounted for 31.5% of variation in perceived cognitive function (sociodemographic 4.5%; medical 6.6%; exercise frequency 6.6%; sleep quality 2.1%; fatigue 2.8%; anxiety combined with depression 9.0%). Education level, chemotherapy type, number of chemotherapy cycles, and cyclophosphamide drug use were significant predisposing factors of perceived cognitive function (p < 0.001). Exercising ≥3 times/week (p < 0.001) was a significant factor positively influencing perceived cognitive function, meanwhile, anxiety (p < 0.001) and depression (p < 0 0.001) were negative factors. CONCLUSION: Our findings suggest that patients with low education levels, postoperative chemotherapy, cyclophosphamide treatment, and a greater number of chemotherapy cycles need more assessment. Sedentary patients, those who have never exercised, and those with anxiety or depression all showed greater cognitive decline. By identifying susceptible populations, encouraging regular exercise, and addressing anxiety and depression, healthcare professionals can contribute significantly to prevent patients' cognitive decline throughout chemotherapy.

Multi-centre analytical performance verification of an IVD assay to quantify donor-derived cell-free DNA in solid organ transplant recipients.

Donor-derived cell-free DNA (dd-cfDNA) has been widely studied as biomarker for non-invasive allograft rejection monitoring. Earlier rejection detection enables more prompt diagnosis and intervention, ultimately improving patient treatment and outcomes. This multi-centre study aims to verify analytical performance of a next-generation sequencing-based dd-cfDNA assay at end-user environments. Three independent laboratories received the same experimental design and 16 blinded samples to perform cfDNA extraction and the dd-cfDNA assay workflow. dd-cfDNA results were compared between sites and against manufacturer validation to evaluate concordance, reproducibility, repeatability and verify analytical performance. A total of 247 sample libraries were generated across 18 runs, with completion time of <24 h. A 96.0% first pass rate highlighted minimal failures. Overall observed versus expected dd-cfDNA results demonstrated good concordance and a strong positive correlation with linear least squares regression r2 = 0.9989, and high repeatability and reproducibility within and between sites, respectively (p > 0.05). Manufacturer validation established limit of blank 0.18%, limit of detection 0.23% and limit of quantification 0.23%, and results from independent sites verified those limits. Parallel analyses illustrated no significant difference (p = 0.951) between dd-cfDNA results with or without recipient genotype. The dd-cfDNA assay evaluated here has been verified as a reliable method for efficient, reproducible dd-cfDNA quantification in plasma from solid organ transplant recipients without requiring genotyping. Implementation of onsite dd-cfDNA testing at clinical laboratories could facilitate earlier detection of allograft injury, bearing great potential for patient care.

Construction and validation of a risk-prediction model for chemotherapy-related cognitive impairment in patients with breast cancer.

PURPOSE: To identify risk factors of chemotherapy-related cognitive impairment (CRCI) and construct and validate a visual prediction model of such for patients with breast cancer. METHODS: A multicenter, descriptive, and cross-sectional design was adopted. Data were collected from ten public tertiary hospitals in China. Cognitive function was assessed by using Functional Assessment of Cancer Therapy-cognitive function. Socio-demographic, clinical, psychological, and physical indicators were also assessed. The logistic prediction model was constructed by fivefold cross-validation. Then, a nomogram was utilized to visualize the prediction model, which was also evaluated via discrimination, calibration, and decision curve analysis. RESULTS: A total of 71 breast cancer patients had CRCI with a prevalence of 9.58%. This visual prediction model was constructed based on education background, exercise frequency, chemotherapy times, and fatigue and demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.882. The calibration curve indicated good agreement between experimental and projected values, and the decision curve proved good clinical applicability. CONCLUSION: Education background, exercise frequency, chemotherapy times, and fatigue were associated with high incidence of CRCI. The prediction model exhibits superior performance and has promise as a useful instrument for assessing the likelihood of CRCI in breast cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: Our findings could provide breast cancer survivors with risk screening based on CRCI predictors to implement prevention and early intervention, and help patients integrate into society and achieve comprehensive recovery.

Single-cell analysis reveals insights into epithelial abnormalities in ovarian endometriosis.

Ovarian endometriosis is characterized by the growth of endometrial tissue within the ovary, causing infertility and chronic pain. However, its pathophysiology remains unclear. Utilizing high-precision single-cell RNA sequencing, we profile the normal, eutopic, and ectopic endometrium from 34 individuals across proliferative and secretory phases. We observe an increased proportion of ciliated cells in both eutopic and ectopic endometrium, characterized by a diminished expression of estrogen sulfotransferase, which likely confers apoptosis resistance. After translocating to ectopic lesions, endometrial epithelium upregulates nicotinamide N-methyltransferase expression that inhibits apoptosis by promoting deacetylation and subsequent nuclear exclusion of transcription factor forkhead box protein O1, thereby leading to the downregulation of the apoptotic gene BIM. Moreover, epithelial cells in ectopic lesions elevate HLA class II complex expression, which stimulates CD4+ T cells and consequently contributes to chronic inflammation. Altogether, our study provides a comprehensive atlas of ovarian endometriosis and highlights potential therapeutic targets for modulating apoptosis and inflammation.

Absence of functional deficits in rats following systemic administration of an AAV9 vector despite moderate peripheral nerve and dorsal root ganglia findings: A clinically silent peripheral neuropathy.

Adeno-associated virus (AAV)-based vectors are commonly used for delivering transgenes in gene therapy studies, but they are also known to cause dorsal root ganglia (DRG) and peripheral nerve toxicities in animals. However, the functional implications of these pathologic findings and their time course remain unclear. At 2, 4, 6, and 8 weeks following a single dose of an AAV9 vector carrying human frataxin transgene in rats, non-standard functional assessments, including von Frey filament, electrophysiology, and Rotarod tests, were conducted longitudinally to measure allodynia, nerve conduction velocity, and coordination, respectively. Additionally, DRGs, peripheral nerves, brain and spinal cord were evaluated histologically and circulating neurofilament light chain (NfL) was quantified at 1, 2, 4, and 8 weeks, respectively. At 2 and 4 weeks after dosing, minimal-to-moderate nerve fiber degeneration and neuronal degeneration were observed in the DRGs in some of the AAV9 vector-dosed animals. At 8 weeks, nerve fiber degeneration was observed in DRGs, with or without neuronal degeneration, and in sciatic nerves of all AAV9 vector-dosed animals. NfL values were higher in AAV9 vector-treated animals at weeks 4 and 8 compared with controls. However, there were no significant differences in the three functional endpoints evaluated between the AAV9 vector- and vehicle-dosed animals, or in a longitudinal comparison between baseline (predose), 4, and 8 week values in the AAV9 vector-dose animals. These findings demonstrate that there is no detectable functional consequence to the minimal-to-moderate neurodegeneration observed with our AAV9 vector treatment in rats, suggesting a functional tolerance or reserve for loss of DRG neurons after systemic administration of AAV9 vector.

Effects of a 12-week exercise-based intervention on weight management in overweight or obese breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivors face dual challenges: long-term sequelae of treatment and the risk of recurrent disease. Furthermore, obesity and a sedentary lifestyle can complicate both challenges. We aimed to assess the effect of a 12-week exercise-based weight-management program in overweight/obese breast cancer survivors. METHODS: A two-arm, single-blinded, randomized controlled trial was conducted among 60 overweight/obese, stage 0-III breast cancer survivors. During the 12-week program, the intervention group received weekly information support, fortnightly exercise prescriptions, including aerobic and resistance exercises to perform at home, and one dietary instruction. The control group received information support about weight management and exercise. Weight, body composition, and physical fitness data were collected at baseline, postintervention, and the 3-month follow-up. RESULTS: The intervention group showed significant improvements in body weight and all adiposity indices, including body mass index, waist circumference, and %body fat, in comparison with baseline (P < 0.001) and the control group (P < 0.05). Both groups showed no significant changes in fat-free mass during the 6-month period (P > 0.05). International Physical Activity Questionnaire scores and left grip strength increased significantly in the intervention group in comparison with the baseline (P < 0.01) and the control group (P < 0.05). Right grip strength, lower-body strength, and aerobic endurance showed no significant intergroup differences (P > 0.05). CONCLUSIONS: A combination of exercise prescription and weight-loss interventions yielded clinically meaningful weight loss in overweight/obese breast cancer survivors. These findings may facilitate the incorporation of home-based exercise and weight management into breast cancer treatment and survivorship care.

Effectiveness of Nonpharmacologic Interventions for Chemotherapy-Induced Peripheral Neuropathy in Patients With Breast Cancer: A Systematic Review and Network Meta-analysis.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient. OBJECTIVE: To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC. METHODS: We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas). RESULTS: A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59). CONCLUSIONS: Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings. IMPLICATIONS FOR PRACTICE: This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.

Effectiveness of Nonpharmacologic Interventions for Chemotherapy-Related Cognitive Impairment in Breast Cancer Patients: A Systematic Review and Network Meta-analysis.

BACKGROUND: Neurotoxicity is a major adverse effect of chemotherapy in breast cancer (BC) patients. A number of nonpharmacologic interventions are used to alleviate chemotherapy-related cognitive impairment (CRCI), but no studies have compared their effectiveness. OBJECTIVES: The aim of this study was to identify and compare the effectiveness of different nonpharmacologic interventions for CRCI in BC patients. METHODS: A systematic review and network meta-analysis was conducted following the Cochrane guidelines. All randomized controlled trials were searched in the Cochrane Library, PubMed, MEDLINE (via OVID), Web of Science, EMBASE, and CINAHL databases from inception to September 2021. Studies using nonpharmacologic interventions to manage CRCI symptoms were included. A network meta-analysis and a comparative effects ranking were completed by STATA v14.0. RESULTS: Twelve studies with 8 nonpharmacologic interventions were included. For subjective outcomes on CRCI, there was no significant difference between nonpharmacologic interventions. For objective outcomes, qigong and exercise were more effective than the psychotherapy. Qigong and exercise were also more effective than music therapy. The top 3 interventions were psychotherapy (83.4%), music therapy (60.8%), and electroacupuncture (52.5%) for subjective outcomes and qigong (87.7%), exercise (82.1%), and electroacupuncture (70.3%) for objective outcomes. CONCLUSION: In the subjective evaluation, it was difficult to judge which interventions are best, but psychotherapy had the greatest probability. For objective evaluation, qigong and exercise may be the best nonpharmacologic interventions. IMPLICATIONS FOR PRACTICE: This study provides evidence for the effectiveness of nonpharmacologic interventions for CRCI in BC patients and facilitates support for future clinical trials and work.

Divergent Evolutionary Pathways of Myxoma Virus in Australia: Virulence Phenotypes in Susceptible and Partially Resistant Rabbits Indicate Possible Selection for Transmissibility.

To characterize the ongoing evolution of myxoma virus in Australian rabbits, we used experimental infections of laboratory rabbits to determine the virulence and disease phenotypes of recent virus isolates. The viruses, collected between 2012 and 2015, fell into three lineages, one of which, lineage c, experienced a punctuated increase in evolutionary rate. All viruses were capable of causing acute death with aspects of neutropenic septicemia, characterized by minimal signs of myxomatosis, the occurrence of pulmonary edema and bacteria invasions throughout internal organs, but with no inflammatory response. For the viruses of highest virulence all rabbits usually died at this point. In more attenuated viruses, some rabbits died acutely, while others developed an amyxomatous phenotype. Rabbits that survived for longer periods developed greatly swollen cutaneous tissues with very high virus titers. This was particularly true of lineage c viruses. Unexpectedly, we identified a line of laboratory rabbits with some innate resistance to myxomatosis and used these in direct comparisons with the fully susceptible rabbit line. Importantly, the same disease phenotype occurred in both susceptible and resistant rabbits, although virulence was shifted toward more attenuated grades in resistant animals. We propose that selection against inflammation at cutaneous sites prolongs virus replication and enhances transmission, leading to the amyxomatous phenotype. In some virus backgrounds this creates an immunosuppressive state that predisposes to high virulence and acute death. The alterations in disease pathogenesis, particularly the overwhelming bacterial invasions that characterize the modern viruses, suggest that their virulence grades are not directly comparable with earlier studies. IMPORTANCE The evolution of the myxoma virus (MYXV) following its release as a biological control for European rabbits in Australia is the textbook example of the coevolution of virus virulence and host resistance. However, most of our knowledge of MYXV evolution only covers the first few decades of its spread in Australia and often with little direct connection between how changes in virus phenotype relate to those in the underlying virus genotype. By conducting detailed experimental infections of recent isolates of MYXV in different lines of laboratory rabbits, we examined the ongoing evolution of MYXV disease phenotypes. Our results reveal a wide range of phenotypes, including an amyxomatous type, as well as the impact of invasive bacteria, that in part depended on the level of rabbit host resistance. These results provide a unique insight into the complex virus and host factors that combine to shape disease phenotype and viral evolution.

PEACE-S risk coping: A qualitative study exploring protective behavioral strategies of first-degree relatives of breast cancer survivors.

PURPOSE: Breast cancer is a major cause of morbidity worldwide and first-degree relatives of breast cancer survivors have a significantly higher risk of breast cancer that can be reduced by altering controllable risk factors. This study examined protective behavioral strategies used to cope with the risk in female first-degree relatives based on descriptions of their experiences, as well as their reason(s) for choosing a particular coping strategy. METHODS: A total of 25 first-degree relatives of breast cancer survivors in 13 families were recruited for this descriptive qualitative study. Data were collected between January and November 2020 through individual interviews, and a thematic analysis was performed using MAXQDA software. RESULTS: Three themes under an overarching theme of 'competition with breast cancer risk' were identified: (1) protective behavioral strategies for coping with breast cancer risk (four coping types); (2) barriers and facilitators for behavior change (five unfavorable and favorable factors related to the type of coping); and (3) significant determinants of coping strategy types. Based on these three themes, we developed a Personal restrictions, Exposure hazards, Adverse circumstances, Coping ability, Endorsement from social network, and Significant determinants ('PEACE-S') scale model of first-degree relatives' strategies for coping with breast cancer risk. CONCLUSIONS: First-degree relatives present different risk coping strategies that are shaped by individual and external factors and specific determinants. Our results provide insights that can help healthcare professionals design targeted interventions based on first-degree relatives' individual circumstances to mitigate breast cancer risk in this group through the adoption of healthy lifestyle choices.

Machine learning revealed molecular classification of colorectal cancer with negative lymph node metastasis.

Purpose: Accurate preoperative staging directly affects the treatment decision of patients with rectal cancer. However, our understanding of the immune subclasses of CRC without lymph node metastasis is still incomplete.Materials and methods: Here, we first analyzed the subclasses of CRC without lymph node metastasis on the Cancer Genome Atlas (TCGA) and verified its stability in the GSE39582 dataset. Four immune subclasses (C1-C4) were identified and verified by non-negative matrix factorization (NMF) of gene expression profiles. Then, ICI scores of six genes were constructed to characterize subclasses.Results: There were significant differences in metabolic and progression-associated signatures, immune characteristics, and clinical characteristics among subclasses. C3 represented a good prognosis with high TMB. C4 showed unique immune characteristics. We believe that C3 is the initial stage of CRC. After the C1 and C2 stages, it progresses to the C4 stage, and finally, lymph node metastasis occurs.Conclusions: This work may help to provide a basis for immunotherapy decision-making in early CRC and may guide personalized methods of cancer immunotherapy.

Biodistribution and Tolerability of AAV-PHP.B-CBh-SMN1 in Wistar Han Rats and Cynomolgus Macaques Reveal Different Toxicologic Profiles.

Recombinant adeno-associated viruses (AAVs) have emerged as promising vectors for human gene therapy, but some variants have induced severe toxicity in Rhesus monkeys and piglets following high-dose intravenous (IV) administration. To characterize biodistribution, transduction, and toxicity among common preclinical species, an AAV9 neurotropic variant expressing the survival motor neuron 1 (SMN1) transgene (AAV-PHP.B-CBh-SMN1) was administered by IV bolus injection to Wistar Han rats and cynomolgus monkeys at doses of 2 × 1013, 5 × 1013, or 1 × 1014 vg/kg. A dose-dependent degeneration/necrosis of neurons without clinical manifestations occurred in dorsal root ganglia (DRGs) and sympathetic thoracic ganglia in rats, while liver injury was not observed in rats. In monkeys, one male at 5 × 1013 vg/kg was found dead on day 4. Clinical pathology data on days 3 and/or 4 at all doses suggested liver dysfunction and coagulation disorders, which led to study termination. Histologic evaluation of the liver in monkeys showed hepatocyte degeneration and necrosis without inflammatory cell infiltrates or intravascular thrombi, suggesting that hepatocyte injury is a direct effect of the vector following hepatocyte transduction. In situ hybridization demonstrated a dose-dependent expression of SMN1 transgene mRNA in the cytoplasm and DNA in the nucleus of periportal to panlobular hepatocytes, while quantitative polymerase chain reaction confirmed the dose-dependent presence of SMN1 transgene mRNA and DNA in monkeys. Monkeys produced a much greater amount of transgene mRNA compared with rats. In DRGs, neuronal degeneration/necrosis and accompanying findings were observed in monkeys as early as 4 days after test article administration. The present results show sensory neuron toxicity following IV delivery of AAV vectors at high doses with an early onset in Macaca fascicularis and after 1 month in rats, and suggest adding the autonomic system in the watch list for preclinical and clinical studies. Our data also suggest that the rat may be useful for evaluating the potential DRG toxicity of AAV vectors, while acute hepatic toxicity associated with coagulation disorders appears to be highly species-dependent.

The effectiveness of non-pharmacological interventions on cancer related fatigue in breast cancer patients: A protocol for systematic review and network meta-analysis.

AIM: To assess the effect of different non-pharmacological interventions on cancer-related fatigue (CRF) in breast cancer (BC) patients and identify the most effective method for improving CRF. DESIGN: A systematic review and network meta-analysis. METHODS: Literature will be searched in the ongoing trail in the Clinical Trials.gov, World Health Organization, the International Clinical Trials Registry Platform, Cochrane Library, PubMed, EMBASE, Web of Science and CINAHL, from the inception until December 31, 2020. Two independent researchers will rigorously screen the literature according to the inclusion and exclusion criteria and assess the risk of bias based on the Cochrane Collaboration's Tool of RCTs. Stata 13.0 and Aggregate Data Drug Information System will be used for data analysis. RESULTS: This protocol has been registered on the PROSPERO website (registration number is CRD42020222093). This study will provide the reliable evidence of the most effective non-pharmacological intervention to improving CRF.

m6Am-seq reveals the dynamic m6Am methylation in the human transcriptome.

N6,2'-O-dimethyladenosine (m6Am), a terminal modification adjacent to the mRNA cap, is a newly discovered reversible RNA modification. Yet, a specific and sensitive tool to directly map transcriptome-wide m6Am is lacking. Here, we report m6Am-seq, based on selective in vitro demethylation and RNA immunoprecipitation. m6Am-seq directly distinguishes m6Am and 5'-UTR N6-methyladenosine (m6A) and enables the identification of m6Am at single-base resolution and 5'-UTR m6A in the human transcriptome. Using m6Am-seq, we also find that m6Am and 5'-UTR m6A respond dynamically to stimuli, and identify key functional methylation sites that may facilitate cellular stress response. Collectively, m6Am-seq reveals the high-confidence m6Am and 5'-UTR m6A methylome and provides a robust tool for functional studies of the two epitranscriptomic marks.

Development and validation of a nomogram to predict the risk of breast cancer-related lymphedema among Chinese breast cancer survivors.

PURPOSE: Breast cancer-related lymphedema (BCRL) is a major long-term complication for post-surgery breast cancer survivors. Although several risk factors have been identified, lifestyle characteristics have been neglected in previous studies. The aim of this study was to develop and validate a nomogram for estimating this population's risk of developing lymphedema, taking into consideration their demographic, clinical, and personal lifestyle behaviors. METHODS: In a cross-sectional study, we collected data from 775 post-operative breast cancer survivors who had attended a follow-up session in the recent 10 years (primary cohort). Lymphedema was assessed using the Norman telephone questionnaire, self-reported by patients. Multiple logistic regression was used to identify risk factors for lymphedema, including demographic, clinical, and lifestyle-related factors. A nomogram was constructed based on those factors and was validated using a separate group of 314 breast cancer patients (validation cohort). RESULTS: The factors independently associated with lymphedema were higher body mass index (BMI), modified radical mastectomy (MRM), postsurgical infection, chemotherapy, radiotherapy, exercise of the affected arm, and the active participation in physical activity (P<0.05). The area under the curve (AUC) values of the primary and the validation cohorts were 0.721 (95% confidence interval: 0.685-0.756) and 0.702 (95% confidence interval: 0.646-0.759), respectively. CONCLUSIONS: BCRL risk factors include MRM, radiotherapy, chemotherapy, and higher BMI, while the active physical activity behavior of patients appears to be a factor against lymphedema. The nomogram incorporating the patients' clinical and lifestyle factors might be useful for predicting lymphedema in breast cancer survivors.

Prevalence and predictors of breast cancer-related arm lymphedema over a 10-year period in postoperative breast cancer patients: A cross-sectional study.

PURPOSE: Breast cancer (BC) survivors have a lifelong risk of developing lymphedema. This study investigated the prevalence of BC-related arm lymphedema among Chinese BC survivors diagnosed in the last 10 years and examined the demographic and clinical variables as well as lifestyle factors associated with lymphedema status. METHODS: In this cross-sectional study, women with BC (N = 866) who had been diagnosed and followed up in the previous 10 years were recruited from the outpatient clinic of 4 general hospitals and one cancer association in China between August 2018 and October 2019. Lymphedema status was determined using the Norman telephone questionnaire as the patient-reported occurrence of hand/lower arm/upper arm swelling. Multiple logistic regression was used to identify risk factors for lymphedema. RESULTS: The median time from BC diagnosis was 4.0 years (interquartile range, 2.0-5.0 years). 81.4% of the patients had undergone mastectomy. The prevalence of arm lymphedema among BC survivors was 49.0%. Age ≥50 years, monthly income <3000 RMB, modified radical mastectomy, postsurgical wound infection, chemotherapy, and radiotherapy were associated with an increased risk of BC-related arm lymphedema, whereas exercise of the affected arm, engagement in active physical activity, and timely reporting of symptoms of infection to a physician decreased the risk (P < 0.05). CONCLUSIONS: Arm lymphedema is a common complication for postoperative BC survivors within 10 years. It is essential to identify patients at risk of lymphedema based on demographic, clinical, and lifestyle factors and implement interventions targeting modifiable lifestyle behaviors-eg, active physical activity during the postoperative period.

The m6A methylome of SARS-CoV-2 in host cells.

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency because of its rapid spread and high mortality. The molecular mechanism of interaction between host and viral genomic RNA is yet unclear. We demonstrate herein that SARS-CoV-2 genomic RNA, as well as the negative-sense RNA, is dynamically N6-methyladenosine (m6A)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 m6A sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified m6A sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that m6A methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host m6A methylome, exhibiting altered localization and motifs of m6A methylation in mRNAs. Altogether, our results identify m6A as a dynamic epitranscriptomic mark mediating the virus-host interaction.

Physician-Nurse Communication Surrounding Computerized Physician Order Entry Systems From Social and Technical Perspective: An Ethnographic Study.

Although computerized physician order entry systems improve order transmission and patient safety, overdependence on these systems can impede users' communication. This ethnographic study explored physician-nurse communication surrounding computerized physician order entry systems using a sociotechnical framework. Fieldwork conducted in a tertiary teaching hospital comprised 89 hours of participant observation, and individual semistructured interviews were held with seven nurses and five physicians. In addition, documents and artifacts were collected. Three core themes emerged. First, computerized physician order entry quality-related issues undermined the work efficiency of physicians and nurses. Specifically, usability was error prone because of cognitive overload, and the system was unable to perform relevant traces and raise alerts, demonstrating poor interoperability. Second, social factors, including insufficient training, unclear responsibilities, and a lack of awareness concerning interdisciplinary communication, compounded communication problems. Last, environmental factors, including noncoterminous spaces and times and insufficient technical support, impeded the resolution of communication problems. Technical and social contextual factors relating to computerized physician order entry systems jointly affected physician-nurse communication. Cognitive issues and insufficient alerts impacted work efficiency the most and were compounded by contextual individual- and team-related factors and environmental factors. Therefore, improved functions of computerized physician order entry systems and interprofessional communication training are required to optimize technical and social aspects of physician-nurse communication.

Effects of mindfulness-based cognitive therapy on breast cancer survivors with insomnia: A randomised controlled trial.

OBJECTIVE: We investigated the effects of mindfulness-based cognitive therapy on insomnia (MBCT-I) in breast cancer survivors. METHODS: In total, 136 participants were allocated randomly to a MBCT-I group or a waitlist control (WLC) group. Indicators of insomnia and mindfulness were evaluated using the Insomnia Severity Index, actigraphy and the Five Facet Mindfulness Questionnaire. Data were collected at baseline (T1), post-intervention (T2), 3-month follow-up (T3) and 6-month follow-up (T4) time points. RESULTS: Insomnia severity decreased significantly in the MBCT-I group, compared with the WLC group, at T2, T3 and T4 (all p < .001). We found that 59.6% of the MBCT-I group with moderate and severe insomnia improved to no insomnia and subclinical insomnia at T4 relative to T1, accounting for 7.9% and 55.3%, respectively. Compared with the WLC group, the MBCT-I group improved on actigraphy measures of sleep; they exhibited a pattern of decreased sleep onset latency and waking after sleep onset, as well as increased total sleep time and sleep efficiency. Mindfulness also increased more in the MBCT-I group than in the WLC group at T2, T3 and T4 (all p < .001). CONCLUSIONS: MBCT-I may be an efficacious non-pharmacologic intervention to improve sleep quality in breast cancer survivors.