The giant diploid faba genome unlocks variation in a global protein crop.

Increasing the proportion of locally produced plant protein in currently meat-rich diets could substantially reduce greenhouse gas emissions and loss of biodiversity1. However, plant protein production is hampered by the lack of a cool-season legume equivalent to soybean in agronomic value2. Faba bean (Vicia faba L.) has a high yield potential and is well suited for cultivation in temperate regions, but genomic resources are scarce. Here, we report a high-quality chromosome-scale assembly of the faba bean genome and show that it has expanded to a massive 13 Gb in size through an imbalance between the rates of amplification and elimination of retrotransposons and satellite repeats. Genes and recombination events are evenly dispersed across chromosomes and the gene space is remarkably compact considering the genome size, although with substantial copy number variation driven by tandem duplication. Demonstrating practical application of the genome sequence, we develop a targeted genotyping assay and use high-resolution genome-wide association analysis to dissect the genetic basis of seed size and hilum colour. The resources presented constitute a genomics-based breeding platform for faba bean, enabling breeders and geneticists to accelerate the improvement of sustainable protein production across the Mediterranean, subtropical and northern temperate agroecological zones.

Factors influencing older women's decision-making related to treatment of operable breast cancer: A qualitative systematic review.

OBJECTIVE: There is variation in practice in the treatment of older women with breast cancer. International guidelines highlight the importance of patient autonomy in treatment decision-making. The aim of this study is to identify factors which influence decision-making in older women with operable breast cancer, which will enable us to further understand how to support these patients. METHODS: Systematic review in accordance with the PRISMA guidelines was performed to identify factors which influence treatment decision-making in older women with operable breast cancer. Medline, Web of Science and SCOPUS were searched. RESULTS: The search yielded 5840 results; 13 articles met the inclusion criteria and reported on a total of 1118 women. Thematic analysis identified three key themes in which decision-making factors could be categorised. These were healthcare-related factors, patient-related factors and impact of treatment. Healthcare-related factors included communication with clinicians and provision of information. Patient-related factors were age, pre-existing knowledge, preconceptions of breast cancer and treatment, decision-making style and co-morbidities. The impact of treatment considerations included body image and effect on quality of life. Decision-making style was frequently reported; older women did not demonstrate one preferred style. CONCLUSIONS: The findings have highlighted the complex interplay of factors which influence how older women make breast cancer treatment-decisions. Clinicians should have an awareness of the factors highlighted to maximise their ability to provide support and personalised care to older women with breast cancer whilst treatment decisions are made.

Mask-Pyramid Network: A Novel Panoptic Segmentation Method.

In this paper, we introduce a novel panoptic segmentation method called the Mask-Pyramid Network. Existing Mask RCNN-based methods first generate a large number of box proposals and then filter them at each feature level, which requires a lot of computational resources, while most of the box proposals are suppressed and discarded in the Non-Maximum Suppression process. Additionally, for panoptic segmentation, it is a problem to properly fuse the semantic segmentation results with the Mask RCNN-produced instance segmentation results. To address these issues, we propose a new mask pyramid mechanism to distinguish objects and generate much fewer proposals by referring to existing segmented masks, so as to reduce computing resource consumption. The Mask-Pyramid Network generates object proposals and predicts masks from larger to smaller sizes. It records the pixel area occupied by the larger object masks, and then only generates proposals on the unoccupied areas. Each object mask is represented as a H × W × 1 logit, which fits well in format with the semantic segmentation logits. By applying SoftMax to the concatenated semantic and instance segmentation logits, it is easy and natural to fuse both segmentation results. We empirically demonstrate that the proposed Mask-Pyramid Network achieves comparable accuracy performance on the Cityscapes and COCO datasets. Furthermore, we demonstrate the computational efficiency of the proposed method and obtain competitive results.

The Association Between Medication Use in Older Women with Early-Stage Operable Primary Breast Cancer and Decision Regarding Primary Treatment.

BACKGROUND: Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status. METHODS: A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of diagnosis of breast cancer. Association was determined between number of medications and treatment decision and physical status as measured by the CGA outcomes. Additional analysis was performed to determine the associations above with polypharmacy defined by ≥5 daily medications, and if cardiovascular-related diseases have a role in the treatment decision. RESULTS: Polypharmacy was present in 48% of patients (n = 139). CGA determined that polypharmacy was associated with greater comorbidity (P < .001), reduced physical status rated by physicians (P = .009) and patients (P = .019), and reduced ability to perform activities of instrumental ADLs (P = .008). Similar findings were present in the analysis of cardiovascular-related diseases. CONCLUSIONS: This work suggests that patients with polypharmacy are more likely to be frail. The number of medications could help us screen patients who should go on to receive full CGA.

Oncoplastic breast surgery in older women with primary breast cancer: systematic review.

BACKGROUND: Oncoplastic procedures allow excision of larger breast tumours, or unfavourable tumour/breast ratio lesions while achieving a good cosmetic outcome. This increases the pool of patients eligible for breast conservation over mastectomy, reducing the need for more extensive surgery in older women and potentially improving their quality of life. Nonetheless, studies to date suggest a poor uptake of oncoplastic breast surgery in the older group. This review aimed to establish whether a disparity in uptake of oncoplastic breast surgery exists between older and younger women, and to explore the underlying reasons for this. METHODS: A literature search was conducted on 17 January 2022 using MEDLINE and Embase. Eligible studies comprised full-text articles of patients who underwent oncoplastic breast surgery for primary invasive breast cancer, and included those aged at least 65 years. RESULTS: Ten published studies were identified. One study was ranked as providing level 2 evidence, and the remainder were level 3. A total of 567 women underwent oncoplastic breast surgery for primary breast cancer, of whom only 61 (10.8 per cent) were aged 65 years or older. None of the studies directly compared younger with older women, or explored the underlying factors contributing to this discrepancy in uptake. CONCLUSION: This review has demonstrated a lower uptake of oncoplastic breast surgery in older compared with younger women. Given the increasing number of older women living with breast cancer who may be eligible for breast-conserving surgery, further research into this area is required.

Revisiting primary endocrine therapy versus surgery in older women with breast cancer: meta-analysis.

BACKGROUND: Old age is associated with increased co-morbidities, resulting in reduced life expectancy. Primary endocrine therapy is an alternative to primary surgical therapy for patients with breast cancer and increased co-morbidities. The aim was to review outcomes of primary endocrine therapy versus primary surgical therapy in older women with breast cancer. METHODS: PubMed, Embase (Ovid), Scopus, and the Cochrane Library were searched systematically from January 2000 to May 2022. Single-arm studies were excluded. Primary outcomes were overall survival and breast cancer-specific survival. Secondary outcomes were local and regional failure of primary endocrine therapy, recurrence after primary surgical therapy, and health-related quality of life. RESULTS: There were 14 studies including 14 254 patients (primary endocrine therapy 2829, 19.8 per cent; primary surgical therapy 11 425, 80.2 per cent), with the addition of four major studies (9538 patients) compared with the latest review in 2014. Seven studies defined primary surgical therapy as surgery plus adjuvant endocrine therapy, and six studies included patients with oestrogen receptor-positive tumours only. Patients in the primary endocrine therapy group were older than the primary surgical therapy group (mean difference 2.43 (95 per cent c.i. 0.73 to 4.13) years). Primary endocrine therapy led to worse overall survival than primary surgical therapy (HR 1.42, 95 per cent c.i. 1.06 to 1.91). Subgroup analysis of RCTs and prospective studies, however, showed comparable overall survival. Breast cancer-specific survival was also comparable (HR 1.28, 95 per cent c.i. 0.87 to 1.87). At 6 weeks, operated patients had significant arm symptoms and illness burden following major breast surgery compared with patients receiving primary endocrine therapy. Health-related quality of life, measured by the European Organization for Research and Treatment of Cancer QLQ-C30 and EuroQol EQ-5D-5L™, was comparable in the two treatment groups. CONCLUSION: Overall survival was worse among older women receiving primary endocrine therapy in an analysis including all studies, but comparable in RCTs and prospective studies. This may be due to confounding by age and co-morbidities in retrospective cohort studies of primary endocrine therapy.

Immediate breast reconstruction uptake in older women with primary breast cancer: systematic review.

BACKGROUND: Postmastectomy immediate breast reconstruction (PMIBR) may improve the quality of life of patients with breast cancer, of whom older women (aged 65 years or more) are a growing proportion. This study aimed to assess PMIBR in older women with regard to underlying impediments (if any). METHODS: MEDLINE, Embase, and PubMed were searched by two independent researchers up to June 2022. Eligible studies compared PMIBR rates between younger and older women with invasive primary breast cancer. RESULTS: A total of 10 studies (2012-2020) including 466 134 women were appraised, of whom two-thirds (313 298) were younger and one-third (152 836) older. Only 10.0 per cent of older women underwent PMIBR in contrast to 45.0 per cent of younger women. Two studies explored factors affecting uptake of PMIBR in older women; surgeon-associated (usual practice), patient-associated (socioeconomic status, ethnicity, and co-morbidities), and system-associated (insurance status and hospital location) factors were identified. CONCLUSION: Uptake of PMIBR in older women is low with definable (and some correctable) barriers.

Concordance between core needle biopsy and surgical excision specimens for Ki-67 in breast cancer - a systematic review of the literature.

AIMS: The biomarkers oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are routinely measured in patients with breast cancer with international consensus on how they should be interpreted. There is evidence to support use of other biomarkers to give more detailed predictive and prognostic information. Ki-67 is one example, and measures the proliferative activity of cancer cells. It is important that this can be performed at diagnosis of breast cancer for patients who do not have initial surgical treatment (mainly older women) and those receiving neoadjuvant therapies. METHODS AND RESULTS: A systematic review was performed to assess concordance of measurement of Ki-67 between core needle biopsy (CNB) samples and surgical excision (SE) samples in patients with invasive breast cancer. MEDLINE and Embase databases were searched. Studies were eligible if performed within the last 10 years; included quantitative measurement of Ki-67 in both CNB and SE samples with no prior breast cancer treatment; measured concordance between two samples; and had full text available. A total of 22 studies, including 5982 paired CNB and SE samples on which Ki-67 was measured, were appraised. Overall, there appeared to be concordance; however, reliability was unclear. Where given, the Cohen's kappa coefficient (κ) of correlation between samples ranged from 0.261 to 0.712. The concordance rate between CNB and SE where measured as a percentage had a range from 70.3 to 92.7% CONCLUSIONS: Assessment of level of concordance of Ki-67 between CNB and SE samples is hampered by different methodologies. International consensus on Ki-67 measurement is urgently needed.

Systematic review of the evidence sources applied to cost-effectiveness analyses for older women with primary breast cancer.

OBJECTIVE: To appraise the sources of evidence and methods to estimate input parameter values in decision-analytic model-based cost-effectiveness analyses of treatments for primary breast cancer (PBC) in older patients (≥ 70 years old). METHODS: Two electronic databases (Ovid Medline, Ovid EMBASE) were searched (inception until 5 September-2021) to identify model-based full economic evaluations of treatments for older women with PBC as part of their base-case target population or age-subgroup analysis. Data sources and methods to estimate four types of input parameters including health-related quality of life (HRQoL); natural history; treatment effect; resource use were extracted and appraised. Quality assessment was completed by reference to the Consolidated Health Economic Evaluation Reporting Standards. RESULTS: Seven model-based economic evaluations were included (older patients as part of their base-case (n = 3) or subgroup (n = 4) analysis). Data from younger patients (< 70 years) were used frequently to estimate input parameters. Different methods were adopted to adjust these estimates for an older population (HRQoL: disutility multipliers, additive utility decrements; Natural history: calibration of absolute values, one-way sensitivity analyses; Treatment effect: observational data analysis, age-specific behavioural parameters, plausible scenario analyses; Resource use: matched control observational data analysis, age-dependent follow-up costs). CONCLUSION: Improving estimated input parameters for older PBC patients will improve estimates of cost-effectiveness, decision uncertainty, and the value of further research. The methods reported in this review can inform future cost-effectiveness analyses to overcome data challenges for this population. A better understanding of the value of treatments for these patients will improve population health outcomes, clinical decision-making, and resource allocation decisions.

The impact of age on health utility values for older women with early-stage breast cancer: a systematic review and meta-regression.

INTRODUCTION: An increasing number of postmenopausal women are diagnosed with breast cancer at an older age (≥ 70 years). There is a lack of synthesised health utility data to support decision-making for managing breast cancer in this older population. This study aimed to identify the availability of, and the subsequent impact of age on, health state utility values (HSUVs) measured by the EQ-5D for older women with early-stage breast cancer. METHOD: This systematic review identified EQ-5D (3L or 5L version) HSUVs for postmenopausal women with early-stage breast cancer. Studies were identified from a previous systematic review (inception to 2009) and an electronic database search (Medline and Embase; 2009 to September 2021). Mean HSUVs were summarised by health state. Quality appraisal was performed on studies reporting HSUVs for older ages (≥ 70 years). Multivariable meta-regression assessed the association between HSUVs and age, health state, treatments received, and time of measuring the utility values (greater or less than one year post-treatment). RESULTS: Fifty EQ-5D HSUVs were identified from 13 studies. Mean HSUVs decreased as health state worsened: from the stable (mean=0.83) to progression (mean=0.79) and advanced (mean=0.68) states. Two studies reported six HSUVs estimated from the sample of women with a mean age ≥ 70. Meta-regression model fit improved by including age as an independent variable and attenuated the estimated utility decrements associated with worse health states. Utility decrements for the progression and advanced states were -0.052 (95%CI: -0.097, -0.007) and -0.143 (95%CI: -0.264, -0.022) respectively. The breast cancer-specific utility decrement associated with a one-year increase in age was -0.001 (95%CI: -0.004, 0.002). CONCLUSION: Relevant and accurate HSUVs are essential to help support decision-making about the most effective and cost-effective ways to manage early-stage breast cancer in older women. Age has a vital role in determining health utility values in this population. This study provides analysts and decision-makers with HSUVs and utility decrements that reflect the disease process in this older population.

Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG).

Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences. A multidisciplinary taskforce, including members of the European Society of Breast Cancer Specialists and International Society of Geriatric Oncology, gathered to expand and update the previous 2012 evidence-based recommendations for the management of breast cancer in older individuals with the endorsement of the European Cancer Organisation. These guidelines were expanded to include chemotherapy toxicity prediction calculators, cultural and social considerations, surveillance imaging, genetic screening, gene expression profiles, neoadjuvant systemic treatment options, bone-modifying drugs, targeted therapies, and supportive care. Recommendations on geriatric assessment, ductal carcinoma in situ, screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and secondary breast cancer were updated.

Priorities for the global advancement of care for older adults with cancer: an update of the International Society of Geriatric Oncology Priorities Initiative.

In 2011, the International Society of Geriatric Oncology (SIOG) published the SIOG 10 Priorities Initiative, which defined top priorities for the improvement of the care of older adults with cancer worldwide.1 Substantial scientific, clinical, and educational progress has been made in line with these priorities and international health policy developments have occurred, such as the shift of emphasis by WHO from communicable to non-communicable diseases and the adoption by the UN of its Sustainable Development Goals 2030. Therefore, SIOG has updated its priority list. The present document addresses four priority domains: education, clinical practice, research, and strengthening collaborations and partnerships. In this Policy Review, we reflect on how these priorities would apply in different economic settings, namely in high-income countries versus low-income and middle-income countries. SIOG hopes that it will offer guidance for international and national endeavours to provide adequate universal health coverage for older adults with cancer, who represent a major and rapidly growing group in global epidemiology.

Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.

BACKGROUND: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. METHODS: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. RESULTS: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19-0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20-0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08-0.49];BCSS: HR 0.12 [95% CI 0.03-0.44]).Transient negative quality-of-life impacts were observed. CONCLUSIONS: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. TRIAL REGISTRATION: ISRCTN 46099296.

ASNet: Auto-Augmented Siamese Neural Network for Action Recognition.

Human action recognition methods in videos based on deep convolutional neural networks usually use random cropping or its variants for data augmentation. However, this traditional data augmentation approach may generate many non-informative samples (video patches covering only a small part of the foreground or only the background) that are not related to a specific action. These samples can be regarded as noisy samples with incorrect labels, which reduces the overall action recognition performance. In this paper, we attempt to mitigate the impact of noisy samples by proposing an Auto-augmented Siamese Neural Network (ASNet). In this framework, we propose backpropagating salient patches and randomly cropped samples in the same iteration to perform gradient compensation to alleviate the adverse gradient effects of non-informative samples. Salient patches refer to the samples containing critical information for human action recognition. The generation of salient patches is formulated as a Markov decision process, and a reinforcement learning agent called SPA (Salient Patch Agent) is introduced to extract patches in a weakly supervised manner without extra labels. Extensive experiments were conducted on two well-known datasets UCF-101 and HMDB-51 to verify the effectiveness of the proposed SPA and ASNet.

Edge-Sensitive Left Ventricle Segmentation Using Deep Reinforcement Learning.

Deep reinforcement learning (DRL) has been utilized in numerous computer vision tasks, such as object detection, autonomous driving, etc. However, relatively few DRL methods have been proposed in the area of image segmentation, particularly in left ventricle segmentation. Reinforcement learning-based methods in earlier works often rely on learning proper thresholds to perform segmentation, and the segmentation results are inaccurate due to the sensitivity of the threshold. To tackle this problem, a novel DRL agent is designed to imitate the human process to perform LV segmentation. For this purpose, we formulate the segmentation problem as a Markov decision process and innovatively optimize it through DRL. The proposed DRL agent consists of two neural networks, i.e., First-P-Net and Next-P-Net. The First-P-Net locates the initial edge point, and the Next-P-Net locates the remaining edge points successively and ultimately obtains a closed segmentation result. The experimental results show that the proposed model has outperformed the previous reinforcement learning methods and achieved comparable performances compared with deep learning baselines on two widely used LV endocardium segmentation datasets, namely Automated Cardiac Diagnosis Challenge (ACDC) 2017 dataset, and Sunnybrook 2009 dataset. Moreover, the proposed model achieves higher F-measure accuracy compared with deep learning methods when training with a very limited number of samples.

In Search of Molecular Markers for Cerebellar Neurons.

The cerebellum, the region of the brain primarily responsible for motor coordination and balance, also contributes to non-motor functions, such as cognition, speech, and language comprehension. Maldevelopment and dysfunction of the cerebellum lead to cerebellar ataxia and may even be associated with autism, depression, and cognitive deficits. Hence, normal development of the cerebellum and its neuronal circuitry is critical for the cerebellum to function properly. Although nine major types of cerebellar neurons have been identified in the cerebellar cortex to date, the exact functions of each type are not fully understood due to a lack of cell-specific markers in neurons that renders cell-specific labeling and functional study by genetic manipulation unfeasible. The availability of cell-specific markers is thus vital for understanding the role of each neuronal type in the cerebellum and for elucidating the interactions between cell types within both the developing and mature cerebellum. This review discusses various technical approaches and recent progress in the search for cell-specific markers for cerebellar neurons.

Posterior Oropharyngeal Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on the healthcare system worldwide. Diagnostic testing remained one of the limiting factors for early identification and isolation of infected patients. This study aimed to evaluate posterior oropharyngeal saliva (POPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection among patients with confirmed or suspected COVID-19. METHODS: The laboratory information system was searched retrospectively for all respiratory specimens and POPS requested for SARS-CoV-2 RNA detection between 1 February 2020 and 15 April 2020. The agreement and diagnostic performance of POPS against NPsp were evaluated. RESULTS: A total of 13772 specimens were identified during the study period, including 2130 POPS and 8438 nasopharyngeal specimens (NPsp). Two hundred and twenty-nine same-day POPS-NPsp paired were identified with POPS and NPsp positivity of 61.5% (95% confidence interval [CI] 55.1-67.6%) and 53.3% (95% CI 46.8-59.6%). The overall, negative and positive percent agreement were 76.0% (95% CI 70.2-80.9%), 65.4% (95% CI 55.5-74.2%), 85.2% (95% CI 77.4-90.8%). Better positive percent agreement was observed in POPS-NPsp obtained within 7 days (96.6%, 95% CI 87.3-99.4%) compared with after 7 days of symptom onset (75.0%, 95% CI 61.4-85.2%). Among the 104 positive pairs, the mean difference in Cp value was 0.26 (range: 12.63 to -14.74), with an overall higher Cp value in NPsp (Pearson coefficient 0.579). No significant temporal variation was noted between the 2 specimen types. CONCLUSIONS: POPS is an acceptable alternative specimen to nasopharyngeal specimen for the detection of SARS-CoV-2.

Protective Effects of Melatonin on Neurogenesis Impairment in Neurological Disorders and Its Relevant Molecular Mechanisms.

Neurogenesis is the process by which functional new neurons are generated from the neural stem cells (NSCs) or neural progenitor cells (NPCs). Increasing lines of evidence show that neurogenesis impairment is involved in different neurological illnesses, including mood disorders, neurogenerative diseases, and central nervous system (CNS) injuries. Since reversing neurogenesis impairment was found to improve neurological outcomes in the pathological conditions, it is speculated that modulating neurogenesis is a potential therapeutic strategy for neurological diseases. Among different modulators of neurogenesis, melatonin is a particularly interesting one. In traditional understanding, melatonin controls the circadian rhythm and sleep-wake cycle, although it is not directly involved in the proliferation and survival of neurons. In the last decade, it was reported that melatonin plays an important role in the regulation of neurogenesis, and thus it may be a potential treatment for neurogenesis-related disorders. The present review aims to summarize and discuss the recent findings regarding the protective effects of melatonin on the neurogenesis impairment in different neurological conditions. We also address the molecular mechanisms involved in the actions of melatonin in neurogenesis modulation.

Effect of mycophenolate and rapamycin on renal fibrosis in lupus nephritis.

Lupus nephritis (LN) leads to chronic kidney disease (CKD) through progressive fibrosis. Mycophenolate inhibits inosine monophosphate dehydrogenase and is a standard treatment for LN. The mammalian or mechanistic target of rapamycin (mTOR) pathway is activated in LN. Rapamycin inhibits mTOR and is effective in preventing kidney transplant rejection, with the additional merits of reduced incidence of malignancies and viral infections. The effect of mycophenolate or rapamycin on kidney fibrosis in LN has not been investigated. We investigated the effects of mycophenolate and rapamycin in New Zealand Black and White first generation (NZB/W F1) murine LN and human mesangial cells (HMCs), focusing on mechanisms leading to kidney fibrosis. Treatment of mice with mycophenolate or rapamycin improved nephritis manifestations, decreased anti-double stranded (ds) DNA antibody titer and reduced immunoglobulin G (IgG) deposition in the kidney. Both mycophenolate and rapamycin, especially the latter, decreased glomerular mTOR Ser2448 phosphorylation. Renal histology in untreated mice showed mesangial proliferation and progressive glomerulosclerosis with tubular atrophy, and increased expression of transforming growth factor ß1 (TGF-ß1), monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle actin (α-SMA), fibronectin (FN) and collagen. Both mycophenolate and rapamycin ameliorated the histopathological changes. Results from in vitro experiments showed that both mycophenolate and rapamycin decreased mesangial cell proliferation and their binding with anti-dsDNA antibodies. Mycophenolate and rapamycin also down-regulated mTOR and extracellular signal-regulated kinase (ERK) phosphorylation and inhibited fibrotic responses in mesangial cells that were induced by anti-dsDNA antibodies or TGF-ß1. Our findings suggest that, in addition to immunosuppression, mycophenolate and rapamycin may reduce fibrosis in LN, which has important implications in preventing CKD in patients with LN.

Tumour boards in geriatric oncology.

Multidisciplinary tumour board is an integral part of cancer treatment planning. Although no definite survival benefits have yet been shown by mostly observational studies, other benefits of multidisciplinary tumour board have been identified. Traditionally the multidisciplinary tumour board involves participation of treating clinicians-medical, radiation and surgical oncologists. They tend to focus on the cancer alone. There is an increasing awareness that the treatment goal for cancer in older adults is not primarily on prolonging survival, with functional preservation and quality of life being particularly important for this population. The use of Comprehensive Geriatric Assessment and the input of the geriatrician in informing the oncologists regarding treatment decision have increasingly been shown to be beneficial. The integration of the geriatrician into the multidisciplinary tumour board should be urgently explored.