Balancing growth amidst salt stress - lifestyle perspectives from the extremophyte model Schrenkiella parvula.

Schrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its lifecycle under multiple environmental stresses, including high salinity. Yet, the key physiological and structural traits underlying its stress-adapted lifestyle are unknown along with trade-offs when surviving salt stress at the expense of growth and reproduction. We aimed to identify the influential adaptive trait responses that lead to stress-resilient and uncompromised growth across developmental stages when treated with salt at levels known to inhibit growth in Arabidopsis and most crops. Its resilient growth was promoted by traits that synergistically allowed primary root growth in seedlings, the expansion of xylem vessels across the root-shoot continuum, and a high capacity to maintain tissue water levels by developing thicker succulent leaves while enabling photosynthesis during salt stress. A successful transition from vegetative to reproductive phase was initiated by salt-induced early flowering, resulting in viable seeds. Self-fertilization in salt-induced early flowering was dependent upon filament elongation in flowers otherwise aborted in the absence of salt during comparable plant ages. The maintenance of leaf water status promoting growth, and early flowering to ensure reproductive success in a changing environment, were among the most influential traits that contributed to the extremophytic lifestyle of S. parvula.

Robotic transanal minimally invasive surgery (R-TAMIS): current evidence in the treatment of early rectal neoplasia.

INTRODUCTION: Robotic transanal minimally invasive surgery (R-TAMIS) was introduced in 2012 for the excision of benign rectal polyps and low grade rectal cancer. Ergonomic improvements over traditional laparoscopic TAMIS (L-TAMIS) include increased dexterity within a small operative field, with possibility of better surgical precision. We aim to collate the existing data surrounding the use of R-TAMIS to treat rectal neoplasms from cohort studies and larger case series, providing a foundation for future, large-scale, comparative studies. METHODS: Medline, EMBASE and Web of Science were searched as part of our review. Randomised controlled trials (RCTs), cohort studies or large case series (≥ 5 patients) investigating the use of R-TAMIS to resect rectal neoplasia (benign or malignant) were eligible for inclusion in our analysis. Quality assessment of included studies was performed via the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, operative details and histopathological/oncological outcomes. RESULTS: Eighteen studies on 317 participants were included in our analysis. The quality of studies was generally satisfactory. Overall complication rate from R-TAMIS was 9.7%. Clear margins (R0) were reported in 96.2% of patients. Local recurrence (benign or malignant) occurred in 2.2% of patients during the specified follow-up periods. CONCLUSION: Our review highlights the current evidence for R-TAMIS in the local excision of rectal lesions. While R-TAMIS appears to have complication, margin negativity and recurrence rates superior to those of published L-TAMIS series, comparative studies are needed.

Assessing circulating tumour DNA (ctDNA) as a prognostic biomarker in locally advanced rectal cancer: a systematic review and meta-analysis.

INTRODUCTION: Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC. METHODS: PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS). RESULTS: Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91-16.03) and 15.15 (95% CI 8.21-27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively. CONCLUSION: Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.

Assessing Circulating Tumour DNA (ctDNA) as a Biomarker for Anal Cancer Management: A Systematic Review.

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a 'fast elimination' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.

Transcription Factor PecS Mediates Agrobacterium fabrum Fitness and Survival.

The transcriptional regulator PecS is encoded by select bacterial pathogens. For instance, in the plant pathogen Dickeya dadantii, PecS controls a range of virulence genes, including pectinase genes and the divergently oriented gene pecM, which encodes an efflux pump through which the antioxidant indigoidine is exported. In the plant pathogen Agrobacterium fabrum (formerly named Agrobacterium tumefaciens), the pecS-pecM locus is conserved. Using a strain of A. fabrum in which pecS has been disrupted, we show here that PecS controls a range of phenotypes that are associated with bacterial fitness. PecS represses flagellar motility and chemotaxis, which are processes that are important for A. fabrum to reach plant wound sites. Biofilm formation and microaerobic survival are reduced in the pecS disruption strain, whereas the production of acyl homoserine lactone (AHL) and resistance to reactive oxygen species (ROS) are increased when pecS is disrupted. AHL production and resistance to ROS are expected to be particularly relevant in the host environment. We also show that PecS does not participate in the induction of vir genes. The inducing ligands for PecS, urate, and xanthine, may be found in the rhizosphere, and they accumulate within the plant host upon infection. Therefore, our data suggest that PecS mediates A. fabrum fitness during its transition from the rhizosphere to the host plant. IMPORTANCE PecS is a transcription factor that is conserved in several pathogenic bacteria, where it regulates virulence genes. The plant pathogen Agrobacterium fabrum is important not only for its induction of crown galls in susceptible plants but also for its role as a tool in the genetic manipulation of host plants. We show here that A. fabrum PecS controls a range of phenotypes, which would confer the bacteria an advantage while transitioning from the rhizosphere to the host plant. This includes the production of signaling molecules, which are critical for the propagation of the tumor-inducing plasmid. A more complete understanding of the infection process may inform approaches by which to treat infections as well as to facilitate the transformation of recalcitrant plant species.

Real-time prediction of intradialytic hypotension using machine learning and cloud computing infrastructure.

BACKGROUND: In maintenance hemodialysis patients, intradialytic hypotension (IDH) is a frequent complication that has been associated with poor clinical outcomes. Prediction of IDH may facilitate timely interventions and eventually reduce IDH rates. METHODS: We developed a machine learning model to predict IDH in in-center hemodialysis patients 15-75 min in advance. IDH was defined as systolic blood pressure (SBP) <90 mmHg. Demographic, clinical, treatment-related and laboratory data were retrieved from electronic health records and merged with intradialytic machine data that were sent in real-time to the cloud. For model development, dialysis sessions were randomly split into training (80%) and testing (20%) sets. The area under the receiver operating characteristic curve (AUROC) was used as a measure of the model's predictive performance. RESULTS: We utilized data from 693 patients who contributed 42 656 hemodialysis sessions and 355 693 intradialytic SBP measurements. IDH occurred in 16.2% of hemodialysis treatments. Our model predicted IDH 15-75 min in advance with an AUROC of 0.89. Top IDH predictors were the most recent intradialytic SBP and IDH rate, as well as mean nadir SBP of the previous 10 dialysis sessions. CONCLUSIONS: Real-time prediction of IDH during an ongoing hemodialysis session is feasible and has a clinically actionable predictive performance. If and to what degree this predictive information facilitates the timely deployment of preventive interventions and translates into lower IDH rates and improved patient outcomes warrants prospective studies.

Survival outcomes after synchronous para-aortic lymph node metastasis in colorectal cancer: A systematic review.

BACKGROUND: Synchronous para-aortic lymph node metastasis (PALNM) in colorectal cancer (CRC) is a relatively rare clinical entity. There is a lack of consensus on management of these patients, and the role of para-aortic lymph node dissection (PALND) remains controversial. This systematic review aims to describe the survival outcomes in colorectal cancer with synchronous PALNM when lymph node dissection is performed. METHODS: A systematic review of Pubmed, Embase and Web of Science databases for PALND in CRC was performed. Studies including patients with synchronous PALNM undergoing resection with curative intent, published from the year 2000 onwards, were included. RESULTS: Twelve retrospective studies were included. Four studies reported survival outcomes for rectal cancer, two for colon cancer and six as colorectal. Survival outcomes for 356 patients were included. Average 5-year overall survival (OS) was 22.4%, 33.9% and 37.7% in the rectal, colon and colorectal groups respectively. Three year OS in the groups was 53.6%, 46.2% and 65.7%. CONCLUSION: There remains a lack of quality data to confidently make recommendations regarding the management of synchronous PALNM in colon and rectal cancer cohorts. Retrospective data suggests a benefit in highly selective cohorts and therefore a case-by-case evaluation remains the standard of care.

High Protein Whole Food Snack and Albumin Outcomes in Patients With Dialysis-Dependent Chronic Kidney Disease.

OBJECTIVE: Protein-energy wasting is common among patients on hemodialysis (HD). This study sought to define effects that a novel, post-HD, high-calorie, high-protein whole food snack had on patients' serum albumin (serum alb), serum phosphorus and equilibrated normalized protein catabolic rate (enPCR). METHODS: A 12-month (6 months intervention, 6 months pre/post data collection), single-center, unblinded study was conducted. Participants (n = 67) consumed, ad libitum, a whole food snack post-HD for 6 treatments each month. Upon analysis, regression models identified relationships between serum alb and whole food snack consumption across follow up. Predefined effect size anticipated was + 0.2 g/dL. Patients were stratified by high (≥4 g/dL) or low (<4 g/dL) mean serum alb during a 3-month baseline period. Paired t-tests compared mean per patient difference in serum alb, enPCR and serum phosphorus from baseline to each month of follow up, stratified by high (≥640 g) or low (<640 g) consumption of the whole food snack (a priori caloric estimation). RESULTS: Linear regression models showed positive associations between higher serum alb and enPCR with higher whole food snack consumption across follow up (all P < .05). Assessments from baseline to each follow-up month show some increases in serum alb, yet t test comparisons were not significant. No significant changes were seen in serum phosphorus levels during follow-up. CONCLUSION: Albeit the catabolic effects of HD are well-known, effective nutritional interventions are scarce. Results showed that providing a whole food snack post-HD to individuals with serum alb <4.0 g/dL may be beneficial but further studies are recommended.

Medication Safety in Dialysis Care.

The outpatient dialysis setting presents unique challenges in the medication process. Dialysis staff conduct all steps in the medication process, including transcribing and verifying orders, preparing and administering medications, and monitoring for therapeutic and adverse effects. When addressing best medication practices, consideration should be given to education and resources provided to staff. This article explores the multiple strategies taken by a national dialysis network to support clinical staff and improve patient safety.

Application of PREVENA (Surgical Incision Protection System) in reducing surgical site infections following reversal of ileostomy or colostomy: the PRIC study protocol.

AIM: There is a current lack of evidence in the literature to support the routine use of negative pressure wound therapy (NPWT) to reduce the risk of surgical site infections (SSI) in the setting of ileostomy or colostomy reversal. The aim of this study is to examine whether routine NPWT confers a lower rate of SSI than conventional dressings following reversal of ileostomy or colostomy. METHODS: The PRIC study is a randomized, controlled, open-label, multi-centre superiority trial to assess whether routine NPWT following wound closure confers a lower rate of SSI following reversal of ileostomy or colostomy when compared to conventional dressings. Participants will be consecutively identified and recruited. Eligible participants will be randomized in a 1:1 allocation ratio, to receive either the NPWT (PREVENA) dressings or conventional dressings which will be applied immediately upon completion of surgery. PREVENA dressings will remain applied for a duration of 7 days. Surgical wounds will then be examined on post-operative day seven as well as during follow-up appointments in OPD for any evidence of SSI. In the interim, public health nurses (PHN) will provide out-patient support services incorporating wound assessment and care as part of a routine basis. Study investigators will liaise with PHN to gather the relevant data in relation to the time to wound healing. Our primary endpoint is the incidence of SSI within 30 days of stoma reversal. Secondary endpoints include measuring time to wound healing, evaluating wound healing and aesthetics and assessing patient satisfaction. CONCLUSION: The PRIC study will assess whether routine NPWT following wound closure is superior to conventional dressings in the reduction of SSI following reversal of ileostomy or colostomy and ascertain whether routine NPWT should be considered the new standard of care.

Prostate radiotherapy and the risk of secondary rectal cancer-a meta-analysis.

PURPOSE: Radiotherapy is being used increasingly in the treatment of prostate cancer. However, ionising radiation may confer a small risk of a radiation-induced secondary malignancy. We aim to assess the risk of rectal cancer following pelvic radiotherapy for prostate cancer. METHODS: A search was conducted of the PubMed/MEDLINE, EMBASE and Web of Science databases identifying studies reporting on the risk of rectal cancer following prostatic radiotherapy. Studies must have included an appropriate control group of non-irradiated prostate cancer patients. A meta-analysis was performed to assess the risk of prostatic radiotherapy on subsequent rectal cancer diagnosis. RESULTS: In total, 4757 articles were screened with eight studies meeting the predetermined criteria. A total of 796,386 patients were included in this meta-analysis which showed an increased odds ratio (OR) for subsequent rectal cancer in prostate cancer patients treated with radiotherapy compared to those treated by non-radiotherapy means (OR 1.45, 1.07-1.97, p = 0.02). CONCLUSION: These findings confirm that prostate radiotherapy significantly increases the risk of subsequent rectal cancer. This risk has implications for treatment selection, surveillance and patient counselling. However, it is crucial that this information is presented in a rational and comprehensible manner that does not disproportionately frighten or deter patients from what might be their most suitable treatment modality.

Quality of life meta-analysis following coloanal anastomosis versus abdominoperineal resection for low rectal cancer.

AIM: In low rectal cancers without sphincter involvement a permanent stoma can be avoided without compromising oncological safety. Functional outcomes following coloanal anastomosis (CAA) compared to abdominoperineal excision (APR) may be significantly different. This study examines all available comparative quality of life (QoL) data for patients undergoing CAA versus APR for low rectal cancer. METHODS: Published studies with comparative data on QoL outcomes following CAA versus APR for low rectal cancer were extracted from electronic databases. The study was registered with PROSPERO and adhered to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. RESULTS: Seven comparative series examined QoL in 527 patients. There was no difference in the numbers receiving neoadjuvant radiotherapy in the APR and CAA groups (OR: 1.19, 95% CI: 0.78-1.81, p = 0.43). CAA was associated with higher mean scores for physical functioning(std mean diff -7.08, 95% CI: -11.92 to -2.25, p = 0.004) and body image (std. mean diff 11.11, 95% CI: 6.04-16.18, p < 0.0001). Male sexual problems were significantly increased in patients who had undergone APR compared to CAA (std. mean diff -16.20, 95% CI: -25.76 to -6.64, p = 0.0009). Patients who had an APR reported more fatigue, dyspnoea and appetite loss. Those who had a CAA reported higher scores for both constipation and diarrhoea. DISCUSSION: It is reasonable to offer a CAA to motivated patients where oncological outcomes will not be threatened. QoL outcomes appear to be superior when intestinal continuity is maintained, and permanent stoma avoided.

Optimal surgical management strategy for treatment of primary anorectal malignant melanoma-a systematic review and meta-analysis.

BACKGROUND: Primary mucosal anorectal malignant melanoma (AMM) is an invasive malignancy with poor survival. Management options have been variable, due to limited data and lack of randomised control trials available on the optimal surgical strategy. The aim of this review was to compare local excision versus radical resection. METHODS: A systematic search of articles in PubMed, Ovid, Scopus, and the Cochrane Library database was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The outcomes of interest were the impact that surgical strategy had on survival (primary) and recurrence rates (secondary) for the treatment of AMM, comparing sphincter sparing local excision (LE) versus extensive abdominoperineal resection (APR). RESULTS: Ten studies met the predefined criteria. Overall, there were 303 patients, with a median age of 58.2 years. Sixty-one percent (n = 187/303) had radical surgery (abdominoperineal resection) for the primary treatment of AMM. Overall, 5-year survival for the APR and LE was 23% and 32% respectively. Meta-analysis on the median OS noted no statistical difference between the two groups. However, local recurrence occurred in 20.82% and 47.04% in the APR and LE groups respectively. Meta-analysis observed a statistically significant reduction in recurrence when patients had an APR as primary treatment (OR 0.15, 95% CI = 0.08-0.28, p < 0.00001). CONCLUSION: Though local recurrence rates are more common with local excision of AMM, this does not confer an inferior OS when comparing LE versus APR. The decision to proceed with LE vs. APR should be made on a case-by-case basis.

Cephalic arch restenosis rates in hemodialysis patients with brachiocephalic fistulae: a retrospective multicenter analysis of 3301 patients.

BACKGROUND: We evaluated restenosis rates at the cephalic arch after percutaneous angioplasty and stenting procedures in patients with brachial artery to cephalic vein arteriovenous fistula (BCAVF) hemodialysis access. METHODS: We used data from adult hemodialysis patients treated at a national network of 44 outpatient interventional facilities during Oct 2011-2015. We included data from patients with BCAVF who received an exclusive angioplasty, or stent with angioplasty, for treatment of cephalic arch stenosis and had ≥1 subsequent evaluation of the cephalic arch. Median percent restenosis per month at cephalic arch and days between encounters was calculated from the 1st index to 2nd procedure, and for up to 4 subsequent encounters. Analyses were stratified by intervention and device types. RESULTS: We identified a cohort of 3301 patients (mean age 62.2 ± 13.9 years, 58.5% male, 33.2% white race) with a BCAVF who had an angioplasty, or stent, at the cephalic arch for an index and ≥ 1 follow-up procedure. Between the 1st index to 2nd procedure, patients who received an angioplasty (n = 2663) or stent (n = 933) showed a median decrease of 18.9 and 16.5% in luminal diameter per month and a median time of 93 and 91 days between encounters, respectively. Restenosis and day rates were similar for standard versus high-pressure angioplasties. Bare metal stents showed 10.1 percentage point higher restenosis rate compared to stent grafts. Restenosis rates and time to restenosis were relatively consistent across subsequent encounters. CONCLUSIONS: Findings suggest hemodialysis patients with a BCAVF who require an angioplasty or stent to treat a stenosis at the cephalic arch will have stenosis reformed at a rate of 18.9 and 16.5% per month after the first intervention, respectively. Findings suggest patients are at risk of having significant lesions at the cephalic arch within 3 months after the previous intervention.

Predictors of shorter- and longer-term mortality after COVID-19 presentation among dialysis patients: parallel use of machine learning models in Latin and North American countries.

BACKGROUND: We developed machine learning models to understand the predictors of shorter-, intermediate-, and longer-term mortality among hemodialysis (HD) patients affected by COVID-19 in four countries in the Americas. METHODS: We used data from adult HD patients treated at regional institutions of a global provider in Latin America (LatAm) and North America who contracted COVID-19 in 2020 before SARS-CoV-2 vaccines were available. Using 93 commonly captured variables, we developed machine learning models that predicted the likelihood of death overall, as well as during 0-14, 15-30, > 30 days after COVID-19 presentation and identified the importance of predictors. XGBoost models were built in parallel using the same programming with a 60%:20%:20% random split for training, validation, & testing data for the datasets from LatAm (Argentina, Columbia, Ecuador) and North America (United States) countries. RESULTS: Among HD patients with COVID-19, 28.8% (1,001/3,473) died in LatAm and 20.5% (4,426/21,624) died in North America. Mortality occurred earlier in LatAm versus North America; 15.0% and 7.3% of patients died within 0-14 days, 7.9% and 4.6% of patients died within 15-30 days, and 5.9% and 8.6% of patients died > 30 days after COVID-19 presentation, respectively. Area under curve ranged from 0.73 to 0.83 across prediction models in both regions. Top predictors of death after COVID-19 consistently included older age, longer vintage, markers of poor nutrition and more inflammation in both regions at all timepoints. Unique patient attributes (higher BMI, male sex) were top predictors of mortality during 0-14 and 15-30 days after COVID-19, yet not mortality > 30 days after presentation. CONCLUSIONS: Findings showed distinct profiles of mortality in COVID-19 in LatAm and North America throughout 2020. Mortality rate was higher within 0-14 and 15-30 days after COVID-19 in LatAm, while mortality rate was higher in North America > 30 days after presentation. Nonetheless, a remarkable proportion of HD patients died > 30 days after COVID-19 presentation in both regions. We were able to develop a series of suitable prognostic prediction models and establish the top predictors of death in COVID-19 during shorter-, intermediate-, and longer-term follow up periods.

The components of personal passports for people living with dementia in an acute healthcare setting: an integrative review.

AIM: To explore the components of personal passports for people living with dementia in an acute healthcare setting. BACKGROUND: Globally, supporting people with dementia poses a prominent health and social care challenge. Importance for people with dementia in an acute healthcare setting includes social relationships and communication with healthcare staff. A personal passport is an international initiative designed to support the personhood of the person living with dementia. METHODS: This integrative review is based on the methodology of Whittmore and Knafl (2005). The Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist were adhered to. A database search of PubMed, MEDLINE, CINAHL, Scopus and EBSCO databases was systematically performed. RESULTS: This integrative review identified nine research studies on the components of personal passports that met the inclusion and exclusion criteria. A constant comparative method of data analysis identified five key pivotal themes: person-centredness, communication, family/carer involvement, education and leadership. CONCLUSION: The use of personal passports supports the provision of person-centred care for people living with dementia through enhancing the well-being of both the person and their families/caregivers. RELEVANCE TO CLINICAL PRACTICE: Personal passports are an important document and should be determined by the person with dementia, their care needs and the caregiver's role in meeting these needs.

The CDK Inhibitor SIAMESE Targets Both CDKA;1 and CDKB1 Complexes to Establish Endoreplication in Trichomes.

Endoreplication, also known as endoreduplication, is a modified cell cycle in which DNA is replicated without subsequent cell division. Endoreplication plays important roles in both normal plant development and in stress responses. The SIAMESE (SIM) gene of Arabidopsis (Arabidopsis thaliana) encodes a cyclin-dependent kinase (CDK) inhibitor that plays a central role in establishing endoreplication, and is the founding member of the SIAMESE-RELATED (SMR) family of plant-specific CDK inhibitor genes. However, there has been conflicting evidence regarding which specific cyclin/CDK complexes are inhibited by SIM in vivo. In this work, we use genetic evidence to show that SIM likely inhibits both CDKA;1- and CDKB1-containing CDK complexes in vivo, thus promoting endoreplication in developing Arabidopsis trichomes. We also show that SIM interacts with CYCA2;3, a binding partner of CDKB1;1, via SIM motif A, which we previously identified as a CDK-binding motif. By contrast, SIM motif C, which has been indicated as a cyclin binding motif in other contexts, appears to be relatively unimportant for interaction between SIM and CYCA2;3. Together with earlier results, our work suggests that SIM and other SMRs likely have a multivalent interaction with CYC/CDK complexes.

A Spatiotemporal DNA Endoploidy Map of the Arabidopsis Root Reveals Roles for the Endocycle in Root Development and Stress Adaptation.

Somatic polyploidy caused by endoreplication is observed in arthropods, molluscs, and vertebrates but is especially prominent in higher plants, where it has been postulated to be essential for cell growth and fate maintenance. However, a comprehensive understanding of the physiological significance of plant endopolyploidy has remained elusive. Here, we modeled and experimentally verified a high-resolution DNA endoploidy map of the developing Arabidopsis thaliana root, revealing a remarkable spatiotemporal control of DNA endoploidy levels across tissues. Fitting of a simplified model to publicly available data sets profiling root gene expression under various environmental stress conditions suggested that this root endoploidy patterning may be stress-responsive. Furthermore, cellular and transcriptomic analyses revealed that inhibition of endoreplication onset alters the nuclear-to-cellular volume ratio and the expression of cell wall-modifying genes, in correlation with the appearance of cell structural changes. Our data indicate that endopolyploidy might serve to coordinate cell expansion with structural stability and that spatiotemporal endoreplication pattern changes may buffer for stress conditions, which may explain the widespread occurrence of the endocycle in plant species growing in extreme or variable environments.

Effect of hemodiafiltration on measured physical activity: primary results of the HDFIT randomized controlled trial.

BACKGROUND: Dialysis patients are typically inactive and their physical activity (PA) decreases over time. Uremic toxicity has been suggested as a potential causal factor of low PA in dialysis patients. Post-dilution high-volume online hemodiafiltration (HDF) provides greater higher molecular weight removal and studies suggest better clinical/patient-reported outcomes compared with hemodialysis (HD). METHODS: HDFIT was a randomized controlled trial at 13 clinics in Brazil that aimed to investigate the effects of HDF on measured PA (step counts) as a primary outcome. Stable HD patients (vintage 3-24 months) were randomized to receive HDF or high-flux HD. Treatment effect of HDF on the primary outcome from baseline to 3 and 6 months was estimated using a linear mixed-effects model. RESULTS: We randomized 195 patients (HDF 97; HD 98) between August 2016 and October 2017. Despite the achievement of a high convective volume in the majority of sessions and a positive impact on solute removal, the treatment effect HDF on the primary outcome was +538 [95% confidence interval (CI) -330 to 1407] steps/24 h after dialysis compared with HD, and was not statistically significant. Despite a lack of statistical significance, the observed size of the treatment effect was modest and driven by steps taken between 1.5 and 24.0 h after dialysis, in particular between 20 and 24 h (+197 steps; 95% CI -95 to 488). CONCLUSIONS: HDF did not have a statistically significant treatment effect on PA 24 h following dialysis, albeit effect sizes may be clinically meaningful and deserve further investigation.

Artificial intelligence enabled applications in kidney disease.

Artificial intelligence (AI) is considered as the next natural progression of traditional statistical techniques. Advances in analytical methods and infrastructure enable AI to be applied in health care. While AI applications are relatively common in fields like ophthalmology and cardiology, its use is scarcely reported in nephrology. We present the current status of AI in research toward kidney disease and discuss future pathways for AI. The clinical applications of AI in progression to end-stage kidney disease and dialysis can be broadly subdivided into three main topics: (a) predicting events in the future such as mortality and hospitalization; (b) providing treatment and decision aids such as automating drug prescription; and (c) identifying patterns such as phenotypical clusters and arteriovenous fistula aneurysm. At present, the use of prediction models in treating patients with kidney disease is still in its infancy and further evidence is needed to identify its relative value. Policies and regulations need to be addressed before implementing AI solutions at the point of care in clinics. AI is not anticipated to replace the nephrologists' medical decision-making, but instead assist them in providing optimal personalized care for their patients.