Association between investigator-measured body-mass index and colorectal adenoma: a systematic review and meta-analysis of 168,201 subjects.

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran's Q statistic and I2 analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25-30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30-1.61; I2 = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24-1.63; I2 = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger's regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30-1.58 vs. SOR 1.16, 95% CI 1.07-1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation.

The Hippo-YAP/TAZ-TEAD axis promotes multipotency in bone marrow stromal cells.

The mechanisms by which bone marrow stromal cells (BMSCs) maintain multilineage potency in vitro remain elusive. To identify the transcriptional regulatory circuits that contribute to BMSC multipotency, we performed paired single-nucleus multiomics of the expansion of freshly isolated BMSCs and of BMSCs undergoing tri-lineage differentiation. By computationally reconstructing the regulatory programs associated with initial stages of differentiation and early expansion, we identified the TEAD family of transcription factors, which is inhibited by Hippo signaling, as highly active in the BMSC in vitro multipotent state. Pharmacological inhibition of TEAD enhanced BMSC osteogenic and adipogenic differentiation, whereas its activation maintained BMSCs in an undifferentiated state, supporting a model whereby isolation of BMSCs coincides with a TEAD-controlled transcriptional state linked to multipotency. Our study highlights the Hippo pathway as a pivotal regulator of BMSC multipotency, and our regulatory network inferences are a reservoir of testable hypotheses that link transcription factors and their regulons to specific aspects of BMSC behavior.

Dried Blood Spot Postmortem Metabolic Autopsy With Genotype Validation for Sudden Unexpected Deaths in Infancy and Childhood in Hong Kong.

Background Inborn errors of metabolism (IEM) are collectively rare but potentially preventable causes of sudden unexpected death (SUD) in infancy or childhood, and metabolic autopsy serves as the final tool for establishing the diagnosis. We conducted a retrospective review of the metabolic and molecular autopsy on SUD and characterized the biochemical and genetic findings. Methodology A retrospective review of postmortem metabolic investigations (dried blood spot acylcarnitines and amino acid analysis, urine metabolic profiling where available, and next-generation sequencing on a panel of 75 IEM genes) performed for infants and children who presented with SUD between October 2016 and December 2021 with inconclusive autopsy findings or autopsy features suspicious of underlying IEM in our locality was conducted. Clinical and autopsy findings were reviewed for each case. Results A total of 43 infants and children aged between zero days to 10 years at the time of death were referred to the authors' laboratories throughout the study period. One positive case of multiple acyl-CoA dehydrogenase deficiency was diagnosed. Postmortem reference intervals for dried blood spot amino acids and acylcarnitines profile were established based on the results from the remaining patients. Conclusions Our study confirmed the importance of metabolic autopsy and the advantages of incorporating biochemical and genetic testing in this setting.

A do it yourself (DIY) point-of-care wrist ultrasound phantom for joint access training.

BACKGROUND: Joint access is essential for arthrocentesis, or joint aspiration of fluids. Joint treatments that are not performed properly can result in avoidable patient issues such as damage to the muscles, tendons, and blood vessels surrounding the joint. The use of ultrasound has become the gold standard for this procedure and proven to be a support in the skill learning process. However, success with this equipment, particularly in small joints like the wrist, depends on a clinician's capacity to recognize the crucial landmarks that guide these procedures. Prior to executing on a real patient, task trainers have proven to be an effective way for doctors to practice and prepare for procedures. However, shortcomings of current solutions include high purchase costs, incompatibility with ultrasound imaging, and low reusability. In addition, since this is a procedure that is not performed frequently, there may not be space or resources available in healthcare facilities to accommodate one at the point of care. This study aimed to close the existing gap by developing a DIY ultrasound compatible task trainer for wrist joint access training. RESULTS: We developed a novel ultrasound compatible wrist joint model that can be made from sustainable materials and reusable parts, thus reducing the costs for acquisition and environmental impact. Our model, which was produced utilizing small-batch production methods, is made up of 3D-printed bones enclosed in an ultrasound-compatible gelatin mixture. It can be easily remade after each practice session, removing needle tracks that are visible under ultrasound for conventional phantoms. The ultrasonic properties of this model were tested through pixel brightness analysis and visual inspection of simulated anatomical structures. CONCLUSION: Our results report the advantages and limitations of the proposed model regarding production, practice, and ultrasound compatibility. While future work entails the transfer to patients of the same skill, this reusable and replicable model has proven, when presented to experts, to be successful in representing the physical characteristics and ultrasound profile of significant anatomical structures. This novel DIY product could be an effective alternative to teach procedures in the context of resource-restrained clinical simulation centers.

Polymeric nanoparticle gel for intracellular mRNA delivery and immunological reprogramming of tumors.

Immuno-oncology therapies have been of great interest with the goal of inducing sustained tumor regression, but clinical results have demonstrated the need for improved and widely applicable methods. An antigen-free method of cancer immunotherapy can stimulate the immune system to recruit lymphocytes and produce immunostimulatory factors without prior knowledge of neoantigens, while local delivery reduces the risk of systemic toxicity. To improve the interactions between tumor cells and cytotoxic lymphocytes, a gene delivery nanoparticle platform was engineered to reprogram the tumor microenvironment (TME) in situ to be more immunostimulatory by inducing tumor-associated antigen-presenting cells (tAPCs) to activate cytotoxic lymphocytes against the tumor. Biodegradable, lipophilic poly (beta-amino ester) (PBAE) nanoparticles were synthesized and used to co-deliver mRNA constructs encoding a signal 2 co-stimulatory molecule (4-1BBL) and a signal 3 immuno-stimulatory cytokine (IL-12), along with a nucleic acid-based immunomodulatory adjuvant. Nanoparticles are combined with a thermoresponsive block copolymer for gelation at the injection site for local NP retention at the tumor. The reprogramming nanoparticle gel synergizes with immune checkpoint blockade (ICB) to induce tumor regression and clearance in addition to resistance to tumor rechallenge at a distant site. In vitro and in vivo studies reveal increases in immunostimulatory cytokine production and recruitment of immune cells as a result of the nanoparticles. Intratumoral injection of nanoparticles encapsulating mRNA encoding immunostimulatory agents and adjuvants via an injectable thermoresponsive gel has great translational potential as an immuno-oncology therapy that can be accessible to a wide range of patients.

Nephrogenic syndrome of inappropriate antidiuresis - An ethnically, genetically and phenotypically diverse disorder: First report in a Chinese adult and review of published cases.

BACKGROUND: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare inherited disorder characterised by hyponatraemia. To date, most reported cases are Caucasians with gain-of-function variants in AVPR2, an X-linked gene which encodes the vasopressin V2 receptor (V2R). Recently, germline gain-of-function variants in the stimulatory G protein α-subunit (Gsα) were reported to cause dominantly inherited NSIAD. CASE REPORT: We report the first Chinese adult diagnosed with NSIAD. He was found to be hemizygous for R137C-V2R, the most prevalent pathogenic variant among Caucasians. After the genetic diagnosis and counselling on the importance of fluid restriction, he had no recurrence of hyponatraemia to date. LITERATURE REVIEW: Case reports of NSIAD published in the English literature in PubMed were reviewed to summarise the genetic and phenotypic heterogeneity of this disorder. CONCLUSION: NSIAD is ethnically, genetically and phenotypically diverse. The diagnosis should especially be considered in young patients with otherwise unexplained hyponatraemia. Target analysis of R137C-V2R should make the diagnosis in most cases. Genetic testing could confirm the diagnosis, motivate adherence to treatment, offer the possibility of genotype-guided therapy, and allow cascade screening to prevent hyponatraemia.

A convolutional neural network segments yeast microscopy images with high accuracy.

The identification of cell borders ('segmentation') in microscopy images constitutes a bottleneck for large-scale experiments. For the model organism Saccharomyces cerevisiae, current segmentation methods face challenges when cells bud, crowd, or exhibit irregular features. We present a convolutional neural network (CNN) named YeaZ, the underlying training set of high-quality segmented yeast images (>10 000 cells) including mutants, stressed cells, and time courses, as well as a graphical user interface and a web application ( www.quantsysbio.com/data-and-software ) to efficiently employ, test, and expand the system. A key feature is a cell-cell boundary test which avoids the need for fluorescent markers. Our CNN is highly accurate, including for buds, and outperforms existing methods on benchmark images, indicating it transfers well to other conditions. To demonstrate how efficient large-scale image processing uncovers new biology, we analyze the geometries of ≈2200 wild-type and cyclin mutant cells and find that morphogenesis control occurs unexpectedly early and gradually.

The adoption of hypertension reference framework: An investigation among primary care physicians of Hong Kong.

BACKGROUND: The Hong Kong Government released a Reference Framework (RF-HT) for Hypertension Care for Adults in Primary Care Settings since 2010. No studies have evaluated its adoption by primary care physicians (PCPs) since its release. AIM: We aimed to evaluate the level of PCPs' adoption of the RF-HT and the potential barriers of its use in family practice. DESIGN AND SETTING: A cross-sectional study was conducted by a self-administered validated survey among all PCPs in Hong Kong through various means. METHODS: We assessed the level of and factors associated with its adoption by multivariate logistic regression modelling. RESULT: A total of 3,857 invitation episodes were sent to 2,297 PCPs in 2014-2015. We received 383 completed questionnaires. The average score of adoption was 3.43 out of 4.00, and 47.5% of PCPs highly adopted RF-HT in their daily consultations. Male practitioners (adjusted odds ratio [aOR] = 0.524, 95% CI = 0.290-0.948, p = 0.033) and PCPs of public sector (aOR = 0.524, 95% CI = 0.292-0.940, p = 0.030) were significantly less likely to adopt the RF-HT. PCPs with higher training completion or being academic fellow are more likely to adopt RF-HT than those who were "nil to basic training completion" (aOR = 0.479, 95% CI = 0.269-0.853, p = 0.012) or "higher trainee" (aOR = 0.302, 95% CI = 0.093-0.979, p = 0.046). Three most-supported suggestions on RF-HT improvement were simplification of RF-HT, provision of pocket version and promoting in patients. CONCLUSION: Among PCP respondents, the adoption level of the RF-HT was high. These findings also highlighted some factors associated with its adoption that could inform targeted interventions for enhancing its use in clinical practice.

Benefits and limitations of implementing Chronic Care Model (CCM) in primary care programs: A systematic review.

BACKGROUND: Chronic Care Model (CCM) has been developed to improve patients' health care by restructuring health systems in a multidimensional manner. This systematic review aims to summarize and analyse programs specifically designed and conducted for the fulfilment of multiple CCM components. We have focused on programs targeting diabetes mellitus, hypertension and cardiovascular disease. METHOD AND RESULTS: This review was based on a comprehensive literature search of articles in the PubMed database that reported clinical outcomes. We included a total of 25 eligible articles. Evidence of improvement in medical outcomes and the compliance of patients with medical treatment were reported in 18 and 14 studies, respectively. Two studies demonstrated a reduction of the medical burden in terms of health service utilization, and another two studies reported the effectiveness of the programs in reducing the risk of heart failure and other cardiovascular diseases. However, CCMs were still restricted by limited academic robustness and social constraints when they were implemented in primary care. Higher professional recognition, tighter system collaborations and increased financial support may be necessary to overcome the limitations of, and barriers to CCM implementation. CONCLUSION: This review has identified the benefits of implementing CCM, and recommended suggestions for the future development of CCM.

Assessing the clinical utility of genomic expression data across human cancers.

Cancer molecular profiling provides better understanding of tumor mechanisms and helps to improve the existing cancer management. Here we present the gene expression signatures from ~9000 human tumors with clinical information across 32 malignancies from The Cancer Genome Atlas project (TCGA). Major predictors from the RNA sequencing data that were significantly correlated with cancer survival were identified. The expression level of these prognostic genes revealed significant genomic pathways that were clinically relevant to survival outcomes across human cancers. Furthermore, it is shown that in most cancer types, combinations of these genomic signatures with clinical information might yield improved predictions. Thus, with respect to clinical utility, our study reveals the promising values of genomic data from the pan-cancer perspective.