The impact of machine learning on the prediction of diabetic foot ulcers - A systematic review.

INTRODUCTION: Globally, diabetes mellitus poses a significant health challenge as well as the associated complications of diabetes, such as diabetic foot ulcers (DFUs). The early detection of DFUs is important in the healing process and machine learning may be able to help inform clinical staff during the treatment process. METHODS: A PRISMA-informed search of the literature was completed via the Cochrane Library and MEDLINE (OVID), EMBASE, CINAHL Plus and Scopus databases for reports published in English and in the last ten years. The primary outcome of interest was the impact of machine learning on the prediction of DFUs. The secondary outcome was the statistical performance measures reported. Data were extracted using a predesigned data extraction tool. Quality appraisal was undertaken using the evidence-based librarianship critical appraisal tool. RESULTS: A total of 18 reports met the inclusion criteria. Nine reports proposed models to identify two classes, either healthy skin or a DFU. Nine reports proposed models to predict the progress of DFUs, for example, classing infection versus non-infection, or using wound characteristics to predict healing. A variety of machine learning techniques were proposed. Where reported, sensitivity = 74.53-98 %, accuracy = 64.6-99.32 %, precision = 62.9-99 %, and the F-measure = 52.05-99.0 %. CONCLUSIONS: A variety of machine learning models were suggested to successfully classify DFUs from healthy skin, or to inform the prediction of DFUs. The proposed machine learning models may have the potential to inform the clinical practice of managing DFUs and may help to improve outcomes for individuals with DFUs. Future research may benefit from the development of a standard device and algorithm that detects, diagnoses and predicts the progress of DFUs.

Elf1 promotes transcription-coupled repair in yeast by using its C-terminal domain to bind TFIIH.

Transcription coupled-nucleotide excision repair (TC-NER) removes DNA lesions that block RNA polymerase II (Pol II) transcription. A key step in TC-NER is the recruitment of the TFIIH complex, which initiates DNA unwinding and damage verification; however, the mechanism by which TFIIH is recruited during TC-NER, particularly in yeast, remains unclear. Here, we show that the C-terminal domain (CTD) of elongation factor-1 (Elf1) plays a critical role in TC-NER in yeast by binding TFIIH. Analysis of genome-wide repair of UV-induced cyclobutane pyrimidine dimers (CPDs) using CPD-seq indicates that the Elf1 CTD in yeast is required for efficient TC-NER. We show that the Elf1 CTD binds to the pleckstrin homology (PH) domain of the p62 subunit of TFIIH in vitro, and identify a putative TFIIH-interaction region (TIR) in the Elf1 CTD that is important for PH binding and TC-NER. The Elf1 TIR shows functional, structural, and sequence similarities to a conserved TIR in the mammalian UV sensitivity syndrome A (UVSSA) protein, which recruits TFIIH during TC-NER in mammalian cells. These findings suggest that the Elf1 CTD acts as a functional counterpart to mammalian UVSSA in TC-NER by recruiting TFIIH in response to Pol II stalling at DNA lesions.

The Surprising Diversity of UV-Induced Mutations.

Ultraviolet (UV) light is the most pervasive environmental mutagen and the primary cause of skin cancer. Genome sequencing of melanomas and other skin cancers has revealed that the vast majority of somatic mutations in these tumors are cytosine-to-thymine (C>T) substitutions in dipyrimidine sequences, which, together with tandem CC>TT substitutions, comprise the canonical UV mutation "signature". These mutation classes are caused by DNA damage directly induced by UV absorption, namely cyclobutane pyrimidine dimers (CPDs) or 6-4 pyrimidine-pyrimidone photoproducts (6-4PP), which form between neighboring pyrimidine bases. However, many of the key driver mutations in melanoma do not fit this mutation signature, but instead are caused by T>A, T>C, C>A, or AC>TT substitutions, frequently occurring in non-dipyrimidine sequence contexts. This article describes recent studies indicating that UV light causes a more diverse spectrum of mutations than previously appreciated, including many of the mutation classes observed in melanoma driver mutations. Potential mechanisms for these diverse mutation signatures are discussed, including UV-induced pyrimidine-purine photoproducts and indirect DNA damage induced by UVA light. Finally, the article reviews recent findings indicating that human DNA polymerase eta normally suppresses these non-canonical UV mutation classes, which can potentially explain why canonical C>T substitutions predominate in human skin cancers.

Rapid implementation of blood pressure self-monitoring in pregnancy at a UK NHS Trust during the COVID-19 pandemic: a quality improvement evaluation.

BACKGROUND: This service evaluation describes the rapid implementation of self-monitoring of blood pressure (SMBP) into maternity care at a tertiary referral centre during the COVID-19 pandemic. It summarises findings, identifies knowledge gaps and provides recommendations for further research and practice. INTERVENTION: Pregnant and postpartum women monitored their blood pressure (BP) at home, with instructions on actions to take if their BP exceeded pre-determined thresholds. Some also conducted proteinuria self-testing. DATA COLLECTION AND ANALYSIS: Maternity records, app data and staff feedback were used in interim evaluations to assess process effectiveness and guide adjustments, employing a Plan-Do-Study-Act and root cause analysis approach. RESULTS: Between March 2020 and August 2021, a total of 605 women agreed to self-monitor their BP, including 10 women with limited English. 491 registered for telemonitoring (81.2%). 21 (3.5%) took part in urine self-testing. Engagement was high and increased over time with no safety issues. Biggest concerns related to monitor supply and postnatal monitoring. In December 2020, SMBP was integrated into the standard maternity care pathway. CONCLUSIONS: This project demonstrated successful integration of SMBP into maternity care. Early stakeholder engagement and clear guidance were crucial and community midwifery support essential. Supplying BP monitors throughout pregnancy and post partum could improve the service and fully digitised maternity records would aid data collection. More research is needed on SMBP in the postnatal period and among non-English speakers. These findings support efforts to implement app-supported self-monitoring and guide future research.

Evaluating antibiotic prophylaxis adherence: Implications for surgical site infections and wound care management.

AIM: This study aimed to evaluate adherence to an antibiotic prophylaxis protocol and its impact on incidence of surgical site infection (SSI). MATERIALS AND METHOD: A prospective observational cohort study was conducted at a teaching hospital in São Paulo, Brazil, from September to November 2015. The population were adults who underwent surgery with surgical antibiotic prophylaxis. The main outcomes measured were incidence of SSI at 30-days postoperatively, protocol adherence and surgical wound complications. STROBE guidelines were followed. RESULTS: Among the 527 participants recruited, a 30-day follow-up was completed by 78.7 % (n = 415). Within this cohort, 57.6 % were females aged over 60 years (36.4 %). The incidence of SSI stood at 9.4 % (n = 39), with dehiscence being the most prevalent complication at 64.1 % (n = 25), followed by increased exudate at 51.3 % (n = 20). Notably, full adherence to the antibiotic prophylaxis protocol was low at 1.7 % (n = 7). The study observed a 60 % increased risk of SSI for every protocol mistake made. Alarmingly, 17.8 % (n = 74) of participants received antibiotic treatment exceeding the stipulated protocol duration. The overall mortality rate stood at 13.5 % (n = 56), with 1 % (n = 4) of these deaths attributed to SSI. CONCLUSION: There is a pressing global necessity to enhance antibiotic management, as underscored by this study's revelation of low adherence to the antibiotic prophylaxis protocol. This lack of adherence correlated with a notable incidence of SSI and subsequent wound complications. Nearly 20 % of participants received prolonged antibiotic treatment. Adhering strictly to the protocol could substantially impact SSI-related outcomes and enhance global antibiotic management.

Relative handgrip strength as a vitality measure in US stroke survivors.

PURPOSE: Stroke is a leading cause of long-term disability in the US, yet a feasible assessment measure with predictive value for components of the International Classification of Functioning, Disability, and Health (ICF) Core Set for Stroke is lacking. The purpose of the present study was to explore the predictive value of potential assessment measures on factors within each ICF component in stroke survivors. MATERIALS AND METHODS: Demographic, anthropometric, blood-based biomarker, physical functioning, and Global Physical Activity Questionnaire data were collected on stroke survivors in the 2011-2018 NHANES cycles. Potential predictors (handgrip strength relative to weight, age, sex, race, education level, marital status, poverty ratio, stroke chronicity) of physical function, activities of daily living (ADLs), participation in social activities, metabolic syndrome, and meeting physical activity recommendations were evaluated using weighted linear and ordinal logistic regression. RESULTS: Relative handgrip strength was a significant predictor of physical function, difficulty participating in ADLs and social activities, and odds of meeting physical activity recommendations. As relative handgrip strength increased, these factors improved among stroke survivors. CONCLUSIONS: To decrease disability rates and optimize function among stroke survivors, the use of assessment measures like relative handgrip strength that may predict multiple ICF components is warranted.

Handgrip strength relative to weight may be a significant predictor of multiple components of the International Classification of Functioning, Disability, and Health (ICF) Core Set for Stroke, including physical function, difficulty completing activities of daily living, difficulty participating in social activities, and the odds of meeting physical activity recommendations.Environmental and personal factors, such as income and education, may influence outcomes; thus, education and appropriate resources may need to be included as an aspect of stroke rehabilitation.The heterogenous and pervasive effects of chronic stroke highlight the need to identify outcome measures, like relative handgrip strength, that can influence multiple domains of stroke recovery.

Self-monitoring blood pressure in Pregnancy: Evaluation of health professional experiences of the BUMP trials.

BACKGROUND: The BUMP trials evaluated a self-monitoring of blood pressure intervention in addition to usual care, testing whether they improved detection or control of hypertension for women at risk of hypertension or with hypertension during pregnancy. This process evaluation aimed to understand healthcare professionals' perspectives and experiences of the BUMP trials of self-monitoring of blood pressure during pregnancy. METHODS: Twenty-two in-depth qualitative interviews and an online survey with 328 healthcare professionals providing care for pregnant people in the BUMP trials were carried out across five maternity units in England. RESULTS: Analysis used Normalisation Process Theory to identify factors required for successful implementation and integration into routine practice. Healthcare professionals felt self-monitoring of blood pressure did not over-medicalise pregnancy for women with, or at risk of, hypertension. Most said self-monitored readings positively affected their clinical encounters and professional roles, provided additive information on which to base decisions and enriched their relationships with pregnant people. Self-monitoring of blood pressure shifts responsibilities. Some healthcare professionals felt women having responsibility to decide on timing of monitoring and whether to act on self-monitored readings was unduly burdensome, and resulted in healthcare professionals taking additional responsibility for supporting them. CONCLUSIONS: Despite healthcare professionals' early concerns that self-monitoring of blood pressure might over-medicalise pregnancy, our analysis shows the opposite was the case when used in the care of pregnant people with, or at higher risk of, hypertension. While professionals retained ultimate clinical responsibility, they viewed self-monitoring of blood pressure as a means of sharing responsibility and empowering women to understand their bodies, to make judgements and decisions, and to contribute to their care.

The correlation between sub-epidermal moisture measurement and other early indicators of pressure ulcer development-A prospective cohort observational study. Part 1. The correlation between sub-epidermal moisture measurement and ultrasound.

The correlation between sub-epidermal moisture (SEM) and other early indicators of pressure ulcer (PU) development is yet to be determined. This three-part series aims to bridge this knowledge gap, through investigating SEM and its correlation with evidence-based technologies and assessments. This article focuses on the correlation between SEM and ultrasound. A prospective cohort observational study was undertaken between February and November 2021. Patients undergoing three surgery types were consecutively enrolled to the study following informed consent. Assessments were performed prior to and following surgery for 3 days at the sacrum, both heels and a control site, using a SEM scanner and high-frequency ultrasound scanner (5-15 MHz). Spearman's rank (rs ) explored the correlation between SEM and ultrasound. A total of 60 participants were included; 50% were male with a mean age of 58 years (±13.46). A statistically significant low to moderately positive correlation was observed between SEM and ultrasound across all anatomical sites (rs range = 0.39-0.54, p < 0.05). The only exception was a correlation between SEM and ultrasound on day 0 at the right heel (rs = 0.23, p = 0.09). These results indicate that SEM and ultrasound agreed in the presence of injury; however, SEM was able to identify abnormalities before ultrasound.

Genome-wide impact of cytosine methylation and DNA sequence context on UV-induced CPD formation.

Exposure to ultraviolet (UV) light is the primary etiological agent for skin cancers because UV damages cellular DNA. The most frequent form of UV damage is the cyclobutane pyrimidine dimer (CPD), which consists of covalent linkages between neighboring pyrimidine bases in DNA. In human cells, the 5' position of cytosine bases in CG dinucleotides is frequently methylated, and methylated cytosines in the TP53 tumor suppressor are often sites of mutation hotspots in skin cancers. It has been argued that this is because cytosine methylation promotes UV-induced CPD formation; however, the effects of cytosine methylation on CPD formation are controversial, with conflicting results from previous studies. Here, we use a genome-wide method known as CPD-seq to map UVB- and UVC-induced CPDs across the yeast genome in the presence or absence in vitro methylation by the CpG methyltransferase M.SssI. Our data indicate that cytosine methylation increases UVB-induced CPD formation nearly 2-fold relative to unmethylated DNA, but the magnitude of induction depends on the flanking sequence context. Sequence contexts with a 5' guanine base (e.g., GCCG and GTCG) show the strongest induction due to cytosine methylation, potentially because these sequence contexts are less efficient at forming CPD lesions in the absence of methylation. We show that cytosine methylation also modulates UVC-induced CPD formation, albeit to a lesser extent than UVB. These findings can potentially reconcile previous studies, and define the impact of cytosine methylation on UV damage across a eukaryotic genome.

An impaired ubiquitin-proteasome system increases APOBEC3A abundance.

Apolipoprotein B messenger RNA (mRNA) editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases cause genetic instability during cancer development. Elevated APOBEC3A (A3A) levels result in APOBEC signature mutations; however, mechanisms regulating A3A abundance in breast cancer are unknown. Here, we show that dysregulating the ubiquitin-proteasome system with proteasome inhibitors, including Food and Drug Administration-approved anticancer drugs, increased A3A abundance in breast cancer and multiple myeloma cell lines. Unexpectedly, elevated A3A occurs via an ∼100-fold increase in A3A mRNA levels, indicating that proteasome inhibition triggers a transcriptional response as opposed to or in addition to blocking A3A degradation. This transcriptional regulation is mediated in part through FBXO22, a protein that functions in SKP1-cullin-F-box ubiquitin ligase complexes and becomes dysregulated during carcinogenesis. Proteasome inhibitors increased cellular cytidine deaminase activity, decreased cellular proliferation and increased genomic DNA damage in an A3A-dependent manner. Our findings suggest that proteasome dysfunction, either acquired during cancer development or induced therapeutically, could increase A3A-induced genetic heterogeneity and thereby influence therapeutic responses in patients.

The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD.

Chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD-MBD is unknown. To determine the effect of fiber on CKD-MBD, we fed the Cy/+ rat with progressive CKD a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30% and ~15% of normal kidney function; CKD 4 and 5). We assessed CKD-MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut-derived uremic toxins. Results were analyzed by two-way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor-23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short-chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD-MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut-derived uremic toxins. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Population Genome Programs across the Middle East and North Africa: Successes, Challenges, and Future Directions.

In this review, we discuss the current state of population genome programs (PGPs) conducted in the Middle East and North African (MENA) region. This region has high prevalence of genetic diseases and significant health challenges as well as being a significantly underrepresented population in public genetic databases. The majority of ongoing PGPs represent regions in Europe, North and South America, South Asia, Australia, and Africa, with little to no descriptive information highlighted only on the MENA Region when it comes to genome programs databases, outcomes, or the challenges that MENA region countries may face establishing their own national programs. This review has identified 6 PGPs currently underway in the MENA region, namely in the Kingdom of Saudi Arabia, Qatar, Egypt, the United Arab Emirates, Bahrain, and Iran. Due to the rapidly growing involvement of the MENA region in national-scale genomic data collection, an increase in representation in public genetic databases is to be expected to occur in the near future. Whilst significant progress is being made in some MENA countries, future initiatives as well as ongoing programs will be facing several challenges related to collaboration, finance, infrastructure and institutional data access, data analysis, sustainability, health records, and biobanks. The review also reiterates the need for ensuring ethical and regulated genomic initiatives which can drive developments in personalized medicine treatments to improve patient prognosis and quality of life.

Development of an Fe2+ sensing system based on the inner filter effect between upconverting nanoparticles and ferrozine.

The ferrozine (FZ) assay is a vital oxidation state-specific colorimetric assay for the quantification of Fe2+ ions in environmental samples due to its sharp increase in absorbance at 562 nm upon addition of Fe2+. However, it has yet to be applied to corresponding fluoresence assays which typically offer higher sensitivites and lower detection limits. In this article we present for the first time its pairing with upconverting luminescent nanomaterials to enable detection of Fe2+via the inner filter effect using a low-power continuous wave diode laser (45 mW). Upon near infra-red excitation at 980 nm, the overlap of the upconversion emission of Er3+ at approximately 545 nm and the absorbance of the FZ:Fe2+ complex at 562 nm enabled measurement in the change of UCNP emission response as a function of Fe2+ concentration in a ratiometric manner. We first applied large, ultra-bright poly(acrylic acid) (PAA)-capped Gd2O2S:Yb3+,Er3+ UCNPs upconverting nanoparticles (UCNPs) for the detection of Fe2+ using FZ as the acceptor. The probe displayed good selectivity and sensitivity for Fe2+, with a low limit of detection (LoD) of 2.74 µM. Analogous results employing smaller (31 nm) PAA-capped hexagonal-phase NaYF4:Yb3+,Er3+ UCNPs synthesised in our lab were achieved, with a lower LoD towards Fe2+ of 1.43 µM. These results illustrate how the ratiometric nature of the system means it is applicable over a range of particle sizes, brightnesses and nanoparticle host matrices. Preliminary investigations also found the probes capable of detecting micromolar concentrations of Fe2+ in turbid solutions.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Diet Quality Outcomes of a Cooperative Extension Diabetes Prevention Program.

OBJECTIVE: The effectiveness of the National Diabetes Prevention Program (DPP) in improving diet quality (DQ) in community settings is largely unknown. This study aimed to evaluate the DQ changes of Extension DPP participants. METHODS: A single-group, repeated-measures design was used to evaluate an Extension-implemented DPP using the PreventT2 curriculum. Participants were overweight adults with or at high risk for prediabetes (n = 88). Weight and DQ (Healthy Eating Index-2015, Dietary Screener Questionnaire) were evaluated using mixed-effects regression. RESULTS: There was no change in the Healthy Eating Index-2015 total score. Predicted fiber, fruit, and vegetable intake increased (P < 0.05) but remained below recommendations. CONCLUSIONS AND IMPLICATIONS: Clinically meaningful DQ changes of Extension DPP participants were limited. The effect of the DPP on DQ in Extension and other implementation settings should be evaluated through randomized controlled trials. Diabetes Prevention Program curriculum revisions that include more specific dietary goals and educational tools may promote greater DQ changes in DPP participants.

Genome-wide maps of UVA and UVB mutagenesis in yeast reveal distinct causative lesions and mutational strand asymmetries.

Ultraviolet (UV) light primarily causes C > T substitutions in lesion-forming dipyrimidine sequences. However, many of the key driver mutations in melanoma do not fit this canonical UV signature, but are instead caused by T > A, T > C, or C > A substitutions. To what extent exposure to the UVB or UVA spectrum of sunlight can induce these noncanonical mutation classes, and the molecular mechanism involved is unclear. Here, we repeatedly exposed wild-type or repair-deficient yeast (Saccharomyces cerevisiae) to UVB or UVA light and characterized the resulting mutations by whole genome sequencing. Our data indicate that UVB induces C > T and T > C substitutions in dipyrimidines, and T > A substitutions that are often associated with thymine-adenine (TA) sequences. All of these mutation classes are induced in nucleotide excision repair-deficient cells and show transcriptional strand asymmetry, suggesting they are caused by helix-distorting UV photoproducts. In contrast, UVA exposure induces orders of magnitude fewer mutations with a distinct mutation spectrum. UVA-induced mutations are elevated in Ogg1-deficient cells, and the resulting spectrum consists almost entirely of C > A/G > T mutations, indicating they are likely derived from oxidative guanine lesions. These mutations show replication asymmetry, with elevated G > T mutations on the leading strand, suggesting there is a strand bias in the removal or bypass of guanine lesions during replication. Finally, we develop a mutation reporter to show that UVA induces a G > T reversion mutation in yeast that mimics the oncogenic NRAS Q61K mutation in melanoma. Taken together, these findings indicate that UVA and UVB exposure can induce many of the noncanonical mutation classes that cause driver mutations in melanoma.

Partnering with charity-care services to manage cirrhosis with ascites in an adult experiencing homelessness: A case report.

Charity care services can be an important tool for reducing healthcare disparities among populations with housing instability.