Recommendations for the use of pediatric data in artificial intelligence and machine learning ACCEPT-AI.

ACCEPT-AI is a framework of recommendations for the safe inclusion of pediatric data in artificial intelligence and machine learning (AI/ML) research. It has been built on fundamental ethical principles of pediatric and AI research and incorporates age, consent, assent, communication, equity, protection of data, and technological considerations. ACCEPT-AI has been designed to guide researchers, clinicians, regulators, and policymakers and can be utilized as an independent tool, or adjunctively to existing AI/ML guidelines.

Characterizing injury patterns and outcomes in hospitalized trauma patients with non-English Language Preferences.

INTRODUCTION: Patients with Non-English Language Preferences (NELP) experience challenges navigating the US healthcare system which can lead to disparate outcomes. This study sought to investigate injury patterns and outcomes in hospitalized trauma patients with NELP. METHODS: A retrospective review was performed at a trauma center from January 2019-December 2020. An institutional database of all emergency department video consultations for interpreter services was cross-referenced with the trauma registry and comparisons were made between NELP and English-preferred (EP) speaking patients. RESULTS: During the study, 257 NELP patients were hospitalized after traumatic injury. Twenty-two percent had work related injuries compared to only 3.0% in the EP cohort (p < 0.001). When propensity score matched, there were no significant differences in ICU and hospital length of stay or mortality between NELP and EP patients. DISCUSSION: Trauma patients are linguistically diverse and understanding their injury patterns and outcomes is crucial for guiding culturally and linguistically appropriate injury prevention.

Presentation, clinical course and complications in trauma patients with concomitant COVID-19 infection.

BACKGROUND: This study investigated the impact of COVID-19 infection on hospitalized trauma patients. METHODS: A retrospective review of hospitalized trauma patients at a level I trauma center was performed from March-December 2020. Data pertaining to patient demographics, presentation and hospital course was compared between COVID positive and negative trauma patients. RESULTS: There were 4,912 patients and 179 (3.64%) were COVID-19 positive. Demographics and clinical presentation did not differ significantly between those with and without concomitant COVID-19. However, COVID positive trauma patients had higher rates of acute kidney injury (p = 0.016), sepsis (p = 0.016), unplanned intubation (p = 0.002) and unplanned return to the ICU (p = 0.01). The COVID positive cohort also had longer hospital stays (p < 0.01) with no significant difference in mortality. CONCLUSIONS: In the setting of an ongoing pandemic, awareness of the complications COVID positive trauma patients are predisposed to is important for providers.

The Design, Synthesis, and Evaluation of Diaminopimelic Acid Derivatives as Potential dapF Inhibitors Preventing Lysine Biosynthesis for Antibacterial Activity.

We created thiazole and oxazole analogues of diaminopimelic acid (DAP) by replacing its carboxyl groups and substituting sulphur for the central carbon atom. Toxicity, ADME, molecular docking, and in vitro antimicrobial studies of the synthesized compounds were carried out. These compounds displayed significant antibacterial efficacy, with MICs of 70-80 µg/mL against all tested bacteria. Comparative values of the MIC, MBC, and ZOI of the synthesized compound were noticed when compared with ciprofloxacin. At 200 µg/mL, thio-DAP (1) had a ZOI of 22.67 ± 0.58, while ciprofloxacin had a ZOI of 23.67 ± 0.58. To synthesize thio-DAP (1) and oxa-DAP (2), l-cysteine was used as a precursor for the L-stereocenter (l-cysteine), which is recognized by the dapF enzyme's active site and selectively binds to the ligand's L-stereocenter. Docking studies of these compounds were carried out using the programme version 11.5 Schrodinger to reveal the hydrophobic and hydrophilic properties of these complexes. The docking scores of compounds one and two were -9.823 and -10.098 kcal/mol, respectively, as compared with LL-DAP (-9.426 kcal/mol.). This suggests that compounds one and two interact more precisely with dapF than LL-DAP. Chemicals one and two were synthesized via the SBDD (structure-based drug design) approach and these act as inhibitors of the dapF in the lysine pathway of bacterial cell wall synthesis.

Microsurgical clipping versus newer endovascular techniques in treatment of unruptured anterior communicating artery-complex aneurysms: a meta-analysis and systematic review.

The aim of this study is to compare occlusion rate, complication rate, and clinical outcome of microsurgical clipping (MC) and advanced endovascular techniques (EVT) in unruptured anterior communicating artery-complex aneurysms (ACoCAs). We reviewed the scientific literature reporting occlusion rate, time of occlusion assessment, and clinical outcome of MC and EVT in patients with unruptured ACoCAs, from January 2009 to December 2019. We included in our analysis 25 studies and 872 patients with unruptured ACoCAs (434 treated with endovascular techniques and 438 with MC). Ninety-three (10.7%), 320 (36.7%), 21 (2.4%), and 438 (50.2%) were treated with flow diverter (FD), stent-assisted coiling (SAC), endosaccular devices (ES), and microsurgical clipping (MC) respectively. FD, SAC, ES, and MC subgroups presented minor complications in 11.8%, 3.8%, 14.3%, and 7.1% of cases (p=.016), and major complications in 3.2%, 4.4%, 0%, and 7.1% (p=.136) of patients. A total occlusion rate post-treatment has been achieved in 4.3%, 87.1%, 47.6%, and 98.2% of cases (p=.000), while at 12 months' follow-up in 50%, 66%, 83.3%, and 80% of patients (p=.001). FD, SAC, ES, and MC subgroups had a good clinical outcome at 12 months in 93.5%, 90.5%, 100%, and 67.8% of cases. MC is associated with higher post-treatment total occlusion rate, but higher complication and lower good clinical outcome rates. EVT are promising in treating unruptured anterior cerebral artery aneurysms with high margin of safety and good clinical outcome, despite the lower total occlusion rate.

Prevalence of hypoxia and correlation with glycolytic metabolism and angiogenic biomarkers in metastatic colorectal carcinoma.

PURPOSE: Hypoxia is associated with aggressive tumour behaviour and can influence response to systemic therapy and radiotherapy. The prevalence of hypoxia in metastatic colorectal cancer is poorly understood, and the relationship of hypoxia to patient outcomes has not been clearly established. The aims of the study were to evaluate hypoxia in metastatic colorectal cancer with [18F]Fluoromisonidazole ([18F]FMISO PET) and correlate these findings with glycolytic metabolism ([18F]FDG PET) and angiogenic blood biomarkers and patient outcomes. METHODS: Patients with metastatic colorectal cancer received routine staging investigations and both [18F] FMISO PET and [18F] FDG PET scans. Correlative blood specimens were also obtained at the time of the [18F] FMISO PET scan. Patient follow-up was performed to establish progression-free survival. RESULTS: A total of 40 patients were recruited into the trial. [18F]FMISO and [18F]FDG PET scans showed a significant correlation of SUVmax (p = 0.003). A significant correlation of progression-free survival and [18F] FMISO TNR (p = 0.02) and overall survival with [18F]FMISO TNR (p = 0.003) and [18F]FDG TGV (p = 0.02) was observed. Serum levels of osteopontin, but not VEGF, correlated with [18F] FMISO and [18F]FDG PET scan parameters. CONCLUSION: [18F]FMISO PET uptake in metastatic colorectal cancer significantly correlates with glycolytic metabolism and is predictive of progression-free and overall survival. These findings have implications for the assessment and treatment of metastatic colorectal cancer patients with novel therapies which affect tumour angiogenesis and hypoxia.

Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome.

Malaria is caused by the protozoan parasite Plasmodium, which undergoes a complex life cycle in a human host and a mosquito vector. The parasite's cyclic GMP (cGMP)-dependent protein kinase (PKG) is essential at multiple steps of the life cycle. Phosphoproteomic studies in Plasmodium falciparum erythrocytic stages and Plasmodium berghei ookinetes have identified proteolysis as a major biological pathway dependent on PKG activity. To further understand PKG's mechanism of action, we screened a yeast two-hybrid library for P. falciparum proteins that interact with P. falciparum PKG (PfPKG) and tested peptide libraries to identify its phosphorylation site preferences. Our data suggest that PfPKG has a distinct phosphorylation site and that PfPKG directly phosphorylates parasite RPT1, one of six AAA+ ATPases present in the 19S regulatory particle of the proteasome. PfPKG and RPT1 interact in vitro, and the interacting fragment of RPT1 carries a PfPKG consensus phosphorylation site; a peptide carrying this consensus site competes with the RPT1 fragment for binding to PfPKG and is efficiently phosphorylated by PfPKG. These data suggest that PfPKG's phosphorylation of RPT1 could contribute to its regulation of parasite proteolysis. We demonstrate that proteolysis plays an important role in a biological process known to require Plasmodium PKG: invasion by sporozoites of hepatocytes. A small-molecule inhibitor of proteasomal activity blocks sporozoite invasion in an additive manner when combined with a Plasmodium PKG-specific inhibitor. Mining the previously described parasite PKG-dependent phosphoproteomes using the consensus phosphorylation motif identified additional proteins that are likely to be direct substrates of the enzyme.

The effect of a surgery-specific cardiac output-guided haemodynamic algorithm on outcomes in patients undergoing pancreaticoduodenectomy in a high-volume centre: a retrospective comparative study.

In this retrospective observational study performed in a high-volume hepatobiliary-pancreatic unit, we evaluated the effect of a surgery-specific goal-directed therapy (GDT) physiologic algorithm on complications and length of hospital stay. We compared patients who underwent pancreaticoduodenectomy with either a standardised Enhanced Recovery After Surgery program (usual care group), or a standardised Enhanced Recovery After Surgery program in combination with a surgery-specific cardiac output-guided algorithm (GDT group). We included 145 consecutive patients: 47 in the GDT group and 98 in the usual care group. Multivariable associations between GDT and lengths of stay and complications were investigated using negative binomial regression. Postoperative complications were common and occurred at similar frequencies amongst the GDT and usual care groups: 64% versus 68% respectively, P=0.71; odds ratio 0.82; (95% confidence interval 0.39-1.70). There were fewer cardiorespiratory complications in the GDT group. Median (interquartile range) length of hospital stay was ten days (8.0-14.0) in the GDT group compared to 13 days (8.8-21.3) in the usual care group, P=0.01. Median (interquartile range) total intraoperative fluid was 3,000 ml (2,050-4,175) in the GDT group compared to 4,500 ml (3,275-5,325) in the usual care group, P <0.0001; but by day one, the median (interquartile range) fluid balance was similar (1,198 ml [700-1,729] in the GDT group versus 977 ml [419-2,044] in the usual care group, P=0.96). Use of vasoactive medications was higher in the GDT group. In our patients undergoing pancreaticoduodenectomy, GDT was associated with restrictive intraoperative fluid intervention, fewer cardiorespiratory complications and a shorter hospital length of stay compared to usual care. However, we could not exclude an influence of surgical caseload, which we have previously found to be an important variable. We also could not relate the increased hospital length of stay to cardiorespiratory complications in individual patients. Therefore, these observational retrospective findings would require confirmation in a prospective randomised study.

Early Outcome of Liver Resections in Octogenarians.

BACKGROUND: Reports on safety and feasibility of liver resection in patients 80 years and older are very limited. OBJECTIVE: Here, we intend to analyze the perioperative outcomes of liver resections in octogenarians performed at a single tertiary level teaching hospital over a ten years period. METHOD: Retrospective review of the medical records (between 2004 to 2014) of patients of the defined age group was performed. Clinicopathological features, indications, extent of resections, intraoperative parameters, postoperative complications and final outcome were analyzed. Findings were compared with similar studies published in literature. RESULT: Total 19 (11 male, 8 female, maximum age 85 years) patients of the study group underwent liver resection during the defined period. Commonest indication was colorectal liver metastasis (9 patients). One patient had pancreaticodudenectomy for periampullary malignancy four years prior to present with liver metastasis and subsequently had liver resection for recurrence of disease. Except one, all had open surgery. Types of resection ranged from sub segmental to major right (8 patients) and left (1 patient) hepatectomy. Total 3 (27%) out of 11 patients on whom drain was not placed required radiological drainage of abdominal collection. One patient developed liver abscess postoperatively and was also successfully drained under radiological guidance. Only 2 (10.5%) had prolonged Intensive Care Unit (ICU) stay and remaining patients were discharged to ward after 24 hrs of observation in high dependency/Intensive care unit. Median hospital stay was 11 days. Postoperative complications were 3 of grade II, 4 of grade IIIa, 1 of IIIb and 2 of IVa. Total 9 patients were discharged to rehabilitation centers and remaining 10 could be discharged home. There was 0% mortality. CONCLUSION: In appropriately selected cases, when performed in specialized tertiary centers excellent perioperative outcomes of liver resections can be achieved even in patients of 80 years of age and above.

Blockade of the renin-angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver.

Partial hepatectomy (PH), the preferred option for selected patients with colorectal cancer liver metastases (CRCLM), is associated with 40-80% tumor recurrence rates. Renin-angiotensin system (RAS) blockade inhibits tumor growth and has been suggested to improve liver regeneration. We documented the effect of RAS blockade on tumor growth and liver regeneration in a murine model. CRCLM induction followed by 70% PH was performed on 78 CBA mice. Liver regeneration (days 2, 6) and CRCLM tumor load were measured by liver (and tumor) weights, percentage of CRCLM burden and tumor nodule count (days 16, 21). mRNA expression of the RAS components was characterised. Statistical analysis was performed using 2-independent sample T test or Mann-Whitney test (SPSS). Captopril did not impair liver regeneration. By day 21, Captopril decreased tumor burden (percentage of CRCLM in the liver) (48.7 ± 4.7% control, 24.4 ± 6.2 Captopril; p = 0.008), tumor volume (1046.2 ± 200.2 mm(3), 388.3 ± 150.4; p = 0.02), tumor nodule count per image field (181.1 ± 28.5, 68 ± 17.6; p = 0.005) and tumor angiogenesis (71.8 ± 6.4 vessels/mm(2), 43.1 ± 7.6; p = 0.015) compared to controls. Captopril enhanced tumor apoptosis (1 ± 0.2%, 2.5 ± 0.7; p = 0.028). Liver regeneration and tumor development increased liver ACE levels. Blockade of the RAS effectively retarded CRCLM tumor growth at the late stage of tumor development within the regenerating liver without impeding liver regeneration following PH, via anti-angiogenesis and pro-tumor apoptosis. Captopril may be of therapeutic benefit in patients undergoing PH for CRCLM.

Improved the electrochemical performance of LiCe(1-x)Ni(x)O2 cathode material for rechargeable lithium ion battery.

Cerium substituted LiCe(1-x)Ni(x)O2 (0.00 < X < 0.20) (Ce = 0.00 < X < 0.20) nano-particles were synthesized by sol-gel method using nitrate as precursor at 800 degrees C for 12 hrs. XRD studies were revealed a well defined layer structure and a linear variation of lattice parameters with the addition of Cerium confirmed phase pure compounds in a rhombohedral structure for all materials. The surface morphological and particles agglomeration changes by the substitution of Cerium in LiNiO2 particles were examined by scanning electron microscope technique and TEM techniques. Ce3+ has prevented Jahn-Teller distortion and contained the NiO6 in LiCe(1-x)Ni(x)O2 through charge transfer from Ce-3d orbital to nearby Ni-3d orbital. The preferential occupation of Ce3+ in the Li sites was decreased the mixing of Ni2+ into the Li sites and improved the electrochemical properties of LiNiO2. The galvanostatic charge/discharge studies using assembled cells were carried out at 0.5 C rates. Cyclic voltammetric studies were carried out in the potential range between 3.5 V and 4.7 V at a scan rate of 0.1 mV s(-1). Electrochemical impedance spectroscopy revealed that, LiCe0.15Ni0.85O2 augmented charge transfer resistance upon cycling. The variations of cerium mixing and hexagonal ordering with the element (increase in R-factor) were favoured the first discharge capacity with the substituted element. LiCe0.15Ni0.85O2 nano cathode materials have superior electrochemical performances, such as, high charge-discharge capacity, high coulombic efficiency, high electrical conductivity and low irreversible capacity loss.

Electrodeposition and characterization of Ni-ZrO2 nanocomposites by direct and pulse current methods.

Direct Current (DC) and Pulse current (PC) methods were used to get nanocrystalline Ni-ZrO2 composites from tri-ammonium citrate bath. In the electrocomposite formation, the ZrO2 particles were transported to the surface by mechanical action and got entrapped in the nickel matrix. Incorporation of ZrO2 in the nickel matrix was found to increase with current densities when DC was employed. Beyond 2 A/dm2, their incorporation became saturated when PC was used. PC method offered better electrocomposites than DC method producing finer grains and uniform surface. Scanning electron micrographs (SEM) reveals that smaller grains and uniform distribution of Zirconia particles in the nickel matrix. The increased hardness of Ni-ZrO2 electrocomposite coatings is due to incorporation of ZrO2 particles in the nickel matrix and also changes in grain size. Incorporation of ZrO2 particles in Ni-matrix favoured the enhanced microhardness and corrosion resistance of the deposit.

Influence of health and environmental information on hedonic evaluation of organic and conventional bread.

Grain from paired samples of the hard red spring wheat cultivar "Park" grown on both conventionally and organically managed land was milled and baked into 60% whole wheat bread. Consumers (n= 384) rated their liking of the bread samples on a 9-point hedonic scale before (blind) and after (labeled) receiving information about organic production. Consumers liked organic bread more (P < 0.05) than conventional bread under blind and labeled conditions. Environmental information about organic production did not impact consumer preference changes for organic bread, but health information coupled with sensory evaluation increased liking of organic bread. Ordinary least squares (OLS) and binary response (probit) regression models identified that postsecondary education, income level, frequency of bread consumption, and proenvironmental attitudes played a significant role in preference changes for organic bread. The techniques used in this study demonstrate that a combination of sensory and econometric techniques strengthens the evaluation of consumer food choice.

Patterns of heat shock protein (HSP70) expression and Kupffer cell activity following thermal ablation of liver and colorectal liver metastases.

The time course and extent of thermal ablative injury differs in liver compared to tumour tissue. This may be influenced by differences in the expression of heat shock proteins (HSP) and the response of Kupffer cells to thermal injury. This study determines the expression and response of HSP70 and Kupffer cells to thermal ablative injury in a Murine model of colorectal liver metastases. Thermal ablation by laser (Nd-YAG wavelength 1064 nm) was induced in liver and colorectal cancer liver metastases in CBA strain mice. Laser energy was applied at 2 W for 50 s and produced incomplete tumour ablation. Established tissue injury was assessed in separate groups of animals at time points ranging from 12 h to 21 days following therapy. HSP70 and Kupffer cell expression at the margins of coagulated tissue was determined by immunohistochemical staining for HSP70 and F4/80 antigens, respectively. HSP70 was faintly expressed in the cytoplasm of all tumour cells, with distinct clusters exhibiting intense cytoplasmic and nuclear HSP70 staining (130+/-19 cells mm-2). Comparatively, HSP70 expression was uncommon in untreated control liver specimens (2+/-2 cells mm-2, p<0.001). Thermal ablation increased expression of HSP70 at coagulated tissue margins. The peak response in tumours occurred at 2 days post-ablation and was significantly greater than the peak response in liver, occurring at 12 h (809+/-80 cells mm-2 vs. 454+/-52 cells mm-2, p<0.001). HSP70 expression remained significantly elevated for 7 days following therapy in tumour tissue, compared to 3 days in liver. Kupffer cell numbers in untreated control tumours were significantly lower than in untreated control livers (285+/-23 cells mm-2 vs. 451+/-30 cells mm-2, p<0.001). Following thermal ablation, there was an initial decrease in Kupffer cell numbers at the margin of coagulation with subsequent persistent increases thereafter. In liver tissue, the peak Kupffer cell response occurred at 5 days post-therapy and was significantly greater than the peak response in tumour tissue 3 days post-thermal ablation (1074+/-34 cells mm-2 vs. 860+/-53 cells mm-2, p=0.007). Thermal ablation produces a greater and more prolonged HSP70 response in colorectal liver metastases than in liver tissue. It also induces persistent increases in Kupffer cell activity in liver and tumour tissue.

Primary hepatic carcinoid tumours.

BACKGROUND: Carcinoid tumours of the liver are predominantly metastases from the gastrointestinal tract. Primary hepatic carcinoids are extremely rare. DISCUSSION: In contrast to metastases, primary hepatic carcinoids are usually solitary and resectable. It is important that these tumours are differentiated from metastases. Complete surgical resection should be contemplated and is generally curative.

Scanning electron microscopy study of the blood supply of human colorectal liver metastases.

AIMS: The failure of hepatic artery directed treatment of colorectal liver metastases may reflect a major portal venous contribution to tumour blood supply. This study provides ultrastructural details of the blood supply of colorectal liver metastases and their association with the portal vein and hepatic artery. METHODS: Resected liver specimens from six patients with colorectal liver metastases were examined by histology and scanning electron microscopy (SEM), following vascular resin casting. RESULTS: Nine metastatic colorectal adenocarcinomas were identified. The main feature of all tumours on SEM was direct communication between hepatic sinusoids and tumour vessels. A direct portal venous connection with tumour vessels was observed in a single specimen, whilst a direct arteriole connection was not identified. CONCLUSIONS: It appears that both the hepatic artery and portal vein contribute to the blood supply of colorectal liver metastases through sinusoidal connections with tumour specific blood vessels. SEM provides useful additional information on the morphological features of tumour vasculature.

Interstitial laser hyperthermia and the biological characteristics of tumor: study in a murine model of colorectal liver metastases.

BACKGROUND DATA: Percutaneously applied interstitial laser hyperthermia (ILH) is a minimally invasive therapy that is currently used in the treatment of liver metastases. Despite its documented efficacy, theoretical considerations and evidence based on animal studies suggest the potential for stimulating tumor growth, especially following surgery. This study investigates the influence of ILH on tumor behaviour in an animal model of colorectal liver metastases. MATERIALS AND METHODS: A model of colorectal cancer liver metastases in male inbred CBA mice was used. Laser hyperthermia was applied to tumor tissue using a bare optical quartz from a Medilas fibertom 4100 Nd:YAG surgical laser generator. Liver injury by ILH was initially produced in three experimental groups of animals at different time points in the development of metastases. ILH was applied (i) to normal liver 10 days prior to tumor induction, (ii) immediately prior to tumor induction, and (iii) 15 days after tumor induction to achieve approximately 8% liver destruction. Animals were killed 21 days after tumor induction, and the effects of ILH on overall tumor development were compared with controls using stereological assessment of tumor volume and by histology. In a separate experimental group, the effects of ILH on fully established tumors were examined. Suitable tumors were selected 21 days after induction and partially destroyed by ILH at a standard energy setting. Animals were then killed 15 days later, and the growth rate of the residual viable tumors was compared to control tumors having undergone sham procedures. RESULTS: No significant stimulation of tumor growth was evident in any of the experimental groups following ILH, irrespective of the time of application. Incomplete tumor destruction also had no influence on subsequent tumor growth. CONCLUSION: ILH does not influence the biological characteristics of tumors during any stage of the metastatic process.