Recent advances in nano and micro formulations of Ginsenoside to enhance their therapeutic efficacy.

BACKGROUND AND AIMS: Ginsenosides, the main component of Panax ginseng, have long been recognized for their therapeutic benefits and are thought to have neuroprotective, antidiabetic, anti-depressant, antioxidant, anti-cancer, and anti-stress properties. However, due to their low water solubility, low biomembrane permeability, gastrointestinal dysfunction, and total metabolism in the body, ginsenosides have a poor absorption profile that has hindered the therapeutic potential of these organic molecules. METHODS: Initially, we broadly illuminated the several techniques of extraction of Ginsenosides using Panax quinquefolius and Panax ginseng. Subsequently, we focused on different delivery methods to improve the stability, permeability, and solubility of natural chemicals, which raises the bioavailability of ginsenoside. Lastly, we explained significance of a variety of nano and microscale delivery systems, including liposomes, ethosomes, transfersomes, metal/metal oxide systems, micro/nanoemulsions, polymeric micro/nanoparticles (NPs), liposomes, transfersomes, and micelles to increase the bioavailability of ginsenosides. RESULTS: The utilization of micro/nanoscale delivery methods, such as liposome-based delivery, polymer micro/nanoparticle distribution, and micro/nanoemulsion, to increase the bioavailability of ginsenosides has recently advanced, and we have emphasized these advances in this study. Furthermore, the disadvantages of ginsenosides were also discussed, including the challenges associated with putting these delivery systems into practice in clinical settings and suggestions for further research. CONCLUSION: In summary, ginsenosides-based administration has several benefits that make it a potentially useful substance for a range of therapeutic purposes.

Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population.

PURPOSE: To identify the impact of CYP2C9*2, *3, VKORC1-1639 G>A and CYP4F2*3 on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing algorithms (GWD) during warfarin initiation. METHODS: A cohort of Arab patients newly starting on warfarin had their dose calculated using CWD published in www.warfarindosing.org and were followed for 1 month. Each patient provided a saliva sample. DNA was extracted, purified and genotyped for VKORC-1639 G>A, CYP2C9*2, CYP2C9*3 and CYP4F2*3. After reaching warfarin maintenance dose, the dose was recalculated using the GWD and median absolute error (MAE) and the percentage of warfarin doses within 20% of the actual dose were calculated and compared for the two algorithms. RESULTS: The study enrolled 130 patients from 12 Arabian countries. Compared to those with wild type, carriers of reduced function alleles in CYP2C9 required significantly lower median (IQR) warfarin weekly dose [24.5 (15.3) vs. 35 (29.8) mg/week, p=0.006]. With regards to VKORC, patients with AA genotype had a significantly lower median (IQR) weekly warfarin dose compared to AG and GG [21(10.5) vs 29.4 (21), p<0.001 for AA vs AG, p<0.001 for AA vs GG]. The MAE (IQR) for the weekly dose of the GWD was significantly lower compared to CWD [8.1 (10.5) vs 12.4 (12.6) (p<0.001)]. CONCLUSION: CYP2C9 and VKORC1 variants are important determinants of warfarin dose in the Arab population. The use of the genetic and clinical factors led to better warfarin dose estimation when compared to clinical factors alone.

Health Care Access, Socioeconomic Status, and Acute Kidney Injury Outcomes: A Prospective National Study.

Rationale & Objectives: Acute kidney injury (AKI) incidence and outcome in Kuwait are unknown. Moreover, non-Kuwaitis, who represent 66% of the population, have lower income, and their access to public health services is restricted compared with Kuwaitis who have free full access. Study Design: Observational prospective multicenter cohort study. Setting & Participants: Adult inpatients with AKI in 7 public hospitals from January 1 to December 31, 2021. Exposure: AKI identified using Kidney Disease: Improving Global Outcomes serum creatinine-based criteria. Outcomes: For hospitalized patients with AKI, the outcomes included 30-day outcomes of mortality, need for dialysis, kidney recovery rates, and differences in outcomes between Kuwaitis and non-Kuwaitis. Analytical Approach: A backward stepwise multiple logistic regression analysis was performed to assess possible independent risk factors for the outcomes. Results: We recruited 3,744 patients (mean age: 63 years; mean baseline estimated glomerular filtration rate [eGFR]: 66.7 mL/min; non-Kuwaitis: 42.3%), representing 3.2% of hospitalizations and 19.5% of intensive care unit (ICU) admissions. Non-Kuwaitis were significantly younger (57.6 vs 66.9 years), with higher baseline eGFR (73.1 vs. 62 mL/min), more frequent community acquired AKI (53.8% vs 46.7%), and AKI in summer (34.7% vs 26.9%). Dialysis was provided to 33.5% of patients, with a higher need for non-Kuwaitis (35.5% vs 32.1%). At 30 days, 34.4% of patients died, representing 24.8% of hospital mortality and 59.8% of ICU mortality. No differences in mortality or kidney recovery were noted between Kuwaitis and non-Kuwaitis. Low eGFR did not affect the mortality rate. Limitations: Observational nature and short follow-up period of 30 days only. Conclusions: AKI was associated with high dialysis need and mortality. Non-Kuwaitis accounted for less cases despite representing 66% of the population because they were younger with higher baseline eGFR and fewer comorbid conditions. Non-Kuwaitis had higher rates of community acquired AKI and AKI in summer and a higher need for dialysis but had similar mortality and complete kidney recovery rates.

Incidences of acute kidney injury (AKI), its management, and its outcomes are unknown in Kuwait. In addition, Kuwait has a large population of ethnically diverse expatriates who have lower income and do not enjoy the same level of access to public hospital services. We recruited hospitalized adults who have a diagnosis of AKI in several public hospitals in Kuwait. We analyzed characteristics, management, and outcomes data for more than 3,700 patients and found that AKI affects 3.2% of hospitalized patients. AKI leads to high dialysis utilization rates and causes high mortality rates. Although more Kuwaitis were affected by AKI, the mortality rates for Kuwaitis and non-Kuwaitis were similar. Non-Kuwaitis were younger with better baseline kidney function and fewer chronic diseases than Kuwaitis.

The characteristics of frozen-thawed rooster sperm using various intracellular cryoprotectants.

Cryopreservation of rooster semen is essential for conserving genetic resources, genetic improvement, and increasing productivity. However, the nature of avian sperm presents a global issue in ensuring superior frozen semen for artificial insemination. Thus, the present study aimed to evaluate the impact of using dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), and ethylene glycol (EG) as cryoprotectants on post-thawed sperm motility, quality, antioxidant indicators, and fertilizing capacity. Twice a week, fresh semen ejaculates were collected from 15 adult roosters and immediately evaluated to constitute a pool from clean and qualified samples. The pooled semen was further diluted at a ratio of 1:2 (v/v) with an extender and then subjected to a freezing protocol in a liquid nitrogen vapor after adding a cryoprotectant solution containing 6% of either DMA, DMSO, or EG, respectively. After thawing, characteristics of sperm motion, quality, antioxidants, and fertilizing ability were evaluated and compared to fresh and cooled semen as controls. The results demonstrated that semen cooling negatively affected some parameters of sperm motility, quality, antioxidant biomarkers, and fertility. In comparison to the DMSO and EG groups, employing DMA considerably (P < 0.05) raised the percentages of sperm progressive motility, viability, plasma membrane intactness, and DNA integrity. The DMA group showed a significant increase in the catalase and glutathione reduced antioxidant enzyme activity and a reduction in nitric oxide and lipid peroxidation. After artificial insemination, the DMA and DMSO groups exhibited considerably (P < 0.05) better rates of hatchability and fertility than the EG group. It is concluded that freezing extenders containing 6% DMA is better than DMSO or EG to improve the post thaw semen quality and fertility in chickens.

Determining the role of statins in Parkinson's disease risk reduction and disease modification: A comprehensive meta-analysis of 4 million participants' data.

BACKGROUND: Many observational studies have examined the association between statins and the incidence of Parkinson's disease (PD) in high-risk populations. On the other hand, clinical trials as well as other observational studies investigated the safety and efficacy of statins in slowing disease progression in PD patients. However, the evidence has been inconclusive in both questions. To that end, we conducted this systematic review and meta-analysis to synthesize evidence on the role of statins in decreasing the risk of PD among high-risk populations and as a possible disease-modifying agent for patients with PD. METHODS: A comprehensive literature search of electronic databases including PubMed, Scopus, Cochrane, and Web of Science has been performed. Relevant studies were chosen and data were extracted and analyzed using RevMan software version 5.4.1. RESULTS: Twenty-five studies (14 cohort, 9 case-control, and 2 randomized controlled trials) have been included in the present systematic review. Of them, 21 studies reported the association between statins and PD risk. Statins were found to significantly reduce the risk of developing PD (pooled RR 0.86, 95% CI [0.77-0.95], p < 0.005). Four studies investigated statins as a disease-modifying agent. The pooled mean difference (MD) in the UPDRS-III from baseline to endpoint did not differ significantly between the statin and control groups (MD -1.34 points, 95% CI [-3.81 to 1.14], p = 0.29). CONCLUSION: Although epidemiological observational studies showed that statin use was associated with a reduced risk of PD, current evidence is insufficient to support the role of statins in slowing the progression of PD. These findings are limited by the fact that most of the included studies are observational studies which carry a high risk of confounding bias which highlights the need for future well-designed RCTs.

Comprehensive Orthopedic Management of an Open-Book Pelvic Fracture: A Multidisciplinary Approach in Trauma Care.

Open-book pelvic fractures are an uncommon orthopedic emergency that requires prompt recognition and treatment. A 37-year-old male was involved in high-energy trauma, resulting in an open-book pelvic fracture with bilateral sacroiliac joint diastasis, bilateral superior and inferior pubic rami fractures, a comminuted sacral fracture, and a traumatic hernia. On presentation, he was hemodynamically unstable, with bruising in the right hemipelvis. Acute treatment included a cervical collar, transfusion protocol, central venous access, and pelvic binder. Trauma and orthopedic services were consulted to manage the patient with an interdisciplinary approach. The patient initially underwent external fixation with concomitant exploratory laparotomy. Definitive treatment concluded with colorectal anastomosis, diverting loop ileostomy creation, abdominal closure, open-reduction internal fixation (ORIF) of the pelvis, and removal and reapplication of external fixation.

Transcriptome-Wide Association Study Reveals New Molecular Interactions Associated with Melanoma Pathogenesis.

A transcriptome-wide association study (TWAS) was conducted on genome-wide association study (GWAS) summary statistics of malignant melanoma of skin (UK Biobank dataset) and The Cancer Genome Atlas-Skin Cutaneous Melanoma (TCGA-SKCM) gene expression weights to identify melanoma susceptibility genes. The GWAS included 2465 cases and 449,799 controls, while the gene expression testing was conducted on 103 cases. Afterward, a gene enrichment analysis was applied to identify significant TWAS associations. The melanoma's gene-microRNA (miRNA) regulatory network was constructed from the TWAS genes and their corresponding miRNAs. At last, a disease enrichment analysis was conducted on the corresponding miRNAs. The TWAS detected 27 genes associated with melanoma with p-values less than 0.05 (the top three genes are LOC389458 (RBAK), C16orf73 (MEIOB), and EIF3CL). After the joint/conditional test, one gene (AMIGO1) was dropped, resulting in 26 significant genes. The Gene Ontology (GO) biological process associated the extended gene set (76 genes) with protein K11-linked ubiquitination and regulation of cell cycle phase transition. K11-linked ubiquitin chains regulate cell division. Interestingly, the extended gene set was related to different skin cancer subtypes. Moreover, the enriched pathways were nsp1 from SARS-CoV-2 that inhibit translation initiation in the host cell, cell cycle, translation factors, and DNA repair pathways full network. The gene-miRNA regulatory network identified 10 hotspot genes with the top three: TP53, BRCA1, and MDM2; and four hotspot miRNAs: mir-16, mir-15a, mir-125b, and mir-146a. Melanoma was among the top ten diseases associated with the corresponding (106) miRNAs. Our results shed light on melanoma pathogenesis and biologically significant molecular interactions.

Association of Endoplasmic Reticulum Aminopeptidase 1 Gene Polymorphism with Susceptibility and Severity of Axial Spondyloarthritis in Egyptian Population: A Single-center Case-Control Study.

BACKGROUND: Axial spondyloarthritis (axSpA) is a systemic, progressive, autoimmune disease. Complex interactions between environmental factors and host immune responses are the origin of axSpA. Together with human leukocyte antigen (HLA-B27), endoplasmic reticulum aminopeptidase 1 (ERAP1) gene is a potential non-HLA contributor to axSpA susceptibility. AIM: This study aimed to identify the role of ERAP1 single-nucleotide polymorphisms (SNPs) (rs30187, rs27044, and rs27037) in susceptibility to and severity of axSpA in Egyptian patients. METHODS: In this case-control study, we enrolled 120 patients with axSpA and 120 healthy individuals as controls. Real-time polymerase chain reaction was used to identify ERAP1 polymorphisms. RESULTS: The present study revealed no significant association between ERAP1 SNPs (rs30187, rs27044, and rs27037) and axSpA susceptibility in Egyptian patients. A significant relationship was found only between the ERAP1 SNP rs27037 "GT" genotype and axSpA HLA-B27-positive cases, demonstrating a functional interaction between ERAP1 and HLA-B27-positive cases. Our analysis revealed a significant association between the ERAP1 SNP rs27037 "GT and TT" genotypes and Bath Ankylosing Spondylitis Disease Activity Index, in addition to an association between the ERAP1 SNP rs27037 "TT" genotype and active enthesitis. The ERAP1 SNP rs27044 "GG" genotype was significantly associated with active enthesitis, but not with clinical axial involvement. Finally, we did not observe a significant relationship between HLA-B27 positivity and disease severity in the studied cases. CONCLUSION: Three SNPs (rs30187, rs27044, and rs27037) in ERAP1 do not confer susceptibility to axSpA in Egyptian patients. This association existed exclusively between the ERAP1 SNP (rs27037) "GT" genotype and axSpA HLA-B27-positive cases.

Résumé Contexte:la spondyloarthrite axiale (SpAx) est une maladie auto-immune systémique et progressive. Les interactions complexes entre les facteurs environnementaux et les réponses immunitaires de l'hôte sont à l'origine de la SpAx. En plus de l'antigène leucocytaire humain (HLAB27), le gène de l'aminopeptidase du réticulum endoplasmique 1 (ERAP1) est un contributeur potentiel non-HLA à la susceptibilité à la SpAx.Objectif:cette étude visait à identifier le rôle des polymorphismes mononucléotidiques (SNP) de l'ERAP1 (rs30187, rs27044 et rs27037) dans la susceptibilité et la gravité de la SpAx chez les patients égyptiens.Méthodes:dans cette étude cas-témoins, nous avons inclus 120 patients atteints de SpAx et 120 individus en bonne santé comme témoins. La réaction en chaîne de la polymérase en temps réel a été utilisée pour identifier les polymorphismes de l'ERAP1.Résultats:cette étude a révélé qu'il n'y avait pas d'association significative entre les SNP de l'ERAP1 (rs30187, rs27044 et rs27037) et la susceptibilité à la SpAx chez les patients égyptiens. Une relation significative a été trouvée uniquement entre le génotype "GT" du SNP rs27037 de l'ERAP1 et les cas de SpAx positifs pour le HLA-B27, démontrant une interaction fonctionnelle entre l'ERAP1 et les cas positifs pour le HLA-B27. Notre analyse a révélé une association significative entre les génotypes "GT et TT" du SNP rs27037 de l'ERAP1 et l'indice d'activité de la maladie de spondylarthrite ankylosante de Bath, ainsi qu'une association entre le génotype "TT" du SNP rs27037 de l'ERAP1 et l'enthésite active. Le génotype "GG" du SNP rs27044 de l'ERAP1 était significativement associé à l'enthésite active, mais non à l'atteinte axiale clinique. Enfin, nous n'avons pas observé de relation significative entre la positivité du HLA-B27 et la gravité de la maladie dans les cas étudiés.Conclusion:trois SNP (rs30187, rs27044 et rs27037) dans l'ERAP1 ne confèrent pas de susceptibilité à la SpAx chez les patients égyptiens. Cette association existait exclusivement entre le génotype "GT" du SNP rs27037 de l'ERAP1 et les cas de SpAx positifs pour le HLA-B27.

Advancing clinical understanding of surface electromyography biofeedback: bridging research, teaching, and commercial applications.

INTRODUCTION: Expanding the use of surface electromyography-biofeedback (EMG-BF) devices in different therapeutic settings highlights the gradually evolving role of visualizing muscle activity in the rehabilitation process. This review evaluates their concepts, uses, and trends, combining evidence-based research. AREAS COVERED: This review dissects the anatomy of EMG-BF systems, emphasizing their transformative integration with machine-learning (ML) and deep-learning (DL) paradigms. Advances such as the application of sophisticated DL architectures for high-density EMG data interpretation, optimization techniques for heightened DL model performance, and the fusion of EMG with electroencephalogram (EEG) signals have been spotlighted for enhancing biomechanical analyses in rehabilitation. The literature survey also categorizes EMG-BF devices based on functionality and clinical usage, supported by insights from commercial sectors. EXPERT OPINION: The current landscape of EMG-BF is rapidly evolving, chiefly propelled by innovations in artificial intelligence (AI). The incorporation of ML and DL into EMG-BF systems augments their accuracy, reliability, and scope, marking a leap in patient care. Despite challenges in model interpretability and signal noise, ongoing research promises to address these complexities, refining biofeedback modalities. The integration of AI not only predicts patient-specific recovery timelines but also tailors therapeutic interventions, heralding a new era of personalized medicine in rehabilitation and emotional detection.

Clinical versus fixed warfarin dosing and the impact on quality of anticoagulation (The ClinFix trial).

Different dosing strategies exist to initiate warfarin, most commonly fixed warfarin dosing (FWD), clinical warfarin dosing (CWD), and genetic-guided warfarin dosing (GWD). Landmark trials have shown GWD to be superior when compared to FWD in the EU-PACT trial or CWD in the GIFT trial. COAG trial did not show differences between GWD and CWD. We aim to compare the anticoagulation quality outcomes of CWD and FWD. This is a prospective cohort study with a retrospective comparator. Recruited subjects in the CWD (prospective) arm were initiated on warfarin according to the clinical dosing component of the algorithm published in www.warfarindosing.org. The primary efficacy outcome was the percentage time in the therapeutic range (PTTR) from day 3 to 6 till day 28 to 35. The study enrolled 122 and 123 patients in the CWD and FWD, respectively. The PTTR did not differ statistically between CWD and FWD (62.2 ± 26.2% vs. 58 ± 25.4%, p = 0.2). There was also no difference between both arms in the percentage of visits with extreme subtherapeutic international normalized ratio (INR) (<1.5; 15 ± 18.3% vs. 16.8 ± 19.1%, p = 0.44) or extreme supratherapeutic INR (>4; 7.7 ± 14.7% vs. 7.5 ± 12.4%, p = 0.92). We conclude that CWD did not improve the anticoagulation quality parameters compared to the FWD method.

The predictors of successful methotrexate treatment of tubal ectopic pregnancy.

BACKGROUND: The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy remain controversial. This study investigated the outcomes of ectopic pregnancy after one and two MTX doses and their independent predictors. METHODS: Retrospective cross-sectional study of women who consented to MTX treatment in 2017-2018 at our institution (N = 317). Of these, patients with Caesarean scar pregnancies were excluded because they require different treatment protocols (n = 25). All patients were treated according to our institution's protocol based on international guidelines and standardised across the three hospitals included in the current study. We retrieved patients' demographics, laboratory, ultrasonography, and clinical characteristics from our hospital database. Serum ß-human chorionic gonadotropin (ß-hCG) was measured using electrochemiluminescence immunoassay; ectopic pregnancy was diagnosed using ultrasonography (transvaginal probe). RESULTS: Two ninety-two patients were included in the current analysis. Age, pre-treatment ß-hCG levels, sonographic presence of yolk sac, presence of foetal cardiac activity, and pelvic pain were significantly different between patients with successful and unsuccessful outcomes. Younger age (adjusted odds ratio [aOR] 2.33, 95% confidence interval (CI) 1.16-4.66, p = .017), no pelvic pain (aOR 2.65, 95%CI 1.03-6.83, p = .043), lower initial ß-hCG level (aOR 1.32, 95%CI 1.08-1.59, p = .005), and absence of foetal cardiac activity (aOR 12.63; 95% CI 1.04-153.6; p = .047) were independently associated with success. Treatment failure odds were >2 folds higher for each 10-year age increase (p = .017), 32% higher for each 1000 IU/L increase in initial ß-hCG level (p = .005), and >2 folds higher in presence of pelvic pain (p = .043). CONCLUSIONS: MTX is effective in most patients, averting invasive surgery, which might affect fertility. Pre-treatment ß-hCG levels, age, pelvic pain, and foetal cardiac activity was independently associated with outcomes. Research should assess the relationship between the ectopic pregnancy size and treatment outcomes and refine ß-hCG titres where treatment would be ineffective.

Ectopic pregnancy is a pregnancy that occurs outside the uterus. It needs to be identified and treated quickly to prevent serious health complications. Ectopic pregnancies can be treated surgically or medically using a drug called methotrexate. Medical treatment of ectopic pregnancy is not always successful. Identifying the factors that predict the failure of medical treatment helps patients and doctors to choose more accurately between surgical and medical treatment options.A total of 292 women who received methotrexate for ectopic pregnancy and the factors that influence the outcomes of treatment were examined, 39 patients had treatment failure and required surgery. Older age, higher initial levels of ß-human chorionic gonadotropin (ß-hCG) hormone, the presence of pelvic pain, and foetal cardiac activity had increased risk of treatment failure. In the future, research could consider the relationship between the size of the ectopic pregnancy and the treatment outcomes and refine the ß-hCG level cut-off for better treatment effects.

Low dose insulin infusion versus the standard dose in children with diabetic ketoacidosis: a meta-analysis.

Aim: This systematic review aims to consolidate findings from current clinical trials that compare the effectiveness of insulin infusion at 0.05 IU/kg/h versus 0.1 IU/kg/h in managing pediatric diabetic ketoacidosis. Methods: We searched several databases, including PubMed, Embase, Scopus, Cochrane Central and Web of Science. Our primary outcomes were time to reach blood glucose ≤250 mg/dl and time to resolution of acidosis. Secondary outcomes included rate of blood glucose decrease per hour, incidence of hypoglycemia, hypokalemia, treatment failure, and cerebral edema. Results & conclusion: The present study establishes that a low insulin dose exhibits comparable efficacy to the standard dosage for managing pediatric patients suffering from diabetic ketoacidosis, with a lower incidence of complications.

When kids with type 1 Diabetes (T1DM) face a serious complication called Diabetic Ketoacidosis (DKA), it becomes a life-threatening situation. This condition, responsible for significant mortality, involves high blood sugar, ketone buildup and acidity. Our study delves into a critical aspect of DKA treatment-finding the right insulin dose. By pooling the studies on this point, we discovered that using a lower insulin dose is just as effective as the standard dose in managing DKA in children, with fewer complications. This insight is crucial for improving the care and outcomes for young patients dealing with this challenging condition.

Statistical Analysis of Factors Associated with Diarrhea in Yemeni Children under Five: Insights from the 2022-2023 Multiple Indicator Cluster Survey.

Diarrheal disease remains a significant cause of preventable morbidity and mortality in the pediatric population, particularly among children below five years of age. Although the occurrence of diarrheal episodes is on the decline, its impact continues to escalate at a concerning rate among children under the age of five, especially in developing countries. The objective of this paper is to investigate the factors associated with diarrhea in Yemeni children younger than five years, drawing on data from the latest edition of the Multiple Indicator Cluster Survey (MICS) Yemen conducted in 2022-2023. To identify factors associated with the prevalence of childhood diarrhea, bivariate analysis and multivariable logistic regression were utilized. The findings of this study suggest that age group 6-23, unimproved sanitation, and low-income households are associated with high risk of diarrhea in children under five years of age in Yemen. The study contributes additional evidence regarding factors that should be prioritized in public health strategies geared towards reducing diarrheal prevalence among Yemeni children.

Decision tree-based approach to extrapolate life cycle inventory data of manufacturing processes.

Life cycle assessment (LCA) plays a crucial role in green manufacturing to uncover the critical aspects for alleviating the environmental burdens due to manufacturing processes. However, the scarcity of life cycle inventory (LCI) data for the manufacturing processes is a considerable challenge. This paper proposes a novel approach to extrapolate LCI data of manufacturing processes. Taking advantage of LCI data in the Ecoinvent datasets, decision tree-based supervised machine learning models, namely decision tree, random forest, gradient boosting, and adaptive boosting, have been developed to extrapolate the data of GHG emissions, i.e., carbon dioxide, nitrous oxide, methane, and water vapor. Initially, a correlation analysis was conducted to derive the most influential factors on GHG quantities resulting from manufacturing activities. First, the collected data have been preprocessed and split into train and test sets (70% and 30%, respectively). Second, a five-fold cross-validation method was applied to tune the hyperparameters of the models. Then, the models were re-trained using the best hyperparameters and evaluated using the test set. The results reveal that the Gradient Boosting model has a superior predictive performance for extrapolating the GHG emission data, with average coefficients of determination (R2) on the test set <0.95. Moreover, the model predictions involve relatively low values of the average root mean squared error and an average mean percentage of error on the test set. The correlation and feature importance analyses emphasized that the workpiece material and manufacturing technology have a considerable effect on natural resource consumption, i.e., energy, material, and water inflows into the process. Meanwhile, energy consumption, water usage, and raw aluminum depletion were the most influential factors in GHG emissions. Eventually, a case study to extrapolate the inflows and the outflows for new manufacturing activities has been conducted using the validated models. The proposed GraBoost model provides a computational supplementary approach to estimate and extrapolate the GHG emissions for different manufacturing processes when LCI data are incomplete or don't exist within LCI databases.

Patient-Derived Xenograft Models in Cancer Research: Methodology, Applications, and Future Prospects.

Patient-derived xenografts (PDXs) have emerged as a pivotal tool in translational cancer research, addressing limitations of traditional methods and facilitating improved therapeutic interventions. These models involve engrafting human primary malignant cells or tissues into immunodeficient mice, allowing for the investigation of cancer mechanobiology, validation of therapeutic targets, and preclinical assessment of treatment strategies. This chapter provides an overview of PDXs methodology and their applications in both basic cancer research and preclinical studies. Despite current limitations, ongoing advancements in humanized xenochimeric models and autologous immune cell engraftment hold promise for enhancing PDX model accuracy and relevance. As PDX models continue to refine and extend their applications, they are poised to play a pivotal role in shaping the future of translational cancer research.

Cytosolic DNA sensor AIM2 promotes KRAS-driven lung cancer independent of inflammasomes.

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co-operators of oncogenic KRAS in the lung remains ill-defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent-in-melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS-addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine-derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome-associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK-induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D-driven LAC in both hematopoietic (immune) and non-hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2-deficient mice is associated with unaltered protein levels of mature Caspase-1 and IL-1ß inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D-driven LAC. In support of these in vivo findings, AIM2, but not mature Caspase-1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor-promoting role, independent of inflammasomes, in mutant KRAS-addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer.

Patient-Derived Xenografts: A Valuable Preclinical Model for Drug Development and Biomarker Discovery.

Patient-derived xenografts (PDXs), established by implanting patient tumor cells into immunodeficient mice, offer a platform for faithfully replicating human tumors. They closely mimic the histopathology, genomics, and drug sensitivity of patient tumors. This chapter highlights the versatile applications of PDXs, including studying tumor biology, metastasis, and chemoresistance, as well as their use in biomarker identification, drug screening, and personalized medicine. It also addresses challenges in using PDXs in cancer research, including variations in metastatic potential, lengthy establishment timelines, stromal changes, and limitations in immunocompromised models. Despite these challenges, PDXs remain invaluable tools guiding patient treatment and advancing preclinical drug development.

Patient-Derived Xenografts: Historical Evolution, Immunocompromised Host Models, and Translational Significance.

Patient-derived xenografts (PDXs) represent a critical advancement in preclinical cancer research, wherein human tumor samples are implanted into animal models for evaluation of therapeutic responses. PDXs have emerged as indispensable tools in translational cancer research, facilitating investigation into tumor microenvironments and personalized medicine. This chapter elucidates the historical evolution of PDXs, from early attempts in the eighteenth century to contemporary immunocompromised host models that enhance engraftment success.

Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. DATA SOURCES: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. STUDY SELECTION AND DATA EXTRACTION: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. DATA SYNTHESIS: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. CONCLUSIONS: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.