Exploring the role of PARP1 inhibition in enhancing antibody-drug conjugate therapy for acute leukemias: insights from DNA damage response pathway interactions.

Background: The introduction of antibody-drug conjugates represents a significant advancement in targeted therapy of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Our study aims to investigate the role of the DNA damage response pathway and the impact of PARP1 inhibition, utilizing talazoparib, on the response of AML and ALL cells to Gemtuzumab ozogamicin (GO) and Inotuzumab ozogamicin (INO), respectively.

Methods: AML and ALL cells were treated with GO, INO and γ-calicheamicin in order to induce severe DNA damage and activate the G2/M cell-cycle checkpoint in a dose- and time-dependent manner.

Impulsivity and Anger in Obese Patients Undergoing Bariatric Surgery.

Introduction: Several studies show an association between obesity, impulsivity, and anger. The condition of obesity has moreover an important correlation with Eating Disorders (EDs), the most frequent of which is Binge Eating Disorder (BED). Obese patients seem to express peculiarities regarding the expression of some emotional processes, including impulsivity, aggression and anger, compared with regular-weight patients and those without an ED.

In vivo dissection of the mouse tyrosine catabolic pathway with CRISPR-Cas9 identifies modifier genes affecting hereditary tyrosinemia type 1.

Hereditary tyrosinemia type 1 is an autosomal recessive disorder caused by mutations (pathogenic variants) in fumarylacetoacetate hydrolase, an enzyme involved in tyrosine degradation. Its loss results in the accumulation of toxic metabolites that mainly affect the liver and kidneys and can lead to severe liver disease and liver cancer. Tyrosinemia type 1 has a global prevalence of approximately 1 in 100,000 births but can reach up to 1 in 1,500 births in some regions of Québec, Canada.

Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible.

Feeding and Eating Disorders in Bariatric Surgery: A Retrospective Study.

Introduction: Obese subjects undergoing bariatric surgery often display medical and psychiatric comorbidities, influencing post-operative course and long-term prognosis. Candidates for bariatric surgery are evaluated through a multidisciplinary assessment in the pre-operative phase, including a psychiatric visit. The psychiatric examination aims to screen psychiatric comorbidities, including feeding and eating disorders (FEDs).

Pushing ML Predictions Into DBMSs.

In the past decade, many approaches have been suggested to execute ML workloads on a DBMS. However, most of them have looked at in-DBMS ML from a training perspective, whereas ML inference has been largely overlooked. We think that this is an important gap to fill for two main reasons: (1) in the near future, every application will be infused with some sort of ML capability; (2) behind every web page, application, and enterprise there is a DBMS, whereby in-DBMS inference is an appealing solution both for efficiency (e.

circPVT1 and PVT1/AKT3 show a role in cell proliferation, apoptosis, and tumor subtype-definition in small cell lung cancer.

Small cell lung cancer (SCLC) is treated as a homogeneous disease, although the expression of NEUROD1, ASCL1, POU2F3, and YAP1 identifies distinct molecular subtypes. The MYC oncogene, amplified in SCLC, was recently shown to act as a lineage-specific factor to associate subtypes with histological classes. Indeed, MYC-driven SCLCs show a distinct metabolic profile and drug sensitivity.

Swedish High School Students' Drug and Alcohol Use Habits throughout 2020.

This study describes gender-specific patterns in alcohol and drug use among Swedish high school students throughout 2020 and questions the current cutoffs for identifying addiction in this population. From September 2020 to February 2021, 1590 Swedish upper secondary high school students (mean age 17.15 years, age range 15-19 years, 39.

Early predictors of unfavourable outcome in progressive cholestasis of northwestern Quebec.

Background: Progressive cholestasis of northwestern Quebec (PCNQ) is a rare and severe form of cirrhosis affecting children from Quebec's First Nations. First described by our group in 1981 and historically named North American Indian childhood cirrhosis, such a condition often requires liver transplantation during the pediatric age. This study aimed at suggesting a more culturally sensitive name for the disease and identifying early prognostic factors for an unfavourable outcome.

Have we really understood when the efforts of laparoscopic liver resection are justified?-a complexity-based appraisal of the differential benefit.

Background: The implementation of minimally invasive liver resection surgery (MILS) programs starts from procedures with a low degree of technical difficulty. Data regarding the real short-term advantage of laparoscopy according to technical difficulty are still lacking. The aim of the present study is to evaluate the differential benefit of laparoscopic over open technique according to the technical difficulty of the procedures and to investigate if efforts associated with laparoscopic approach are always justified.

Autologous humanized mouse models of iPSC-derived tumors enable characterization and modulation of cancer-immune cell interactions.

Modeling the tumor-immune cell interactions in humanized mice is complex and limits drug development. Here, we generated easily accessible tumor models by transforming either primary skin fibroblasts or induced pluripotent stem cell-derived cell lines injected in immune-deficient mice reconstituted with human autologous immune cells. Our results showed that fibroblastic, hepatic, or neural tumors were all efficiently infiltrated and partially or totally rejected by autologous immune cells in humanized mice.

Generation of Complex Syngeneic Liver Organoids from Induced Pluripotent Stem Cells to Model Human Liver Pathophysiology.

The study of human liver pathophysiology has been hampered for decades by the lack of easily accessible, robust, and representative in vitro models. The discovery of induced pluripotent stem cells (iPSCs)-which can be generated from patients' somatic cells, engineered to harbor specific mutations, and differentiated into hepatocyte-like cells-opened the way to more meaningful modeling of liver development and disease. Nevertheless, representative modeling of many complex liver conditions requires the recreation of the interplay between hepatocytes and nonparenchymal liver cells.

Physicochemical and biopharmaceutical aspects influencing skin permeation and role of SLN and NLC for skin drug delivery.

The skin is a complex and multifunctional organ, in which the static versus dynamic balance is responsible for its constant adaptation to variations in the external environment that is continuously exposed. One of the most important functions of the skin is its ability to act as a protective barrier, against the entry of foreign substances and against the excessive loss of endogenous material. Human skin imposes physical, chemical and biological limitations on all types of permeating agents that can cross the epithelial barrier.

Leveraging interacting signaling pathways to robustly improve the quality and yield of human pluripotent stem cell-derived hepatoblasts and hepatocytes.

Pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs) have shown great potential as an alternative to primary human hepatocytes (PHHs) for in vitro modeling. Several differentiation protocols have been described to direct PSCs toward the hepatic fate. Here, by leveraging recent knowledge of the signaling pathways involved in liver development, we describe a robust, scalable protocol that allowed us to consistently generate high-quality bipotent human hepatoblasts and HLCs from both embryonic stem cells and induced PSC (iPSCs).

Psychiatric Comorbidity in Bariatric Surgery: A Retrospective Study in a General Hospital.

Background: Candidates for bariatric surgery undergo a multidisciplinary evaluation in the pre-operative phase, including a psychiatric visit aimed at the screening for psychiatric comorbidities, including feeding and eating disorders (FEDs), which are shortcomings to the intervention or predictors of worse prognosis. The presence of FEDs, such as Binge Eating Disorder (BED) and Bulimia Nervosa (BN), is associated with higher rates of other psychiatric disorders. Furthermore, there is evidence of the association between obesity and Depressive Disorders, as well as B and C Cluster Personality Disorders.

Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells.

Doxorubicin (Dox) is one of the most commonly used anthracyclines for the treatment of solid and hematological tumors such as B-/T cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase II enzyme functionality, thus inducing structural damages during DNA replication and causes direct damages intercalating into DNA double helix. Eukaryotic cells respond to DNA damages by activating the ATM-CHK2 and/or ATR-CHK1 pathway, whose function is to regulate cell cycle progression, to promote damage repair, and to control apoptosis.

The SMART-ALPPS Protocol: Strategy to Minimize ALPPS Risks by Targeting Invasiveness.

Background: The range of procedures with documented feasibility by laparoscopic approach is widening in the setting of liver resections. Many technical limits have been overcome in the attempt to reduce the biological impact of major procedures [1-8]. Similarly, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS)-which could be assumed as the paradigm of maxi-invasiveness-has recently been proposed in a minimally invasive fashion to reduce the impact of this procedure [9-12].

Perioperative and oncologic outcomes of open radical nephrectomy and inferior vena cava thrombectomy with liver mobilization and Pringle maneuver for Mayo III level tumor thrombus: single institution experience.

Background: Scarce data are available regarding the technique and outcomes for patients with RCC and Mayo III caval thrombi. The aim of this study was to report surgical and oncological outcomes of RCC patients with Mayo III thrombi treated with radical nephrectomy and thrombectomy after liver mobilization (LM) and Pringle maneuver (PM).

Methods: Retrospective analysis of surgical technique, outcomes and cancer control in 19 patients undergoing LM and PM in a single tertiary care institution were analyzed.

Pure laparoscopic right hepatectomy: A risk score for conversion for the paradigm of difficult laparoscopic liver resections. A single centre case series.

Background: Converted laparoscopic hepatectomies are known to lose some advantages of the minimally-invasiveness, and factors are identified to predict patients at risk. Specific evidence for laparoscopic right hepatectomy is expected of usefulness in clinical practice, given its technical peculiarities. The purpose of the study was the identification of risk factors and the development of a risk score for conversion of laparoscopic right hepatectomy.

Hydroxycarboxylate combinations for increasing solubility and robustness of supersaturated solutions of whey mineral residues.

Calcium phosphates present in whey mineral residue is a potential source of calcium for dietary purposes. Combinations of aqueous isocitrate and citrate were found more efficient than each of the isomers in dissolving dried insoluble whey processing mineral residues spontaneously forming supersaturated solutions. Hydrogen isocitrate was found around 30% less efficient in these non thermal dissolution processes compared to hydrogen citrate based on amount of dissolved calcium.

Correlation Between Type of Retrieval Incision and Postoperative Outcomes in Laparoscopic Liver Surgery: A Critical Assessment.

At the end of a laparoscopic major hepatectomy, an incision wide enough for specimen retrieval is required. Classically, Pfannenstiel (PF) incision is the type of access favored as service incision in laparoscopy. However, in specific settings the use of a midline (ML) incision can be favorable, with doubtful impaction on the outcomes of a purely laparoscopic operation.

High-throughput assessment of mutations generated by genome editing in induced pluripotent stem cells by high-resolution melting analysis.

Background And Aims: Genome editing of induced pluripotent stem cells (iPSCs) holds great potential for both disease modeling and regenerative medicine. Although clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 provides an efficient and precise genome editing tool, iPSCs are especially difficult to transfect, resulting in a small percentage of cells carrying the desired correction. A high-throughput method to identify edited clones is required to reduce the time and costs of such an approach.