Comparative analysis of iPSC-derived NK cells from two differentiation strategies reveals distinct signatures and cytotoxic activities.

Purpose: The ability to generate natural killer (NK) cells from induced pluripotent stem cells (iPSCs) has given rise to new possibilities for the large-scale production of homogeneous immunotherapeutic cellular products and opened new avenues towards the creation of "off-the-shelf" cancer immunotherapies. However, the differentiation of NK cells from iPSCs remains poorly understood, particularly regarding the ontogenic landscape of iPSC-derived NK (iNK) cells produced and the influence that the differentiation strategy employed may have on the iNK profile.

Methods: To investigate this question, we conducted a comparative analysis of two sets of iNK cells generated from the same iPSC line using two different protocols: (i) a short-term, clinically compatible feeder-free protocol corresponding to primitive hematopoiesis, and (ii) a lymphoid-based protocol representing the definitive hematopoietic step.

Enhancing natural killer cells proliferation and cytotoxicity using imidazole-based lipid nanoparticles encapsulating interleukin-2 mRNA.

mRNA applications have undergone unprecedented applications-from vaccination to cell therapy. Natural killer (NK) cells are recognized to have a significant potential in immunotherapy. NK-based cell therapy has drawn attention as allogenic graft with a minimal graft-versus-host risk leading to easier off-the-shelf production.

Development and validation of a fully automated tool to quantify 3D foot and ankle alignment using weight-bearing CT.

Introduction: Foot and ankle alignment plays a pivotal role in human gait and posture. Traditional assessment methods, relying on 2D standing radiographs, present limitations in capturing the dynamic 3D nature of foot alignment during weight-bearing and are prone to observer error. This study aims to integrate weight-bearing CT (WBCT) imaging and advanced deep learning (DL) techniques to automate and enhance quantification of the 3D foot and ankle alignment.

Spatially distinct epithelial and mesenchymal cell subsets along progressive lineage restriction in the branching embryonic mammary gland.

How cells coordinate morphogenetic cues and fate specification during development remains a fundamental question in organogenesis. The mammary gland arises from multipotent stem cells (MaSCs), which are progressively replaced by unipotent progenitors by birth. However, the lack of specific markers for early fate specification has prevented the delineation of the features and spatial localization of MaSC-derived lineage-committed progenitors.

Extracting, filtering and simulating cellular barcodes using CellBarcode tools.

Identifying true DNA cellular barcodes among polymerase chain reaction and sequencing errors is challenging. Current tools are restricted in the diversity of barcode types supported or the analysis strategies implemented. As such, there is a need for more versatile and efficient tools for barcode extraction, as well as for tools to investigate which factors impact barcode detection and which filtering strategies to best apply.

First results from the releases of Cinereous Vultures () aiming at re-introducing the species in Bulgaria - the start of the establishment phase 2018-2022.

The current work presents the preliminary results of the Cinereous Vulture () releases in the Balkan Mountains in 2018-2022, aiming at the species re-introduction in Bulgaria, where it was listed as locally extinct since 1985. The first imports and releases of Cinereous Vultures in Bulgaria started in 2018. Until mid-2022, 72 individuals were released in the Eastern Balkan Mountains (Kotlenska Planina SPA and Sinite Kamani Nature Park) and Vrachanski Balkan Nature Park.

Chimeric antigen-receptor (CAR) engineered natural killer cells in a chronic myeloid leukemia (CML) blast crisis model.

During the last two decades, the introduction of tyrosine kinase inhibitors (TKIs) to the therapy has changed the natural history of CML but progression into accelerated and blast phase (AP/BP) occurs in 3-5% of cases, especially in patients resistant to several lines of TKIs. In TKI-refractory patients in advanced phases, the only curative option is hematopoietic stem cell transplantation. We and others have shown the relevance of the expression of the Interleukin-2-Receptor α subunit (IL2RA/CD25) as a biomarker of CML progression, suggesting its potential use as a therapeutic target for CAR-based therapies.

Prevention of Incisional Hernias by Prophylactic Mesh-augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: Five-year Follow-up of a Randomized Controlled Trial.

Introduction: The incidence of incisional hernias (IHs) after open repair of an abdominal aortic aneurysm (AAA) is high. Several randomized controlled trials have reported favorable results with the use of prophylactic mesh to prevent IHs, without increasing complications. In this analysis, we report on the results of the 60-month follow-up of the PRIMAAT trial.

Paracrine signalling between intestinal epithelial and tumour cells induces a regenerative programme.

Tumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, using mouse intestinal organoids, we uncover a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative YAP-associated transcriptional programmes in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context.

In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation.

Real-time in vivo imaging provides an essential window into the spatiotemporal cellular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we capture the earliest cellular events arising in response to active Wnt/β-catenin signaling and the ensuing impact on the organization and differentiation of the mammary epithelium. This enables us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time.

Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells.

Colon tumours are hierarchically organized and contain multipotent self-renewing cells, called Cancer Stem Cells (CSCs). We have previously shown that the Notch1 receptor is expressed in Intestinal Stem Cells (ISCs); given the critical role played by Notch signalling in promoting intestinal tumourigenesis, we explored Notch1 expression in tumours. Combining lineage tracing in two tumour models with transcriptomic analyses, we found that Notch1+ tumour cells are undifferentiated, proliferative and capable of indefinite self-renewal and of generating a heterogeneous clonal progeny.

A prospective study on ultra-wide diameter dental implants for immediate molar replacement.

Background: Although wide diameter implants are well documented, little is known about ultra-wide diameter implants (>6 mm). This study evaluates the clinical outcome of ultra-wide diameter implants, placed in molar extraction sockets.

Materials And Methods: Ultra-wide diameter implants (7-9 mm) were placed immediately after molar extraction in a 1-stage protocol, without raising a flap or using any bone grafts.

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.

Palpitations, headache and night sweats caused by a retroperitoneal mass: case report and short review.

A 31-year-old West-African female attended our emergency department presenting with palpitations, headache, fatigue and night sweats during the last 2 weeks. Clinical examination revealed tachycardia and a painful, palpable infraumbilical mass. Ultrasound examination of the abdomen showed a smoothly rounded soft-tissue mass with a diameter of 5 cm.

Prevention of Incisional Hernias by Prophylactic Mesh-augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: A Randomized Controlled Trial.

Background: The incidence of incisional hernias after abdominal aortic aneurysm repair is high. Prophylactic mesh-augmented reinforcement during laparotomy closure has been proposed in patients at high risk of incisional hernia.

Methods: A multicenter randomized trial was conducted on patients undergoing elective abdominal aortic aneurysm repair through a midline laparotomy (Clinical.

Thrombolysis for Severe Intestinal Ischemia due to Midgut Volvulus in a Neonate.

Intestinal malrotation complicated by the development of midgut volvulus presents a difficult management dilemma because of the risk of short bowel syndrome. Here, we present our experience with a case of severe intestinal ischemia after derotation in a newborn successfully managed using systemic tissue plasminogen activator. The present report supports the usefulness of thrombolysis as a therapeutic option for reperfusion of ischemic small bowel due to midgut volvulus in neonates.

Perirectal sepsis after rubber band ligation of haemorrhoids : a case report.

Rubber band ligation (Barron ligation, RBL) is a widely used method for the treatment of symptomatic -haemorrhoids. In general, it is considered as a safe, effective and easily performed way of treating second and third -degree haemorrhoids. Perineal and pelvic sepsis was already known to be a rare, but possible complication after stapled haemorrhoidopexy.

Luminal progenitors restrict their lineage potential during mammary gland development.

The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing.

Tripartite interactions between Wnt signaling, Notch and Myb for stem/progenitor cell functions during intestinal tumorigenesis.

Deletion studies confirm Wnt, Notch and Myb transcriptional pathway engagement in intestinal tumorigenesis. Nevertheless, their contrasting and combined roles when activated have not been elucidated. This is important as these pathways are not ablated but rather are aberrantly activated during carcinogenesis.

Ultrasound guided femoral nerve block and lateral femoral cutaneous nerve block for postoperative pain control after primary hip arthroplasty: a retrospective study.

Purpose: The purpose of this study was to evaluate the use of an ultrasound guided femoral nerve (FN) block together with an ultrasound guided lateral femoral cutaneous nerve (LFCN) block in addition to a patient controlled intravenous analgesia (PCIA) pump with piritramide as a strategy for postoperative pain-management after primary hip arthroplasty.

Methods: In a retrospective study, data recorded from 32 patients undergoing primary hip arthroplasty in 2008, before peripheral blocks were used, were compared with data from 38 patients undergoing primary hip arthroplasty in 2011, when an ultrasound guided single shot FN and LFCN block was used. As primary endpoint the total piritramide consumption after 48 hours was analyzed.

Granular cell tumor of the abdominal wall: case report and review of the literature.

Granular cell tumors (GCT's) are uncommon soft tissue neoplasms most likely of neural or neuroectodermal origin. They can be found in virtually any body site, but they are rarely located in the abdominal wall. We report the case of a patient with a history of breast cancer presenting with a slow-growing, firm and painless nodule in the abdominal wall.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer.

Gallstone ileus in a patient with Crohn's disease: a case report.

Gallstone ileus is a rare complication of cholelithiasis. Only 0,3-0,5% of all patients with gallstones will eventually suffer from this condition. It is well known that there is an increased prevalence of gallstones among patients with Crohn's disease, but gallstone ileus remains even in these patients an unfrequent condition.

Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice.

The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells.

A standardized resident training program in endoscopic surgery in general and in laparoscopic totally extraperitoneal (TEP) inguinal hernia repair in particular.

The need for acquisition of specific laparoscopic skills has emphasized the role of a preclinical laboratory-training program. However, for laparoscopic inguinal hernia repair with a steep learning curve, especially for totally extraperitoneal repair, preclinical skill training remains a challenge. A standardized preclinical resident training program in endoscopic surgery is described.