License for a CAR T: Examining patient eligibility.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape of lymphoma and is now approved by the FDA for multiple indications. Given that the indications for CAR T-cell therapy are expanding, a larger patient population will be eligible to receive this treatment in the coming years. Pivotal clinical trials leading to FDA approval of CAR T-cell products required patients to have adequate organ function and good performance status.

Enhancing automated vehicle identification by integrating YOLO v8 and OCR techniques for high-precision license plate detection and recognition.

Vehicle identification systems are vital components that enable many aspects of contemporary life, such as safety, trade, transit, and law enforcement. They improve community and individual well-being by increasing vehicle management, security, and transparency. These tasks entail locating and extracting license plates from images or video frames using computer vision and machine learning techniques, followed by recognizing the letters or digits on the plates.

A real-world study of pneumonitis in non-small cell lung cancer patients receiving durvalumab following concurrent chemoradiation.

Background: Locally advanced non-small cell lung cancer (LA-NSCLC) treated with the programmed death-ligand 1 inhibitor durvalumab has been associated with significant rates of pneumonitis, which has led to higher rates of discontinuation of therapy in real-world populations. Thus far there has been no consensus in the literature on the impact of pneumonitis on survival.

Methods: This is a retrospective cohort study of veterans receiving durvalumab between 12/5/2017 and 4/15/2020.

Leucocytosis and Stroke in a Lung Cancer Patient.

Unlabelled: Significant leucocytosis in the setting of an underlying malignancy may be attributed to several causes and is not uncommon; however, extreme leucocytosis (>50×10 cells/l) and hypereosinophilia is less common and may represent a paraneoplastic syndrome. The underlying mechanism is thought to be bone marrow stimulation by tumour-produced cytokines, most notably interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF). This paraneoplastic syndrome is likely reflective of extensive disease and dissemination, and options for treatment are limited but include tumour resection, corticosteroids and hydroxyurea.

The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression.

We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4 T cells and CD8 T-cell activation.

Burnout of Physicians Working in Primary Health Care Centers under Ministry of Health Jeddah, Saudi Arabia.

Introduction The levels of physicians' job satisfaction and burnout directly affect their professionalism, punctuality, absenteeism, and ultimately, patients' care. Despite its crucial importance, little is known about professional burnout of the physicians in Saudi Arabia. The objectives of this research are two-fold: (1) To assess the prevalence of burnout in physicians working in primary health care centers under Ministry of Health; and (2) to find the modifiable factors which can decrease the burnout ratio.

NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA.

Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance.

The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined.

γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation.

Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals.

A cohort study of the impact and acquisition of naspharyngeal carriage of Streptococcus pneumoniae during the Hajj.

Background: The annual Muslim pilgrimage attracts over two million pilgrims who gather in a limited time and space. The pilgrimage carries the potential risk of increase risk of the acquisition of Streptococcus pneumonia. In this cohort study, we evaluate the effect of the Hajj on the prevalence of pneumococcal serotype nasopharyngeal carriage in the Hajj pilgrim population.

Impact of the Hajj on pneumococcal transmission.

Over two million Muslim pilgrims assemble annually in Mecca and Medina, Saudi Arabia, to complete the Hajj. The large number of people in a crowded environment increases the potential for pneumococcal carriage amplification. We evaluated pneumococcal carriage prevalence with four cross-sectional studies conducted at beginning-Hajj (Mecca) and end-Hajj (Mina) during 2011 and 2012.

HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification.

The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8(+) T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ~30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs.

Census of cytosolic aminopeptidase activity reveals two novel cytosolic aminopeptidases.

Activation of CD8(+) cytotoxic T cells is crucial for the adaptive immune response against viral infections and the control of malignant transformed cells. Together with activation of costimulatory molecules like CD3 and CD28, CD8(+) T cells need activation of their unique T cell receptor via recognition of foreign peptide epitopes in combination with major histocompatibility complexes class I on the cell surface of professional antigen-presenting cells. Presentation of pathogen-associated proteins is the result of a complex proteolytic process.

Distinct molecular mechanisms leading to deficient expression of ER-resident aminopeptidases in melanoma.

Immune surveillance of tumour cells by CD8(+) cytotoxic T cells plays a key role in the establishment and control of an anti-tumour response. This process requires the generation of antigenic peptides, which are largely produced by the proteasome in combination with other proteases located in either the cytoplasm and/or the endoplasmic reticulum (ER). The ER-resident aminopeptidases ERAP1 and ERAP2 trim or even destroy HLA class I-binding peptides thereby shaping the peptide repertoire presented for T cell recognition.

Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance.

Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group-associated antigen proteins p17 and p24 correlated with epitope abundance, which was strongly influenced by proteasomal digestion profiles, affinity for the transporter protein TAP, and trimming mediated by the endoplasmatic reticulum aminopeptidase ERAAP, and was moderately influenced by HLA affinity. Structural and functional analyses demonstrated that proteasomal cleavage 'preferences' modulated the number and length of epitope-containing peptides, thereby affecting the response avidity and clonality of T cells.

Characterizing the N-terminal processing motif of MHC class I ligands.

Most peptide ligands presented by MHC class I molecules are the product of an intracellular pathway comprising protein breakdown in the cytosol, transport into the endoplasmic reticulum, and successive N-terminal trimming events. The efficiency of each of these processes depends on the amino acid sequence of the presented ligand and its precursors. Thus, relating the amino acid composition N-terminal of presented ligands to the sequence specificity of processes in the pathway gives insight into the usage of ligand precursors in vivo.

A National Guard outbreak of Burkholderia cepacia infection and colonization secondary to intrinsic contamination of albuterol nebulization solution.

Background: Burkholderia cepacia, a gram-negative pathogen, has been a known cause of hospital outbreaks because of a contaminated common source such as multidose medications. We describe an outbreak with Burkholderia cepacia infection in 2 major hospitals affiliated to the National Guard, related to an intrinsic contamination of a locally manufactured, multidose Albuterol nebulization solution (Tabouk Pharmaceutical Company, Tabouk, Saudi Arabia) and we report the interventions taken to interrupt this outbreak.

Methods: During the outbreak period between May 2003 and March 2004, a combined prospective surveillance and a retrospective chart and microbiologic data review were conducted in 4 major hospitals affiliated to the National Guard.

Shotgun slug injuries: case report and literature review.

Shotguns are usually used to fire multiple pellets; however, they are capable of firing a single projectile in the form of a slug. Although rare, shotgun slug injuries are severe, producing wounds comparable to those inflicted by high-velocity weapons with the potential for even more tissue destruction because of the slug's size and mass. We report the first survivor of a close range shotgun slug injury, with a review of this weapon's unique projectile ballistics and the relevant literature.

Is a low-osmolarity ORS solution more efficacious than standard WHO ORS solution?

The clinical efficacy of a diluted oral rehydration salts (ORS) solution was compared in a pilot study with that of intravenous (i.v.) therapy and of standard World Health Organization (WHO)/United Nations Childrens Fund (UNICEF) ORS solution in children with acute diarrhea.

Controlled clinical trial on the efficacy of rice powder-based oral rehydration solution on the outcome of acute diarrhea in infants.

We report a controlled clinical trial of rice powder-based oral rehydration solution (ORS) versus glucose ORS on the outcome of acute diarrhea in infants. The rice ORS group (n = 30) received ORS containing 50 g rice powder instead of standard WHO solution (20 g glucose, n = 30). Formula-fed male infants were enrolled to enable calculation of milk intake and excretion of urine.