Phase 1 Study of Adjuvant Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Transduced Pancreatic Tumor Cell Vaccine, Low-Dose Cyclophosphamide, and Stereotactic Body Radiation Therapy Followed by FOLFIRINOX in High-Risk Resected Pancreatic Ductal Adenocarcinoma.

Purpose: Local and distant progression remains common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase 1 trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy), and stereotactic body radiation therapy (SBRT) followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC.

Patients And Methods: The study design was a modified 3+3.

Convergence to the Asymptotic Large Deviation Limit.

Large deviation theory offers a powerful and general statistical framework to study the asymptotic dynamical properties of rare events. The application of the formalism to concrete experimental situations is, however, often restricted by finite statistics. Data might not suffice to reach the asymptotic regime or judge whether large deviation estimators converge at all.

No Evidence for the Superiority of 3 Tesla Magnetic Resonance Imaging Over 1.5 Tesla Magnetic Resonance Imaging for Diagnosing Wrist Ligamentous Lesions: A Systematic Review and Meta-analysis.

Purpose: To determine the diagnostic accuracy of native magnetic resonance imaging (MRI) regarding different ligamentous lesions of the wrist and to analyze the influence of technical characteristics, such as field strength, application of fat saturation, 3-dimensional sequences, and wrist coils.

Methods: A systematic search was performed using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Studies that were published before February 12, 2024, were included.

amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma.

gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare amplification detected by fluorescence hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung.

CD8 T cell priming that is required for curative intratumorally anchored anti-4-1BB immunotherapy is constrained by Tregs.

Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical success has been limited by on-target, off-tumor activity. Here, we report the development of a tumor-anchored ɑ4-1BB agonist (ɑ4-1BB-LAIR), which consists of a ɑ4-1BB antibody fused to the collagen-binding protein LAIR. While combination treatment with an antitumor antibody (TA99) shows only modest efficacy, simultaneous depletion of CD4+ T cells boosts cure rates to over 90% of mice.

Measurement-Induced Quantum Synchronization and Multiplexing.

Measurements are able to fundamentally affect quantum dynamics. We here show that a continuously measured quantum many-body system can undergo a spontaneous transition from asynchronous stochastic dynamics to noise-free stable synchronization at the level of single trajectories. We formulate general criteria for this quantum phenomenon to occur and demonstrate that the number of synchronized realizations can be controlled from none to all.

Monitoring of carbon dioxide and equilibrium moisture content for early detection of physicochemical and morphological changes in soybeans stored in vertical silos.

In the context of grain storage, impurities and soybeans defects in soybeans can significantly impact the equilibrium moisture content. This, cause moisture migration and heating of the stored product, leading to increased respiratory activity. Furthermore, temperature measurements within stored grain mass do not provide sufficient information for effective grain quality monitoring, primarily due to the grains excellent thermal insulating properties.

Enhanced Vaccine Immunogenicity Enabled by Targeted Cytosolic Delivery of Tumor Antigens into Dendritic Cells.

Molecular vaccines comprising antigen peptides and inflammatory cues make up a class of therapeutics that promote immunity against cancer and pathogenic diseases but often exhibit limited efficacy. Here, we engineered an antigen peptide delivery system to enhance vaccine efficacy by targeting dendritic cells and mediating cytosolic delivery. The delivery system consists of the nontoxic anthrax protein, protective antigen (PA), and a single-chain variable fragment (scFv) that recognizes the XCR1 receptor on dendritic cells (DCs).

A quantum engine in the BEC-BCS crossover.

Heat engines convert thermal energy into mechanical work both in the classical and quantum regimes. However, quantum theory offers genuine non-classical forms of energy, different from heat, which so far have not been exploited in cyclic engines. Here we experimentally realize a quantum many-body engine fuelled by the energy difference between fermionic and bosonic ensembles of ultracold particles that follows from the Pauli exclusion principle.

Both intratumoral regulatory T cell depletion and CTLA-4 antagonism are required for maximum efficacy of anti-CTLA-4 antibodies.

Anti-CTLA-4 antibodies have successfully elicited durable tumor regression in the clinic; however, long-term benefit is limited to a subset of patients for select cancer indications. The incomplete understanding of their mechanism of action has hindered efforts at improvement, with conflicting hypotheses proposing either antagonism of the CTLA-4:B7 axis or Fc effector-mediated regulatory T cell (Treg) depletion governing efficacy. Here, we report the engineering of a nonantagonistic CTLA-4 binding domain (b1s1e2) that depletes intratumoral Tregs as an Fc fusion.

Efficiency at Maximum Power of a Carnot Quantum Information Engine.

Optimizing the performance of thermal machines is an essential task of thermodynamics. We here consider the optimization of information engines that convert information about the state of a system into work. We concretely introduce a generalized finite-time Carnot cycle for a quantum information engine and optimize its power output in the regime of low dissipation.

Can ultra-low-dose computed tomography reliably diagnose and classify maxillofacial fractures in the clinical routine?

Purpose: Maxillofacial trauma predominantly affects young adults between 20 and 40 years of age. Although radioprotection is a legal requirement, the significant potential of dose reduction in computed tomography (CT) is still underused in the clinical routine. The objective of this study was to evaluate whether maxillofacial fractures can be reliably detected and classified using ultra-low-dose CT.

Tregs constrain CD8 T cell priming required for curative intratumorally anchored anti-4-1BB immunotherapy.

Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical development has been hampered by on-target, off-tumor toxicity. Here, we report the development of a tumor-anchored ɑ4-1BB agonist (ɑ4-1BB-LAIR), which consists of an ɑ4-1BB antibody fused to the collagen binding protein LAIR. While combination treatment with an antitumor antibody (TA99) displayed only modest efficacy, simultaneous depletion of CD4 T cells boosted cure rates to over 90% of mice.

Intratumoral nanobody-IL-2 fusions that bind the tumor extracellular matrix suppress solid tumor growth in mice.

Confining cytokine exposure to the tumors would greatly enhance cancer immunotherapy safety and efficacy. Immunocytokines, cytokines fused to tumor-targeting antibodies, have been developed with this intention, but without significant clinical success to date. A critical limitation is uptake by receptor-expressing cells in the blood, that decreases the dose at the tumor and engenders toxicity.

Fundamental energy cost of finite-time parallelizable computing.

The fundamental energy cost of irreversible computing is given by the Landauer bound of [Formula: see text]/bit, where k is the Boltzmann constant and T is the temperature in Kelvin. However, this limit is only achievable for infinite-time processes. We here determine the fundamental energy cost of finite-time parallelizable computing within the framework of nonequilibrium thermodynamics.

Noise-Induced Quantum Synchronization.

Synchronization is a widespread phenomenon in science and technology. Here, we study noise-induced synchronization in a quantum spin chain subjected to local Gaussian white noise. We demonstrate stable (anti)synchronization between the endpoint magnetizations of a quantum XY model with transverse field of arbitrary length.

Multibiomarker disease activity score: an objective tool for monitoring rheumatoid arthritis? A systematic review and meta-analysis.

Objectives: The multibiomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in RA. Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA.

Methods: We performed a systematic literature search in five medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, Scopus and Web of Science-from inception to 13 October 2021.

Cancer cell survival depends on collagen uptake into tumor-associated stroma.

Collagen I, the most abundant protein in humans, is ubiquitous in solid tumors where it provides a rich source of exploitable metabolic fuel for cancer cells. While tumor cells were unable to exploit collagen directly, here we show they can usurp metabolic byproducts of collagen-consuming tumor-associated stroma. Using genetically engineered mouse models, we discovered that solid tumor growth depends upon collagen binding and uptake mediated by the TEM8/ANTXR1 cell surface protein in tumor-associated stroma.

Alum-anchored intratumoral retention improves the tolerability and antitumor efficacy of type I interferon therapies.

Effective antitumor immunity in mice requires activation of the type I interferon (IFN) response pathway. IFNα and IFNβ therapies have proven promising in humans, but suffer from limited efficacy and high toxicity. Intratumoral IFN retention ameliorates systemic toxicity, but given the complexity of IFN signaling, it was unclear whether long-term intratumoral retention of type I IFNs would promote or inhibit antitumor responses.

An affinity threshold for maximum efficacy in anti-PD-1 immunotherapy.

Monoclonal antibodies targeting the programmed cell death protein 1 (PD-1) remain the most prevalent cancer immunotherapy both as a monotherapy and in combination with additional therapies. Despite the extensive success of anti-PD-1 monoclonal antibodies in the clinic, the experimental relationship between binding affinity and functional potency for anti-PD-1 antibodies in vivo has not been reported. Anti-PD-1 antibodies with higher and lower affinity than nivolumab or pembrolizumab are entering the clinic and show varied preclinical efficacy.

Thermodynamics of a Minimal Algorithmic Cooling Refrigerator.

We investigate, theoretically and experimentally, the thermodynamic performance of a minimal three-qubit heat-bath algorithmic cooling refrigerator. We analytically compute the coefficient of performance, the cooling power, and the polarization of the target qubit for an arbitrary number of cycles, taking realistic experimental imperfections into account. We determine their fundamental upper bounds in the ideal reversible limit and show that these values may be experimentally approached using a system of three qubits in a nitrogen-vacancy center in diamond.

Use of electronic cigarettes among U.S. Military service members - prevalence and associated risk factors.

Background: Decreased physical fitness, loss of vision and hearing, and increased risk of chronic diseases are significant primary and secondary implications associated with the health of U.S. Military Service members who use tobacco, including electronic cigarettes.

Use of Telehealth Services for Prenatal Care in Mississippi: Comparison of Pre-COVID-19 Pandemic and Pandemic Obstetric Management.

Background: The SARS-CoV-2 (COVID-19) pandemic resulted in major shifts in service delivery for patient care not involving COVID-19 illness. The preexisting telehealth infrastructure in Mississippi allowed the state to rapidly expand the scope of telehealth programs. Little research has been done to examine the use of telehealth during the COVID-19 pandemic and its impact on the delivery of care during pregnancy and outcomes associated with pregnancy.

Non-Markovian Feedback Control and Acausality: An Experimental Study.

Causality is an important assumption underlying nonequilibrium generalizations of the second law of thermodynamics known as fluctuation relations. We here experimentally study the nonequilibrium statistical properties of the work and of the entropy production for an optically trapped, underdamped nanoparticle continuously subjected to a time-delayed feedback control. Whereas the non-Markovian feedback depends on the past position of the particle for a forward trajectory, it depends on its future position for a time-reversed path, and is therefore acausal.

A cytotoxic-skewed immune set point predicts low neutralizing antibody levels after Zika virus infection.

Although generating high neutralizing antibody levels is a key component of protective immunity after acute viral infection or vaccination, little is known about why some individuals generate high versus low neutralizing antibody titers. Here, we leverage the high-dimensional single-cell profiling capacity of mass cytometry to characterize the longitudinal cellular immune response to Zika virus (ZIKV) infection in viremic blood donors in Puerto Rico. During acute ZIKV infection, we identify widely coordinated responses across innate and adaptive immune cell lineages.