Results from a phase 1b study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) after progression on prior osimertinib.

Background: Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutated NSCLC. However, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (Teliso-V) is an antibody-drug conjugate that targets c-Met protein overexpression.

Efficient scaling of large language models with mixture of experts and 3D analog in-memory computing.

Large language models (LLMs), with their remarkable generative capacities, have greatly impacted a range of fields, but they face scalability challenges due to their large parameter counts, which result in high costs for training and inference. The trend of increasing model sizes is exacerbating these challenges, particularly in terms of memory footprint, latency and energy consumption. Here we explore the deployment of 'mixture of experts' (MoEs) networks-networks that use conditional computing to keep computational demands low despite having many parameters-on three-dimensional (3D) non-volatile memory (NVM)-based analog in-memory computing (AIMC) hardware.

Homologation of Carboxylic Acids Using a Radical-Polar Conjunctive Reagent.

Homologations of organic molecules that add a carbon atom to the substrate are useful in drug discovery to access compounds with improved properties that otherwise present a synthetic challenge. Carboxylic acids are present in many bioactive molecules and are widely available building blocks for chemical synthesis, yet their direct homologation is unknown. This valuable transformation currently necessitates implementation of multistep processes that require the use of carboxylic acid derivatives rather than the native substrates, and commonly involves highly reactive and toxic reagents.

Demonstration of 4-quadrant analog in-memory matrix multiplication in a single modulation.

Analog in-memory computing (AIMC) leverages the inherent physical characteristics of resistive memory devices to execute computational operations, notably matrix-vector multiplications (MVMs). However, executing MVMs using a single-phase reading scheme to reduce latency necessitates the simultaneous application of both positive and negative voltages across resistive memory devices. This degrades the accuracy of the computation due to the dependence of the device conductance on the voltage polarity.

Validating the use of body mass index with computed tomography in a racially and ethnically diverse cohort of patients admitted with SARS-CoV-2.

Background: Body mass index (BMI) is criticized for being unjust and biased in relatively healthy racial and ethnic groups. Therefore, the current analysis examines if BMI predicts body composition, specifically adiposity, in a racially and ethnically diverse acutely ill patient population.

Methods: Patients admitted with SARS-CoV-2 having an evaluable diagnostic chest, abdomen, and/or pelvic computed tomography (CT) study (within 5 days of admission) were included in this retrospective cohort.

Discovery of N-X anomeric amides as electrophilic halogenation reagents.

Electrophilic halogenation is a widely used tool employed by medicinal chemists to either pre-functionalize molecules for further diversity or incorporate a halogen atom into drugs or drug-like compounds to solve metabolic problems or modulate off-target effects. Current methods to increase the power of halogenation rely on either the invention of new reagents or activating commercially available reagents with various additives such as Lewis or Brønsted acids, Lewis bases and hydrogen-bonding activators. There is a high demand for new reagents that can halogenate otherwise unreactive compounds under mild conditions.

General Synthesis of -Alkylindoles from ,-Dialkylanilines via [4 + 1] Annulative Double C-H Functionalization.

Strategies enabling the construction of indoles and novel polycyclic heterocycles from simple building blocks streamline syntheses in synthetic and medicinal chemistry. Herein, we report a C-H functionalization approach to -alkylindoles proceeding via a double, site-selective C(sp)-H/C(sp)-H [4 + 1] annulation of readily accessed -dialkylanilines. This protocol features a site-selective hydrogen atom transfer by a tuned -Bu amidyl radical and addition of a sulfonyl diazo coupling partner, which promotes highly site-selective homolytic aromatic substitution of the (hetero)aromatic core.

Two-dimensional dilute Baxter-Wu model: Transition order and universality.

We investigate the critical behavior of the two-dimensional spin-1 Baxter-Wu model in the presence of a crystal-field coupling Δ with the goal of determining the universality class of transitions along the second-order part of the transition line as one approaches the putative location of the multicritical point. We employ extensive Monte Carlo simulations using two different methodologies: (i) a study of the zeros of the energy probability distribution, closely related to the Fisher zeros of the partition function, and (ii) the well-established multicanonical approach employed to study the probability distribution of the crystal-field energy. A detailed finite-size scaling analysis in the regime of second-order phase transitions in the (Δ,T) phase diagram supports previous claims that the transition belongs to the universality class of the four-state Potts model.

Benzylic C-H Esterification with Limiting C-H Substrate Enabled by Photochemical Redox Buffering of the Cu Catalyst.

Copper-catalyzed radical-relay reactions provide a versatile strategy for selective C-H functionalization; however, reactions with peroxide-based oxidants often require excess C-H substrate. Here, we report a photochemical strategy to overcome this limitation by using a Cu/2,2'-biquinoline catalyst that supports benzylic C-H esterification with limiting C-H substrate. Mechanistic studies indicate that blue-light irradiation promotes carboxylate-to-copper charge transfer, reducing resting-state Cu to Cu, which activates the peroxide to generate an alkoxyl radical hydrogen-atom-transfer species.

Di(2-picolyl)amines as Modular and Robust Ligands for Nickel-Catalyzed C(sp)-C(sp) Cross-Electrophile Coupling.

Ni-catalyzed aryl-alkyl coupling reactions are reliant on using a limited set of commercially available bidentate nitrogenous ligands to enable the reaction, because noncommercial analogues usually entail challenging syntheses. In this work, di(2-picolyl)amines (DPAs) are explored as an alternative modular ligand class for the nickel-catalyzed aryl-alkyl cross-electrophile coupling. Novel DPA ligands were synthesized directly from inexpensive amine and pyridine building blocks in a single step.

Factors underlying denial of and disbelief in COVID-19.

Objective: To investigate factors that influence or promote disbelief and negative attitudes toward COVID-19.

Methods: This was cross-sectional study involving 544 males and females ≥ 18 years of age in Greece between December of 2020 and January of 2021. All participants were informed about the purpose of the study, protection of anonymity, and volunteer participation.

A Retrospective, Single-Center Study of Technical-Procedural Factors Affecting Radiation Dose During Prostatic Artery Embolization.

Introduction This study aims to evaluate the effect of technical-procedural factors on radiation dose during prostatic artery embolization (PAE). Methods This was a single-center, retrospective study of 59 patients with benign prostatic hyperplasia (BPH) who underwent prostatic artery embolization from March 2020 to September 2021. Computed tomography angiography (CTA) was performed for vascular planning prior to PAE in all patients.

Investigation of Healthcare Satisfaction of Roma Living in Camps or Urban Complex of Central Greece.

Background: Roma in Greece face multiple discrimination, particularly in the areas of housing, education, employment and health.

Objective: The aim of this study is to explore the perceptions and beliefs of Greek Roma living both in camps and in urban neighborhoods for public health structures as well as to assess their satisfaction with health care services.

Methods: The study sample consisted of 185 subjects (94 females and 91 males) with a mean age of 39.

Universality in the two-dimensional dilute Baxter-Wu model.

We study the question of universality in the two-dimensional spin-1 Baxter-Wu model in the presence of a crystal field Δ. We employ extensive numerical simulations of two types, providing us with complementary results: Wang-Landau sampling at fixed values of Δ and a parallelized variant of the multicanonical approach performed at constant temperature T. A detailed finite-size scaling analysis in the regime of second-order phase transitions in the (Δ,T) phase diagram indicates that the transition belongs to the universality class of the four-state Potts model.

Monte Carlo study of the two-dimensional kinetic Blume-Capel model in a quenched random crystal field.

We investigate by means of Monte Carlo simulations the dynamic phase transition of the two-dimensional kinetic Blume-Capel model under a periodically oscillating magnetic field in the presence of a quenched random crystal-field coupling. We analyze the universality principles of this dynamic transition for various values of the crystal-field coupling at the originally second-order regime of the corresponding equilibrium phase diagram of the model. A detailed finite-size scaling analysis indicates that the observed nonequilibrium phase transition belongs to the universality class of the equilibrium Ising ferromagnet with additional logarithmic corrections in the scaling behavior of the heat capacity.

C(sp)-H methylation enabled by peroxide photosensitization and Ni-mediated radical coupling.

The "magic methyl" effect describes the change in potency, selectivity, and/or metabolic stability of a drug candidate associated with addition of a single methyl group. We report a synthetic method that enables direct methylation of C(sp)-H bonds in diverse drug-like molecules and pharmaceutical building blocks. Visible light-initiated triplet energy transfer promotes homolysis of the O-O bond in di--butyl or dicumyl peroxide under mild conditions.

Copper-Catalyzed C-H Fluorination/Functionalization Sequence Enabling Benzylic C-H Cross Coupling with Diverse Nucleophiles.

Site-selective transformation of benzylic C-H bonds into diverse functional groups is achieved via Cu-catalyzed C-H fluorination with -fluorobenzenesulfonimide (NFSI), followed by substitution of the resulting fluoride with various nucleophiles. The benzyl fluorides generated in these reactions are reactive electrophiles in the presence of hydrogen-bond donors or Lewis acids, allowing them to be used without isolation in C-O, C-N, and C-C coupling reactions.

Copper-Catalyzed Functionalization of Benzylic C-H Bonds with -Fluorobenzenesulfonimide: Switch from C-N to C-F Bond Formation Promoted by a Redox Buffer and Brønsted Base.

A copper catalyst in combination with -fluorobenzenesulfonimide (NFSI) has been reported to functionalize benzylic C-H bonds to the corresponding benzylic sulfonimides via C-N coupling. Here, we reported a closely related Cu-catalyzed method with NFSI that instead leads to C-F coupling. This switch in selectivity arises from changes to the reaction conditions (Cu/ligand ratio, temperature, addition of base) and further benefits from inclusion of MeB(OH) in the reaction.

Odontoid Process and Femur: A Novel Bond in Anatomy.

Objective The morphology and quantitative anatomy of the axis vertebra (C2) attracts a lot of attention between anatomists, surgeons and radiologists. However, no report exists in the literature correlating the height of the dens with the length of the femur. Our paper aims to determine such a correlation.

A rare triple skeletal bone variation, including a median cleft of the posterior arch of the atlas, a sternal foramina and a bifid xiphoid process.

Bone variations are usually a result of abnormal ossification during embryonic life. Separately or in combination, sternal foramina and bifid xiphoid process are well documented skeletal alternations, as well as the median cleft of the posterior arch of the atlas. However, their appearance in combination is not yet celebrated in the literature.

A Case of Early FAP Diagnosis with Extraintestinal Manifestations on the Face.

Objective: Gardner's syndrome is a variant of familial adenomatous polyposis, characterized by gastrointestinal polyps, multiple osteomas, and skin and soft tissue lesions. Diagnosis by means of an understanding of its various symptoms is of great importance.

Case Reposrt: This report presents the case of a 32-year-old man with obvious asymmetry and disfigurement on his face, due to multiple osteomas and soft tissue lesions.

Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis.

The aerobic Cu/ABNO catalyzed oxidative coupling of alcohols and amines is highlighted in the synthesis of amide bonds in diverse drug-like molecules (ABNO=9-azabicyclo[3.3.1]nonane N-oxyl).

An aperture in the sagittal plane of the dorsal wall of the sacrum.

The dorsal wall of the sacrum presents various anatomical variations, while the dorsal bony wall of the sacral canal suffers more. We report a case of a sacrum with a series of variants in the midline due to abnormal ossification and a bizarre aperture on the sagittal plane between the 1st and the 2nd sacral spinous processes. A failure of the ossification patter during embryological life, or an ossification of the supraspinous ligament may result in such an aperture.