Military influences on the evolution of clinical trials throughout history.

Clinical trials of drugs, procedures, and other therapies play a crucial role in advancing medical science by evaluating the safety, efficacy, and optimal use of medical interventions. The design and implementation of these trials have evolved significantly over time, reflecting advancements in medicine, ethics, and methodology. Early historical examples, such as King Nebuchadnezzar II's and his captives' dietary experiment and Ambroise Paré's treatment of gunshot wounds, laid some foundational principles of trial design.

Clinical Outcomes of a New Foot-Worn Non-Invasive Biomechanical Intervention Compared to Traditional Physical Therapy in Patients With Chronic Low Back Pain. A Randomized Clinical Trial.

Study Design: Randomized Controlled Trial.

Objective: Chronic low back pain (CLBP) is a major public health concern that will continue to grow with the expected aging of the population. The purpose of this study was to examine the clinical effect of a personalized, home-based biomechanical intervention compared to traditional physical therapy in patients with CLBP.

Stabilizing Contorted Doubly-Reduced Tetraphenylene with Heavy Alkali Metal Complexation: Crystallographic and Theoretical Evidence.

The two-fold reduction of tetrabenzo[a,c,e,g]cyclooctatetraene (TBCOT, or tetraphenylene, 1) with K, Rb, and Cs metals reveals a distinctive core transformation pathway: a newly formed C-C bond converts the central eight-membered ring into a twisted core with two fused five-membered rings. This C-C bond of 1.589(3)-1.

Smokers' perceived cancer risks: attributions of the risks and the roles of risks in planning to quit smoking.

This study proposed that smokers' perceived cancer risks differ emotionally and cognitively; the former is based on perceived smoking-related causes, while the latter is based more on perceived non-smoking related causes. It further examined the role of perceived reasons for cancer risk, as well as perceived risks, in planning smoking cessation. The study drew a sample of daily smokers, intermittent smokers and previous smokers (as a reference category) from the Health Information National Trends Survey (HINTS).

Identification of Behavioral, Clinical, and Psychological Antecedents of Acute Stimulant Poisoning: Development and Implementation of a Mixed Methods Psychological Autopsy Study.

Background: Despite increasing fatal stimulant poisoning in the United States, little is understood about the mechanism of death. The psychological autopsy (PA) has long been used to distinguish the manner of death in equivocal cases, including opioid overdose, but has not been used to explicitly explore stimulant mortality.

Objective: We aimed to develop and implement a large PA study to identify antecedents of fatal stimulant poisoning, seeking to maximize data gathering and ethical interactions during the collateral interviews.

Refinement of a meaning-centered counseling program for Chinese patients with advanced cancer: integrating cultural adaptation and implementation science approaches.

Background: This mixed methods study identified needed refinements to a telehealth-delivered cultural and linguistic adaptation of Meaning-Centered Psychotherapy for Chinese patients with advanced cancer (MCP-Ch) to enhance acceptability, comprehensibility, and implementation of the intervention in usual care settings, guided by the Ecological Validity Model (EVM) and the Practical, Robust Implementation and Sustainability Model (PRISM).

Methods: Fifteen purposively sampled mental health professionals who work with Chinese cancer patients completed surveys providing Likert-scale ratings on acceptability and comprehensibility of MCP-Ch content (guided by the EVM) and pre-implementation factors (guided by PRISM), followed by semi-structured interviews. Survey data were descriptively summarized and linked to qualitative interview data.

Two-stage revision anterior cruciate ligament reconstruction reduces failure risk but leads to lesser clinical outcomes than single-stage revision after primary anterior cruciate ligament graft failure: a retrospective cohort study.

Background: There are no studies that compare the outcomes and complications of single-versus two-stage revision anterior cruciate ligament reconstruction (ACLR) after primary ACLR failure. This purpose of this study is to examine clinical and functional outcomes and complications associated with single and two-stage revision ACLR after primary ACLR failure.

Methods: All patients who underwent single or two-stage revision ACLR after primary ACLR failure between 2012 and 2021 with a minimum of a 2 year follow-up were included.

Shear-Mediated Stabilization of Spin Spiral Order in Multiferroic NiI.

Type-II multiferroicity from non-collinear spin order is recently explored in the van der Waals material NiI. Despite the importance for improper ferroelectricity, the microscopic mechanism of the helimagnetic order remains poorly understood. Here, the magneto-structural phases of NiI are investigated using resonant magnetic X-ray scattering (RXS) and X-ray diffraction.

A conceptual model for advanced/metastatic gastric or gastroesophageal junction cancer: a review of qualitative studies and results from patient interviews.

Background: Despite approvals of new first-line immunotherapies for advanced/metastatic gastric cancer/gastroesophageal junction cancer (aGC/GEJC), patients' median survival is around 14 months and their health-related quality of life (HRQoL) is affected by disease-related symptoms and treatment-related side effects. Using a targeted literature review (TLR) and patient interviews, this study identified disease- and treatment-related concepts that are important to patients with aGC/GEJC and their HRQoL.

Methods: A TLR was conducted to identify primary qualitative studies from 2018 to 2021 on patients' experiences with aGC/GEJC.

Patients with DCIS Seen at a Specialized High-Risk Breast Clinic Run by Surgical Advanced Practice Providers Have High Rates of Preventive Medication Uptake.

Background: Preventative medication (PM) uptake is low among patients at an elevated risk of breast cancer, largely due to fears of intolerance. This study aimed to investigate whether a new, surgical advanced practice provider (APP)-run clinic was effectively prescribing PM. We hypothesized equivalent rates of PM uptake compared to consultation with medical oncologists (MD).

Spatiotemporal imaging of nonlinear optics in van der Waals waveguides.

Van der Waals (vdW) semiconductors have emerged as promising platforms for efficient nonlinear optical conversion, including harmonic and entangled photon generation. Although major efforts are devoted to integrating vdW materials in nanoscale waveguides for miniaturization, the realization of efficient, phase-matched conversion in these platforms remains challenging. Here, to address this challenge, we report a far-field ultrafast imaging method to track the propagation of both fundamental and harmonic waves within vdW waveguides with femtosecond and sub-50 nanometre spatiotemporal precision.

Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.

Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates.

The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organization and dynamics of chromatin compacted by gene-repressing factors are unknown.

Diffusion-weighted MRI of advanced gastric cancer: correlations of the apparent diffusion coefficient with Borrmann classification, proliferation and aggressiveness.

Objectives: This study aimed to compare apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) of different Borrmann types of advanced gastric cancer (AGC) and correlate these ADC values with Ki-67 expression and serum CEA levels in AGC.

Methods: A total of 84 patients with AGC who underwent DWI of the upper abdomen before tumor resection in our hospital between June 2014 and July 2018 were included in the present study. DWI was obtained with a single-shot echo planar imaging sequence in the axial plane (b values: 0, 100, 700 and 1000 s/mm).

A predictive clinical-radiomics nomogram for early diagnosis of mesenteric arterial embolism based on non-contrast CT and biomarkers.

Purpose: Mesenteric artery embolism (MAE) is a relatively uncommon abdominal surgical emergency, but it can lead to catastrophic clinical outcomes if the diagnosis is delayed. This study aims to build a prediction model of clinical-radiomics nomogram for early diagnosis of MAE based on non-contrast computed tomography (CT) and biomarkers.

Method: In this retrospective study, a total of 364 patients confirmed as MAE (n = 131) or non-MAE (n = 233) who were randomly divided into a training cohort (70%) and a validation cohort (30%).

Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.

Neural mechanisms of relational learning and fast knowledge reassembly in plastic neural networks.

Humans and animals have a striking ability to learn relationships between items in experience (such as stimuli, objects and events), enabling structured generalization and rapid assimilation of new information. A fundamental type of such relational learning is order learning, which enables transitive inference (if A > B and B > C, then A > C) and list linking (A > B > C and D > E > F rapidly 'reassembled' into A > B > C > D > E > F upon learning C > D). Despite longstanding study, a neurobiologically plausible mechanism for transitive inference and rapid reassembly of order knowledge has remained elusive.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Delayed onset of ocean acidification in the Gulf of Maine.

The Gulf of Maine holds significant ecological and economic value for fisheries and communities in north-eastern North America. However, there is apprehension regarding its vulnerability to the effects of increasing atmospheric CO. Substantial recent warming and the inflow of low alkalinity waters into the Gulf of Maine have raised concerns about the impact of ocean acidification on resident marine calcifiers (e.

Auditory decision-making deficits after permanent noise-induced hearing loss.

Loud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we investigate the specific underlying cognitive processes during auditory perceptual decision-making that are impacted by NIHL.

Training data diversity enhances the basecalling of novel RNA modification-induced nanopore sequencing readouts.

Accurately basecalling sequence backbones in the presence of nucleotide modifications remains a substantial challenge in nanopore sequencing bioinformatics. It has been extensively demonstrated that state-of-the-art basecallers are less compatible with modification-induced sequencing signals. A precise basecalling, on the other hand, serves as the prerequisite for virtually all the downstream analyses.

Photoreceptor metabolic window unveils eye-body interactions.

Photoreceptors are specialized neurons at the core of the retina's functionality, with optical accessibility and exceptional sensitivity to systemic metabolic stresses. Here we show the ability of risk-free, in vivo photoreceptor assessment as a window into systemic health and identify shared metabolic underpinnings of photoreceptor degeneration and multisystem health outcomes. A thinner photoreceptor layer thickness is significantly associated with an increased risk of future mortality and 13 multisystem diseases, while systematic analyses of circulating metabolomics enable the identification of 109 photoreceptor-related metabolites, which in turn elevate or reduce the risk of these health outcomes.

Morphological and functional convergence of visual projection neurons from diverse neurogenic origins in Drosophila.

The Drosophila visual system is a powerful model to study the development of neural circuits. Lobula columnar neurons-LCNs are visual output neurons that encode visual features relevant to natural behavior. There are ~20 classes of LCNs forming non-overlapping synaptic optic glomeruli in the brain.