Highly multiplexed spatial transcriptomics in bacteria.

Single-cell decisions made in complex environments underlie many bacterial phenomena. Image-based transcriptomics approaches offer an avenue to study such behaviors, yet these approaches have been hindered by the massive density of bacterial messenger RNA. To overcome this challenge, we combined 1000-fold volumetric expansion with multiplexed error-robust fluorescence in situ hybridization (MERFISH) to create bacterial-MERFISH.

Scientists as advocates Columbia University Press, 2025. 312 pp.

A sociologist rejects the notion that science is inherently apolitical, urging scholars to join the public square.

CASTER: Direct species tree inference from whole-genome alignments.

Genomes contain mosaics of discordant evolutionary histories, challenging the accurate inference of the tree of life. While genome-wide data are routinely used for discordance-aware phylogenomic analyses, due to modeling and scalability limitations, the current practice leaves out large chunks of genomes. As more high-quality genomes become available, we urgently need discordance-aware methods to infer the tree directly from a multiple genome alignment.

Basal ganglia components have distinct computational roles in decision-making dynamics under conflict and uncertainty.

The basal ganglia (BG) play a key role in decision-making, preventing impulsive actions in some contexts while facilitating fast adaptations in others. The specific contributions of different BG structures to this nuanced behavior remain unclear, particularly under varying situations of noisy and conflicting information that necessitate ongoing adjustments in the balance between speed and accuracy. Theoretical accounts suggest that dynamic regulation of the amount of evidence required to commit to a decision (a dynamic "decision boundary") may be necessary to meet these competing demands.

Policy Options for Contributory Health Insurance Schemes in Low and Lower-Middle Income Countries to Enable Progress Towards Universal Health Coverage.

The promise of contributory health insurance to generate additional, self-sustaining funding for the health sector has not been achieved in many low- and lower-middle-income countries. Instead, contributory health insurance has been found to exacerbate inequities in access to health care because entitlements are linked to contributions. For these countries with contributory health insurance schemes, with separate institutional arrangements for revenue collection and purchasing, that operate alongside budget-funded and other health financing schemes, it is usually not politically or technically feasible to reverse or eliminate these arrangements even when they fragment the health system.

Outpatient Palliative Care and End-of-Life Care Intensity: Linking Massachusetts Cancer Registry with All-Payer Claims.

Background: Early palliative care is associated with better outcomes for patients with advanced-stage cancers. Using a novel data linkage, we assessed outpatient palliative care use before death and its association with end-of-life care intensity and variation across eight provider networks.

Methods: We linked Massachusetts Cancer Registry and the All-Payer Claims Database for individuals with commercial insurance, Medicaid or Medicare Advantage diagnosed with colorectal, lung, prostate, and breast cancers from 2010 through 2013 who died by December 31, 2014.

Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence.

Background: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear.

Methods: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated.

Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.

Influences of gonad developmental stage on ovary selenium concentrations in fish-implications for ovary selenium monitoring.

Monitoring selenium (Se) concentrations in fish ovaries is an important tool for evaluating the ecological risk posed by Se in aquatic systems. Most guidance recommends sampling fish ovaries as closely as possible to when fish spawn on the premise that Se is mobilized from the liver to the ovary during vitellogenesis, and therefore, sampling ovaries during the early phases of oocyte maturation may underestimate egg Se concentrations at the time of spawning. In this study, we evaluated ovary Se data from two species with synchronous oocyte development (Ptychocheilus oregonensis and Prosopium williamsoni), one species with asynchronous oocyte development (Richardsonius balteatus), and one where the mode of development is unclear (Mylocheilus caurinus).

Ceftobiprole: A therapeutic update.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.

Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy.

Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in the hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits.

CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells.

Localized prostate cancer can be cured by radiation or surgery, but advanced prostate cancer continues to be a clinical challenge. Altered alternative polyadenylation occurs in numerous cancers and can downregulate tumor-suppressor genes and upregulate oncogenes. We found that the cleavage and polyadenylation specificity factor (CPSF) complex factor CPSF1 is upregulated in patients with advanced prostate cancer, with high CPSF1 expression correlating with worse progression-free survival.

Influence of birthplace and age at migration on cognitive aging among Hispanic/Latino populations in the U.S.: Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Background And Objectives: While Hispanic/Latino populations in the U.S. are remarkably diverse in terms of birthplace and age at migration, we poorly understand how these factors are associated with cognitive aging.

Modeling Biases from Low-Pass Genome Sequencing to Enable Accurate Population Genetic Inferences.

Low-pass genome sequencing is cost-effective and enables analysis of large cohorts. However, it introduces biases by reducing heterozygous genotypes and low-frequency alleles, impacting subsequent analyses such as model-based demographic history inference. Several approaches exist for inferring an unbiased allele frequency spectrum (AFS) from low-pass data, but they can introduce spurious noise into the AFS.

Changes in Axial Length in Patients of Acute Retinal Necrosis Undergoing Vitrectomy.

Purpose: To observe the changes in the axial length (AL) in patients of acute retinal necrosis (ARN) undergoing vitrectomy and investigate the correlated factors.

Methods: Retrospective case series. Patients diagnosed as ARN undergoing vitrectomy with silicone oil (SO) tamponade, and with attached retina more than one year after silicone oil removal (SOR) were included.

Pharmacogenetics: Opportunities for the Research Program and Other Large Data Sets to Advance the Field.

Pharmacogenetic variation is common and an established driver of response for many drugs. There has been tremendous progress in pharmacogenetics knowledge over the last 30 years and in clinical implementation of that knowledge over the last 15 years. But there have also been many examples where translation has stalled because of the lack of available data sets for discovery or validation research.

Decoding the Therapeutic Target SVEP1: Harnessing Molecular Trait GWASs to Unravel Mechanisms of Human Disease.

Although human genetics has substantial potential to illuminate novel disease pathways and facilitate drug development, identifying causal variants and deciphering their mechanisms remain challenging. We believe these challenges can be addressed, in part, by creatively repurposing the results of molecular trait genome-wide association studies (GWASs). In this review, we introduce techniques related to molecular GWASs and unconventionally apply them to understanding , a human coronary artery disease risk locus.

Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms.

Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is a primary target whether exposure is accidental, occupational, or recreational. Interventions to prevent/revert brain damage by toluene are curtailed by the scarce information on the molecular targets and mechanisms mediating toluene's brain toxicity and the common exposure to other neurotoxins and/or coexistence of neurological/psychiatric disorders.

Influence of Source of Origin and Region of Finishing on Growth Performance and Carcass Characteristics of Finishing Heifers Fed in the United States.

The objective was to evaluate growth performance and carcass traits of finishing beef heifers sourced and finished in different regions in the U.S. Heifers [n = 190; initial body weight (BW) 483 ± 0.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.