Acapedia

🧠 Why Hesitation Isn’t Weakness—It’s a Brain Feature

A new study published in Nature Neuroscience (2025) reveals that hesitation—the brief pause before acting under uncertainty—is not a failure of decision-making, but an actively regulated neural process.

In “The striatal indirect pathway mediates hesitation”, MATTHEW A GERAMITA, Susanne Ahmari, and Eric Yttri demonstrate that neurons in the indirect pathway of the dorsomedial striatum specifically control hesitation when outcomes are uncertain. Importantly, this mechanism is distinct from the brain circuits that drive action.

🔬 Key takeaways:

- Hesitation increases only under uncertainty, not predictable outcomes

- The indirect pathway suppresses action to prevent costly mistakes

- Optogenetic activation increases hesitation; silencing removes it

- Hesitation is purposeful, adaptive, and precisely timed

🏒⛷️ Why it matters beyond the lab

From Olympic athletes timing a perfect start, to firefighters making split-second decisions, to everyday choices under uncertainty—this neural system helps balance impulsivity and restraint.

These findings also have implications for conditions involving disrupted timing and control, including anxiety disorders, OCD, and Tourette syndrome.

This work reframes hesitation not as something to eliminate, but something to calibrate.

📖 Published in Nature Neuroscience

https://www.nature.com/articles/s41593-025-02135-6

The striatal indirect pathway mediates hesitation - Nature Neuroscience Hesitation—pausing in the face of uncertainty—is ubiquitous in daily life and disrupted in several psychiatric disorders. Unlike other forms of response inhibition, hesitation is mediated by indirect, but not direct, pathway striatal neurons.

🌍 Advancing Diagnostics in Rural Africa with Handheld Ultrasound

A remarkable study highlights the power of handheld ultrasonography to support frontline clinicians in rural sub-Saharan Africa when diagnosing heart failure and pulmonary disease.

Conducted at a referral center in rural Tanzania, the study evaluated 438 patients with respiratory symptoms and compared lung ultrasound findings between:

🔹 Primary care clinicians using a handheld device

🔹 Expert board-certified sonographers using high-end machines

🔹 Senior physicians providing final diagnoses

Despite receiving just a few hours of focused training, clinicians achieved:

✅ 93% median agreement with expert sonographers on ultrasonographic findings

✅ 90% agreement on key diagnoses

✅ Substantial agreement with senior physicians for heart failure (κ = 0.69)

✅ Moderate agreement for tuberculosis (κ = 0.57)

While agreement for pneumonia remained low, the results strongly suggest that handheld ultrasound—paired with clinical examination—can significantly strengthen diagnostic capability where resources are limited.

Why it matters:

Handheld ultrasound continues to emerge as one of the most impactful tools for global health equity. It offers real-time insights, portability, and affordability—empowering clinicians in remote settings to identify critical conditions earlier and more accurately.

Study Authors:

Andrew Katende, Johanna Oehri, Victor Z Urio, Evance Mahundi, Lulu Wilson, Victor Myovela, Chipegwa Mlula, Christamonica Chitimbwa, Caspar Mbawala, Fanuel Faustine, Valentine Mteki, FR. WINFRID GINGO, Faraja Kitila, Ipyana Mwasongwe, Claudia Bucher, Luigia Elzi, James Okuma, Thomas Zoller, Daniel H Paris, Maja Weisser, Martin Rohacek

Interests: Focused ultrasound, pulmonary disease, heart failure, tuberculosis

CME: AMA PRA Category 1 Credit | Eligible for MOC or Patient Safety credit

Acapedia CME | Handheld Ultrasonography for Cardiac & Pulmonary Diseases Earn CME credits at Acapedia with this insightful article on the use of handheld ultrasonography for diagnosing cardiac and pulmonary diseases in rural Africa. Read now!

🎓 1.0 CME | Breast Cancer Screening Among Females With and Without Schizophrenia

A large Ontario-based study explored how breast cancer screening rates differ between women with and without schizophrenia, revealing important insights into healthcare access and equity.

📊 Among over 127,000 participants, only 69.3% of females with schizophrenia completed a mammogram within two years of turning 50, compared to 77.1% of those without schizophrenia.

💡 The analysis also showed that primary care payment models make a difference. Women cared for by physicians in Family Health Team models had higher screening rates than those in fee-for-service systems.

These findings emphasize the need to expand team-based, coordinated primary care to ensure better preventive care and early cancer detection among women living with schizophrenia.

Authors: Braden O’Neill, Abban Yusuf, Aisha Lofters, Anjie Huang, Ngozi Ekeleme, Tara Kiran, Michelle Greiver, Frank Sullivan, Paul Kurdyak

🏅 Accreditation: 1.0 AMA PRA Category 1 Credit™ | Eligible for MOC or Patient Safety credit

https://www.acapedia.com/article/breast-cancer-screening-schizophrenia-ontario

Acapedia CME | Breast Cancer Screening in Schizophrenia Patients Earn CME credits with Acapedia by understanding the impact of schizophrenia on breast cancer screening completion in Ontario. Read now!

🧬 Spatially mapping DLBCL’s immune microenvironments reveals targetable inflammatory niches

Nature Genetics (2025) — MD Anderson & collaborators

Using high-plex single-cell spatial transcriptomics (CosMx) and spatial proteomics (CODEX) across 78 DLBCL tumors, this study defines seven stereotyped cellular niches (CNs) that shape T-cell and tumor B-cell phenotypes via distinct neighbor interactions and signaling.

Key insights:

• Seven niches (e.g., T-cell–rich CN1, myeloid-rich CN3, tumor-B–dense CN5, diffuse CN6) organize how cells co-localize and communicate.

• Immune-privileged site (IPS) DLBCL (CNS/testis/eye): surprisingly robust T-cell infiltration with strong cytotoxic and proliferative signatures, yet co-inhibitory signaling (PD-1/PD-L1, LAG3, TIM3) → immunotherapy-amenable “inflammatory” niches.

• EBV-positive DLBCL: enriched T-cell and mixed niches; T cells show high cytotoxicity plus exhaustion, supporting checkpoint blockade, CAR-T, and bispecific strategies.

• Tumor-B–dense CN5: driven by the CXCL12–CXCR4 axis, high proliferation and BCL2 expression, leading to suppressed T-cell function—a rationale for CXCR4/BCL2-targeted therapies.

• Why spatial matters: Directly captures neighborhoods and ligand–receptor wiring that bulk RNA or deconvolution methods miss—unlocking new mechanistic and therapeutic insights.

Clinical & translational takeaways:

✅ Use spatial niche profiling to guide immunotherapy selection.

✅ Combine checkpoint targets (PD-1 + LAG3/TIM3) for IPS/EBV+ cases.

✅ Target CXCR4/BCL2 in dense tumor niches (CN5).

✅ Provide AI-ready spatial data to predict microenvironment features from H&E slides.

Yibo Dai, Atish Kizhakeyil, Dai Chihara, Xubin Li, Yunhe Liu, Tania Patricia Sainz Zuniga, Ashley Wilson, Jared Henderson, Daniil Vibe, Arman A Petrosyants, Connor Jacobson, Alexander Sarachakov, Krystle Nomie, Kirill Kryukov, Alexander Bagaev, Ayushi Chauhan, Jason Westin, MD MS FASCO, Christopher R. Flowers, MD, Francisco Vega, Linghua Wang & Michael Green

https://www.nature.com/articles/s41588-025-02353-5

Multi-modal spatial characterization of tumor immune microenvironments identifies targetable inflammatory niches in diffuse large B cell lymphoma - Nature Genetics Analysis of the immune microenvironment of diffuse B cell lymphomas using spatial transcriptomics, proteomics and genomics highlights discrete cellular niches with divergent patterns of cell–cell communication that contribute to the phenotypic heterogeneity of both tumor and immune cells.