The hypothalamus coordinates energy-balance regulation and is also a neurogenic/plastic region in the adult brain. Tanycytes, a specialized population of radial glial-like cells lining the third ventricle, reside at the critical interface between the blood, cerebrospinal fluid, and hypothalamic parenchyma. This unique positioning enables them to sense metabolic and nutrient-derived signals, and to shuttle molecules between periphery and brain. Tanycytes can respond to glucose and lipids, as demonstrated by a calcium transient down their long processes that extend into the hypothalamic nuclei. Tanycytes are also capable of self-renewal and differentiation after brain injury, supporting their classification as putative neural stem cells in the adult hypothalamus. Bone morphogenetic protein (BMP) signaling regulates neuroplasticity and contributes to metabolic regulation, including appetite and sympathetic drive to adipose. We previously demonstrated that central administration of BMP7 suppresses appetite, and BMP receptor 1A (BMPR1A) in anorectic hypothalamic POMC neurons impacts appetite regulation. BMPR1A is also tightly and highly co-expressed in hypothalamic tanycytes. Here, we attempted to genetically inactivate BMPR1A in adult tanycytes to explore its functional roles. Using the Rax-CreERT2xBMPR1Aflox mouse line, we tested multiple routes of tamoxifen administration, as well as its metabolite, without success. Cre recombinase activity was successfully induced via dietary tamoxifen (shown by recombination of the BMPR1A locus and fluorescent reporter induction), but efficient BMPR1A knockout in adult tanycytes was not achieved. Similarly, adeno-associated viral (AAV)-mediated BMPR1A knockdown via the Dio2 promoter and intracerebroventricular delivery yielded limited efficiency, despite confirmed Cre activity indicated by reporter expression. We also observed a compensatory increase in BMPR1A in cells not targeted by these knock-out/knockdown systems, as we observed previously with POMC-Cre knockout of BMPR1A, indicating a responsiveness of the hypothalamic niche to manipulation of BMPR1A levels. Together, our findings support that Cre-driven reporter activity doesn't guarantee gene depletion, and demonstrate that current strategies for loss of function of BMPR1A in adult hypothalamic tanycytes remain technically challenging and require careful validation before interpretation of phenotypes. More efficient and reliable methods are required to elucidate the molecular signaling and functional roles of molecules expressed in adult tanycytes.

Carbazoles are desirable products with ample usage in the fields of pharmaceutical and materials chemistry. Usual methods for their synthesis often focus on the formation of a single C-C or C-N bond from complex diphenylamine- or biphenyl-derived substrates - i.e., multiple reaction steps are necessary for obtaining the desired carbazole product. Furthermore, regioselectivity issues arise when unsymmetrically substituted phenyl rings are involved in the reaction. We report the use of o-borylaryl triflates in a single-step palladium-catalyzed annulation reaction to yield carbazoles. Twenty-six carbazoles were obtained in up to 99% yield. In addition, this report includes an unexplored tandem cross-coupling reactivity mode for o-borylaryl triflates, which is in contrast to previous reports which invoke them as aryne precursors. Utilizing Hammett parameters as a rationale, we developed a predictive approach to optimize the placement of substituents on the starting materials to maximize yields.

Buying from a friend via Online Platforms? A cautionary tale of using friendship to support transactions

Synthetic cationic fluorophores are widely used as probes to measure the membrane potentials of bacterial cells, eukaryotic cells, and organelles (such as mitochondria) in electrophysiology experiments and live/dead assays. We applied an external oscillating electric field toEscherichia coliusing microelectrodes and observed that AC electro-osmosis caused fluorescence transients independent of bacterial electrophysiology, which could be mistaken for membrane depolarisation events. The fluorophores migrated within the microfluidic device in vortices, leading to concentration fluctuations manifested as dips in fluorescence. These fluorescent dips were universally present when using cationic fluorophores such as thioflavin-T, propidium iodide, Syto9, and Sytox Green, with or withoutE. colipresent, whenever AC voltages were applied. Furthermore, we also demonstrate that fluorescence dips in dense bacterial communities can arise from AC electro-osmosis rather than ion-channel activity. This cautionary tale highlights how electrical stimulation experiments in microbial communities can yield misleading results if electrokinetic effects are not accounted for. We quantified the relaxation times of fluorophores under AC electro-osmosis, which depended on the community, the cells, and the dye used: PI showed the shortest relaxation time and Syto9 the longest. Removing cells resulted in longer relaxation times, and introducing dense communities did not significantly alter the relaxation times compared with single-cell experiments. Furthermore, fluorescently labelled DNA and fluorescent colloidal beads (30-130 nm) also exhibited fluorescence dips due to AC electro-osmosis, demonstrating that charged molecules and particles readily penetrate and accumulate within these assemblies. To our knowledge, this is the first study to characterise AC electro-osmosis in dense bacterial communities, revealing the high mobility of charged molecules in such systems and suggesting possible applications for enhancing antibiotic delivery.

To evaluate the extent to which the appearance of HOD in the brain following systemic administration of a deuterated substrate is due to local brain metabolism versus body metabolism. [6,6-2H2]glucose, which is transported across the blood-brain barrier (BBB), and [6,6-2H2]fructose (Fruc), which does not cross the BBB, were administered to four mouse cohorts. Cohorts included wild-type mice, glucose transporter deficiency mice, which have decreased brain glucose uptake from the blood, and littermate control mice. A separate wild-type cohort received a 15-μL intramuscular (leg) injection of D2O. Brain-localized DMRS experiments employed the ISIS single-voxel protocol at 11.74 T. Following leg D2O injection, semi-heavy water (HOD) appears within the brain in minutes, reaching steady state shortly thereafter. Body metabolism of [6,6-2H2]fructose produces HOD that also appears in the brain within minutes following subcutaneous administration, with an initial rate (mM/min) substantially greater than following administration of [6,6-2H2]glucose. Deuterated glucose from body metabolism of [6,6-2H2]fructose also appears in the brain. The terminal rates for HOD appearance in the brain are indistinguishable for the four cohorts examined despite there being up to a five-fold difference in brain concentration (mM) of deuterium-labeled glucose. Body production of HOD dominates the initial increase of HOD in brain following administration of [6,6-2H2]fructose and likely contributes significantly to the increase of HOD in brain following administration of [6,6-2H2]glucose. Interpretation of HOD concentrations as representative of organ-specific metabolism requires careful consideration of control experiments and assessment of HOD contributions from body metabolism of the administered deuterated substrate.

Animal intelligence is not purely a product of abstract computation in the brain, but emerges from dynamic interactions between the nervous system and the body. New connectome datasets and musculoskeletal models now enable integrated, closed-loop simulations of the neural and biomechanical systems of the fruit flyDrosophila, an ideal model organism to investigate embodied intelligence. However, many biological parameters of the nervous system and the body, as well as how they interface, remain unknown. To fill such gaps, researchers are turning to deep reinforcement learning (DRL), a data-driven optimization framework, to create virtual animals that imitate the behavior of real animals. Here, we provide a cautionary tale about the interpretation of such models. We constructed a virtual chimera of two phylogenetically distant species: a connectome of theC. elegansnematode worm and a biomechanical model of the fly body. The worm connectome receives sensory information from the fly body, and an artificial neural network is trained with DRL to map worm motor neuron activations to the fly’s leg actuators. The resulting digital sphinx produces highly realistic fly walking—yet it is biologically meaningless. This exercise teaches us nothing about either animal and exposes a core peril of connectome-body models: behavioral fidelity is achievable without biological fidelity, making such models easy to overinterpret. Done carefully, virtual animals can be powerful partners to biological experiments, but only if their components and interfaces are grounded in biology.

This paper scrutinizes Paolo Bacigalupi’s The Windup Girl through the lens of the ethical and theoretical dimensions of genetic engineering, corporate greed, and apocalypticism. It examines the novel’s exposition of a dystopian future constructed by the rampant adoption of genetic advancements. The paper sheds light on how genetic modification in agriculture, motivated by financial greed, has led to ecological and environmental disasters, including destructive plagues, climate change, and imbalanced biodiversity. The unrestrained corporate monopoly of genetic resources, controlled by companies such as AgriGen and PurCal, is presented as a compelling force behind this apocalyptic dystopia. Furthermore, the research critiques the ethical implications of genetic manipulation and crystallizes the preference for economic gain over ecological sustainability. This paper draws the attention of contemporary society by referencing ecological criticism and ethical theory. It argues that Bacigalupi’s work serves as a cautionary tale, warning against the long-term byproducts of exploiting nature and intervening in environmental originality for corporate profit. In a nutshell, The Windup Girl challenges readers, critics, and all human beings to reconsider the moral responsibility and future accountability surrounding genetic technologies and their environmental impact.

This article examines African Americans’ engagement with the League of Nations. Despite U.S. nonmembership, Black activists quickly recognized global governance as a valuable new platform for advancing racial equality and the demands they carried from Washington to Geneva were substantially transformed in the process. The article traces the strategies activists employed to translate U.S. race relations into the framework of liberal internationalism—from minorities’ rights and colonial advocacy to appeals grounded in “civilized” status. Positioning these figures as geographical thinkers, it reconceptualizes liberal internationalism from the margins, showing how race reformers theorized their struggle as a spatial and scalar problem: How to achieve racial equality became inseparable from where to achieve it. The 1935 Abyssinian crisis, however, exposed the limits of this framework, revealing that the League’s measure of “civilized” status was always racially tuned. The case offers both a richer account of Black internationalist thought and a cautionary tale about liberal internationalism as a vehicle for racial equality.

This essay examines the evolving landscape of content regulation within the American Forces Network (AFN), a U.S. Department of Defense broadcaster serving military personnel and their families overseas. Tracing AFN’s historical adherence to commercial broadcasting standards and its complex relationship with military, political, and diplomatic pressures, the essay highlights how content decisions have been shaped by institutional constraints, host nation sensitivities, and shifting definitions of the public interest. Special attention is given to recent developments under the second Trump administration, particularly the elimination of diversity, equity, and inclusion (DEI) initiatives and the resulting censorship of media content. Through this case study, the essay explores broader tensions between free speech, state power, and market forces in media governance. It argues that AFN’s experience illustrates the precarious balance between democratic ideals and institutional control, offering a cautionary tale about the consequences of unchecked state and corporate influence over public communication channels.

This article examines Ladjablès, femme sauvage by Martinican playwright Daniely Francisque as a theatrical intervention into questions of justice, temporality, and colonial legacy in the Caribbean. Reworking the folkloric figure of Ladjablès, Francisque stages an encounter between a predatory man and a mythic woman during Carnival night, transforming a traditional cautionary tale into a meditation on colonial subjectivity, gendered violence, and ethical relation. The article argues that the play articulates a dramaturgy of relational justice, in which justice is not juridical or retributive but emerges through temporal rupture, linguistic transformation, and embodied ritual. By opposing colonial chronos with a kairotic temporality rooted in Carnival, opacity, and creolized language, the play dismantles colonial masculinity and opens the possibility of ethical transformation grounded in relation rather than domination. Ultimately, Ladjablès, femme sauvage demonstrates how theater can enact decolonial justice as an ongoing practice rather than a final resolution.

Artificial intelligence (AI) and machine learning (ML) have seen remarkable growth in mental health applications over the past few decades, demonstrating significant potential to transform psychiatric care. Despite these advancements, the translation of AI systems into clinical practice remains fraught with challenges. This Perspective examines critical hurdles in psychiatric AI research, emphasizing limitations in research rigor, model reliability, interpretability, clinical utility, and ethical considerations. We argue that a human-assisted AI framework-incorporating incremental feedback, self-adaptation, and dynamic collaboration-can address biases, enhance transparency, and build trust in AI systems. Moreover, initiatives in clinical education, cultural adaptation, and data/software sharing are essential to fostering public engagement, data transparency, and research reproducibility. By focusing on these areas, we aim to bridge the gap between AI potential and its successful, ethical implementation in mental health care, guiding the development of trustworthy, effective, and culturally adaptive AI-powered psychiatric tools.

Altered Mental Status Secondary to Clonidine Addiction and Withdrawal: A Cautionary Tale: Erratum.

This case report highlights the first documented instance of anaphylaxis caused by Withania coagulans, a natural remedy widely used in traditional medicine. Given the popularity of W coagulans among Asian communities worldwide, the report’s findings carry essential global clinical relevance.

This paper describes a process for generating academic papers using large language models (LLMs) and demonstrates this process’s efficacy by producing hundreds of complete papers on stock return predictability, a topic well-suited for our illustration. After mining over 30,000 potential return predictors from accounting data, we generate template reports for 95 signals passing rigorous criteria from the Novy-Marx and Velikov (2024) Assaying Anomalies protocol. These templates detail signal performance predicting returns using a wide array of tests and benchmark performance against more than 200 documented anomalies. Finally, for each template we use state-of-the-art LLMs to generate multiple complete versions of academic papers with distinct theoretical justifications for the observed return predictability, incorporating citations to literature supporting their respective claims. This experiment illustrates the potential of artificial intelligence (AI) for enhancing financial research efficiency, but also serves as a cautionary tale, illustrating how it can be abused to industrialize hypothesizing after results are known (HARKing). ( JEL C12, C45, G12, G17)

Test-retest reliability of clinical supine-to-stand tests in patients with postural orthostatic tachycardia syndrome: A cautionary tale.

ABSTRACT This article explores how police actors perceive the probation service in the wake of its outsourcing and reunification during a decade of profound structural reform, offering a unique perspective on multi-agency collaboration within criminal justice. Drawing on interviews with senior leaders, frontline officers and staff immersed within partnership arrangements, the study examines how probation’s organisational legitimacy is evaluated from outside. Using the conceptual lens of organisational legitimacy, we reveal how legitimacy is experienced as transitional – shaped by professional encounters and institutional memory. Participants frequently described probation as a service in crisis, citing operational instability and diminished capacity as barriers to effective collaboration. Yet these critiques were tempered by reflections on probation’s enduring moral legitimacy, grounded in shared values and long-standing relationships. The failed Transforming Rehabilitation reforms of probation services emerged as a cautionary tale, sharpening police awareness of the fragility of interagency partnerships and fuelling anxieties about the marketisation of criminal justice. Despite concerns, many expressed cautious optimism about the reunification of probation services and reaffirmed their belief in public service collaboration as essential to public protection. This paper contributes to a more nuanced understanding of how legitimacy is co-constructed across organisational boundaries and how police perceptions illuminate the relational dynamics underpinning effective multi-agency work in criminal justice.

The 1990s pedicle screw litigation saga was a pivotal clash between medical innovation, regulatory oversight, and legal accountability. The controversy arose from the widespread use of pedicle screws, which became a standard practice despite lacking explicit Food and Drug Administration approval for spinal applications. This regulatory ambiguity was ignited by a 1993 ABC 20/20 segment that triggered an avalanche of mass tort litigation. This article dissects the landmark legal battle, analyzing the Food and Drug Administration's slow reclassification and the contrasting strategies of key industry players, AcroMed and Sofamor Danek. We evaluate the lasting impact on legal precedents, clinical practice around off-label use, and the regulatory pathways for new devices. This history offers a cautionary tale on the tension between legal accountability and innovation, with enduring relevance for today's debates on medical regulation and patient rights.

Cautionary Tale—The Details Are in the Data

This study discusses the economic threats facing Iraq because of the global shift towards a low-carbon economy. It focuses on the concept of "stranded assets"—oil resources or infrastructure that may lose their economic value before being fully depleted due to changes in climate policies, technology, or global demand. Oil constitutes more than 90% of Iraq's revenues, making the economy vulnerable to any decline in global oil demand. The study employs a theoretical and analytical approach, reviewing three potential climate scenarios and their projected impacts up to 2050. It indicates that the most severe scenario (a 1.5° trajectory) could lead to a collapse in oil revenues exceeding 80%, rendering a significant portion of Iraq's reserves unusable. The study recommends restructuring the Iraqi economy by diversifying income sources, investing in renewable energy, establishing a sovereign wealth fund to manage oil revenues, and restructuring oil contracts to align with the global shift. It also calls for the establishment of a national council for economic transformation. The study emphasizes that ignoring these transformations is a gamble with Iraq's future, and that successful models like Norway and Saudi Arabia should be studied as examples, while Nigeria serves as a cautionary tale about the failure of wealth management. This research constitutes a call for a radical rethinking of Iraq's development model to ensure the sustainability of its post-oil economy.

This article addresses the dynamics of climate and anthropogenic changes that coastal cities are facing, specifically in the east Mediterranean Basin. It explores the challenges by focusing on Lebanon’s densely urbanized coastal strip of the Greater Beirut Area (GBA). Despite Lebanon’s subscription to coastal protection laws and international protocols, instability, weak planning and its ineffective implementation, and real estate speculation have led to significant degradation of the coastline. Using a combination of spatio-temporal mapping (1985–2025) and a photographic documentation, the article identifies some implications of land reclamation, urban development, and infrastructural projects on the experience of being by the sea. Findings indicate that the land–sea interface is fragmented, natural resources are significantly depleted, the shoreline is mostly privatized by dominant development, and access to the coast is limited. The remaining natural and public spaces signal hope for recovery. Nonetheless, several initiatives by civic society, researchers, and NGOs highlight pathways for re-establishing human–nature coastal relations. Starting with the GBA, the article argues for an integrated approach in which diverse stakeholders join efforts to reinstate multispecies ecosystems and prioritize inclusive access to the sea. Lebanon’s small scale, geopolitical volatility, and context-sensitive interventions that are supported by trans-Mediterranean collaborations foreground the path to sustainable coastal futures. The GBA serves as both a cautionary tale and context of potential transformation, offering insights relevant to coastal planning across the Mediterranean Basin.