Background: Sexual dysfunction (SD) is common among childhood cancer survivors, affecting approximately 20% to 50% of patients. National guidelines recommend discussions about sexuality throughout cancer care, and prior work demonstrates patient interest in SD conversations. Despite its prevalence and importance, SD is widely underrecognized and undertreated, creating gaps in comprehensive whole-person care. Objective: Our research aims to collaborate with provider partners to co-design an SD screening intervention prototype for implementation in a clinical oncology setting. This study outlines the co-design process to serve as a case study, highlighting challenges and strategies to achieve a consensus-driven intervention and implementation plan. Methods: We engaged pediatric cancer providers in a series of co-design sessions at a National Cancer Institute–designated cancer center within an academic children’s hospital. For each co-design session, the research team created a template outlining considerations from formative work (eg, patient privacy) and key decisions to be made (eg, screening modality). Co-design session moderators facilitated discussion, guiding participants toward a consensus decision for each intervention component. A final process mapping session reviewed and outlined the entire SD prototype. We conducted a rapid qualitative analysis, compiling a templated summary synthesizing and organizing findings by discussion topic and decision point. Based on co-design discussions, the research team compiled a menu of options outlining key thematic findings, core screening intervention functions, and intervention form options to allow for future expansion and tailoring of the SD prototype. Results: Six provider participants, including attending physicians, advanced practice providers, and registered nurses representing multiple oncology subspecialty groups, engaged in a series of 5 co-design sessions. Participants assessed specific intervention component options, reached consensus on component decisions, and determined an intervention and implementation workflow for each. Throughout, providers needed to ensure workflows aligned with patient and provider priorities from foundational work and to ensure design feasibility, acceptability, and appropriateness. Key intervention and implementation decisions included target population, screening frequency, screening modality and workflow, management of screening results, clinic reminders and cues, and provider education and training. With several decisions being interconnected, there was often a cascade effect in which one decision influenced or limited future decisions and, in some cases, required revisiting prior decisions to ensure cohesive alignment into a single prototype. Co-design session moderators used several strategies (eg, reminders, redirection, providing information on feasibility, etc) to facilitate decision-making and implementation strategy selection. Conclusions: Engaging provider partners in co-design sessions allowed for the collaborative development of a preliminary SD screening approach for adolescents and young adults with and surviving cancer. The dynamic co-design process and moderator strategies ensured that intervention and implementation decisions reflected the patient and provider priorities identified in prior work. Future work will test, adapt, and refine the prototype SD screening approach prior to effectiveness testing and eventual dissemination.
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Smart contact lens monitors eye pressure and delivers glaucoma drugs in early tests
Glaucoma is the second-leading cause of blindness, and a silent one at that. It’s estimated that half of the patients who develop it are unaware of their condition, as they lose peripheral vision only when the disease is more advanced, and the damage is irreversible.
There isn’t a cure, and while medication can control hypertension in the eye to slow or stop further damage to the optical nerve, it has shortcomings.
New Single-Cell Platform Expands View of Immune Function in Cancer Research
A newly developed single-cell sequencing approach, dubbed CIPHER-Seq, is designed to capture a more complete picture of immune cell behavior—an advance that could sharpen how researchers study responses to immunotherapy and mechanisms of resistance. The technique is described in a paper in Nature Scientific Reports.
Co-senior investigator Justin Taylor, MD, from the Sylvester Comprehensive Cancer Center at the University of Miami described the method as an effort to bridge a longstanding gap in single-cell analysis: the inability to simultaneously measure intracellular immune activity alongside gene expression and surface markers in the same cells.
“The main difference…is we’re trying to also look at the intracellular proteins,” Taylor said. “A lot of current approaches can measure proteins on the surface of the cell and RNA, but they can’t go inside the cell without disrupting the RNA.”
That limitation has been particularly consequential in immuno-oncology, where understanding immune cell function—especially cytokine production—is critical. Cytokines, which are typically secreted outside the cell, are central to defining T cell activation states and functional subtypes, but are difficult to capture alongside RNA using standard workflows.
CIPHER-Seq, or Cytokine Intracellular Protein High‑throughput Expression with RNA sequencing, addresses this by introducing a carefully optimized permeabilization step that allows antibodies to enter the cell without degrading RNA. At the same time, the protocol uses the Golgi stop reagent to trap cytokines inside cells, enabling their measurement.
“So instead of just what type of cell,” Taylor explained, “you can ask how they’re activated—are they secreting cytokines?”
Five layers of data in a single assay
The platform integrates five distinct data layers: cell surface markers, RNA sequencing, intracellular proteins, cytokines, and sample multiplexing via hashing antibodies. This multiomic approach builds on earlier technologies such as CITE-seq but extends them into intracellular territory.
Technically, the method relies on commercially available reagents and widely used sequencing platforms. Antibodies from multiple vendors can be used, and no proprietary components are required—an intentional design choice to encourage adoption.
“We’re not trying to sell it,” Taylor said. “There’s nothing proprietary about the protocol…you can buy all the reagents separately. It’s really about how we put them together and optimize the timing.”
Timing, in fact, proved critical during development. Excessive permeabilization can degrade RNA or induce cellular stress, while insufficient exposure prevents antibodies from entering the cell. The team iteratively optimized these conditions to preserve both RNA integrity and intracellular protein detection.
Reducing technical artifacts
Beyond enabling new measurements, CIPHER-Seq may also improve data quality by reducing technical artifacts. In benchmarking experiments using identical donor samples, the researchers observed that standard single-cell workflows induced higher levels of stress-related gene expression—signals that could be mistakenly attributed to biological processes.
“When we compared CIPHER-Seq to other methods…we found less stress,” Taylor said. “The same sample, same donor—just different processing. The other assays showed higher mitochondrial and metabolic stress markers.”
This finding has particular relevance for cancer studies, where cellular stress is often interpreted as a hallmark of disease or treatment response. If assay-induced stress is not accounted for, it could confound conclusions about tumor biology or immune activation.
“If you’re doing research on cancer patients getting immunotherapy, and one of your readouts is stress on the T cells,” Taylor added, “you might attribute that to the cancer—but maybe that’s from your technique.”
Applications in immuno-oncology
The primary envisioned applications for CIPHER-Seq lie in immuno-oncology, including studies of checkpoint inhibitors, CAR T-cell therapies, and bispecific antibodies. By enabling detailed profiling of T-cell subsets based on cytokine production, the method could help clarify how immune cells behave in different therapeutic contexts.
One potential use case, not yet demonstrated in the current study, would involve analyzing peripheral blood samples from patients before and after immunotherapy to compare immune activation states between responders and non-responders.
“That would be kind of the ideal use case,” Taylor said. “You could compare T cells in responders versus non-responders, or look at patients who develop resistance.”
Such analyses could ultimately help identify biomarkers of response or resistance, informing the development of targeted interventions.
“The whole point is to try to improve outcomes for patients,” he said. “If you can identify a resistant T cell marker, then you might develop a treatment targeting that.”
Why single-cell resolution matters
A key rationale for the approach is the need to detect rare immune cell populations that may drive treatment outcomes. Bulk sequencing methods average signals across many cells, potentially masking critical subsets.
“When you do bulk sequencing, it’s a mixture of all the cells,” Taylor noted. “You might miss rare subsets—and for immunotherapy, those rare cells might be very important.”
Path to clinical translation
While CIPHER-Seq is currently positioned as a research tool, Taylor sees a plausible path toward clinical application, drawing parallels to earlier sequencing technologies that were once considered impractical.
“When I started, people said whole genome sequencing would never work in patients,” he said. “And the same for RNA sequencing—that it was too unstable. But now both are routine.”
He anticipates similar skepticism around single-cell approaches but believes those barriers may also fall.
“Right now, people might say single-cell sequencing is too expensive or too technical,” Taylor said. “But I think that will change.”
For now, the team’s priority is encouraging adoption within the research community. By publishing the full protocol and relying on accessible reagents, they hope other groups will apply, refine, and extend the method.
“Our hope is that people start using it,” Taylor said. “Maybe they optimize it further for their own applications.”
The post New Single-Cell Platform Expands View of Immune Function in Cancer Research appeared first on Inside Precision Medicine.
STAT+: Steve Ubl to step down as CEO of PhRMA
WASHINGTON — Steve Ubl is stepping down as CEO of the Pharmaceutical Research and Manufacturers of America after more than a decade leading the brand drug industry’s main trade group.
Ubl plans to depart by the end of the year and will remain in his position until a new leader is found, according to a PhRMA statement.
Ubl led the organization during tumultuous times that included the Covid-19 pandemic and aggressive political attacks on drug prices. Democrats passed a law directing Medicare to negotiate drug prices, and the Trump administration struck voluntary deals with individual drugmakers aimed at lowering U.S. prices to levels in other high-income countries.
This Week in The Journal
Early Development of Direction Selectivity in the Higher Visual Cortex
A fundamental aspect of visual motion processing is the computation of motion direction. In ferrets, as in primates, selectivity for motion direction is found both in early cortical stages like the primary visual cortex (V1) and in higher visual areas like the middle temporal area in primates and the posteromedial lateral suprasylvian (PMLS) area in ferrets. Little is known about how this critical tuning function develops in higher visual cortex. Here, by studying the development of the ferret’s motion pathway, we first reveal the surprising finding that direction selectivity (DS) develops earlier in PMLS than in V1, contrary to the areas’ hierarchical positions. Our data, collected in animals of either sex, furthermore show that while DS is sensitive to visual experience in both areas, the sensitivity profile differs between them: presentation of drifting gratings, containing the full complement of spatial and temporal cues generated by visual motion, can promote DS development in V1 and PMLS. In contrast, flashing stationary stimuli, which lack the spatial displacement of moving stimuli and only contain temporal changes, induce DS only in PMLS, not V1. Collectively our findings reveal significant deviations in PMLS development from that in V1, which will be important to account for in models of motion pathway development and of the developmental disorders that affect this pathway. The complex pattern of relative PMLS and V1 development also highlights the need to address interactions between areas in developmental research.
The Parafascicular Role in Updating Action from a Spatial to a Visual Strategy Is Driven by Its Glutamatergic Mesencephalic Locomotor Region Inputs
The ability to update actions depends on the thalamus’s parafascicular nucleus (PF); however, which PF’s inputs control this function is unknown. Here, using fiber photometry, retrograde labeling, ex vivo electrophysiology, and optogenetic manipulations, we identify the contribution of the PF and its glutamatergic inputs to the update from a spatial to a visually guided strategy in a set-shifting task conducted in mice (of either sex). Our results show the following: (1) GCaMP signals from the PF recorded along the update from a spatial to a visual strategy correlate with the probability of selecting the correct action based on a light stimulus. (2) Optogenetic inhibition of the PF during this update decreases the probability of selecting the correct action. (3) The mesencephalic locomotor region (MLR) was found to have the highest probability of synaptic connections with the PF. (4) GCaMP recordings from the MLR->PF input support it as a main driver in allowing the PF update function. (5) Inhibition of the MLR->PF connection decreases the probability of updating the contingency. These findings identify the inputs from the MLR as a crucial driver of the PF’s role in controlling the update of actions.
Corticotropin-Releasing Factor and Somatostatin Neurons in the Central Amygdala Mediate Dynamic Defensive Behaviors during Fear Extinction
Traumatic experiences can result in heightened fear responses to trauma-associated stimuli. These symptoms can be difficult to extinguish, so identifying neuronal targets for facilitating fear extinction is critical. Many studies investigating fear learning in mice measure conditioned fear via freezing, but other defensive behaviors, such as flight, can also be present during conditioning. The central amygdala (CEA) mediates conditioned freezing and flight responses via corticotropin-releasing factor-positive (CRF+) and somatostatin-positive (SOM+) neuron populations. However, it is unknown how these populations regulate changes in freezing and flight responses as fear extinction is learned. Thus, we investigated the roles of CRF+ and SOM+ CEA neurons in modulating defensive behaviors during extinction. To elicit dynamic defensive responses in male and female mice, we used a modified pavlovian conditioned flight paradigm that paired an aversive footshock with a serial compound stimulus (SCS) consisting of tone followed by white noise (WN), resulting in freezing during the tone that rapidly transitioned into flight (escape jumping and darting) during WN. We used optogenetics in CRF-Cre and SOM-Cre mice to selectively excite and inhibit CRF+ and SOM+ CEA populations during WN presentation within extinction. Within early extinction, CRF+ inhibition reduced WN-evoked jumping and led to subsequent context-specific reduction in tone-evoked freezing. During extinction, SOM+ excitation replaced early WN-evoked flight with freezing, and both SOM+ excitation and inhibition reduced WN-evoked darting. Collectively, these data demonstrate modulation of jumping and darting behaviors within extinction via CRF+ and SOM+ CEA activity. These findings suggest mechanisms of attenuating multiple defensive behaviors during extinction.
MTCL2 Is Essential for the Bipolar-to-Multipolar Transition in the Dendrite Extension of Cerebellar Granule Neurons
The dynamic regulation of neuronal polarity is essential for the formation of neural networks during brain development. Primary cultures of rodent neurons recapitulate several aspects of this polarity regulation, providing valuable insights into the molecular mechanisms underlying axon specification, dendrite formation, and neuronal migration. However, the process by which the preexisting bipolarity of migrating neurons is disrupted to form multipolar dendrites remains to be elucidated. In this study, we demonstrate that MTCL2, a microtubule-crosslinking protein associated with the Golgi apparatus, plays a crucial role in this type of polarity transformation exhibited by cerebellar granule neurons (CGNs) in mice of either sex. MTCL2 is highly expressed in CGNs and gradually accumulates in dendrites as the cells develop polarity. MTCL2 knockdown inhibited the bipolar-to-multipolar transition of dendrite extension observed in their differentiation in vitro as well as in vivo. During this transformation, the Golgi apparatus shifts from the base of the preexisting bipolar neurites to the lateral or apical side of the nucleus in the cell body. There, it forms a close association with the microtubule cage that wraps around the nucleus. The resulting upward extension of the Golgi apparatus is tightly coupled with the randomization of its position in the x–y plane. Knockdown and rescue experiments demonstrated MTCL2 promotes these changes in the Golgi position in a microtubule- and Golgi-binding activity-dependent manner. These results suggest that MTCL2 promotes the development of multipolar short dendrites by sequestering the Golgi apparatus from the base of the preexisting neurite into the microtubule cage.
Base Editing Shows Early Promise for Treating Beta Thalassemia
The Chinese biotech CorrectSequence Therapeutics, also known as Correctseq, reports good results from a Phase I study of its technology involving editing a person’s hematopoietic stem cells to treat beta thalassemia.
The trial, published in Nature, included five patients with transfusion dependent beta thalassemia who were able to stop red blood cell transfusions, the standard treatment for the condition, after receiving the base-edited treatment CS-101. The participants continued to have good levels of hemoglobin with no serious side effects during follow-up.
Beta thalassemia is a rare inherited condition affecting around one in 100,000 people in the U.S. Mutations in the beta‑globin gene HBB reduce or stop production of the beta chains of hemoglobin, leading to chronic anemia that varies in its severity.
There are already several therapies on the market for beta thalassemia. The most common treatment is still regular blood transfusions to treat the anemia, but recently the genetic therapies Zynteglo, a lentiviral gene therapy developed by Bluebird Bio, and Casgevy, a CRISPR edited therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics were approved by the FDA.
Casgevy works by boosting fetal hemoglobin levels to treat the anemia seen in thalassemia patients. It uses CRISPR–Cas9 to cut both strands of DNA at the BCL11A enhancer site, which relies on error‑prone repair and can theoretically generate insertions, deletions, and larger rearrangements.
Correctseq is also aiming to raise fetal hemoglobin levels with CS-101, targeting the same site, but is only changing individual bases without making a full cut, which should reduce risks linked to double‑strand breaks, such as large deletions or chromosomal translocations.
In this study, CS-101 was given to five patients with beta thalassemia, previously treated with blood transfusions. The process involves extracting their stem cells, reactivating fetal hemoglobin production using base editing, giving the patients chemotherapy to clear existing stem cells and make way for the newly edited population, and finally injecting the patients with the edited stem cells.
All five patients were able to stop red blood cell transfusions and had maintained good levels of hemoglobin at three months. These levels stayed at a similar level through a median follow up period of 23 months. No deaths or reported cancers due to the chemotherapy treatment were observed and the safety profile so far is acceptable.
Although these results are promising, this trial is just a small initial study and further work is needed to confirm safety and efficacy of CS-101.“The planned Phase II/III trial will be crucial for evaluating a larger and more genetically diverse patient population across multiple centers,” write the authors.
“Extended follow-up will be required to enable comprehensive analyses of chimerism and clonality, which will facilitate more definitive assessment of long-term safety, engraftment dynamics and clinical benefit.”
One Correctseq’s main competitors is U.S.-based Beam Therapeutics, which is developing a similar base edited treatment. Beam is behind Correctseq in developing its edited therapy for beta thalassemia, but ahead with its therapy for sickle cell disease, something Correctseq are also targeting using a similar pathway.
The Chinese biotech industry is currently on an upward trajectory. Correctseq is one of many Chinese biotech companies currently working to produce competitors for gene therapies like Casgevy and Zynteglo at a more affordable price than those seen in the U.S.
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