Ultrathin All-Solid-State MoS2-Based Electrolyte Gated Synaptic Transistor with Tunable Organic-Inorganic Hybrid Film.

Electrolyte-gated synaptic transistors (EGSTs) have attracted considerable attention as synaptic devices owing to their adjustable conductance, low power consumption, and multi-state storage capabilities. To demonstrate high-density EGST arrays, 2D materials are recommended owing to their excellent electrical properties and ultrathin profile. However, widespread implementation of 2D-based EGSTs has challenges in achieving large-area channel growth and finding compatible nanoscale solid electrolytes. This study demonstrates large-scale process-compatible, all-solid-state EGSTs utilizing molybdenum disulfide (MoS2) channels grown through chemical vapor deposition (CVD) and sub-30 nm organic-inorganic hybrid electrolyte polymers synthesized via initiated chemical vapor deposition (iCVD). The iCVD technique enables precise modulation of the hydroxyl group density in the hybrid matrix, allowing the modulation of proton conduction, resulting in adjustable synaptic performance. By leveraging the tunable iCVD-based hybrid electrolyte, the fabricated EGSTs achieve remarkable attributes: a wide on/off ratio of 109, state retention exceeding 103, and linear conductance updates. Additionally, the device exhibits endurance surpassing 5 × 104 cycles, while maintaining a low energy consumption of 200 fJ/spike. To evaluate the practicality of these EGSTs, a subset of devices is employed in system-level simulations of MNIST handwritten digit recognition, yielding a recognition rate of 93.2%.

Activation of hypoactive parvalbumin-positive fast-spiking interneuron restores dentate inhibition to prevent epileptiform activity in the mouse intrahippocampal kainate model of temporal lobe epilepsy.

Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus. The development of compensatory modifications related to PV+ interneuron circuits in the months following status epilepticus is unknown, although reduced dentate GABAergic inhibition persists long after status epilepticus. We employed PV immunostaining and whole-cell patch-clamp recordings from dentate PV+ interneurons and DGCs in slices from male and female sham controls and intrahippocampal kainate (IHK) treated mice that developed spontaneous seizures months after status epilepticus to study epilepsy-associated changes in dentate PV+ interneuron circuits. We found that the number of dentate PV+ cells was reduced in IHK treated mice. Electrical recordings showed that: 1) Action potential firing rates of dentate PV+ interneurons were reduced in IHK treated mice up to four months after status epilepticus; 2) Spontaneous inhibitory postsynaptic currents (sIPSCs) in DGCs exhibited reduced frequency but increased amplitude in IHK treated mice; and 3) The amplitude of evoked IPSCs in DGCs by optogenetic activation of dentate PV+ cells was upregulated without changes in short-term plasticity. Video-EEG recordings revealed that IHK treated mice showed spontaneous epileptiform activity in the dentate gyrus and that chemogenetic activation of PV+ interneurons abolished the epileptiform activity. Our results suggest not only that the compensatory changes in PV+ interneuron circuits develop after IHK treatment, but also that increased PV+ interneuron mediated inhibition in the dentate gyrus may compensate for cell loss and reduced intrinsic excitability of dentate PV+ interneurons to stop seizures in temporal lobe epilepsy. Highlights: Reduced number of dentate PV+ interneurons in TLE micePersistently reduced action potential firing rates of dentate PV+ interneurons in TLE miceEnhanced amplitude but decreased frequency of spontaneous IPSCs in the dentate gyrus in TLE miceIncreased amplitude of evoked IPSCs mediated by dentate PV+ interneurons in TLE miceChemogenetic activation of PV+ interneurons prevents epileptiform activity in TLE mice.

Cervical sagittal parameters in degenerative cervical spondylolisthesis versus degenerative cervical kyphosis with myeloradiculopathy treated by anterior cervical discectomy and fusion.

Background: Adult spinal deformity, especially sagittal imbalance, is affecting health-related quality-of-life (HRQOL) scores. There is a lack of emphasis in the comparison of cervical sagittal parameters in patients with degenerative cervical spondylolisthesis and degenerative cervical kyphosis. The aim of study is to determine the preoperative and postoperative cervical sagittal parameters in myeloradiculopathic patients with degenerative cervical spondylolisthesis and degenerative cervical kyphosis treated by anterior cervical discectomy and fusion (ACDF). Methods: A retrospective medical records and radiographic study of 30 adult patients were reviewed. Fifteen patients with degenerative cervical spondylolisthesis and 15 patients with degenerative cervical kyphosis have been performed ACDF from 2010-2020. We measured the preoperative and postoperative cervical sagittal parameters: C0-C2 angle, C1-C2 angle, C2-C7 angle, C2-C7 sagittal vertical axis (SVA), T1 slope, neck tilt angle and thoracic inlet angle. Minimum follow-up period was at least 2 years. Results: Patients in degenerative cervical kyphosis group have C2-C7 angle less than degenerative cervical spondylolisthesis group (-14.88±7.32 vs. 9.60±13.60), leading to increase the mismatch between T1 slope and C2-C7 angle in kyphotic group and hyperlordosis of C0-C2 angle and C1-C2 angle (31.13±7.68, 37.88±5.08) compare with spondylolisthesis group (13±10.20, 24.60±10.70). Whereas patients with degenerative cervical spondylolisthesis have C2-C7 SVA (33.22±13.92) more than kyphosis group (13.70±13.60). After surgery, there is significant increase of the C2-C7 angle in the kyphosis group compare before and after surgery (-14.88±7.32 vs. 4.10±11.80). While the spondylolisthesis group has no significantly different parameters compare to before surgery. However, the postoperative cervical sagittal parameters of all patients are within the normal thresholds (T1-Slope minus C2-C7 lordosis <15° and C2-C7 SVA <40 mm). Conclusions: The study demonstrates the difference of sagittal parameters between degenerative cervical spondylolisthesis and kyphosis before and after surgery. ACDF not only provides neural decompressive procedure, but also corrects the regional cervical sagittal parameters.

Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin.

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.

Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin.

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.

Safety and efficacy of pelvic arterial embolization for primary postpartum hemorrhage in hemodynamically stable and hemodynamically unstable patients: Is it "time" for a paradigm change?

BACKGROUND: Pelvic artery embolization (PAE) is an effective and safe technique for treating postpartum hemorrhage (PPH) with hemodynamic stability. However, its use in hemodynamically unstable patients remains controversial. PURPOSE: To determine the safety and efficacy of pelvic arterial embolization (PAE) according to the hemodynamic state of primary postpartum hemorrhage (PPH) patients. METHODS: This cohort study was conducted retrospectively, using data from January 2004 to December 2021, in a resource-rich setting at a tertiary Level 1 trauma academic center. A total of 437 patients were diagnosed with PPH during the study period. Of these 437 patients, 161 with primary PPH who underwent PAE were enrolled in the study. The outcomes assessed included the clinical success rate, mortality, the overall success rate, predictive factors for failed PAE, and time-dependent changes in hemodynamic parameters, such as systolic blood pressure (SBP), heart rate (HR), and shock index (SI). Propensity score (PS) matching analysis was performed to assess the influence of specific variables or conditions on the outcomes. RESULTS: Of the 161 patients who underwent PAE for primary PPH (mean age, 32.9 ± 4.3 [SD]), 85 were retrospectively categorized as having hemodynamic stability (mean age, 32.6 ± 4.1 [SD]), while 76 were categorized as having hemodynamic instability (mean age, 33.3 ± 4.4 [SD]). This study showed PAE for primary PPH had a success rate of 91.9 %, with no significant difference in mortality rates between the groups. The clinical success rate was 98.8 % for patients with hemodynamic stability and 84.2 % for those with hemodynamic instability (p < .001). The overall success rate was 98.8 % for hemodynamic stability and 89.5 % for hemodynamic instability (p = .014). After propensity score matching, the clinical success rate was higher in hemodynamically stable patients than in unstable ones (100 % vs. 86.3 %, p = .013). However, there was no significant difference in the overall success rate (100 % vs. 90.2 %, p = .056). Among the PS-matched population, predictive factors for the failed PAE in primary PPH were hemodynamic instability (adjusted odds ratio [aOR] 21.22, 95 % CI 1.27-355.76; p = .034) and emergency Cesarean delivery with accompanying hemorrhag (aOR 54.00, 95 % CI 11.93-244.56; p = .008). In three groups within a PS-matched population - hemodynamically stable, unstable with successful outcomes, and unstable with unsuccessful outcomes, a generalized linear mixed model (GLMM) analysis for time-dependent changes in hemodynamic parameters revealed a statistically significant difference in SBP, HR, and SI at various time points. CONCLUSION: Pelvic arterial embolization of primary postpartum bleeding in hemodynamic instability has been identified as an alternative, safe, and effective life-saving procedure for multidisciplinary treatment in resource-rich environments even after the baseline characteristics are balanced by the PS matching, suggesting it is a primary care option.

High-frequency ultrasound-assisted perforator mapping enhances efficiency in microsurgical reconstruction using thin ALT and SCIP flaps.

BACKGROUND: With the growing demand for the use of thin perforator flaps, obtaining knowledge on the superficial anatomy of perforators is imperative for stable flap elevation. Conventional modalities for perforator mapping fall short in providing such information. High-frequency ultrasound (HFUS), known for visualizing the superficially located anatomic structures, may potentially fill this void. This study aimed to evaluate the effectiveness of HFUS in the outcome of anterolateral thigh (ALT) and superficial circumflex iliac artery perforator (SCIP) flap-based reconstructions. METHODS: Consecutive patients who underwent free ALT or SCIP flap-based reconstruction from January 2021 to November 2022 were retrospectively reviewed. Perforator mapping was conducted using a handheld Doppler during the first year, while HFUS was used in the latter part. The two techniques were compared in terms of flap harvesting time and perfusion-related complication rates while considering the flap elevation plane. RESULTS: In total, 123 cases were analyzed, including 82 ALT flaps (41 in each group) and 41 SCIP flaps (16 in the Doppler and 25 in the HFUS group). The time required for flap elevation exhibited a tendency to decrease in the HFUS group, with a significant difference observed in cases involving thin flap elevation (super-thin ALT flaps and pure-skin-perforator SCIP flaps). Compared with the Doppler group, the HFUS group demonstrated significantly lower rates of PRCs, particularly partial flap necrosis. This difference remained significant in multivariable analyses. CONCLUSION: Our results suggest that HFUS might be an appealing modality for perforator mapping in cases requiring thin ALT and SCIP flap.

Preparation of human astrocytes with potent therapeutic functions from human pluripotent stem cells using ventral midbrain patterning.

INTRODUCTION: Astrocytes are glial-type cells that protect neurons from toxic insults and support neuronal functions and metabolism in a healthy brain. Leveraging these physiological functions, transplantation of astrocytes or their derivatives has emerged as a potential therapeutic approach for neurodegenerative disorders. METHODS: To substantiate the clinical application of astrocyte-based therapy, we aimed to prepare human astrocytes with potent therapeutic capacities from human pluripotent stem cells (hPSCs). To that end, we used ventral midbrain patterning during the differentiation of hPSCs into astrocytes, based on the roles of midbrain-specific factors in potentiating glial neurotrophic/anti-inflammatory activity. To assess the therapeutic effects of human midbrain-type astrocytes, we transplanted them into mouse models of Parkinson's disease (PD) and Alzheimer's disease (AD). RESULTS: Through a comprehensive series of in-vitro and in-vivo experiments, we were able to establish that the midbrain-type astrocytes exhibited the abilities to effectively combat oxidative stress, counter excitotoxic glutamate, and manage pathological protein aggregates. Our strategy for preparing midbrain-type astrocytes yielded promising results, demonstrating the strong therapeutic potential of these cells in various neurotoxic contexts. Particularly noteworthy is their efficacy in PD and AD-specific proteopathic conditions, in which the midbrain-type astrocytes outperformed forebrain-type astrocytes derived by the same organoid-based method. CONCLUSION: The enhanced functions of the midbrain-type astrocytes extended to their ability to release signaling molecules that inhibited neuronal deterioration and senescence while steering microglial cells away from a pro-inflammatory state. This success was evident in both in-vitro studies using human cells and in-vivo experiments conducted in mouse models of PD and AD. In the end, our human midbrain-type astrocytes demonstrated remarkable effectiveness in alleviating neurodegeneration, neuroinflammation, and the pathologies associated with the accumulation of α-synuclein and Amyloid ß proteins.

Bounded contribution of human early visual cortex to the topographic anisotropy in spatial extent perception.

To interact successfully with objects, it is crucial to accurately perceive their spatial extent, an enclosed region they occupy in space. Although the topographic representation of space in the early visual cortex (EVC) has been favored as a neural correlate of spatial extent perception, its exact nature and contribution to perception remain unclear. Here, we inspect the topographic representations of human individuals' EVC and perception in terms of how much their anisotropy is influenced by the orientation (co-axiality) and radial position (radiality) of stimuli. We report that while the anisotropy is influenced by both factors, its direction is primarily determined by radiality in EVC but by co-axiality in perception. Despite this mismatch, the individual differences in both radial and co-axial anisotropy are substantially shared between EVC and perception. Our findings suggest that spatial extent perception builds on EVC's spatial representation but requires an additional mechanism to transform its topographic bias.

Association of cranial base suture/synchondrosis fusion with severity of increased intracranial pressure in Crouzon syndrome.

This study investigated how the fusion states of the cranial base is related to the degree of increased intracranial pressure (ICP) in patients with Crouzon syndrome. This retrospective cohort study enrolled patients who were diagnosed with Crouzon syndrome between May 2007 and April 2022. We categorized the patients into three groups: A, B, and C, according to the severity of increased ICP and the number of cranial vault remodeling procedures for corrective operation. The preoperative fusion states of the cranial base sutures/synchondroses were examined using facial bone computed tomography and compared between groups. Overall, 22 patients were included in Groups A, B, and C, including 8, 7, and 7 patients, respectively. The preoperative average grades of the total cranial base suture/synchondrosis fusion appeared to significantly increase with severity, except for the frontoethmoidal suture, which showed the opposite tendency. In the subgroup analysis, frontosphenoidal, sphenoparietal, sphenosquamosal, parietomastoid, and occipitomastoid suture and petro-occipital synchondrosis were associated with earlier fusion in the more severe group. Premature closure of the cranial base sutures/synchodroses seems to be associated with increased ICP severity in patients with Crouzon syndrome. Precise evaluation of minor sutures/synchondroses at the first visit might help build subsequent operative plans and predict disease prognosis.

Enzymatic Activity and Amino Acids Production of Predominant Fungi from Traditional Meju during Soybean Fermentation.

To investigate the effect of the predominant fungal species from Korean traditional meju and doenjang on soybean fermentation, the enzymatic activity and amino acid production of twenty-two fungal strains were assessed through solid- and liquid-state soybean fermentation. Enzymatic activity analyses of solid-state fermented soybeans revealed different enzyme activities involving protease, leucine aminopeptidase (LAP), carboxypeptidase (CaP), glutaminase, γ-glutamyl transferase (GGT), and amylase, depending on the fungal species. These enzymatic activities significantly affected the amino acid profile throughout liquid-state fermentation. Strains belonging to Mucoromycota, including Lichtheimia, Mucor, Rhizomucor, and Rhizopus, produced smaller amounts of total amino acids and umami-producing amino acids, such as glutamic acid and aspartic acid, than strains belonging to Aspergillus subgenus circumdati. The genera Penicillium and Scopulariopsis produced large amounts of total amino acids and glutamic acid, suggesting that these genera play an essential role in producing umami and kokumi tastes in fermented soybean products. Strains belonging to Aspergillus subgenus circumdati, including A. oryzae, showed the highest amino acid content, including glutamic acid, suggesting the potential benefits of A. oryzae as a starter for soybean fermentation. This study showed the potential of traditional meju strains as starters for soybean fermentation. However, further analysis of processes such as the production of G-peptide for kokumi taste and volatile compounds for flavor and safety is needed.

Effects of repetitive transcranial magnetic stimulation on improving cerebral blood flow in patients with middle cerebral artery steno-occlusion.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been reported to induce neurogenesis and angiogenesis. As increased neural activity can induce a hemodynamic response, we investigated the effect of rTMS on perfusion in patients with middle cerebral artery steno-occlusion. METHODS: This was a prospective, randomized, open-label, blinded end-point, pilot study. Patients were divided into two groups (rTMS intervention and non-intervention) which were both administered antiplatelet drugs to treat vascular steno-occlusion. In the intervention group, additional rTMS was performed on the area with stenosis and obstruction. Perfusion rates were compared using single-photon emission computed tomography / computed tomography (SPECT/CT). RESULTS: From June 2020 to May 2022, 16 patients were subjected to 1:1 randomization. Using the standardized uptake value ratio (SUVr) to quantify perfusion in the affected brain region, the corresponding SPECT/CT values before and after rTMS were obtained. Imaging analysis was compared between eight and seven patients in the rTMS and control groups, respectively. Based on the comparison between the target and ipsilateral cerebellum SUVmeans, four patients had a ≥ 20% increase in SUVr in the rTMS group and none in the control group. Changes in SUVr were significantly different between the initial and follow-up SPECT/CT in the rTMS group (p = 0.033); no significant difference was observed in the control group (p = 0.481). CONCLUSION: We observed a significant improvement in perfusion in the stimulation group in a perfusion test performed between 6 and 12 months after rTMS stimulation in stroke patients with steno-occlusion of the middle cerebral artery.

Predicting Mortality Following Odontoid Fracture Fixation in Elderly Patients: CAADS-16 Score.

STUDY DESIGN: Retrospective Review of a National Database. INTRODUCTION: By utilizing a national database, this study aims to quantify the predictors of 30-day mortality after odontoid fixation and guide appropriate management for patients in whom the choice between operative and non-operative management is unclear. METHODS: The American College of Surgeons National Surgical Quality Improvement Database was queried using Current Procedural Terminology (CPT) codes and International Classification of Disease (ICD) codes to identify patients 60 or older who underwent surgical fixation of an odontoid fracture from 2005 to 2020. Risk factors for mortality significant in univariate and subsequent multivariate analysis were used to develop a scoring system to predict post-operative mortality. RESULTS: 608 patients were identified. Patients were split into a non-mortality 30 days post-op group, and into a mortality 30 days post-op group. The following risk factors were included in the scoring system: functional dependency, disseminated cancer, albumin less than 3.5, WBC count greater than 16 k, anterior surgical approach, and pre-op SIRS. Using a cutoff value of 2, the CAAD-16 score had a sensitivity and specificity of 82% and 81%, respectively. The ASA score, cutoff at 4, showed a sensitivity and specificity of 64% and 75% respectively. CONCLUSIONS: This sample of 294 patients represents one of the largest samples of odontoid fracture fixation patients available in the literature and comes from a nationally representative database. We structure relevant risk factors into the CAADS-16 score, which has the potential to be a clinically relevant tool to prevent short-term postoperative mortality.

Xerogel-Derived Manganese Oxide/N-Doped Carbon as a Non-Precious Metal-Based Oxygen Reduction Reaction Catalyst in Microbial Fuel Cells for Energy Conversion Applications.

Current study provides a novel strategy to synthesize the nano-sized MnO nanoparticles from the quick, ascendable, sol-gel synthesis strategy. The MnO nanoparticles are supported on nitrogen-doped carbon derived from the cheap sustainable source. The resulting MnO/N-doped carbon catalysts developed in this study are systematically evaluated via several physicochemical and electrochemical characterizations. The physicochemical characterizations confirms that the crystalline MnO nanoparticles are successfully synthesized and are supported on N-doped carbons, ascertained from the X-ray diffraction and transmission electron microscopic studies. In addition, the developed MnO/N-doped carbon catalyst was also found to have adequate surface area and porosity, similar to the traditional Pt/C catalyst. Detailed investigations on the effect of the nitrogen precursor, heat treatment temperature, and N-doped carbon support on the ORR activity is established in 0.1 M of HClO4. It was found that the MnO/N-doped carbon catalysts showed enhanced ORR activity with a half-wave potential of 0.69 V vs. RHE, with nearly four electron transfers and excellent stability with just a loss of 10 mV after 20,000 potential cycles. When analyzed as an ORR catalyst in dual-chamber microbial fuel cells (DCMFC) with Nafion 117 membrane as the electrolyte, the MnO/N-doped carbon catalyst exhibited a volumetric power density of ~45 mW m2 and a 60% degradation of organic matter in 30 days of continuous operation.

Observation of aligned dipoles and angular chromism of exciplexes in organic molecular heterostructures.

The dipole characteristics of Frenkel excitons and charge-transfer excitons between donor and acceptor molecules in organic heterostructures such as exciplexes are important in organic photonics and optoelectronics. For the bilayer of the organic donor 4,4',4''-tris[(3-methylphenyl)phenylamino]triphenylamine and acceptor 2,4,6-tris(biphenyl-3-yl)-1,3,5-triazine molecules, the exciplexes form aligned dipoles perpendicular to the Frenkel excitons, as observed in back focal plane photoluminescence images. The angular chromism of exciplexes observed in the 100 meV range indicates possible delocalization and angle-sensing photonic applications. The blue shift of the peak position and increase in the linewidth of photoluminescene spectra with increasing excitation power are caused by the repulsive aligned exciplex dipole moments with a long lifetime (4.65 µs). Electroluminescence spectra of the exciplex from organic light-emitting diodes using the bilayer are blue-shifted with increasing bias, suggesting unidirectional alignment of the exciplex dipole moments. The observation of exciplex dipole moment alignments across molecular interfaces can facilitate the controlled coupling of exciton species and increase efficiency of organic light-emitting diodes.

Corrective feedback guides human perceptual decision-making by informing about the world state rather than rewarding its choice.

Corrective feedback received on perceptual decisions is crucial for adjusting decision-making strategies to improve future choices. However, its complex interaction with other decision components, such as previous stimuli and choices, challenges a principled account of how it shapes subsequent decisions. One popular approach, based on animal behavior and extended to human perceptual decision-making, employs "reinforcement learning," a principle proven successful in reward-based decision-making. The core idea behind this approach is that decision-makers, although engaged in a perceptual task, treat corrective feedback as rewards from which they learn choice values. Here, we explore an alternative idea, which is that humans consider corrective feedback on perceptual decisions as evidence of the actual state of the world rather than as rewards for their choices. By implementing these "feedback-as-reward" and "feedback-as-evidence" hypotheses on a shared learning platform, we show that the latter outperforms the former in explaining how corrective feedback adjusts the decision-making strategy along with past stimuli and choices. Our work suggests that humans learn about what has happened in their environment rather than the values of their own choices through corrective feedback during perceptual decision-making.

Dermis resident macrophages orchestrate localized ILC2 eosinophil circuitries to promote non-healing cutaneous leishmaniasis.

Tissue-resident macrophages are critical for tissue homeostasis and repair. We previously showed that dermis-resident macrophages produce CCL24 which mediates their interaction with IL-4+ eosinophils, required to maintain their M2-like properties in the TH1 environment of the Leishmania major infected skin. Here, we show that thymic stromal lymphopoietin (TSLP) and IL-5+ type 2 innate lymphoid cells are also required to maintain dermis-resident macrophages and promote infection. Single cell RNA sequencing reveals the dermis-resident macrophages as the sole source of TSLP and CCL24. Generation of Ccl24-cre mice permits specific labeling of dermis-resident macrophages and interstitial macrophages from other organs. Selective ablation of TSLP in dermis-resident macrophages reduces the numbers of IL-5+ type 2 innate lymphoid cells, eosinophils and dermis-resident macrophages, and ameliorates infection. Our findings demonstrate that dermis-resident macrophages are self-maintained as a replicative niche for L. major by orchestrating localized type 2 circuitries with type 2 innate lymphoid cells and eosinophils.