The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique

Objective To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. Methods Women aged 30­49 years were prospectively enrolled and offered primary HPV testing using either self- collected or provider- collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. Results Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30­49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self- collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV- positive patients, 2588 (92.3%) returned for all steps of their diagnostic work- up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty- one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. Conclusion It is feasible to perform cervical cancer screening with primary HPV testing and follow- up in low- resource settings. Participants preferred self- collection, and the majority of screen- positive patients completed all steps of their diagnostic work- up and treatment. Our findings provide important information for further implementation and scale- up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Identifying digital biomarkers of illness activity and treatment response in bipolar disorder with a novel wearable device (TIMEBASE): protocol for a pragmatic observational clinical study.

BACKGROUND: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions. AIMS: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder. METHOD: We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients. RESULTS: Recruitment is ongoing. CONCLUSIONS: This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

Toxicity of a management bait for grass carp (Ctenopharyngodon idella) incorporated with Antimycin A.

No current technology can specifically target grass carp (Ctenopharyngodon idella) for control within aquatic ecosystems. Rotenone and Carbon Dioxide-Carp are currently the only available registered pesticides for grass carp; they are nonselective and typically applied throughout the water, equally exposing target and native species. A more selective control tool or pesticide application could be used by resource managers to support mitigation efforts. Development of delivery systems that exploit carp feeding strategies could increase selectivity of pesticides and minimize effects on native fishes. A pesticide with selective delivery could be less labor intensive and used within an integrative pest management strategy. The present study examined Antimycin A toxicity in juvenile and sub-adult grass carp and rainbow trout (Oncorhynchus mykiss) across two routes of exposure. Water-based toxicity studies were used to calculate the concentration to cause lethality in 50% of treated fish (LC50) at 24-h, while oral gavage toxicity studies were used to calculate the dose to cause lethality in 50% of treated grass carp and rainbow trout (LD50) 24- to 96-h. Although rainbow trout were more sensitive than grass carp to Antimycin A through water-based exposure, oral toxicity was similar between species, even with inherent gastrointestinal morphological differences. Successful delivery of a lethal dose of Antimycin A to grass carp was achieved through an oral route of exposure using the rapeseed bait and shows promise for registration as a control tool and eventual use in pest management plans. Although a lethal dose of Antimycin A could be incorporated into a single bait pellet, more bait was required to achieve desired mortality when fed to fish under laboratory conditions.

Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.

PURPOSE: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC). METHODS: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures. RESULTS: Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (P = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS. CONCLUSION: This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.

Patient Preferences for Graft Selection in Anterior Cruciate Ligament Reconstruction.

Background: Selecting an appropriate graft for anterior cruciate ligament (ACL) reconstruction requires consideration of a patient's preferences, goals, age, and physical demands alongside the risks and benefits of each graft choice. Purpose: To determine the most popular ACL reconstruction grafts among patients and the most important factors influencing their decisions. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients undergoing ACL reconstruction between October 2022 and April 2023 completed a survey either before (nonconsult group) or after (consult group) speaking with their surgeon, who provided an evidence-based description of the pros and cons of an allograft and the following autografts: bone-patellar tendon-bone (BPTB), hamstring tendon (HT), and quadriceps tendon (QT). Patient characteristics, graft choice, information influencing their graft choice, and surgeon recommendation were collected and compared between the groups. Results: Among the 100 included patients, 59.0% were male, and the mean age was 28.3 ± 10.4 years. The most popular grafts were the BPTB (56.0%), followed by the QT (29.0%), HT (8.0%), and allograft (7.0%). No significant difference was observed in the graft selection between the consult group (n = 60; BPTB, 46.7%; QT, 38.3%; HT, 8.3%; allograft, 6.7%) and nonconsult group (n = 40; BPTB, 70.0%; QT, 15.0%; HT, 7.5%; allograft, 7.5%) (P = .0757). In the consult group, 81.7% of patients selected the graft recommended to them by their surgeon. The top 2 graft selection reasons were usage in professional athletes and failure rates, while the top 2 ACL surgery concerns were returning to their desired level of athletics and graft failure risk. Among the 93 patients who researched their ACL graft options before their visit, the most popular information source was some form of media (72.0% [67/93]). Conclusion: The study findings underscore the importance of patient preference and surgeon recommendation in a patient's graft selection and highlight the need to be cognizant of the information sources available to patients when researching their graft options.

Taphonomic signatures of early scavenging by black and turkey vultures.

Scavenging is critical for nutrient cycling and maintenance of healthy ecosystems. While there is substantial research into the identification of taphonomic signatures from facultative mammalian scavengers, early stage scavenging signatures by vultures remain unknown. Further, some vulture species are opportunistic predators, highlighting the need to define signatures observed in the course of normal scavenging behavior. We placed stillborn neonatal calves in an unoccupied pasture and used motion-trigger camera traps to quantify scavenging effort, then conducted necropsies to evaluate the effect of black vulture (Coragyps atratus) and turkey vulture (Cathartes aura) scavenging effort on carcass consumption. We measured the order of consumption of different tissue types to delineate which anatomic structures vultures consume first. Scavenging trials with higher numbers of vultures feeding on the carcass for longer were associated with decreased remaining tongue and abdominal viscera, and a larger umbilical wound. Greater maximum flock sizes were associated with decreased remaining tongue and abdominal viscera, a larger umbilical wound, and greater biomass consumption. Black vultures targeted the perineum and tongue earlier, while turkey vultures targeted the eyes, perineum, and tongue. These results are consistent with the idea that vultures prefer tissues that are easy to access and contain high nutrient content. These patterns form a distinctive taphonomic signature that can be used to identify early scavenging by black and turkey vultures. Our results demonstrate that criteria commonly used to identify livestock depredation by black vultures only document vulture presence and not predation. This distinction implies that new and more definitive criteria need to be developed and put into practice for more accurate decision criteria in livestock depredation compensation programs.

Clinical Outcomes of a Novel Hybrid Transtibial Technique for Femoral Tunnel Drilling in Anterior Cruciate Ligament Reconstruction: A Large Single-Center Case Series With a Minimum 2-Year Follow-up.

Background: A novel hybrid transtibial (HTT) approach to femoral tunnel drilling in anterior cruciate ligament reconstruction (ACLR) has been developed that circumvents the need for knee hyperflexion and orients the graft in the most anatomic position without sacrificing the tunnel length or aperture. Hypothesis: Patients who underwent ACLR utilizing the HTT technique would achieve excellent patient-reported outcome scores and experience low rates of graft failure and reoperations. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent primary ACLR at a single institution between 2005 and 2020 were retrospectively reviewed. Patients treated with the HTT, anteromedial portal (AMP), and transtibial (TT) approaches were matched based on age, sex, and body mass index ±3 kg/m2. Demographic and surgical data as well as femoral tunnel angle measurements on anteroposterior and lateral radiographs were collected for the 3 groups. However, clinical outcomes were only reported for the HTT group because of concerns of graft heterogeneity. Results: A total of 170 patients (median age, 26.5 years [interquartile range (IQR), 18.0-35.0 years]) who underwent ACLR using the HTT approach were included. The median coronal- and sagittal-plane femoral tunnel angles were 47° (IQR, 42°-53°) and 40° (IQR, 34°-46°), respectively. The sagittal-plane femoral tunnel angles in the HTT group were significantly more horizontal compared with those in the TT group (P < .0001), whereas the coronal-plane femoral tunnel angles in the HTT group were found to be significantly more vertical compared with those in the AMP group (P = .001) and more horizontal compared with those in the TT group (P < .0001). The graft failure and reoperation rates in the HTT group at a minimum 2-year follow-up were 1.8% (3/170) and 4.7% (8/170), respectively. The complication rate was 6.5% (11/170), with the most common complication being subjective stiffness in 7 patients. The median Lysholm score was 89.5 (IQR, 79.0-98.0); the median International Knee Documentation Committee score was 83.9 (IQR, 65.5-90.8); and the median Veterans RAND 12-Item Health Survey physical and mental component summary scores were 55.0 (IQR, 52.6-55.9) and 56.2 (IQR, 49.1-59.3), respectively. Conclusion: ACLR using the HTT technique was associated with low graft retear and revision surgery rates and good patient-reported outcome scores at medium-term follow-up and demonstrated femoral tunnel obliquity on postoperative radiographs that correlated with optimal parameters previously reported in cadaveric and biomechanical studies.

Learning in context: Undergraduate students' knowledge and the content retention of anatomy between discipline-specific and integrated course approaches.

Undergraduate introductory human anatomy and human physiology courses are either taught as discipline-specific or integrated anatomy and physiology (A&P) sequences. An institution underwent a curricular revision to change the course approach from discipline-specific Human Anatomy and Human Physiology to an integrated A&P I and II sequence, allowing the unique opportunity to explore the potential role of contextual learning in academic achievement and content retention. Mediation and moderation analysis was used to evaluate lecture examinations, laboratory practical examinations, and anatomical content retention between the different course approaches. Undergraduate students in the integrated A&P I course approach performed significantly better on lecture assessments and had a higher anatomy content retention rate at the end of the year than students enrolled in the standalone Human Anatomy course. The lecture examination averages between Human Physiology and A&P II (the second course in the sequence), as well as the anatomy laboratory practical examinations, were not significantly different between discipline-specific and integrated course approaches. The results suggest contextual learning-providing physiological context to anatomical structures-increases the anatomical content retention and academic achievement overall.

Epigenetic disease markers in primary sclerosing cholangitis and primary biliary cholangitis-methylomics of cholestatic liver disease.

BACKGROUND: The epigenome, the set of modifications to DNA and associated molecules that control gene expression, cellular identity, and function, plays a major role in mediating cellular responses to outside factors. Thus, evaluation of the epigenetic state can provide insights into cellular adaptions occurring over the course of disease. METHODS: We performed epigenome-wide association studies of primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) using the Illumina MethylationEPIC Bead Chip. RESULTS: We found evidence of increased epigenetic age acceleration and differences in predicted immune cell composition in patients with PSC and PBC. Epigenetic profiles demonstrated differences in predicted protein levels including increased levels of tumor necrosis factor receptor superfamily member 1B in patients with cirrhotic compared to noncirrhotic PSC and PBC. Epigenome-wide association studies of PSC discovered strongly associated 5'-C-phosphate-G-3' sites in genes including vacuole membrane protein 1 and SOCS3, and epigenome-wide association studies of PBC found strong 5'-C-phosphate-G-3' associations in genes including NOD-like receptor family CARD domain containing 5, human leukocyte antigen-E, and PSMB8. Analyses identified disease-associated canonical pathways and upstream regulators involved with immune signaling and activation of macrophages and T-cells. A comparison of PSC and PBC data found relatively little overlap at the 5'-C-phosphate-G-3' and gene levels with slightly more overlap at the level of pathways and upstream regulators. CONCLUSIONS: This study provides insights into methylation profiles of patients that support current concepts of disease mechanisms and provide novel data to inspire future research. Studies to corroborate our findings and expand into other -omics layers will be invaluable to further our understanding of these rare diseases with the goal to improve and individualize prognosis and treatment.

Wearable Data From Subjects Playing Super Mario, Taking University Exams, or Performing Physical Exercise Help Detect Acute Mood Disorder Episodes via Self-Supervised Learning: Prospective, Exploratory, Observational Study.

BACKGROUND: Personal sensing, leveraging data passively and near-continuously collected with wearables from patients in their ecological environment, is a promising paradigm to monitor mood disorders (MDs), a major determinant of the worldwide disease burden. However, collecting and annotating wearable data is resource intensive. Studies of this kind can thus typically afford to recruit only a few dozen patients. This constitutes one of the major obstacles to applying modern supervised machine learning techniques to MD detection. OBJECTIVE: In this paper, we overcame this data bottleneck and advanced the detection of acute MD episodes from wearables' data on the back of recent advances in self-supervised learning (SSL). This approach leverages unlabeled data to learn representations during pretraining, subsequently exploited for a supervised task. METHODS: We collected open access data sets recording with the Empatica E4 wristband spanning different, unrelated to MD monitoring, personal sensing tasks-from emotion recognition in Super Mario players to stress detection in undergraduates-and devised a preprocessing pipeline performing on-/off-body detection, sleep/wake detection, segmentation, and (optionally) feature extraction. With 161 E4-recorded subjects, we introduced E4SelfLearning, the largest-to-date open access collection, and its preprocessing pipeline. We developed a novel E4-tailored transformer (E4mer) architecture, serving as the blueprint for both SSL and fully supervised learning; we assessed whether and under which conditions self-supervised pretraining led to an improvement over fully supervised baselines (ie, the fully supervised E4mer and pre-deep learning algorithms) in detecting acute MD episodes from recording segments taken in 64 (n=32, 50%, acute, n=32, 50%, stable) patients. RESULTS: SSL significantly outperformed fully supervised pipelines using either our novel E4mer or extreme gradient boosting (XGBoost): n=3353 (81.23%) against n=3110 (75.35%; E4mer) and n=2973 (72.02%; XGBoost) correctly classified recording segments from a total of 4128 segments. SSL performance was strongly associated with the specific surrogate task used for pretraining, as well as with unlabeled data availability. CONCLUSIONS: We showed that SSL, a paradigm where a model is pretrained on unlabeled data with no need for human annotations before deployment on the supervised target task of interest, helps overcome the annotation bottleneck; the choice of the pretraining surrogate task and the size of unlabeled data for pretraining are key determinants of SSL success. We introduced E4mer, which can be used for SSL, and shared the E4SelfLearning collection, along with its preprocessing pipeline, which can foster and expedite future research into SSL for personal sensing.

Pathophysiology and Management of Chest Wall Pain after Surgical and Non-Surgical Local Therapies for Lung Cancer.

Chest wall pain syndromes can emerge following local therapies for lung cancer and can adversely affect patients' quality-of-life. This can occur after lung surgery, radiation therapy, or percutaneous image-guided thermal ablation. This review describes the multifactorial pathophysiology of chest wall pain syndromes that develop following surgical and non-surgical local therapies for lung cancer and summarizes evidence-based management strategies for inflammatory, neuropathic, myofascial, and osseous pain. It discusses a step-wise approach to treating chest wall pain that begins with non-opioid oral analgesics and includes additional pharmacologic treatments as clinically indicated, such as anticonvulsants, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, and various topical treatments. For myofascial pain, physical medicine techniques, such as acupuncture, trigger point injections, deep tissue massage, and intercostal myofascial release can also offer pain relief. For severe or refractory cases, opioid analgesics, intercostal nerve blocks, or intercostal nerve ablations may be indicated. Fortunately, palliation of treatment-related chest wall pain syndromes can be managed by most clinical providers, regardless of the type of local therapy utilized for a patient's lung cancer treatment. In cases where a patient's pain fails to respond to initial medical management, clinicians can consider referring to a pain specialist who can tailor a more specific pharmacologic approach or perform a procedural intervention to relieve pain.

Binding Energies and Optical Properties of Power-Exponential and Modified Gaussian Quantum Dots.

We examine the optical and electronic properties of a GaAs spherical quantum dot with a hydrogenic impurity in its center. We study two different confining potentials: (1) a modified Gaussian potential and (2) a power-exponential potential. Using the finite difference method, we solve the radial Schrodinger equation for the 1s and 1p energy levels and their probability densities and subsequently compute the optical absorption coefficient (OAC) for each confining potential using Fermi's golden rule. We discuss the role of different physical quantities influencing the behavior of the OAC, such as the structural parameters of each potential, the dipole matrix elements, and their energy separation. Our results show that modification of the structural physical parameters of each potential can enable new optoelectronic devices that can leverage inter-sub-band optical transitions.

Vitamin D Maintains Growth and Bone Mineral Density against a Background of Severe Vitamin A Deficiency and Moderate Toxicity in a Swine Model.

Excessive vitamin A (VA) negatively impacts bone. Interactions between VA and vitamin D (VD) in bone health are not well-understood. This study used a traditional two-by-two factorial design. Pigs were weaned and randomized to four treatments (n = 13/group): -A-D, -A+D, +A-D, and +A+D for 3 and 5 wk. Serum, liver, kidney, adrenal glands, spleen, and lung were analyzed by ultra-performance LC. Growth was evaluated by weight measured weekly and BMD by DXA. Weights were higher in -A+D (18.1 ± 1.0 kg) and +A+D (18.2 ± 2.3 kg) at 5 wk than in -A-D (15.5 ± 2.1 kg) and +A-D (15.8 ± 1.5 kg). Serum retinol concentrations were 0.25 ± 0.023, 0.22 ± 0.10, 0.77 ± 0.12, and 0.84 ± 0.28 µmol/L; and liver VA concentrations were 0.016 ± 0.015, 0.0065 ± 0.0035, 2.97 ± 0.43, 3.05 ± 0.68 µmol/g in -A-D, -A+D, +A-D, and +A+D, respectively. Serum 25(OH)D3 concentrations were 1.5 ± 1.11, 1.8 ± 0.43, 27.7 ± 8.91, and 23.9 ± 6.67 ng/mL in -A-D, +A-D, -A+D, +A+D, respectively, indicating a deficiency in -D and adequacy in +D. BMD was highest in +D (p < 0.001). VA and the interaction had no effect on BMD. Dietary VD influenced weight gain, BMD, and health despite VA status.

Point-of-care ultrasound in skin and soft tissue infections.

BACKGROUND: Skin and soft tissue infections (SSTIs) are commonly encountered in clinical practice. Point-of-care ultrasound (POCUS) is becoming an increasingly valuable tool in hospital medicine, especially with advancements in ultrasound technology that make it easier to perform. POCUS can augment the history and physical exam in patients with suspected SSTIs. POCUS can detect deeper infections, such as abscesses, and expedite time to surgical debridement for life-threatening infections such as necrotizing fasciitis (NF). OBJECTIVES: This review provides an introduction on how to perform and interpret a skin and soft tissue POCUS exam, the key sonographic findings for SSTIs, and how to incorporate these findings into clinical reasoning and management. METHODS: SSTI POCUS literature was reviewed using PubMed. All relevant studies with a defined protocol and reported sensitivity and specificity pertaining to the use of POCUS to diagnose SSTIs in adults were included. The authors provide additional input based on their ultrasound expertise and clinical experience. RESULTS: A total of seven studies met the criteria to be included in this review. CONCLUSIONS: Soft tissue POCUS is a valuable tool for hospitalists to improve diagnostic accuracy and patient care when assessing suspected SSTIs. Access to equipment, POCUS training, and experience are barriers to widespread use. However, performing a soft tissue POCUS exam is straightforward. It requires less training compared to other POCUS exams, and it has notable potential for routine future practice in the evaluation and management of suspected SSTIs and other dermatologic conditions.

Developmental changes in mouse motor skill learning and cortical circuitry.

Learning motor skills requires plasticity in the primary motor cortex (M1), including changes in inhibitory circuitry. But how inhibitory synaptic connections change during skill acquisition and whether this varies over development is not fully understood. This study assesses the normal developmental trajectory of motor learning and then addresses inhibitory connectivity changes after motor learning. We trained mice of both sexes to run on a custom accelerating rotarod at ages from postnatal day (P) 20 to P120, tracking paw position and quantifying time to fall and changes in gait pattern. Performance improved most rapidly between P30-60, while paw position and gait patterns change with learning, though differently between age groups. To address circuit changes, we labeled task-active and task-inactive pyramidal cells with CaMPARI2, a genetically encoded activity marker. We then evoked inhibitory responses (IPSCs) from two major interneuron types: parvalbumin-expressing (PV+) interneurons and somatostatin-expressing (SOM+) interneurons. After one training day, PV-mediated inhibition is greater in task-active cells, while SOM-mediated inhibition is not different. These results suggest early changes in PV-mediated inhibition may support motor skill acquisition in mice. Whether PV-mediated inhibitory changes persist or changes in SOM+ interneuron connections arise later in training remains to be tested.

Retrospective for the Dynamic Sensorium Competition for predicting large-scale mouse primary visual cortex activity from videos.

Understanding how biological visual systems process information is challenging because of the nonlinear relationship between visual input and neuronal responses. Artificial neural networks allow computational neuroscientists to create predictive models that connect biological and machine vision. Machine learning has benefited tremendously from benchmarks that compare different model on the same task under standardized conditions. However, there was no standardized benchmark to identify state-of-the-art dynamic models of the mouse visual system. To address this gap, we established the SENSORIUM 2023 Benchmark Competition with dynamic input, featuring a new large-scale dataset from the primary visual cortex of ten mice. This dataset includes responses from 78,853 neurons to 2 hours of dynamic stimuli per neuron, together with the behavioral measurements such as running speed, pupil dilation, and eye movements. The competition ranked models in two tracks based on predictive performance for neuronal responses on a held-out test set: one focusing on predicting in-domain natural stimuli and another on out-of-distribution (OOD) stimuli to assess model generalization. As part of the NeurIPS 2023 competition track, we received more than 160 model submissions from 22 teams. Several new architectures for predictive models were proposed, and the winning teams improved the previous state-of-the-art model by 50%. Access to the dataset as well as the benchmarking infrastructure will remain online at www.sensorium-competition.net.

Kit foxes demonstrate adaptive compromise characteristics under intraguild predation pressure by coyotes in the Great Basin desert.

Coyotes (Canis latrans) are believed to contribute to declining kit fox (Vulpes macrotis) numbers in the Great Basin desert through intraguild predation. Intraguild prey have been shown to exhibit adaptive compromise, whereby an animal increases selection for risky, but food-rich areas during times of food stress (i.e. winter). We evaluated the habitat selection of kit foxes in the Great Basin desert to elucidate if they demonstrated adaptive compromise as a method of coexisting with coyotes. We created 2nd order resource selection functions to analyze kit fox habitat selection associated with coyote relative probability of use (RPU), prey abundance, and type of soil substrate. In the summer, we found that kit fox selection for areas of relatively more abundant prey was not significant, and there was a small positive selection for coyote RPU. In the winter, we found a positive relationship between kit fox selection and prey abundance as well as a stronger selection for coyote RPU. These findings do follow the pattern of adaptive compromise. We also found kit foxes selected for silty and sandy soils, which are conducive to den construction, as they use dens seasonally for breeding but also year-round for multiple uses, including refugia from predators and extreme heat. Soil substrate appeared to be an important factor impacting kit fox habitat selection.

Sleep-wake variations of electrodermal activity in bipolar disorder.

BACKGROUND: Affective states influence the sympathetic nervous system, inducing variations in electrodermal activity (EDA), however, EDA association with bipolar disorder (BD) remains uncertain in real-world settings due to confounders like physical activity and temperature. We analysed EDA separately during sleep and wakefulness due to varying confounders and potential differences in mood state discrimination capacities. METHODS: We monitored EDA from 102 participants with BD including 35 manic, 29 depressive, 38 euthymic patients, and 38 healthy controls (HC), for 48 h. Fifteen EDA features were inferred by mixed-effect models for repeated measures considering sleep state, group and covariates. RESULTS: Thirteen EDA feature models were significantly influenced by sleep state, notably including phasic peaks (p < 0.001). During wakefulness, phasic peaks showed different values for mania (M [SD] = 6.49 [5.74, 7.23]), euthymia (5.89 [4.83, 6.94]), HC (3.04 [1.65, 4.42]), and depression (3.00 [2.07, 3.92]). Four phasic features during wakefulness better discriminated between HC and mania or euthymia, and between depression and euthymia or mania, compared to sleep. Mixed symptoms, average skin temperature, and anticholinergic medication affected the models, while sex and age did not. CONCLUSION: EDA measured from awake recordings better distinguished between BD states than sleep recordings, when controlled by confounders.

Dopamine-mediated plasticity preserves excitatory connections to direct pathway striatal projection neurons and motor function in a mouse model of Parkinson's disease.

The cardinal symptoms of Parkinson's disease (PD) such as bradykinesia and akinesia are debilitating, and treatment options remain inadequate. The loss of nigrostriatal dopamine neurons in PD produces motor symptoms by shifting the balance of striatal output from the direct (go) to indirect (no-go) pathway in large part through changes in the excitatory connections and intrinsic excitabilities of the striatal projection neurons (SPNs). Here, we report using two different experimental models that a transient increase in striatal dopamine and enhanced D1 receptor activation, during 6-OHDA dopamine depletion, prevent the loss of mature spines and dendritic arbors on direct pathway projection neurons (dSPNs) and normal motor behavior for up to 5 months. The primary motor cortex and midline thalamic nuclei provide the major excitatory connections to SPNs. Using ChR2-assisted circuit mapping to measure inputs from motor cortex M1 to dorsolateral dSPNs, we observed a dramatic reduction in both experimental model mice and controls following dopamine depletion. Changes in the intrinsic excitabilities of SPNs were also similar to controls following dopamine depletion. Future work will examine thalamic connections to dSPNs. The findings reported here reveal previously unappreciated plasticity mechanisms within the basal ganglia that can be leveraged to treat the motor symptoms of PD.

Nonlinear ray tracing in focused fields, part 1. Calculation of 3D focused wavefields: tutorial.

In this three-part paper series, we develop a method to trace the lines of flux through a three-dimensional wavefield by following a direction that is governed by the derivative of the phase at each point, a process that is best described as flux tracing but which we interchangeably name "nonlinear ray tracing." In this first part, we provide a tutorial on the high-speed calculation of three-dimensional complex wavefields, which is a necessary precursor to flux tracing. The basis of this calculation is the angular spectrum method, a well-known numerical algorithm that can be used to efficiently and accurately calculate diffracted fields for numerical apertures <0.7. It is known that this approach yields identical predictions to the first Rayleigh-Sommerfeld solution. We employ the angular spectrum method to develop two algorithms that generate the 3D complex wavefield in the region of focus of a lens. The first algorithm is based on the thin lens approximation, and the second is based on the concept of an ideal lens, which can be modeled using an optical Fourier transform. We review how these algorithms can be used to calculate focused laser beams with T E M 00 and T E M 01 laser profiles. The three-dimensional sampling requirements of the focused field are explained in detail, and expressions for the computational and memory efficiency of the two algorithms are developed. These two algorithms generate the 3D scaffold for the flux tracing method developed in the second paper, and in the third paper we highlight the application of the method to understanding monochromatic lens aberration. Disregarding the second and third papers, this first paper will serve as a practical tutorial for anyone seeking to compute focused fields in three dimensions.