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Tracing human genetic histories and natural selection with precise local ancestry inference
Naïve ants reach a food source quicker when encountering returning ants
Abstract Pheromone guidance of ant foraging activity is well described, but less is known about how the presence of inward ant traffic on the trail affects the behavior of naive nestmates and if these influences are dependent or independent of pheromone signaling. Here, we examined whether the flow of foraging Lasius niger ants coming from a feeder influences the movements of naive nestmates traversing a pheromone trail. We used a device that permitted individual ants to travel from the nest to a feeder via a single bridge under four conditions; unidirectional inward ant traffic, where naive foraging ants contacted only colony members returning from the feeder along a pheromone trail; foraging following a pheromone trail without ant traffic; foraging with neither a pheromone trail nor ant traffic; foraging with bidirectional ant traffic, where naive ants encountered other ants moving both toward the feeder and returning on the pheromone trail. The time required by inexperienced ants to reach the feeder was shorter in the unidirectional condition (returning from the feeder) than the other three conditions. These findings suggest that specific cues can regulate the movement of pheromone-guide foraging by ants.
Modulating cortical excitability and cortical arousal by pupil self-regulation
Abstract The brain’s arousal state (i.e., central arousal) is regulated by multiple neuromodulatory nuclei in the brainstem and significantly influences high-level cognitive processes. By exploiting the mechanistic connection between the locus coeruleus, a key regulator of central arousal, and pupil dynamics, we recently demonstrated that participants could gain volitional control over arousal-regulating centers including the locus coeruleus using a pupil-based biofeedback approach. Here, we test whether pupil-based biofeedback modulates electrophysiological markers of cortical excitability, cortical arousal, and P300 responses. Combining pupil-based biofeedback with single-pulse transcranial magnetic stimulation, electroencephalography, and an auditory oddball task reveals three main results: pupil self-regulation significantly modulates (i) cortical excitability, (ii) the electroencephalogram spectral slope, a marker of cortical arousal, and (iii) the P300 response to target tones, an event-related potential suggested to be linked to phasic locus coeruleus activity. Here, we show that pupil-based biofeedback modulates fundamental aspects of brain function. Whether this method can further be used to modulate these aspects in case of disturbances associated with neurological and psychiatric disorders needs to be investigated in future studies.
A novel LncRNA risk model for disulfidptosis-related prognosis prediction and response to chemotherapy in acute myeloid leukemia
CryoPROS: Correcting misalignment caused by preferred orientation using AI-generated auxiliary particles
Bacterial biodiversity and optimization of pilot plant-based storage parameters of beet thick juice under Egyptian environmental conditions
Abstract In hot-weather regions such as Egypt, where maintaining lower storage temperatures is both economically unfeasible and a significantly difficult, this study was directed towards optimizing the storage of beet thick juice in order to enhance white sugar yield and reduce the impact of climate change. In this study, a pilot plant consisting of 12 storage cylinders was used to maintain thick beet juice with total soluble solids (ºBrix) of 67, 68, and 69 at 15, 25, and 35 ºC, respectively. Betastab® XL (Hop ß-acids) and KEBOCID 310 (sodium dimethyldithiocarbamate) were employed as biocides at 40 ppm. Surface sealing using 25.0% NaOH along with air removal was also applied. The relationships between bacterial count (CFUs), pH, lactic acid (LA) concentration, and reducing sugars (RS) content were evaluated. CFUs increased gradually with the length of the storage period in all tanks, reaching its peak (350 CFU/mL) in the control tank at 35 °C. LA and RS values were determined in all tanks and occurred at very low concentrations. pH exhibited a stable behavior with the exception of the control tank at 35 ºC that displayed degradation correlated to a pH drop to 7.32. Species of bacteria associated with the stored thick juice were isolated and identified by sequencing the 16 S rRNA. These included Bacillus cereus, B. licheniformis, B. paralicheniformis, B. subtilis, Bordetella muralis, Brevibacillus agri, Pseudomonas juntendi, and Stenotrophomonas geniculata. Antibacterial activity of both biocides at three concentrations—20, 40, and 60 ppm—was investigated against the species isolated. Hop ß-acid concentrations showed significant effects on the investigated bacteria with the exception of B. muralis and P. juntendi. All bacteria, with the exception of B. licheniformis AUMC B-550, were significantly affected by KEBOCID 310 concentrations. However, S. geniculata responded negatively to 20 ppm of KEBOCID 310. For the investigated strains, the effects of KEBOCID 310 at 40 and 60 ppm were almost identical. Along with better control over juice solids content and storage temperature, identifying the source and type of the bacterial infection can assist with managing the process and reduce thick juice deterioration. Sugar industry designers could potentially benefit from this study’s elucidation of the ideal circumstances for cost-effective storage in hot temperature zones.
Fast single metal cation conduction in ion-water aggregated aqueous battery electrolytes
Relationships between disease severity and measures of health status in people with interstitial lung disease in India: an observational study
Abstract The severity and progression of Interstitial Lung Disease (ILD) can vary due to environmental, cultural and genetic factors. The relationship between disease severity and factors that determine the health status of people with ILD living in lower middle-income countries like India has not been evaluated. This study aimed to determine whether there were relationships between disease severity with functional exercise capacity and Health Related Quality of Life (HRQoL) among people with ILD in India. This was a prospective, single center observational study. All participants performed Pulmonary Function Test (PFT) including Forced Vital Capacity (FVC) % predicted, Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) % predicted, 6 min Walk Distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale. Eighty participants with ILD were recruited from September 2020 and December 2022. There were strong correlations between 6MWD with DLCO % pred (Spearman rho 0.891) and between SGRQ Total score and DLCO % pred (Spearman rho 0.906). There were no correlations between 6MWD and FVC % pred (Spearman rho 0.206) or between SGRQ and FVC % pred (Spearman rho 0.113). This study demonstrated strong correlations between disease severity measured by DLCO % pred with both functional exercise capacity and HRQoL in people with ILD in India.
Dynamic single-cell metabolomics reveals cell-cell interaction between tumor cells and macrophages
Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of approximately 5–7%, and complete surgical resection remains the only curative treatment but is often unfeasible. Fluorescence-guided surgery (FGS) using tumor-targeted probes may improve tumor visualization and facilitate complete resection. This study aimed to identify and validate tumor targets for FGS during PDAC resection procedures. RNA expression data from over 4000 cell surface genes, obtained from public genomic databases, were analyzed to identify genes encoding PDAC-associated proteins. Eleven potential tumor targets were identified, including CEACAM5, TMPRSS4, COL17A1, CLDN18, and AQP5. Protein expression was evaluated by immunohistochemistry (IHC) in tissues from 44 PDAC and 7 chronic pancreatitis (CP) patients. All targets, except COL17A1, showed significantly higher expression in PDAC tissue compared to healthy pancreatic, CP, and duodenal tissue (p < 0.001), as well as in tumor-positive versus tumor-negative lymph nodes. Especially CEACAM5, TMPRSS4, and AQP5 were identified as the most promising targets for distinguishing PDAC from healthy tissues and detecting lymph node metastasis during FGS. The development of probes targeting multiple markers, such as AQP5 with CEACAM5 and/or TMPRSS4, may help overcome interpatient variability and enhance detection across patients.
Alternative splicing across the C. elegans nervous system
Vertical equilibrium simulation for industrial-scale CO2 storage in heterogeneous aquifers
Tifcemalimab as monotherapy or in combination with toripalimab in patients with relapsed/refractory lymphoma: a Phase I trial
Abstract Preclinical studies of tifcemalimab (anti-BTLA antibody) in combination with toripalimab (anti-PD-1 antibody) demonstrated synergistic anti-tumor effects. We present the outcomes of tifcemalimab with or without toripalimab in lymphoma patients. This is a 2-part, phase I study (NCT04477772). In Part A (dose escalation based on 3 + 3 design), patients with relapsed or refractory lymphoma received tifcemalimab monotherapy 1, 3 or 10 mg/kg for dose escalation and 3 mg/kg or 200 mg for dose expansion. For Part B (indication expansion), only classical Hodgkin’s lymphoma (cHL) patients were included to receive tifcemalimab 100 or 200 mg plus toripalimab 240 mg due to poor tumor response in other subtypes. The primary endpoints were safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). 25 patients in Part A and 46 in Part B were enrolled. No dose-limiting toxicities were observed, and MTD was not reached. The RP2D for tifcemalimab was 200 mg. Adverse events were predominantly Grade 1/2. Grade 3/4 treatment-related adverse events occurred in 3 patients (12·0%) in Part A and 15 patients (32·6%) in Part B. No fatal adverse events were observed. Tifcemalimab with or without toripalimab demonstrated a favorable safety profile in lymphoma patients.
Massive acquisition of conjugative and mobilizable integrated elements fuels Faecalibacterium plasticity and hints at their adaptation to the gut
Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism
Comparing interpretable machine learning models for fall risk in middle-aged and older adults with and without pain
Abstract Pain is common in middle-aged and older adults, has also been identified as a fall risk factor, whereas the mechanism of falls in pain is unclear. This study included 13,074 middle-aged and older adults from the China health and retirement longitudinal study (wave 2011–2015) to separately develop four-year fall risk prediction models for older adults with and without pain, using five machine learning algorithms with 145 input variables as candidate features. Shapley Additive exPlanations (SHAP) was used for the prediction model explanations. Adjusted logistic regression (LR) models showed that pain (OR 1.40 [1.29, 1.53]) was associated with a higher fall risk. Among pain characteristics, lower limb pain had the highest risk (OR 1.71 [1.22, 2.18]), followed by severe pain (OR 1.53 [1.36, 1.73]) and multisite pain (OR 1.43 [1.28, 1.55]). Among the fall prediction models for pain and non-pain, the LR model performed best with AUC-ROC values of 0.732 and 0.692, respectively. Common important features included fall history and height. Unique features for the pain model were functional limitation, SPPB, WBC, chronic disease score, life satisfaction, platelets, cooking fuel, and pain quantity, while marital status, age, depressive symptoms, cognitive function, hearing, rainy days, tidiness, and sleep duration were exclusive to the non-pain model. Pain characteristics are associated with falls among middle-aged and older adults. Prediction model can help identify people at high risk of falls with pain. Important features of falls differ between pain and non-pain populations, and prevention strategies should target specific populations for fall risk prediction.
Reassessing gas generation from oil thermal cracking associated with the Emeishan Large Igneous Province
Novel modified frailty index predicts completion of adjuvant chemotherapy in resectable pancreatic cancer in a dual center study
Deep transcriptomics reveals cell-specific isoforms of pan-neuronal genes
Abstract Profiling alternative splicing in single neurons using RNA-seq is challenging due to low capture efficiency and sensitivity. We therefore know much less about splicing patterns and regulation across neurons than we do about gene expression. Here we leverage unique attributes of C. elegans to investigate deep neuron-specific transcriptomes with biological replicates generated by the CeNGEN consortium, enabling high-confidence assessment of splicing across neuron types even for lowly-expressed genes. Global splicing maps reveal several striking observations, including pan-neuronal genes harboring cell-specific splice variants, and abundant differential intron retention across neuron types. We develop an algorithm to identify unique cell-specific expression patterns, which reveals both cell-specific isoforms and potential regulatory factors establishing these isoforms. Genetic interrogation of these factors in vivo identifies three distinct splicing factors employed to control splicing in a single neuron. Finally, we develop a user-friendly platform for spatial transcriptomic visualization of these splicing patterns with single-neuron resolution.