bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explainable Automated Recognition of Emotional States from Canine Facial Expressions: The Case of Positive Anticipation and Frustration
Authors: Boneh-Shitrit Tali , Feighelstein Marcelo , Bremhorst Annika , Amir Shir , Distelfeld Tomer , Dassa Yaniv , Yaroshetsky Sharon , Riemer Stefanie , Shimshoni Ilan , Mills Daniel S. , Zamansky Anna 
Published: August 2022

Abstract
Internal affective states are closely linked to facial expressions in both human and many non-human animals. For some animal species, objective tools for facial expression analysis such as AnimalFACS are available and are only just beginning to be increasingly used. However, their use requires special expertise, training, and certification, while there is still some remaining risk for human bias, and its application is time-consuming. Automation of facial analysis offers a promising alternative and is already being addressed by a large body of research in the human domain.
In animal research, automation has so far been addressed for a few species in the context of pain, while emotional state recognition remains underexplored, especially in canine species due to the complexity of their facial morphology and expressions. The contribution of the present study is twofold. First, this is the first study to address automated recognition of emotional states in dogs using a dataset obtained in a controlled experimental setting, including videos from (n=29) Labrador Retrievers assumed to be in two experimentally induced emotional states: negative (frustration) and positive (anticipation). Two different approaches are compared in relation to our aim: (1) A DogFACS-based approach with a two-step pipeline consisting of (i) an Action Unit (AU) detector and (ii) a positive/negative state Decision Tree classifier; (2) An approach using deep learning techniques with no intermediate representation. The approaches reach accuracy of above 71% and 89%, respectively, with the deep learning approach performing better.
Secondly, this study is the first to address the explainability of AI models in the context of understanding the expression of emotion in animals. The DogFACS-based approach provides decision trees, that is a mathematical representation which reflects previous findings by human experts in relation to certain DogFACS variables being correlates of specific emotional states. The deep learning approach offers a different, visual form of explainability in the form of heatmaps reflecting regions of focus of the network's attention, which in some cases show focus clearly related to the nature of particular AUs. These heatmaps may hold the key to novel insights on the sensitivity of the network to nuanced pixel patterns reflecting information invisible to the human eye.
CXCR4 enhances the inhibitory effects of bone mesenchymal stem cells on lung cell apoptosis in a rat model of smoking-induced COPD
Authors: GAO JIANSHENG , LIANG YULI , CHEN JIABAO , SHEN HUIHUI , LIU HUA 
Published: August 2022

Abstract
Objective
Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death worldwide, and treatments are unsatisfactory, resulting in a major economic burden. Cellular therapy is commonly used for lung disease. We investigated treatment with CXCR4-overexpressing BMSCs during COPD model establishment.
Methods
We extracted and purified BMSCs from SD rats. Apoptosis induced by COPD was established by cigarette smoke exposure. BMSCs were transplanted in vivo twice a month during model establishment, and alveolar rupture in the lung was assessed. Lung cell apoptosis was assessed by TUNEL analysis, and the concentrations of apoptotic proteins in the lungs were detected by Western blotting.
Results
We successfully isolated BMSCs and established CXCR4-overexpressing BMSCs. Continuous cigarette smoke exposure caused alveolar septal rupture: in the model group, the 1-month alveolar MLI was significantly lower than that at the third month (p < 0.05). In the third month, the alveolar MLIs of the control and CXCR4-BMSC groups were lower than those of the model group (control group p < 0.01, CXCR4-BMSC group p < 0.05), and as shown by TUNEL staining, the apoptosis rates of the control and CXCR4-BMSC groups were significantly lower than those of the model groups (p < 0.01). The levels of the apoptotic proteins cleaved caspase-8, cleaved caspase-3 and cleaved PARP-1 were higher in the model group than in the control group (p < 0.05) and significantly lower in the CXCR4-BMSC group than in the model group (p < 0.05).
Conclusion
Transplantation of CXCR4-overexpressing BMSCs during COPD model generation significantly inhibited apoptosis via the extrinsic apoptosis pathway.
Community - Minimal Invasive Tissue Sampling (cMITS) using modified ambulance for ascertaining cause of death: A novel approach piloted in remote inaccessible rural area in India
Authors: Satav Ashish , Wairagkar Niteen , Khirwadkar Shubhada , Dani Vibhawari , Rasaily Reeta , Agrawal Usha , Thakar Yagnesh , Raje Dhananjay , Siraj Fouzia , Garge Pradyot , Palaskar Sameer , Kumbhare Shraddha , Simões Eric A. F. 
Published: August 2022

Abstract
BACKGROUND: Melghat in India is a hilly, forested, difficult to access, impoverished rural area with high mortality. Home deaths contribute to 67% of deaths, which are difficult to track and cause of death is mostly unknown. METHODS: A feasibility study was carried out in 93 rural villages and 5 hospitals to assess feasibility of tracking real-time community mortality and to ascertain cause of death in 0-60 months and 16-60 years age group using Minimal Invasive Tissue Sampling (MITS) in purpose-modified ambulance. We used the network of village health workers (VHW)s, to establish real-time community mortality tracking. Upon receipt of reports of home death, we performed MITS within 4 hours of death in the vicinity of the village. RESULTS: We conducted 16 MITS. Nine, in MITS ambulance in community and seven at MAHAN hospital. The acceptance rate of MITS was 59.26%. Standard operating procedure (SOP) of conducting community MITS in an ambulance, is established. Major challenges were, Covid19 lockdown, reluctance of tribal parents for consent for MITS due to illiteracy, superstitions and fear of organ removal. Ambulance was an easy to reach transport means in remote area, provided a well-designed and discrete facility to perform MITS in community, winning the confidence of bereaved family. This has reduced time interval between time of death and performing MITS. CONCLUSIONS: MITS in purpose-modified Ambulance can be used worldwide for community MITS especially in areas which are remote and lack healthcare access. This solution needs to be assessed in different cultural settings to document culture specific issues.
Diagnostic value of a nanopore sequencing assay of bronchoalveolar lavage fluid in smear- negative pulmonary tuberculosis
Authors: Liu Zhifeng , Yang Yang , Wang Qingfeng , Wang Lei , Nie Wenjuan , Chu Naihui 
Published: August 2022

Abstract
Purpose: To determine the diagnostic accuracy of a nanopore sequencing assay for testing of bronchoalveolar lavage ﬂuid (BALF) samples or sputum samples from suspected PTB patients and compare the results to results obtained for MGIT and Xpert assays. Methods: Cases with suspected PTB (n = 55) were diagnosed from January 2019 to December 2021 based on results of nanopore sequencing, MGIT culture, and Xpert MTB/RIF testing of BALF and sputum samples collected during hospitalization. Diagnostic accuracies of assays were compared. Results: Ultimately, data from 29 PTB patients and 26 non-PTB cases were analyzed. PTB diagnostic sensitivities of MGIT, Xpert MTB/RIF, and nanopore sequencing assays were 48.28%, 41.38%, and 75.86%, respectively, thus demonstrating that nanopore sequencing provided greater sensitivity than was provided by MGIT culture and Xpert assays (P<0.05). PTB diagnostic specificities of the respective assays were 65.38%, 100%, and 80.77%, which corresponded with kappa coefficient (κ) values of 0.14, 0.40, and 0.56, respectively. These results indicate that nanopore sequencing provided superior overall performance as compared to Xpert and MGIT culture assays and provided significantly greater PTB diagnostic accuracy than Xpert and sensitivity comparable to that of the MGIT culture assay. Conclusion: Our ﬁndings suggest that improved detection of PTB in suspected cases was achieved using nanopore sequencing-based testing of BALF or sputum samples than was achieved using Xpert and MGIT culture-based assays, and nanopore sequencing results alone cannot be used to rule out PTB.
Dopamine signals integrate innate and learnt valences to regulate memory dynamics
Authors: Schnitzer Mark , Huang Cheng , Luo Junjie , Woo Seung Je , Roitman Lucas , Li Jizhou , Pieribone Vincent , Kannan Madhuvanthi , Vasan Ganesh 
Published: August 2022

Abstract

To survive in dynamic environments, animals make behavioral decisions based on innate and learnt information about the valences of sensory cues. In the brains of multiple species, innate and learnt sensory valence signals are initially encoded by distinct neural populations1–7 but then reconverge in downstream brain structures that guide behavioral choices6–9. This reconvergence hinges on the prior acquisition of learnt valence information, which in turn might depend upon innate valence signals. However, it remains unknown whether and how innate sensory valence cues shape the acquisition of learnt valence information. Here we show that in the fruit fly brain, interactions between innate and learnt sensory valence signals within interconnected short- and long-term memory units of the mushroom body jointly regulate memory formation and expression via modulation of dopamine teaching signals. By using time-lapse, in vivo optical voltage imaging to record neural spiking with millisecond-resolution in flies undergoing olfactory associative conditioning, we found that PPL1 dopamine neurons (PPL1-DANs) heterogeneously and bi-directionally encode punishment, reward, and innate and learnt odor-valence cues. Learning modulates these representations in a way that combines innate and learnt valence information and allows the PPL1-DANs to regulate memory storage in their downstream targets, mushroom body output neurons (MBONs). PPL1-γ1pedc and PPL1-γ2α’1 neurons control short-term memory formation. After repeated conditioning, feedback signals carrying short-term memory data from MBON-γ1pedc>α/β to PPL1-α’2α2 and PPL1-α3 allow these dopamine cells to encode previously learnt valences and promote long-lasting memory formation. A computational model constrained by the mushroom body connectome and our spiking data explains how dopamine signals integrate innate and learnt valence data to regulate memory storage, extinction, and the interactions between short- and long-term memory traces. The model yields non-intuitive predictions about the effects of different training protocols, which our experiments confirm. Overall, the mushroom body achieves flexible learning through dopamine-mediated integration of innate and learnt valences in parallel sets of DAN/MBON learning units with feedback interconnections. This hybrid physiologic-anatomic mechanism may be a general means by which ecological information regulates learning and memory in other species and brain structures relying on dopaminergic signaling, including the vertebrate basal ganglia10.
Utility of novel echocardiographic measurements to improve prenatal diagnosis of coarctation of the aorta
Authors: Fujisaki Takuya , Ishii Yoichiro , Takahashi Kunihiko , Mori Masayoshi , Matsuo Kumiyo , Asada Dai , Aoki Hisaaki , Tsumura Sanae , Iwai Shigemitsu , Kayatani Futoshi 
Published: August 2022

Abstract
Objective
Prenatal recognition of coarctation of the aorta (CoA) may improve neonatal survival and reduce morbidity. However, prenatal diagnosis of CoA remains challenging, with relatively high false–positive and false–negative rates. This study aimed to identify a novel formula based on fetal echocardiographic measures to predict prenatal identification of CoA.
Methods
A retrospective comparison on the echocardiographic evaluation of 30 patients with suspected CoA between May 2016 and April 2021 was performed. Fetal echocardiograms were measured for the following: Z-score of right and left ventricular diameters, tricuspid and mitral valve diameters, pulmonary artery and ascending aorta diameters, pulmonary valve and aortic valve diameters, ductus arteriosus and aortic isthmus diameters and their respective ratios, and distal aortic arch (DA) index, which is the distance between the second and third branches of the aortic arch / distal aortic arch diameter. The patients were divided into a postnatal surgical intervention group (n = 13) and a non-intervention group (n = 17).
Results
The measurements that showed significant differences were aortic isthmus diameter Z-score (p < 0.001), ductus arteriosus diameter/aortic isthmus diameter (p < 0.001) and DA index (p < 0.001). In the receiver operating characteristic curves analysis, the DA index was the largest with an area under the curve of 0.941 and a cutoff value of 1.28, with a sensitivity of 85% and a specificity of 94%. Among the three parameters that showed significant differences, the DA index had the lowest false-positive rate (5.9%).
Conclusions
The DA index ≧ 1.28 allows for the extraction of fetal CoA cases requiring surgical intervention.
Chemoproteomic identification of a dipeptidyl peptidase 4 (DPP4) homolog in Bacteroides thetaiotaomicron important for envelope integrity and fitness
Authors: Keller Laura , Nguyen Taylor , Liu Lawrence , Lakemeyer Markus , Gelsinger Danielle , Chanin Rachel , Ngo Nhi , Lum Kenneth , Faucher Franco , Ipock Phillip , Niphakis Micah , Bhatt Ami , O'Donoghue Anthony , Huang Kerwyn , Bogyo Matthew 
Published: August 2022

Abstract
Serine hydrolases play important roles in signaling and human metabolism, yet little is known about the functions of these enzymes in gut commensal bacteria. Using bioinformatics and chemoproteomics, we identify serine hydrolases in the gut commensal Bacteroides thetaiotaomicron that are specific to the Bacteroidetes phylum. Two are predicted homologs of the human protease dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Functional studies reveal that BT4193 is a true homolog of hDPP4 while the other is misannotated and is a proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and is inhibited by FDA-approved type 2 diabetes drugs that target hDPP4. Loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. Taken together, our findings suggest that serine hydrolases contribute to gut microbiota dynamics and may be off-targets for existing drugs that could cause unintended impact on the microbiota.
Photothermal Effects of Terahertz-band and Optical Electromagnetic Radiation on Human Tissues
Authors: Reddy Innem Venkata Anudeep Kumar , Jornet Josep , Furlani Edward 
Published: August 2022

Abstract
The field of wireless communication has witnessed tremendous advancements in the past few decades, leading to more pervasive and ubiquitous networks. Human bodies are continually exposed to electromagnetic radiation, but typically this does not impact the body as the radiation is non-ionizing and the waves carry low power. However, with progress in the sixth generation (6G) of wireless networks and the adoption of the spectrum above 100~GHz in the next few years, higher power radiation is needed to cover larger areas, exposing humans to stronger and more prolonged radiation. Also, water has a high absorption coefficient at these frequencies and could lead to thermal effects on the skin. Hence, there is a need to study the radiation effects on human tissues, specifically the photothermal effects. In this paper, we present a custom-built, multi-physics model to investigate electromagnetic wave propagation in human tissue and study its subsequent photothermal effects. The proposed finite-element model consists of two segments -- the first one estimates the intensity distribution along the beam path, while the second calculates the increase in temperature due to the wave distribution inside the tissue. We determine the intensity variation in the tissue using the radiative transfer equation and compare the results with Monte Carlo analysis and existing analytical models. The intensity information is then utilized to predict the rise in temperature with a bio-heat transfer module, powered by Pennes' bioheat equation. The model is parametric, and we perform a systematic photothermal analysis to recognize the crucial variables responsible for the temperature growth inside the tissue, particularly for terahertz and near-infrared optical frequencies. Our numerical model can serve as a benchmark for studying the high-frequency radiation effects on complex heterogeneous media such as human tissue.
High reliability model of mechanical response in drilling of CFRP/Al stacks
Authors: Gong Qinghong , Li Liang , Yuan Xinman , Hu Zhiqin , Chen Jie , Ma Ke 
Published: August 2022

Abstract
CFRP/Al laminate material is widely used in aerospace due to its advantages of light weight and high machinability. For assembling, crowded assembly holes need to be drilled for CFRP/Al laminate products. However, the damages of burr, delamination, and tearing appear frequently in drilling without precise guidance by mechanical response model. In order to reduce the machining damages, in this paper, a high-reliability mechanical response model is established for each stage in laminate materials drilling to ascertain the matching method between materials, tools, and cutting parameters. The theoretical expression of drilling thrust based on the thin plate theory is established considering the influence of cutting parameters, and further corrected with the cutting parameter correction terms to predict drilling thrust force, and further guiding the optimization of drilling parameters. According to the experimental results, the proposed model has a reliability greater than 97.3% and a prediction deviation lower than 13.2% in CFRP/Al laminate material drilling thrust force prediction. In the cutting with optimized parameters from the proposed model, the inlet orifice of the laminated material has no flanging burr, and the CFRP layer exit orifice has no defects as burr, delamination, or tearing.
PACAP signaling is not involved in GTN- and levcromakalim-induced hypersensitivity in mouse models of migraine
Authors: Guo Song , Ernstsen Charlotte , Hay-Schmidt Anders , Ashina Messoud , Olesen Jes , Christensen Sarah Louise 
Published: August 2022

Abstract
Background
Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only effective in 50–60% of patients. Recent studies have shown that the pituitary adenylate cyclase-activating peptide (PACAP38) pathway is independent from the CGRP signaling pathway. Here, we investigate PACAP38 signaling pathways in relation to glyceryl trinitrate (GTN), levcromakalim and sumatriptan.
Methods
In vivo mouse models of PACAP38-, GTN-, and levcromakalim-induced migraine were applied using tactile sensitivity to von Frey filaments as measuring readout. Signaling pathways involved in the three models were dissected using PACAP-inhibiting antibodies (mAbs) and sumatriptan.
Results
We showed that PACAP mAbs block PACAP38 induced hypersensitivity, but not via signaling pathways involved in GTN and levcromakalim. Also, sumatriptan has no effect on PACAP38-induced hypersensitivity relevant to migraine. This is the first study testing the effect of a PACAP-inhibiting drug on GTN- and levcromakalim-induced hypersensitivity.
Conclusions
Based on the findings in our mouse model of migraine using migraine-inducing compounds and anti-migraine drugs, we suggest that PACAP acts via a distinct pathway. Using PACAP38 antagonism may be a novel therapeutic target of interest in a subgroup of migraine patients who do not respond to existing therapies.
CDCP1 expression is frequently increased in aggressive urothelial carcinoma and promotes urothelial tumor progression
Authors: Saponaro Miriam , Flottmann Sina , Eckstein Markus , Hommerding Oliver , Klümper Niklas , Corvino Dillon , Hosni Sana , Schmidt Anja , Mönig Nicolas , Schmidt Doris , Ellinger Jörg , Toma Marieta , Kristiansen Glen , Bald Tobias , Alimonti Andrea , Ritter Manuel , Hölzel Michael , Alajati Abdullah 
Published: August 2022

Abstract
The prognosis of patients with advanced urothelial carcinoma (UC) remains poor and improving its treatment continues to be a major medical need. CUB domain containing protein 1 (CDCP1) is a known oncogene in various types of solid cancers and its overexpression is associated with impaired prognosis. However, its role in UC remains undetermined. Here we assessed the clinical relevance of CDCP1 in two cohorts of UC at different stages of the disease. Immunohistochemistry showed that CDCP is highly expressed in advanced UC, which significantly correlates with shorter overall survivals. Importantly, the basal/squamous (Ba/Sq) UC subtype showed significantly enriched protein and mRNA levels for CDCP1. Moreover, ex-vivo organoids derived from CDCP1pcLSL/+ transgenic mouse model were used to assess the functional role of CDCP1 overexpression, while UC cell lines knockouts for CDCP1 were generated using CRISPR-Cas9-technology to model the effect of targeting CDCP1. Interestingly, CDCP1 overexpression significantly induced proliferation and activation of MAPK pathways in ex-vivo organoids. In addition, CDCP1 knockout in UC cell lines reduced their proliferation and migration, concomitant with MAPK pathway activity reduction. Our results showed highlight the relevance of CDCP1 in advanced UC and demonstrate its oncogenic role in UC, suggesting that targeting CDCP1 could be a rational therapeutic strategy for advanced UC.
Synergetic Therapeutic Efficacy of Fasudil and Bone Marrow Derived-Neuronal Stem Cell in a Parkinson's Disease Mouse Model
Authors: Yan Yu-Chen , Li Yan-Hua , Xiao Bao-Guo , Xi Jian-Ying , Yu Wen-Bo 
Published: August 2022

Abstract
Bone marrow-derived neural stem cells (BM-NSCs) have shed light on novel therapeutic approaches for PD with the potential to halt or even reverse disease progression. Various strategies have been developed to promote therapeutic efficacy via optimizing implanted cells and the microenvironment of transplantation in the central nervous system (CNS). This current study further proved that the combination of fasudil, a Rho-kinase inhibitor, and BM-NSCs exhibited a synergetic effect on restoring neuron loss in the MPTP-PD mice model. It simultaneously unveiled cellular mechanisms underlying synergistic neuron-protection effects of fasudil and NSCs, which included promoting the proliferation, differentiation, and maturation of exogenous and endogenous NSCs, and contributing to microglia shift into the M2 phenotype. Corresponding molecular mechanisms were observed, including the inhibition of inflammatory responses, the elevation of neurotrophic factors, and the induction of WNT/β-catenin and PI3K/Akt/mTOR signaling pathways. Our study provides evidence for the co-intervention of BM-NSCs and fasudil as a promising therapeutic method with enhanced efficacy in treating neurodegenerative diseases.