Miracle-dz/UniFAR-FTUs huggingface dataset:
Social Repercussion of Translocating a Jaguar in Brazil

The translocation of “problem-animals” is a common non-lethal strategy to deal with human-wildlife conflict. While processes of wildlife translocation have been widely documented, little is known about the social repercussions that take place once the capture and the return of a problem-animal to its natural habitat fail and it has to be permanently placed in captivity. We investigated how the public, an important stakeholder in wildlife conservation, perceived the translocation of a female jaguar to a wildlife captivity center. The objectives were to (1) assess the public's perceptions (e.g., attitudes, emotions, awareness) toward the jaguar and its translocation process, and (2) how these psychological constructs are related. We used the social media profiles of the three institutions involved in the process (one responsible for the jaguar rescues, one that supported its recovery, and the one responsible for the jaguar's final destination) and analyzed the comments left by their followers on posts related to the jaguar and the translocation itself during 25 days. A total of 287 comments were analyzed through coding, a categorizing strategy of qualitative analysis; 33 codes were identified. Results showed high admiration for the work done, positive attitudes and emotions, and concern toward the animal. Lack of awareness about the translocation process was high, with comments of curiosity toward the situation being one of the most commonly found. To a lesser extent, people felt sad for the jaguar not being able to return to the wild and criticized the need for translocation. Admiration for the work had a strong relation with gratitude and broader positive perceptions toward the jaguar's story. Criticism related to concern, which was also related to a need for more information and curiosity. Our findings suggest that the public who engaged with those institutions through their Instagram accounts were grateful for seeing the jaguar safe, but were not aware of the complexity of the operation nor about the nature of the conflict with farmers. The public can either reinforce a particular action or jeopardize an entire operation, depending on their perceptions of the matter. In the case of this jaguar, the public held a positive view; however, we acknowledge the limitations of our sample and recommend further analyses of social repercussions among people who are not followers of these organizations. Furthermore, we recommend engaging other stakeholders to fully understand the human dimensions of translocating this jaguar. Finally, for social acceptance, we highlight the importance of transparency and reliability of the organizations operating the translocation.
The Crosstalk Between Malignant Cells and Tumor-Promoting Immune Cells Relevant to Immunotherapy in Pancreatic Ductal Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is dominated by an immunosuppressive microenvironment, which makes immune checkpoint blockade (ICB) often non-responsive. Understanding the mechanisms by which PDAC forms an immunosuppressive microenvironment is important for the development of new effective immunotherapy strategies. Methods: This study comprehensively evaluated the cell-cell communications between malignant cells and immune cells by integrative analyses of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC. A Malignant-Immune cell crosstalk (MIT) score was constructed to predict survival and therapy response in PDAC patients. Immunological characteristics, enriched pathways, and mutations were evaluated in high- and low MIT groups. Results: We found that PDAC had high level of immune cell infiltrations, mainly were tumor-promoting immune cells. Frequent communication between malignant cells and tumor-promoting immune cells were observed. 15 ligand-receptor pairs between malignant cells and tumor-promoting immune cells were identified. We selected genes highly expressed on malignant cells to construct a Malignant-Immune Crosstalk (MIT) score. MIT score was positively correlated with tumor-promoting immune infiltrations. PDAC patients with high MIT score usually had a worse response to immune checkpoint blockade (ICB) immunotherapy. Conclusion: The ligand-receptor pairs identified in this study may provide potential targets for the development of new immunotherapy strategy. MIT score was established to measure tumor-promoting immunocyte infiltration. It can serve as a prognostic indicator for long-term survival of PDAC, and a predictor to ICB immunotherapy response.
Aprepitant Inhibits JNK and p38/MAPK to Attenuate Inflammation and Suppresses Inflammatory Pain

Substance P contributes to the pathogenesis of pain by acting on NK-1R, specialized sensory neurons that detect noxious stimuli. Aprepitant, an antagonist of NK-1R, is widely used to treat chemotherapy-induced nausea and vomiting. In this study, we used LPS-stimulated BV-2 microglia cell line and animal models of inflammatory pain to explore the analgesic effect of aprepitant on inflammatory pain and its underlying mechanism. The excitability of DRG neurons were measured using whole-cell patch-clamp recordings. The behavioral tests were measured and the morphological changes on inflamed paw sections were determined by HE staining. Changes in the expressions of cytokine were measured by using real-time quantitative PCR analysis and ELISA method. Immunofluorescence and western blotting were used to detect the microglia activation and MAPK. Aprepitant treatment significantly inhibited the excitability of DRG neurons. The pain behavior and the paw tissues inflammatory damage were significantly relived after the administration of aprepitant compared to formalin group. Aprepitant significantly suppressed the activation of microglia, phosphorylation of JNK and p38 MAPK, as well as the mRNA and protein expressions of MCP-1, TNF-α, IL-6, and IL-1β, in vivo and in vitro. The LPS-induced over-translocation into nucleus of NF-κBp65 was down-regulated following aprepitant treatment in BV-2 cells. The present study suggests that aprepitant attenuates inflammatory pain in mice via suppressing the phosphorylation of JNK and p38, and inhibiting the NF-κB signaling pathway.
Comparative Study of Brain fMRI of Olfactory Stimulation in Neuromyelitis Optica Spectrum Disease and Multiple Sclerosis

Objective: To observe the characteristics of brain fMRI during olfactory stimulation in patients with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS), compare the differences of brain functional activation areas between patients with NMOSD and MS, and explore the characteristics of olfactory-related brain networks of NMOSD and MS. Methods: Nineteen patients with NMOSD and 16 patients with MS who met the diagnostic criteria were recruited, and 19 healthy controls matched by sex and age were recruited. The olfactory function of all participants was assessed using the visual analog scale (VAS). Olfactory stimulation was alternately performed using a volatile body (lavender and rose solution) and the difference in brain activation was evaluated by task-taste fMRI scanning simultaneously. Results: Activation intensity was weaker in the NMOSD group than in the healthy controls, including the left rectus, right superior temporal gyrus, and left cuneus. The activation intensity was stronger for the NMOSD than the controls in the left insula and left middle frontal gyrus (P < 0.05). Activation intensity was weaker in the MS group than the healthy controls in the bilateral hippocampus, right parahippocampal gyrus, right insula, left rectus gyrus, and right precentral gyrus, and stronger in the left paracentral lobule among the MS than the controls (P < 0.05). Compared with the MS group, activation intensity in the NMOSD group was weaker in the right superior temporal gyrus and left paracentral lobule, while it was stronger among the NMOSD group in the bilateral insula, bilateral hippocampus, bilateral parahippocampal gyrus, left inferior orbital gyrus, left superior temporal gyrus, left putamen, and left middle frontal gyrus (P < 0.05). Conclusion: Olfactory-related brain networks are altered in both patients, and there are differences between their olfactory-related brain networks. It may provide a new reference index for the clinical differentiation and disease evaluation of NMOSD and MS. Moreover, further studies are needed.
Aberrant GATA2 Activation in Pediatric B-Cell Acute Lymphoblastic Leukemia

GATA2 is a transcription factor that is critical for the generation and survival of hematopoietic stem cells (HSCs). It also plays an important role in the regulation of myeloid differentiation. Accordingly, GATA2 expression is restricted to HSCs and hematopoietic progenitors as well as early erythroid cells and megakaryocytic cells. Here we identified aberrant GATA2 expression in B-cell acute lymphoblastic leukemia (B-ALL) by analyzing transcriptome sequencing data obtained from St. Jude Cloud. Differentially expressed genes upon GATA2 activation showed significantly myeloid-like transcription signature. Further analysis identified several tumor-associated genes as targets of GATA2 activation including BAG3 and EPOR. In addition, the correlation between KMT2A-USP2 fusion and GATA2 activation not only indicates a potential trans-activating mechanism of GATA2 but also suggests that GATA2 is a target of KMT2A-USP2. Furthermore, by integrating whole-genome and transcriptome sequencing data, we showed that GATA2 is also cis activated. A somatic focal deletion located in the GATA2 neighborhood that disrupts the boundaries of topologically associating domains was identified in one B-ALL patient with GATA2 activation. These evidences support the hypothesis that GATA2 could be involved in leukemogenesis of B-ALL and can be transcriptionally activated through multiple mechanisms. The findings of aberrant activation of GATA2 and its molecular function extend our understanding of transcriptional factor dysregulation in B-ALL.
Current Tolerance-Associated Peripheral Blood Gene Expression Profiles After Liver Transplantation Are Influenced by Immunosuppressive Drugs and Prior Cytomegalovirus Infection

Spontaneous operational tolerance to the allograft develops in a proportion of liver transplant (LTx) recipients weaned off immunosuppressive drugs (IS). Several previous studies have investigated whether peripheral blood gene expression profiles could identify operational tolerance in LTx recipients. However, the reported gene expression profiles differed greatly amongst studies, which could be caused by inadequate matching of clinical parameters of study groups. Therefore, the purpose of this study was to validate differentially expressed immune system related genes described in previous studies that identified tolerant LTx recipients after IS weaning. Blood was collected of tolerant LTx recipients (TOL), a control group of LTx recipients with regular IS regimen (CTRL), a group of LTx recipients with minimal IS regimen (MIN) and healthy controls (HC), and groups were matched on age, sex, primary disease, time after LTx, and cytomegalovirus serostatus after LTx. Quantitative Polymerase Chain Reaction was used to determine expression of twenty selected genes and transcript variants in PBMCs. Several genes were differentially expressed between TOL and CTRL groups, but none of the selected genes were differentially expressed between HC and TOL. Principal component analysis revealed an IS drug dosage effect on the expression profile of these genes. These data suggest that use of IS profoundly affects gene expression in peripheral blood, and that these genes are not associated with operational tolerance. In addition, expression levels of SLAMF7 and NKG7 were affected by prior cytomegalovirus infection in LTx recipients. In conclusion, we found confounding effects of IS regimen and prior cytomegalovirus infection, on peripheral blood expression of several selected genes that were described as tolerance-associated genes by previous studies.
Factors Determining Long-Term Antitumor Responses to Immune Checkpoint Blockade Therapy in Melanoma

With the increasing promise of long-term survival with immune checkpoint blockade (ICB) therapies, particularly for patients with advanced melanoma, clinicians and investigators are driven to identify prognostic and predictive factors that may help to identify individuals who are likely to experience durable benefit. Several ICB combinations are being actively developed to expand the armamentarium of treatments for patients who may not achieve long-term responses to ICB single therapies alone. Thus, negative predictive markers are also of great interest. This review seeks to deepen our understanding of the mechanisms underlying the durability of ICB treatments. We will discuss the currently available long-term data from the ICB clinical trials and real-world studies describing the survivorship of ICB-treated melanoma patients. Additionally, we explore the current treatment outcomes in patients rechallenged with ICB and the patterns of ICB resistance based on sites of disease, namely, liver or CNS metastases. Lastly, we discuss the landscape in melanoma in the context of prognostic or predictive factors as markers of long-term response to ICB.
Transitional and Long-Term Care System in Japan and Current Challenges for Stroke Patient Rehabilitation

In Japan, the national medical insurance system and long-term care insurance (LTCI) system cover rehabilitation therapy for patients with acute, convalescent, and chronic stroke. Medical insurance covers early and multidisciplinary rehabilitation therapy during acute phase hospitalizations. Patients requiring assistance in their activities of daily living (ADL) after hospitalization are transferred to kaifukuki (convalescent) rehabilitation wards (KRW), which the medical insurance system has also covered. In these wards, patients can receive intensive and multidisciplinary rehabilitation therapy to improve their ADL and transition to a smooth home discharge. After discharge from these hospitals, elderly patients with stroke can receive outpatient (day-care) rehabilitation and home-based rehabilitation using the LTCI system. The Japanese government has proposed building a community-based integrated care system by 2025 to provide comprehensive medical services, long-term care, preventive care, housing, and livelihood support for patients. This policy aims to promote smooth coordination between medical insurance services and LTCI providers. Accordingly, the medical insurance system allows hospitals to receive additional fees by providing patient information to rehabilitation service providers in the LTCI system. A comprehensive database on acute, convalescent, and chronic phase stroke patients and seamless cooperation between the medical care system and LTCI system is expected to be established in the future. There are only 2,613 board-certified physiatrists in Japan, and many medical schools lack a department for rehabilitation medicine; establishing such a department at each school is encouraged to teach students efficient medical care procedures, to conduct research, and to facilitate the training of personnel in comprehensive stroke rehabilitation.
Perspective on Micro-Supercapacitors

The rapid development of portable, wearable, and implantable electronic devices greatly stimulated the urgent demand for modern society for multifunctional and miniaturized electrochemical energy storage devices and their integrated microsystems. This article reviews material design and manufacturing technology in different micro-supercapacitors (MSCs) along with devices integrate to achieve the targets of their various applications in recent years. Finally, We also critically prospect the future development directions and challenges of MSCs.
Positive Interactions Between Lactic Acid Bacteria Could Be Mediated by Peptides Containing Branched-Chain Amino Acids

Lactic acid bacteria (LAB) are responsible for the sanitary, organoleptic, and health properties of most fermented products. Positive interactions between pairs of LAB strains, based on nitrogen dependencies, were previously demonstrated. In a chemically defined medium, using milk and lupin proteins as sole nitrogen source, two proteolytic strains were able to sustain the growth of non-proteolytic strains, but one did not. The objective of the present study was, thus, to determine which specific peptides were implicated in the positive interactions observed. Peptides produced and involved in the bacterial interactions were quantified using tandem mass spectrometry (LC-MS/MS). About 2,000 different oligopeptides ranging from 6 to more than 50 amino acids in length were identified during the time-course of the experiment. We performed a clustering approach to decipher the differences in peptide production during fermentation by the three proteolytic strains tested. We also performed sequence alignments on parental proteins and identified the cleavage site profiles of the three bacterial strains. Then, we characterized the peptides that were used by the non-proteolytic strains in monocultures. Hydrophobic and branched-chain amino acids within peptides were identified as essential in the interactions. Ultimately, better understanding how LAB can positively interact could be useful in multiple food-related fields, e.g., production of fermented food products with enhanced functional properties, or fermentation of new food matrices.
Replication of Dengue Virus in K562-Megakaryocytes Induces Suppression in the Accumulation of Reactive Oxygen Species

Dengue virus can infect human megakaryocytes leading to decreased platelet biogenesis. In this article, we report a study of Dengue replication in human K562 cells undergoing PMA-induced differentiation into megakaryocytes. PMA-induced differentiation in these cells recapitulates steps of megakaryopoiesis including gene activation, expression of CD41/61 and CD61 platelet surface markers and accumulation of intracellular reactive oxygen species (ROS). Our results show differentiating megakaryocyte cells to support higher viral replication without any apparent increase in virus entry. Further, Dengue replication suppresses the accumulation of ROS in differentiating cells, probably by only augmenting the activity of the transcription factor NFE2L2 without influencing the expression of the coding gene. Interestingly pharmacological modulation of NFE2L2 activity showed a simultaneous but opposite effect on intracellular ROS and virus replication suggesting the former to have an inhibitory effect on the later. Also cells that differentiated while supporting intracellular virus replication showed reduced level of surface markers compared to uninfected differentiated cells.
First Results From a Propensity Matching Trial of Mycophenolate Mofetil vs. Azathioprine in Treatment-Naive AIH Patients

Background/Aims As previous real-world studies and meta-analyses have shown that mycophenolate mofetil (MMF) might have better efficacy than azathioprine (AZA) in autoimmune hepatitis (AIH), we conducted a propensity matching study to assess the efficacy and safety of MMF vs. AZA. Methods All 126 consecutive treatment-naive adult AIH patients, diagnosed and followed in our department since 2016, were included. Patients received prednisolone 0.5–1 mg/kg/day plus either AZA 1–2 mg/kg/day or 1.5–2 g/day MMF. The tapering of prednisolone was identical between groups. Results After propensity matching score and adjustment for known factors affecting response to treatment and outcome, 64 patients were included in the study (MMF = 32 and AZA = 32). Rates of non-response, complete biochemical response (CBR) at 6 and 12 months, and prednisolone withdrawal (6 months, 12 months, and end of follow-up) were identical between groups. However, MMF treatment was significantly associated with CBR at the end of follow-up [odds ratio (OR) 11.259; 95% CI: 1.3–97.4, p = 0.028]. AZA patients were more prone to stop treatment due to AZA intolerance/insufficient response (p = 0.0001). At the end of follow-up, the overall efficacy of each schedule was also significantly higher in the MMF group compared to the AZA group (p = 0.0001). Conclusion We showed for the first time in a propensity matching study that MMF can be used as first-line therapy in AIH as attested by the significantly higher CBR at end of follow-up compared to AZA. Whether this better efficacy is also associated with higher histological remission rates and sustained CBR off immunosuppression needs further evaluation.
Comparison of Using Second-Generation Cryoballoon and Radiofrequency Catheter for Atrial Fibrillation Ablation in Patients With the Common Ostium of Inferior Pulmonary Veins

Aims: To compare the procedural outcomes of cryoballoon ablation (CBA) and radiofrequency ablation (RFA) in atrial fibrillation (AF) patients with the common ostium of inferior pulmonary veins (COIPV) and to explore the effect of COIPV on CBA performance through the assessment of anatomical factors. Methods: A total of 18 AF patients with COIPV were included. Pulmonary vein isolation (PVI) was performed with second-generation CBA or RFA. The anatomical characteristics of COIPV and procedural outcomes were collected. Results: The prevalence of COIPV was 0.82% in the enrolled population. PVI was achieved in all pulmonary veins (PVs) without any complications. The “tricircle” strategy was applied for RFA, and the segmental freeze strategy was performed for CBA. Compared with RFA, CBA had shorter procedural time (median: 53.0 vs. 78.0 min, p < 0.001) and longer fluoroscopy time (median: 13.5 vs. 6.0 min, p < 0.001). Higher ovality index of the ostium was seen in patients with ≥4 freezes in inferior PVs [IPVs; 0.95 (0.78–1.05) vs. 0.49 (0.21–0.83), p = 0.047]. During a median of 23.5 months of follow-up, the atrial arrhythmias-free survival after the procedure was comparable between CBA and RFA (p = 0.729). Conclusion: The second-generation CBA is an efficient and safe alternative for RFA in AF patients with COIPV. Anatomical characteristics of COIPV bring the challenge to the procedure performance of RFA and CBA.