Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters

Recently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including acute myeloid leukemia (AML). Our group demonstrated promising clinical response using adoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cells in AML patients. Moreover, the antileukemic effect was correlated with the dose of infused alloreactive NK cells (“functional NK cell dose”). Herein, we update the results of our previous study on a cohort of adult AML patients (median age at enrollment 64) in first morphological complete remission (CR), not eligible for allogeneic stem cell transplantation. After an extended median follow-up of 55.5 months, 8/16 evaluable patients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2 × 105/kg).
Sotalol Treatment may Interfere With Retrieval, Expression, and/or Reconsolidation Processes Thus Disrupting Traumatic Memories in a Post-Traumatic Stress Disorder Mice Model

The processes by which fear memory is encoded, consolidated, and re-consolidated are extremely complex and appear to require the release of stress hormones, especially adrenaline (AD). AD improves contextual fear memory, acting specifically on peripheral β2-adrenoceptors. Propranolol (peripheral and central β-adrenoceptor antagonist) treatment was shown to prevent post-traumatic stress disorder (PTSD) development and reduce its symptoms. However, propranolol has several side effects. Thus, we aimed to evaluate if sotalol (a peripheral β-adrenoceptor antagonist) treatment interferes with retrieval, expression, and/or reconsolidation of traumatic memories in a validated mice model that mimics the signs/symptoms of PTSD, thus intending to decrease them. Female mice were induced with PTSD following an established protocol. Sotalol (2.0 mg/kg) or vehicle were administered on days 2, 7, and 14. The percentage of freezing was calculated, and behavioral tests were carried out. Catecholamines in plasma were quantified by HPLC with electrochemical detection. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of NR4A family genes in hippocampus. Following the submission of the animals to the same aversive context on days 2, 7, and 14, sotalol-treated mice exhibited significant less freezing behavior. In the elevated plus-maze test, the time spent and number of entries in the open arms, and total arm entries were increased in sotalol-treated mice. Also, the light-dark transition test revealed higher time spent, number of transitions to the light, and total number of transitions in sotalol-treated mice. Moreover, plasma AD was significantly decreased in sotalol-treated mice. On day 14, sotalol-treated mice exhibited a decrease in mRNA expression of Nr4a1 in the hippocampus. In conclusion, in PTSD mice model, sotalol appears to decrease traumatic memories and anxiety-like behavior, probably due to a decrease in peripheral adrenergic activity, which influences traumatic memories. The effects of sotalol upon re-exposure to the traumatic context may be consistent with interference in the retrieval, expression, and/or reconsolidation processes of contextual traumatic memory, resulting in a long-term reduction of PTSD symptoms and signs. The decreased Nr4a1 mRNA expression in the hippocampal formation may be crucial for these mice to develop diminished traumatic contextual memories after sotalol therapy in PTSD.
Current Perspectives on Gastrointestinal Models to Assess Probiotic-Pathogen Interactions

There are different models available that mimic the human intestinal epithelium and are thus available for studying probiotic and pathogen interactions in the gastrointestinal tract. Although, in vivo models make it possible to study the overall effects of a probiotic on a living subject, they cannot always be conducted and there is a general commitment to reduce the use of animal models. Hence, in vitro methods provide a more rapid tool for studying the interaction between probiotics and pathogens; as well as being ethically superior, faster, and less expensive. The in vitro models are represented by less complex traditional models, standard 2D models compromised of culture plates as well as Transwell inserts, and newer 3D models like organoids, enteroids, as well as organ-on-a-chip. The optimal model selected depends on the research question. Properly designed in vitro and/or in vivo studies are needed to examine the mechanism(s) of action of probiotics on pathogens to obtain physiologically relevant results.
Practical issues of pragmatic case marking variations in the Kenhat varieties of Ladakh

The two Ladakhi dialect groups: Kenhat (Upper Ladakh) and Shamskat (Lower Ladakh) behave differently with respect to case marking variation. The Kenhat dialects are more sensitive to downgrading on the transitivity scale and allow more pragmatically conditioned variation between ergative and absolutive marking of agents. The more transitive a verb is, the more likely the 'subject' is to receive an ergative marker and vice versa. Pragmatic alternations occur mainly in the middle field, and are less likely to occur on the highest or lowest level. Several other Tibetan varieties have reduced case marking to a minimum. Depending on how severely case marking is reduced, there may be different solutions to the problems of elicitation and of creating an appropriate lexical entry. In this contribution, I will mainly focus on that type of varieties where case marking is (still) quite robust, and will exemplify this type with the dialect of Gya-Miru of the Kenhat group.
Identification of Ferroptosis-Related Biomarkers for Prognosis and Immunotherapy in Patients With Glioma

Ferroptosis is a novel type of iron- and ROS-dependent cell death and is involved in various diseases. LncRNAs are involved and play important roles in the occurrence and development of several cancers. However, researches about the role of ferroptosis-related lncRNAs in glioma are relatively rare. Here, we identified nine ferroptosis-related lncRNAs and then constructed a prognostic model by the LASSO and Cox analysis. The model could predict overall survival with high sensitivity and specificity according to ROC curves. In addition, the cell cycle, p53 signaling, apoptosis, and oxidative phosphorylation pathways were obviously enriched in the pathogenesis of glioma by gene set enrichment analysis. A nomogram was constructed by integrating several independent prognostic clinicopathological features, and it could provide a valuable predictive tool for overall survival. Furthermore, a strong correlation between these nine lncRNAs and immunotherapy was found. Glioma patients in the high-risk group had higher TMB using somatic mutation data, different immune infiltration, and higher expression of immune checkpoints, indicating these patients might benefit from immune checkpoint inhibitor therapy. In summary, these nine ferroptosis-related lncRNAs were promising biomarkers for predicting overall survival and guiding immunotherapy or future immune checkpoint inhibitor development for glioma patients.
Chimeric Mice Engrafted With Canine Hepatocytes Exhibits Similar AAV Transduction Efficiency to Hemophilia B Dog

Adeno-associated virus (AAV) mediated gene therapy has been successfully applied in clinical trials, including hemophilia. Novel AAV vectors have been developed with enhanced transduction and specific tissue tropism. Considering the difference in efficacy of AAV transduction between animal models and patients, the chimeric xenograft mouse model with human hepatocytes has unique advantages of studying AAV transduction efficiency in human hepatocytes. However, it is unclear whether the results in humanized mice can predict AAV transduction efficiency in human hepatocytes. To address this issue, we studied the AAV transduction efficacy in canine hepatocytes in both canine hepatocyte xenografted mice and real dogs. After administration of AAV vectors from different serotypes into canine hepatocyte xenograft mice, AAV8 induced the best canine hepatocyte transduction followed by AAV9, then AAV3, 7, 5 and 2. After administration of AAV/cFIX (cFIX-opt-R338L) vectors in hemophilia B dogs, consistent with the result in chimeric mice, AAV8 induced the highest cFIX protein expression and function, followed by AAV9 and then AAV2. These results suggest that mice xenografted with hepatocytes from different species could be used to predict the AAV liver transduction in real species and highlight this potential platform to explore novel AAV variants for future clinical applications.
Avoidant Attachment, Withdrawal-Aggression Conflict Pattern, and Relationship Satisfaction: A Mediational Dyadic Model

This study was conducted with the purpose of analyzing the combined and mediating effect of actor’s withdrawal–partner’s demand conflict resolution strategies between avoidance attachment dimension and relationship satisfaction. We conducted a dyadic study with 175 heterosexual couples (aged between 18 and 72 years) who filled in the questionnaires. Six hypotheses were tested using the actor–partner interdependence model with mediation analysis (APIMeM). Results showed that the avoidance dimension of attachment was more strongly associated with actor’s withdrawal strategy than with demand/aggression strategy. Furthermore, avoidance attachment was negatively associated with both actor’s and partner’s relationship satisfaction, the actor effect being higher. Withdrawal strategy was a mediator between actor’s avoidance and actor’s relationship satisfaction, but it was not a mediator for partner’s relationship satisfaction. The interactive pattern of actor’s withdrawal–partner’s demand/aggression was associated with low levels of both actor’s and partner’s relationship satisfaction. These results point out to the need of discerning the interactive pattern of conflict-solving strategies as well as their intertwined effect on relationship satisfaction.
Comparison of the Detection and Ligation of Patent Processus Vaginalis Between Laparoscopy-Assisted Transscrotal Orchiopexy and Single Scrotal Incision Orchiopexy

This study aimed to compare the detection and ligation of patent processus vaginalis (PPV) between laparoscopy-assisted transscrotal orchidopexy (LATO) and single scrotal incision orchiopexy (SSIO) for low palpable undescended testis (UDT). We performed a retrospective medical record review of transscrotal orchidopexies performed for low palpable UDT at our institution from 2017 to 2019; 33 and 39 boys underwent LATO and SSIO, respectively. Data collection included patient demographics, incidence of PPV, operative time, and clinical outcomes. All 95 testes were delivered into the scrotum. There was no significant difference between the two groups with respect to patients' age, side, and mean operative time. The incidence of PPV in the LATO group was significantly higher than that in the SSIO group (56.52 vs. 34.69%, P = 0.04). The incidence of contralateral PPV in the LATO group was 45%. One patient in the SSIO group underwent unilateral PV ligation and laparoscopic exploration revealed bilateral PPV owing to metachronous contralateral hydrocele. One patient in the LATO group demonstrated obliterated PV in the initial transscrotal procedure, but an ipsilateral PPV was found in the latter laparoscopic procedure. In conclusion, LATO has a higher detection rate and higher ligation of the PPV than SSIO, suggesting that, LATO may help reduce recurrent PPV-related issues. However, long-term follow-up results are needed to evaluate the advantages and disadvantages in a larger case series.
Multifocal Cerebral Microinfarcts Modulate Early Alzheimer’s Disease Pathology in a Sex-Dependent Manner

Alzheimer’s disease (AD) constitutes a major cause of dementia, affecting more women than men. It is characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles (NFTs) formation, associated with a progressive cognitive decline. Evidence indicates that AD onset increases the prevalence of cerebral microinfarcts caused by vascular pathologies, which occur in approximately in half of AD patients. In this project, we postulated that multifocal cerebral microinfarcts decisively influence early AD-like pathology progression in a sex dependent manner in young APP/PS1 mice. For this purpose, we used a novel approach to model multifocal microinfarcts in APP/PS1 mice via the sporadic occlusions of the microvasculature. Our findings indicate that microinfarcts reduced Aβ deposits without affecting soluble Aβ levels in the brain of male and female APP/PS1 mice, while causing rapid and prolonged cognitive deficits in males, and a mild and transient cognitive decline in females. In male APP/PS1 mice, microinfarcts triggered an acute hypoperfusion followed by a chronic hyperperfusion. Whereas in female APP/PS1 mice, microinfarcts caused an acute hypoperfusion, which was recovered in the chronic phase. Microinfarcts triggered a robust microglial activation and recruitment of peripheral monocytes to the lesion sites and Aβ plaques more potently in female APP/PS1 mice, possibly accounting for the reduced Aβ deposition. Finally, expression of Dickkopf-1 (DKK1), which plays a key role in mediating synaptic and neuronal dysfunction in AD, was strongly induced at the lesion sites of male APP/PS1 mice, while its expression was reduced in females. Our findings suggest that multifocal microinfarcts accelerate AD pathology more potently in young males compared to young females independently upon Aβ pathology via modulation of neurovascular coupling, inflammatory response, and DKK1 expression. Our results suggest that the effects of microinfarcts should be taken into consideration in AD diagnosis, prognosis, and therapies.
Augmented Features Synergize Radiomics in Post-Operative Survival Prediction and Adjuvant Therapy Recommendation for Non-Small Cell Lung Cancer

Background Owing to the cytotoxic effect, it is challenging for clinicians to decide whether post-operative adjuvant therapy is appropriate for a non-small cell lung cancer (NSCLC) patient. Radiomics has proven its promising ability in predicting survival but research on its actionable model, particularly for supporting the decision of adjuvant therapy, is limited. Methods Pre-operative contrast-enhanced CT images of 123 NSCLC cases were collected, including 76, 13, 16, and 18 cases from R01 and AMC cohorts of The Cancer Imaging Archive (TCIA), Jiangxi Cancer Hospital and Guangdong Provincial People’s Hospital respectively. From each tumor region, 851 radiomic features were extracted and two augmented features were derived therewith to estimate the likelihood of adjuvant therapy. Both Cox regression and machine learning models with the selected main and interaction effects of 853 features were trained using 76 cases from R01 cohort, and their test performances on survival prediction were compared using 47 cases from the AMC cohort and two hospitals. For those cases where adjuvant therapy was unnecessary, recommendations on adjuvant therapy were made again by the outperforming model and compared with those by IBM Watson for Oncology (WFO). Results The Cox model outperformed the machine learning model in predicting survival on the test set (C-Index: 0.765 vs. 0.675). The Cox model consists of 5 predictors, interestingly 4 of which are interactions with augmented features facilitating the modulation of adjuvant therapy option. While WFO recommended no adjuvant therapy for only 13.6% of cases that received unnecessary adjuvant therapy, the same recommendations by the identified Cox model were extended to 54.5% of cases (McNemar’s test p = 0.0003). Conclusions A Cox model with radiomic and augmented features could predict survival accurately and support the decision of adjuvant therapy for bettering the benefit of NSCLC patients.
Long-Term Effects of Aircraft Noise Exposure on Vascular Oxidative Stress, Endothelial Function and Blood Pressure: No Evidence for Adaptation or Tolerance Development

Transportation noise is recognized as an important cardiovascular risk factor. Key mechanisms are noise-triggered vascular inflammation and oxidative stress with subsequent endothelial dysfunction. Here, we test for adaptation or tolerance mechanisms in mice in response to chronic noise exposure. C57BL/6J mice were exposed to aircraft noise for 0, 4, 7, 14 and 28d at a mean sound pressure level of 72 dB(A) and peak levels of 85 dB(A). Chronic aircraft noise exposure up to 28d caused persistent endothelial dysfunction and elevation of blood pressure. Likewise, reactive oxygen species (ROS) formation as determined by dihydroethidium (DHE) staining and HPLC-based measurement of superoxide formation in the aorta/heart/brain was time-dependently increased by noise. Oxidative burst in the whole blood showed a maximum at 4d or 7d of noise exposure. Increased superoxide formation in the brain was mirrored by a downregulation of neuronal nitric oxide synthase (Nos3) and transcription factor Foxo3 genes, whereas Vcam1 mRNA, a marker for inflammation was upregulated in all noise exposure groups. Induction of a pronounced hearing loss in the mice was excluded by auditory brainstem response audiometry. Endothelial dysfunction and inflammation were present during the entire 28d of aircraft noise exposure. ROS formation gradually increases with ongoing exposure without significant adaptation or tolerance in mice in response to chronic noise stress at moderate levels. These data further illustrate health side effects of long-term noise exposure and further strengthen a consequent implementation of the WHO noise guidelines in order to prevent the development of noise-related future cardiovascular disease.
Dominance of Diffusive Methane Emissions From Lowland Headwater Streams Promotes Oxidation and Isotopic Enrichment

Inland waters are the largest natural source of methane (CH4) to the atmosphere, yet the contribution from small streams to this flux is not clearly defined. To fully understand CH4 emissions from streams and rivers, we must consider the relative importance of CH4 emission pathways, the prominence of microbially-mediated production and oxidation of CH4, and the isotopic signature of emitted CH4. Here, we construct a complete CH4 emission budgets for four lowland headwater streams by quantifying diffusive CH4 emissions and comparing them to previously published rates of ebullitive emissions. We also examine the isotopic composition of CH4 along with the sediment microbial community to investigate production and oxidation across the streams. We find that all four streams are supersaturated with respect to CH4 with diffusive emissions accounting for approximately 78–100% of total CH4 emissions. Isotopic and microbial data suggest CH4 oxidation is prevalent across the streams, depleting approximately half of the dissolved CH4 pool before emission. We propose a conceptual model of CH4 production, oxidation, and emission from small streams, where the dominance of diffusive emissions is greater compared to other aquatic ecosystems, and the impact of CH4 oxidation is observable in the emitted isotopic values. As a result, we suggest the CH4 emitted from small streams is isotopically heavy compared to lentic ecosystems. Our results further demonstrate streams are important components of the global CH4 cycle yet may be characterized by a unique pattern of cycling and emission that differentiate them from other aquatic ecosystems.
Mucus Hypersecretion and Ciliary Impairment in Conducting Airway Contribute to Alveolar Mucus Plugging in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease attributed to the complex interplay of genetic and environmental risks. The muco-ciliary clearance (MCC) system plays a critical role in maintaining the conduit for air to and from the alveoli, but it remains poorly understood whether the MCC abnormalities in conducting airway are involved in IPF pathogenesis. In this study, we obtained the surgically resected bronchi and peripheral lung tissues from 31 IPF patients and 39 control subjects, and we sought to explore the morphologic characteristics of MCC in conducting airway by using immunostaining and scanning and transmission electron microscopy. In the submucosal regions of the bronchi, we found that the areas of mucus glands (MUC5B+) were significantly larger in IPF patients as compared with control subjects (p < 0.05). In the surface epithelium of three airway regions (bronchi, proximal bronchioles, and distal bronchioles), increased MUC5B and MUC5AC expression of secretory cells, decreased number of ciliated cells, and increased ciliary length were observed in IPF patients than control subjects (all p < 0.05). In addition, the mRNA expression levels of MUC5B were up-regulated in both the bronchi and peripheral lung of IPF patients than those of control subjects (p < 0.05), accompanied with 93.55% IPF subjects who had obvious MUC5B+ mucus plugs in alveolar regions. No MUC5B rs35705950 single-nucleotide polymorphism allele was detected in both IPF patients and control subjects. Our study shows that mucus hypersecretion and ciliary impairment in conducting airway are major causes of mucus plugs in alveolar regions and may be closely related to the alveolar injuries in IPF patients.
Impact of the COVID-19 Lockdown on Quality of Life in Pregnant Women

Background The COVID-19 pandemic has been associated with significant impacts on mental health and well-being of populations worldwide. However, little is known about its significant impact on psychological aspects of vulnerable population groups such as pregnant women. Therefore, the aim of the study was to determine the psychological impact of the COVID-19 pandemic among pregnant women in mainland China. Methods A cross-sectional survey was performed between July and August 2020 using a modified validated 40-item questionnaire which consisted of sociodemographics, attitude, lifestyle changes and the Impact of Event Scale (IES) toward COVID-19 using snowball and convenience samplings. Results A total of 1,078 participants were included in the study. The mean age of participants was 29.4 ± 4.0 years. Overall, the mean IES of participants was 30.6 ± 12.8 (i.e., moderate-to-severe stressful impact) amidst the COVID-19 pandemic, with 63.9% of participants had an IES score ≥26. Despite increased family and social support, more than half of participants also reported increased feeling of being horrified, apprehensive and helpless. Conclusions The COVID-19 pandemic has several psychological impacts on pregnant women. Therefore, based on these valuable data of pregnant women collected, we recommend that a thoughtful planning and time preparation by the government would definitely help to reduce the negative impacts caused by the COVID-19 pandemic and restore the quality of life among pregnant women. Further research is needed to identify vulnerable groups including pregnant women to better adapt and inform mental health interventions and policies by health authorities.
AMPA Receptor Function in Hypothalamic Synapses

AMPA receptors (AMPARs) are critical for mediating glutamatergic synaptic transmission and plasticity, thus playing a major role in the molecular machinery underlying cellular substrates of memory and learning. Their expression pattern, transport and regulatory mechanisms have been extensively studied in the hippocampus, but their functional properties in other brain regions remain poorly understood. Interestingly, electrophysiological and molecular evidence has confirmed a prominent role of AMPARs in the regulation of hypothalamic function. This review summarizes the existing evidence on AMPAR-mediated transmission in the hypothalamus, where they are believed to orchestrate the role of glutamatergic transmission in autonomous, neuroendocrine function, body homeostasis, and social behavior.