Miracle-dz/UniFAR-FTUs huggingface dataset:
Academic Self-Regulation, Chronotype and Personality in University Students During the Remote Learning Phase due to COVID-19

During the COVID-19 shutdown phase in Germany, universities stopped presence teaching and students had to turn to digital instruction. To examine their capability to cope with the changed learning situation, we assessed how basic psychological need satisfaction and frustration, motivational regulation, vitality, and self-efficacy of 228 German biology-teaching students (75% female) relate to their chronotype and personality (Big Five). Specifically, we were interested in possible effects of chronotype and personality dimensions on variables related to successful remote learning. Since the pandemic and remote learning will accompany teaching and learning at university in 2021, predictors of successful remote learning need to be identified to support student learning optimally in digital learning environments. In our study, morning-oriented, conscientious, and open students with low neuroticism seem to better cope with the shutdown environment due to vitality, self-efficacy, and partly their self-determined motivation. Moreover, our findings implicate students might need different support depending on their chronotype and personality during the digital learning phase.
Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide

Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications.
Movement Synchrony in the Psychotherapy of Adolescents With Borderline Personality Pathology – A Dyadic Trait Marker for Resilience?

Movement synchrony describes the coordination of body movements. In psychotherapy, higher movement synchrony between therapist and patient has been associated with higher levels of empathy, therapeutic alliance, better therapy outcome, and fewer drop-outs. The current study investigated movement synchrony during the psychotherapeutic treatment of female adolescents with borderline personality disorder. It was hypothesized that there are higher levels of movement synchrony in the analyzed therapy sessions compared to pseudo-interactions. Further, we tested whether higher levels of movement synchrony correlate with stronger patients’ symptom reduction and whether higher movement synchrony predicts higher post-session ratings. A total of 356 sessions from 16 completed psychotherapies of adolescent patients with BPD were analyzed. Movement synchrony was assessed with motion energy analysis and an index of synchrony was calculated by lagged cross-correlation analysis. As hypothesized, the findings support higher levels of movement synchrony in therapy sessions compared to pseudo-interactions (Cohen’s d = 0.85). Additionally, a correlation of movement synchrony with better therapy outcome was found (standardized beta = −0.43 indicating stronger personality functioning impairment reduction). The post-session ratings were negatively associated with higher levels of movement synchrony (standardized beta = −0.1). The relevance of movement synchrony and potential implications for clinical practice are discussed.
The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

Background: Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis. Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures. Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels. Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation. Clinical Trial Registration: https://clinicaltrials.gov/, identifier: NCT04389762.
Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

The tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of “hot” tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an “anti-tumor school” and an “antibody factory” to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy.
EGF-Induced miR-223 Modulates Goat Mammary Epithelial Cell Apoptosis and Inflammation via ISG15

The health of mammary gland is essential for lactation. Epidermal growth factor (EGF) is reported to play an important role in lactation initiation and miR-223 is a conserved microRNA in anti-inflammation. In this study, EGF was found to induce a higher expression of miR-223 in goat mammary epithelial cell (gMEC). The downstream genes of miR-223 were screened by RNA sequencing, including Interferon-stimulated gene product 15 (ISG15), a pivotal immune responder, which was detected to be downregulated by EGF and miR-223. Due to the correlation between inflammation and apoptosis, the gMEC apoptosis modulated by EGF, miR-223, and ISG15 was investigated, and the protein expressions of Bcl-2/Bax, Caspase 3 and p53 were examined to evaluate the apoptosis of gMEC. The protein expressions of p-STAT3/STAT3, PR, FOXC1, and HOXA10, which had been shown to be related to inflammation, were detected to assess the inflammation of gMEC. This study provided a regulation axis, EGF/miR-223/ISG15, and illustrated its regulation to gMEC apoptosis and inflammation.
When Is Simultaneous Recording Necessary? A Guide for Researchers Considering Combined EEG-fMRI

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provide non-invasive measures of brain activity at varying spatial and temporal scales, offering different views on brain function for both clinical and experimental applications. Simultaneous recording of these measures attempts to maximize the respective strengths of each method, while compensating for their weaknesses. However, combined recording is not necessary to address all research questions of interest, and experiments may have greater statistical power to detect effects by maximizing the signal-to-noise ratio in separate recording sessions. While several existing papers discuss the reasons for or against combined recording, this article aims to synthesize these arguments into a flow chart of questions that researchers can consider when deciding whether to record EEG and fMRI separately or simultaneously. Given the potential advantages of simultaneous EEG-fMRI, the aim is to provide an initial overview of the most important concepts and to direct readers to relevant literature that will aid them in this decision.
Immunohistochemical Expressions of Senescence-Associated Secretory Phenotype and Its Association With Immune Microenvironments and Clinicopathological Factors in Invasive Breast Cancer

This study was undertaken to investigate immunohistochemical expression of the senescence-associated secretory phenotype (SASP) in invasive breast cancer (IBC) tissues and to determine relationships between SASP positivity and tumor microenvironments and the clinicopathological characteristics of IBC. Immunohistochemistry for senescence markers, that is, high mobility group box-1 (HMGB1), p16, p15, and decoy receptor 2 (DCR2), was performed in tissue microarrays of 1140 IBC samples. Cases positive for at least one of these four markers were considered SASP-positive. Relations between SASP and tumor characteristics, including immune microenvironments (stromal tumor-infiltrating lymphocytes [sTILs] density and numbers of intraepithelial CD103-positive [iCD103 + ] lymphocytes) and clinical outcomes were retrospectively evaluated. HMGB1, p16, p15, or DCR2 was positive in 6.7%, 26.6%, 21.1%, and 26.5%, respectively, of the 1,140 cases. Six hundred and five (53.1%) cases were SASP positive, and SASP positivity was significantly associated with histologic grade 3, high-sTIL and iCD103 + lymphocyte counts, absence of ER or PR, and a high Ki-67 index. Although SASP did not predict breast cancer-specific survival (BCSS) or disease-free survival (DFS) in the entire cohort, SASP positivity in luminal A IBC was associated with poor BCSS and DFS. However, patients with SASP-positive TNBC showed better survival than those with SASP-negative TNBC. In multivariate analysis, SASP positivity was an independent prognostic factor in both luminal A IBC and TNBC, although the effect on prognosis was the opposite. In conclusion, SASP would be involved in the modulation of immune microenvironments and tumor progression in IBC, and its prognostic significance depends on molecular subtype.
Influence of Group Identification on Malicious and Benign Envy: A Cross-Sectional Developmental Study

Envy is the result of a social comparison that shows us a negative image of ourselves. The present study addresses the effect of the context of group comparison and group identification on children's expression of this emotion. Through different stories, participants aged between 6 and 11 years were exposed to four contexts of upward social comparison in which they had to adopt the role of the disadvantaged character. From their emotional responses and their decisions in a resource allocation task, three response profiles were created: malicious envy, benign envy, and non-envy. Although we found important differences between verbal and behavioral responses, the results showed greater envy, both malicious and benign, when the envied was an out-group. On the other hand, when the envied belonged to the in-group and competed with a member of the out-group, malicious but not benign envy practically disappeared. With age, envious responses decreased, and non-envious responses increased. The role of social identity in the promotion and inhibition of envy is discussed, as well as the acquisition of emotional display rules in the benign envy and non-envy profiles.
Coffee Consumption Modulates Amoxicillin-Induced Dysbiosis in the Murine Gut Microbiome

The microbiome is essential for host health, and perturbations resulting from antibiotic use can lead to dysbiosis and disease. Diet can be a powerful modulator of microbiome composition and function, with the potential to mitigate the negative effects of antibiotic use. Thus, it is necessary to study the impacts of diet and drug interactions on the gut microbiome. Coffee is a commonly consumed beverage containing many compounds that have the potential to affect the microbiome, including caffeine, polyphenols, and fiber. We supplemented mice with caffeinated and decaffeinated coffee in conjunction with amoxicillin, and used 16S rRNA amplicon sequencing of fecal samples to investigate changes in diversity and composition of the murine fecal microbiome. We found that antibiotics, regardless of coffee supplementation, caused significant disruption to the murine fecal microbiome, enriching for Proteobacteria, Verrucomicrobia, and Bacteroidetes, but reducing Firmicutes. While we found that coffee alone did not have a significant impact on the composition of the fecal microbiome, coffee supplementation did significantly affect relative abundance metrics in mice treated with amoxicillin. After caffeinated coffee supplementation, mice treated with amoxicillin showed a smaller increase in Proteobacteria, specifically of the family Burkholderiaceae. Correspondingly we found that in vitro, Burkholderia cepacia was highly resistant to amoxicillin, and that it was inhibited by concentrations of caffeine and caffeinated coffee comparable to levels of caffeine in murine ceca. Overall, this work shows that coffee, and possibly the caffeine component, can impact both the microbiome and microbiome members during antibiotic exposure.
Malaria in Europe: A Historical Perspective

Endemic malaria, which claimed 229 million new cases and 409,000 deaths in 2019 mainly in Africa, was eradicated from Europe by the mid-20th century. Historical descriptions of intermittent tertian and quartan fever reported in texts of Hippocrates in Greece and Celsus in Italy suggest malaria. A few paleomicrobiology investigations have confirmed the presence of malarial parasite Plasmodium falciparum in 1st, 2nd, and 5th century infected individuals in diverse regions of Italy, and Plasmodium sp. later in Bavaria. The causative Plasmodium pathogens, discovered in the 19th century in Algeria, were controversially used as therapeutic agents in the European pharmacopeia more than two centuries after effective quinine-based treatments had been introduced in Europe. How Europe managed to eradicate malaria and what the history of malaria was in Europe are of medical interest, and this review traces research pathways for a renewed understanding of malaria eradication in Europe through combined historical and paleomicrobiological investigations.
Pharmacological Assessment of the Antiprotozoal Activity, Cytotoxicity and Genotoxicity of Medicinal Plants Used in the Treatment of Malaria in the Greater Mpigi Region in Uganda

We investigated the potential antimalarial and toxicological effects of 16 medicinal plants frequently used by traditional healers to treat malaria, fever, and related disorders in the Greater Mpigi region in Uganda. Species studied were Albizia coriaria, Cassine buchananii, Combretum molle, Erythrina abyssinica, Ficus saussureana, Harungana madagascariensis, Leucas calostachys, Microgramma lycopodioides, Morella kandtiana, Plectranthus hadiensis, Securidaca longipedunculata, Sesamum calycinum subsp. angustifolium, Solanum aculeastrum, Toddalia asiatica, Warburgia ugandensis, and Zanthoxylum chalybeum. In addition, the traditional healers indicated that P. hadiensis is used as a ritual plant to boost fertility and prepare young women and teenagers for motherhood in some Ugandan communities where a high incidence of rapidly growing large breast masses in young female patients was observed (not necessarily breast cancer). We present results from various in vitro experiments performed with 56 different plant extracts, namely, 1) an initial assessment of the 16 species regarding their traditional use in the treatment of malaria by identifying promising plant extract candidates using a heme biocrystallization inhibition library screen; 2) follow-up investigations of antiprotozoal effects of the most bioactive crude extracts against chloroquine-resistant P. falciparum K1; 3) a cytotoxicity counterscreen against human MRC-5SV2 lung fibroblasts; 4) a genotoxicity evaluation of the extract library without and with metabolic bioactivation with human S9 liver fraction; and 5) an assessment of the mutagenicity of the ritual plant P. hadiensis. A total of seven extracts from five plant species were selected for antiplasmodial follow-up investigations based on their hemozoin formation inhibition activity in the heme biocrystallization assay. Among other extracts, an ethyl acetate extract of L. calostachys leaves exhibited antiplasmodial activity against P. falciparum K1 (IC50 value: 5.7 µg/ml), which was further characterized with a selectivity index of 2.6 (CC50 value: 14.7 µg/ml). The experiments for assessment of potential procarcinogenic properties of plant extracts via evaluation of in vitro mutagenicity and genotoxicity indicated that few extracts cause mutations. The species T. asiatica showed the most significant genotoxic effects on both bacterial test strains (without metabolic bioactivation at a concentration of 500 µg/plate). However, none of the mutagenic extracts from the experiments without metabolic bioactivation retained their genotoxic activity after metabolic bioactivation of the plant extract library through pre-incubation with human S9 liver fraction. While this study did not show that P. hadiensis has genotoxic properties, it did provide early stage support for the therapeutic use of the medicinal plants from the Greater Mpigi region.
Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors

Immunotherapy explores several strategies to enhance the host immune system’s ability to detect and eliminate cancer cells. The use of antibodies that block immunological checkpoints, such as anti–programed death 1/programed death 1 ligand and cytotoxic T-lymphocyte–associated protein 4, is widely recognized to generate a long-lasting antitumor immune response in several types of cancer. Evidence indicates that the elimination of tumors by T cells is the key for tumor control. It is well known that costimulatory and coinhibitory pathways are critical regulators in the activation of T cells. Besides blocking checkpoints inhibitors, the agonistic signaling on costimulatory molecules also plays an important role in T-cell activation and antitumor response. Therefore, molecules driven to costimulatory pathways constitute promising targets in cancer therapy. The costimulation of tumor necrosis factor superfamily receptors on lymphocytes surface may transduce signals that control the survival, proliferation, differentiation, and effector functions of these immune cells. Among the members of the tumor necrosis factor receptor superfamily, there are 4-1BB and OX40. Several clinical studies have been carried out targeting these molecules, with agonist monoclonal antibodies, and preclinical studies exploring their ligands and other experimental approaches. In this review, we discuss functional aspects of 4-1BB and OX40 costimulation, as well as the progress of its application in immunotherapies.