Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Exercise on Immunometabolism in Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS.
Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real‐world setting. A GIMEMA‐ERIC and US study

Limited information is available on the efficacy of front‐line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real‐world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty‐seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression‐free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02‐1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33‐0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first‐line regimen in a real‐world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.
NASTAVNO-NAUČNOM VEĆU FARMACEUTSKOG FAKULTETA UNIVERZITETA U BEOGRADU TO THE ACADEMIC COUNCIL OF THE FACULTY OF PHARMACY – UNIVERSITY OF BELGRADE KOMISIJI ZA POSLEDIPLOMSKE STUDIJE TO THE COMMITTEE FOR POSTGRADUATE STUDIES

Na sednici Nastavno-naučnog veća Farmaceutskog fakulteta u Beogradu, održanoj 22.12. 2016. godine imenovani su članovi Komisije za ocenu i odbranu završene doktorske disertacije, kandidata dipl. farm. Musbah Salem Mohamed Shenger, pod naslovom: The Academic Council of the Faculty of Pharmacy at the University of Belgrade on the meeting held on December 22, 2016 has nominated the Commission for evaluation and defence of doctoral dissertation of the candidate BSc in pharmacy Musbah Salem Mohamed Shenger, entitled:
The battle for survival between severe acute respiratory syndrome coronavirus 2 and human beings.

DOI:10.1097/COH.0000000000000651 In December 2019, the coronavirus disease 2019 (COVID-19) outbreak was discovered among a group of pneumonia patients primarily associated with a seafood market in Wuhan city, China [1]. Almost simultaneously, several groups of scientists confirmed that the causative agent was indeed a novel coronavirus (CoV), now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1–4]. The prompt isolation and sequence sharing of SARS-CoV-2 has remarkably led to rapid diagnosis and paved the way for drug and vaccine discovery. By the end of August 2020, SARS-CoV-2 infection has resulted in over 24 million confirmed cases and over 831 000 deaths worldwide based on data from the WHO. Like the HIV/AIDS pandemic, COVID-19 has overstepped geographic borders and become a not only scientific, but also social, economic and political crisis. As a microorganism, SARS-CoV-2 must rely on host cells for survival. On the contrary, SARS-CoV-2 selecting humans as its host has led to a 3.4% mortality rate across the world. To prevent further loss of lives, we must fight SARS-CoV-2 by implementing effective evidence-based measures including rapid diagnosis, patient quarantine, universal masking, social distancing and early treatment before the success of a safe and effective vaccine. In this special issue on COVID-19, we invite a group of frontline scientists to share their professional experiences in the fight against the global crisis. With the COVID-19 pandemic occurring in the same era as the persisting AIDS pandemic, we hope that this sharing of scientific experiences will inspire more effective measures for disease control. With this opportunity, I am also grateful to share my own views and research experience on COVID-19 as follows. Mounting evidence has indicated that COVID19 is likely a consequence of zoonotic transmission [1–5]. Based on viral genome analysis, SARS-CoV-2 is suspected to have originated from a novel betaCoV [1–4]. Nevertheless, there are still a range of reasons why the definitive origin of SARS-CoV-2 remains an unanswered scientific question. First,
Epitranscriptomic regulation by m6A RNA methylation in brain development and diseases

Cellular RNAs are pervasively tagged with diverse chemical moieties, collectively called epitranscriptomic modifications. The methylation of adenosine at N6 position generates N6-methyladenosine (m6A), which is the most abundant and reversible epitranscriptomic modification in mammals. The m6A signaling is mediated by a dedicated set of proteins comprised of writers, erasers, and readers. Contrary to the activation–repression binary view of gene regulation, emerging evidence suggests that the m6A methylation controls multiple aspects of mRNA metabolism, such as splicing, export, stability, translation, and degradation, culminating in the fine-tuning of gene expression. Brain shows the highest abundance of m6A methylation in the body, which is developmentally altered. Within the brain, m6A methylation is biased toward neuronal transcripts and sensitive to neuronal activity. In a healthy brain, m6A maintains several developmental and physiological processes such as neurogenesis, axonal growth, synaptic plasticity, circadian rhythm, cognitive function, and stress response. The m6A imbalance contributes to the pathogenesis of acute and chronic CNS insults, brain cancer, and neuropsychiatric disorders. This review discussed the molecular mechanisms of m6A regulation and its implication in the developmental, physiological, and pathological processes of the brain.
Subgroups of Pediatric Patients With Functional Abdominal Pain

Supplemental Digital Content is available in the text. Objectives: Prior work in a cohort of youth with functional abdominal pain (FAP) identified patient subgroups (High Pain Dysfunctional, High Pain Adaptive, Low Pain Adaptive) that predicted differences in the course of FAP from childhood into young adulthood. We aimed to replicate these subgroups in a new sample of adolescents with FAP using the original classification algorithm and to extend subgroup characteristics to include parental characteristics and health service use. Methods: Adolescents (n=278; ages 11 to 17 y, 66% females) presenting to a gastroenterology clinic for abdominal pain, and their parents (92% mothers) completed self-report measures; adolescents also completed a 7-day pain diary. Results: The replicated patient subgroups exhibited distress and impairment similar to subgroups in the original sample. Moreover, in novel findings, the High Pain Dysfunctional subgroup differed from other subgroups by the predominance of mother-daughter dyads jointly characterized by high levels of anxiety, depressive symptoms, pain behavior, and pain catastrophizing. The High Pain Dysfunctional subgroup used more health care services than Low Pain Adaptive but did not differ from High Pain Adaptive. Discussion: Findings replicate and extend the original FAP classification and suggest that the subgroups have unique patient and parent features that may reflect distinct illness mechanisms requiring different treatments.
Early impact of COVID-19 outbreak on eye care: Insights from EUROCOVCAT group

The recent outbreak of coronavirus disease 2019 (COVID-19) has been declared a public health emergency worldwide. The scientific community has put in much effort and published studies that described COVID-19’s biology, transmission, clinical diagnosis, candidate therapeutics, and vaccines. However, to date, only a few data are available on the impact of COVID-19 pandemic on ophthalmological care in different health care systems, its future consequences in terms of disability, and access to sight-saving cures for many patients. To reduce human-to-human transmission of the virus and also ensure supply of infrastructures, human resources, and disposable medical devices to many regions, it is crucial to assess risks and postpone non-essential outpatient visits and elective surgical procedures, especially in older patients and those with comorbidities. This delay or suspension in essential eye procedures may cause significant and rapid vision impairment to irreversible blindness. Determining the risk-benefit profile of treating these ocular pathologies is a public health issue of supreme priority, even though many patients benefiting from therapeutic treatments are elderly, who are more vulnerable to COVID-19. If not reversible, this process could lead to a dramatic increase in disability and unsustainable social costs for many Governments.
Open- and Closed-Label Placebo and Nocebo Suggestions About a Sham Transdermal Patch

Supplemental digital content is available in the text. ABSTRACT Objective Placebo effects may occur when it is known that an inert substance is given (i.e., open-label placebo). It is not yet clear whether these effects are similar to concealed (i.e., closed-label) placebo effects for itch or whether nocebo effects can be induced under open-label conditions. Methods Healthy volunteers (n = 112) were randomized to an open-label (I) or closed-label (II) positive suggestions group, or an open-label (III) or closed-label (IV) negative suggestions group. Participants were told, as cover story, that a transdermal caffeine patch would be applied that positively influences cognitive abilities and, as a side effect, positively or negatively (depending on group allocation) influences itch. Participants in the open-label groups were given a rationale explaining placebo and nocebo effect mechanisms. Itch (the primary outcome) was induced at baseline and postsuggestions by histamine iontophoresis. Results Analyses of variance revealed significantly lower itch in the positive compared with the negative suggestions groups for both open- and closed-label contexts (all, p ≤ .008, Cohen d ≥ 0.47). Self-rated skin response was less severe after positive versus negative suggestions (all, p ≤ .017, Cohen d ≥ 0.33), but no effects on physical skin response were found (all, p ≥ .23, Cohen d ≤ 0.30). Conclusions Itch can be reduced by positive compared with negative suggestions under both open- and closed-label conditions. These findings indicate that open-label suggestions may potentially be a tool to use placebo effects for self-reported outcomes in clinical practice, for example, by explaining the role of expectancy in treatment. It needs to be investigated further under which circumstances an open-label rationale may impact placebo and nocebo effects. Trial Registration: www.trialregister. nl; NTR7174
Evidence for a robust, estradiol-associated sex difference in narrative-writing fluency.

Objective: Despite evidence for an estradiol-linked sex difference in verbal fluency favoring women, recent reviews question this difference. We therefore examined the issue based on a narrative task that we have administered to different populations for over 20 years. Method: We meta-analyzed 98 studies (N = 11,528) conducted by our laboratories and that featured measures of biological sex and storytelling. We ran primary-data analyses (N = 797) on an overlapping subset of these studies that also included salivary hormone and digit ratio measures. Results: Women told longer stories than men, d = 0.31, 95% CI [0.24, 0.38], an effect that did not vary by geographic region but was moderated by cue type (verbal: d = 0.57, [0.44, 0.71]; pictures: d = 0.29, [0.22, 0.36]), response modality (oral: d = -0.04, [-0.18, 0.09]; handwriting: d = 0.39, [0.31, 0.47]; typing: d = 0.31, [0.21, 0.42]), and age (prepubertal children: d = 0.13, [-0.04, 0.30]; pubescents: d = 0.48, [0.23, 0.74]; premenopausal adults: d = 0.36, [0.29, 0.42]; postmenopausal adults: d = -0.09, [-0.35, 0.16]). Consistent with the age effect, estradiol, a sex-dimorphic hormone during the reproductive life stage, was a specific mediator of the sex difference in narrative-writing fluency. This mediation effect was moderated by prenatal hormone exposure, estimated via digit ratio. Conclusions: When verbal fluency is assessed through narrative writing, a robust female advantage becomes evident. It is associated with the reproductive life stage and variations in current estradiol concentrations, particularly in individuals prenatally exposed to relatively more estradiol than testosterone. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Photoperiod Responses in Monoecious and Dioecious Hydrilla verticillata

Thirty-eight percent of monoecious hydrilla [Hydrilla verticillata (L.f.) Royle # HYLLI] grown from tubers produced new tubers after 28 days exposure to a 10-h photoperiod. One hundred percent of the plants grown at a 10-h photoperiod produced tubers by 56 days while only thirty-eight percent of those grown at a 12-h photoperiod did so. Plants grown at 14- or 16-h photoperiods did not produce tubers. Tubers appeared to be produced at the expense of new root and shoot tissue. Dioecious hydrilla (female) grown under similar conditions did not produce tubers by 56 days at any photoperiod examined. Relative growth rates (total dry weight) for both types did not differ with photoperiod and ranged between 81 ± 63 and 284 ± 52 mg·g-1·wk-1 (regression coefficient ± standard error; n = 30). In general, total chlorophyll (a+b) was greater for dioecious than for monoecious plants. The ratios of chlorophyll “a” to chlorophyll “b” and carotenoids to chlorophyll a changed with increasing photoperiod and plant age in a similar manner for both monoecious and dioecious plants.
An Age--Altitude Matrix Analysis of Hawaiian Rain-Forest Succession

Species composition and biomass of vascular plants were determined in a matrix of 29 sites on the wet eastern slope of Mauna Loa volcano, Hawaii. Sites were sampled at five or six altitudes (914-2438 m a.s.l.) on each of five known-age lava flows (5, 47, 137, 300 and 3400 years BP). The resultant age-climate matrix was used to examine patterns of biomass accumulation, species distribution, and diversity during primary succession. Biomass increased with substrate age and ranged from 0 to over 36 000 g m −2 across the matrix. Generally, biomass increased as altitude decreased, although the maximum value was observed at intermediate altitude on the oldest flow (.)
Competence and Benevolence as Dimensions of Trust: Lecturers’ Trustworthiness in the Words of Italian Students

Trustworthiness includes at least two dimensions: one dimension captures the authority’s benevolence; the other captures authority’s competence. This qualitative study explores the representation of the two dimensions of authority trustworthiness: competence and benevolence. We collected free-associations about what lecturers’ competence and benevolence actually mean for Italian psychology students (n = 125). The data corpus was content-analyzed. Text units were categorized according to meaning using both a bottom-up strategy, with some categories stemming from the data (inductive reasoning), and a top-down strategy, with some categories following from the analysis of the relevant literature (deductive reasoning). Qualitative content analysis showed that these two dimensions overlapped. Students listed theoretically-defined competence characteristics as indications of both benevolence and competence. The same applied to benevolence. Overall, associations were grouped into two main dimensions: (1) the “can-do” dimension, describing a lecturer’s competence and social skill; (2) the “will-do” dimension, describing a lecturer’s good intentions, integrity, and personal motivation. In conclusion, the two conceptually distinct dimensions of trust are indistinguishable in the students’ words. These preliminary results are in line with scholars debating the multifactorial or mono-factorial nature of trust.
Vocal Communication and Reproductive Behavior of the Frog Colostethus beebei in Guyana

The endemic, dendrobatid frog, Colostethus beebei, lived and bred only in water-filled axils of a giant terrestrial bromeliad, Brocchinia micrantha, at Kaieteur National Park, Guyana, South America. Vocalizations initiate reproduction in frogs, and male C. beebei employed three types: advertisement, terri- torial encounter, and courtship calls. Males responded aggressively to advertisement calls from strangers played in their territories but vocalized antiphonally in response to calls from neighbors. Male C. beebei spent 40% of their time-activity budget vocalizing. Females preferred advertisement calls delivered at rep- etition rates above that of the population mean and from larger males. Courtship was prolonged and in- cluded close-range vocal, visual, and tactile stimulation between the sexes. Clutches of four pigmented eggs were laid on leaves above the water of bromeliad tanks. After ovipositing, females spent much time on their mates' territories. Both parents provided care-males tended clutches, moistened eggs with fluid squirt- ed from their cloacae during low humidity times of the day, and transported tadpoles. Tadpoles occasionally fed on unfertilized eggs deposited directly in their pool by their mother. Most tadpole nutrition was ob- tained by grazing on algal mats and by capturing mobile prey in bromeliad pools. Although we observed con- and heterospecific cannibalism among C. beebei tadpoles, cannibalism seemed to be rare. Overall, our observations suggest that C. beebei exhibits long-term pair bonding and facultative nutritive egg provision- ing. These behaviors have not yet been reported for other members of the genus Colostethus but seems essential to C. beebei's obligate life on B. micrantha with its food-limited larval microhabitats. Comparisons with other frog species that feed eggs to their progeny suggests that this strategy is an evolutionarily derived
THE EFFECTS OF EXTRACELLULAR MATRICES AND CO-CULTURE SYSTEMS ON CULTURED LIMBAL STEM CELLS

Received: 23/Jul/2007, Accepted: 29/Jan/2007 Objective: To study the effects of different matrices and co-culture systems on cultured limbal stem cells (LSCs). Materials and Methods: Limbal explants were co-cultured with limbal fibroblasts (LF) and/or mouse embryonic fibroblasts (MEF) on filter inserts coated with amniotic membrane (AM), matrigel (MAT) and collagen type I (COL). Results: This study revealed that AM facilitated the cell migration and expansion significantly in comparison with other matrices. However, the gene expression profile of stemness markers of LSCs showed no significant differences among the experimental groups. The data indicated that at least in two-dimensional culture systems, the mentioned matrices have no significant effect on switching the expression of genes involved in differentiation process. In addition, the results of the two co-culture systems in case of different feeders, including MEF and LF were similar in growth rate and also preserving stemness quality of cultured limbal cells. Conclusion: To exclude the pollution of transplantable cultivated cells with probable mouse viruses, LF with human origin is recommended as feeder. Hence, limbal explants grown on AM in co-culture with LF will promise a quick and safe model for preparing undifferentiated epithelial sheets suitable for transplantation.
Achievement Goals and Goal Progress as Drivers of Work Engagement

In two studies, we investigated the role of self-regulatory behavior in terms of achievement goals and goal progress for work engagement. Study 1 (N = 205) revealed that trait learning goals were positively related to work engagement and performance-approach and performance-avoidance goals were unrelated to work engagement. In a second study, employees were asked to either set a (state) learning, performance-approach, or performance-avoidance goal for the upcoming work week. Goal progress and work engagement were measured one week later (N = 106). Learning goals at the trait and state level were associated with higher work engagement and performance-avoidance goals were unrelated to work engagement. We found a positive relationship of goal progress with work engagement, in particular for employees who pursued learning or performance-approach goals. Our studies contribute to theory building by delineating the (combined) role of goal orientations (trait), state achievement goals, and goal progress for work engagement, as well as generating practical implications for the design of effective interventions to enhance work motivation in organizational practice.
Redundancy and multi-functionality among spinal locomotor networks.

C-fos is used to identify system-wide neural activation with cellular resolution in vivo. However, c-fos can only capture neural activation of one event. Targeted recombination in active populations (TRAP) allows the capture of two different c-fos activation patterns in the same animal. So far, TRAP has only been used to examine brain circuits. This study uses TRAP to investigate spinal circuit activation during resting and stepping, giving novel insights of network activation during these events. The level of co-labeled (c-fos+ and TRAP+) neurons observed after performing two bouts of stepping suggests that there is a probabilistic-like phenomenon that can recruit many combinations of neural populations (synapses) when repetitively generating many step cycles. Between two 30-minute bouts of stepping, each consisting of thousands of steps, only ~20% of the neurons activated from the first bout of stepping were also activated by the second bout. We also show co-labeling of interneurons that have been active during stepping and resting. The use of the FosTRAP methodology in the spinal cord provides a new tool to compare the engagement of different populations of spinal interneurons in vivo under different motor tasks or under different conditions.