Miracle-dz/UniFAR-FTUs huggingface dataset:
A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy—A Systematic Review and Meta-Analysis

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI −0.54 [−1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI −0.2 [−0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [−12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [−0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients’ age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles.
A Review of Ambient Air Pollution as a Risk Factor for Posterior Segment Ocular Diseases

Purpose. To review the most recent evidence on the association of ambient air pollution with posterior segment ocular diseases. Methods. A search of the most recently published medical literature was performed in PubMed and Google Scholar on 10 December 2022. Articles published between 2018 and December 2022 were included in this rapid review. Studies that evaluated the association between ambient air pollutants (nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), particulate matters (PMs), total hydrocarbons (THC), nonmethane hydrocarbons (NMHC), benzene), and ocular posterior segment diseases (glaucoma, age-related macular degeneration (AMD), and retinal vascular diseases) were included. Results. Nineteen research articles met the inclusion criteria. Significant associations were found between PM2.5 and glaucoma, including primary open angle, primary angle closure, and normal tension glaucoma. An increased risk of AMD was linked to increased exposure to PM2.5, NO2, and CO. Single studies suggested that increased exposure to PM2.5 and PM10 is associated with diabetic retinopathy; THC and NMHC increased the risk of retinal vein occlusion; and CO, NO2, and PM10 are linked to an increased risk of central retinal artery occlusion. Conclusions. There is increasing evidence that toxic air pollutants have an impact on posterior segment ocular diseases, hence determining it as a potential modifiable risk factor for visual impairment.
Lattice-Boltzmann Modeling of Natural Convection Between a Square Outer Cylinder and an Inner Isosceles Triangular Heating Body

The present study confirms the robustness and the computational effectiveness of the lattice-Boltzmann method in simulating natural convection between a triangular isosceles heating body and a square outer cylinder isothermally cooled/(insulated) from its vertical/(horizontal) walls. The heated body is symmetrically placed on the vertical centerline of the cavity with the summit opposite to its horizontal base pointing upwards. A detailed parametric study is conducted to investigate the effect of three positions (MB, MM, and MT) of the heating body on fluid flow and heat transfer characteristics for a wide range of Rayleigh number (103 ≤ Ra ≤ 107) and Pr = 7 (water). The method used is validated against previous works using classical numerical methods to solve Navier–Stokes and energy equations in similar geometries with a circular heating body. In the conductive and convective regimes, useful correlations for the total Nusselt number are deduced as for the three positions of the heating block.
Repeatedly Northwards and Upwards: Southern African Grasslands Fuel the Colonization of the African Sky Islands in Helichrysum (Compositae)

The Afromontane and Afroalpine areas constitute some of the main biodiversity hotspots of Africa. They are particularly rich in plant endemics, but the biogeographic origins and evolutionary processes leading to this outstanding diversity are poorly understood. We performed phylogenomic and biogeographic analyses of one of the most species-rich plant genera in these mountains, Helichrysum (Compositae-Gnaphalieae). Most previous studies have focused on Afroalpine elements of Eurasian origin, and the southern African origin of Helichrysum provides an interesting counterexample. We obtained a comprehensive nuclear dataset from 304 species (≈50% of the genus) using target-enrichment with the Compositae1061 probe set. Summary-coalescent and concatenation approaches combined with paralog recovery yielded congruent, well-resolved phylogenies. Ancestral range estimations revealed that Helichrysum originated in arid southern Africa, whereas the southern African grasslands were the source of most lineages that dispersed within and outside Africa. Colonization of the tropical Afromontane and Afroalpine areas occurred repeatedly throughout the Miocene–Pliocene. This timing coincides with mountain uplift and the onset of glacial cycles, which together may have facilitated both speciation and intermountain gene flow, contributing to the evolution of the Afroalpine flora.
Frailty Syndrome as a Transition from Compensation to Decompensation: Application to the Biomechanical Regulation of Gait

Most gait parameters decrease with age and are even more importantly reduced with frailty. However, other gait parameters exhibit different or even opposite trends for aging and frailty, and the underlying reason is unclear. Literature focuses either on aging, or on frailty, and a comprehensive understanding of how biomechanical gait regulation evolves with aging and with frailty seems to be lacking. We monitored gait dynamics in young adults (19–29 years, n = 27, 59% women), middle-aged adults (30–59 years, n = 16, 62% women), and non-frail (>60 years, n = 15, 33% women) and frail older adults (>60 years, n = 31, 71% women) during a 160 m walking test using the triaxial accelerometer of the Zephyr Bioharness 3.0 device (Zephyr Technology, Annapolis, MD, USA). Frailty was evaluated using the Frail Scale (FS) and the Clinical Frailty Scale (CFS). We found that in non-frail older adults, certain gait parameters, such as cadence, were increased, whereas other parameters, such as step length, were decreased, and gait speed is maintained. Conversely, in frail older adults, all gait parameters, including gait speed, were decreased. Our interpretation is that non-frail older adults compensate for a decreased step length with an increased cadence to maintain a functional gait speed, whereas frail older adults decompensate and consequently walk with a characteristic decreased gait speed. We quantified compensation and decompensation on a continuous scale using ratios of the compensated parameter with respect to the corresponding compensating parameter. Compensation and decompensation are general medical concepts that can be applied and quantified for many, if not all, biomechanical and physiological regulatory mechanisms of the human body. This may allow for a new research strategy to quantify both aging and frailty in a systemic and dynamic way.
Expression of RsPORB Is Associated with Radish Root Color

Radish (Raphanus sativus) plants exhibit varied root colors due to the accumulation of chlorophylls and anthocyanins compounds that are beneficial for both human health and visual quality. The mechanisms of chlorophyll biosynthesis have been extensively studied in foliar tissues but remain largely unknown in other tissues. In this study, we examined the role of NADPH:protochlorophyllide oxidoreductases (PORs), which are key enzymes in chlorophyll biosynthesis, in radish roots. The transcript level of RsPORB was abundantly expressed in green roots and positively correlated with chlorophyll content in radish roots. Sequences of the RsPORB coding region were identical between white (948) and green (847) radish breeding lines. Additionally, virus-induced gene silencing assay with RsPORB exhibited reduced chlorophyll contents, verifying that RsPORB is a functional enzyme for chlorophyll biosynthesis. Sequence comparison of RsPORB promoters from white and green radishes showed several insertions and deletions (InDels) and single-nucleotide polymorphisms. Promoter activation assays using radish root protoplasts verified that InDels of the RsPORB promoter contribute to its expression level. These results suggested that RsPORB is one of the key genes underlying chlorophyll biosynthesis and green coloration in non-foliar tissues, such as roots.
A Systematic Ex-Vivo Study of the Anti-Proliferative/Cytotoxic Bioactivity of Major Olive Secoiridoids’ Double Combinations and of Total Olive Oil Phenolic Extracts on Multiple Cell-Culture Based Cancer Models Highlights Synergistic Effects

Several individual olive oil phenols (OOPs) and their secoiridoid derivatives have been shown to exert anti-proliferative and pro-apoptotic activity in treatments of human cancer cell lines originating from several tissues. This study evaluated the synergistic anti-proliferative/cytotoxic effects of five olive secoiridoid derivatives (oleocanthal, oleacein, oleuropein aglycone, ligstroside aglycone and oleomissional) in all possible double combinations and of total phenolic extracts (TPEs) on eleven human cancer cell lines representing eight cell-culture-based cancer models. Individual OOPs were used to treat cells for 72 h in half of their EC50 values for each cell line and their synergistic, additive or antagonistic interactions were evaluated by calculating the coefficient for drug interactions (CDI) for each double combination of OOPs. Olive oil TPEs of determined OOPs’ content, originating from three different harvests of autochthonous olive cultivars in Greece, were evaluated as an attempt to investigate the efficacy of OOPs to reduce cancer cell numbers as part of olive oil consumption. Most combinations of OOPs showed strong synergistic effect (CDIs < 0.9) in their efficacy, whereas TPEs strongly impaired cancer cell viability, better than most individual OOPs tested herein, including the most resistant cancer cell lines evaluated.
Better Late Than Never: The Impact of Steroidal Treatment on the Outcome of Melanoma Patients Treated with Immunotherapy

Simple Summary In the era of immunotherapy, advanced melanoma patients have unprecedentedly higher survival rates. However, the application of immunotherapy may lead to immune-related adverse events (irAEs), which are often managed with steroids. The potential negative impact of steroids on the effectiveness of immunotherapy remains uncertain, as studies often report contradictory results. This retrospective analysis of 415 first-line immunotherapy patients showed that steroid exposure increased progression-free survival (PFS) compared to no exposure, but early initiation (within four weeks) was linked to a shorter PFS compared to late or no exposure. This suggests that administering steroids during the immunotherapy priming phase may hinder the establishment of an effective immunotherapy-induced immune response. The implications of these findings are significant for managing irAEs, indicating a need for the cautious use of steroids in the initial stages of treatment. Abstract Background: Successful treatment with Immune Checkpoint Inhibitors (ICI) requires the balanced activation of the immune system. Over-activation may result in immune-related adverse events (irAEs), which often require steroidal treatment. This study examined the possible impact of steroids on treatment efficacy in melanoma patients concerning initiation timing and dosage. Methods: A retrospective, single-center analysis of patients with advanced melanoma who underwent first-line ICI therapy during 2014–2020 was conducted. Results: Among the 415 patients, two-hundred patients (48.3%) were exposed to steroids during the first line, most of them due to irAEs (n = 169, 84.5%). Nearly a quarter of them were exposed to steroids within the first four weeks of treatment. Surprisingly, steroidal exposure was associated with better progression-free survival (PFS; HR = 0.74, p = 0.015); however, early exposure (within four weeks of treatment) resulted in a significantly shorter PFS compared to late exposure (adjusted HR 3.2, p < 0.001). Conclusions: Early exposure to corticosteroids during the priming phase of ICI therapy could impede the establishment of an effective immune response. These results suggest that caution should be exercised when considering the use of steroids for the management of early-onset irAEs.
Characterization of the role of Ume6 C-terminal tail in C. albicans morphological plasticity

C. albicans is an important human fungal pathogen and filamentation is essential for its virulence. Ume6 is a transcription factor critical for filamentation. Ume6 is composed of three domains, a long N terminal domain, Zn-finger domain, and a C-terminal domain. Previously, it was shown that the Zn-finger domain is essential for filamentation, as removal of this domain led to a lack of filamentation. However, the role for the C-terminal domain has not been defined. We find deletion of the C-terminal domain leads to a filamentation defect and the defect is not as severe as removal of the Zn-finger or ume6 deletion. We mutated a number of residues in the C-terminal domain to try to identify specific residues important for filamentation, but all of our mutants displayed wild type filamentation. Alpha fold predictions suggest the C-terminal domain forms a single alpha helix that is predicted to interact with the Zn-finger domain via hydrogen bond. Our data suggests the C-terminal domain binds the Zn-finger domain and through this interaction is important for filamentation.
The Nursing Work Environment, Supervisory Support, Nurse Characteristics, and Burnout as Predictors of Intent to Stay among Hospital Nurses in the Republic of Korea: A Path Analysis

This study aimed to examine the comprehensive impact of five aspects of the nursing work environment as well as supervisory support, nurse characteristics, and burnout on intent to stay (ITS) among Korean hospital nurses. A cross-sectional questionnaire was distributed in seven general hospitals from May to July of 2019. Data were collected from a sample of 631 Korean nurses. The hypothesized model was evaluated using the STATA program for path models. Findings demonstrated that burnout played a mediating role on the relationships between the nursing work environment, supervisory support, nurse characteristics, and ITS. Burnout was the most influential predictor of ITS (β = −0.36, p < 0.001). Nurse participation in hospital affairs (β = 0.10, p = 0.044) and collegial nurse–physician relationships (β = 0.08, p = 0.038) had a direct effect on ITS. Supervisory support had a significant direct effect on ITS (β = 0.19, p < 0.001). Therefore, to increase nurses’ ITS, it is necessary to improve their participation in hospital affairs and collegial relationships, as well as strengthen support from supervisors and reduce burnout.
Body Weight Reduction by Bariatric Surgery Reduces the Plasma Levels of the Novel Orexigenic Gut Hormone Insulin-like Peptide 5 in Patients with Severe Obesity

Insulin-like factor 5 (INSL5), a novel hormone secreted by the enteroendocrine cells of the distal colon, has been implicated in appetite and body weight regulation in animals given its orexigenic properties. We investigated basal INSL5 plasma levels in a group of morbidly obese subjects before and after laparoscopic sleeve gastrectomy. Furthermore, we analyzed the expression of INSL5 in human adipose tissue. Before bariatric surgery, obese subjects showed basal INSL5 plasma levels that were positively correlated with BMI, fat mass, and leptin plasma levels. After weight loss by laparoscopic sleeve gastrectomy, INSL5 plasma levels in obese subjects were significantly lower than those observed before surgery. Finally, we did not detect any expression of the INSL5 gene in human adipose tissue, both at the mRNA and protein levels. The present data show that subjects with obesity have INSL5 plasma levels positively correlating with adiposity markers. After bariatric surgery, INSL5 plasma levels decreased significantly, and this decrease was not directly due to the loss of adipose tissue since this tissue does not express INSL5. Considering the orexigenic properties of INSL5, the reduction of its plasma levels after bariatric surgery in obese subjects could participate in the still unclear mechanisms leading to appetite reduction that characterize bariatric surgery procedures.
Sustaining Life versus Altering Life-Saving Drugs: Insights to Explain the Paradoxical Effect of Extracorporeal Membrane Oxygenation on Drugs

There has been a substantial increase in the use of extracorporeal membrane oxygenation (ECMO) support in critically ill adults. Understanding the complex changes that could affect drugs’ pharmacokinetics (PK) and pharmacodynamics (PD) is of suitable need. Therefore, critically ill patients on ECMO represent a challenging clinical situation to manage pharmacotherapy. Thus, clinicians’ ability to predict PK and PD alterations within this complex clinical context is fundamental to ensure further optimal and, sometimes, individualized therapeutic plans that balance clinical outcomes with the minimum drug adverse events. Although ECMO remains an irreplaceable extracorporeal technology, and despite the resurgence in its use for respiratory and cardiac failures, especially in the era of the COVID-19 pandemic, scarce data exist on both its effect on the most commonly used drugs and their relative management to achieve the best therapeutic outcomes. The goal of this review is to provide key information about some evidence-based PK alterations of the drugs used in an ECMO setting and their monitoring.
3D-Printable PLA/Mg Composite Filaments for Potential Bone Tissue Engineering Applications

Magnesium (Mg) is a promising material for bone tissue engineering applications due to it having similar mechanical properties to bones, biocompatibility, and biodegradability. The primary goal of this study is to investigate the potential of using solvent-casted polylactic acid (PLA) loaded Mg (WE43) composites as filament feedstock for fused deposition modeling (FDM) 3D Printing. Four PLA/Magnesium (WE43) compositions (5, 10, 15, 20 wt%) are synthesized and produced into filaments, then used to print test samples on an FDM 3D printer. Assessments are made on how Mg incorporation affected PLA’s thermal, physicochemical, and printability characteristics. The SEM study of the films shows that the Mg particles are uniformly distributed in all the compositions. The FTIR results indicate that the Mg particles blend well with the polymer matrix and there is no chemical reaction between the PLA and the Mg particles during the blending process. The thermal studies show that the addition of Mg leads to a small increase in the melting peak reaching a maximum of 172.8 °C for 20% Mg samples. However, there are no dramatic variations in the degree of crystallinity among the Mg-loaded samples. The filament cross-section images show that the distribution of Mg particles is uniform up to a concentration of 15% Mg. Beyond that, non-uniform distribution and an increase in pores in the vicinity of the Mg particles is shown to affect their printability. Overall, 5% and 10% Mg composite filaments were printable and have the potential to be used as composite biomaterials for 3D-printed bone implants.
Impact of end-stage knee osteoarthritis on perceived physical function and quality of life: A descriptive study from Jordan

Objective Of the present study was to evaluate the impact of end-stage knee OA on patient’s perception of their functional abilities and quality of life (QoL) using the self-reported questionnaire; the Knee Injury and Osteoarthritis Outcome Score (KOOS), and to determine the contribution of knee pain on patient’s perceived outcomes. Methods Patients with end-stage knee OA who are on the waiting list for total knee arthroplasty were recruited in this cross-sectional study. Patients were asked to fill out the KOOS questionnaire. Knee pain for both sides was quantified on a continuous scale from 0–10. Age, and anthropometric data were recorded. Descriptive statistics were calculated for patients’ characteristics, and for the scores of each KOOS subscale. Hierarchical linear regression models were created to determine the contributions of knee pain on two KOOS subscales; the function in daily living (KOOS-ADL), and the knee-related quality of life (KOOS-QoL). Results Patients in this study scored low across KOOS subscales (27.7% - 54.2%) with the QoL subscale being the lowest. After accounting for age and BMI, hierarchical linear regressions revealed that knee pain in both sides were determinants of self-perceived KOOS-ADLs, while only knee pain in the most-affected side significantly contributed to lower KOOS-QOL scores. Conclusion End-stage knee OA negatively impact the patients’ perceived function and quality of life. Patients’ KOOS scores were similar to those reported in other countries, with QoL being the domain most affected. Our findings demonstrate that the level of knee pain has a determinant effect on our patients’ perceptions of functional abilities and QoL. As waiting-list patients, addressing knee pain with a targeted regimen prior to TKA, as well as increasing patient’s awareness about knee pain management, may improve/ or minimize deterioration in perceived functional ability and QoL while awaiting TKA.
How Can We Best Diagnose Severity Levels of Dry Eye Disease: Current Perspectives

Abstract Dry eye disease (DED) is a common ocular condition, but the diagnosis relative to other ocular conditions and the evaluation of severity of the condition has often been difficult. This challenge can be due to clinical signs and symptoms not always correlating with each other. An understanding of the various components which create the condition, as well as the diagnostic measures used to evaluate these components, is useful to the clinician working with DED patients. This review paper will discuss traditional diagnostic options, diagnostic imaging, and Advanced Point of Care testing capabilities to determine the severity level of dry eye disease more adequately.