Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Different Loading Doses of Dexmedetomidine on Controlled Hypotension and the Incidence of Bradycardia During Rhinoplasty: A Clinical Trial

Controlled hypotension, with a mean arterial pressure (MAP) of 60 mmHg - 70 mmHg, provides a bloodless and visible surgical field during rhinoplasty. It has been shown that dexmedetomidine, an α2-adrenoreceptor agonist, is a suitable choice in this regard. One of the disadvantages of this drug is the possibility of severe bradycardia during infusion. Therefore, we compared lower intravenous (IV) loading doses to determine whether the hypotensive effect of the drug was preserved and the bradycardia incidence decreased. In this randomized, double-blinded clinical trial, 81 patients aged 18 to 50 years with the American Society of Anesthesiologists physical status (ASA-PS) class I and II, scheduled for rhinoplasty randomly received 1.0, 0.9, and 0.8 µg/kg (named as groups 1.0, 0.9, and 0.8, respectively) of IV dexmedetomidine before the induction of anesthesia followed by infusion (0.3 - 0.7 µg/kg/h) during operation. The patients’ heart rate (HR), MAP, the requirements for nitroglycerin (NTG) and extra fentanyl, as well as the incidence of bradycardia, were recorded. Bleeding and visibility of the surgical field were scored by the surgeon using a 6-point visual scale. MAPs, HRs, and consumption of NTG and extra fentanyl were similar in the studied groups. The surgical field was more visible and bloodless in group 1.0 compared to group 0.8 (P < 0.001); the differences were not significant between groups 1.0 and 0.9 (P = 0.605). The incidence (P = 0.027) and the severity of bradycardia (P = 0.017) were higher in the groups with higher loading doses. We concluded that dexmedetomidine is an acceptable agent to provide controlled hypotension. A loading dose of 0.9 µg/kg, but not 0.8 µg/kg, provides similar surgical field conditions as the dose of 1 µg/kg. Furthermore, despite the decrease in the incidence of bradycardia, the hypotensive effect of the drug is preserved.
Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction

The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals.
Clinical Efficacy of Repeated Applications of Local Drug Delivery and Adjunctive Agents in Nonsurgical Periodontal Therapy: A Systematic Review

The aim of this systematic review is to compare the clinical efficacy of repeated applications of local drug delivery and adjunctive agents (LDAs) in nonsurgical periodontal therapy (NSPT) compared to subgingival mechanical debridement (SMD) alone. The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EMBASE, Web of Science, hand-searched literature and grey literature databases were searched for randomized controlled clinical trials (RCTs) with a minimum of 6-month follow-up. The outcomes of interest were changes in probing pocket depth and clinical attachment level as well as patient-centred outcomes. Of 1094 studies identified, 16 RCTs were included in the qualitative analysis. Across 11 different adjuncts analysed, only two studies utilizing minocycline gel/ointment and antimicrobial photodynamic therapy (aPDT) with indocyanine green photosensitizer had statistically significant differences in primary outcomes when compared to their control groups. Only one study on aPDT methylene blue 0.005% had compared single versus multiple applications against its control group. A mean range of 0.27–3.82 mm PD reduction and −0.09–2.82 mm CAL gain were observed with repeated LDA application. Considerable clinical heterogeneity and methodological flaws in the included studies preclude any definitive conclusions regarding the clinical efficacy of repeated LDA applications. Future RCTs with a direct comparison between single and repeated applications should be conducted to confirm or refute the clinical advantages of repeated LDA application in the nonsurgical management of periodontitis.
Diagnostic, Prognostic, Predictive, and Monitoring Role of Neutrophil CD11b and Monocyte CD14 in Neonatal Sepsis

Background Sepsis is a critical medical condition that requires additional diagnostic considerations. Recently, focus has shifted to the diagnosis of sepsis using new markers to overcome the limitations of traditional laboratory diagnostic modalities. Neutrophil CD11b (nCD11b) and monocyteCD14 (mCD14) cell surface antigens have been shown to be useful in such diagnostic consideration. Aim To investigate the diagnostic, monitoring, prognostic, and predictive roles of nCD11b and mCD14 as sepsis biomarkers in comparison to each other and to traditional laboratory sepsis parameters in order to select the best fit for routine daily use in neonatal intensive care units (NICUs). Subject The study included 188 neonates from Ain Shams University Hospitals' NICUs, who were divided into two groups: the control group (n = 100) and the sepsis group (n = 88). Highly sensitive CRP (hs-CRP), complete blood count (CBC), blood culture, and nCD11b and mCD14 evaluations were all part of the laboratory sepsis evaluation (done by flow cytometry technology). Positive blood culture results (BACT/ALERT system) confirmed the sepsis diagnosis. Twenty-four enrolled sepsis neonates were subjected to follow-up assessments, and they were divided into two groups based on clinical improvement: improved sepsis and sepsis without improvement. In order to predict performance evaluation, the subjected neonates were reclassified according to their outcome into survivors' and nonsurvivors' group. Results Sepsis patients had a significant increase in mCD14 MFI values when compared to controls. With sensitivity 75.4 percent, specificity 71.9 percent, efficacy 73.3 percent, and AUC 0.703, mCD14 MFI at cutoff 9.36 could distinguish the presence of septicemia. Significant increases in both mCD14 MFI and nCD11b MFI (P = 0.001) were observed in the severe sepsis/septic shock group compared to the nonsevere sepsis group. The combined measurement of CD14 MFI at cutoff 9.97 and CD14 percent at cutoff 44.7 percent yielded the best predictive performance. Conclusion Sepsis patients had a significant increase in mCD14 MFI comparable to the controls. mCD14 MFI demonstrated better diagnostic, prognostic, and predictive results than nCD11b. hs-CRP outperformed mCD14 and nCD11b in terms of diagnostic efficacy and AUC. In the monitoring of sepsis patients, both mCD14 and nCD11b produced unsatisfactory results. Currently, the routine use of mCD14 or nCD11b as sepsis biomarkers in neonatal ICUs is not justified.
The Potential Impact of Digital Biomarkers in Multiple Sclerosis in The Netherlands: An Early Health Technology Assessment of MS Sherpa

(1) Background: Monitoring of Multiple Sclerosis (MS) with eHealth interventions or digital biomarkers provides added value to the current care path. Evidence in the literature is currently scarce. MS sherpa is an eHealth intervention with digital biomarkers, aimed at monitoring symptom progression and disease activity. To show the added value of digital biomarker–based eHealth interventions to the MS care path, an early Health Technology Assessment (eHTA) was performed, with MS sherpa as an example, to assess the potential impact on treatment switches. (2) Methods: The eHTA was performed according to the Dutch guidelines for health economic evaluations. A decision analytic MS model was used to estimate the costs and benefits of MS standard care with and without use of MS sherpa, expressed in incremental cost-effectiveness ratios (ICERs) from both societal and health care perspectives. The efficacy of MS sherpa on early detection of active disease and the initiation of a treatment switch were modeled for a range of assumed efficacy (5%, 10%, 15%, 20%). (3) Results: From a societal perspective, for the efficacy of 15% or 20%, MS sherpa became dominant, which means cost-saving compared to the standard of care. MS sherpa is cost-effective in the 5% and 10% scenarios (ICERs EUR 14,535 and EUR 4069, respectively). From the health care perspective, all scenarios were cost-effective. Sensitivity analysis showed that increasing the efficacy of MS sherpa in detecting active disease early leading to treatment switches be the most impactful factor in the MS model. (4) Conclusions: The results indicate the potential of eHealth interventions to be cost-effective or even cost-saving in the MS care path. As such, digital biomarker–based eHealth interventions, like MS sherpa, are promising cost-effective solutions in optimizing MS disease management for people with MS, by detecting active disease early and helping neurologists in decisions on treatment switch.
Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities

Simple Summary Neoadjuvant radiotherapy has gained popularity as a treatment strategy for locally advanced soft tissue sarcoma of the extremities. However, little is yet known about the benefits and risks of adding preoperative chemotherapy. High-risk patients with soft tissue sarcomas of the extremities are treated with a combined preoperative radiochemotherapy at our institution. This study reports an analysis of patients treated either with primary surgery or with preoperative radiochemotherapy, followed by surgery. This kind of multimodal therapy leads to excellent oncological outcomes and is associated with low rates of severe postoperative complications in highly specialized centers. Abstract Background: Neoadjuvant treatment modalities in soft tissue sarcoma (STS) of the extremities have become more popular in recent years, but because of the rarity and heterogeneity of STS, there are yet few studies on the long-term impact of neoadjuvant treatment modalities, especially in terms of neoadjuvant radiochemotherapy. Methods: The study enrolled 136 patients with primary STS of the extremities who underwent surgery with curative intent or neoadjuvant therapy, followed by surgery in a 15-year period. Neoadjuvant treatment consisted of radiotherapy (RT) with 60 Gy and in most cases simultaneous chemotherapy (CTx) with ifosfamide (1.5 g/m2/d, d1–5, q28) and doxorubicine (50 mg/m2/d, d3, q28). We investigated the clinical, (post)-operative and histopathological data and the oncological follow-up as well. The median follow-up period was 82 months (range 6–202). Results: A total of 136 patients (M:F = 73:63) with a mean age of 62 years (range; 21–93) was observed. Seventy-four patients (54.4%) received neoadjuvant therapy (NT), 62 patients (45.6%) received primary surgery (PS). When receiving NT, patients with high-risk STS had a lower risk to develop distant metastasis (p = 0.025). Age, histological type, tumor size and surgical margins (R0 vs. R1) had no influence on any survival rates. There was an association between NT and the occurrence of postoperative complications (p = 0.001). The 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), disease free survival (DFS) and overall survival (OS) rate of the whole cohort was 89.9%, 77.0%, 70.6% and 72.6%; whereas the 5-year LRFS, MFS, DFS and OS rate was 90.5%, 67.2%, 64.1% and 62.8% for the NT group and 89.5%, 88.3%. 78.4% and 83.8% for the PS group. Conclusions: Multimodal treatment strategies in patients with STS of extremities lead to excellent oncological outcomes. Patients with high-risk STS had a significantly better MFS when receiving NT than patients with low-risk STS. NT was associated with a higher probability of postoperative but well-manageable complications.
Experiences of Patients With Diabetes Attending a Publicly Funded Eye Care Pathway in Western Sydney: A Qualitative Study

Diabetic retinopathy (DR) complications can be prevented with regular screening and timely access to an ophthalmologist for treatment. But there are patient and health system barriers that can impact access to DR services. This study aims to identify enablers and barriers for accessing public DR eye care services in a low socio-economic urban area of Australia. We conducted a qualitative study using semi-structured interviews for patients with diabetes aged 35 years and older attending public ophthalmology services. Interviews were analyzed to identify themes and subthemes; and the COM-B framework was used to interpret the complex behavioral mechanisms, including capability, opportunity, and motivation factors, to explain adherence to DR eye care. Three main themes and 7 sub-themes relating to patient experiences of DR care were derived. Patients were found to be passive actors in their DR eye care, but patients trusted clinicians and were determined to maintain their vision and quality of life. The barriers and facilitators of care related to the health system (service availability and recall–reminder systems) and patient experiences (choices, knowledge, and fear). The findings of this study will guide patient-centered initiatives to target and improve access to DR care. Strategies should focus on improving communication between eye care providers, and communication with patients to empower them to become more active players in healthcare decisions.
A Systematic Comparison of the Intrinsic Properties of Wheat and Oat Bran Fractions and Their Effects on Dough and Bread Properties: Elucidation of Chemical Mechanisms, Water Binding, and Steric Hindrance

This study aimed at elucidating the contribution of chemical interactions, water binding, and steric hindrance on the effect of wheat and oat brans and of their fractions, i.e., soluble and insoluble, on dough and bread properties. For such purpose, an inert filler, i.e., glass beads of comparable particle size and with no water binding capacity and moisture sorption properties, was also studied. The glass beads provided breads most similar to the control, indicating the limited role of steric hindrance. Brans and bran fractions showed distinct compositional and physical properties. The soluble fraction from oat bran, rich in β-glucan, was less hygroscopic than the wheat counterpart and could bind more water, resulting in larger detrimental effects on bread quality. The β-glucan content showed a prevalent role in affecting gluten development, the thermo-setting behaviour of the dough, and crumb texture, i.e., cohesiveness and resilience. Overall, the comparison between the two brans and their fractions indicated that the interplay between water binding, mainly provided by the insoluble fraction, and the plasticizing properties of the soluble bran fraction controlled the effects on bread volume and texture. From a compositional standpoint, β-glucan content was a determining factor that discriminated the effects of wheat and oat brans.
Immunotherapies in Genitourinary Oncology: Where Are We Now? Where Are We Going?

Simple Summary Genitourinary malignancies include cancers along the urinary tract and the male reproductive tract, encompassing the adrenal glands, kidneys, bladder, prostate, and testicles. Immunotherapy, which treats cancer by using the immune system to attack malignant cells, has historically been successful in treating some types of genitourinary cancers, especially of the bladder and kidney. In the past decade, a more precise method of immunotherapy, known as immune checkpoint inhibition, has gained popularity as it enhances the immune system’s ability to recognize and destroy tumor cells. Several immune checkpoint inhibitors have achieved success in patients with advanced genitourinary cancers. This review provides a brief overview of traditional immunotherapies, focuses on how immune checkpoint inhibitors have achieved success in patients with advanced cancers, and investigates the role for immunotherapy in genitourinary malignancies in the future. Abstract For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette–Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials.
Incidence of Tetracycline and Erythromycin Resistance in Meat-Associated Bacteria: Impact of Different Livestock Management Strategies

The extensive use of antibiotics as growth promoters, or their continued abusive misuse to cure or prevent the onset of bacterial infections as occurs in the intensive farming, may have played a pivotal role in the spread of reservoirs of antibiotic resistance (AR) among food-associated bacteria including pathogens representing risks to human health. The present study compares the incidence of tetracycline and erythromycin resistances in lactic acid bacteria (LAB) and coagulase negative staphylococci (CNS) from fermented products manufacturing using meat from intensive animal husbandry (industrialized manufacturing Italian salami) and from extensive farms (artisanal sausages facilities pork and llama Argentinean sausages). A higher incidence of tetracycline resistance (TET-R) compared to erythromycin resistance (ERY-R) was observed among the 205 isolates. Unlike CNS strains, the LAB showed a significant correlation between the TET-R and the ERY-R phenotypes. Genotypic assessment shows a high correlation with tetK and tetM for the TET-R strains and with ermB and ermC for the ERY-R strains. Multiple correspondence analyses have highlighted the association between AR phenotypes and CNS species isolated from Italian salami, while the susceptible phenotypes were associated with the LAB species from Argentinean sausages. Since antibiotic resistance in meat-associated bacteria is a very complex phenomenon, the assessment of bacterial resistance in different environmental contexts with diverse farming practices and food production technologies will help in monitoring the factors influencing AR emergence and spread in animal production.
SOD2 Enhancement by Long-Term Inhibition of the PI3K Pathway Confers Multi-Drug Resistance and Enhanced Tumor-Initiating Features in Head and Neck Cancer

The phosphoinositide-3-kinase (PI3K) pathway has widely been considered as a potential therapeutic target for head and neck cancer (HNC); however, the application of PI3K inhibitors is often overshadowed by the induction of drug resistance with unknown mechanisms. In this study, PII3K inhibitor resistant cancer cells were developed by prolonged culturing of cell lines with BEZ235, a dual PI3K and mammalian target of rapamycin (mTOR) inhibitor. The drug resistant HNC cells showed higher IC50 of the proliferation to inhibitors specifically targeting PI3K and/or mTOR, as compared to their parental cells. These cells also showed profound resistance to drugs of other classes. Molecular analysis revealed persistent activation of phosphorylated AKT at threonine 308 in the drug resistant cells and increased expression of markers for tumor-initiating cells. Interestingly, increased intra-cellular ROS levels were observed in the drug resistant cells. Among anti-oxidant molecules, the expression of SOD2 was increased and was associated with the ALDH-positive tumor-initiating cell features. Co-incubation of SOD inhibitors and BEZ235 decreased the stemness feature of the cells in vitro, as shown by results of the spheroid formation assay. In conclusion, dysregulation of SOD2 might contribute to the profound resistance to PI3K inhibitors and the other drugs in HNC cells.
Supplementation with Lactiplantibacillus plantarum IMC 510 Modifies Microbiota Composition and Prevents Body Weight Gain Induced by Cafeteria Diet in Rats

Changes in functionality and composition of gut microbiota (GM) have been associated and may contribute to the development and maintenance of obesity and related diseases. The aim of our study was to investigate for the first time the impact of Lactiplantibacillus (L.) plantarum IMC 510 in a rat model of diet-induced obesity, specifically in the cafeteria (CAF) diet. This diet provides a strong motivation to voluntary overeat, due to the palatability and variety of selected energy-dense foods. The oral administration for 84 days of this probiotic strain, added to the CAF diet, decreased food intake and body weight gain. Accordingly, it ameliorated body mass index, liver and white adipose tissue weight, hepatic lipid accumulation, adipocyte size, serum parameters, including glycemia and low-density lipoprotein levels, in CAF fed rats, potentially through leptin control. In this scenario, L. plantarum IMC 510 showed also beneficial effects on GM, limiting the microbial imbalance established by long exposure to CAF diet and preserving the proportion of different bacterial taxa. Further research is necessary to better elucidate the relationship between GM and overweight and then the mechanism of action by which L. plantarum IMC 510 modifies weight. However, these promising results prompt a clear advantage of probiotic supplementation and identify a new potential probiotic as a novel and safe therapeutic approach in obesity prevention and management.