Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti SARS-CoV-2 Monoclonal Antibodies in Pre-Exposure or Post-Exposure in No- or Weak Responder to Vaccine Kidney Transplant Recipients: Is One Strategy Better than Another?

Background: Kidney transplant recipients (KTRs) are likely to develop severe COVID-19 and are less well-protected by vaccines than immunocompetent subjects. Thus, the use of neutralizing anti–SARS-CoV-2 monoclonal antibodies (mAbs) to confer a passive immunity appears attractive in KTRs. Methods: This retrospective monocentric cohort study was conducted between 1 January 2022 and 30 September 2022. All KTRs with a weak antibody response one month after three doses of mRNA vaccine (anti spike IgG < 264 (BAU/mL)) have received tixagevimab-cilgavimab in pre-exposure (group 1), post-exposure (group 2) or no specific treatment (group 3). We compared COVID-19 symptomatic hospitalizations, including intensive care unit hospitalizations, oxygen therapy, and death, between the three groups. Results: A total of 418 KTRs had SARS-CoV-2 infection in 2022. During the study period, we included 112 KTRs in group 1, 40 KTRs in group 2, and 27 KTRs in group 3. The occurrence of intensive care unit hospitalization, oxygen therapy, and COVID-19 death was significantly increased in group 3 compared to group 1 or 2. In group 3, 5 KTRs (18.5%) were admitted to the intensive care unit, 7 KTRs (25.9%) needed oxygen therapy, and 3 KTRs (11.1%) died. Patients who received tixagevimab-cilgavimab pre- or post-exposure had similar outcomes. Conclusions: This retrospective real-life study supports the relative effectiveness of tixagevimab-cilgavimab on COVID-19 infection caused by Omicron, used as a pre- or post-exposure therapy. The continued evolution of Omicron variants has made tixagevimab-cilgavimab ineffective and reinforces the need for new therapeutic monoclonal antibodies for COVID-19 active on new variants.
A critical assessment of the Aurignacian: Insights from Fumane Cave in northern Italy

In the scenario of the spread of the anatomically modern humans (AMHs) into Europe, the techno-complex known as Protoaurignacian is defined by the production of blades and bladelets within a single and continuous stone knapping sequence from the same core as the result of its progressive reduction. However, the growing re-evaluation of some assemblages is revealing that bladelets are frequently obtained from independent reduction sequences, hence discouraging the direct application of the model developed in southwestern France. High-resolution regional signatures are thus needed to reconstruct a more accurate portrait of the AMH colonization dynamic. Northeastern Italy, with the key site of Fumane Cave, is one among the regions of Mediterranean Europe worthy of consideration for reconstructing this colonization process and its cultural dynamics. Within the framework of a critical discussion of the technological definition of the Protoaurignacian and its relationship with contemporaneous industries on a regional and supra-regional scale, we present the results of a detailed analysis of the lithic technology from units A2-A1 based on reduction sequence and attribute analyses. Results show that bladelets are the first goal of production and they do not originate from reduced blade cores but from a broad range of independent and simultaneous core reduction strategies. One implication is that the most commonly used technological trait that is said to define the Protoaurignacian has been over-emphasized and that the Protoaurignacian is technologically consistent across its geographical extent. Additional data based on carinated core technology imply that this techno-complex shares a common technological background with the Early Aurignacian and that no features are restricted to one of the two facies. Furthermore, the major difference between the Protoaurignacian and Early Aurignacian appears to be more typological in nature, with retouched bladelets being less common in the Early Aurignacian. PLOS ONE | https://doi.org/10.1371/journal.pone. 0189241 December 7, 2017 1 / 43 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
Cost-Effectiveness of Treatment Optimisation with Biomarkers for Immunotherapy in Solid Tumours: A Systematic Review

Simple Summary Researchers aim to assess the economic impact of testing predictive biomarkers for immunotherapy in solid tumour treatment using immune checkpoint inhibitors (ICIs). Despite recent advancements, concerns persist regarding the cost-effectiveness and budgetary implications of ICIs. This study systematically reviewed the economic evaluations of biomarker testing from various databases. The team assessed studies from June 2010 to February 2022, evaluating their quality and synthesising findings by tumour type. Understanding the economic implications of these tests could help drive future research, optimise treatment strategies, potentially influencing health care decisions and resource allocation in solid tumour therapy, impacting how we approach and fund immunotherapy for better patient outcomes. Abstract This study investigated the health economic evaluations of predictive biomarker testing in solid tumours treated with immune checkpoint inhibitors (ICIs). Searching PubMed, EMBASE, and Web of Science from June 2010 to February 2022, 58 relevant articles were reviewed out of the 730 screened. The focus was predominantly on non-small cell lung cancer (NSCLC) (65%) and other solid tumours (40%). Among the NSCLC studies, 21 out of 35 demonstrated cost-effectiveness, notably for pembrolizumab as first-line treatment when preceded by PD-L1 assessment, cost-effective at a threshold of $100,000/QALY compared to the standard of care. However, for bladder, cervical, and triple-negative breast cancers (TNBCs), no economic evaluations met the affordability threshold of $100,000/QALY. Overall, the review highlights a certain degree of uncertainty about the cost-effectiveness of ICI. In particular, we found PD-L1 expression associated with ICI treatment to be a cost-effective strategy, particularly in NSCLC, urothelial, and renal cell carcinoma. The findings suggest the potential value of predictive biomarker testing, specifically with pembrolizumab in NSCLC, while indicating challenges in achieving cost-effectiveness for certain other solid tumours.
Efficacy of Continuous vs. Intermittent Administration of Cefepime in Adult ICU Patients with Gram-Negative Bacilli Bacteremia: A Randomized Double-Blind Clinical Study

Introduction: The objective of this study was to compare the continuous infusion of cefepime with the intermittent infusion in patients with sepsis caused by Gram-negative bacilli (GNB). Methods: Randomized 1:1 multicenter double-blinded placebo-controlled study with allocation concealment; multicenter study in the intensive care units of Colombia. Patients with sepsis, severe sepsis or septic shock, and GNB-suspected bacteremia. Cefepime was administered for 7 to 14 days over 30 m intermittently every 8 h over 24 h plus continuous saline solution (0.9%) (G1) or 3 g administered continuously plus saline solution every 8 h (0.9%) (G2). The percentage of clinical response at 3, 7, and 14 days, relapse at 28 days, and mortality at discharge were measured. Results: The recruitment was stopped at the suggestion of the Institutional Review Board (IRB) following an FDA alert about cefepime. Thirty-two patients were randomized; 25 received the intervention, and GNB bacteremia was confirmed in 16 (9 G1 and 7 G2). Favorable clinical response in days 3, 7, and 14 was 88.8%, 88.8%, and 77.8% (G1) and was similar for G2 (85.7%). There were no relapses or deaths in G2, while in G1, one relapse and two deaths were observed. Conclusions: The results of this study support the use of cefepime for the treatment of Gram-negative infections in critically ill patients, but we could not demonstrate differences between continuous or intermittent administration because of the small sample size, given the early suspension of the study.
Early detection of optic nerve head changes using optical coherence tomography after using mesenchymal stromal cells as intravitreal therapy in rabbit models of ocular hypertension

Background and Aim: Stem cell therapy is considered a promising treatment for several neurodegenerative diseases. However, there are very few studies on the use of this therapy in glaucoma models. By detecting the changes produced by glaucoma early, cell therapy could help prevent the events that lead to blindness. In this study, early changes in the optic nerve head (ONH) as detected by optical coherence tomography (OCT) after the application of human Wharton’s jelly-derived mesenchymal stromal cells (hWJ-MSCs) in an experimental model of ocular hypertension (OH) were evaluated. Materials and Methods: Fifteen New Zealand rabbits were randomly divided into the following three groups: G1: OH, G2: hWJ-MSCs, and G3: OH + hWJ-MSCs. An OH model was constructed, and the intraocular pressure (IOP) was measured regularly. At week 7, 105/100 μL hWJ-MSCs were intravitreally injected. Retinography and OCT were used to evaluate structural changes in ONH. Results: IOP increased significantly in G1 and G3 from week 3 onward. Retinography revealed more significant optic nerve changes, that is, papillary asymmetry suggestive of optic nerve excavation, vascular alterations, and irregular hypopigmentation peripheral to the optic disk margin, in G1 compared with G3. OH locates the hWJ-MSCs solution in the vitreous in front of the optic nerve. OCT revealed retinal nerve fiber layer (RNFL) reduction in all groups, reduced optic cup volume in G2 and G3 between weeks 1 and 9, and significant ganglion cell layer thickness reduction in G1 and a slight increase in G3. Conclusion: Intravitreal hWJ-MSCs injection produced changes in optic cup volume, which were detected early on by OCT; however, RNFL could not be restored in this OH model. Keywords: glaucoma, mesenchymal stromal cell, ocular hypertension, optic nerve head, optical coherence tomography, rabbit.
Checkpoint CD24 function on tumor and immunotherapy

CD24 is a protein found on the surface of cells that plays a crucial role in the proliferation, invasion, and spread of cancer cells. It adheres to cell membranes through glycosylphosphatidylinositol (GPI) and is associated with the prognosis and survival rate of cancer patients. CD24 interacts with the inhibitory receptor Siglec-10 that is present on immune cells like natural killer cells and macrophages, leading to the inhibition of natural killer cell cytotoxicity and macrophage-mediated phagocytosis. This interaction helps tumor cells escape immune detection and attack. Although the use of CD24 as a immune checkpoint receptor target for cancer immunotherapy is still in its early stages, clinical trials have shown promising results. Monoclonal antibodies targeting CD24 have been found to be well-tolerated and safe. Other preclinical studies are exploring the use of chimeric antigen receptor (CAR) T cells, antibody-drug conjugates, and gene therapy to target CD24 and enhance the immune response against tumors. In summary, this review focuses on the role of CD24 in the immune system and provides evidence for CD24 as a promising immune checkpoint for cancer immunotherapy.
Geophysical log characterization of the Flamborough Chalk Formation (Late Cretaceous, Santonian – Early Campanian), East Yorkshire, UK: implications for understanding the onshore and offshore occurrence of the Late Campanian Rowe Chalk Formation

Whilst borehole geophysical log profiles have been matched with formational subdivisions for large parts of the Chalk Group in Lincolnshire and Yorkshire, characterization of the youngest and thickest part of the outcropping succession, represented by the marl-rich and largely flint-free Flamborough Chalk Formation, has been hindered by lack of cored and geophysically logged boreholes. In the absence of optimal primary data, a stratigraphical interpretation of geophysical logs in the Flamborough Chalk has been developed by comparison of logs from deep hydrocarbons boreholes (penetrating more than 260 m of Flamborough Chalk) beneath Holderness (East Yorkshire) with generalized patterns of outcrop stratigraphy. This approach reveals geophysical log patterns that are consistent with lithology and thickness variations seen at outcrop, compatible with core and geophysical data for a deep borehole in the Flamborough Chalk at Carnaby (near Bridlington), and traceable northwards and westwards towards the margin of the Flamborough Chalk outcrop. These interpretations, and comparisons with geophysically logged offshore successions, suggest the presence of Flamborough Chalk beneath Holderness that is younger (? Late Campanian) than anything seen at outcrop, and, with the exception of possible ex-situ chalk rafts of glacial origin, cast doubt on the likely subsurface onshore extent of typically flint-rich Rowe Chalk Formation.
Pricing Decisions for Competitive Ride-Hailing Platforms with the Combination of Inner-Group and Inter-Group Network Externalities

Based on two-sided market theory, this paper has studied the pricing problem of ride-hailing platforms with a combination of inter-group network externality and inner-group network externality. Two scenarios of user structure are considered. In scenario 1, both travellers and drivers are single-homing. In scenario 2, travellers are single-homing while drivers are multi-homing. Moreover, time sensitive factors and driver’s commission rate are introduced to reflect the characteristics of transport industry. Finally, the impact of network externality, time sensitivity, driver’s commission rate and entry cost on ride-hailing platform pricing, user scale and profits are analysed. The results show that inter-group network externality and inner-group network externality have a negative effect on platform prices charged to both travellers and drivers. However, when travellers are multi-homing, the price charged to travellers is positive with respect to the inter-group network externality from drivers. In the relationship between travellers’ scale and inter-group network externality, inner-group network externality is positive. Further, in both scenarios, the network externalities from the two sides affect platform profits negatively.
Ocean Tide Influences on the Antarctic and Greenland Ice Sheets

Ocean tides are the main source of high‐frequency variability in the vertical and horizontal motion of ice sheets near their marine margins. Floating ice shelves, which occupy about three quarters of the perimeter of Antarctica and the termini of four outlet glaciers in northern Greenland, rise and fall in synchrony with the ocean tide. Lateral motion of floating and grounded portions of ice sheets near their marine margins can also include a tidal component. These tide‐induced signals provide insight into the processes by which the oceans can affect ice sheet mass balance and dynamics. In this review, we summarize in situ and satellite‐based measurements of the tidal response of ice shelves and grounded ice, and spatial variability of ocean tide heights and currents around the ice sheets. We review sensitivity of tide heights and currents as ocean geometry responds to variations in sea level, ice shelf thickness, and ice sheet mass and extent. We then describe coupled ice‐ocean models and analytical glacier models that quantify the effect of ocean tides on lower‐frequency ice sheet mass loss and motion. We suggest new observations and model developments to improve the representation of tides in coupled models that are used to predict future ice sheet mass loss and the associated contribution to sea level change. The most critical need is for new data to improve maps of bathymetry, ice shelf draft, spatial variability of the drag coefficient at the ice‐ocean interface, and higher‐resolution models with improved representation of tidal energy sinks.
Bond Strength Variability in Pullout Specimens with Plain Reinforcement

Bond strength results from 252 plain bar pullout specimens are presented. Parameters investigated include: concrete compressive strength, bar size, bar shape, concrete cover, and bar surface roughness. All load-slip curves displayed a characteristic shape: the maximum tensile load occurred at a very small slip (∼0.01 mm) and the load then dropped asymptotically to a residual value as the slip increased to 10 mm. Empirical equations based on least-squares analysis are presented to predict maximum and residual average bond stresses. The load-slip curve can be represented with load as a linear function of the logarithm of slip. The average bond strength was 0.98 MPa for as-received bars, and increased by 124% to 2.2 MPa for bars sandblasted to simulate realistic surface roughness. Coefficients of variation were 8% for maximum average bond stress and 24% for residual average bond stress.
IL-17 and IL-21: Their Immunobiology and Therapeutic Potentials

Studies over the last 2 decades have identified IL-17 and IL-21 as key cytokines in the modulation of a wide range of immune responses. IL-17 serves as a critical defender against bacterial and fungal pathogens, while maintaining symbiotic relationships with commensal microbiota. However, alterations in its levels can lead to chronic inflammation and autoimmunity. IL-21, on the other hand, bridges the adaptive and innate immune responses, and its imbalance is implicated in autoimmune diseases and cancer, highlighting its important role in both health and disease. Delving into the intricacies of these cytokines not only opens new avenues for understanding the immune system, but also promises innovative advances in the development of therapeutic strategies for numerous diseases. In this review, we will discuss an updated view of the immunobiology and therapeutic potential of IL-17 and IL-21.
Human resource management practices and organizational outcomes in the accommodation facilities in central philippines

HRM practices are management tools that contribute to the success of an organization. This study investigates the HRM practices and organizational outcomes in the accommodation facilities in Central Philippines using correlational research. 805 total participants answered the survey questionnaires were 123 are supervisors/managers and 682 are from the personnel of the accommodation facilities. The results showed that the respondents were satisfied with the HRM practices in the accommodation facilities where they are working. All provinces in Central Philippines, the type of accommodation facilities, and participants by generation moderately agreed that the accommodation facilities they are working in have excellent HRM practices. In terms of organizational outcomes, the accommodation facilities experience minor turn-over and absenteeism rates of their employees, a good level of productivity, substantially above average goals, and higher profit/surplus on their financial performance. The researcher concluded that there is a relationship between HRM practices and organizational outcomes that accommodation facilities that implement favorable HRM practices are more likely to have positive organizational outcomes. Higher levels of HRM practices are associated with higher organizational outcomes.
Fracture Characterization and Prediction in Unconventional Reservoirs of the “Mississippian Limestone,” North-Central Oklahoma, United States

Natural Fractures are common in several unconventional reservoirs in the U.S. and around the world and, even when sealed with cements, can facilitate the propagation of induced fractures during hydraulic fracturing. This study is focused on correlating fracture types and intensity to distinct petrophysically-significant facies and to an established sequence stratigraphic framework in the unconventional carbonate reservoirs of the “Mississippian Limestone” of the U.S. Mid-Continent region. Four fracture types are observed: ptygmatic, vertical extension, shear, and mixed types of fractures. Most of the fractures have been completely sealed with predominantly calcite cement. Fractured zones are vertically heterogeneous at various scales, indicating the variability in rock mechanical properties. At the millimeter scale, fractures are commonly discontinuous and exhibit variable width. At the centimeter scale, ptygmatic fractures exhibit variable termination modes in relation to bedding planes, suggesting a mineralogical control on rock mechanical properties. At the meter scale, the highest fracture abundance corresponds to facies with the highest calcite content. The mineralogical control of fracture distribution is also represented by the higher fracture intensity within the regressive phases of “third-order” sequences, indicating the value of sequence stratigraphic approach in characterizing and predicting fracture distribution in these unconventional reservoirs.
Esophageal squamous cell carcinoma transformed into neuroendocrine carcinoma after neoadjuvant immunochemotherapy: A case report

Immunotherapy provides durable responses for locally advanced esophageal carcinoma clinical therapy in numerous patients. However, the mechanisms of resistance to immunotherapy have not been elucidated. The phenomenon of the histological transformation of non-small cell lung cancer to small cell lung cancer resulting in resistance to immune checkpoint inhibitors (ICIs) has been reported. It remains unclear whether ICIs or chemotherapy could cause a similar transformation from esophageal squamous cell carcinoma (ESCC) to esophageal neuroendocrine carcinoma (ENEC). The present study report the case of a patient initially diagnosed with stage II ESCC who underwent radical surgery after three cycles of neoadjuvant therapy with cisplatin, albumin bound paclitaxel and ICIs. Immunohistochemical staining confirmed the absence of the SCC component and the presence of the NEC component, with negativity for CK5/6 and tumor protein p40, but positive expression of tumor protein p53, pan-cytokeratin, synaptophysin and CD56. The patient was followed up for 5 months with no treatment or postoperative complications. In conclusion, histological transformation to ENEC is a potential mechanism of acquired resistance to ICIs in ESCC. Prospective larger studies are warranted to further characterize ESCC-to-NEC transformation on use of ICIs.
65+ in the United States.

This report focuses on the elderly population of the United States. Particular attention is paid to future implications of the growth of the elderly population. "We will focus on the diversity of Americas older population in terms of age race ethnicity gender economic status longevity health and social characteristics and geographic distribution. Throughout we will examine possible implications of the demographic changes. " Data are from the 1990 census and recent official surveys. (EXCERPT)