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Eukaryotic organisms are composed of different cell types with defined shapes and functions. Specific cell types are produced by the process of cell differentiation, which is regulated by signal transduction pathways. Signaling pathways regulate cell differentiation by sensing cues and controlling the expression of target genes whose products generate cell types with specific attributes. In studying how cells differentiate, fungi have proved valuable models because of their ease of genetic manipulation and striking cell morphologies. Many fungal species undergo filamentous growth—a specialized growth pattern where cells produce elongated tube-like projections. Filamentous growth promotes expansion into new environments, including invasion into plant and animal hosts by fungal pathogens. The same signaling pathways that regulate filamentous growth in fungi also control cell differentiation throughout eukaryotes and include highly conserved mitogen-activated protein kinase (MAPK) pathways, which is the focus of this review. In many fungal species, mucin-type sensors regulate MAPK pathways to control filamentous growth in response to diverse stimuli. Once activated, MAPK pathways reorganize cell polarity, induce changes in cell adhesion, and promote the secretion of degradative enzymes that mediate access to new environments. However, MAPK pathway regulation is complicated because related pathways can share components with each other yet induce unique responses (i.e. signal specificity). In addition, MAPK pathways function in highly integrated networks with other regulatory pathways (i.e. signal integration). Here, we discuss signal specificity and integration in several yeast models (mainly Saccharomyces cerevisiae and Candida albicans) by focusing on the filamentation MAPK pathway. Because of the strong evolutionary ties between species, a deeper understanding of the regulation of filamentous growth in established models and increasingly diverse fungal species can reveal fundamentally new mechanisms underlying eukaryotic cell differentiation. [ABSTRACT FROM AUTHOR]

Abstract Background The non-communicable disease (NCD) epidemic among Pacific Islanders prompted the declaration of a regional state of NCD emergency throughout the United States-Affiliated Pacific Islands (USAPIs) in 2010. Subsequently, the University of Guam Health Science Program launched a pilot study on NCD research in its undergraduate curriculum modeled after the Pacific Data for Decision Making (DDM) framework – a field epidemiology training program employed in the USAPIs. The primary objective of the research is to conduct annual assessments of student health indicators with plans for longitudinal follow-up. Here, development and evaluation of the undergraduate research curriculum are described. Methods The Pacific DDM framework covering knowledge and skills in resourcing, types of data and indicators, data sources, data management, information products, and data dissemination and use were incorporated in undergraduate core courses of the Health Science Program. During the data collection pilot years, 2013 and 2014, a survey containing questions predominantly on NCD risk factors was launched at the university. The survey was administered by upperclassmen in the Health Science Program and evolved into the Pacific Islands Cohort of College Students (PICCS) research study. The initial years were spent developing the infrastructure. Program outputs were tracked annually to measure program success. Results Students in the Health Science Program obtained research knowledge and skills through various courses while enrolled in the program. The PICCS data collection continued annually as a cross-sectional survey from 2015 to current. Numerous successes have resulted including student abstracts and publications, acceptances to summer programs and fellowships, a sustained annual health fair for college students, a grant award, and other program-related impacts. Conclusion The PICCS framework provided the organizational structure and documented tools, protocols, roles, and responsibilities to enhance consistency and reproducibility. Undergraduate students applied their knowledge and skills to an ongoing study focused on NCD risk factor surveillance of college students. Additionally, multiple research successes have been achieved through the PICCS curriculum. Plans are underway to begin the longitudinal design of the PICCS research study and sustain it through the curriculum, with room for adaptation as courses are updated over time.

Aim: To explore enablers and barriers to the creation of an oral health training for care workers at specialized centres for children with disabilities in Ouagadougou. Design: This was a formative study informed by the Theoretical Domains Framework using qualitative methods. Methods: Qualitative observations and 14 semi‐structured interviews were conducted with care workers from six specialized centres for disability. Results: Carer workers emphasized that a successful oral health training must account for available resources and competencies in each specific centre. Part of the training must be dedicated to oral hygiene targeted for people with disabilities and provide knowledge about risk factor management. Care workers must be empowered through the training with practical skills and tools to manage regular toothbrushing and identify oral health needs of their dependents. Conclusion: This study gathered valuable and unique perspectives about the roles of care workers of children with disabilities in Ouagadougou and underscores the need for improving access to oral health and care services for children with disabilities in low‐resourced settings. Implications for Patient Care: Teams planning oral health promotion activities in low resourced settings for vulnerable population groups can benefit from the methodology and results of this research for ensuring their interventions are appropriate and relevant. Impact: This is a unique field study conducted in a scarcely researched area of caregiving practices for children with disabilities in a low‐income country, Burkina Faso. Results from the disability centre observations and interviews with local caregivers are of great value to any team planning health projects in similar low‐resourced settings. Psychiatric and mental health nursing practices are highly context‐dependent, thus using proposed qualitative methods can help to ensure that planned interventions are appropriate and relevant. Patient or Public Contribution: There was no patient contribution in this study. [ABSTRACT FROM AUTHOR]

To tailor electrical properties of often degenerate pristine CuI, Ni is introduced as alloy constituent. Cosputtering in a reactive, but also in an inert atmosphere as well as pulsed laser deposition (PLD), is used to grow NixCu1−xI$\left(\text{Ni}\right)_{x} \left(\text{Cu}\right)_{1 - x} \text{I}$ thin films. The Ni content within the alloy thin films is systematically varied for different growth techniques and growth conditions. A solubility limit is evidenced by an additional NiI2(H2O)6$\left(\text{NiI}\right)_{2} \left(\left(\text{(H}\right)_{2} \text{O)}\right)_{6}$ phase for Ni contents x≥0.31$x \geq 0.31$, observed in X‐Ray diffraction and atomic force microscopy by a change in surface morphology. Furthermore, metallic, nanoscaled nickel clusters, revealed by X‐Ray photoelectron spectroscopy and high‐resolution transmission electron microscopy (HRTEM), underpin a solubility limit of Ni in CuI. Although no reduction of charge carrier density is observed with increasing Ni content, a dilute magnetic behavior of the thin films is observed in vibrating sample magnetometry. Further, independent of the deposition technique, unique multilayer features are observed in HRTEM measurements for thin films of a cation composition of x≈0.06$x \approx $. Opposite to previous claims, no transition to n‐type behavior was observed, which was also confirmed by density functional theory calculations of the alloy system. [ABSTRACT FROM AUTHOR]

Background: Limited clinical data exists regarding use of direct oral anticoagulants (DOACs) in extreme obesity, specifically those ≥140 kg or having a body mass index (BMI) ≥ 50 kg/m2. Objective: Evaluate the safety and efficacy of DOACs in extreme obesity. Patients/Methods: A retrospective chart review was performed at a single center of patients aged 18-89 years and weight ≥140 kg or BMI ≥50 kg/m2 receiving warfarin or DOAC therapy. Patients were followed for 1 year from prescribing/study inclusion. The primary outcome was the difference in rates of any bleed (composite of major, nonmajor clinically relevant, or minor bleeding events as defined by International Society of Thrombosis and Haemostasis (ISTH) criteria) between groups. Secondary outcomes included individual components of the composite primary outcome and effectiveness in preventing thrombotic events within 12 months. Post-hoc multivariate analysis evaluated potential predictors of bleeding events within overall patient population. Results: Two-hundred eighty-five patients were included, 80 and 205 in the DOAC and warfarin groups, respectively. Rates of any documented bleeding event were comparable in DOAC and warfarin groups (17.5% vs 17.1%, P >.05). No significant difference in rates of minor (P =.067), nonmajor clinically relevant (P =.825), and major (P = 1) bleeding events were observed. Two thrombotic events occurred in the warfarin group compared to none in the DOAC group. Increasing weight was associated with bleeding events in multivariate analysis. Conclusions: This data did not demonstrate a difference in safety or efficacy outcomes between DOACs and warfarin when utilized in patients with extreme obesity. [ABSTRACT FROM AUTHOR]

Background Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). Methods This was a retrospective study of all patients in the Veteran's Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count 96-hours of treatment before the incident antimicrobial was started. The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Results Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received >96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs 13.04% 9/69); P <.001). The pathogen most prevalent was methicillin susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (P =.34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs 3.7% (1/27); P =.01). Conclusions ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs. [ABSTRACT FROM AUTHOR]

Platelets are generated by specialized cells called megakaryocytes (MKs). However, MK's origin and platelet release mode have remained incompletely understood. Here, we established direct visualization of embryonic thrombopoiesis in vivo by combining multiphoton intravital microscopy (MP-IVM) with a fluorescence switch reporter mouse model under control of the platelet factor 4 promoter (Pf4CreRosa26mTmG). Using this microscopy tool, we discovered that fetal liver MKs provide higher thrombopoietic activity than yolk sac MKs. Mechanistically, fetal platelets were released from MKs either by membrane buds or the formation of proplatelets, with the former constituting the key process. In E14.5 c-Myb-deficient embryos that lack definitive hematopoiesis, MK and platelet numbers were similar to wild-type embryos, indicating the independence of embryonic thrombopoiesis from definitive hematopoiesis at this stage of development. In summary, our novel MP-IVM protocol allows the characterization of thrombopoiesis with high spatio-temporal resolution in the mouse embryo and has identified membrane budding as the main mechanism of fetal platelet production. [ABSTRACT FROM AUTHOR]

Pulsed laser deposition (PLD) is one of the most flexible physical growth techniques for thin films of functional materials at the research and demonstrator level. We describe here a relatively simple and reliable concept of the PLD hardware that allows both deposition on large areas up to 4 in. diameter and deposition of tailored lateral and vertical composition spreads without time-consuming hardware changes. Different PLD approaches have been implemented in various chambers via specific and correlated computer-controlled movements of the target, substrate, and masks in conjunction with an appropriate target phase composition. The design of the chambers benefits from our long-term experience to find the most reliable solutions for the critical mechanical and high-temperature parts. [ABSTRACT FROM AUTHOR]

Anion doping is an efficient method for modifying the electrical property of the p‐type semiconductor CuI. However, adjustment of the hole density is still challenging. Using sputtering and spin coating techniques, well‐controlled S‐doping of CuI thin films has been realized. The spin‐coated samples present a single (111) out‐of‐plane orientation and very high crystallinity, which is comparable with previously reported epitaxial CuI thin films. The sputtered thin films have advantages in surface morphology and conductivity. Substituting S for I can achieve efficient acceptor doping of CuI for both the physical and chemical growth methods. The highest conductivity of CuI appears at 2.0 at% of S doping, and the doping efficiency is influenced by the self‐compensation effect. [ABSTRACT FROM AUTHOR]