Updates in Mucormycosis.

Mucormycosis is an aggressive and frequently lethal disease. Most patients with mucormycosis have poorly controlled diabetes mellitus and rhino-orbito-cerebral disease. Patients with hematologic malignancy and transplant recipients mostly present with rhino-orbito-cerebral or pulmonary disease.

Excess Mortality and its Determinants During the COVID-19 Pandemic in 21 Countries: An Ecological Study from the C-MOR Project, 2020 and 2021.

Introduction: The COVID-19 pandemic overwhelmed health systems, resulting in a surge in excess deaths. This study clustered countries based on excess mortality to understand their response to the pandemic and the influence of various factors on excess mortality within each cluster.

Materials And Methods: This ecological study is part of the COVID-19 MORtality (C-MOR) Consortium.

Cost-effectiveness of nonavalent vs bivalent HPV vaccine in Polish setting.

Objectives: Human papillomavirus (HPV) is a prevalent sexually transmitted infection with significant implications for public health. In Poland, a nationwide vaccination program offers a choice between the 9-valent (9v) and 2-valent (2v) HPV vaccines. We aimed to assess the cost-effectiveness of the 9v vs 2v vaccine from the public payer perspective in Poland.

Infections and antimicrobial prophylaxis in patients with myelodysplastic syndromes.

Infectious complications are an important cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). Preventing infections could significantly improve both survival and quality of life. Unfortunately, both infections and antimicrobial prophylaxis in patients with MDS are incompletely assessed due to the heterogeneity of disorders included in each publication, changing definitions over time, and lack of standardized prophylaxis practices.

Facilitators and Barriers of Incremental Innovation by Fixed Dose Combinations in Cardiovascular Diseases.

Despite the availability of affordable pharmaceuticals treating cardiovascular diseases (CVDs), many of the risk factors remain poorly controlled. Fixed-dose combinations (FDCs), a form of incremental innovation, have already demonstrated improvements over combinations of single medicines in adherence and hard clinical endpoints. Nevertheless, there are many barriers related to the wider use of FDCs in CVDs.

Knowledge and Beliefs about Clinical Trials among Adults in Poland: A Cross-Sectional Study.

Unlabelled: Clinical trials, by contributing to the development of diagnostics and to the search for modern, more effective, and safer therapies, have become one of the most important elements of the healthcare system. They enable the introduction of innovative drugs and treatments that can significantly improve patients' quality of life. Not only does this research help to understand disease mechanisms, but it also enables the personalization of therapy, which often increases the effectiveness of treatment.

Cost saving analysis of prediabetes intervention modalities in comparison with inaction using Markov state transition model-A multiregional case study.

Background: Prediabetes management is a priority for policymakers globally, to avoid/delay type 2 diabetes (T2D) and reduce severe, costly health consequences. Countries moving from low to middle income are most at risk from the T2D "epidemic" and may find implementing preventative measures challenging; yet prevention has largely been evaluated in developed countries.

Methods: Markov cohort simulations explored costs and benefits of various prediabetes management approaches, expressed as "savings" to the public health care system, for three countries with high prediabetes prevalence and contrasting economic status (Poland, Saudi Arabia, Vietnam).

Estimation of daylight spectral power distribution from uncalibrated hyperspectral radiance images.

This paper introduces a novel framework for estimating the spectral power distribution of daylight illuminants in uncalibrated hyperspectral images, particularly beneficial for drone-based applications in agriculture and forestry. The proposed method uniquely combines image-dependent plausible spectra with a database of physically possible spectra, utilizing an image-independent principal component space (PCS) for estimations. This approach effectively narrows the search space in the spectral domain and employs a random walk methodology to generate spectral candidates, which are then intersected with a pre-trained PCS to predict the illuminant.

Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis.

Circulating lactate is a fuel source for liver metabolism but may exacerbate metabolic diseases such as nonalcoholic steatohepatitis (NASH). Indeed, haploinsufficiency of lactate transporter monocarboxylate transporter 1 (MCT1) in mice reportedly promotes resistance to hepatic steatosis and inflammation. Here, we used adeno-associated virus (AAV) vectors to deliver thyroxin binding globulin (TBG)-Cre or lecithin-retinol acyltransferase (Lrat)-Cre to MCT1 mice on a choline-deficient, high-fat NASH diet to deplete hepatocyte or stellate cell MCT1, respectively.

Improving Vaccine Assessment Pathways and Decision Making in the Polish Immunization Program.

This study examines the vaccine market access pathway in Poland to evaluate its efficiency and propose recommendations for its improvement. The research spans a comprehensive analysis of the vaccine assessment process, ranging from pre-registration to sustainability, encompassing critical components such as national immunization technical advisory groups (NITAGs), health technology assessments, resource evaluations, and decision making. This investigation utilizes a multi-phase approach.

Improved measurement of disease progression in people living with early Parkinson's disease using digital health technologies.

Background: Digital health technologies show promise for improving the measurement of Parkinson's disease in clinical research and trials. However, it is not clear whether digital measures demonstrate enhanced sensitivity to disease progression compared to traditional measurement approaches.

Methods: To this end, we develop a wearable sensor-based digital algorithm for deriving features of upper and lower-body bradykinesia and evaluate the sensitivity of digital measures to 1-year longitudinal progression using data from the WATCH-PD study, a multicenter, observational digital assessment study in participants with early, untreated Parkinson's disease.

Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), for which therapeutic options are limited. Strategies to promote intestinal tissue tolerance during aGVHD may improve patient outcomes. Using single-cell RNA sequencing, we identified a lipocalin-2 (LCN2)-expressing neutrophil population in mice with intestinal aGVHD.

Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis.

Cotranslational protein folding depends on general chaperones that engage highly diverse nascent chains at the ribosomes. Here we discover a dedicated ribosome-associated chaperone, Chp1, that rewires the cotranslational folding machinery to assist in the challenging biogenesis of abundantly expressed eukaryotic translation elongation factor 1A (eEF1A). Our results indicate that during eEF1A synthesis, Chp1 is recruited to the ribosome with the help of the nascent polypeptide-associated complex (NAC), where it safeguards eEF1A biogenesis.

Leveraging the holistic benefits of biosimilars in Europe - part 2: how payers can safeguard the future of a healthy biosimilar market environment.

Introduction: Biosimilars have improved access to biologic medicines; however, historical thinking may jeopardize the viability of future markets.

Areas Covered: An expert panel of eight diverse European stakeholders provided insights about rethinking biosimilars and cost-savings, reducing patient access inequalities, increasing inter-market equity, and improving education. The insights reported here (Part 2) follow a study that provides perspectives on leveraging the holistic benefits of biosimilars for market sustainability based on independent survey results and telephone interviews of stakeholders from diverse biosimilar markets (Part 1).

Capturing the holistic value of biosimilars in Europe - part 1: a historical perspective.

Introduction: Approved biosimilars exhibit comparable efficacy, safety, and immunogenicity to reference products. This report provides perspectives on the societal value of biosimilars within Europe and potential factors that have influenced market dynamics.

Methods: An independent, self-administered survey or one-on-one in-depth interview was used to collect viewpoints about the impact of biosimilar medicines within European markets.

Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status.

Bone formation is a highly energy-demanding process that can be impacted by metabolic disorders. Glucose has been considered the principal substrate for osteoblasts, although fatty acids are also important for osteoblast function. Here, we report that osteoblasts can derive energy from endogenous fatty acids stored in lipid droplets via lipolysis and that this process is critical for bone formation.

Awareness, Attitudes and Willingness to Donate Biological Samples to a Biobank: A Survey of a Representative Sample of Polish Citizens.

Biotechnology is developing at an ever-increasing pace, and the progressive computerization of health care and research is making it increasingly easy to share data. One of the fastest growing areas is biobanking. However, even with the best equipment and the best trained staff, a biobank will be useless without donors.

Fatty acid availability controls autophagy and associated cell functions.

Macroautophagy/autophagy requires enormous membrane expansions during concerted actions of transient autophagic vesicles and lysosomes, yet the source of the membrane lipids is poorly understood. Recent work in adipocytes has now pinpointed the de novo lipogenesis pathway as the preferred source of fatty acids for phospholipid in autophagic membrane synthesis, as loss of FASN (fatty acid synthase) disrupts autophagic flux and lysosome function and . These data indicate fatty acid synthesis channels lipid for membrane expansions, whereas fatty acids from circulating lipoproteins provide for adipose lipid storage.

Crosstalk between corepressor NRIP1 and cAMP signaling on adipocyte thermogenic programming.

Objectives: Nuclear receptor interacting protein 1 (NRIP1) suppresses energy expenditure via repression of nuclear receptors, and its depletion markedly elevates uncoupled respiration in mouse and human adipocytes. We tested whether NRIP1 deficient adipocytes implanted into obese mice would enhance whole body metabolism. Since β-adrenergic signaling through cAMP strongly promotes adipocyte thermogenesis, we tested whether the effects of NRIP1 knock-out (NRIP1KO) require the cAMP pathway.

Recommendations for patient involvement in health technology assessment in Central and Eastern European countries.

Introduction: Meaningful patient involvement in health technology assessment (HTA) is essential in ensuring that the interests of the affected patient population, their families, and the general public are accurately reflected in coverage and reimbursement decisions. Central and Eastern European (CEE) countries are generally at less advanced stages of implementing HTA, which is particularly true for patient involvement activities. As part of the Horizon2020 HTx project, this research aimed to form recommendations for critical barriers to patient involvement in HTA in CEE countries.

Dual targeting of hepatocyte DGAT2 and stellate cell FASN alleviates nonalcoholic steatohepatitis in mice.

Nonalcoholic steatohepatitis (NASH) is a malady of multiple cell types associated with hepatocyte triglyceride (TG) accumulation, macrophage inflammation, and stellate cell-induced fibrosis, with no approved therapeutics yet available. Here, we report that stellate cell fatty acid synthase (FASN) in de novo lipogenesis drives the autophagic flux that is required for stellate cell activation and fibrotic collagen production. Further, we employ a dual targeting approach to NASH that selectively depletes collagen through selective stellate cell knockout of FASN (using AAV9-LRAT Cre in FASN mice), while lowering hepatocyte triglyceride by depleting DGAT2 with a GalNac-conjugated, fully chemically modified siRNA.