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As part of the digitalization strategy for medical documentation, we introduced a vendor-neutral archive (VNA) at the Jena University Hospital. The VNA provides data based on interoperable formats for all clinical systems and for communication with other actors as well as for secondary data use. HL7 FHIR is used as a standard for structuring individual data. Using the example of allergy documentation, the paper describes objectives, work status, and experiences from several sub-projects currently being pursued in Jena to establish FHIR. Challenges in information modelling, semantic annotation, connection of clinical sub-systems and integration of FHIR resources in archiving structures and processes are discussed and the necessary cooperation for profiling technical standards is indicated.

BackgroundGermany is the first country worldwide that has introduced a digital care act as an incentive system to enhance the use of digital health devices, namely health apps and wearables, among its population. The act allows physicians to prescribe statutory financed and previously certified health apps and wearables to patients. This initiative has the potential to improve treatment quality through better disease management and monitoring. ObjectiveThe aim of this paper was to outline the key concepts related to the potential risks and benefits discussed in the current literature about health apps and wearables. Furthermore, this study aimed to answer the research question: Which risks and benefits may result from the implementation of the digital care act in Germany? MethodsWe conducted the scoping study by searching the databases PubMed, Google Scholar, and JMIR using the keywords health apps and wearables. We discussed 55 of 136 identified articles published in the English language from 2015 to March 2019 in this paper using a qualitative thematic analysis approach. ResultsWe identified four key themes within the articles: Effectivity of health apps and wearables to improve health; users of health apps and wearables; the potential of bring-your-own, self-tracked data; and concerns and data privacy risks. Within these themes, we identified three main stages of benefits for the German health care system: Usage of health apps and wearables; continuing to use health apps and wearables; and sharing bring-your-own; self-tracked data with different agents in the health care sector. ConclusionsThe digital care act could lead to an improvement in treatment quality through better patient monitoring, disease management, personalized therapy, and better health education. However, physicians should play an active role in recommending and supervising health app use to reach digital-illiterate or health-illiterate people. Age must not be an exclusion criterion. Yet, concerns about data privacy and security are very strong in Germany. Transparency about data processing should be provided at all times for continuing success of the digital care act in Germany.

Coffee (Coffea arabica L.) is a globally important agricultural crop with increasing quality requirements. However, the challenges posed by climate change impact cup quality. Therefore, the objective was to evaluate the influence of tree diversity and crop segmentation under agroforestry systems on the sensory characteristics of coffee. The study employed a 4A*3B factorial design, with factor A: agroforestry systems (mixed system, shade-free system, system with Erythrina edulis and system with Inga edulis) and factor B: segmented harvest (upper, middle, and lower third cherries). Fragrance/aroma, flavor, residual flavor, acidity, body, uniformity, balance, clean cup, sweetness, cupper's score, and final score were evaluated. The results suggest that coffee trees planted in mixed systems provide the best sensory characteristics of coffee in the cup since the highest averages were obtained in most of the variables evaluated. Likewise, it is concluded that the diversity of trees (mixed system and system with Erythrina edulis) has a positive influence on the sensory quality of the coffee, reaching a score of 82.86 and 82.64 for the mixed system and the system with Erythrina edulis respectively; categorizing them as specialty coffees. Agroforestry systems constitute an option for developing sustainable agriculture while improving the sensory quality of coffee in the Peruvian Amazon.

Natural resources policies that promote sustainable management are critical for protecting diverse stakeholders against depletion. Although integrating diverse stakeholders into these policies has been theorized to improve protection, empirical evidence is lacking. Here, we evaluate 108 Sustainability Plans under Californias Sustainable Groundwater Management Act to quantify how well stakeholders are integrated into plans and protected from groundwater depletion. We find that the majority of Sustainability Plans do not integrate or protect the majority of their stakeholders. Nevertheless, our results show that when stakeholders are more integrated into a Sustainability Plan, they are more likely to be protected, particularly for those that lack formal access to decision-making processes. Our findings provide strong empirical evidence that integrating diverse stakeholders into sustainability planning is beneficial for stakeholders who are vulnerable to the impacts of natural resource depletion.

IntroductionAmyloid-specific antibodies have been shown to opsonize and enhance amyloid clearance in systemic amyloidosis mouse models. However, the immunological mechanisms by which amyloid is removed have not been clearly defined. Previous reports from preclinical in vivo studies suggest polymorphonuclear cells (i.e., neutrophils) can affect amyloid removal. Therefore, we sought to analyze how neutrophils may contribute to the clearance of human AL amyloid extracts, using a murine amyloidoma model.MethodsImmunocompromised nude mice injected subcutaneously with patient-derived AL amyloid extract (generating a localized “amyloidoma”) were used to circumvent confounding factors contributed by the adaptive immune system and served as the model system. Two representative AL amyloid extracts were used, ALλ(CLA), which is refractory to clearance, and ALκ(TAL), which is readily cleared in mice. Neutrophil recruitment to the amyloid masses, cellular activation, and propensity to engulf amyloid were assessed.ResultsImmunophenotyping of amyloidomas from animals implanted with 2 mg of either ALλ or ALκ revealed that more neutrophils were recruited to ALκ amyloid masses as compared to the ALλ material, which was generally devoid of neutrophils. Ex vivo analyses indicated neutrophils do not efficiently phagocytose amyloid directly. However, histological evaluation of the ALκ amyloidoma revealed the abundant presence of neutrophil extracellular traps, which were absent in the ALλ amyloidomas. Using neutrophil depletion experiments in mice, we determined that mice devoid of neutrophils cleared the human amyloid lesions less efficiently. Moreover, mice devoid of neutrophils also had significantly reduced intra-amyloid expression of inflammatory cytokines.DiscussionNeutrophils may not directly mediate amyloid clearance through phagocytosis; however, these cells can be stimulated by the amyloid and may function to facilitate phagocytosis and amyloid clearance by professional phagocytes (e.g., macrophages).

Background: The incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer (UBC) has continued to increase, despite an absent survival benefit except in populations at highest risk for developing contralateral breast cancer (CBC). CPM rates may be higher in rural populations but causes remain unclear. A study performed at our institution previously found that 21.8 % of patients with UBC underwent CPM from 2000 to 2009. This study aimed to evaluate the CPM trend at a single institution serving a rural population and identify the CPM rate in average-risk patients. Methods: Retrospective review of patients who underwent mastectomies for UBC at our institution from 2017 to 2021 was performed. Analysis utilized frequencies and percentages, descriptive statistics, chi-square, and independent sample t-tests. Results: A total of 438 patients were included, of whom 64.4 % underwent bilateral mastectomy for UBC (CPM). Patients who underwent CPM were significantly younger, underwent genetic testing, had germline pathogenic variants, had a family history of breast cancer, had smaller tumors, underwent reconstruction, and had more wound infections. Of CPM patients, 50.4 % had no identifiable factors for increased risk of developing CBC. Conclusions: The rate of CPM in a rural population at a single institution increased from 21.8 % to 64.4 % over two decades, with an average-risk CPM rate of 50.4 %. Those that undergo CPM are more likely to undergo reconstruction and have more wound infections. Identifying characteristics of patients undergoing CPM in a rural population and the increased associated risks allows for a better understanding of this trend to guide conversations with patients. Key message: This study demonstrates that the rate of contralateral prophylactic mastectomy for unilateral breast cancers performed at a single institution serving a largely rural population has nearly tripled over the last two decades, with half of these patients having no factors that increase the risk for developing contralateral breast cancers. Contralateral prophylactic mastectomy was significantly associated with smaller tumors, younger age, genetic testing, germline pathogenic variants, family history of breast cancer, breast reconstruction, and increased wound infections.

Abstract Pharmacologic targeting of chromatin-associated protein complexes has shown significant responses in KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) but resistance frequently develops to single agents. This points to a need for therapeutic combinations that target multiple mechanisms. To enhance our understanding of functional dependencies in KMT2A-r AML, we have used a proteomic approach to identify the catalytic immunoproteasome subunit PSMB8 as a specific vulnerability. Genetic and pharmacologic inactivation of PSMB8 results in impaired proliferation of murine and human leukemic cells while normal hematopoietic cells remain unaffected. Disruption of immunoproteasome function drives an increase in transcription factor BASP1 which in turn represses KMT2A-fusion protein target genes. Pharmacologic targeting of PSMB8 improves efficacy of Menin-inhibitors, synergistically reduces leukemia in human xenografts and shows preserved activity against Menin-inhibitor resistance mutations. This identifies and validates a cell-intrinsic mechanism whereby selective disruption of proteostasis results in altered transcription factor abundance and repression of oncogene-specific transcriptional networks. These data demonstrate that the immunoproteasome is a relevant therapeutic target in AML and that targeting the immunoproteasome in combination with Menin-inhibition could be a novel approach for treatment of KMT2A-r AML.

Introduction: From the perspective of social determinants, homelessness perpetuates poor health and creates barriers to effective chronic disease management, necessitating frequent use of emergency department (ED) services. In this study we developed a screening algorithm (checklist) from common comorbidities observed in the homeless population in the United States. The result was a theoretical screening tool (checklist) to aid healthcare workers in the ED, including residents, medical students, and other trainees, to provide more efficacious treatment and referrals for discharge.Methods: In this retrospective cohort study we used the Nationwide Emergency Department Sample (NEDS) to investigate comorbidities and ED utilization patterns relating to 23 injury-related, psychiatric, and frequent chronic medical conditions in the US adult (≥18 years of age) homeless population. Cases were identified from the NEDS database for 2014–2017 using International Classification of Diseases, 9th and 10 revisions, and Clinical Classification Software diagnosis codes. We performed a two-step cluster analysis including pathologies with ≥10% prevalence in the sample to identify shared comorbidities. We then compared the clusters by sociodemographic and ED-related characteristics, including age, gender, primary payer, and patient disposition from the ED. Chi-square analysis was used to evaluate categorical variables (ie, gender, primary payer, patient disposition from the ED), and analysis of variance for continuous variables (age).Results: The study included 1,715,777 weighted cases. The two-step cluster analysis identified nine groups denominated by most prevalent disease: 1) healthy; 2) mixed psychiatric; 3) major depressive disorder (MDD); 4) psychosis; 5) addiction; 6) essential hypertension; 7) chronic obstructive pulmonary disease (COPD); 8) infectious disease; and (9) injury. The MDD, COPD, infectious disease, and Injury clusters demonstrated the highest prevalence of co-occurring disease, with the MDD cluster displaying the highest proportion of comorbidities. Although the addiction cluster existed independently, substance use was pervasive in all except the healthy cluster (prevalence 36-100%). We used the extracted screening algorithm to establish a screening tool (checklist) for ED healthcare workers, with physicians as the first point of contact for the initial use of the screening tool.Conclusion: Healthcare workers in the ED, including residents, medical students, and other trainees, provide services for homeless ED users. Screening tools (checklists) can help coordinate care to improve treatment, referrals, and follow-up care to reduce hospital readmissions. The screening tool may expedite targeted interventions for homeless patients with commonly occurring patterns of disease.

Background: The aim of our study was to investigate associations of spleen volume with blood count markers and lipid profile in the general population. Materials & methods: Cross-sectional data from 1,106 individuals aged 30–90 years from the population-based Study of Health in Pomerania (SHIP-START-2) were analyzed. Blood count markers included red blood cell (RBC) counts, hemoglobin, platelet count, and white blood cell (WBC) counts. Lipid profile included total-cholesterol, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) as well as triglycerides. Linear regression models adjusted for age, sex, body height, and weight were used to associate standardized spleen volume with blood counts and lipid profile markers. Results: Spleen volume was positively associated with RBC (β = 0.05; 95% confidence interval [CI] = 0.03 to 0.08) and hemoglobin (β = 0.05; 95% CI = 0.01 to 0.09) but inversely with platelet count (β = −16.3; 95% CI = –20.5 to −12.1) and WBC (β = −0.25; 95% CI = −0.37 to −0.14). Furthermore, spleen volume showed inverse associations with total cholesterol (β = −0.17; 95% CI = −0.24 to −0.09), HDL-C (β = −0.08; 95% CI = −0.10 to −0.05), and LDL-C (β = −0.12; 95% CI = −0.17 to −0.06). There was no significant association of spleen volume with triglycerides. Conclusion: Our study showed that the spleen volume is associated with markers of the blood count and lipid profile in the general population.

Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference-based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial (NCT03020017) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment-related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129-treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.

Entomopathogenic fungi represent the pinnacle of efficacy among biological control agents when combating insect pests within natural ecosystems, combating them without altering the environment. This study aimed to isolate and characterize the morphology, physiology, and pathogenicity of native isolates of Metarhizium sp. isolated from soil samples from the province of Rodriguez de Mendoza. Eighteen native isolates of Metarhizium sp. were isolated and characterized. Colony coloration varied between yellow-gray, white, brown, and olive, with feathery or wavy edges. As for radial growth, the highest averages were obtained by isolates LLM-M2 and TOR-M16, with 43.15 mm and 42.85 mm, respectively. Conidia production at 15 days was higher for isolate LLM-M2 with 9.8 × 107 conidia/mL; in the percentage of germination at 14 h, the treatment that reached 100% germination was TOR-M16. Isolate CMR-M7 reached 97.49% mycelial growth percentage at 288 h, being the best result; in the percentage of mortality in CBB adults, the treatments that reached 100% were TOR-M9, TOR-M16, and MNR-M1. In general, the results demonstrate the entomopathogenic potential of native isolates of Metarhizium sp. acting as biocontrol agents of Hypothenemus hampei, being a low-cost, easily accessible, and environmentally friendly alternative.

Researchers examined the correlation between the physician's subjective assessment of health literacy rates and actual health literacy rates among patients as determined by the Newest Vital Sign (NVS). A sample of n = 150 patients, 18 years of age or older, were verbally interviewed using NVS tool before seeing their physician. After the physician met with the patient, the physician was asked to measure that patient's level of health literacy on a Likert-type scale and a “yes/no” scale. Frequency and percentage statistics were performed in SPSS to describe the distributions of patient and physician responses. Between-subjects statistics were used. Analysis of the patient surveys revealed one in 4 patients has a high likelihood of low health literacy. Analysis revealed there were significant positive correlations between physician response to perception of a patient's low health literacy risk and NVS survey responses. Despite the risk of limited literacy, 97.3% of physicians perceived the patient to understand what the physician was saying. Physicians should use teach-back and other health literacy principles with each patient, regardless of perceived risk.

Extinction rates are expected to increase during the Anthropocene. Current extinction rates of plants and many animals remain unknown. We quantified extinctions among the vascular flora of the continental United States and Canada since European settlement. We compiled data on apparently extinct species by querying plant conservation databases, searching the literature, and vetting the resulting list with botanical experts. Because taxonomic opinion varies widely, we developed an index of taxonomic uncertainty (ITU). The ITU ranges from A to F, with A indicating unanimous taxonomic recognition and F indicating taxonomic recognition by only a single author. The ITU allowed us to rigorously evaluate extinction rates. Our data suggest that 51 species and 14 infraspecific taxa, representing 33 families and 49 genera of vascular plants, have become extinct in our study area since European settlement. Seven of these taxa exist in cultivation but are extinct in the wild. Most extinctions occurred in the west, but this outcome may reflect the timing of botanical exploration relative to settlement. Sixty-four percent of extinct plants were single-site endemics, and many occurred outside recognized biodiversity hotspots. Given the paucity of plant surveys in many areas, particularly prior to European settlement, the actual extinction rate of vascular plants is undoubtedly much higher than indicated here.

Introduction: Plasma transfusion is a common therapeutic strategy used to lower international normalized ratio (INR) values in the non-emergent setting. However, due to lack of evidence of its efficacy, standardized guidelines for this practice have not been well established. Methods: This retrospective observational cohort study analyzed 276 inpatient encounters that involved plasma transfusions focusing on change in INR values from pre- to post-transfusion, with respect to the following predictor variables: vitamin K co-administration, number of plasma units transfused, order indication and body mass index (BMI). Results: The overall average change in the INR was 1.35. Patients who received vitamin K showed an average change of 2.51, while patients that did not receive vitamin K demonstrated an average change of 0.70. Increased numbers of plasma units transfused showed benefit up to three-unit orders. Greater decreases in the INR were observed for patients requiring plasma for anticoagulation reversal or active bleeding. There was no significant difference in the change in INR based on the BMI. By multivariate and regression analyses, the stepwise addition of each successive predictor variable demonstrated an increase in the shared variance in the outcome of the post-transfusion INR: the pre-transfusion INR and vitamin K co-administration alone was not significant (p = 0.45); the additional number of plasma units transfused was significant (R² = 0.13, p < 0.001), and; the subsequent additional plasma order indications (R² = 0.19, p < 0.001) and BMI (R² = 0.18, p < 0.001) were increasingly significant. Conclusion: Taking into consideration the combination of multiple predictive factors may aid in a more efficient use of plasma products.

Immune system function declines with age, a consequence of defects in hematopoietic stem cells (HSCs). Here the authors show that TAZ buffers age-related loss of PU.1 activity to maintain HSC functionality and identify the surface protein Clca3a1 as a marker of “young-like” HSCs, even in old mice.