Miracle-dz/UniFAR-FTUs huggingface dataset:
Designing and Implementing an IT Architecture for a Digital Multicenter Dementia Registry: digiDEM Bayern

Abstract Background Registries are an essential research tool to investigate the long-term course of diseases and their impact on the affected. The project digiDEM Bayern will set up a prospective dementia registry to collect long-term data of people with dementia and their caregivers in Bavaria (Germany) supported by more than 300 research partners. Objective The objective of this article is to outline an information technology (IT) architecture for the integration of a registry and comprehensive participant management in a dementia study. Measures to ensure high data quality, study governance, along with data privacy, and security are to be included in the architecture. Methods The architecture was developed based on an iterative, stakeholder-oriented process. The development was inspired by the Twin Peaks Model that focuses on the codevelopment of requirements and architecture. We gradually moved from a general to a detailed understanding of both the requirements and design through a series of iterations. The experience learned from the pilot phase was integrated into a further iterative process of continuous improvement of the architecture. Results The infrastructure provides a standardized workflow to support the electronic data collection and trace each participant's study process. Therefore, the implementation consists of three systems: (1) electronic data capture system for Web-based or offline app-based data collection; (2) participant management system for the administration of the identity data of participants and research partners as well as of the overall study governance process; and (3) videoconferencing software for conducting interviews online. First experiences in the pilot phase have proven the feasibility of the framework. Conclusion This article outlines an IT architecture to integrate a registry and participant management in a dementia research project. The framework was discussed and developed with the involvement of numerous stakeholders. Due to its adaptability of used software systems, a transfer to other projects should be easily possible.
Dissection-independent production of Plasmodium sporozoites from whole mosquitoes

Overcoming limitations of traditional dissection-dependent methods for malarial sporozoite isolation from mosquitoes, a new dissection-free method is presented that yields pure, infective sporozoites. Progress towards a protective vaccine against malaria remains slow. To date, only limited protection has been routinely achieved following immunisation with either whole-parasite (sporozoite) or subunit-based vaccines. One major roadblock to vaccine progress, and to pre-erythrocytic parasite biology in general, is the continued reliance on manual salivary gland dissection for sporozoite isolation from infected mosquitoes. Here, we report development of a multi-step method, based on batch processing of homogenised whole mosquitoes, slurry, and density-gradient filtration, which combined with free-flow electrophoresis rapidly produces a pure, infective sporozoite inoculum. Human-infective Plasmodium falciparum and rodent-infective Plasmodium berghei sporozoites produced in this way are two- to threefold more infective than salivary gland dissection sporozoites in in vitro hepatocyte infection assays. In an in vivo rodent malaria model, the same P. berghei sporozoites confer sterile protection from mosquito-bite challenge when immunisation is delivered intravenously or 60–70% protection when delivered intramuscularly. By improving purity, infectivity, and immunogenicity, this method represents a key advancement in capacity to produce research-grade sporozoites, which should impact delivery of a whole-parasite based malaria vaccine at scale in the future.
Association between type 2 diabetes and long-term outcomes in middle-aged and older trauma patients

Supplemental digital content is available in the text. BACKGROUND Diabetes is associated with increased hospital complications and mortality following trauma. However, there is limited research on the longer-term recovery of trauma patients with diabetes. The aim of this study was to explore the association between type 2 diabetes (T2D) and in-hospital and 24-month outcomes in major trauma patients. METHODS In this cohort study using the Victorian State Trauma Registry, middle-aged and older adults (≥45 years) with major trauma were followed up at 24 months postinjury. Logistic regression (univariable and multivariable) analyses were used to determine the association between diabetes status and 24-month patient-reported outcomes. In-hospital outcomes were compared between groups using χ2 tests. RESULTS Of the 11,490 participants who survived to hospital discharge, 8,493 survived to 24 months postinjury and were followed up at that time point: 953 people (11%) with and 7540 (89%) without T2D. People with T2D had a higher in-hospital death rate (19%) compared with people without T2D (16%; p < 0.001). After adjusting for confounders, people with T2D had poorer outcomes 24 months postinjury than people without T2D, with respect to functional recovery (Glasgow Outcome Scale Extended) (adjusted odds ratio [AOR], 0.58; 95% confidence interval [CI], 0.48–0.69) and return to work/study (AOR, 0.51; 95% CI, 0.37–0.71]). People with T2D experienced higher odds of problems with mobility (AOR, 1.92; 95% CI, 1.60–2.30), self-care (AOR, 1.94; 95% CI, 1.64, 2.29), usual activities (AOR, 1.50; 95% CI, 1.26–1.79), pain and discomfort (AOR, 1.75; 95% CI, 1.49–2.07), anxiety and depression (AOR, 1.45; 95% CI, 1.24, 1.70), and self-reported disability (AOR, 1.51; 95% CI, 1.28–1.79) than people without T2D. CONCLUSION Major trauma patients with T2D have a poorer prognosis than patients without T2D, both during their hospital admission and 24 months postinjury. Patients with T2D may need additional health care and support following trauma to reach their recovery potential. LEVEL OF EVIDENCE Prognostic, level III.
WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation

Guerreiro et al. show that loss of the primary microcephaly gene WDR62 in human cells mislocalizes the microtubule-severing enzyme katanin from mitotic spindle poles. This mislocalization reduces microtubule minus-end depolymerization, slowing poleward microtubule flux and promoting asynchronous chromosome segregation in anaphase.
Renal Regeneration: The Role of Extracellular Matrix and Current ECM‐Based Tissue Engineered Strategies

Natural extracellular matrices (ECM) are currently being studied as an alternative source for organ transplantation or as new solutions to treat kidney injuries, which can evolve to end‐stage renal disease, a life devastating condition. This paper provides an overview on the current knowledge in kidney ECM and its usefulness on future investigations. The composition and structure of kidney ECM is herein associated with its intrinsic capacity of remodeling and repair after insult. Moreover, it provides a deeper insight on altered ECM components during disease. The use of decellularized kidney matrices is discussed in the second part of the review, with emphasis on how these matrices contribute to tissue‐specific differentiation of embryonic, pluripotent, and other stem cells. The evolution on the field toward different uses of xenogeneic ECM as a biological scaffold material is discussed, namely the major outcomes on whole kidney recellularization and its in vivo implantation. At last, the recent literature on the use of processed kidney decellularized ECM to produce diverse biomaterial substrates, such as hydrogels, membranes, and bioinks are reviewed, with emphasis on future perspectives of its translation into the clinic.
A meta‐analysis of neonatal outcomes in pregnant women with immune thrombocytopenic purpura

Thrombocytopenia is an autoimmune disorder characterized by reduced platelet counts. Neonatal thrombocytopenia incidence has been linked with immune thrombocytopenic purpura in mothers during pregnancy, possibly because antiplatelet antibodies can cross the placental barrier. To date, no study has attempted to evaluate the actual prevalence of neonatal thrombocytopenia in infants born to mothers with immune thrombocytopenic purpura. In this meta‐analysis of the available literature, we attempt to fill this gap. We want to evaluate the overall prevalence of neonatal thrombocytopenia, its severity, and the incidence of hemorrhage in infants with thrombocytopenia born from mothers with immune thrombocytopenic purpura.
Gonadotropin-Releasing Hormone (GnRH) Neuron Potassium Currents and Excitability in Both Sexes Exhibit Minimal Changes upon Removal of Negative Feedback

Abstract Gonadotropin-releasing hormone (GnRH) drives pituitary secretion of luteinizing hormone and follicle-stimulating hormone, which in turn regulate gonadal functions including steroidogenesis. The pattern of GnRH release and thus fertility depend on gonadal steroid feedback. Under homeostatic (negative) feedback conditions, removal of the gonads from either females or males increases the amplitude and frequency of GnRH release and alters the long-term firing pattern of these neurons in brain slices. The neurobiological mechanisms intrinsic to GnRH neurons that are altered by homeostatic feedback are not well studied and have not been compared between sexes. During estradiol-positive feedback, which is unique to females, there are correlated changes in voltage-gated potassium currents and neuronal excitability. We thus hypothesized that these same mechanisms would be engaged in homeostatic negative feedback. Voltage-gated potassium channels play a direct role in setting excitability and action potential properties. Whole-cell patch-clamp recordings of GFP-identified GnRH neurons in brain slices from sham-operated and castrated adult female and male mice were made to assess fast and slow inactivating potassium currents as well as action potential properties. Surprisingly, no changes were observed among groups in most potassium current properties, input resistance, or capacitance, and this was reflected in a lack of differences in excitability and specific action potential properties. These results support the concept that, in contrast to positive feedback, steroid-negative feedback regulation of GnRH neurons in both sexes is likely conveyed to GnRH neurons via mechanisms that do not induce major changes in the biophysical properties of these cells.
Sliding-Mode-Based Admissible Consensus Tracking of Nonlinear Singular Multiagent Systems Under Jointly Connected Topologies

The admissible consensus tracking problem of nonlinear singular multiagent systems (SMASs) with time-varying delay, uncertainties, and external disturbances under jointly connected topologies is investigated in this article. First, the sliding-mode control (SMC) is applied to effectively reduce the adverse effects of uncertainties and nonlinearities of systems. Then, by the combination of admissible analysis, the Cauchy convergence criterion, and SMC, the sufficient conditions for the admissible consensus tracking and disturbance rejection of SMASs under jointly connected topologies are provided. Furthermore, a distributed SMC law is designed such that the sliding-mode dynamics trajectories reach the sliding surface in finite time. Finally, the simulation results are utilized to indicate the effectiveness of the presented methods.
The presence of headache at onset in SARS-CoV-2 infection is associated with long-term post-COVID headache and fatigue: A case-control study

Objective To investigate the association of headache during the acute phase of SARS-CoV-2 infection with long-term post-COVID headache and other post-COVID symptoms in hospitalised survivors. Methods A case-control study including patients hospitalised during the first wave of the pandemic in Spain was conducted. Patients reporting headache as a symptom during the acute phase and age- and sex-matched patients without headache during the acute phase participated. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview 7 months after hospital discharge. Participants were asked about a list of post-COVID symptoms and were also invited to report any additional symptom they might have. Anxiety/depressive symptoms and sleep quality were assessed with the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. Results Overall, 205 patients reporting headache and 410 patients without headache at hospitalisation were assessed 7.3 months (Standard Deviation 0.6) after hospital discharge. Patients with headache at onset presented a higher number of post-COVID symptoms (Incident Rate Ratio: 1.16, 95% CI: 1.03–1.30). Headache at onset was associated with a previous history of migraine (Odd Ratio: 2.90, 95% Confidence Interval: 1.41–5.98) and with the development of persistent tension-type like headache as a new post-COVID symptom (Odd Ratio: 2.65, 95% CI: 1.66–4.24). Fatigue as a long-term symptom was also more prevalent in patients with headache at onset (Odd Ratio: 1.55, 95% CI: 1.07–2.24). No between-group differences in the prevalence of anxiety/depressive symptoms or sleep quality were seen. Conclusion Headache in the acute phase of SARS-CoV-2 infection was associated with higher prevalence of headache and fatigue as long-term post-COVID symptoms. Monitoring headache during the acute phase could help to identify patients at risk of developing long-term post-COVID symptoms, including post-COVID headache.
Face burns: A four-year experience.

INTRODUCTION Burns on the face pose unique management challenges because they are in a place that is constantly visible, so scars are hard to hide. The goal of this study was to review our experience of adult patients who had face burns. METHODS We performed a retrospective review of adult patients (≥ 18 years old) who were admitted to a regional burn center from July 2015 - June 2019 with face burns. Sex, age, ethnicity, burn etiology, burn size, and discharge status were collected from electronic medical records of the patients who met study criteria. Descriptive statistics, student's t-tests, and chi-square tests were performed in Stata/SE 16.1. Significance was defined as a p-value <0.05. RESULTS In four years, 595/1705 patients (~35% of admissions) were admitted with face burns. The mean age was 44.9 ± 17.0 (mean ± SD) years, with the majority being men (475, 80%). The mean burn size was 19.8 ± 20.9% total body surface area (TBSA) with 10.1 ± 19.8% TBSA being third degree. The mean head burn size for any face burn was 2.8 ± 1.8% TBSA. The majority of burns were due to flames (478, 80%) and of those 122 (21%) were from accelerant use and 43 (7%) resulted from propane or butane use. Scalds caused 53 (9%), electric 25 (4%), hot tar 5 (1%), and chemical 5 (1%). Overall, 208 (35%) patients had grafting of some portion of their body, but only 31 patients (5.2%) had face grafting. The mean age of those with face grafting compared to patients who did not need grafting was 45.9 ± 13.8 and 44.9 ± 17.2 years, respectively. Patients who needed grafting had a mean third degree burn size of 31.7 ± 25.4% TBSA and a mean head (including face) burn size of 4.7 ± 2.0% TBSA, whereas patients who did not need grafting had a mean third degree burn size of 8.9 ± 18.7% TBSA and a mean head burn size of 2.7 ± 1.8% head TBSA. Patients requiring face grafts had longer lengths of stay, intensive unit stays, ventilator days, and mortality than those whose face burns healed spontaneously. DISCUSSION Overall, head burns in adults were common within the four-year time span we studied, but only a small fraction (5%) had face grafts. The patients who needed grafting for their head burns had significantly larger total body and face burns, and had a 2.4-fold higher mortality rate compared to patients who did not need grafting. Most face burns were caused by flame, especially the use of accelerants or flammable gases. Prevention efforts should focus on avoiding the use of accelerants and being careful with flammable gases.
Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity

Infection of highly pathogenic coronaviruses triggers apoptosis that can be targeted to reduce disease severity. Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R–like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2– and SARS-CoV–induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2–inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.
Biological control of Western flower thrips, Frankliniella occidentalis using a self-sustaining granular fungal treatment

Abstract Western flower thrips (WFT), Frankliniella occidentalis, is one of the most destructive pests of vegetables, fruits and ornamental crops worldwide, causing extensive damage by direct feeding of the crop and transmitting economically important viruses. Despite the successes of biocontrol agents to control WFT, more efficient and cost-effective ways must be found to encourage grower adoption of integrated pest management. A sustainable fungal treatment was developed to preserve fungal inoculum in potting soil and reduce thrips populations. Combining cooked, oven-dried millet with BotaniGard® (a commercial form of Beauveria bassiana strain GHA) to potting soil increased spore production and persistence of the fungus in the soil. In treated pots with millet, spore concentrations were 3–4 times greater after 30 days compared with spore yields at 10 days. The number of WFT adults was significantly lower in the marigold pots treated with GHA mix + millet than untreated controls, 12% and 10% in treated pots and 70% and 68% in untreated pots in sterile and non-sterile soil, respectively. Incorporation of millet in the potting mix enhanced the effect of the fungal treatments by providing a nutritive substrate on which the fungus could become established. This method is relatively inexpensive and easy for growers to use in greenhouses because granular formulations of B. bassiana are not commercially available.
Correlating indoor and outdoor temperature and humidity in a sample of buildings in tropical climates.

The incidence of several respiratory viral infections has been shown to be related to climate. Because humans spend most of their time indoors, measures of indoor climate, rather than outdoor climate, may be better predictors of disease incidence and transmission. Therefore, understanding the relationship between indoor and outdoor climate will help illuminate their influence on the seasonality of diseases caused by respiratory viruses. Indoor-outdoor relationships between temperature and humidity have been documented in temperate regions, but little information is available for tropical regions, where seasonal patterns of respiratory viral diseases differ. We have examined indoor-outdoor correlations of temperature, relative humidity (RH), and absolute humidity (AH) over a 1-year period in each of seven tropical cities. Across all cities, the average monthly indoor temperature was 25 ± 3°C (mean ± standard deviation) with a range of 20-30°C. The average monthly indoor RH was 66 ± 9% with a range of 50-78%, and the average monthly indoor AH was 15 ± 3 g/m3 with a range of 10-23 g/m3 . Indoor AH and RH were linearly correlated with outdoor AH when the air conditioning (AC) was off, suggesting that outdoor AH may be a good proxy of indoor humidity in the absence of AC. All indoor measurements were more strongly correlated with outdoor measurements as distance from the equator increased. Such correlations were weaker during the wet season, especially when AC was in operation. These correlations will provide insight for assessing the seasonality of respiratory viral infections using outdoor climate data, which is more widely available than indoor data, even though transmission of these diseases mainly occurs indoors.
Presence of surfactant proteins in the uteri and placentae of pregnant mares

Immunohistochemical investigations of the expression of surfactant protein A (SP-A) and surfactant protein D (SP-D) in the uterine and placental tissues of 13 pregnant mares were performed using anti-horse monoclonal primary antibodies. Strong positive reactions for both SP-A and SP-D were observed in the trophoblasts in the microcotyledons of the placentae at 182 to 314 days of gestation; in uterine glandular epithelial cells, faint-to-weak reactions were observed during gestation. This study describes, for the first time, the changes in the SP-A and SP-D expression levels in the endometrium of mares during gestation; the SP-A and SP-D expression levels increased after the second trimester of gestation.
Phase I Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844)

Purpose: Epigenetic modulators improve immune checkpoint inhibitor (ICI) efficacy and increase CD8+ effector:FoxP3+ regulatory T cell ratios in preclinical models. We conducted a multicenter phase I clinical trial combining the histone deacetylase inhibitor entinostat with nivolumab ± ipilimumab in advanced solid tumors. Patients and Methods: Patients received an entinostat run-in (5 mg, weekly × 2) prior to the addition of ICIs. Dose escalation followed a modified 3+3 design [dose level (DL)1/2: entinostat + nivolumab; DL 3/4: entinostat + nivolumab + ipilimumab]. Blood and tissue samples were collected at baseline, after entinostat run-in, and after 8 weeks of combination therapy. Primary endpoints included safety and tolerability, and the recommended phase II dose (RP2D). Secondary endpoints included antitumor activity and change in tumor CD8/FoxP3 ratio pre- and post-therapy. Results: Thirty-three patients were treated across four dose levels. Treatment-related adverse events (AE) included fatigue (65%), nausea (41%), anemia (38%), diarrhea (26%), and anorexia (26%). Grade 3/4 AEs included fatigue (n = 7, 21%), anemia (n = 9, 27%), and neutropenia (n = 4, 12%). The RP2D was 3 mg entinostat weekly, 3 mg/kg every 2 weeks nivolumab, and 1 mg/kg every 6 weeks ipilimumab (max four doses). The objective response rate by RECIST 1.1 was 16%, including a complete response in triple-negative breast cancer. A statistically significant increase in CD8/FoxP3 ratio was seen following the addition of ICIs to entinostat, but not post-entinostat alone. Conclusions: The combination of entinostat with nivolumab ± ipilimumab was safe and tolerable with expected rates of immune-related AEs. Preliminary evidence of both clinical efficacy and immune modulation supports further investigation.