Miracle-dz/UniFAR-FTUs huggingface dataset:
Hantavirus pulmonary syndrome outbreaks associated with climate variability in Northwestern Argentina, 1997–2017

Background Rodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%–50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors. Methodology and main findings We compiled reported HPS cases in northwestern Argentina during the 1997–2017 period and divided our data into biannual, quarterly, and bimestrial time periods to allow annual and shorter time delays to be observed. To evaluate the relationship of hantavirus transmission with mean temperature and precipitation we used dynamic regression analysis. We found a significant association between HPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months. For the biannual and quarterly models, hantavirus transmission was positively associated with lagged rainfall and temperature; whereas the bimestrial models indicate a direct relationship with the rainfall but inverse for temperature in the second lagged period. Conclusions/Significance This work demonstrates that climate variability plays a significant role in the transmission of hantavirus in northwestern Argentina. The model developed in this study provides a basis for the forecast of potential HPS outbreaks based on climatic parameters. Our findings are valuable for the development of public health policies and prevention strategies to mitigate possible outbreaks. Nonetheless, a surveillance program on rodent population dynamics would lead to a more accurate forecast of HPS outbreaks.
A wireless, skin-interfaced biosensor for cerebral hemodynamic monitoring in pediatric care

Significance Continuous monitoring of cerebral hemodynamics is critical for safeguarding the healthy neurodevelopment of pediatric patients. This paper introduces a soft, flexible, miniaturized wireless system for real-time, continuous monitoring of systemic and cerebral hemodynamics for such purposes. Clinical studies on pediatric subjects with ages between 0.2 and 15 y and with various racial backgrounds validate opportunities for practical use in operating hospital environments. This platform may significantly enhance the quality of care of pediatric patients, particularly those at risk for cerebral and neurodevelopmental impairments in developed and developing world settings alike. The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source–detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries.
First Line Systemic Treatment for MALT Lymphoma—Do We Still Need Chemotherapy? Real World Data from the Medical University Vienna

Simple Summary The Division of Oncology at the Medical University Vienna is a tertiary referral center for extranodal lymphoma of mucosa-associated lymphoid tissue (MALT)-type and currently oversees more than 400 patients with this diagnosis, including a relevant percentage of patients being treated with systemic therapies. In the current analysis, we present response and long-term data of 159 patients (not eligible for Helicobacter pylori eradication) treated upfront with systemic treatment focusing on chemotherapy- versus immunotherapy-based strategies. We show that despite higher response and complete remission rates for chemo- versus immunotherapy, there appears to be no difference in progression-free survival, thus suggesting comparable long-term results. Considering the biological background of MALT lymphoma—and particularly its high dependence on the tumor microenvironment—but also the favorable toxicity profile of assessed immunomodulatory agents such as IMiD lenalidomide or macrolide clarithromycin, we suggest that these data support further investigation of chemotherapy-free treatment concepts for MALT lymphoma. Abstract There is no clear therapeutic algorithm for mucosa-associated lymphoid tissue (MALT) lymphoma beyond Helicobacter pylori eradication and while chemotherapy-based regimens are standard for MALT lymphoma patients in need of systemic treatment, it appears of interest to also investigate chemotherapy-free strategies. We have retrospectively assessed MALT lymphoma patients undergoing upfront systemic treatment, classified either as chemotherapy (=classical cytostatic agents +/− rituximab) or immunotherapy (=immunomodulatory agents or single anti-CD20 antibodies) at the Medical University Vienna 1999–2019. The primary endpoint was progression-free survival (PFS). In total, 159 patients were identified with a median follow-up of 67 months. The majority of patients had extragastric disease (80%), but we also identified 32 patients (20%) with Helicobacter pylori negative or disseminated gastric lymphoma. Regarding the type of first line treatment and outcome, 46% (74/159) received a chemotherapy-based regimen and 54% (85/159) immunotherapy including IMiDs lenalidomide/thalidomide (37%), anti-CD20-anitbodies rituximab/ofatumumab (27%), macrolides clarithromycin/azithromycin (27%) and proteasome inhibitor bortezomib (9%). Median PFS was 76 months (95%CI 50–102), and while the overall response (90% vs. 68%, p < 0.01) and the complete remission rate (75% vs. 43%, p < 0.01) was significantly higher for chemotherapy, there was no difference in PFS between chemotherapy (median 81 months, 95%CI 47–116) and immunotherapy (76 months, 95%CI 50–103, p = 0.57), suggesting comparable long-term outcomes. To conclude, our data show higher response rates with chemo- compared to immunotherapy, but this did not translate into a superior PFS. Given the biological background of MALT lymphoma, and the favorable toxicity profile of novel immunomodulatory treatments, this should be further investigated.
Chronic High Glucose Concentration Induces Inflammatory and Remodeling Changes in Valvular Endothelial Cells and Valvular Interstitial Cells in a Gelatin Methacrylate 3D Model of the Human Aortic Valve

Calcific aortic valve disease (CAVD), a degenerative disease characterized by inflammation, fibrosis and calcification, is accelerated in diabetes. Hyperglycemia contributes to this process by mechanisms that still need to be uncovered. We have recently developed a 3D model of the human aortic valve based on gelatin methacrylate and revealed that high glucose (HG) induced osteogenic molecules and increased calcium deposits in a pro-osteogenic environment. To further understand the events leading to calcification in diabetic conditions in CAVD, we analyzed here the inflammatory and remodeling mechanisms induced by HG in our 3D model. We exposed valvular endothelial cells (VEC) and interstitial cells (VIC) to normal glucose (NG) or HG for 7 and 14 days, then we isolated and separated the cells by anti-CD31 immunomagnetic beads. The changes induced by HG in the 3D model were investigated by real-time polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. Our results showed that HG induced expression of different cytokines, cell adhesion molecules and matrix metalloproteinases in VEC and VIC. In addition, protein kinase C was increased in VEC and VIC, indicating molecular mechanisms associated with HG induced inflammation and remodeling in both valvular cells. These findings may indicate new biomarkers and targets for therapy in diabetes associated with CAVD.
Natural History, Not Lead Time.

Jonas et al. analyze longitudinal data from a sample of individuals with schizophrenia who suffered delayed access (median DUP > 300 days) to, and “intermittent and inconsistent” treatment after, a first admission for psychosis. Despite inadequate aftercare, shorter delays from psychosis onset to first admission predicted better outcomes at 2, but unsurprisingly not 10 or 20 years later(1). We were thus puzzled with the authors’ conclusion: “The association between DUP and psychosocial function may be an artifact of early detection creating the illusion that early intervention is associated with improved outcomes. ” We believe this incorrect inference reveals a conceptual confusion about lead time and other sources of bias.
Pachychoroid spectrum disease

Recent improvements in ophthalmic imaging have led to the identification of a thickened choroid or pachychoroid to be associated with a number of retinal diseases. The number of conditions linked to this phenotype has continued to widen with specific endophenotypes found within the pachychoroid spectrum. The spectrum includes choroidal features such as focal or diffuse choroidal thickening and thinning of the overlying inner choroid, and choroidal hyperpermeability as demonstrated by indocyanine green angiography. In addition, these diseases are associated with overlying retinal pigmentary changes and retinal pigment epithelial dysfunction and may also be associated with choroidal neovascularization. This article provides a comprehensive review of the literature looking at diseases currently described within the pachychoroid spectrum including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, peripapillary pachychoroid disease and focal choroidal excavation. We particularly focus on clinical imaging, genetics and pathological findings in these conditions with the aim of updating evidence suggesting a common aetiology between diseases within the pachychoroid spectrum.
A comparative study of complete blood count inflammatory markers in substance‐free acute psychotic disorder and substance‐induced psychosis

Recent studies showed a compare complete blood count (CBC) with its related measurements, including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio, are a simple and affordable test for inflammatory markers. The aim of this controlled study is to compare CBC inflammatory markers in substance‐induced psychosis (SIP) and substance‐free acute psychotic disorder (SF‐APD) and to evaluate whether these CBC inflammation values can be used in diagnosis.
Parametric study of anterior percutaneous endoscopic cervical discectomy (APECD)

Abstract Anterior percutaneous endoscopic cervical discectomy (APECD) is a common treatment for cervical spondylotic radiculopathy (CSR). In this study, the effects of various channel diameters and approach angles on cervical vertebrae on postoperative outcomes in APECD surgery were explored. A finite element model of intact cervical C3-C7 was constructed and then modified to obtain six surgical models. Range of motion (ROM) and intradiscal pressure (IDP) were calculated under different conditions of flexion (Fle), extension (Ext), lateral bending, and axial rotation. During Fle and bending to the left (LB), the ROM was closer to the intact model when the angle of approach was 90°. During bending to the left (LB) and rotation to the left (LR), the ROM changed considerably (43.2%, 33.7%, respectively) where the angle of approach was 45°. As the surgical channel diameter increased, the extent of the change in ROM compared with the intact model also increased. IDP decreased by 48% and 49%, respectively, compared with the intact model at the C5-C6 segment where the angle of approach was 45° and 60° during Fle, while it changed little at 90°, by less than 10%. The IDP was increased noticeably by 117.6%, 82.1%, and 105.8%, for channel diameters of 2, 3 and 4 mm, respectively. And declined noticeably during LB and LR (LB: 27.1%, 27.1%, 38.5%; LR: 37.4%, 35.5%, 48.7%). The results demonstrated that the shorter the surgical path, the smaller surgical diameter, the less the biomechanical influence on the cervical vertebra.
Acetate and glycerol are not uniquely suited for the evolution of cross-feeding in E. coli

The evolution of cross-feeding among individuals of the same species can help generate genetic and phenotypic diversity even in completely homogeneous environments. Cross-feeding Escherichia coli strains, where one strain feeds on a carbon source excreted by another strain, rapidly emerge during experimental evolution in a chemically minimal environment containing glucose as the sole carbon source. Genome-scale metabolic modeling predicts that cross-feeding of 58 carbon sources can emerge in the same environment, but only cross-feeding of acetate and glycerol has been experimentally observed. Here we use metabolic modeling to ask whether acetate and glycerol cross-feeding are especially likely to evolve, perhaps because they require less metabolic change, and thus perhaps also less genetic change than other cross-feeding interactions. However, this is not the case. The minimally required metabolic changes required for acetate and glycerol cross feeding affect dozens of chemical reactions, multiple biochemical pathways, as well as multiple operons or regulons. The complexity of these changes is consistent with experimental observations, where cross-feeding strains harbor multiple mutations. The required metabolic changes are also no less complex than those observed for multiple other of the 56 cross feeding interactions we study. We discuss possible reasons why only two cross-feeding interactions have been discovered during experimental evolution and argue that multiple new cross-feeding interactions may await discovery.
Executive functions form a single construct and are associated with schooling: Evidence from three low- and middle- income countries

Measuring executive function (EF) among adults is important, as the cognitive processes involved in EF are critical to academic achievement, job success and mental health. Current evidence on measurement and structure of EF largely come from Western, Educated, Industrialized, Rich and Democratic (WEIRD) countries. However, measuring EF in low-and-middle-income countries (LMICs) is challenging, because of the dearth of EF measures validated across LMICs, particularly measures that do not require extensive training, expensive equipment, or professional administration. This paper uses data from three LMIC cohorts to test the feasibility, validity and reliability of EF assessment in adults using three sub-tests (representing key components of EF) of the NIH Toolbox Cognitive battery. For each cohort, all three EF measures (inhibition, flexibility and working memory) loaded well onto a unidimensional latent factor of EF. Factor scores related well to measures of fluid intelligence, processing speed and schooling. All measures showed good test-retest reliability across countries. This study provides evidence for a set of sound measures of EF that could be used across different cultural, language and socio-economic backgrounds in future LMIC research. Furthermore, our findings extend conclusions on the structure of EF beyond those drawn from WEIRD countries.
Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Simple Summary The emergence of immunotherapy for cancer treatment bears considerable clinical promise. The role of NK cells in tumor immunosurveillance and their potential for successful cancer immunotherapy strategies is currently established. Specific focus is placed on the use of specialized monoclonal antibodies against NK cell immune checkpoints (ICI). The recent discovery that also helper ILCs express inhibitory IC suggests that these molecules might be also targeted on ILCs to modulate their functions in the tumor microenvironment. Herein, we provide an overview of the current knowledge on IC on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies. Overall, we believe that, in our near future, immunotherapy protocols will need to be designed taking into account all ILCs, both cytotoxic (NK) and non-cytotoxic (helper ILCs) ones, and most importantly, ILCs targeting should be tailored according to the disease. Abstract Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies.
Changes in cAMP effector predominance are associated with increased oxytocin receptor expression in twin but not infection-associated or idiopathic preterm labour

We previously reported that at term pregnancy, a decline in myometrial protein kinase A (PKA) activity leads to an exchange protein activated by cyclic AMP (Epac1)-dependent increase in oxytocin receptor (OTR) expression, promoting the onset of labour. Here, we studied the changes in the cyclic adenosine monophosphate (cAMP) effector system present in different phenotypes of preterm labour (PTL). Myometrial biopsies obtained from women with phenotypically distinct forms of PTL and the levels of PKA and OTR were examined. Although we found similar changes in the cAMP effector pathway in all forms of PTL, only in the case of twin PTL (T-PTL) was myometrial OTR levels increased in association with these results. Although there were several changes in the mRNA levels of components of the cAMP synthetic pathway, the total myometrial cAMP levels did not change with the onset of any subtype of PTL. With regards to the expression of cAMP-responsive genes, we found that the mRNA levels of 4 of the 5 cAMP-down-regulated genes were increased in T-PTL, similar to our findings in term labour. These data signify that although changes in the cAMP effector system were common to all forms of PTL, only in T-PTL were OTR levels increased. Similarly, the mRNA levels of cAMP-repressed genes were only increased in T-PTL supporting the concept that the decline in PKA levels influences myometrial function driving the onset of T-PTL.
The relationship between health mindsets and health protective behaviors: An exploratory investigation in a convenience sample of American Indian adults during the COVID-19 pandemic

The Novel-coronavirus disease-2019 (COVID-2019) outbreak was declared a national emergency on March 13, 2020. To reduce the spread of the virus, Americans were asked to physically distance and to increase disinfecting behaviors such as hand washing. Previous research indicates that one’s mindset about health, or the degree to which they view health as fixed or modifiable, influences health behaviors. Current data indicates that American Indians (AIs) are at greater risk for COVID-19. As such, it is important to understand whether mindsets about health may affect behaviors which could prevent spread of the virus in AIs. In this exploratory investigation, a convenience sample of two hundred AI adults completed a questionnaire one month prior to the declaration of the COVID-19 pandemic as a national emergency. They provided demographic information and completed a measure of health mindsets. The second wave of data was collected approximately one month later, where we collected a measure of physical distancing behavior and a measure of disinfecting behaviors. In AI adults, health mindset predicted frequency of physical distancing behaviors and disinfecting behaviors, with individuals who viewed health as less fixed engaging in more physical distancing and disinfecting behaviors, while individuals who viewed health as more fixed reported less physical distancing and less disinfecting behaviors. In AIs, growth health mindsets predicted physical distancing and disinfecting behaviors, both of which are important in reducing the spread of COVID-19. Interventions which are designed to promote growth mindsets of health may promote health-protective behaviors in the context of the COVID-19 pandemic.
Measurement of CeO2 Nanoparticles in Natural Waters Using a High Sensitivity, Single Particle ICP-MS

As the production and use of cerium oxide nanoparticles (CeO2 NPs) increases, so does the concern of the scientific community over their release into the environment. Single particle inductively coupled plasma mass spectrometry is emerging as one of the best techniques for NP detection and quantification; however, it is often limited by high size detection limits (SDL). To that end, a high sensitivity sector field ICP-MS (SF-ICP-MS) with microsecond dwell times (50 µs) was used to lower the SDL of CeO2 NPs to below 4.0 nm. Ag and Au NPs were also analyzed for reference. SF-ICP-MS was then used to detect CeO2 NPs in a Montreal rainwater at a concentration of (2.2 ± 0.1) × 108 L−1 with a mean diameter of 10.8 ± 0.2 nm; and in a St. Lawrence River water at a concentration of ((1.6 ± 0.3) × 109 L−1) with a higher mean diameter (21.9 ± 0.8 nm). SF-ICP-MS and single particle time of flight ICP-MS on Ce and La indicated that 36% of the Ce-containing NPs detected in Montreal rainwater were engineered Ce NPs.