julilili42/papers huggingface dataset:
Automated human temporal-bone experiments
2022-08-01

Abstract Temporal-bone (TB) experiments are useful for the investigation of middle-ear and inner-ear transfer properties, and the analysis and development of active or passive middleear prostheses or related devices. To acquire the mechanical middle-ear (ME) response, the Laser-Doppler vibrometry (LDV) is utilized as a preferred method. In most setups, the exact measurement point chosen on the biological structure of interest as well as the direction of the corresponding vibration measurement is not precisely defined and of unknown reproducibility. Hence, an automated setup controlling coordinates of TB and measurement direction is developed and tested. To test the reproducibility, TBs were measured with ER7C and ER10C probe microphones employing a small industrial robot to position the TB to the ME points of interest and align it to the laser beam. The position and vibration data acquired at the same locations at different points of time were processed and compared. Measured transfer functions indicate noticeable differences at some frequency ranges. Nonetheless, the reproducibility of positioning to repeatedly measured points proved itself relatively accurate, if no manipulations in the setup are made. In conclusion, the current study shows that automated LDV TB measurement system is in principle capable to adapt to the changes in setup during intermediate preparation steps. With more acquired data, the setup stability and reproducibility can be more precisely verified, and additional improvements can be made.
Manager Delegation, Owner Coordination and Firms’ Investment in Automation
2022-08-01

Abstract This paper studies the combined effects of mixed ownership structures and manager delegation on firms’ investment in automation processes in a multi-stage triopoly game. We show that, in accordance with empirical evidence, firms owned by common shareholders invest less in automation and realize lower profits compared to a firm owned by independent shareholders. Direct collusion of owners in terms of coordinated investment increases the profits, the one of the independent firm even more than the profits of the commonly owned firms. Delegation of operational decisions to managers results in higher investment and lower profits. In markets with favorable technological opportunities for automation, common ownership combined with manager delegation leads to the highest social welfare.
Proof of Concept of a 6-Month Person-Oriented Exercise Intervention ‘MultiPill-Exercise’ among Patients at Risk of or with Multiple Chronic Diseases: Results of a One-Group Pilot Trial
2022-08-02

Physical exercise has been shown to be effective in the treatment of non-communicable chronic diseases. However, patients with multiple chronic diseases (multimorbidity) have received little attention in health policy. This pilot trial served as a proof of concept of a 6-months person-oriented exercise intervention for people at risk of or with diagnosed cardiovascular diseases, diabetes mellitus type 2, overweight and/or hip/knee osteoarthritis, regarding effects on health outcomes as well as adherence and safety. The intervention (‘MultiPill-Exercise’) was designed to promote physical exercise participation, considering an individual perspective by addressing personal and environmental factors. Outcomes were assessed at baseline (t0) and after three- (t3) and six-months (t6). The primary outcome was self-reported physical exercise participation in minutes/week comparing t3 and t6 vs. t0. Secondary outcomes included cardio-respiratory fitness (maximum oxygen uptake VO2peak during incremental cycling ergometry), isometric peak torque of knee extensors and flexors, health-related quality of life (Veterans Rand 12 with its subscales of perceived general health (GH), mental health (MCS), and physical health (PCS)) and blood levels. Adherence to exercise (% of attended sessions during the first 12-weeks of the intervention) and adverse events were monitored as well. Data were analyzed using a non-parametric procedure for longitudinal data, estimating rank means (MRank) and relative treatment effects (RTE) as well as linear-mixed effect models for parametric data. The primary endpoint of physical exercise participation was significantly higher at t3 and t6 compared to baseline (t3 vs. t0: MRank = 77.1, p &lt; 0.001, RTE: 0.66; t6 vs. t0: MRank = 70.6, p &lt; 0.001, RTE = 0.60). Improvements at both follow-up time points compared to t0 were also found for relative VO2peak (t3 vs. t0 = 2.6 mL/kg/min, p &lt; 0.001; t6 vs. t0 = 2.0 mL/kg/min, p = 0.001), strength of knee extensors (t3 vs. t0 = 11.7 Nm, p = 0.007; t6 vs. t0= 18.1 Nm, p &lt; 0.001) and GH (t3 vs. t0 = 16.2, p = 0.003; t6 vs. t0 = 13.4, p = 0.008). No changes were found for MCS, PCS and for blood levels. Overall exercise adherence was 77%. No serious adverse events were recorded. Results of this pilot trial represent a first proof of concept for the intervention ‘MultiPill-Exercise’ that will now be implemented and evaluated in a real-world health care setting.
Pharmacologic Targeting of MMP2/9 Decreases Peritoneal Metastasis Formation of Colorectal Cancer in a Human Ex Vivo Peritoneum Culture Model
2022-08-02

Background: Matrix metalloproteinases (MMPs) play a crucial role in tumour initiation, progression, and metastasis, including peritoneal carcinosis (PC) formation. MMPs serve as biomarkers for tumour progression in colorectal cancer (CRC), and MMP overexpression is associated with advanced-stage metastasis and poor survival. However, the molecular mechanisms of PC from CRC remain largely unclear. Methods: We investigated the role of MMPs during peritoneal colonisation by CRC cell lines in a human ex vivo peritoneum model and in patient-derived CRC and corresponding PC samples. MMP2 and MMP9 were inhibited using the small-molecule inhibitors batimastat and the specific MMP2/9 inhibitor III. Results: MMP2 and MMP9 were strongly upregulated in patient-derived samples and following peritoneal colonisation by CRC cells in the ex vivo model. MMP inhibition with batimastat reduced colonisation of HT29 and Colo205 cells by 36% and 68%, respectively (p = 0.0073 and p = 0.0002), while MMP2/9 inhibitor III reduced colonisation by 50% and 41%, respectively (p = 0.0003 and p = 0.0051). Fibronectin cleavage was enhanced in patient-derived samples of PC and during peritoneal colonisation in the ex vivo model, and this was inhibited by MMP2/9 inhibition. Conclusion: MMPs were upregulated in patient-derived samples and during peritoneal attachment of CRC cell lines in our ex vivo model. MMP2/9 inhibition prevented fibronectin cleavage and peritoneal colonisation by CRC cells. MMP inhibitors might thus offer a potential treatment strategy for patients with PC.
Vegetation strategies for nitrogen and potassium acquisition along a climate and vegetation gradient: From semi-desert to temperate rainforest
2022-08-02

Nutrient acquisition strategies of plants regulate water flow and mass transport within ecosystems, shaping earth surface processes. Understanding plant strategies under current conditions is important to assess and predict responses of natural ecosystems to future climate and environmental changes. Nitrogen (N) and potassium (K) (re-)utilization from topsoil and their acquisition from subsoil and saprolite were evaluated in a continental transect, encompassing three study sites – an arid shrubland, a mediterranean woodland, and a temperate rainforest – on similar granitoid parent material in the Chilean Coastal Cordillera. The short-term (&amp;lt;1 year) plant N and K acquisition was traced with 15N and the K analogs rubidium and cesium. To do so, the tracers were either injected into topsoil, subsoil, or saprolite, in the immediate vicinity of eight individual plants per study site and injection depth. The long-term (&amp;gt;decades) K uplift by plants was investigated by the vertical distribution of exchangeable K+ and Na+. Recoveries of 15N and K analogs by arid shrubland plants were similar from topsoil, subsoil, and saprolite. Mediterranean woodland shrubs recovered the tracers primarily from topsoil (i.e., 89 % of recovered 15N and 84 % of recovered K analogs). Forest plants recovered the tracers from topsoil (15N = 49 %, K analogs = 57 %) and partially from greater depth: 38 % of recovered 15N and 43 % of recovered K analogs were acquired from subsoil and saprolite, respectively. Low nutrient accessibility in the topsoil (e.g., because of frequent droughts) drives shrubland plants to expand their N and K uptake to deeper and moister soil and saprolite. Woodland and forest plants dominantly recycled nutrients from topsoil. In the forest, this strategy was complemented by short-term uplift of N and K from depth. The vertical distribution of exchangeable K indicated long-term uplift of K by roots in all three sites. This highlighted that long-term K uplift from depth complements the nutrient budget across the continental transect.
Coupled Aerobic Methane Oxidation and Arsenate Reduction Contributes to Soil-Arsenic Mobilization in Agricultural Fields
2022-08-03

Microbial oxidation of organic compounds can promote arsenic release by reducing soil-associated arsenate to the more mobile form arsenite. While anaerobic oxidation of methane has been demonstrated to reduce arsenate, it remains elusive whether and to what extent aerobic methane oxidation (aeMO) can contribute to reductive arsenic mobilization. To fill this knowledge gap, we performed incubations of both microbial laboratory cultures and soil samples from arsenic-contaminated agricultural fields in China. Incubations with laboratory cultures showed that aeMO could couple to arsenate reduction, wherein the former bioprocess was carried out by aerobic methanotrophs and the latter by a non-methanotrophic bacterium belonging to a novel and uncultivated representative of <i>Burkholderiaceae</i>. Metagenomic analyses combined with metabolite measurements suggested that formate served as the interspecies electron carrier linking aeMO to arsenate reduction. Such coupled bioprocesses also take place in the real world, supported by a similar stoichiometry and gene activity in the incubations with natural paddy soils, and contribute up to 76.2% of soil-arsenic mobilization into pore waters in the top layer of the soils where oxygen was present. Overall, this study reveals a previously overlooked yet significant contribution of aeMO to reductive arsenic mobilization.
SARS-CoV-2 Infection in Pregnancy: Placental Histomorphological Patterns, Disease Severity and Perinatal Outcomes
2022-08-03

The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p &lt; 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p &lt; 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.
Neural networks for self-adjusting mutation rate estimation when the recombination rate is unknown
2022-08-03

Estimating the mutation rate, or equivalently effective population size, is a common task in population genetics. If recombination is low or high, optimal linear estimation methods are known and well understood. For intermediate recombination rates, the calculation of optimal estimators is more challenging. As an alternative to model-based estimation, neural networks and other machine learning tools could help to develop good estimators in these involved scenarios. However, if no benchmark is available it is difficult to assess how well suited these tools are for different applications in population genetics. Here we investigate feedforward neural networks for the estimation of the mutation rate based on the site frequency spectrum and compare their performance with model-based estimators. For this we use the model-based estimators introduced by Fu, Futschik et al., and Watterson that minimize the variance or mean squared error for no and free recombination. We find that neural networks reproduce these estimators if provided with the appropriate features and training sets. Remarkably, using the model-based estimators to adjust the weights of the training data, only one hidden layer is necessary to obtain a single estimator that performs almost as well as model-based estimators for low and high recombination rates, and at the same time provides a superior estimation method for intermediate recombination rates. We apply the method to simulated data based on the human chromosome 2 recombination map, highlighting its robustness in a realistic setting where local recombination rates vary and/or are unknown.
Spatial neglect after stroke is reduced when lying inside a 3T MRI scanner
2022-08-03

Abstract Recently, it was discovered that the static magnetic field of an MRI scanner not only causes horizontal vestibular nystagmus in healthy individuals but, in addition, leads to a horizontal bias of spatial orienting and exploration that closely resembles the one observed in stroke patients with spatial neglect (a disorder of spatial attention and exploration). The present study asked whether the behavioral effects of this magnetic vestibular stimulation (MVS) can be inverted and thus be used to reduce the pathological bias of stroke patients with spatial neglect. Indeed, when patients with left-sided spatial neglect entered the scanner with their feet first, i.e., with the magnetic field vector pointing from head to toes, MVS inside the scanner reduced the ipsilesionally biased distribution of overt attention and the corresponding neglect of the left parts of the search-space. Thus, an intervention as simple as lying in a 3T MRI scanner bears the potential to become an integral part of a future strategy for treating spatial neglect.
Resolving colistin resistance and heteroresistance in Enterobacter species
2022-08-03

<title>Abstract</title> Enterobacter cloacae complex (ECC) represent globally important nosocomial pathogens. A three-year study of ECC in Germany identified Enterobacter xiangfangensis as the most common species (65.5%) detected, a result replicated by examining a global pool of 3246 isolates. Antibiotic resistance profiling revealed widespread resistance and heteroresistance to the antibiotic colistin and detected the mobile colistin resistance (mcr)-9 gene in 19.2% of all isolates. We show that resistance and heteroresistance properties depend on the chromosomal arnBCADTEF gene cassette whose products catalyze transfer of L-Ara4N to lipid A. Using comparative genomics, mutational analysis, and quantitative lipid A profiling we demonstrate that intrinsic lipid A modification levels are genospecies-dependent and governed by allelic variations in phoPQ and mgrB, that encode a two-component sensor-activator system and specific inhibitor peptide. By generating phoPQ chimeras and combining them with mgrB alleles, we show that interactions at the pH-sensing interface of the sensory histidine kinase phoQ dictate arnBCADTEF expression levels. To minimize therapeutic failures, we developed an assay that accurately detects colistin resistance levels for any ECC isolate.
Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19
2022-08-04

<b>Rationale:</b> Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. <b>Objectives:</b> To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. <b>Methods:</b> We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. <b>Measurements and Main Results:</b> IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. <b>Conclusions:</b> Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.
Insight into Potential Interactions of Thyroid Hormones, Sex Hormones and Their Stimulating Hormones in the Development of Non-Alcoholic Fatty Liver Disease
2022-08-04

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common manifestation of metabolic syndrome. In addition to lifestyle, endocrine hormones play a role in the dysregulation of hepatic metabolism. The most common endocrine hormones contributing to metabolic syndrome are alterations in the levels of thyroid hormones (THs, predominantly in subclinical hypothyroidism) and of sex hormones (in menopause). These hormonal changes influence hepatic lipid and glucose metabolism and may increase hepatic fat accumulation. This review compares the effects of sex hormones, THs and the respective stimulating hormones, Thyroid-Stimulating Hormone (TSH) and Follicle-Stimulating Hormone (FSH), on the development of hepatosteatosis. TSH and FSH may be more relevant to the dysregulation of hepatic metabolism than the peripheral hormones because metabolic changes were identified when only levels of the stimulating hormones were abnormal and the peripheral hormones were still in the reference range. Increased TSH and FSH levels appear to have additive effects on the development of NAFLD and to act independently from each other.
Direct Oral Anticoagulants (DOACs) for Therapeutic Targeting of Thrombin, a Key Mediator of Cerebrovascular and Neuronal Dysfunction in Alzheimer’s Disease
2022-08-04

Although preclinical research and observer studies on patients with atrial fibrillation concluded that direct oral anticoagulants (DOACs) can protect against dementia like Alzheimer’s disease (AD), clinical investigation towards therapeutical approval is still pending. DOACs target pathological thrombin, which is, like toxic tau and amyloid-ß proteins (Aß), an early hallmark of AD. Especially in hippocampal and neocortical areas, the release of parenchymal Aß into the blood induces thrombin and proinflammatory bradykinin synthesis by activating factor XII of the contact system. Thrombin promotes platelet aggregation and catalyzes conversion of fibrinogen to fibrin, leading to degradation-resistant, Aß-containing fibrin clots. Together with oligomeric Aß, these clots trigger vessel constriction and cerebral amyloid angiopathy (CAA) with vessel occlusion and hemorrhages, leading to vascular and blood–brain barrier (BBB) dysfunction. As consequences, brain blood flow, perfusion, and supply with oxygen (hypoxia) and nutrients decrease. In parenchymal tissue, hypoxia stimulates Aß synthesis, leading to Aß accumulation, which is further enhanced by BBB-impaired perivascular Aß clearance. Aß trigger neuronal damage and promote tau pathologies. BBB dysfunction enables thrombin and fibrin(ogen) to migrate into parenchymal tissue and to activate glial cells. Inflammation and continued Aß production are the results. Synapses and neurons die, and cognitive abilities are lost. DOACs block thrombin by inhibiting its activity (dabigatran) or production (FXa-inhibitors, e.g., apixaban, rivaroxaban). Therefore, DOAC use could preserve vascular integrity and brain perfusion and, thereby, could counteract vascular-driven neuronal and cognitive decline in AD. A conception for clinical investigation is presented, focused on DOAC treatment of patients with diagnosed AD in early-stage and low risk of major bleeding.
A Quick and Reproducible Silanization Method by Using Plasma Activation for Hydrophobicity‐Based Kinesin Single Molecule Fluorescence–Microscopy Assays
2022-08-04

Abstract Single‐molecule assays often require functionalized surfaces. One approach for microtubule assays renders surfaces hydrophobic and uses amphiphilic blocking agents. However, the optimal hydrophobicity is unclear, protocols take long, produce toxic waste, and are susceptible to failure. Our method uses plasma activation with hydrocarbons for hexamethyldisilazane (HMDS) silanization in the gas phase. We measured the surface hydrophobicity, its effect on how well microtubule filaments were bound to the surface, and the number of nonspecific interactions with kinesin motor proteins. Additionally, we tested and discuss the use of different silanes and activation methods. We found that even weakly hydrophobic surfaces were optimal. Our environmentally friendly method significanty reduced the overall preparation effort and resulted in reproducible, high‐quality surfaces with low variability. We expect the method to be applicable to a wide range of other single‐molecule assays.
Homo bodoensis and why it matters
2022-08-04

Abstract In our original paper, we proposed a new species, Homo bodoensis , to replace the problematical taxa Homo heidelbergensis and Homo rhodesiensis , with the goal of streamlining communication about human evolution in the Chibanian. We received two independent responses. Given their substantial overlap, we provide one combined reply. In this response: (1) we are encouraged that the primary proposal in our paper, to discontinue the use of H. heidelbergensis (as a junior synonym to Homo neanderthalensis ) due to its' nomenclatural problems, is acknowledged. (2) we provide additional clarification about the rules governing taxonomic nomenclature as outlined by the International Code of Zoological Nomenclature and join the growing calls for a revision to these rules. (3) we discuss further why H. rhodesiensis should be abandoned, particularly in light of the current sensitivity to using culturally inappropriate names. We conclude that H. bodoensis is a better solution than the proposed alternatives.