Miracle-dz/UniFAR-FTUs huggingface dataset:
AMBAR, an Encouraging Alzheimer's Trial That Raises Questions

Grifols' recent Alzheimer Management by Albumin Replacement (“AMBAR”) study investigated the effects of plasmapheresis with albumin replacement, plus intravenous immunoglobulin (IVIG) in some subjects, in patients with mild-to-moderate Alzheimer's disease (AD). AMBAR was a phase IIb trial in the United States and a phase III trial in Europe. There were three treatment groups (plasmapheresis with albumin replacement; plasmapheresis with low dose albumin and IVIG; plasmapheresis with high dose albumin and IVIG) and sham-treated controls. Disease progression in pooled treated patients was 66% less than control subjects based on ADAS-Cog scores (p = 0.06) and 52% less based on ADCS-ADL scores (p = 0.03). Moderate AD patients had 61% less progression, based on both ADAS-Cog and ADCS-ADL scores, than their sham-treated counterparts (p-values 0.05 and 0.002), and their CDR-Sb scores declined 53% less than their sham-treated counterparts. However, ADAS-Cog and ADCS-ADL scores were not significantly different between actively-treated and sham-treated mild AD patients, although CDR-Sb scores improved vs. baseline for treated mild AD patients. Patients administered both IVIG and albumin had less reduction in brain glucose metabolism than sham-treated patients. Questions raised by these findings include: what mechanism(s) contributed to slowing of disease progression? Is this approach as effective in mild AD as in moderate AD? Must IVIG be included in the protocol? Does age, sex, or ApoE genotype influence treatment response? Does the protocol increase the risk for amyloid-related imaging abnormalities? How long does disease progression remain slowed post-treatment? A further study should allow this approach to be optimized.
Effect of Nuclear Stiffness on Cell Mechanics and Migration of Human Breast Cancer Cells

The migration and invasion of cancer cells through 3D confined extracellular matrices is coupled to cell mechanics and the mechanics of the extracellular matrix. Cell mechanics is mainly determined by both the mechanics of the largest organelle in the cell, the nucleus, and the cytoskeletal architecture of the cell. Hence, cytoskeletal and nuclear mechanics are the major contributors to cell mechanics. Among other factors, steric hindrances of the extracellular matrix confinement are supposed to affect nuclear mechanics and thus also influence cell mechanics. Therefore, we propose that the percentage of invasive cells and their invasion depths into loose and dense 3D extracellular matrices is regulated by both nuclear and cytoskeletal mechanics. In order to investigate the effect of both nuclear and cytoskeletal mechanics on the overall cell mechanics, we firstly altered nuclear mechanics by the chromatin de-condensing reagent Trichostatin A (TSA) and secondly altered cytoskeletal mechanics by addition of actin polymerization inhibitor Latrunculin A and the myosin inhibitor Blebbistatin. In fact, we found that TSA-treated MDA-MB-231 human breast cancer cells increased their invasion depth in dense 3D extracellular matrices, whereas the invasion depths in loose matrices were decreased. Similarly, the invasion depths of TSA-treated MCF-7 human breast cancer cells in dense matrices were significantly increased compared to loose matrices, where the invasion depths were decreased. These results are also valid in the presence of a matrix-metalloproteinase inhibitor GM6001. Using atomic force microscopy (AFM), we found that the nuclear stiffnesses of both MDA-MB-231 and MCF-7 breast cancer cells were pronouncedly higher than their cytoskeletal stiffness, whereas the stiffness of the nucleus of human mammary epithelial cells was decreased compared to their cytoskeleton. TSA treatment reduced cytoskeletal and nuclear stiffness of MCF-7 cells, as expected. However, a softening of the nucleus by TSA treatment may induce a stiffening of the cytoskeleton of MDA-MB-231 cells and subsequently an apparent stiffening of the nucleus. Inhibiting actin polymerization using Latrunculin A revealed a softer nucleus of MDA-MB-231 cells under TSA treatment. This indicates that the actin-dependent cytoskeletal stiffness seems to be influenced by the TSA-induced nuclear stiffness changes. Finally, the combined treatment with TSA and Latrunculin A further justifies the hypothesis of apparent nuclear stiffening, indicating that cytoskeletal mechanics seem to be regulated by nuclear mechanics.
The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria

Lactoferrin is a nutrient classically found in mammalian milk. It binds iron and is transferred via a variety of receptors into and between cells, serum, bile, and cerebrospinal fluid. It has important immunological properties, and is both antibacterial and antiviral. In particular, there is evidence that it can bind to at least some of the receptors used by coronaviruses and thereby block their entry. Of importance are Heparan Sulfate Proteoglycans (HSPGs) and the host receptor angiotensin-converting enzyme 2 (ACE2), as based on other activities lactoferrin might prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from attaching to the host cells. Lactoferrin (and more specifically enteric-coated LF because of increased bioavailability) may consequently be of preventive and therapeutic value during the present COVID-19 pandemic.
Hspa13 Promotes Plasma Cell Production and Antibody Secretion

The generation of large numbers of plasma cells (PCs) is a main factor in systemic lupus erythematosus (SLE). We hypothesize that Hspa13, a member of the heat shock protein family, plays a critical role in the control of PC differentiation. To test the hypothesis, we used lipopolysaccharide (LPS)-activated B cells and a newly established mouse line with a CD19cre-mediated, B cell–specific deletion of Hspa13: Hspa13 cKO mice. We found that Hspa13 mRNA was increased in PCs from atacicept-treated lupus-prone mice and in LPS-stimulated plasmablasts (PBs) and PCs. A critical finding was that PBs and PCs [but not naïve B cells and germinal center (GC) B cells] expressed high levels of Hspa13. In contrast, the Hspa13 cKO mice had a reduction in BPs, PCs, and antibodies induced in vitro by LPS and in vivo by sheep red blood cells (SRCs)- or 4-hydroxy-3-nitrophenylacetyl (NP)-immunization. Accordingly, the Hspa13 cKO mice had reduced class-switched and somatically hypermutated antibodies with defective affinity maturation. Our work also showed that Hspa13 interacts with proteins (e.g., Bcap31) in the endoplasmic reticulum (ER) to positively regulate protein transport from the ER to the cytosol. Importantly, Hspa13 mRNA was increased in B220+ cells from patients with multiple myeloma (MM) or SLE, whereas Hspa13 cKO led to reduced autoantibodies and proteinuria in both pristane-induced lupus and lupus-prone MRL/lpr mouse models. Collectively, our data suggest that Hspa13 is critical for PC development and may be a new target for eliminating pathologic PCs.
The role of historic and climatic factors in the distribution of crustacean communities in Iberian Mediterranean ponds

SUMMARY 1. We studied 140 freshwater ponds in eastern Spain spanning a wide range of water source, hydroperiod and regional heterogeneity attributable to orographic and climatic differences. Our aim was to provide a typology for Mediterranean ponds using crustacean assemblages and to find key environmental thresholds that define these pond types. 2. To search for the environmental variables that define these communities, two complementary analyses were used: correspondence analyses (CA) and multivariate regression trees (MRT). We found a high level of specificity of crustaceans defining the different pond types. Three ponds, which were not associated with any of the large set of environmental variables used, were clearly separated from the rest in the CA. These held a very specific and probably relict community, characterised by the large calanoid Hemidiaptomus: we refer to these as ‘Hemidiaptomus’ ponds. Taxonomic information suggests a fundamental influence of historical events. 3. The MRT analysis applied to the rest of the ponds allowed us to create a hierarchical order of several current environmental factors that account for their crustacean community composition. Thus, we defined four further pond types. The most important factor structuring communities was hydroperiod, separating temporary ponds, mainly fed by rain, from permanent ponds, fed from more stable sources. Climate-related factors subsequently separated two groups of temporary ponds: (i) temporary ponds in semi-arid areas (mean rainfall <600 mm year 1 , spring rainfall <150 mm), which contained Neolovenula alluaudi and (ii) temporary ponds in semi-humid areas, which contained Mixodiaptomus incrassatus. Amongst the permanent ponds, (iii) lowland coastal spring-fed ponds with quite constant temperatures hosted a singular crustacean community that was well separated from that found in (iv) inland mountain ponds consisting of more ubiquitous crustaceans. 4. These results provide a typology of ponds useful for conservation planning and freshwater biodiversity maintenance. Moreover, the identified ecological thresholds should be helpful in predicting the communities to be expected as a result of changes to land use or climate.
The Tail of the Late Jurassic Sauropod Giraffatitan brancai: Digital Reconstruction of Its Epaxial and Hypaxial Musculature, and Implications for Tail Biomechanics

Dinosaur locomotion and biomechanics, especially of their pelvic girdles and hindlimbs, have been analyzed in numerous studies. However, detailed volumetric musculoskeletal models of their tails are rarely developed. Here, we present the first detailed three-dimensional volumetric reconstruction of the caudal epaxial and hypaxial musculature of the Late Jurassic sauropod Giraffatitan brancai, and highlight the importance and necessity of 3D modeling in musculoskeletal reconstructions. The tail of this basal macronarian is relatively short compared to diplodocids and other coexisting macronarians. The center of mass lies well in front of the hindlimbs, which support only ca. half the body weight. Still, our reconstruction suggests a total weight for the entire tail of ca. 2500 kg. We conclude that the hypaxial and tail-related hindlimb muscles (most specifically the M. caudofemoralis longus and its counterpart the M. ilioischiocaudalis) in Giraffatitan were well developed and robustly built, compensating for the shorter length of the M. caufodemoralis longus, the main hindlimb retractor muscle, in comparison with other sauropods. Our methodology allows a better-constrained reconstruction of muscle volumes and masses in extinct taxa, and thus force and weight distributions throughout the tail, than non-volumetric approaches.
Self-Harming and Sense of Agency in Patients With Borderline Personality Disorder

Self-harm is considered a pervasive problem in several psychopathologies, and especially in Borderline Personality Disorder (BPD). Self-harming behaviors may be enacted for many purposes for example to regulate emotions and to reduce dissociation. BPD patients often report dissociative episodes, which may be related to an altered body awareness, and in particular to an altered awareness of the sense of agency. The sense of agency draws in part upon perceptions of being in control of our bodies and our physical movements, of being able to act upon environments. In this study, we aim to investigate whether dissociative experiences of BPD patients may be linked to an altered sense of agency and whether self-injurious actions may, through strong sensorial stimulation, constitute a coping strategy for the reduction of the distress associated with these dissociative experiences. A group of 20 BPD patients, of whom 9 presented self-harming behaviors, took part in the study and were compared with an age-matched control group of 20 healthy individuals. Sense of agency was evaluated through the Sensory Attenuation paradigm. In this paradigm, in a comparison with externally generated sensations, the degree to which perceived intensity of self-generated sensations is reduced is considered an implicit measure of sense of agency. As we expected, we found a significant difference in the perceptions of the two groups. The attenuation effect appeared to be absent in the BPD group while it was present in the control group. However, further analysis revealed that those BPD patients who engaged in self-harming behaviors presented a degree of attenuation which was similar to that of the control group. These results confirm the hypothesis that self-injurious actions constitute a coping strategy for increasing the sense of agency. We finally discuss the correlation of these experimental results with some clinical self-evaluation measures assessing dissociation, anxiety, depression, and affective dysregulation.
Hybridization Between Yuccas From Baja California: Genomic and Environmental Patterns

Hybridization can occur when two geographically isolated species are reproductively compatible and have come into sympatry due to range shifts. Yucca and yucca moths exhibit obligate pollination mutualism; yucca moths are responsible for the gene flow mediated by pollen among yucca populations. In the Baja California Peninsula, there are two yucca sister species, Y. capensis and Y. valida, that have coevolved with the same pollinator, Tegeticula baja. Both yucca species are endemic to the peninsula, and their current distributions are allopatric. Based on their morphological characteristics, it has been suggested that some plants growing in the southern part of the Magdalena flatland, a spatially disjunct part of Yucca valida’s range, have hybrid origins. We conducted genomic and climatic analyses of the two yucca species as well as the putative hybrid populations. We genotyped 3,423 single nucleotide polymorphisms in 120 individuals sampled from 35 localities. We applied Bayesian tests and geographic cline analyses to the genomic data. Using climatic information from the occurrence sites, we projected species distribution models in different periods to assess changes in the distributional range, and we performed a statistical test to define the niche divergence between the paternal species and the putative hybrid populations. Structure analysis revealed mixed ancestry in the genome of hybrid populations, and the Bayesian models supported a scenario of post-divergence gene flow between the yucca species. Our species distribution models reveal that the geographical ranges of the parental species overlapped mainly during the Last Glacial Maximum, which could facilitate genetic admixture between those species. Finally, we found that most of the assessed environmental axes between the parents and hybrid populations are divergent, indicating that the climatic niche of the hybrid populations is shifting from that of the populations’ progenitors. Our results show that the populations in the southern part of the Magdalena flatland are the result of combination of the genetic components of two species. Hybrid individuals with this novel genomic combination arose in a different habitat than their parental species, and they exhibit ecological divergence, which contributes to reproductive isolation through spatial and temporal barriers.
Intercropped field beans (Vicia faba) and wheat (Triticum aestivum) for whole crop forage: effect of nitrogen on forage yield and quality

Sole crops and intercrops of field beans (Vicia faba L.) and wheat (Triticum aestivum L.), at three nitrogen rates, were evaluated for production of whole crop forage in two field experiments, one spring and one autumn drilled, on Imperial College at Wye farm, UK, during 1997–1998. Forage quality attributes measured were crude protein (CP), neutral detergent fibre (NDF), acid detergent fibre (ADF), water-soluble carbohydrate (WSC) and ash content. In both experiments, dry matter (DM) and percentage dry matter (DM%) were improved by intercropping compared with beans sole crops. Intercropping enhanced CP and NDF contents and WSC compared with beans and wheat sole crops, respectively. Nitrogen (N) applications up to 75 kg/ha produced the optimal intercrop forage yield and crude protein content. This input of N is smaller than that for other forage crops.
External Validation of the WORSEN Score for Prediction the Deterioration of Acute Ischemic Stroke in a Chinese Population

Background: Early neurological deterioration (END) has been recognized as a serious neurological complication after acute ischemic stroke. However, to date, the WORSEN score was the only one scoring system specifically developed to detect END events in acute ischemic stroke patients. The purpose of this study was to investigate the WORSEN score's utility in China, and to determine the potential predictors of END in acute stroke patients. Methods: Consecutive patients with acute ischemic stroke admitted to the Department of Neurology, Aerospace Center Hospital between March 2015 to February 2017 were recruited into the study's cohort and divided into two groups: patients with and without END. END was defined as either an increase in two or more NIHSS points, an increment of at least one point in motor power or a description of fluctuating of clinical symptoms in medical reports during the first 7 days after admission. Severe END was defined as an increase of NIHSS ≥ 4 points from baseline during the first 7 days after admission. Results: Three hundred fifty four patients with acute ischemic stroke were enrolled in the present study and 67.5% were male. END occurred in 90 of these patients and severe END occurred in 55 of these patients. Logistic regression analysis showed that an initial NIHSS score ≥8, diameter of infarction, striatocapsular infarction, and TOAST type of large arterial atherosclerosis were independent predictors for END. The area under the ROC curve (AUC) of the WORSEN score for the prediction of END was 0.80 (95%CI 0.75–0.84), with a sensitivity of 62.22%, a specificity of 88.26%, positive predictive values of 64.37% and negative predictive values of 87.27%. Meanwhile, the AUC of the WORSEN score for the prediction of severe END was 0.82 (95%CI 0.78–0.86), with a sensitivity of 70.91%, specificity of 83.95%, positive predictive values of 44.83% and negative predictive values of 94.01%. Conclusion: END is a relatively common neurological complication in patients with acute ischemic stroke. Our findings showed that the WORSEN score had a good predictive value for identifying patients with END in a Chinese population. Moving forward, multi-center studies are required for further validations
School-Based Prevention Targeting Non-Suicidal Self-injury: A Pilot Study

Non-suicidal self-injury (NSSI) is prevalent in adolescence and is associated with increased risk for a variety of subsequent negative mental health outcomes, necessitating an evidence-based preventive approach. This pilot study examines the potential iatrogenic effects and feasibility of an evidence-based school program for the prevention of NSSI. Differences are examined between a general in-classroom prevention program (Happyles) and this program combined with a 1-h in-classroom psychoeducation module on NSSI (HappylesPLUS) in terms of primary (e.g., delay in NSSI onset and decrease in NSSI frequency, urges, probability of future engagement) and secondary outcomes (e.g., psychological distress, emotion regulation, help-seeking, and stigma) using a mixed-method design. A total of 651 secundary school pupils (Mage = 12.85 years; 49.8% female versus 50.2% male) were assigned to the Happyles program and HappylesPLUS. Participants filled out validated self-report questionnaires pre (T0) and post (T1, 6 weeks after T0) the school prevention program, including the Youth Outcome Questionnaire (YOQ), the Brief Non-Suicidal Self-Injury Assessment Test (BNSSI-AT), the Difficulties in Emotion Regulation Scale (DERS), the Attitudes Toward Seeking Professional Psychological Help Scale—Short Form (ATSPPH-SF), and the Peer Mental Health Stigmatization Scale (PMHSS). Qualitative semi-structured interviews (at T2,6 weeks after T1) were conducted with participants with and without a history of NSSI. Overall, results show no iatrogenic effects of the NSSI-focused psychoeducation module. In terms of our primary outcome, both groups reported a reduced likelihood of future NSSI engagement from T0 to T1. Regarding secondary outcome measures, we also observed increased emotional awareness in both groups. The qualitative data suggest that the addition of the NSSI-specific module to the Happyles program may have direct benefits to some students with lived experience, such as increased help-seeking behavior for NSSI. Findings of this pilot study show that incorporating NSSI-specific modules into evidence-based school prevention programs is feasible and does not lead to iatrogenic effects. Future work is needed to evaluate the potential (longer-term) benefits of incorporating NSSI-focused modules to evidence-based mental health programs in the prevention of NSSI.
The Effects of Digital Predistortion in a CO-OFDM System—A Stochastic Approach

Digital predistortion is topic of significant interest in telecommunications – both in the wireless radio field and, more recently, in photonics. In the present letter, the authors undertake a sensitivity analysis of various digital predistortion algorithms. Using recent metamodeling techniques designed for efficient stochastic analysis, the authors show that using predistortion not only leads to a reduction of the error vector magnitude in general but can also make the system less sensitive to uncertainties.
High On-Off Ratio Graphene Switch via Electrical Double Layer Gating

This paper discusses the production and investigation of novel graphene switches by gating through an electrical double layer (EDL). Controlled voltage biases across a liquid dielectric and graphene induce electrochemical reactions within the dielectric and produce high electric fields in an EDL at the surface of graphene. As the electrochemical reactions occur within the dielectric, the EDL strength separates the electrochemically-produced ions based on their polarity, and provides the necessary molecular activation and deactivation energies to form weak, reversible molecular bonds between the produced ions and graphene. The reversible bonds between the ions and graphene are used to dynamically alter the electronic transport through graphene, which introduces an exciting assortment of device possibilities. Whereas traditional graphene devices are unuseful for electronic switches or digital logic due to an insufficient bandgap of graphene, the presented graphene electrochemical field-effect transistors (GEC-FETs) exhibit ON-OFF ratios larger than 104 with OFF-resistances as high as 10 $\text{M}\Omega $ . Channel current, gate voltage, and dielectric medium are varied and compared to show their effect on device performance. The presented device and associated techniques show potential for integration in graphene digital-logic architectures.
Changes in mechanical and dielectric properties of silicone rubber induced by severe aging

Sheets of silicone rubber (SiR) were aged under various aging conditions to examine its effects on the mechanical and dielectric properties of SiR. Mainly by analyzing the results obtained by mid-infrared absorption spectroscopy, it has become clear that cross-linked structures with siloxane bonds are formed under all the conditions. This makes SiR hard and then brittle, but it also makes better the dielectric properties apparently. An early stage of degradation in SiR can be detected by EAB and complex electric modulus, which is defined as the reciprocal of complex permittivity. Therefore, EAB and complex electric modulus are useful to monitor the aging status of SiR.