Miracle-dz/UniFAR-FTUs huggingface dataset:
Can Paraplegia by Disruption of the Spinal Cord Tissue Be Reversed? The Signs of a New Perspective

Central nervous system (CNS) trauma is often related to tissue loss, leading to partial or complete disruption of spinal cord function due to neuronal death. Although generally irreversible, traditional therapeutic efforts, such as physical therapy exercises, are generally recommended, but with a poor or reduced improvement of the microenvironment, which in turn stimulates neuroplasticity and neuroregeneration. Mesenchymal stem cells (MSCs) have paracrine, immunomodulatory, and anti‐inflammatory effects. Here we use stem cells to see if they can promote not only physical but also the functional regeneration of neuronal tissue in dogs with CNS traumas. Two dogs, one with chronic spinal cord injury and one with subacute spinal cord injury, underwent infusion of autologous MSCs in association with physiotherapy. The two treatments in combination were able to partially or completely recover the dog's walking movement again. The treatment of MSCs in association with physical therapy improved the microenvironment, which could be evidence of a paradigm shift that the CNS is not capable of functional regeneration after aggressive traumas. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1812–1820, 2020. © 2019 American Association for Anatomy
EAACI position paper on diet diversity in pregnancy, infancy and childhood: Novel concepts and implications for studies in allergy and asthma

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes.
Alloparental care in the sea: Brood parasitism and adoption within and between two species of coral reef Altrichthys damselfish?

The evolution of parental care opens the door for the evolution of brood parasitic strategies that allow individuals to gain the benefits of parental care without paying the costs. Here we provide the first documentation for alloparental care in coral reef fish and we discuss why these patterns may reflect conspecific and interspecific brood parasitism. Species‐specific barcodes revealed the existence of low levels (3.5% of all offspring) of mixed interspecific broods, mostly juvenile Amblyglyphidodon batunai and Pomacentrus smithi damselfish in Altrichthys broods. A separate analysis of conspecific parentage based on microsatellite markers revealed that mixed parentage broods are common in both species, and the genetic patterns are consistent with two different modes of conspecific brood parasitism, although further studies are required to determine the specific mechanisms responsible for these mixed parentage broods. While many broods had offspring from multiple parasites, in many cases a given brood contained only a single foreign offspring, perhaps a consequence of the movement of lone juveniles between nests. In other cases, broods contained large numbers of putative parasitic offspring from the same parents and we propose that these are more likely to be cases where parasitic adults laid a large number of eggs in the host nest than the result of movements of large numbers of offspring from a single brood after hatching. The evidence that these genetic patterns reflect adaptive brood parasitism, as well as possible costs and benefits of parasitism to hosts and parasites, are discussed.
A simulation‐based method for evaluating geometric tests of a linac c‐arm in quality control in radiotherapy

Abstract Purpose Assessment of the accuracy of geometric tests of a linac used in external beam therapy is crucial for ensuring precise dose delivery. In this paper, a new simulation‐based method for assessing accuracy of such geometric tests is proposed and evaluated on a set of testing procedures. Methods Linac geometry testing methods used in this study are based on an established design of a two‐module phantom. Electronic portal imaging device (EPID) images of fiducial balls contained in these modules can be used to automatically reconstruct linac geometry. The projection of the phantom modules fiducial balls onto the EPID detector plane is simulated for assumed nominal geometry of a linac. Then, random errors are added to the coordinates of the projections of the centers of the fiducial balls and the linac geometry is reconstructed from these data. Results Reconstruction is performed for a set of geometric test designs and it is shown how the dispersion of the reconstructed values of geometric parameters depends on the design of a geometric test. Assuming realistic accuracy of EPID image analysis, it is shown that for selected testing plans the reconstruction accuracy of geometric parameters can be significantly better than commonly used action thresholds for these parameters. Conclusions Proposed solution has the potential to improve geometric testing design and practice. It is an important part of a fully automated geometric testing solution.
The Escherichia coli MarA protein regulates the ycgZ‐ymgABC operon to inhibit biofilm formation

The Escherichia coli marRAB operon is a paradigm for chromosomally encoded antibiotic resistance. The operon exerts its effect via an encoded transcription factor called MarA that modulates efflux pump and porin expression. In this work, we show that MarA is also a regulator of biofilm formation. Control is mediated by binding of MarA to the intergenic region upstream of the ycgZ‐ymgABC operon. The operon, known to influence the formation of curli fibres and colanic acid, is usually expressed during periods of starvation. Hence, the ycgZ‐ymgABC promoter is recognised by σ38 (RpoS)‐associated RNA polymerase (RNAP). Surprisingly, MarA does not influence σ38‐dependent transcription. Instead, MarA drives transcription by the housekeeping σ70‐associated RNAP. The effects of MarA on ycgZ‐ymgABC expression are coupled with biofilm formation by the rcsCDB phosphorelay system, with YcgZ, YmgA and YmgB forming a complex that directly interacts with the histidine kinase domain of RcsC.
Theory of mind performance in younger and older adults with elevated autistic traits

Little is known about the impact of aging with Autism Spectrum Disorder on theory of mind (ToM). While ToM difficulties appear to abate with age in older autistic populations, this has yet to be explored in the Broad Autism Phenotype (BAP). The current study examined ToM performance among younger (n = 49, aged 18–46) and older adults (n = 47, aged 60–91) who were classified as on the BAP (younger n = 18; older n = 21) or not (younger n = 31; older n = 26) using the BAP Questionnaire. ToM was assessed using the ecologically valid Strange Stories Film Task (SSFT) and the dynamic Happé–Frith Triangle Animations task (TA). A 2 × 2 analysis of variance examined the effects of autistic traits (BAP vs. non‐BAP) and age (young vs. old). For both SSFT and TA, results showed autistic trait main effects on task performance (non‐BAP > BAP). Age main effects were observed for some but not all metrics on TA (younger better than older), with no differences in SSFT. An interaction of autistic traits and age was observed in TA Intentionality, with younger non‐BAP and younger BAP performing similarly but older non‐BAP performing better than older BAP. Results show that younger and older adults with elevated autistic traits show poorer ToM performance. Despite ToM difficulties being common in later life in the general population, this effect was not observed when using a ToM task designed to reflect real‐world scenarios. However, results suggest that autistic traits and age could interact to increase risk for poor ToM performance in older adults who endorse elevated autistic traits. Autism Res 2020, 13: 751–762. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Impact of NF-κB pathway on the apoptosis-inflammation-autophagy crosstalk in human degenerative nucleus pulposus cells

The NF-κB pathway has been reported to play a very important role in the process of intervertebral disc degeneration (IVDD). Our results demonstrated that knockdown of NF-κB with P65-siRNA can significantly decrease cell apoptosis and the expression of pro-inflammation factors TNF-α and IL-1β in LPS-induced nucleus pulposus cells (NPCs). However, the molecular mechanism of NF-κB pathway exerting anti-inflammation and anti-apoptosis function remains unclear. Some researchers reported that inhibiting NF-κB pathway can attenuate the catabolic effect by promoting autophagy during inflammatory conditions in rat nucleus pulposus cells. Therefore, we hypothesized that in human NPCs, inhibiting NF-κB pathway may also promote autophagy. Our results indicated that after knockdown of NF-κB, the autophagy was significantly increased and the expression of p-AKT and p-mTOR protein markedly decreased, but the level of autophagy was inhibited after treatment with AKT activator SC79, suggesting the involvement of AKT/mTOR–mediated autophagy was under autophagy activation. However, both LPS-induced NPCs apoptosis and expression of pro-inflammation factors were further increased by pretreatment with the autophagy inhibitor chloroquine (CQ). These suggested that inhibiting NF-κB pathway can promote autophagy and decrease apoptosis and inflammation response in LPS-induced NPCs. Meanwhile, autophagy triggered by NF-κB inhibition plays a protective role against apoptosis and inflammation.
Comparison of the Word Memory Test and the Test of Memory Malingering in detecting invalid performance in neuropsychological testing

Abstract Given the prevalence of compensation seeking patients who exaggerate or fabricate their symptoms, the assessment of performance and symptom validity throughout testing is vital in neuropsychological evaluations. Two of the most commonly utilized performance validity tests (PVTs) are the Word Memory Test (WMT) and the Test of Memory Malingering (TOMM). While both have proven successful in detecting invalid performance, some studies suggest greater sensitivity in the WMT relative to the TOMM. To improve upon previous research, this study compared performance in individuals who completed both the WMT and TOMM during a neuropsychological evaluation. Participants included 268 cases from a clinical private practice consisting of primarily disability claimants. One-way multivariate analysis of variance (MANOVA) compared neuropsychological performance of participants who passed both PVTs (n = 198) versus those who failed the WMT but passed the TOMM (n = 70). Global suppression of neuropsychological scores was found for participants who failed the WMT but passed the TOMM, as well as more psychiatric symptoms reported on questionnaires, relative to those who passed both PVTs. These findings suggest that those passing the TOMM but failing the WMT demonstrated performance invalidity, which illustrates the WMT’s enhanced sensitivity.
Biotechnology and Bioengineering

National Research Council, Institute for Microelectronics and Microsystems, Departments of Naples, Naples, Italy Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Naples, Italy Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy Department of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, Naples, Italy
Density and distribution of western chimpanzees around a bauxite deposit in the Boé Sector, Guinea‐Bissau

The Boé sector in southeast Guinea‐Bissau harbors a population of western chimpanzees (Pan troglodytes verus) that inhabits a mosaic of forest and savanna. The Boé sector contains a substantial bauxite deposit in a region called Ronde Hill, and there are plans for the construction of a mine, which may endanger the chimpanzee population. In 1‐week survey in May 2013, we used the standing crop nest counts method to obtain the number of chimpanzee nests and from that estimate the density and abundance of chimpanzees. We carried out five 1‐km line transects that covered the bauxite deposit and surrounding valleys. We used density surface modeling to analyze habitat preferences, then predicted chimpanzee nest density and distribution based on environmental variables. We found the projected location of the mine partially coincides with an area of high predicted abundances of chimpanzee nests and is surrounded by highly suitable areas for chimpanzees (northeast and southwest). We conclude the mine could have significant direct and indirect effects on this population of chimpanzees whose impacts must be carefully considered and properly mitigated if the mine is built.
Impact of slope on dynamics of running and climbing

By combining biological studies and modeling work, the dynamics of running on horizontal terrain and climbing pure vertical surfaces have been distilled down to simple reduced order models. These models have inspired distinct control and design considerations for robots operating in each terrain. However, while the extremes are understood, the intermediate regions of moderate slopes have yet to be fully explored. In this paper, we examine how cockroaches vary their behavior as slope is changed from horizontal to vertical, with special care to examine individual leg forces when possible. The results are then compared with a lateral leg spring based (LLS, horizontal running) and Full–Goldman based (FG, vertical running) models. Overall, from the experimental data, there appears to be a continuous shift in the dynamics as slope varies, which is confirmed by similar behaviors exhibited by the LLS and FG models. Finally, by examining the stability and efficiency of the models, it is shown that there are stability limits related to the amount of energy added by the front versus rear legs. This corresponds to the shift in leg usage demonstrated by the biological experiments and may have significant implications for the design and control of multi-modal robotic systems.
The role of adiponectin system in acute fasting-impaired mouse ovaries.

Adiponectin is an important white adipose-derived adipokine linked to energy homeostasis and reproductive function. This study aims to reveal the expression and role of adiponectin system in ovaries under the acute malnutrition. In this study, 48 h food deprivation significantly inhibited ovarian growth by suppressing cell proliferation and inducing cell apoptosis in the ovaries of gonadotrophin-primed immature mice. It was also accompanied by significantly decelerated basic metabolism (glucose, triacylglycerol and cholesterol), varied steroid hormones (follicle-stimulating hormone, luteinizing hormone and estradiol) and vanishment of the peri-ovarian fat. It is noteworthy that after acute fasting, the adiponectin levels in ovaries rather than in blood were significantly elevated. Immunohistochemical study demonstrated that adiponectin and its receptors (AdipoR1 and AdipoR2) primarily appeared in ovarian somatic and/or germ cells, and their protein expressions were up-regulated in the ovaries from fasted mice. Further in vitro study verified that adipoR1/2 agonist obviously inhibited follicle-stimulating hormone-induced oocyte meiotic resumption, while the antagonist significantly enhanced the percentage of oocyte maturation in the absence of follicle-stimulating hormone. Furthermore, the building up of peri-ovarian fat under physiological status in mice showed a positive correlation with both the hypertrophy of adipocytes and growth of ovaries. Taken together, these findings indicate that the up-regulation of adiponectin system disturb the normal female reproductive function under the malnutrition status, and it may be associated with the loss of peri-ovarian fat depots.
Improving Contrast and Detectability: Imaging with [55Co]Co-DOTATATE in Comparison with [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE

PET imaging at late time points after injection may allow tracer clearance from normal tissue and hence improve image contrast and detectability. 55Co is a promising isotope with high positron yield and a long half-life suitable for imaging at delayed time points. Here, we compared the 3 radioconjugates [68Ga]Ga-DOTATATE, [64Cu]Cu-DOTATATE, and [55Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor–expressing AR42J tumors. Methods: 55Co and 64Cu were produced by the 54Fe(d,n)55Co and 64Ni(p,n)64Cu nuclear reactions, whereas 68Ga was obtained from a 68Ge/68Ga generator. 55Co and 64Cu were labeled with DOTATATE by heating in a sodium acetate buffer and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, respectively. AR42J tumor–bearing mice were dynamically scanned 0–1 h after injection. For 64Cu and 55Co, additional imaging was also performed at late time points after 4 and 24 h. Dose calculations were based on a known biodistribution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent doses were calculated by OLINDA/EXM using the MIRD formalism. Results: Tumor uptake was rapid from 0 to 1 h after injection for all 3 radioconjugates. Normal-tissue ratios as represented by tumor-to-liver, tumor-to-kidney, and tumor-to-muscle ratios increased significantly over time, with [55Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [55Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65 ± 16 at 4 h and 50 ± 6 at 24 h, which were 15 (P < 0.001) and 30 (P < 0.001) times higher, respectively, than the corresponding ratios for [64Cu]Cu-DOTATATE and 5 (P < 0.001) times higher than that of [68Ga]Ga-DOTATATE at 1 h. Correspondingly, tumor-to-kidney and tumor-to-muscle ratios for [55Co]Co-DOTATATE were 4 (P < 0.001) and 11 (P < 0.001) times higher than that of [64Cu]Cu-DOTATATE at 24 h. An equivalent dose was calculated as 9.6E−02 mSv/MBq for [55Co]Co-DOTATATE. Conclusion: [55Co]Co-DOTATATE demonstrated superior image contrast compared with [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE for PET imaging of somatostatin receptor–expressing tumors, warranting translation into clinical trials. Dosimetry calculations found that effective doses for [55Co]Co-DOTATATE were comparable to those for both [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE.
MT1-MMP recruits the ER-Golgi SNARE Bet1 for efficient MT1-MMP transport to the plasma membrane

Invasive cancer cells degrade and invade into the extracellular matrix by expressing the matrix metalloproteinase MT1-MMP at invadopodia. Miyagawa et al. show that MT1-MMP uses the ER-Golgi SNARE Bet1 to facilitate its own transport to the plasma membrane through their interaction in a cholesterol-rich milieu.
Advancing Biologics Development Programs with Legacy Cell Lines: Advantages and Limitations of Genetic Testing for Addressing Clonality Concerns Prior to Availability of Late Stage Process and Product Consistency Data

The bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. To ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. Regulatory agencies and the biotechnology industry consider cell line “clonal origin” an important aspect of maintaining process control. Demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few years, and the industry has improved methods and devised standards to increase the probability and/or assurance of clonal derivation. However, older production cell lines developed before the implementation of these methods, herein referred to as “legacy cell lines,” may not meet current regulatory expectations for demonstration of clonal derivation. In this article, the members of the IQ Consortium Working Group on Clonality present our position that the demonstration of process consistency and product comparability of critical quality attributes throughout the development life cycle should be sufficient to approve a license application without additional genetic analysis to support clonal origin, even for legacy cell lines that may not meet current day clonal derivation standards. With this commentary, we discuss advantages and limitations of genetic testing methods to support clonal derivation of legacy cell lines and wish to promote a mutual understanding with the regulatory authorities regarding their optional use during early drug development, subsequent to Investigational New Drug (IND) application and before demonstration of product and process consistency at Biologics License Applications (BLA) submission.
The effect of primary care availability on antibiotic consumption in Hungary: a population based panel study using unfilled general practices

Objective We analyse the effect of primary care availability on antibiotic consumption and on the quality of antibiotic prescribing behaviour. Design Retrospective panel design, secondary analysis of settlement-level administrative panel data (n=2320 settlements, T=72 months). Participants and setting We analyse antibiotic consumption of the population of villages in Hungary, over years 2010 to 2015. We exploit the geographical and time variation in unfilled (mainly single-handed) general practices as a source of exogenous variation in the availability of primary care. We control for socioeconomic characteristics and settlement fixed effects in a panel regression framework. Outcome measures Antibiotic expenditures and days of therapy (DOT); consumption of narrow-spectrum and broad-spectrum antibiotics; consumption of Access, Watch and Reserve antibiotics according to the AWaRe categorisation; number of visits to the general practitioner (GP). Results If the general practice of a village becomes unfilled, the number of GP visits decreases on average by 9.3% (95% CI 5.6% to 12.9%), antibiotics DOT decrease on average by 3.2% (95% CI 1.0% to 5.4%) and expenditures on antibiotics decrease on average by 2.5% (95% CI 0.3% to 4.7%). The negative effect on antibiotic consumption is stronger in settlements where secondary care is less available, and where antibiotics were previously overprescribed. The quality of prescribing behaviour measured by the relative changes in the narrow-spectrum vs broad-spectrum as well as the Access versus Watch and Reserve antibiotics deteriorates significantly as a consequence of worse primary care availability. Conclusions Limited availability of primary care reduces the consumption of antibiotics and at the same time impairs the quality of prescriptions through a decrease of the number of doctor-patient encounters.