Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Immunogenicity of Heterologous and Homologous 2-Dose Regimens of Adenovirus Serotype 26– and Modified Vaccinia Ankara–Vectored Ebola Vaccines: A Randomized, Controlled Phase 1 Study

Abstract Background This phase 1 placebo-controlled study assessed the safety and immunogenicity of 2-dose regimens of Ad26.ZEBOV (adenovirus serotype 26 [Ad26]) and MVA-BN-Filo (modified vaccinia Ankara [MVA]) vaccines with booster vaccination at day 360. Methods Healthy US adults (N = 164) randomized into 10 groups received saline placebo or standard or high doses of Ad26 or MVA in 2-dose regimens at 7-, 14-, 28-, or 56-day intervals; 8 groups received booster Ad26 or MVA vaccinations on day 360. Participants reported solicited and unsolicited reactogenicity; we measured immunoglobulin G binding, neutralizing antibodies and cellular immune responses to Ebola virus glycoprotein. Results All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA [dose 1, dose 2] or MVA,Ad26) and homologous (Ad26,Ad26) regimens induced humoral and cellular immune responses 21 days after dose 2; responses were higher after heterologous regimens. Booster vaccination elicited anamnestic responses in all participants. Conclusions Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous 2-dose Ad26,MVA regimens containing an Ebola virus insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting that Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the 2-dose regimen.
ROR2 blockade as a therapy for osteoarthritis

ROR2 blockade improves the functional and structural outcomes of osteoarthritis in preclinical animal models by inhibiting YAP signaling. Countering cartilage breakdown Receptor tyrosine kinase–like orphan receptor 2 (ROR2) is expressed in the cartilage during development. Here, Thorup et al. found that ROR2 signaling was increased in damaged osteoarthritic cartilage tissue and that its overexpression inhibited chondrocyte differentiation. Blocking ROR2 in a mouse model of surgically induced osteoarthritis lessened pain and improved joint architecture, and silencing ROR2 in cells promoted formation of the healthy cartilage. Results suggest that ROR2 could be a potential therapeutic target for osteoarthritis. Osteoarthritis is characterized by the loss of the articular cartilage, bone remodeling, pain, and disability. No pharmacological intervention can currently halt progression of osteoarthritis. Here, we show that blocking receptor tyrosine kinase–like orphan receptor 2 (ROR2) improves cartilage integrity and pain in osteoarthritis models by inhibiting yes-associated protein (YAP) signaling. ROR2 was up-regulated in the cartilage in response to inflammatory cytokines and mechanical stress. The main ligand for ROR2, WNT5A, and the targets YAP and connective tissue growth factor were up-regulated in osteoarthritis in humans. In vitro, ROR2 overexpression inhibited chondrocytic differentiation. Conversely, ROR2 blockade triggered chondrogenic differentiation of C3H10T1/2 cells and suppressed the expression of the cartilage-degrading enzymes a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)–4 and ADAMTS-5. The chondrogenic effect of ROR2 blockade in the cartilage was independent of WNT signaling and was mediated by down-regulation of YAP signaling. ROR2 signaling induced G protein and Rho-dependent nuclear accumulation of YAP, and YAP inhibition was required but not sufficient for ROR2 blockade–induced chondrogenesis. ROR2 silencing protected mice from instability-induced osteoarthritis with improved structural outcomes, sustained pain relief, and without apparent side effects or organ toxicity. Last, ROR2 silencing in human articular chondrocytes transplanted in nude mice led to the formation of cartilage organoids with more and better differentiated extracellular matrix, suggesting that the anabolic effect of ROR2 blockade is conserved in humans. Thus, ROR2 blockade is efficacious and well tolerated in preclinical animal models of osteoarthritis.
Brain α-Tocopherol Concentration and Stereoisomer Profile Alter Hippocampal Gene Expression in Weanling Mice.

BACKGROUND Alpha-tocopherol (αT), the bioactive constituent of vitamin E, is essential for fertility and neurological development. Synthetic αT (8 stereoisomers; all rac-αT) is added to infant formula at higher concentrations than natural αT (RRR-αT only) to adjust for bio-potency differences, but its effects on brain development are poorly understood. OBJECTIVES The objective was to determine the impact of bio-potency-adjusted dietary all rac-αT versus RRR-αT, fed to dams, on the hippocampal gene expression in weanling mice. METHODS Male/female pairs of C57BL/6J mice were fed AIN 93-G containing RRR-αT (NAT) or all rac-αT (SYN) at 37.5 or 75 IU/kg (n = 10/group) throughout gestation and lactation. Male pups were euthanized at 21 days. Half the brain was evaluated for the αT concentration and stereoisomer distribution. The hippocampus was dissected from the other half, and RNA was extracted and sequenced. Milk αT was analyzed in separate dams. RESULTS A total of 797 differentially expressed genes (DEGs) were identified in the hippocampi across the 4 dietary groups, at a false discovery rate of 10%. Comparing the NAT-37.5 group to the NAT-75 group or the SYN-37.5 group to the SYN-75 group, small differences in brain αT concentrations (10%; P < 0.05) led to subtle changes (<10%) in gene expression of 600 (NAT) or 487 genes (SYN), which were statistically significant. Marked differences in brain αT stereoisomer profiles (P < 0.0001) had a small effect on fewer genes (NAT-37.5 vs. SYN-37.5, 179; NAT-75 vs. SYN-75, 182). Most of the DEGs were involved in transcription regulation and synapse formation. A network analysis constructed around known vitamin E interacting proteins (VIPs) revealed a group of 32 DEGs between NAT-37.5 vs. SYN-37.5, explained by expression of the gene for the VIP, protein kinase C zeta (Pkcz). CONCLUSIONS In weanling mouse hippocampi, a network of genes involved in transcription regulation and synapse formation was differentially affected by dam diet αT concentration and source: all rac-αT or RRR-αT.
Medial forebrain bundle structure is linked to human impulsivity

Reduced medial forebrain bundle coherence is associated with greater trait impulsivity, as well as stimulant use disorder. Comparative research indicates that projections from midbrain dopamine nuclei [including the ventral tegmental area (VTA)] to the ventral striatum [including the nucleus accumbens (NAcc)] critically support motivated behavior. Using diffusion-weighted imaging and probabilistic tractography in humans, we characterized the trajectory and structure of two tracts connecting the VTA and NAcc, as well as others connecting the substantia nigra and dorsal striatum. Decreased structural coherence of an inferior VTA–NAcc tract was primarily and replicably associated with increased trait impulsivity and also distinguished individuals with a stimulant use disorder from healthy controls. These findings suggest that decreased coherence of the inferior VTA–NAcc tract is associated with increased impulsivity in humans and identify a previously uncharacterized structural target for diagnosing disorders marked by impulsivity.
De Novo Transcriptomic and Metabolomic Analyses Reveal the Ecological Adaptation of High-Altitude Bombus pyrosoma

Simple Summary Bumblebees are very important pollinators for many wild and agricultural flowers and play significant roles in natural and agricultural ecosystems. The distribution of bumblebees varies between the species; some species occupy narrow areas, while others have a varied distribution from low to high elevation. Bombus pyrosoma is one of the bumblebee species with a highly varied geomorphological distribution range in China. To answer why some bumblebee species have a varied distribution, we compared the transcriptomic and metabolomic data of B. pyrosoma from the low-altitude North China Plain and the high-altitude Tibet Plateau. The results showed that energy metabolism and innate immunity of the high-altitude B. pyrosoma had been enhanced in order to adapt to the extreme environment of hypoxia and low temperature, compared to the low-altitude bumblebees. This study highlights the ecological adaptation of bumblebees distributed from low- to high-altitude conditions. Abstract Bombus pyrosoma is one of the most abundant bumblebee species in China, with a distribution range of very varied geomorphology and vegetation, which makes it an ideal pollinator species for research into high-altitude adaptation. Here, we sequenced and assembled transcriptomes of B. pyrosoma from the low-altitude North China Plain and the high-altitude Tibet Plateau. Subsequent comparative analysis of de novo transcriptomes from the high- and low-altitude groups identified 675 common upregulated genes (DEGs) in the high-altitude B. pyrosoma. These genes were enriched in metabolic pathways and corresponded to enzyme activities involved in energy metabolism. Furthermore, according to joint analysis with comparative metabolomics, we suggest that the metabolism of coenzyme A (CoA) and the metabolism and transport of energy resources contribute to the adaptation of high-altitude B. pyrosoma. Meanwhile, we found many common upregulated genes enriched in the Toll and immune deficiency (Imd)signaling pathways that act as important immune defenses in insects, and hypoxia and cold temperatures could induce the upregulation of immune genes in insects. Therefore, we suppose that the Toll and Imd signaling pathways also participated in the high-altitude adaptation of B. pyrosoma. Like other organisms, we suggest that the high-altitude adaptation of B. pyrosoma is controlled by diverse mechanisms.
Microstructure and in‐situ tensile strength of propodus of mantis shrimp

Effects of microstructure and phase component on mechanical property of spearer propodus of mantis shrimp were investigated. The spearer propodus consisted of three layers including epicuticle (outer layer), exocuticle (middle layer), and endocuticle (inner layer). The outer layer was composed of fluorapatite, which was treated as permeability barrier to environment. The compact middle layer and inner layer were constituted of chitin‐protein fibers, which exhibited the layered spiral structure. Under the in‐situ tensile test environment, spearer propodus owned high mechanical strength, which bore maximum tensile fore of 320 N. In the in‐situ tensile process, cracks extended along with zigzag lines on spearer propodus surface. The middle layer and inner layer resisted the damage of force via the fracture and pulling of fibers. The crack deflection and delamination phenomena were the mechanical property mechanisms of spearer propodus of mantis shrimp. The investigations provided typical bionic models for the design and preparation of bionic structure materials, bionic anti‐impact materials, and bionic soft materials in engineering fields.
A multiple case study investigating changes in organizations serving residents with intellectual disabilities and challenging behaviours

Abstract Background the present authors examined changes made in disability service organizations supporting residents with intellectual disabilities and challenging behaviours, because these changes may influence residents’ support and subsequently their challenging behaviours. Method In this multiple case study, the present authors collected and qualitatively analysed data (organizational documents, meetings records and focus group reports) on organizational changes made in two specialized Dutch disability service organizations, using ecological theory as a sensitizing framework and the constant comparative method. Results Themes describing organizational changes in this context were as follows: a messy start to the transition; staff, professionals and managers remain at a distance; staff members’ ability to change; clear boundaries between formal and informal caregivers; and staff’s feelings of being unheard. Conclusions Organizational changes can enhance, but also limit, the quality of residential support services provided to people with intellectual disabilities and challenging behaviours. The change process and impact of organizational changes on residents must be examined closely.
Developmental distribution of primary cilia in the retinofugal visual pathway

The mammalian visual system is composed of circuitry connecting sensory input from the retina to the processing core of the visual cortex. The two main retinorecipient brain targets, the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN), bridge retinal input and visual output. The primary cilium is a conserved organelle increasingly viewed as a critical sensor for the regulation of developmental and homeostatic pathways in most mammalian cell types. Moreover, cilia have been described as crucial for neurogenesis, neuronal maturation, and survival in the cortex and retina. However, cilia in the visual relay center remain to be fully described. In this study, we characterized the ciliation profile of the SC and dLGN and found that the overall number of ciliated cells declined during development. Interestingly, shorter ciliated cells in both regions were identified as neurons, whose numbers remained stable over time, suggesting that cilia retention is a critical feature for optimal neuronal function in SC and dLGN. Our study suggests that primary cilia are important for neuronal maturation and function in cells of the SC and dLGN.
Interactions in Model Ionic Dyads and Triads Containing Tetrel Atoms

The interactions in model ionic YTX3···Z (Y = NC, F, Cl, Br; X = F, Cl, Br, Z = F−, Cl−, Br−, Li+) dyads containing the tetrel atoms, T = C, Si, Ge, were studied using ab initio computational methods, including an energy decomposition analysis, which found that the YTX3 molecules were stabilized by both anions (via tetrel bonding) and cations (via polarization). For the tetrel-bonded dyads, both the electrostatic and polarization forces make comparable contributions to the binding in the C-containing dyads, whereas, electrostatic forces are by far the largest contributor to the binding in the Si- and Ge-containing analogues. Model metastable Li+···NCTCl3···F− (T = C, Si, Ge) triads were found to be lower in energy than the combined energy of the Li+ + NCTCl3 + F− fragments. The pair energies and cooperative energies for these highly polar triads were also computed and discussed.
Intra-Individual Double Burden of Malnutrition among Adults in China: Evidence from the China Health and Nutrition Survey 2015

Few studies have focused on quantifying the double burden of malnutrition (DBM) phenomenon in China. We aimed to clarify the prevalence of DBM among Chinese adults as well as to examine whether daily dietary micronutrient status varies by body mass index (BMI) categories. In this study, a sample of 6602 adults aged 18–59 years from the China Health and Nutrition Survey (CHNS) was analyzed. Information was obtained on dietary intake and anthropometric measurements. Dietary intakes of 11 micronutrients were estimated based on the data collected by three consecutive days of 24 h recalls combined with the weighing of household seasonings. Dietary micronutrient deficiency was defined according to the cutoff of the Chinese estimated average requirement (EARs). 44% of Chinese adults faced the problem of DBM, of which nearly 40% experienced overweight/obesity and micronutrient deficiency simultaneously. Comparable percentages (>50%) of Chinese adults had dietary intake less than the Chinese EARs for key micronutrients including retinol, thiamin, riboflavin, vitamin C, calcium, selenium, zinc, and magnesium, and the percentages varied by body weight status. More than 80% participants had at least two selected vitamin or mineral deficiencies in all BMI categories. These findings indicate that Chinese adults have a high DBM and micronutrient inadequacies prevail among and within gender and all BMI categories. All body weight groups need advice on the changing needs for dietary variety to ensure optimal health.
Investigating the capabilities of information technologies to support policymaking in COVID‐19 crisis management; a systematic review and expert opinions

Today, numerous countries are fighting to protect themselves against the Covid‐19 crisis, while the policymakers are confounded and empty handed in dealing with this chaotic circumstance. The infection and its impacts have made it difficult to make optimal and suitable decisions. New information technologies play significant roles in such critical situations to address and relieve stress during the coronavirus crisis. This article endeavours to recognize the challenges policymakers have typically experienced during pandemic diseases, including Covid‐19, and, accordingly, new information technology capabilities to encounter with them.
Miniaturization and 3D Printing of Bioreactors: A Technological Mini Review

Many articles have been published on scale-down concepts as well as additive manufacturing techniques. However, information is scarce when miniaturization and 3D printing are applied in the fabrication of bioreactor systems. Therefore, garnering information for the interfaces between miniaturization and 3D printing becomes important and essential. The first goal is to examine the miniaturization aspects concerning bioreactor screening systems. The second goal is to review successful modalities of 3D printing and its applications in bioreactor manufacturing. This paper intends to provide information on anaerobic digestion process intensification by fusion of miniaturization technique and 3D printing technology. In particular, it gives a perspective on the challenges of 3D printing and the options of miniature bioreactor systems for process high-throughput screening.
Health and human rights are inextricably linked in the COVID-19 response

To mitigate the spread of COVID-19, governments throughout the world have introduced emergency measures that constrain individual freedoms, social and economic rights and global solidarity. These regulatory measures have closed schools, workplaces and transit systems, cancelled public gatherings, introduced mandatory home confinement and deployed large-scale electronic surveillance. In doing so, human rights obligations are rarely addressed, despite how significantly they are impacted by the pandemic response. The norms and principles of human rights should guide government responses to COVID-19, with these rights strengthening the public health response to COVID-19.
A comparison of fuzzy logic and TOPSIS methods for landfill site selection according to field visits, engineering geology approach and geotechnical experiments (case study: Rudbar County, Iran)

The present study evaluated and selected the best location among susceptible landfill sites in Rudbar County using 27 criteria, as the maximum effective criteria, in the decision-making process. The emergence and comparison between the two methods of fuzzy and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) with an engineering–geological approach have been conducted to obtain the best results. In this regard, inappropriate regions for landfill construction have been restricted after the conflation of two maps based on the restriction criteria. Then, the direction of prevailing winds and proper area for landfill construction was investigated for a 20-year perspective, and the regions that had more than 35-hectare area and were not located in the direction of the prevailing winds have been identified as responsive sites for landfill construction. Ultimately, selected susceptible regions were prioritized separately based on the TOPSIS and fuzzy methods. To ascertain the accuracy of the results and the reality of the resulted models, complementary field studies, geotechnical digging, and engineering–geological experiments have been used as verification parameters. According to the results of the verification, the fuzzy model having maximum matches with the verified data has been suggested for prioritizing susceptible regions.
Effect of vitamin E on low density lipoprotein oxidation at lysosomal pH

Abstract Many cholesterol-laden foam cells in atherosclerotic lesions are macrophages and much of their cholesterol is present in their lysosomes and derived from low density lipoprotein (LDL). LDL oxidation has been proposed to be involved in the pathogenesis of atherosclerosis. We have shown previously that LDL can be oxidised in the lysosomes of macrophages. α-Tocopherol has been shown to inhibit LDL oxidation in vitro, but did not protect against cardiovascular disease in large clinical trials. We have therefore investigated the effect of α-tocopherol on LDL oxidation at lysosomal pH (about pH 4.5). LDL was enriched with α-tocopherol by incubating human plasma with α-tocopherol followed by LDL isolation by ultracentrifugation. The α-tocopherol content of LDL was increased from 14.4 ± 0.2 to 24.3 ± 0.3 nmol/mg protein. LDL oxidation was assessed by measuring the formation of conjugated dienes at 234 nm and oxidised lipids (cholesteryl linoleate hydroperoxide and 7-ketocholesterol) by HPLC. As expected, LDL enriched with α-tocopherol was oxidised more slowly than control LDL by Cu2+ at pH 7.4, but was not protected against oxidation by Cu2+ or Fe3+ or a low concentration of Fe2+ at pH 4.5 (it was sometimes oxidised faster by α-tocopherol with Cu2+ or Fe3+ at pH 4.5). α-Tocopherol-enriched LDL reduced Cu2+ and Fe3+ into the more pro-oxidant Cu+ and Fe2+ faster than did control LDL at pH 4.5. These findings might help to explain why the large clinical trials of α-tocopherol did not protect against cardiovascular disease.
The MEK inhibitor selumetinib reduces spinal neurofibroma burden in patients with NF1 and plexiform neurofibromas.

Background Spinal neurofibromas (SNFs) in neurofibromatosis type 1 (NF1) can cause progressive spinal cord compression and neurological dysfunction. The MEK inhibitor selumetinib shrinks the majority of plexiform neurofibromas (PNs) in patients with NF1. We assessed the effect of selumetinib on SNF. Methods Pediatric and adult patients with NF1 and inoperable PN participating in phase 2 studies of selumetinib for PN were included in this analysis if they had SNF and serial spine magnetic resonance imaging (MRI). Selumetinib was administered orally at the recommended dose of 25 mg/m2/dose twice daily (max 50 mg b.i.d.; 1 cycle = 28 days). We qualitatively assessed the effect of selumetinib on SNF-related spinal canal distortion, cerebrospinal fluid distribution, and spinal cord deformity on MRI. Results Twenty-four patients (18 male), median age 16.9 years (range, 6.2-60.3), had SNF, 22 of which were associated with the same nerves as the target PN assessed on the clinical trial. Twenty patients had spinal cord deformity. Twenty-three patients completed at least 12 treatment cycles to date. Eighteen patients showed subtle to a marked improvement in SNF burden, 5 remained stable, and no worsening was observed during treatment. Conclusions This is the first study describing the effect of selumetinib on SNF. Of 24 patients, 18 exhibited some improvement of SNF burden on imaging. These findings suggest that selumetinib may prevent the worsening of cord compression, potentially reducing the need for surgical interventions in select patients or benefitting patients who do not have a surgical option. Prospective evaluation of the clinical benefit of selumetinib for SNF is warranted.