Miracle-dz/UniFAR-FTUs huggingface dataset:
A Consecutive 25-Week Program of Gait Training, Using the Alternating Hybrid Assistive Limb (HAL®) Robot and Conventional Training, and its Effects on the Walking Ability of a Patient with Chronic Thoracic Spinal Cord Injury: A Single Case Reversal Design

Background and Objectives: In this study, we examined the effect of a consecutive 25-week gait training program, consisting of 5-week alternating phases of Hybrid Assistive Limb (HAL)-assisted robot gait training and conventional gait training, on the walking ability of a 50-year-old man with a chronic thoracic spinal cord injury (SCI). Materials and Methods: Clinical features of this patient’s paraplegia were as follows: neurological level, T7; American Spinal Cord Injury Association Impairment Scale Score, C; Lower Extremity Motor Score, 20 points; Berg Balance Scale score, 15 points; and Walking Index for Spinal Cord Injury, 6 points. The patient completed a 100 m walk, under close supervision, using a walker and bilateral ankle-foot orthoses. The intervention included two phases: phase A, conventional walking practice and physical therapy for 5 weeks, and phase B, walking using the HAL robot (3 d/week, 30 min/session), combined with conventional physical therapy, for 5 weeks. A consecutive A-B-A-B-A sequence was used, with a 5-week duration for each phase. Results: The gait training intervention increased the maximum walking speed, cadence, and 2-min walking distance, as well as the Berg Balance and Walking Index for Spinal Cord Injury from 15 to 17 and 6 to 7, respectively. Walking speed, stride length, and cadence improved after phase A (but not B). Improved standing balance was associated with measured improvements in measured gait parameters. Conclusion: The walking ability of patients with a chronic SCI may be improved, over a short period by combining gait training, using HAL-assisted and conventional gait training and physical therapy.
Transient Chemogenetic Inhibition of D1-MSNs in the Dorsal Striatum Enhances Methamphetamine Self-Administration

The dorsal striatum is important for the development of drug addiction; however, the role of dopamine D1 receptor (D1R) expressing medium-sized spiny striatonigral (direct pathway) neurons (D1-MSNs) in regulating excessive methamphetamine intake remains elusive. Here we seek to determine if modulating D1-MSNs in the dorsal striatum alters methamphetamine self-administration in animals that have demonstrated escalation of self-administration. A viral vector-mediated approach was used to induce expression of the inhibitory (Gi coupled-hM4D) or stimulatory (Gs coupled-rM3D) designer receptors exclusively activated by designer drugs (DREADDs) engineered to specifically respond to the exogenous ligand clozapine-N-oxide (CNO) selectively in D1-MSNs in the dorsal striatum. CNO in animals expressing hM4D increased responding for methamphetamine compared to vehicle in a within subject treatment paradigm. CNO in animals that did not express DREADDs (DREADD naïve-CNO) or expressed rM3D did not alter responding for methamphetamine, demonstrating specificity for hM4D-CNO interaction in increasing self-administration. Postmortem tissue analysis reveals that hM4D-CNO animals had reduced Fos immunoreactivity in the dorsal striatum compared to rM3D-CNO animals and DREADD naïve-CNO animals. Cellular mechanisms in the dorsal striatum in hM4D-CNO animals reveal enhanced expression of D1R and Ca2+/calmodulin-dependent kinase II (CaMKII). Conversely, rM3D-CNO animals had enhanced activity of extracellular signal-regulated kinase (Erk1/2) and Akt in the dorsal striatum, supporting rM3D-CNO interaction in these animals compared with drug naïve controls, DREADD naïve-CNO and hM4D-CNO animals. Our studies indicate that transient inhibition of D1-MSNs-mediated strengthening of methamphetamine addiction-like behavior is associated with cellular adaptations that support dysfunctional dopamine signaling in the dorsal striatum.
Policy Debates Regarding Nicotine Vaping Products in Australia: A Qualitative Analysis of Submissions to a Government Inquiry from Health and Medical Organisations

Australia has maintained a highly restrictive regulatory framework for nicotine vaping products (NVPs) and the regulatory approach differs from most other high income countries. This paper employed a thematic analysis to assess policy consultation submissions made to a government inquiry regarding use and marketing of NVPs. We included in the analysis submissions (n = 40) made by Australian institutions that influence or contribute to health policy-making including government agencies, health bodies and charities (n = 23), and public health academics and healthcare professionals (n = 18). Submissions from commercial entities and consumers were excluded. The majority of submissions from representatives of government agencies, health bodies and charities recommended maintaining current restrictions on NVPs. Arguments against widening access to NVPs included the demand for long-term evidence on safety and efficacy of an unusually high standard. There was widespread support for restrictions on sales, advertising and promotion, with most submissions supporting similar controls as for tobacco products. In contrast, the majority of individual submissions from healthcare professionals and public health academics advocated for widening access to NVPs for smokers and emphasized the potential benefits of smokers switching to vaping and the policy incoherence of regulating less harmful nicotine products more strictly than tobacco cigarettes. Progress in resolving the policy debate concerning NVP regulation in Australia will require policy makers, clinicians and the public health community to engage in a meaningful dialogue which gives due consideration to both intended and unintended consequences of proposed policies.
Causative factors of eating problems among adolescents with type 1 diabetes mellitus: A qualitative study

Adolescents with type 1 diabetes mellitus are prone to have eating problems. This study aimed to determine factors of eating problems among this population in University Malaya Medical Centre. Fifteen adolescents who scored more than 20 marks in the Diabetes Eating Problem Survey – Revised questionnaire were invited for an in-depth interview. Questions were asked based on their questionnaire’s response. The interview sessions were recorded, transcribed verbatim, and thematic analysis was used. Five main themes emerged: pressure, physiological factor, psychological factor, patient’s low compliances to insulin intake and food control and fear. Early referral to child psychologist would prevent it from developing.
Diagnosis of canine brucellosis: comparison of various serologic tests and PCR

Canine brucellosis is an infectious and contagious disease associated with reproductive losses in breeding kennels. As a zoonotic disease, it poses a risk to human health, especially for veterinarians and breeders who handle materials potentially contaminated with Brucella canis. However, canine brucellosis is a neglected and underestimated disease given the difficulties in establishing a definitive diagnosis. We evaluated the frequency of detection of B. canis in 5 breeding kennels by using various serologic methods and PCR. Circulation of B. canis in these kennels was confirmed by bacterial isolation. The frequency of positive serologic results varied from 6.3% by AGID to 16.5% by dot-ELISA. There was no positive serology for smooth Brucella. PCR testing was positive in 13.9% of samples. The only detection tests with reasonable agreement were PCR and 2ME-MAT. The diagnosis of canine brucellosis remains challenging. The use of a single laboratory method, or even the use of different laboratory methods, may not be sufficient to reach a definitive diagnosis.
Heatwave Events and Mortality Outcomes in Memphis, Tennessee: Testing Effect Modification by Socioeconomic Status and Urbanicity

Heatwave studies typically estimate heat-related mortality and morbidity risks at the city level; few have addressed the heterogeneous risks by socioeconomic status (SES) and location within a city. This study aimed to examine the impacts of heatwaves on mortality outcomes in Memphis, Tennessee, a Mid-South metropolitan area top-ranked in morbidity and poverty rates, and to investigate the effects of SES and urbanicity. Mortality data were retrieved from the death records in 2008–2017, and temperature data from the Applied Climate Information System. Heatwave days were defined based on four temperature metrics. Heatwave effects on daily total-cause, cardiovascular, and respiratory mortality were evaluated using Poisson regression, accounting for temporal trends, sociodemographic factors, urbanicity, and air pollution. We found higher cardiovascular mortality risk (cumulative RR (relative risk) = 1.25, 95% CI (confidence interval): 1.01–1.55) in heatwave days defined as those with maximum daily temperature >95th percentile for more than two consecutive days. The effects of heatwaves on mortality did not differ by SES, race, or urbanicity. The findings of this study provided evidence to support future heatwave planning and studies of heatwave and health impacts at a coarser geographic resolution.
Neuroprotective Effects of Phlorotannin-Rich Extract from Brown Seaweed Ecklonia cava on Neuronal PC-12 and SH-SY5Y Cells with Oxidative Stress

Neurodegenerative disorders in the elderly are characterized by gradual loss of memory and cognitive function. Oxidative stress caused by reactive oxygen species is associated with progressive neuronal cell damage and death in Alzheimer’s disease, one of the most common neurodegenerative disorders. An edible brown seaweed, Ecklonia cava, contains a variety of biologically active compounds such as phlorotannins. In this study, we comparatively evaluated the total phenolic content, antioxidant capacity, and neuroprotective effects of the phlorotannin-rich extract from E. cava (PEEC). The total phenolic content of PEEC and dieckol was 810.8 mg gallic acid equivalents (GAE)/g and 996.6 mg GAE/g, respectively. Antioxidant capacity of PEEC was 1,233.8 mg vitamin C equivalents (VCE)/g and 392.1 mg VCE/g determined using ABTS and DPPH assays, respectively, while those of dieckol were 2,238.4 mg VCE/g and 817.7 mg VCE/g. High-performance liquid chromatography results revealed 48.08 ± 0.67 mg dieckol/g of PEEC. PEEC had neuroprotective effects in pheochromocytoma (PC-12) and human neuroblastoma (SH-SY5Y) cells against H2O2- and AAPH-induced oxidative damage, partly due to reduced intracellular oxidative stress. PEEC treatment inhibited acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner. Taken together, these findings suggest that PEEC is a good source of antioxidants and neuroprotective materials.
The Driver of Extreme Human-Specific Olduvai Repeat Expansion Remains Highly Active in the Human Genome

Olduvai (formerly DUF1220) protein domains have undergone the largest human-specific increase in copy number of any coding region in the genome (∼300 copies of which 165 are human-specific) and have been implicated in human brain evolution. Sequences encoding Olduvai protein domains (formerly DUF1220) show the greatest human lineage-specific increase in copy number of any coding region in the genome and have been associated, in a dosage-dependent manner, with brain size, cognitive aptitude, autism, and schizophrenia. Tandem intragenic duplications of a three-domain block, termed the Olduvai triplet, in four NBPF genes in the chromosomal 1q21.1-0.2 region, are primarily responsible for the striking human-specific copy number increase. Interestingly, most of the Olduvai triplets are adjacent to, and transcriptionally coregulated with, three human-specific NOTCH2NL genes that have been shown to promote cortical neurogenesis. Until now, the underlying genomic events that drove the Olduvai hyperamplification in humans have remained unexplained. Here, we show that the presence or absence of an alternative first exon of the Olduvai triplet perfectly discriminates between amplified (58/58) and unamplified (0/12) triplets. We provide sequence and breakpoint analyses that suggest the alternative exon was produced by an nonallelic homologous recombination-based mechanism involving the duplicative transposition of an existing Olduvai exon found in the CON3 domain, which typically occurs at the C-terminal end of NBPF genes. We also provide suggestive in vitro evidence that the alternative exon may promote instability through a putative G-quadraplex (pG4)-based mechanism. Lastly, we use single-molecule optical mapping to characterize the intragenic structural variation observed in NBPF genes in 154 unrelated individuals and 52 related individuals from 16 families and show that the presence of pG4-containing Olduvai triplets is strongly correlated with high levels of Olduvai copy number variation. These results suggest that the same driver of genomic instability that allowed the evolutionarily recent, rapid, and extreme human-specific Olduvai expansion remains highly active in the human genome.
Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation

Biological and biochemical functions of immunity transcription factor NF-κB in basal metazoans are largely unknown. Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq), in the phylum Porifera. Structurally and phylogenetically, the Aq-NF-κB protein is most similar to NF-κB p100 and p105 among vertebrate proteins, with an N-terminal DNA-binding/dimerization domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile more similar to human NF-κB proteins than Rel proteins. Aq-NF-κB also resembles the mammalian NF-κB protein p100 in that C-terminal truncation results in translocation of Aq-NF-κB to the nucleus and increases its transcriptional activation activity. Overexpression of a human or sea anemone IκB kinase (IKK) can induce C-terminal processing of Aq-NF-κB in vivo, and this processing requires C-terminal serine residues in Aq-NF-κB. Unlike human NF-κB p100, however, the C-terminal sequences of Aq-NF-κB do not effectively inhibit its DNA-binding activity when expressed in human cells. Tissue of another demosponge, a black encrusting sponge, contains NF-κB site DNA-binding activity and an NF-κB protein that appears mostly processed and in the nucleus of cells. NF-κB DNA-binding activity and processing is increased by treatment of sponge tissue with LPS. By transcriptomic analysis of A. queenslandica we identified likely homologs to many upstream NF-κB pathway components. These results present a functional characterization of the most ancient metazoan NF-κB protein to date, and show that many characteristics of mammalian NF-κB are conserved in sponge NF-κB, but the mechanism by which NF-κB functions and is regulated in the sponge may be somewhat different.
The application of Strategy-based Training to Enhance Memory (STEM) in multiple sclerosis: A pilot RCT

ABSTRACT New learning and memory (NLM) impairments are common in multiple sclerosis (MS), negatively impacting daily life. Few studies seek to remediate these deficits to improve everyday functioning. Self-generation, spaced learning and retrieval practice have been shown to improve NLM in healthy persons and have been incorporated into an 8-session treatment protocol, Strategy-based Training to Enhance Memory (STEM). STEM teaches participants about each of the techniques, how to apply them in daily life and provides practice. Participants are taught to restructure a memory-demanding situation to optimize self-generation, spaced learning and retrieval practice. This pilot double-blind, placebo-controlled, randomized clinical trial (RCT) tested the efficacy of STEM in 20 learning-impaired participants with clinically definite MS (9 treatment, 11 control). Significant treatment effects were noted on self-report measures of daily functioning (primary outcome). Objective neuropsychological testing approached significance, showing a medium-large effect on verbal NLM. Results suggest that STEM may improve everyday functioning in individuals with MS. A full-scale RCT is warranted to validate findings in a larger sample so that findings may be generalized to the broader MS community.
Enhanced Population Control in a Synthetic Bacterial Consortium by Interconnected Carbon Cross-Feeding.

Engineered microbial consortia can provide several advantages over monocultures in terms of utilization of mixed substrates, resistance to perturbations, and division of labor in complex tasks. However, maintaining stability, reproducibility, and control over population levels in variable conditions can be challenging in multi-species cultures. In our study, we modeled and constructed a synthetic symbiotic consortium with a genetically encoded carbon cross-feeding system. The system is based on strains of Escherichia coli and Acinetobacter baylyi ADP1, both engineered to be incapable of growing on glucose on their own. In a culture supplemented with glucose as the sole carbon source, growth of the two strains is afforded by the exchange of gluconate and acetate, resulting in inherent control over carbon availability and population balance. We investigated the system robustness in terms of stability and population control under different inoculation ratios, substrate concentrations, and cultivation scales, both experimentally and by modeling. To illustrate how the system might facilitate division of genetic circuits among synthetic microbial consortia, a green fluorescent protein sensitive to pH and a slowly-maturing red fluorescent protein were expressed in the consortium as measures of a circuit's susceptibility to external and internal variability, respectively. The symbiotic consortium maintained stable and linear growth and circuit performance regardless of the initial substrate concentration or inoculation ratio. The developed cross-feeding system provides simple and reliable means for population control without expression of non-native elements or external inducer addition, being potentially exploitable in consortia applications involving precisely defined cell tasks or division of labor. Keywords: Synthetic consortium, cross-feeding, population control, consortium modeling.
hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status

Gemcitabine is still one of the standard chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine uptake into tumor cells is mainly through the human equilibrative nucleoside transport 1 (hENT1). It was therefore proposed as a potential predictive biomarker of gemcitabine efficacy but reports are conflicting, with an important heterogeneity in methods to assess hENT1 expression. A multicenter cohort of 471 patients with a resected PDAC was used to assess simultaneously the predictive value of the 2 best described hENT1 antibodies (10D7G2 and SP120). Three additional antibodies and the predictive value of hENT1 mRNA were also tested on 251 and 302 patients, respectively. hENT1 expression was assessed in 54 patients with matched primary tumors and metastases samples. The 10D7G2 clone was the only hENT1 antibody whose high expression was associated with a prolonged progression free survival and overall survival in patients who received adjuvant gemcitabine. hENT1 mRNA level was also predictive of gemcitabine benefit. hENT1 status was concordant in 83% of the cases with the best concordance in synchronous metastases. The 10D7G2 clone has the best predictive value of gemcitabine benefit in PDAC patients. Since it is not commercially available, hENT1 mRNA level could represent an alternative to assess hENT1 status.
The Impact of Sorghum Growth Stage and Resistance on Life History of Sugarcane Aphids (Hemiptera: Aphididae)

Abstract Recent invasion of a new haplotype of sugarcane aphid (Melanaphis sacchari Zehntner) resulted in severe outbreaks of the aphids in sorghum (Sorghum bicolor L. Moench [Poales: Poaceae]) across the United States. Previous research and field observations suggested that both sorghum resistance and growth stage were important to their population dynamics in the field and hence effective and timely management to minimize economic losses associated with this pest.To explore this, we designed greenhouse experiments to quantify fecundity, prereproductive period, and longevity of sugarcane aphids across several vegetative and reproductive growth stages of a resistant (DKS 37-07) and susceptible (M77GB52 and DKS 38–88) sorghum hybrids commonly used in sorghum production. We found significant effects of sorghum resistance and growth stage on several life history traits and demographics parameters of sugarcane aphids. We did not, however, note any significant interactive effects of resistance and phenology on any of the response variables. Sugarcane aphids exposed to the susceptible sorghum produced significantly more offspring, had significantly greater intrinsic and finite rates of increase, and significantly shorter population doubling time than the aphids feeding on resistant sorghum. On the other hand, the impact of sorghum growth stage had more variable effects on life history of sugarcane aphids that were most frequently evident at the late reproductive stages. These outcomes support our hypothesis that sorghum in late stages of growth tends to be a better host for sugarcane aphids and highlight the importance of sorghum growth stage to sugarcane aphid life history and population growth potential.
Fast-Seq, a simple method for rapid and inexpensive validation of packaged ssAAV genomes in academic settings.

Adeno-associated viral (AAV) vectors have shown great promise in gene delivery as evidenced by recent FDA approvals. Despite efforts to optimize manufacturing for GMP productions, few academic labs have the resources to assess vector composition. One critical component of vector quality is packaged genome fidelity. Errors in viral genome replication and packaging can result in the incorporation of faulty genomes with mutations, truncations or rearrangements, compromising vector potency. Thus, sequence validation of packaged genome composition is an important quality control, even in academic settings. We developed Fast-Seq, an end-to-end method for extraction, purification, sequencing and data analysis of packaged ssAAV genomes intended for non-GMP preclinical environments. We validated Fast-Seq on ssAAV vectors with 3 different genome compositions (CAG-tdTomato, EF1⍺-FLuc, CAG-GFP), 3 different genome sizes (2.9kb, 3.6kb, 4.3kb), packaged in 4 different capsid serotypes (AAV1, AAV2, AAV5, AAV8), and produced using the two most common production methods (Baculovirus-Sf9, human HEK293), from both common commercial vendors and academic core facilities supplying academic laboratories. We achieved an average genome coverage of >1,400X and an average ITR coverage of >280X, despite the many differences in composition of each ssAAV sample. When compared to other ssAAV NGS methods for GMP settings, Fast-Seq has several unique advantages: Tn5 transposase-based fragmentation rather than sonication, 125x less input DNA, simpler adapter ligation, compatibility with commonly available inexpensive sequencing instruments, and free open-source data analysis code in a pre-assembled customizable Docker container designed for novices. Fast-Seq can be completed in 18 hours, is more cost-effective than other NGS methods, and is more accurate than Sanger sequencing which is generally only applied at 1-2x sequencing depth. Fast-Seq is a rapid, simple, and inexpensive methodology to validate packaged ssAAV genomes in academic settings.