Miracle-dz/UniFAR-FTUs huggingface dataset:
Upper Extremity Function Assessment Using a Glove Orthosis and Virtual Reality System

Hand motor control deficits following stroke can diminish the ability of patients to participate in daily activities. This study investigated the criterion validity of upper extremity (UE) performance measures automatically derived from sensor data during manual practice of simulated instrumental activities of daily living (IADLs) within a virtual environment. A commercial glove orthosis was specially instrumented with motion tracking sensors to enable patients to interact, through functional UE movements, with a computer-generated virtual world using the SaeboVR software system. Fifteen stroke patients completed four virtual IADL practice sessions, as well as a battery of gold-standard assessments of UE motor and hand function. Statistical analysis using the nonparametric Spearman rank correlation reveals high and significant correlation between virtual world-derived measures and the gold-standard assessments. The results provide evidence that performance measures generated during manual interactions with a virtual environment can provide a valid indicator of UE motor status.
Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7

Nuclear and mitochondrial genome mutations lead to various mitochondrial diseases, many of which affect the mitochondrial respiratory chain. The proteome of the intermembrane space (IMS) of mitochondria consists of several important assembly factors that participate in the biogenesis of mitochondrial respiratory chain complexes. The present study comprehensively analyzed a recently identified IMS protein cytochrome c oxidase assembly factor 7 (COA7), or RESpiratory chain Assembly 1 (RESA1) factor that is associated with a rare form of mitochondrial leukoencephalopathy and complex IV deficiency. We found that COA7 requires the mitochondrial IMS import and assembly (MIA) pathway for efficient accumulation in the IMS. We also found that pathogenic mutant versions of COA7 are imported slower than the wild‐type protein, and mislocalized proteins are degraded in the cytosol by the proteasome. Interestingly, proteasome inhibition rescued both the mitochondrial localization of COA7 and complex IV activity in patient‐derived fibroblasts. We propose proteasome inhibition as a novel therapeutic approach for a broad range of mitochondrial pathologies associated with the decreased levels of mitochondrial proteins.
Acceptance of Online Medical Websites: An Empirical Study in China

As a new type of public health service product, online medical websites (OMWs) are becoming quite popular. OMWs can address patients’ basic medical problems remotely and give health guidance online. Compared to traditional hospitals, OMWs are more convenient and inexpensive, they can usually provide a better service for patients with poor medical conditions (especially in rural areas), and they also contribute to the rational distribution of medical resources. Therefore, key factors that affect patients’ acceptance of OMWs must be identified to contribute to public health. By integrating perceived risk (PR) and the technology acceptance model (TAM), we proposed a modified TAM and clarified how PR and other factors affect patients’ behavioral intention (BI) towards OMWs. A sample of 245 research participants in China took part in this study and the structural equation model (SEM) was used to test our hypotheses. The results revealed that perceived usefulness (PU) is a positive predictor of BI but has no significant effect on attitude (ATT), while perceived ease of use (PEOU) can affect BI through PU and attitude (ATT). Moreover, trust (TRU) was identified as a mediator of PR and PU/PEOU. Also, the doctor–patient relationship (DPR) was shown to moderate PR and TRU. In order to increase patients’ BI, OMW providers need further innovations to improve patients’ TRU and reduce their PR.
Annexin A2 expression and partners during epithelial cell differentiation.

The members of the annexin family of calcium- and phospholipid-binding proteins participate in different cellular processes. Annexin A2 binds to S100A10 forming a functional heterotetrameric protein that has been involved in many cellular functions such as exocytosis, endocytosis, cell junction formation and actin cytoskeleton dynamics. Herein, we studied annexin A2 cellular movements and looked for its partners during epithelial cell differentiation. By using immunofluorescence, mass spectrometry and western blot analyses after S100A10 affinity column separation, we identified several annexin A2-S100A10 partner candidates. The association of putative annexin A2-S100A10 partner candidates obtained by MS after column affinity was validated by immunofluorescence and sucrose density gradient separation. The results show that three proteins were clearly associated to AnxA2: E-cadherin, actin and caveolin 1. Overall the data show that annexin A2 is able to associate to molecular complexes containing actin, caveolin 1 and flotillin 2 before epithelial differentiation and to complexes containing E-Cadherin, actin and caveolin 1, but not flotillin 2 after cell differentiation. The results indicate that actin, caveolin 1 and E-cadherin are the principal protein partners of annexin A2 in epithelial cells and that the serine phosphorylation of the N-terminal domain does not play an essential role during epithelial cell differentiation.
RecBCD, SbcCD and ExoI process a substrate created by convergent replisomes to complete DNA replication

The accurate completion of DNA replication on the chromosome requires RecBCD and structure specific SbcCD and ExoI nucleases. However, the substrates and mechanism by which this reaction occurs remains unknown. Here we show that these completion enzymes operate on plasmid substrates containing two replisomes, but are not required for plasmids containing one replisome. Completion on the two‐replisome plasmids requires RecBCD, but does not require RecA and no broken intermediates accumulate in its absence, indicating that the completion reaction occurs normally in the absence of any double‐strand breaks. Further, similar to the chromosome, we show that when the normal completion reaction is prevented, an aberrant RecA‐mediated recombination process leads to amplifications that drive most of the instabilities associated with the two‐replisome substrates. The observations imply that the substrate SbcCD, ExoI and RecBCD act upon in vivo is created specifically by two convergent replisomes, and demonstrate that the function of RecBCD in completing replication is independent of double‐strand break repair, and likely promotes joining of the strands of the convergent replication forks.
Effect of New Zealand Blackcurrant Extract on Cycling Performance and Substrate Oxidation in Normobaric Hypoxia in Trained Cyclists

New Zealand blackcurrant (NZBC) extract enhanced exercise-induced fat oxidation and 16.1 km cycling time trial (TT) in normobaric normoxia. The effect of NZBC extract on physiological and metabolic responses was examined during steady state cycling and a 16.1 km TT in normobaric hypoxia. This study used a randomized, double-blind, crossover design. Eleven healthy male cyclists (age: 38 ± 11 y, height: 179 ± 4 cm, body mass: 76 ± 8 kg, V˙O2max: 47 ± 5 mL·kg−1·min−1, mean ± SD) ingested NZBC extract (600 mg·day−1 CurraNZ® containing 210 mg anthocyanins) or a placebo (600 mg microcrystalline cellulose M102) for seven days (washout 14 days) and performed a steady state cycling test (3 × 10 min at 45%, 55% and 65% V˙O2max) followed by a 16.1 km TT at a simulated altitude of ~2500 meters (~15% of O2). Indirect calorimetry was used to measure substrate oxidation during steady state cycling. Intake of NZBC extract had no effect on blood glucose and lactate, heart rate, substrate oxidation, and respiratory exchange ratio during steady state cycling at 45%, 55% and 65% V˙O2max, and on 16.1 km TT performance (placebo: 1685 ± 92 s, NZBC extract: 1685 ± 99 s, P = 0.97). Seven days intake of New Zealand blackcurrant extract does not change exercise-induced metabolic responses and 16.1 km cycling time trial performance for moderately endurance-trained men in normobaric hypoxia.
Molecular regulation of adhesion and biofilm formation in high and low biofilm producers of Bacillus licheniformis using RNA-Seq

Abstract RNA sequencing was used to reveal transcriptional changes during the motile-to-sessile switch in high and low biofilm-forming dairy strains of B. licheniformis isolated from Chinese milk powders. A significant part of the whole gene content was affected during this transition in both strains. In terms of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, seven metabolic pathways were significantly downregulated in the planktonic state compared to the biofilm state in both strains. Lipid and sugar metabolism seemed to play an important role in matrix production. Several genes involved in adhesion, matrix production and the matrix coating were either absent or less expressed in the biofilm state of the low biofilm producer compared to the high biofilm producer. Genes related to sporulation and the production of extracellular polymeric substances were concomitantly expressed in the biofilm state of both strains. These comprehensive insights will be helpful for future research into mechanisms and targets.
Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction–induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan—a precursor amino acid for serotonin biosynthesis in the brain—and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.
Key Genes of Lipid Metabolism and WNT-Signaling Are Downregulated in Subcutaneous Adipose Tissue with Moderate Weight Loss

Smaller cross-sectional studies and bariatric surgery trials suggest that weight loss may change the expression of genes in adipose tissue that have been implicated in the development of metabolic diseases, but well-powered intervention trials are lacking. In post hoc analyses of data from a 12-week dietary intervention trial initially designed to compare metabolic effects of intermittent vs. continuous calorie restriction, we analyzed the effects of overall weight loss on the subcutaneous adipose tissue (SAT) transcriptome. Changes in the transcriptome were measured by microarray using SAT samples of 138 overweight or obese individuals (age range: 35–65 years, BMI range: 25–40, non-smokers, non-diabetics). Participants were grouped post hoc according to the degree of their weight loss by quartiles (average weight loss in quartiles 1 to 4: 0%, −3.2%, −5.9%, and −10.7%). Candidate genes showing differential expression with weight loss according to microarray analyses were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and fold changes (FCs) were calculated to quantify differences in gene expression. A comparison of individuals in the highest vs. the lowest weight loss quartile revealed 681 genes to be differentially expressed (corrected p < 0.05), with 40 showing FCs of at least 0.4. Out of these, expression changes in secreted frizzled-related protein 2 (SFRP2, FC = 0.65, p = 0.006), stearoyl-CoA desaturase (SCD, FC = −1.00, p < 0.001), and hypoxia inducible lipid droplet-associated (HILPDA, FC = −0.45, p = 0.001) with weight loss were confirmed by RT-qPCR. Dietary weight loss induces significant changes in the expression of genes implicated in lipid metabolism (SCD and HILPDA) and WNT-signaling (SFRP2) in SAT.
Region 1p13.2 including the RSBN1, PTPN22, AP4B1 and long non‐coding RNA genes does not bear risk factors for endemic pemphigus foliaceus (fogo selvagem)

Pemphigus foliaceus (PF) is an autoimmune skin disease characterized by autoantibodies directed mainly against desmoglein‐1. The purpose of this study was to determine whether differential susceptibility to endemic PF in Brazil (fogo selvagem) is associated with polymorphisms at the cytogenetic location 1p13.2. Four single nucleotide polymorphisms that together tag 28 SNPs on a segment of approximately 312,000 bp encompassing the protein‐coding genes MAGI3, PHTF1, RSBN1, PTPN22, BCL2L15, AP4B1, DCLRE1B, the pseudogenes MTND5P20, RPS2P14 (AL133517.1) and the long non‐coding RNA genes AL137856.1, and AP4B1‐AS1 were used as markers for association analysis in a case–control study. Allele, genotype and haplotype frequencies of rs33996649, rs2476601, rs3789604 and rs3195954 were compared between patient and control samples. No significant association was found. Lack of association with rs2476601 of the PTPN22 gene agrees with previous results for pemphigus vulgaris and the Tunisian form of endemic pemphigus foliaceus. The other three SNPs had never been analysed before in any form of pemphigus. We conclude that variants in structural and regulatory sites of region 1p13.2 are not susceptibility factors for fogo selvagem. We suggest careful investigation of this genomic region in diseases that had been previously associated with PTPN22, since there are several other genes relevant for immune‐mediated diseases located in 1p13.2.
Antiviral Candidates for Treating Hepatitis E Virus Infection

Globally, hepatitis E virus (HEV) causes significant morbidity and mortality each year. Despite this burden, there are no specific antivirals available to treat HEV patients, and the only licensed vaccine is not available outside China. ABSTRACT Globally, hepatitis E virus (HEV) causes significant morbidity and mortality each year. Despite this burden, there are no specific antivirals available to treat HEV patients, and the only licensed vaccine is not available outside China. Ribavirin and alpha interferon are used to treat chronic HEV infections; however, severe side effects and treatment failure are commonly reported. Therefore, this study aimed to identify potential antivirals for further development to combat HEV infection. We selected 16 compounds from the nucleoside and nonnucleoside antiviral classes that range in developmental status from late preclinical to FDA approved and evaluated them as potential antivirals for HEV infection, using genotype 1 replicon luminescence studies and replicon RNA quantification. Two potent inhibitors of HEV replication included NITD008 (half-maximal effective concentration [EC50], 0.03 μM; half-maximal cytotoxic concentration [CC50], >100 μM) and GPC-N114 (EC50, 1.07 μM, CC50, >100 μM), and both drugs reduced replicon RNA levels in cell culture (>50% reduction with either 10 μM GPC-N114 or 2.50 μM NITD008). Furthermore, GPC-N114 and NITD008 were synergistic in combinational treatment (combination index, 0.4) against HEV replication, allowing for dose reduction indices of 20.42 and 8.82 at 50% inhibition, respectively. Sofosbuvir has previously exhibited mixed results against HEV as an antiviral, both in vitro and in a few clinical applications; however, in this study it was effective against the HEV genotype 1 replicon (EC50, 1.97 μM; CC50, >100 μM) and reduced replicon RNA levels (47.2% reduction at 10 μM). Together these studies indicate drug repurposing may be a promising pathway for development of antivirals against HEV infection.
PDLIM2 Is a Marker of Adhesion and β-Catenin Activity in Triple-Negative Breast Cancer.

The PDLIM2 protein regulates stability of transcription factors including NF-κB and STATs in epithelial and hemopoietic cells. PDLIM2 is strongly expressed in certain cancer cell lines that exhibit an epithelial-to-mesenchymal phenotype, and its suppression is sufficient to reverse this phenotype. PDLIM2 supports the epithelial polarity of nontransformed breast cells, suggesting distinct roles in tumor suppression and oncogenesis. To better understand its overall function, we investigated PDLIM2 expression and activity in breast cancer. PDLIM2 protein was present in 60% of tumors diagnosed as triple-negative breast cancer (TNBC), and only 20% of other breast cancer subtypes. High PDLIM2 expression in TNBC was positively correlated with adhesion signaling and β-catenin activity. Interestingly, PDLIM2 was restricted to the cytoplasm/membrane of TNBC cells and excluded from the nucleus. In breast cell lines, PDLIM2 retention in the cytoplasm was controlled by cell adhesion, and translocation to the nucleus was stimulated by insulin-like growth factor-1 or TGFβ. Cytoplasmic PDLIM2 was associated with active β-catenin and ectopic expression of PDLIM2 was sufficient to increase β-catenin levels and its transcriptional activity in reporter assays. Suppression of PDLIM2 inhibited tumor growth in vivo, whereas overexpression of PDLIM2 disrupted growth in 3D cultures. These results suggest that PDLIM2 may serve as a predictive biomarker for a large subset of TNBC whose phenotype depends on adhesion-regulated β-catenin activity and which may be amenable to therapies that target these pathways. SIGNIFICANCE: This study shows that PDLIM2 expression defines a subset of triple-negative breast cancer that may benefit from targeting the β-catenin and adhesion signaling pathways. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals. org/content/canres/79/10/2619/F1.large. jpg.
Vascular smooth muscle cell‐specific progerin expression in a mouse model of Hutchinson–Gilford progeria syndrome promotes arterial stiffness: Therapeutic effect of dietary nitrite

Vascular stiffness is a major cause of cardiovascular disease during normal aging and in Hutchinson–Gilford progeria syndrome (HGPS), a rare genetic disorder caused by ubiquitous progerin expression. This mutant form of lamin A causes premature aging associated with cardiovascular alterations that lead to death at an average age of 14.6 years. We investigated the mechanisms underlying vessel stiffness in LmnaG609G/G609G mice with ubiquitous progerin expression, and tested the effect of treatment with nitrites. We also bred LmnaLCS/LCSTie2Cre+/tgand LmnaLCS/LCSSM22αCre+/tg mice, which express progerin specifically in endothelial cells (ECs) and in vascular smooth muscle cells (VSMCs), respectively, to determine the specific contribution of each cell type to vascular pathology. We found vessel stiffness and inward remodeling in arteries of LmnaG609G/G609G and LmnaLCS/LCSSM22αCre+/tg, but not in those from LmnaLCS/LCSTie2Cre+/tgmice. Structural alterations in aortas of progeroid mice were associated with decreased smooth muscle tissue content, increased collagen deposition, and decreased transverse waving of elastin layers in the media. Functional studies identified collagen (unlike elastin and the cytoskeleton) as an underlying cause of aortic stiffness in progeroid mice. Consistent with this, we found increased deposition of collagens III, IV, V, and XII in the media of progeroid aortas. Vessel stiffness and inward remodeling in progeroid mice were prevented by adding sodium nitrite in drinking water. In conclusion, LmnaG609G/G609G arteries exhibit stiffness and inward remodeling, mainly due to progerin‐induced damage to VSMCs, which causes increased deposition of medial collagen and a secondary alteration in elastin structure. Treatment with nitrites prevents vascular stiffness in progeria.
Is minimally invasive plate osteosynthesis superior to open plating for fixation of two-part fracture of the proximal humerus?

Purpose: Displaced two-part fractures of the proximal humerus are generally treated with open plate (OP) fixation. Recently, minimally invasive plate osteosynthesis (MIPO) has been increasingly favored for fracture healing and functional recovery. We aimed to compare OP and MIPO for two-part fractures of the proximal humerus to identify outcome differences. Methods: All patients who underwent OP or MIPO for a displaced two-part fracture of the proximal humerus at a single level I trauma center between 2007 and 2013 were retrospectively evaluated. Of the patients, 17 were treated using the OP method through the delto-pectoral approach and 19 with MIPO through deltoid splitting. Radiographic results were evaluated to determine the union rate, time to union, and alignment. Functional outcomes were measured with Constant and UCLA scores. Radiation exposure and operative time were also evaluated. Results: All patients achieved bone union without complication. In the OP and MIPO groups, no significant difference was observed in the neck shaft angles, constant scores, or UCLA scores. The OP group required less radiation exposure time than the MIPO group (p < 0.001). However, the OP group showed more operation time than the MIPO group (p < 0.001). Conclusions: Both techniques showed satisfactory radiographic and functional outcomes in two-part fractures of the proximal humerus. Although MIPO technique offers advantages, including minimal soft tissue damage and short operation time, surgeons and patients should be warned of the invisible risk from the radiation hazard.
Ongoing Pediatric Health Care for the Child Who Has Been Maltreated

Pediatricians provide continuous medical care and anticipatory guidance for children who have been reported to state child protection agencies, including tribal child protection agencies, because of suspected child maltreatment. Because families may continue their relationships with their pediatricians after these reports, these primary care providers are in a unique position to recognize and manage the physical, developmental, academic, and emotional consequences of maltreatment and exposure to childhood adversity. Substantial information is available to optimize follow-up medical care of maltreated children. This new clinical report will provide guidance to pediatricians about how they can best oversee and foster the optimal physical health, growth, and development of children who have been maltreated and remain in the care of their biological family or are returned to their care by Child Protective Services agencies. The report describes the pediatrician’s role in helping to strengthen families’ and caregivers’ capabilities and competencies and in promoting and maximizing high-quality services for their families in their community. Pediatricians should refer to other reports and policies from the American Academy of Pediatrics for more information about the emotional and behavioral consequences of child maltreatment and the treatment of these consequences.
Bifactor analysis confirmation of the factorial structure of the Functional Assessment of Cancer Therapy–General (FACT‐G)

Patient‐reported outcomes are now pervasive in oncology, and the Functional Assessment of Cancer Therapy (FACT) measures have been among the most commonly used instruments. The FACT general (FACT‐G) instrument is appropriate for all cancer sites, and it is included as the general cancer core questionnaire for each FACT cancer site‐specific instrument. In this capacity, the FACT‐G includes four core dimensions of health‐related quality of life (HRQOL), including physical, social, emotional, and functional well‐being. In addition, a total FACT‐G score representing the sum of these four dimensions is derived from the subscales. Over the course of its history, empirical evidence for this scoring practice of aggregating four distinct dimensions into one summary score has been examined rarely. Therefore, the objective of this study was to examine the factorial structure of the FACT‐G, with particular interest in empirical support for a general HRQOL factor and its relationship to the FACT‐G subscales.