Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerated Trajectories of Walking Capacity Across the Adult Life Span in Persons With Multiple Sclerosis: An Underrecognized Challenge

Background. In the general population, trajectories of walking capacity is accelerated and nonlinear with advanced age. Whether this is more pronounced in persons with multiple sclerosis (pwMS), along with the prevalence of dismobility (ie, slow gait speed), are currently unknown. Our objective was to investigate trajectories of walking capacity and prevalence of dismobility across the adult life span in pwMS versus healthy controls (HC). Methods. Data on maximal timed 25-foot walk test (T25FWT), 2-minute walk test (2MWT), and 6-minute walk test (6MWT) along with prevalence of dismobility were assembled from 2 RIMS multicenter studies (n = 502 pwMS; age range 21-77 years, 6 age groups: 20-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years). HC data were extracted from studies containing normative reference values (n = 1070-3780 HC). Results. Age trajectories of walking capacity was nonlinear and accelerated in pwMS versus HC. While measures of walking capacity in pwMS were suppressed already early in life, the gap between pwMS and HC significantly widened across the 6 age groups (pwMS performed 64%, 70%, 57%, 59%, 51%, and 37% of HC, respectively). This coincided with high prevalences of dismobility in pwMS across the 6 age groups when using usual gait speed cut-point values <1.0 m/s (corresponding to 33%, 32%, 51%, 59%, 75%, and 100%) and <0.6 m/s (corresponding to 19%, 12%, 26%, 23%, 33%, and 43%), markedly exceeding that observed in HC. Conclusion. The present data on walking capacity provide evidence for an accelerated deterioration in pwMS with advanced age, coinciding with high prevalences of dismobility (ie, slow gait speed).
A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus

Protein prenylation is essential for many cellular processes including signal transduction, cytoskeletal reorganization, and membrane trafficking. Here, we identify a novel type of protein prenyltransferase, which we named geranylgeranyltransferase type‐III (GGTase‐III). GGTase‐III consists of prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the β subunit of RabGGTase. Using a biotinylated geranylgeranyl analogue, we identified the Golgi SNARE protein Ykt6 as a substrate of GGTase‐III. GGTase‐III transfers a geranylgeranyl group to mono‐farnesylated Ykt6, generating doubly prenylated Ykt6. The crystal structure of GGTase‐III in complex with Ykt6 provides structural basis for Ykt6 double prenylation. In GGTase‐III‐deficient cells, Ykt6 remained in a singly prenylated form, and the Golgi SNARE complex assembly was severely impaired. Consequently, the Golgi apparatus was structurally disorganized, and intra‐Golgi protein trafficking was delayed. Our findings reveal a fourth type of protein prenyltransferase that generates geranylgeranyl‐farnesyl Ykt6. Double prenylation of Ykt6 is essential for the structural and functional organization of the Golgi apparatus.
Minerals play key roles in driving prokaryotic and fungal community in the surface sediments of the Qinghai-Tibetan lakes.

There is limited knowledge on the relative influences of deterministic and stochastic processes on prokaryotic and fungal communities in lake sediments. In this study, we surveyed the prokaryotic and fungal community compositions and their influencing factors in 23 surface sediments from six lakes on the Qinghai-Tibetan Plateau (QTP) with the use of Illumina sequencing. The results showed the distribution of prokaryotic and fungal communities in the studied QTP lake sediments was shaped by different assembly processes, with prokaryotes primarily governed by variable selection and homogenizing dispersal (accounting for 57.9% and 37.3% of the observed variations) and fungi being mainly regulated by variable selection, non-dominant processes and homogenizing dispersal (38.3%, 43.7% and 13.7%, respectively). Regarding the variable selection, mineralogical variables played key roles in shaping prokaryotic and fungal community structures. Collectively, these findings expand current knowledge concerning the influences of deterministic (e.g. variable selection) and stochastic processes (e.g. homogenizing dispersal and non-dominant processes) on the prokaryotic and fungal distribution in the QTP lakes.
Evaluation of the relationship between blood cell parameters and vascular calcification in dialysis-dependent end-stage renal disease patients

Coronary artery calcification is an acceptable tool for cardiovascular risk assessment in end-stage renal disease (ESRD) population. We aimed to identify the association and predictive value of components of blood cell parameters with coronary and thoracic aorta vascular calcification (VC) in ESRD population on dialysis. All ESRD patients receiving hemodialysis or peritoneal dialysis aged between 18 and 60 years were included in the study. Exclusion criteria comprised patients with active infection or inflammatory disease, autoimmune disease, congestive heart failure, angina pectoris and/or documented coronary artery disease, thyroid disease, and hepatic dysfunction. Agatston scoring was used for the evaluation of coronary aorta calcification (CAC) score (CACS) and thoracic aorta calcification (TAC) score (TACS). Compared to participants with no VC, those who had VC were statistically significantly older (P <0.001) and had higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (P = 0.02 and <0.001, respectively). On multivariate logistic regression analysis, increasing age (P = 0.00) and higher PLR (P = 0.04) were associated with an increased likelihood of exhibiting VC (CAC or TAC). There was a positive correlation between CACS and age (rs = 0.495, P = 0.00). A statistically significant positive correlation existed between TACS and age (rs = 0.516, P = 0.00). Similarly, a positive correlation was found between NLR, PLR, and TACS (rs = 0.334, P = 0.001, and rs = 0.438, P = 0.00, respectively). On multivariate linear regression analysis, increased age and red cell distribution width were found to be significant predictors of log(n) TACS. PLR of 135 gave a sensitivity of 80% and a specificity of 50% for predicting VC. Being a cost-effective and easily available investigation, the utilization of the correlation of NLR and PLR with CAC and TAC appears promising, particularly in the age group of 30–60 years.
Contemporary nursing graduates' transition to practice: A critical review of transition models.

AIM To critically review contemporary transition theories to determine how they apply to the newly qualified graduate registered nurse programs. BACKGROUND Graduate nurse transition to employment is time of significant change which has resulted in high attrition rates. Graduates are often challenged by their expectation of nursing practice and the reality of the role. The transition from hospital-based training to university-based training has resulted in the need for primary employment to commence with graduate/orientation/internship programs to help support new graduates transition into clinical practice. One transition model, Duchscher's Stages of Transition Theory, utilised three former theories to develop a final model. DESIGN A narrative critical literature review METHOD: The theories selected for the review were Kramer's Reality Shock theory, Benner's Novice-to-Expert theory, Bridges Transition theory and Duchscher's Stages of Transition theory. CONCLUSION Duchscher's stages of transition theory reflects the experiences of registered nursing transition into the workforce directly from university. The application of the theory is effective to guide understanding of the current challenges that new graduate nurse's experience today. There is a need for new graduates to complete their university degree as advanced beginners in order to decrease the experience of transition shock and keep pace with rapidly changing demands of the clinical environment. This may be achieved by increasing ward based simulation in university education. A theoretical framework can provide a deep understanding of the various stages and processes of transition and enable development of successful programs. RELEVANCE TO CLINICAL PRACTICE Both universities and hospitals need to adapt their current practice to align with the needs of new graduates due to large student numbers and ongoing systematic advancements to decrease the attrition rate.
A safety evaluation of dimethyl fumarate in moderate-to-severe psoriasis

ABSTRACT Introduction: Psoriasis is a chronic inflammatory disorder affecting skin, nails and joints. Systemic therapy of psoriasis is based upon several drugs which include fumaric acid esters (FAEs), initially introduced in 1959. Since 2017, one of the key substances among FAE spectrum (dimethyl fumarate; DMF) was registered by the European Medicines Agency (EMA) for the treatment of moderate-to-severe psoriasis vulgaris. Areas covered: This article covers the basic concepts underlying usefulness of DMF in psoriasis and extensively reviews the studies, which included its use in monotherapy of this dermatosis, with a particular emphasis on safety aspects and adverse events (AEs). Expert opinion: DMF monotherapy is a valuable systemic modality in the management of moderate-to-severe psoriasis as proved by a recent phase III study. AEs associated with DMF therapy are frequent, usually of mild severity, with a dose-independent manner. Occasionally they are burdensome and require drug discontinuation. The most common AEs comprise gastrointestinal symptoms, flushing and white blood cell count abnormalities. The latter require strict monitoring to prevent serious complications. Acknowledging the possibility of AEs, the use of DMF in moderate-to-severe psoriasis is encouraged while the need of further studies still remains.
Prevalence and clustering of diarrhoea within households in India: some evidence from NFHS-4, 2015–16

Abstract Diarrhoeal disease is one of the major causes of morbidity and mortality in children and is usually measured at individual level. Shared household attributes, such as improved water supply and sanitation, expose those living in the same household to these same risk factors for diarrhoea. The occurrence of diarrhoea in two or more children in the same household is termed ‘diarrhoea clustering’. The aim of this study was to examine the role of improved water supply and sanitation in the occurrence of diarrhoea, and the clustering of diarrhoea in households, among under-five children in India. Data were taken from the fourth round of the National Family and Health Survey (NFHS-4), a nationally representative survey which interviewed 699,686 women from 601,509 households in the country. If any child was reported to have diarrhoea in a household in the 2 weeks preceding the survey, the household was designated a diarrhoeal household. Household clustering of diarrhoea was defined the occurrence of diarrhoea in more than one child in households with two or more children. The analysis was done at the household level separately for diarrhoeal households and clustering of diarrhoea in households. The presence of clustering was tested using a chi-squared test. The overall prevalences of diarrhoea and clustering of diarrhoea were examined using exogenous variables. Odds ratios, standardized to allow comparison across categories, were computed. The household prevalence of diarrhoea was 12% and that of clustering of diarrhoea was 2.4%. About 6.5% of households contributed 12.6% of the total diarrhoeal cases. Access to safe water and sanitation was shown to have a great impact on reducing diarrhoeal prevalence and clustering across different household groups. Safe water alone had a greater impact on reducing the prevalence in the absence of improved sanitation when compared with the presence of improved sanitation. It may be possible to reduce the prevalence of diarrhoea in households by targeting those households with more than one child in the under-five age group with the provision of safe water and improved sanitation.
YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy

The transcriptional co‐activators YAP (or YAP1) and TAZ (or WWTR1) are frequently activated during the growth and progression of many solid tumors, including lung, colorectal, breast, pancreatic, and liver carcinomas as well as melanoma and glioma. YAP/TAZ bind to TEAD‐family co‐activators to drive cancer cell survival, proliferation, invasive migration, and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP‐TEAD cooperates with the RAS‐induced AP‐1 (FOS/JUN) transcription factor to drive tumor growth and cooperates with MRTF‐SRF to promote activation of cancer‐associated fibroblasts, matrix stiffening, and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2‐LATS1/2) pathway and the key upstream activators are mechanically induced Integrin‐SRC and E‐cadherin‐AJUBA/TRIP6/LIMD1, growth factor induced PI3K‐AKT, and inflammation‐induced G‐protein coupled receptor (GPCR) signals, all of which antagonize the Hippo pathway. In this review, strategies to target YAP/TAZ activity in cancer are discussed along with the prospects for synergy with established pillars of cancer therapy.
Maternal serum levels of asymmetric dimethylarginine in normal and preeclamptic pregnancies

Abstract The study aims to investigate maternal serum levels of asymmetric dimethylarginine (ADMA) in preeclampsia. Serum samples were collected from 57 women with preeclamptic pregnancies and 30 women with normal pregnancies during the third trimester. ADMA levels were measured with the ELISA method. ADMA levels in preeclamptic pregnancies were significantly higher when compared with normal pregnancies (2.35 ± 3.20 nmol/l versus 0.35 ± 0.10 nmol/l; p < .05). ADMA levels show a significant positive correlation with systolic and diastolic pressure, urea, and creatinine but a negative correlation with proteinuria. ADMA levels have a significant strong correlation with PE. ADMA levels are significantly higher in preeclamptic pregnancy compared with normal pregnancy.
Rwandan nursing students’ knowledge, attitudes and application of evidence-based practice

Background Evidence-based practice (EBP) plays a key role in improving health outcomes of a country’s population; however, the teaching of EBP is often theoretical and inconsistent, resulting in negative attitudes and limited application. Objectives The aim of this study was to determine the knowledge, attitudes and application of EBP by nursing students at a school of nursing in Rwanda. Method A total of 82 third- and fourth-year nursing students completed the survey. Univariate statistical analyses were performed to explore the distribution of data. Chi-square tests were utilised to examine the relation between knowledge, attitudes and application of EBP with the year of study. Results Most students reported being knowledgeable of the steps of EBP, with a range of 84% – 92%. However, 50% reported negative attitudes and only 12% reported daily searches for evidence. The main reported barriers to the application of EBP were lack of knowledge, lack of time and lack of examples or role models. Conclusion Knowledge about EBP does not necessarily positively influence student attitudes. Evidence-based practice should be integrated into the theoretical and practical component of the nursing curriculum to promote the effective application of EBP by nursing students.
Hes1 deficiency causes hematopoietic stem cell exhaustion

The transcriptional repressor Hairy Enhancer of Split 1 (HES1) plays an essential role in the development of many organs by promoting the maintenance of stem/progenitor cells, controlling the reversibility of cellular quiescence, and regulating both cell fate decisions. Deletion of Hes1 in mice results in severe defects in multiple organs and is lethal in late embryogenesis. Here we have investigated the role of HES1 in hematopoiesis using a hematopoietic lineage‐specific Hes1 knockout mouse model. We found that while Hes1 is dispensable for steady‐state hematopoiesis, Hes1‐deficient hematopoietic stem cells (HSCs) undergo exhaustion under replicative stress. Loss of Hes1 upregulates the expression of genes involved in PPARγ signaling and fatty acid metabolism pathways, and augments fatty acid oxidation (FAO) in Hes1 f/fVav1Cre HSCs and progenitors. Functionally, PPARγ targeting or FAO inhibition ameliorates the repopulating defects of Hes1 f/fVav1Cre HSCs through improving quiescence in HSCs. Lastly, transcriptome analysis reveals that disruption of Hes1 in hematopoietic lineage alters expression of genes critical to HSC function, PPARγ signaling, and fatty acid metabolism. Together, our findings identify a novel role of HES1 in regulating stress hematopoiesis and provide mechanistic insight into the function of HES1 in HSC maintenance.
Relative importance of lower extremity net joint moments in relation to bar velocity and acceleration in weightlifting

ABSTRACT The purpose of this study was to investigate the relative importance of net joint moments (NJM) in relation to bar kinematics during the clean. Ground reaction force and 3-D motion data were recorded as seven weightlifters performed cleans at 85% of their competition maximum, and were used to calculate hip, knee, and ankle NJM. Vertical bar kinematics were also calculated. NJM were used as inputs to a three-layer feedforward artificial neural network (ANN), which was trained to predict bar kinematics. Subject-specific ANN with 15 hidden neurons could effectively model the association between NJM and bar kinematics for each individual weightlifter (r: 0.965 ± 0.031; MSE: 0.169 ± 0.152). The relative importance (%) of hip, knee, and ankle NJM to bar velocity were 23%, 31%, and 46%, respectively, whereas the relative importance of hip, knee, and ankle NJM to bar acceleration were 23%, 39%, and 38%, respectively. Non-parametric statistics indicated that the ankle NJM exhibited the greatest relative importance in relation to bar velocity, whereas the knee and ankle NJM showed the greatest relative importance in relation to bar acceleration. These results indicate that the NJM produced at the knee and ankle joint are of great importance in contributing to bar kinematics during weightlifting.
The risk of Salmonella spp. from small poultry operations in Oregon

approved: ______________________________________________________ Joy Waite-Cusic Salmonella is a bacterium responsible for several illnesses, including typhoid fever, paratyphoid fever, and salmonellosis. It is commonly found in animal products, including poultry. Determination of potential reservoirs of Salmonella contamination is important to mitigate the risk of transmission and possible outbreaks. Outbreaks can negatively impact the livelihood of local Oregon farmers exempt from continuous federal inspection. The objective of this study was to determine potential reservoirs for Salmonella contamination at an Oregon poultry operation. Results indicated that chicken litter and water fountains were the reservoirs for contamination. Future studies could identify mitigation strategies that prevent Salmonella transmission through treatments targeting these reservoirs.
METTL3/YTHDF2 m6A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

N6‐Methyladenosine (m6A) modification, the most prevalent modification of eukaryotic messenger RNA (mRNA), is involved in the progression of various tumours. However, the specific role of m6A in bladder cancer (BCa) is still poorly understood. In this study, we demonstrated the tumour‐promoting function and specific regulatory mechanism of m6A axis, consisting of the core ‘writer’ protein METTL3 and the major reader protein YTHDF2. Depletion of METTL3 impaired cancer proliferation and cancer metastasis in vitro and in vivo. Through transcriptome sequencing, m6A methylated RNA immunoprecipitation (MeRIP) and RIP, we determined that the METTL3/YTHDF2 m6A axis directly degraded the mRNAs of the tumour suppressors SETD7 and KLF4, contributing to the progression of BCa. In addition, overexpression of SETD7 and KLF4 revealed a phenotype consistent with that induced by depletion of the m6A axis. Thus, our findings on the METTL3/YTHDF2/SETD7/KLF4 m6A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for BCa.
Inactivation of Plasmodium falciparum in whole blood using the amustaline and glutathione pathogen reduction technology

Risk of transfusion‐transmitted (TT) malaria is mainly associated with whole blood (WB) or red blood cell (RBC) transfusion. Risk mitigation relies mostly on donor deferral while a limited number of countries perform blood testing, both negatively impacting blood availability. This study investigated the efficacy of the pathogen reduction system using amustaline and glutathione (GSH) to inactivate Plasmodium falciparum in WB.
Alternative Methods for Testing Botulinum Toxin: Current Status and Future Perspectives

Botulinum toxins are neurotoxic modular proteins composed of a heavy chain and a light chain connected by a disulfide bond and are produced by Clostridium botulinum. Although lethally toxic, botulinum toxin in low doses is clinically effective in numerous medical conditions, including muscle spasticity, strabismus, hyperactive urinary bladder, excessive sweating, and migraine. Globally, several companies are now producing products containing botulinum toxin for medical and cosmetic purposes, including the reduction of facial wrinkles. To test the efficacy and toxicity of botulinum toxin, animal tests have been solely and widely used, resulting in the inevitable sacrifice of hundreds of animals. Hence, alternative methods are urgently required to replace animals in botulinum toxin testing. Here, the various alternative methods developed to test the toxicity and efficacy of botulinum toxins have been briefly reviewed and future perspectives have been detailed.
Timely Initiation of Complementary Feeding Practices in Gondar Town Northwest Ethiopia: A Cross-sectional Study

ABSTRACT Background The time of introduction and nutritionally adequate, safe, age-appropriate complementary feeding is extremely important for the child’s optimal growth, development, and health within the first 2 years of life. Despite a number of interventions to improve infant and young child feeding practices and nutritional status, appropriate feeding practices are far away from the recommendation. Therefore, the study aimed to assess timely initiation of complementary feeding practices and associated factors among children aged 6–23 months in Gondar town, northwest Ethiopia. Methods A community-based cross-sectional study was conducted in December 2017. A multistage sampling technique was employed to select 632 mother-child pairs. Pretested structured and interviewer-administered questionnaire was used to collect data. Data were entered into Epi–info version 7 and transferred to SPSS version 20.0 for analysis. Both bivariable and multivariable logistic regression analysis were used to identify factors associated with timely initiation of complementary feeding. Finally, variables with a P-value of <0.05 were considered as statistically significant. Results The prevalence of timely initiation of complementary feeding was 47.3% (95%CI: 43.0, 51.3). Being housewife in maternal occupation (AOR = 2.03, 95%CI: 1.21, 3.43), good mother’s knowledge about complementary feeding (AOR = 1.80, 95% CI: 1.28, 2.53) and attending post-natal care checkup (AOR = 3.90, 95%CI: 1.26, 12.04) were significantly associated with timely initiation of complementary feeding. Conclusion This study revealed that timely initiation of complementary feeding was low within the study area. Around half of the children started complementary feeding at their 6 months of age. Therefore, special emphasis should be given to mothers who have poor knowledge about complementary feeding and encourage all mothers to have postnatal follow-up is crucial.