Miracle-dz/UniFAR-FTUs huggingface dataset:
Liposomal Nanomedicines: An Emerging Field

Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal nanomedicines (LNMs), represent one of the most advanced classes of drug delivery systems, with several currently on the market and many more in clinical trials. During the past 20 years, a variety of techniques have been developed for encapsulating both conventional drugs and the new genetic drugs (plasmid DNA–containing therapeutic genes, anti-sense oligonucleotides, and small, interfering RNA [siRNA]) within LNs encompassing a very specific set of properties: a diameter centered on 100 nm, a high drug-to-lipid ratio, excellent retention of the encapsulated drug, and a long (> 6 hours) circulation lifetime. Particles with these properties tend to accumulate at sites of disease, such as tumors, where the endothelial layer is “leaky” and allows extravasation of particles with small diameters. Thus, LNs protect the drug during circulation, prevent it from reaching healthy tissues, and permit its accumulation at sites of disease. We will discuss recent advances in this field involving conventional anticancer drugs as well as gene-delivery, immunostimulatory, and gene-silencing applications involving the new genetic drugs. LNMs have the potential to offer new treatments in such areas as cancer therapy, vaccine development, and cholesterol management.
Association Between a Polymorphism in the IL-12p40 Gene and Cytomegalovirus Reactivation After Kidney Transplantation

Background. Cytomegalovirus (CMV) infection is associated with a significant rate of morbidity after organ transplantation. The genetic factors influencing its occurrence have been little investigated. IL-12 plays a crucial role in anti-infectious immune responses, especially by stimulating IFNγ production. An A-to-C single nucleotide polymorphism (SNP) within the 3′-untranslated region of the IL-12p40 gene has been characterized and was reported to be both functionally and clinically relevant. However, the impact of this single nucleotide polymorphism on events after organ transplantation has never been reported. Methods. In this study, we investigated the impact of the 3′-untranslated region polymorphism on the occurrence of CMV infection in 469 kidney recipients transplanted at the University Hospital of Tours between 1995 and 2005. The polymorphism was genotyped using the restriction fragment length polymorphism method and CMV infection was determined by pp65 antigenemia. Results. Multifactorial Cox regression analysis demonstrated that the presence of the C allele was an independent risk factor for CMV infection (OR=1.52, P=0.043), the risk being even higher when study was restricted to patients with positive CMV serological status before the graft and who did not receive any CMV prophylaxis (OR=1.88, P=0.028). Conclusions. This study identified a new genetic risk factor for CMV reactivation after kidney transplantation. The results of our study suggest that C carriers might especially benefit from CMV prophylaxis.
Development and Characterization of Florfenicol-Loaded BSA Nanoparticles as Controlled Release Carrier

Florfenicol (FLO) is a broad-spectrum fluorinated antibiotic used for the treatment of bacterial diseases such as bovine respiratory disease (BRD) in cattle. FLO is a poorly soluble drug in aqueous solution, and its encapsulation in various nanovehicles has been reported to be less than 30%. In this context, the use of bovine serum albumin (BSA) as a nanocarrier for FLO is an interesting approach. BSA is a biocompatible, biodegradable, nontoxic, and nonimmunogenic natural protein, allowing the vehiculization of hydrophilic and hydrophobic drugs with a well-tolerated administration. The present work focuses on the fabrication and characterization of florfenicol-loaded BSA (FLO-BSA NPs), incorporation efficiency, and in vitro release pattern. FLO-BSA NPs nanoparticles were successfully obtained by a simple, low-cost and in a few steps method. The physicochemical properties of the obtained nanoparticles such as size (~ 120 nm), polydispersity index (0.04), and zeta potential (approximately − 40 mV) suggest a high colloidal stability and suitable characteristics for drug delivery. The drug loading reveals a high incorporation of florfenicol in the nanoparticles, in which 33.6 molecules of FLO are encapsulated per each molecule of BSA. The in vitro release profile exhibits an initial stage characterized by the burst effect and then a prolonged release of FLO from the albumin matrix, which is compatible with the Higuchi model and which follows a Fickian diffusion. The results together suggest a suitable tool for future investigations in drug delivery field in order to use this nanomaterial in food, pharmaceutical, and veterinary industry.
Convolutional Networks with Dense Connectivity

Recent work has shown that convolutional networks can be substantially deeper, more accurate, and efficient to train if they contain shorter connections between layers close to the input and those close to the output. In this paper, we embrace this observation and introduce the Dense Convolutional Network (DenseNet), which connects each layer to every other layer in a feed-forward fashion. Whereas traditional convolutional networks with <inline-formula><tex-math notation="LaTeX">$L$</tex-math><alternatives><mml:math><mml:mi>L</mml:mi></mml:math><inline-graphic xlink:href="huang-ieq1-2918284.gif"/></alternatives></inline-formula> layers have <inline-formula><tex-math notation="LaTeX">$L$</tex-math><alternatives><mml:math><mml:mi>L</mml:mi></mml:math><inline-graphic xlink:href="huang-ieq2-2918284.gif"/></alternatives></inline-formula> connections—one between each layer and its subsequent layer—our network has <inline-formula><tex-math notation="LaTeX">$\frac{L(L+1)}{2}$</tex-math><alternatives><mml:math><mml:mfrac><mml:mrow><mml:mi>L</mml:mi><mml:mo>(</mml:mo><mml:mi>L</mml:mi><mml:mo>+</mml:mo><mml:mn>1</mml:mn><mml:mo>)</mml:mo></mml:mrow><mml:mn>2</mml:mn></mml:mfrac></mml:math><inline-graphic xlink:href="huang-ieq3-2918284.gif"/></alternatives></inline-formula> direct connections. For each layer, the feature-maps of all preceding layers are used as inputs, and its own feature-maps are used as inputs into all subsequent layers. DenseNets have several compelling advantages: they alleviate the vanishing-gradient problem, encourage feature reuse and substantially improve parameter efficiency. We evaluate our proposed architecture on four highly competitive object recognition benchmark tasks (CIFAR-10, CIFAR-100, SVHN, and ImageNet). DenseNets obtain significant improvements over the state-of-the-art on most of them, whilst requiring less parameters and computation to achieve high performance.
Mycophenolate Mofetil Reduces Intimal Thickness by Intravascular Ultrasound After Heart Transplant: Reanalysis of the Multicenter Trial

The mycophenolate mofetil (MMF) trial involved 650 heart transplant patients from 28 centers who received MMF or azathioprine (AZA), both in combination with cyclosporine and corticosteroids. Baseline and 1‐year intravascular ultrasound (IVUS) were performed in 196 patients (102 MMF and 94 AZA) with no differences between groups in IVUS results analyzed by morphometric analysis (average of 10 evenly spaced sites, without matching sites between studies). Baseline to first‐year IVUS data can also be analyzed by site‐to‐site analysis (matching sites between studies), which has been reported to be more clinically relevant. Therefore, we used site‐to‐site analysis to reanalyze the multicenter MMF IVUS data. Results: IVUS images were reviewed and interpretable in 190 patients (99 MMF and 91 AZA) from the multicenter randomized trial. The AZA group compared to the MMF group had a larger number of patients with first‐year maximal intimal thickness (MIT) ≥0.3 mm (43% vs. 23%, p = 0.005), a greater decrease in the mean lumen area (p = 0.02) and a decrease in the mean vessel area (the area actually increased in the MMF group, p = 0.03). Conclusion: MMF‐treated heart transplant patients compared to AZA‐treated patients, both concurrently on cyclosporine and corticosteroids, in this study have significantly less progression of first‐year intimal thickening.
The Expanding Role of Nurse Practitioners in Home-Based Primary Care: Opportunities and Challenges.

Approximately 93% of Medicare spending is for beneficiaries with multiple chronic conditions. Costs of poorly coordinated or delayed care for this vulnerable population are staggering-not just measured in dollars and cents, but in overall psychosocial burdens of poor health and diminished quality of life. Home-based primary care (HBPC) practices are an effective way to meet needs of frail older adults who find it difficult, if not impossible, to leave home for medical care with an overall cost savings to Medicare. Nurse practitioners (NPs) provide more than 825,000 HBPC visits per year. Their training and education uniquely prepare them to address whole person aspects of health, including medical, psychosocial, and quality of life realms. Despite proven benefits of NPs providing HBPC, Medicare regulatory barriers disallow NPs from certifying or recertifying Medicare home health or certifying terminal illness for hospice patients. These barriers decrease patient access to timely care and increase Medicare costs. [Journal of Gerontological Nursing, 45(6), 9-14. ].
Bacillus subtilis FolE is sustained by the ZagA zinc metallochaperone and the alarmone ZTP under conditions of zinc deficiency

Bacteria tightly regulate intracellular zinc levels to ensure sufficient zinc to support essential functions, while preventing toxicity. The bacterial response to zinc limitation includes the expression of putative zinc metallochaperones belonging to subfamily 1 of the COG0523 family of G3E GTPases. However, the client proteins and the metabolic processes served by these chaperones are unclear. Here, we demonstrate that the Bacillus subtilis YciC zinc metallochaperone (here renamed ZagA for ZTP activated GTPase A) supports de novo folate biosynthesis under conditions of zinc limitation, and interacts directly with the zinc‐dependent GTP cyclohydrolase IA, FolE (GCYH‐IA). Furthermore, we identify a role for the alarmone ZTP, a modified purine biosynthesis intermediate, in the response to zinc limitation. ZTP, a signal of 10‐formyl‐tetrahydrofolate (10f‐THF) deficiency in bacteria, transiently accumulates as FolE begins to fail, stimulates the interaction between ZagA and FolE, and thereby helps to sustain folate synthesis despite declining zinc availability.
Frequent Dose Interruptions are Required for Patients Receiving Oral Kinase Inhibitor Therapy for Advanced Renal Cell Carcinoma

Objective:Recent advances for patients with advanced or metastatic renal cell carcinoma (RCC) have been shown to improve progression-free survival with both response rates and disease stabilizing activity. Sorafenib, a multikinase inhibitor, and sunitinib, an inhibitor of vascular endothelial growth factor-r and platelet-derived growth factor-r, have been approved by the Food and Drug Administration since 2005/2006. This retrospective analysis of patients treated with both aforementioned kinase inhibitors for advanced RCC presents data related to their antitumor effects as well as safety profile with particular attention to dose interruption and modification requirements. Methods:This was a retrospective review of patients diagnosed with RCC either with advanced disease at initial presentation or after first-line therapy, who received either continuous sorafenib 400 mg bid or sunitinib 50 mg Qday for 4 weeks on and 2 weeks off until disease progression or untoward drug reaction. Tumor response was evaluated by response evaluation criteria in solid tumors criteria, and adverse events were graded by National Cancer Institute-Common Toxicity Criteria. Results:From December 2005 to May 2008, 34 patients were followed. Twenty-two patients received sorafenib first line, 10 received sunitinib first line, and 2 patients received sorafenib as third-line therapy. Twenty-nine were evaluable for response rates. There were 10 patients (34%) who had stabilization of disease, 8 patients (28%) who had a partial response, and 11 patients (38%) who had progression of disease. The progression-free survival median was 8 months. Of the 34 patients evaluable for toxicities, grade 3 or 4 adverse event occurred in 19 patients (56%). These patients required either dose modifications and/or treatment interruptions within an average of the first 2 weeks of treatment. Eight patients (24%) required drug discontinuation. Eleven patients (32%) required dose reductions, but were able to resume the targeted dose after slow dose escalation. Three patients (9%) remain dose reduced for greater than 12 weeks. Conclusions:Sorafenib and sunitinib have extended patients' disease-free survival by several months; however, the initial grade 3 or 4 adverse event presented in the literature appear to have been under-reported. Our experience suggests that the first 4 weeks of treatment is the most likely timeframe within which drug reactions occur. Therefore, careful monitoring and possibly additional clinical visits are warranted during this time period. Although a significant percentage of patients require dose modification, many can be restarted and titrated up to the targeted dose.
Multi-Site Meta-Analysis of Morphometry

Genome-wide association studies (GWAS) link full genome data to a handful of traits. However, in neuroimaging studies, there is an almost unlimited number of traits that can be extracted for full image-wide big data analyses. Large populations are needed to achieve the necessary power to detect statistically significant effects, emphasizing the need to pool data across multiple studies. Neuroimaging consortia, e.g., ENIGMA and CHARGE, are now analyzing MRI data from over 30,000 individuals. Distributed processing protocols extract harmonized features at each site, and pool together only the cohort statistics using meta analysis to avoid data sharing. To date, such MRI projects have focused on single measures such as hippocampal volume, yet voxelwise analyses (e.g., tensor-based morphometry; TBM) may help better localize statistical effects. This can lead to $10^{13}$1013 tests for GWAS and become underpowered. We developed an analytical framework for multi-site TBM by performing multi-channel registration to cohort-specific templates. Our results highlight the reliability of the method and the added power over alternative options while preserving single site specificity and opening the doors for well-powered image-wide genome-wide discoveries.
Massive outbreak of anthrax in wildlife in the Malilangwe Wildlife Reserve, Zimbabwe

A massive outbreak of anthrax in the wildlife of the Malilangwe Wildlife Reserve in Zimbabwe between August and November 2004 resulted in the death of almost all the reserve's estimated 500 kudu (Tragelaphus strepsiceros). Other species badly affected were nyala (Tragelaphus angasi), bushbuck (Tragelaphus scriptus), waterbuck (Kobus ellipsiprymnus) and roan antelope (Hippotragus equinus), which suffered losses of approximately 68 per cent, 48 per cent, 44 per cent and 42 per cent of their populations, respectively. Buffalo (Syncerus caffer) were also badly affected and although their population suffered only a 6 per cent loss, the numbers of deaths ranked second highest after kudu. To the authors' knowledge, this is the first record of anthrax in wildlife in Zimbabwe.
Sex differences in neurodevelopmental disorders.

PURPOSE OF REVIEW There continues to be more males than females diagnosed with neurodevelopmental disorders, which may provide clues about their cause. This review will focus on the two most common neurodevelopmental disorders - autism spectrum disorder (autism) and attention deficit hyperactivity disorder (ADHD), and explore recent research to understand recent developments in the field. RECENT FINDINGS Biological mechanisms including genetics, hormones and their interaction with other risk factors, such as stress and lead exposure, point to complex causal pathways for neurodevelopmental disorders. Over recent years, the research focus on sex differences in symptom profiles in autism has continued; however, a meta-analysis of existing studies indicated minimal sex differences in core autism symptoms. In ADHD, changes in the sex ratio from disparity in childhood to parity in adulthood may relate to the onset and trajectory of hyperactivity symptoms in females. Research into medical and psychiatric comorbidities, such as polycystic ovary syndrome and gender dysphoria, is also providing insights into the role of early androgen exposure as a potential causal factor for neurodevelopmental disorders. SUMMARY The factors, which contribute to an increased number of males with neurodevelopmental disorders in most cases are complex involving interactions between genetics, hormones and environmental factors.
Plus size and obese workers: anthropometry estimates to promote inclusive design

Abstract A significant proportion of the adult population globally is overweight, obese or classed as ‘plus size’. This has led to variability in size and shape across the working population and exclusion in the workplace. A new dataset of the anthropometry of plus size people has been created. Length dimensions were similar to other data, but breadth, circumference, and depth measurements were substantially larger. The hip breadth and abdominal depth were important for predicting largeness in this population. These data help explain the high exclusion rates from design and the number of fit, reach, posture and clearance issues reported by participants with a high BMI: generally, the higher the BMI the greater prevalence of problems. It is hoped that a better understanding of the anthropometric characteristics of the plus size worker will inform the design of safe, productive work environments to promote inclusion for a wider range of people. Practitioner Summary: A new anthropometry dataset of plus size people has been created. The higher the BMI the greater the problems with design in the workplace for fit, reach, posture and clearance. To ensure inclusion and reduce stigma it is important to understand more about the size and shape of this population.
Prevalence, clinical relevance and predictive factors of medication discrepancies revealed by medication reconciliation at hospital admission: prospective study in a Swiss internal medicine ward

Objective Medication reconciliation (MedRec) is a relevant safety procedure in medication management at transitions of care. The aim of this study was to evaluate the impact of MedRec, including a best possible medication history (BPMH) compared with a standard medication history in patients admitted to an internal medicine ward. Design Prospective interventional study. Data were analysed using descriptive statistics followed by univariate and multivariate Poisson regression models and a zero-inflated Poisson regression model. Setting Internal medicine ward in a secondary care hospital in Southern Switzerland. Participants The first 100 consecutive patients admitted in an internal medicine ward. Primary and secondary outcome measures Medication discrepancies between the medication list obtained by the physician and that obtained by a pharmacist according to a systematic approach (BPMH) were collected, quantified and assessed by an expert panel that assigned a severity score. The same procedure was applied to discrepancies regarding allergies. Predicting factors for medication discrepancies were identified. Results The median of medications per patient was 8 after standard medication history and 11 after BPMH. Total admission discrepancies were 524 (5.24 discrepancies per patient) with at least 1 discrepancy per patient. For 47 patients, at least one discrepancy was classified as clinically relevant. Discrepancies were classified as significant and serious in 19% and 2% of cases, respectively. Furthermore, 67% of the discrepancies were detected during the interview conducted by the pharmacist with the patients and/or their caregivers. The number of drugs used and the autonomous management of home therapy were associated with an increased number of clinically relevant discrepancies in a multivariable Poisson regression model. Conclusion Even in an advanced healthcare system, a standardised MedRec process including a BPMH represents an important strategy that may contribute to avoid a notable number of clinically relevant discrepancies and potential adverse drug events.
Involvement of Cot/Tp12 in Bone Loss during Periodontitis

Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-α mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.
Bronchoalveolar lavage cell and mediator responses to hyperpnea-induced bronchoconstriction in the guinea pig.

We studied the association between bronchoconstriction and bronchoalveolar lavage (BAL) cell and mediator profiles in unsensitized guinea pigs (GP) after hyperpnea to determine whether eicosanoids or histamine are released during hyperpnea-induced bronchoconstriction (HIB). Twelve animals were challenged with warm, moist (WM) air (T = 35 degrees C, relative humidity = 91 to 94%), 14 with room dry (RD) air (T = 25 degrees C, relative humidity less than 2.1%), and 18 with cold, dry (CD) air (T = 7 degrees C, relative humidity less than 2.1%). Lung resistance (RL) and elastance (EL) were recorded at baseline and at 2-min intervals after hyperventilation. Challenges were terminated either when a greater than or equal to 100% increase in RL was observed postchallenge or after completion of a 135 breaths/min challenge if RL did not increase. BAL was performed, and samples were analyzed for total cells, white cell and epithelial cell differentials, total protein concentration, and mediator content. (ABSTRACT TRUNCATED AT 250 WORDS)
Neuromelanin or DaT‐SPECT: which is the better marker for discriminating advanced Parkinson's disease?

Whether the neuromelanin‐positive substantia nigra pars compacta area (NM‐SNc) on neuromelanin magnetic resonance imaging (NM‐MRI) and the specific binding ratio (SBR) on 123I‐N‐v‐fluoropropyl‐2b‐carbomethoxy3b‐(4‐iodophenyl)nortropane single photon emission computed tomography (DaT‐SPECT) can be correlated with motor fluctuations (MFs) in advanced Parkinson's disease (PD) was investigated.
Second-Person in-Depth Phenomenological Inquiry as an Approach for Studying Enaction of Beliefs

Phenomenology and empirical research are not naturally compatible and devising an empirical technique aiming at researching experience is a challenge. This article presents second - person in - depth pheno menological inquiry – a technique that tries to meet this challenge by allowing the transformation of a participant greatly interested in the investigation of their own subjective experience, into a co - researcher. It then provides an example of this techni que being used in a study on enaction of beliefs, more closely showing the cooperative research process of researcher and co - researcher and its result: a grounded theory. The article ends with a discussion on the techniques strengths and weaknesses.