Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantifying the dilution effect for models in ecological epidemiology

The dilution effect, where an increase in biodiversity results in a reduction in the prevalence of an infectious disease, has been the subject of speculation and controversy. Conversely, an amplification effect occurs when increased biodiversity is related to an increase in prevalence. We explore the conditions under which these effects arise, using multi species compartmental models that integrate ecological and epidemiological interactions. We introduce three potential metrics for quantifying dilution and amplification, one based on infection prevalence in a focal host species, one based on the size of the infected subpopulation of that species and one based on the basic reproduction number. We introduce our approach in the simplest epidemiological setting with two species, and show that the existence and strength of a dilution effect is influenced strongly by the choices made to describe the system and the metric used to gauge the effect. We show that our method can be generalized to any number of species and to more complicated ecological and epidemiological dynamics. Our method allows a rigorous analysis of ecological systems where dilution effects have been postulated, and contributes to future progress in understanding the phenomenon of dilution in the context of infectious disease dynamics and infection risk.
Hypoxia Inducible Factor Expression and Angiogenesis - Analysis in the Pituitary Gland and Patterns of Death.

BACKGROUND/AIM We investigated the expression of angiogenesis and hypoxia markers in the adenohypophysis and neurohypophysis of patients who died from various acute or chronic diseases. MATERIALS AND METHODS Paraffin-embedded material of pituitary glands (97 patients) was investigated immunohistochemically for vascular density (CD31) and the expression of vascular endothelial growth factor (VEGF) and of hypoxia inducible factors HIF1α and HIF2α. RESULTS Vascular density, and HIF1α/HIF2α reactivity is directly related with VEGF expression in the pituitary gland, suggesting that the HIF pathway may regulate the vascular density and blood flow in the gland under hypoxic conditions. HIF2α appears to be a key regulator in neurohypophysis, whilst in adenohypophysis HIF1α and HIF2α are equally expressed. Chronic conditions, including alcoholism and substance abuse, seem to activate the HIF pathway in both neuro- and adeno-hypophysis. CONCLUSION The HIF pathway has an important role in regulating vascular density and blood flow in the pituitary gland.
Mutations in Extracellular Matrix Genes NID1 and LAMC1 Cause Autosomal Dominant Dandy–Walker Malformation and Occipital Cephaloceles

We performed whole‐exome sequencing of a family with autosomal dominant Dandy–Walker malformation and occipital cephaloceles and detected a mutation in the extracellular matrix (ECM) protein‐encoding gene NID1. In a second family, protein interaction network analysis identified a mutation in LAMC1, which encodes a NID1‐binding partner. Structural modeling of the NID1–LAMC1 complex demonstrated that each mutation disrupts the interaction. These findings implicate the ECM in the pathogenesis of Dandy–Walker spectrum disorders.
Analysis of Follicle-Stimulating Hormone Receptor in Infantile Hemangioma

Introduction The life cycle of infantile hemangioma (IH) and secretion of follicle-stimulating hormone (FSH) are identical. We previously have shown that IH contains the FSH receptor (FSHR). The purpose of this study was to identify which cell type(s) in IH expresses FSHR. Methods Human proliferating IH tissues obtained during a clinically indicated surgical procedure were used. Paraffin sections and isolated cell populations (endothelial, pericyte, stem cell) were subjected to immunofluorescence for FSHR. Tissues were costained with DAPI, anti-&agr; smooth muscle actin, or biotinylated Ulex Europaeus Agglutinin I to identify nuclei, pericytes, and endothelial cells, respectively. Whole tissue and purified single cell populations underwent polymerase chain reaction (PCR) for FSHR. Positive control specimens (ovary, sertoli cells) and negative control tissues (skin/subcutis, hepatic cells) were included. Results Immunofluorescence of 9 IHs demonstrated that FSHR was enriched in pericytes compared with endothelial cells. Follicle-stimulating hormone receptor was expressed in 6 of 6 whole tissue IHs along with the positive control via PCR. Follicle-stimulating hormone receptor was not present in the negative control samples. Four of 5 sets of pericytes expressed FSHR by PCR. Neither IH endothelial cells, IH stem cells, nor negative control cells exhibited FSHR by PCR. Conclusions Because the secretion of FSH correlates with the growth pattern of IH, FSH might be involved in the disease process. Follicle-stimulating hormone receptor is enriched in the pericytes of IH, suggesting that this cell type may be involved in the pathogenesis of the tumor.
Inhibition of the Cysteine Protease Human Cathepsin L by Triazine Nitriles: Amide⋅⋅⋅Heteroarene π‐Stacking Interactions and Chalcogen Bonding in the S3 Pocket

We report an extensive “heteroarene scan” of triazine nitrile ligands of the cysteine protease human cathepsin L (hCatL) to investigate π‐stacking on the peptide amide bond Gly67–Gly68 at the entrance of the S3 pocket. This heteroarene⋅⋅⋅peptide bond stacking was supported by a co‐crystal structure of an imidazopyridine ligand with hCatL. Inhibitory constants (Ki) are strongly influenced by the diverse nature of the heterocycles and specific interactions with the local environment of the S3 pocket. Binding affinities vary by three orders of magnitude. All heteroaromatic ligands feature enhanced binding by comparison with hydrocarbon analogues. Predicted energetic contributions from the orientation of the local dipole moments of heteroarene and peptide bond could not be confirmed. Binding of benzothienyl (Ki=4 nm) and benzothiazolyl (Ki=17 nm) ligands was enhanced by intermolecular C−S⋅⋅⋅O=C interactions (chalcogen bonding) with the backbone C=O of Asn66 in the S3 pocket. The ligands were also tested for the related enzyme rhodesain.
Optimizing Digital Integrated Care via Micro‐Randomized Trials

Mobile health (mHealth) interventions are a promising tool in providing digitally mediated integrative care. They can extend care outside of the clinic by providing reminders to take medications, assisting in managing symptoms, and supporting healthy behaviors including physical activity, healthy eating, and stress management. mHealth interventions can adapt the delivery of care across time in order to optimize treatment effectiveness. Yet there exists limited empirical evidence useful to the development of adaptive mHealth interventions. This article describes a new randomized trial design, the Micro‐Randomized Trial (MRT), for informing the development of mHealth interventions. We provide examples of scientific questions important to the development of an mHealth intervention, and describe how these questions can be answered using an MRT.
A Novel Way To Radiolabel Human Butyrylcholinesterase for Positron Emission Tomography through Irreversible Transfer of the Radiolabeled Moiety

The enzyme butyrylcholinesterase (BChE) is known to be involved in the detoxification of xenobiotics in blood plasma and is associated with the progress of neurodegenerative disorders, diabetes type 2, obesity, and diseases of the cardiovascular system. In the present study, we developed carbamate‐based inhibitors serving as positron emission tomography (PET) radiotracers with 18F and 11C as radioisotopes to visualize BChE distribution. These inhibitors are radiolabeled at the carbamate site and transfer this moiety onto BChE, which thus results in covalent and permanent radiolabeling of the enzyme. There are no comparable radiotracers for cholinesterases described to date. By ex vivo autoradiography experiments on mice brain slices and kinetic investigations, selective and covalent transfer of the radiolabeled carbamate moiety onto BChE was proven. These tracers might provide high resolution of BChE distribution in vivo to enable investigations into the pathophysiological mechanisms of diseases associated with alterations in BChE occurrence.
A 24-Month Follow-Up of a Custom-Made Suture-Button Assembly for Syndesmotic Injuries of the Ankle

ABSTRACT In the present retrospective analysis, we introduce a custom suture‐button fixation device for acute ankle syndesmotic injuries that allows for early weightbearing without another planned operation for hardware removal. We evaluated 87 consecutive ankles in 87 patients (49 males [56.32%] and 38 females [43.68%]). Of the 87 patients, 15 (17.24%) withdrew or were lost to follow‐up, leaving 72 patients (82.76%) in the present study. Their mean age was 35.2 (range 17 to 67) years. Nineteen patients (26.39%) presented with a pure syndesmotic disruption, and 53 (73.61%) had associated malleolar fractures. The American Orthopaedic Foot and Ankle Society scale score improved significantly from 31.2 ± 4.2 preoperatively to 88.5 ± 5.3 at an average of 24 months postoperatively (p < .0043). Revision was undertaken because of implant failure in 4 ankles (5.56%). Two revisions (2.78%) were performed in 2 ankles because of early weightbearing in the first 2 weeks after surgery. The third patient (1.39%) underwent revision at 5 weeks postoperatively. This syndesmotic reduction failure was attributed to failure of the threads, which was noted at the second surgery. The fourth patient (1.39%), a 66‐year‐old male, underwent revision at 5 months postoperatively because of persistent infection. An 18‐month postoperative radiograph was available for all patients. The medial clear space had significantly decreased, from 8.2 ± 3.1 mm preoperatively to 3.5 ± 2.2 mm at 18 months postoperatively (p < .0344). Likewise, the tibiofibular clear space had decreased significantly, from a mean of 8.8 ± 3.7 mm preoperatively to a mean of 3.7 ± 2.2 mm at 18 months postoperatively (p < .0322). In conclusion, suture‐button fixation described in the present report delivered satisfactory functional outcomes and anatomic reduction at minimum of 18 months after surgery. &NA; Level of Clinical Evidence: 4
Temperature-Time Superposition Effect on Compressive Properties of AZ31B Magnesium Composite Foams

Magnesium composite foams with 10 vol. % of hollow ceramic microspheres (CMs) were prepared by modified melt foaming method. Specimens with homogeneous pore structures were subjected to various heating temperature (150, 250, 320, 400, and 500 °C, respectively) and enduring times (1, 2, 4, 6, and 24 h, respectively). Evolution of microstructure and mechanical properties of the samples, before and after the heating processes were examined by applying X-ray diffraction technique (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and quasi-static uniaxial compression test. The results showed that as heating temperature and enduring time increasing, β-Mg17Al12 phases gradually dissolved, resulting in a solid-solution strengthening effect. Meanwhile, internal stress relaxation in the matrix leads to the decrease of yield strength and micro hardness of the specimens. When compared with the unheated foams, the treated specimens possessed lower micro-hardness, yield strength, and energy absorption capacity due to the dissolution of β-Mg17Al12 phases and the release of internal stress. However, higher strain hardening exponents for almost all of the treated composite foams were observed and the reasons were discussed. It is proposed that more factors should be taken into account when using heated composite foams in practical applications.
Uterine Carcinosarcomas: Clinical, Histopathologic and Immunohistochemical Characteristics

Carcinosarcomas (malignant mixed Müllerian tumors or MMMT) are rare malignant tumors in the female genital tract composed of both malignant epithelial and malignant mesenchymal components. They comprise <5% of all neoplasms in the gynecologic tract and have an aggressive clinical course. The purpose of this study is to evaluate the immunophenotype and possible histogenesis of carcinosarcomas of the uterus. Sixty-two cases of uterine carcinosarcomas diagnosed between 1995 and 2011 were retrieved from the gynecologic pathology files at Columbia University Medical Center. Representative tissue blocks containing both epithelial and mesenchymal components were selected from each case for histologic and immunohistochemical studies. Clinical data from each case were retrieved. The epithelial component was poorly differentiated adenocarcinoma in the majority (80.7%) of cases; in 17.7%, the carcinoma was moderately differentiated, and in only 1.6% the carcinoma was well differentiated. 53% of the tumors had homologous stromal elements and 47% displayed heterologous stromal elements. Immunohistochemical study revealed almost equal staining in both epithelial and mesenchymal components of carcinosarcomas for p16 and p53. PAX8 positivity was noted in 73% of epithelial components, but only 13% of stromal components, and PAX8 stromal positivity was never seen in the absence of PAX8 epithelial positivity. Expression of p16, p53, and PAX8 in both malignant components lends support to the monoclonal theory of uterine carcinosarcoma tumorigenesis. The roles of these tumor markers in the diagnosis and pathogenesis of this tumor and associations between clinical characteristics, tumor pathologic features, and prognosis are discussed.
Using the ecological framework to identify barriers and enablers to implementing Namaste Care in Canada's long-term care system.

BACKGROUND Higher acuity of care at the time of admission to long-term care (LTC) is resulting in a shorter period to time of death, yet most LTC homes in Canada do not have formalized approaches to palliative care. Namaste Care is a palliative care approach specifically tailored to persons with advanced cognitive impairment who are living in LTC. The purpose of this study was to employ the ecological framework to identify barriers and enablers to an implementation of Namaste Care. METHODS Six group interviews were conducted with families, unlicensed staff, and licensed staff at two Canadian LTC homes that were planning to implement Namaste Care. None of the interviewees had prior experience implementing Namaste Care. The resulting qualitative data were analyzed using a template organizing approach. RESULTS We found that the strongest implementation enablers were positive perceptions of need for the program, benefits of the program, and fit within a resident-centred or palliative approach to care. Barriers included a generally low resource base for LTC, the need to adjust highly developed routines to accommodate the program, and reliance on a casual work force. CONCLUSIONS We conclude that within the Canadian LTC system, positive perceptions of Namaste Care are tempered by concerns about organizational capacity to support new programming.
Shallow whole genome sequencing for robust copy number profiling of formalin-fixed paraffin-embedded breast cancers

Pathology archives with linked clinical data are an invaluable resource for translational research, with the limitation that most cancer samples are formalin-fixed paraffin-embedded (FFPE) tissues. Therefore, FFPE tissues are an important resource for genomic profiling studies but are under-utilised due to the low amount and quality of extracted nucleic acids. We profiled the copy number landscape of 356 breast cancer patients using DNA extracted FFPE tissues by shallow whole genome sequencing. We generated a total of 491 sequencing libraries from 2 kits and obtained data from 98.4% of libraries with 86.4% being of good quality. We generated libraries from as low as 3.8ng of input DNA and found that the success was independent of input DNA amount and quality, processing site and age of the fixed tissues. Since copy number alterations (CNA) play a major role in breast cancer, it is imperative that we are able to use FFPE archives and we have shown in this study that sWGS is a robust method to do such profiling.
Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab

ABSTRACT ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.
Independent Living Functions for the Elderly (IN-LIFE): Supporting Communication in Dementia

Independent Living Functions for the Elderly (IN-LIFE) is a 3 year multidisciplinary, multisite European project that aims to prolong and support independent living for people with cognitive impairments, through (ICT) services. Sheffield is one of six research sites and is focused on enhancing communication and conversations using touch screen computers.
Intimate Partner Violence, Small for Gestational Age Birth and Cigarette Smoking in the Pregnancy Risk Assessment Monitoring System.

BACKGROUND Exposure to intimate partner violence (IPV) in the perinatal period is associated with obstetric complications, poor maternal mental health, neonatal complications, and increased risk of infant mortality and morbidity. Less is known about how IPV may influence small for gestational age (SGA) birth. MATERIALS AND METHODS Data were obtained for 231,081 United States mothers who delivered neonates from 2004 to 2011 and completed the Pregnancy Risk Assessment Monitoring System survey 2-9 months after delivery. Weighted descriptive statistics and multivariate logistic regression models were used. RESULTS IPV in the year before or during pregnancy was related to SGA bivariately (odds ratio 1.39, 95% confidence interval [CI] 1.28, 1.51), and after adjustment for demographic and obstetric factors, this association attenuated after further adjustment for perinatal smoking patterns, (adjusted odds ratio [aOR] 1.06, 95% CI 0.97, 1.15). Compared with nonabused women, women experiencing perinatal IPV were more than twice as likely to smoke before pregnancy (aOR 2.34, 95% CI 2.19, 2.49), and nearly 1.5 times as likely to report sustained smoking into the last 3 months of pregnancy (aOR 1.45, 95% CI 1.32, 1.59). In turn, among prepregnancy smokers, sustained smoking was associated with delivery of a SGA neonate (aOR 1.87, 95% CI 1.72, 2.03), fully attenuating the association of perinatal IPV with SGA. CONCLUSION Women who experienced perinatal IPV were significantly more likely to smoke prepregnancy and sustain smoking into the last 3 months of pregnancy. Through behavioral and physiological pathways, smoking cessation may be uniquely challenging for women experiencing IPV, yet critical to address clinically to mitigate risk for SGA.
From the wound to the bench: exoproteome interplay between wound-colonizing Staphylococcus aureus strains and co-existing bacteria

ABSTRACT Wound-colonizing microorganisms can form complex and dynamic polymicrobial communities where pathogens and commensals may co-exist, cooperate or compete with each other. The present study was aimed at identifying possible interactions between different bacteria isolated from the same chronic wound of a patient with the genetic blistering disease epidermolysis bullosa (EB). Specifically, this involved two different isolates of the human pathogen Staphylococcus aureus, and isolates of Bacillus thuringiensis and Klebsiella oxytoca. Particular focus was attributed to interactions of S. aureus with the two other species, because of the high staphylococcal prevalence among chronic wounds. Intriguingly, upon co-cultivation, none of the wound isolates inhibited each other's growth. Since the extracellular proteome of bacterial pathogens is a reservoir of virulence factors, the exoproteomes of the staphylococcal isolates in monoculture and co-culture with B. thuringiensis and K. oxytoca were characterized by Mass Spectrometry to explore the inherent relationships between these co-exisiting bacteria. This revealed a massive reduction in the number of staphylococcal exoproteins upon co-culturing with K. oxytoca or B. thuringiensis. Interestingly, this decrease was particularly evident for extracellular proteins with a predicted cytoplasmic localization, which were recently implicated in staphylococcal virulence and epidemiology. Furthermore, our exoproteome analysis uncovered potential cooperativity between the two different S. aureus isolates. Altogether, the observed exoproteome variations upon co-culturing are indicative of unprecedented adaptive mechanisms that set limits to the production of secreted staphylococcal virulence factors.
CARUSO - Project Goals and Principal Approach

This paper proposes CARUSO – a new SoC approach that emphasizes Connectivity, Autonomic/Organic computing principles, Real-time, and Ultra-low power requirements. The requirements shall be fulfilled by a multithreaded processor core within a reconfigurable SoC. Helper threads running with low priority in own thread slots concurrent to the application implement autonomic/organic managers that monitor the application and decide if selfconfiguration, self-healing, self-optimization, or self-protection must be triggered.