Miracle-dz/UniFAR-FTUs huggingface dataset:
Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1

Microbial storage compounds, such as wax esters (WE), are potential high‐value lipids for the production of specialty chemicals and medicines. Their synthesis, however, is strictly regulated and competes with cell growth, which leads to trade‐offs between biomass and product formation. Here, we use metabolic engineering and synergistic substrate cofeeding to partition the metabolism of Acinetobacter baylyi ADP1 into two distinct modules, each dedicated to cell growth and WE biosynthesis, respectively. We first blocked the glyoxylate shunt and upregulated the WE synthesis pathway to direct the acetate substrate exclusively for WE synthesis, then we controlled the supply of gluconate so it could be used exclusively for cell growth and maintenance. We show that the two modules are functionally independent from each other, allowing efficient lipid accumulation while maintaining active cell growth. Our strategy resulted in 7.2‐ and 4.2‐fold improvements in WE content and productivity, respectively, and the product titer was enhanced by 8.3‐fold over the wild type strain. Notably, during a 24‐h cultivation, a yield of 18% C‐WE/C‐total‐substrates was achieved, being the highest reported for WE biosynthesis. This study provides a simple, yet powerful, means of controlling cellular operations and overcoming some of the fundamental challenges in microbial storage lipid production.
Palliative care and aggressive interventions after falling: A Nationwide Inpatient Sample analysis

Abstract Objective The purpose of this study is to identify whether there is an opportunity for improvement to provide palliative care services after a serious fall. We hypothesized that (1) palliative care services would be utilized in less than 10% of patients over the age of 65 who fall and (2) more than 20% of patients would receive aggressive life-sustaining treatments (LSTs) prior to death. Methods Using the 2017 Nationwide Inpatient Sample, we identified patients who were admitted to the hospital with a fall (ICD-10 W00-W19) and were hospitalized at least two days with valid discharge data. Palliative care services (Z51.5) or LSTs (cardiopulmonary resuscitation, ventilation, reintubation, tracheostomy, feeding tube placement, vasopressors, transfusion, total parenteral nutrition, and hemodialysis) were identified with ICD-10 codes. We examined the use of palliative care or LSTs by discharge destination (home, facility, and death). Logistic regression was used to identify factors associated with palliative care. Results In total, 155,241 patients were identified (median 82 years old, interquartile range 74–88); 2.5% died in hospital, and 69.4% were transferred to a facility. Palliative care occurred in 4.5% of patients, and LST occurred in 15.1%. Patients who died were significantly more likely to have had palliative care (50.1% vs. 3.4% of home or facility discharges) and were more likely to have an LST [53.0% vs. 9.8% (home) vs. 15.9% (facility)]. Palliative care was associated with both death [adjusted odds ratio (AOR) 19.84, 95% confidence interval (CI) 18.39–21.41, p < 0.001] and LST (AOR 1.36, 95% CI 1.27–1.46, p < 0.001). Significance of results Palliative care is associated with both death and LST, suggesting that physicians use palliative care as a last resort after aggressive measures have been exhausted. Patients who fall would likely benefit from the early use of palliative care to align future goals of care.
Breakdown and prebreakdown phenomena in liquids under positive impulse voltages

We examine the breakdown and prebreakdown behavior of two insulating liquids: benzyl-toluene and mineral oil in a nonuniform electric field at large distances (up to 20 cm) under a positive impulse voltage. We evaluate and compare the breakdown strengths of both liquids in these conditions as a function of interelectrode distance via Weibull type plots, a method commonly used when dealing with insulating gases and solids. The comparative behaviors of the liquids change greatly when the cumulative probability of breakdown is decreased from 100%. The second part of this study concerns streamer stopping lengths and the corresponding current and light emission signals. >
Predictive biomarkers and clinical evidence

Predictive biomarkers play an important role in our efforts to individualize pharmacotherapy, and within recent years, a number of different types of assays have been introduced. These biomarkers may potentially support the selection and dosage of specific drugs in order to maximize efficacy and minimize adverse reactions in the individual patient. However, in many instances, the scientific and clinical evidence is insufficient to support the prescribing decision. When predictive biomarkers are used to guide pharmacotherapy, it is important to secure that decisions are based on solid clinical evidence. Here, the regulatory authorities, especially the FDA, have been at the forefront in relation to regulate this type of biomarker assay in order to secure patient safety. The approval process for companion diagnostics is an example of this effort, where the scientific validity of the biomarker and assay is in focus. With the approaching implementation of the new IVD Regulation, greater attention will also be paid to analytical and clinical validity of biomarker assays in the EU. For any type of predictive biomarker assay, including pharmacogenetic and tumour profiling tests, the clinical evidence needs to be in place before they are used routinely in the clinic.
Effects of Osmolytes on Amyloid-beta Protein Surface Activity and Membrane Interactions

The misfolding and aggregation of proteins into fibrillar aggregates in the brain are linked to the pathogenesis of over 20 neurodegenerative diseases. Specifically, the toxicity and neurodegenerative symptoms of Alzheimer’s disease are directly related to the aggregation of the amyloid-β (Aβ) protein into β-sheet rich insoluble fibrils. However, the mechanism and driving forces of Aβ fibril formation in vivo are still unknown. It has been shown previously that Aβ’s surface activity and favorable interaction with lipid membranes can induce the formation of fibrils, suggesting a possible membrane-based mechanism of Aβ aggregation in Alzheimer’s disease. Unlike dilute solutions used for in vitro experiments, the cellular environment is highly crowded, with macromolecules and osmolytes occupying up to 40% of the cellular volume. The resulting molecular crowding and preferential exclusion modulate the thermodynamics of protein reactions to favor those that reduce total system volume and minimize solvent
Economic evaluation of whole genome sequencing for pathogen identification and surveillance – results of case studies in Europe and the Americas 2016 to 2019

Background Whole genome sequencing (WGS) is increasingly used for pathogen identification and surveillance. Aim We evaluated costs and benefits of routine WGS through case studies at eight reference laboratories in Europe and the Americas which conduct pathogen surveillance for avian influenza (two laboratories), human influenza (one laboratory) and food-borne pathogens (five laboratories). Methods The evaluation focused on the institutional perspective, i.e. the ‘investment case’ for implementing WGS compared with conventional methods, based on costs and benefits during a defined reference period, mostly covering at least part of 2017. A break-even analysis estimated the number of cases of illness (for the example of Salmonella surveillance) that would need to be avoided through WGS in order to ‘break even’ on costs. Results On a per-sample basis, WGS was between 1.2 and 4.3 times more expensive than routine conventional methods. However, WGS brought major benefits for pathogen identification and surveillance, substantially changing laboratory workflows, analytical processes and outbreaks detection and control. Between 0.2% and 1.1% (on average 0.7%) of reported salmonellosis cases would need to be prevented to break even with respect to the additional costs of WGS. Conclusions Even at cost levels documented here, WGS provides a level of additional information that more than balances the additional costs if used effectively. The substantial cost differences for WGS between reference laboratories were due to economies of scale, degree of automation, sequencing technology used and institutional discounts for equipment and consumables, as well as the extent to which sequencers are used at full capacity.
The Buffering Effect of Perceived Organizational Support on the Relationships Among Workload, Work–Family Interference, and Affective Commitment: A Study on Nurses

ABSTRACT Background Minimal research has been conducted to explore the associations among workload, work-to-family conflict, family-to-work conflict, support, and affective commitment. Purpose This study was designed to explore the moderating role of perceived organizational support on the mediating effects of work-to-family conflict, family-to-work conflict in perceived workload, and affective commitment linkage. Methods The data were collected using a self-report survey from 164 nurses working at two public hospitals. The hypothesized model was tested using PROCESS macro. Results Perceived organizational support was found to influence the mediating effect of work-to-family conflict on the linkage between workload and affective commitment, yet not to moderate the mediating effect of family-to-work conflict. The results revealed that workload predicts affective commitment negatively and work-to-family conflict positively. However, perceived organizational support was found to change the effect that workload has on affective commitment. The negative effect of workload on affective commitment was found to be weaker for nurses with adequate organizational support. Conclusions/Implications for Practice Perceived organizational support was found to have both main and buffering effects on the emotional attachment of nurses toward their organizations. The findings support the importance of creating supportive work settings to alleviate the adverse effects on nurses of workload and work–family interference.
Morphological Characteristics of Passive and Active Structures of the Foot Across Populations With Different Levels of Physical Activity.

BACKGROUND Imaging diagnosis plays a fundamental role in the evaluation and management of injuries suffered in sports activities. OBJECTIVE To analyze the differences in the thickness of the Achilles tendon, patellar tendon, plantar fascia, and posterior tibial tendon in the following levels of physical activity: persons who run regularly, persons otherwise physically active, and persons with a sedentary lifestyle. DESIGN Cross-sectional and observational. PARTICIPANTS The 91 volunteers recruited from students at the university and the Triathlon Club from December 2016 to June 2019. The data were obtained (age, body mass index, and visual analog scale for quality of life together with the ultrasound measurements). RESULTS Tendon and ligament thickness was greater in the runners group than in the sedentary and active groups with the exception of the posterior tibial tendon. The thickness of the Achilles tendon was greater in the runners than in the other groups for both limbs (P = .007 and P = .005). This was also the case for the cross-sectional area (P < .01) and the plantar fascia at the heel insertion in both limbs (P = .034 and P = .026) and for patellar tendon thickness for the longitudinal measurement (P < .01). At the transversal level, however, the differences were only significant in the right limb (P = .040). CONCLUSION The thickness of the Achilles tendon, plantar fascia, and patellar tendon is greater in runners than in persons who are otherwise active or who are sedentary.
Solidarity, support and competition among communities of female and male sex workers in Mombasa, Kenya

Abstract Female and male sex workers are at elevated risk for HIV infection, psychological distress and other adverse health outcomes. It is therefore important to understand how sex workers’ social relationships with one another might inform psychosocial support services for this population. We conducted semi-structured interviews to examine the formation and nature of social networks of 25 female and 25 male sex workers recruited from bars and clubs in Mombasa, Kenya. Relationships between and among female and male participants were often formed based on a mutual understanding of the challenging nature of sex work. Both groups described their relationships in terms of friendship and brotherhood/sisterhood and highlighted the following benefits of sex worker social networks: economic benefits, access to information about HIV/STIs and protection, and support against violence from clients and law enforcement agents. Social networks were often threatened by competition for clients and hence could result in conflict. However, sex workers explained that their sense of solidarity and reliance on one another for health, protection and economic well-being helped minimise conflict. The social networks of sex workers could therefore be used to leverage or optimise access to HIV prevention and care.
Hybrid Solar Cells Using HgTe Nanocrystals and Nanoporous TiO2 Electrodes

HgTe nanocrystals are demonstrated to increase the photon‐harvesting efficiency of hybrid solar cells over a broad spectral region between 350 and 1500 nm. Devices combining two solar cell concepts, a solid‐state nanocrystal‐sensitized solar cell and a nanocrystal/polymer‐blend solar cell, are described. These devices give incident photon to current efficiencies up to 10 % at around 550 nm monochromatic irradiation and short‐circuit current densities of 2 mA cm–2 under simulated AM1.5 (100 mW cm–2) illumination (AM: air mass).
Copolymer SAFT Equation of State. Thermodynamic Perturbation Theory Extended to Heterobonded Chains

Thermodynamic perturbation theory of the first order (TPT1) is extended to heterobonded chains, such as heteronuclear and branched copolymers. The TPT1 formalism provides the basis for a copolymer equation of state. This new copolymer equation of state, referred to as Copolymer SAFT (Statistical Associating Fluid Theory), explicitly accounts for the effects of chain heterogeneity and microstructure. In order to illustrate potential future applications, Copolymer SAFT is used to calculate high-pressure cloud points in real polymer solutions of supercritical propane + poly(ethylene-co-butene).
Machine Learning–Based Prediction of Small Intracranial Aneurysm Rupture Status Using CTA-Derived Hemodynamics: A Multicenter Study

BACKGROUND AND PURPOSE: Small intracranial aneurysms are being increasingly detected while the rupture risk is not well-understood. We aimed to develop rupture-risk models of small aneurysms by combining clinical, morphologic, and hemodynamic information based on machine learning techniques and to test the models in external validation datasets. MATERIALS AND METHODS: From January 2010 to December 2016, five hundred four consecutive patients with only small aneurysms (<5 mm) detected by CTA and invasive cerebral angiography (or surgery) were retrospectively enrolled and randomly split into training (81%) and internal validation (19%) sets to derive and validate the proposed machine learning models (support vector machine, random forest, logistic regression, and multilayer perceptron). Hemodynamic parameters were obtained using computational fluid dynamics simulation. External validation was performed in other hospitals to test the models. RESULTS: The support vector machine performed the best with areas under the curve of 0.88 (95% CI, 0.85–0.92) and 0.91 (95% CI, 0.74–0.98) in the training and internal validation datasets, respectively. Feature ranks suggested hemodynamic parameters, including stable flow pattern, concentrated inflow streams, and a small (<50%) flow-impingement zone, and the oscillatory shear index coefficient of variation, were the best predictors of aneurysm rupture. The support vector machine showed an area under the curve of 0.82 (95% CI, 0.69–0.94) in the external validation dataset, and no significant difference was found for the areas under the curve between internal and external validation datasets (P = .21). CONCLUSIONS: This study revealed that machine learning had a good performance in predicting the rupture status of small aneurysms in both internal and external datasets. Aneurysm hemodynamic parameters were regarded as the most important predictors.
The neurocognitive profile of post‐traumatic stress disorder (PTSD), major depressive disorder (MDD), and PTSD with comorbid MDD

Neurocognitive dysfunction has been associated with post‐traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, although PTSD is often comorbid with MDD, there is little neurocognitive work to date on individuals who suffer from both PTSD and MDD. Here, we compared neurocognitive domains in individuals with PTSD, MDD, and comorbid PTSD and MDD with those of healthy controls.
Differential diagnostic and treatment difficulties in a patient with acquired von Willebrand syndrome

ABSTRACT Background Acquired von Willebrand syndrome (AVWS) is a rare, frequently underdiagnosed and underestimated bleeding disorder. Careful personal and family history and late-onset mucocutaneous bleeding could help clarify the etiology of bleeding deficiency. Case presentation An 82-year-old male patient was admitted to our clinic with a severe nosebleed on 30.05. 2018. Laboratory results revealed thrombocytosis, elevated white blood cell count and high LDH. Basic coagulation parameters were normal. He was referred to our clinic, where a bone marrow biopsy was taken. His personal and family history had no mention of bleeding disorders, nor was he on anticoagulant therapy. We detected elevated VWF antigen and decreased VWF ristocetin cofactor activity. Loss of high molecular weight multimers was detected by using agarose gel electrophoresis. These laboratory results were indicative of AVWS. Hydroxyurea treatment was initiated, leading to a gradual decrease in platelet count. The histological examination revealed essential thrombocytosist while mutation analysis was JAK2/CALR/MPL negative. However, due to severe nosebleeds, the patient was hospitalized and needed blood transfusion. A cardiological check-up revealed the progression of aortic valve stenosis. After, balloon-dilation a transcatheter aortic valve implantation was performed. As a result, VWF activity and activity to antigen ratio returned to normal as did multimeric structure. In July 2019, the follow-up examination showed that the patient was in a satisfactory condition, with normal hematological parameters, and no new nosebleed episode occurred Conclusions The patient complained of recurring nosebleeds, which stopped completely after the resolution of both underlying conditions successful cytoreductive treatment of triple-negative ET and transcatheteric aortic valve replacement.
Combining direct current and kilohertz frequency alternating current to mitigate onset activity during electrical nerve block

Objective. Electrical nerve block offers the ability to immediately and reversibly block peripheral nerve conduction and would have applications in the emerging field of bioelectronics. Two modalities of electrical nerve block have been investigated—kilohertz frequency alternating current (KHFAC) and direct current (DC). KHFAC can be safely delivered with conventional electrodes, but has the disadvantage of having an onset response, which is a period of increased neural activation before block is established and currently limits clinical translation. DC has long been known to block neural conduction without an onset response but creates damaging reactive species. Typical electrodes can safely deliver DC for less than one second, but advances in high capacitance electrodes allow DC delivery up to 10 s without damage. The present work aimed to combine DC and KHFAC into a single waveform, named the combined reduced onset waveform (CROW), which can initiate block without an onset response while also maintaining safe block for long durations. This waveform consists of a short, DC pre-pulse before initiating KHFAC. Approach. Simulations of this novel waveform were carried out in the axonal simulation environment NEURON to test feasibility and gain insight into the mechanisms of action. Two sets of acute experiments were then conducted in adult Sprague–Dawley rats to determine the effectiveness of the waveform in mitigating the onset response. Main results. The CROW reduced the onset response both in silico and in vivo. The onset area was reduced by over 90% with the tested parameters in the acute experiments. The amplitude of the DC pulse was shown to be particularly important for effective onset mitigation, requiring amplitudes 6–8 times the DC block threshold. Significance. This waveform can reliably reduce the onset response due to KHFAC and could allow for wider clinical implementation of electrical nerve block.
Correlation of Patient-Reported Outcomes After Periacetabular Osteotomy With Femoral Head Coverage and Acetabular Orientation: A Single-Center Cohort Study

Background: Gaining a better understanding of the underlying pattern of acetabular dysplasia 3-dimensionally can help better guide treatment and optimize clinical outcomes after periacetabular osteotomy (PAO). Purpose: (1) To examine the relationship between femoral head coverage before and after PAO for dysplasia and patient-reported outcome measure (PROM) scores and (2) to assess if the direction/orientation of correction of the acetabulum can be predicted based on the Ottawa classification. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective analysis of a prospectively collected database from a single-center institutional registry of PAO was conducted, and PROM scores at a minimum of 2 years were analyzed. A total of 79 hips (67 patients [56 female]; mean age at surgery, 27.5 years [range, 15.8-53.7 years]) were available for inclusion. According to the Ottawa classification, 54 hips (68.4%) had global deficiency, 15 hips (18.9%) had posterior deficiency, and 10 hips (12.7%) had anterior deficiency. Hip2Norm software was used to analyze the 3-dimensional coverage of the femoral head. Statistical analysis was conducted to look at significant predictors of improvements in PROMs using the minimal clinically important difference (MCID) for the Hip disability and Osteoarthritis Outcome Score (HOOS) Activities of Daily Living subscale. Results: At a mean follow-up of 3.1 years (range, 2.0-7.4 years), all functional outcome scores improved significantly. A postoperative total femoral coverage <75.7%, posterior coverage (PC) <45.2%, and femoral head extrusion index >15.5% were all associated with not reaching the MCID for the HOOS Activities of Daily Living subscale. Multivariate analysis showed that PC was the single most important significant modifier influencing functional outcomes after PAO for the treatment of acetabular dysplasia, with an odds ratio of 6.0 (95% CI, 1.8-20.4; P = .004). One-way analysis of variance showed a significant difference comparing the mean change in radiographic measurements, that is, anterior coverage, PC, and total femoral coverage, per the Ottawa classification (P < .001). Conclusion: Our study demonstrated that postoperative femoral head coverage and acetabular orientation were significant predictors of PROM scores. Classifying acetabular dysplasia into 3 groups based on the plane of instability could optimize the planning of PAO by giving a better understanding of the 3-dimensional deformity.