Miracle-dz/UniFAR-FTUs huggingface dataset:
Organization of Work Factors Associated with Work Ability among Aging Nurses

The United States (U.S.) workforce is aging. There is a paucity of literature exploring aging nurses’ work ability. This study explored the work-related barriers and facilitators influencing work ability in older nurses. We conducted a qualitative descriptive study of aging nurses working in direct patient care (N = 17). Participants completed phone or in-person semi-structured interviews. We used a content analysis approach to analyzing the data. The overarching theme influencing the work ability of aging nurses was intrinsically motivated. This was tied to the desire to remain connected with patients at bedside. We identified factors at the individual, unit-based work level and the organizational level associated with work ability. Individual factors that were protective included teamwork, and feeling healthy and capable of doing their job. Unit-based level work factors included having a schedule that accommodated work-life balance, and one’s chronotype promoted work ability. Organizational factors included management that valued worker’s voice supported work ability.
Role of glucocorticoid- and monoamine-metabolizing enzymes in stress-related psychopathological processes

Abstract Glucocorticoid signaling is fundamental in healthy stress coping and in the pathophysiology of stress-related diseases, such as post-traumatic stress disorder (PTSD). Glucocorticoids are metabolized by cytochrome P450 (CYP) as well as 11-β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2). Acute stress-induced increase in glucocorticoid concentrations stimulates the expression of several CYP sub-types. CYP is primarily responsible for glucocorticoid metabolism and its increased activity can result in decreased circulating glucocorticoids in response to repeated stress stimuli. In addition, repeated stress-induced glucocorticoid release can promote 11βHSD1 activation and 11βHSD2 inhibition, and the 11βHSD2 suppression can lead to apparent mineralocorticoid excess. The activation of CYP and 11βHSD1 and the suppression of 11βHSD2 may at least partly contribute to development of the blunted glucocorticoid response to stressors characteristic in high trait anxiety, PTSD, and other stress-related disorders. Glucocorticoids and glucocorticoid-metabolizing enzymes interact closely with other biomolecules such as inflammatory cytokines, monoamines, and some monoamine-metabolizing enzymes, namely the monoamine oxidase type A (MAO-A) and B (MAO-B). Glucocorticoids boost MAO activity and this decreases monoamine levels and induces oxidative tissue damage which then activates inflammatory cytokines. The inflammatory cytokines suppress CYP expression and activity. This dynamic cross-talk between glucocorticoids, monoamines, and their metabolizing enzymes could be a critical factor in the pathophysiology of stress-related disorders. Lay summary Glucocorticoids, which are produced and released under the control by brain regulatory centers, are fundamental in the stress response. This review emphasizes the importance of glucocorticoid metabolism and particularly the interaction between the brain and the liver as the major metabolic organ in the body. The activity of enzymes involved in glucocorticoid metabolism is proposed to play not only an important role in positive, healthy glucocorticoid effects, but also to contribute to the development and course of stress-related diseases.
Petri Nets Model of Implicit Data and Control in Program Code

To describe the implicit data and the implicit control in program code, CNets, one extension of Petri nets, is applied. By data view nets and control view nets, data and control of the program code are modeled. Based on the CNets specification, interactions between data flow and control flow, relations among data, operations, and resources are also captured respectively. Meanwhile, mapping rules from CNets specification to Petri nets are presented. According to the rules, from CNets specification, properties of the program are analysized through Petri nets techniques without a running a program.
Level of motor, sensory and functional impairment from stroke at admission and hospital discharge in Brazil

ABSTRACT Primary Objective: To compare the level of motor, sensory and functional impairment of individuals hospitalized in a stroke unit in Brazil at the time of admission and the profile observed at hospital discharge. Design: Observational and longitudinal outcome study. Methods and Procedure: We assessed 41 patients with ischemic stroke at admission and hospital discharge by using the National Institute of Health Stroke Scale (NIHSS), Fugl-Meyer Physical Performance Scale (FM), Functional Independence Measure (FIM) and Modified Rankin Scale (mRS) and divided in the group that received or not the thrombolytic therapy. Were used wilcoxon and spearman tests. Results: Significant differences were found between admission and hospital discharge assessment (p < .0001) indicating clinical improvement for individuals submitted to thrombolytic treatment. A moderate correlation was observed for total FM and total FIM (ρ = 0.729; p value<.0001); total FM and motor FIM (ρ = 0.705; p value<.0001); and a moderate negative correlation for NIHSS and total FM (ρ = −0.709; p value<.0001). Strong correlation between motor FIM and total FIM was also observed (ρ = 0.972; p value<.0001). Conclusions: Clinical severity was softened along the hospitalization period. The clinical, motor, sensory and functional characterization enlarges the understanding of the stroke sequelae, besides monitoring the deficits and the level of disability in this population in Brazil.
Direct Anterior Total Hip Arthroplasty.

Introduction In theory, the direct anterior approach offers the only path to performing minimally invasive total hip arthroplasty in an intermuscular, internervous plane. Step 1 Position and Drape Patient Careful positioning is necessary to complete this procedure on a standard operating room table. Step 2 Superficial Exposure Incise the fascia overlying the tensor fasciae latae and lift up the anterior edge, avoiding the perforating vessels. Step 3 Deep Exposure The hip is flexed 30° during the deep dissection. Step 4 Prepare Acetabulum and Implant Acetabular Component Ream the acetabulum in 10° to 15° of anteversion with an abduction angle of 40° to 45°. Step 5 Prepare Femur and Implant Femoral Component Use offset broaches to access the femur and prevent perforation through the greater trochanter. Step 6 Trial and Close Specifically check for impingement of bone on the implant with the hip flexed 90°. Results This approach has been used successfully for total hip arthroplasty for decades. What to Watch For IndicationsContraindicationsPitfalls & Challenges.
Endoplasmic Reticulum Export of GPI-Anchored Proteins

Protein export from the endoplasmic reticulum (ER) is an essential process in all eukaryotes driven by the cytosolic coat complex COPII, which forms vesicles at ER exit sites for transport of correctly assembled secretory cargo to the Golgi apparatus. The COPII machinery must adapt to the existing wide variety of different types of cargo proteins and to different cellular needs for cargo secretion. The study of the ER export of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs), a special glycolipid-linked class of cell surface proteins, is contributing to address these key issues. Due to their special biophysical properties, GPI-APs use a specialized COPII machinery to be exported from the ER and their processing and maturation has been recently shown to actively regulate COPII function. In this review, we discuss the regulatory mechanisms by which GPI-APs are assembled and selectively exported from the ER.
Draft Genome Sequence of Geotoga petraea Strain HO-Geo1, Isolated from a Petroleum Reservoir in Russia

The draft genome sequence of Geotoga petraea strain HO-Geo1, a bacterium isolated from production water of the Vostochno-Anzirskoe petroleum reservoir in Russia, is presented. The genome of strain HO-Geo1 is annotated for elucidation of the metabolic potential and its possible function in the subsurface microbial community and biotechnological application. ABSTRACT The draft genome sequence of Geotoga petraea strain HO-Geo1, a bacterium isolated from production water of the Vostochno-Anzirskoe petroleum reservoir in Russia, is presented. The genome of strain HO-Geo1 is annotated for elucidation of the metabolic potential and its possible function in the subsurface microbial community and biotechnological application.
The cost burden of falls in people with glaucoma in National Health Service Hospital Trusts in the UK

Abstract Aims: Falls have devastating consequences in older people with a considerable cost burden. Glaucoma is a risk factor for falls, and patients with glaucoma who fall are at high risk of hospital admission. The aim was to quantify the cost burden of falls to NHS Trusts in people with glaucoma in the UK. Methods: Financial data were used to identify non-elective episodes and associated costs from 2012 to 2018, for all admissions where glaucoma was recorded as a secondary diagnosis and admissions for falls (all, with and without a glaucoma secondary diagnosis). A secondary diagnosis is only recorded by the admitting clinician if it is clinically relevant; therefore, a secondary diagnosis of glaucoma was used as a proxy for glaucoma as a contributory factor to falls. Limitations: Use of financial records means that data on other falls risk factors was unavailable and we cannot be certain that glaucoma was the only relevant factor in all falls. Although this methodology is imperfect, case capture was biased towards cases with clinically significant glaucoma, and financial data is robust. Potential coding errors mean that we may have excluded patients in whom glaucoma was a factor in their fall. Results: At Maidstone and Tunbridge Wells (MTW) NHS Trust, 11.7% (95% confidence intervals [CI] = 10.7–12.8) of admissions for falls were in patients with a secondary diagnosis of glaucoma. This extrapolates to an estimated annual 10,056 admissions at a cost of £28.6 million across the UK. This is an under-estimate of cost, as A&E attendance without admission and outpatient appointments are excluded. Conclusions: At MTW, glaucoma potentially plays a part in around one in eight falls resulting in hospital admission, at considerable personal and financial cost. It is suggested that further work should explore early diagnosis of glaucoma, treatment, and mitigation of falls risk.
Self-reported Daily, Weekly, and Monthly Cannabis Use Among Women Before and During Pregnancy

Key Points Question Has the frequency of cannabis use among pregnant women in the year before and during pregnancy increased in recent years? Findings In this serial cross-sectional study of 367 403 pregnancies among women in Kaiser Permanente Northern California who were universally screened for self-reported cannabis use as part of standard prenatal care, annual relative rates of daily, weekly, and monthly cannabis use in the year before pregnancy and during pregnancy increased from 2009 to 2017. Relative rates of self-reported daily cannabis use in the year before and during pregnancy increased fastest. Meaning Results of this study demonstrate that frequency of cannabis use in the year before pregnancy and during pregnancy has increased among women in Northern California in recent years, with relative rates of daily cannabis use increasing most rapidly.
Parallel G-triplexes and G-hairpins as potential transitory ensembles in the folding of parallel-stranded DNA G-Quadruplexes

Abstract Guanine quadruplexes (G4s) are non-canonical nucleic acids structures common in important genomic regions. Parallel-stranded G4 folds are the most abundant, but their folding mechanism is not fully understood. Recent research highlighted that G4 DNA molecules fold via kinetic partitioning mechanism dominated by competition amongst diverse long-living G4 folds. The role of other intermediate species such as parallel G-triplexes and G-hairpins in the folding process has been a matter of debate. Here, we use standard and enhanced-sampling molecular dynamics simulations (total length of ∼0.9 ms) to study these potential folding intermediates. We suggest that parallel G-triplex per se is rather an unstable species that is in local equilibrium with a broad ensemble of triplex-like structures. The equilibrium is shifted to well-structured G-triplex by stacked aromatic ligand and to a lesser extent by flanking duplexes or nucleotides. Next, we study propeller loop formation in GGGAGGGAGGG, GGGAGGG and GGGTTAGGG sequences. We identify multiple folding pathways from different unfolded and misfolded structures leading towards an ensemble of intermediates called cross-like structures (cross-hairpins), thus providing atomistic level of description of the single-molecule folding events. In summary, the parallel G-triplex is a possible, but not mandatory short-living (transitory) intermediate in the folding of parallel-stranded G4.
Effect of the Tryptophan Hydroxylase Inhibitor Telotristat on Growth and Serotonin Secretion in 2D and 3D Cultured Pancreatic Neuroendocrine Tumor Cells

Serotonin, a biologically active amine, is related to carcinoid syndrome in functioning neuroendocrine tumors (NETs). Telotristat ethyl is a novel inhibitor of the tryptophan hydroxylase (TPH), a key enzyme in the production of serotonin. While its use in patients with carcinoid syndrome and uncontrolled diarrhea under somatostatin analogs (SSAs) has been recently approved, in vitro data evaluating its effectiveness are lacking. For this reason, we aimed to evaluate the effect of telotristat as monotherapy, and in combination with SSAs, on proliferation and secretion in a NET cell line model. The human pancreatic NET cell lines BON-1/QGP-1 were used as 2D and 3D cultured models; somatostatin receptor and TPH mRNA expression, as well as the potential autocrine effect of serotonin on tumor cell proliferation using a 3D culture system were evaluated. Telotristat decreased serotonin production in a dose-dependent manner at a clinically feasible concentration, without affecting cell proliferation. Its combination with pasireotide, but not with octreotide, had an additive inhibitory effect on serotonin secretion. The effect of telotristat was slightly less potent, when BON-1 cells were co-treated with octreotide. Octreotide and pasireotide had no effect on the expression of TPH. Telotristat did not have an effect on mRNA expression of somatostatin receptor subtypes. Finally, we showed that serotonin did not have an autocrine effect on NET cell proliferation on the 3D cell model. These results suggest that telotristat is an effective drug for serotonin inhibition, but the effectiveness of its combination with SST2 (somatostatin receptor subtype 2)-preferring SSA should be evaluated in more detail.
Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia

Purpose: To investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) and the underlying molecular mechanism. Experimental Design: Using both FLT3-ITD cell lines and primary patient samples, Annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11–derived xenograft mouse model was used to assess in vivo efficacy of the combination of gilteritinib and venetoclax. Lentiviral overexpression of Mcl-1 was used to confirm its role in cell death induced by midostaurin or gilteritinib with venetoclax. Changes of Mcl-1 transcript levels were assessed by RT-PCR. Results: The combination of midostaurin or gilteritinib with venetoclax potently and synergistically induces apoptosis in FLT3-ITD AML cell lines and primary patient samples. The FLT3 inhibitors induced downregulation of Mcl-1, enhancing venetoclax activity. Phosphorylated-ERK expression is induced by venetoclax but abolished by the combination of venetoclax with midostaurin or gilteritinib. Simultaneous downregulation of Mcl-1 by midostaurin or gilteritinib and inhibition of Bcl-2 by venetoclax results in “free” Bim, leading to synergistic induction of apoptosis. In vivo results show that gilteritinib in combination with venetoclax has therapeutic potential. Conclusions: Inhibition of Bcl-2 via venetoclax synergistically enhances the efficacy of midostaurin and gilteritinib in FLT3-mutated AML. See related commentary by Perl, p. 6567
Nkx2-5 defines a subpopulation of pacemaker cells and is essential for the physiological function of the sinoatrial node in mice

ABSTRACT The sinoatrial node (SAN), the primary cardiac pacemaker, consists of a head domain and a junction/tail domain that exhibit different functional properties. However, the underlying molecular mechanism defining these two pacemaker domains remains elusive. Nkx2-5 is a key transcription factor essential for the formation of the working myocardium, but it was generally thought to be detrimental to SAN development. However, Nkx2-5 is expressed in the developing SAN junction, suggesting a role for Nkx2-5 in SAN junction development and function. In this study, we present unambiguous evidence that SAN junction cells exhibit unique action potential configurations intermediate to those manifested by the SAN head and the surrounding atrial cells, suggesting a specific role for the junction cells in impulse generation and in SAN-atrial exit conduction. Single-cell RNA-seq analyses support this concept. Although Nkx2-5 inactivation in the SAN junction did not cause a malformed SAN at birth, the mutant mice manifested sinus node dysfunction. Thus, Nkx2-5 defines a population of pacemaker cells in the transitional zone. Despite Nkx2-5 being dispensable for SAN morphogenesis during embryogenesis, its deletion hampers atrial activation by the pacemaker. Summary: Mouse lines in which two distinct pacemaker cell populations can be distinguished reveal a novel role for Nkx2-5 in pacemaking function in the sinoatrial node.
Draft Genome Sequences of 16 Strains of Escherichia Cryptic Clade II Isolated from Intertidal Sediment in Hong Kong

The genus Escherichia includes several cryptic clades. Among them, the members of cryptic clade II have rarely been found, and their genome sequences remain largely uninvestigated. Here, we report the draft genome sequences of 16 strains of Escherichia cryptic clade II that were isolated from intertidal sediment in Hong Kong. ABSTRACT The genus Escherichia includes several cryptic clades. Among them, the members of cryptic clade II have rarely been found, and their genome sequences remain largely uninvestigated. Here, we report the draft genome sequences of 16 strains of Escherichia cryptic clade II that were isolated from intertidal sediment in Hong Kong.
Optimising pacemaker therapy and medical therapy in pacemaker patients for heart failure: protocol for the OPT-PACE randomised controlled trial

Introduction Permanent artificial pacemaker implantation is a safe and effective treatment for bradycardia and is associated with extended longevity and improved quality of life. However, the most common long-term complication of standard pacemaker therapy is pacemaker-associated heart failure. Pacemaker follow-up is potentially an opportunity to screen for heart failure to assess and optimise patient devices and medical therapy. Methods and analysis The study is a multicentre, phase-3 randomised trial. The 1200 participants will be people who have a permanent pacemaker for bradycardia for at least 12 months, randomly assigned to undergo a transthoracic echocardiogram with their pacemaker check, thereby tailoring their management directed by left ventricular function or the pacemaker check alone, continuing with routine follow-up. The primary outcome measure is time to all-cause mortality or heart failure hospitalisation. Secondary outcomes include external validation of our risk stratification model to predict onset of heart failure and quality of life assessment. Ethics and Dissemination The trial design and protocol have received national ethical approval (12/YH/0487). The results of this randomised trial will be published in international peer-reviewed journals, communicated to healthcare professionals and patient involvement groups and highlighted using social media campaigns. Trial registration number NCT01819662.
Associations between genetic polymorphisms of TLRs and susceptibility to tuberculosis: A meta-analysis

Some genetic association studies have tried to investigate potential associations between TLR polymorphisms and tuberculosis. However, the results of these studies have not been consistent. Thus, we performed the present meta-analysis to explore associations between TLR polymorphisms and tuberculosis in a larger combined population. A systematic literature research of PubMed, Web of Science and Embase was performed to identify eligible studies for combined analyses. I2 statistics were employed to assess between-study heterogeneities. If I2 was >50%, random-effects models were used to combine the data. Otherwise, fixed-effects models were applied for synthetic analyses. A total of 39 genetic association studies were included in the analyses. The combined analyses showed that TLR1 rs4833095, TLR1 rs5743557, TLR1 rs5743596, TLR2 rs3804099, TLR2 rs5743704, TLR2 rs5743708, TLR6 rs5743810 and TLR8 rs3764879 polymorphisms were significantly associated with susceptibility to TB in the overall population. Further subgroup analyses revealed similar significant findings for TLR1 rs4833095, TLR1 rs5743557, TLR1 rs5743596, TLR1 rs5743618, TLR2 rs3804099, TLR2 rs5743704, TLR2 rs5743708, TLR4 rs4986790 and TLR4 rs4986791 polymorphisms in certain ethnicities. In conclusion, our findings support that these TLR polymorphisms may be used to identify individuals at high risk of developing tuberculosis.
A prefix brachial plexus with two trunks and one anterior cord.

The brachial plexus presents a great variability in formation, division and branching pattern. Its variants are of immense importance during axillary and arm surgery and nerve blockade. The current case highlights a unilateral atypical formation of brachial plexus, the so called prefix, in which the C₄ root contributed a large branch to the superior trunk and further anastomosis with the inferior trunk. Thus, the prefix or high brachial plexus consisted of a superior and inferior trunk and one anterior cord. Coexisted neural and arterial variations are also discussed in relation to the data literature.