Miracle-dz/UniFAR-FTUs huggingface dataset:
Red, orange, green: Light- and Temperature-dependent Color Tuning in a Cyanobacteriochrome.

Cyanobacteriochromes (CBCRs) are photoreceptor proteins that photoconvert between two parent states and thereby regulate various biological processes. An intriguing property is their variable UV-vis absorption that covers the entire spectral range from the far-red to the near-UV region and thus makes CBCRs promising candidates for optogenetic applications. Here, we have studied Slr1393, a CBCR that photoswitches between red- and green-absorbing states (Pr and Pg, respectively). Using UV-vis absorption, fluorescence, and resonance Raman (RR) spec-troscopy, a further orange-absorbing state O600 was identified which is in thermal equilibrium with Pr. The different absorp-tion properties of the three states were attributed to different lengths of the conjugated -electron system of the phycocya-nobilin (PCB) chromophore. In agreement with available crystal structures and supported by quantum mechanics/molecular mechanics (QM/MM) calculations the most extended conjuga-tion holds for Pr whereas it is substantially reduced in Pg. Here, the two outer pyrrole rings D and A are twisted out of the plane defined by the inner pyrrole rings B and C. For the O600 state, the comparison of the experimental RR spectra with QM/MM-calculated spectra indicate a partially distorted ZZZssa geometry in which ring A is twisted, while ring D and the adjacent me-thine bridge display essentially the same geometry as Pr. The quantitative analysis of temperature-dependent spectra yields an enthalpy barrier of ca. ~30 kJ/mol for the transition from Pr to O600. This reaction is associated with the movement of a conserved tryptophan (Trp) residue from the chromophore binding pocket to a solvent exposed position.
Commissioning and Beam Characterization of The First Gantry-Mounted Accelerator Pencil Beam Scanning Proton System.

PURPOSE To present and discuss beam characteristics and commissioning process of the first gantry-mounted accelerator single room pencil beam scanning (PBS) proton system. METHODS The Mevion HYPERSCAN employs a design configuration with a synchrocyclotron mounted on the gantry to eliminate the traditional beamline and a nozzle that contains the dosimetry monitoring chambers, the energy modulator (Energy Selector (ES)), and an Adaptive Aperture (AA). To characterize the beam, we measured the integrated depth dose (IDDs) for 12 energies, from highest energy of 227 MeV down to 28 MeV with a range difference ~2 cm between the adjacent energies, using a large radius Bragg peak chamber; single-spot profiles in air at five locations along the beam central axis using radiochromic EBT3 film and cross compared with a scintillation detector; and determined the output using a densely packed spot map. To access the performance of AA, we measured interleaf leakage and the penumbra reduction effect. Monte Carlo simulation using TOPAS was performed to study spot size variation along the beam path, beam divergence, and energy spectrum. RESULTS This proton system is calibrated to deliver 1 Gy dose at 5 cm depth in water using the highest beam energy by delivering 1 MU/spot to a 10 ×10 cm2 map with a 2.5 mm spot spacing. The spot size in air varies from 4 mm to 26 mm from 227 MeV to 28 MeV at the isocenter plane. The beam divergence of 28 MeV beam is ~52.7 mrad, which is nearly 22 times that of 227 MeV proton beam. The binary design of the ES has resulted in shifts of the effective SSD towards the isocenter as the energy is modulated lower. The peaks of IDD curves have a constant 80%-80% width of 8.4 mm at all energies. The interleaf leakage of the AA is less than 1.5% at the highest energy; and the AA can reduce the penumbra by 2 mm to 13 mm for the 227 and 28 MeV energies at isocenter plane in air. CONCLUSIONS The unique design of the HYPERSCAN proton system has yielded beam characteristics significantly different from that of other proton systems in terms of the Bragg peak shapes, spot sizes and the penumbra sharpening effect of the AA. The combination of the ES and AA has made PBS implementation possible without using beam transport line and range shifter devices. Different considerations may be required in treatment planning optimization to account for different design and beam characteristics.
Diversity of extracellular matrix morphology in vertebrate skeletal muscle

Existing data suggest the extracellular matrix (ECM) of vertebrate skeletal muscle consists of several morphologically distinct layers: an endomysium, perimysium, and epimysium surrounding muscle fibers, fascicles, and whole muscles, respectively. These ECM layers are hypothesized to serve important functional roles within muscle, influencing passive mechanics, providing avenues for force transmission, and influencing dynamic shape changes during contraction. The morphology of the skeletal muscle ECM is well described in mammals and birds; however, ECM morphology in other vertebrate groups including amphibians, fish, and reptiles remains largely unexamined. It remains unclear whether a multilayered ECM is a common feature of vertebrate skeletal muscle, and whether functional roles attributed to the ECM should be considered in mechanical analyses of non‐mammalian and non‐avian muscle. To explore the prevalence of a multilayered ECM, we used a cell maceration and scanning electron microscopy technique to visualize the organization of ECM collagen in muscle from six vertebrates: bullfrogs (Lithobates catesbeianus), turkeys (Meleagris gallopavo), alligators (Alligator mississippiensis), cane toads (Rhinella marina), laboratory mice (Mus musculus), and carp (Cyprinus carpio). All muscles studied contained a collagen‐reinforced ECM with multiple morphologically distinct layers. An endomysium surrounding muscle fibers was apparent in all samples. A perimysium surrounding groups of muscle fibers was apparent in all but carp epaxial muscle; a muscle anatomically, functionally, and phylogenetically distinct from the others studied. An epimysium was apparent in all samples taken at the muscle periphery. These findings show that a multilayered ECM is a common feature of vertebrate muscle and suggest that a functionally relevant ECM should be considered in mechanical models of vertebrate muscle generally. It remains unclear whether cross‐species variations in ECM architecture are the result of phylogenetic, anatomical, or functional differences, but understanding the influence of such variation on muscle mechanics may prove a fruitful area for future research.
Comparison of Raja Isteri Pengiran Anak Saleha Appendicitis and modified Alvarado scoring systems in the diagnosis of acute appendicitis

The diagnosis of acute appendicitis (AA) is mainly dependent on clinical evaluation. There are several scoring systems developed for an accurate and early diagnosis of AA. Modified Alvarado score is one of the most common systems. The Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) scoring system was developed in 2010. The aim of this study is to evaluate and compare the accuracy of modified Alvarado and RIPASA scoring systems for the diagnosis of AA.
How I investigate chronic myelomonocytic leukemia

The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 109/L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of “overlapping” myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing “dysplastic” features and others a predominant “proliferative” phenotype. Accounting for this diversity, two variants of CMML are recognized: “dysplastic” CMML defined by WBC < 13 × 109/L and “proliferative” CMML with WBC ≥ 13 × 109/L often showing features mimicking a myeloproliferative neoplasm. Although not an official WHO category, the “oligomonocytic” variant of CMML is defined by relative monocytosis with an absolute monocyte count of 0.5‐0.9 × 109/L. It can be considered a “pre‐phase,” as it frequently anticipates the development of an overt, classic CMML. In an attempt at improving disease prognostication, the blast count based grading system for CMML of the WHO 2008 Classification has been expanded in 2016 to include a new “CMML‐0” category. Lastly, the large body of knowledge on the molecular events occurring in CMML has been used to assist diagnosis and assess prognosis. Despite the step forwards, diagnosis of CMML still remains one of exclusion as no clinical, pathologic or molecular findings are specific for this disease. The current review brings insight into the spectrum of CMML and provides practical advice to approach suspected cases of CMML.
Metabolic changes in mice cardiac tissue after low-dose irradiation revealed by 1H NMR spectroscopy

Abstract Ionizing radiation may cause cardiotoxicity not only at high, but even at low (considered as harmless) doses, yet the molecular mechanisms of the heart’s response to low doses are not clear. In this work, we used high-resolution nuclear magnetic resonance (NMR) spectroscopy to detect the early and late effects of radiation on the metabolism of murine hearts. The hearts of C57Bl/6NCrl female mice were irradiated in vivo with single 0.2 Gy or 2 Gy doses using 6 MV photons, then tissues were collected 48 h and 20 weeks after exposure. The most distinct changes in the profile of polar metabolites were detected 48 h after irradiation with 2 Gy, and included increased levels of pantothenate and glutamate as well as decreased levels of alanine, malonate, acetylcarnitine, glycine and adenosine. Significant effects of the 2 Gy dose were also observed 20 weeks after irradiation and included decreased levels of glutamine and acetylcarnitine when compared with age-matched controls. Moreover, several differences were observed between hearts irradiated with 2 Gy and analyzed either 48 h or 20 weeks after the exposure, which included changes in levels of acetylcarnitine, alanine, glycine, glutamate, glutamine, formate, myo-inositol and trimethylamine. No statistically significant effects induced by the 0.2 Gy dose were observed 20 weeks after irradiation. In general, radiation-affected compounds were associated with energy metabolism, fatty acid beta-oxidation, oxidative stress and damage to cell structures. At the same time, radiation-related effects were not detected at the level of tissue histology, which indicated a higher sensitivity of metabolomics-based tests for cardiac tissue response to radiation.
Double‐Layered M2e‐NA Protein Nanoparticle Immunization Induces Broad Cross‐Protection against Different Influenza Viruses in Mice

The development of a universal influenza vaccine is an ideal strategy to eliminate public health threats from influenza epidemics and pandemics. This ultimate goal is restricted by the low immunogenicity of conserved influenza epitopes. Layered protein nanoparticles composed of well‐designed conserved influenza structures have shown improved immunogenicity with new physical and biochemical features. Herein, structure‐stabilized influenza matrix protein 2 ectodomain (M2e) and M2e‐neuraminidase fusion (M2e‐NA) recombinant proteins are generated and M2e protein nanoparticles and double‐layered M2e‐NA protein nanoparticles are produced by ethanol desolvation and chemical crosslinking. Immunizations with these protein nanoparticles induce immune protection against different viruses of homologous and heterosubtypic NA in mice. Double‐layered M2e‐NA protein nanoparticles induce higher levels of humoral and cellular responses compared with their comprising protein mixture or M2e nanoparticles. Strong cytotoxic T cell responses are induced in the layered M2e‐NA protein nanoparticle groups. Antibody responses contribute to the heterosubtypic NA immune protection. The protective immunity is long lasting. These results demonstrate that double‐layered protein nanoparticles containing structure‐stabilized M2e and NA can be developed into a universal influenza vaccine or a synergistic component of such vaccines. Layered protein nanoparticles can be a general vaccine platform for different pathogens.
Investigation of burnout syndrome and job‐related risk factors in veterinary technicians in specialty teaching hospitals: a multicenter cross‐sectional study

Abstract Objectives To investigate veterinary technician burnout and associations with frequency of self‐reported medical error, resilience, and depression and job‐related risk factors. Design Cross‐sectional observational study using an anonymous survey conducted between November 2017 and June 2018. Setting Four referral teaching hospitals in the United States and Canada. Subjects A total of 344 veterinary technicians were invited to participate. Response rate was 95%. Overall 256 surveys were ultimately analyzed. Interventions Burnout, depression, and resilience were measured using validated instruments. Respondents reported perceptions of workload, working environment, and medical error frequency. Associations between burnout and factors related to physical work environment, workload and schedule, compensation package, interpersonal relationships, intellectual enrichment, and exposure to ethical conflicts were analyzed. Measurements and Main Results Burnout, characterized by high emotional exhaustion, depersonalization, and low sense of personal accomplishment was common, and was positively associated with perceived medical errors, desire to change career, and depression. Burnout levels on all 3 burnout subscales were higher in this population than previously reported for a contemporaneous group of trauma nurses working with human patients (P < 0.05). Burnout was negatively associated with resilience. Respondents’ feelings of fear or anxiety around supervisor communications, perception that patient load was too high to allow for excellent patient care, and perceived lack of available assistance during sudden workload increases were all associated with burnout. Conclusions Burnout in veterinary technicians is common and is associated with numerous undesirable outcomes. Work‐related interventions to reduce burnout should focus on improving supervisor relationships and maintaining an appropriate patient:caregiver ratio.
Regulation of rhythmic behaviors by astrocytes

Glial astrocytes of vertebrates and invertebrates are important modulators of nervous system development, physiology, and behavior. In all species examined, astrocytes of the adult brain contain conserved circadian clocks, and multiple studies have shown that these glial cells participate in the regulation of circadian behavior and sleep. This short review summarizes recent work, using fruit fly (Drosophila) and mouse models, that document participation of astrocytes and their endogenous circadian clocks in the control of rhythmic behavior.
Características clínicas y evolución de niños con desnutrición aguda

Malnutrition is the set of clinical manifestations and anthropometric and biochemical alterations caused by an inadequate intake or the incorrect biological utilization (or both) of macro and micronutrients, causing that the nutritional requirements are not met. A prospective observational study was conducted from September 1 to November 30, 2010 in patients with acute malnutrition who were admitted to the Pediatric Department of the Dr. Antonio Penados del Barrio Hospital, in San Benito, Peten, Guatemala. The objective was to describe the clinical characteristics and evolution of acutely malnourished children. The study included all patients who met the criteria for acute, moderate or severe malnutrition. Of them, 62.5% were admitted with a weight-height index, as measured by the Z-score, of less than -3 (severe acute malnutrition), and 37.5% had a Z-score between -2 and -3 (moderate acute malnutrition); 75% of children were discharged alive with a normal nutritional status. Marasmic kwashiorkor was the most frequently clinical form of severe malnutrition observed in children between one and two years of age, without showing an incidence linked to gender. Pallor, anemia, glossitis, cheilitis and diarrhea were signs frequently observed at admission. The low educational level of the parents, the low per capita income, food taboos and mother's age (under 18) are conditions likely to favor the development of acute malnutrition; and it is after the sixth day of admission that the weight gain of children progressing to nutritional recovery becomes evident.
Associations of white matter hyperintensities with cognitive decline: A longitudinal study

White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI‐2 dataset from August 2010 to May 2017.
Sex Differences in the Expression of the α5 Subunit of the GABAA Receptor in Alcoholics with and without Cirrhosis of the Liver.

INTRODUCTION Alcohol exposure alters the expression of a large number of genes, resulting in neuronal adaptions and neuronal loss, but the underlying mechanisms are largely unknown. MiRNAs are gene repressors that are abundant in the brain. A recent study identified ~35 miRNAs that are up-regulated in the prefrontal cortex of human alcoholics and predicted to target genes that are down-regulated in the same region. Although interactions between alcohol-responsive miRNAs and their target genes have been predicted, few studies have validated these predictions. METHODS We measured the expression of GABAA α5 mRNA in the prefrontal and motor cortices of human alcoholics and matched controls using real time PCR. The expression of miR-203 was measured in a subset of these cases. The predicted interaction of miR-203 and GABRA5 was validated for miR-203 using a luciferase reporter assay. RESULTS In both frontal and motor cortices the expression of GABAA α5 was significantly lower in cirrhotic alcoholics compared with controls. Further, the pattern of expression between the groups was significantly different between males and females. The expression of miR-203 was higher in the prefrontal cortex of cirrhotic alcoholics compared with controls and uncomplicated alcoholics. These differences were particularly marked in female cases. Co-transfection of GABRA5 with miR-203 in HEK293T cells reduced luciferase reporter activity. CONCLUSION There are sex differences in the expression of GABAA α5 and miR-203 in the brain of human alcoholics which are particularly marked in alcoholics with cirrhosis of the liver. Further, miR-203 may mediate the changes in expression of this GABAA receptor isoform that is brought about by alcohol exposure.
Leptin controls glutamatergic synaptogenesis and NMDA-receptor trafficking via Fyn kinase regulation of NR2B.

Activation of the leptin receptor, LepRb, by the adipocytokine/neurotrophic factor leptin in the central nervous system has pro-cognitive and anti-depressive effects. Leptin has been shown to increase glutamatergic synaptogenesis in multiple brain regions. In contrast, mice that have a mutation in the LepRb gene show abnormal synapse development in the hippocampus, as well as deficits in cognition and increased depressive-like symptoms. Leptin increases glutamatergic synaptogenesis, in part, through enhancement of NMDA receptor function; yet the underlying signaling pathway is not known. In this study, we examine how leptin regulates surface expression of NR2B-containing NMDA receptors in hippocampal neurons. Leptin stimulation increases NR2BY1472 phosphorylation, which is inhibited by the Src family kinase inhibitor, PP1. Moreover, we show that Fyn, a member of the Src family kinases, is required for leptin stimulated NR2BY1472 phosphorylation. Furthermore, inhibiting Y1472 phosphorylation with either a dominant negative Fyn mutant or an NR2B mutant that lacks the phosphorylation site (NR2BY1472F), blocks leptin stimulated synaptogenesis. Additionally, we show that LepRb forms a complex with NR2B and Fyn. Taken together these findings expand our knowledge of the LepRb interactome and the mechanisms by which leptin stimulates glutamatergic synaptogenesis in the developing hippocampus. Comprehending these mechanisms is key for understanding dendritic spine development and synaptogenesis, alterations of which are associated with many neurological disorders.
A Qualitative Assessment of the Living Donor Navigator Program to Identify Core Competencies and Promising Practices for Implementation

Introduction: The best strategy to increase awareness of and access to living kidney donation remains unknown. To build upon the existing strategies, we developed the Living Donor Navigator program, combining advocacy training of patient advocates with enhanced health-care systems training of patient navigators to address potential living donor concerns during the evaluation process. Herein, we describe a systematic assessment of the delivery and content of the program through focus group discussion. Methods: We conducted focus groups with 9 advocate participants in the Living Donor Navigator program to identify knowledge, skills, and abilities needed for both advocates and navigators. We focused on 2 organizational levels: (1) the participant level or the advocacy training of the advocates and (2) the programmatic level or the support role provided by the navigators and administration of the program. Findings: From 4 common themes (communication, education, support, and commitment), we identified several core competencies and promising practices, at both the participant and programmatic levels. These themes highlighted the potential for several improvements of program content and delivery, the importance of cultural sensitivity among the Living Donor navigators, and the opportunity for informal caregiver support and accountability provided by the program. Discussion: These competencies and promising practices represent actionable strategies for content refinement, optimal training of advocates, and engagement of potential living donors through the Living Donor Navigator program. These findings may also assist with program implementation at other transplant centers in the future.