Miracle-dz/UniFAR-FTUs huggingface dataset:
Photolyase: Dynamics and Mechanisms of Repair of Sun‐Induced DNA Damage

Photolyase, a photomachine discovered half a century ago for repair of sun‐induced DNA damage of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6‐4) pyrimidone photoproducts (6‐4PPs), has been characterized extensively in biochemistry (function), structure and dynamics since 1980s. The molecular mechanism and repair photocycle have been revealed at the most fundamental level. Using femtosecond spectroscopy, we have mapped out the entire dynamical evolution and determined all actual timescales of the catalytic processes. Here, we review our recent efforts in studies of the dynamics of DNA repair by photolyases. The repair of CPDs in three life kingdoms includes seven electron transfer (ET) reactions among 10 elementary steps through initial bifurcating ET pathways, a direct tunneling route and a two‐step hopping path both through an intervening adenine from the cofactor to CPD, with a conserved folded structure at the active site. The repair of 6‐4PPs is challenging and requires similar ET reactions and a new cyclic proton transfer with a conserved histidine residue at the active site of (6‐4) photolyases. Finally, we also summarize our efforts on multiple intraprotein ET of photolyases in different redox states and such mechanistic studies are critical to the functional mechanism of homologous cryptochromes of blue‐light photoreceptors.
Integration of Temperature and Blue‐Light Sensing in Acinetobacter baumannii Through the BlsA Sensor

BlsA is a BLUF photoreceptor present in Acinetobacter baumannii, responsible for modulation of motility, biofilm formation and virulence by light. In this work, we have combined physiological and biophysical evidences to begin to understand the basis of the differential photoregulation observed as a function of temperature. Indeed, we show that blsA expression is reduced at 37°C, which correlates with negligible photoreceptor levels in the cells, likely accounting for absence of photoregulation at this temperature. Another point of control occurs on the functionality of the BlsA photocycle itself at different temperatures, which occurs with an average quantum yield of photoactivation of the signaling state of 0.20 ± 0.03 at 15°C < T < 25°C, but is practically inoperative at T > 30°C, as a result of conformational changes produced in the nanocavity of FAD. This effect would be important when the photoreceptor is already present in the cell to avoid almost instantaneously further signaling process when it is no longer necessary, for example under circumstances of temperature changes possibly faced by the bacteria. This complex interplay between light and temperature would provide the bacteria clues of environmental location and dictate/modulate light photosensing in A. baumannii.
Commentary by Pletsch

The authors of this article address important issues of symptom experiences and quality of life of economically disadvantaged women living with HIV/AIDS. Increasing numbers of women are living with HIV/AIDS, and there is growing evidence that women experience the illness differently than men (Cohen, 2003; Levine, 2002; O’Connell, Skevignton, & Saxena, 2003). There is also substantial evidence that women with HIV/AIDS are at risk for a variety of gynecologic abnormalities including cervical dysplasia, vaginosis, and herpes simplex virus Type 2 (Pereira et al., 2003; Warren et al. 2001), and that health care services need to be attentive to women’s gynecologic needs (Abercrombie, 2003; Massad et al, 2001; Stein et al., 2000, 2001). Uncovering the sometimes complex relationships among cell counts, symptom experiences, and quality of life is important if we are to provide high quality health care to people with HIV/AIDS (Call et al., 2000; Huba et al., 2000; Lechner et al., 2003; Vidrine, Amick, Gritz, & Arduino, 2003; Vosvick et al., 2003). This article provides useful information on the frequency and intensity of a variety of symptoms that women with HIV/AIDS experience and examines several quality of life domains, with an emphasis on physical functioning and role functioning. Although page limitations for manuscripts require authors to be succinct, the generalizability of this article’s findings would be enhanced if the authors had provided the reader with more information about the sample and their rationale for data analysis decisions. The findings would be more useful if the authors provided a more in-depth discussion of the types of symptoms that were most prevalent, how they clustered conceptually, and if there were any special characteristics of this sample that were important in interpreting the findings. The reader is left with a number of unanswered questions about the sample and the data analysis decisions that limit the generalizability of the findings. For example, women are described as low income, however we have no data regarding actual economic resources and how much variation there was among women. Because the primary study variables are symptoms and quality of life, it would be useful to know the distribution of women who were HIV asymptomatic, HIV symptomatic, or had a diagnosis of AIDS. The percentage of women who were “recently hospitalized with AIDS diagnosis” was reported, however it was unclear if the variable was an indicant of degree of illness as represented by being hospitalized, or if it reflected the
Various LED Wavelengths Affected Myofiber Development and Satellite Cell Proliferation of Chick Embryos via the IGF‐1 Signaling Pathway

An effect of monochromatic light illumination on muscle mass has been discovered in chickens; however, its effect on the development of embryonic muscle remains unclear. Our previous studies demonstrated that monochromatic green light promoted satellite cell proliferation and muscle growth in posthatching broilers. In this study, we investigated the effects and mechanisms of monochromatic light exposure on muscle development in late embryogenesis. Seven hundred and fifty fertile broiler eggs were randomly assigned to blue (B‐group), green (G‐group), red (R‐group), white (W‐group) lights or darkness (D‐group) throughout the incubation period. The muscle weight and fiber size were highest in the G‐group compared to the other groups during embryonic days (E) 17 to E20. The proliferation of satellite cells isolated from the G‐group was highest, and in vivo green light remarkably increased the number of proliferating cell nuclear antigen (PCNA)‐positive cells in skeletal muscle. Meanwhile, plasma IGF‐1 was higher (15.5–16.2%) in the G‐group than that in D‐ and R‐groups, and the satellite cells isolated from the G‐group had a more sensitive response to IGF‐1. These findings demonstrate green monochromatic photobiomodulation promoted the muscle growth and satellite cell proliferation was related to the IGF‐1 signaling pathway in late embryogenesis.
Assessing the impact of England's National Health Service R&D Health Technology Assessment program using the “payback” approach

Objectives: This study assesses the impact of the English National Health Service (NHS) Health Technology Assessment (HTA) program using the “payback” framework. Methods: A survey of lead investigators of all research projects funded by the HTA program 1993–2003 supplemented by more detailed case studies of sixteen projects. Results: Of 204 eligible projects, replies were received from 133 or 65 percent. The mean number of peer-reviewed publications per project was 2.9. Seventy-three percent of projects claimed to have had had an impact on policy and 42 percent on behavior. Technology Assessment Reports for the National Institute for Health and Clinical Excellence (NICE) had fewer than average publications but greater impact on policy. Half of all projects went on to secure further funding. The case studies confirmed the survey findings and indicated factors associated with impact. Conclusions: The HTA program performed relatively well in terms of “payback. ” Facilitating factors included the program's emphasis on topics that matter to the NHS, rigorous methods and the existence of “policy customers” such as NICE.
Facile Synthesis of BiOI Nanoparticles at Room Temperature and Evaluation of their Photoactivity Under Sunlight Irradiation

In this study, highly photoactive BiOI nanoparticles (NPs) under sunlight irradiation were synthesized by a facile precipitation method using polyvinylpyrrolidone (PVP) at room temperature. The as‐prepared catalysts were characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transition electron microscopy (TEM), energy‐dispersive X‐ray spectroscopy (EDX), Fourier transform infrared (FTIR) and UV–vis diffuse reflectance spectra (UV–vis DRS). The results of XRD showed that PVP did not have any significant effect on tetragonal crystalline structure of BiOI. Also, using different amounts of PVP in the synthesis led to different morphologies and sizes of BiOI particles. It was found that using 0.2 g of PVP in the synthesis method changed morphology from 1‐μm platelets to NPs with size under 10 nm. In addition, the photocatalytic performance of prepared photocatalysts was evaluated in the photodegradation of reactive blue 19 (RB19) dye under sunlight irradiation. The BiOI synthesized using 0.2 g PVP (BiOI0.2) showed higher degradation efficiency compared to BiOI prepared without any additive. Excellent visible light photocatalytic properties of nano‐scaled BiOI0.2 samples compared to BiOI platelets could be attributed to higher surface‐to‐volume ratio and narrow band‐gap energy of as‐prepared BiOI0.2 NPs.
New Perspectives on an Old Issue: A Comparative MS‐CASPT2 and OM2‐MRCI Study of Polyenes and Protonated Schiff Bases

Polyenic systems are involved in light perception of numerous living organisms. Although a π‐conjugated backbone is a common feature of all polyenes, their photophysics may vary. We provide a comparative quantum mechanical study of low‐lying S1 and S2 excited states in short (3‐5 double bonds) symmetric all‐trans linear polyenes and corresponding protonated Schiff bases. In our investigation, we use the well‐established ab initio multireference CASPT2 approach and benchmark the efficient semiempirical OM2‐MRCI approach against it. For all protonated Schiff bases, MS‐CASPT2 results in two distinct S1 minima with inverted and noninverted bond length pattern, respectively. We find that OM2‐MRCI is a computationally affordable and reliable alternative to MS‐CASPT2 for investigations of polyenic systems, particularly when highly demanding calculations (e.g. excited‐state dynamics) need to be performed.
Lesion Formation in Abraded Human Enamel

Sound human premolars were cut transversely and polished. The polished surface of the buccal enamel was exposed to buffer solutions of different degrees of saturation with respect to hydroxyapatite. The mineral content of the surface layers of artificial lesions created by one particular solution depended on the gradient in solubility and susceptibility for transformation of the enamel mineral. In a series of lesions created by a series of buffer solutions with increasing degree of saturation, a particular mineral content of the surface layer moved inwards, proportional to the maintenance of the strength of the driving force for dissolution and for reprecipitation.
Inflammatory bowel disease increases the risk of atrial fibrillation, particularly during active disease stages. a nationwide cohort study

Purpose: Inflammation plays a role in the development of atrial fibrillation (AF). Thus, inflammatory bowel disease (IBD) may increase the risk of AF. We therefore investigated the risk of AF in patients with IBD in a Danish nationwide cohort. Methods: We included all incident patients with IBD from 1996-2011. Each IBD patient was matched by age and sex with ten population controls. An IBD flare was defined as the first 120 days after either hospital admission, prescription(s) of glucocorticoids or initiation of biological treatment. Persistent activity succeeded flares in cases with repeated glucocorticoid prescriptions or hospitalizations within 120 days of onset of a flare, and remissions started after 120 days without IBD activity. Poisson regression analysis was used to estimate the relative risk (RR) of AF controlling for comorbidity and concomitant medications as time-dependent covariates. Results: We identified 24,527 IBD patients with a mean age of 43.9 years and 236,550 matched controls. A total of 685 IBD patients and 4,390 controls were diagnosed with AF corresponding to incidence rates of 4.16 and 2.70 per 1000 person-years. Patients with IBD had an increased risk of AF (Figure) with age- sex- and calendar-year adjusted RR 1.60 (95% confidence interval [CI] 1.47-1.74) and fully adjusted RR 1.17 (1.08-1.27). During flares and periods with persistent activity the RRs of AF increased to 2.36 (2.03-2.75) and 1.68 (1.36-2.08), respectively. In remission periods the risk of AF was similar to controls and lower (p<0.01) than during flares and persistent activity. [Figure][1] Atrial fibrillation in IBD vs controls Conclusion: IBD is associated with an increased risk of AF particularly during active disease stages. This finding suggests that treatment strategies for AF risk reduction in periods of IBD activity should be explored further. [1]: pending:yes
Genetic profiling in Graves' disease: further evidence for lack of a distinct genetic contribution to Graves' ophthalmopathy.

BACKGROUND Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy (GO), is an autoimmune disease with an environmental and genetic component to its etiology. The genetic contribution to the GO clinical phenotype remains unclear. Previous data from our laboratory and others have suggested that GO has no specific genetic component distinct from GD itself, while other reports have occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and IL23R specifically increase the risk for GO. One of the criticisms of all these reports has been the clinical definition of the GO phenotype as distinct from hyperthyroid GD devoid of clinically significant eye involvement. The objective of this study was to take advantage of a phenotypically pure group of GD patients with GO and examine a series of genes associated with GD to determine if any were more definitively associated with GO rather than Graves' thyroid disease itself. METHODS To further examine whether specific susceptibility genes are associated with GO, we have performed further genetic association studies using highly characterized GO patients, many of whom had undergone orbital decompression surgery for their exophthalmos. We genotyped HLA, CTLA4, IL23R, and TSHR genes in a group of 256 Caucasian patients with severe GO (n=199) and less severe GO (n=57), and 90 patients with GD but no clinically apparent GO. RESULTS We found that the allele and genotype frequencies were not statistically different between GO and non-GO patients for any of the genes and gene combinations assessed. CONCLUSIONS These results provide further evidence that patients with GO do not have a distinct genetic susceptibility to their eye disease and again suggest that environmental and/or epigenetic influences are at play.
Complications of central neck dissection in patients with papillary thyroid carcinoma: results of a study on 1087 patients and review of the literature.

BACKGROUND Prophylactic central neck dissection (CND) has been proposed in the treatment of patients affected by papillary thyroid carcinoma (PTC) with clinically negative neck lymph nodes. The procedure allows pathologic staging of lymph nodes of the central compartment and treatment of the micrometastases. Nevertheless, the morbidity that its routine use adds to the total thyroidectomy must be taken into account. The aim of this study was to characterize the morbidity that CND adds to the total thyroidectomy. METHODS This was a retrospective study of 1087 patients with PTC and clinically negative neck lymph nodes. Patients were divided into three study groups: Group A, total thyroidectomy; Group B, total thyroidectomy and ipsilateral CND; Group C, total thyroidectomy and bilateral CND. Primary endpoints of the study were evaluated by comparing the rates of transient and permanent recurrent laryngeal nerve (RLN) injury and hypoparathyroidism in the three study groups. RESULTS Analysis of data showed no significant differences in the rate of transient (Group A: 3.6%, Group B: 3.9%, and Group C: 5.5%; p=0.404) and permanent (Group A: 1%, Group B: 0.5%, and Group C: 2.3%; p=0.099) RLN injury between the three study groups. Both ipsilateral CND and bilateral CND were associated with a higher rate of transient hypoparathyroidism (Group: A 27.7%, Group B: 36.1%, and Group C: 51.9%; p=0.014; odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.091-2.001; p<0.001; OR: 2.827; 95% CI: 2.065-3.870, respectively). Bilateral CND had a higher rate of permanent hypoparathyroidism (Group A: 6.3%, Group B: 7%, and Group C: 16.2%; p<0.001; OR: 2.860; 95% CI: 1.725-4.743). CONCLUSIONS The increased rates of transient and permanent hypoparathyroidism in our series suggest a critical review of indications for the routine use of prophylactic CND for PTC. Prophylactic CND ipsilateral to the tumor associated with total thyroidectomy may represent an effective strategy for reducing the rate of permanent hypoparathyroidism. Concomitant completion contralateral paratracheal lymph node neck dissection should be performed in presence of lymph node metastasis on intraoperative frozen-section pathology. This approach limits the use of bilateral CND to patients with intraoperative pathological findings of lymph node metastases.
Photosensitizing medications and photocarcinogenesis

Photosensitivity is an exaggerated or abnormal response to ultraviolet (UV) or visible light exposure. Many current medications are known photosensitizers; however, the effects of the sensitization can be subclinical and go unnoticed by the person affected. While some of these drugs are used for short and defined periods, others are used indefinitely for the treatment of chronic disease. The question of whether either of these practices translates into an increased risk of skin cancer is an important one. Numerous medications have real, distinct and well‐elucidated mechanisms that potentiate the development of skin cancer, while with some medications the mechanism for the observed carcinogenesis remains unclear. In this article we will discuss the clinical, mechanistic and epidemiological evidence supporting photochemical genotoxicity and carcinogenesis.
EUROPEAN DRUG REIMBURSEMENT SYSTEMS' LEGITIMACY: FIVE-COUNTRY COMPARISON AND POLICY TOOL

Objectives. In a democratic system, decision makers are accountable for the reasonableness of their decisions. This presumes (i) transparency, (ii) relevance of the decision criteria, (iii) revisability of decisions, and (iv) enforcement/regulation. We aim to (i) evaluate the extent to which drug reimbursement decision-making processes in different contexts meet these conditions and (ii) develop, starting from these findings, a framework for improving the transparency and the relevance of used decision criteria. Methods. We evaluated the Austrian, Belgian, French, Dutch, and Swedish drug reimbursement systems. Based on this evaluation, we developed a framework for improving the transparency of drug reimbursement decision-making processes. It makes explicit the questions often addressed implicitly during decision-making processes as well as criteria for answering each question. Results. Transparency of appraisal processes varies across systems. Justification with explicit criteria is generally limited. Although relevant criteria are similar across systems, their operationalization varies and their role in the appraisal process is not always clear. All systems seem to implicitly address five key questions, relating to (i) the medical, therapeutic, and societal need for treatment; (ii) preparedness to pay for treating the condition as a principle and (iii) for using the treatment under consideration; (iv) preparedness to pay more compared with alternatives; and (v) actual willingness to pay from public resources. Conclusions. Transparency of the appraisal process can be improved by using an explicit decision framework. Systematic use of such a framework enhances consistency across decisions, allows justification of value judgments, and thus enhances legitimacy of societal decision making.
Adult worm‐specific IgE/IgG4 balance is associated with low infection levels of Schistosoma mansoni in an endemic area

Field studies have suggested an immune‐mediated mechanism associated with resistance to Schistosoma mansoni infection. Overall, levels of specific IgE have been correlated with resistance to infection, whereas levels of IgG4 have been associated with susceptibility. This study aimed to evaluate serum levels of soluble adult worm antigen preparation (SWAP)‐specific IgE and IgG4 in relation to current infection in a large casuistic of individuals living in an endemic area of schistosomiasis in Bahia, Brazil. The prevalence of S. mansoni infection was 37·7% and the mean parasite burden was 55·4 (0–2100) epg/faeces. There was no significant difference in the levels of SWAP‐specific IgE in individuals with different parasite burden, whereas high producers of parasite‐specific IgG4 presented higher parasite burden when compared to low IgG4 producers. Additionally, S. mansoni parasite load was positively correlated with the levels of specific IgG4 or total IgE. No significant correlation was observed between parasite burden and SWAP‐specific IgE. Nevertheless, SWAP‐specific IgE/IgG4 ratio was higher in uninfected or lightly infected individuals (1–99 epg/faeces) than in heavily infected ones (≥400 epg/feces). These findings highlight the important role of IgE/IgG4 ratio in the resistance to infection, which could be useful for further studies in schistosomiasis vaccine candidates.