Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
traumatic arterial occlusion following major or minor blunt trauma , especially in the absence of any other bony injury , is a rare phenomenon .
motor - scooter handlebar syndrome is one such type of arterial occlusion affecting vascular structures following direct blow by a handlebar of a motorbike or bicycle to the groin .
given their superficial course at this location , femoral vessels are the most common vascular structures affected . in all instances ,
injury to iliac vessels remains exceedingly rare , given its posterior position within the pelvis , representing only 0.4% of vascular injuries . in this case , we highlight a delayed presentation of external iliac artery occlusion secondary to  motor - scooter handlebar syndrome , in a paediatric patient .
pathophysiology and management of vascular injuries in the paediatric population vary significantly compared with the adult population .
additional factors which need to be considered include : smaller vessel size or vessel spasm , higher risk of infection , tendency for re - stenosis and continuing growth .
we review previous paediatric cases of this unusual vascular injury to highlight the pathology and most appropriate management option .
a 15-year - old male presented to the emergency department following a direct blow from his bicycle handlebars to his groin .
his abdominal examination was unremarkable , except for a small abrasion and visible mass in his right groin .
after exclusion of other abdominal or chest injuries , he was discharged on the same day with a diagnosis of right groin haematoma and follow - up in 68 weeks .
his symptoms included pain and paraesthesia in his right buttocks on mobilization > 100 m. he was found to have absent peripheral pulses in his right leg , although it appeared well perfused with a normal capillary refill .
an arterial doppler ultrasound showed a right external iliac artery thrombus occluding the proximal two - thirds of the vessel .
a computed tomography scan of the abdomen and pelvis with intravenous contrast identified complete occlusion of the right external iliac artery 1 cm beyond its origin . however , the common femoral artery and profunda femoris remained patent via collaterals ( fig .  1 ) .

he underwent a right external iliac thromboendarterectomy with patch repair using a saphenous vein graft .
a suprainguinal incision was initially made in attempt to expose the proximal external iliac artery .
due to its extent , retrieval of the entire thrombus was incomplete and a second groin incision near the junction of the common femoral with external iliac ( at the inguinal ligament level ) was required .
the patient subsequently underwent a proximal and distal thrombectomy , and the arteriotomy was extended between the two incisions identifying an intimal stricture with significant fibrosis ( fig .  2 ) .
an intimal flap was identified in the distal region and tacked down with a 7 - 0 prolene suture .
the long saphenous vein was harvested and the defect closed with patch repair extending from proximal iliac to proximal femoral vessel .
at the initial 2-week follow - up , the vessels remained patent and patient was progressing well .
subsequently , regular biannual follow - up was planned to monitor for any longer - term complications .

figure  2:occlusion of right external iliac artery 1 cm below its origin ( white arrow ) .
occlusion of right external iliac artery 1 cm below its origin ( white arrow ) .
 motor - scooter handlebar syndrome is an uncommon form of arterial blunt injury following a direct blow by the handlebar of motorbikes or bicycles .
only a handful of paediatric cases have been reported [ 1 , 2 , 47 ] . the common femoral vessel is the most commonly affected vascular structure .
a common site for these injuries is at the inguinal ligament , where the femoral artery is superficial and courses anterior to the superior pubic ramus and femoral head . as such , it is prone to compression between the handlebar and posterior osseous structures .
in addition , it is a relatively immobile structure , tethered by arterial branches , periadventitial connective tissue and the femoral sheath .
they proposed that a circumferential tear of the intima leads to dissection and prolapse of the inner aortic layers , causing complete luminal occlusion .
, patients may remain asymptomatic until a period of growth spurt or they resume more rigorous physical activity .
this can lead to delay in the diagnosis , and a high index of suspicion needs to be maintained to avoid ischaemic complications such as limb length discrepancy [ 8 , 9 ] .
in such instances , it is important to rule out any secondary occlusion of the femoral artery and vein that may predispose to the development of thrombosis within these vessels .
duplex sonography should be carried out to assess flow velocities and waveform characteristics in these patients , and is especially suited to the paediatric population as they have reduced abdominal fat , and there is no radiation .
identified ultrasound , in the right hands , to be highly sensitive ( 100% ) and specific ( 97.5% ) for the detection of arterial injuries when compared with surgical findings .
open arterial thromboendarterectomy with graft or patch repair is the standard of care for such cases in trauma centres .
previously documented cases include patch repair or bypass using saphenous vein , bovine pericardium and synthetic material [ 13 , 5 , 6 ] .
one case was successfully treated with iv heparinzation alone . however , in most injuries , the presence of significant groin haematoma may limit anticoagulation , requiring more urgent operative re - vascularization . in our patient , delayed presentation and presence of significant collaterals meant definitive operative management could be planned as a semi - elective procedure .
the role of endovascular intervention in this paediatric population has previously been documented mainly as a temporizing measure for revascularization [ 4 , 5 ] .
used a nitinol stent in the distal superficial femoral artery of a 13-year - old patient whose arterial and venous calibre at the time of injury were of inappropriate size for reconstruction .
the main disadvantage of endovascular interventions in paediatric patients is the constantly enlarging calibre of the vessel with a fixed stent diameter .
this can predispose to complications such as restenosis , stent fracture , stent dislocation and acute on chronic ischaemia . as a result , future vascular reconstruction may be compromised and in extreme cases , this may progress to significant ischaemia and even limb loss .
we provide an unusual cause of external iliac occlusion secondary to bicycle handlebar injury to the groin .
all patients presenting with groin injury from this mechanism should be carefully investigated with duplex sonography and monitored for risk of vascular injury .
the presence of collaterals , particularly in the paediatric population , can lead to delay in diagnosis .
literature seems to advocate open primary surgery for management of these injuries ; however , endovascular and conservative medical management have also been used successfully .
the latter two were contraindicated in our patient and open surgery was the most appropriate option .
long - term follow - up , beyond the 12-month period , is needed , particularly in relation to known vascular complications including pseudoaneurysms , arteriovenous fistula formation and restenosis .

Answer:
arterial occlusion following blunt trauma is an uncommon occurrence .
 we report an unusual case of delayed external iliac artery occlusion in a young male following blunt abdominal injury .
 he was successfully treated with thromboendarterectomy and saphenous vein patch repair .
 there have only been a handful of documented cases occurring in the paediatric population .
 all patients presenting with groin injury from this mechanism should be carefully investigated and monitored for risk of vascular injury .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
positron emission tomography ( pet ) is a non - invasive imaging technique used to diagnose neurological and neuropsychiatric disorders .
this method facilitates longitudinal studies of various animal models of alzheimer 's disease , cerebral ischemia , depression , epilepsy , parkinson 's disease , and schizophrenia .
this compound is a radioactive analogue of glucose and altered fdg uptake indicates metabolic changes of neuronal activity in the brain .
application of fdg - pet in rodents for neuroscience research may be limited by unwanted extracranial accumulation of fdg in the harderian gland . unlike humans , small laboratory rodents have harderian glands that show strong fdg uptake within the orbit near the frontal region of the brain .
however , one major secretory product of the gland is porphyrin , which affects photoreception and lubrication of the eyeball .
fdg uptake in the harderian gland varies greatly depending on study conditions prior to pet imaging such as the use of anesthesia during the uptake period .
moreover , other radioactive tracers like c - pib and f - fallypride reportedly accumulate in the harderian gland as well .
this characteristic of the harderian gland makes it difficult to obtain exact measurements of fdg uptake near the frontal brain region because it is impossible to account for the radioactive spillover coming from the adjacent harderian gland . to resolve these problems , surgical procedures for harderian adenectomy ( ha )
since the mouse brain is significantly smaller compared to rat brain , the additive effect of the harderian gland on fdg uptake measurement is much greater .
the purposes of the present study were to develop a surgical procedure for ha in mice and to assess the effectiveness of this procedure for improving fdg - pet .
adult balb / c mice ( 22.0  1.9 g ; orientbio , korea ) were used for all experiments .
two mice were used for unilateral ha , and six mice underwent bilateral ha and control operations , respectively .
the experimental procedure was approved by the institutional animal care and use committee of konkuk university , korea .
ha was performed in mice anesthetized intraperitoneally with zoletil ( 90 mg / kg ; virbac , france ) and xylazine ( 10 mg / kg ; bayer , germany ) .
the whiskers were clipped , and then the conjunctival sac and periocular skin were disinfected with povidone - iodine diluted ( 1 : 50 ) in saline .
mice were placed in a lateral recumbent position and the nictitating membrane was pulled toward the lateral canthus using serrated micro - dissecting forceps ( fig .
at the base of the nictitating membrane , the medially protruding , cream - colored harderian gland could be seen under the thin conjunctival tissue ( fig .
the conjunctival tissue that covered the gland was incised using the tip of a surgical blade .
once removed , the space between the eye and orbital rim was examined for residual glandular tissue . during the resection procedure ,
a small amount of bleeding occurred but stopped once slight pressure was applied with a cotton swab .
postoperative care was immediately provided and performed once a day for the next 3 days .
ophthalmic antibiotic ointment ( terramycin ; pfizer , usa ) and solcoseryl eye gel ( solcorin ; hanlim pharm , korea ) were applied for protection against infection and to lubricate the eyes .
an analgesic ( ketoprofen , 5 mg / kg ; unibiotech , korea ) was also administered subcutaneously daily for 3 days .
the adenectomized mice were subjected to fdg - pet scans on postoperative days 5 , 10 , 15 , and 30 .
fdg ( 300 ci ; korea institute of radiological and medical sciences , korea ) was injected via the lateral tail vein while the mice were anesthetized with 2% isoflurane ( jw pharmaceutical , korea ) .
the mice were positioned on the scanning bed , and pet was performed for 20 min in an inveon pet / ct system ( siemens healthcare , usa ) .
the acquired pet emission data were reconstructed using a fourier re - binning algorithm with three span and 31 ring difference , and ordered subsets expectation maximization 2d algorithm with 16 subsets and four iterations . in order to improve the anatomical localization of fdg uptake in the brain , computed tomography ( ct )
the ct images were acquired with 70 kvp , 500 a , and 200 msec exposure times for each step ( inveon ; siemens healthcare ) .
cone - beam reconstruction was performed with four down - sample factors using bilinear interpolation and shepp.logan filters as previously described . in order to demonstrate the influence of the harderian gland on fdg uptake in specific brain regions , statistical parametric mapping ( spm5 ; wellcome trust centre for neuroimaging institute of neurology , uk )
pet images were realigned to a template image so that the static bounding box could be used to tightly crop the region of interest .
the template image was created from the mean image , which was realigned and provided an average representation of all images .
the normalize function determines the transformation that minimizes the differences between two images by minimizing the sum of squares of intensity differences . during normalization ,
16 nonlinear warping iterations and trilinear interpolation of the images were performed . to improve normalization accuracy , we used a full affine transformation and nonlinear deformations , which facilitate the correction of subtle differences between subjects .
global calculation was performed using standard mean voxel values . using this method , voxels with values less than 1/8 of the overall mean value were deemed extracranial . for the statistical analysis
, we defined t contrast and p value adjustments to the control associated with significantly active regions and rest regions ( p < 0.005 ) . in order to compare regional standard uptake values ( suvs ) affected by ha ,
suv from brain regions including areas of removed harderian glands , frontal brain and the cerebellum were measured .
then the changes of suvs of the regions in relation to postoperative time were statistically analyzed using one - way anova and post - hoc analysis ( prism ver .
when the last pet / ct scan was completed on postoperative day 30 , a visual limb - placing test was performed to evaluate visual acuity and determine if any complication had arisen following the ha .
the whisker - clipped mice were lifted by the tail over the wire bar lid of a mouse cage to a height of 20 cm and then lowered onto the lid within a second .
mice with normal vision extended their forelimbs toward the lid before their noses reached it .
the ha mice recovered from surgery without any postoperative complications and the incision site healed without suturing .
all adenectomized mice were found to have normal visual acuity according to the visual placing test , indicating there were no surgical complications .
strong fdg uptake of the harderian gland was observed in the intact side and radioactive spillover into the brain was also apparent ( fig .
this result suggests that excess signals emitted from the harderian gland interfere with the net measurement of brain fdg uptake , especially in the frontal brain region .
bilateral ha efficiently eliminated extracranial accumulation of fdg in the harderian gland and subsequent radioactive spillover into the brain ( fig .
3 ) . in particular , pet images of the ha mice showed more defined frontal regions of the brain than those of mice that did not undergo ha .
analyses of suvs revealed significant reductions in the regions of harderian gland and frontal brain ( fig .
after bilateral ha , fdg uptake in the regions of the removed harderian glands was significantly reduced starting on postoperative day 5 ( figs .
the reduction in fdg uptake was approximately 55% , and the left and right harderian glands both showed similar levels of reduction .
suvs for the frontal brain region decreased significantly from postoperative day 10 since harderian gland fdg accumulation was eliminated ( fig .
we also measured suvs for the cerebellum and the entire brain region but no statistical differences were found ( fig .
these results indicate that the effect of the harderian gland on fdg - pet analysis was limited to the frontal brain region .
to localize the brain regions affected by harderian gland fdg uptake , we carried out a statistical analysis using the spm tool .
we were able to obtain parametric maps for mice with intact harderian glands and the adenectomized animals . when parametric maps were overlaid on a pet template , regions that had significantly high fdg uptake ( fig .
results of the spm analysis concur with those obtained for manually measured suvs ( figs .
our study demonstrates that ha in mice is a simple and effective method which enables accurate measurement of fdg uptake in the frontal brain region .
we found that the surgical procedure used for rat ha was equally effective in mice   although more caution is required for successful surgeries in the latter species .
for instance , bleeding must be strictly controlled because blood obstructs views of the limited surgical area that is available in mice .
the shape of the resected harderian glands should be carefully checked to avoid potential tearing during resection .
this is because any residual harderian gland left behind may result in an inaccurate fdg uptake reading along with the additional concern that the gland will regenerate .
moreover , the remaining tissue may cause inflammation that in turn could increase fdg uptake over a short - term period . the simple surgical procedure performed in our study
can be carried out by non - veterinarians and should take no more than 5 min . if the surgery is successful , the animal should recover readily without any postsurgical complications including vision impairment . a limitation associated with fdg - pet scanning
is known as the " partial volume effect " , which stems from the finite spatial resolution of the images during sampling and reconstruction .
a partial volume effect can distort both the contour and signal intensity of images for an actual subject .
due to the partial volume effect , small pieces of tissues that accumulate high level of fdg such as harderian glands could appear larger than the actual size and obscure images of the brain during pet imaging .
interference attributed to harderian gland radioactive spillover in the rodent brain has previously been described in rats and mice .
thus , the adverse effects of harderian gland fdg uptake are an unavoidable issue since anesthesia is essential for obtaining pet scans of rodents .
we found that ha in mice was feasible and had the same effect as it did in rats .
after ha , strong fdg uptake signals were excluded from the regions of the gland and distorted fdg - pet images were corrected .
it should be pointed out that it took at least 10 days before significant differences in suvs were achieved .
we were also interested in assessing the range of signal spillover in the brain due to harderian gland fdg uptake .
using spm analysis , we were able to demonstrate the additive effect that the harderian gland has on measuring fdg uptake in the frontal brain region .
our results support a previous finding that fdg uptake by the harderian gland results in a slight over - estimation of fdg uptake in the frontal lobe of rats .
we found that the level of fdg uptake stabilized starting 10 days after the surgery and was maintained for the remainder of the study .
this result suggests that the glandular tissue did not regenerate , which is important for long - term experiments . in conclusion
when performed prior to pet scanning of mice brains , ha may be useful for visualizing the frontal lobe with 18f - fdg micro pet / ct imaging .

Answer:
positron emission tomography ( pet ) using 2-deoxy-2-[18f ] fluoro - d - glucose ( fdg ) as a radioactive tracer is a useful technique for in vivo brain imaging .
 however , the anatomical and physiological features of the harderian gland limit the use of fdg - pet imaging in the mouse brain .
 the gland shows strong fdg uptake , which in turn results in distorted pet images of the frontal brain region .
 the purpose of this study was to determine if a simple surgical procedure to remove the harderian gland prior to pet imaging of mouse brains could reduce or eliminate fdg uptake .
 measurement of fdg uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact harderian gland distorts frontal brain region images .
 spatial parametric measurement analysis demonstrated that the presence of the harderian gland could prevent accurate assessment of brain pet imaging .
 bilateral harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative day 10 .
 harderian adenectomy did not cause any post - operative complications during the experimental period .
 these findings demonstrate the benefits of performing a harderian adenectomy prior to pet imaging of mouse brains .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Sirtuin 2 Regulates Protein LactoylLys Modifications

Paper sections:

Post-translational modifications (PTMs) expand the functional proteome by regulating enzyme structure and function.[1] Many PTMs are derived from intermediates produced during cell metabolism and can serve as sensors for metabolic feedback providing proper nutrients to maintain cell growth and homeostasis.[1b, 1c] Due to their critical role in preserving homeostasis, site-specificity and abundance are tightly regulated, often through enzymatic addition ('writers') and removal ('erasers')[1c]. Mounting evidence, however, points to significant roles for non-enzymatic PTMs in the regulation of transcription, metabolism, and signaling.[2] We recently identified a PTM derived from the glyoxalase cycle intermediate, lactoylglutathione (LGSH) (Figure 1).[2b] When glycolytic flux exceeds the capacity of the glyoxalase cycle, glyoxalase 2 (GLO2), the rate limiting enzyme, becomes overwhelmed resulting in the accumulation of LGSH and subsequent non-enzymatic acylation of protein Lys residues (i.e. lactoylLys) (Figure 1).[2b] This modification is enriched on glycolytic enzymes, serving as a negative feedback mechanism for glycolysis.[2b] Coinciding with our report, Zhang, et al. observed lactoylLys modifications on histones, linking this modification to inflammatory signaling.[3]

Due to the novelty of this PTM, little is known about their regulation. With the non-enzymatic acyl-transfer mechanism defined in our report[2b] lactoylLys modifications would presumably accumulate in the absence of a dedicated 'eraser' protein. Thus, we hypothesized that a molecular 'eraser' protein(s) must exist for this PTM. LactoylLys modifications contain the necessary acyl-moiety required for the deacylase enzymes, sirtuins.[2b] Sirtuins play a role in both metabolism and inflammation through the regulation of Lys PTMs.[4] The sirtuin family is comprised of seven NAD+-dependent enzymatic deacylases (SIRT1-7), defined broadly by their subcellular localization (Figure 2A).[5] As we previously reported, our proteomic inventory of lactoylLys-modified proteins revealed an enrichment for glycolytic enzymes,[2b] suggesting the cytosolic sirtuins (SIRT1 and SIRT2) as potential candidates for a lactoylLys eraser. SIRT2 recognizes a more diverse group of substrates; furthermore, SIRT2 plays a regulatory role in both glycolysis and inflammation.[4a-c, 5a, 6] While SIRT2 is primarily localized to the cytosol in cells, it can translocate to the nucleus to interact with acylated chromatin.[5, 6b, 7] This substrate promiscuity and subcellular localization make SIRT2 a likely enzymatic deacylase for lactoylLys modifications.

To investigate this hypothesis, we screened the activity of recombinant sirtuins (SIRT1-7) against a lactoylated peptide from a known lactoylated protein, pyruvate kinase M2 (PKM2) (Figure 2B).[2b] This Lys residue (EIPAE-K*-VFLAQ) is also reported to be acetylated and regulated by SIRT2.[6a] The acyl transfer from LGSH to Lys residues defined in our previous work occurs at the carbonyl carbon rather than at the chiral carbon; thus, we predict the lactoylLys modification outlined in our report is generated in the D orientation in the same manner as D-lactate formation.[2b] In contrast, the hypothesized mechanism reported by Zhao et al. suggests enzymatic addition through L-lactyl-CoA, thus yielding L-lactoylLys modifications.[3]

As shown in Figure 2B, SIRT1, 2, 3, and 5 removed their canonical acetylated peptide. The L- enantiomer of lactoylLys, however, displayed significantly reduced removal with SIRT1 and 5 while SIRT2 was able to remove the L-enantiomer. In contrast, all SIRTs displayed minimal activity towards the D-enantiomer. To control for non-enzymatic hydrolysis of the acyl moiety, peptides were incubated without recombinant enzyme (CTRL, Figure 2B) or without NAD+ (Figure S1). A kinetic analysis confirms these findings; SIRT2 catalyzes the deacylation of the acetyl peptide at a faster rate than the lactoylated peptides (Figure 2C, S2). In further support of Figure 2B, SIRT2 displayed a greater propensity for the L-enantiomer vs the D-enantiomer, whereby steady-state could not be achieved, resulting in a large Km and standard error (Figure 2C, S2). This data suggests that SIRT2 is capable of removing the L- enantiomer suggesting this to be the predominant form in vivo. Further investigation is needed to determine the enantiomeric species generated from this non-enzymatic acyl transfer from LGSH.

To further investigate the interaction of SIRT2 and lactoylLys, we performed molecular docking experiments (Figure 3). This docking provides in silico insight into the enantiomeric preference of SIRT2 for lactoylated substrates. Unsurprisingly, docking of an acetylLys peptide to the catalytic pocket of SIRT2 results in the acetyl group being placed in a catalytically competent conformation. The acetyl oxygen points toward NAD+, able to attack the C1' of the nicotinamide ribose ring with a distance of 4.3 Å (Figure 3A). Docking of this peptide modified with L-lactoylLys results in the same catalytically favorable conformation for the L-lactoyl group, with the oxygen of the lactoyl carbonyl also oriented toward the nicotinamide ribose ring of NAD+ with a distance of 4.1 Å (Figure 3B). However, molecular docking of the D-lactoylLys peptide results in a different orientation within the catalytic pocket of SIRT2 with the oxygen of the lactoyl carbonyl 6.4 Å from the C1' of the nicotinamide ribose ring of NAD+. D-lactoylLys is positioned with the lactoyl hydroxyl pointing toward NAD+ and the oxygen of the lactoyl carbonyl pointing away from the nicotinamide ribose ring of NAD+ (Figure 3C), resulting in a conformation that is catalytically incompetent for deacylation. The positioning of the lactoyl group within the catalytic pocket of SIRT2 may explain the enhanced propensity for deacylation of L- over D-lactoylLys by SIRT2.

LactoylLys PTMs are dependent on the intracellular concentrations of LGSH.[2b] As GLO2 is the only reported enzyme to hydrolyze LGSH,[8] we generated SIRT2−/− cell lines in wildtype (WT) and GLO2−/− HEK293 cells using CRISPR-Cas9 (Figure 4A).[2b] To evaluate the abundance of lactoylated PTMs in each cohort, we performed reactivity-based protein profiling using an alkyne analog of methylglyoxal (aMGO).[9] Cells were treated with 50 μM aMGO for 6h, which is consistent with our previous report.[2b] An evaluation of whole cell lysates reveals protein labeling in GLO2−/− cells. Cells lacking both GLO2 and SIRT2, however, displayed a marked elevation over GLO2−/− alone (Figure 4B). These effects are more pronounced in chromatin fractions isolated from each cohort, indicative of tighter SIRT2 regulation on chromatin (Figure 4C).

Lastly, to quantify elevated abundance of lactoylLys in the SIRT2−/−/GLO2−/− cell line we used stable isotope labeling of amino acids in cell culture (SILAC) and QuARKMod (a method for the quantitative analysis of arginine (R) and lysine (K) modifications)[2b, 10] in cells treated with high glucose (25 mM, Figure 4D). GLO2−/− cells were cultured in 'heavy' media containing 13C615N2 Lys and 13C615N4 Arg and SIRT2−/−/GLO2−/− cells were cultured in 'light' media containing natural abundance isotope amino acids. Both cell lines were treated with high glucose to evaluate the impact of lactoylLys PTMs in the context of increased glycolytic flux. As shown in Figure 4E, SIRT2−/−/GLO2−/− cells have a 5.4-fold elevation in lactoylLys modifications and no significant changes in the MGO derived modifications CEL, MG-H, and CEA compared to GLO2−/− cells indicating SIRT2's role as an eraser of lactoylLys PTMs.

Here, we present the first report of a lactoylLys eraser. LactoylLys modifications play regulatory roles in situations of elevated glycolytic flux, which are found in both hyperglycemic and inflammatory states.[2b, 3] SIRT2 regulates a diverse array of physiological and pathophysiological processes, including inflammation, response to infections, cell metabolism, ageing, cell structure, oxidative stress, and neurological disorders.[4, 11] Consistent with a lack of lactoylLys modifications on histones in our published proteomic inventory,[2b] our results show only SIRT2−/−/GLO2−/− chromatin have dramatically elevated levels of labeled proteins, indicating tighter regulation by SIRT2 on chromatin. In addition to acetylation, SIRT2 regulates Lys benzoylation and 4-oxo-2-nonenal modifications on histones, further indicating a role for SIRT2 PTM regulation at the chromatin level.[12] Collectively, these data provide evidence for the enzymatic regulation of non-enzymatically-derived protein PTMs. Future work will be dedicated to identifying the site-specificity of this regulation in vitro and in vivo.

Answer: Post-translational modifications (PTMs) play roles in both physiological and pathophysiological processes through the regulation of enzyme structure and function. We recently identified a novel PTM, lactoylLys, derived through a non-enzymatic mechanism from the glycolytic by-product, lactoylglutathione. Under physiologic scenarios, glyoxalase 2 prevents the accumulation of lactoylglutathione and thus lactoylLys modifications. What dictates the site-specificity and abundance of lactoylLys PTMs, however, remains unknown. Here, we report sirtuin 2 as a lactoylLys eraser. Using chemical biology and CRISPR-Cas9, we show that SIRT2 controls the abundance of this PTM both globally and on chromatin. These results address a major gap in our understanding of how non-enzymatic PTMs are regulated and controlled.


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a 72-year - old patient who had undergone bilateral uneventful cataract surgery 6 years ago , presented with visual loss in her left eye .
patient had a medical history of multiple intravitreal and periocular steroid injections for the treatment of recalcitrant uveitis that was diagnosed 21 years ago .
her visual acuity decreased to hand motion in left eye , and slit - lamp biomicroscopy revealed in - the - bag iol with an intact posterior capsule , and severe flare in the anterior chamber .
an unclear image of macular edema was hardly detected on flourescein angiography ( fa ) that revealed flue images of posterior - segment obscured by media opacity .
after obtaining a signed informed consent , we scheduled to perform the intravitreal ozurdex application under the sterile conditions of the operation room .
a drop of 0.5% topical proparacaine hydrochloride with a drop of 5% povidone iodine was installed before the patient underwent an uncomplicated intravitreal dexamethasone implant application .
after significant regression of inflammatory cells secondary to uveitis , mild macular edema and an epiretinal membrane were precisely demonstrated with both optical coherence tomography and fa at 2 weeks after ozurdex application . on the postoperative 5 week , best corrected visual acuity ( bcva ) was improved to 0.4 logmar , and slit - lamp examination revealed the implant mislocated just behind the iol in an intact capsular bag , although there was no reaction in the anterior chamber , and no corneal edema was observed [ fig
it was thought that such implant anteriorly migrated toward into the posterior chamber through weak zonules in the present case as she had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber iol .
slit - lamp biomicroscopy revealed the dexamethasone implant mislocated just behind the intraocular lens in an intact capsular bag , and localized in the lower center of the visual axis ( white arrow ) any repositioning procedure was not considered since no sign of corneal edema or iop rise was present , as well as patient did not have any complaints although dexamethasone implant mislocated in the lower center of the visual axis .
close follow - up was scheduled for the case in order to find out any signs of anterior segment pathology . in the affected eye ,
bcva and iop were found as 0.5 logmar and 17 mmhg with a quiescent anterior chamber and a clear cornea at the 4 month of postoperative follow - up , besides dexamethasone implant completely degraded .
steroid - induced ocular complications such as cataract formation and iop elevation have been more commonly reported according to the accelerating ozurdex application in the treatment of macular edema .
anterior migration of dexamethasone implant has also been published as a rare complication in the literature .
migration of ozurdex into the anterior chamber was firstly described by pardo - lpez et al . in a patient with iris fixated iol .
after the patient had been referred with blurred vision in his left eye at the postoperative 3 week , authors noticed anterior migration of the implant with a diffuse corneal edema .
patient had to be undergone corneal transplantation since corneal edema did not resolve even though surgical removal of the implant from the anterior chamber was performed .
jonas and schmidbauer reported dislocation of a steroid implant into the anterior chamber in an aphakic vitrectomized eye .
vela et al . also reported the migration of ozurdex into the anterior chamber in a patient who previously underwent cataract surgery with iris - claw iol implantation .
the anterior migration of the ozurdex implant can cause complications such as secondary corneal decompensation . in these cases ,
bansal et al . published the migration of the implant into the anterior chamber in three noninfectious posterior uveitic eyes with the history of postlensectomy - vitrectomy aphakia .
authors reported that the implant was relocated in the vitreous cavity in two of the cases .
nonsurgical management of a dislocated dexamethasone implant into the anterior chamber with supine positioning after pharmacologic pupillary dilation was described by kishore and schaal .
published the scleral fixation of dexamethasone intravitreal implant with 10 - 0 nonabsorbable polypropylene suture in an angle - supported iol implanted case in order to prevent the risk of anterior segment complications associated with the migration of such implant into the anterior chamber .
it was recommended that dexamethasone implant which migrated into the anterior chamber ought to be removed as soon as possible in cases with incipient corneal edema .
on the other hand , no corneal edema was reported in patients with late migration of such intravitreally injected implant .
mentioned that only the patients in whom dexamethasone implant anteriorly migrated into the anterior chamber within 3 weeks after the intravitreal application developed corneal edema in their series .
any sign of corneal edema also did not occur in our case who was faced with the anterior migration of such implant 5 weeks after the uncomplicated intravitreal application .
anterior migration of a dexamethasone implant in eyes without perfect zonular or the posterior capsular integrity after cataract surgery , and with a history of the prior vitrectomy has been well - defined .
reported five patients with an anteriorly migrated dexamethasone implant despite within the same lens and capsular status , although they had previous uncomplicated dexamethasone implant injections without any anterior chamber migration .
anterior migration of a dexamethasone posterior implant into the anterior chamber through weak zonules was also described in cases with intact posterior capsule .
implant was surgically removed from the anterior chamber immediately by daudin and brzin , however turaka et al . reported that , without any surgical intervention , implant was spontaneously relocated back into the vitreous cavity with significant resolution of the corneal edema .
herein , we report the first case with anterior migration of a dexamethasone intravitreal implant that mislocated just behind the iol in an intact capsular bag . in the present case ,
the migrated implant was well tolerated as there was no sign of the corneal complication , iop rise , and anterior chamber reaction .
as this is a report of unique case with short follow - up , it is very difficult to comment that mislocation of a dexamethasone intravitreal implant on an intact posterior capsule is an innocent complication .
it is mandatory to observe more cases with long follow - up in order to estimate possible side effects of ozurdex implant attached on the posterior capsule .

Answer:
intravitreal application of ozurdex ( allergan , inc . , irvine , ca , usa ) which is a biodegradable ,
 sustained - release dexamethasone implant has been reported to be effective in the treatment of macular edema .
 migration of such implant into the anterior chamber has been recently described in cases without perfect zonular or the posterior capsular integrity .
 herein , we report the first case with anterior migration of ozurdex implant that mislocated just behind the intraocular lens ( iol ) in an intact capsular bag .
 it is thought that such implant migrated anteriorly towards into the posterior chamber through weak zonules as the present case had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber iol .
 however , the migrated implant was well tolerated since there was no sign of the corneal complication , rise in intraocular pressure , and anterior chamber reaction .
 close follow - up was scheduled to find out any signs of anterior segment pathology .
 meanwhile dexamethasone implant completely degraded at the 4th month of postoperative follow - up .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
ependymomas are relatively rare neuroepithelial tumors and account for 3 to 7% of all central nervous system tumors .
the incidence of ependymomas is more frequent in children , and 50% occur in children  <  5 years of age .
infratentorial locations of ependymomas are more frequent in infants and childhood , whereas supratentorial ependymomas are more often seen in adults.1 ependymal tumors are closely related to the ventricular system and central canal .
they can be observed extradurally in the sacral region and in the subarachnoidal space of the hemispheres . the most common location for infratentorial ependymomas is inside the fourth ventricle.2
  the clinical signs and symptoms of intracranial ependymomas depend on the location , size of the tumor , and the age of the patient .
the symptoms in posterior fossa ependymomas are related to increased intracranial pressure from hydrocephalus caused by obstruction of the fourth ventricle .
ataxia , dizziness , hemiparesis , and visual disturbance may add to the clinical picture.1
 2
  the current imaging protocol for the diagnosis is magnetic resonance imaging ( mri ) .
the most characteristic finding on mri is a downward extrusion of the tumor through the foramen of magendie into the cervical subarachnoid cervical space or through the foramen of luschka into the cerebellopontine cistern.3
 4 this presentation highlights the requirement for close follow - up of grade ii ependymomas for anaplastic transformation .
his eyes were open spontaneously ; however , his left eye was looking at medial and downside , and his left eye gaze was limited to upside and lateral .
an infratentorial brain tumor in the median and right cerebellar area was found on contrast mri .
axial initial magnetic resonance imaging scans show posterior fossa mass filled in fourth ventricle ( a ) with nonhomogeneous slight contrast enhancement ( b ) .
severe hydrocephalus can be seen with temporal horn filling secondary to the obstruction of the fourth ventricle .
postoperative axial ( c ) and coronal contrasted images ( d ) show complete resection of the mass with opening of the fourth ventricle and relaxation of the temporal horns .
the patient presented with vomiting and visual disturbance to the pediatric emergency department 12 months later .
on the second operation , the tumor was hard to aspirate with the cavitron ultrasonic surgical aspirator ( sonoca 400 , sring gmbh , quickborn , germany ) and was adherent to the brainstem and lower cranial nerves . only subtotal extirpation could be achieved ( fig .
the recurrent tumor showed anaplastic features such as nuclear pleomorphisms and necrosis with pseudopalisading ( fig .
3 ) .
 postcontrast axial ( a ) and coronal ( b ) images show regrowth of the mass lesion with strong contrast uptake .
( a ) moderately cellular tumor composed of monomorphic cells with round to oval nuclei containing  salt and pepper  pattern of chromatin .
radially arranged ependymal cell processes become thinner toward the vascular wall leaving an acellular zone around the blood vessel , called
perivascular pseudorosette ,  a key histologic feature for ependymoma ( hematoxylin and eosin [ h&e ] 100 ) . after the second operation ( b )
abundant endothelial proliferation , microvascular proliferation , hypercellularity with nuclear hyperchromasia , pleomorphism , numerous mitoses , and pseudopalisading necrosis warrants a diagnosis of anaplastic ependymoma when seen throughout the lesion ( h&e 200 ) .
moreover ( c ) , focus of coagulative necrosis , nuclear pseudopalisading was prominent around the necrotic areas , tumor cells oriented closer to viable areas emphasizing anaplastic changes ( h&e 200 ) .
ki-67 immunolabeling index is an independent prognostic factor and accurate predictor of outcome in patients with intracranial ependymoma ( d ) .
the index was 10% in the first operation that increased to 35% for our case in this image ( ki-67 200 ) .
bailey and cushing recognized ependymomas as an independent entity in their first brain tumor classification in 1926 .
variants were subsequently established . the most recent world health organization ( who ) classification identified four variants of ependymal tumors in addition to three grades of malignancy.5
 6 these four variants are myxopapillary ependymoma , subependymoma , tanycytic ependymoma , and clear cell ependymoma.3
 6
 7
  myxopapillary ependymomas and subependymomas are slow - growing tumors classified as grade i. both lesions are easily recognizable lesions ;
grade iii ependymomas have  increased cellularity and brisk mitotic activity , often associated with microvascular proliferation and pseudo palisading necrosis .
their results showed that poor clinical results paralleled histopathologic grade.8
  the outcome of children with intracranial ependymomas has improved significantly during the last few years .
recent reports demonstrate a 5-year overall survival rate not more than 40 to 65% in children with intracranial ependymomas.9
 10
 11
 12 pediatric oncology group findings suggest that the poor survival estimates frequently reported for infants are most likely related to the higher incidence of infratentorial tumors , the lower rate of complete resection , and the delay of the administration of radiation therapy.13
  the extent of surgical resection appears to be the other important prognostic factor in outcome for children with intracranial ependymomas . in patients with complete removal , 5-year survival is 67 to 80% ; 5-year progression - free survival is 51 to 75%.14
 15
 16
  studies have shown that patients with ependymoma who receive radiation therapy have a better outcome than who are not treated with irradiation.17
 18 however , there is no standard protocol for optimal management for children with intracranial ependymomas .
total / near - total surgical resection with an acceptable neurologic outcome combined with postoperative radiation therapy is the current treatment modality .
immediate postoperative irradiation is not widely accepted in the treatment of children  <  3 years of age .
stereotactic radiosurgery has been applied to manage recurrent or residual intracranial tumor in some institutions .
some reports described that adjuvant chemotherapy did not influence survival of patient with anaplastic ependymomas.18
 19
 20
  the most common location for infratentorial ependymoma is within the fourth ventricle .
the selected surgical approach may be a suboccipital craniotomy with or without c1 laminectomy depending on the extension of the tumor in the cervical region .
surgical resection appears to the most important prognostic factor ; therefore the best effort to perform total or near - total resection should be made.21
 22
  in conclusion , the ependymomas of the children are difficult to control , and surgical removal remains the mainstay of the treatment . despite a gross total resection ,
the correct grading of intracranial ependymomas may be difficult for the anaplastic variant because the common criteria for anaplasia are not completely reliable for all cases.13
 22 ependymomas in young infants have a worse prognosis than older children , so we need a grading scheme with a proven general ability to distinguish grades and to predict the evolution of individual cases.23 also new radiation therapy techniques and chemotherapeutic agents need to be developed .
postoperative irradiation is not recommended in the treatment of grade ii ependymomas for children  <  3 years of age .

Answer:
ependymomas are central nervous system neoplasms that account for a third of all posterior fossa tumors in children . the most common location for infratentorial ependymoma is within the fourth ventricle .
 we present a case report of malignant transformation of an infratentorial grade ii ependymoma in a 2-year - old child who presented with vomiting and visual disturbance .
 an infratentorial brain tumor in the left cerebellar area was totally removed , and the initial pathologic diagnosis was grade ii ependymoma .
 the tumor recurred aggressively 1  year later ; subtotal removal and adjuvant chemotherapy were performed . after a second operation , a histopathologic study was performed .
 the second specimen was defined as a grade iii anaplastic ependymoma .
 transformation to grade iii anaplastic ependymoma is possible for a grade ii ependymoma but very rare .
 the diagnosis of the anaplastic variant of intracranial ependymomas is difficult .
 surgical treatment remains the mainstay of the treatment for all cases .
 ependymomas in young infants have a worse prognosis than older children , so we need individual clinical evaluation and close follow - up of such cases .
 this article highlights the requirement of a close follow - up for grade ii ependymomas for anaplastic transformation .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
hemorrhage after percutaneous nephrolithotomy ( pcnl ) is a significant complication that occurs in a small percentage of cases .
however , arterial injuries sometimes require transarterial embolization to control the refractory bleeding . in patient presenting with refractory bleeding ,
pseudoaneurysm formation is the most common cause with a reported incidence of 0.6 - 1% .
we report a case of early erosion of an embolization coil from the renal vasculature into the urinary collecting system causing urinary tract obstruction and urosepsis .
a 23-year - old male underwent left urs and pcnl for a left upper ureteric calculus and a 2.5-cm lower pole renal calculus in a community hospital in december , 2010 .
one week after nephrostomy tube removal , the patient experienced gross hematuria with clot retention .
the patient underwent endoscopic bladder clot evacuation and dj stent removal in the same hospital .
two weeks later , again he developed gross hematuria with fever and a significant decrease in hematocrit .
after resuscitation the patient was referred to our centre . on angiography , there was a pseudoaneurysm in the lower segmental renal artery .
after 3 months of embolization , the patient presented with high - grade fever , left flank pain and burning micturiton . on x - ray kub 2 coils were seen in left renal area , whereas 1 coil was seen in l3 transverse process area .
axial noncontrast and contrast - enhanced ct images showed left hydronephrosis with dilated upper ureter and an embolization coil in the upper ureter [ figure 1 ] .
x ray kub shows 2 coils in left renal area , 1 coil in l3 transverse process area .
ct urogram shows left hydronephrosis with dilated upper ureter and 2 coils in left kidney & 1 coil in upper ureter
in 1975 , angioembolization for renal pseudoaneurysm was reported in a human patient when an autologous blood clot was used to embolize a bleeding pseudoaneurysm as a temporary measure before nephrectomy .
we found only three case reports in which embolization coil migrated to the collecting system.[810 ] in all these case reports the coil eroded after 1 year following embolization .
all the three patients presented with hematuria and renal colic . in our case , patient presented early ( 3 months ) with complaints of renal colic and persistent fever after coil embolization . hypothetically three mechanisms of coil erosion have been proposed .
first , the diameter of arteriocaliceal communication might be larger than the embolization coil , and the coil gets extruded through the communication soon after placement .
second , the arteriocaliceal communication could get dilated over time because of inflammation due to infection or the constant irritation from the indwelling coil itself , leading to eventual erosion into the collecting system .
finally , rupture of the weakened wall of a pseudoaneurysm exposed to high arterial pressure may lead to erosion . according to the first hypothesis ,
if the arteriocaliceal communication was larger than the embolization coil than all three coils would have extruded through the communication and gross hematuria would have reappeared .
the third mechanism would have lead to massive hematuria in addition to the coil migration . in this case
the patient presented with high - grade fever and left flank pain but not hematuria .
therefore in this case the second mechanism seems to be the most likely cause of erosion of the embolization coil .
one of the important but rare causes of urinary tract obstruction is the migration of embolization coil into urinary collecting system .

Answer:
refractory bleeding following percutaneous nephrolithotomy ( pcnl ) is mainly due to formation of pseudoaneurysm .
 transarterial embolization is required to control the bleeding in such cases .
 we report a case of post - pcnl hematuria in whom angioembolization was done .
 an early erosion of the embolization coil from the renal vasculature into the urinary collecting system occurred , causing urinary tract obstruction and urinary tract infection ( uti ) .
 the coil was retrieved ureteroscopically after control of uti with antibiotics .
 migration of embolization coil into urinary collecting system is a rare but important cause of urinary tract obstruction .
 the treating physician as well as the patient should be aware of this complication .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the world health organization has defined health literacy ( hl ) as  the cognitive and social abilities which determine the incentive and ability of individuals to increase access to understand and use information in ways , which promote and preserve good health .
the hl of patients has obtained more attention as a risk factor for poor adherence to treatment and adverse outcomes in chronic disease 's management particular in diabetes care .
diabetes is the most common metabolic disease with a dramatic increase rate of prevalence throughout the world , which has an important impact on the public health and quality of life of the patients .
there is a developing frame of the literature that discovers the association between hl and health outcomes in people with diabetes .
older studies of low hl reported adverse effects on diabetes - related health outcomes ; however , more recent studies showed no association between hl levels and intensity , frequency or incidence of outcomes , and thus the effect of hl on the health of people with diabetes is yet unclear .
based on national reports , the prevalence of diabetes has been raised during three decades in iran and also a recent national survey about hl has shown that majority of people has inadequate knowledge .
however , there are different tools to measure hl and numeracy skills in general population in different languages , only diabetes numeracy test-15 ( dnt-15 ) has been developed specifically to measure numeracy skills in patients with diabetes as first scale by huizinga et al .
, in english language . with regard to lacking of appropriate measurement tool for patients with diabetes in persian ( farsi ) language , this study aimed to provide evidence for the psychometric properties of the iranian ( persian language ) version of dnt-15 .
the dnt was designed to evaluate nutrition , exercise , glucose monitoring , oral medication , and insulin skills that patients may encounter during daily diabetes self - management .
blood - glucose monitoring skills are evaluated by three items about number hierarchy , glaciated hemoglobin , and calculating supplies needed .
eight items assess the oral medication use and insulin use . oral medication ( one question )
use refill patterns and dates , and oral titration schemes and insulin use ( seven questions ) including interpretation of syringes , correction or sliding - scale insulin use , insulin adjustment for carbohydrate intake , and titration instructions [ table 1 ] .
items are scored as binary outcomes  correct or incorrect  and no partial credit is given .
many patients with diabetes use calculators ; therefore , participants were allowed to use calculators during the administration of the dnt to emulate real - life circumstances .
dnt scores are reported as percent correct ( with a possible range of 0% to be 100% ) .
description of diabetes numeracy test items in this phase , the original questionnaire was translated by two independent health professionals from english to persian .
after translation , by consultation with the principal investigators , the results were rechecked . finally , they achieved a precision translation for the questionnaire . in this phase ,
the questionnaire that translated in the previous step , gave to two professional translators whose native language were english , and they are sufficient dominance in persian language .
the translators did not communicate with one another and did not know the original english version .
translated versions by consultation with the principal investigators of conversion backward translation were combined . in this phase ,
a group of experts was reviewed , all phases , including verification and cross - cultural equivalent ( cross - cultural equivalence ) .
cultural equivalent to the word ( semantic ) , a term equivalent ( idiomatic ) , and equivalent experience ( experiential ) , and conceptually equivalent ( conceptual ) were performed by an expert panel .
this group included experts in diabetes , certified diabetes educators , methodologist , primary care providers , and registered dietitians , behavioral researchers in diabetes , and literacy and numeracy experts . finally , the dnt was to address the clarity of items for patients with diabetes .
interviewees were asked specific questions about each item to evaluate the understandability of the wording .
if an item was unclear , the interviewee was told the purpose of the item and then encouraged to suggest a different format or wording . in response to the interviews , the scale was reformatted and slightly reduced to the final 15-items .
reliability was evaluated by internal consistency ( kuder - richardson 20 ) , and validity was evaluated through content validity ratio ( cvr ) and content validity index ( cvi ) .
a convenience sample of 120 patients with diabetes was interviewed in the diabetes clinic affiliated to institute of endocrinology and metabolismof an item at clinic visits . any person diagnosed with type 1 and or type 2 diabetes which was able to read ( at least eight grades ) and speak persian language .
potential participants were excluded if they corrected visual acuity was > 20/50 using a rosenbaum pocket vision screener , or if they had a diagnosis of significant dementia , psychosis , or blindness .
the dnt was designed to evaluate nutrition , exercise , glucose monitoring , oral medication , and insulin skills that patients may encounter during daily diabetes self - management .
blood - glucose monitoring skills are evaluated by three items about number hierarchy , glaciated hemoglobin , and calculating supplies needed .
eight items assess the oral medication use and insulin use . oral medication ( one question )
use refill patterns and dates , and oral titration schemes and insulin use ( seven questions ) including interpretation of syringes , correction or sliding - scale insulin use , insulin adjustment for carbohydrate intake , and titration instructions [ table 1 ] .
items are scored as binary outcomes  correct or incorrect  and no partial credit is given .
many patients with diabetes use calculators ; therefore , participants were allowed to use calculators during the administration of the dnt to emulate real - life circumstances .
dnt scores are reported as percent correct ( with a possible range of 0% to be 100% ) .
in this phase , the original questionnaire was translated by two independent health professionals from english to persian .
in this phase , the questionnaire that translated in the previous step , gave to two professional translators whose native language were english , and they are sufficient dominance in persian language .
the translators did not communicate with one another and did not know the original english version .
in this phase , a group of experts was reviewed , all phases , including verification and cross - cultural equivalent ( cross - cultural equivalence ) .
cultural equivalent to the word ( semantic ) , a term equivalent ( idiomatic ) , and equivalent experience ( experiential ) , and conceptually equivalent ( conceptual ) were performed by an expert panel .
this group included experts in diabetes , certified diabetes educators , methodologist , primary care providers , and registered dietitians , behavioral researchers in diabetes , and literacy and numeracy experts . finally , the dnt was to address the clarity of items for patients with diabetes .
interviewees were asked specific questions about each item to evaluate the understandability of the wording . if an item was unclear , the interviewee was told the purpose of the item and then encouraged to suggest a different format or wording . in response to the interviews , the scale was reformatted and slightly reduced to the final 15-items .
reliability was evaluated by internal consistency ( kuder - richardson 20 ) , and validity was evaluated through content validity ratio ( cvr ) and content validity index ( cvi ) .
a convenience sample of 120 patients with diabetes was interviewed in the diabetes clinic affiliated to institute of endocrinology and metabolismof an item at clinic visits . any person diagnosed with type 1 and or type 2 diabetes which was able to read ( at least eight grades ) and speak persian language .
potential participants were excluded if they corrected visual acuity was > 20/50 using a rosenbaum pocket vision screener , or if they had a diagnosis of significant dementia , psychosis , or blindness .
difficult issues for participants included titration schemas , food label interpretation , insulin adjustment instructions , and items that required multi - step math ( e.g. , calculating insulin dosage based on carbohydrate intake and glucose level ) .
questions 2 , 5 , 6 , 7 , 8 , 9 , and 11 were answered accurately respectively by 89.1% , 78.2% , 87.4% , 72.3% , 85.7% , 84% , and 83% of participants for this study .
however , questions 14 and 15 , which required patients to interpret a word problem and apply multiple numerical steps to determine their insulin dosage , was only answered correctly , respectively by 41% , 54% of the participants .
the 15-item persian version of the dnt has highly reliable , as determined by internal consistency kuder - richardson ( kr-20 = 0.90 ) .
content validity was examined by the expert panel ( cvr : 089 and cvi : 0.86 ) .
the short version of the dnt-15 demonstrated internal consistency and construct validity in relation to reading skills in persian ( farsi ) language in iranian population .
scores on the dnt-15 showed a direct correlation with level of education in this study which is consistent with other reports .
although there have been some reports about hl in iran they were not specific about diabetes in iran .
other studies have identified the role of hl techniques in the improvement of health outcomes in diabetes and congestive heart failure .
patients with low hl may benefit from interventions that address numeracy , particularly in the setting of diabetes management .
the dnt-15 can provide a measurement of diabetes - specific numeracy and provide more information on the role of disease - specific numeracy in future studies .
more studies are needed to further understand the role of numeracy tailored interventions for the management of diabetes .
for example , study participants had a difficult time with the multi - step math required to calculate a correction dosage of insulin when instructions were presented as a sequence of sentences .
this item was encompassed to mirror clinical practice regarding how patients are currently instructed to take their insulin .
this example provides an important lesson for health care providers and educators in effective communication styles for all clinical care recommendations .
the persion ( farsi ) version of dnt-15 is a reliable and valid tool to measure of diabetes - specific numeracy skills for patients with diabetes .

Answer:
background : low health literacy ( hl ) of patients has obtained more attention as a risk factor for poor adherence to treatment and adverse outcomes in chronic disease 's management particular in diabetes care .
 diabetes numeracy test-15 ( dnt-15 ) has been developed specifically for this purpose .
 the objective of the current study is to evaluate psychometric properties of iranian ( persian ) version of the dnt-15.methods:the shortened version of the dnt ( 15-items ) was completed by 120 patients with diabetes .
 the kuder
 richardson formula 20 for internal consistency was conducted .
 content validity , criterion - related validity , and construct validity were also evaluated.results:the average score on the dnt was 72% and took an average of 25 minutes to complete .
 the dnt-15 had a very good internal reliability ( kr-20 = 0.90 ) and also content validity ( content validity ratio : 089 and content validity index : 0.86).conclusions : the dnt-15 ( persian version ) is a reliable and valid measure of diabetes - related numeracy skills for iranian patients with diabetes ; however , additional studies are needed to further explore the association between diabetes - specific numeracy and acculturation and their impact on diabetes - related outcomes in iranian population .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a girl weighing 3,190 g was delivered by a caesarean section at 38 weeks and five days of gestation . at the time of birth , a systolic murmur
was noted during a physical examination , and transthoracic echocardiography revealed a peri - membranous ventricular septal defect ( vsd ) with a septal aneurysm , a small patent foramen ovale ( pfo ) , and a small right - sided patent ductus arteriosus ( pda ) from the innominate artery .
the vsd was measured as having a diameter of 3.5 mm and a shunt flow less than 2.5 m / sec .
due to the presence of neonatal hyperbilirubinemia , echoencephalography was conducted , and no abnormalities were found .
five months later , the patient was referred to konkuk university medical center for vsd and pda .
her body weight was 6,700 g ( 25th percentile ) , and her height was 61.6 cm ( 10th percentile ) .
transthoracic echocardiography revealed a vsd approximately 6 mm in size with a minimal aneurysm , a left - sided pda 3.6 mm in diameter from the right aortic arch and an aberrant left subclavian artery .
a subsequent computed tomographic scan demonstrated isolation of the left subclavian artery with a right aortic arch , a left pda , and a vsd ( fig .
the intraoperative findings were a perimembranous vsd , a pfo , a mildly patent right ductus arteriosus , and isolation of the left subclavian artery connected to the left pulmonary artery via a left pda .
the left subclavian artery was disconnected from the left pulmonary artery and reimplanted to the left common carotid artery by end - to - side anastomosis with monofilament polypropylene 6 - 0 sutures ( fig .
ductus arteriosus is usually located on the left side , between the descending aorta and the junction of the main pulmonary artery and left pulmonary artery .
however , ductus arteriosus may also be present on the right side or , very rarely , may occur bilaterally in association with aortic arch anomalies or conotruncal anomalies .
in such aortic arch anomalies , isolation of the left subclavian artery with right aortic arch is also uncommon . here
, isolation refers to the fact that the left subclavian artery connects to the pulmonary artery via either the ligamentum arteriosum or a patent ductus arteriosus without any connection to the aorta .
isolation of the left subclavian artery with a right aortic arch is known to be commonly associated with congenital heart disease , but may also occur with normal intracardiac anatomy , although few such cases have been described .
isolation of the left subclavian artery with a right aortic arch may be related to the 22q11 deletion .
bilateral ductus arteriosus and isolation of the left subclavian artery with a right aortic arch can be explained through the hypothetical double aortic arch plan suggested by edward .
regression takes place on two levels in the double aortic arch plan : on one level , regression occurs between the left common carotid artery and the left subclavian artery ; and on the other level , regression occurs at the left dorsal aortic root distal to the left ductus arteriosus .
and then right ductus arteriosus remains persistent , left ductus arteriosus connects the left subclavian artery to the left pulmonary artery ( fig .
however , the right ductus arteriosus regressed , and only the left ductus arteriosus remained patent .
if the left ductus arteriosus is patent , blood may be supplied to the left subclavian artery via the left ductus arteriosus .
if the left ductus arteriosus regresses , the blood supply to the left subclavian artery may involve a mediastinal , thoracic anastomosis , or vertebral pathway .
isolation of the left subclavian artery usually presents with no apparent symptoms in neonates , but it may present with congenital pulmonary steal syndrome , subclavian steal syndrome , or may even present in adults with late symptoms due to sporadic progression .
hayabuchi et al .   reported the case of a three - month - old girl with cerebral atrophy and an underdeveloped left arm .
reported the case of a 15-year - old boy with an underdeveloped left arm . due to these symptoms and signs ,
the therapeutic management of isolation of the left subclavian artery remains controversial , especially when it is associated with complicated congenital heart disease .
some authors have suggested that adequate collateral circulation must be ensured , meaning that reconstruction of the isolated subclavian artery is optional , regardless of the symptoms and signs .
successful results have been reported after ligation or device closure of the pda and ligation of the left subclavian artery .
however , reconstruction of the left subclavian artery due to pulmonary steal syndrome after right pda closure in bilateral pda has been reported . in one report , ischemic symptoms in the left arm and vertebrobasilar insufficiency occurred years after ligation of the left subclavian artery .
hokari et al .   reported that a man with peutz - jeghers syndrome presented with his first vertigo attacks due to subclavian steal syndrome at 29 years of age .
our patient presented with no symptoms and signs related to subclavian or pulmonary steal syndrome , and had shown normal findings on an echoencephalography study conducted at our medical center due to neonatal hyperbilirubinemia .
however , brain computed tomography angiography performed after surgery revealed hypoplasia of the left vertebral artery .
we suggest that this hypoplasia would have led to vertebrobasilar insufficiency or underdevelopment of the left arm without surgical reconstruction .
since surgical reconstruction of the isolated left subclavian artery leads to antegrade flow in the left subclavian artery , it can prevent hypoplasia of the left vertebral artery and subclavian / pulmonary steal syndrome .
our case shows that early surgical reconstruction is reasonable , regardless of the symptoms , in cases of isolation of the left subclavian artery .

Answer:
right aortic arch with isolation of the left subclavian artery is a rare anomaly .
 the incidence of bilateral ductus arteriosus is sporadic , and a right aortic arch with isolation of the left subclavian artery in association with bilateral ductus arteriosus is therefore extremely rare .
 since the symptoms and signs of isolation of the left subclavian artery can include the absence or underdevelopment of the left arm , subclavian steal syndrome , or pulmonary artery steal syndrome , the proper therapeutic approach is controversial .
 we report a case in which surgical reconstruction was used to treat isolation of the left subclavian artery with right aortic arch in association with bilateral ductus arteriosus and a ventricular septal defect .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a 73-year - old female was admitted for surgical removal of a left renal pelvic mass . she has taken antihypertensive agents for 30 years and received percutaneous coronary intervention due to stable angina 3 years ago . during routine follow - up , a renal mass was incidentally detected 2 months ago .
laboratory values revealed a marginal elevation of serum creatinine ( 1.21 mg / dl ) .
the ultrasonography showed an echogenic mass within the renal pelvis and mild dilation of several calyces .
the calcified lesion was not found on plain radiograph of the abdomen ( kidneys , ureters , and bladder ) .
an abdominopelvic computed tomography revealed a noncalcified soft tissue mass in the left renal pelvis on precontrast enhancement scan .
the cut surface of the resected specimen revealed a 532 cm - sized , well - defined ovoid , cystic mass which was compactly filled with white and reddish tan - colored amorphous materials in the pelvis .
histologically , the cystic lumen contained multiple keratinous materials and much of the cystic lining epithelia were denuded .
, santa cruz , ca , usa ) and cytokeratin 7 ( ck7 ) ( 1:100 ; dako , glostrup , denmark ) was performed to identify epithelium - specificdifferentiation .
in contrast , most of the cells in the lining of squamous epithelia were negative for these urothelial specific antibodies .
however , some portion of the squamous epithelia interestingly contained a few uroplakin - positive cells ( fig .
even though the epidermoid cyst of the kidney is a very rare to be characterized , the typical features of the lesion can be summarized as follows .
the clinical symptoms are flank pain , gross hematuria , or lower urinary tract symptoms .
the calcified inhomogeneous lesion , combined renal stone , and previous renal surgery are other important clinical clues for the renal epidermoid cyst ( table 1 ) .
to date , two cases of epidermoid cyst in the renal pelvis have been reported .
they also showed a typical calcified lesion combined with renal stone like other renal epidermoid cysts . with these reasons
, it seemed hard to think of epidermoid cyst as a presumptive diagnosis before surgery in this case . to the best of our knowledge ,
this case of a noncalcified epidermoid cyst in the renal pelvis is the first report in the english literature .
the histology of a typical epidermal cyst that was lined by stratified squamous cells with laminated keratins .
although epidermoid cyst of the skin is a common lesion resulted from implantation of epidermis into the dermis , histogenesis of epidermoid cyst in the kidney remains uncertain . as a possible histogenetic mechanism , either epidermal embryonic remnants of wolffian ducts or traumatic implantation of transformed epithelial cells during renal operation have been proposed .
the extension of squamous metaplastic changes from the upper ureter to the pelvocalyceal system in prolonged irritative condition induced mostly by stones is considered as the other plausible explanation .
however , the cellular basis of squamous metaplasia is not fully understood in this rare condition .
the apical surface of urothelium is highly specialized as it is covered almost by urothelial plaques which are composed of uroplakins .
four uroplakins ( ia , ib , ii , and iii ) have been isolated and are considered to be biochemical markers of terminal urothelial differentiation .
ck7 is an intermediate filament proteins expressed in a wide variety of simple epithelia but not in the squamous epithelia .
it is well known that vitamin a deficiency can induce keratinizing squamous metaplasia in a variety of epithelia including urothelium .
the urothelial keratinization in the vitamin a - deficient mice bladder occurred heterogeneously adjacent to areas lined with normal appearing urothelium .
the sharp boundary between the keratinized epithelium and the seemingly normal urothelium was maintained with no intermediated cells .
according to the our histologic examination , nearly almost of the urothelial cells in the cystic lining were positively stained against both uroplakin ii and ck7 , but most of the squamous epithelial cells were negative for these antibodies .
the two epithelia were sharply delineated and more distinctly distinguishable in the immunohistochemical stained sections .
these features were similar with heterogenous metaplasia of the animal urothelium in the previous study .
however , some squamous epithelia contained a few uroplakin - positive cells and ck7-positive cells to some extent . even though the significance of few uroplakin expressions in squmous epithelium should be evaluated by other studies , is this an indirect evidence of the direct transformation of umbrella cells to squamous metaplasia or dedifferenctiation of metaplastic squamous epithelium to urothelium ?

Answer:
since the renal epidermoid cyst is too rare , the mechanisms of squamous morphogenesis have not well characterized .
 a 73-year - old female was referred with an incidentally detected renal pelvis mass .
 abdominopelvic computed tomography scan revealed a noncalcified soft tissue mass in the renal pelvis .
 total nephroureterectomy was performed under the impression of a renal pelvis malignancy .
 the patient was discharged without postoperative complication .
 the outer surface of mass lesion was lined with urothelia and squamous epithelia , containing keratinous materials .
 the urothelia were positively stained against uroplakin ii and cytokeratin 7 , whereas almost of the squamous epithelia were negative with uroplakin ii .
 the two different epithelia were generally sharply demarcated .
 interestingly , some part of squamous epithelia contained uroplakin - positive and many more cytokeratin 7-positive cells .
 the atypical clinical features in our case can reconsider the diagnostic clues of renal epidermoid cysts that have been reported before , and the unique immunohistochemical results may understand the histogenetic implications of the lesion .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
eq . 2 can be generalized to the case where the charge moves continuously , corresponding to an infinite number of steps . if we makezi = qmax / n ,  i=1  n ,  vi = vo ,  i=1  n , then all i =  , and we can write eq .
4 can also be written as(5)qnor(v)=12[1+coth[qmax(vvo)2kt]2ktqmax(vv0)],which is of the same form of the classical equation of paramagnetism ( see kittel , 2005 ) .
typically , the experimental value of the charge plotted is normalized to its maximum because there is no knowledge of the absolute amount of charge per molecule and the number of molecules .
the normalized q - v curve , qnor , is obtained by dividing q(v ) by the sum of all the partial charges .
1 shows qnor computed using eq . 2 for one , two , three , four , and six transitions and for the continuous case using eq .
5 ( squares ) with superimposed fits to a two - state boltzmann distribution ( eq . 1 , lines ) .
the computations were done with equal charge in each step ( for a total charge qmax = 4e0 ) and also the same vi = 25 mv value for all the steps .
it is clear that fits are quite acceptable for cases up to four transitions , but the fit significantly deviates in the continuous case .
examples of normalized q - v curves for a qmax = 4 computed with eq . 2 for the cases of one , two , three , four , and six transitions and the continuous case using eq . 5 ( squares ) .
all the q - v curves were fitted with eq . 1 ( lines ) .
the insets show the fitted valence ( qmax ) and half - point ( v1/2 ) . considering that experimental data normally have significant scatter , it is then quite likely that the experimenter will accept the single - transition fit even for cases where there are six or more transitions ( see fig .
1 ) . in general , the case up to four transitions will look as a very good fit , and the fitted qmax value may be inaccurately taken and the total charge transported might be underestimated . to illustrate how bad the estimate can be for these cases ,
we have included as insets the fitted value of qmax for the cases presented in fig .
it is clear that the estimated value can be as low as a fourth of the real total charge .
the estimated value of v1/2 is very close to the correct value for all cases , but we have only considered cases in which all vi s are the same . it should be noted that if i of the rightmost transition is heavily biased to the last state ( vi is very negative ) , then the qmax estimated by fitting a two - state model is much closer to the total gating charge . in a three - state model , it can be shown that the fitted value is exact when v1 and v2 because in that case , it converts into a two - state model .
although these values of v are unrealistic , the fitted value of qmax can be very close to the total charge when v2 is much more negative than v1 ( that is , v1 > > v2 ) .
on the other hand , if v1 < < v2 , the q - v curve will exhibit a plateau region and , as the difference between v1 and v2 decreases , the plateau becomes less obvious and the curve looks monotonic .
these cases have been discussed in detail for the two - transition model in lacroix et al .
we conclude that it is not possible to estimate unequivocally the gating charge per sensor from a  single - boltzmann  fit to a q - v curve of a charge moving in multiple transitions .
the estimated qmax value will be a low estimate of the gating charge qmax , except in the case of the two - state model or the case of a heavily biased late step , which are rare occurrences .
it is then safer to call  apparent gating charge  the fitted qmax value of the single - boltzmann fit .
the most general case in which transitions between states include loops , branches , and steps can be derived directly from the partition function and follows the general thermodynamic treatment by sigg and bezanilla ( 1997 ) , chowdhury and chanda ( 2012 ) , and sigg ( 2013 ) .
the reaction coordinate is the charge moving in the general case where it evolves from q = 0 to q = qmax by means of steps , loops , or branches . in that case , the partition function is given by(6)z=iexp(qi(vvi)kt).we can compute the mean gating charge , also called the q - v curve , as(7)q(v)=q=ktzz = ktdlnzdv=iqiexp(qi(vvi)kt)iexp(qi(vvi)kt).the slope of the q - v is obtained by taking the derivative of q with respect to v:(8)dq(v)dv=(kt)2d2lnzdv2 .
the charge fluctuation will depend on the number of possible conformations of the charge and is expected to be a maximum when there are only two possible charged states to dwell . as the number of intermediate states increases , the charge fluctuation decreases .
now , a measure of the charge fluctuation is given by the variance of the gating charge , which can be computed from the partition function as:(9)q2=q2q2=(kt)2(zz(zz)2)=(kt)2d2lnzdv2.but the variance ( eq .
this implies that the slope of the q - v is maximum when there are only two states .

Answer:
the voltage dependence of charges in voltage - sensitive proteins , typically displayed as charge versus voltage ( q - v ) curves , is often quantified by fitting it to a simple two - state boltzmann function .
 this procedure overlooks the fact that the fitted parameters , including the total charge , may be incorrect if the charge is moving in multiple steps .
 we present here the derivation of a general formulation for q - v curves from multistate sequential models , including the case of infinite number of states .
 we demonstrate that the commonly used method to estimate the charge per molecule using a simple boltzmann fit is not only inadequate , but in most cases , it underestimates the moving charge times the fraction of the field .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the incidence of primary cardiac tumors is low , at 0.001% to 0.03% [ 1 - 3 ] .
the advent of variable cardiac imaging modalities , including echocardiography and multidetector computed tomography ( ct ) , has led to the identification of an increasing number of cases of asymptomatic cardiac tumors .
cardiac papillary fibroelastoma ( cpf ) is a rare and benign cardiac tumor that can arise anywhere in the heart , but usually involves cardiac valves .
moreover , the incidence of cpf in the left ventricle is lower than that in other parts of the heart .
here we report a case of left ventricular cpf detected by echocardiography and successfully surgically resected .
a 65-year - old woman was referred to our cardiology department for evaluation of a cardiac mass of the left ventricle .
prior to the referral , she was admitted to another hospital with a complaint of chest pain of 3 days ' duration . coronary angiography and echocardiography
coronary angiography showed no significant coronary disease , but a mass was found by echocardiography .
she had been treated for hypertension and a stroke she suffered 5 years prior . on physical examination , her blood pressure was 110/70 mmhg , and her pulse rate was 62 beats / min .
transthoracic echocardiography revealed a 1.8  1.7 cm highly mobile round mass attached by a stalk on the apical inferior wall of the left ventricle with an echolucent area ( fig .
ct of the chest showed a 1.9  1.6 cm round and pedunculated mass with soft tissue density on the apical inferior wall of the left ventricle ( fig .
on opening the left atrium , there was a mass attached deep to the inferior wall of the left ventricle .
the resected tumor was 1.8  1.5 cm and had the appearance of a sea anemone ( fig .
histology showed that the lesion had a papillary configuration with an avascular connective tissue core ( fig .
among primary cardiac neoplasms , benign tumors account for 63% and malignant tumors for 37% .
the mean age at diagnosis of cpf is approximately 60 years , although it has been reported in teenagers and children .
cpf affects both sexes , but males predominate in most series . in the study of a series at the mayo clinic from 1957 to 2001 , of 110 primary cardiac tumors that were surgically removed
a recent study reported that cpf represented 5% of primary cardiac tumors in 21 patients . in a report of 110 cpf cases ,
about 90% of cpfs appeared on cardiac valves , and the remainder originated from nearly all portions of the non - valvular endocardium , including the left ventricular septum , the left ventricular mural endocardium , the right ventricular outflow tract , the right atrium , the atrial septum , the papillary muscle , the chordate tendinea , the eustachian valve , and the chiari network .
they have a gelatinous membrane on the surface and a stalk with multiple papillary projections .
microscopically , cpfs are composed of a central stalk with radiating villus - like projections .
the papillae are avascular structures , containing a core of dense collagen fibers admixed with varying amounts of reticulin and elastin fibers .
the microscopic structure of a cpf closely resembles that of chordea tendineae , which prompted some to propose a hamartomatous - like pathogenesis .
a cpf is a collection of avascular fronds of dense connective tissue lined by endothelium .
however , it is deemed to be a reactive process rather than a true neoplasm .
it is suggested that cpf may be associated with lambl 's excrescence and shear stress , and congenital factors may be involved in its development ; however , the cause remains unclear . with improved echocardiographic resolution due to higher transducers and new imaging modalities ,
cpf was considered to be an incidental autopsy finding and to have no clinical significance in the past .
the clinical presentation of a cardiac tumor is determined by its location , size , and mobility .
in particular , left - sided , larger sized (  1 cm ) and highly mobile tumors have a higher incidence of embolization .
cpfs have a predilection for the left side of the heart . in a review of the literature regarding complications in 79 cases of cpf
, 61 lesions occurred on the left side of the heart , whereas only 18 were right - sided .
cpfs are generally slow growing tumors , but may serve as nidi , allowing formation of large superimposed thrombi over a short period of time .
symptoms include cerebral infarction and transient cerebral ischemic attack associated with soft and fragile fibroelastoma in 44% of patients , angina pectoris in 18% , myocardial infarction in 10% , cardiac failure in 9% , and sudden death in 8% .
symptomatic cpf should be resected surgically ; however , there are no guidelines for the treatment of asymptomatic cpf .
large , left - sided mobile tumors should be excised to prevent sudden death and emboli .
small , non - mobile tumors may be followed with serial echocardiography and removed if they increase in size or become mobile or symptomatic .
various methods have been proposed for complete excision of left - sided cpfs to avoid a left ventriculotomy due to further complications . for tumors deep within the left ventricular cavity close to the apex , the use of a cardioscope passing through the aortic or mitral valve is recommended to avoid damage to the valvular apparatus . in our case
, we used a surgical approach through the left atrium and mildly pushed up the left ventricular apical inferior wall for easy resection of the mass .
recently , a case in which a cpf deep in the left ventricle was resected under the guidance of a gastrointestinal fiberscope was reported . in this report
, we present a case of cpf attached to the left ventricular apical inferior wall , which was successfully removed surgically .

Answer:
cardiac papillary fibroelastoma ( cpf ) is a rare and benign primary cardiac neoplasm of unknown prevalence .
 the incidence of cpf in the left ventricle is lower than that in other parts of the heart .
 a 65-year - old female was referred to our cardiology department for evaluation of a cardiac mass of the left ventricle .
 transthoracic echocardiography revealed a 1.8  1.7 cm highly mobile round mass attached by a stalk to the apical inferior wall of the left ventricle with an echolucent area .
 the mass was successfully removed without any postoperative complications and was identified as a cpf .