Miracle-dz/UniFAR-FTUs huggingface dataset:
MreB Drives De Novo Rod Morphogenesis in Caulobacter crescentus via Remodeling of the Cell Wall

ABSTRACT MreB, the bacterial actin-like cytoskeleton, is required for the rod morphology of many bacterial species. Disruption of MreB function results in loss of rod morphology and cell rounding. Here, we show that the widely used MreB inhibitor A22 causes MreB-independent growth inhibition that varies with the drug concentration, culture medium conditions, and bacterial species tested. MP265, an A22 structural analog, is less toxic than A22 for growth yet equally efficient for disrupting the MreB cytoskeleton. The action of A22 and MP265 is enhanced by basic pH of the culture medium. Using this knowledge and the rapid reversibility of drug action, we examined the restoration of rod shape in lemon-shaped Caulobacter crescentus cells pretreated with MP265 or A22 under nontoxic conditions. We found that reversible restoration of MreB function after drug removal causes extensive morphological changes including a remarkable cell thinning accompanied with elongation, cell branching, and shedding of outer membrane vesicles. We also thoroughly characterized the composition of C. crescentus peptidoglycan by high-performance liquid chromatography and mass spectrometry and showed that MreB disruption and recovery of rod shape following restoration of MreB function are accompanied by considerable changes in composition. Our results provide insight into MreB function in peptidoglycan remodeling and rod shape morphogenesis and suggest that MreB promotes the transglycosylase activity of penicillin-binding proteins.
Superior survival of females among 10,538 Dutch melanoma patients is independent of Breslow thickness, histologic type and tumor site.

BACKGROUND Worldwide, female melanoma patients have superior survival compared with males, which is usually ascribed to earlier detection among women and/or a more favorable site distribution. We studied gender difference in melanoma survival in a large population-based setting after adjusting for tumor-related variables and offer clues for further research. PATIENTS AND METHODS A total of 10,538 patients diagnosed with melanoma from 1993 to 2004 in The Netherlands were included. Multivariate analyses were carried out to estimate adjusted relative excess risk (RER) of dying for men compared with women, adjusted for the patient and tumor characteristics. RESULTS Univariate relative survival analyses showed a RER of dying of 2.70 [95% confidence interval (CI) 2.38-3.06] for men compared with women. After adjusting for time period of diagnosis, region, age, Breslow thickness, histologic subtype, body site, nodal and metastatic status, a significant excess mortality risk was still present for males (RER 1.87, 95% CI 1.65-2.10). Among patients with advanced disease and in those < 45 or > or = 60, the adjusted risk estimates were similar. CONCLUSIONS The superior survival of women compared with men persisted after adjusting for multiple confounding variables indicating that factors other than stage at diagnosis and body site reduce mortality risk in female melanoma patients.
Imaging, morphologic, and immunohistochemical correlation in gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) recently have been distinguished morphologically, immunohistochemically, and genetically from other gastrointestinal‐tract spindle cell neoplasms. The objective of this study was to correlate clinical and imaging findings with morphology and immunohistochemistry to diagnose GISTs and to differentiate them from other spindle cell lesions in the gastrointestinal tract.
Action tremor during object manipulation in Parkinson's disease

In previous studies of fingertip forces during precision grip in subjects with Parkinson's disease (PD), we observed regular oscillations in isometric force. The present study characterizes the nature of these oscillations. Fingertip forces were recorded from the index finger and thumb during precision grip‐lifts with a 300 g and 900 g object in 10 subjects with PD and 20 healthy control subjects. Fourier analysis confirmed that all subjects with PD exhibited force oscillations with a clearly definable frequency (∼7–11 Hz). Five of these subjects also exhibited a second lower frequency peak (∼5 Hz). Approximately half of the 20 control subjects displayed a single frequency peak (∼8–12 Hz), which was generally lower in amplitude than in the subjects with PD (representing enhanced physiological tremor), whereas the remaining control subjects had low‐amplitude, broad‐based spectra (representing physiological tremor). The amplitude of the force oscillations was higher for lifts with the heavier object in both the control subjects and subjects with PD. l‐Dopa resulted in a decreased tremor amplitude but did not influence the frequency. The force oscillations of the two opposing digits normal to the grip surfaces were in phase, whereas the oscillations tangential to the grip surfaces were often out of phase. The results suggest that the multipeaked force rate trajectories reported previously are caused by action tremor. The similarity of force oscillations in subjects with PD and healthy control subjects suggests common tremor‐generating mechanisms and supports the notion that the parkinsonian action tremor (AT) is an exaggerated form of physiological tremor. These findings provide insight into the impaired hand function observed in individuals with PD.
Action Mechanism of Antitubercular Isoniazid

Activation of the antitubercular isoniazid (INH) by the Mycobacterium tuberculosis KatG produces an inhibitor for enoyl reductase (InhA). The mechanism for INH activation remains poorly understood, and the inhibitor has never been isolated. We have purified the InhA-inhibitor complex generated in the M. tuberculosis KatG-catalyzed INH activation. The complex exhibited a 278-nm absorption peak and a shoulder around 326 nm with a characteristicA 326/A 278 ratio of 0.16. The complex was devoid of enoyl reductase activity. The inhibitor noncovalently binds to InhA with a K d < 0.4 nm and can be dissociated from denatured InhA for chromatographic isolation. The free inhibitor showed absorption peaks at 326 (ε326 6900 m −1cm−1) and 260 nm (ε260 27,000m −1 cm−1). The inactive complex can be reconstituted from InhA and the isolated inhibitor. The InhA inhibitor from the KatG-catalyzed INH activation was identical to that from a slow, KatG-independent, Mn2+-mediated reaction based on high pressure liquid chromatography analysis and absorption and mass spectral characteristics. By monitoring the formation of the InhA-inhibitor complex, we have found that manganese is not essential to the INH activation by M. tuberculosis KatG. Furthermore, the formation of the InhA inhibitor in the KatG reaction was independent of InhA.
Palliation of Gastric Outlet Obstruction and Proximal Small Bowel Obstruction With Self-expandable Metal Stents: A Single Center Series

Background: Self-expandable metal stents (SEMS) are being increasingly used to palliate malignant stenoses of the gastric outlet and proximal small bowel. Accordingly, we reviewed our experience in this setting. Methods: Patients with gastric outlet or proximal small bowel stents were identified by reviewing hospital charts. Outcome criteria included survival data, need for reintervention, and clinical improvement. Results: A total of 52 SEMS were placed in 36 patients with nonesophageal upper GI stenosis. Initial stent placement was successful in 92% and clinical improvement documented in 75%. Mean survival of patients who eventually died was 3.5 months. Seven patients are alive (mean follow-up, 5.0 months). Stent dysfunction occurred in 36% and required subsequent interventions. Biliary obstruction was documented in 50% of patients, 12 of whom had previously undergone biliary stenting and 5 who needed subsequent biliary decompression. Conclusions: Enteral stent placement has been reported to be an effective alternative for palliation of high-risk surgical patients with malignant gastric outlet and small bowel obstruction. Considering the short life expectancy of these patients and significant complications including stent migration, perforation, biliary obstruction, and need for subsequent endoscopic, radiologic and surgical interventions, the authors suggest that this procedure be performed in experienced centers on selected patients only and that biliary decompression be ensured early.
A 3T MR Imaging Investigation of the Topography of Whole Spinal Cord Atrophy in Multiple Sclerosis

BACKGROUND AND PURPOSE: Spinal cord atrophy is a common feature of MS. However, it is unknown which cord levels are most susceptible to atrophy. We performed whole cord imaging to identify the levels most susceptible to atrophy in patients with MS versus controls and also tested for differences among MS clinical phenotypes. MATERIALS AND METHODS: Thirty-five patients with MS (2 with CIS, 27 with RRMS, 2 with SPMS, and 4 with PPMS phenotypes) and 27 healthy controls underwent whole cord 3T MR imaging. The spinal cord contour was segmented and assigned to bins representing each C1 to T12 vertebral level. Volumes were normalized, and group comparisons were age-adjusted. RESULTS: There was a trend toward decreased spinal cord volume at the upper cervical levels in PPMS/SPMS versus controls. A trend toward increased spinal cord volume throughout the cervical and thoracic cord in RRMS/CIS versus controls reached statistical significance at the T10 vertebral level. A statistically significant decrease was found in spinal cord volume at the upper cervical levels in PPMS/SPMS versus RRMS/CIS. CONCLUSIONS: Opposing pathologic factors impact spinal cord volume measures in MS. Patients with PPMS demonstrated a trend toward upper cervical cord atrophy. However patients with RRMS showed a trend toward increased volume at the cervical and thoracic levels, which most likely reflects inflammation or edema-related cord expansion. With the disease causing both expansion and contraction of the cord, the specificity of spinal cord volume measures for neuroprotective therapeutic effect may be limited.
Adverse reactions to thalidomide in patients infected with human immunodeficiency virus.

Thalidomide is emerging as a useful agent in the management of several complications of disease due to human immunodeficiency virus (HIV). We conducted three prospective studies of 56 HIV-infected patients who were treated with thalidomide for 14-21 days; 24 (43%) of these patients discontinued therapy owing to adverse reactions. Cutaneous and/or febrile reactions were the most frequent toxicities, arising in 20 (36%) of the patients. These reactions occurred after a mean interval (+/-SD) of 10 +/- 3 days and were associated with significantly lower CD4 T lymphocyte counts in reactors than in nonreactors (median count, 52.5/mm3 vs. 242 cells/mm3, respectively; P = .009). Four of four rechallenged patients experienced accelerated hypersensitivity; hypotension occurred in one case. Although sedation was an almost universal side effect among the patients, it was moderate or severe in only seven (13%); constipation was moderate or severe in five (9%) of the patients. Severe neuropathic symptoms and mood changes were each noted in two (4%) of the 56 patients. We conclude that the increasing use of thalidomide to treat HIV-infected patients must be accompanied by recognition of the drug's increased potential for toxicity in this population.
Dynamic Antigen Presentation Patterns of Listeria monocytogenes-Derived CD8 T Cell Epitopes In Vivo1

Little information exists regarding the presentation of antigenic peptides in infected tissues. In this study the in vivo presentation of four different CD8 T cell epitopes of Listeria monocytogenes was monitored. Peptide presentation was measured by a new, highly sensitive, ex vivo Ag presentation assay that was based on the testing of freshly isolated cells from infected spleens with peptide-specific CD8 T cell lines in an IFN-γ-specific ELISPOT assay. Remarkably, the peptide presentation pattern of splenocytes and that of macrophages purified from spleens of L. monocytogenes-infected mice were different from those of in vitro infected macrophage-like cell lines. The in vivo Ag presentation pattern of splenocytes also exhibited dynamic changes during the first 48 h of infection. In vivo peptide presentation at later time points postinfection was biased toward immunodominant CD8 T cell epitopes, while at an early time point, 6 h postinfection, subdominant and dominant CD8 T cell epitopes were presented with similar strength. In summary, our studies show that Ag presentation during an infection is a highly dynamic process that only can be fully appreciated by the study of cells infected in their physiological environment.
Comparison of the effect of topical and systemic melatonin administration on delayed wound healing in rats that underwent pinealectomy

Abstract Objectives. Melatonin is a hormone which has many systemic effects in addition to its strong antioxidant properties. The aim of the present study was to investigate the difference between sytemic and topical administration of melatonin by forming a chronic wound model in rats whose release of basal melatonin was supressed by pinealectomy. Material and methods. Experimental animals used in the study were divided into four equal groups: (i) a group of normal animals with wound formation (control), (ii) a group of animals who underwent pinelaectomy and wound formation (PINx), (iii) a group that underwent PINx + systemic melatonin administration, and (iv) a group that underwent PINx + topical melatonin administration. Fifteen days after pinealectomy, a bipediculed flap was formed on the back of the rats under anesthesia and then six excisional skin wounds were produced in all groups. Following the treatment that lasted 7 days, on day 8 the wound surface areas were measured and wound tissues were removed under anesthesia. In these tissues the levels of malondialdehit (MDA) and hydroxyproline (OH-proline) and the activities of superoxide dismutase(SOD) and glutathion peroxidase (GSH-Px) were measured. Results. In the PINx group, OH-prolin levels decreased significantly compared to the control group and wound surface areas increased. MDA levels increased compared to the control group, and SOD and GSH-Px decreased accordingly. Conversely, in two melatonin groups in which melatonin was administered systemically or topically MDA decreased while SOD ve GSH-Px enzymes increased. Conclusion. In conclusion, in the present study it was shown that wound healing was prolonged in experimental animals deprived of melatonin through pinealectomy. Melatonin exerts positive effects on wound healing, whether it is administered topically or systemically.
Flemish experience using the Advanta V12 stent-graft for the treatment of iliac artery occlusive disease.

AIM The aim of this study was to evaluate the technical feasibility and safety of implanting a polytetrafluoroethylene (PTFE) covered balloon expandable stent to treat iliac artery stenoses and occlusions. Additionally, the primary patency and clinical and hemodynamic efficacy at 1 year were analysed. METHODS This nonrandomized, prospective study involved patients with claudication and iliac artery occlusive disease at 2 participating centres. Patients with suitable lesions determined by clinical examination, ankle-brachial indices (ABIs), colour-flow duplex ultrasound (CFDU), magnetic resonance angiogram (MRA) and confirmed with biplanar digital subtraction angiography (DSA) were treated with PTFE-covered stainless steel stents. Procedural and 30-day periprocedural complications were recorded prospectively. According to in-hospital standards, follow-up with clinical ischemia category determination, ABI and CFDU was performed at 1, 6 and 12 months to determine treatment efficacy and primary limb patency. RESULTS In total, 91 limbs were treated in 65 patients (51 male; mean age 65 years). Stent-graft deployment was successful in 91 (100%) limbs. There were no limbs with residual stenosis >30%. There were no procedural or 30-day complications. The clinical ischemia category distribution improved significantly at 1, 6 and 12 months. The mean ABI rose significantly from 0.59 before treatment to 0.98, 0.98 and 0.99 at 1, 6 and 12 months after the procedure. Primary limb patency at 1-year was 91.1% CONCLUSIONS Implantation of Advanta V12 PTFE-covered stent for iliac occlusive disease shows to be safe and feasible with excellent clinical results at 1 year in the investigated patient cohort.
Life satisfaction and status among adolescent law offenders.

BACKGROUND Life satisfaction among young offenders may be affected by the subjective experience of their social status and by the feeling of being a 'loser' compared with others, but it is not clear what variables affect such experiences in this group. AIMS To examine relationships of type of sentence (prison or probation) and of gender with subjective social status, sense of defeat and life satisfaction among young offenders. METHODS One hundred and five participants were randomly selected from a cohort of young offenders, stratifying for sentence type and for gender. They were interviewed by trained and experienced interviewers. RESULTS Young people in a correctional facility experienced lower life satisfaction and greater sense of defeat than those on probation. Independently of judicial measure, low life satisfaction was correlated with sense of defeat among young men but not young women, whereas among young women, but not young men, low life satisfaction was associated with low subjective status. CONCLUSIONS AND IMPLICATIONS Our findings of a correlation between sentence type and life satisfaction needs new, longitudinal research to determine the direction of this relationship. Whether low life satisfaction is predictive of a custodial disposal for young offenders or such a sentence lowers life satisfaction, those trying to supervise or help these young people may need to take account of it. Further, our findings suggest that young male and young female offenders should perhaps be treated in different ways to improve their sense of satisfaction with life, which may, in turn, reduce their risk of reoffending.
Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: a systematic review.

OBJECT The goal of this study was to evaluate the obliteration rate of intracranial dural arteriovenous fistulas (DAVFs) in patients treated with stereotactic radiosurgery (SRS), and to compare obliteration rates between cavernous sinus (CS) and noncavernous sinus (NCS) DAVFs, and between DAVFs with and without cortical venous drainage (CVD). METHODS A systematic literature review was performed using PubMed. The CS DAVFs and the NCS DAVFs were categorized using the Barrow and Borden classification systems, respectively. The DAVFs were also categorized by location and by the presence of CVD. Statistical analyses of pooled data were conducted to assess complete obliteration rates in CS and NCS DAVFs, and in DAVFs with and without CVD. RESULTS Nineteen studies were included, comprising 729 patients harboring 743 DAVFs treated with SRS. The mean obliteration rate was 63% (95% CI 52.4%-73.6%). Complete obliteration for CS and NCS DAVFs was achieved in 73% and 58% of patients, respectively. No significant difference in obliteration rates between CS and NCS DAVFs was found (OR 1.72, 95% CI 0.66-4.46; p=0.27). Complete obliteration in DAVFs with and without CVD was observed in 56% and 75% of patients, respectively. A significantly higher obliteration rate was observed in DAVFs without CVD compared with DAVFs with CVD (OR 2.37, 95% CI 1.07-5.28; p=0.03). CONCLUSIONS Treatment with SRS offers favorable rates of DAVF obliteration with low complication rates. Patients harboring DAVFs that are refractory or not amenable to endovascular or surgical therapy may be safely and effectively treated using SRS.
Adversary Models Account for Imperfect Crime Data: Forecasting and Planning against Real-world Poachers

Poachers are engaged in extinction level wholesale slaughter, so it is critical to harness historical data for predicting poachers' behavior. However, in these domains, data collected about adversarial actions are remarkably imperfect, where reported negative instances of crime may be mislabeled or uncertain. Unfortunately, past attempts to develop predictive and prescriptive models to address this problem suffer from shortcomings from a modeling perspective as well as in the implementability of their techniques. Most notably these models i) neglect the uncertainty in crime data, leading to inaccurate and biased predictions of adversary behavior, ii) use coarse-grained crime analysis and iii) do not provide a convincing evaluation as they only look at a single protected area. Additionally, they iv) proposed time-consuming techniques which cannot be directly integrated into low resource outposts. In this innovative application paper, we (I) introduce iWare-E a novel imperfect-observation aWare Ensemble (iWare-E) technique\footnoteiWare-E is a predictive model integrated into Protection Assistant for Wildlife Security system (PAWS) developed at the University of Southern California, which is designed to handle the uncertainty in crime information efficiently. This approach leads to superior accuracy for adversary behavior prediction (up to 34% increase in AUC) compared to the previous state-of-the-art. We also demonstrate the country-wide efficiency of the models and are the first to (II) evaluate our adversary behavioral model across different protected areas in Uganda, i.e., Murchison Fall and Queen Elizabeth National Park, (totaling about 7500 square km) as well as (III) on fine-grained temporal resolutions. Lastly, (IV) we provide a scalable planning algorithm to design fine-grained patrol routes for the rangers, which achieves up to 150% improvement in number of predicted attacks detected.
MHC class I expression dependent on bacterial infection and parental factors in whitefish embryos (Salmonidae)

Ecological conditions can influence not only the expression of a phenotype, but also the heritability of a trait. As such, heritable variation for a trait needs to be studied across environments. We have investigated how pathogen challenge affects the expression of MHC genes in embryos of the lake whitefish Coregonus palaea. In order to experimentally separate paternal (i.e. genetic) from maternal and environmental effects, and determine whether and how stress affects the heritable variation for MHC expression, embryos were produced in full‐factorial in vitro fertilizations, reared singly, and exposed at 208 degree days (late‐eyed stage) to either one of two strains of Pseudomonas fluorescens that differ in their virulence characteristics (one increased mortality, while both delayed hatching time). Gene expression was assessed 48 h postinoculation, and virulence effects of the bacterial infection were monitored until hatching. We found no evidence of MHC class II expression at this stage of development. MHC class I expression was markedly down‐regulated in reaction to both pseudomonads. While MHC expression could not be linked to embryo survival, the less the gene was expressed, the earlier the embryos hatched within each treatment group, possibly due to trade‐offs between immune function and developmental rate or further factors that affect both hatching timing and MHC expression. We found significant additive genetic variance for MHC class I expression in some treatments. That is, changes in pathogen pressures could induce rapid evolution in MHC class I expression. However, we found no additive genetic variance in reaction norms in our study population.