Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurologists and end-of-life decision-making: The role of "protective paternalism".

Most end-of-life care situations that neurologists mediate in intensive care units (ICUs) involve surrogate decision-makers for patients who have lost their capacity to make—or even weigh in on—such decisions. While a decision to limit life-sustaining treatment is optimally shared between a patient's medical team and family, practical difficulties often complicate this dynamic.1 Surrogates are understandably emotionally wrought and often are unsure of the patient's own wishes for prioritizing prolongation of life vs pursuing comfort measures. Efforts of a medical team to communicate with and educate surrogates on a patient's disease and prognosis may be ineffective. Moreover, a neurologist's personal or cultural background may exert a strong influence on the extent and manner to which he or she involves families in end-of-life decision-making, especially when conflict arises. Data have been published on international variations of the degree to which physicians involve families in such decisions.2 However, data specific to neurologists and ICU shared decision-making remain sparse.
Endometrial adenocarcinoma in Norway. A study of a total population

Fifteen hundred sixty‐six patients with adenocarcinoma of the endometrioid type (AC) were studied. These accounted for 78.9% of all 1985 patients with confirmed endometrial carcinoma diagnosed in Norway in the period 1970 through 1978. Four hundred and sixty‐nine patients (29.9%) had well‐differentiated tumors, 677 (43.2%) were moderately and 420 (26.8%) poorly differentiated. Eighty‐one percent of the patients had surgicopathologic Stage I disease, 11% Stage II, 6% Stage III, and 2% Stage IV. Mean age at diagnosis was 62.1 years (range, 36 to 91). The crude 5‐year and 10‐year survival rates for all patients were 74.1% and 62.2%, respectively. Five‐year crude survival was 86.8% for Grade 1 and 58.3% for Grade 3 tumors. The 5‐year crude survival for patients with intramucosal tumors was 88.7% as opposed to 46.9% for patients with tumors infiltrating to the serosa. Sixty‐six percent of the patients with vessel invasion survived for 5 years in contrast to 88.6% for patients without vessel invasion. Histologic grade, myometrial infiltration, vessel invasion, and lymphocyte reaction surrounding the tumor were strongly interrelated. Multivariate analysis showed that the age of the patient at the time of diagnosis was the most important single prognostic factor. Disregarding age, survival in operated patients was more dependent on the depth of myometrial invasion than on grade and stage of disease.
Efficient Rebalancing of B-Trees with Relaxed Balance

B-trees with relaxed balance have been defined to facilitate fast updating on shared-memory asynchronous parallel architectures. To obtain this, rebalancing has been uncoupled from the updating so that extensive locking can be avoided in connection with updates. We analyze B-trees with relaxed balance, and prove that each update gives rise to at most [loga(N/2)]+1 rebalancing operations, where a is the degree of the B-tree, and N is the bound on its maximal size since it was last in balance. Assuming that the size of nodes is at least twice the degree, we prove that rebalancing can be performed in amortized constant time. So, in the long run, rebalancing is constant time on average, even if any particular update could give rise to a logarithmic number of rebalancing operations. We also prove that the amount of rebalancing done at any particular level decreases exponentially going from the leaves towards the root. This is important since the higher up in the tree a lock due to a rebalancing operation occurs, the larger a subtree which cannot be accessed by other processes for the duration of that lock. All of these results are in fact obtained for the more general (a, b)-trees, so we have results for both of the common B-tree versions as well as 2-3 trees and 2-3-4 trees.
Disparities in deep brain stimulation surgery among insured elders with Parkinson disease

Objective: To identify sociodemographic, clinical, and physician/practice factors associated with deep brain stimulation (DBS). DBS is a proven surgical therapy for Parkinson disease (PD), but is recommended only for patients with excellent health, results in significant out-of-pocket costs, and requires substantial physician involvement. Methods: Retrospective cohort study of more than 657,000 Medicare beneficiaries with PD. Multivariable logistic regression models examined the association between demographic, clinical, socioeconomic status (SES), and physician/practice factors, and DBS therapy. Results: There were significant disparities in the use of DBS therapy among Medicare beneficiaries with PD. The greatest disparities were associated with race: black (adjusted odds ratio [AOR] 0.20, 95% confidence interval [CI] 0.16–0.25) and Asian (AOR 0.55, 95% CI 0.44–0.70) beneficiaries were considerably less likely to receive DBS than white beneficiaries. Women (AOR 0.79, 95% CI 0.75–0.83) also had lower odds of receiving DBS compared with men. Eighteen percent of procedures were performed on patients with PD who had cognitive impairment/dementia, a reported contraindication to DBS. Beneficiaries treated in minority-serving PD practices were less likely to receive DBS, regardless of individual race (AOR 0.76, 95% CI 0.66–0.87). Even after adjustment for demographic and clinical covariates, high neighborhood SES was associated with 1.4-fold higher odds of receiving DBS (AOR 1.42, 95% CI 1.33–1.53). Conclusions: Among elderly Medicare beneficiaries with PD, race, sex, and neighborhood SES are strong independent predictors of DBS receipt. Racial disparities are amplified when adjusting for physician/clinic characteristics. Future investigations of the demographic differences in clinical need/usefulness of DBS, ease of DBS attainment, and actual/opportunity DBS costs are needed to inform policies to reduce DBS disparities and improve PD quality of care.
Left atrial appendage occlusion in atrial fibrillation after intracranial hemorrhage

Objective: To evaluate the safety and feasibility of percutaneous left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) and previous intracranial hemorrhage (ICH). Methods: In an explorative, prospective, single-center, observational study, LAAO was performed in patients with previous ICH and AF using the Amplatzer Cardiac Plug device. Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2Vasc score and the HAS-BLED score. Before and 1, 6, 12, and 24 months after the procedure, clinical status and complications were recorded. Major complications were predefined as periprocedural stroke, death, pericardial effusion, and device embolism. Results: LAAO was performed in 20 patients. Based on CHA2DS2Vasc score (mean 4.5 ± 1.4) and HAS-BLED score (mean 4.7 ± 1.0), annual risks of stroke and hemorrhagic complications were 4.0%–6.7% and 8.7%–12.5%, respectively. No patient had a procedure-related complication. Minor postprocedural complications were observed in 4/20 patients (2 inguinal hematoma, 1 self-limiting asystole, and 1 thrombus formation on device). No ischemic or hemorrhagic stroke occurred during a mean follow-up of 13.6 ± 8.2 months. Conclusions: In this first study of LAAO in patients with previous ICH, LAAO appears feasible and safe. A larger, controlled trial is needed to assess the efficacy and safety of the procedure compared to other preventive measures. Classification of evidence: This study provides Class III evidence that in patients with a history of previous ICH and AF, percutaneous LAAO is safe and feasible.
Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise.

BACKGROUND Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. METHODS AND RESULTS We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. CONCLUSIONS These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.
Mystery Case: A 63-year-old man with progressive proximal pain and weakness

A 63-year-old man with a history of type 2 diabetes presented with hip and shoulder pain in June 2010. He was on atorvastatin 80 mg daily and his creatine kinase (CK) was mildly elevated, so he was switched to simvastatin 20 mg daily. Three months later, he was referred to a rheumatologist. His CK was 142 U/L and his erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were mildly elevated (28 mm/hour and 14 mg/L, respectively). He was diagnosed with polymyalgia rheumatica. He was started on a methylprednisolone taper starting at 16 mg going to 8 mg daily with mild, although transient, improvement. He remained on 8 mg daily methylprednisolone for several months. Eight months later, he began to notice progressive proximal leg weakness and difficulty climbing stairs. His serum CK was 1,600 U/L. He stopped the simvastatin and was started on gemfibrozil. An EMG was normal. His CK rose to the 3,000s U/L 3 months later. Nine months later, 8-day methylprednisolone tapers starting at 16 mg daily were symptomatically ineffective, as was prednisone 60 mg daily tapered over 2 weeks.
Software Reliability Prediction Using Recurrent Neural Network With Bayesian Regularization

A recurrent neural network modeling approach for software reliability prediction with respect to cumulative failure time is proposed. Our proposed network structure has the capability of learning and recognizing the inherent internal temporal property of cumulative failure time sequence. Further, by adding a penalty term of sum of network connection weights, Bayesian regularization is applied to our network training scheme to improve the generalization capability and lower the susceptibility of overfitting. The performance of our proposed approach has been tested using four real-time control and flight dynamic application data sets. Numerical results show that our proposed approach is robust across different software projects, and has a better performance with respect to both goodness-of-fit and next-step-predictability compared to existing neural network models for failure time prediction.
On-road driving impairments in Huntington disease

Objective: To determine the driving skill impairments and underlying visual, motor, and cognitive deficits that lead to failure on road testing in manifest Huntington disease (HD). Methods: Certified driving assessment experts scored performance on 13 specific on-road driving skills in 30 persons with HD and 30 controls and issued a pass/fail decision based on their overall impression. These on-road skill items were mapped onto an existing theoretical framework that categorized driving skills into operational, tactical, visuo-integrative, and mixed clusters. The HD group additionally completed a detailed off-road battery of motor, visual, and neuropsychological tests. Results: The HD group performed worse on all on-road items. Fourteen drivers with HD (47%) failed the road test compared with none of the controls. Scores on the Total Functional Capacity scale discriminated significantly between pass and fail groups. Total on-road score and performance in operational, tactical, and visuo-integrative clusters correlated strongly (Spearman ρ >0.50) with the pass/fail decision. The off-road tests showed variable strengths of association depending on the level of driving skill. Selective attention was strongly associated (Spearman ρ >0.50) with the total on-road score and all driving clusters. Conclusions: HD affects driving at many levels due to motor and cognitive deficits and leads to unsafe road performance even in mild stages. The high failure rate on the road test and difficulties in all aspects of on-road driving suggest that monitoring of fitness to drive should be initiated in the early course of HD.
Pyridoxine responsiveness in novel mutations of the PNPO gene

Objective: To determine whether patients with pyridoxine-responsive seizures but normal biomarkers for antiquitin deficiency and normal sequencing of the ALDH7A1 gene may have PNPO mutations. Methods: We sequenced the PNPO gene in 31 patients who fulfilled the above-mentioned criteria. Results: We were able to identify 11 patients carrying 3 novel mutations of the PNPO gene. In 6 families, a homozygous missense mutation p.Arg225His in exon 7 was identified, while 1 family was compound heterozygous for a novel missense mutation p.Arg141Cys in exon 5 and a deletion c. 279_290del in exon 3. Pathogenicity of the respective mutations was proven by absence in 100 control alleles and expression studies in CHO-K1 cell lines. The response to pyridoxine was prompt in 4, delayed in 2, on EEG only in 2, and initially absent in another 2 patients. Two unrelated patients homozygous for the p.Arg225His mutation experienced status epilepticus when switched to pyridoxal 5′-phosphate (PLP). Conclusions: This study challenges the paradigm of exclusive PLP responsiveness in patients with pyridoxal 5′-phosphate oxidase deficiency and underlines the importance of consecutive testing of pyridoxine and PLP in neonates with antiepileptic drug–resistant seizures. Patients with pyridoxine response but normal biomarkers for antiquitin deficiency should undergo PNPO mutation analysis.
Immune therapy for pharmacoresistant epilepsy

Despite the introduction of almost 20 new antiseizure drugs in the last several decades, approximately 30% of patients with epilepsy have pharmacoresistant seizures. Although many genetic disorders and cerebral structural lesions are known causes of difficult-to-treat epilepsy, some refractory patients do not fall into these categories. In the search for other etiologic factors, the multiple and close interactions between the immune system and epilepsy have gained substantial interest.1
Structure–activity relationship of caffeic acid phenethyl ester analogs as new 5‐lipoxygenase inhibitors

Leukotrienes (LTs) are a class of lipid mediators implicated in numerous inflammatory disorders. Caffeic acid phenethyl ester (CAPE) possesses potent anti‐LTs activity through the inhibition of 5‐lipoxygenase (5‐LO), the key enzyme in the biosynthesis of LTs. In this study, we describe the design and synthesis of CAPE analogs as radical scavengers and 5‐LO inhibitors. Caffeic esters bearing propargyl and allyl linkers between the caffeoyl and aryl moieties (4a–i and 5a–i, respectively) were synthesized by Sonogashira and Heck cross‐coupling reactions to probe the effects of flexibility and aryl substitution on 5‐LO inhibition. Caffeoyl alcohol and ethers (6, 7a–b) as well as caffeoyl aldehyde and ketones (8a–e) were synthesized to elucidate the importance of the ester linkage for inhibitory activity. All tested compounds proved to be good radical scavengers (IC50 of 10–30 μm). After preliminary anti‐LTs activity screening in HEK293 cell models, 5‐LO inhibition potential of selected compounds was determined in human polymorphonuclear leukocytes (PMNL). Most screened compounds outperformed CAPE 3 in concentration‐dependent assays on PMNL, with ester dimers 4i and 5i along with caffeoyl ethers 7a–b being roughly eight‐, seven‐, and 16‐fold more potent than Zileuton, with IC50 values of 0.36, 0.43, and 0.18 μm, respectively.
Topology of brainstem lesions associated with subjective visual vertical tilt

Objective: We aimed to determine the topology of anatomical pathways for verticality perception in the brainstem. Methods: We measured the subjective visual vertical (SVV) in 82 patients with acute unilateral infarction of the brainstem alone. The topology of the brainstem lesions responsible for pathologic SVV tilt were determined using MRI-based voxel-wise lesion-behavior mapping, from which probabilistic lesion maps were constructed. Results: Fifty percent of patients (41/82) with acute unilateral brainstem infarcts had abnormal SVV tilt, of which 76% (31/41) had ipsiversive tilt and 24% (10/41) had contraversive tilt. Patients with contraversive SVV tilt exhibited overlapping lesions of the rostral medial vestibular nucleus, medial longitudinal fasciculus, rostral interstitial medial longitudinal fasciculus, and interstitial nucleus of Cajal. In contrast, patients with ipsiversive SVV tilt and oculomotor disturbances exhibited lesions of the medial and inferior vestibular nuclei in the caudal medulla, while those with isolated vertical perceptual changes had injury to the medial side of the medial lemniscus. Conclusions: Our findings provide evidence of a pathway transmitting ipsiversive otolithic signals that bypass the oculomotor system at the medial side of the medial lemniscus, called the ipsilateral vestibulothalamic tract.
Postganglionic sudomotor denervation in patients with multiple system atrophy

Objective: To evaluate postganglionic autonomic involvement in multiple system atrophy (MSA). Methods: We quantified sudomotor innervation in skin biopsy of 29 patients with MSA (19 male and 10 female; age 60.0 ± 7.7 years) and 29 age- and sex-matched healthy subjects. Samples were obtained from thigh and leg and, in 20 out of the 29 cases, also from fingertip. Dysautonomic complaints were evaluated by SCOPA-AUT, a self-administered questionnaire. Sudomotor function was evaluated in a subgroup of patients by the silastic imprint test. Skin samples were processed by indirect immunofluorescence using pan-neuronal and selective cholinergic markers. Total length of sudomotor nerves was measured on digital confocal images using a semiautomated morphometric approach. Results: Measurements of sudomotor nerve density (total length of nerve per volume of glandular tissue) favorably correlated to values obtained using a stereologic unbiased method. Sudomotor nerve density was lower in patients compared to controls in all the examined sites (0.9 ± 0.2 vs 1.9 ± 0.4 nm/μm3, p < 0.001, in fingertip; 0.7 ± 0.2 vs 1.9 ± 0.5 nm/µm3, p < 0.001, in thigh; 0.6 ± 0.2 vs 1.8 ± 0.4 nm/µm3, p < 0.001, in leg). Conclusions: Our data support the hypothesis that postganglionic impairment occurs in MSA and may contribute with the coexisting degeneration of central structures to the development of dysautonomic disorders in this condition.
The relationship between subclinical atherosclerosis and electrocardiographic abnormalities as biomarkers of cardiovascular risk

Abstract Electrocardiographic findings indicating myocardial disease, such as left ventricular hypertrophy or ST-T wave abnormalities, or the presence of coronary artery calcium, indicating atherosclerotic coronary artery disease, are both biomarkers of future cardiovascular (CV) risk. Although the risk factors for myocardial and coronary artery disease are similar, their concomitant expression has implications for CV disease screening and prevention programmes. The relationship between the resting 12-lead ECG and subclinical atherosclerosis measured as coronary artery calcium (CAC) with electron beam tomography was examined in 937 healthy participants (aged 40–50 years) enrolled in a CV risk screening study. Electrocardiograms and CAC were interpreted in blinded fashion, using standard criteria. An abnormal ECG was coded in 268 (28.6%) participants, most commonly left ventricular hypertrophy (3.1%), delayed precordial R wave transition (5.7%), T-wave abnormalities (10.0%) and intraventricular conduction delay (10.4%). Although abnormal ECG findings were associated with CV risk variables, the prevalence of any CAC was similar in subjects with any ECG finding (43 of 268, 16.0%) compared with those with normal ECGs (125 of 669, 18.7%, p=NS). In a logistic model controlling for CV risk factors including systolic blood pressure, low-density lipoprotein cholesterol (LDL-C), body mass index (BMI), glycosylated haemoglobin, race, age and gender, significant associations with CAC were found for LDL-C, race and BMI. There was no significant relationship between CAC and ECG abnormalities (odds ratio 0.80, 95% confidence interval 0.54–1.20). In conclusion, electrocardiographic abnormalities and subclinical calcified atherosclerosis were not significantly associated with each other in this middle-aged screening population. This suggests these two biomarkers may be complementary towards broader detection of latent CV risk.
Cerebral perfusion alterations and cerebral amyloid in autosomal dominant Alzheimer disease

Objective: To evaluate alterations in cerebral blood flow (CBF) using arterial spin-labeled MRI in autosomal dominant Alzheimer disease (ADAD) mutation carriers (MCs) in relation to cerebral amyloid and compared with age-matched healthy controls. Background: Recent work has identified alterations in CBF in elderly subjects with mild cognitive impairment and Alzheimer dementia using MRI. However, similar studies are lacking in ADAD. Subjects with ADAD are generally free of significant vascular disease and offer the opportunity to measure CBF early in the pathologic process before significant symptom onset when unique markers might be identified. Methods: Fourteen MCs (presenilin-1 and amyloid beta precursor protein) (Clinical Dementia Rating [CDR] 0 = 9, CDR 0.5 = 4, CDR 1 = 1) and 50 controls underwent 3-tesla pulsed arterial spin-labeled MRI. SPM8 was used to test the effect of MC status at the voxel level on CBF before and after controlling for age and CDR. Results: MCs had decreased perfusion in the caudate and inferior striatum bilaterally even after controlling for age and CDR. In MCs, separate areas of decreased CBF were associated with increasing cerebral amyloid and to decreased performance of attention and executive function. Conclusions: Early CBF changes were identified in asymptomatic and mildly symptomatic subjects with ADAD, particularly in the anterior striatum. Furthermore, amyloid deposition was associated with decreased CBF in a number of regions including anterior and posterior cortical areas. Both amyloid and decreased CBF were associated with declines primarily in executive cognitive function.