Miracle-dz/UniFAR-FTUs huggingface dataset:
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission?

PURPOSE Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, ≥ 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution. PATIENTS AND METHODS We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive. RESULTS Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups. CONCLUSION The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments.
Segregation of Ipsilateral Retinal Ganglion Cell Axons at the Optic Chiasm Requires the Shh Receptor Boc

The pattern of contralaterally and ipsilaterally projecting retinal ganglion cell (RGC) axons at the optic chiasm is essential for the establishment of binocular vision. Contralateral axons cross the chiasm midline as they progress from the optic nerve to the optic tract. In contrast, ipsilateral axons deviate from the chiasm and continue in the ipsilateral optic tract, avoiding the chiasm midline. The molecular mechanism underlying this phenomenon is not completely understood. Here we show that the Sonic Hedgehog (Shh) receptor Boc is enriched in ipsilateral RGCs of the developing retina. Together with the presence of Shh at the midline, this complementary expression pattern led us to hypothesize that Shh might repel ipsilateral RGC axons at the chiasm. Consistent with this hypothesis, we found that only Boc-positive RGC axons retract in vitro in response to Shh and that this response is lost in Boc mutant RGCs. In vivo, we show that Boc is required for the normal segregation of ipsilateral axons at the optic chiasm and, conversely, that Boc expression in contralateral RGCs prevents their axons from crossing the optic chiasm. Together, these results suggest that Shh repels ipsilateral RGC axons at the optic chiasm via its receptor Boc. This work identifies a novel molecular pathway required for the segregation of axons at the optic chiasm.
Meandering Main Pancreatic Duct as a Relevant Factor to the Onset of Idiopathic Recurrent Acute Pancreatitis

Background Meandering main pancreatic duct (MMPD), which comprises loop type and reverse-Z type main pancreatic duct (MPD), has long been discussed its relation to pancreatitis. However, no previous study has investigated its clinical significance. We aimed to determine the non-biased prevalence and the effect of MMPD on idiopathic pancreatitis using non-invasive magnetic resonance (MR) technique. Methods and Findings A cross-sectional study performed in a tertiary referral center. The study enrolled 504 subjects from the community and 30 patients with idiopathic pancreatitis (7 acute, 13 chronic, and 10 recurrent acute). All subjects underwent MR scanning and medical examination. MMPD was diagnosed when the MPD in the head of pancreas formed two or more extrema in the horizontal direction on coronal images of MR cholangiopancreatography, making a loop or a reverse-Z shaped hairpin curves and not accompanied by other pancreatic ductal anomaly. Statistical comparison was made among groups on the rate of MMPD including loop and reverse-Z subtypes, MR findings, and clinical features. The rate of MMPD was significantly higher for all idiopathic pancreatitis/idiopathic recurrent acute pancreatitis (RAP) (20%/40%; P<0.001/0.0001; odds ratio (OR), 11.1/29.0) than in the community (2.2%) but was not higher for acute/chronic pancreatitis (14%/8%; P = 0.154/0.266). Multiple logistic regression analysis revealed MMPD to be a significant factor that induces pancreatitis/RAP (P<0.0001/0.0001; OR, 4.01/26.2). Loop/reverse-Z subtypes were found more frequently in idiopathic RAP subgroup (20%/20%; P = 0.009/0.007; OR, 20.2/24.2) than in the community (1.2%/1.0%). The other clinical and radiographic features were shown not associated with the onset of pancreatitis. Conclusions MMPD is a common anatomical variant and might be a relevant factor to the onset of idiopathic RAP.
Patient Outcomes in the Operative and Nonoperative Management of High-Grade Spondylolisthesis in Children

Background: The optimal management of high-grade spondylolisthesis in the growing child is controversial. Some authors have advocated for surgery in all cases regardless of symptoms. Surgical intervention results in a >10% risk of complications with increased risk of neurological injury associated with slip reduction maneuvers. There is a paucity of literature regarding nonoperative management in this setting. This study sought to obtain outcome measures in pediatric patients with high-grade spondylolisthesis managed either operatively or nonoperatively. Methods: Database review was performed to identify patients with a high-grade (Meyerding grade III to V) spondylolisthesis managed either operatively or nonoperatively. Retrospective radiographic and chart review was performed. Patients were then contacted by phone to obtain current quality-of-life measurements using the Scoliosis Research Society (SRS)-30 questionnaire. Results: Fifty-three patients were identified for inclusion in the study and 49 were contacted for 92% follow-up. Twenty-four patients were treated with operative intervention, and 25 patients were initially treated nonoperatively, but 10 went on to require surgical intervention. Mean age at presentation was 12.6 years (range, 8 to 17 y) and mean age at follow-up was 20.1 years (range, 10 to 29 y). There were no outcome differences between the groups. A more kyphotic slip angle was associated with worse SRS-30 outcome scores across all groups. In the nonoperative group, the slip angle was significantly larger in patients who failed conservative treatment (34±17 degrees) than in those who remained nonsurgical at final follow-up (20±14 degrees). Slip angle in the operative group was 27±14 degrees. In surgical patients, an older age at surgery was associated with better SRS-30 outcome scores. Conclusions: Nonoperative management or “watchful waiting” of the minimally symptomatic or asymptomatic child with a high-grade spondylolisthesis is safe and does not lead to significant problems. Operative intervention for the symptomatic patient achieves similar long-term results compared with patients whose minimal symptoms do not warrant surgery. Delayed surgical intervention does not result in worse outcomes. Regardless of treatment modality, patients with a more kyphotic slip angle tend to have a poorer prognosis. Level of Evidence: Level III.
Leukotriene Production Is Increased in Abdominal Obesity

Obesity is a major risk factor for insulin resistance and type-2 diabetes. A chronic low grade inflammatory state has been described during obesity and associated with insulin resistance pathogenesis. Results from animal studies are in favor of a role of the leukotriene (LT) pathway in obesity induced-insulin resistance. However, there is a paucity of data regarding this association in human obesity. Therefore, the aim of this study was to investigate whether LT production was associated with insulin resistance and other metabolic parameters in a cohort of obese subjects. Forty-six (70% females) obese subjects (BMI≧30 kg/m2) without known diabetes and without inflammatory disease (CRP<10 mg/l) were included. Median age was 44 years (16–80) with a median BMI of 36.8 kg/m2 (30–51). Insulin resistance was evaluated by HOMA-IR index and glucose tolerance test. Urinary LTE4 (U-LTE4) concentration was measured by enzyme immune assay. Screening for obstructive sleep apnea was performed. There was a positive association of U-LTE4 with waist to hip ratio, systolic blood pressure and HOMA-IR in univariate analysis. Further, waist to hip ratio remained the only parameter significantly correlated with U-LTE4, in adjusted multivariate analysis. Taken together, these results confirm the previously established notion of chronic low grade inflammation in obesity and further suggests a role for the LT pathway in obesity-associated development of insulin resistance in humans.
Functional Clustering of Neurons in Motor Cortex Determined by Cellular Resolution Imaging in Awake Behaving Mice

Macroscopic (millimeter scale) functional clustering is a hallmark characteristic of motor cortex spatial organization in awake behaving mammals; however, almost no information is known about the functional micro-organization (∼100 μm scale). Here, we optically recorded intracellular calcium transients of layer 2/3 neurons with cellular resolution over ∼200-μm-diameter fields in the forelimb motor cortex of mobile, head-restrained mice during two distinct movements (running and grooming). We showed that the temporal correlation between neurons was statistically larger the closer the neurons were to each other. We further explored this correlation by using two separate methods to spatially segment the neurons within each imaging field: K-means clustering and correlations between single neuron activity and mouse movements. The two methods segmented the neurons similarly and led to the conclusion that the origin of the inverse relationship between correlation and distance seen statistically was twofold: clusters of highly temporally correlated neurons were often spatially distinct from one another, and (even when the clusters were spatially intermingled) within the clusters, the more correlated the neurons were to each other, the shorter the distance between them. Our results represent a direct observation of functional clustering within the microcircuitry of the awake mouse motor cortex.
A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group.

BACKGROUND Preoperative transfusions are frequently given to prevent perioperative morbidity in patients with sickle cell anemia. There is no consensus, however, on the best regimen of transfusions for this purpose. METHODS We conducted a multicenter study to compare the rates of perioperative complications among patients randomly assigned to receive either an aggressive transfusion regimen designed to decrease the hemoglobin S level to less than 30 percent (group 1) or a conservative regimen designed to increase the hemoglobin level to 10 g per deciliter (group 2). RESULTS Patients undergoing a total of 604 operations were randomly assigned to group 1 or group 2. The severity of the disease, compliance with the protocol, and the types of operations were similar in the two groups. The preoperative hemoglobin level was 11 g per deciliter in group 1 and 10.6 g per deciliter in group 2. The preoperative value for hemoglobin S was 31 percent in group 1 and 59 percent in group 2. The most frequent operations were cholecystectomies (232), head and neck surgery (156), and orthopedic surgery (72). With the exception of transfusion-related complications, which occurred in 14 percent of the operations in group 1 and in 7 percent of those in group 2, the frequency of serious complications was similar in the two groups (31 percent in group 1 and 35 percent in group 2). The acute chest syndrome developed in 10 percent of both groups and resulted in two deaths in group 1. A history of pulmonary disease and a higher risk associated with surgery were significant predictors of the acute chest syndrome. CONCLUSIONS A conservative transfusion regimen was as effective as an aggressive regimen in preventing perioperative complications in patients with sickle cell anemia, and the conservative approach resulted in only half as many transfusion-associated complications.
Knowledge of Pregnant Women About the Importance of Fulfillment of Folic Acid in the Optimization of Fetal Development During Pregnancy at the Giopani Simbolon Clinic

Prevalence rates per 1000 live births regarding folic acid fulfillment were reported in Native Americans (2.7%), Japanese (2.1%), African Americans (0.42%). The purpose of this study was to find out the knowledge of pregnant women about the importance of fulfilling folic acid during pregnancy at the Giopani Simbolon Am.Keb Midwife Clinic, Padangmatinggi Village, South Padangsidimpuan District in 2020. This type of research is descriptive using accidental sampling with 20 respondents. Data collection uses a questionnaire sheet, using primary and secondary data based on variables of knowledge, age, education, employment, parity, and sources of information. Based on the results of the study of 20 respondents, the majority lacked knowledge, namely 14 respondents (70%), based on age the majority was less, namely 10 respondents (50%), based on education the majority was lacking, namely 8 respondents (40%), based on work the majority was lacking, namely 10 respondents (50%), based on parity the majority was lacking, namely 8 respondents (40%), and based on information sources the majority was lacking, namely 11 respondents (55%). Based on the results of the study it can be concluded that the majority of pregnant women's knowledge about the importance of fulfilling folic acid is still lacking so it is expected that pregnant women will increase their knowledge about folic acid either through health workers, print media, and electronic media.
Alterations of Nutritional Status in Children and Adolescents with Acute Lymphoblastic Leukemia

Malnutrition is often observed in pediatric cancer patients and has been recognized as a risk factor for relapse and survival. Maintaining an appropriate nutritional status during anticancer treatment has, therefore, been more and more frequently perceived as an additional requirement for optimal therapy outcomes. The aim of our study was to establish alterations of nutritional status in 26 children and adolescents treated for acute lymphoblastic leukemia (ALL) at the Children’s Hospital in Zagreb, Croatia, between 2016 and 2021, by using anthropometric measures and serum albumin levels. The majority of patients (53.8% female, median 4 years, 52.2% intermediate-risk leukemia group) had normal weight at the beginning of chemotherapy. The percentage of overweight/obese patients increased from 4.2% at diagnosis to 37.5% at the end of intensive therapy. Apart from a significant increase in body weight (BW) and body mass index (BMI) for age, a notable decline in body height/body length (BH/BL) for age in the observed period was recorded, especially in high-risk leukemia patients. The alterations in serum albumin values were not significant, nor was their correlation with BMI. Dietary consultation was offered to all patients, while children with a decline in BMI and BH/BL received additional nutritional support.
Methylmercury Production in Two Northern Fen Peatlands

Mercury is a naturally occurring element in the Earth’s lithosphere. Although natural processes result in mercury releases into the atmosphere and subsequent cycling through ecosystems, anthropogenic activities have greatly exceeded these natural processes. Methylmercury (MeHg) is the form of mercury produced in anoxic environments, mainly by sulphate reducing bacteria, which methylate mercury as a by product to their respiration. Northern peatlands are sites of MeHg production, particularly those dominated by mosses. Experiments have shown that climate change may drive a shift from mossto sedgedominance and may then alter mercury biogeochemistry and downstream water quality. Measurements made in a moss-dominated poor fen and sedge-dominated intermediate fen were used to compare MeHg to assess if contrasting peatland type, nutrients status and/or hydrologic regime control MeHg production. Chapter 2 compared porewater MeHg and ancillary chemistry across two Northern Ontario fens. In the poor fen, the lower water table (mean = -21.1 cm) and pH (median = 4.90), and higher dissolved organic carbon (median = 27.46 mg L), resulted in 3.1 times greater MeHg (median = 0.54 ng-Hg L) compared the intermediate fen (0.17 ng-Hg L) where the higher water table (-5.4 cm) and pH (5.63), and lower dissolved organic carbon (19.20 mg L) limited MeHg concentrations. A seasonal water table drawdown period resulted in increased sulphate availability in both the intermediate and poor fen leading to greater MeHg in September. In Chapter 3, riparian zones in the intermediate fen were evaluated to see if groundwater nutrient supply controlled MeHg production and transport adjacent to two incised peatland streams. Rather than groundwater supply, riparian zones with a lower water table and greater fluctuations resulted in higher available sulphate (> 1.0 mg L) and MeHg (> 0.5 ng-Hg L) concentrations compared to those with a higher overall waters tables and smaller fluctuations. Increased sulphate availability following a seasonal water table drawdown resulted in August (1.67 ngHg L) and September (3.36 ng-Hg L) maximums in MeHg in riparian zones. The proximity (≤ 2 m) of riparian zones to stream waters then facilitated methylmercury transport to surface waters. Hydrologic variability and sulphate availability were the main drivers leading to greater MeHg in both the poor and intermediate fen.
Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome

Individuals with Down syndrome (DS) develop the pathological hallmarks of Alzheimer's disease at an early age, later followed by memory decline and dementia. Women with DS are twice as likely to undergo early menopause, and levels of estradiol correlate with onset of cognitive decline in these women. We have demonstrated that a mouse model of DS, mice with segmental trisomy of chromosome 16 (Ts65Dn), develop a significant deficit in both reference and working memory as young adults (6–10 months of age), coupled with phenotypic loss of cholinergic neurons in the basal forebrain and altered growth factor levels. In the present study we examined cholinergic and dendritic markers in the hippocampal formation and levels of the amyloid precursor protein (APP) in different brain regions of Ts65Dn mice treated with estradiol for 60 days. The density of the dendritic marker Map2 was significantly decreased in the hippocampal formation of middle‐aged trisomic mice (9–15 months old), and the density of cholinergic neurites (acetylcholinesterase [AChE] histochemistry) was also decreased in specific layers of the hippocampus. Treatment with 17β‐estradiol alleviated the decreases in Map2 and AChE staining, but had no effect on full‐length APP levels in the hippocampus. In contrast, a main effect of treatment on APP levels in the striatum was noted, with significant elevations observed in controls and trisomics. These findings demonstrate that estrogen can alleviate deficits in cholinergic and dendritic elements in the hippocampal formation and further strengthens the rationale to explore estrogen replacement therapy in women with DS. © 2003 Wiley‐Liss, Inc.
Effects of Blue Oak Canopy on Annual Forage Production

Production of annual forage was compared at four sites under four blue oak (Quercus douglasii) canopy levels (0, 25, 50, and 75 percent), over 5 years, at the University of California Sierra Foothill Research and Extension Center in Yuba County, California. Long-term annual precipitation averages 28.5 inches. Significant differences in herbaceous forage production occurred among years, with the highest rainfall season being the most productive and the drier years generally being less productive. There was a significant (approximately 100 percent) difference in production among sites. The effects of canopy cover varied from year to year; canopy significantly depressed forage yield in 2 of the 5 years. High rainfall years appeared to favor herbaceous plant growth under the higher canopy levels. Clearing of blue oaks (Quercus douglasii) from northern California hardwood rangelands has been shown to increase the production of forage for livestock (Jansen 1987; Johnson and others 1959; Kay 1987; Murphy and Crampton 1964). However, forage enhancement due to clearing is not consistent throughout the state, and at other California locations, higher herbage levels have been found under oak canopy (Duncan and Clawson 1980; Duncan and Reppert 1960; Frost and McDougald 1989; Holland 1973, 1980 ). Bartolome and others (1994) found no difference in forage yield due to oak canopy. Duncan and Clawson (1980), Kay (1987), and Menke (1987) discussed reasons for the variable effects of oak canopy on forage growth throughout the state. These include tree density, climate, and soil factors. McClaran and Bartolome (1989) identified mean annual precipitation as a factor influencing the relationship between forage yield and oak canopy; they reported reductions in forage production due to oak canopy only where mean annual precipitation is greater than 20 inches. Kay (1987) demonstrated that increased forage yield due to blue oak clearing continued only for a limited time (15 years). He also showed that naturally open grasslands produced more forage than areas with trees, suggesting that cleared areas will return to a forage production level that is higher than that under canopies. Oak woodlands are valuable for wildlife habitat and protection of soil and water quality. Because oak management practices have long-term implications, and because canopy effects vary widely, it is important to determine the longterm results of oak clearing under specific conditions. The objective of this study was to compare herbaceous forage production under a range of blue oak canopy levels, across a number of sites, in the northern Sierra Nevada foothills.
Text Analysis of Aberdeen Burgh Records 1530-1531

The paper outlines a text analytic project in progress on a corpus of entries in the historical burgh and council registers from Aberdeen, Scotland. Some preliminary output of the analysis is described. The registers run in a near-unbroken sequence form 1398 to the present day; the early volumes are a UNESCO UK listed cultural artefact. The study focusses on a set of transcribed pages from 1530-1531 originally hand written in a mixture of Latin and Middle Scots. We apply a text analytic tool to the corpus, providing deep semantic annotation and making the text amenable to linking to web-resources.