Miracle-dz/UniFAR-FTUs huggingface dataset:
Smoothing spline regression estimates for randomly right censored data

This thesis investigates a class of nonparametric regression estimates (smoothing spline estimates) in the presence randomly right censored data. In particular, it is shown that suitably defined estimates of the conditional mean lifetime, the conditional survival function, and the conditional variance of the lifetime achieve the optimal rates of convergence up to a logarithmic factor. These results are valid without any regularity assumption on the distribution of the covariates (beside boundedness) and for adaptive estimators. Furthermore, the consistency of the considered smoothing spline estimates is discussed and the estimators are applied to simulated and real data sets. Die vorliegende Arbeit analysiert eine Klasse von nichtparametrischen Regressionsschatzern (Smoothing-Splineschatzer) in der Gegenwart zufallig rechtszensierter Daten. Besonderes Augenmerk gilt dabei dem Nachweis fast – d.h. bis auf einen logarithmischen Faktor – optimaler Konvergenzraten geeignet definierter Schatzer der bedingten mittleren Uberlebenszeit, der bedingten Uberlebenszeitfunktion sowie der bedingten Varianz der Uberlebenszeit. Diese Resultate sind gultig, ohne Regularitatsannahmen an die zugrundeliegende Verteilung der Kovariablen zu stellen (auser Beschranktheit) und gelten auch fur adaptive Schatzer. Ferner wird die Konsistenz der betrachteten Smoothing-Splineschatzer erortert und die Schatzer werden auf simulierte sowie reale Datensatze angewendet.
Tailored magnetic resonance fingerprinting of post-operative pediatric brain tumor patients

Purpose: Brain and spinal cord tumors are the second most common cancer in children and account for one out of four cancers diagnosed. However, the long acquisition times associated with acquiring both data types prohibit using quantitative MR (qMR) in pediatric imaging protocols. This study aims to demonstrate the tailored magnetic resonance fingerprinting's (TMRF) ability to simultaneously provide quantitative maps (T1, T2) and multi-contrast qualitative images (T1 weighted, T1 FLAIR, T2 weighted) rapidly in pediatric brain tumor patients. Methods: In this work, we imaged five pediatric patients with brain tumors (resected/residual) using TMRF at 3T. We compared the TMRF-derived T2 weighted images with those from the vendor-supplied sequence (as the gold standard, GS) for healthy and pathological tissue signal intensities. The relaxometric maps from TMRF were subjected to a region of interest (ROI) analysis to differentiate between healthy and pathological tissues. We performed the Wilcoxon rank sum test to check for significant differences between the two tissue types. Results: We found significant differences (P < 0.05) in both T1 and T2 ROI values between the two tissue types. A strong correlation was found between the TMRF-based T2 weighted and GS signal intensities for the healthy (correlation coefficient, r = 0.99) and pathological tissues (r = 0.88). Conclusion: The TMRF implementation provides the two relaxometric maps and can potentially save ~2 minutes if it replaces the T2-weighted imaging in the current protocol.
Assessment tools and incidence of hospital-associated disability: a rapid systematic review

Background During hospitalization older people have a high risk of developing functional impairments unrelated to the reasons for their admission. This is termed hospital associated disability. The aims of this systematic review were to assess the incidence of hospital associated disability among older patients admitted to acute care, to identify the tools used to assess activities of daily living in these patients, and to evaluate which functional task is most sensitive for detecting changes in disability among older hospitalized patients. Methods A rapid systematic review was performed according to the recommendations of the Cochrane Rapid Reviews Methods Group and the PRISMA statement. A literature search was performed in Medline (via Ovid), EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases on 26 August 2021. Inclusion criteria: older people (equal or more than 65 years), assessment of activities of daily living at baseline and discharge. Exclusion criterion: diseases affecting functional decline. Results Eleven studies were included in the final review. Incidence of hospital-associated disability (overall score) was 37% (95% CI 0.31, 0.42). Insufficient data prevented meta analysis of the individual items. The most sensitive measure for detecting changes in disability was the overall score of assessment of activities of daily living. Conclusions Incidence of hospital-associated disability in older patients might be overestimated, due to the combination of disease-related disability and hospital associated disability. The tools used to assess these patients presented some limitations. These results should be interpreted with caution, as a limited number of studies reported adequate information to assess the incidence of hospital associated disability. Risk of bias in the included studies raised some concerns. Keywords Functional decline, hospitalization; activities of daily living; older patients
A Clinically Applicable Predictive Score in Lumbar Disc Disease for Formulating a Surgical Plan

Study Design Case control study Objective Micro-lumbar discectomy or Interbody fusion procedure are work-horse surgical procedures in management of lumbar disc disease. Spine surgeon in their early years of practice gets confused in choosing ideal surgical plan when dealing with a complex scenario. A clinical score is needed to guide spine surgeons in choosing an optimal surgical plan. Materials and methods Study was done with research grant approval from AO Spine. A predictive score was formulated as per hypothesis following a pilot study. Two fellowship trained spine surgeons-one using the score (Group A) and other not using score (Group B-control) treated 40 patients included in their respective group. All patients were analysed preoperatively, post-surgery at 12 months follow-up with Visual analog scale score for back pain, leg pain, Oswestry disability index score, SF-36 score. Change in parameters at 12 months follow-up were analysed statistically. P ≤ . 05 was considered statistically significant. Success rate of individual surgeon who managed respective group of patients and Difficulty index of surgeon who managed without using score was evaluated at 12 months follow-up. Results Success rate of Group A-surgeon was higher than Group B-surgeon . 15% of Group B patients had poor surgical outcome at follow-up. Statistically significant improvement in Group A patients were seen in all 3 evaluated parameters when compared to Group B patients at 12 months of follow-up (P ≤ .05). Difficulty index of surgeon who didn’t use the score was 15%. Conclusion The proposed predictive score comprising all risk factors, can be used by spine surgeons when they are confronted with difficult scenario in decision-making. Accuracy, reliability and validity of the score needs to be evaluated in a larger scale. Level of evidence Ⅲ
Effect of Irisin on Human Nucleus Pulposus Cells: New Insights into the Biological Cross-talk Between Muscle and Intervertebral Disk

Study Design. In vitro study. Objective. To investigate the effect of irisin on human nucleus pulposus cells (hNPCs) in vitro. Summary of Background Data. Physical exercise (PE) favours weight loss and ameliorates function in patients with low back pain. Although there is no biological evidence that the intervertebral disk (IVD) can respond to PE, recent studies have shown that running is associated with increased IVD hydration and hypertrophy. Irisin, a myokine released upon muscle contraction, has demonstrated anabolic effects on different cell types, including chondrocytes. Materials and Methods. hNPCs were exposed to 5, 10, and 25 ng/mL irisin. Cell proliferation, glycosaminoglycan (GAG) content, metabolic activity, gene expression of collagen type II (COL2), matrix metalloproteinase (MMP)-13, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-3, aggrecan (ACAN), interleukin (IL)-1β, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 were assessed. In addition, MTT assay and ADAMTS-5, COL2, TIMP-1, and IL-1β gene expression were evaluated following incubation with irisin for 24 hours and subsequent culture with 10 ng/mL IL-1β and vice versa (incubation for 24 hours with IL-1β and subsequent culture with irisin). Results. Irisin increased hNPC proliferation, metabolic activity, and GAG content, as well as COL2, ACAN, TIMP-1 and TIMP-3 gene expression, while decreasing MMP-13 and IL-1β mRNA levels. Irisin pretreatment of hNPCs cultured in proinflammatory conditions resulted in a rescue of metabolic activity and a decrease of IL-1β levels. Similarly, incubation of hNPCs with IL-1β and subsequent exposure to irisin led to an increment of metabolic activity, COL2 gene expression, and a reduction of IL-1β and ADAMTS-5 levels. Conclusions. Irisin increases hNPC proliferation, GAG content, metabolic activity, and promotes anabolic gene expression while reducing catabolic markers. Irisin may be one of the mediators by which PE and muscle tissues modulate IVD metabolism, suggesting the existence of a biological cross-talk between the muscle and IVD.
The Particle-In-Cell Method for Hydrodynamic Calculations

This report supersedes LAMS-1956 and LAMS-2052. A method is presented for solving hydrodynamic problems involving large distortions and compressions of the fluid in several space dimensions. The calculation proce- dure introduces finite difference approximations to the differential equations; the solution in practice is carried out by means of high-speed electronic computers. The characteristics of the method are discussed and these are illustrated by presenting results of representative calculations. (auth)
Status of the HIV epidemic in Manicaland, east Zimbabwe prior to the outbreak of the COVID-19 pandemic

Background Manicaland province in eastern Zimbabwe has a high incidence of HIV. Completion of the seventh round of the Manicaland Survey in 2018–2019 provided the opportunity to assess the state of the epidemic prior to the start of the COVID-19 pandemic. The study aims were to: a) estimate HIV seroprevalence and assess whether prevalence has declined since the last round of the survey (2012–2013), b) describe and analyse the socio-demographic and behavioural risk factors for HIV infection and c) describe the HIV treatment cascade. Methods Participants were administered individual questionnaires collecting data on socio-demographic characteristics, sexual relationships, HIV prevention methods and treatment access, and were tested for HIV. Descriptive analyses were followed by univariate and multivariate analyses of risk factors for HIV seropositvity using logistic regression modelling based on the proximate-determinants framework. Results HIV prevalence was 11.3% [95% CI; 10.6–12.0] and was higher in females than males up to 45–49 years. Since 2012–2013 HIV prevalence has significantly declined in 30–44 year-olds in males, and 20–44 year-olds in females. The HIV epidemic has aged since 2012–2013, with an increase in the mean age of HIV positive persons from 38 to 41 years. Socio-demographic determinants of HIV prevalence were church denomination in males, site-type, wealth-status, employment sector and alcohol use in females, and age and marital status in both sexes. Behavioural determinants associated with increased odds of HIV were a higher number of regular sexual partners (lifetime), non-regular sexual partners (lifetime) and condom use in both sexes, and early sexual debut and concomitant STIs in females; medical circumcision was protective in males. HIV status awareness among participants testing positive in our study was low at 66.2%. ART coverage amongst all participants testing positive for HIV in our study was 65.0% and was lower in urban areas than rural areas, particularly in males. Conclusions Prevalence has declined, and ART coverage increased, since 2012–2013. Majority of the associations with prevalence hypothesised by the theoretical framework were not observed in our data, likely due to underreporting of sexual risk behaviours or the treatment-as-prevention effect of ART curtailing the probability of transmission despite high levels of sexual risk behaviour. Further reductions in HIV incidence require strengthened primary prevention, HIV testing and linkage to risk behaviour counselling services. Our results serve as a valuable baseline against which to measure the impact of the COVID-19 pandemic on HIV prevalence and its determinants in Manicaland, Zimbabwe, and target interventions appropriately.
A value-based approach to optimize red blood cell transfusion in patients receiving extracorporeal membrane oxygenation

Introduction The risk, cost, and adverse outcomes associated with packed red blood cell (RBC) transfusions in patients with cardiopulmonary failure requiring extracorporeal membrane oxygenation (ECMO) have raised concerns regarding the overutilization of RBC products. It is, therefore, necessary to establish optimal transfusion criteria and protocols for patients supported with ECMO. The goal of this study was to establish specific criteria for RBC transfusions in patients undergoing ECMO. Methods This was a retrospective cohort study conducted at Stanford University Hospital. Data on RBC utilization during the entire hospital stay were obtained, which included patients aged ≥18 years who received ECMO support between 1 January 2017, and 30 June 2020 (n = 281). The primary outcome was in-hospital mortality. Results Hemoglobin (HGB) levels >10 g/dL before transfusion did not improve in-hospital survival. Therefore, we revised the HGB threshold to ≤10 g/dL to guide transfusion in patients undergoing ECMO. To validate this intervention, we prospectively compared the pre- and post-intervention cohorts for in-hospital mortality. Post-intervention analyses found 100% compliance for all eligible records and a decrease in the requirement for RBC transfusion by 1.2 units per patient without affecting the mortality. Conclusions As an institution-driven value-based approach to guide transfusion in patients undergoing ECMO, we lowered the threshold HGB level. Validation of this revised intervention demonstrated excellent compliance and reduced the need for RBC transfusion while maintaining the clinical outcome. Our findings can help reform value-based healthcare in this cohort while maintaining the outcome.
Depression symptoms in neurological patients: A survey of a large cohort of patients with focal brain lesions

ABSTRACT Introduction Examining depression following neurological injury is useful for understanding post-lesion depression and depression more generally. The extant literature shows variability in the incidence and severity of depression post-lesion, likely due to heterogeneity in study methodology, patient samples, measures of depression, and time of assessment. Here, we aim to characterize depression symptoms and their demographic correlates in a large sample of individuals in the chronic epoch following a focal brain lesion. Method We sampled 492 individuals who had focal, stable brain lesions and were in the chronic epoch (≥3 months post-onset). Demographic (gender, years of education), temporal (age at lesion onset, time since lesion onset), and lesion (lesion laterality, lesion etiology, lesion volume) factors were used to predict depression symptoms measured by the Beck Depression Inventory (BDI). Results We found that on average, neurological patients exhibited elevated levels of depression symptoms (although not clinically significant) relative to a community sample, and the neurological patients showed higher rates of mild and moderate depression symptoms than are typical in a community sample. Gender and lesion etiology were predictive of depression symptoms, whereby women and patients with ischemic stroke had higher levels of depression symptoms. Conclusions Our results suggest that depression symptom severity may be elevated following a focal brain lesion. Moreover, some individuals may be more likely to develop depression symptoms post-lesion than others. This may be mediated by individual factors such as gender and lesion etiology. The findings have important implications for the diagnosis, prognosis, and treatment of depression in neurological patients.
Rickettsial Infections Causing Acute Febrile Illness in Urban Slums, Brazil

We conducted enhanced acute febrile illness surveillance in an urban slum community in Salvador, Brazil. We found that rickettsial infection accounted for 3.5% of urgent care visits for acute fever. Our results suggest that rickettsiae might be an underrecognized, treatable cause of acute febrile illness in impoverished urban populations in Brazil.
2‐month ketogenic diet preferentially alters skeletal muscle and augments cognitive function in middle aged female mice

The effect of a ketogenic diet (KD) on middle aged female mice is poorly understood as most of this work have been conducted in young female mice or diseased models. We have previously shown that an isocaloric KD started at middle age in male mice results in enhanced mitochondrial mass and function after 2 months on diet and improved cognitive behavior after being on diet for 14 months when compared with their control diet (CD) fed counterparts. Here, we aimed to investigate the effect of an isocaloric 2‐month KD or CD on healthy 14‐month‐old female mice. At 16 months of age cognitive behavior tests were performed and then serum, skeletal muscle, cortex, and hippocampal tissues were collected for biochemical analysis. Two months on a KD resulted in enhanced cognitive behavior associated with anxiety, memory, and willingness to explore. The improved neurocognitive function was associated with increased PGC1α protein in the gastrocnemius (GTN) muscle and nuclear fraction. The KD resulted in a tissue specific increase in mitochondrial mass and kynurenine aminotransferase (KAT) levels in the GTN and soleus muscles, with a corresponding decrease in kynurenine and increase in kynurenic acid levels in serum. With KAT proteins being responsible for converting kynurenine into kynurenic acid, which is unable to cross the blood brain barrier and be turned into quinolinic acid—a potent neurotoxin, this study provides a potential mechanism of crosstalk between muscle and brain in mice on a KD that may contribute to improved cognitive function in middle‐aged female mice.
Formal Semantics for the Java Modeling Language.

Diese Arbeit beschaftigt sich mit der Semantik der Java Modeling Language (JML). JML is eine weitverbreitete Spezifikationssprache, die speziell auf Java zugeschnitten ist und sowohl zur statischen als auch zur Laufzeitanalyse von Programmen verwandt wird. Bislang beschrankt sich die offizielle Spezifikation von JML auf eine weitgehend verbale Definition der Semantik, die zudem teilweise unvollstandig oder widerspruchlich ist. Daraus erwachst unter anderem, dass die verschiedenen Software-Werkzeuge, die JML implementieren, Sprachelemente der JML unterschiedlich auslegen. Bisherige Arbeiten zur formalen Semantik basieren auf Logiken hoherer Ordnung oder dynamischen Logiken. In dieser Arbeit wird ein Ansatz vorgestellt, der nur auf elementaren mathematischen Konzepten wie Mengen, Funktionen und Pradikatenlogik erster Ordnung beruht. In dieser Arbeit wird eine simple Abstraktion einer Maschine vorgestellt, auf der der semantische Unterbau basiert, auf welchen Ausdrucke und Spezifikationen von JML abgebildet werden, um eine nahezu vollstandige Ubersicht der Spezifikationen fur sequentielle Java-Programme zu entwickeln.
Comparison of Deep Learning and Classical Machine Learning Algorithms to Predict Postoperative Outcomes for Anterior Cervical Discectomy and Fusion Procedures With State-of-the-art Performance

Study Design. Retrospective cohort. Objective. Due to anterior cervical discectomy and fusion (ACDF) popularity, it is important to predict postoperative complications, unfavorable 90-day readmissions, and two-year reoperations to improve surgical decision-making, prognostication, and planning. Summary of Background Data. Machine learning has been applied to predict postoperative complications for ACDF; however, studies were limited by sample size and model type. These studies achieved ≤0.70 area under the curve (AUC). Further approaches, not limited to ACDF, focused on specific complication types and resulted in AUC between 0.70 and 0.76. Materials and Methods. The IBM MarketScan Commercial Claims and Encounters Database and Medicare Supplement were queried from 2007 to 2016 to identify adult patients who underwent an ACDF procedure (N=176,816). Traditional machine learning algorithms, logistic regression, and support vector machines, were compared with deep neural networks to predict: 90-day postoperative complications, 90-day readmission, and two-year reoperation. We further generated random deep learning model architectures and trained them on the 90-day complication task to approximate an upper bound. Last, using deep learning, we investigated the importance of each input variable for the prediction of 90-day postoperative complications in ACDF. Results. For the prediction of 90-day complication, 90-day readmission, and two-year reoperation, the deep neural network-based models achieved AUC of 0.832, 0.713, and 0.671. Logistic regression achieved AUCs of 0.820, 0.712, and 0.671. Support vector machine approaches were significantly lower. The upper bound of deep learning performance was approximated as 0.832. Myelopathy, age, human immunodeficiency virus, previous myocardial infarctions, obesity, and documentary weakness were found to be the strongest variable to predict 90-day postoperative complications. Conclusions. The deep neural network may be used to predict complications for clinical applications after multicenter validation. The results suggest limited added knowledge exists in interactions between the input variables used for this task. Future work should identify novel variables to increase predictive power.
Lambda‐PCR for precise DNA assembly and modification

Lambda‐polymerase chain reaction (λ‐PCR) is a novel and open‐source method for DNA assembly and cloning projects. λ‐PCR uses overlap extension to ultimately assemble linear and circular DNA fragments, but it allows the single‐stranded DNA (ssDNA) primers of the PCR extension to first exist as double‐stranded DNA (dsDNA). Having dsDNA at this step is advantageous for the stability of large insertion products, to avoid inhibitory secondary structures during direct synthesis, and to reduce costs. Three variations of λ‐PCR were created to convert an initial dsDNA product into an ssDNA “megaprimer” to be used in overlap extension: (i) complete digestion by λ‐exonuclease, (ii) asymmetric PCR, and (iii) partial digestion by λ‐exonuclease. Four case studies are presented that demonstrate the use of λ‐PCR in simple gene cloning, simultaneous multipart assemblies, gene cloning not achievable with commercial kits, and the use of thermodynamic simulations to guide λ‐PCR assembly strategies. High DNA assembly and cloning efficiencies have been achieved with λ‐PCR for a fraction of the cost and time associated with conventional methods and some commercial kits.