Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting B Cells to Modify MS, NMOSD, and MOGAD

Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell–related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD), or are in advanced stages of clinical development. Currently, ocrelizumab, ofatumumab, and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This review focuses on the current state of knowledge about the role of B lymphocytes in immune-mediated pathophysiology and its implications for the mode of action. To understand the significance of this breakthrough in the context of the current MS therapeutic armamentarium, this review more closely examines the clinical development of CD20 depletion and the pioneering contribution of rituximab. Phase 3 and the recently published postmarketing studies will be highlighted to better understand the relevant efficacy data and safety aspects of long-term B-cell depletion.
Determinants of governance institutional quality in sub-saharan africa

ABSTRACT The paper hypothesizes that the quality of institutions tends to evolve slowly and in a piecemeal nature over time. In this process policy is seen to be a mechanism through which this evolutionary process takes place. Policy influences intermediary variables, which in turn create opportunities for institutional innovation. There are two hypotheses derived from this analysis and tested empirically in the paper. It is hypothesized that improvements in institutional quality lead to increases in economic development (using two different measures). It is also hypothesized that changes in intermediary variables resulting from policy changes lead to improvements in institutional quality. These two hypotheses are tested using a panel data set made up of twenty-five countries in Africa. The results indicate that improvements in the quality of governance institutions do lead to improvements in economic development and that policies aimed at influencing intermediary variables lead to improvements in governance institutional quality.
Europa 2020

In retrospect, the decade from 2010 to 2020 has provoked a crisis in human progress. In this book, the author proves this thesis using six occurrences, while also paying particular atten-tion to Europe’s role in relation to them: the refugee crisis the conflict in Ukraine Brexit the environment as a political issue nationalism the new coronavirus These six examples, which have had a staggering influence on the past decade, will also de-termine the political agenda in the coming decade. In view of this, the European Union has no future in its current state and thus needs to be reconceived.
Explaining Electricity Tariffs in Kenya

JEL Classification: L94; L51; L11. Kenya has been struggling with increasing electricity tariffs. Several regulatory reforms introduced in the sector have not succeeded in lowering the electricity tariffs necessitating the need to investigate the push factors of tariffs. This study explained electricity tariffs by exploring the drivers of Kenya Power and Lighting Company (KPLC) tariffs and the scale of operation of KPLC. Using cost time series data from KPLC for the period 1986 to 2016 and Autoregressive distributed lag model (ARDL) an average cost function for KPLC was estimated. The results indicated average tariffs of electricity increased with price of labour and system losses and decreased with output and system load factor. KPLC was found to be enjoying economies of scale and density. Transmission and distribution of power should therefore be retained as a natural monopoly. The Government of Kenya should continue reforming power supply to reduce the system losses and price of labour. Incentives aimed at increasing the system load factor such as special tariffs should be introduced.
Clustering electricity market participants via FRM models

Collateral mechanism in the Electricity Market ensures the payments are executed on a timely manner; thus maintains the continuous cash flow. In order to value collaterals, Takasbank, the authorized central settlement bank, creates segments of the market participants by considering their short-term and long-term debt/credit information arising from all market activities. In this study, the data regarding participants’ daily and monthly debt payment and penalty behaviors is analyzed with the aim of discovering high-risk participants that fail to clear their debts on-time frequently. Different clustering techniques along with different distance metrics are considered to obtain the best clustering. Moreover, data preprocessing techniques along with Recency, Frequency, Monetary Value (RFM) scoring have been used to determine the best representation of the data. The results show that Agglomerative Clustering with cosine distance achieves the best separated clustering when the non-normalized dataset is used; this is also acknowledged by a domain expert.
Controlled release of theophylline from interpenetrating blend microspheres of poly(vinyl alcohol) and methyl cellulose

Received 22 June 2008; accepted 1 November 2008DOI 10.1002/app.29625Published online 18 December 2009 in Wiley InterScience (www.interscience.wiley.com). ABSTRACT: Interpenetrating polymer network (IPN)microspheres of poly(vinyl alcohol) (PVA) and methylcellu-lose (MC) prepared by a water-in-oil emulsion method werecrosslinked by glutaraldehyde and loaded with theophylline(THP), an antiasthmatic drug, with various ratios of PVA toMC. Microspheres were characterized with X-ray diffractionto determine the crystalline nature of the drug after encap-sulation. Fourier transform infrared spectroscopy was usedto assess the formation of the IPN structure and to conﬁrmthe absence of chemical interactions between the drug, poly-mer, and crosslinking agent. Differential scanning calorime-try conﬁrmed the molecular-level distribution of THP in thepolymer matrix, whereas scanning electron microscopy sug-gested the formation of clustered spherical particles. Zeta-sizer indicated that the particle sizes ranged from 4 to 57lm. A THP encapsulation efﬁciency of up to 84% wasachieved, as conﬁrmed by ultraviolet spectrophotometry.Dynamic/equilibrium swelling experiments performed inpH 7.4 buffer media provided important information ondrug diffusion characteristics.Invitrorelease studies per-formed in pH 1.2 and 7.4 buffer media indicated that thedrug release depended on the extent of crosslinking as wellas the amount of MC in the microspheres. Drug release wasextended up to 3 h, and the results, as analyzed with anempirical equation, indicated non-Fickian transport for therelease of THP.
The contract-type choice for short-term software development outsourcing: The role of behaviour-based formal control

With this article, we contribute to the recent debate regarding the role of transaction cost economics in IT outsourcing and software development outsourcing research. Our focus is on the contract-type choice for short-term software development outsourcing. For this purpose, we critically examine transaction cost economics and the extant IT outsourcing/software development outsourcing literature and propose a framework which classifies software development outsourcing transactions according to transaction frequency and transaction investment characteristics. The framework identifies short-term software development outsourcing as an occasional, idiosyncratic transaction. Based on this groundwork, we clarify the concept of short-term contract and put forward that such a transaction is governed by a short-term contract. Following transaction cost economics and control theory, our resulting theoretical considerations infer that for short-term software development outsourcing, the vendor’s high human asset specificity and the resulting behaviour-based outcome control, the monitoring of the developer staff, are the triggers for contract-type decisions. Accordingly, staff monitoring by the client should result in Time & Material contracts, whereas staff monitoring by the vendor should result in Fixed Price contracts. We develop corresponding hypotheses which we test with 468 specific contract records for short-term software development outsourcing. The results confirm the transaction cost economics–based recommendations for contract-type choice. We therefore conclude that the advice of the transaction cost economics to use certain governance structures according to transaction attributes is also applicable to IT outsourcing/software development outsourcing transactions. We suggest further exploration of specific contract records to substantiate our results.
Endoscopic ultrasound efficacy in staging gastric linitis plastica lesion: a retrospective multicentric French study

Background Endoscopic ultrasound (EUS) is a key imaging technique in gastric cancer (GC). The aim of this study was to evaluate the performance of EUS in the staging of parietal and lymph node involvement in linitis plastica (LP) compared to “classical” GC. Methods A retrospective multicentric French study was conducted on patients with no metastatic LP and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed with GC. Results Forty-three patients were included, sixteen patients in the LP group and 27 in the control group. Sensitivity and specificity of EUS for diagnosis of T3-T4 parietal invasion were 77% and 100% respectively in the LP group and 89% and 56% respectively in the control group. Sensitivity and specificity of EUS for diagnosis of lymph node involvement were 73% and 80%, respectively in the LP group and 88% and 50%, respectively in the control group. Patients from LP group had significantly more advanced histological lesion, and frequent undiagnosed peritoneal carcinomatosis. Conclusions This study evaluated for the first time in a European population, the preoperative EUS performance in LP. Our study identified a similar sensitivity and specificity of the EUS in LP compared to “classical” GC paving for a broader use of EUS in preoperative settings.
Treadmill running regulates adult neurogenesis, spatial and non-spatial learning by ErbB4 signaling

Recent studies have shown exercise is effective for adult hippocampus neurogenesis and memory. However, the molecular mechanism of exercise is unclear. In this study, AG1478, an ErbB4 inhibitor, was used to explore the involvement of ErbB4 receptors. Four weeks post-running, cognitive impairment was analyzed using T-maze, Morris water maze (MWM) and contextual fear discrimination learning tests, followed by histological assessment of the proliferation and survival of hippocampal neurons using Ki67, NeuN and BrdU immunostaining respectively. Expression of total and phosphate ErbB4 protein level was evaluated by Western blotting. The results showed that AG1478 significantly impaired the performances in T-maze and MWM (spatial learning and memory), contextual fear conditioning and discrimination learning paradigm (non-spatial working and reference memory), enhanced neurogenesis loss, downregulated the expression of p-ErbB4 and total ErbB4 protein, which could be reversed by running. Taken together, our study suggested that running ameliorates cognitive impairment and neurogenesis via ErbB4 signaling.
Knowledge management model for effective technology transfer at universities

Industry engagement and the application of universities’ research outcomes for shaping society to achieve a habitable environment are possible as a result of technology transfer. With reference to universities in the Czech Republic, this paper proposes a model of effective knowledge management for intellectual property created by university employees according to the structure of individual faculties and their main research focus. The ultimate goal is to achieve effective technology transfer through knowledge management. A review of previous technology transfer models, such as appropriability, dissemination, knowledge utilization, communication, use of a university technology transfer office, and the Triple Helix, shows that these models cannot effectively transfer technology individually but can do so in combination at different levels. Consequently, a knowledge management model is introduced in this study for the transfer of technology from universities. The introduction of technology transfer offices (TTOs) is expected to protect intellectual property, generate new knowledge and create access to valuable knowledge, among other benefits.
Understanding the triggers and communicative processes that constitute resilience in the context of migration to the United States

ABSTRACT There are approximately 244 million migrants worldwide and 40 million migrants living in the US. These migrants face a myriad of stressors that they need to overcome. Framed by the communication theory of resilience, this study explores the resilience triggers and processes migrants discuss during their migration experience. Findings from 43 narrative interviews reveal three resilience triggers, four resilience processes, and two relationships between resilience triggers and processes. Similar to the ways that migrants experienced resilience triggers less, more, or ambivalently, the resilience processes were tensional and complex. Practical applications for organizations, migrants, teachers, and researchers are described. Theoretical implications related to migrants’ existing privilege and triggers, resilience processes as tensional, and co-occurrences between triggers and processes are discussed.
Evaluation and management of blunt injury abdomen based on focussed assessment with sonography in trauma

Background: The initial evaluation of patient with multiple trauma is a challenging task. FAST (focussed assessment with sonography in trauma) provides a viable alternative to computed tomography in blunt abdominal trauma patient. The aim of this study was to find the accuracy and utility of FAST in clinical decision making, as well as limitations.Methods: A total of 100 patients with blunt abdominal trauma who underwent FAST examination were included. Positive scan was defined as the presence of free intraperitoneal fluid. The sonographic scoring for operating room triage in trauma (SSORTT Score) was calculated using cumulative sum of ultrasound score, systolic blood pressure, and pulse rate. FAST findings were compared with computed tomography findings and in operated cases compared with surgical findings & clinical outcome.Results: We determined SSORTT score in all 100 cases. In our study, the sensitivity, specificity, positive and negative predictive values for FAST in identifying intraabdominal injuries were 93.9%, 94.2%, 87.5%, and 97.2%. In our study we found out that patients with a SSORTT score of 2 and above had a high likelihood of requiring a therapeutic laparotomy.Conclusions: In our study we found that FAST is a rapid, reproducible, portable and non-invasive bedside test, and can be performed at the same time as resuscitation. Ultrasound is limited mainly by its low sensitivity in directly demonstrating solid organs injuries.
The Data-Driven Multi-Step Approach for Dynamic Estimation of Buildings’ Interior Temperature

Buildings are among the main protagonists of the world’s growing energy consumption, employing up to 45%. Wide efforts have been directed to improve energy saving and reduce environmental impacts to attempt to address the objectives fixed by policymakers in the past years. Meanwhile, new approaches using Machine Learning regression models surged in the modeling and simulation research context. This research develops and proposes an innovative data-driven black box predictive model for estimating in a dynamic way the interior temperature of a building. Therefore, the rationale behind the approach has been chosen based on two steps. First, an investigation of the extant literature on the methods to be considered for tests has been conducted, shrinking the field of investigation to non-recursive multi-step approaches. Second, the results obtained on a pilot case using various Machine Learning regression models in the multi-step approach have been assessed, leading to the choice of the Support Vector Regression model. The prediction mean absolute error on the pilot case is 0.1 ± 0.2 °C when the offset from the prediction instant is 15 min and grows slowly for further future instants, up to 0.3 ± 0.8 °C for a prediction horizon of 8 h. In the end, the advantages and limitations of the new data-driven multi-step approach based on the Support Vector Regression model are provided. Relying only on data related to external weather, interior temperature and calendar, the proposed approach is promising to be applicable to any type of building without needing as input specific geometrical/physical characteristics.
Evaluation of Hepatitis B Virus Nucleos(t)ide Analogues Resistance mutations in Treatment-Naïve Patients: A Systematic Review and Meta-Analysis

Background: For detection of the nucleus(t)ide analog resistance (NAr) mutants among Hepatitis B virus (HBV) quasispecies, the selection of appropriate methodologies is necessary. Here, we aimed to investigate the role of different methods for the detection of NAr mutations among treatment-naïve patients with chronic HBV (CHB) infection.Methods: In this systematic review and meta-analysis study, five databases were searched. Desired data were extracted from the selected studies. The I2 was used as an indicator of heterogeneity. The NAr mutations rate was investigated with a 95% confidence interval (CI). Results: The overall ratio of occurrence of NAr within treatment-naïve CHB patients (14653) from 128 studies was 0.085 (95% CI, 0.069-0.103, p-value < 0.0001). Direct sequencing was the most prevalent method of DNA sequencing (56.25%). The rates of NAr mutations in the different methodologies, including the direct sequencing, InnoLipa, NGS, and PASS, were 0.079 (0.037-0.160, p < 0.0001), 0.058 (0.021-0.152, p < 0.0001), 0.729 (0.441-0.902, p = 0.114), and 0.448 (0.281-0.628, p = 0.001), respectively.Conclusions: Drug-resistant quasispecies of HBV exist in treatment-naïve patients in relatively high abundance. More sensitive methodologies like NGS should be used for detecting NAr fractions of the viral population. Replacement of current therapy with novel anti-HBV candidates also should be considered.
Thin-Film Morphology Control in Naphthalene-Diimide-Based Semiconductors: High Mobility n-Type Semiconductor for Organic Thin-Film Transistors

In organic thin film transistors (OTFT), the morphology and microstructure of an organic thin film has a strong impact on the charge carrier mobility and device characteristics. To have well-defined and predictable thin film morphology, it is necessary to adapt the basic structure of semiconducting molecules in a way that results in an optimum crystalline packing motif. Here we introduce a new molecular design feature for organic semiconductors that provides the optimized crystalline packing and thin film morphology that is essential for efficient charge-carrier transport. Thus, cyclohexyl end groups in naphthalene diimide assist in directing intermolecular stacking leading to a dramatic improvement in field effect mobility. Accordingly, OTFT devices prepared with vapor deposited N,N′-bis(cyclohexyl) naphthalene-1,4,5,8-bis(dicarboximide) (1) regularly exhibit field effect mobility near 6 cm2/(V s), which is one of the highest carrier mobilities reported for either n- or p-type organic semiconducting thin.
New sequence stratigraphic framework on a ‘passive’ margin: implications for the post-break-up depositional environment and onset of glaciomarine conditions in NE Greenland

Detailed sequence stratigraphic frameworks have been produced for most of the Cenozoic deposits around the North Atlantic and Greenland Sea. However, the sequence stratigraphic evolution of the NE Greenland shelf, a significant part of the Atlantic Ocean margin, has so far never been interpreted. This study provides, for the first time, a detailed sequence stratigraphic interpretation of the NE Greenland shelf since the late Eocene. The tectonic evolution, eustatic sea-level change and the impact of glaciations are integrated into a consistent geological history. Based on the identification of pronounced unconformities and their correlative conformities, ten stratigraphic sequences are identified. The onset of deposition is defined by a pronounced erosional event, where late Paleocene tectonic activity caused mass wasting of the uplifted footwall of the Danmarkshavn Ridge along a c. 200 km section of the ridge. A second pronounced unconformity developed across the margin during the mid-Miocene, which caused forced regressive submarine fans to prograde across the margin. The following tectonic quiet period is overlain by glaciomarine deposits, with evidence of ice deformation reaching the present day shelf break. Unknown super-regional plate tectonic forces are suggested as a driver of sequence formation based on correlation with the Canadian Arctic.
High sensitivity of PD-L1 analysis from pleural effusion in nonsmall cell lung cancer

Background: Programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) immune checkpoint inhibitors have been approved for monotherapy of metastatic nonsmall cell lung cancer (mNSCLC) depending on tumour cells' PD-L1 expression. Pleural effusion is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from pleural effusion samples is unclear. Aim: The aim of the study was to analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of pleural effusion in NSCLC as compared to immunohistochemistry of pleural biopsies. Patients and Methods: Fifty consecutive subjects (17 female, median age 72.5 years, seven never-smokers) were enrolled in this prospective controlled two-centre study. Inclusion criteria were pleural effusion, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, and written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, and positive and negative predictive value was performed for PD-L1 detection from pleural effusion. Results: 50 subjects underwent pleural puncture and thoracoscopy. Pathological diagnoses were lung cancer (48), lymphoma (1) and mesothelioma (1). Sensitivity, specificity, positive predictive value and negative predictive value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% CI 46–100%), 63% (36–84%), 45% (18–75%) and 100% (66–100%), and with expression ≥1% defined as positive 86% (56–97%), 43% (12–80%), 75% (47–92%) and 60% (17–93%). Conclusion: PD-L1 analysis in tumour-positive pleural effusion samples shows a very high sensitivity and negative predictive value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negative predictive value, making other invasive procedures necessary (NCT02855281). PD-L1 analysis in tumour-positive pleural effusion samples is characterised by a very high sensitivity and negative predictive value. Negative results seem very reliable and could thus help in the decision against a first-line checkpoint inhibitor therapy. https://bit.ly/2GPCLYS