Miracle-dz/UniFAR-FTUs huggingface dataset:
Detecting and predicting neutralization of alemtuzumab responses in MS

Objective To test the hypothesis that antidrug antibodies (ADAs) against alemtuzumab could become relevant after repeated treatments for some individuals, possibly explaining occasional treatment resistance. Methods Recombinant alemtuzumab single-chain variable fragment antibody with a dual tandem nanoluciferase reporter linker was made and used to detect binding ADAs. Alemtuzumab immunoglobulin G Alexa Fluor 488 conjugate was used in a competitive binding cell-based assay to detect neutralizing ADAs. The assays were used to retrospectively screen, blinded, banked serum samples from people with MS (n = 32) who had received 3 or more cycles of alemtuzumab. Lymphocyte depletion was measured between baseline and about 1 month postinfusion. Results The number of individuals showing limited depletion of lymphocytes increased with the number of treatment cycles. Lack of depletion was also a poor prognostic feature for future disease activity. ADA responses were detected in 29/32 (90.6%) individuals. Neutralizing antibodies occurred before the development of limited depletion in 6/7 individuals (18.8% of the whole sample). Preinfusion, ADA levels predicted limited, postinfusion lymphocyte depletion. Conclusions Although ADAs to alemtuzumab have been portrayed as being of no clinical significance, alemtuzumab-specific antibodies appear to be clinically relevant for some individuals, although causation remains to be established. Monitoring of lymphocyte depletion and the antidrug response may be of practical value in patients requiring additional cycles of alemtuzumab. ADA detection may help to inform on retreatment or switching to another treatment.
Carbamoyl-Phosphate Synthase 1 as a Novel Target of Phomoxanthone A, a Bioactive Fungal Metabolite

Phomoxanthone A, a bioactive xanthone dimer isolated from the endophytic fungus Phomopsis sp. , is a mitochondrial toxin weakening cellular respiration and electron transport chain activity by a fast breakup of the mitochondrial assembly. Here, a multi-disciplinary strategy has been developed and applied for identifying phomoxanthone A target(s) to fully address its mechanism of action, based on drug affinity response target stability and targeted limited proteolysis. Both approaches point to the identification of carbamoyl-phosphate synthase 1 as a major phomoxanthone A target in mitochondria cell lysates, giving also detailed insights into the ligand/target interaction sites by molecular docking and assessing an interesting phomoxanthone A stimulating activity on carbamoyl-phosphate synthase 1. Thus, phomoxanthone A can be regarded as an inspiring molecule for the development of new leads in counteracting hyperammonemia states.
Incidence of viral and fungal complications after utilization of alternative donor sources in hematopoietic cell transplantation

Allogeneic hematopoietic cell transplantation (HCT) remains the only curable option for adult patients with hematologic malignancies. According to guidelines published by the American Society for Transplantation and Cellular Therapy, allogeneic HCT should be offered to all intermediate‐ and high‐risk patients with acute leukemia. While matched‐related donor (MRD) grafts continue to be the preferred stem cell source for allogeneic HCT, studies comparing MRD grafts to matched‐unrelated donor (MUD) grafts showed comparable outcomes in patients with acute leukemia. Unfortunately, for those without a suitable matched‐related graft, the probability of finding a suitable matched‐unrelated donor varies significantly depending on racial and ethnic background. With allogeneic HCT procedures increasing year after year due to the increased availability of suitable donors, each of these alternative donor sources merits special clinical considerations, specifically with regard to infections. Infections remain a significant cause of morbidity and mortality after allogeneic transplant, especially in those receiving alternative donor grafts. Due to the high‐risk nature associated with these donor grafts, it is important to understand the true risk of developing infectious complications. While there are a multitude of infections that have been described in patients post‐allogeneic HCT, this review seeks to focus on the incidence of cytomegalovirus (CMV) and invasive fungal infections (IFI) in adult patients receiving alternative donor source transplantation for hematologic malignancies.
Requirement Engineering and the Role of Design Thinking

Recently, interest in the use of Design Thinking (DT) has been on the rise as a field to study related to HumanComputer Interaction (HCI). Companies today are seeking innovation and user-centricity in the software development projects regardless of the field they are in. Companies like IBM and SAP among others have taken steps forward to innovate their software development processes using Design Thinking, by creating academies and innovation labs. DT is used as a method to improve the User Experience (UX) while interacting with a computer software. Requirement Engineering (RE) is a process of defining, documenting and maintaining requirements in the system design and software engineering process, while RE takes on the initial phase in software engineering. This position paper reviews the practices of RE as well as how DT could have a role to mitigate the challenges that RE could have.
Blockchain Study and Analysis with a View to Optimizing Security on the Aspects of Land Registry

Land, according to most governments, is an important asset in development. All over the world, it expresses family cohesion to a certain extent, and presents itself as a basis for the development of any human project. Thus, the regulation of its use and occupation is required. In Cameroonian legislation, the land system is using a special book called "land Book". This book represents a document used by a registrar to record users ‘land titles, in order to prove the authenticity, availability, and confidentiality of its holder. To date, its land system still suffers from several problems, in particular: the dilapidated state and disappearance of land books, the existence of several geodetic systems, disappearance of leaflet, sale of false land titles, double sales of land titles, and attempts to expropriate a person or a community by the administration or by third parties. Today, most of the cases pending in the courts are land disputes, and since then they have continued to increase due to demographic pressure, and the rate of urbanization in Cameroon. The objective of this paper is to solve these problems by designing a Framework via a particular type of blockchain approach in order to improve the security and scalability of the land register in Cameroon.
SMARTINSUR: A Platform for Digitizing Business Transactions in the Insurance Industry

: For the digitization of business processes in insurance, the concept of a platform is presented that is based on the design principles of modern software architectures (domain-driven design, micro services). This raises the question of whether the complex application scenario can be realized with this software development approach and whether the advantages of agile development come into play. The complex interplay of the different roles involved in the processes, namely insurance companies, sales organizations and brokers, is illustrated using the example of a document service. The advantages resulting from the digitization of the example process, such as labor and cost savings, but also quality improvement and increased customer satisfaction are worked out. In the near future, process events will be recorded via the integration of a process mining service that can be of great help for further process optimization.
A new species of Rhododendron (Ericaceae) from the Gaoligong Mountains, Yunnan, China, supported by morphological and DNA barcoding data

Rhododendron baihuaense sp. nov. is described as a new species endemic to Yunnan, China, that has, to date, only been found in Baihualing on the eastern side of the Gaoligong Mountains. Morphologically, R. baihuaense can be readily distinguished from R. hanceanum and R. genestierianum, by its absent scales on mature leaves, only 2-5 flowers per inflorescence, the funnel-shaped flower and white corolla, and its slender and erect style. A molecular analysis based on the four standard DNA barcodes (rbcL, matK, trnH-psbA and ITS) indicates that R. baihuaense is genetically distinct from R. hanceanum and R. genestierianum, and, together with the morphological differences, is described here as a new species.
Cloud-native Deploy-ability: An Analysis of Required Features of Deployment Technologies to Deploy Arbitrary Cloud-native Applications

: The adoption of cloud computing combined with DevOps enables companies to react to new market requirements more rapidly and fosters the use of automation technologies. This inﬂuences the way software solutions are built, which is why the concept of cloud-native applications has emerged over the last few years to build highly scalable applications, and to automatically deploy and run them in modern cloud environments. However, there is currently no reference work clearly stating the features that a deployment technology must offer to support the deployment of arbitrary cloud-native applications. In this paper, we derive three essential features for deployment technologies based on the current cloud-native research and characteristics discussed therein. The presented features can be used to compare and categorize existing deployment technologies, and they are intended to constitute a ﬁrst step towards a comprehensive framework to assess deployment technologies.
ProcDefense - A Game Framework for Procedural Player Skill Training

A challenge of game design is in providing affordances to players so that they can learn and improve their skills. Ad- vances in Procedural Content Generation (PCG) suggest this type of game content is a candidate for automatic creation. Some work in PCG has been successful in customizing game difficulty to achieve desired player experience; however, this often involves bringing the difficulty of the game to a level appropriate for the player’s current skills. Players desiring to improve their performance in a particular game may be will- ing to tolerate relatively higher levels of frustration and anx- iety than are targeted in experience-based approaches. As an initial step in this line of inquiry, we introduce ProcDefense, an action game with a modular difficulty control interface, as a platform for future inquiry into the effectiveness of differing PCG techniques for performance-training, dynamic difficulty adjustment.
TIPU outcomes for hypospadias treatment and predictive factors causing urethrocutaneous fistula and external urethral meatus stenosis in TIPU: Clinical study

Our aim is to present patient outcomes for the TIPU method, currently mostly used for distal and sometimes proximal hypospadias treatment, and to identify predictive factors for the most commonly encountered complications of this surgery of urethrocutaneous fistula and urethral meatus stenosis. TIPU is a versatile, reliable, cosmetic and functionally successful surgical method mainly used for distal hypospadias patients but also in recent times for some proximal hypospadias patients. The main complications are urethrocutaneous fistula, urethral meatus stenosis, glans dehiscence and urethral meatus dehiscence. The pre‐operative anatomic features of patients were assessed with the glans–meatus–shaft (GMS) scoring. Post‐operative assessment of surgical outcomes was performed with the hypospadias objective scoring evaluation (HOSE). The mean total urethrocutaneous fistula and meatal stenosis development rates were 20 (12.3%) and 25 (15.4%). Both complications were found to be significantly high among hypospadias patients with narrow urethral plate, flat glandular groove and small glans (p < .001). Multivariate binary logistic regression analysis found urethral plate, glandular groove and glans shape were predictive factors for fistula and stenosis development.
Sorghum qTGW1a encodes a G-protein subunit and acts as a negative regulator of grain size.

Grain size is a major determinant of grain yield in sorghum [Sorghum bicolor (L.) Moench] and other cereals. Over 100 quantitative trait loci (QTLs) of grain size have been identified in sorghum. However, no gene underlying any grain size QTL has been cloned. Here, we describe the fine mapping and cloning of one grain size QTL. From an F8 RIL population derived from a cross between inbred lines 654 and LTR108, we identified 44 grain size QTLs. One QTL, qTGW1a, was detected consistently on the long arm of chromosome 1 in the span of four years. Using the extreme recombinants from an F2:3 fine-mapping population, qTGW1a was delimited within a ~33-kb region, containing three predicted genes. Of them, SORBI_3001G341700, predicted to encode a G-protein γ subunit homologous to the GS3 in rice, is likely to be the causative gene for qTGW1a. qTGW1a appears to act as a negative regulator of grain size in sorghum. The functional allele of the putatively causative gene of qTGW1a from the inbred line 654 decreased grain size, plant height, and grain yield in transgenic rice. Identification of the gene underlying qTGW1a advanced our understanding of the regulatory mechanisms of grain size in sorghum and provided a target to manipulate grain size through genome editing.
Online Algorithms for Weighted Paging with Predictions

In this article, we initiate the study of the weighted paging problem with predictions. This continues the recent line of work in online algorithms with predictions, particularly that of Lykouris and Vassilvitski (ICML 2018) and Rohatgi (SODA 2020) on unweighted paging with predictions. We show that unlike unweighted paging, neither a fixed lookahead nor a knowledge of the next request for every page is sufficient information for an algorithm to overcome the existing lower bounds in weighted paging. However, a combination of the two, which we call strong per request prediction (SPRP), suffices to give a 2-competitive algorithm. We also explore the question of gracefully degrading algorithms with increasing prediction error, and give both upper and lower bounds for a set of natural measures of prediction error.
Dydrogesterone‐primed ovarian stimulation is an effective alternative to gonadotropin‐releasing hormone antagonist protocol for freeze‐all cycles in polycystic ovary syndrome

To compare the effects of progestin‐primed ovarian stimulation using dydrogesterone (DYD) and a gonadotropin‐releasing hormone (GnRH) antagonist protocol on cycle characteristics and pregnancy rates in freeze‐all cycles in patients with polycystic ovary syndrome (PCOS).
The geography of sentiment towards the Women’s March of 2017

The Women’s March of 2017 generated unprecedented levels of participation in the largest, single day, protest in history to date. The marchers protested the election of President Donald Trump and rallied in support of several civil issues such as women’s rights. “Sister marches” evolved in at least 680 locations across the United States. Both positive and negative reactions to the March found their way into social media, with criticism stemming from certain, conservative, political sources and other groups. In this study, we investigate the extent to which this notable, historic event influenced sentiment on Twitter, and the degree to which responses differed by geographic area within the continental U.S. Tweets about the event rose to an impressive peak of over 12% of all geo-located tweets by mid-day of the March, Jan. 21. Messages included in tweets associated with the March tended to be positive in sentiment, on average, with a mean of 0.34 and a median of 0.07 on a scale of -4 to +4. In fact, tweets associated with the March were more positive than all other geo-located tweets during the day of the March. Exceptions to this pattern of positive sentiment occurred only in seven metropolitan areas, most of which involved very small numbers of tweets. Little evidence surfaced of extensive patterns of negative, aggressive messages towards the event in this set of tweets. Given the widespread nature of online harassment and sexist tweets, more generally, the results are notable. In sum, online reactions to the March on this social media platform suggest that this modern arm of the Women’s Movement received considerable, virtual support across the country.
Automated diagnoses of age-related macular degeneration and polypoidal choroidal vasculopathy using bi-modal deep convolutional neural networks

Aims To investigate the efficacy of a bi-modality deep convolutional neural network (DCNN) framework to categorise age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) from colour fundus images and optical coherence tomography (OCT) images. Methods A retrospective cross-sectional study was proposed of patients with AMD or PCV who came to Peking Union Medical College Hospital. Diagnoses of all patients were confirmed by two retinal experts based on diagnostic gold standard for AMD and PCV. Patients with concurrent retinal vascular diseases were excluded. Colour fundus images and spectral domain OCT images were taken from dilated eyes of patients and healthy controls, and anonymised. All images were pre-labelled into normal, dry or wet AMD or PCV. ResNet-50 models were used as the backbone and alternate machine learning models including random forest classifiers were constructed for further comparison. For human-machine comparison, the same testing data set was diagnosed by three retinal experts independently. All images from the same participant were presented only within a single partition subset. Results On a test set of 143 fundus and OCT image pairs from 80 eyes (20 eyes per-group), the bi-modal DCNN demonstrated the best performance, with accuracy 87.4%, sensitivity 88.8% and specificity 95.6%, and a perfect agreement with diagnostic gold standard (Cohen’s κ 0.828), exceeds slightly over the best expert (Human1, Cohen’s κ 0.810). For recognising PCV, the model outperformed the best expert as well. Conclusion A bi-modal DCNN for automated classification of AMD and PCV is accurate and promising in the realm of public health.
Predictive value of the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to-monocyte ratio in lupus nephritis

Objective To evaluate the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), and neutrophil-to-monocyte ratio (NMR) as predictors for lupus nephritis (LN) patients without infection or as biomarkers for distinguishing between infection or flare with LN patients. Methods LN patients were divided into three groups: LN without infection, LN with infection, and LN with flare. A total of 57 healthy subjects were enrolled as controls. The differentiation was analyzed between LN without infection and control group, and LN with infection and LN with flare. Correlations among variables were assessed in the LN group without infection. Receiver operating characteristic curves were constructed in two comparable groups. Results NLR, PLR, and MLR were increased significantly in the LN group without infection as compared with those in healthy controls. NLR (area under the curve (AUC): 0.75) and MLR (AUC: 0.79) were useful for distinguishing between LN patients without infection and healthy subjects. In differentiating LN patients without infection from the controls, optimal cutoffs of NLR and MLR were 3.43 (sensitivity: 45.6%, specificity: 96.5%, and overall accuracy: 68.8%) and 0.24 (sensitivity: 75.0%, specificity: 73.7%, and overall accuracy: 73.6%), respectively. In addition, NLR (r = 0.322, p = 0.011) and PLR (r = 0.283, p = 0.026) were positively correlated with CRP. Importantly, NLR and NMR were increased while PNR was decreased in the LN group with infection in comparison with those in the LN group with flare. NLR (AUC: 0.80), NMR (AUC: 0.78), and PNR (AUC: 0.74) were useful in differentiating LN patients with infection and flare, and their optimal cutoffs were 4.02 (sensitivity: 82.6%, specificity: 69.6%, and overall accuracy: 75.5%), 12.19 (sensitivity: 80.4%, specificity: 73.9%, and overall accuracy: 77.5%), and 28.26 (sensitivity: 65.2%, specificity: 76.8%, and overall accuracy: 71.6%), respectively. Conclusions We demonstrated, for the first time, that MLR or NMR had the best accuracy in differentiating LN patients without infection from healthy subjects, or differentiating infection from flare in LN patients, respectively. Our results implied that NLR, MLR, PNR, and NMR may be useful biomarkers in predicting LN.
Within- and between-session reliability of secondary hyperalgesia induced by electrical high-frequency stimulation.

BACKGROUND An increasing number of studies are focusing on secondary hyperalgesia to better understand central sensitization, as this phenomenon may play an important role in persistent pain. Recent studies have shown that, compared to the classical high frequency stimulation protocol (HFS) at 100 Hz, a protocol using 42 Hz stimulation induces a more intense and a larger area of secondary hyperalgesia (SH). OBJECTIVES The aim of this study was to investigate the within- and between-session reliability of SH induced by this optimized HFS protocol. METHODS Thirty-two healthy subjects received HFS to their volar forearm in two sessions, separated by at least two weeks. SH was assessed by measuring the area size of increased sensitivity to pinprick stimuli after applying HFS, the sensitivity to pinprick stimuli after applying HFS, and the change in pinprick sensitivity after vs. before HFS. Assessments were made before HFS, and 30, 35 and 40 minutes after HFS. Relative and absolute reliability were analyzed using intra-class correlation coefficients (ICCs), coefficients of variation (CVs), standard error of means (SEMs) and the minimum detectable changes (MDCs). RESULTS The area of SH showed good to excellent within-session and between-session relative reliability (ICCs > 0.80), except for the change in pinprick sensitivity, which showed close to poor between-session relative reliability (ICC=0.53). Furthermore, measures of absolute reliability generally demonstrated large between-subject variability and significant fluctuations across repeated measurements. CONCLUSIONS HFS-induced hyperalgesia is suitable to discriminate or compare individuals but it may not be sensitive to changes due to an intervention.