Miracle-dz/UniFAR-FTUs huggingface dataset:
The Half-Yearly Oscillations in Middle and High Southern Latitudes and the Coreless Winter

Abstract In mid-tropospheric levels of the Southern Hemisphere, the temperature contrast between middle and high latitudes reaches two maxima near the times of the equinoxes, the strongest contrast being at the autumnal equinox. This variation is dominated by the seasonal changes over the Antarctic Ocean where the second (semiannual) harmonic of the mid-tropospheric meridional temperature gradient has a magnitude exceeding that of the first (annual) harmonic. The existence of the marked semiannual component in this region is shown to be a consequence of the difference between the heating and cooling rates in different latitudes where the mid-tropospheric annual temperature ranges are similar. In latitude 50S cooling in autumn is rapid compared with the warming in spring, the reverse being true at latitude 65S. This behavior is related to the heat budget of the oceanic upper layers. The semiannual maximum temperature gradients in the middle troposphere over the Antarctic Ocean, through increased cyclonic a.
CAR-NK cells: a promising cellular immunotherapy in lymphoma

ABSTRACT Introduction New methods in cancer immunotherapy, such as chimeric antigen receptor (CAR)-T cells, have shown promising results in destroying malignant cells. However, limitations and side effects of CAR-T cell therapy, such as graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome, have motivated researchers to investigate safer alternative cells like natural killer (NK) cells. Area covered NK cells can effectively recognize hematologic malignant cells and destroy them. Many clinical and preclinical studies investigate the efficacy of CAR-NK cells in treating lymphoma and other hematologic malignancies. The results of published clinical trials and preclinical studies have shown that CAR-NK cells could be an appropriate choice for treating lymphoma. In this review, we discuss the characteristics of CAR-NK cells, their role in treating B-cell and T-cell lymphoma, and the challenges faced by using them. We also highlight clinical trials using CAR-NK cells for treating lymphoma. Expert opinion CAR-NK cells have shown promising results in cancer therapy, especially B-cell lymphoma, with a much lower risk for GVHD, cytokine release syndrome, and neurotoxicity than CAR-T cells. Further investigations are required to overcome the obstacles of CAR-NK cell therapy, both generally, and in cancers like T-cell lymphoma.
Decentralized sliding mode control design for hybrid systems

This paper proposes a decentralized sliding mode control law for a class of large scale switching systems. It is assumed that some parts of the switching structures are fixed, and the design of the decentralized sliding mode control laws for the switching and fixed parts are carried out independently. The inclusion principle is developed so that one can expand a switching system, possibly performing sliding modes, into a higher dimensional switching system, design decentralized sliding mode controllers in the expanded space, then contract the solution for implementation on the original system. Some design issues, like connective reachability of the sliding manifold and the stability of the sliding mode equations in the expanded and original state spaces are examined. Finally, an example is given to illustrate the effectiveness of the design methodology.
Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study

Purpose To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in combination with a PD-1 inhibitor in patients with unresectable hepatocellular carcinoma (uHCC) and liver-only disease ineligible for chemoembolization. Patients and methods NASIR-HCC is a single-arm, multicenter, open-label, phase 2 trial that recruited from 2017 to 2019 patients who were naïve to immunotherapy and had tumors in the BCLC B2 substage (single or multiple tumors beyond the up-to-7 rule), or unilobar tumors with segmental or lobar portal vein invasion (PVI); no extrahepatic spread; and preserved liver function. Patients received SIRT followed 3 weeks later by nivolumab (240 mg every 2 weeks) for up to 24 doses or until disease progression or unacceptable toxicity. Safety was the primary endpoint. Secondary objectives included objective response rate (ORR), time to progression (TTP), and overall survival (OS). Results 42 patients received SIRT (31 BCLC-B2, 11 with PVI) and were followed for a median of 22.2 months. 27 patients discontinued and 1 never received Nivolumab. 41 patients had any-grade adverse events (AE) and 21 had serious AEs (SAE). Treatment-related AEs and SAEs grade 3–4 occurred in 8 and 5 patients, respectively. Using RECIST 1.1 criteria, ORR reported by investigators was 41.5% (95% CI 26.3% to 57.9%). Four patients were downstaged to partial hepatectomy. Median TTP was 8.8 months (95% CI 7.0 to 10.5) and median OS was 20.9 months (95% CI 17.7 to 24.1). Conclusions The combination of SIRT and nivolumab has shown an acceptable safety profile and signs of antitumor activity in the treatment of patients with uHCC that were fit for SIRT. Trial registration number NCT03380130
Solving very large distributed constraint satisfaction problems

This thesis investigates issues with existing approaches to distributed constraint satisfaction, and proposes a solution in the form of a new algorithm. These issues are most evident when solving large distributed constraint satisfaction problems, hence the title of the thesis. We will first survey existing algorithms for centralised constraint satisfaction, and describe how they have been modified to handle distributed constraint satisfaction. The method by which each algorithm achieves completeness will be investigated and analysed by application of a new theorem. We will then present a new algorithm, Support-Based Distributed Search, developed explicitly for distributed constraint satisfaction rather than being derived from centralised algorithms. This algorithm is inspired by the inherent structure of human arguments and similar mechanisms we observe in real-world negotiations. A number of modifications to this new algorithm are considered, and comparisons are made with existing algorithms, effectively demonstrating its place within the field. Empirical analysis is then conducted, and comparisons are made to state-of-the-art algorithms most able to handle large distributed constraint satisfaction problems. Finally, it is argued that any future development in distributed constraint satisfaction will necessitate changes in the algorithms used to solve small ‘embedded’ constraint satisfaction problems. The impact on embedded constraint satisfaction problems is considered, with a brief presentation of an improved algorithm for hypertree decomposition. Previously published work includes [HG03, HCG05, HCG06a, HCG06b, HCG06c].
Addressing people’s current and future states in a reinforcement learning algorithm for persuading to quit smoking and to be physically active

Behavior change applications often assign their users activities such as tracking the number of smoked cigarettes or planning a running route. To help a user complete these activities, an application can persuade them in many ways. For example, it may help the user create a plan or mention the experience of peers. Intuitively, the application should thereby pick the message that is most likely to be motivating. In the simplest case, this could be the message that has been most effective in the past. However, one could consider several other elements in an algorithm to choose a message. Possible elements include the user’s current state (e.g., self-efficacy), the user’s future state after reading a message, and the user’s similarity to the users on which data has been gathered. To test the added value of subsequently incorporating these elements into an algorithm that selects persuasive messages, we conducted an experiment in which more than 500 people in four conditions interacted with a text-based virtual coach. The experiment consisted of five sessions, in each of which participants were suggested a preparatory activity for quitting smoking or increasing physical activity together with a persuasive message. Our findings suggest that adding more elements to the algorithm is effective, especially in later sessions and for people who thought the activities were useful. Moreover, while we found some support for transferring knowledge between the two activity types, there was rather low agreement between the optimal policies computed separately for the two activity types. This suggests limited policy generalizability between activities for quitting smoking and those for increasing physical activity. We see our results as supporting the idea of constructing more complex persuasion algorithms. Our dataset on 2,366 persuasive messages sent to 671 people is published together with this article for researchers to build on our algorithm.
Thyroidal ACE2 protein expression and thyroid function tests in patients with COVID-19: results from a retrospective case series and a prospective cohort study.

BACKGROUND Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is due to fatal inflammatory responses apart of lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to non-thyroidal illness syndrome (NTI) have been described. Furthermore, Angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland. OBJECTIVE To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients that died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFT with the severity of the disease in a prospective cohort study. METHODS Thyroid tissue of deceased COVID-19 patients (n=23) were analyzed for histopathology and ACE2 expression by immunohistochemical staining. One hundred and fifty-three patients with confirmed SARS-CoV-2 were evaluated regarding TFT and divided into a severe (intubation, intensive care treatment) and an intermediate group. RESULTS Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and TSH was associated significantly with deadly disease. CONCLUSION The high percentage of positive ACE2 immunostaining in deceased patients compared to normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L was associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFT is crucial in the treatment of severely ill COVID-19 patients.
The Importance of Timing, Fundamental Attitudes, and Appropriate Interventions as Key Aspects of Chaplain Suicide Prevention: A European Expert Panel of Mental Health Chaplains

An expert panel consisting of six mental health chaplains from several European countries was convened to ascertain the specific contribution of mental health chaplains to suicide prevention, and to generate good practices for suicide prevention. Three themes emerged: (1) the importance of timing; (2) fundamental attitudes of the chaplain towards the patient, and (3) appropriate interventions.
Elevated serum progesterone levels on the hCG trigger day have a negative impact on the live birth rate in the first fresh IVF-ET cycle

Abstract To investigate whether there is a relationship between elevated serum progesterone (PROG) on the hCG trigger day and the live birth rate (LBR) in IVF/ICSI cycles, the retrospective analysis was carried out from the patients undergoing the first ART cycles throughout 2016. The PROG levels were measured on the hCG trigger day. The LBR, clinical pregnancy rate (CPR), implantation rate (IR) and other parameter rate values were compared among the three different PROG elevations. A total of 2550 IVF/ICSI cycles fulfilling all the inclusion and exclusion criteria were selected. Finally, three groups [PROG <0.40 ng/mL, 0.40 ≤ PROG < 1.5 ng/mL, PROG ≥ 1.5 ng/mL] were categorised based on the serum PROG levels. LBR, CPR and IR declined as the PROG value increased, while there was no difference in the embryo utilisation rates. Serum PROG levels on the day of hCG administration were negatively associated with the LBR, even in ETs with a good prognosis. Impact Statement What is already known on this subject? The clinical effects of PROG are still controversial. Some studies have confirmed that there was not too much association between premature elevation of PROG and live birth, some are still convincing that there is a negative correlation and will result in ART cycles of pregnancy and LBR reduction. What do the results of this study add? Our data substantiated that the high serum PROG level had the lowest LBR, IR and CPR, but the embryo utilisation rate may not have too much to do with the elevated PROG. What are the implications of these findings for clinical practice and/or further research? This study further strengthens the negative impact of elevated PROG levels on pregnancy outcomes, and suggests that frozen thawed embryo transfer appears to be a reasonable and advantageous approach for this subset of patients.
PAX6 disease models for aniridia

Aniridia is a pan-ocular genetic developmental eye disorder characterized by complete or partial iris and foveal hypoplasia, for which there is no treatment currently. Progressive sight loss can arise from cataracts, glaucoma, and aniridia-related keratopathy, which can be managed conservatively or through surgical intervention. The vast majority of patients harbor heterozygous mutations involving the PAX6 gene, which is considered the master transcription factor of early eye development. Over the past decades, several disease models have been investigated to gain a better understanding of the molecular pathophysiology, including several mouse and zebrafish strains and, more recently, human-induced pluripotent stem cells (hiPSCs) derived from aniridia patients. The latter provides a more faithful cellular system to study early human eye development. This review outlines the main aniridia-related animal and cellular models used to study aniridia and highlights the key discoveries that are bringing us closer to a therapy for patients.
Temporal analysis of GBIF data reveals the restructuring of communities following climate change

Abstract Multiple studies revealed an effect of climate change on biodiversity by investigating long‐term changes in species distributions and community composition. However, many taxa do not benefit from systematic long‐term monitoring programmes, leaving gaps in our current knowledge of climate‐induced community turnover. We used data extracted from the Global Biodiversity Information Facility to characterize community reorganization under climate change for nine animal taxonomic groups (ants, bats, bees, birds, butterflies, earthworms, frogs, rodents and salamanders), which, for most of them, had never been studied before in this regard. Using a presence‐only community temperature index (CTI), reflecting the relative proportion of warm‐ and cold‐adapted species, we tested whether and how species' assemblages were affected by climate change over the last 30 years. Across Europe and North America, we observed an average increase in CTI, consistent with a gradual species turnover driven by climate change. At the local scale, we could observe that the composition of most species assemblages changed according to temperature variations. However, this change in composition always occurred with a lag compared to climate change, suggesting that communities are experiencing a climatic debt. Results suggest that anthropization may play a role in the decoupling between the change in CTI and the change in local temperature. The results of our study highlight an overall thermophilization of assemblages as a response of temperature warming. We demonstrated that this response may exist for a large range of understudied terrestrial animals, and we introduced a framework that can be used in a broader context, opening new opportunities for global change research.
Deep problems with neural network models of human vision

Abstract Deep neural networks (DNNs) have had extraordinary successes in classifying photographic images of objects and are often described as the best models of biological vision. This conclusion is largely based on three sets of findings: (1) DNNs are more accurate than any other model in classifying images taken from various datasets, (2) DNNs do the best job in predicting the pattern of human errors in classifying objects taken from various behavioral datasets, and (3) DNNs do the best job in predicting brain signals in response to images taken from various brain datasets (e.g., single cell responses or fMRI data). However, these behavioral and brain datasets do not test hypotheses regarding what features are contributing to good predictions and we show that the predictions may be mediated by DNNs that share little overlap with biological vision. More problematically, we show that DNNs account for almost no results from psychological research. This contradicts the common claim that DNNs are good, let alone the best, models of human object recognition. We argue that theorists interested in developing biologically plausible models of human vision need to direct their attention to explaining psychological findings. More generally, theorists need to build models that explain the results of experiments that manipulate independent variables designed to test hypotheses rather than compete on making the best predictions. We conclude by briefly summarizing various promising modeling approaches that focus on psychological data.
CONTINUUM DAMAGE THEORY - APPLICATION TO CONCRETE

This paper presents a review of the different models for concrete based on continuum damage theory, formulated at the Laboratoire de Mecanique et Technologie (Cachan, France). Derived in the framework of the thermodynamics of irreversible processes, each formulation is based on physical observation. Induced anisotropy, ductile behavior, and directional effects such as the closure of cracks are discussed and adequate damage models are proposed. Finally, the numerical implementations performed give a good description of the failure process as well as an accurate prediction of the behavior of concrete and reinforced concrete structures.
Clinical SARS-CoV-2 Kinetic Profiles Are Dependent on the Viral Strain and Host Vaccination Status

We are conducting an ongoing SARS-CoV-2 workplace clinical study based on frequent, longitudinal disease surveillance of staff and household members. Here, we investigated the viral dynamics in two recently vaccinated participants who became infected with the same Omicron variant of SARS-CoV-2. ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection kinetics in a real-world, clinical setting represent a knowledge gap in understanding the underlying coronavirus disease 2019 (COVID-19) pathogenesis. There are scant reports of the dynamics describing the two principal components of the viral life cycle, namely, the rapid proliferation and slower clearance phases. Here, we present results from an ongoing workplace clinical surveillance study during which two vaccinated participants became infected with SARS-CoV-2 Omicron variant (BA.1. lineage). The subjects were followed longitudinally with high temporal resolution, allowing the kinetics of both viral phases to be characterized. The viral doubling times in the proliferation phase (3.3 to 3.5 h) and maximum measured viral loads were similar to those observed for unvaccinated individuals infected with an earlier SARS-CoV-2 strain. However, the clearance phase was much shorter in the current study and unexpectedly displayed a multimodal profile. Longitudinal whole-genome SARS-CoV-2 sequencing identified a stable mutation that arose in one of the participants over the 2-week period of positivity. Our small study provides rare insight into the clinical SARS-CoV-2 dynamics, with significance for public health measures and the biology underlying COVID-19. IMPORTANCE We are conducting an ongoing SARS-CoV-2 workplace clinical study based on frequent, longitudinal disease surveillance of staff and household members. Here, we investigated the viral dynamics in two recently vaccinated participants who became infected with the same Omicron variant of SARS-CoV-2. Because the subjects were enrolled in our study, we were able to track the entire viral life cycle with high temporal resolution, with samples collected every 12 h. Surprisingly, the short viral proliferation phase and maximum viral loads in nasal swab samples were similar to our previous observations with unvaccinated participants and an earlier viral strain. However, the decay phase, indicative of viral clearance, was much shorter here. Our results provide a rare, real-world glimpse of the clinical SARS-CoV-2 replication kinetics, potentially impacting immediate therapies and awareness of earlier and greater transmission potential.
Expansion of the genotypic and phenotypic spectrum of CTCF‐related disorder guides clinical management: 43 new subjects and a comprehensive literature review

Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF‐related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with CRD included intellectual disability/developmental delay (91%) with speech delay (65%), motor delay (53%), feeding difficulties/failure to thrive (66%), ocular abnormalities (56%), musculoskeletal anomalies (53%), and behavioral problems (52%). Other congenital anomalies were also reported, but none of them were common. Our findings expanded the genotypic and phenotypic spectrum of CRD that will guide genetic counseling, management, and surveillance care for patients with CRD. Additionally, a newly built facial gestalt on the Face2Gene tool will facilitate prompt recognition of CRD by physicians and shorten a patient's diagnostic odyssey.