Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of a human-serum-based in vitro growth method for drug screening on juvenile development stages of Schistosoma mansoni

Background Schistosomiasis affects over 200 million people worldwide but only praziquantel is available for treatment and control. Drug discovery is often based on phenotypic drug screening, involving different parasite stages retrieved from infected mice. Aiming to reduce animal use, we validated an in vitro growth method for juvenile Schistosoma mansoni for the purpose of drug sensitivity assays. Methodology/Principal findings We compared inter–batch variability of serum, worm size and organ development, gender distribution, and drug sensitivity between in vitro and in vivo grown worms over different life stages. In vitro developed S. mansoni in Hybridoma medium supplemented with 20% human serum were similar in size as in vivo worms until 28 days of incubation (males 1.4 ± 0.2 mm, females 1.1 ± 0.5 mm long). qPCR analysis revealed similar gender distribution both on newly transformed schistosomula and worms grown for 21 days. Worms developed in vitro and in vivo were similarly sensitive to praziquantel from 7 to 35 days of development with the exception of 21 days of development, where a slightly lower activity was observed for the in vitro grown worms (IC50: 0.54 μM in vitro, 0.14 μM in vivo 72 hours post-incubation). The evaluation of five additional drugs revealed a similar sensitivity on worms developed for 21 days, with the exception of mefloquine, where we observed a 10-fold lower sensitivity on in vitro developed schistosomes when compared to in vivo grown (IC50: 4.43 μM in vitro, 0.48 μM in vivo). Conclusion A large number of juvenile S. mansoni worms can be grown in vitro, which show similar drug sensitivity, gender distribution, size and morphology as the worms recovered from rodents, supporting the use of this method in drug screening efforts.
Spatial-Temporal Relationship Between Population Mobility and COVID-19 Outbreaks in South Carolina: Time Series Forecasting Analysis

Background Population mobility is closely associated with COVID-19 transmission, and it could be used as a proximal indicator to predict future outbreaks, which could inform proactive nonpharmaceutical interventions for disease control. South Carolina is one of the US states that reopened early, following which it experienced a sharp increase in COVID-19 cases. Objective The aims of this study are to examine the spatial-temporal relationship between population mobility and COVID-19 outbreaks and use population mobility data to predict daily new cases at both the state and county level in South Carolina. Methods This longitudinal study used disease surveillance data and Twitter-based population mobility data from March 6 to November 11, 2020, in South Carolina and its five counties with the largest number of cumulative confirmed COVID-19 cases. Population mobility was assessed based on the number of Twitter users with a travel distance greater than 0.5 miles. A Poisson count time series model was employed for COVID-19 forecasting. Results Population mobility was positively associated with state-level daily COVID-19 incidence as well as incidence in the top five counties (ie, Charleston, Greenville, Horry, Spartanburg, and Richland). At the state level, the final model with a time window within the last 7 days had the smallest prediction error, and the prediction accuracy was as high as 98.7%, 90.9%, and 81.6% for the next 3, 7, and 14 days, respectively. Among Charleston, Greenville, Horry, Spartanburg, and Richland counties, the best predictive models were established based on their observations in the last 9, 14, 28, 20, and 9 days, respectively. The 14-day prediction accuracy ranged from 60.3%-74.5%. Conclusions Using Twitter-based population mobility data could provide acceptable predictions of COVID-19 daily new cases at both the state and county level in South Carolina. Population mobility measured via social media data could inform proactive measures and resource relocations to curb disease outbreaks and their negative influences.
Antigen‐dependent multistep differentiation of T follicular helper cells and its role in SARS‐CoV‐2 infection and vaccination

T follicular helper (Tfh) cells play an essential role in regulating the GC reaction and, consequently, the generation of high‐affinity antibodies and memory B cells. Therefore, Tfh cells are critical for potent humoral immune responses against various pathogens and their dysregulation has been linked to autoimmunity and cancer. Tfh cell differentiation is a multistep process, in which cognate interactions with different APC types, costimulatory and coinhibitory pathways, as well as cytokines are involved. However, it is still not fully understood how a subset of activated CD4+ T cells begins to express the Tfh cell‐defining chemokine receptor CXCR5 during the early stage of the immune response, how some CXCR5+ pre‐Tfh cells enter the B‐cell follicles and mature further into GC Tfh cells, and how Tfh cells are maintained in the memory compartment. In this review, we discuss recent advances on how antigen and cognate interactions are important for Tfh cell differentiation and long‐term persistence of Tfh cell memory, and how this is relevant to the current understanding of COVID‐19 pathogenesis and the development of potent SARS‐CoV‐2 vaccines.
Adult Urology Oncology: Adrenal/Renal/Upper Tract/Bladder JU Insight Partial Adrenalectomy Carries a Considerable Risk of Incomplete Cure in Primary Aldosteronism

Study Need and Importance: Laparoscopic adre-nalectomy is standard treatment for patients with unilateral aldosterone-producing adenomas (APA), but surgeons are increasingly tempted to perform partial adrenalectomy. This study aimed to assess the diagnostic value of endoscopic ultrasound (EUS) for differentiating solitary adenomas from multi-nodularity by examining in depth adrenal pathology with ex vivo ultra-high ﬁeld magnetic resonance imaging (MRI) and immunohistochemistry (IHC). What We Found: The sensitivity and speciﬁcity of EUS to identify multinodularity was 46%, and 50%, respectively. We found multinodularity in 87% of adrenals (n [ 13) with ex vivo MRI combined with detailed histopathological examination and six ad-renals contained multiple CYP11B2 producing nodules. Every CYP11B2 positive nodule and 61% of CYP11B2 negative nodules showed CXCR4 staining. Limitations: Although our patient number seems adequate for its purposes, it is relatively low. Assessment of EUS images is subjective, but it was performed in consensus. The EUS images are difﬁ-cult to accurately correlate with histopathology because the image plane differs from the pathology slices. Finally, interpretation of IHC may also be subjective, although our kappa values reﬂect substantial agreement. Interpretation for Patient Care: Intraoperative EUS in patients with primary aldosteronism (PA) has low accuracy to identify multinodularity. Ex vivo MRI
Covid-19 and repercussions in mental health: a narrative review of literature.

OBJECTIVE To identify the repercussions on mental health of groups and populations in the context of the new coronavirus pandemic. METHOD Narrative review carired out in three databases, in March 2020, using the descriptors mental health and coronavirus. A total of 19 publications were analyzed, organized in a synoptic chart, containing type of publication, authors, country, sample, objective, and main results. From this analysis, two thematic axes emerged: identification of problems and vulnerable groups in mental health; and mental health interventions and actions. RESULTS The first axis showed manifestations of suffering - anguish, insomnia, anger, stress, fear. The second revealed the need to build government policies and general guidelines; production of information and communication; and mental health care practices. CONCLUSIONS The repercussions on mental health in the population intensified with the pandemic, identifying vulnerable groups, and the need to build coping strategies and policies aimed at mental health during epidemics.
Cognitive-emotional processing in alexithymia: an integrative review

ABSTRACT Alexithymia is a multifaceted personality construct characterised by difficulties identifying one’s feelings and distinguishing them from bodily sensations, difficulties describing one’s feelings to others, and an externally oriented cognitive style. Over the past 25 years, a burgeoning body of research has examined how alexithymia moderates processing at the cognition–emotion interface. We review the findings in five domains: attention, appraisals, memory, language, and behaviours. The preponderance of studies linked alexithymia with deficits in emotion processing, which was apparent across all domains, except behaviours. All studies on behaviours and a proportion of studies in other domains demonstrated emotional over-responding. Analysis at the facet level revealed deficits in memory and language that are primarily associated with externally oriented thinking, while over-responding was most often linked to difficulty identifying feelings and difficulty describing feelings. The review also found evidence for contextual modulation: The pattern of deficits and over-responding was not restricted to emotional contexts but also occurred in neutral contexts, and in some circumstances, emotional over-responding in alexithymia was beneficial. Taken together, this review highlights alexithymia as a central personality dimension in the interplay between cognition and emotion.
Management practices of dog and cat owners in France (pet traveling, animal contact rates and medical monitoring): impacts on the introduction and the spread of directly transmitted infectious pet diseases.

A number of owner practices among the pet dog and cat population can influence the dynamics of directly transmitted infectious dog and cat diseases, including zoonotic ones. To better depict these management practices, which include pet traveling, contact rates with other companion animals and their medical monitoring (which herein includes prevention aspects), we surveyed 2,122 dog- and/or cat-owning French households through an anonymous online questionnaire. Trips with dogs within the European Union (EU) were frequent while cats traveled less frequently within the EU and both cats and dogs traveled less frequently outside the EU. Recurrent illegal trips with dogs and cats (non-compliant with regulatory measures) were observed in a context of non-systematic pet border controls. We found that a large proportion of dogs are taken for walks in metropolitan France, with frequent intraspecific contacts (1.4 contacts/day on average), but only a minority (1.4%) of dogs were allowed to roam freely. On the other hand, 59.7% of cat owners allowed their cats to roam freely. We classified pet owners according to different profiles, some of which may be considered "at risk" for directly transmitted infectious pet diseases. Indeed, one dog owner profile and one cat owner profile depict "spreaders" of pet diseases (high connectivity with other individuals, little medical monitoring but no traveling) and another dog owner profile describes a potential "introducer" and "spreader" of pet diseases (foreign travel, high connectivity with other individuals, and intermediate medical monitoring). While these "at risk" profiles represent only a minority of French pet owners, they should be better characterized to reinforce targeted prevention designed to minimize the risk of (re)introduction and (re)emergence of directly transmitted infectious dog and cat diseases in France, especially when considering zoonoses with a significant potential impact, such as rabies.
Powerful helicity inducers: axially chiral binaphthyl derivatives

Axially chiral binaphthyl derivatives with highly twisting powers were synthesised by substituting phenylcyclohexyl (PCH) mesogenic moieties into 2,2′ positions or 2,2′,6,6′ positions of binaphthyl rings. The di‐ and tetra‐substituted binaphthyl derivatives were adopted as chiral dopants to induce chiral nematic liquid crystals (N*‐LCs). The helical twisting power (βM) of tetra‐substituted binaphthyl derivative, D‐3, having direct linkages between the PCH moieties and the binaphthyl rings at the 6,6′ positions, was 449 µm−1. This is ca. 2.6 times larger than that (171 µm−1) of di‐substituted one, D‐1. For systematic investigation of helical twisting power in the binaphthyl derivatives, several tetra‐substituted binaphthyl derivatives (D‐2–D‐9) were synthesised by introducing different aromatic moieties into the 6,6′ positions of the binaphthyl rings without methylene spacer. When the substituents group changed from p‐hexaoxyphenyl to p‐hexaoxybiphenyl, the helical twisting powers of the binaphthyl derivatives increased from 234 to 757 µm−1. Interestingly, D‐3 and D‐9 exhibited liquid crystallinity. Although the liquid crystallinity of the chiral dopant has no direct influence on the helical twisting power of the N*‐LC, it plays a role in increasing the miscibility of the chiral dopant to host N‐LC, leading to a raise of the upper limit in concentration of the chiral dopant. Consequently, both the high helical twisting power and the high miscibility of D‐3 allowed us to prepare a highly twisted N*‐LC, the helical pitch of which is in the nano‐order, e.g. 270 nm.
Microbiology of soils at opencast coal sites. I. Short‐and long‐term transformations in stockpiled soils

SUMMARY The microbiology of soils subjected to stripping and stockpiling at opencast mine sites was investigated using a combination of and biomass fumigation plate-count techniques. Mounds varied in age from a few weeks to 11 years, and soils included both mineral and organic variants. Results showed that after an initial stimulation of bacteria, microbial populations declined in stockpiles. Numbers of viable fungal propagules, and to a lesser extent actinomycetes, declined with depth in mounds, particularly below about 1 m, and this trend was accentuated with increased time of storage. However, stockpiled soils were highly variable in terms of microbiological status and displayed considerable lateral as well as vertical heterogeneity.
A comparison of double single suture-button fixation, suture-button fixation, and screw fixation for ankle syndesmosis injury

Abstract Different methods have been used throughout the years for syndesmotic injury but there is no consensus on the ideal treatment. Some methods are expensive and some have more complications. The aim of this study is to compare single suture endobutton with double suture endobutton and screw fixation for syndesmotic injury. Sixty nine patients with syndesmotic injury with fibular fractures whom were treated with a single interosseous suture endobutton system (ZipTightTM, Zimmer Biomet), a double interosseous suture endobutton system (ZipTightTM, Zimmer Biomet) and 1 syndesmotic screw (TST, Istanbul, Turkey) were included in this study. Functional and radiological results from patient records between 2015 and 2018 were retrospectively evaluated. Twenty patients were treated with the double interosseous suture endobutton, 23 were treated with the single interosseous suture endobutton, and 26 were treated with traditional AO screw fixation. Three patients from the screw fixation group (11.5%) required revision surgery (P < .05). All the radiologic and clinical outcomes were statistical similar in all 3 groups. Our findings showed that the interosseous suture endobutton system is at least as safe as the screw fixation technique for treatment of syndesmosis joint injuries and can be used as an alternative to the screw method. The interosseous suture endobutton system eliminates the need for a second surgery to remove the hardware, which minimizes the probability of re-diastasis. Since our results showed no statistical difference between single and double interosseous suture endobutton systems, the less costly single endobutton system may be the better alternative.
Light chain skewing in autoantibodies and B-cell receptors of the citrullinated antigen-binding B-cell response in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 1% of the world population. RA is associated with the presence of autoantibodies, of which anti-citrullinated protein antibodies (ACPA) are most prominent. ACPA are produced by citrullinated antigen-binding B cells that have presumably survived tolerance checkpoints. So far, it is unclear how and when such autoreactive B cells emerge. Light chain (LC) rearrangement and mutation rates can be informative with regard to selection steps during B-cell development. Therefore, we studied LC characteristics of ACPA-expressing B cells and secreted ACPA with the aim to better understand the development of this disease-specific, autoreactive B-cell response. Paired ACPA-IgG and ACPA-depleted IgG were isolated from serum (n = 87) and synovial fluid (SF, n = 21) of patients with established RA. We determined the LC composition for each fraction by ELISA using kappa(Igκ)- and lambda(Igλ) LC-specific antibodies. Cellular LC expression was determined using flow cytometry. In addition, we used a B-cell receptor (BCR)-specific PCR to obtain LC variable region sequences of citrullinated antigen- and tetanus toxoid (TT)-binding B cells. In serum, we observed an increased frequency of lambda LC in ACPA-IgG (1.64:1) compared to control IgG (2.03:1) and to the κ/λ ratio reported for healthy individuals (2:1). A similar trend towards higher frequencies of lambda LCs was observed for ACPA-IgG in SF (1.84:1). Additionally, the percentage of Igλ-expressing B cells was higher for citrullinated antigen-binding B cells (51%) compared to TT-specific (43%) and total CD19+CD20+ B cells (36%). Moreover, an increased Igλ percentage was observed in BCR-sequences derived from ACPA-expressing (49%) compared to TT-specific B cells (34%). Taken together, we report an enhanced frequency of lambda LCs in the secreted ACPA-IgG repertoire and, on the cellular level, in BCR sequences of ACPA-expressing B cells compared to control. This skewing in the autoreactive B-cell repertoire could reflect a process of active selection.
Atmospheric pathways of phosphorous to the Bay of Bengal: contribution from anthropogenic sources and mineral dust

ABSTRACT The continental outflow from the Indo-Gangetic Plain and Southeast Asia, during the late NE monsoon (January–March), dominates the transport of chemical constituents to the marine atmospheric boundary layer (MABL) of the Bay of Bengal (BoB). During the rest of the year, prevailing wind regimes and meteorological conditions do not favour the atmospheric transport of continental products. Here we report on the spatio-temporal variability of inorganic phosphorous (PInorg= ) in the MABL and its dry-deposition flux to the surface BoB. On the basis of the abundance of PInorg in PM2.5 (0.1–0.8 nmol m−3) and PM10 (0.3–2.8 nmol m−3), we document its dominant occurrence in the coarse mode (Da≥2.5 µm). The analytical data also provide evidence for the chemical processing of mineral dust by acidic species and mobilisation of PInorg during the long-range atmospheric transport. However, significantly high PInorg/non-sea-salt Ca2+ ratios over the BoB suggest dominant contribution from anthropogenic sources (fertilisers and biomass burning emissions). PInorg concentration over the Arabian Sea is about 4 to 5 times lower and is primarily associated with the mineral dust from desert regions. The dry-deposition flux of PInorg to the BoB varies by one order of magnitude (0.5–5.0 µmol P m−2 d−1; Av: 0.02 Tg P yr−1). These results have implications to the air-sea deposition of phosphorous over oceanic regions downwind of the pollution sources and impact on the biogeochemistry of surface waters.
Decreased toxicity of Al to Juvenile Atlantic salmon (Salmo salar) in acidic soft water containing natural organic matter: A test of the free‐ion model

Toxicological experiments were designed to test the predictions of the free‐ion model (FIM) in a soft, acidic water containing Al and a natural fulvic acid (FA). Juvenile Atlantic salmon (Salmo salar) were exposed to Al in either inorganic or organic acidic soft waters, at pH 5.0, and 50% lethal concentrations (LC50) values were determined for both exposure solutions. Contrary to the predictions of the FIM, the LC50s, expressed as inorganic Al (Ali), were significantly higher (p < 0.05) in the organic solution (6.1–8.0 μM Ali) than in the inorganic medium (2.9–4.0 μM Ali). Preexposure of the fish to a 10‐mg/L FA solution at pH 5.0, without Al, did not protect the animals from a subsequent Al challenge in solutions without FA. A regression model related mortality with Ali and total organic carbon (TOC) and was highly significant (proportion mortality [arcsine] = −0.215 + [0.81]log[Ali] — [0.44]TOC; p < 0.0001, R2 = 0.71). We conclude that natural FA may play an independent protective role in solutions containing Al, in addition to that of decreasing Al toxicity by complexation of the metal and reducing the free Al3+ concentration.
The 3Rs in animal welfare bodies at Swedish universities - knowledge, attitudes, implementation.

The implementation of the 3Rs (replacement, reduction and refinement) is emphasized in EU Directive 2010/63. The task of the animal welfare bodies (AWB) is to strengthen animal welfare and develop the 3Rs at research animal facilities. In 2016, we surveyed the knowledge, attitudes towards and implementation of the 3Rs within AWBs at eight major Swedish universities. Based on responses of 34 closed-ended questions from 44 of 90 AWB members, the overall attitude towards the 3Rs was positive. Animal Welfare Body members did not believe that the 3Rs slow down innovation or result in increased costs, and refinement is considered beneficial for research quality. Animal Welfare Body members were particularly positive towards refinement questions in the survey. A majority of the AWB members answered that alternative methods will never replace animal use. Researchers as a group represented in the AWBs were significantly less positive towards the 3Rs, compared to the group of veterinarians. The tasks of the AWBs, e.g., giving advice on the 3Rs and following up on animal use in projects, was often not carried out in the AWB or "not known" by the respondents. Our results indicate a need for more practical and regulatory guidance and support to the AWBs. To reach the goal of the EU Directive to phase out animal use in research and education, we suggest that technical expertise in replacement techniques is included in the AWBs. We emphasize the need to strengthen the 3R awareness among researchers at Swedish universities.