Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of an In Vitro Co-Culture Model of the Piglet Gut to Study Inflammatory Response and Barrier Integrity

Abstract In intensive farming, piglets are exposed to various challenges that activate intestinal inflammatory processes, negatively affecting animal health and leading to economic losses. To study the role of the inflammatory response on epithelial barrier integrity, co-culture systems that mimic in vivo complexity are more and more preferred over cell monocultures. In this study, an in vitro gut co-culture model consisting of intestinal porcine epithelial cells and porcine peripheral blood mononuclear cells was established. The model provides an appropriate tool to study the role of the inflammatory response on epithelial barrier integrity and to screen for feed and food components, exerting beneficial effects on gut health. In the established model, inflammation-like reactions and damage of the epithelial barrier, indicated by a decrease of transepithelial electrical resistance, were elicited by activation of peripheral blood mononuclear cells via one of 3 stimuli: lipopolysaccharide, lipoteichoic acid, or concanavalin A. Two phytogenic substances that are commonly used as feed additives, licorice extract and oregano oil, have been shown to counteract the drop in transepithelial electrical resistance values in the gut co-culture model. The established co-culture model provides a powerful in vitro tool to study the role of intestinal inflammation on epithelial barrier integrity. As it consists of porcine epithelial and porcine blood cells it perfectly mimics in vivo conditions and imitates the inter-organ communication of the piglet gut. The developed model is useful to screen for nutritional components or drugs, having the potential to balance intestinal inflammation and strengthen the epithelial barrier integrity in piglets.
Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.
Emotion elicitation during music listening: Subjective self-reports, facial expression, and autonomic reactivity.

The use of music as emotional stimuli in experimental studies has grown in recent years. However, prior studies have mainly focused on self-reports and central measures, with a few works exploring the time course of psychophysiological correlates. Moreover, most of the previous research has been carried out either from the dimensional or categorical model but not combining both approaches to emotions. This study aimed to investigate subjective and physiological correlates of emotion elicitation through music, following the three-dimensional and the discrete emotion model. A sample of 50 healthy volunteers (25 women) took part in this experiment by listening to 42 film music excerpts (14 pleasant, 14 unpleasant, 14 neutral) presented during 8 s, while peripheral measures were continuously recorded. After music offset, affective dimensions (valence, energy arousal, and tension arousal) as well as discrete emotions (happiness, sadness, tenderness, fear, and anger) were collected using a 9-point scale. Results showed an effect of the music category on subjective and psychophysiological measures. In peripheral physiology, greater electrodermal activity, heart rate acceleration, and zygomatic responses, besides lower corrugator amplitude, were observed for pleasant excerpts in comparison to neutral and unpleasant music, from 2 s after stimulus onset until the end of its duration. Overall, our results add evidence for the efficacy of standardized film music excerpts to evoke powerful emotions in laboratory settings; thus, opening a path to explore interventions based on music in pathologies with underlying emotion deregulatory processes.
Comparison of Vandenbos procedure or Winograd method for ingrown toenail

Objectives This study aims to compare the outcomes of the Winograd method and Vandenbos procedure used to treat an ingrown toenail. Patients and methods Between January 2017 and February 2020, a total of 145 patients (65 males, 80 females; mean age: 31.45 years; range, 13 to 61 years) who were treated with Winograd or Vandenbos procedure for an ingrown toenail were retrospectively analyzed. Of the patients, 70 underwent the Winograd method (Group 1) and 75 underwent the Vandenbos procedure (Group 2). Postoperative Visual Analog Scale (VAS) scores, demographic data, recurrence/complication rates, and satisfaction of patients were recorded. Results The mean recovery time was 11.8±2.6 days in Group 1 and 18.0±2.1 days in Group 2 (p<0.001). The mean VAS score was 3.9±0.7 in Group 1 and 7.2±1.0 in Group 2 (p<0.001) during the first postoperative week. Of the patients, 56 (80%) of 70 patients in Group 1 and 74 (98%) of 75 patients in Group 2 were satisfied with the surgery (p<0.001). In terms of cosmetics, 60 (85%) of the patients in Group 1 and 74 (98%) of the patients in Group 2 were satisfied (p=0.003). Recurrence was observed in 10 (14%) patients in Group 1, while no recurrence was observed in Group 2. Six (8.7%) patients in Group 1 and one (1.3%) patient in Group 2 developed complications. Conclusion Low recurrence rates, high satisfaction, and good cosmetic results can be achieved with the Vandenbos procedure, while recovery time and return to work are faster with the Winograd method. The appropriate surgical technique should be selected based on the individual patient.
Comparative genome analysis revealed gene inversions, boundary expansions and contractions, and gene loss in the Stemona sessilifolia (Miq.) Miq. chloroplast genome

Stemona sessilifolia (Miq.) Miq. , commonly known as Baibu, is one of the most popular herbal medicines in Asia. In the Chinese Pharmacopoeia, Baibu has multiple authentic sources and there are many similar herbs sold as Baibu in herbal medicine markets. The existence of counterfeits of Baibu brings challenges to its identification. To assist in its accurate identification, we sequenced and analyzed the complete chloroplast genome of S. sessilifolia using next-generation sequencing technology. The genome was found to be 154,037 bp in length, possessing a typical quadripartite structure consisting of a pair of inverted repeats (IRs: 27,090 bp) separated by a large single copy (LSC: 81,949 bp) and a small single copy (SSC: 17,908 bp). A total of 112 unique genes were identified, including 80 protein-coding, 28 transfer RNA and four ribosomal RNA genes. In addition, 45 tandem, 27 forward, 23 palindromic and 104 simple sequence repeats were detected in the genome by repeated analysis. Compared with its counterfeits (Asparagus officinalis and Carludovica palmata) we found that IR expansion and SSC contraction events of S. sessilifolia resulted in two copies of the rpl22 gene in the IR regions and a partial duplication of the ndhF gene in the SSC region. An approximately 3-kb-long inversion was also identified in the LSC region, leading to the petA and cemA genes being presented in the complementary strand of the chloroplast DNA molecule. Comparative analysis revealed some highly variable regions, including trnF-GAA_ndhJ, atpB_rbcL, rps15_ycf1, trnG-UCC_trnR-UCU, ndhF_rpl32, accD_psaI, rps2_rpoC2, trnS-GCU_trnG-UCC, trnT-UGU_trnL-UAA and rps16_trnQ-UUG. Finally, gene loss events were investigated in the context of phylogenetic relationships. In summary, the complete plastome of S. sessilifolia will provide valuable information for the distinction between Baibu and its counterfeits and assist in elucidating the evolution of S. sessilifolia.
Schistosome W-Linked Genes Inform Temporal Dynamics of Sex Chromosome Evolution and Suggest Candidate for Sex Determination

Abstract Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating “evolutionary strata” of various ages. Although the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around 100 candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost. W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of nonrecombining regions. Among these, the splicing factor u2af2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group. Keywords: sex chromosomes, evolutionary strata, W-linked gene, sex determining gene, schistosome parasites.
PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial

Background Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. Methods and findings HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted. Conclusions In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. Trial registration ClinicalTrials.gov NCT02732730.
Multiple imputation of maritime search and rescue data at multiple missing patterns

Based on the missing situation and actual needs of maritime search and rescue data, multiple imputation methods were used to construct complete data sets under different missing patterns. Probability density curves and overimputation diagnostics were used to explore the effects of multiple imputation. The results showed that the Data Augmentation (DA) algorithm had the characteristics of high operation efficiency and good imputation effect, but the algorithm was not suitable for data imputation when there was a high data missing rate. The EMB algorithm effectively restored the distribution of datasets with different data missing rates, and was less affected by the missing position; the EMB algorithm could obtain a good imputation effect even when there was a high data missing rate. Overimputation diagnostics could not only reflect the data imputation effect, but also show the correlation between different datasets, which was of great importance for deep data mining and imputation effect improvement. The Expectation-Maximization with Bootstrap (EMB) algorithm had a poor estimation effect on extreme data and failed to reflect the dataset’s variability characteristics.
Endogenous fungal endophthalmitis following intensive corticosteroid therapy in severe COVID-19 disease

Purpose: To report endogenous fungal endophthalmitis, postrecovery from severe COVID-19 infection in otherwise immunocompetent individuals, treated with prolonged systemic steroids. Methods: Retrospective chart review of cases with confirmed and presumed fungal endogenous endophthalmitis, following severe COVID-19 disease, treated at two tertiary care referral eye institutes in North India. Results: Seven eyes of five cases of endogenous fungal endophthalmitis were studied. All cases had been hospitalized for severe COVID-19 pneumonia and had received systemic steroid therapy for an average duration of 42 ± 25.1 days (range 18–80 days). All the cases initially complained of floaters with blurred vision after an average of 6 days (range 1–14 days) following discharge from hospital. They had all been misdiagnosed as noninfectious uveitis by their primary ophthalmologists. All eyes underwent pars plana vitrectomy (PPV) with intravitreal antifungal therapy. Five of the seven eyes grew fungus as the causative organism (Candida sp. in four eyes, Aspergillus sp. in one eye). Postoperatively, all eyes showed control of the infection with a marked reduction in vitreous exudates and improvement in vision. Conclusion: Floaters and blurred vision developed in patients after they recovered from severe COVID-19 infection. They had received prolonged corticosteroid treatment for COVID-19 as well as for suspected noninfectious uveitis. We diagnosed and treated them for endogenous fungal endophthalmitis. All eyes showed anatomical and functional improvement after PPV with antifungal therapy. It is important for ophthalmologists and physicians to be aware of this as prompt treatment could control the infection and salvage vision.
Studies of the self-assembled growth mechanism on nanocrystalline silicon nanodots

Nanocrystalline silicon (nc-Si) nanodots have been grown on corning glass (7059) substrate using a self-assembly VHF-PECVD method under the following experimental conditions: Fixed deposition temperatures of 300/400 °C, deposition times 30/60 s, plasma power of 10 W, silane gas flow rate of 10 sccm, as well as deposition pressure of 10-2 torr. It is predicted that the onset of nucleation began immediately after the deposition and start to appear clearly after 20-60 s during which growth mechanisms occur. Essentially, the nanodots were formed onto the substrate in dome-like shapes by virtue of equilibrium surface energies, γLS, γLN andγNS. The associated liquid/solid nucleation mechanism was then simulated and related parameters were obtained: Free energy change per unit volume ΔGv ∼-104 Jmol-1; Surface energies per unit area, γLN = 1.44 Jm-2, γNS = 19 - 60 Jm-2 and γLS = 0.74 Jm-2; Critical energies ΔG* ∼10-15 J; Critical radii r* = 16 - 48 nm. These results were experimentally verified, in particular for selected critical radius r* less than 50 nm.Other measurements were also carried out: PL analysis gave bandgap energies ∼ 1.8-2.4 eV, whilst Raman spectra revealed the coexistence of nc-Si and amorphous Si. It is strongly suggested that, the nc-Si nanodot grown on glass substrate fulfills the Volmer-Weber growth mode with a minor modification.
Adaptive Finite-Time Command Filtered Controller Design for Nonlinear Systems With Output Constraints and Input Nonlinearities

This work addresses a finite-time tracking control issue for a class of nonlinear systems with asymmetric time-varying output constraints and input nonlinearities. To guarantee the finite-time convergence of tracking errors, a novel finite-time command filtered backstepping approach is presented by using the command filtered backstepping technique, finite-time theory, and barrier Lyapunov functions. The newly proposed method can not only reduce the complexity of computation of the conventional backstepping control and compensate filtered errors caused by dynamic surface control but also can ensure that the output variables are restricted in compact bounding sets. Moreover, the proposed controller is applied to robot manipulator systems, which guarantees the practical boundedness of all the signals in the closed-loop system. Finally, the effectiveness and practicability of the developed control strategy are validated by a simulation example.
In vitro assessment of the sensitivity to APR‐246 + azacitidine combination predicts response to this combination in myelodysplastic/acute myeloid leukaemia patients

TP53 mutations, which abrogate normal p53 protein functions and may also induce deleterious ‘gain of function’ of the protein, are a poor prognostic factor in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), especially when mutations are biallelic. 1 Restoration of mutant p53 normal functions in those cases, especially by protein ‘reconformation’, has been considered a relevant strategy and many drugs have been tested. 2 APR-246 (Eprenetapopt) is a pro-drug that induces structural changes to mutant p53 and restores the active conformation of the protein. 3 We recently reported the in vitro and in vivo syn-ergy of azacitidine (AZA) in combination with APR-246. In vitro , using a clonogenic culture model of AML/MDS patient cells we observed a signiﬁcant reduction in the clonogenic activity of TP53 -mutated patients’ progenitors when treated with this drug combination. 4 In a phase 2 clinical trial, the AZA and APR-246 combination in TP53 -mutated high-risk MDS yielded an overall response rate (ORR) of 62%, complete response (CR) of 47 % and median response duration of 10 (cid:1) 4 months (ORR and CR of 33% and 17% in AML), 5 and our results were conﬁrmed in a US study. 6 However, in our study no haematological, cytogenetic or molecular parameter (including whether TP53 mutation was mono- or biallelic, or its variant allele frequency) had any prognostic value for response or survival. As a signiﬁcant proportion of patients were poor responders to this combination, deﬁning predictors to response in vivo would be important for future use of these drugs. Culture-based preclinical models were previously used for the evaluation of various drugs in MDS. Therefore, we assessed the prognostic value of in vitro clonogenic
Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women

Abstract Background Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life. Methods In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo. Results Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4%–53.2%) versus placebo (0%–15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with prevaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8- to 14-fold and 12- to 21-fold at day 8 and persisted 5- to 6-fold and 6- to 8-fold higher until day 91 in the RSVPreF3 groups versus 1-fold in placebo. Comparisons at day 8 and day 31 showed that the higher dose levels were significantly more immunogenic than the lowest one. Conclusions The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women. Clinical Trials Registration NCT03674177.
First description of Nodding Syndrome in the Central African Republic

Background The term Nodding Syndrome (NS) refers to an atypical and severe form of childhood epilepsy characterized by a repetitive head nodding (HN). The disease has been for a long time limited to East Africa, and the cause is still unknown. The objective of this study was to confirm the existence of NS cases in Central African Republic (CAR). Methodology/Principal findings This was a cross-sectional descriptive study in the general population. The identification of NS cases was conducted through a door-to-door survey in a village near Bangui along the Ubangui River. Based on Winkler’s 2008 and the World Health Organization (WHO)’s 2012 classifications, the confirmation of cases was done by a neurologist who also performed the electroencephalograms. No laboratory tests were done during this investigation. Treatment was offered to all patients. A total of 6,175 individuals was surveyed in 799 households. After reviewing the cases, we identified 5 NS cases in girls aged between 8 and 16. The age of onset of the seizures was between 5 and 12 years of age. Two cases were classified as "HN plus" according to Winkler’s 2008 classification. Four NS cases were classified as probable and one as confirmed according to the WHO’s 2012 classification. Three of them presented with developmental delay and cognitive decline, and one had an abnormally low height-for-age z-score. Electroencephalographic abnormalities were found in four patients. Conclusions/Significance Nodding Syndrome cases were described in CAR for the first time. Despite certain peculiarities, these cases are similar to those described elsewhere. Given that only a small part of the affected area was investigated, the study area along the Ubangui River needs to be expanded in order to investigate the association between Onchocerca volvulus and NS and also evaluate the real burden of NS in CAR.