Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenomic fingerprinting of tempo and functions of horizontal gene transfer within ochrophytes

Significance The ochrophytes are an ancient and important group of eukaryotic algae, including diatoms, the most important photosynthesisers in the modern ocean, and a wide range of other species. Throughout their history, ochrophytes have exchanged genes with bacteria and eukaryotes through horizontal gene transfer (HGT), diversifying their cell biology. Here, we profile thousands of phylogenetic trees, showing that HGTs from bacteria contribute particularly to the recent evolution of diatoms, occurring more frequently than HGTs from eukaryotes and, potentially, more frequently in diatoms than other ochrophytes. Using experimental and computational techniques, we show that bacterial HGTs predominantly impact the diatom secreted proteome, which may contribute to the striking evolutionary success of diatoms. Horizontal gene transfer (HGT) is an important source of novelty in eukaryotic genomes. This is particularly true for the ochrophytes, a diverse and important group of algae. Previous studies have shown that ochrophytes possess a mosaic of genes derived from bacteria and eukaryotic algae, acquired through chloroplast endosymbiosis and from HGTs, although understanding of the time points and mechanisms underpinning these transfers has been restricted by the depth of taxonomic sampling possible. We harness an expanded set of ochrophyte sequence libraries, alongside automated and manual phylogenetic annotation, in silico modeling, and experimental techniques, to assess the frequency and functions of HGT across this lineage. Through manual annotation of thousands of single-gene trees, we identify continuous bacterial HGT as the predominant source of recently arrived genes in the model diatom Phaeodactylum tricornutum. Using a large-scale automated dataset, a multigene ochrophyte reference tree, and mathematical reconciliation of gene trees, we note a probable elevation of bacterial HGTs at foundational points in diatom evolution, following their divergence from other ochrophytes. Finally, we demonstrate that throughout ochrophyte evolutionary history, bacterial HGTs have been enriched in genes encoding secreted proteins. Our study provides insights into the sources and frequency of HGTs, and functional contributions that HGT has made to algal evolution.
Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer

Background and Objectives: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. Methods: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. Results: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. Conclusions: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.
The Optimizing Background Infusion Mode Decreases Intravenous Patient-Controlled Analgesic Volume and Opioid Consumption Compared to Fixed-Rate Background Infusion in Patients Undergoing Laparoscopic Cholecystectomy: A Prospective, Randomized, Controlled, Double-Blind Study

Background and objectives: The fixed-rate continuous background infusion mode with bolus dosing is a common modality for intravenous patient-controlled analgesia (PCA). However, some patients suffer from inadequate analgesia or opioid-related adverse effects due to the biphasic pattern of postoperative pain. Therefore, we investigated the postoperative analgesic efficacy of PCA using an optimizing background infusion mode (OBIM) where the background injection rate varies depending on the patient’s bolus demand. Materials and Methods: We prospectively enrolled 204 patients who underwent laparoscopic cholecystectomy in a randomized, controlled, double-blind study. Patients were allocated to either the optimizing (group OBIM) or the traditional background infusion group (group TBIM). The numeric rating scale (NRS) score for pain was evaluated at admission to and discharge from the recovery room, as well as at the 6th, 24th, and 48th postoperative hours. Data on bolus demand count, total infused volume, and background infusion rate were downloaded from the PCA device at 30-min intervals until the 48th postoperative hour. Results: The NRS score was not significantly different between groups throughout the postoperative period (p = 0.621), decreasing with time in both groups (p < 0.001). The bolus demand count was not significantly different between groups throughout (p = 0.756). The mean total cumulative infused PCA volume was lower in group OBIM (84.0 (95% confidence interval: 78.9−89.1) mL) than in group TBIM (102 (97.8−106.0) mL; p < 0.001). The total cumulative opioid dose in fentanyl equivalents, after converting sufentanil to fentanyl using an equipotential dose ratio, was lower in group OBIM (714.1 (647.4−780.9) μg) than in group TBIM (963.7 (870.5−1056.9) μg); p < 0.001). The background infusion rate was significantly different between groups throughout the study period (p < 0.001); it was higher in group OBIM than in group TBIM before the 12th postoperative hour and lower from the 18th to the 48th postoperative hour. Conclusions: The OBIM combined with bolus dosing reduces the cumulative PCA volume and opioid consumption compared to the TBIM combined with bolus dosing, while yielding comparable postoperative analgesia and bolus demand in patients undergoing laparoscopic cholecystectomy.
Immunological Determinants of Liver Transplant Outcomes Uncovered by the Rat Model

For many individuals with end-stage liver disease, the only treatment option is liver transplantation. However, liver transplant rejection is observed in 24%–80% of transplant patients and lifelong drug regimens that follow the transplant procedure lead to serious side effects. Furthermore, the pool of donor livers available for transplantation is far less than the demand. Well-characterized and physiologically relevant models of liver transplantation are crucial to a deeper understanding of the cellular processes governing the outcomes of liver transplantation and serve as a platform for testing new therapeutic strategies to enhance graft acceptance. Such a model has been found in the rat transplant model, which has an advantageous size for surgical procedures, similar postoperative immunological progression, and high genome match to the human liver. From rat liver transplant studies published in the last 5 years, it is clear that the rat model serves as a strong platform to elucidate transplant immunological mechanisms. Using the model, we have begun to uncover potential players and possible therapeutic targets to restore liver tolerance and preserve host immunocompetence. Here, we present an overview of recent literature for rat liver transplant models, with an aim to highlight the value of the models and to provide future perspectives on how these models could be further characterized to enhance the overall value of rat models to the field of liver transplantation.
Influenza virus infection increases ACE2 expression and shedding in human small airway epithelial cells

Background Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrate high rates of co-infection with respiratory viruses, including influenza A (IAV), suggesting pathogenic interactions. Methods We investigated how IAV may increase the risk of COVID-19 lung disease, focusing on the receptor angiotensin-converting enzyme (ACE)2 and the protease TMPRSS2, which cooperate in the intracellular uptake of SARS-CoV-2. Results We found, using single-cell RNA sequencing of distal human nondiseased lung homogenates, that at baseline, ACE2 is minimally expressed in basal, goblet, ciliated and secretory epithelial cells populating small airways. We focused on human small airway epithelial cells (SAECs), central to the pathogenesis of lung injury following viral infections. Primary SAECs from nondiseased donor lungs apically infected (at the air–liquid interface) with IAV (up to 3×105 pfu; ∼1 multiplicity of infection) markedly (eight-fold) boosted the expression of ACE2, paralleling that of STAT1, a transcription factor activated by viruses. IAV increased the apparent electrophoretic mobility of intracellular ACE2 and generated an ACE2 fragment (90 kDa) in apical secretions, suggesting cleavage of this receptor. In addition, IAV increased the expression of two proteases known to cleave ACE2, sheddase ADAM17 (TACE) and TMPRSS2 and increased the TMPRSS2 zymogen and its mature fragments, implicating proteolytic autoactivation. Conclusion These results indicate that IAV amplifies the expression of molecules necessary for SARS-CoV-2 infection of the distal lung. Furthermore, post-translational changes in ACE2 by IAV may increase vulnerability to lung injury such as acute respiratory distress syndrome during viral co-infections. These findings support efforts in the prevention and treatment of influenza infections during the COVID-19 pandemic. Influenza virus infection of cells lining the small airways increases the expression of molecules required for SARS-CoV-2 uptake in a manner that predicts increased severity of lung disease in those co-infected with influenza and coronaviruses https://bit.ly/3nu1WAo
Rise of ‘Lonely’ Consumers in the Post-COVID-19 Era: A Synthesised Review on Psychological, Commercial and Social Implications

Loneliness is a pervasive problem recognised as a serious social issue, and the prevailing COVID-19 pandemic has exacerbated loneliness to greater prominence and concern. We expect a rise of a massive group of ‘lonely’ consumers who are deeply entrenched in the social isolation caused by COVID-19. There is an urgent need to revisit the phenomenon of lonely consumers to better prepare academic researchers, public policy makers and commercial managers in the post-COVID-19 era. Thus, this study conducts a synthesised review on past studies of lonely consumers. Based on an inductive analysis of 56 articles, 74 key themes are identified. These key themes are further categorised into five major clusters by way of a co-occurrence network analysis. Respectively, the five clusters address the psychological implications related to the dynamics between nonhuman attachment and consumers’ loneliness, the commercial implications related to the paradoxical motivations of affiliation and self-affirmation in product selection and the dual information processing mechanism in response to advertisement appeals, and the social implications related to consumers’ well-being in an ageing society and the anthropomorphic companionship in a virtual world. A list of research questions is proposed that concludes the review study.
Studying GGDEF Domain in the Act: Minimize Conformational Frustration to Prevent Artefacts

GGDEF-containing proteins respond to different environmental cues to finely modulate cyclic diguanylate (c-di-GMP) levels in time and space, making the allosteric control a distinctive trait of the corresponding proteins. The diguanylate cyclase mechanism is emblematic of this control: two GGDEF domains, each binding one GTP molecule, must dimerize to enter catalysis and yield c-di-GMP. The need for dimerization makes the GGDEF domain an ideal conformational switch in multidomain proteins. A re-evaluation of the kinetic profile of previously characterized GGDEF domains indicated that they are also able to convert GTP to GMP: this unexpected reactivity occurs when conformational issues hamper the cyclase activity. These results create new questions regarding the characterization and engineering of these proteins for in solution or structural studies.
Exploring the Effects of Blur and Deblurring to Visual Object Tracking

The existence of motion blur can inevitably influence the performance of visual object tracking. However, in contrast to the rapid development of visual trackers, the quantitative effects of increasing levels of motion blur on the performance of visual trackers still remain unstudied. Meanwhile, although image-deblurring can produce visually sharp videos for pleasant visual perception, it is also unknown whether visual object tracking can benefit from image deblurring or not. In this paper, we present a Blurred Video Tracking (BVT) benchmark to address these two problems, which contains a large variety of videos with different levels of motion blurs, as well as ground-truth tracking results. To explore the effects of blur and deblurring to visual object tracking, we extensively evaluate 25 trackers on the proposed BVT benchmark and obtain several new interesting findings. Specifically, we find that light motion blur may improve the accuracy of many trackers, but heavy blur usually hurts the tracking performance. We also observe that image deblurring is helpful to improve tracking accuracy on heavily-blurred videos but hurts the performance of lightly-blurred videos. According to these observations, we then propose a new general GAN-based scheme to improve a tracker’s robustness to motion blur. In this scheme, a fine-tuned discriminator can effectively serve as an adaptive blur assessor to enable selective frames deblurring during the tracking process. We use this scheme to successfully improve the accuracy of 6 state-of-the-art trackers on motion-blurred videos.
Predicting Radiotherapy Impact on Late Bladder Toxicity in Prostate Cancer Patients: An Observational Study

Simple Summary Prostate cancer (PC) is the most common cancer in men over 70 years old, with heterogeneous characteristics and, nowadays, multiple treatment strategies obtaining optimal outcomes and improving survival. Personalized medicine and even more morbidity treatment reduction are increasing needs. The development of decision support systems to personalize treatments is a key challenge in oncology. The study PRODIGE 1.1 aimed to elaborate on a model analyzing dosimetric parameters in Prostate Cancer patients treating by radiation therapy, predicting late bladder toxicity in order to customize treatments and reduce late morbidity. Abstract Background and purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique. Materials and methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann–Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer–Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3. 1 and an in house developed software package “Moddicom” were used. Results: Data from 175 patients were collected. The median follow-up was 39 months (min–max 3.00–113.00). We performed Mann–Whitney rank-sum test with continuity correction in the subset of patients with late bladder toxicity grade ≥ 2: a statistically significant p-value with a Vdose of 51.43 Gy by applying a logistic regression model (coefficient 4.3, p value 0.025) for the prediction of the development of late G ≥ 2 GU toxicity was observed. The performance for the model’s internal validation was evaluated, with an AUC equal to 0.626. Accuracy was estimated through the elaboration of a calibration plot. Conclusions: Our preliminary results could help to optimize treatment planning procedures and customize treatments.
Survival Outcomes and Predictors for Patients who Failed Chemoradiotherapy/Radiotherapy and Underwent Salvage Total Laryngectomy

Background: To assess the presence of adverse pathological features at the time of salvage total laryngectomy (TL) associated with oncologic outcome. Methods: Ninety patients with persistent/locally recurrent disease and who subsequently underwent salvage TL after definitive treatment by radiation alone (RTO) or concurrent chemo-radiation (CCRT) from 2009 to 2018 were retrospectively enrolled. Kaplan–Meier methods were used to estimate overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Results: Lymphovascular invasion (LVI), perineural invasion, positive margin, and stage IV disease were associated with worse survival in the univariate analysis. In the multivariate analysis, the presence of LVI and positive margin were both independent negative predictors in OS (LVI: adjusted hazard ratio (aHR) = 2.537, 95% CI: 1.163–5.532, p = 0.019; positive margin: aHR = 5.68, 95% CI: 1.996–16.166, p = 0.001), DSS (LVI: aHR = 2.975, 95% CI: 1.228–7.206, p = 0.016); positive margin: aHR = 11.338, 95% CI: 2.438–52.733, p = 0.002), and DFS (LVI: aHR 2.705, 95% CI: 1.257–5.821, p = 0.011; positive margin (aHR = 6.632, 95% CI: 2.047–21.487, p = 0.002). Conclusions: The presence of LVI and positive margin were both associated with poor OS, DSS, and DFS among patients who underwent salvage TL after failure of RTO/CCRT. The role of adjuvant therapy for high-risk patients after salvage TL to improve the chance of survival requires more investigation in the future.
Genomic Characterization of VIM and MCR Co-Producers: The First Two Clinical Cases, in Italy

Background: the co-production of carbapenemases and mcr-genes represents a worrisome event in the treatment of Enterobacteriaceae infections. The aim of the study was to characterize the genomic features of two clinical Enterobacter cloacae complex (ECC) isolates, co-producing VIM and MCR enzymes, in Italy. Methods: species identification and antibiotic susceptibility profiling were performed using MALDI-TOF and broth microdilution methods, respectively. Transferability of the blaVIM- and mcr- type genes was verified through conjugation experiment. Extracted DNA was sequenced using long reads sequencing technology on the Sequel I platform (PacBio). Results: the first isolate showed clinical resistance against ertapenem yet was colistin susceptible (EUCAST 2020 breakpoints). The mcr-9.2 gene was harbored on a conjugative IncHI2 plasmid, while the blaVIM-1 determinant was harbored on a conjugative IncN plasmid. The second isolate, resistant to both carbapenems and colistin, harbored: mcr-9 gene and its two component regulatory genes for increased expression on the chromosome, mcr-4.3 on non-conjugative (yet co-transferable) ColE plasmid, and blaVIM-1 on a non-conjugative IncA plasmid. Conclusions: to our knowledge, this is the first report of co-production of VIM and MCR in ECC isolates in Italy.
bFGF-chitosan scaffolds effectively repair 20 mm sciatic nerve defects in adult rats

The repair of peripheral nerve injury is still a great challenge in clinic. Autologous nerve transplantation is the gold standard for the treatment of long-distance peripheral nerve defects, but this method remains associated with high morbidity of the donor site and lack of matching donor. In this study, a novel chitosan scaffold (CS) loaded with control-released basic fibroblast growth factor (bFGF) was used to repair 20 mm sciatic nerve defects in adult rat. The ultrastructure of bFGF-CS was observed by scanning electron microscope. The tensile tester and nano-indentation were used to evaluate its mechanical properties. Cholera toxin B-subunit (CTB) tracing, sciatic nerve function index, electromyography, immunofluorescence staining of regenerated nerve and motor endplate were used to evaluate the regeneration of sciatic nerve in rats. The results showed that the structure and mechanical properties of bFGF-CS was beneficial to the regeneration of sciatic nerve. At 12 weeks after operation, bFGF-CS facilitated sciatic nerve regeneration in rat. CTB successfully crossed the sciatic nerve defect area to reach the cell body of sciatic nerve. The motor endplate was reconstructed, thus promoting the behavioral recovery. These findings suggest that the bFGF-CS provides an effective means of repairing 20 mm sciatic nerve defects and shows great potential for clinical application.
Selfie consents, remote rapport, and Zoom debriefings: collecting qualitative data amid a pandemic in four resource-constrained settings

In-person interactions have traditionally been the gold standard for qualitative data collection. The COVID-19 pandemic required researchers to consider if remote data collection can meet research objectives, while retaining the same level of data quality and participant protections. We use four case studies from the Philippines, Zambia, India and Uganda to assess the challenges and opportunities of remote data collection during COVID-19. We present lessons learned that may inform practice in similar settings, as well as reflections for the field of qualitative inquiry in the post-COVID-19 era. Key challenges and strategies to overcome them included the need for adapted researcher training in the use of technologies and consent procedures, preparation for abbreviated interviews due to connectivity concerns, and the adoption of regular researcher debriefings. Participant outreach to allay suspicions ranged from communicating study information through multiple channels to highlighting associations with local institutions to boost credibility. Interviews were largely successful, and contained a meaningful level of depth, nuance and conviction that allowed teams to meet study objectives. Rapport still benefitted from conventional interviewer skills, including attentiveness and fluency with interview guides. While differently abled populations may encounter different barriers, the included case studies, which varied in geography and aims, all experienced more rapid recruitment and robust enrollment. Reduced in-person travel lowered interview costs and increased participation among groups who may not have otherwise attended. In our view, remote data collection is not a replacement for in-person endeavours, but a highly beneficial complement. It may increase accessibility and equity in participant contributions and lower costs, while maintaining rich data collection in multiple study target populations and settings.