Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase II study of laser interstitial thermal therapy combined with doxorubicin in patients with recurrent glioblastoma

Abstract Background The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability. Methods Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6–8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared to historical controls treated with bevacizumab salvage therapy (n = 50) or LITT with standard BBB-permeable salvage therapy (n = 28). Cox proportional-hazards models examined the contribution of age, gender, MGMT promoter status, and IDH-mutation status on any PFS and OS. Adverse events were also cataloged. Results The Late Arm and all patients (Early Arm + Late Arm) demonstrated significant improvement in OS compared to historical controls treated with bevacizumab (p < 0.001) and LITT with standard salvage therapy (p < 0.05). No significant difference in any PFS was observed between either arm and historical controls. Low-dose doxorubicin was well tolerated with comparable adverse event rates between the arms. Conclusions Low-dose doxorubicin given after LITT is well tolerated and correlated with higher OS compared to historical controls treated with bevacizumab or LITT with standard salvage chemotherapy. A larger study is needed to further characterize survival and progression patterns.
Early Fall in C-Reactive Protein (CRP) Level Predicts Response to Tocilizumab in Rapidly Progressing COVID-19: Experience in a Single-Arm Pakistani Center

Introduction There are conflicting studies regarding the efficacy of tocilizumab use in coronavirus disease 2019 (COVID-19) disease. There is a special need to identify the parameters that could predict its response in early COVID-19 disease. Objective To report our experience with tocilizumab and correlate the magnitude of fall in c-reactive protein (CRP) as a predictor of its response to treatment in early COVID-19 disease. Methods All confirmed COVID-19 cases admitted to a tertiary healthcare hospital in Peshawar Pakistan, receiving ≥1 dose of intravenous tocilizumab, between March and September 2020 were included. Relevant clinical data of the patients were recorded and further divided into two categories based on the relative fall in CRP levels, 48 hours after tocilizumab administration. Adequate response (≥50% fall from baseline CRP), primary outcomes (fall in oxygen requirement and inflammatory biomarkers), and secondary outcome (all-cause mortality at day 28) were recorded. All outcomes were compared based on falls in CRP levels. Results A total of 27 patients were included. Males were 24 (88.8%) while females were three (11.1%). The mean age was 60.9±11.6 years. The mean day of illness at the time of tocilizumab administration was 4.26±3 days. After 48 hours of tocilizumab administration, 17 (62.9%) patients showed clinical improvement, with the mean SaO2/FiO2 ratio prior to treatment significantly increased (p<0.01). A significant reduction in CRP and ferritin levels was seen post-treatment (p <0.01 and p<0.01, respectively). Twenty (74.1%) patients demonstrated adequate response to tocilizumab while seven (25.9%) showed an inadequate response. Patients with adequate response had higher chances of improvement in oxygenation and lower in-hospital mortality (p-value 0.009 and 0.020, respectively). Conclusions Tocilizumab shows clinical improvement in a vast majority of patients. Being an early and sensitive predictor, a fall of ≥50% in CRP at 48 hours can be used to predict the overall response to tocilizumab as a guide to treatment.
Effect of incremental proportions of Desmanthus spp. in isonitrogenous forage diets on growth performance, rumen fermentation and plasma metabolites of pen-fed growing Brahman, Charbray and Droughtmaster crossbred beef steers

Desmanthus (Desmanthus spp.), a tropically adapted pasture legume, is highly productive and has the potential to reduce methane emissions in beef cattle. However, liveweight gain response to desmanthus supplementation has been inconclusive in ruminants. This study aimed to evaluate weight gain, rumen fermentation and plasma metabolites of Australian tropical beef cattle in response to supplementation with incremental levels of desmanthus forage legume in isonitrogenous diets. Forty-eight Brahman, Charbray and Droughtmaster crossbred beef steers were pen-housed and fed a basal diet of Rhodes grass (Chloris gayana) hay supplemented with 0, 15, 30 or 45% freshly chopped desmanthus forage on dry matter basis, for 140 days. Varying levels of lucerne (Medicago sativa) hay were added in the 0, 15 and 30% diets to ensure that all diets were isonitrogenous with the 45% desmanthus diet. Data were analyzed using the Mixed Model procedures of SAS software. Results showed that the proportion of desmanthus in the diet had no significant effect on steer liveweight, rumen volatile fatty acids molar proportions and plasma metabolites (P ≥ 0.067). Total bilirubin ranged between 3.0 and 3.6 μmol/L for all the diet treatments (P = 0.67). All plasma metabolites measured were within the expected normal range reported for beef cattle. Rumen ammonia nitrogen content was above the 10 mg/dl threshold required to maintain effective rumen microbial activity and maximize voluntary feed intake in cattle fed low-quality tropical forages. The average daily weight gains averaged 0.5 to 0.6 kg/day (P = 0.13) and were within the range required to meet the target slaughter weight for prime beef markets within 2.5 years of age. These results indicate that desmanthus alone or mixed with other high-quality legume forages can be used to supplement grass-based diets to improve tropical beef cattle production in northern Australia with no adverse effect on cattle health.
Terrestrial reproduction and parental care drive rapid evolution in the trade-off between offspring size and number across amphibians

The trade-off between offspring size and number is central to life history strategies. Both the evolutionary gain of parental care or more favorable habitats for offspring development are predicted to result in fewer, larger offspring. However, despite much research, it remains unclear whether and how different forms of care and habitats drive the evolution of the trade-off. Using data for over 800 amphibian species, we demonstrate that, after controlling for allometry, amphibians with direct development and those that lay eggs in terrestrial environments have larger eggs and smaller clutches, while different care behaviors and adaptations vary in their effects on the trade-off. Specifically, among the 11 care forms we considered at the egg, tadpole and juvenile stage, egg brooding, male egg attendance, and female egg attendance increase egg size; female tadpole attendance and tadpole feeding decrease egg size, while egg brooding, tadpole feeding, male tadpole attendance, and male tadpole transport decrease clutch size. Unlike egg size that shows exceptionally high rates of phenotypic change in just 19 branches of the amphibian phylogeny, clutch size has evolved at exceptionally high rates in 135 branches, indicating episodes of strong selection; egg and tadpole environment, direct development, egg brooding, tadpole feeding, male tadpole attendance, and tadpole transport explain 80% of these events. By explicitly considering diversity in parental care and offspring habitat by stage of offspring development, this study demonstrates that more favorable conditions for offspring development promote the evolution of larger offspring in smaller broods and reveals that the diversity of parental care forms influences the trade-off in more nuanced ways than previously appreciated.
Linking socio-sexual and vocal behaviour with faecal progesterone and oestrogen metabolite levels in Southern white rhinoceros females

Behaviour, vocalization and faecal metabolite concentrations of progesterone (fPM) and oestrogen were compared between receptive and non-receptive periods in female white rhinoceroses. Affiliative and olfactory-related behaviour peaked during receptive period, coinciding with hormonal oestrus and nadirs in fPM concentrations. The results reveal a sexual behavioural repertoire reflecting the hormonal state.
Anterior Chamber Paracentesis Offers a Less Painful Experience During Intravitreal Anti-vascular Endothelial Growth Factor Administration: An Intraindividual Study

Introduction: In order to improve comfort and compliance to treatment of the patient during the intravitreal injections (IVIs), relieving pain may help and provide getting better results. The purpose of the study was to evaluate the efficacy of anterior chamber paracentesis on pain perception and the factors related to pain perception during intravitreal injection procedures. Material and methods: This prospective randomized study includes 212 eyes of 106 patients scheduled for bilateral IVI of ranibizumab 0.5 mg/0.05 cc under topical anesthesia. All patients underwent full ophthalmologic examination, including intraocular pressure (IOP), anterior chamber depth (ACD), and axial length (AL) measurements. Group 1 received IVI following anterior chamber paracentesis (ACP) and group 2 received IVI without ACP. Intraocular pressure was measured five minutes and 30 minutes after the procedure. Pain perception was assessed by visual analogue scale (VAS) grading from 0 to 10. Results: Mean VAS score for groups 1 and 2 was recorded as 0.51±1.00 and 1.32±1.50, respectively. Correlation analysis revealed a positive correlation between VAS score and history of previous IVI, preinjection IOP values, and an inverse correlation with the presence of reflux in both groups, in addition to inverse correlation with ACD in group 2. Conclusions: ACP may offer a comfortable, effective, and less painful alternative to prevent the acute rise in IOP after IVI, especially in patients with small anterior chambers, small vitreous volumes, with a history of multiple injections, and in patients with advanced glaucomatous optic neuropathy.
Genetic diversity in enhancer II region of HBV genotype D and its association with advanced liver diseases

Background Hepatitis B Virus (HBV) is one of the most common human infectious agents, and the mutations in its genome may cause chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). This study was designed to characterize the enhancer-II (Enh-II) region of X gene in HBV positive patients to assess the association of such mutations with CH, LC, and HCC. Methods HBV positive samples (N = 200) with patients’ demographic and clinical data were collected from different regions of Khyber Pakhtunkhwa (KP), Pakistan. The Enh-II region of the HBx gene was sequenced and zanalyzed for polymorphism associated with advanced liver disease. Univariate and logistic regression analyses were performed to evaluate potent mutations associated with a risk for LC and HCC. Results HBV Enh-II region sequences analysis revealed 25 different mutations. The highest frequency of mutations S101F (62.2%), A102V/R/G/I (56.25%), M103L/A (68.75%)were found in HCC, followed in LC and CH patients as 57.1%, 42.8%, 28.52% 16%, 15.2% and 18.4% respectively. H94 deletion in the α-box of the Enh-II region, associated with a high risk of HCC was found in half of the HCC patients. This deletion was present in 28.5% of LC and 6.5% of CH patients. Importantly, the high frequency of some notable mutations such as E109A/Y, A110S/K, Y111D/E, and F112L was first time reported in the entire study population. The frequencies of these mutations were high in HCC (43.75%, 37.5%, 50% and 43.75% respectively) as compared to LC (14.28%, 14.28%, 28.2% and 42.8%) and CH patients (12.8%, 15.2%, 16.8% and 16% respectively). Conclusion Mutations associated with LC and HCC are prevalent in the Enh-II region in Pakistani HBV isolates. The mutations found are alarming in CH patients as these may progress to LC and HCC in a large number of patients.
IgG3 and IgM Identified as Key to SARS-CoV-2 Neutralization in Convalescent Plasma Pools

Analysis of convalescent plasma derived from individuals has shown that IgG3 has the most important role in binding to SARS-CoV-2 antigens; however, this has not yet been confirmed in large studies, and the link between binding and neutralization has not been confirmed. By analyzing plasma pools consisting of 247–567 individual convalescent donors, we demonstrated the binding of IgG3 and IgM to Spike-1 protein and the receptor-binding domain correlates strongly with viral neutralization in vitro. Furthermore, despite accounting for only approximately 12% of total immunoglobulin mass, collectively IgG3 and IgM account for approximately 80% of the total neutralization. This may have important implications for the development of potent therapies for COVID-19, as it indicates that hyperimmune globulins or convalescent plasma donations with high IgG3 concentrations may be a highly efficacious therapy.
Immunological and prognostic significance of novel ferroptosis-related genes in soft tissue sarcoma

Background Ferroptosis has exhibited great potential in the treatment of cancer and has gained widespread attention in soft tissue sarcoma (STS). The aim was to explore the immunological and prognostic significance of novel ferroptosis-related genes in STS. Methods We identified ferroptosis-related differentially expressed genes (DEGs) in STS to construct the networks of enrichment analysis and protein-protein interaction. Subsequently, hub genes with prognostic significance were localized and a series of prognostic and immune analyses were performed. Results 40 ferroptosis-related DEGs were identified, of which HELLS, STMN1 EPAS1, CXCL2, NQO1, and IL6 were classified as hub genes and were associated with the prognosis in STS patients. In the results of the immune analysis, PDCD1, CTLA4, TIGIT, IDO1 and CD27 exhibited consistent intense correlations as immune checkpoint genes, as well as macrophage, neutrophil, cytotoxic cell, dendritic cell, interdigitating dendritic cell and plasmacytoid dendritic cell as immune cells. EPAS1 and HELLS might be independent prognostic factors for STS patients, and separate prognostic models were constructed by using them. Conclusions We recognized novel ferroptosis-related genes with prognostic value in STS. Furthermore, we searched out potential immune checkpoints and critical immune cells.
Rose without prickle: genomic insights linked to moisture adaptation

Abstract Prickles act against herbivores, pathogens or mechanical injury, while also preventing water loss. However, whether prickles have new function and the molecular genetics of prickle patterning remain poorly explored. Here, we generated a high-quality reference genome assembly for ‘Basye's Thornless’ (BT), a prickle-free cultivar of Rosa wichuraiana, to identify genetic elements related to stem prickle development. The BT genome harbors a high level of sequence diversity in itself and with cultivar ‘Old Blush’ (R. chinensis), a founder genotype in rose domestication. Inheritance of stem prickle density was determined and two QTL were identified. Differentially expressed genes in QTL were involved in water-related functions, suggesting that prickle density may hitchhike with adaptations to moist environments. While the prickle-related gene-regulatory-network (GRN) was highly conserved, the expression variation of key candidate genes was associated with prickle density. Our study provides fundamental resources and insights for genome evolution in the Rosaceae. Ongoing efforts on identification of the molecular bases for key rose traits may lead to improvements for horticultural markets.
Nucleotide Usage Biases Distort Inferences of the Species Tree

Despite the importance of natural selection in species’ evolutionary history, phylogenetic methods that take into account population-level processes typically ignore selection. The assumption of neutrality is often based on the idea that selection occurs at a minority of loci in the genome and is unlikely to compromise phylogenetic inferences significantly. However, genome-wide processes like GC-bias and some variation segregating at the coding regions are known to evolve in the nearly neutral range. As we are now using genome-wide data to estimate species trees, it is natural to ask whether weak but pervasive selection is likely to blur species tree inferences. We developed a polymorphism-aware phylogenetic model tailored for measuring signatures of nucleotide usage biases to test the impact of selection in the species tree. Our analyses indicate that while the inferred relationships among species are not significantly compromised, the genetic distances are systematically underestimated in a node-height dependent manner: i.e., the deeper nodes tend to be more underestimated than the shallow ones. Such biases have implications for molecular dating. We dated the evolutionary history of 30 worldwide fruit fly populations, and we found signatures of GC-bias considerably affecting the estimated divergence times (up to 23%) in the neutral model. Our findings call for the need to account for selection when quantifying divergence or dating species evolution. Significance statement Although little is known about the impact of natural selection on species tree estimation, expectations are that it occurs at a minority of loci in eukaryotic genomes and is thus unlikely to affect the divergence process. However, growing evidence suggests that a large amount of the genomic variation evolves under weak but pervasive selection (e.g., fixation biases created by GC-bias gene conversion). We tested the impact of unaccounted-for nearly neutral selection on species tree estimation and found that the estimated branch lengths are systematically biased. Our results highlight the need for selection-aware models in species tree estimation and molecular dating.
STAnet: A Spatiotemporal Attention Network for Decoding Auditory Spatial Attention from EEG

Objective: Humans are able to localize the source of a sound. This enables them to direct attention to a particular speaker in a cocktail party. Psycho-acoustic studies show that the sensory cortices of the human brain respond to the location of sound sources differently, and the auditory attention itself is a dynamic and temporally based brain activity. In this work, we seek to build a computational model which uses both spatial and temporal information manifested in EEG signals for auditory spatial attention detection (ASAD). Methods: We propose an end-to-end spatiotemporal attention network, denoted as STAnet, to detect auditory spatial attention from EEG. The STAnet is designed to assign differentiated weights dynamically to EEG channels through a spatial attention mechanism, and to temporal patterns in EEG signals through a temporal attention mechanism. Results: We report the ASAD experiments on two publicly available datasets. The STAnet outperforms other competitive models by a large margin under various experimental conditions. Its attention decision for 1-second decision window outperforms that of the state-of-the-art techniques for 10-second decision window. Experimental results also demonstrate that the STAnet achieves competitive performance on EEG signals ranging from 64 to as few as 16 channels. Conclusion: This study provides evidence suggesting that efficient low-density EEG online decoding is within reach. Significance: This study also marks an important step towards the practical implementation of ASAD in real life applications.
The Dark Side of Microbial Processes: Accumulation of Nitrate During Storage of Surface Water in the Dark and the Underlying Mechanism

Microbial communities play an essential role in maintaining a healthy aquatic ecosystem. For example, in surface water reservoirs, microorganisms produce oxygen, break down toxic contaminants, and remove excess nitrogen. ABSTRACT In densely populated cities with limited land, storage of surface water in underground spaces is a potential solution to meet the rising demand of clean water. In addition, due to the imperative need of renewable solar energy and limited land resources, the deployment of floating solar photovoltaic (PV) systems over water has risen exponentially. In both scenarios, microbial communities in the water do not have access to sunlight. How the absence of sunlight influences microbial community function and the water quality is largely unknown. The objective of this study was to reveal microbial processes in surface water stored in the dark and water quality dynamics. Water from a freshwater reservoir was stored in the dark or light (control) for 6 months. Water quality was monitored at regular intervals. RNA sequencing was performed on the Illumina MiSeq platform and qPCR was used to substantiate the findings arising from the sequencing data. Our results showed that storage of surface water in the dark resulted in the accumulation of nitrate in the water. Storage in the dark promoted the decay of algal cells, increasing the amount of free nitrogen in the water. Most of the free nitrogen was eventually transformed into nitrate through microbial processes. RNA sequencing-based microbial community analyses and pure culture experiments using nitrifying bacteria Nitrosomonas europaea and Nitrobacter sp. revealed that the accumulation of nitrate in the dark was likely due to an increase in nitrification rate and a decrease in the assimilation rate of nitrate back into the biomass. IMPORTANCE Microbial communities play an essential role in maintaining a healthy aquatic ecosystem. For example, in surface water reservoirs, microorganisms produce oxygen, break down toxic contaminants and remove excess nitrogen. In densely populated cities with limited land, storing surface water in underground spaces and deploying floating solar photovoltaic (PV) systems over water are potential solutions to address water and energy sustainability challenges. In both scenarios, surface water is kept in the dark. In this work, we revealed how the absence of sunlight influences microbial community function and water quality. We showed that storage of surface water in the dark affected bacterial activities responsible for nitrogen transformation, resulting in the accumulation of nitrate in the water. Our findings highlight the importance of monitoring nitrate closely if raw surface water is to be stored in the dark and the potential need of downstream treatment to remove nitrate.
Perinatal depression is associated with a higher polygenic risk for major depressive disorder than non‐perinatal depression

Distinctions between major depressive disorder (MDD) and perinatal depression (PND) reflect varying views of PND, from a unique etiological subtype of MDD to an MDD episode that happens to coincide with childbirth. This case–control study investigated genetic differences between PND and MDD outside the perinatal period (non‐perinatal depression or NPD).