Miracle-dz/UniFAR-FTUs huggingface dataset:
Classifying Dissemination Processes in Temporal Graphs

Many real-world graphs are temporal, for example, in a social network, persons only interact at specific points in time. This temporal information directs dissemination processes on the graph, such as the spread of rumors, fake news, or diseases. However, the current state-of-the-art methods for supervised graph classification are mainly designed for static graphs and may not capture temporal information. Hence, they are not powerful enough to distinguish between graphs modeling different dissemination processes. We introduce a framework to lift standard graph kernels and graph-based neural networks to the temporal domain to address this. We explore three different approaches and investigate the trade-offs between loss of temporal information and efficiency. Moreover, to handle large-scale graphs, we propose stochastic variants of our kernels with provable approximation guarantees. We evaluate our methods, both kernel and neural architectures, on various real-world social networks to validate our theoretical findings. Our methods beat static approaches by a large margin in terms of accuracy while still being scalable to large graphs and data sets. Moreover, we show that our framework reaches high classification accuracy in scenarios where most of the dissemination process information is incomplete.
Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways

Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.
Magnitude and regulation of zooplankton community production across boreal lakes

A major outstanding question in plankton ecology is whether the regulation of zooplankton production at the community level follows the same patterns that have been observed for individual populations. We used a novel biochemical approach to estimate in situ rates of crustacean zooplankton community production in 83 boreal lakes, with the objective of identifying the main drivers of zooplankton production at the community level across the boreal landscape. Our results show that the relationship of zooplankton community production to average community body size, total biomass, and temperature is comparable to what has been observed for individual populations. At the community level, however, there are additional drivers, including lake morphometry, and catchment properties, which further influence zooplankton production and which cannot be inferred from population level patterns.
Genetic alterations in MENX-associated pheochromocytoma

Rats developing multiple endocrine neoplasia-like syndrome (MENX) carry a homozygous frameshift mutation in Cdkn1b, encoding the cyclin-dependent kinase inhibitor p27(KIP1). In the current study genome-wide scan for loss of heterozygosity (LOH) and allelic imbalance (AI) of the MENX-related pheochromocytomas (PCs) and comparative genomic hybridization array revealed rat candidate regions which have a synteny to human chromosomal regions known to be involved in adrenal and extra-adrenal PC development and highly affected in pituitary adenomas. Using different methods rat homologs of genes predisposing to PC development and candidate tumor suppressor genes were analysed. Overexpression of Cdkn2a, Cdkn2c and Sctr was detected.
Hyperspectral Shortwave Infrared Image Analysis for Detection of Adulterants in Almond Powder with One-Class Classification Method

The widely used techniques for analyzing the quality of powdered food products focus on targeted detection with a low-throughput screening of samples. Owing to potentially significant health threats and large-scale adulterations, food regulatory agencies and industries require rapid and non-destructive analytical techniques for the detection of unexpected compounds present in products. Accordingly, shortwave-infrared hyperspectral imaging (SWIR-HSI) for high throughput authenticity analysis of almond powder was investigated in this study. Two different varieties of almond powder, adulterated with apricot and peanut powder at different concentrations, were imaged using the SWIR-HSI system. A one-class classifier technique, known as data-driven soft independent modeling of class analogy (DD-SIMCA), was used on collected data sets of pure and adulterated samples. A partial least square regression (PLSR) model was further developed to predict adulterant concentrations in almond powder. Classification results from DD-SIMCA yielded 100% sensitivity and 89–100% specificity for different validation sets of adulterated samples. The results obtained from the PLSR analysis yielded a high determination coefficient (R2) and low error values (<1%) for each variety of almond powder adulterated with apricot; however, a relatively higher error rates of 2.5% and 4.4% for the two varieties of almond powder adulterated with peanut powder, which indicates the performance of quantitative analysis model could vary with sample condition, such as variety, originality, etc. PLSR-based concentration mapped images visually characterized the adulterant (apricot) concentration in the almond powder. These results demonstrate that the SWIR-HSI technique combined with the one-class classifier DD-SIMCA can be used effectively for a high-throughput quality screening of almond powder regarding potential adulteration.
Human Isogenic Cell Line Models for Neutrophils and Myeloid-Derived Suppressor Cells

Neutrophils with immunosuppressive activity are polymorphonuclear myeloid-derived suppressor cells (MDSCs) and may contribute to the resistance to cancer immunotherapy. A major gap for understanding and targeting these cells is the paucity of cell line models with cardinal features of human immunosuppressive neutrophils and their normal counterparts, especially in an isogenic manner. To address this issue, we employ the human promyelocytic cell line HL60 and use DMSO and cytokines (granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin 6 (IL6)) to induce the formation of either neutrophils or MDSCs. The induced MDSCs are CD11b+ CD33+ HLA-DR−/low and are heterogeneous for CD15 and CD14 expression. The induced MDSCs abrogate IL2 production and activation-induced cell death of the human T cell line Jurkat stimulated by CD3/CD28 antibodies, whereas the induced neutrophils enhance IL2 production from Jurkat cells. The induced MDSCs upregulate the expression of C/EBPβ, STAT3, VEGFR1, FATP2 and S100A8. Lastly, the immunosuppressive activity of the induced MDSCs is inhibited by all-trans retinoic acid and STAT3 inhibitor BP-1-102 through cellular differentiation and dedifferentiation mechanisms, respectively. Together, our study establishes a human isogenic cell line system for neutrophils and MDSCs and this system is expected to facilitate future studies on the biology and therapeutics of human immunosuppressive neutrophils.
Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial

Purpose: We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods: This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight <50 kg) every 2 weeks plus oral apatinib 250 mg daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) per RECIST v1.1. Results: Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3–46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4–31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4–7.4) and 5.5 months (95% CI, 3.7–5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5–83.5) and 68.2% (95% CI, 59.0–75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred. Conclusions: Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients. See related commentary by Pinato et al., p. 908
Cystocele Repair by a Modified Surgical Technique of Bilateral Pubococcygeus Plication: Long-Term Surgical and Functional Results

Here we describe our modified surgical technique of bilateral pubococcygeus plication (BPCP) for cystocele repair and assess its safety and long-term outcomes. This is a prospective study of 147 consecutive women who underwent BPCP for cystocele between January 2010 to January 2018. Inclusion criteria was naïve women with symptomatic cystocele ≥ POP-Q 2nd stage. Exclusion criteria: stress urinary incontinence (SUI), urgency urinary incontinence, other associated vaginal wall prolapses ≥ stage 2, neurological diseases, previous SUI surgeries, and previous radiation/surgery of the pelvic area. BPCP was performed by obtaining the medialization of the pubococcygeus muscle fibers of the right and left sides. Statistical analysis was performed. Objective cure was POP-Q < 2nd stage. Subjective cure and functional outcomes were evaluated by validated questionnaires. Patient’s satisfaction was assessed by a Likert-type scale. Mean operative time was 64 min. At a mean follow-up of 82.4 months, objective and subjective success rates were 89.8% and 92.2% respectively. De novo urgency was 3.2%. Surgery did not alter sexual function. Complications occurred in 4.8%, and were: wrong dissection plane, hematoma, and pain lasting between 24–72 h. BPCP for correction of cystocele is safe and effective, with limited risk of complication and good long-term results.
Immunosuppressive Therapy and Risk of COVID-19 Infection in Patients With Inflammatory Bowel Diseases

Abstract Background The effect of immunosuppressive treatment for immune-mediated diseases on risk of the novel coronavirus disease 2019 (COVID-19) has not been established. We aimed to define the effect of targeted biologic and immunomodulator therapy on risk of COVID-19 in a multi-institutional cohort of patients with inflammatory bowel disease (IBD). Methods We identified patients 18 years and older who received care for IBD at Partners Healthcare between January 2019 and April 2020. The primary outcome was development of COVID-19 defined as a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. Multivariable regression models were used to examine the effect of immunosuppression on risk of COVID-19 and its outcomes. Results In a cohort of 5302 IBD patients, 39 (0.7%) developed COVID-19. There was no difference in age, sex, or race between IBD patients with and without COVID-19. The rate of COVID-19 was similar between patients treated with immunosuppression (0.8%) compared with those who were not (0.64%; P = 0.55). After adjusting for age, sex, race, and comorbidities, use of immunosuppressive therapy was not associated with an increased risk of COVID-19 (odds ratio, 1.73; 95% confidence interval, 0.82–3.63). The presence of obesity was associated with a higher risk of COVID-19 (odds ratio, 8.29; 95% confidence interval, 3.72–18.47). There were 7 hospitalizations, 3 intensive care unit stays, and 1 death. Older age and obesity but not immunosuppressive treatment were associated with severe COVID-19 infection. Conclusions The use of systemic immunosuppression was not associated with an increased risk of COVID-19 in a multi-institutional cohort of patients with IBD.
Contribution of DNA barcoding to the study of the bees (Hymenoptera: Apoidea) of Canada: progress to date

Abstract Bees (Hymenoptera: Apoidea, Apiformes) are taxonomically and ecologically diverse, with a wide range of social complexity, nesting preferences, floral associations, and biogeographic restrictions. A Canadian bee checklist, greatly assisted by the gene-assisted approach of DNA barcoding, is nearing completion. Previous evaluation of bee diversity in Canada, assisted by DNA barcoding, was restricted to Nova Scotia, which contains about 25% of the bee species in the country. Here, we summarise efforts to date to build a comprehensive DNA barcode library supporting bee taxonomic studies in Canada, consisting of more than 12 500 barcode-compliant sequences yielding 811 distinct barcode index numbers (BINs). This appears to represent ~95% of the 856 bee species presently recorded from Canada, but comparison with known morphological species in each genus shows that some genera are still under-sampled or may contain cryptic taxa, with much taxonomic work still to be done on bees in Canada. This is particularly true within the taxonomically difficult genera Andrena Fabricius (Andrenidae), Hylaeus Fabricius (Colletidae), Melissodes Latreille (Apidae), Nomada Scopoli (Apidae), Osmia Panzer (Megachilidae), and Sphecodes Latreille (Halictidae). DNA analysis will likely be a key asset in resolving bee taxonomic issues in Canada in the future, and to date has even assisted studies of well-known bee taxa. Here we present summaries of our results, and discuss the use of DNA barcoding to assist future taxonomic work, faunal lists, and ecological studies.
CAR‐T therapy in solid organ transplant recipients with treatment refractory posttransplant lymphoproliferative disorder

Chimeric antigen receptor T cells (CAR‐T) are genetically modified T cells with a chimeric antigen receptor directed against a specific tumor‐associated antigen like CD19 in lymphoma. CAR‐T cells have shown encouraging activity against recurrent and refractory diffuse large B cell lymphomas (DLBCL). However concurrent use of immunosuppressive agents was prohibited in most CAR‐T trials effectively excluding patients with prior solid organ transplantation (SOT) and posttransplant lymphoproliferative disorders (PTLD). We report the outcomes for three patients with PTLD refractory to immunochemotherapy 10‐20 years after SOT who received CAR‐T therapy between January 2018 and December 2019. One patient had an orthotopic heart transplant, the second had a deceased donor kidney transplant, and the third had a pancreas after kidney transplant (PAK). All patients developed complications of CAR‐T therapy such as cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, and acute kidney injury requiring renal replacement therapy in the two out of three patients. All patients expired after withdrawal of care due to lack of response to CAR‐T therapy. In addition, the PAK patient developed acute pancreatitis after CAR‐T therapy. This case series identifies the challenges of using CAR‐T therapy to manage refractory PTLD in SOT recipients and its possible complications.
Epiphytic bacteria on lettuce affect the feeding behavior of an invasive pest slug

Plant–animal interactions are not isolated pairwise relationships but are always accompanied by diverse assemblages of microbes. Additional to direct effects of microorganisms on their hosts, recent investigations demonstrated that bacteria associated with plants can modify the behavior of organisms of higher trophic levels. However, in the context of herbivory, functions of non-phytopathogenic bacteria colonizing leaf surfaces remain understudied. This study showed that naturally occurring epiphytic bacteria affect the feeding behavior of a generalist herbivore. Epiphytic bacteria isolated from leaves of Lactuca sativa var. capitata were screened for their potential to influence feeding choices of the slug Arion vulgaris . Cultivated bacteria were inoculated in artificial food substrates or on sterile leaves of gnotobiotic lettuce plants and were offered to slugs in different behavioral bioassays. A large proportion of bacterial strains tested induced behavioral alterations in the feeding choices of slugs. Behavioral responses of slugs were further modified by antibiotic treatment of slugs prior to choice tests indicating that both bacteria associated with plants and animals affect plant–animal interactions. Our results emphasize the important role of bacteria in plant–animal interactions and suggest a prominent role of bacteria in herbivory in natural, horticultural, and agricultural systems.
Hearing care and management priority among parents of children with Down syndrome: a grounded theory

Abstract Objective This study qualitatively explored the factors that influence how parents of children who are Deaf or hard-of-hearing with Down syndrome prioritise hearing care and management and developed an associated theory to explain that priority. Design Grounded theory was used for the purposes of this qualitative study. Data were collected using in-depth interviews which were analysed using a three-tiered qualitative coding process. Study Sample Eighteen mothers of children who are Deaf or hard-of-hearing with Down syndrome participated in this study. Results The higher the extent of engaged professional support, perception of benefit for child, parent activation, and family engagement, the higher the priority for hearing care and management will likely be among parents of children who are Deaf or hard-of-hearing with Down syndrome. Conclusions Understanding how parents of children who are Deaf or hard-of-hearing with Down syndrome decide to prioritise hearing care and management has implications for how hearing health providers and others provide care to parents to enhance priority for hearing-related needs.
Two new species in Fuscosporellaceae from freshwater habitats in Thailand

A survey of freshwater fungi in Thailand resulted in the discovery of two new species in Fuscosporellaceae, herein described as Fuscosporella aquatica and Mucispora phangngaensis. Fuscosporella aquatica has sporodochial colonies, irregular ellipsoidal and dark brown conidia with vesicular conidiogenous cells. Mucispora phangngaensis has macronematous, solitary conidiophores with percurrent proliferations and dark brown obovoid conidia. Phylogenetic analysis based on combined LSU and ITS sequence data support their placement in Fuscosporella and Mucispora (Fuscosporellaceae, Fuscosporellales). Both species formed distinct clades from their type species and present as the second species in each genus. Descriptions and illustrations of the new taxa are provided. DNA sequence data of Parafuscosporella mucosa (from ex-type strain) are provided in this study, and confirmed its phylogenetic placement.
Synthesis, Structure, and Function of Human Adenovirus Small Non-Coding RNAs

Human adenoviruses (HAdVs) are common pathogens causing a variety of respiratory, ocular and gastrointestinal diseases. To accomplish their efficient replication, HAdVs take an advantage of viral small non-coding RNAs (sncRNAs), which have multiple roles during the virus lifecycle. Three of the best-characterized HAdV sncRNAs; VA RNA, mivaRNA and MLP-TSS-sRNA will be discussed in the present review. Even though VA RNA has been extensively characterized during the last 60 years, this multifunctional molecule continues to surprise us as more of its structural secrets unfold. Likely, the recent developments on mivaRNA and MLP-TSS-sRNA synthesis and function highlight the importance of these sncRNA in virus replication. Collectively, we will summarize the old and new knowledge about these three viral sncRNAs with focus on their synthesis, structure and functions.
Decreased Cerebrospinal Fluid Orexin-A (Hypocretin-1) Concentrations in Patients after Generalized Convulsive Status Epilepticus

The effects of status epilepticus on the orexin/hypocretin system have yet to be investigated. The present study aimed to assay orexin-A/hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized convulsive status epilepticus (GCSE). The study groups included 20 GCSE patients, 24 patients diagnosed with epilepsy but remaining in remission (ER), and 25 normal controls (CTR). Diagnostic lumbar puncture was performed in GCSE patients within 3–10 days of seizure cessation, as well as in the ER and to CTR subjects. Among all GCSE patients, the outcome was graded according to the modified Rankin Scale (mRS) at 1-month follow-up. Orexin-A levels were measured in unextracted CSF samples, using a commercial radioimmunoassay. There was a significant overall difference in median CSF orexin-A concentrations between GCSE, RE, and CTR patients (p < 0.001). The lowest concentrations were noted in the GCSE group compared to ER (p < 0.001) or CTR (p < 0.001). CSF orexin-A levels in GCSE patients inversely correlated with clinical outcome as assessed on the mRS at 1-month follow-up (r = −0.55; p = 0.1). In conclusion, CSF orexin-A levels may serve as a biomarker of increased turn-over of the peptide or post-SE neuronal damage, and implicates the orexin system in the pathogenesis of SE.