Miracle-dz/UniFAR-FTUs huggingface dataset:
ABVD followed by BV consolidation in risk-stratified patients with limited-stage Hodgkin lymphoma.

Approximately 90% of limited-stage Hodgkin lymphoma (HL) patients are projected to be cured with standard therapy, but many do not live their expected life span because of late treatment-related complications. New treatment paradigms are needed to reduce the use of radiation therapy (RT) as well as conventional chemotherapy drugs while improving upon current standard-of-care survival outcomes. In this phase 2 multicenter study, patients with non-bulky limited-stage HL received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by brentuximab vedotin (BV) consolidation. Forty-one patients were enrolled, and patient characteristics included median age of 29 years (range, 19 to 67 years), 58% were female, 45% had unfavorable disease, and 98% had stage II disease. Based on positron emission tomography (PET)-based risk stratification, patients received 2 to 6 cycles of ABVD followed by 6 cycles of BV. After ABVD followed by BV, 95% of evaluable patients (37 out of 39; 95% confidence interval [CI], 83%-99%) achieved PET-negative status. In the intent-to-treat patient population, the estimated 3-year progression-free survival (PFS) rate was 92%, and the overall survival (OS) rate was 97%, with a median follow-up of 47 months. All 37 patients who achieved negative PET status after BV consolidation effectively avoided RT and remain in remission with estimated 3-year PFS and OS rates of 100%. In conclusion, BV demonstrates encouraging clinical activity when it follows ABVD therapy in limited-stage HL. Early incorporation of BV may reduce the use of RT as well as conventional chemotherapy drugs while achieving favorable survival outcomes in risk-stratified patients with non-bulky limited-stage HL. This trial was registered at www.clinicaltrials. gov as #NCT01578967.
Additively Manufactured Continuous Cell-Size Gradient Porous Scaffolds: Pore Characteristics, Mechanical Properties and Biological Responses In Vitro

Porous scaffolds with graded open porosity combining a morphology similar to that of bone with mechanical and biological properties are becoming an attractive candidate for bone grafts. In this work, scaffolds with a continuous cell-size gradient were studied from the aspects of pore properties, mechanical properties and bio-functional properties. Using a mathematical method named triply periodic minimal surfaces (TPMS), uniform and graded scaffolds with Gyroid and Diamond units were manufactured by selective laser melting (SLM) with Ti-6Al-4V, followed by micro-computer tomography (CT) reconstruction, mechanical testing and in vitro evaluation. It was found that gradient scaffolds were preferably replicated by SLM with continuous graded changes in surface area and pore size, but their pore size should be designed to be ≥ 450 μm to ensure good interconnectivity. Both the Gyroid and Diamond structures have superior strength compared to cancellous bones, and their elastic modulus is comparable to the bones. In comparison, Gyroid exhibits better performances than Diamond in terms of the elastic modulus, ultimate strength and ductility. In vitro cell culture experiments show that the gradients provide an ideal growth environment for osteoblast growth in which cells survive well and distribute uniformly due to biocompatibility of the Ti-6Al-4V material, interconnectivity and suitable pore size.
The High-Fat Diet Based on Extra-Virgin Olive Oil Causes Dysbiosis Linked to Colorectal Cancer Prevention

The present study aims to examine the effects of three different high-fat diet (HFD) on mice gut microbiota in order to analyse whether they create the microenvironmental conditions that either promote or prevent colorectal cancer (CRC). We evaluated colonic mucosa-associated microbiota in CD1 mice fed with HFD, based on 60% kcal from fat-containing coconut, sunflower or extra-virgin olive oil as the only source of fat. The main findings were as follows: (a) All HFD produced a decrease in the richness and diversity of the intestinal microbiota that was independent of mouse weight, (b) HFD switched Lactobacillus to Lactococcus. In general, the results showed that both sunflower- and coconut-HFD generated a pro-inflammatory intestinal microenvironment. In brief, coconut-HFD decreased Akkermansia and increased Staphylococcus, Prevotella and Bacteroides spp. abundance. Sunflower-HFD reduced Akkermansia and Bifidobacterium, while enhancing Sphingomonas and Neisseria spp. abundance. In contrast, EVOO-HFD produced an anti-inflammatory microenvironment characterised by a decreased Enterococcus, Staphylococcus, Neisseria and Pseudomonas spp. abundance. At the same time, it increased the Firmicutes/Bacteroidetes ratio and maintained the Akkermansia population. To conclude, EVOO-HFD produced changes in the gut microbiota that are associated with the prevention of CRC, while coconut and sunflower-HFD caused changes associated with an increased risk of CRC.
In vitro activity of sulbactam/durlobactam against global isolates of carbapenem-resistant Acinetobacter baumannii.

OBJECTIVES To evaluate the activity of the novel broad-spectrum serine β-lactamase inhibitor durlobactam (ETX2514) combined with sulbactam against global isolates of carbapenem-resistant Acinetobacter baumannii with defined carbapenem resistance mechanisms compared with reference antimicrobials with known activity against Acinetobacter spp. METHODS The susceptibility of 246 carbapenem-resistant non-duplicate A. baumannii isolates to sulbactam/durlobactam, amikacin, colistin, imipenem/sulbactam/durlobactam, imipenem, meropenem, minocycline and sulbactam was tested using broth microdilution. Isolates were obtained from various body sites from patients in 37 countries and from six world regions between 2012 and 2016. Identification of carbapenem resistance mechanisms and assignment to A. baumannii clonal lineages was based on WGS. RESULTS Sulbactam/durlobactam showed excellent activity comparable to colistin but superior to amikacin, minocycline and sulbactam. The sulbactam/durlobactam MIC50/90 values were 1/4 and 2/4 mg/L and the colistin MIC50/90 values were 0.5 and 1 mg/L, respectively. Comparatively, amikacin, minocycline and sulbactam MIC50/90 values were 256/≥512, 2/16 and 16/64 mg/L, respectively. CONCLUSIONS Sulbactam/durlobactam had excellent in vitro potency against A. baumannii isolates, including those that were resistant to imipenem/meropenem, amikacin, minocycline and colistin, compared with other compounds. Sulbactam/durlobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen.
Low levels of AMPK promote epithelial‐mesenchymal transition in lung cancer primarily through HDAC4‐ and HDAC5‐mediated metabolic reprogramming

AMP‐activated protein kinase (AMPK) serves as a “supermetabolic regulator” that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non–small‐cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up‐regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK‐induced metabolism can promote epithelial‐mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.
Laboratory evaluation of a new strain CCM 8367 of Isaria fumosorosea (syn. Paecilomyces fumosoroseus) on Spodoptera littoralis (Boisd.)

Laboratory experiments were conducted to assess the efficiency of the new strain CCM 8367 of Isaria fumosorosea on different stages of the Egyptian cotton leafworm, Spodoptera littoralis (Boisd.), including soil treatments with pre-pupal and pupal stages. Treatments of larval instars showed a high susceptibility with 3rd, 5th and last instars to suspension of this fungus with concentration 5 × 107 spores/ml. Larval mortality was over 90%. There were no significant differences (P = 0.7929, F = 0.2346) between instar treatments. The commercial fungus, PreFeRal® strain Apopka 97 of I. fumosorosea, which was used in comparison with this new strain caused mortality rates of between 63.33 and 90%. Statistically, differences between the effects of CCM 8367 strain and Apopka 97 were highly significant on the last instar (P = 0.0064, F = 6.479) and extremely significant on the 3rd instar (P < 0.0001, F = 13.29). No significant differences were recorded between the two strains on the 5th instar (P = 0.0597, F = 3.233). Fungal treatments with the late stage insects (end of the last instar or pupal stage) in soil yielded interesting results: the mortality rate on end of final instar larvae was 16.66% when treated with Apopka 97 and 83.33% when treated with CCM 8367. Soil containing pupae of S. littoralis that were inoculated with CCM8367 resulted in a high number of malformed adults, and the mortality rate was 64.52% (32.27% of malformed adults died and 32.25% of pupae fully infected by fungus). Only 3.23% of samples produced morphologically normal adults in this test. The results conclude that the strain of I. fumosorosea CCM 8367 has strong insecticidal effects on S. littoralis and has the potential to be implemented as a novel biocontrol agent.
Stabilization of extensive fine-scale diversity by ecologically driven spatiotemporal chaos

Significance The diversity of living organisms is a fundamental feature of biology, yet still challenging to understand. Genomic data reveal that many closely related strains of bacteria can coexist for far longer than expected from “survival of the fittest. ” To explain this, is it necessary to assume a multitude of specialist niches, or are other mechanisms possible? We investigate, from simple but general models, an alternate scenario: coexistence of a large number of closely related strains in a chaotic state driven by ecological interactions. The chaos is characterized by local blooms and busts that are out of sync at different spatial locations. A natural example is multiple nonspecialist strains of a pathogen species infecting multiple strains of a host species. It has recently become apparent that the diversity of microbial life extends far below the species level to the finest scales of genetic differences. Remarkably, extensive fine-scale diversity can coexist spatially. How is this diversity stable on long timescales, despite selective or ecological differences and other evolutionary processes? Most work has focused on stable coexistence or assumed ecological neutrality. We present an alternative: extensive diversity maintained by ecologically driven spatiotemporal chaos, with no assumptions about niches or other specialist differences between strains. We study generalized Lotka–Volterra models with antisymmetric correlations in the interactions inspired by multiple pathogen strains infecting multiple host strains. Generally, these exhibit chaos with increasingly wild population fluctuations driving extinctions. But the simplest spatial structure, many identical islands with migration between them, stabilizes a diverse chaotic state. Some strains (subspecies) go globally extinct, but many persist for times exponentially long in the number of islands. All persistent strains have episodic local blooms to high abundance, crucial for their persistence as, for many, their average population growth rate is negative. Snapshots of the abundance distribution show a power law at intermediate abundances that is essentially indistinguishable from the neutral theory of ecology. But the dynamics of the large populations are much faster than birth–death fluctuations. We argue that this spatiotemporally chaotic “phase” should exist in a wide range of models, and that even in rapidly mixed systems, longer-lived spores could similarly stabilize a diverse chaotic phase.
A Glycosaminoglycan-Rich Fraction from Sea Cucumber Isostichopus badionotus Has Potent Anti-Inflammatory Properties In Vitro and In Vivo

Sea cucumber body wall contains several naturally occurring bioactive components that possess health-promoting properties. Isostichopus badionotus from Yucatan, Mexico is heavily fished, but little is known about its bioactive constituents. We previously established that I. badionotus meal had potent anti-inflammatory properties in vivo. We have now screened some of its constituents for anti-inflammatory activity in vitro. Glycosaminoglycan and soluble protein preparations reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory responses in HaCaT cells while an ethanol extract had a limited effect. The primary glycosaminoglycan (fucosylated chondroitin sulfate; FCS) was purified and tested for anti-inflammatory activity in vivo. FCS modulated the expression of critical genes, including NF-ĸB, TNFα, iNOS, and COX-2, and attenuated inflammation and tissue damage caused by TPA in a mouse ear inflammation model. It also mitigated colonic colitis caused in mice by dextran sodium sulfate. FCS from I. badionotus of the Yucatan Peninsula thus had strong anti-inflammatory properties in vivo.
Iota-carrageenan Oligosaccharides as Model Compounds for Structural Analysis of Iota-carrageenan by 13C-NMR Spectroscopy

C-NMR spectroscopy is a powerful tool for structural analysis of carrageenans, but the assignments for some of the carbon atoms in the repeating disaccharide have not been determined conclusively. lota-neocarratetraose sulfate and iota-neocarrahexaose sulfate, generated by enzymatic hydrolysis of iota-carrageenan, provided model compounds for determining the correct assignments of carbons in the repeat unit of the parent polymer. A comparison of integrated values of resonance peaks in the C-NMR spectra was used to assign peaks to carbons of the repeat units at the non-reducing and reducing extremities and the internal repeat uni t of the iota-oligosaccharides. The correct assignments for C-2 of 3-O-ß-D-galactopyranosyl-4-sulfate and C-6 of 4-O-3,6-anhydro-a-D-galactopyranosyl-2-sulfate were obtained using a specialized NMR technique (distortionless enhancement by polarization transfer).
Depression, Anxiety and Stress during COVID-19: Associations with Changes in Physical Activity, Sleep, Tobacco and Alcohol Use in Australian Adults

The novel coronavirus (COVID-19) has enforced dramatic changes to daily living including economic and health impacts. Evidence for the impact of these changes on our physical and mental health and health behaviors is limited. We examined the associations between psychological distress and changes in selected health behaviors since the onset of COVID-19 in Australia. An online survey was distributed in April 2020 and included measures of depression, anxiety, stress, physical activity, sleep, alcohol intake and cigarette smoking. The survey was completed by 1491 adults (mean age 50.5 ± 14.9 years, 67% female). Negative change was reported for physical activity (48.9%), sleep (40.7%), alcohol (26.6%) and smoking (6.9%) since the onset of the COVID-19 pandemic. Significantly higher scores in one or more psychological distress states were found for females, and those not in a relationship, in the lowest income category, aged 18–45 years, or with a chronic illness. Negative changes in physical activity, sleep, smoking and alcohol intake were associated with higher depression, anxiety and stress symptoms. Health-promotion strategies directed at adopting or maintaining positive health-related behaviors should be utilized to address increases in psychological distress during the pandemic. Ongoing evaluation of the impact of lifestyle changes associated with the pandemic is needed.
Irrelevant Predictions: Distractor Rhythmicity Modulates Neural Encoding in Auditory Cortex

Dynamic Attending Theory suggests that predicting the timing of upcoming sounds can assist in focusing attention towards them. However, whether similar predictive processes are also applied to background noises and assist in guiding attention away from potential distractors, remains an open question. Here we address this question by manipulating the temporal predictability of distractor sounds in a dichotic listening selective attention task. We tested the influence of distractors’ temporal predictability on performance and on the neural encoding of sounds, by comparing the effects of Rhythmic vs. Non-rhythmic distractors. Using Magnetoencephalography (MEG) we found that, indeed, the neural responses to both attended and distractor sounds were affected by distractors’ rhythmicity. Baseline activity preceding the onset of Rhythmic distractor sounds was enhanced relative to Non-rhythmic distractor sounds, and sensory response were suppressed. Moreover, when distractors were Rhythmic, responses to attended sounds were more strongly lateralized to the contra-lateral hemisphere. Behavioral performance also improved in the Rhythmic condition. These combined behavioral and neural results suggest that not only are temporal predictions formed for task-irrelevant sounds, but that these predictions bear functional significance for promoting selective attention and reducing distractibility.
Anti‐A isohaemagglutinin titres and SARS‐CoV‐2 neutralization: implications for children and convalescent plasma selection

I read with interest the recent article by Li et al (1) detailing the risk for COVID-19 pneumonia and ABO blood group. After demonstration that group O healthcare workers were less likely to become infected with SARS-CoV (2), a research group proved that anti-A blood group natural isoagglutinins inhibit SARS-CoV entry into competent cells (3) and could opsonize viral particles leading to complement-mediated neutralization (4). Since SARS-CoV2 uses the same receptor as SARS-CoV, anti-A isoagglutinins are expected to have similar effects against SARS-CoV2: accordingly, clusters of glycosylation sites exist proximal to the receptor-binding motif of the SARS-CoV and SARS-CoV2 S protein (5).
Efficacy and acceptability of a pilot dietary intervention focusing on self-compassion, goal-setting and self-monitoring

Abstract Objective: Overweight and obesity are universal health challenges. Recent evidence emphasises the potential benefits of addressing psychological factors associated with obesity in dietary programmes. This pilot study investigated the efficacy and acceptability of a combined online and face-to-face dietary intervention that used self-compassion, goal-setting and self-monitoring to improve dietary behaviour, as well as psychological factors associated with dietary behaviour. Design: Embedded mixed methods including a 4-week before-after trial and a one-on-one interview. Quantitative outcomes of the study were the levels of self-compassion; eating pathology; depression, anxiety and stress; and dietary intake. Qualitative outcomes were participants’ perceptions about the acceptability of the intervention. Setting: UNSW Kensington campus. Participants: Fourteen participants with overweight and obesity aged between 18 and 55 years old. Results: Results showed that the intervention significantly improved self-compassion and some aspects of dietary intake (e.g. decrease in energy intake) at Week Four compared with Week Zero. Some aspects of eating pathology also significantly decreased (e.g. Eating Concern). However, changes in self-compassion over the 4 weeks did not significantly predict Week Four study outcomes, except for level of stress. Most participants found self-compassion, goal-setting and self-monitoring to be essential for dietary behaviour change. However, participants also indicated that an online programme needed to be efficient, simple and interactive. Conclusions: In conclusion, the current study provides preliminary but promising findings of an effective and acceptable combined online and face-to-face intervention that used self-compassion, goal-setting and self-monitoring to improve dietary habits. However, the results need to be examined in future long-term randomised controlled trials.
Metabolic signatures associated with Western and Prudent dietary patterns in women.

BACKGROUND The Western dietary pattern (WD) is positively associated with risk of coronary artery disease (CAD) and cancer, whereas the Prudent dietary pattern (PD) may be protective. Foods may influence metabolite concentrations as well as oxidative stress and lipid dysregulation, biological mechanisms associated with CAD and cancer. OBJECTIVE The aim was to assess the association of 2 derived dietary pattern scores with serum metabolites and identify metabolic pathways associated with the metabolites. METHODS We evaluated the cross-sectional association between each dietary pattern (WD, PD) and metabolites in 2199 Women's Health Initiative (WHI) participants. With FFQ and factor analysis, we determined 2 dietary patterns consistent with WD and PD. Metabolites were measured with LC-tandem MS. Metabolite discovery among 904 WHI Observational Study (WHI-OS) participants was replicated among 1295 WHI Hormone Therapy Trial (WHI-HT) participants. We analyzed each of 495 metabolites with each dietary score (WD, PD) in linear regression models. RESULTS The PD included higher vegetables and fruit intake compared with the WD with higher saturated fat and meat intake. Independent of energy intake, BMI, physical activity, and other confounding variables, 45 overlapping metabolites were identified (WHI-OS) and replicated (WHI-HT) with an opposite direction of associations for the WD compared with the PD [false discovery rate (FDR) P < 0.05]. In metabolite set enrichment analyses, phosphatidylethanolamine (PE) plasmalogens were positively enriched for association with WD [normalized enrichment score (NES) = 2.01, P = 0.001, FDR P = 0.005], and cholesteryl esters (NES = -1.77, P = 0.005, FDR P = 0.02), and phosphatidylcholines (NES = -1.72, P = 0.01, P = 0.03) were negatively enriched for WD. PE plasmalogens were positively correlated with saturated fat and red meat. Phosphatidylcholines and cholesteryl esters were positively correlated with fatty fish. CONCLUSIONS Distinct metabolite signatures associated with Western and Prudent dietary patterns highlight the positive association of mitochondrial oxidative stress and lipid dysregulation with a WD and the inverse association with a PD.