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Infiltrating the Watchtower to gain information about an alien villain, Batman reminisces with the Justice League about their first meeting before he became a hero.

COVID-19 infection is associated with a variety of vascular occlusive morbidities. However, a comprehensive understanding of how this virus can induce vascular complications remains lacking. Here, we show that a peptide fragment of SARS-CoV-2 spike protein, S192 (sequence 192-211), is capable of forming amyloid-like aggregates that can induce agglutination of red blood cells, which was not observed with low- and non-aggregated S192 peptide. We subsequently screened eight amyloid-binding molecules and identified BAM1-EG 6 , a benzothiazole amphiphile, as a promising candidate capable of binding to aggregated S192 and partially inhibiting its agglutination activity. These results provide new insight into a potential molecular mechanism for the capability of spike protein metabolites to contribute to COVID-19-related blood complications and suggest a new therapeutic approach for combating microvascular morbidities in COVID-19 patients.

Among healthcare personnel (HCP), hesitancy has been linked to concerns about adverse effects, a desire to hear the experiences of others, and distrust of the rapid approval process.1,2 Willingness to undergo vaccination appears associated with identity, with differences based on gender, race, and political beliefs.1 For these reasons and others, as of early March, approximately half of HCP were unvaccinated.3 Unvaccinated HCP present a threat to patient safety because they are more likely than vaccinated HCP to expose patients to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). The Centers for Medicare and Medicaid Services (CMS) recently proposed changes to the Hospital Inpatient Quality-Reporting Program that include an important new measure for COVID-19 vaccination coverage among HCP.4 We applaud the CMS for moving quickly to add this measure. Coworkers and patients bear the consequences alongside the unvaccinated individual. [...]improving vaccination coverage is ultimately the responsibility of the healthcare facility.

Strain engineering has played a key role in modern silicon electronics, having been introduced as a mobility booster in the 1990s and commercialized in the early 2000s. Achieving similar advances with two-dimensional (2D) semiconductors in a complementary metal–oxide–semiconductor (CMOS)-compatible manner could improve the industrial viability of 2D material transistors. Here, we show that silicon nitride capping layers can impart strain to monolayer molybdenum disulfide (MoS 2 ) transistors on conventional silicon substrates, improving their performance with a CMOS-compatible approach, at a low thermal budget of 350 °C. Strained back-gated and dual-gated MoS 2 transistors exhibit median increases in on-state current of up to 60% and 45%, respectively. The greatest improvements are found when reducing both transistor channels and contacts from micrometre-scale to 200 nm, reaching saturation currents of 488 µA µm −1 in devices with just 400 nm contact pitch. Simulations show that the performance enhancement is mainly due to tensile strain lowering the contact Schottky barriers, and that further reducing device dimensions, including contacts, could lead to additional increases in strain and performance. The on-current performance of MoS 2 -based transistors can be improved by using silicon nitride capping layers that apply strain to the devices.

MoS 2 nanosheet, a new two-dimensional transition metal dichalcogenides nanomaterial, has attracted significant attentions lately due to many potential promising biomedical applications. Meanwhile, there is also a growing concern on its biocompatibility, with little known on its interactions with various biomolecules such as proteins. In this study, we use all-atom molecular dynamics simulations to investigate the interaction of a MoS 2 nanosheet with Villin Headpiece (HP35), a model protein widely used in protein folding studies. We find that MoS 2 exhibits robust denaturing capability to HP35, with its secondary structures severely destroyed within hundreds of nanosecond simulations. Both aromatic and basic residues are critical for the protein anchoring onto MoS 2 surface, which then triggers the successive protein unfolding process. The main driving force behind the adsorption process is the dispersion interaction between protein and MoS 2 monolayer. Moreover, water molecules at the interface between some key hydrophobic residues (e.g. Trp-64) and MoS 2 surface also help to accelerate the process driven by nanoscale drying, which provides a strong hydrophobic force. These findings might have shed new light on the potential nanotoxicity of MoS 2 to proteins with atomic details, which should be helpful in guiding future biomedical applications of MoS 2 with its nanotoxicity mitigated.

Background This study aimed to evaluate the cost-effectiveness of a breast cancer screening programme that incorporates genetic testing using breast cancer associated single nucleotide polymorphisms (SNPs), against the current biennial mammogram-only screening programme to aid in its implementation into the current programme in Singapore. Methods A Markov model was used to compare the costs and health outcomes of the current screening programme, against a polygenic risk-tailored screening programme, which can advise a long-term screening strategy depending on the individual’s polygenic risk. The model took the perspective of the healthcare system, with a time horizon of 40 years, following women from the age of 35 to 74. Epidemiological and cost data were taken from Asian studies, and an annual discount rate of 3% was used. The model outcome was the incremental cost-effectiveness ratio (ICER), calculated from the difference in costs per quality-adjusted life year (QALY). Scenarios with varying risk thresholds for each polygenic risk group were examined. One-way and probabilistic sensitivity analyses were performed to assess parameter uncertainty. Results The ICER for a polygenic risk-tailored breast cancer screening programme, compared with the current biennial mammogram-only screening programme, was − 3713.80 SGD/QALY, with incremental costs < 0 and incremental effects > 0. The scenario analysis of different polygenic risk cutoffs showed that the ICERs remain negative, with all ICERs falling within the south-east quadrant of the cost-effectiveness plane, indicating that tailored screening is more cost effective than mammogram-only screening, with lower costs and higher QALYs to be gained. This suggests that a polygenic risk-tailored breast cancer screening programme is cost effective, entailing lower cost than the current mammogram-only programme, while causing no additional harm to women. Conclusion Results from this cost-effectiveness analysis show that polygenic risk-tailored screening is cost effective with an ICER of − 3713.80 SGD/QALY. Tailored screening remains cost effective even across varying percentile cutoffs for each risk group. While the results look promising for incorporating polygenic risk into the current breast cancer screening programme, further studies should be conducted to address various limitations.

Aggregates of amyloid-beta (Aβ) peptides are thought to be involved in the development of Alzheimer's disease because they can change synaptic plasticity and induce neuronal cell death by inflammation, oxidative damage, and transmembrane pore formation. Exactly which oligomeric species underlie these cytotoxic effects remains unclear. The work presented here established well-controlled aggregation conditions of Aβ₁₋₄₀ or Aβ₁₋₄₂ peptides over a 20-day period and characterized these preparations with regard to their β-sheet content, degree of fibril formation, relative abundance of various oligomer sizes, and propensity to induce membrane pore formation and cytotoxicity. Using this multivariate data set, a systematic and inherently unbiased partial least squares (PLS) approach showed that for both peptides the abundance of oligomers in the tetramer to 13-mer range contributed positively to both pore formation and cytotoxicity, while monomers, dimers, trimers, and the largest oligomers (>210 kDa) were negatively correlated to both phenomena. Multivariate PLS analysis is ideally suited to handle complex data sets and interdependent variables such as relative oligomer concentrations, making it possible to elucidate structure function relationships in complex mixtures. This approach, therefore, introduces an enabling tool to the field of amyloid research, in which it is often difficult to interpret the activity of individual species within a complex mixture of bioactive species.

Background and Objectives: This study sought to identify predictors for peripartum patients admitted to non-intensive care wards who later upgraded to the Intensive Care Unit (ICU). Materials and Methods: This was a retrospective observational study of patients admitted to the Maternal Fetal Ward between 01/2017 and 12/2022, who later upgraded to the ICU. Upgraded patients were 1:1 propensity score matched with those who remained on the Maternal Fetal Ward (control). The Classification And Regression Tree, a machine learning algorithm, was used to identify significant predictors of ICU upgrade. Multivariable ordinal regression analysis was used to assess the time interval to upgrade. Results: From 1855 peripartum patients, we analyzed 37 control and 34 upgrade patients. Mean maternal age (±Standard Deviation) and gestational age for the group was 29.5 (±5.8) years and 31.5 (±7.5) weeks, respectively. The Median Sequential Organ Failure Assessment Score [Interquartile] at ward admission for the controls was 0 [0–1] versus 2 [0–3.3, p = 0.001] for upgrade patients. The Sequential Organ Failure Assessment score at Maternal Fetal Ward admission was most predictive, followed by the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and lactate dehydrogenase levels. The APACHE II score was also associated with ICU upgrade within 12 h of hospital admission (OR 1.4, 95% CI 1.08–1.91, p = 0.01). Conclusions: Compared to control patients, peripartum patients upgraded to the ICU are associated with higher physiologic scores at Maternal Fetal Ward admission. Until further studies are performed to confirm our observation, clinicians should pay attention to these physiologic scores, since they may be associated with higher-risk patients.

Background We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer’s disease (AD). However, the effects of CA140 on Aβ/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. Methods To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. Results In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aβ/tau fibrillation, Aβ plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10 , a marker of AD-associated reactive astrocytes (RAs), and c1qa , a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100β and cxcl10 , markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia ( cx3cr1 and p2ry12 ) and decreased the mRNA levels of a marker of proliferative region-associated microglia ( gpnmb ) and a marker of lipid-droplet-accumulating microglia ( cln3 ). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. Conclusions Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aβ/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.

Dual language learners (DLLs) are sensitive to teachers’ language influence in early childhood classrooms. In this mixed methods study incorporating 53 teachers from 28 preschools in Northern California, we investigated the characteristics of teachers’ language use in preschools teaching Chinese–English and Spanish–English DLLs. We further examined the links of teachers’ language use to the DLLs’ expressive vocabulary in English and their heritage language (HL), controlling for home language exposure and other confounding variables. Finally, we conducted interviews with teachers to understand how they make meaning of their daily language practices. The sample of children consisted of 190 Chinese–English (N = 125) and Spanish–English (N = 65) DLLs (mean age = 48.3 months; 48% females). The teacher survey showed that most teachers spoke two or more languages and used a mix of English and their HL during their interactions with DLLs. The results of random-intercept models showed that teachers’ language use did not uniquely predict children’s vocabulary, controlling for family-level factors. However, the teachers with more years of teaching DLLs oversaw children with a higher HL vocabulary. The interview data revealed that teachers employ several strategies to communicate with DLLs and support HL maintenance. Our study reveals the multilingual backgrounds of preschool teachers and the rich language strategies they implement in multilingual classrooms. Future directions concerning the quality and development of teachers’ language use are discussed.