Miracle-dz/UniFAR-FTUs huggingface dataset:
Spontaneous Construction of Nucleophilic Carbonyl‐Containing Interphase toward Ultrastable Zinc‐Metal Anodes

Multifunctional interfacial engineering on the Zn anode to conquer dendrite growth, hydrogen evolution, and the sluggish kinetics associated with Zn deposition is highly desirable for boosting the commercialization of aqueous zinc‐ion batteries. Herein, a spontaneous construction of carbonyl‐containing layer on a Zn anode (Zn@ZCO) is rationally designed as an ion redistributor and functional protective interphase. It has strong zincphilicity and dendrite suppression ability due to the significant interaction of the highly electronegative and highly nucleophilic carbonyl oxygen, favoring ion transport and homogenizing Zn deposition effectively. On the other side, the hydrogen bond formed by the proton acceptor of oxygen atom in ZCO regulates the Zn‐ion desolvation process at the interfaces, thus bounding water activity and then mitigating water‐induced parasitic reactions. Consequently, the Zn@ZCO anode exhibits an extended cycling lifespan of 5000 h (>208 days) with a dendrite‐free surface and negligible by‐products. More encouragingly, the effectiveness is also convincing in NH4V4O10‐based full‐cells with excellent rate performance and cyclic stability. The stabilized Zn anode enabled by the strategy of spontaneous construction of functional solid electrolyte interphase brings forward a facile and instructive approach toward high‐performance zinc‐storage systems.
Redefining the Koizumi model of mouse cerebral ischemia: A comparative longitudinal study of cerebral and retinal ischemia in the Koizumi and Longa middle cerebral artery occlusion models

Cerebral and retinal ischemia share similar pathogenesis and epidemiology, each carrying both acute and prolonged risk of the other and often co-occurring. The most used preclinical stroke models, the Koizumi and Longa middle cerebral artery occlusion (MCAO) methods, have reported retinal damage with great variability, leaving the disruption of retinal blood supply via MCAO poorly investigated, even providing conflicting assumptions on the origin of the ophthalmic artery in rodents. The aim of our study was to use longitudinal in vivo magnetic resonance assessment of cerebral and retinal vascular perfusion after the ischemic injury to clarify whether and how the Koizumi and Longa methods induce retinal ischemia and how they differ in terms of cerebral and retinal lesion evolution. We provided anatomical evidence of the origin of the ophthalmic artery in mice from the pterygopalatine artery. Following the Koizumi surgery, retinal responses to ischemia overlapped with those in the brain, resulting in permanent damage. In contrast, the Longa method produced only extensive cerebral lesions, with greater tissue loss than in the Koizumi method. Additionally, our data suggests the Koizumi method should be redefined as a model of ischemia with chronic hypoperfusion rather than of ischemia and reperfusion.
Protein corona: challenges and opportunities for targeted delivery of nanomedicines

ABSTRACT Introduction Targeted drug delivery has been widely explored as a promising way to improve the performance of nanomedicines. However, protein corona formed on the nano-surface represents a major issue that has great impacts on the in vivo fate of targeting nanomedicines, which has been overlooked in the past. With the increasing understanding of protein corona in the recent decade, many efforts have been made to improve targeting efficacy. Areas covered In this review, we briefly summarize insights of targeted delivery systems inspired by protein corona, and discuss the promising strategies to regulate protein corona for better targeting. Expert opinion The interaction between nanomedicines and endogenous proteins brings great uncertainty and challenges, but it also provides great opportunities for the development of targeting nanomedicines at the same time. With increasing understanding of protein corona, the strategies to regulate protein corona pave new avenues for the development of targeting nanomedicines.
Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia

Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long‐bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3). Genetic studies by whole genome, whole exome, and ciliome panel sequencing identified in all affected individuals biallelic missense variants in KIF24, which encodes a kinesin family member controlling ciliogenesis. In families 1 and 3, with the more severe phenotype, the affected subjects harbored homozygous variants (c.1457A>G; p.(Ile486Val) and c.1565A>G; p.(Asn522Ser), respectively) in the motor domain which plays a crucial role in KIF24 function. In family 2, compound heterozygous variants (c.1697C>T; p.(Ser566Phe)/c.1811C>T; p.(Thr604Met)) were found C‐terminal to the motor domain, in agreement with a genotype–phenotype correlation. In vitro experiments performed on amnioblasts of one affected fetus from family 3 showed that primary cilia assembly was severely impaired, and that cytokinesis was also affected. In conclusion, our study describes novel forms of skeletal dysplasia associated with biallelic variants in KIF24. To our knowledge this is the first report implicating KIF24 variants as the cause of a skeletal dysplasia, thereby extending the genetic heterogeneity and the phenotypic spectrum of rare bone disorders and underscoring the wide range of monogenetic skeletal ciliopathies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Running Head: PERCEPTION OF ACTION CAPABILITIES IN PARKINSON’S 1 How far can I reach? The perception of upper body action capabilities in Parkinson’s Disease

Successful interaction within the environment is contingent upon one’s ability to accurately perceive the extent over which they can successfully perform actions, known as action boundaries. Healthy young adults are accurate in estimating their action boundaries and can flexibly update them to accommodate stable changes in their action capabilities. However, there are conditions in which motor abilities are subject to variability over time such as in Parkinson’s disease (PD). PD impairs the ability to perform actions and can lead to variability in perceptual-motor experience, but the effect on the perceptions of their action boundaries remains unknown. This study investigated the influence of altered perceptual-motor experience during PD, on the perceptions of action boundaries for reaching, grasping and aperture passing. Thirty participants with mild-to-moderate idiopathic PD and twenty-six healthy older adults provided estimates of their reaching, grasping and aperture passing ability. Participants’ estimates were compared to their actual capabilities. There was no evidence that individuals with PD’s perceptions were less accurate than healthy controls. Furthermore, there was some evidence for more conservative estimates than seen in young healthy adults in reaching (both groups) and aperture passing (PD group). This suggests that the ability to judge action capabilities is preserved in mild to moderate PD.
Effects of experimental hypovolemia and pain on pre‐ejection period and pulse transit time in healthy volunteers

Trauma patients may suffer significant blood loss, and noninvasive methods to diagnose hypovolemia in these patients are needed. Physiologic effects of hypovolemia, aiming to maintain blood pressure, are largely mediated by increased sympathetic nervous activity. Trauma patients may however experience pain, which also increases sympathetic nervous activity, potentially confounding measures of hypovolemia. Elucidating the common and separate effects of the two stimuli on diagnostic methods is therefore important. Lower body negative pressure (LBNP) and cold pressor test (CPT) are experimental models of central hypovolemia and pain, respectively. In the present analysis, we explored the effects of LBNP and CPT on pre‐ejection period and pulse transit time, aiming to further elucidate the potential use of these variables in diagnosing hypovolemia in trauma patients. We exposed healthy volunteers to four experimental sequences with hypovolemia (LBNP 60 mmHg) or normovolemia (LBNP 0 mmHg) and pain (CPT) or no pain (sham) in a 2 × 2 fashion. We calculated pre‐ejection period and pulse transit time from ECG and ascending aortic blood velocity (suprasternal Doppler) and continuous noninvasive arterial pressure waveform (volume‐clamp method). Fourteen subjects were available for the current analyses. This experimental study found that pre‐ejection period increased with hypovolemia and remained unaltered with pain. Pulse transit time was reduced by pain and increased with hypovolemia. Thus, the direction of change in pulse transit time has the potential to distinguish hypovolemia and pain.
Cognitive control mechanisms in language processing: are there both within- and across-task conflict adaptation effects?

Cognitive conflict is regarded as a crucial factor in triggering subsequent adjustments in cognitive control. Recent studies have suggested that the implementation of control following conflict detection might be domain-general in that conflict experienced in the language domain recruits control processes that deal with conflict experienced in non-linguistic domains. During language comprehension, humans often have to recover from conflicting interpretations as quickly and accurately as possible. In this study, we investigate how people adapt to conflict experienced during processing semantically ambiguous sentences. Experiments 1 to 3 investigated whether such semantic conflict produces the congruency sequence effect (CSE) within a subsequent manual Stroop task and whether Stroop conflict leads to adjustments in semantic processing. Experiments 4 to 6 investigated whether semantic conflict results in conflict adaptation in subsequent sentence processing. Although processing conflict was consistently experienced during sentence reading and in the Stroop task, we did not observe any within-task or cross-task adaptation effects. Specifically, there were no cross-task CSEs from the linguistic task to the Stroop task and vice versa (experiments 1–3)—speaking against the assumption of domain-general control mechanisms. Moreover, experiencing conflict within a semantically ambiguous sentence did not ease the processing of a subsequent ambiguous sentence (experiments 4–6). Implications of these findings will be discussed.
Modeling undetected live type 1 wild poliovirus circulation after apparent interruption of transmission: Pakistan and Afghanistan

Since 2013, wild poliovirus (WPV) transmission occurred only for type 1 (WPV1). Following several years of increasing reported incidence (2017–2019) and programmatic disruptions caused by COVID‐19 (early 2020), Pakistan and Afghanistan performed a large number of supplementary immunization activities (late 2020–2021). This increased intensity of immunization, following widespread transmission, substantially decreased WPV1 cases and positive environmental samples during 2021. Modeling the potential for undetected circulation of WPV1 after apparent interruption can support regional and global decisions about certification of the eradication of indigenous WPV1 transmission. We apply a stochastic model to estimate the confidence about no circulation (CNC) of WPV1 in Pakistan and Afghanistan as a function of time since the last reported case and/or positive environmental sample. Exploration of different assumptions about surveillance quality suggests a range for CNC for WPV1 as a function of time since the last positive surveillance signal, and supports the potential use of a time with no evidence of transmission of less than 3 years as sufficient to assume die out in the context of good acute flaccid paralysis (AFP) surveillance. We show high expected CNC based on AFP surveillance data alone, even with imperfect surveillance and some use of inactivated poliovirus vaccine masking the ability of AFP surveillance to detect transmission. Ensuring high quality AFP and environmental surveillance may substantially shorten the time required to reach high CNC. The time required for high CNC depends on whether immunization activities maintain high population immunity and the quality of surveillance data.
Cognitive profile in mild cognitive impairment with Lewy bodies

Introduction: This study aimed to elucidate the cognitive profile of patients with mild cognitive impairment with Lewy bodies (MCI-LB) and to compare it to that of patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD). Methods: Subjects older than 60 years with probable MCI-LB (n = 60) or MCI-AD (n = 60) were recruited. All patients were tested with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to assess their global cognitive profile. Results: The MCI-AD and MCI-LB patients did not differ in total MMSE and MoCA scores. However, some sub-items in MMSE and MoCA were shown to be screening markers for differentiating MCI-LB from MCI-AD. In the visuoconstructive test, the total score and hands subitem score in the clock-drawing test were significantly lower in MCI-LB than in MCI-AD. As for the executive function, the 'animal fluency test', 'repeat digits backward test' and 'take paper by your right hand' in MMSE all showed lower scores in MCI-LB compared with MCI-AD. As for memory, 'velvet' and 'church' in MoCA and 'ball' and 'national flag' in MMSE had lower scores in MCI-AD than in MCI-LB. Conclusion: This study presents the cognitive profile of patients with MCI-LB. In line with the literature on Dementia with Lewy bodies, our results showed lower performance on tests for visuoconstructive and executive function, whereas memory remained relatively spared in the early period.
Simulation of febuxostat pharmacokinetics in healthy subjects and patients with impaired kidney function using physiologically based pharmacokinetic modeling

Febuxostat is recommended by the American College of Rheumatology Gout Management Guidelines as a first‐line therapy for lowering the level of urate in patients with gout. At present, this drug is being prescribed mainly based on the clinical experience of doctors. The potential effects of clinical and demographic variables on the bioavailability and therapeutic effectiveness of febuxostat are not being considered. In this study a physiologically based pharmacokinetic (PBPK) model of febuxostat was developed, thereby providing a theoretical basis for the individualized dosing of this drug in gout patients. The plasma concentration–time profiles corresponding to healthy subjects and gout patients with normal kidney function were simulated and validated; then, the model was used to predict the pharmacokinetic (PK) data of the drug in gout patients suffering from varying degrees of impaired kidney function. The error values (the predicted value/observed value) were used to validate the simulated PK parameters predicted by the PBPK model, including the area under the plasma concentration–time curve, the maximum plasma concentration, and time to maximum plasma concentration. Considering that to all error fold changes were smaller than 2, the PBPK model was. In subjects suffering from mild kidney impairment, moderate kidney impairment, severe kidney impairment, and endstage kidney disease (ESRD), the predicted AUC0‐24h values increased by 1.62, 1.74, 2.27, and 2.65‐fold, respectively, compared to gout patients with normal kidney function. Overall, the results showed that the PBPK model constructed in this study predict the pharmacokinetic changes in gout patients suffering from varying degrees of impaired kidney function.
LsNRL4 enhances photosynthesis and decreases leaf angles in lettuce

Summary Lettuce (Lactuca sativa) is one of the most important vegetables worldwide and an ideal plant for producing protein drugs. Both well‐functioning chloroplasts that perform robust photosynthesis and small leaf angles that enable dense planting are essential for high yields. In this study, we used an F2 population derived from a cross between a lettuce cultivar with pale‐green leaves and large leaf angles to a cultivar with dark‐green leaves and small leaf angles to clone LsNRL4, which encodes an NPH3/RPT2‐Like (NRL) protein. Unlike other NRL proteins in lettuce, the LsNRL4 lacks the BTB domain. Knockout mutants engineered using CRISPR/Cas9 and transgenic lines overexpressing LsNRL4 verified that LsNRL4 contributes to chloroplast development, photosynthesis and leaf angle. The LsNRL4 gene was not present in the parent with pale‐green leaves and enlarged leaf angles. Loss of LsNRL4 results in the enlargement of chloroplasts, decreases in the amount of cellular space allocated to chloroplasts and defects in secondary cell wall biosynthesis in lamina joints. Overexpressing LsNRL4 significantly improved photosynthesis and decreased leaf angles. Indeed, the plant architecture of the overexpressing lines is ideal for dense planting. In summary, we identified a novel NRL gene that enhances photosynthesis and influences plant architecture. Our study provides new approaches for the breeding of lettuce that can be grown in dense planting in the open field or in modern plant factories. LsNRL4 homologues may also be used in other crops to increase photosynthesis and improve plant architecture.
Reimagining Language

Since its inception, the study of language has been a central pillar to Cognitive Science. Despite an "amodal view," where language is thought to "flow into" modalities indiscriminately, speech has always been considered the prototypical form of the linguistic system. However, this view does not hold up to the evidence about language and expressive modalities. While acknowledgment of both the nonvocal modalities and multimodality has grown over the last 40 years in linguistics and psycholinguistics, this has not yet led to a necessary shift in the mainstream linguistic paradigm. Such a shift requires reconfiguring models of language to account for multimodality, and demands a different view on what the linguistic system is and how it works, necessitating a Cognitive Science sensitive to the full richness of human communication.
Changes in laboratory value improvement and mortality rates over the course of the pandemic: an international retrospective cohort study of hospitalised patients infected with SARS-CoV-2

Objective To assess changes in international mortality rates and laboratory recovery rates during hospitalisation for patients hospitalised with SARS-CoV-2 between the first wave (1 March to 30 June 2020) and the second wave (1 July 2020 to 31 January 2021) of the COVID-19 pandemic. Design, setting and participants This is a retrospective cohort study of 83 178 hospitalised patients admitted between 7 days before or 14 days after PCR-confirmed SARS-CoV-2 infection within the Consortium for Clinical Characterization of COVID-19 by Electronic Health Record, an international multihealthcare system collaborative of 288 hospitals in the USA and Europe. The laboratory recovery rates and mortality rates over time were compared between the two waves of the pandemic. Primary and secondary outcome measures The primary outcome was all-cause mortality rate within 28 days after hospitalisation stratified by predicted low, medium and high mortality risk at baseline. The secondary outcome was the average rate of change in laboratory values during the first week of hospitalisation. Results Baseline Charlson Comorbidity Index and laboratory values at admission were not significantly different between the first and second waves. The improvement in laboratory values over time was faster in the second wave compared with the first. The average C reactive protein rate of change was –4.72 mg/dL vs –4.14 mg/dL per day (p=0.05). The mortality rates within each risk category significantly decreased over time, with the most substantial decrease in the high-risk group (42.3% in March–April 2020 vs 30.8% in November 2020 to January 2021, p<0.001) and a moderate decrease in the intermediate-risk group (21.5% in March–April 2020 vs 14.3% in November 2020 to January 2021, p<0.001). Conclusions Admission profiles of patients hospitalised with SARS-CoV-2 infection did not differ greatly between the first and second waves of the pandemic, but there were notable differences in laboratory improvement rates during hospitalisation. Mortality risks among patients with similar risk profiles decreased over the course of the pandemic. The improvement in laboratory values and mortality risk was consistent across multiple countries.
The evolutionary history and mechanistic basis of female ornamentation in a tropical songbird

Ornamentation, such as the showy plumage of birds, is widespread among female vertebrates, yet the evolutionary pressures shaping female ornamentation remain uncertain. In part this is due to a poor understanding of the mechanistic route to ornamentation in females. To address this issue, we evaluated the evolutionary history of ornament expression in a tropical passerine bird, the White‐shouldered Fairywren, whose females, but not males, strongly vary between populations in occurrence of ornamented black‐and‐white plumage. We first use phylogenomic analysis to demonstrate that female ornamentation is derived and that female ornamentation evolves independently of changes in male plumage. We then use exogenous testosterone in a field experiment to induce partial ornamentation in naturally unornamented females. By sequencing the transcriptome of experimentally induced ornamented and natural feathers, we identify genes expressed during ornament production and evaluate the degree to which female ornamentation in this system is associated with elevated testosterone, as is common in males. We reveal that some ornamentation in females is linked to testosterone and that sexes differ in ornament‐linked gene expression. Lastly, using genomic outlier analysis we identify a candidate melanogenesis gene that lies in a region of high genomic divergence among populations that is also differentially expressed in feather follicles of different female plumages. Taken together, these findings are consistent with sex‐specific selection favoring the evolution of female ornaments and demonstrate a key role for testosterone in generating population divergence in female ornamentation through gene regulation. More broadly, our work highlights similarities and differences in how ornamentation evolves in the sexes.