Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal muscle single fiber force production declines early in juvenile male mice with chronic kidney disease

Children with chronic kidney disease (CKD) frequently exhibit delayed physical development and reduced physical performance, presumably due to skeletal muscle dysfunction. However, the cellular and molecular basis of skeletal muscle impairment in juvenile CKD remains poorly understood. Cellular (single fiber) and molecular (myosin‐actin interactions and myofilament properties) function was examined ex vivo in slow (soleus) and fast (extensor digitorum longus) contracting muscles of juvenile male (6 weeks old) CKD and control mice. CKD was induced by 0.2% adenine diet for 3 weeks starting at 3 weeks of age. Specific tension (maximal isometric force divided by cross‐sectional area) was reduced in larger myosin heavy chain (MHC) I and IIA fibers and in all IIB fibers in juvenile male mice with CKD due to fewer strongly bound myosin‐actin cross‐bridges. Fiber cross‐sectional area in juvenile CKD mice was unchanged in MHC I and IIB fibers and increased in MHC IIA fibers, compared to controls. CKD slowed cross‐bridge kinetics (slower rate of myosin force production and longer myosin attachment time, ton) in MHC IIA fibers, and accelerated kinetics (shorter ton) in MHC IIB fibers, which may indicate fiber type dependent shifts in contractile velocity in juvenile CKD. Overall, our findings show that single fiber myopathy is an early event during juvenile CKD, manifesting prior to the development of cellular atrophy as reduced force generation due to fewer strongly bound myosin heads. These results warrant clinical translation and call for early interventions to preserve physical function in children with CKD.
Microscale Neuronal Activity Collectively Drives Chaotic and Inflexible Dynamics at the Macroscale in Seizures

Neuronal activity propagates through the network during seizures, engaging brain dynamics at multiple scales. Such propagating events can be described through the avalanches framework, which can relate spatiotemporal activity at the microscale with global network properties. Interestingly, propagating avalanches in healthy networks are indicative of critical dynamics, where the network is organized to a phase transition, which optimizes certain computational properties. Some have hypothesized that the pathologic brain dynamics of epileptic seizures are an emergent property of microscale neuronal networks collectively driving the brain away from criticality. Demonstrating this would provide a unifying mechanism linking microscale spatiotemporal activity with emergent brain dysfunction during seizures. Here, we investigated the effect of drug-induced seizures on critical avalanche dynamics, using in vivo whole-brain two-photon imaging of GCaMP6s larval zebrafish (males and females) at single neuron resolution. We demonstrate that single neuron activity across the whole brain exhibits a loss of critical statistics during seizures, suggesting that microscale activity collectively drives macroscale dynamics away from criticality. We also construct spiking network models at the scale of the larval zebrafish brain, to demonstrate that only densely connected networks can drive brain-wide seizure dynamics away from criticality. Importantly, such dense networks also disrupt the optimal computational capacities of critical networks, leading to chaotic dynamics, impaired network response properties and sticky states, thus helping to explain functional impairments during seizures. This study bridges the gap between microscale neuronal activity and emergent macroscale dynamics and cognitive dysfunction during seizures. SIGNIFICANCE STATEMENT Epileptic seizures are debilitating and impair normal brain function. It is unclear how the coordinated behavior of neurons collectively impairs brain function during seizures. To investigate this we perform fluorescence microscopy in larval zebrafish, which allows for the recording of whole-brain activity at single-neuron resolution. Using techniques from physics, we show that neuronal activity during seizures drives the brain away from criticality, a regime that enables both high and low activity states, into an inflexible regime that drives high activity states. Importantly, this change is caused by more connections in the network, which we show disrupts the ability of the brain to respond appropriately to its environment. Therefore, we identify key neuronal network mechanisms driving seizures and concurrent cognitive dysfunction.
‘I have never bounced back’: resilience and living with dementia

Abstract Objective This work responds to the limited research about resilience when living with dementia and develops a conceptual model to inform service development and healthcare practices for this population. Methods An iterative process of theory building across four phases of activity (scoping review n = 9 studies), stakeholder engagement (n = 7), interviews (n = 11) generated a combined sample of 87 people living with dementia and their carers, including those affected by rare dementias to explore their lived experiences. An existing framework of resilience developed in other populations served as the starting point to analyse and synthesise the findings, inspiring a new conceptual model of resilience unique to the experience of living with dementia. Results The synthesis suggests resilience encompasses the daily struggles of living with a dementia; people are not flourishing, thriving or ‘bouncing back’, but are managing and adapting under pressure and stress. The conceptual model suggests resilience may be achieved through the collective and collaborative role of psychological strengths, practical approaches to adapting to life with dementia, continuing with hobbies, interests and activities, strong relationships with family and friends, peer support and education, participating in community activities and support from healthcare professionals. Most of these themes are not reflected in resilience outcome measures. Conclusions Practitioners adopting a strengths-based approach utilising the conceptual model at the point of diagnosis and post-diagnosis support may help individuals achieve resilience through appropriately tailored services and support. This ‘resilience practice’ could also extend to other degenerative or debilitating chronic conditions a person faces in their life course.
Tuber rugosum, a new species from northeastern North America: Slug mycophagy aides in electron microscopy of ascospores

ABSTRACT Species in the genus Tuber are ascomycetous fungi that produce hypogeous fruiting bodies commonly called truffles. These fungi are ecologically relevant owing to the ectomycorrhizal symbiosis they establish with plants. One of the most speciose lineages within Tuber is the Rufum clade, which is widely distributed throughout Asia, Europe, and North America and is estimated to include more than 43 species. Most species in this clade have spiny spores, and many still have not been formally described. Here, we describe T. rugosum based on multigene phylogenetic analysis and its unique morphological characters. Tuber rugosum (previously designated in literature as Tuber sp. 69) has been collected throughout the Midwest, USA, and Quebec, Canada, and is an ectomycorrhizal symbiont of Quercus trees, as confirmed through morphological and molecular analyses of root tips presented here. We also present a novel method for preparing Tuber ascospores for scanning electron microscope imaging that includes feeding, digestion, and spore excretion by the slug Arion subfuscus. Following this method, spores become free from ascus and other mycelial debris that could obscure morphological traits during their passage through the snail gut while maintaining ornamentation. Finally, we report the fatty acid analysis, a fungicolous species association, and we provide an updated taxonomic key of the Rufum clade.
Forecasting the Aegean Sea hydrodynamics within the POSEIDON-II operational system

The development and first assessment of a high resolution eddy-resolving forecasting system for the Aegean Sea hydrodynamics, developed as part of the POSEIDON-II European Economic Area (EEA) Grants project and the European Coastal Sea Operational Observing and Forecasting (ECOOP) European Union (EU) project, is presented.The system uses an assimilation scheme based on a localized version of the Singular Evolutive Extended Kalman (SEEK) filter with partial evolution of its correction directions.The filter is used to correct the forecast state of a 1/30o Princeton Ocean Model (POM) of the Aegean Sea on a weekly basis. Data assimilation experiments are performed over a 12-month period to estimate the impact of observations insertion on the forecasting skill of the modelling system.The accuracy of the hydrodynamic state identification is assessed by the relevance of the assimilation system in fitting the data, and in forecasting future variability. The results of the assimilation system are also inter-compared with the forecasts estimated by an identical forecasting system that is re-initialized on a weekly basis from the basin wide MFS model analysis using a proper downscaling technique.
Mechanical bowel preparation with pre‐operative oral antibiotics in elective colorectal resections: an Australian single institution experience

Anastomotic leaks (AL) and surgical site infections (SSI) are serious complications after colorectal resection. Studies have shown the benefits of pre‐operative oral antibiotics (OAB) with mechanical bowel preparation (MBP) in reducing AL and SSI rates. We aim to investigate our experience with the short‐term outcomes of AL and SSI following elective colorectal resections in patients receiving OAB with MBP versus MBP only.
Seasonality of Respiratory Syncytial Virus — United States, 2017–2023

In the United States, respiratory syncytial virus (RSV) infections cause an estimated 58,000-80,000 hospitalizations among children aged <5 years (1,2) and 60,000-160,000 hospitalizations among adults aged ≥65 years each year (3-5). U.S. RSV epidemics typically follow seasonal patterns, peaking in December or January (6,7), but the COVID-19 pandemic disrupted RSV seasonality during 2020-2022 (8). To describe U.S. RSV seasonality during prepandemic and pandemic periods, polymerase chain reaction (PCR) test results reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS)* during July 2017-February 2023 were analyzed. Seasonal RSV epidemics were defined as the weeks during which the percentage of PCR test results that were positive for RSV was ≥3% (9). Nationally, prepandemic seasons (2017-2020) began in October, peaked in December, and ended in April. During 2020-21, the typical winter RSV epidemic did not occur. The 2021-22 season began in May, peaked in July, and ended in January. The 2022-23 season started (June) and peaked (November) later than the 2021-22 season, but earlier than prepandemic seasons. In both prepandemic and pandemic periods, epidemics began earlier in Florida and the Southeast and later in regions further north and west. With several RSV prevention products in development,† ongoing monitoring of RSV circulation can guide the timing of RSV immunoprophylaxis and of clinical trials and postlicensure effectiveness studies. Although the timing of the 2022-23 season suggests that seasonal patterns are returning toward those observed in prepandemic years, clinicians should be aware that off-season RSV circulation might continue.
Analytical characterization of host‐cell‐protein‐rich aggregates in monoclonal antibody solutions

Host‐cell proteins (HCPs) and high molecular weight (HMW) species have historically been treated as independent classes of impurities in the downstream processing of monoclonal antibodies (mAbs), but recent indications suggest that they may be partially linked. We have explored this connection with a shotgun proteomic analysis of HMW impurities that were isolated from harvest cell culture fluid (HCCF) and protein A eluate using size‐exclusion chromatography (SEC). As part of the proteomic analysis, a cross‐digest study was performed in which samples were analyzed using both the standard and native digest techniques to enable a fair comparison between bioprocess pools. This comparison reveals that the HCP profiles of HCCF and protein A eluate overlap substantially more than previous work has suggested, because hundreds of HCPs are conserved in aggregates that may be up to ~50 nm in hydrodynamic radius and that persist through the protein A capture step. Quantitative SWATH proteomics suggests that the majority of the protein A eluate's HCP mass is found in such aggregates, and this is corroborated by ELISA measurements on SEC fractions. The SWATH data also show that intra‐aggregate concentrations of individual HCPs are positively correlated between aggregates that were isolated from HCCF and protein A eluate, and species that have generally been considered difficult to remove tend to be more concentrated than their counterparts. These observations support prior hypotheses regarding aggregate‐mediated HCP persistence through protein A chromatography and highlight the importance of this persistence mechanism.
Perception of threat and intent to harm from vocal and facial cues

What constitutes a “threatening tone of voice”? There is currently little research exploring how listeners infer threat, or the intention to cause harm, from speakers’ voices. Here, we investigated the influence of key linguistic variables on these evaluations (Study 1). Results showed a trend for voices perceived to be lower in pitch, particularly those of male speakers, to be evaluated as sounding more threatening and conveying greater intent to harm. We next investigated the evaluation of multimodal stimuli comprising voices and faces varying in perceived dominance (Study 2). Visual information about the speaker’s face had a significant effect on threat and intent ratings. In both experiments, we observed a relatively low level of agreement among individual listeners’ evaluations, emphasising idiosyncrasy in the ways in which threat and intent-to-harm are perceived. This research provides a basis for the perceptual experience of a “threatening tone of voice,” along with an exploration of vocal and facial cue integration in social evaluation.
Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States

Abstract Background: Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period. Methods: Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States. Results: The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas. Conclusions: The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.
Potential response of dark carbon fixation to global warming in estuarine and coastal waters

Dark carbon fixation (DCF), through which chemoautotrophs convert inorganic carbon to organic carbon, is recognized as a vital process of global carbon biogeochemical cycle. However, little is known about the response of DCF processes in estuarine and coastal waters to global warming. Using radiocarbon labelling method, the effects of temperature on the activity of chemoautotrophs were investigated in benthic water of the Yangtze estuarine and coastal areas. A dome‐shaped thermal response pattern was observed for DCF rates (i.e., reduced rates at lower or higher temperatures), with the optimum temperature (Topt) varying from about 21.9 to 32.0°C. Offshore sites showed lower Topt values and were more vulnerable to global warming compared with nearshore sites. Based on temperature seasonality of the study area, it was estimated that warming would accelerate DCF rate in winter and spring but inhibit DCF activity in summer and fall. However, at an annual scale, warming showed an overall promoting effect on DCF rates. Metagenomic analysis revealed that the dominant chemoautotrophic carbon fixation pathways in the nearshore area were Calvin‐Benson‐Bassham (CBB) cycle, while the offshore sites were co‐dominated by CBB and 3‐hydroxypropionate/4‐hydroxybutyrate cycles, which may explain the differential temperature response of DCF along the estuarine and coastal gradients. Our findings highlight the importance of incorporating DCF thermal response into biogeochemical models to accurately estimate the carbon sink potential of estuarine and coastal ecosystems in the context of global warming.
Type I Interferon Orchestrates Demand-Adapted Monopoiesis during Influenza A Virus Infection via STAT1-Mediated Upregulation of Macrophage Colony-Stimulating Factor Receptor Expression

Our findings show that influenza A virus infection induces type I interferon (IFN)-mediated emergency hematopoiesis to expand the GMP population in the bone marrow. The type I IFN-STAT1 axis was identified as being involved in mediating the viral-infection-driven demand-adapted monopoiesis by upregulating M-CSFR expression in the GMP population. ABSTRACT Whether and how a local virus infection affects the hematopoietic system in the bone marrow is largely unknown, unlike with systemic infection. In this study, we showed that influenza A virus (IAV) infection leads to demand-adapted monopoiesis in the bone marrow. The beta interferon (IFN-β) promoter stimulator 1 (IPS-1)–type I IFN–IFN-α receptor 1 (IFNAR1) axis-mediated signaling was found to induce the emergency expansion of the granulocyte-monocyte progenitor (GMP) population and upregulate the expression of the macrophage colony-stimulating factor receptor (M-CSFR) on bipotent GMPs and monocyte progenitors via the signal transducer and activator of transcription 1 (STAT1), leading to a scaled-back proportion of granulocyte progenitors. To further address the influence of demand-adapted monopoiesis on IAV-induced secondary bacterial infection, IAV-infected wild-type (WT) and Stat1−/− mice were challenged with Streptococcus pneumoniae. Compared with WT mice, Stat1−/− mice did not demonstrate demand-adapted monopoiesis, had more infiltrating granulocytes, and were able to effectively eliminate the bacterial infection. IMPORTANCE Our findings show that influenza A virus infection induces type I interferon (IFN)-mediated emergency hematopoiesis to expand the GMP population in the bone marrow. The type I IFN-STAT1 axis was identified as being involved in mediating the viral-infection-driven demand-adapted monopoiesis by upregulating M-CSFR expression in the GMP population. As secondary bacterial infections often manifest during a viral infection and can lead to severe or even fatal clinical complications, we further assessed the impact of the observed monopoiesis on bacterial clearance. Our results suggest that the resulting decrease in the proportion of granulocytes may play a role in diminishing the IAV-infected host’s ability to effectively clear secondary bacterial infection. Our findings not only provide a more complete picture of the modulatory functions of type I IFN but also highlight the need for a more comprehensive understanding of potential changes in hematopoiesis during local infections to better inform clinical interventions.
Finite-Time Stability of Fractional-Order Neural Networks with Delay

Finite-time stability of a class of fractional-order neural networks is investigated in this paper. By Laplace transform, the generalized Gronwall inequality and estimates of Mittag—Leffler functions, sufficient conditions are presented to ensure the finite-time stability of such neural models with the Caputo fractional derivatives. Furthermore, results about asymptotical stability of fractional-order neural models are also obtained.
Roadmap on thermoelectricity

The increasing energy demand and the ever more pressing need for clean technologies of energy conversion pose one of the most urgent and complicated issues of our age. Thermoelectricity, namely the direct conversion of waste heat into electricity, is a promising technique based on a long-standing physical phenomenon, which still has not fully developed its potential, mainly due to the low efficiency of the process. In order to improve the thermoelectric performance, a huge effort is being made by physicists, materials scientists and engineers, with the primary aims of better understanding the fundamental issues ruling the improvement of the thermoelectric figure of merit, and finally building the most efficient thermoelectric devices. In this Roadmap an overview is given about the most recent experimental and computational results obtained within the Italian research community on the optimization of composition and morphology of some thermoelectric materials, as well as on the design of thermoelectric and hybrid thermoelectric/photovoltaic devices.
Metaplastic breast cancer: an all-round multidisciplinary consensus

Metaplastic breast cancer (MpBC) is a rare and aggressive histologic subtype of breast cancer (BC) characterized by the presence of at least two cellular types, commonly epithelial and mesenchymal components. Despite growing evidence that MpBC is a unique entity, it has long been treated as a variant of nonspecial type (NST) BC. MpBC typically shows the phenotype of triple-negative breast cancer (TNBC), but compared to NST-TNBC, it is a relatively chemorefractory tumor associated with worse outcomes. Therefore, there is an urgent need to develop management guidelines specifically for MpBC to improve the prognosis of patients with early MpBC. This expert consensus aims to guide diagnosis and standardize clinical management of early MpBC among treating physicians. We provide guidance on the challenging radiological and pathological diagnosis of MpBC. Evidence on the involvement of genetic predisposition in the development of MpBC is also explored. We emphasize the importance of a multidisciplinary approach for the treatment of patients with early MpBC. The optimal surgery and radiotherapy approach is presented, as well as the opportunity offered by novel therapeutic approaches to increase treatment response in this chemoresistant subtype. Appropriate management of patients with MpBC is critical to reduce the high risk of local and distant recurrence that characterizes this disease.