Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab11FIP1 maintains Rab35 at the intercellular bridge to promote actin removal and abscission.

Cytokinesis occurs at the end of mitosis/meiosis wherein the cytoplasms of daughter cells are separated. Prior to abscission, an intercellular bridge containing the remaining furrowing machinery, mitotic spindle and actin cytoskeleton connects the two daughter cells. To remove this actin and allow for separation of daughter cells, Rab35 vesicles, loaded with the actin oxidizer MICAL1 and the inositol polyphosphate 5-phosphatase OCRL are recruited to the midbody in a fine-tuned spatiotemporal manner. Importantly however, the means by which these vesicles are recruited is currently unclear. Here, we demonstrate that Rab11FIP1 is recruited to the midbody after Rab35 to scaffold it at the bridge and maintain Rab35 in this region. In the absence of Rab11FIP1, Rab35 dramatically drops from the midbody, inducing defects such as cytokinetic delays and binucleation due to actin overaccumulation at the intercellular bridge, defects which can be rescued with Latrunculin A treatment. Importantly, we show that Rab11FIP1 is critical for Rab35 function in actin removal prior to cytokinesis.
Harmonization of Finnish Vaccination Data

Vaccination information is needed at individual and at population levels, as it is an important part of public health measures. In Finland, a vaccination data structure has been developed for centralized information services that include patient access to information. Harmonization of data with national vaccination registry is ongoing. New requirements for vaccination certificates have emerged because of COVID-19 pandemic. We explore, what is the readiness of Finnish development of vaccination data structures and what can be learned from Finnish harmonization efforts in order to accomplish required level of interoperability.
Pathophysiology of cardiogenic shock

Purpose of review We describe the pathophysiology of cardiogenic shock (CS), from the main pathways to the inflammatory mechanisms and the proteomic features. Recent findings Although the classical pathophysiological pathways underlying CS, namely reduced organ perfusion due to inadequate cardiac output and peripheral vasoconstriction, have been well-established for a long time, the role of macro-and micro-hemodynamics in the magnitude of the disease and its prognosis has been investigated extensively only over the last few years. Moreover, to complete the complex picture of CS pathophysiology, the study of cytokine cascade, inflammation, and proteomic analysis has been addressed recently. Summary Understanding the pathophysiology of CS is important to treat it optimally.
Brief Overview and Updates on Infantile Hypertrophic Pyloric Stenosis: Focus on Perioperative Management.

Infantile hypertrophic pyloric stenosis is the most common surgical cause of vomiting in infancy. After adequate resuscitation, surgical pyloromyotomy is the standard of care for infants with pyloric stenosis. This article provides a brief overview and updates on hypertrophic pyloric stenosis in infants, with a focus on the surgical approach as well as perioperative management of this pathology. The most controversial aspect of the management of infants with pyloric stenosis is post-pyloromyotomy feeding, as there is no clear consensus in the literature on the best regimen. More randomized controlled trials are needed to establish the optimal resuscitation protocol in the preoperative phase and the ideal feeding regimen in the postoperative phase for infants with hypertrophic pyloric stenosis. [Pediatr Ann. 2021;50:(3):e136-e141. ].
Pharmacovigilance and Clinical Environment: Utilizing OMOP-CDM and OHDSI Software Stack to Integrate EHR Data

Information Technology (IT) and specialized systems could have a prominent role towards the support of drug safety processes, both in the clinical context but also beyond that. PVClinical project aims to build an IT platform, enabling the investigation of potential Adverse Drug Reactions (ADRs). In this paper, we outline the utilization of Observational Medical Outcomes Partnership - Common Data Model (OMOP-CDM) and the openly available Observational Health Data Sciences and Informatics (OHDSI) software stack as part of PVClinical platform. OMOP-CDM offers the capacity to integrate data from Electronic Health Records (EHRs) (e.g., encounters, patients, providers, diagnoses, drugs, measurements and procedures) via an accepted data model. Furthermore, the OHDSI software stack provides valuable analytics tools which could be used to address important questions regarding drug safety quickly and efficiently, enabling the investigation of potential ADRs in the clinical environment.
Ventilatory parameters measured during a physiological study of simulated powered air-purifying respirator failure in healthy volunteers

Powered air-purifying respirators (PAPR) are a high level of respiratory personal protective equipment. Like all mechanical devices, they are vulnerable to failure. The precise physiological consequences of failure in live subjects have not previously been reported. We conducted an observational safety study simulating PAPR failure in a group of nine healthy volunteers, wearing loose-fitting hoods, who were observed for a period of ten minutes, or until they requested the experiment be aborted, with continuous monitoring of gas exchange. Relative to baseline, participants demonstrated median reductions in peripheral oxygen saturation of 3.5% (95% confidence interval (CI) –4% to –2%; P = 0.0039) and fraction of inspired oxygen of 0.045 (95% CI –0.05 to –0.04; P = 0.0039), and median increases in inspired partial pressure of carbon dioxide of 27 mmHg (95% CI 23.5–32 mmHg; P = 0.0039), end-tidal partial pressure of carbon dioxide of 11 mmHg (95% CI 7–16 mmHg; P = 0.0039) and minute ventilation of 30 l/min (95% CI 19.4–35.9 l/min; P = 0.0039). Median collateral entrainment of room air into the hood was 17.6 l/min (interquartile range 12.3–27.0 l/min). All subjects reported thermal discomfort, with two (22.2%) requesting early termination of the experiment. Whilst the degree of rebreathing in this experiment was not sufficient to cause dangerous physiological derangement, the degree of reported thermal discomfort combined with the consequences of entrainment of possibly contaminated air into the hood, pose a risk to wearers in the event of failure.
Insights into β-amyloid transition prevention by cucurbit[7]uril from molecular modeling

Abstract In this study, comparable molecular dynamic (MD) simulations of 1.2 microseconds were performed to clarify the prevention of the β-amyloid peptide (Aβ1–42) aggregation by cucurbit[7]uril (CB[7]). The accumulation of this peptide in the brain is one of the most harmful in Alzheimer’s disease. The inhibition mechanism of Aβ1–42 aggregation by different molecules is attributed to preventing of Aβ1–42 conformational transition from α-helix to the β-sheet structure. However, our structural analysis shows that the pure water and aqueous solution of the CB[7] denature the native Aβ1–42 α-helix structure forming different compactness and unfolded conformations, not in β-sheet form. On the other hand, in the three CB[7]@Aβ1–42 complexes, it was observed the encapsulation of N-terminal (Asp1), Lys16, and Val36 by CB[7] along the MD trajectory, and not with aromatic residues as suggested by the literature. Only in one CB[7]@Aβ1–42 complex was observed stable Asp23-Lys28 salt bridge with an average distance of 0.36 nm. All CB[7]@Aβ1–42 complexes are very stable with binding free energy lowest than ∼–50 kcal/mol between the CB[7] and Aβ1-42 monomer from MM/PBSA calculation. Therefore, herein we show that the mechanism of the prevention of elongation protofibril by CB[7] is due to the disruption of the Asp23-Lys28 salt bridge and steric effects of CB[7]@Aβ1–42 complex with the fibril lattice, and not due to the transition from α-helix to β-sheet following the dock-lock mechanism. Communicated by Ramaswamy H. Sarma
AMA Code of Medical Ethics' Opinions Related to "Ending the HIV Epidemic: A Plan for America".

The AMA Code of Medical Ethics offers guidance on HIV screening that respects patient autonomy and protects public health in Opinion 8.1, "Routine Universal Screening for HIV. " This article examines the relationship between this opinion and the Ending the HIV Epidemic: A Plan for America initiative and discusses the Code's guidance on the role that physicians can play in diagnosing and treating patients with HIV and mitigating the stigma surrounding the disease.
M2 macrophage accumulation contributes to pulmonary fibrosis, vascular dilatation, and hypoxemia in rat hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS) markedly increases the mortality of patients. However, its pathogenesis remains incompletely understood. Rat HPS develops in common bile duct ligation (CBDL)‐induced, but not thioacetamide (TAA)‐induced cirrhosis. We investigated the mechanisms of HPS by comparing these two models. Pulmonary histology, blood gas exchange, and the related signals regulating macrophage accumulation were assessed in CBDL and TAA rats. Anti‐polymorphonuclear leukocyte (antiPMN) and anti‐granulocyte‐macrophage colony stimulating factor (antiGM‐CSF) antibodies, clodronate liposomes (CL), and monocyte chemoattractant protein 1 (MCP1) inhibitor (bindarit) were administrated in CBDL rats, GM‐CSF, and MCP1 were administrated in bone marrow‐derived macrophages (BMDMs). Pulmonary inflammatory cell recruitment, vascular dilatation, and hypoxemia were progressively developed by 1 week after CBDL, but only occurred at 4 week after TAA. Neutrophils were the primary inflammatory cells within 3 weeks after CBDL and at 4 week after TAA. M2 macrophages were the primary inflammatory cells, meantime, pulmonary fibrosis, GM‐CSFR, and CCR2 were specifically increased from 4 week after CBDL. AntiPMN antibody treatment decreased neutrophil and macrophage accumulation, CL or the combination of antiGM‐CSF antibody and bindarit treatment decreased macrophage recruitment, resulting in pulmonary fibrosis, vascular dilatation, and hypoxemia in CBDL rats alleviated. The combination treatment of GM‐CSF and MCP1 promoted cell migration, M2 macrophage differentiation, and transforming growth factor‐β1 (TGF‐β1) production in BMDMs. Conclusively, our results highlight neutrophil recruitment mediates pulmonary vascular dilatation and hypoxemia in the early stage of rat HPS. Further, M2 macrophage accumulation induced by GM‐CSF/GM‐CSFR and MCP1/CCR2 leads to pulmonary fibrosis and promotes vascular dilatation and hypoxemia, as a result, HPS develops.
The cajal body protein coilin is a regulator of the miR-210 hypoxamiR and influences MIR210HG alternative splicing.

Hypoxia is a severe stressor to cellular homeostasis. At the cellular level, low oxygen triggers the transcription of a variety of genes supporting cell survival and oxygen homeostasis mediated by transcription factors such as hypoxia inducible factors (HIFs). Among many determinants dictating cell response to hypoxia and HIFs are microRNAs (miRNAs). Cajal Bodies (CBs), subnuclear structures involved in ribonucleoprotein biogenesis, have been recently proven to contribute to microRNA processing and biogenesis but have not been studied under hypoxia. Here, we show for the first time a hypoxia dependent increase in CB number in WI-38 primary fibroblasts which normally have very few CBs. Additionally, the CB marker protein, coilin, is upregulated in hypoxic WI-38 cells. However, the hypoxic coilin upregulation was not seen in transformed cell lines. Furthermore, we found that coilin is needed for the hypoxic induction of a well-known hypoxamiR, miR-210, as well as the hypoxia induced alternative splicing of the miR-210 host gene, MIR210HG. These findings provide a new link in the physiological understanding of coilin, CBs and miRNA dysregulation in hypoxic pathology.
Movement preparation time determines movement variability.

Faster movements are typically more variable - a speed-accuracy tradeoff known as Fitts' law. Are movements that are initiated faster also more variable? Neurophysiological work has associated larger neural variability during motor preparation with longer reaction time (RT) and larger movement variability, implying that movement variability decreases with increasing RT. Here, we recorded over 30000 reaching movements in eleven human participants who moved to visually-cued targets. Half of the visual cues was accompanied by a beep to evoke a wide RT range in each participant. Results show that initial reach variability decreases with increasing RT, for voluntarily produced RTs up to ~300 ms, while other kinematic aspects and endpoint accuracy remained unaffected. We conclude that movement preparation time determines initial movement variability. We suggest that the chosen movement preparation time reflects a trade-off between movement initiation and precision.
The diversity of the plasmablast signature across species and experimental conditions: A meta‐analysis

Antibody‐secreting cells (ASC) are divided into two principal subsets, including the long‐lived plasma cell (PC) subset residing in the bone marrow and the short‐lived subset, also called plasmablast (PB). PB are described as a proliferating subset circulating through the blood and ending its differentiation in tissues. Due to their inherent heterogeneity, the molecular signature of PB is not fully established. The purpose of this study was to decipher a specific PB signature in humans and mice through a comprehensive meta‐analysis of different data sets exploring the PB differentiation in both species and across different experimental conditions. The present study used recent analyses using whole RNA sequencing in prdm1‐GFP transgenic mice to define a reliable and accurate PB signature. Next, we performed similar analysis using current data sets obtained from human PB and PC. The PB‐specific signature is composed of 155 and 113 genes in mouse and human being, respectively. Although only nine genes are shared between the human and mice PB signature, the loss of B‐cell identity such as the down‐regulation of PAX5, MS4A1, (CD20) CD22 and IL‐4R is a conserved feature across species and across the different experimental conditions. Additionally, we observed that the IRF8 and IRF4 transcription factors have a specific dynamic range of expression in human PB. We thus demonstrated that IRF4/IRF8 intranuclear staining was useful to define PB in vivo and in vitro and able to discriminate between atypical PB populations and transient states.
Atypical neurological manifestations in Wernicke’s encephalopathy due to hyperemesis gravidarum

ABSTRACT Objectives: Hyperemesis gravidarum is known to induce nutritional, water and electrolyte deficiencies which can be fatal if not treated urgently. Thiamine deficiency may lead to a constellation of neurological symptoms that include Wernicke encephalopathy. Moreover, Wernicke encephalopathy is typically manifested as ocular paresis, ataxia and confusion. Methods: Retrospective review of 6 women who developed neurological abnormalities following hyperemesis gravidarum and were treated with varying dosage of parenteral thiamine. Results: Five women developed atypical neurological symptoms, namely, slurred speech, visual loss, seizure and aggressive behaviour while one woman developed typical clinical triad of Wernicke encephalopathy after hyperemesis gravidarum. Magnetic Resonance Imaging (MRI) scans revealed abnormalities suggestive of Wernicke encephalopathy in three women only. All women improved after parenteral thiamine administration during hospital stay and had a complete neurological recovery during 2 months follow up. Discussion: Wernicke encephalopathy may not be necessarily associated with the typical neurological triad and may not have noticeable hyperintensity signal in dorsomedial thalami, mammillary bodies, hippocampus and periaqueductal region during magnetic resonance imaging. Atypical neurological signs and symptoms following hyperemesis gravidarum would invariably respond immediately to appropriate dosage of parenteral thiamine. A lower loading dosage of thiamine (100 mg thrice daily) appeared adequate for management in women with normal MRI scans.
Modeling of Activity-Induced Changes in Signal Propagation Speed of Mechano-Electrically Stimulated Nerve Fiber

One of the important questions in the research on neural coding is how the preceding axonal activity affects the signal propagation speed of the following one. We present an approach to solving this problem by introducing a multi-level spike count for activity quantification and fitting a family of linear regression models to the data. The best-achieved score is R2=0.89 and the comparison of different models indicates the importance of long and very short nerve fiber memory. Further studies are required to understand the complex axonal mechanisms responsible for the discovered phenomena.
A hindbrain dopaminergic neural circuit prevents weight gain by reinforcing food satiation

A dopaminergic neural circuit projecting from the VTA to the hindbrain regulates feeding by transducing meal satiation signals. The neural circuitry mechanism that underlies dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons situated in the caudal ventral tegmental area (cVTA) directly innervating DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake via enhanced satiation response. Notably, this cohort of DAcVTA neurons is activated immediately before the cessation of each feeding bout. Acute inhibition of these DA neurons before bout termination substantially suppresses satiety and prolongs the consummatory feeding. Activation of postsynaptic DRD1LPBN neurons inhibits feeding, whereas genetic deletion of Drd1 within the LPBN causes robust increase in food intake and subsequent weight gain. Furthermore, the DRD1LPBN signaling manifests the central mechanism in methylphenidate-induced hypophagia. In conclusion, our study illuminates a hindbrain DAergic circuit that controls feeding through dynamic regulation in satiety response and meal structure.
Contributions of h- and Na+/K+ Pump Currents to the Generation of Episodic and Continuous Rhythmic Activities

Developing spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and their transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-center oscillator (HCO). Following predictions of our computational model, we tested the contributions of key properties to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model recapitulates the diverse state-dependent rhythms evoked by dopamine. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with Na+/K+ ATPase pump (IPump) and hyperpolarization-activated currents (Ih) playing key roles. Modulation of either IPump or Ih produced transitions between episodic and continuous rhythms and silence. As maximal activity of IPump decreased, the interepisode interval and period increased along with a reduction in episode duration. Decreasing maximal conductance of Ih decreased episode duration and increased interepisode interval. Pharmacological manipulations of Ih with ivabradine, and IPump with ouabain or monensin in isolated spinal cords produced findings consistent with the model. Our modeling and experimental results highlight key roles of Ih and IPump in producing episodic rhythms and provide insight into mechanisms that permit a single CPG to produce multiple patterns of rhythmicity.
Archaeology of the Perishable

Selection and transport of materials for tools is ubiquitous throughout our species’ evolutionary history. Yet our understanding of early human material culture is heavily skewed toward lithic technology. This poses challenges when reconstructing our technical origins, as organic raw materials, especially plants, likely played a significant role despite their absence from the record until 300 kya. Studies of plant-tool use by living apes can serve as a proxy to reconstruct such aspects of human behavior. Employing archaeological methods, we investigated raw material procurement for termite-fishing tools by three chimpanzee (Pan troglodytes schweinfurthii) populations in Tanzania: Gombe, Issa, and Mahale. All communities exploited plant sources from the immediate vicinity of termite mounds, as well as farther away, and reused them. However, at Issa, more parts were sourced per plant, with the number of removals decreasing as distance from the mound increased. These disparities are likely caused by environmental differences. Issa apes might try to minimize transport costs in what is a comparably more open and drier habitat with fewer suitable sources available near mounds. Despite similar raw material types being available, Issa and Mahale chimpanzees exclusively used bark for tool manufacture, while at Gombe, various materials were employed; these differences may reflect cultural variants. Our study highlights how environmental and cultural factors shape chimpanzee technology and identifies similarities to raw material selection processes inferred for Oldowan tool users. The archaeology of the perishable, even if at its infancy, is providing a new framework for reconstructing archaeologically invisible aspects of early human behavior and our own technological origins.
Effects of a Paraphrasing Strategy on the Text Comprehension of Fourth-Grade Striving Readers

Reading comprehension is a complex and multifaceted process that is often difficult for striving readers to access. Researchers have reported that an explicit and systematic approach to teaching text comprehension strategies is effective for accelerating the growth of striving readers. In this study, the Self-Regulated Strategy Development model was used to teach a paraphrasing strategy (TRAP strategy) to striving fourth-grade readers. A multiple baseline design across pairs of participants with multiple probes in baseline was used. Students were placed in pairs according to independent word recognition levels, and the intervention was enacted in pairs by the classroom teacher. Reading comprehension was measured by percentage of text recalled and number of correct explicit and implicit comprehension questions. Results indicated that learning the TRAP strategy to independent performance produced higher percentages of text recall and a greater number of correct comprehension short-answer questions. Recommendations for future research and practice are included.