bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic status is not associated with survival in patients with brain metastases treated with stereotactic radiotherapy
Authors: Nagtegaal S.H.J. , Elias S.G. , Snijders T.J. , Verkooijen H.M. , Verhoeff J.J.C. 
Published: October 2022

AbstractBackground and purposeIn most cancer sites a low socioeconomic status (SES) is consistently associated with poorer survival. For brain metastasis, this relation is not well understood. Therefore, we studied the effect of SES on survival in Dutch brain metastasis patients treated with stereotactic radiosurgery in a tertiary radiotherapy facility.Materials and methodsWe retrospectively studied 404 consecutive patients treated with stereotactic radiosurgery for brain metastases in a tertiary referral centre between 2012 and 2017. Baseline prognostic factors for survival were collected. The SES score was based on education, income and employment. Cox proportional hazard models were made, corrected for the relevant variables identified from a directed acyclic graph (DAG). Adjustments were made in two ways in order to obtain comprehensive results: correcting for confounders (total effect), and correcting for confounders and mediating factors (direct effect).ResultsUnadjusted, estimation of the linear effect of SES on survival resulted in a HR of 0.92 (95%CI 0.82 – 1.04). The total effect of SES was achieved by correcting for age, resulting in a HR of 0.95, with a 95% CI of 0.84 – 1.07. The direct effect gave a HR of 0.96 (95%CI 0.84 – 1.10).ConclusionSES was not associated with survival in patients with brain metastases undergoing radiation therapy. When correcting for clinical variables, we found no significant relationship between SES and survival, with HRs suggesting limited clinical impact. The results suggest that patients’ survival outcomes after contemporary cancer treatment are unrelated to their employment status, education status and annual income.
A Mixed Methods Comparison of Artificial Intelligence-Powered Clinical Decision Support System Interfaces for Multiple Criteria Decision Making in Antidepressant Selection
Authors: Kleinerman Akiva , Benrimoh David , Golden Grace , Tanguay-Sela Myriam , Margolese Howard C. , Rosenfeld Ariel 
Published: October 2022

AbstractBACKGROUNDArtificial intelligence-powered clinical decision support systems (AI-CDSS) have recently become foci of research. When clinicians face decisions about treatment selection, they must contemplate multiple criteria simultaneously. The relative importance of these criteria often depends on the clinical scenario, as well as clinician and patient preferences. It remains unclear how AI-CDSS can optimally assist clinicians in making these complex decisions. In this work we explore clinician reactions to different presentations of AI results in the context of multiple criteria decision-making during treatment selection for major depressive disorder.METHODSWe developed an online platform for depression treatment selection to test three interfaces. In the probabilities alone (PA) interface, we presented probabilities of remission and three common side effects for five antidepressants. In the clinician-determined weights (CDW) interface, participants assigned weights to each of the outcomes and obtained a score for each treatment. In the expert-derived weights interface (EDW), outcomes were weighted based on expert opinion. Each participant completed three clinical scenarios, and each scenario was randomly paired with one interface. We collected participants’ impressions of the interfaces via questionnaires and written and verbal feedback.RESULTSTwenty-two physicians completed the study. Participants felt that the CDW interface was most clinically useful (H=10.29, p<0.01) and more frequently reported that it had an impact on their decision making (PA: in 55.5% of experienced scenarios, CDW: in 59.1%, EDW: in 36.6%). Clinicians most often chose a treatment different from their original choice after reading the clinical scenario in the CDW interface (PA: 26.3%, CDW: 33.3%, EDW: 15.8%).CONCLUSIONClinicians found a decision support interface where they could set the weights for different potential outcomes most useful for multi-criteria decision making. Allowing clinicians to weigh outcomes based on their expertise and the clinical scenario may be a key feature of a future clinically useful multi-criteria AI-CDSS.
Evaluation of primary allied healthcare in patients recovering from COVID-19: first results after six months follow-up in a Dutch nationwide prospective cohort study
Authors: Slotegraaf Anne I. , Gerards Marissa H.G. , Verburg Arie C. , de van der Schueren Marian A.E. , Kruizenga Hinke M. , Graff Maud J.L. , Cup Edith H.C. , Kalf Johanna G. , Lenssen Antoine F. , Meijer Willemijn M. , Kool Renée A. , de Bie Rob A. , van der Wees Philip J. , Hoogeboom Thomas J. 
Published: October 2022

AbstractObjectivesTo report the recovery of patients receiving primary allied healthcare after a COVID-19 infection at a six-month follow-up, and to explore which patient characteristics are associated with the changes in outcomes between the baseline and six-month follow-up.DesignProspective cohort study.SettingAllied healthcare in Dutch primary care.Participants1,451 adult patients recovering from COVID-19 and receiving treatment from one or more primary care allied health professional(s) (i.e., dietitian, exercise therapist, occupational therapist, physical therapist and/or speech and language therapist).ResultsFor participation (USER-P range 0 to 100), estimated mean differences of at least 2.3 points were observed after six months. For HRQoL (EQ-VAS range 0 to 100), the mean increase was 12.31 at six months. Furthermore, significant improvements were found for fatigue (FSS range 1 to 7): the mean decrease was –0.7 at six months. For physical functioning (PROMIS-PF range 13.8 to 61.3), the mean increase was 5.9 at six months. Mean differences of –0.8 for anxiety (HADS range 0 to 21), and –1.5 for depression (HADS range 0 to 21), were found after six months. Having a worse baseline score, hospital admission and male sex were associated with greater improvement between the baseline and six-month follow-up, whereas age, BMI, comorbidities and smoking status were not associated with mean changes in any outcome measure.ConclusionsPatients recovering from COVID-19 who receive primary allied healthcare make progress in recovery, but still experience many limitations in their daily activities after six months. Our findings provide reference values to healthcare providers and healthcare policy-makers regarding what to expect from the recovery of patients who received health care from one or more primary care allied health professionals.Trial registrationClinicaltrials.govregistry (NCT04735744).
Experimenter familiarization is a crucial prerequisite for assessing behavioral outcomes and reduces stress in mice not only under chronic pain conditions
Authors: Segelcke Daniel , Talbot Steven R. , Palme Rupert , La Porta Carmen , Pogatzki-Zahn Esther , Bleich André , Tappe-Theodor Anke 
Published: October 2022

ABSTARCTRodent behavior is affected by different environmental conditions. These do not only comprise experimental and housing conditions but also familiarization with the experimenter. However, specific effects on pain-related behavior and chronic pain conditions have not been examined. Therefore, we aimed to investigate the impact of different housing conditions, inverted day-night cycles, and experimenter familiarization on male mice following peripheral neuropathy using the spared nerve injury (SNI) model. Using a multimodal approach, we evaluated evoked pain-related-, anxiety- and depression-like behavior, corticosterone metabolite levels and utilized an integrative approach for relative-severity-assessment.Different environmental conditions are represented by individually ventilated cages and standard open cages combined with a reversed day-night-light cycle and experimenter habituation, inducing differentially modulated multidimensional pain- and emotion-like phenotypes in SNI mice. In addition, familiarization reduced the stress level caused by behavioral tests. Although no environmental condition significantly modulated the severity in SNI mice, it influenced pain-affected phenotypes and is, therefore, crucial for designing and interpreting preclinical pain studies. Moreover, environmental conditions should be considered more in the reporting guidelines, described in more detail, and discussed as a potential influence on pain phenotypes.
Emerging variants of canine enteric coronavirus associated with seasonal outbreaks of severe canine gastroenteric disease
Authors: Cunningham-Oakes Edward , Pilgrim Jack , Darby Alistair C. , Appleton Charlotte , Jewell Chris , Rowlingson Barry , Cuartero Carmen Tamayo , Newton Richard , Sánchez-Vizcaíno Fernando , Fins Ivo Salgueiro , Brant Bethaney , Smith Shirley , Penrice-Randal Rebekah , Clegg Simon R. , Roberts Ashley P.E. , Millson Stefan H. , Pinchbeck Gina L. , Noble P-J. M. , Radford Alan D. 
Published: October 2022

AbstractCanine enteric coronavirus (CECoV) variants have an emerging role in severe outbreaks of canine gastroenteritis. Here we used syndromic health data from a sentinel network of UK veterinary practices to identify an outbreak of severe canine gastroenteritis. Affected dogs frequently presented with vomiting, diarrhoea and inappetence. Data from sentinel diagnostic laboratories showed similar seasonal increases in CECoV diagnosis. Membrane glycoprotein (M) gene sequence analysis implied wide geographical circulation of a new CECoV variant. Whole genome sequencing suggested the main circulating 2022 variant was most closely related to one previously identified in 2020 with additional spike gene recombination; all variants were unrelated to CECoV-like viruses recently associated with human respiratory disease. Identifying factors that drive population-level evolution, and its implications for host protection and virulence, will be important to understand the emerging role of CECoV variants in canine and human health, and may act as a model for coronavirus population adaptation more widely.
Cell wall damage increases macromolecular crowding effects in the Escherichia coli cytoplasm
Authors: Pittas Theodoros , Zuo Weiyan , Boersma Arnold J. 
Published: October 2022

AbstractThe intracellular milieu is crowded with biomacromolecules. Macromolecular crowding changes the interactions, diffusion, and conformations of the biomacromolecules. Changes in intracellular crowding effects have been mostly ascribed to differences in biomacromolecule concentration. However, the spatial organization of these molecules should play a significant role in crowding effects. Here, we find that cell wall damage causes increased macromolecular crowding effects in the Escherichia coli cytoplasm. Using a genetically-encoded macromolecular crowding sensor, we see that crowding effects in E. coli spheroplasts and Penicillin G-treated cells well surpass crowding effects obtained using hyperosmotic stress. The crowding increase is not due to osmotic pressure, cell shape, crowder synthesis, or volume changes, and therefore not crowder concentration. Instead, a genetically-encoded nucleic acid stain and a small molecule DNA stain show nucleoid expansion and cytoplasmic mixing, which could cause these increased crowding effects. Our data demonstrate that cell stress from antibiotics or cell wall damage alters the biochemical organization in the cytoplasm and induces significant conformational changes in a probe protein.
Capsaicin-induced endocytosis of endogenous presynaptic CaV2.2 in DRG-spinal cord co-cultures inhibits presynaptic function
Authors: Ramgoolam Krishma H , Dolphin Annette C 
Published: October 2022

AbstractThe N-type calcium channel, CaV2.2 is key to neurotransmission from the primary afferent terminals of dorsal root ganglion (DRG) neurons to their post-synaptic targets in the spinal cord. In this study we have utilized CaV2.2_HA knock-in mice, because the exofacial epitope tag in CaV2.2_HA enables accurate detection and localization of endogenous CaV2.2. CaV2.2_HA knock-in mice were used as a source of DRGs to exclusively study the presynaptic expression of N-type calcium channels in co-cultures between DRG neurons and wild-type spinal cord neurons. CaV2.2_HA is strongly expressed on the cell surface, particularly in TRPV1-positive small and medium DRG neurons. Super-resolution images of the presynaptic terminals revealed an increase in CaV2.2_HA expression and increased association with the post-synaptic marker Homer over time in vitro. Brief application of the TRPV1 agonist, capsaicin, resulted in a significant down-regulation of cell surface CaV2.2_HA expression in DRG neuron somata. At their presynaptic terminals, capsaicin caused a reduction in CaV2.2_HA proximity to and co-localization with the active zone marker RIM 1/2, as well as a lower contribution of N-type channels to single action potential-mediated Ca2+ influx. The mechanism of this down-regulation of CaV2.2_HA involves a Rab 11a-dependent trafficking process, since dominant-negative Rab11a(S25N) occludes the effect of capsaicin on presynaptic CaV2.2_HA expression, and also prevents the effect of capsaicin on action potential induced Ca2+ influx. Taken together, these data suggest that capsaicin causes a decrease in cell surface CaV2.2_HA expression in DRG terminals via a Rab11a-dependent endosomal trafficking pathway.
What moves when mice move a single whisker to touch? Individuality and stereotypy in behavior
Authors: Staab Marcel , Sehara Keisuke , Bahr Nora-Laurine , Dominiak Sina E. , Larkum Matthew E. , Sachdev Robert N. S. 
Published: October 2022

AbstractA key function of the brain is to move the body through a rich, complex environment. When rodents engage their environment, they move their whiskers as they extract tactile information. Even though the study of whisking has a long history, the details of what mice move when they move a whisker actively to touch are still unknown. Here we trained head fixed mice in a simple go-cue task to move a whisker on one side of the face to touch a sensor and tracked facial movements. Our analysis shows that mice specifically control the movement of the whisker they use to touch and that as they move their whiskers, they move their nose and apply forces on the head-post in a manner that reflects the behavioral epoch. Importantly, mice controlled the setpoint, amplitude and frequency of movement of whiskers bilaterally and individually. Additionally, even though mice achieved the goal of the task -- to touch the sensor within 2 seconds -- how they did so, how they coordinated movement of the nose and forces on head post with movement of individual whiskers was stereotyped, specific and related to the distance they needed to move a whisker to touch the sensor. Our work shows how stereotyped mouse behavior can be, and it emphasizes both the level of fine motor control mice can exert over individual whiskers and the extent of facial movements in a goal directed whisking-to-touch task.
Rapid Cell Type-Specific Nascent Proteome Labeling in Drosophila
Authors: Villalobos-Cantor Stefanny , Barrett Ruth M. , Condon Alec F. , Arreola-Bustos Alicia , Rodriguez Kelsie M. , Cohen Michael S. , Martin Ian 
Published: October 2022

ABSTRACTControlled protein synthesis is required to regulate gene expression and is often carried out in a cell type-specific manner. Protein synthesis is commonly measured by labeling the nascent proteome with amino acid analogs or isotope-containing amino acids. These methods have been difficult to implement in vivo as they require lengthy amino acid replacement procedures. O-propargyl-puromycin (OPP) is a puromycin analog that incorporates into nascent polypeptide chains. Through its terminal alkyne, OPP can be conjugated to a fluorophore-azide for directly visualizing nascent protein synthesis, or to a biotin-azide for capture and identification of newly-synthesized proteins. To achieve cell type-specific OPP incorporation, we developed phenylacetyl-OPP (PhAc-OPP), a puromycin analog harboring an enzyme-labile blocking group that can be removed by Penicillin G acylase (PGA). Here, we show that cell type-specific PGA expression in Drosophila can be used to achieve OPP labeling of newly-synthesized proteins in targeted cell populations within the brain. Following a brief 2-hour incubation of intact brains with PhAc-OPP, we observe robust imaging and affinity purification of OPP-labeled nascent proteins in PGA-targeted cell populations. We apply this method to show a pronounced age-related decline in neuronal protein synthesis in the fly brain, demonstrating the capability to quantitatively capture in vivo protein synthesis states using PhAc-OPP. This method, which we call POPPi (PGA-dependent OPP incorporation), should be applicable for rapidly visualizing protein synthesis and identifying nascent proteins synthesized under diverse physiological and pathological conditions with cellular specificity in vivo.
Host’s genetic background determines the outcome of reciprocal faecal transplantation on life-history traits and microbiome composition
Authors: Juottonen Heli , Moghadam Neda N. , Murphy Liam , Mappes Johanna , Galarza Juan A. 
Published: October 2022

AbstractBackgroundMicrobes play a role in fundamental ecological, chemical, and physiological processes of their host. Host life-history traits from defence to growth are therefore determined not only by abiotic environment and genotype but also by microbiota composition. However, the relative importance and interactive effects of these factors may vary between organisms. Such connections remain particularly elusive in Lepidoptera, which have been argued to lack a permanent microbiome and have microbiota primarily determined by their diet and environment.We tested the microbiome specificity and its influence on life-history traits of two colour genotypes of the wood tiger moth (Arctia plantaginis) that differ in several traits, including growth. All individuals were grown in the laboratory for several generations with standardised conditions. We analysed the bacterial community of the genotypes before and after a reciprocal frass (i.e., larval faeces) transplantation and followed growth rate, pupal mass, and the production of defensive secretion.ResultsAfter transplantation, the fast-growing genotype grew at a significantly slower rate compared to the controls, but the slow-growing genotype did not change its growth rate. The frass transplant also increased the volume of defensive secretions in the fast-growing genotype but did not affect pupal mass. Overall, the fast-growing genotype appeared more susceptible to the transplantation than the slow-growing genotype.Microbiome differences between the genotypes strongly suggest genotype-based selective filtering of bacteria from the diet and environment. A novel cluster of insect-associated Erysipelotrichaceae was exclusive to the fast-growing genotype, and specific Enterococcaceae were characteristic to the slow-growing genotype. These Enterococcaceae became more prevalent in the fast-growing genotype after the transplant, which suggests that the slower growth rate was potentially related to their presence.ConclusionsWe show that some genotype-specific life-history traits in a lepidopteran host can be reversed by a reciprocal frass transplantation. The results indicate that genotype-specific selective filtering can fine-tune the bacterial community at specific life stages, particularly the larval gut, even against a background of a highly variable community with stochastic assembly. Altogether, our findings suggest that the genotype of the host can influence its susceptibility to be colonized by microbiota with impact on key life-history traits.
Proteomics analysis of autophagy cargos reveals distinct adaptations in PINK1 and LRRK2 models of Parkinson disease
Authors: Goldsmith Juliet , Ordureau Alban , Boecker CA C Alexander , Arany Madeleine , Harper J Wade , Holzbaur Erika LF 
Published: October 2022

ABSTRACTAutophagy is essential for neuronal homeostasis, while defects in autophagy are implicated in Parkinson disease (PD), a prevalent and progressive neurodegenerative disorder. We used unbiased proteomics to compare cargos degraded by basal autophagy in the brain from two mouse models of PD, PINK1-/-and LRRK2G2019Smice. We find evidence for the upregulation of adaptive pathways to support homeostasis in both PD models. In PINK1-/-mice, we observed increased expression of the selective receptor BNIP3 along with evidence of engagement of other alternative pathways for mitophagy. Despite these changes, we find the rate of autophagic flux in PINK1-/-neurons is decreased. In LRRK2G2019Smice, hyperactive kinase activity known to impair autophagosomal and lysosomal function results in increased secretion of extracellular vesicles and autophagy cargo. In support of this observation, we find reduced levels of PIKFYVE, a negative regulator of extracellular vesicle secretion, in both brain and cortical neurons from LRRK2G2019Smice. Thus, distinct adaptive pathways are activated to compensate for perturbations induced by either loss of PINK1 or hyperactivation of LRRK2. Our findings highlight the engagement of compensatory pathways to maintain homeostasis in the brain, and provide insights into the vulnerabilities these compensatory changes may introduce that may further contribute to PD progression.
A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – Implications for Long COVID?
Authors: Haunhorst Simon , Bloch Wilhelm , Javelle Florian , Krüger Karsten , Baumgart Sabine , Drube Sebastian , Lemhöfer Christina , Reuken Philipp , Stallmach Andreas , Müller Michael , Zielinski Christina E. , Pletz Mathias W. , Gabriel Holger H.W. , Puta Christian 
Published: October 2022

AbstractBackgroundRecovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms.ObjectiveThe aim of this scoping review was to investigate if regulatory T cell (Treg) dysregulation is observable beyond the acute illness and if it might be involved in Long COVID immunopathology.DesignA systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science.ResultsThe literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome’s etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population.ConclusionsPersistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.