bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sut-6/NIPP1 modulates tau toxicity
Authors: Kow R L , Black A H , Henderson B P , Kraemer B C 
Published: March 2023

Abstract
Neurodegenerative diseases exhibiting the pathological accumulation of tau such as Alzheimer’s disease and related disorders still have no disease-modifying treatments and the molecular mechanisms of neurodegeneration remain unclear. To discover additional suppressor of tauopathy (sut) genes that mediate or modulate the toxicity of pathological tau, we performed a classical genetic screen using a tau transgenic Caenorhabditis elegans model. From this screen, we identified the suppressing mutation W292X in sut-6, the C. elegans homolog of human NIPP1, which truncates the C-terminal RNA-binding domain. Using CRISPR-based genome editing approaches, we generated null and additional C-terminally truncated alleles in sut-6 and found that loss of sut-6 or sut-6(W292X) suppresses tau-induced behavioral locomotor deficits, tau protein accumulation and neuron loss. The sut-6(W292X) mutation showed stronger and semi-dominant suppression of tau toxicity while sut-6 deletion acted recessively. Neuronal overexpression of SUT-6 protein did not significantly alter tau toxicity, but neuronal overexpression of SUT-6 W292X mutant protein reduced tau-mediated deficits. Epistasis studies showed tauopathy suppression by sut-6 occurs independent of other known nuclear speckle-localized suppressors of tau such as sut-2, aly-1/aly-3 and spop-1. In summary, we have shown that sut-6/NIPP1 modulates tau toxicity and found a dominant mutation in the RNA-binding domain of sut-6 which strongly suppresses tau toxicity. This suggests that altering RNA-related functions of SUT-6/NIPP1 instead of complete loss of SUT-6/NIPP1 will provide the strongest suppression of tau.
Terrestrial fatty acids from feed oil in feed for farmed salmonids are transferred to the liver, gonads, and muscle of wild Atlantic cod (Gadus morhua)
Authors: Meier Sonnich , van der Meeren Terje , Skjæraasen Jon Egil , Bannister Raymond J , Rasinger Josef Daniel , Karlsen Ørjan 
Published: March 2023

Abstract
Wild fish attracted to salmon farms feed on waste feed that presently contain high levels of fatty acids of terrestrial origin. This study examines whether mature Atlantic cod (Gadus morhua) caught at spawning grounds has eaten salmon waste feed. Cod were caught at four spawning grounds around Smøla (Norway), an area with multiple salmon farms, during the spawning season in 2018 (n = 327) and 2019 (n = 488). The fatty acid (FA) profile of their livers, gonads (ovary and testis), and muscles (2019) were determined. Multivariate k-mean cluster analysis of liver FA profiles revealed three main clusters, which could be allocated to trophic niches using known fatty acid trophic markers (FATMs). Of the sampled cod in 2018 and 2019, 13 % and 20 % respectively had high liver concentrations of terrestrial FATMs (18:1n-9, 18:2n-6, and 18:3n-3), indicating waste feed feeding. The remaining cod could be assigned to either the pelagic or benthic food chain. The cod identified as feeding on waste feed had large, fatty livers. The terrestrial FAs were also transferred to the muscle and gonad lipids. It is postulated that the latter may result in gametes with sub-optimal lipid composition, potentially impacting fitness, which warrants further investigation.
Torsion Motives
Authors: Vishik Alexander 
Published: March 2023

Abstract
In this paper, we study Chow motives whose identity map is killed by a natural number. Examples of such objects were constructed by Gorchinskiy and Orlov [ 10]. We introduce various invariants of torsion motives, in particular, the $p$-level. We show that this invariant bounds from below the dimension of the variety a torsion motive $M$ is a direct summand of and imposes restrictions on motivic and singular cohomology of $M$. We study in more details the $p$-torsion motives of surfaces, in particular, the Godeaux torsion motive. We show that such motives are in $1$-to-$1$ correspondence with certain Rost cycle submodules of free modules over $H^*_{et}$. This description is parallel to that of mod-$p$ reduced motives of curves.
The Continuity Equation on Hopf and Inoue Surfaces
Authors: Shen Xi Sisi , Smith Kevin 
Published: March 2023

Abstract
We study the continuity equation of La Nave–Tian, extended to the Hermitian setting by Sherman–Weinkove, on Hopf and Inoue surfaces. We prove a priori estimates for solutions in both cases and Gromov–Hausdorff convergence of Inoue surfaces to a circle.
Programmatic Implications of National Recent HIV Infection Surveillance in Cambodia
Authors: Suthar Amitabh Bipin , Ouk Vichea , Samreth Sovannarith , Ngauv Bora , Bain Rommel , Eng Bunthoeun , Hy Chhaily , Ernst Alexandra , Rutherford George W , Yang Chunfu , Ly Vanthy , Albalak Rachel 
Published: March 2023

Abstract
We compared characteristics of HIV diagnosis and recent HIV infection (ie, likely acquired within the last year) in Cambodia. We included individuals ≥ 15 years old accessing HIV testing. From August 2020 to August 2022, 53 031 people were tested for HIV, 6868 were newly diagnosed, and 192 were recently infected. We found differences in geographical burden and risk behaviors with diagnosis and recency (eg, men who have sex with men, transgender women, and entertainment workers had a nearly 2-fold increased odds of testing positive for recent infection compared to being diagnosed with HIV). Recent infection surveillance may provide unique insights into ongoing HIV acquisition to inform programs.
Forum: Making Peace with Un-Certainty: Reflections on the Role of Digital Technology in Peace Processes beyond the Data Hype
Authors: Hirblinger Andreas T , Wählisch Martin , Keator Kate , McNaboe Chris , Duursma Allard , Karlsrud John , Sticher Valerie , Verjee Aly , Kyselova Tetiana , Kwaja Chris M A , Perera Suda 
Published: March 2023

Abstract
Recent years have seen the acceleration of data- and evidence-based approaches in support of peace processes, creating a renewed confidence that conflicts can be predicted, known, and resolved, based on objective information about the world. However, new technologies employed by conflict parties, stakeholders, and those who aim to make or build peace have also made peace processes less ascertainable, intelligible, and predictable. Technology can thus create both more certainty and uncertainty in (and about) peace processes. This forum article presents a first collaborative attempt to explore how the use of technology by conflict parties and peacebuilding actors influences these dynamics. We examine various fields of engagement, ranging from conflict prevention to peace mediation, peacekeeping, and longer-term peacebuilding. Our discussion engages with a variety of related activities, including predictive analysis and foresight, conflict analysis, cease-fire monitoring, early warning and early action, and problem-solving and trust-building dialogues. We suggest approaching un-certainty as a spectrum between uncertainty and certainty that can be studied across epistemic, ontological, and normative dimensions, thus inviting further academic research and policy reflection. The article is coauthored by scholars and current or former practitioners and underlines the necessity, benefits, and feasibility of research–practice exchanges on this topic.
Emergence of KPC-3- and OXA-181-producing ST13 and ST17 Klebsiella pneumoniae in Portugal: genomic insights on national and international dissemination
Authors: Elias Rita , Spadar Anton , Hendrickx Antoni P A , Bonnin Remy A , Dortet Laurent , Pinto Margarida , Phelan Jody E , Portugal Isabel , Campino Susana , da Silva Gabriela Jorge , Clark Taane G , Duarte Aida , Perdigão João 
Published: March 2023

Abstract

Background
Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains are of particular concern, especially strains with mobilizable carbapenemase genes such as blaKPC, blaNDM or blaOXA-48, given that carbapenems are usually the last line drugs in the β-lactam class and, resistance to this sub-class is associated with increased mortality and frequently co-occurs with resistance to other antimicrobial classes.

Objectives
To characterize the genomic diversity and international dissemination of CRKP strains from tertiary care hospitals in Lisbon, Portugal.

Methods
Twenty CRKP isolates obtained from different patients were subjected to WGS for species confirmation, typing, drug resistance gene detection and phylogenetic reconstruction. Two additional genomic datasets were included for comparative purposes: 26 isolates (ST13, ST17 and ST231) from our collection and 64 internationally available genomic assemblies (ST13).

Results
By imposing a 21 SNP cut-off on pairwise comparisons we identified two genomic clusters (GCs): ST13/GC1 (n = 11), all bearing blaKPC-3, and ST17/GC2 (n = 4) harbouring blaOXA-181 and blaCTX-M-15 genes. The inclusion of the additional datasets allowed the expansion of GC1/ST13/KPC-3 to 23 isolates, all exclusively from Portugal, France and the Netherlands. The phylogenetic tree reinforced the importance of the GC1/KPC-3-producing clones along with their rapid emergence and expansion across these countries. The data obtained suggest that the ST13 branch emerged over a decade ago and only more recently did it underpin a stronger pulse of transmission in the studied population.

Conclusions
This study identifies an emerging OXA-181/ST17-producing strain in Portugal and highlights the ongoing international dissemination of a KPC-3/ST13-producing clone from Portugal.
The ketone body acetoacetate activates human neutrophils through FFAR2
Authors: Mårtensson Jonas , Björkman Lena , Lind Simon , Viklund Moa Bjerhem , Zhang Linjie , Gutierrez Saray , Dahlgren Claes , Sundqvist Martina , Xie Xin , Forsman Huamei 
Published: March 2023

Abstract
Neutrophils express many surface receptors that sense environmental changes. One such sensor is FFAR2 (free fatty acid receptor 2), a receptor that detects gut microbiota-derived short-chain fatty acids. As such, FFAR2 has been regarded as a molecular link between metabolism and inflammation. Our recent studies on FFAR2, using its endogenous agonist propionate in combination with allosteric modulators, have identified several novel aspects of FFAR2 regulation. A recent study has also identified the ketone body acetoacetate as an endogenous ligand for mouse FFAR2. Whether human FFAR2 also recognizes acetoacetate and how this recognition modulates human neutrophil functions has not been investigated. In this study, we found that acetoacetate can induce a decrease of cAMP and translocation of β-arrestin in cells overexpressing FFAR2. In addition, we show that similar to propionate, FFAR2-specific allosteric modulators enhance acetoacetate-induced transient rise in cytosolic calcium, production of reactive oxygen species, and cell migration in human neutrophils. In summary, we demonstrate that human neutrophils recognize the ketone body acetoacetate through FFAR2. Thus, our data further highlight the key role of FFAR2 in inflammation and metabolism.
Psilocybin
Authors: Rucker James J. , Erritzoe David 
Published: March 2023

Abstract
Psilocybin is a psychoactive drug found in a variety of mushroom species around the world. It induces an altered state of consciousness that has been used in ceremonial settings since antiquity. It is now known beyond doubt that the psychoactive effect of psilocybin (more particularly, its active metabolite psilocin) is due to a functionally selective effect on type 2A serotonin receptors found in the brain. Users of psilocybin reliably report visual misperceptions, mystical experiences, and heightened emotions that can range from elation and euphoria to (less frequently) panic and paranoia. Psilocybin is often legally designated as a drug with high potential for abuse, dependence, and harm. This is not supported by scientific evidence. Early phase clinical trials with psilocybin given in a comfortable, medically controlled setting suggest that, in combination with psychological support from trained therapists, it may have a clinically useful therapeutic effect in a variety of mental health problems, ranging from addictions to depression, with the best evidence thus far in treatment resistant depression. Meanwhile, societal narratives of hype and hyperbole around psilocybin are reminiscent of events in the 1960s that ultimately led to criminalization of nonmedical use. The results of later phase clinical trials of psilocybin therapy are awaited. Until then, we remain in a position of equipoise.
Live Like Nobody Is Watching
Authors: Ho Anita 
Published: March 2023

Abstract
Respect for patient autonomy and data privacy is generally accepted as one of the foundational Western bioethical values. Nonetheless, as our society embraces expanding forms of personal and health monitoring, particularly in the context of an aging population and the increasing prevalence of chronic diseases, questions abound how artificial intelligence (AI) may change the way we define or understand what it means to live a free and healthy life. Drawing on different use cases of AI health monitoring, this book explores the socio-relational contexts that frame the promotion of AI health monitoring, as well as the potential consequences of such monitoring for people’s autonomy. It argues that the evaluation, design, and implementation of AI health monitoring should be guided by a relational conception of autonomy, which addresses both people’s capacity to exercise their agency and broader issues of power asymmetry and social justice. It explores how interpersonal and socio-systemic conditions shape the cultural meanings of personal responsibility, healthy living/aging, trust, and caregiving. These norms in turn structure the ethical space within which expectations regarding predictive analytics, risk tolerance, privacy, self-care, and trust relationships are expressed. Through an analysis of home health monitoring for older and disabled adults, direct-to-consumer health monitoring devices, and medication adherence monitoring, this book proposes ethical strategies at both the professional and systemic levels that can help preserve and promote people’s relational autonomy in the digital era.
Spine-Related Procedures
Authors: Ghaly Mary , Zaky Sherif 
Published: March 2023

Abstract
Neuraxial anesthesia types (i.e., epidural, spinal, and caudal anesthesia) are the most commonly used regional anesthetic techniques. These techniques not only provide means for anesthesia during surgery but also are commonly used for perioperative analgesia, in-labor analgesia, and chronic pain management. Preoperative evaluation is crucial and involves detailed history and examination as well as evaluation for contraindications. Different approaches are described and are dictated by a patient’s anatomy and medical condition. Midline is the most common approach used for spinal, epidural, and combined spinal epidural anesthesia. The paramedian approach has its advantages and can be used alternatively. The paramedian approach bypasses supraspinal and interspinal ligaments and provides direct access to the ligamentum flavum. The caudal epidural is commonly used in the pediatric population and chronic pain management. A transforaminal approach provides a more selective epidural spread in some painful conditions, such as lumbar radiculopathy and postlaminectomy syndrome. Axial low back pain due to facet arthropathy can be managed by facet joint injection or medial branch blocks, which are usually done under fluoroscopy. Ultrasound guidance is becoming more popular as it provides additional safety and improved accuracy during performance of regional anesthesia.
Clinical Pearls and Red Flags
Authors: Bernstein Carolyn , Begasse de Dhaem Olivia 
Published: March 2023

Abstract
A good history is crucial. Listen to the patient uninterrupted first. Assess whether the headache is new and/or different. Look for the presence of “red flags.” Red flags can be remembered with the SNNOOP10 and SAIL mnemonics. If any, obtain work-up such as brain MRI rapidly. Most of headache diagnoses are made based on history. Patients recording headache days, symptoms, and medication use on a calendar is very helpful longitudinal data for both diagnostic purposes and monitoring. Make sure you address the patients’ expectations of their visit. Screen for aura and ask about exogenous estrogen use. Evaluate for and address comorbidities and risk factors for migraine chronification.
“Why Do I Have So Many Headaches?”
Authors: Murinova Natalia 
Published: March 2023

Abstract
Chronic migraine (CM) is a disabling headache condition characterized by the International Classification of Headache Disorders 3rd edition (ICHD-3) as primary headache with at least 15 headache days a month for the past 3 months, of which at least 8 are migraine. The difference between episodic migraine and chronic migraine is how many days per month the headache occurs. In the United States, approximately 1 out of 100 adults suffer from CM. Patients with CM have lower health-related quality of life and higher comorbid medical conditions like anxiety and depression and sleep disorders compared to patients with episodic migraine. CM is a leading cause of suffering and disability. Since 2018 we have seen an explosion of new treatments for patients with CM, and more are on the way. We have new, exciting drugs such as anti-CGRP antibodies, gepants, and ditans, as well as many new neuromodulation options.
Half of My Head Hurts
Authors: Kanaan Saad 
Published: March 2023

Abstract
The chapter “Half of My Head Hurts” examines the diagnosis, differential diagnosis, evaluation, and management of hemicrania continua. Hemicrania continua is an uncommon headache disorder that belongs to the family of trigeminal autonomic cephalalgias (TACs) which all have many features in common including the location of the pain in the distribution of the V1 (ophthalmic) division of the trigeminal nerve, the side-locked nature of the pain, and the associated autonomic symptoms ipsilateral to the headache including conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhea, eyelid edema, forehead and facial sweating, and miosis and/or ptosis. The most important distinguishing feature of hemicrania continua is the constant, albeit fluctuating, nature of the pain, which differentiates it from other TACs. Another important distinguishing feature is its exquisite response to indomethacin, which can differentiate it from chronic migraine and chronic cluster headache. There are reports of secondary hemicrania continua due to cerebral vascular malformations or neoplastic etiologies, and head imaging should therefore be considered for all cases of hemicrania continua.
“Itis” Means There Is Inflammation Somewhere . . .
Authors: Orlova Yulia , Buchowicz Bryce 
Published: March 2023

Abstract
A new onset of headache in older individual should raise the concern for secondary cause, and when associated with transient visual loss and jaw claudication, giant cell arteritis (GCA) should be considered. CGA is a chronic systemic vasculitis that can involve cranial or extracranial vessels and is related to polymyalgia rheumatica. Clinical symptoms of GCA are related to inflammatory state and ischemic complications of medium and large arteries vasculitis. Cranial form GCA commonly affects temporal, ophthalmic, ciliary, and posterior occipital arteries. Headache is common in this form but is nonspecific and not sufficient to establish diagnosis. Patients with extracranial form of GCA are less likely to have headache. Diagnostic challenges, including role of inflammatory markers, temporal artery biopsy, and advanced vascular imaging are discussed. Treatment with steroids and indications for steroid-sparing therapies such as methotrexate and tocilizumab are reviewed.
In Search of a Durable Dural Patch
Authors: Haight Elena , Carroll Ian 
Published: March 2023

Abstract
Cerebrospinal fluid (CSF) leaks are a cause of severe chronic headache, often accompanied by neck pain, hearing alterations, tinnitus, vertigo, nausea, difficulty with memory or concentration, and fatigue. When chronic, CSF leaks often appear quite different from acute post–dural puncture headaches. Most importantly, the orthostatic nature of the headache is less prominent. The varied presentation between acute and chronic CSF leaks, and low awareness for their ability to occur atraumatically and in the absence of a dural puncture, creates the opportunity for CSF leaks to evade diagnosis—typically for years before being accurately diagnosed. While an acute CSF leak typically presents as a severe orthostatic headache, chronic CSF leak may present as a second-half of the day headache, exertional headache, non-orthostatic chronic daily headache, thunderclap headache, or even a reverse orthostatic headache. The combination of severe head pain and nausea may cause the patient to be diagnosed with chronic migraine. Yet patients with CSF leaks can benefit from, and even find total resolution with, epidural blood patching or surgery. In this chapter we explore the case of a patient presenting with a chronic CSF leak characterized by persistent headaches, nausea and vomiting, and tachycardia following an unintended dural puncture.
Unexpected Findings in the Sella
Authors: Kaiser Eric A. 
Published: March 2023

Abstract
The book chapter “Unexpected Findings in the Sella” examines how to approach an incidental finding of pituitary adenoma in a patient presenting with headache. It reviews the epidemiology and differential diagnosis of pituitary lesions. It discusses the potential complications of pituitary adenomas, especially lesions &gt;10 mm. The chapter provides recommendations on additional work-up including which hormones levels to measure to determine if the adenoma is oversecreting or causing hypopituitarism. It also reviews when to check visual fields, refer to endocrinology for further work-up and medical management, or refer to neurosurgery for transsphenoidal resection, as well as how to monitor for tumor growth with repeat MR imaging. It also discusses the challenges of determining whether the headache is secondary to the pituitary lesion, and how headache may present like a primary headache disorder such as migraine or trigeminal autonomic cephalalgias (TAC).
Improving Spatial and Elemental Associations in Analytical Field Ion Microscopy
Authors: F. Morgado Felipe , Stephenson Leigh , Rousseau Loic , Vurpillot François , Evertz Simon , Schneider Jochen M , Gault Baptiste 
Published: March 2023

Abstract
Chemically resolved atomic resolution imaging can give fundamental information about material properties. However, even today, a technique capable of such achievement is still only an ambition. Here, we take further steps in developing the analytical field ion microscopy (aFIM), which combines the atomic spatial resolution of field ion microscopy (FIM) with the time-of-flight spectrometry of atom probe tomography (APT). To improve the performance of aFIM that are limited in part by a high level of background, we implement bespoke flight path time-of-flight corrections normalized by the ion flight distances traversed in electrostatic simulations modeled explicitly for an atom probe chamber. We demonstrate effective filtering in the field evaporation events upon spatially and temporally correlated multiples, increasing the mass spectrum's signal-to-background. In an analysis of pure tungsten, mass peaks pertaining to individual W isotopes can be distinguished and identified, with the signal-to-background improving by three orders of magnitude over the raw data. We also use these algorithms for the analysis of a CoTaB amorphous film to demonstrate application of aFIM beyond pure metals and binary alloys. These approaches facilitate elemental identification of the FIM-imaged surface atoms, making analytical FIM more precise and reliable.