bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decolonizing Middle East anthropology
Authors: Bishara Amahl 
Published: July 2023

AbstractIn the anthropology of Southwest Asia and North Africa (SWANA), there is an effort underway to decolonize the field. This process is taking shape in academic writing, in academic institutions, in field practices, and among broader publics. It must arise from priorities in the region; it also builds on wider scholarship on race, indigeneity, and militarism. It requires an expansion of the bounds of politics, consideration of who can participate, and reconsideration of what the goals of political action are. It entails working toward liberations that are always plural. Decolonizing SWANA anthropology faces distinct challenges in the field, the university, and publication processes because scholars produce critiques that expose contemporary colonialisms, including those related to the long war on terror, Israeli settler colonialism, and other colonialisms in the region. Thus, scholars equip themselves with tools to confront and transform academic institutions. Collaborative research designed to produce change can be an important part of decolonizing anthropology, but such research is not possible across all settings.
The man‐eaters of Tsavo and the untapped potential of natural history collections
Authors: Patterson Bruce D. 
Published: July 2023

AbstractOne of the best‐known exhibits at Chicago's Field Museum of Natural History features the man‐eating lions of Tsavo. Over a period of nine months in 1898, this pair of lions systematically hunted, killed and consumed railroad workers engaged in building a bridge over the Tsavo River in East Africa. The lions were eventually killed by an engineer, J. H. Patterson, who afterwards wrote a best‐selling book about the episode. His dramatic story has been retold in countless articles, books, and motion pictures, each more sensational and gory than the last. What parts are true? Fortunately, the lions' skins and skulls offer an independent and verifiable chronicle of events that actually transpired. These two specimens effectively re‐wrote their own history through the scientific research sparked by their notoriety, reminding us that the collections of natural history museums hold almost limitless potential to illuminate the world around us and its history.
Testing the interpersonal theory of suicide in adolescents: A multi‐wave longitudinal study
Authors: Pagliaccio David , Bitran Alma , Kirshenbaum Jaclyn S. , Alqueza Kira L. , Durham Katherine , Chernick Lauren S. , Joyce Karla , Lan Ranqing , Porta Giovanna , Brent David A. , Allen Nicholas B. , Auerbach Randy P. 
Published: July 2023

BackgroundSuicide is a major public health crisis among youth. Several prominent theories, including the Interpersonal Theory of Suicide (IPTS), aim to characterize the factors leading from suicide ideation to action. These theories are largely based on findings in adults and require testing and elaboration in adolescents.MethodsData were examined from high‐risk 13–18‐year‐old adolescents (N = 167) participating in a multi‐wave, longitudinal study; 63% of the sample exhibited current suicidal thoughts or recent behaviors (n = 105). The study included a 6‐month follow‐up period with clinical interviews and self‐report measures at each of the four assessments as well as weekly smartphone‐based assessments of suicidal thoughts and behaviors. Regression and structural equation models were used to probe hypotheses related to the core tenets of the IPTS.ResultsFeelings of perceived burdensomeness were associated with more severe self‐reported suicidal ideation (b = 0.58,t(158) = 7.64,p < .001). Similarly, burdensomeness was associated with more frequent ideation based on weekly smartphone ratings (b = 0.11,t(1460) = 3.41,p < .001). Contrary to IPTS hypotheses, neither feelings of thwarted belongingness, nor interactions between burdensomeness and thwarted belongingness were significantly associated with ideation (ps > .05). Only elevated depression severity was associated with greater odds of suicide events (i.e., suicide attempts, psychiatric hospitalizations, and/or emergency department visits for suicide concerns) during the follow‐up period (OR = 1.83,t(158) = 2.44,p = .01). No effect of acquired capability was found.ConclusionsPerceptions of burdensomeness to others reflect a critical risk factor for suicidal ideation among high‐risk adolescents. Null findings with other IPTS constructs may suggest a need to adopt more developmentally sensitive models or measures of interpersonal and acquired capability risk factors for youth. Refining methods and theoretical models of suicide risk may help improve the identification of high‐risk cases and inform clinical intervention.
Personality, self‐knowledge, and meat reduction intentions
Authors: Hopwood Christopher J. , Stahlmann Alexander G. , Bleidorn Wiebke , Thielmann Isabel 
Published: July 2023

AbstractObjectiveMeat consumption has a host of serious negative consequences for nonhuman animals, underprivileged humans, and the natural environment. Several interventions have been developed to encourage meat reduction but to relatively limited effect. There is also a range of established predictors of meat consumption, but much less is known about the factors that predict intentions to reduce meat consumption. The goal of this study was to determine the roles of personality and self‐knowledge in meat reduction intentions.MethodIn this set of three preregistered studies, we tested brief interventions to encourage meat reduction intentions and examined personality predictors of intentions to reduce meat consumption.ResultsWe found no evidence that brief interventions with or without a self‐knowledge component had a meaningful effect on changing meat reduction intentions. However, we found robust evidence for relatively small associations between intending to eat less meat and high Openness to Experience, high Emotionality, and perceiving meat reduction as moral behaviors.ConclusionIndividual differences may be a more influential predictor of meat reduction intentions than brief interventions. Implications for promoting meat reduction are discussed.
High‐affinity iron uptake is required for optimal Epichloë festucae colonization of Lolium perenne and seed transmission
Authors: Zhang Wei , Forester Natasha T. , Applegate Emma R. , Liu Xinqi , Johnson Linda J. 
Published: July 2023

AbstractEpichloë festucae uses a siderophore‐mediated system to acquire iron, which is important to maintain endophyte–grass symbioses. Here we investigate the roles of the alternative iron acquisition system, reductive iron assimilation (RIA), via disruption of the fetC gene, which encodes a multicopper ferroxidase, either alone (i.e., ΔfetC) or in combination with disruption of the gene sidA, which encodes a siderophore biosynthesis enzyme (i.e., ΔfetC/ΔsidA). The phenotypic characteristics of these mutants were compared to ΔsidA and wild‐type (WT) strains during growth under axenic culture conditions (in culture) and in symbiosis with the host grass, perennial ryegrass (in planta). Under iron deficiency, the colony growth rate of ΔfetC was slightly slower than that of WT, while the growth of ΔsidA and ΔfetC/ΔsidA mutants was severely suppressed. Siderophore analyses indicated that ΔfetC mutants hyperaccumulate ferriepichloënin A (FEA) at low iron concentrations and ferricrocin and FEA at higher iron concentrations. When compared to WT, all mutant strains displayed hyperbranching hyphal structures and a reduced ratio of Epichloë DNA to total DNA in planta. Furthermore, host colonization and vertical transmission through infection of the host seed were significantly reduced in the ΔfetC/ΔsidA mutants, confirming that high‐affinity iron uptake is a critical process for Epichloë transmission. Thus, RIA and siderophore iron uptake are complementary systems required for the maintenance of iron metabolism, fungal growth, and symbiosis between E. festucae and perennial ryegrass.
Risk mapping for Taenia solium: Applying multicriteria decision analysis in Lao PDR
Authors: Larkins Andrew , Bruce Mieghan , Phetsouvanh Rattanxay , Ash Amanda 
Published: July 2023

AbstractObjectivesTaenia solium is ranked the most significant global foodborne parasite and the leading cause of epilepsy in low and middle‐income countries. Diagnostic challenges have hampered disease control efforts to date and WHO has called for the development of risk mapping tools to assist endemic countries. This study describes the application of multicriteria decision analysis to map the risk of T. solium in Lao PDR and acts as a case study for other endemic countries.MethodsMulticriteria decision analysis was completed using census data on relevant risk factors in Lao PDR. Factors were weighted using an analytical hierarchy process. Village risk scores were calculated using a weighted linear combination and categorised using the Fisher‐Jenks algorithm into low, medium, and high risk. District risk scores and categories were calculated using the mean village risk score for a district. Sensitivity analysis was completed by doubling and halving risk factor weights, one at a time, and assessing the standard deviation of scores and categories across all scenarios.ResultsA total of 2017 (23.7%) villages were classified as high risk, with 3312 (39.0%) medium and 3170 (37.3%) low risk. This resulted in 21 (14.2%) high‐risk districts, 83 (56.1%) medium and 44 (29.7%) low‐risk districts. The risk maps highlight two areas of interest which are high risk and low variation. The first is the northern province of Phongsaly, which is consistent with literature and anecdotal reports. The second is the southern Salavan and Xekong provinces, which have yet to be investigated in detail.ConclusionsMulticriteria decision analysis has provided a simple, rapid, and flexible approach to mapping the risk of T. solium in Lao PDR. The nature of the method means that it can be completed in any endemic country with available and appropriate risk factor data.
What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria
Authors: Dasí Albert , Pope Michael T.B. , Wijesurendra Rohan S. , Betts Tim R. , Sachetto Rafael , Bueno‐Orovio Alfonso , Rodriguez Blanca 
Published: July 2023

AbstractThe best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti‐arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG. AF sustained in 494 (62%) atria, with large inward rectifier K+ current (IK1) and Na+/K+ pump (INaK) densities (IK1 0.11 ± 0.03 vs. 0.07 ± 0.03 S mF–1; INaK 0.68 ± 0.15 vs. 0.38 ± 26 S mF–1; sustained vs. un‐sustained AF). In severely remodelled left atrium, with LVA extensions of more than 40% in the posterior wall, higher IK1 (median density 0.12 ± 0.02 S mF–1) was required for AF maintenance, and rotors localized in healthy right atrium. For lower LVA extensions, rotors could also anchor to LVA, in atria presenting short refractoriness (median L‐type Ca2+ current, ICaL, density 0.08 ± 0.03 S mF–1). This atrial refractoriness, modulated by ICaL and fast Na+ current (INa), determined pharmacological treatment success for both small and large LVA. Vernakalant was effective in atria presenting long refractoriness (median ICaL density 0.13 ± 0.05 S mF–1). For short refractoriness, atria with high INa (median density 8.92 ± 2.59 S mF–1) responded more favourably to amiodarone than flecainide, and the opposite was found in atria with low INa (median density 5.33 ± 1.41 S mF–1). In silico drug trials in 800 human atria identify inward currents as critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics.
imageKey points
Atrial fibrillation (AF) maintenance is facilitated by small L‐type Ca2+ current (ICaL) and large inward rectifier K+ current (IK1) and Na+/K+ pump.
In severely remodelled left atrium, with low voltage areas (LVA) covering more than 40% of the posterior wall, sustained AF requires higher IK1 and rotors localize in healthy right atrium. For lower LVA extensions, rotors can also anchor to LVA, if the atria present short refractoriness (low ICaL)
Vernakalant is effective in atria presenting long refractoriness (high ICaL). For short refractoriness, atria with fast Na+ current (INa) up‐regulation respond more favourably to amiodarone than flecainide, and the opposite is found in atria with low INa.
The inward currents (ICaL and INa) are critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics.
Dual localization of receptor-type adenylate cyclases and cAMP response protein 3 unveils the presence of two putative signaling microdomains in
Trypanosoma cruzi
Authors: Chiurillo Miguel A. , Carlson Joshua , Bertolini Mayara S. , Raja Aqsa , Lander Noelia 
Published: July 2023

ABSTRACT

Trypanosoma cruzi
is the etiologic agent of Chagas disease, a leading cause of disability and premature death in the Americas. This parasite spends its life between a triatomine insect and a mammalian host, transitioning between developmental stages in response to microenvironmental changes. Among the second messengers driving differentiation in
T. cruzi
, cAMP has been shown to mediate metacyclogenesis and response to osmotic stress, but this signaling pathway remains largely unexplored in this parasite. Adenylate cyclases (ACs) catalyze the conversion of ATP to cAMP. They comprise a multigene family encoding putative receptor-type ACs in
T. cruzi
. Using protein sequence alignment, we classified them into five groups and chose a representative member from each group to study their localization (TcAC1–TcAC5). We expressed an HA-tagged version of each protein in
T. cruzi
and performed immunofluorescence analysis. A peculiar dual localization of TcAC1 and TcAC2 was observed in the flagellar distal domain and in the contractile vacuole complex (CVC), and their enzymatic activity was confirmed by gene complementation in yeast. Furthermore, TcAC1 overexpressing parasites showed an increased metacyclogenesis, a defect in host cell invasion, and a reduced intracellular replication, highlighting the importance of this protein throughout
T. cruzi
life cycle. These mutants were more tolerant to hypoosmotic stress and showed a higher adhesion capacity during
in vitro
metacyclogenesis, whereas the wild-type phenotype was restored after disrupting TcAC1 localization. Finally, TcAC1 was found to interact with cAMP response protein 3 (TcCARP3), co-localizing with this protein in the flagellar tip and CVC.

IMPORTANCE

We identified three components of the cAMP signaling pathway (TcAC1, TcAC2, and TcCARP3) with dual localization in
Trypanosoma cruzi
: the flagellar distal domain and the CVC, structures involved in cell adhesion and osmoregulation, respectively. We found evidence on the role of TcAC1 in both cellular processes, as well as in metacyclogenesis. Our data suggest that TcACs act as signal sensors and transducers through cAMP synthesis in membrane microdomains. We propose a model in which TcACs sense the harsh conditions in the triatomine hindgut (nutrient deprivation, acidic pH, osmotic stress, ionic composition, hydrophobic interactions) and become active. Synthesis of cAMP then triggers cell adhesion prior completion of metacyclogenesis
,
while mediating a response to osmotic stress in the parasite. These results shed light into the mechanisms driving cAMP-mediated cell differentiation in
T. cruzi
, while raising new questions on the activation of TcACs and the role of downstream components of this pathway.
IMPemBra: a phase 2 study comparing pembrolizumab with intermittent/short-term dual MAPK pathway inhibition plus pembrolizumab in patients with melanoma harboring the BRAFV600 mutation
Authors: Rozeman Elisa A , Versluis Judith M , Sikorska Karolina , Hoefsmit Esmée P , Dimitriadis Petros , Rao Disha , Lacroix Ruben , Grijpink-Ongering Lindsay G , Lopez-Yurda Marta , Heeres Birthe C , van de Wiel Bart A , Flohil Claudie , Sari Aysegul , Heijmink Stijn W T P J , van den Broek Daan , Broeks Annegien , de Groot Jan Willem B , Vollebergh Marieke A , Wilgenhof Sofie , van Thienen Johannes V , Haanen John B A G , Blank Christian U 
Published: July 2023

BackgroundContinuous combination of MAPK pathway inhibition (MAPKi) and anti-programmed death-(ligand) 1 (PD-(L)1) showed high response rates, but only limited improvement in progression-free survival (PFS) at the cost of a high frequency of treatment-related adverse events (TRAE) in patients with BRAFV600-mutated melanoma. Short‐term MAPKi induces T-cell infiltration in patients and is synergistic with anti-programmed death-1 (PD‐1) in a preclinical melanoma mouse model. The aim of this phase 2b trial was to identify an optimal regimen of short-term MAPKi with dabrafenib plus trametinib in combination with pembrolizumab.MethodsPatients with treatment-naïve BRAFV600E/K-mutant advanced melanoma started pembrolizumab 200 mg every 3 weeks. In week 6, patients were randomized to continue pembrolizumab only (cohort 1), or to receive, in addition, intermittent dabrafenib 150 mg two times per day plus trametinib 2 mg one time per day for two cycles of 1 week (cohort 2), two cycles of 2 weeks (cohort 3), or continuously for 6 weeks (cohort 4). All cohorts continued pembrolizumab for up to 2 years. Primary endpoints were safety and treatment-adherence. Secondary endpoints were objective response rate (ORR) at week 6, 12, 18 and PFS.ResultsBetween June 2016 and August 2018, 33 patients with advanced melanoma have been included and 32 were randomized. Grade 3–4 TRAE were observed in 12%, 12%, 50%, and 63% of patients in cohort 1, 2, 3, and 4, respectively. All planned targeted therapy was given in 88%, 63%, and 38% of patients in cohort 2, 3, and 4. ORR at week 6, 12, and 18 were 38%, 63%, and 63% in cohort 1; 25%, 63%, and 75% in cohort 2; 25%, 50%, and 75% in cohort 3; and 0%, 63%, and 50% in cohort 4. After a median follow-up of 43.5 months, median PFS was 10.6 months for pembrolizumab monotherapy and not reached for patients treated with pembrolizumab and intermittent dabrafenib and trametinib (p=0.17). The 2-year and 3-year landmark PFS were both 25% for cohort 1, both 63% for cohort 2, 50% and 38% for cohort 3 and 75% and 60% for cohort 4.ConclusionsThe combination of pembrolizumab plus intermittent dabrafenib and trametinib seems more feasible and tolerable than continuous triple therapy. The efficacy is promising and appears to be favorable over pembrolizumab monotherapy.Trial registration numberNCT02625337.
IgA antibody immunotherapy targeting GD2 is effective in preclinical neuroblastoma models
Authors: Stip Marjolein C , Evers Mitchell , Nederend Maaike , Chan Chilam , Reiding Karli R , Damen Mirjam J , Heck Albert J R , Koustoulidou Sofia , Ramakers Ruud , Krijger Gerard C , de Roos Remmert , Souteyrand Edouard , Cornel Annelisa M , Dierselhuis Miranda P , Jansen Marco , de Boer Mark , Valerius Thomas , van Tetering Geert , Leusen Jeanette H W , Meyer-Wentrup Friederike 
Published: July 2023

BackgroundImmunotherapy targeting GD2 is very effective against high-risk neuroblastoma, though administration of anti-GD2 antibodies induces severe and dose-limiting neuropathic pain by binding GD2-expressing sensory neurons. Previously, the IgG1 ch14.18 (dinutuximab) antibody was reformatted into the IgA1 isotype, which abolishes neuropathic pain and induces efficient neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) via activation of the Fc alpha receptor (FcαRI/CD89).MethodsTo generate an antibody suitable for clinical application, we engineered an IgA molecule (named IgA3.0 ch14.18) with increased stability, mutated glycosylation sites and substituted free (reactive) cysteines. The following mutations were introduced: N45.2G and P124R (CH1 domain), C92S, N120T, I121L and T122S (CH2 domain) and a deletion of the tail piece P131-Y148 (CH3 domain). IgA3.0 ch14.18 was evaluated in binding assays and in ADCC and antibody-dependent cellular phagocytosis (ADCP) assays with human, neuroblastoma patient and non-human primate effector cells. We performed mass spectrometry analysis ofN-glycans and evaluated the impact of altered glycosylation in IgA3.0 ch14.18 on antibody half-life by performing pharmacokinetic (PK) studies in mice injected intravenously with 5 mg/kg antibody solution. A dose escalation study was performed to determine in vivo efficacy of IgA3.0 ch14.18 in an intraperitoneal mouse model using 9464D-GD2 neuroblastoma cells as well as in a subcutaneous human xenograft model using IMR32 neuroblastoma cells. Binding assays and PK studies were compared with one-way analysis of variance (ANOVA), ADCC and ADCP assays and in vivo tumor outgrowth with two-way ANOVA followed by Tukey’s post-hoc test.ResultsADCC and ADCP assays showed that particularly neutrophils and macrophages from healthy donors, non-human primates and patients with neuroblastoma are able to kill neuroblastoma tumor cells efficiently with IgA3.0 ch14.18. IgA3.0 ch14.18 contains a more favorable glycosylation pattern, corresponding to an increased antibody half-life in mice compared with IgA1 and IgA2. Furthermore, IgA3.0 ch14.18 penetrates neuroblastoma tumors in vivo and halts tumor outgrowth in both 9464D-GD2 and IMR32 long-term tumor models.ConclusionsIgA3.0 ch14.18 is a promising new therapy for neuroblastoma, showing (1) increased half-life compared to natural IgA antibodies, (2) increased protein stability enabling effortless production and purification, (3) potent CD89-mediated tumor killing in vitro by healthy subjects and patients with neuroblastoma and (4) antitumor efficacy in long-term mouse neuroblastoma models.
The spectral rank of an element in a ring
Authors: Askes Miles , Brits Rudi , Schulz Francois 
Published: July 2023

The concept of the spectral rank of an element in a ring is defined, and it is shown to be a genuine generalization of the same concept first studied in the setting of a Banach algebra. Furthermore, we prove that many of the desirable properties of this rank are still valid in the more abstract setting and give several examples to support and motivate the given definition. In particular, we are able to show that a nonzero idempotent of a semiprimitive and additively torsion-free ring is minimal if and only if it has a spectral rank of one. We also discover a precise connection between the spectral rank of an element in a ring and a purely algebraic definition of rank considered only recently by N. Stopar in [Rank of elements of general rings in connection with unit-regularity, J. Pure Appl. Algebra 224 (2020) 106211]. Specifically, we are able to show that if an element [Formula: see text] has a finite algebraic rank in a semiprimitive and additively torsion-free ring, then [Formula: see text] has the exact same spectral rank. An extra condition under which the converse holds true is also provided, and connections to the socle are identified. Finally, for both of these extended notions of rank considered in the setting of a ring, we prove a generalized Frobenius Inequality.