bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the abiotic factors that determine the inland range limits of a mesic-adapted lizard species
Authors: Farquhar Jules E , Russell Wyn , Chapple David G
Published: October 2023

Synopsis

For most species, the factors that determine geographical range limits are unknown. In mesic-adapted species, populations occurring near the edge of the species’ distribution provide ideal study systems to investigate what limits distributional ranges. We aimed to identify the abiotic constraints that preclude an east-Australian mesic-adapted lizard (Lampropholis delicata) from occupying arid environments. We performed lizard surveys at sites spanning an elevation/aridity gradient (380–1070 m) and measured the prevalence of habitat features (logs, rocks, leaf litter, bare ground, solar radiation) in addition to hourly temperatures in a variety of microhabitats available to lizards. Species distribution models (SDM) were used to identify the macroclimatic variables limiting the species’ distribution. At its inland range limit, L. delicata is associated with mesic high-elevation forests with complex microhabitat structures, which gradually decline in availability toward lower (and more arid) elevations where the species is absent. Moreover, L. delicata is absent from sites with a shallow leaf litter layer, in which daily temperatures exceed the species’ thermal preference range, which we determined in a laboratory thermal gradient. In regards to macroclimate, SDM revealed that temperature seasonality is the primary variable predicting the species’ distribution, suggesting that L. delicata avoids inland areas owing to their high annual thermal variability. By combining multiple lines of evidence, this research highlights that habitat and microclimate suitability—not solely macroclimate suitability—are important range-limiting factors for mesic ectotherms and should be incorporated in studies addressing range-limiting hypotheses.
Determinantal Varieties From Point Configurations on Hypersurfaces
Authors: Caminata Alessio , Moon Han-Bom , Schaffler Luca
Published: October 2023

We consider the scheme $X_{r,d,n}$ parameterizing $n$ ordered points in projective space $\mathbb {P}^{r}$ that lie on a common hypersurface of degree $d$. We show that this scheme has a determinantal structure, and we prove that it is irreducible, Cohen–Macaulay, and normal. Moreover, we give an algebraic and geometric description of the singular locus of $X_{r,d,n}$ in terms of Castelnuovo–Mumford regularity and $d$-normality. This yields a characterization of the singular locus of $X_{2,d,n}$ and $X_{3,2,n}$.
Adjunct Therapy With All-trans-Retinoic Acid Improves Therapeutic Efficacy Through Immunomodulation While Treating Tuberculosis With Antibiotics in Mice
Authors: Singh Baldeep , Pahuja Isha , Yadav Priyanka , Shaji Aishwarya , Chaturvedi Shivam , Ranganathan Anand , Dwivedi Ved Prakash , Das Gobardhan
Published: October 2023

Tuberculosis is the second leading infectious killer after coronavirus disease 2019 (COVID-19). Standard antitubercular drugs exhibit various limitations like toxicity, long treatment regimens, and lack of effect against dormant and drug-resistant organisms. Here, we report that all-trans-retinoic acid (ATRA) improves Mycobacterium tuberculosis clearance in mice during treatment with the antitubercular drug isoniazid. Interestingly, ATRA promoted activities of lysosomes and mitochondria, and production of various inflammatory mediators in macrophages. Furthermore, ATRA upregulated the expression of genes of lipid metabolism pathways in macrophages. We demonstrated that ATRA activated the MEK/ERK pathway in macrophages in vitro and MEK/ERK and p38 MAPK pathways in mice. Finally, ATRA induced both Th1 and Th17 responses in lungs and spleens of M. tuberculosis-infected mice. Together, these data indicate that ATRA provides beneficial adjunct therapeutic value by modulating MEK/ERK and p38 MAPK pathways and thus warrants further testing for human use.
Characterization of potential probiotic starter cultures of lactic acid bacteria isolated from Ethiopian fermented cereal beverages, Naaqe, and Cheka
Authors: Gizachew Seyoum , Van Beeck Wannes , Spacova Irina , Dekeukeleire Max , Alemu Ashenafi , Mihret Wude , Lebeer Sarah , Engidawork Ephrem
Published: October 2023

Aims

To test the in vitro probiotic potential and starter culture capacity of lactic acid bacteria (LAB) isolated from Naaqe and Cheka, cereal-based Ethiopian traditional fermented beverages.

Methods and results

A total of 44 strains were isolated from spontaneously fermented Ethiopian cereal-based beverages, Naaqe and Cheka with 24 putatively identified as LAB and 14 identified up to the species level. The species Limosilactobacillus fermentum (6/12; 50%) and Weissella confusa (5/12, 41.67%) were the predominant species identified from Naaqe, while the two Cheka isolates were L. fermentum and Pediococcus pentosaceus. Six LAB strains inhibited eight of the nine gastrointestinal indicator key pathogens in Ethiopia, including Escherichia coli, Salmonella enterica subsp. enterica var. Typhimurium, Staphylococcus aureus, Shigella flexneri, and Listeria monocytogenes. Three of the LAB isolates exhibited strain-specific immunostimulation in human monocytes. Based on these probiotic properties and growth, six strains were selected for in situ evaluation in a mock fermentation of Naaqe and Cheka. During primary fermentations, L. fermentum 73B, P. pentosaceus 74D, L. fermentum 44B, W. confusa 44D, L. fermentum 82C, and Weissella cibaria 83E and their combinations demonstrated higher pH-lowering properties and colony-forming unit counts compared to the control spontaneous fermentation. The same pattern was also observed in the secondary mock fermentation by the Naaqe LAB isolates.

Conclusions

In this study, we selected six LAB strains with antipathogenic, immunostimulatory, and starter culture potentials that can be used as autochthonous probiotic starters for Naaqe and Cheka fermentations once their health benefit is ascertained in a clinical trial as a next step.
Participant-guided development of bilingual genomic educational infographics for Electronic Medical Records and Genomics Phase IV study
Authors: Casillan Aimiel , Florido Michelle E , Galarza-Cornejo Jamie , Bakken Suzanne , Lynch John A , Chung Wendy K , Mittendorf Kathleen F , Berner Eta S , Connolly John J , Weng Chunhua , Holm Ingrid A , Khan Atlas , Kiryluk Krzysztof , Limdi Nita A , Petukhova Lynn , Sabatello Maya , Wynn Julia
Published: October 2023

Objective

Developing targeted, culturally competent educational materials is critical for participant understanding of engagement in a large genomic study that uses computational pipelines to produce genome-informed risk assessments.

Materials and Methods

Guided by the Smerecnik framework that theorizes understanding of multifactorial genetic disease through 3 knowledge types, we developed English and Spanish infographics for individuals enrolled in the Electronic Medical Records and Genomics Network. Infographics were developed to explain concepts in lay language and visualizations. We conducted iterative sessions using a modified “think-aloud” process with 10 participants (6 English, 4 Spanish-speaking) to explore comprehension of and attitudes towards the infographics.

Results

We found that all but one participant had “awareness knowledge” of genetic disease risk factors upon viewing the infographics. Many participants had difficulty with “how-to” knowledge of applying genetic risk factors to specific monogenic and polygenic risks. Participant attitudes towards the iteratively-refined infographics indicated that design saturation was reached.

Discussion

There were several elements that contributed to the participants’ comprehension (or misunderstanding) of the infographics. Visualization and iconography techniques best resonated with those who could draw on prior experiences or knowledge and were absent in those without. Limited graphicacy interfered with the understanding of absolute and relative risks when presented in graph format. Notably, narrative and storytelling theory that informed the creation of a vignette infographic was most accessible to all participants.

Conclusion

Engagement with the intended audience who can identify strengths and points for improvement of the intervention is necessary to the development of effective infographics.
Emergency Colorectal Surgery in Those with Cirrhosis: A Population-based Study Assessing Practice Patterns, Outcomes and Predictors of Mortality
Authors: Zhang Lisa , Brennan Kelly , Flemming Jennifer A , Nanji Sulaiman , Djerboua Maya , Merchant Shaila J , Caycedo-Marulanda Antonio , Patel Sunil V
Published: October 2023

Background

Those with cirrhosis who require emergency colorectal surgery are at risk for poor outcomes. Although risk predictions models exists, these tools are not specific to colorectal surgery, nor were they developed in a contemporary setting. Thus, the objective of this study was to assess the outcomes in this population and determine whether cirrhosis etiology and/or the Model for End Stage Liver Disease (MELD-Na) is associated with mortality.

Methods

This population-based study included those with cirrhosis undergoing emergent colorectal surgery between 2009 and 2017. All eligible individuals in Ontario were identified using administrative databases. The primary outcome was 90-day mortality.

Results

Nine hundred and twenty-seven individuals (57%) (male) were included. The most common cirrhosis etiology was non-alcoholic fatty liver disease (NAFLD) (50%) and alcohol related (32%). Overall 90-day mortality was 32%. Multivariable survival analysis demonstrated those with alcohol-related disease were at increased risk of 90-day mortality (hazards ratio [HR] 1.53, 95% confidence interval [CI] 1.2–2.0 vs. NAFLD [ref]). Surgery for colorectal cancer was associated with better survival (HR 0.27, 95%CI 0.16–0.47). In the subgroup analysis of those with an available MELD-Na score (n = 348/927, 38%), there was a strong association between increasing MELD-Na and mortality (score 20+ HR 6.6, 95%CI 3.9–10.9; score 10–19 HR 1.8, 95%CI 1.1–3.0; score <10 [ref]).

Conclusion

Individuals with cirrhosis who require emergent colorectal surgery have a high risk of postoperative complications, including mortality. Increasing MELD-Na score is associated with mortality and can be used to risk stratify individuals.
Cache Valley virus: an emerging arbovirus of public and veterinary health importance
Authors: Hughes Holly R , Kenney Joan L , Calvert Amanda E
Published: October 2023

Cache Valley virus (CVV) is a mosquito-borne virus in the genus Orthobunyavirus (Bunyavirales: Peribunyaviridae) that has been identified as a teratogen in ruminants causing fetal death and severe malformations during epizootics in the U.S. CVV has recently emerged as a viral pathogen causing severe disease in humans. Despite its emergence as a public health and agricultural concern, CVV has yet to be significantly studied by the scientific community. Limited information exists on CVV’s geographic distribution, ecological cycle, seroprevalence in humans and animals, and spectrum of disease, including its potential as a human teratogen. Here, we present what is known of CVV’s virology, ecology, and clinical disease in ruminants and humans. We discuss the current diagnostic techniques available and highlight gaps in our current knowledge and considerations for future research.
Emerging tickborne viruses vectored by Amblyomma americanum (Ixodida: Ixodidae): Heartland and Bourbon viruses
Authors: Dupuis Alan P , Lange Rachel E , Ciota Alexander T
Published: October 2023

Heartland (HRTV) and Bourbon (BRBV) viruses are newly identified tick-borne viruses, isolated from serious clinical cases in 2009 and 2014, respectively. Both viruses originated in the lower Midwest United States near the border of Missouri and Kansas, cause similar disease manifestations, and are presumably vectored by the same tick species, Amblyomma americanum Linnaeus (Ixodida: Ixodidae). In this article, we provide a current review of HRTV and BRBV, including the virology, epidemiology, and ecology of the viruses with an emphasis on the tick vector. We touch on current challenges of vector control and surveillance, and we discuss future directions in the study of these emergent pathogens.
Everglades virus: an underrecognized disease-causing subtype of Venezuelan equine encephalitis virus endemic to Florida, USA
Authors: Burkett-Cadena Nathan D , Fish Durland , Weaver Scott , Vittor Amy Y
Published: October 2023

Everglades virus (EVEV) is subtype II of the Venezuelan equine encephalitis virus (VEEV) complex (Togaviridae: Alphavirus), endemic to Florida, USA. EVEV belongs to a clade that includes both enzootic and epizootic/epidemic VEEV subtypes. Like other enzootic VEEV subtypes, muroid rodents are important vertebrate hosts for EVEV and certain mosquitoes are important vectors. The hispid cotton rat Sigmodon hispidus and cotton mouse Peromyscus gossypinus are important EVEV hosts, based on natural infection (virus isolation and high seropositivity), host competence (experimental infections), and frequency of contact with the vector. The mosquito Culex (Melanoconion) cecedei is the only confirmed vector of EVEV based upon high natural infection rates, efficient vector competence, and frequent feeding upon muroid rodents. Human disease attributed to EVEV is considered rare. However, cases of meningitis and encephalitis are recorded from multiple sites, separated by 250 km or more. Phylogenetic analyses indicate that EVEV is evolving, possibly due to changes in the mammal community. Mutations in the EVEV genome are of concern, given that epidemic strains of VEEV (subtypes IAB and IC) are derived from enzootic subtype ID, the closest genetic relative of EVEV. Should epizootic mutations arise in EVEV, the abundance of Aedes taeniorhynchus and other epizootic VEEV vectors in southern Florida provides a conducive environment for widespread transmission. Other factors that will likely influence the distribution and frequency of EVEV transmission include the establishment of Culex panocossa in Florida, Everglades restoration, mammal community decline due to the Burmese python, land use alteration by humans, and climate change.
The known unknowns of Powassan virus ecology
Authors: Brackney Doug E , Vogels Chantal B F
Published: October 2023

Powassan virus (POWV; Family: Flaviviridae, Genus: Flavivirus) is the sole North American member of the tick-borne encephalitis sero-complex. While associated with high rates of morbidity and mortality, POWV has historically been of little public health concern due to low incidence rates. However, over the last 20 yr, incidence rates have increased highlighting the growing epidemiological threat. Currently, there are no vaccines or therapeutics with tick habitat reduction, acaricide application, and public awareness programs being our primary means of intervention. The effectiveness of these control strategies is dependent on having a sound understanding of the virus’s ecology. In this Forum, we review what is currently known about POWV ecology, identify gaps in our knowledge, and discuss prevailing and alternative hypotheses about transmission dynamics, reservoir hosts, and spatial focality.
The increasing threat of Rift Valley fever virus globalization: strategic guidance for protection and preparation
Authors: Gibson Seth , Noronha Leela E , Tubbs Heidi , Cohnstaedt Lee W , Wilson William C , Mire Chad , Mitzel Dana , Anyamba Assaf , Rostal Melinda , Linthicum Kenneth J
Published: October 2023

Rift Valley fever virus (RVFV) (Bunyavirales: Phlebovirus) is a prominent vector-borne zoonotic disease threat to global agriculture and public health. Risks of introduction into nonendemic regions are tied to changing climate regimes and other dynamic environmental factors that are becoming more prevalent, as well as virus evolutionary factors and human/animal movement. Endemic to the African continent, RVFV has caused large epizootics at the decadal scale since the early 20th century but has spread to the Arabian Peninsula and shows increasing patterns of interepizootic transmission on the annual scale. This virus can be transmitted by mosquitoes as well as through direct contact with infected tissues and can cause sporadic to widespread morbidity and mortality in domestic ungulate livestock as well as humans. High viremias in infected livestock moved for legal and illegal trade as well as in infected mosquitoes or human travelers can spread this virus worldwide. With increasing global commerce, it is likely RVFV will be introduced to new areas with suitable hosts, mosquito vector species, and environments. However, the strong mosquito component of RVFV epidemiology combined with advancements in vaccines, diagnostics, and virus evolutionary factors create opportunities for strategies to leverage models of connectivity among potential source and emerging regions to target surveillance and mitigation activities to reduce the risk of RVFV introduction, or contain the virus should it be introduced, into new regions.
Temporal population genetic structure of Phormia regina (Diptera: Calliphoridae)
Authors: Owings Charity G , Banerjee Aniruddha , Picard Christine J
Published: October 2023

The genetic structure of forensically important blow fly (Brauer & Bergenstamm) (Diptera: Calliphoridae) populations has remained elusive despite high relatedness within wild-caught samples. This research aimed to determine if the implementation of a high-resolution spatiotemporal sampling design would reveal latent genetic structure among blow fly populations and to elucidate any environmental impacts on observed patterns of genetic structure. Adult females of the black blow fly, Phormia regina (Meigen) (Diptera: Calliphoridae), were collected from 9 urban parks in Indiana, USA over 3 yr and genotyped at 6 polymorphic microsatellite loci. The data analysis involved 3 clustering methods: principal coordinate analysis (PCoA), discriminant analysis of principal components (DAPC), and STRUCTURE. While the PCoA did not uncover any discernible clustering patterns, the DAPC and STRUCTURE analyses yielded significant results, with 9 and 4 genetic clusters, respectively. Visualization of the STRUCTURE bar plot revealed N = 11 temporal demarcations indicating barriers to gene flow. An analysis of molecular variance of these STRUCTURE-inferred populations supported strong temporally driven genetic differentiation (FST = 0.048, F’ST = 0.664) relative to geographic differentiation (FST = 0.009, F’ST = 0.241). Integrated Nested Laplace Approximation and Boosted Regression Tree analyses revealed that collection timepoint and 4 main abiotic factors (temperature, humidity, precipitation, and wind speed) were associated with the genetic subdivisions observed for P. regina. A complex interplay between environmental conditions, the unique reproductive strategies of the blow fly, and the extensive dispersal abilities of these organisms likely drives the strong genetic structure of P. regina in the Midwestern US.
National Cancer Institute funding for rapid cycle interventional research in cancer care delivery
Authors: Norton Wynne E , Neta Gila , Jacobsen Paul B
Published: October 2023

Background

Rapid cycle interventional research can accelerate improvements to cancer care delivery and patient health outcomes by answering multiple questions as part of a single research study. To complement ongoing efforts to increase awareness of and support for rapid cycle interventional research, we conducted a systematic portfolio analysis of research grants funded by the National Cancer Institute on the topic.

Methods

We used standard portfolio analytic methods for identifying, coding, and synthesizing rapid cycle interventional research funded by the National Cancer Institute between 2016 and 2022. A codebook was used to standardize assessment of the grants by common study characteristics, intervention topics, and cancer care delivery context.

Results

We identified 26 grants, mostly funded since 2019, as rapid cycle interventional research. Most studies included adult or older adult target populations, used electronic systems for intervention delivery, and focused primarily on testing different components of interventions. Studies also used a range of study designs, intervention content areas, cancer sites, and across the cancer control continuum.

Conclusions

The current portfolio analysis of funded rapid cycle interventional research grants suggests a growing albeit relatively small number of studies in this area. Several efforts are needed to continue to grow this area of research, including training programs, funding opportunities, and strengthening research-practice partnerships. This analysis provides a snapshot of current studies and highlights the opportunity for growing this important area of research to optimize cancer care delivery and improve patient outcomes.
An Analysis of Micro-scale Conflict in Collaborative Governance
Authors: Ulibarri Nicola
Published: October 2023

Conflict is the forgotten sibling of collaborative governance. Variably framed as an alternative to collaboration, a contextual feature shaping interpersonal interactions, or an obstacle to be overcome via deliberation, conflict lurks in the background of discourse about collaboration. However, few theories of collaboration directly address the role of conflict, and those that do focus on conflict as a macro-scale phenomenon, characteristic of a governance forum or participating organizations. Given the importance of short term, person-to-person interactions in shaping the overall trajectory of collaborative dynamics and outcomes, a micro-scale analysis of collaborative conflict is warranted. This article develops a framework for evaluating the role of micro-scale conflict in collaborative governance, drawing on the case of negotiations to relicense hydropower dams in the Central Valley of California, USA. Data sources include 4 years of meeting observations, interviews with participating stakeholders, and written comments submitted during the process. The work first classifies all instances of disagreement observed during the negotiations to develop a typology of micro-scale conflict. It then compares differences in the frequency, type, and management of disagreements in high and low collaboration relicensings to explore the interaction between conflict dynamics and overall collaborative approach. In the high collaboration case, interpersonal disagreements occurred frequently, were more dynamic and mutable over time, and served to elaborate and refine management approaches. By evaluating conflict dynamics that occur at the scale of an individual interaction and the positive and negative roles they play in shaping collaborative outcomes, this research moves conflict from being a static barrier or contextual factor to a dynamic ingredient that can be managed to shape policy outcomes.
A paradoxical internal hernia at Brolin’s anti-obstruction stitch following Roux-en-Y gastric bypass: a case report
Authors: Patel Krishna , Serapiglia Vinnie , Rizzo Anthony N , Varre Jaya , Sonnanstine Thomas
Published: October 2023

Internal hernias are a rare but morbid complication following Roux-en-Y gastric bypass surgery. The incorporation of Brolin’s anti-obstruction stitch has historically demonstrated a significant reduction in the incidence of internal hernias following Roux-en-Y gastric bypass. We present an ironic and unique case of a patient with small bowel herniation into a defect between Brolin’s stitch and the stapled closed common enterotomy of the jejunojejunostomy and technical considerations to decrease internal hernias at this site in the future.
Identification of short protein-destabilizing sequences in Arabidopsis cyclin-dependent kinase inhibitors, ICKs
Authors: Ye Shengjian , Wang Sheng , Chan Ron , Cao Ling , Wang Hong
Published: October 2023

Plants have a family of cyclin-dependent kinase (CDK) inhibitors called interactors/inhibitors of CDK (ICKs) or Kip-related proteins (KRPs). ICK proteins have important functions in cell proliferation, endoreduplication, plant growth, and reproductive development, and their functions depend on the protein levels. However, understanding of how ICK protein levels are regulated is very limited. We fused Arabidopsis ICK sequences to green fluorescent protein (GFP) and determined their effects on the fusion proteins in plants, yeast, and Escherichia coli. The N-terminal regions of ICKs drastically reduced GFP fusion protein levels in Arabidopsis plants. A number of short sequences of 10–20 residues were found to decrease GFP fusion protein levels when fused at the N-terminus or C-terminus. Three of the four short sequences from ICK3 showed a similar function in yeast. Intriguingly, three short sequences from ICK1 and ICK3 caused the degradation of the fusion proteins in E. coli. In addition, computational analyses showed that ICK proteins were mostly disordered and unstructured except for the conserved C-terminal region, suggesting that ICKs are intrinsically disordered proteins. This study has identified a number of short protein-destabilizing sequences, and evidence suggests that some of them may cause protein degradation through structural disorder and instability.
AstroSat observation of the magnetar SGR J1830−0645 during its first detected X-ray outburst
Authors: Sharma Rahul , Jain Chetana , Paul Biswajit , Seshadri T R
Published: October 2023

We present here timing and spectral analyses of SGR J1830−0645 based on an AstroSat observation carried out on 2020 October 16, about a week after the onset of its first detected X-ray outburst. Using data taken with the Soft X-ray Telescope (SXT) and Large Area X-ray Proportional Counter (LAXPC), we have detected 0.9–10 keV coherent pulsations at a period of ∼10.4 s. The pulse profiles were single-peaked, asymmetric, and consisted of minor peaks attributable to hotspots on the neutron star surface. The pulsed fraction evolved significantly with energy, increasing to energies around 5 keV with a steep drop thereafter. The 0.9–25 keV SXT–LAXPC energy spectrum is best described with two thermal components having temperatures ∼0.46 and ∼1.1 keV (emission radii of ∼2.4 and ∼0.65 km, respectively, assuming a distance of 4 kpc) along with a power-law component having a photon index of ∼0.39. We report the detection of 67 X-ray bursts having an average duration of ∼33 ms. The brightest burst lasted for about 90 ms and had a 3–25 keV fluence of ∼5 × 10−9 erg cm−2.
Three young planets around the K-dwarf K2-198: high-energy environment, evaporation history, and expected future
Authors: Ketzer L , Poppenhaeger K , Baratella M , Ilin E
Published: October 2023

Planets orbiting young stars are thought to experience atmospheric evaporation as a result of the host stars’ high-magnetic activity. We study the evaporation history and expected future of the three known transiting exoplanets in the young multiplanet system K2-198. Based on spectroscopic and photometric measurements, we estimate an age of the K-dwarf host star between 200 and 500 Myr, and calculate the high-energy environment of these planets using eROSITA X-ray measurements. We find that the innermost planet K2-198c has likely lost its primordial envelope within the first few 10s of Myr regardless of the age at which the star drops out of the saturated X-ray regime. For the two outer planets, a range of initial envelope mass fractions is possible, depending on the not-yet-measured planetary mass and the stars’ spin-down history. Regarding the future of the system, we find that the outermost planet K2-198b is stable against photoevaporation for a wide range of planetary masses, while the middle planet K2-198d is only able to retain an atmosphere for a mass range between ∼7 and 18 M⊕. Lower mass planets are too susceptible to mass-loss, and a very thin present-day envelope for higher mass planets is easily lost with the estimated mass-loss rates. Our results support the idea that all three planets started out above the radius valley in the (sub-)Neptune regime and were then transformed into their current states by atmospheric evaporation, but also stress the importance of measuring planetary masses for (young) multiplanet systems before conducting more detailed photoevaporation simulations.
Clinical investigation for the mechanisms of anaphylactic symptoms in osteoarthritis patients after diclofenac etalhyaluronate administration
Authors: Nishida Yoshihiro , Yagami Akiko , Takada Shuhei , Muramatsu Dai , Nobuoka Yuji , Okayama Yoshimichi
Published: October 2023

Objective

This study was conducted to investigate the mechanisms of anaphylaxis in patients with osteoarthritis of the knee and hip after diclofenac etalhyaluronate [product name: JOYCLU® (JCL)] intra-articular injection and to determine the utility of tests to investigate the mechanism involved.

Methods

In this observational study in Japan, patients aged ≥20 years with knee or hip osteoarthritis who received JCL intra-articular injection experienced anaphylactic symptoms considered related to JCL (‘experienced patients’) or did not experience allergic symptoms considered related to JCL (‘non-experienced patients’). Basophil activation tests (BATs), specific immunoglobulin E (IgE) antibody testing by enzyme-linked immunosorbent assays (ELISAs) or immunochromatographic kit, and genome-wide association studies (GWASs) were conducted using patient blood and saliva.

Results

Thirteen experienced patients and 14 non-experienced patients were tested. Seven experienced patients tested positive by BAT using diclofenac etalhyaluronate-containing test substances. Diclofenac-specific IgE antibodies were detected in four of seven BAT-positive patients but not in the non-experienced patients. Specific IgE antibody testing by immunochromatographic kit and genome-wide association study showed no clear results.

Conclusions

These findings suggest that anaphylaxis occurs after JCL administration via an IgE-mediated mechanism and that diclofenac etalhyaluronate may be involved in this mechanism. BAT and diclofenac -specific IgE enzyme-linked immunosorbent assay may be useful tests for investigating the mechanisms of anaphylactic reactions after JCL administration.
Diet, cellular, and systemic homeostasis control the cycling of potassium stable isotopes in endothermic vertebrates
Authors: Tacail T , Lewis J , Clauss M , Coath C D , Evershed R , Albalat E , Elliott T R , Tütken T
Published: October 2023

The naturally occurring stable isotopes of potassium (41K/39K, expressed as δ41K) have the potential to make significant contributions to vertebrate and human biology. The utility of K stable isotopes is, however, conditioned by the understanding of the dietary and biological factors controlling natural variability of δ41K. This paper reports a systematic study of K isotopes in extant terrestrial endothermic vertebrates. δ41K has been measured in 158 samples of tissues, biofluids, and excreta from 40 individuals of four vertebrate species (rat, guinea pig, pig and quail) reared in two controlled feeding experiments. We show that biological processing of K by endothermic vertebrates produces remarkable intra-organism δ41K variations of ca. 1.6‰. Dietary δ41K is the primary control of interindividual variability and δ41K of bodily K is +0.5–0.6‰ higher than diet. Such a trophic isotope effect is expected to propagate throughout trophic chains, opening promising use for reconstructing dietary behaviors in vertebrate ecosystems. In individuals, cellular δ41K is related to the intensity of K cycling and effectors of K homeostasis, including plasma membrane permeability and electrical potential. Renal and intestinal transepithelial transports also control fractionation of K isotopes. Using a box-modeling approach, we establish a first model of K isotope homeostasis. We predict a strong sensitivity of δ41K to variations of intracellular and renal K cycling in normal and pathological contexts. Thus, K isotopes constitute a promising tool for the study of K dyshomeostasis.
An ATP-independent role for Prp16 in promoting aberrant splicing
Authors: Chung Che-Sheng , Wai Hsu Lei , Kao Ching-Yang , Cheng Soo-Chen
Published: October 2023

The spliceosome is assembled through a step-wise process of binding and release of its components to and from the pre-mRNA. The remodeling process is facilitated by eight DExD/H-box RNA helicases, some of which have also been implicated in splicing fidelity control. In this study, we unveil a contrasting role for the prototypic splicing proofreader, Prp16, in promoting the utilization of aberrant 5′ splice sites and mutated branchpoints. Prp16 is not essential for the branching reaction in wild-type pre-mRNA. However, when a mutation is present at the 5′ splice site or if Cwc24 is absent, Prp16 facilitates the reaction and encourages aberrant 5′ splice site usage independently of ATP. Prp16 also promotes the utilization of mutated branchpoints while preventing the use of nearby cryptic branch sites. Our study demonstrates that Prp16 can either enhance or impede the utilization of faulty splice sites by stabilizing or destabilizing interactions with other splicing components. Thus, Prp16 exerts dual roles in 5′ splice site and branch site selection, via ATP-dependent and ATP-independent activities. Furthermore, we provide evidence that these functions of Prp16 are mediated through the step-one factor Cwc25.
Glioblastoma in the oldest old: Clinical characteristics, therapy, and outcome in patients aged 80 years and older
Authors: Stadler Christina , Gramatzki Dorothee , Le Rhun Emilie , Hottinger Andreas F , Hundsberger Thomas , Roelcke Ulrich , Läubli Heinz , Hofer Silvia , Seystahl Katharina , Wirsching Hans-Georg , Weller Michael , Roth Patrick
Published: October 2023

Background

Incidence rates of glioblastoma in very old patients are rising. The standard of care for this cohort is only partially defined and survival remains poor. The aims of this study were to reveal current practice of tumor-specific therapy and supportive care, and to identify predictors for survival in this cohort.

Methods

Patients aged 80 years or older at the time of glioblastoma diagnosis were retrospectively identified in 6 clinical centers in Switzerland and France. Demographics, clinical parameters, and survival outcomes were annotated from patient charts. Cox proportional hazards modeling was performed to identify parameters associated with survival.

Results

Of 107 patients, 45 were diagnosed by biopsy, 30 underwent subtotal resection, and 25 had gross total resection. In 7 patients, the extent of resection was not specified. Postoperatively, 34 patients did not receive further tumor-specific treatment. Twelve patients received radiotherapy with concomitant temozolomide, but only 2 patients had maintenance temozolomide therapy. Fourteen patients received temozolomide alone, 35 patients received radiotherapy alone, 1 patient received bevacizumab, and 1 took part in a clinical trial. Median progression-free survival (PFS) was 3.3 months and median overall survival (OS) was 4.2 months. Among patients who received any postoperative treatment, median PFS was 3.9 months and median OS was 7.2 months. Karnofsky performance status (KPS) ≥70%, gross total resection, and combination therapy were associated with better outcomes. The median time spent hospitalized was 30 days, accounting for 23% of the median OS. End-of-life care was mostly provided by nursing homes (n = 20; 32%) and palliative care wards (n = 16; 26%).

Conclusions

In this cohort of very old patients diagnosed with glioblastoma, a large proportion was treated with best supportive care. Treatment beyond surgery and, in particular, combined modality treatment were associated with longer OS and may be considered for selected patients even at higher ages.
Associations between sleep difficulties and health outcomes in treatment-seeking veterans
Authors: Molloy N , Murphy D
Published: October 2023

Background

Sleep disturbance in UK Armed Forces personnel appears to be frequent due to factors such as hostile sleeping environments and can persist even once they have transitioned into civilian life. Despite this, there is currently very limited literature surrounding the prevalence and associated factors of insomnia disorder among UK veterans.

Aims

This study aimed to expand knowledge of the prevalence and associated demographic, military, health and functional outcomes with probable insomnia disorder within a clinical sample of veterans.

Methods

Treatment-seeking veterans from a national UK mental health charity were invited to complete a questionnaire including socio-demographic, military, health and well-being questions.

Results

Of the sample, 489 (43%) completed the questionnaire. Seventy per cent of the sample reported having probable insomnia disorder. Having probable insomnia disorder was significantly associated with being younger and having physical health problems. Moreover, unadjusted models found associations between probable insomnia disorder and common mental health difficulties, obsessive–compulsive disorder and complex post-traumatic stress disorder.

Conclusions

The results suggest that many UK veterans with physical and mental health difficulties experience co-morbid insomnia disorder. Therefore, it is important that clinical services are aware of this prevalence and use targeted interventions to reduce the frequency of insomnia disorder in this population.
Challenging Rationality: Examining the Belief in Cure Among Patients With Advanced Incurable Cancers
Authors: Paiva Carlos Eduardo , Paiva Bianca Sakamoto Ribeiro
Published: October 2023

Citing a recently published study, this letter to the editor highlights again the critical role of prognostic awareness in the decision-making process for cancer therapeutics.
What Do We Call an ‘MP’? On Categories of Thought in the Anthropology of Parliaments
Authors: Chibois Jonathan
Published: October 2023

This article questions what social scientists mean by the term ‘Member of Parliament’ (‘MP’) and explains that they tend to associate it with a universal conception of parliamentary representation. The author starts to present the rationale behind this presupposition, which lies in the resistance of legislative studies to interpretive approaches, and shows its limits. He then defends the necessity of extensive scientific knowledge of deliberative assemblies to distinguish the vernacular meanings of the notion of ‘MP’ from its analytical meaning. Finally, he takes the example of his own research in France to show the concrete difficulties of a singular conception of parliamentary representation and to expose the virtues of using empirical-based ideal types to overcome them.
ATAD3 Proteins: Unique Mitochondrial Proteins Essential for Life in Diverse Eukaryotic Lineages
Authors: Waters Elizabeth R , Bezanilla Magdalena , Vierling Elizabeth
Published: October 2023

ATPase family AAA domain–containing 3 (ATAD3) proteins are unique mitochondrial proteins that arose deep in the eukaryotic lineage but that are surprisingly absent in Fungi and Amoebozoa. These ∼600-amino acid proteins are anchored in the inner mitochondrial membrane and are essential in metazoans and Arabidopsis thaliana. ATAD3s comprise a C-terminal ATPases Associated with a variety of cellular Activities (AAA+) matrix domain and an ATAD3_N domain, which is located primarily in the inner membrane space but potentially extends to the cytosol to interact with the ER. Sequence and structural alignments indicate that ATAD3 proteins are most similar to classic chaperone unfoldases in the AAA+ family, suggesting that they operate in mitochondrial protein quality control. A. thaliana has four ATAD3 genes in two distinct clades that appear first in the seed plants, and both clades are essential for viability. The four genes are generally coordinately expressed, and transcripts are highest in growing apices and imbibed seeds. Plants with disrupted ATAD3 have reduced growth, aberrant mitochondrial morphology, diffuse nucleoids and reduced oxidative phosphorylation complex I. These and other pleiotropic phenotypes are also observed in ATAD3 mutants in metazoans. Here, we discuss the distribution of ATAD3 proteins as they have evolved in the plant kingdom, their unique structure, what we know about their function in plants and the challenges in determining their essential roles in mitochondria.
Self-Effacing Reasons and Epistemic Constraints: Some Lessons from the Knowability Paradox
Authors: Carrara Massimiliano , Fassio Davide
Published: October 2023

A minimal constraint on normative reasons seems to be that if some fact is a reason for an agent to φ (act, believe, or feel), the agent could come to know that fact. This constraint is threatened by a well-known type of counterexamples. Self-effacing reasons are facts that intuitively constitute reasons for an agent to φ, but that if they were to become known, they would cease to be reasons for that agent. The challenge posed by self-effacing reasons bears important structural similarities with a range of epistemic paradoxes, most notably the Knowability Paradox. In this article, we investigate the similarities and differences between the two arguments. Moreover, we assess whether some of the approaches to the Knowability Paradox could help solve the challenge posed by self-effacing reasons. We argue that at least two popular approaches to the paradox can be turned into promising strategies for addressing the self-effacing reasons problem.
Two Ways of Limiting Moral Demands
Authors: Naegeli Lukas
Published: October 2023

How should we respond to moral theories that put excessive demands on individual agents? Intramoral strategies concern the content of morality and set limits on how exacting moral demands may be. Extramoral strategies concern the normative status of morality and set limits on how significant moral demands may be. While both strategies are often discussed separately, I focus on a specific aspect of how they relate to each other: Do intramoral approaches assume that extramoral approaches fail, and if so, does that render them implausible? This challenge becomes apparent when the two strategies are considered together, and my goal is to show how it can be dealt with. In particular, I argue that intramoral strategies do not depend on the failure of extramoral strategies: Even if morality has limited practical significance (which I also doubt), moral theories can be criticised for being too demanding in terms of content.
The Asymmetry of Embeddedness: Illegal Trade Networks and Drug Purchasing Diversity on an Online Illegal Drug Market
Authors: Duxbury Scott W , Haynie Dana L
Published: October 2023

While economic sociology research and theory argue that excessive network embeddedness depresses competition in illegal markets, prior research does not examine how distinct types of embeddedness may have asymmetric effects on the diversity of purchasing behavior—the range of illegal goods that buyers typically purchase. This study considers how network embeddedness can positively or negatively affect drug purchasing diversity in online drug markets by referring buyers to new vendors or “locking” buyers into recurrent trade for the same products. We analyze novel network data on 16,847 illegal drug exchanges between 7205 actors on one online illegal drug market. Consistent with hypothesized network asymmetry, buyers are more likely to purchase a new type of drug when the transaction is part of an indirect network referral. Although histories of exchange increase the overall frequency of drug purchasing, they are associated with decreases in new drug-type purchases. In the aggregate, these processes either contribute to an integrated market where buyers purchase multiple drugs from multiple vendors (in the case of referrals) or a fragmented market characterized by recurrent trade from the same vendors for the same substances (in the case of repeated trade). We discuss the implications of these findings for research on embeddedness, illegal markets, risky exchange, and drug policy.
The elderberry diet protection against intrahippocampal Aβ-induced memory dysfunction; the abrogated apoptosis and neuroinflammation
Authors: Jahanbakhshi Hadiseh , Moghaddam Meysam Hassani , Sani Mojtaba , Parvardeh Siavash , Boroujeni Mahdi Eskandarian , Vakili Kimia , Fathi Mobina , Azimi Helia , Mehranpour Maryam , Abdollahifar Mohammad-Amin , Ghafghazi Shiva , Sadidi Maryam , Aliaghaei Abbas , Bayat Amir-Hossein , Peyvandi Ali Asghar
Published: October 2023

This study evaluates whether elderberry (EB) effectively decreases the inflammation and oxidative stress in the brain cells to reduce Aβ toxicity. In the Aβ + EB group, EB powder was added to rats’ routine diet for eight consecutive weeks. Then, spatial memory, working memory, and long-term memory, were measured using the Morris water maze, T-maze, and passive avoidance test. Also, in this investigation immunohistopathology, distribution of hippocampal cells, and gene expression was carried out. Voronoi tessellation method was used to estimate the spatial distribution of the cells in the hippocampus. In addition to improving the memory functions of rats with Aβ toxicity, a reduction in astrogliosis and astrocytes process length and the number of branches and intersections distal to the soma was observed in their hippocampus compared to the control group. Further analysis indicated that the EB diet decreased the caspase-3 expression in the hippocampus of rats with Aβ toxicity. Also, EB protected hippocampal pyramidal neurons against Aβ toxicity and improved the spatial distribution of the hippocampal neurons. Moreover, EB decreased the expression of inflammatory and apoptotic genes. Overall, our study suggest that EB can be considered a potent modifier of astrocytes’ reactivation and inflammatory responses.
Exposure to Δ9-tetrahydrocannabinol leads to a rise in caspase-3, morphological changes in microglial, and astrocyte reactivity in the cerebellum of rats
Authors: Mohammadpanah Mojtaba , Farrokhi Sheida , Sani Mojtaba , Moghaddam Meysam Hassani , Bayat Amir-Hossein , Boroujeni Mahdi Eskandarian , Abdollahifar Mohammad-Amin , Fathi Mobina , Vakili Kimia , Nikpour Fatemeh , Omran Hossein Salehi , Ahmadirad Hossein , Ghorbani Zeynab , Peyvandi Ali Asghar , Aliaghaei Abbas
Published: October 2023

The present study aimed to elucidate the effect of 10 mg/kg Δ9-tetrahydrocannabinol (THC) on cerebellar neuronal and glial morphology, apoptosis and inflammatory gene expression using a series of histological assays including stereology, Sholl analysis, immunofluorescence and real-time qPCR in male Wistar rats. A decrease in the number of Purkinje neurons and the thickness of the granular layer in the cerebellum was reported in THC-treated rats. Increased expression of Iba-1 and arborization of microglial processes were evidence of microgliosis and morphological changes in microglia. In addition, astrogliosis and changes in astrocyte morphology were other findings associated with THC administration. THC also led to an increase in caspase-3 positive cells and a decrease in autophagy and inflammatory gene expression such as mTOR, BECN1 and LAMP2. However, there were no significant changes in the volume of molecular layers and white matter, the spatial arrangement of granular layers and white matter, or the spatial arrangement of granular layers and white matter in the cerebellum. Taken together, our data showed both neuroprotective and neurodegenerative properties of THC in the cerebellum, which require further study in the future.