bluuebunny/crossref_metadata_2025 huggingface dataset:
Marx Against Techno-Optimism
Authors: Royle Camilla
Published: May 2024

In the influential new book Marx in the Anthropocene: Towards the Idea of Degrowth Communism, Japanese academic Kohei Saito argues that Karl Marx made a theoretical breakthrough in later life. He abandoned his earlier interest in the development of productive forces and the possibilities raised by this for the realization of socialism. Marx intensively studied a range of topics including soil science and communal societies in this time and became what Saito refers to as a degrowth communist. Relatedly, according to Saito, Marx’s ecological work had a different character to that of Friedrich Engels. Saito bases his analysis on a careful analysis of Marx’s written work, including previously unpublished notebooks as well as theoretical engagements with theories of metabolism and metabolic rift. He shows how this remains relevant today in developing an ecological socialism that is cognizant of natural limits to growth and therefore capable of addressing capitalism’s unsustainable relationship to the natural world. Saito argues strongly that socialists cannot rely on technological solutions to ecological breakdown. His conception of ecological Marxism tends to play down discussions of socialist and working-class strategy. However, it nevertheless contributes much to our understanding of Marx as a non-determinist and non-Eurocentric thinker as well as someone whose work was grounded in materialist ecological thought.
Healthcare professionals’ perspectives on the use of PCSK9 inhibitors in cardiovascular disease: an in-depth qualitative study
Authors: Lee Geraldine A , Durante Angela , Baker Edward E , Vellone Ercole , Caggianelli Gabriele , Dellafiore Federica , Khan Mutiba , Khatib Rani
Published: May 2024

Aims

Injectable medicines such as PCSK9 inhibitors are increasingly used to manage risk factors for cardiovascular events with little information around the perceptions of healthcare professionals (HCPs) on the administrative and clinical practicalities. The aim was to identify the facilitators and barriers on the use of injectable therapies with cardiovascular benefits through interviews with HCPs.

Methods and results

Qualitative interviews were conducted in the UK (London and Leeds) and Italy (Rome and Milan) in 2021. Coding was undertaken using NVivo and thematic analysis performed. A total of 38 HCPs were interviewed, 19 in each country composing of physicians (n = 18), pharmacists (n = 10), nurses (n = 9), and pharmacy technician (n = 1). Four themes emerged: (i) clinicians’ previous experiences with injectable therapies, (ii) challenges with patients’ behaviours and beliefs, (iii) clinicians’ knowledge of injectable therapies and therapeutic inertia, and (iv) organizational and governance issues. The behaviour and beliefs from HCPs focused on facilitating behaviour change as well as the poor interdisciplinary working and collaboration. Therapeutic inertia was raised where physicians either lacked awareness of injectable therapies or were unwilling to prescribe them. The importance of facilitating patient education on injection techniques was highlighted, while organizational and governance issues identified the lack of guidance to inform practice. Clear pathways are required to identify those who were eligible for injectable therapies as well as on how injectables should be prescribed.

Conclusion

If medicine optimization is to be achieved, there need to be structured processes in place to identify eligible patients and the development of educational material.
The Intersection of Successful Aging and Family Caregiving
Authors: Bangerter Lauren R , Kim Yijung , Fields Beth , Wittke Michael Reese , Perepezko Kate
Published: May 2024

For the millions of older adults who rely on the support of a family caregiver, successful aging is not an individual achievement but a cooperative process between a care receiver and a caregiver. Yet, family caregivers are rarely incorporated into theoretical models of successful aging. Family caregivers also play an essential role in recent healthcare delivery movements that seek to better align care delivery with successful aging. Greater reliance on family caregivers by the U.S. healthcare system is occurring as an increasingly vocal constituency is tasking policymakers with developing and implementing federal and state health policies that would help build the national infrastructure needed to support them. This paper provides a critical discussion of how family caregivers actualize successful aging for older adults. We highlight the key role of family caregivers in healthcare delivery innovations aimed at facilitating successful aging and discuss policies that support family caregivers. As successful aging continues to evolve as a dominating framework in the literature, we conclude with key recommendations for how research, policy, and practice efforts in successful aging can be more inclusive and supportive of family caregivers.
Full Exceptional Collections and Stability Conditions for Dynkin Quivers
Authors: Otani Takumi
Published: May 2024

For a stability condition $\sigma $ on a triangulated category, Dimitrov–Katzarkov introduced the notion of a $\sigma $-exceptional collection. In this paper, we study full $\sigma $-exceptional collections in the derived category of an acyclic quiver. In particular, we prove that any stability condition $\sigma $ on the derived category of a Dynkin quiver admits a full $\sigma $-exceptional collection.
Dislocation: Toward a Framework for the Study of Crises
Authors: Klopf Nadine , Nabers Dirk
Published: May 2024

The paper develops a conceptual framework for the analysis of crises. It rests on the central argument that crises cannot be restricted to exceptional occurrences or temporarily delimited events, but we approach crisis as ontologically constitutive for our everyday lives. The concept of “discursive dislocation” is the cornerstone of this endeavor, as it grasps multiple aspects of sociopolitical instability, including societal deficiencies, fragilities, and political failures. Through theoretically advancing the concept of dislocation, we systematize three dimensions of crisis as permanent, recurring, and ephemeral dislocation. This allows us to analyze crises not only in their immediate environment but also makes it possible to understand them in their broader sociopolitical context. The conceptual framework is illustrated with the example of the COVID-19 pandemic in the United States, which reveals how the construction of the pandemic as a crisis is embedded in the historically ingrained self-portrayal of the United States, and how crisis responses are invoked to serve particular sociopolitical purposes in retaining an established American identity.
The Case for an Expressive Logic of Action
Authors: Duque Marina G
Published: May 2024

How can scholars theorize about phenomena like the eroding support, within the West, for the liberal democratic practices that once defined the post-1945 international order? Cumulative evidence shows that resentment toward out-groups shapes public attitudes toward issues like immigration and globalization, bolstering support for isolationist foreign policies in Western democracies. Yet, these findings contrast with the logics of action—based on means-end calculations, shared norms, practices, or habit—that IR scholars use to develop theory. Because existing logics provide a limited vocabulary to theorize about group processes with crucial symbolic and affective features, an important dimension of foreign policy behavior remains undertheorized. In this article, I draw on multi-disciplinary research to develop an expressive logic of action, whereby political behavior expresses an actor's social identification. Based on this logic, group attachment provides a compelling motivation for political behavior, whose activation depends on an interaction between issue framing and psychological dispositions. By focusing on the distinctive features of expressive behavior and specifying the mechanisms behind this behavior, an expressive logic encourages theory development and refinement across domains.
Sliding motility of Bacillus cereus mediates vancomycin pseudo-resistance during antimicrobial susceptibility testing
Authors: Schmid Paul J , Forstner Patrick , Kittinger Clemens
Published: May 2024

Background

The glycopeptide vancomycin is the antimicrobial agent-of-choice for the treatment of severe non-gastrointestinal infections with members of Bacillus cereus sensu lato (s.l.). Recently, sporadic detection of vancomycin-resistant phenotypes emerged, mostly for agar diffusion testing such as the disc diffusion method or gradient test (e.g. Etest®) method.

Results

In this work, we were able to disprove a preliminarily assumed high resistance to vancomycin in an isolate of B. cereus s.l. using broth microdilution and agar dilution. Microscopic imaging during vancomycin susceptibility testing showed spreading towards the inhibition zone, which strongly suggested sliding motility. Furthermore, transcriptomic analysis using RNA-Seq on the nanopore platform revealed several key genes of biofilm formation (e.g. calY, tasA, krsEABC) to be up-regulated in pseudo-resistant cells, substantiating that bacterial sliding is responsible for the observed mobility. Down-regulation of virulence (e.g. hblABCD, nheABC, plcR) and flagellar genes compared with swarming cells also confirmed the non-swarming phenotype of the pseudo-resistant isolate.

Conclusions

The results highlight an insufficiency of agar diffusion testing for vancomycin susceptibility in the B. cereus group, and reference methods like broth microdilution are strongly recommended. As currently no guideline mentions interfering phenotypes in antimicrobial susceptibility testing of B. cereus s.l., this knowledge is essential to obtain reliable results on vancomycin susceptibility. In addition, this is the first report of sliding motility undermining accurate antimicrobial susceptibility testing in B. cereus s.l. and may serve as a basis for future studies on bacterial motility in susceptibility testing and its potential impact on treatment efficacy.
Ceftaroline fosamil treatment patterns and outcomes in adults with community-acquired pneumonia: a real-world multinational, retrospective study
Authors: Soriano Alex , Bassetti Matteo , Gogos Charalambos , Ferry Tristan , de Pablo Raul , Ansari Wajeeha , Kantecki Michal , Schweikert Bernd , Luna Gustavo , Blasi Francesco
Published: May 2024

Background

This multicentre, observational, retrospective chart review study assessed ceftaroline fosamil treatment patterns and outcomes in adults hospitalized with community-acquired pneumonia (CAP) in usual care settings.

Methods

Anonymized patient data were extracted from hospital records of adults with CAP who received ≥4 consecutive IV ceftaroline fosamil doses at sites in Brazil, Colombia, France, Greece, Italy, Russia and Spain.

Results

The dataset included 185 patients (58.9% male; mean age 62.2 years), of whom 128 (69.2%) had severe CAP defined by CURB-65, PSI/PORT score or physician judgement. Streptococcus pneumoniae (n = 44; 23.8%) and Staphylococcus aureus [MSSA (n = 15) and MRSA (n = 14)] were the most frequently identified pathogens. Clinical response occurred in 151 (81.6%) patients overall, and in 104 (81.3%) severe CAP patients. Response within ≤4 and >4 days occurred in 79 (42.7%) and 62 (33.5%) patients (unknown, n = 10), respectively. Twenty (10.8%) patients required readmission within 30 days. Thirty-day all-cause mortality rates were 9.7% (n = 18) overall and 10.2% (n = 13) in severe CAP. In sensitivity analysis using ICU admission as a more objective marker of severe CAP (n = 75), clinical response and 30 day mortality occurred in 57 (76.0%) and 10 (13.3%) patients, respectively. Overall, clinical response to ceftaroline fosamil was associated with >60% shorter length of ICU stay (3.6 versus 9.2 days), and >30% lower hospital costs ($8449 versus $12 559) versus non-responders.

Conclusions

Ceftaroline fosamil was effective in treating adults with CAP, including severe CAP, in Europe and Latin America. Clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders.
Knowledge-guided generative artificial intelligence for automated taxonomy learning from drug labels
Authors: Fang Yilu , Ryan Patrick , Weng Chunhua
Published: May 2024

Objectives

To automatically construct a drug indication taxonomy from drug labels using generative Artificial Intelligence (AI) represented by the Large Language Model (LLM) GPT-4 and real-world evidence (RWE).

Materials and Methods

We extracted indication terms from 46 421 free-text drug labels using GPT-4, iteratively and recursively generated indication concepts and inferred indication concept-to-concept and concept-to-term subsumption relations by integrating GPT-4 with RWE, and created a drug indication taxonomy. Quantitative and qualitative evaluations involving domain experts were performed for cardiovascular (CVD), Endocrine, and Genitourinary system diseases.

Results

2909 drug indication terms were extracted and assigned into 24 high-level indication categories (ie, initially generated concepts), each of which was expanded into a sub-taxonomy. For example, the CVD sub-taxonomy contains 242 concepts, spanning a depth of 11, with 170 being leaf nodes. It collectively covers a total of 234 indication terms associated with 189 distinct drugs. The accuracies of GPT-4 on determining the drug indication hierarchy exceeded 0.7 with “good to very good” inter-rater reliability. However, the accuracies of the concept-to-term subsumption relation checking varied greatly, with “fair to moderate” reliability.

Discussion and Conclusion

We successfully used generative AI and RWE to create a taxonomy, with drug indications adequately consistent with domain expert expectations. We show that LLMs are good at deriving their own concept hierarchies but still fall short in determining the subsumption relations between concepts and terms in unregulated language from free-text drug labels, which is the same hard task for human experts.
Spatial and temporal distribution of Scirtothrips dorsalis (Thysanoptera: Thripidae) and their natural enemies in Florida strawberry fields
Authors: Kaur Gagandeep , Stelinski Lukasz L , Martini Xavier , Boyd Nathan , Mallinger Rachel , Lahiri Sriyanka
Published: May 2024

Given the recent invasion of Scirtothrips dorsalis Hood in North America, there is limited information regarding their distribution and population dynamics in cultivated small fruit crops. Therefore, we investigated the spatial and temporal distribution of S. dorsalis and their natural enemies in commercially produced strawberry fields in Florida. During 2 consecutive strawberry production seasons, 4 and 6 geographically separated strawberry fields were sampled and were divided into grids with 30–40 sampling points per field. At each sampling point, 4–5 leaf and flower samples were collected, and sticky traps were deployed. We quantified the occurrence of S. dorsalis as well as potential natural enemies, including Orius spp., Geocoris spp., and other predators such as long-legged flies. During both years, most of the S. dorsalis and natural enemies were found on field borders, and counts progressively diminished further into the interiors of plots and away from field edges. Cluster and outlier analysis revealed that S. dorsalis formed statistically significant clusters and that these “hot spots” remained in the same general locations throughout the season. There was a strong relationship between the occurrence of natural enemies and the presence of S. dorsalis, but the number of natural enemies was generally low compared to S. dorsalis. Our results indicate that targeting field borders for chemical control or planting strawberries away from natural areas containing potential alternative hosts for thrips may be an effective strategy for reducing agricultural inputs; however, future field assessments are needed to determine if these methods could replace the treatment of entire fields.
Three Early Linguistic Layers in Haredi Hebrew
Authors: Sender Dina
Published: May 2024

A close examination of contemporary Hebrew as spoken by Haredi, or ultra-Orthodox, communities in Israel reveals linguistic layers from several historical and cultural contexts. This article looks at elements from three of these layers: Jewish religious literature, the Yiddish language and outdated Israeli Hebrew. An analysis of these elements sheds light on how Haredi Hebrew differs from ‘general’ Israeli Hebrew and how these differences reflect linguistic perceptions and socio-cultural values that distinguish Haredim from the broader Israeli population. In addition to demonstrating the intricate interplay between language and society, analysis offers insight into the dynamic nature of Hebrew language evolution.
Prevalence of PTSD in Active Duty Members with Mild Traumatic Brain Injury: Systematic Review and Meta-analysis
Authors: Lai Choang , Kostas-Polston Elizabeth A , Engler Mary B , Capple Kathryn A , Froelicher Erika Sivarajan
Published: May 2024

Introduction

Traumatic brain injury (TBI), particularly mild TBI (mTBI), is a significant health concern for U.S. active duty service members (ADSMs), with potential implications for psychiatric outcomes including PTSD. Despite recognizing this association, the prevalence of PTSD among ADSMs with mTBI remains unclear.

Materials and Methods

The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A thorough search in PubMed, CINAHL, Embase, and PsycINFO databases from 2008 to 2024 focused on identifying studies involving ADSMs with PTSD and mTBI. The R software (version 4.3.2) was employed for meta-analysis with the “meta” and “meta prop” packages.

Results

Eight reviewed studies revealed a pooled prevalence estimate of PTSD among ADSMs with mTBI at 36% (95% CI, 30%-41%, P < .01, I2 = 96%). Cohort studies indicated a slightly higher prevalence of 38% (95% CI, 19%-59%, P < .01, I2 = 98%), whereas cross-sectional studies provided a marginally lower prevalence of 34% (95% CI, 27%-40%, P < .01, I2 = 92%).

Conclusion

Methodological differences, including diagnostic criteria variability, contribute to the observed variability in prevalence estimates. Despite methodological challenges, this study provides crucial insights into the pooled prevalence of comorbid PTSD and mTBI within the military, emphasizing the need for standardized methodologies and further research to refine understanding and support strategies for affected individuals.
Primordial aminoacyl-tRNA synthetases preferred minihelices to full-length tRNA
Authors: Tang Guo Qing , Hu Hao , Douglas Jordan , Carter Charles W
Published: May 2024

Aminoacyl-tRNA synthetases (AARS) and tRNAs translate the genetic code in all living cells. Little is known about how their molecular ancestors began to enforce the coding rules for the expression of their own genes. Schimmel et al. proposed in 1993 that AARS catalytic domains began by reading an ‘operational’ code in the acceptor stems of tRNA minihelices. We show here that the enzymology of an AARS urzyme•TΨC-minihelix cognate pair is a rich in vitro realization of that idea. The TΨC-minihelixLeu is a very poor substrate for full-length Leucyl-tRNA synthetase. It is a superior RNA substrate for the corresponding urzyme, LeuAC. LeuAC active-site mutations shift the choice of both amino acid and RNA substrates. AARS urzyme•minihelix cognate pairs are thus small, pliant models for the ancestral decoding hardware. They are thus an ideal platform for detailed experimental study of the operational RNA code.
SeqCAT: Sequence Conversion and Analysis Toolbox
Authors: Kornrumpf Kevin , Kurz Nadine S , Drofenik Klara , Krauß Lukas , Schneider Carolin , Koch Raphael , Beißbarth Tim , Dönitz Jürgen
Published: May 2024

Dealing with sequence coordinates in different formats and reference genomes is challenging in genetic research. This complexity arises from the need to convert and harmonize datasets of different sources using alternating nomenclatures. Since manual processing is time-consuming and requires specialized knowledge, the Sequence Conversion and Analysis Toolbox (SeqCAT) was developed for daily work with genetic datasets. Our tool provides a range of functions designed to standardize and convert gene variant coordinates based on various sequence types. Its user-friendly web interface provides easy access to all functionalities, while the Application Programming Interface (API) enables automation within pipelines. SeqCAT provides access to human genomic, protein and transcript data, utilizing various data resources and packages and extending them with its own unique features. The platform covers a wide range of genetic research needs with its 14 different applications and 3 info points, including search for transcript and gene information, transition between reference genomes, variant mapping, and genetic event review. Notable examples are ‘Convert Protein to DNA Position’ for translation of amino acid changes into genomic single nucleotide variants, or ‘Fusion Check’ for frameshift determination in gene fusions. SeqCAT is an excellent resource for converting sequence coordinate data into the required formats and is available at: https://mtb.bioinf.med.uni-goettingen.de/SeqCAT/.
ChemFH: an integrated tool for screening frequent false positives in chemical biology and drug discovery
Authors: Shi Shaohua , Fu Li , Yi Jiacai , Yang Ziyi , Zhang Xiaochen , Deng Youchao , Wang Wenxuan , Wu Chengkun , Zhao Wentao , Hou Tingjun , Zeng Xiangxiang , Lyu Aiping , Cao Dongsheng
Published: May 2024

High-throughput screening rapidly tests an extensive array of chemical compounds to identify hit compounds for specific biological targets in drug discovery. However, false-positive results disrupt hit compound screening, leading to wastage of time and resources. To address this, we propose ChemFH, an integrated online platform facilitating rapid virtual evaluation of potential false positives, including colloidal aggregators, spectroscopic interference compounds, firefly luciferase inhibitors, chemical reactive compounds, promiscuous compounds, and other assay interferences. By leveraging a dataset containing 823 391 compounds, we constructed high-quality prediction models using multi-task directed message-passing network (DMPNN) architectures combining uncertainty estimation, yielding an average AUC value of 0.91. Furthermore, ChemFH incorporated 1441 representative alert substructures derived from the collected data and ten commonly used frequent hitter screening rules. ChemFH was validated with an external set of 75 compounds. Subsequently, the virtual screening capability of ChemFH was successfully confirmed through its application to five virtual screening libraries. Furthermore, ChemFH underwent additional validation on two natural products and FDA-approved drugs, yielding reliable and accurate results. ChemFH is a comprehensive, reliable, and computationally efficient screening pipeline that facilitates the identification of true positive results in assays, contributing to enhanced efficiency and success rates in drug discovery. ChemFH is freely available via https://chemfh.scbdd.com/.
Histone deacetylase Hos2 regulates protein expression noise by potentially modulating the protein translation machinery
Authors: Lin Wei-Han , Opoc Florica J G , Liao Chia-Wei , Roy Kevin R , Steinmetz Lars M , Leu Jun-Yi
Published: May 2024

Non-genetic variations derived from expression noise at transcript or protein levels can result in cell-to-cell heterogeneity within an isogenic population. Although cells have developed strategies to reduce noise in some cellular functions, this heterogeneity can also facilitate varying levels of regulation and provide evolutionary benefits in specific environments. Despite several general characteristics of cellular noise having been revealed, the detailed molecular pathways underlying noise regulation remain elusive. Here, we established a dual-fluorescent reporter system in Saccharomyces cerevisiae and performed experimental evolution to search for mutations that increase expression noise. By analyzing evolved cells using bulk segregant analysis coupled with whole-genome sequencing, we identified the histone deacetylase Hos2 as a negative noise regulator. A hos2 mutant down-regulated multiple ribosomal protein genes and exhibited partially compromised protein translation, indicating that Hos2 may regulate protein expression noise by modulating the translation machinery. Treating cells with translation inhibitors or introducing mutations into several Hos2-regulated ribosomal protein genes—RPS9A, RPS28B and RPL42A—enhanced protein expression noise. Our study provides an effective strategy for identifying noise regulators and also sheds light on how cells regulate non-genetic variation through protein translation.
IRF2BP2 counteracts the ATF7/JDP2 AP-1 heterodimer to prevent inflammatory overactivation in acute myeloid leukemia (AML) cells
Authors: Fischer Sabrina , Weber Lisa Marie , Stielow Bastian , Frech Miriam , Simon Clara , Geller Merle , Könnecke Julie , Finkernagel Florian , Forné Ignasi , Nist Andrea , Bauer Uta-Maria , Stiewe Thorsten , Neubauer Andreas , Liefke Robert
Published: May 2024

Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal proliferation and accumulation of immature myeloid cells in the bone marrow. Inflammation plays a crucial role in AML progression, but excessive activation of cell-intrinsic inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that IRF2BP2 interacts with the AP-1 heterodimer ATF7/JDP2, which is involved in activating inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene-activating function. Loss of IRF2BP2 leads to overactivation of inflammatory pathways, resulting in strongly reduced proliferation. Our research indicates that a precise equilibrium between activating and repressive transcriptional mechanisms creates a pro-oncogenic inflammatory environment in AML cells. The ATF7/JDP2-IRF2BP2 regulatory axis is likely a key regulator of this process and may, therefore, represent a promising therapeutic vulnerability for AML. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.
Evolution of grain size distribution in the circumgalactic medium
Authors: Hirashita Hiroyuki
Published: May 2024

In order to theoretically understand dust properties in the circumgalactic medium (CGM), we construct a dust evolution model that incorporates the evolution of grain size distribution. We treat the galaxy and the CGM as separate one-zone objects, and consider the mass exchange between them. We take into account dust production and interstellar dust processing for the galaxy based on our previous models, and newly incorporate sputtering in the hot phase and shattering in the cool phase for the CGM. We find that shattering increases the dust destruction (sputtering) efficiency in the CGM. The functional shape of the grain size distribution in the CGM evolves following that in the galaxy, but it is sensitive to the balance between sputtering and shattering in the CGM. For an observational test, we discuss the wavelength dependence of the reddening in the CGM traced by background quasar colors, arguing that, in order to explain the observed reddening level, a rapid inflow from the CGM to the galaxy is favored because of quick dust/metal enrichment. Small grain production by shattering in the CGM also helps to explain the rise of dust extinction toward short wavelengths.
Voluntary Disclosure in Asymmetric Contests
Authors: Ewerhart Christian , Lareida Julia
Published: May 2024

This article studies the incentives for interim voluntary disclosure of verifiable information in probabilistic all-pay contests with two-sided incomplete information. Private information may concern marginal cost, valuations, and ability. Our main result says that, if the contest is uniformly asymmetric, then full revelation is the unique perfect Bayesian equilibrium outcome. This is so because the weakest type of the underdog reveals her type in an attempt to moderate the favourite, while the strongest type of the favourite tries to discourage the underdog—so that the contest unravels. This strong-form disclosure principle is robust with respect to correlation, partitional evidence, randomized disclosures, sequential moves, and continuous type spaces. Moreover, the assumption of uniform asymmetry is not needed when incomplete information is one-sided. However, the principle may break down when type distributions are too similar, contestants possess commitment power, or information is unverifiable. In fact, cheap talk will always be ignored, even if mediated by a trustworthy third party.
Modifiable risk factors and inflammation-related proteins in polymyalgia rheumatica: genome-wide meta-analysis and Mendelian randomization
Authors: Zhao Sizheng Steven , Mackie Sarah L , Larsson Susanna C , Burgess Stephen , Yuan Shuai
Published: May 2024

Objective

PMR is an age-related inflammatory disease of unknown cause. We aimed to identify potentially modifiable risk factors and therapeutic targets for preventing or treating PMR.

Methods

We meta-analysed genetic association data from 8156 cases of PMR (defined using diagnostic codes and self-report) and 416 495 controls of European ancestry from the UK Biobank and FinnGen. We then performed Mendelian randomization analyses to estimate the association between eight modifiable risk factors (using data from up to 1.2 million individuals) and 65 inflammation-related circulating proteins (up to 55 792 individuals), using the inverse variance weighted and pleiotropy robust methods.

Results

We identified three novel genome-wide significant loci in the IL1R1, NEK6 and CCDC88B genes and confirmation of previously described associations with HLA-DRB1 and ANKRD55. Genetically predicted smoking intensity (OR 1.32; 95%CI 1.08–1.60; P = 0.006) and visceral adiposity (OR 1.22; 95%CI 1.10–1.37; P = 3.10 × 10−4) were associated with PMR susceptibility. Multiple circulating proteins related to IL-1 family signalling were associated with PMR. IL-1 receptor-like 2, also known as IL-36 receptor (OR 1.25; P = 1.89 × 10−32), serum amyloid A2 (OR 1.06, 9.91 × 10−10) and CXCL6 (OR 1.09, P = 4.85 × 10−7) retained significance after correction for multiple testing.

Conclusion

Reducing smoking and visceral adiposity at a population level might reduce incidence of PMR. We identified proteins that may play causal roles in PMR, potentially suggesting new therapeutic opportunities. Further research is needed before these findings are applied to clinical practice.
A systematic review comparing different approaches for inflatable penile prosthesis revision: partial-component exchange, complete-component exchange, or reservoir “drain and retain”
Authors: El-Achkar Adnan , Khalafalla Kareim , Nguyen Tuan Thanh , Wang Run
Published: May 2024

Introduction

In cases of a noninfected malfunctioning inflatable penile prosthesis (IPP) device, surgeons often opt to exchange all of the device rather than the defective component for fear of an increased infection rate and future mechanical dysfunction.

Objectives

To assess whether partial-component exchange of an IPP device has comparable outcomes to complete explant and replacement of an IPP device with or without a retained reservoir.

Methods

A systematic review was conducted following the PRISMA 2020 and AMSTAR guidelines. Searches were performed on MEDLINE (Ovid), PubMed, and the Cochrane Library from inception to June 2023, identifying studies reporting outcomes and complications of revision surgery for noninfected malfunctioning IPP devices. Three groups were compared: those undergoing single- or 2-component exchange, those with complete explantation and replacement, and those with replacement of all components while retaining the primary reservoir.

Results

Analysis included 11 articles comprising 12 202 patients with complete device replacement, 234 with partial device exchange, and 151 with retained reservoirs following revision. Mean ages ranged from 62 to 68 years, with median follow-up times between 3 and 84 months. Partial-component exchange showed a higher infection rate (6.3%) as compared with complete replacement (2.7%) and reservoir retention (3.9%). Similarly, partial exchange had a higher complication rate (23.9%) when compared with complete replacement (11.3%) and reservoir retention (19.6%). Mechanical failure rates for partial exchange were similar across the 3 groups (10%, 2.8%, and 5.8%, respectively).

Conclusion

Partial-component exchange during IPP revision is associated with higher infection and perioperative complication rates but comparable rates of mechanical failure as compared with complete-component replacement, with or without retaining the original reservoir.
Ontogeny and phylogeny of the anaerobic genus Urostomides with supplementing morphological characterization of the type and one little-known species (Alveolata: Ciliophora: Armophorea)
Authors: Feng Xiaochen , Zhuang Wenbao , Li Ran , Hu Xiaozhong
Published: May 2024

Urostomides is an obligate anaerobic ciliate genus in the family Apometopidae (Metopida). Although most congeners have been described using modern criteria, detailed ontogenetic data for both the family and genus have not been reported yet. In this study, we investigate the morphogenesis of two Urostomides species, viz., U. minimus (Kahl, 1927) comb. nov. and U. striatus (type species) in detail. Our findings reveal that the process closely resembles that of several described Metopidae species, except for a notable difference in the origin of the new adoral membranelles either from all perizonal rows or from other somatic kineties. Additionally, the data of U. minimus on the ciliature and SSU rRNA gene sequence are provided and those of U. striatus are supplemented based on Chinese isolates. We show the diplostichomonad morphology of the paroral membrane, a feature not previously observed in Urostomides species. Furthermore, our phylogenetic analyses confirm the monophyly of Urostomides.
Neuromodulation of Cardiovascular Risks Associated With Cardiotoxic Chemotherapy
Authors: Nagai Michiaki , Ewbank Hallum , Po Sunny S. , Dasari Tarun W.
Published: May 2024

Objectives:

Cardiotoxic chemotherapy is used to treat malignancies such as breast cancer and lymphoma. These treatments predispose patients to cardiotoxicity that can lead to cancer treatment-related cardiac dysfunction (CTRCD). The use of high doses of anthracyclines or in combination with human epidermal growth factor receptor 2 antagonists is associated with a progressively higher risk of CTRCD. CTRCD is preceded by increased activation of the sympathetic nervous system and abnormal left ventricular mechanical deformation as measured by abnormal global longitudinal strain (GLS). Low-level tragus stimulation (LLTS) is a new, safe, noninvasive technique that offers great potential to reduce increased sympathetic activation and improve GLS. Here, we describe a study method to examine the effects of LLTS on autonomic balance and cardiac function in breast cancer or lymphoma patients treated with anthracyclines.

Methods:

A first-in-human pilot, randomized, double-blind feasibility study will evaluate 104 patients (age >50 y) with breast cancer or lymphoma who receive anthracyclines with one additional CTRCD risk factor. Patients undergo 2 weeks of LLTS daily (1 h/d). Autonomic balance will be measured using heart rate variability metrics. Strain imaging using GLS will be performed pre and post-LLTS. Endothelial inflammation and oxidative stress measures will be performed using in vitro assays at baseline and after 2 weeks.

Conclusion:

We hypothesize that LLTS stabilizes sympathovagal imbalance and improves cardiac performance in anthracycline-treated patients with breast cancer or lymphoma.
Response of a von Hippel-Lindau-associated optic nerve hemangioblastoma to belzutifan.
Authors: Meade Julia , Nischal Kanwal , Olsen Karl R.
Published: May 2024

Purpose:

To demonstrate the response of a juxtapapillary retinal hemangioblastoma (JRH) to belzutifan in a patient with Von-Hippel-Lindau syndrome (VHL).

Methods:

This case report includes fundus photography and optical coherence tomography to compare a juxtapapillary retinal hemangioblastoma (JRH) before and 24 months after treatment with belzutifan.

Results:

An 18-year-old woman with VHL was diagnosed with a juxtapapillary retinal hemangioblastoma (JRH) at age 13. The retinal lesion progressively worsened over 5 years and required two sessions of laser therapy with minimal improvement but loss of visual field. She was treated with the oral HIF2a-inhibitor, belzutifan, with minimal side effects. At 24 months of therapy her JRH has decreased in height from 1258 microns to 874 microns and width from 4448 µm to 3786 µm and vision is 20/20.

Conclusion:

Belzutifan demonstrates impressive clinical activity in VHL-associated JRH.
Clinical Characteristics of 427 Unvaccinated Chinese Adult Patients with Maintenance Hemodialysis Infected with the SARS-CoV-2 Omicron Variant: A Retrospective Study
Authors: Ha Xiaowen , Zhao Zhigang , Zhao Tiantian , Muhetaer Gulimire , Wang Xiaoyu , Bao Aihong , Duan Yanya , Zhuang Jing , Song Xue , Zhou Yipeng , Zhang Qingqing , Wu Jianhua , Fan Min , Zhang Li , Tian Xuefei , Jiang Hong
Published: May 2024

Background:

Maintenance hemodialysis (MHD) patients constitute a distinctive population characterized by unique traits, such as hemodialysis-related immune disturbances, and increased vulnerability to infections, heart failure, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite considerable research on MHD patients with coronavirus disease 2019 (COVID-19), there is limited information available on the clinical characteristics and outcomes of unvaccinated adult MHD patients infected with the SARS-CoV-2 Omicron variant.

Methods:

A retrospective investigation was conducted in a cohort of 427 unvaccinated MHD patients diagnosed with SARS-CoV-2 Omicron infection. The clinical symptoms, laboratory results, and treatment regimens were comprehensively examined. Multivariate regression identified independent risk factors for disease severity, and two-month follow-up assessments were conducted.

Results:

The cohort exhibited a spectrum of disease severity, with 37.5% classified as mild, 35.3% as common, 22.5% as severe, and 4.7% as critical. Serum C-reactive protein level, procalcitonin level, and bicarbonate concentration are related to the severity of the disease. Tailored treatment strategies—including nutritional support, hemodialysis management, anti-bacterial interventions, and more—were implemented. There was a 5.6% mortality rate, with a higher prevalence of deaths in the critical subtype. Independent risk factors for disease severity included fever, age, cycle threshold values (Ct values) of ORF1ab gene, and arterial oxygen partial pressure. Follow-up assessments revealed a median duration of 11 days for the negative nucleic acid of SARS-CoV-2. Twelve patients presented a second positive ORF1ab gene during follow-up but remained asymptomatic.

Conclusion:

These findings suggest the intricate clinical characteristics and outcomes of MHD patients with the SARS-CoV-2 Omicron infection. Tailored treatment strategies, continuous surveillance, and understanding prognostic factors are imperative for managing this high-risk population. Further research is warranted to validate these findings.
Factors predicting redislocation or suture break in eyes after scleral-fixated intraocular lens
Authors: Lee Juseok , Lee Junwon , Lee Christopher Seungkyu , Kim Min , Byeon Suk Ho , Kim Sung Soo , Kang Hyun Goo
Published: May 2024

Purpose:

To investigate predictive factors for redislocation in patients with recurrent intraocular lens (IOL) dislocation after secondary scleral-fixated IOL (SF IOL) surgery.

Setting:

2 tertiary referral hospitals.

Design:

Retrospective case series.

Methods:

Patients undergoing SF IOL surgery were grouped into redislocation and no-redislocation groups. Medical records of consecutive patients who underwent SF IOL surgery between June 2014 and December 2019 at 2 tertiary referral centers were reviewed. Data regarding patient demographics, treatment factors, anatomical and functional outcomes, and postoperative complications were recorded.

Results:

237 eyes of 225 patients (169 [75.1%] men) were included. The redislocation group was more likely to have a younger mean age at the initial SF IOL surgery (redislocation vs no-redislocation, 55.4 vs 62.0 years, respectively; P = .008), have a prior history of a previous suture break (23 eyes, 52.3% vs 1 eye, 0.5%; P < .001), and have undergone the initial SF IOL surgery using <1 mm-sized side-port incisions (17 eyes, 38.6% vs 32 eyes, 16.5%; P = .002) than was the no-redislocation group. In addition, the redislocation group had a higher occurrence of complications (P < .001). Multivariate regression revealed that younger age, left eye involvement, aphakic status before the surgery, unremarkable primary IOL dislocation cause, need for ocular hypertension treatment and glaucoma surgery, and no large incision during the initial surgery were significantly (all P < .05) associated with redislocation.

Conclusions:

Younger age, left eye involvement, postoperative complications such as ocular hypertension and glaucoma, and techniques without large incisions increase the risk of redislocation. Conversely, lower risk factors include unremarkable surgery causes and a history of aphakic conditions.
Job stress and chronic low back pain: incidence, number of episodes, and severity in a 4-year follow-up of the ELSA-Brasil Musculoskeletal cohort
Authors: Hubner Fernanda Corsino Lima , Telles Rosa Weiss , Giatti Luana , Machado Luciana A. C. , Griep Rosane Harter , Viana Maria Carmen , Barreto Sandhi Maria , Camelo Lidyane V.
Published: May 2024

We investigated the association between job stress, as assessed by the effort–reward imbalance model, and the incidence of chronic low back pain (CLBP) over a 4-year period. A total of 1733 participants from the ELSA-Brasil Musculoskeletal cohort, who were free from LBP at baseline (2012-2014), were included. Episodes of LBP in the past 30 days, intensity, and the presence of disability were investigated in annual telephone follow-ups (2015-2018). Chronic LBP was defined as episodes of LBP lasting >3 months with at least moderate intensity. We analyzed the incidence of at least one episode of CLBP (yes/no), the number of CLBP episodes (0, 1, ≥2), and CLBP severity/disability (absent, nondisabling, severe/disabling). The association between these outcomes and tertiles of the effort-to-reward ratio, as well as each dimension of the effort–reward imbalance model, was investigated using multinomial logistic and Poisson regression models adjusting for sociodemographic and occupational variables. The cumulative incidence of CLBP over 4 years was 24.8%. High effort–reward imbalance increased the chances of experiencing multiple CLBP episodes and severe/disabling CLBP by 67% (95% confidence interval [CI]: 1.12-2.47) and 70% (95% CI: 1.14-2.53), respectively. High overcommitment increased the incidence of CLBP by 23% (95% CI: 1.01-1.50) and the chances of multiple CLBP episodes and severe/disabling CLBP by 67% (95% CI: 1.11-2.50) and 57% (95% CI: 1.05-2.34), respectively. These results indicate that exposure to job stress is associated with a higher incidence, a greater number of episodes, and increased severity of CLBP over a 4-year period. If this association is causal, measures aimed at reducing exposure to job stress are likely to alleviate the burden of CLBP.
Community Hospital Interventions Addressing the Medical and Social Needs of Patients
Authors: Louis Christopher J. , Koppelman Elisa A. , Bachman Sara S.
Published: May 2024

High utilizers of acute care in nonurban settings are at risk for poor health outcomes. Much of Massachusetts is nonurban, with many residents experiencing limited access to health care providers, fragmented health care services, inadequate housing, and low health literacy. This study examines patient perspectives on the Community Hospital Acceleration, Revitalization, and Transformation (CHART) investment program, a state-based grant program focused on advancing community hospitals toward value-based care. We found that CHART staff engaged patients in care coordination and patient advocacy, promoted patient agency and health literacy, and provided socioemotional support. These findings may help inform future program development around meeting the medical and social needs of high utilizers of health care services.
Pain control during intrauterine device insertion: Transcutaneous electrical nerve stimulation
Authors: Coleman Kellie , Carter Chelsea
Published: May 2024

Current practice lacks effective periprocedural pain management during common gynecological procedures such as intrauterine device insertion, increasing the possibility of significant pain and adverse reaction to such procedures. Because of this, pain can often be a barrier for a patient in choosing a form of contraception that best serves them. Transcutaneous electrical nerve stimulation offers an option for effective pain control during intrauterine device insertion. This case review characterizes five cases where patients were offered transcutaneous electrical nerve stimulation for pain control during intrauterine device insertion. The patients reported a range of no pain to moderate pain during intrauterine device insertion and rated their pain experience as better compared with prior insertions. Although limited to a case review, our findings suggest a promising clinical indication for transcutaneous electrical nerve stimulation as a pain management strategy for intrauterine device insertion.
Accuracy of the Bedside Examination in Patients With Suspected Acute Unilateral Peripheral Vestibulopathy
Authors: von Bernstorff Maximilian , Obermueller Theresa , Blum Julia , Hoxhallari Erdi , Hofmann Veit M. , Pudszuhn Annett
Published: May 2024

Objective:

Acute unilateral peripheral vestibulopathy (AUPVP) is a frequent form of peripheral vestibular vertigo characterized by unilateral vestibular organ dysfunction. Diagnostic challenges in anamnesis and bedside examination can lead to potential misdiagnoses. This study investigated the sensitivity of bedside examinations in diagnosing AUPVP.

Methods:

This retrospective analysis examined 136 AUPVP inpatients at a level 3 university hospital between 2017 and 2019. Demographic data and bedside test results were collected. Instrumental otoneurological tests included caloric testing and video head impulse test (HIT). The sensitivity of each bedside parameter was computed based on the instrumental diagnostics, and statistical analyses were performed.

Results:

The study included 76 men and 60 women, with a mean age of 59.2 years. Spontaneous nystagmus exhibited a sensitivity of 92%, whereas the absence of skew deviation was identified with a sensitivity of 98%. Abnormal bedside HIT showed a sensitivity of 87%. The combined HINTS (HIT, nystagmus, and test of skew) had a sensitivity of 83%. The Romberg test and Fukuda test demonstrated sensitivities of 26% and 48%, respectively.

Conclusion:

The sensitivity of bedside tests varied from 26% to 98%. This aligns with previous literature, highlighting the challenge of differentiating AUPVP from vestibular pseudoneuritis solely through bedside examination. Although the tests excel in excluding central causes, they are insufficient for diagnosing AUPVP with certainty. In addition, the bedside examination sensitivities vary widely, and early radiological imaging can be misleading. Therefore, this study underlines the necessity of prompt otoneurological testing for accurate exclusion of vestibular pseudoneuritis and thus improve patient outcomes.