bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging the gap in author names: building an enhanced author name dataset for biomedical literature system
Authors: Zhang Li , Song Ningyuan , Gui Sisi , Wu Keye , Lu Wei
Published: June 2024

Objective

Author name incompleteness, referring to only first initial available instead of full first name, is a long-standing problem in MEDLINE and has a negative impact on biomedical literature systems. The purpose of this study is to create an Enhanced Author Names (EAN) dataset for MEDLINE that maximizes the number of complete author names.

Materials and methods

The EAN dataset is built based on a large-scale name comparison and restoration with author names collected from multiple literature databases such as MEDLINE, Microsoft Academic Graph, and Semantic Scholar. We assess the impact of EAN on biomedical literature systems by conducting comparative and statistical analyses between EAN and MEDLINE’s author names dataset (MAN) on 2 important tasks, author name search and author name disambiguation.

Results

Evaluation results show that EAN improves the number of full author names in MEDLINE from 69.73 million to 110.9 million. EAN not only restores a substantial number of abbreviated names prior to the year 2002 when the NLM changed its author name indexing policy but also improves the availability of full author names in articles published afterward. The evaluation of the author name search and author name disambiguation tasks reveal that EAN is able to significantly enhance both tasks compared to MAN.

Conclusion

The extensive coverage of full names in EAN suggests that the name incompleteness issue can be largely mitigated. This has significant implications for the development of an improved biomedical literature system. EAN is available at https://zenodo.org/record/10251358, and an updated version is available at https://zenodo.org/records/10663234.
Using large language model to guide patients to create efficient and comprehensive clinical care message
Authors: Liu Siru , Wright Aileen P , Mccoy Allison B , Huang Sean S , Genkins Julian Z , Peterson Josh F , Kumah-Crystal Yaa A , Martinez William , Carew Babatunde , Mize Dara , Steitz Bryan , Wright Adam
Published: June 2024

Objective

This study aims to investigate the feasibility of using Large Language Models (LLMs) to engage with patients at the time they are drafting a question to their healthcare providers, and generate pertinent follow-up questions that the patient can answer before sending their message, with the goal of ensuring that their healthcare provider receives all the information they need to safely and accurately answer the patient’s question, eliminating back-and-forth messaging, and the associated delays and frustrations.

Methods

We collected a dataset of patient messages sent between January 1, 2022 to March 7, 2023 at Vanderbilt University Medical Center. Two internal medicine physicians identified 7 common scenarios. We used 3 LLMs to generate follow-up questions: (1) Comprehensive LLM Artificial Intelligence Responder (CLAIR): a locally fine-tuned LLM, (2) GPT4 with a simple prompt, and (3) GPT4 with a complex prompt. Five physicians rated them with the actual follow-ups written by healthcare providers on clarity, completeness, conciseness, and utility.

Results

For five scenarios, our CLAIR model had the best performance. The GPT4 model received higher scores for utility and completeness but lower scores for clarity and conciseness. CLAIR generated follow-up questions with similar clarity and conciseness as the actual follow-ups written by healthcare providers, with higher utility than healthcare providers and GPT4, and lower completeness than GPT4, but better than healthcare providers.

Conclusion

LLMs can generate follow-up patient messages designed to clarify a medical question that compares favorably to those generated by healthcare providers.
Computational investigation of methanol-based hybrid nanofluid flow over a stretching cylinder with Cattaneo–Christov heat flux
Authors: Farooq Umar , Liu Haihu , Basem Ali , Fatima Nahid , Alhushaybari Abdullah , Imran Muhammad , Ali Naim Ben , Muhammad Taseer
Published: June 2024

This study investigates heat transfer rates in (AA7075-AA7072/Methanol) hybrid nanofluid flows, considering non-uniform heat sources and Cattaneo–Christov heat flux, with significant implications for aerospace engineering by enhancing thermal management in aircraft engines. The findings could revolutionize automotive cooling system efficiency, optimize heat dissipation in electronic devices, and advance the design of renewable energy systems such as concentrated solar power plants. The study aims to conduct a comparative analysis of (AA7075/Methanol) nanofluid and (AA7075-AA7072/Methanol) hybrid nanofluid flow, examining heat transfer rates, non-uniform heat sources, and Cattaneo–Christov heat flux theory around a stretching cylinder. Thermal radiation and the Biot number are also evaluated. Two different nanoparticles, AA7072 and AA7075, are used with methanol to create AA7075/Methanol nanofluid and AA7075-AA7072/Methanol hybrid nanofluid. The study compresses the resultant non-linear partial differential equation system and applies suitable similarity transformations to reduce the governing partial differential equations with boundary conditions to dimensionless form. The BVP4C shooting method in MATLAB is employed to numerically and graphically solve these dimensionless ordinary differential equations. The results indicate that higher curvature parameter values correlate with increased velocity and temperature distribution profiles. A rise in nanoparticle volume fraction reduces the radial velocity profile but increases the temperature profile. Temperature distribution profiles increase with higher thermal radiation parameter and Biot number values, while higher thermal relaxation parameter values decrease temperature. Additionally, thermal distribution profiles rise with increasing values of both the time-dependent heat source constant and space-dependent heat source parameter.
Regulating Platform Fees
Authors: Wang Chengsi , Wright Julian
Published: June 2024

We consider platforms that help consumers discover and transact with suppliers. Such platforms have come to dominate many sectors of the economy, raising issues about the high fees they charge suppliers, especially since they tend to commoditize the suppliers they aggregate. We show that in a baseline setting, the efficient platform fee is determined by a simple formula: it equals the platform’s marginal cost plus the difference between suppliers’ markups on the direct channel and suppliers’ markups on the platform. We explore the extent to which this simple formula provides a robust cap for regulating the platform’s fee more generally.
Ecocide, Sustainable Development and Critical Environmental Law Insights
Authors: Minkova Liana Georgieva
Published: June 2024

Advocates of the criminalization of ecocide face a dilemma: how to address activities that bring socio-economic benefits and cause severe environmental damage. The solution has generally been seen in the integration of international environmental law (IEL) norms, such as balancing sustainability with development, into the definition of ecocide. This article challenges the uncritical adoption of IEL norms in ecocide debates and explores the socio-ecological implications of relying on those norms in future trials at the International Criminal Court. While this article does not offer a new definition of ecocide, by borrowing insights from critical environmental law and studies of law in the Anthropocene it proposes a new approach for engaging with the question of ecocide, namely, by embracing reflexivity and normativity in legal practice.
Substance P regulates memory Th17 cell generation and maintenance in chronic dry eye disease
Authors: Wang Shudan , Naderi Amirreza , Kahale Francesca , Ortiz Gustavo , Forouzanfar Katayoon , Chen Yihe , Dana Reza
Published: June 2024

Substance P is a neuropeptide expressed by nerves and an array of cells that serves as a critical mediator of neuroinflammation. Our recent work has demonstrated that blocking the preferred receptor for substance P, neurokinin 1 receptor, effectively suppresses the induction of acute dry eye disease by preserving regulatory T-cell function, while inhibiting antigen-presenting cell maturation and subsequent generation of effector Th17 cells. Clinically, dry eye disease is a chronic disorder characterized by sustained ocular surface inflammation, which is mediated by long-lived memory Th17 cells demonstrated in our well-established chronic dry eye disease model. The present study aimed to further understand the function of substance P in the chronic phase of dry eye disease and its role in regulating the underlying pathogenic memory Th17. In vitro culture of effector T cells isolated from acute dry eye disease with substance P led to an enhanced conversion of effector Th17 to memory Th17, while culturing memory T cells isolated from chronic dry eye disease with substance P effectively preserved the memory Th17 cells. In contrast, the addition of a neurokinin 1 receptor antagonist in the cultures abolished the substance P–mediated effects. Furthermore, in vivo treatment with the neurokinin 1 receptor antagonist during the resolution phase of acute dry eye disease significantly suppressed memory Th17 generation, and treatment in the chronic phase of dry eye disease disrupted the maintenance of memory Th17. Taken together, our results demonstrate that increased expression of substance P promotes memory Th17 generation and maintenance in chronic dry eye disease, and thus blockade of substance P represents a novel promising memory Th17–targeting strategy in treating chronic ocular surface inflammation.
Fecal, duodenal, and tumor microbiota composition of esophageal carcinoma patients, a longitudinal prospective cohort
Authors: van den Ende Tom , de Clercq Nicolien C , Davids Mark , Goedegebuure Ruben , Doeve Benthe H , Ebrahimi Gati , Buijsen Jeroen , Hoekstra Ronald , Mohammad Nadia Haj , Bijlsma Maarten F , Nieuwdorp Max , van Laarhoven Hanneke W M
Published: June 2024

Background

The microbiome has been associated with chemotherapy and immune checkpoint inhibitor efficacy. How this pertains to resectable esophageal carcinoma is unknown. Our aim was to identify microbial signatures in resectable esophageal carcinoma associated with response to neoadjuvant chemoradiotherapy with or without an immune checkpoint inhibitor.

Methods

From 2 prospectively collected esophageal carcinoma cohorts (n = 172 in total) treated with neoadjuvant chemoradiotherapy alone (n = 132) or a combination of neoadjuvant chemoradiotherapy and an immune checkpoint inhibitor (n = 40), fecal samples were available at baseline, during treatment, and presurgery. Additionally, in the immune checkpoint inhibitor–treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor, and duodenal DNA were extracted for 16S ribosomal RNA sequencing. Associations were investigated between microbiome composition pathological complete response and progression-free survival (PFS).

Results

There was a statistically significant shift in the microbiota profile of the fecal, tumor, and duodenal microbiota over time. In the total cohort, patients with a pathological complete response had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment (P = .036). Presurgery, lower alpha diversity (<4.12) was related to worse PFS (log-rank P = .025). Baseline tumor biopsies of patients with short PFS had more Fusobacterium. A low baseline duodenal alpha diversity (<3.96) was associated with worse PFS (log-rank P = .012).

Conclusions

Lower intestinal alpha diversity was associated with worse response and survival of esophageal carcinoma patients. In tumor biopsies, Fusobacterium was more abundant in patients with poor PFS. After further mechanistic validation, these findings may aid in response prediction and the design of novel microbiome modulating treatments for esophageal carcinoma patients.
Mixed pituitary adenoma/pituitary neuroendocrine tumor-gangliocytoma: Immunohistochemical insights
Authors: Kleinschmidt-DeMasters Bette K
Published: June 2024

Mixed pituitary adenoma/PitNET-gangliocytomas (PA/PitNET-GC) have been reported in small series over the past 20 years; some had limited immunohistochemistry (IHC) data. We interrogated our experience over 20 years, focusing on patterns of the GC component and IHC results for anterior pituitary hormones, transcription factors, NFP, and CAM5.2. A search of cases from 2002 to 2023 yielded 20 cases: 7M:13F, ages 20–71 years; 17 macroadenomas, 1 microadenoma, 2 ectopic. GC was co-associated with 4 corticotroph, 2 densely granulated lactotroph, 5 mixed lactotroph-somatotroph, 1 immature PIT1-lineage tumor, and 8 sparsely granulated GH; the latter all had a minor lactotroph component. Patterns were: discrete nodular foci of GC (9/20), extensive GC differentiation often overshadowing the PA/PitNET (7/20), and intimate admixture of smaller bands of neuropil and individual metaplastic ganglion cells within PA/PitNET (4/20). NFP highlighted small cohesive regions of neuropil and identified greater axonal content, including individual axons within “pure” PA/PitNET areas, than appreciated on H&E. CAM5.2 IHC often revealed cells with neuronal morphologies to a greater extent than NFP and in different areas within the same tumor. These data suggest that the combined use of NFP and CAM5.2 IHC best reveals transition from PA to GC phenotype, with CAM5.2 positivity reflecting earlier stages of transformation.
Arinole, a novel auxin-stimulating benzoxazole, affects root growth and promotes adventitious root formation
Authors: Depaepe Thomas , Prinsen Els , Hu Yuming , Sanchez-Munoz Raul , Denoo Bram , Buyst Dieter , Darouez Hajer , Werbrouck Stefaan , Hayashi Ken-ichiro , Martins José , Winne Johan , Van Der Straeten Dominique
Published: June 2024

The triple response phenotype is characteristic for seedlings treated with the phytohormone ethylene or its direct precursor 1-aminocyclopropane-carboxylic acid, and is often employed to find novel chemical tools to probe ethylene responses. We identified a benzoxazole-urea derivative (B2) partially mimicking ethylene effects in a triple response bioassay. A phenotypic analysis demonstrated that B2 and its closest analogue arinole (ARI) induced phenotypic responses reminiscent of seedlings with elevated levels of auxin, including impaired hook development and inhibition of seedling growth. Specifically, ARI reduced longitudinal cell elongation in roots, while promoting cell division. In contrast to other natural or synthetic auxins, ARI mostly acts as an inducer of adventitious root development, with only limited effects on lateral root development. Quantification of free auxins and auxin biosynthetic precursors as well as auxin-related gene expression demonstrated that ARI boosts global auxin levels. In addition, analyses of auxin reporter lines and mutants, together with pharmacological assays with auxin-related inhibitors, confirmed that ARI effects are facilitated by TRYPTOPHAN AMINOTRANSFERASE1 (TAA1)-mediated auxin synthesis. ARI treatment in an array of species, including Arabidopsis, pea, tomato, poplar, and lavender, resulted in adventitious root formation, which is a desirable trait in both agriculture and horticulture.
Mortality Linked to Bullying and Other Forms of Maltreatment
Authors: Srabstein Jorge C.
Published: June 2024

This chapter highlights some of the hundreds of global news reports about deaths associated with bullying and other forms of maltreatment. The data provide only the tip of the iceberg that is mortality related to bullying and other forms of victimization, because the real dimensions remain, so far, unknown. Yet, there are several studies that have examined the risk of suicide among people who were bullied and/or exposed to other types of victimization, as well as frequency of homicide among victims of different types of maltreatment. As a first step in estimating the global prevalence of mortality associated with bullying and other forms of maltreatment, it is recommended that every coroner or medical examiner report systematically include information about bullying or any other form of victimization or maltreatment experienced by a victim of suicide death. The bullying should be characterized by having been experienced within the previous 1 or 2 months, and it may have been reported to family members or others. Information concerning exposure to victimization should be gathered as part of the investigation to ascertain possible factors related to suicide, in the same context as depression, alcohol and drug abuse, and major life stresses. Thus, while we recognize the multiple correlates of suicide, we should begin to highlight the role of bullying or other forms of victimization and eventually estimate their contribution to this type of unnatural death.
Lactation Initiation During COVID-19 at a Single Military Hospital
Authors: Hutchins-Wiese Heather L , Powell Shawndra , Ford Olivia , Spitzer Trimble
Published: June 2024

Introduction

Human milk is associated with positive short- and long-term health outcomes. Women’s choice to breastfeed is influenced by personal, social, health, and economic factors. The COVID-19 pandemic impacted health care delivery, non-emergent health care services, and family lifestyles, primarily in the early months of 2020. The aim of this study was to determine if breastfeeding initiation rates differed during a global pandemic among women in the military health care system.

Materials and Methods

This was a cross-sectional chart review study. We compiled all birthing event health records from March to August in 2019 and 2020 from a single military medical center. Of the 2,737 maternal-infant dyads available, 1,463 met complete inclusion criteria and were analyzed to determine associations between delivery year, maternal and infant characteristics, and initial feeding methods. Institutional research approvals were obtained from the university and medical center institutional review boards.

Results

There was no significant association between breastfeeding initiation rates and delivery year (X2(1) = 2.898, P = .089). Some maternal and infant characteristics significantly associated with the feeding method in the logistic regression model and differed by delivery year. Black women were 1.9 times less likely to initiate breastfeeding compared to White women; this disparity became more pronounced in 2020. Multiparous mothers, those who gave birth via cesarean section, and those at earlier gestational ages (32–37 weeks) were less likely to initiate breastfeeding. Models differed by delivery year, with only Black race and cesarean birth significantly impacting the overall model in 2020. Maternal age, military status, military rank, marital status, birth complications, and infant gender were not associated with the feeding method.

Conclusions

Overall breastfeeding initiation rates did not differ during the COVID-19 pandemic when rates in 2020 were compared to those in the year prior. Race, birth method, parity, and gestational age were associated with breastfeeding initiation rates in women cared for at military centers.
A comprehensive analysis of 3′UTRs in Caenorhabditis elegans
Authors: Murari Emma , Meadows Dalton , Cuda Nicholas , Mangone Marco
Published: June 2024

3′Untranslated regions (3′UTRs) are essential portions of genes containing elements necessary for pre-mRNA 3′end processing and are involved in post-transcriptional gene regulation. Despite their importance, they remain poorly characterized in eukaryotes. Here, we have used a multi-pronged approach to extract and curate 3′UTR data from 11533 publicly available datasets, corresponding to the entire collection of Caenorhabditis elegans transcriptomes stored in the NCBI repository from 2009 to 2023. We have also performed high throughput cloning pipelines to identify and validate rare 3′UTR isoforms and incorporated and manually curated 3′UTR isoforms from previously published datasets. This updated C. elegans 3′UTRome (v3) is the most comprehensive resource in any metazoan to date, covering 97.4% of the 20362 experimentally validated protein-coding genes with refined and updated 3′UTR boundaries for 23489 3′UTR isoforms. We also used this novel dataset to identify and characterize sequence elements involved in pre-mRNA 3′end processing and update miRNA target predictions. This resource provides important insights into the 3′UTR formation, function, and regulation in eukaryotes.
Aptamer binding footprints discriminate α-synuclein fibrillar polymorphs from different synucleinopathies
Authors: Bouvier-Müller Alix , Fourmy Deborah , Fenyi Alexis , Bousset Luc , Melki Ronald , Ducongé Frédéric
Published: June 2024

Synucleinopathies, including dementia with Lewy bodies (DLB), Parkinson's disease (PD), and multiple system atrophy (MSA), are characterized by the presence of α-synuclein (α-syn) aggregates in the central nervous system. Recent evidence suggests that the heterogeneity of synucleinopathies may be partly explained by the fact that patients may have different α-syn fibrillar polymorphs with structural differences. In this study, we identify nuclease resistant 2′fluoro-pyrimidine RNA aptamers that can differentially bind to structurally distinct α-syn fibrillar polymorphs. Moreover, we introduce a method, AptaFOOT-Seq, designed to rapidly assess the affinity of a mixture of these aptamers for different α-SYN fibrillar polymorphs using next-generation sequencing. Our findings reveal that the binding behavior of aptamers can be very different when they are tested separately or in the presence of other aptamers. In this case, competition and cooperation can occur, providing a higher level of information, which can be exploited to obtain specific ‘footprints’ for different α-Syn fibrillar polymorphs. Notably, these footprints can distinguish polymorphs obtained from patients with PD, DLB or MSA. This result suggests that aptaFOOT-Seq could be used for the detection of misfolded or abnormal protein conformations to improve the diagnosis of synucleinopathies.
Cancer therapy in patients with reduced kidney function
Authors: Karam Sabine , Rosner Mitchell H , Sprangers Ben , Stec Rafal , Malyszko Jolanta
Published: June 2024

Chronic kidney disease (CKD) and cancer constitute two major public health burdens, and both are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. The potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anticancer therapies, i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anticancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia and other metabolic abnormalities because of a decreased glomerular filtration rate. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy are very limited and only single cases or small case series have been published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.
Limitations of biopsy-based transcript diagnostics to detect T-cell-mediated allograft rejection
Authors: Weidmann Lukas , Harmacek Dusan , Castrezana Lopez Kai , Helmchen Birgit Maria , Gaspert Ariana , Korach Raphael , Bortel Nicola , Schmid Nicolas , von Moos Seraina , Rho Elena , Schachtner Thomas
Published: June 2024

Background

Isolated tubulitis, borderline changes and isolated arteritis suspicious for histologic T-cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR).

Methods

In this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with isolated tubulitis (i0, t1–3, v0; n = 101), borderline changes (according to Banff 2022, v0; n = 9), isolated arteritis (no borderline, v1; n = 37), no inflammation (i0, t0, v0; n = 67) and a positive control cohort (hTCMR, n = 27; mixed histologic rejection, n = 8; both according to Banff 2022; total n = 35). The first three groups were summarized as TCMR-suspicion (n = 147). Subcategorization included the presence and absence of microvascular inflammation (MVI); g+ptc ptc ≥2. Molecular rejection rates and differentiation were investigated.

Results

Molecular rejection rates were 37/147 cases (25.2%; 32 with MVI) in TCMR-suspicion, 6/67 (9%; 4 with MVI) in no inflammation and 30/35 (85.7%; 19 with MVI) in the positive control cohort. Molecular antibody-mediated rejection (mAMR) was present in 39/73 (53.4%) of cases. The presence of donor-specific antibodies at the time of the biopsy was high (127/249, 51%). Only 3 mAMR/TCMR and 0 pure mTCMR cases were detected in TCMR-suspicion and no inflammation, compared with 12 mAMR/TCMR and 10 mTCMR cases in the positive control cohort (P < .001). Even though the TCMR-specific molecular (Classifier) score differentiated between TCMR-suspicion and no inflammation (P = 0.005), rejection phenotype scores (R2 and R3) did not (P = .157 and .121).

Conclusions

MMDx did not identify pure mTCMR among isolated tubulitis, borderline changes or isolated arteritis, likely due to low sensitivity for TCMR lesions. However, it identified mAMR or mAMR/TCMR, especially in cases with MVI. Subthreshold findings remain to be further studied.
Outcomes and relapse patterns in primary central nervous system lymphoma: Longitudinal analysis of 559 patients diagnosed from 1983 to 2020
Authors: Tringale Kathryn R , Scordo Michael , Yahalom Joachim , White Charlie , Zhang Zhigang , Vachha Behroze , Cederquist Gustav , Schaff Lauren , DeAngelis Lisa , Grommes Christian , Imber Brandon S
Published: June 2024

Background

Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow-up.

Methods

T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983 to 2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, or other. Progression-free (PFS) and overall survival (OS) were assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse.

Results

Median follow-up was 7.4 years (N = 559). Most (321, 57%) were recursive partitioning analysis class 2 (age ≥50, Karnosfky Performance Status [KPS] ≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5 years for 351 patients with CR/CRu to consolidation was 80% (95% confidence interval [95% CI]: 76%–84%) and 46% (95% CI: 41%–53%), respectively; 1-year cumulative incidence of local versus nonlocal relapse was 1.8% versus 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local versus nonlocal relapse was 57% versus 42%, respectively. Deep structure involvement (HR 1.89, 95% CI: 1.10%–3.27%) was associated with local relapse in refractory patients.

Conclusions

We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.
Effect of Intermittent Fasting on Liver Function Tests: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Ranjbar Mahsa , Shab-Bidar Sakineh , Mohammadi Hamed , Djafarian Kurosh
Published: June 2024

Context

Intermittent fasting (IF) is a diet strategy with alternate intervals of calorie reduction and normal eating. Despite its beneficial effects on weight loss and cardiometabolic risk factors, the effect of IF on liver function tests (LFTs) remains unclear.

Objective

This study aimed to investigate the effect of IF on LFTs through a systematic review and meta-analysis of randomized clinical trials.

Data Sources

An electronic search was performed using predefined search terms in databases including PubMed, Scopus, and ISI Web of Science until February 2023.

Data Extraction

The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for the randomized controlled trials.

Data Analysis

The results of this study are reported as weighted mean differences (WMDs) with 95% CIs. Fourteen RCTs were included in the meta-analysis, with a total sample size of 908. IF significantly reduced alanine aminotransferase (ALT) (WMD: −2.88, 95% CI: −4.72 to −1.04, P-value = .002) and aspartate aminotransferase (AST) levels (WMD: −1.67, 95% CI: −3.12 to −0.22, P-value = .024). The results of the subgroup analysis showed that the impact of IF was significant in both the nonalcoholic fatty liver disease and the healthy groups for ALT. The effects of IF on the serum gamma-glutamyl transpeptidase (GGT) level were significant (WMD: −3.19, 95% CI: −6.00 to −0.39, P-value = .026), but there were no significant changes in the alkaline phosphatase (ALP) level (WMD: 1.06, 95% CI: −0.23 to 2.34, P-value = .106). Furthermore, no substantial heterogeneity between studies was reported.

Conclusion

IF can improve ALT, AST, and GGT levels but not ALP enzyme levels and may have a benefit on liver function.

Systematic Review Registration

PROSPERO registration no. CRD42023396211.
Uncertainties and confidence in stratospheric aerosol injection modelling: a systematic literature review
Authors: Määttänen Anni , Lameille Thibaut , Kloeck Carola , Boucher Olivier , Ravetta François
Published: June 2024

Model projections performed to evaluate the efficacy and impacts of solar geoengineering interventions, such as Stratospheric Aerosol Injection (SAI), include multiple sources of uncertainty, namely scenario, model, and natural variability uncertainty. It is well accepted that a quantitative uncertainty assessment related to SAI modelling is required to provide robust and policy-relevant information on SAI. This study investigates how and to what extent articles using a climate modelling approach on SAI quantify and communicate uncertainty sources. We conducted a systematic literature review of a sample of 60 peer-reviewed articles in order to (i) analyse whether uncertainties were addressed, and if yes, which methods were used to characterize uncertainties, and (ii) study how the articles communicated assumptions and limits that contribute to the estimation of confidence in the used models and the resulting projections. We present statistics on the uncertainty quantification methods used in the articles and we discuss the vocabulary employed for conveying these uncertainties and model confidence. In the studied article sample, the attention paid to uncertainty estimations in the SAI literature increased with time, and overall, uncertainties were treated using a variety of methods. Model confidence was not always explicitly communicated as the models used are already tested in the literature and their strengths and weaknesses are known to the community although this is often implicit. Our results show that it is currently difficult to perform global, quantitative assessments of uncertainty related to SAI research, in line with recent review reports on solar geoengineering.
Defining the Real Mary Magdalene
Authors: Taylor Joan E.
Published: June 2024

This chapter provides an overview of the major evidence and modern works defining Mary Magdalene as a real person. The body of evidence concerning Mary Magdalene is largely comprised of canonical Gospels, early extracanonical Gospels, and other works that may be repositories of independent memories. The most important evidence for the historical Mary Magdalene lies in the canonical Gospels, particularly the Gospel of Mark. The chapter then discusses recent studies of the historical Mary Magdalene within feminist historiography and popular history. It considers the interplay of Mary Magdalene with the divine, free from classical Christian dogma within the contemporary world.
Firefly toxin lucibufagins evolved after the origin of bioluminescence
Authors: Zhu Chengqi , Lu Xiaoli , Cai Tianlong , Zhu Kangli , Shi Lina , Chen Yinjuan , Wang Tianyu , Yang Yaoming , Tu Dandan , Fu Qi , Huang Jing , Zhen Ying
Published: June 2024

Fireflies were believed to originally evolve their novel bioluminescence as warning signals to advertise their toxicity to predators, which was later adopted in adult mating. Although the evolution of bioluminescence has been investigated extensively, the warning signal hypothesis of its origin has not been tested. In this study, we test this hypothesis by systematically determining the presence or absence of firefly toxin lucibufagins (LBGs) across firefly species and inferring the time of origin of LBGs. We confirm the presence of LBGs in the subfamily Lampyrinae, but more importantly, we reveal the absence of LBGs in other lineages, including the subfamilies of Luciolinae, Ototretinae, and Psilocladinae, two incertae sedis lineages, and the Rhagophthalmidae family. Ancestral state reconstructions for LBGs based on firefly phylogeny constructed using genomic data suggest that the presence of LBGs in the common ancestor of the Lampyrinae subfamily is highly supported but unsupported in more ancient nodes, including firefly common ancestors. Our results suggest that firefly LBGs probably evolved much later than the evolution of bioluminescence. We thus conclude that firefly bioluminescence did not originally evolve as direct warning signals for toxic LBGs and advise that future studies should focus on other hypotheses. Moreover, LBG toxins are known to directly target and inhibit the α subunit of Na+, K+-ATPase (ATPα). We further examine the effects of amino acid substitutions in firefly ATPα on its interactions with LBGs. We find that ATPα in LBG-containing fireflies is relatively insensitive to LBGs, which suggests that target-site insensitivity contributes to LBG-containing fireflies' ability to deal with their own toxins.
Understanding underlying physical mechanism reveals early warning indicators and key elements for adaptive infections disease networks
Authors: Wang Linqi , Zhang Kun , Xu Li , Wang Jin
Published: June 2024

The study of infectious diseases holds significant scientific and societal importance, yet current research on the mechanisms of disease emergence and prediction methods still face challenging issues. This research uses the landscape and flux theoretical framework to reveal the non-equilibrium dynamics of adaptive infectious diseases and uncover its underlying physical mechanism. This allows the quantification of dynamics, characterizing the system with two basins of attraction determined by gradient and rotational flux forces. Quantification of entropy production rates provides insights into the system deviating from equilibrium and associated dissipative costs. The study identifies early warning indicators for the critical transition, emphasizing the advantage of observing time irreversibility from time series over theoretical entropy production and flux. The presence of rotational flux leads to an irreversible pathway between disease states. Through global sensitivity analysis, we identified the key factors influencing infectious diseases. In summary, this research offers valuable insights into infectious disease dynamics and presents a practical approach for predicting the onset of critical transition, addressing existing research gaps.
Open-ended versus bounded evolution: Mineral evolution as a case study
Authors: Hazen Robert M , Wong Michael L
Published: June 2024

To what extent are naturally evolving systems limited in their potential diversity (i.e. “bounded”) versus unrestricted (“open-ended”)? Minerals provide a quantitative model evolving system, with well-documented increases in mineral diversity through multiple stages of planetary evolution over billions of years. A recent framework that unifies behaviors of both biotic and abiotic evolving systems posits that all such systems are characterized by combinatorial richness subject to selection. In the case of minerals, combinatorial richness derives from the possible combinations of chemical elements coupled with permutations of their formulas' coefficients. Observed mineral species, which are selected for persistence through deep time, represent a miniscule fraction of all possible element configurations. Furthermore, this model predicts that as planetary systems evolve, stable minerals become an ever-smaller fraction of the “possibility space.” A postulate is that “functional information,” defined as the negative log2 of that fraction, must increase as a system evolves. We have tested this hypothesis for minerals by estimating the fraction of all possible chemical formulas observed from one stage of mineral evolution to the next, based on numbers of different essential elements and the maximum chemical formula complexity at each of nine chronological stages of mineral evolution. We find a monotonic increase in mineral functional information through these nine stages—a result consistent with the hypothesis. Furthermore, analysis of the chemical formulas of minerals demonstrates that the modern Earth may be approaching the maximum limit of functional information for natural mineral systems—a result demonstrating that mineral evolution is not open-ended.
Formation of the pyruvoyl-dependent proline reductase Prd from Clostridioides difficile requires the maturation enzyme PrdH
Authors: Behlendorf Christian , Diwo Maurice , Neumann-Schaal Meina , Fuchs Manuela , Körner Dominik , Jänsch Lothar , Faber Franziska , Blankenfeldt Wulf
Published: June 2024

Stickland fermentation, the coupled oxidation and reduction of amino acid pairs, is a major pathway for obtaining energy in the nosocomial bacterium Clostridioides difficile. D-proline is the preferred substrate for the reductive path, making it not only a key component of the general metabolism but also impacting on the expression of the clostridial toxins TcdA and TcdB. D-proline reduction is catalyzed by the proline reductase Prd, which belongs to the pyruvoyl-dependent enzymes. These enzymes are translated as inactive proenzymes and require subsequent processing to install the covalently bound pyruvate. Whereas pyruvoyl formation by intramolecular serinolysis has been studied in unrelated enzymes, details about pyruvoyl generation by cysteinolysis as in Prd are lacking. Here, we show that Prd maturation requires a small dimeric protein that we have named PrdH. PrdH (CD630_32430) is co-encoded with the PrdA and PrdB subunits of Prd and also found in species producing similar reductases. By producing stable variants of PrdA and PrdB, we demonstrate that PrdH-mediated cleavage and pyruvoyl formation in the PrdA subunit requires PrdB, which can be harnessed to produce active recombinant Prd for subsequent analyses. We further created PrdA- and PrdH-mutants to get insight into the interaction of the components and into the processing reaction itself. Finally, we show that deletion of prdH renders C. difficile insensitive to proline concentrations in culture media, suggesting that this processing factor is essential for proline utilization. Due to the link between Stickland fermentation and pathogenesis, we suggest PrdH may be an attractive target for drug development.
Convicting Corrupt Officials: Evidence from Randomly Assigned Cases
Authors: Axbard Sebastian
Published: June 2024

Can the judiciary help root out government corruption? This article exploits the random assignment of court cases to justices who exhibit varying degrees of strictness to examine how convicting corrupt officials affects local government outcomes in the Philippines. I document that convictions improve the management of local public finances and reduce associated corruption. An exploration of mechanisms suggests that legal deterrence effects contribute to these findings. The results further indicate that convictions are effective at stifling corruption among bureaucrats, but not politicians. Consistent with this heterogeneity, convictions reduce electoral competition and consequently weaken accountability for incumbent politicians.
News Diffusion in Social Networks and Stock Market Reactions
Authors: Hirshleifer David , Peng Lin , Wang Qiguang
Published: June 2024

We study how the social transmission of public news influences investors’ beliefs and the securities markets. Using data on social networks, we find that earnings announcements from firms in higher-centrality counties generate a stronger immediate price, volatility, and trading volume reactions. Post-announcement, such firms experience weaker price drift and faster volatility decay but higher and more persistent volume. These findings suggest greater social connectedness facilitates the timely incorporation of news into prices, as well as opinion divergence and excessive trading. We propose the social churning hypothesis, which is confirmed using granular data from StockTwits messages and household trading records.
Two Polyketide Synthase Genes, VpPKS10 and VpPKS33, Regulated by VpLaeA Are Essential to the Virulence of Valsa pyri
Authors: Zhu Liangliang , Tang Lin , Tian Xiangrong , Bai Yayuan , Huang Lili
Published: June 2024

Valsa pyri, the causal agent of pear canker disease, typically induces cankers on the bark of infected trees and even leads to tree mortality. Secondary metabolites produced by pathogenic fungi play a crucial role in the pathogenic process. In this study, secondary metabolic regulator VpLaeA was identified in V. pyri. VpLaeA was found to strongly affect the pathogenicity, fruiting body formation, and toxicity of secondary metabolites of V. pyri. Additionally, VpLaeA was found to be required for the response of V. pyri to some abiotic stresses. Transcriptome data analysis revealed that many of differentially expressed genes were involved in the secondary metabolite biosynthesis. Among them, about one third of secondary metabolite biosynthesis core genes were regulated by VpLaeA at different periods. Seven differentially expressed secondary metabolite biosynthesis core genes ( VpPKS9, VpPKS10, VpPKS33, VpNRPS6, VpNRPS7, VpNRPS16, and VpNRPS17) were selected for knockout. Two modular polyketide synthase genes ( VpPKS10 and VpPKS33) that were closely related to the virulence of V. pyri from the above seven genes were identified. Notably, VpPKS10 and VpPKS33 also affected the production of fruiting body of V. pyri but did not participate in the resistance of V. pyri to abiotic stresses. Overall, this study demonstrates the multifaceted biological functions of VpLaeA in V. pyri and identifies two toxicity-associated polyketide synthase genes in Valsa species fungi for the first time.
Integrative analysis of Lunatic Fringe variants associated with spondylocostal dysostosis type‐III
Authors: Wengryn Parker , Fenrich Felicity , Silveira Karina da Costa , Oborn Connor , Mizumoto Shuji , Beke Alexander , Soltys Carrie‐Lynn , Yamada Shuhei , Kannu Peter
Published: June 2024

Lunatic Fringe (LFNG) is required for spinal development. Biallelic pathogenic variants cause spondylocostal dysostosis type‐III (SCD3), a rare disease generally characterized by malformed, asymmetrical, and attenuated development of the vertebral column and ribs. However, a variety of SCD3 cases reported have presented with additional features such as auditory alterations and digit abnormalities. There has yet to be a single, comprehensive, functional evaluation of causative LFNG variants and such analyses could unveil molecular mechanisms for phenotypic variability in SCD3. Therefore, nine LFNG missense variants associated with SCD3, c.564C>A, c.583T>C, c.842C>A, c.467T>G, c.856C>T, c.601G>A, c.446C>T, c.521G>A, and c.766G>A, were assessed in vitro for subcellular localization and protein processing. Glycosyltransferase activity was quantified for the first time in the c.583T>C, c.842C>A, and c.446C>T variants. Primarily, our results are the first to satisfy American College of Medical Genetics and Genomics PS3 criteria (functional evidence via well‐established assay) for the pathogenicity of c.583T>C, c.842C>A, and c.446C>T, and replicate this evidence for the remaining six variants. Secondly, this work indicates that all variants that prevent Golgi localization also lead to impaired protein processing. It appears that the FRINGE domain is responsible for this phenomenon. Thirdly, our data suggests that variant proximity to the catalytic residue may influence whether LFNG is improperly trafficked and/or enzymatically dysfunctional. Finally, the phenotype of the axial skeleton, but not elsewhere, may be modulated in a variant‐specific fashion. More reports are needed to continue testing this hypothesis. We anticipate our data will be used as a basis for discussion of genotype–phenotype correlations in SCD3.
Hypertension management in chronic kidney disease
Authors: Liddell Toddra S. , Henry-Okafor Queen , Umeukeje Ebele M.
Published: June 2024

This article offers a guide for NPs for managing hypertension (HTN) in adults in the setting of chronic kidney disease (CKD). It outlines evidence-based strategies, including lifestyle modifications, pharmacologic interventions, and patient education measures, that can be used in patients with CKD to optimize BP control. Special considerations, such as comorbid mental health conditions and individualized treatment plans, are also addressed. NPs play a pivotal role in improving outcomes by fostering patient engagement and adherence. By embracing this holistic approach, NPs are poised to enhance the quality of care and well-being of patients with CKD and HTN.