bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecocide, Sustainable Development and Critical Environmental Law Insights
Authors: Minkova Liana Georgieva 
Published: June 2024

Abstract
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

Abstract
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

Abstract

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 (&lt;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 (&lt;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

Abstract
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

Abstract
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

Abstract
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

ABSTRACT

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

Abstract
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

Abstract
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

ABSTRACT
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

ABSTRACT

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 &lt; .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

Abstract

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.