bluuebunny/crossref_metadata_2025_split huggingface dataset:
Female Immunity Protects from Cutaneous Squamous Cell Carcinoma
Authors: Budden Timothy , Gaudy-Marqueste Caroline , Craig Sarah , Hu Yuan , Earnshaw Charles H. , Gurung Shilpa , Ra Amelle , Akhras Victoria , Shenjere Patrick , Green Ruth , Jamieson Lynne , Lear John , Motta Luisa , Caulín Carlos , Oudit Deemesh , Furney Simon J. , Virós Amaya 
Published: April 2021

Abstract

Purpose:
Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women present with less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation.

Experimental Design:
We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients with primary cSCC (N = 738, N = 160), advanced-stage cSCC (N = 63, N = 20) and FVB/N mice exposed to equal doses of DMBA, as well as in human keratinocytes by whole-exome, bulk, and single-cell RNA sequencing.

Results:
We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test whether sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present with more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T-cell infiltration independently of mutations, a response that is absent in prednisolone-treated animals. In contrast, males increase the rate of mitosis and proliferation in response to carcinogen. Women's skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at UV radiation–damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women.

Conclusions:
This work shows the immune response is sex biased in cSCC and highlights female immunity offers greater protection than male immunity.
Phase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide
Authors: de Bono Johann S. , Fleming Mark T. , Wang Judy S. , Cathomas Richard , Miralles Manuel Selvi , Bothos John , Hinrichs Mary Jane , Zhang Qu , He Peng , Williams Marna , Rosenbaum Anton I. , Liang Meina , Vashisht Kapil , Cho Song , Martinez Pablo , Petrylak Daniel P. 
Published: April 2021

Abstract

Purpose:
MEDI3726 is an antibody–drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This phase I study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.

Patients and Methods:
MEDI3726 was administered at 0.015–0.3 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary objective was to assess safety, dose-limiting toxicities (DLT), and MTD/maximum administered dose (MAD). Secondary objectives included assessment of antitumor activity, pharmacokinetics, and immunogenicity. The main efficacy endpoint was composite response, defined as confirmed response by RECIST v1.1, and/or PSA decrease of ≥50% after ≥12 weeks, and/or decrease from ≥5 to &lt;5 circulating tumor cells/7.5 mL blood.

Results:
Between February 1, 2017 and November 13, 2019, 33 patients received MEDI3726. By the data cutoff (January 17, 2020), treatment-related adverse events (TRAE) occurred in 30 patients (90.9%), primarily skin toxicities and effusions. Grade 3/4 TRAEs occurred in 15 patients (45.5%). Eleven patients (33.3%) discontinued because of TRAEs. There were no treatment-related deaths. One patient receiving 0.3 mg/kg had a DLT of grade 3 thrombocytopenia. The MTD was not identified; the MAD was 0.3 mg/kg. The composite response rate was 4/33 (12.1%). MEDI3726 had nonlinear pharmacokinetics with a short half-life (0.3–1.8 days). The prevalence of antidrug antibodies was 3/32 (9.4%), and the incidence was 13/32 (40.6%).

Conclusions:
Following dose escalation, no MTD was identified. Clinical responses occurred at higher doses, but were not durable as patients had to discontinue treatment due to TRAEs.
Next-Generation Sequencing of 487 Esophageal Adenocarcinomas Reveals Independently Prognostic Genomic Driver Alterations and Pathways
Authors: Sihag Smita , Nussenzweig Samuel C. , Walch Henry S. , Hsu Meier , Tan Kay See , Sanchez-Vega Francisco , Chatila Walid K. , De La Torre Sergio A. , Patel Assem , Janjigian Yelena Y. , Maron Steven , Ku Geoffrey Y. , Tang Laura H. , Hechtman Jaclyn , Shah Pari M. , Wu Abraham J. , Jones David R. , Molena Daniela , Solit David B. , Schultz Nikolaus , Berger Michael F. 
Published: April 2021

Abstract

Purpose:
To delineate recurrent oncogenic driver alterations and dysregulated pathways in esophageal adenocarcinoma and to assess their prognostic value.

Experimental Design:
We analyzed a large cohort of patients with lower esophageal and junctional adenocarcinoma, prospectively sequenced by MSK-IMPACT with high-quality clinical annotation. Patients were subdivided according to treatment intent, curative versus palliative, which closely mirrored clinical staging. Genomic features, alterations, and pathways were examined for association with overall survival using Cox proportional hazard models, adjusted for relevant clinicopathologic factors knowable at the time of diagnosis.

Results:
Analysis of 487 patients revealed 16 oncogenic driver alterations, mostly amplifications, present in ≥5% of patients. Patients in the palliative-intent cohort, compared with those in the curative-intent cohort, were more likely to have metastatic disease, ERBB2 amplifications, Cell-cycle and RTK–RAS pathway alterations, as well as a higher fraction of genome altered and rate of whole-genome doubling. In multivariable analyses, CDKN2A alterations, SMAD4 alterations, KRAS amplifications, Cell-cycle and TGFβ pathways, and overall number of oncogenic drivers were independently associated with worse overall survival. ERBB2 amplification was associated with improved survival, presumably due to trastuzumab therapy.

Conclusions:
Our study suggests that higher levels of genomic instability are associated with more advanced disease in esophageal adenocarcinoma. Furthermore, CDKN2A, KRAS, and SMAD4 represent prognostic biomarkers, given their strong association with poor survival.
High Cardiovascular Risk in Older Men With Severe Peripheral Artery Calcification on High-Resolution Peripheral QCT Scans
Authors: Szulc Pawel , Planckaert Catherine , Foesser Dominique , Patsch Janina , Chapurlat Roland 
Published: April 2021

Objective:
Arterial calcification is associated with high cardiovascular risk. Our aim was to assess the utility of peripheral arterial calcification (PAC) in distal forearm and distal leg for the prediction of acute coronary syndrome (ACS) and major adverse cardiovascular event in older men.

Approach and Results:

In 815 home-dwelling older men, PAC was assessed on the scans of distal forearm and leg obtained by high-resolution peripheral quantitative computed tomography. PAC score (0–12) was calculated on the basis of the number and severity in small peripheral arteries. The information on ACS and major adverse cardiovascular event was collected prospectively for 8 years. PAC severity increased with age and body mass index (
P
<0.001). Median PAC score was higher in men with ischemic heart disease or pharmacologically treated diabetes (
P
<0.001). After adjustment for confounders, the risk of ACS was higher in men with severe PAC (6+) versus men with lower PAC (0–5; hazard ratio, 3.86 [95% CI, 1.65–9.02],
P
<0.005). After adjustment for confounders, the risk of major adverse cardiovascular event was higher in men with severe PAC (6+) versus men with lower PAC (hazard ratio, 2.58 [95% CI, 1.41–4.72],
P
<0.005). In men who did not have cardiovascular risk factors, severe PAC was associated with higher risk of ACS, for example, in men who did not self-report ischemic heart disease (hazard ratio, 6.62 [95% CI, 2.16–20.23],
P
<0.001).

Conclusions:
Severe PAC is associated with higher risk of ACS and major adverse cardiovascular event in older home-dwelling men, also in men without known ischemic heart disease. Incidentally found severe PAC can be a serious warning indicating high cardiovascular risk.
Rosenzweig on Human Redemption: Neither Nothing nor Everything, but Only Something
Authors: Wolfson Elliot R. 
Published: April 2021

Abstract
Despite Franz Rosenzweig’s unequivocal condemnation of Gershom Scholem, his own view of the world and the possibility of human redemption therein is in some respect very close to the nihilistic sensibility and its gnostic underpinning. Although Rosenzweig obviously did not consider himself either a nihilist or a gnostic, the latter term can well be applied even to Rosenzweig’s mature speculation in The Star of Redemption and other writings from the 1920s. In spite of his initial rejection of negative theology in the Star, the swerve of Rosenzweig’s path winds its way to an apophasis of the apophasis, a turn that is encapsulated in the astounding statement, “That God is nothing becomes just as much a figurative sentence as the other one, that he is truth.”
Jurisdictional Challenges and Institutional Novelties – Procedural Developments in Law of the Sea Dispute Settlement in 2020
Authors: Lando Massimo , Oral Nilüfer 
Published: April 2021

Abstract
In 2020, law of the sea tribunals rendered one decision on jurisdiction and decided one case on the merits. First, the arbitral tribunal in the Azov Sea and Kerch Strait dispute dismissed the jurisdictional objections raised by the Russian Federation and thus will proceed to hear the merits of Ukraine’s claims. Second, the arbitral tribunal in the Enrica Lexie Incident case found, after upholding its jurisdiction in relation to the dispute before it, that the Italian marines who had shot an Indian fisherman in India’s Exclusive Economic Zone were entitled to immunity under international law and that Italy had breached certain provisions of the United Nations Convention on the Law of the Sea (UNCLOS). These two arbitral awards have confirmed and developed certain trends in the jurisprudence of law of the sea tribunals. In addition, a novelty in 2020 was the conclusion of a Model Agreement between Singapore and the International Tribunal for the Law of the Sea (ITLOS), for the latter to be able to discharge its judicial business in Singapore. Last, the Meeting of the States Parties to UNCLOS elected five new members of ITLOS and re-elected two.
Zebrus pallaoroi sp. nov.: a new species of goby (Actinopterygii: Gobiidae) from the Mediterranean Sea with a dna-based phylogenetic analysis of the Gobius-lineage
Authors: Kovačić Marcelo , Šanda Radek , Čekovská Katarína , Soukupová Tereza , Vukić Jasna 
Published: April 2021

Abstract
The gobies (Gobiidae) are the most diverse fish family in the Mediterranean Sea. Nevertheless, knowledge on their diversity, taxonomy, and phylogenetic relationships is still inadequate. The phylogenetic analyses reveal two genetically highly distinct clades among specimens identified as Zebrus zebrus. A new species, Zebrus pallaoroi sp. nov., is described based on an integrative approach. The neotype of Zebrus zebrus is designated. Genetic data confirm a pronounced level of divergence between Z. pallaoroi and Z. zebrus, with the mean genetic distance on cytochrome b being 18.1% and 1.07% on rhodopsin. Phylogenetic relationships within the Gobius-lineage were estimated on both markers. Morphologically, Z. pallaoroi is distinguished from the only congener Z. zebrus by having a snout longer than its eye, posterior nostril about 4/5–9/10 of the anterior nostril, eye diameter 4.3−4.7 in head length, ventrolateral head ridges transversally connected on the anterior side by a short transversal ridge, anterior membrane midline depth about 2/3 of the spinous ray, head canal pore α diameter about half of the distance between pore ρ and ρ1, suborbital sensory papillae row 5i going downwards to or near the level of row d, the distance between row 5i and row d absent or much smaller than the length of row 5i, and the body with ten to eleven vertical dark brown bands. Zebrus pallaoroi was recorded from the southern Adriatic, northern Ionian, and northern and western Aegean Seas, and is a cryptobenthic fish from very shallow waters.
Bodies in Motion
Authors: Smith Tyler Jo 
Published: April 2021

Abstract
Drawing on the combined approaches of ancient Greek iconography, dance history, and the archaeology of ritual and religion, this paper examines dance gesture as a mechanism of ritual communication in ancient Greek vase-painting. After presenting the problems and limitations of matching art and text with regard to dance, as both Classical scholars and practitioners of modern dance have attempted, the paper expands on various ways of showing dance on vases. Special attention is given to komast dancers on black-figure vases and to other types of dance scenes and figures. A rethinking of the evidence for dance as ritual on Greek vases is proposed under the two categories of non-repetitive and repetitive gesture. It is posited that such a distinction anticipates the mood, participants, and occasions, and might indicate discrete areas of ritual activity. Dance, gesture, and ritual are also considered according to the gender and sexuality of performers, the presence of the divine, and the relationship between the shape, composition, and function of some vessels.
Pacific Meridional Modes without Equatorial Pacific Influence
Authors: Zhang Yu , Yu Shiyun , Amaya Dillon J. , Kosaka Yu , Larson Sarah M. , Wang Xudong , Yang Jun-Chao , Stuecker Malte F. , Xie Shang-Ping , Miller Arthur J. , Lin Xiaopei 
Published: April 2021

AbstractInvestigating Pacific Meridional Modes (PMM) without the influence of tropical Pacific variability is technically difficult if based on observations or fully coupled model simulations due to their overlapping spatial structures. To confront this issue, the present study investigates both North (NPMM) and South PMM (SPMM) in terms of their associated atmospheric forcing and response processes based on a mechanically decoupled climate model simulation. In this experiment, the climatological wind stress is prescribed over the tropical Pacific, which effectively removes dynamically coupled tropical Pacific variability (e.g., the El Niño-Southern Oscillation). Interannual NPMM in this experiment is forced not only by the North Pacific Oscillation, but also by a North Pacific tripole (NPT) pattern of atmospheric internal variability, which primarily forces decadal NPMM variability. Interannual and decadal variability of the SPMM is partly forced by the South Pacific Oscillation. In turn, both interannual and decadal NPMM variability can excite atmospheric teleconnections over the Northern Hemisphere extratropics by influencing the meridional displacement of the climatological intertropical convergence zone throughout the whole year. Similarly, both interannual and decadal SPMM variability can also excite atmospheric teleconnections over the Southern Hemisphere extratropics by extending/shrinking the climatological South Pacific convergence zone in all seasons. Our results highlight a new poleward pathway by which both the NPMM and SPMM feed back to the extratropical climate, in addition to the equatorward influence on tropical Pacific variability.
Flash Drought in CMIP5 Models
Authors: Hoffmann David , Gallant Ailie J. E. , Hobbins Mike 
Published: April 2021

Abstract‘Flash drought’ (FD) describes the rapid onset of drought on sub-seasonal times scales. It is of particular interest for agriculture as it can deplete soil moisture for crop growth in just a few weeks. To better understand the processes causing FD, we evaluate the importance of evaporative demand and precipitation by comparing three different drought indices that estimate this hazard using meteorological and hydrological parameters from the CMIP5 suite of models. We apply the Standardized Precipitation Index (SPI); the Evaporative Demand Drought Index (EDDI), derived from evaporative demand (E0); and the Evaporative Stress Index (ESI), which connects atmospheric and soil moisture conditions by measuring the ratio of actual and potential evaporation. The results show moderate-to-strong relationships (r2 > 0.5) between drought indices and upper level soil moisture on daily time scales, especially in drought-prone regions. We find that all indices are able to identify FD in the top 10-cm layer of soil moisture in a similar proportion to that in the models’ climatologies. However, there is significant inter-model spread in the characteristics of the FDs identified. This spread is mainly caused by an overestimation of E0, indicating stark differences in the land surface models and coupling in individual CMIP5 models. Of all indices, the SPI provides the highest skill in predicting FD prior to or at the time of onset in soil moisture, while both EDDI and ESI show significantly lower skill. The results highlight that the lack of precipitation is the main contributor to FDs in climate models, with E0 playing a secondary role.
Comparative wave measurements at a wave energy site with a recently developed low-cost wave buoy (Spotter), ADCP and pressure loggers
Authors: Lancaster Orrin , Cossu Remo , Boulay Sebastien , Hunter Scott , Baldock Tom E. 
Published: April 2021

AbstractWave measurements from a new, low-cost, real-time wave buoy (Spotter) are investigated in a comparative study as part of a site characterization study at a wave energy candidate site at King Island, Tasmania, Australia. Measurements from the Sofar Ocean Spotter buoy are compared with concurrent measurements from a Teledyne RD Instrument (RDI) 1200 kHz Work Horse ADCP and two RBRsolo3 D wave16 pressure loggers. The comparison period between 8th August – 12th October 2019 provides both the shallowest and longest continuous published comparison undertaken with the Spotter buoy.Strong agreement was evident between the Spotter buoy and RDI ADCP of key wave parameters including the significant wave height, peak wave period, and mean wave direction, with the mean values of those parameters across the full deployment period agreeing within 3%. Surface wave spectra and directional spectra are also analyzed with good agreement observed over the majority of the frequency domain, although the Spotter buoy records approximately 17% less energy within a narrow frequency band near the peak frequency when compared to the RDI ADCP. Measurements derived from the pressure loggers routinely underestimated the significant wave height and overestimated the mean wave period over the deployment period. The comparison highlights the suitability of the Spotter buoy for low-cost wave resource studies, with accurate measurements of key parameters and spectra observed.
Betacellulin regulates peripheral nerve regeneration by affecting Schwann cell migration and axon elongation
Authors: Wang Yaxian , Zhang Fuchao , Zhang Yunsong , Shan Qi , Liu Wei , Zhang Fengyuan , Zhang Feiyu , Yi Sheng 
Published: April 2021

Abstract
Background
Growth factors execute essential biological functions and affect various physiological and pathological processes, including peripheral nerve repair and regeneration. Our previous sequencing data showed that the mRNA coding for betacellulin (Btc), an epidermal growth factor protein family member, was up-regulated in rat sciatic nerve segment after nerve injury, implying the potential involvement of Btc during peripheral nerve regeneration.

Methods
Expression of Btc was examined in Schwann cells by immunostaining. The function of Btc in regulating Schwann cells was investigated by transfecting cultured cells with siRNA segment against Btc or treating cells with Btc recombinant protein. The influence of Schwann cell-secreted Btc on neurons was determined using a co-culture assay. The in vivo effects of Btc on Schwann cell migration and axon elongation after rat sciatic nerve injury were further evaluated.

Results
Immunostaining images and ELISA outcomes indicated that Btc was present in and secreted by Schwann cells. Transwell migration and wound healing observations showed that transfection with siRNA against Btc impeded Schwann cell migration while application of exogenous Btc advanced Schwann cell migration. Besides the regulating effect on Schwann cell phenotype, Btc secreted by Schwann cells influenced neuron behavior and increased neurite length. In vivo evidence supported the promoting role of Btc in nerve regeneration after both rat sciatic nerve crush injury and transection injury.

Conclusion
Our findings demonstrate the essential roles of Btc on Schwann cell migration and axon elongation and imply the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.
The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling
Authors: Sipos Adrienn , Ujlaki Gyula , Mikó Edit , Maka Eszter , Szabó Judit , Uray Karen , Krasznai Zoárd , Bai Péter 
Published: April 2021

AbstractOvarian cancer is characterized by dysbiosis, referred to as oncobiosis in neoplastic diseases. In ovarian cancer, oncobiosis was identified in numerous compartments, including the tumor tissue itself, the upper and lower female genital tract, serum, peritoneum, and the intestines. Colonization was linked to Gram-negative bacteria with high inflammatory potential. Local inflammation probably participates in the initiation and continuation of carcinogenesis. Furthermore, local bacterial colonies in the peritoneum may facilitate metastasis formation in ovarian cancer. Vaginal infections (e.g.Neisseria gonorrhoeaeorChlamydia trachomatis) increase the risk of developing ovarian cancer. Bacterial metabolites, produced by the healthy eubiome or the oncobiome, may exert autocrine, paracrine, and hormone-like effects, as was evidenced in breast cancer or pancreas adenocarcinoma. We discuss the possible involvement of lipopolysaccharides, lysophosphatides and tryptophan metabolites, as well as, short-chain fatty acids, secondary bile acids and polyamines in the carcinogenesis of ovarian cancer. We discuss the applicability of nutrients, antibiotics, and probiotics to harness the microbiome and support ovarian cancer therapy. The oncobiome and the most likely bacterial metabolites play vital roles in mediating the effectiveness of chemotherapy. Finally, we discuss the potential of oncobiotic changes as biomarkers for the diagnosis of ovarian cancer and microbial metabolites as possible adjuvant agents in therapy.