bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans parents and the gendered law: Critical reflections on the Swedish regulation
Authors: Alaattinoğlu Daniela , Margaria Alice 
Published: June 2023

Abstract
Sweden has attracted international attention for its 2018 legislative provisions which recognize trans parenthood in line with legal gender. This legislation provides that a trans man who gives birth is registered as his child’s father in Sweden, unlike in most countries of the world. This article offers an original engagement with the genesis, peculiarities, and future of the revised Swedish Children and Parents Code, and the criticism it attracts, as an illustrative example of the inherent challenges present in regulating trans parenthood in a gendered, cis- and hetero-normative legal system. The critical analysis of the Swedish provisions investigates two alternative legal models for regulating trans parenthood from a comparative perspective: degendering legal parenthood and misalignment of legal gender and parental status. Looking towards the future, the article normatively embraces a substantive conceptualization of degendering legal parenthood, rather than merely a nominal one, highlighting the need to rethink and redistribute childcare.
Post-Diapause DNA Replication during Oogenesis in a Capital-Breeding Copepod
Authors: Monell K J , Roncalli V , Hopcroft R R , Hartline D K , Lenz P H 
Published: June 2023

Synopsis
In high-latitude environments where seasonal changes include periods of harsh conditions, many arthropods enter diapause, a period of dormancy that is hormonally regulated. Diapause is characterized by very low metabolism, resistance to environmental stress, and developmental arrest. It allows an organism to optimize the timing of reproduction by synchronizing offspring growth and development with periods of high food availability. In species that enter dormancy as pre-adults or adults, termination of diapause is marked by the resumption of physiological processes, an increase in metabolic rates and once transitioned into adulthood for females, the initiation of oogenesis. In many cases, individuals start feeding again and newly acquired resources become available to fuel egg production. However, in the subarctic capital-breeding copepod Neocalanus flemingeri, feeding is decoupled from oogenesis. Thus, optimizing reproduction limited by fixed resources such that all eggs are of high quality and fully-provisioned, requires regulation of the number of oocytes. However, it is unknown if and how this copepod limits oocyte formation. In this study, the phase in oocyte production by post-diapause females that involved DNA replication in the ovary and oviducts was examined using incubation in 5-Ethynyl-2′-deoxyuridine (EdU). Both oogonia and oocytes incorporated EdU, with the number of EdU-labeled cells peaking at 72 hours following diapause termination. Cell labeling with EdU remained high for two weeks, decreasing thereafter with no labeling detected by four weeks post diapause, and three to four weeks before spawning of the first clutch of eggs. The results suggest that oogenesis is sequential in N. flemingeri with formation of new oocytes starting within 24 hours of diapause termination and limited to the first few weeks. Lipid consumption during diapause was minimal and relatively modest initially. This early phase in the reproductive program precedes mid-oogenesis and vitellogenesis 2, when oocytes increase in size and accumulate yolk and lipid reserves. By limiting DNA replication to the initial phase, the females effectively separate oocyte production from oocyte provisioning. A sequential oogenesis is unlike the income-breeder strategy of most copepods in which oocytes at all stages of maturation are found concurrently in the reproductive structures.
The Forum: Global Challenges to Democracy? Perspectives on Democratic Backsliding
Authors: Bartels Larry M , Daxecker Ursula E , Hyde Susan D , Lindberg Staffan I , Nooruddin Irfan 
Published: June 2023

Abstract
There is a widespread perception that we are witnessing a period of democratic decline, manifesting itself in varieties of democratic backsliding such as the manipulation of elections, marginalization and repression of regime opponents and minorities, or more incremental executive aggrandizement. Yet others are more optimistic and have argued that democracy is in fact resilient, or that we are observing coinciding trends of democratic decline but also expansion. This forum highlights key issues in the debate on democracy's decline, which center on conceptual and measurement issues, agreement on the phenomenon but not its nature or severity, the importance of international factors, the emphasis we should put on political elites versus citizens, and the consequences of backsliding for global politics. Staffan I. Lindberg provides an empirical perspective on the scope and severity of democracy's decline, and argues that polarization and misinformation are important drivers for this current wave of autocratization. Susan D. Hyde highlights the detrimental consequences of reduced support for democracy by the international community, which has affected civil society organizations—important arbiters of democracy—especially severely. Challenging some of these conclusions, Irfan Nooruddin claims that any gains for democracy after the end of the Cold War were short-lived, failing to sustain democracy because of an overemphasis on elections and a disregard for structural factors. Finally, Larry M. Bartels argues that we need to look to political elites and not citizens if we want to protect democracy in the United States and elsewhere, which has important implications for how we study democracy and its challenges.
Doravirine responses to HIV-1 viruses bearing mutations to NRTIs and NNRTIs under in vitro selective drug pressure
Authors: Brenner Bluma G , Oliveira Maureen , Ibanescu Ruxandra-Ilinca , Routy Jean-Pierre , Thomas Réjean 
Published: June 2023

Abstract

Objectives
The NNRTI doravirine has been recently approved for the first-line treatment of HIV-infected patients, eliciting favourable responses against viruses bearing the K103N, Y181C and G190A mutations. This study used in vitro drug selections to elaborate the breadth of doravirine responses against viruses bearing NNRTI and NRTI resistance-associated mutations (RAMs).

Methods
WT clinical isolates (n = 6) and viruses harbouring common NRTI and NNRTI RAMs (n = 6) were serially passaged in escalating concentrations of doravirine, doravirine/islatravir, doravirine/lamivudine and rilpivirine over 24 weeks. Genotypic analysis ascertained the appearance and accumulation of NNRTI RAMs. Phenotypic drug susceptibility assays assessed resistance conferred by acquired NNRTI RAMs.

Results
For WT viruses, doravirine pressure led to the appearance of V108I or V106A/I/M RAMs after 8 weeks, conferring low-level (∼2-fold) resistance. After 24 weeks, the accumulation of three to six secondary RAMs, including F227L, M230L, L234I and/or Y318, resulted in high-level (&gt;100-fold) resistance to doravirine. Notably, viruses with these doravirine RAMs remained susceptible to rilpivirine and efavirenz. This contrasted with rilpivirine where acquisition of E138K, L100I and/or K101E resulted in &gt;50-fold cross-resistance to all NNRTIs. Doravirine selection of viruses bearing common NRTI and NNRTI RAMs showed delayed acquisition of RAMs compared with WT virus. Pairing doravirine with islatravir or lamivudine attenuated the development of NNRTI RAMs.

Conclusions
Doravirine showed favourable resistance profiles against viruses harbouring NRTI and NNRTI RAMs. The high barrier to resistance to doravirine coupled with the long intracellular half-life of islatravir may provide the opportunity for long-acting treatment options.
Boundary recognition of tunnel lining void from ground-penetrating radar data
Authors: Li Chuan , Li Minmin , Yang Xiumei , Zhang Weiping , Fan Mingkun , Yang Xi , Wang Lulu 
Published: June 2023

Abstract
Relatively low ground-penetrating radar antenna frequencies are usually selected for tunnel inspection due to the thickness of the lining, which causes the geometric features of voids in the image to be blurred and difficult to identify. Therefore, the boundary points of the voids are determined by combining reflection and attenuation coefficients, and the geometric features are constructed to identify the voids. Depending on the electromagnetic differences between the void and other mediums in the lining, when the electromagnetic wave propagates from the lining concrete to the void, the reflection coefficient is positive, and the phase of the reflected wave is the same as the incident wave. Conversely, the phase of the reflected wave is opposite to the incident wave. Therefore, the boundary point can be determined in the one dimension time-waveform diagram (A-Scan) based on the phase change. Moreover, the amplitude of the electromagnetic wave attenuates exponentially in the concrete, but it attenuates slowly in the void. Also, electromagnetic waves exhibit high-frequency characteristics in the lining but low-frequency characteristics in the voids. Boundary points that conform to the variation of amplitude and frequency characteristics in the void are screened. These boundary points are then constructed in two-dimensional scan data (B-Scan) to identify the voids by using the geometry of the voids. This method is applied to the Hu Sa Tunnel. The voids are successfully identified in the mileage section YK81+310–YK81+422 of the Hu Sa Tunnel, and the depth of cover and the area of voids are correctly estimated.
SIO-ASCO guideline on integrative medicine for cancer pain management: implications for racial and ethnic pain disparities
Authors: Liou Kevin T , Ashare Rebecca , Worster Brooke , Jones Katie F , Yeager Katherine A , Acevedo Amanda M , Ferrer Rebecca , Meghani Salimah H 
Published: June 2023

Abstract
Racial and ethnic disparities in pain management pose major challenges to equitable cancer care delivery. These disparities are driven by complex interactions between patient-, provider-, and system-related factors that resist reductionistic solutions and require innovative, holistic approaches. On September 19, 2022, the Society for Integrative Oncology and the American Society of Clinical Oncology published a joint guideline to provide evidence-based recommendations on integrative medicine for cancer pain management. Integrative medicine, which combines conventional treatments with complementary modalities from cultures and traditions around the world, are uniquely equipped to resonate with diverse cancer populations and fill existing gaps in pain management. Although some complementary modalities, such as music therapy and yoga, lack sufficient evidence to make a specific recommendation, other modalities, such as acupuncture, massage, and hypnosis, demonstrated an intermediate level of evidence, resulting in moderate strength recommendations for their use in cancer pain management. However, several factors may hinder real-world implementation of the Society for Integrative Oncology and the American Society of Clinical Oncology guideline and must be addressed to ensure equitable pain management for all communities. These barriers include, but are not limited to, the lack of insurance coverage for many complementary therapies, the limited diversity and availability of complementary therapy providers, the negative social norms surrounding complementary therapies, the underrepresentation of racial and ethnic subgroups in the clinical research of complementary therapies, and the paucity of culturally attuned interventions tailored to diverse individuals. This commentary examines both the challenges and the opportunities for addressing racial and ethnic disparities in cancer pain management through integrative medicine.
Novel human STING activation by hydrated-prenylated xanthones from Garcinia cowa
Authors: Tran Thi Thu Thuy , Le Phuong Mai , Nguyen Thi Kim An , Hoang Thi Minh Nguyet , Do Thi Quynh An , Martel Alexandrine L , Lewicky Jordan D , Klem Alexandra , Le Hoang-Thanh 
Published: June 2023

Abstract

Objectives
We investigate the anticancer activity and human stimulator of interferon genes pathway activation by a new hydrated-prenylated tetraoxygenated xanthone, garcicowanone I (1) and two known xanthones (2 and 3) that were isolated from the root bark of Garcinia cowa Roxb. ex Choisy.

Methods
The anticancer activity of each compound was evaluated by sulforhodamine B assay in immortalized cancer cell lines. Stimulator of interferon genes pathway activation was assessed by western blot analysis using human THP-1-derived macrophages. The production of pro-inflammatory cytokines from these macrophages was also evaluated via enzyme-linked immunosorbent assay.

Key findings
Both compounds 1 and 3 displayed moderate inhibitory effects on the cancer cells, including a cisplatin-resistant cell line, with IC50 values in the range of 10–20 µM. All three xanthones activated the stimulator of interferon genes, as evidenced by phosphorylation of tank-binding kinase 1, the stimulator of interferon genes protein and interferon regulatory factor 3. Furthermore, treatment of these macrophages with compounds 1–3 led to the production of pro-inflammatory cytokines, including interleukin 6, tumour necrosis factor α and interleukin 1β.

Conclusions
In conclusion, the isolated xanthones, including the novel garcicowanone I, displayed promising anticancer and immunomodulatory activity that warrants further research.
A novel pyrosequencing strategy for RHD zygosity for predicting risk of hemolytic disease of the fetus and newborn
Authors: Lv Piao , Li Jixin , Yao Yuan , Fan Xinxin , Liu Chixiang , Li Hui , Zhou Huayou 
Published: June 2023

Abstract

Objective
The aim of this study was the development of an accurate and quantitative pyrosequence (PSQ) method for paternal RHD zygosity detection to help risk management of hemolytic disease of the fetus and newborn (HDFN).

Methods
Blood samples from 96 individuals were genotyped for RHD zygosity using pyrosequencing assay. To validate the accuracy of pyrosequencing results, all the samples were then detected by the mismatch polymerase chain reaction with sequence-specific primers (PCR-SSP) method and Sanger DNA sequencing. Serological tests were performed to assess RhD phenotypes.

Results
Serological results revealed that 36 cases were RhD-positive and 60 cases were RhD-negative. The concordance rate between pyrosequencing assay and mismatch PCR-SSP assay was 94.8% (91/96). There were 5 discordant results between pyrosequencing and the mismatch PCR-SSP assay. Sanger sequencing confirmed that the pyrosequencing assay correctly assigned zygosity for the 5 samples.

Conclusion
This DNA pyrosequencing method accurately detect RHD zygosity and will help risk management of pregnancies that are at risk of HDFN.
Virtuality: A Theory of Digital Judaism(S)
Authors: Margolis Peter 
Published: June 2023

Abstract
Digital media enable new possibilities in Jewish life and lived religion. This “digital Judaism” combines elements of Jewish tradition with the capabilities to create, modify, and transform digital objects in novel ways. It builds on American media history and has been greatly accelerated in response to the exigencies of the COVID-19 pandemic of 2020–2021. The Internet as a form of media functions as an amplifier of human capabilities and Jewish possibilities that can be integrated into Jewish life. This creates the contemporary online–offline media ecology to which I apply the theoretical concept of “virtuality.” Virtuality extends and builds upon Heidi Campbell’s religious-social shaping of technology (RSST), Michael Satlow’s “maps” for defining a Judaism, Uzi Rebhun’s study of symbolic Judaism, Ananda Mitra and Rae Lynn Schwatrz’s concept of online/offline cybernetic space, and Jack Wertheimer’s remix concept.
Chemical evolution with radial mixing redux: a detailed model for formation and evolution of the Milky Way
Authors: Chen Boquan , Hayden Michael R , Sharma Sanjib , Bland-Hawthorn Joss , Kobayashi Chiaki , Karakas Amanda I 
Published: June 2023

ABSTRACT
We present a multizone galactic chemical evolution (GCE) model for the Milky Way that takes the most recently updated yields of major nucleosynthesis channels into account. It incorporates physical processes commonly found in previous GCE models like gas feedback from supernovae and star formation, the radial flow of gas in the disc, and the infall of fresh gas, along with stellar scattering processes like radial migration. We individually analyse the effect of different physical processes present in our model on the observed properties of the Galaxy. The radial flow of gas in the disc plays an important role in establishing the radial gradient for [Fe/H] in the low-[α/Fe] sequence. Our model with one episode of smooth gas infall and constant star formation efficiency is capable of reproducing the observed ([Fe/H], [α/Fe]) distribution of stars at different (R, |z|) positions in the Milky Way. Our results point to the rapid evolution of [α/Fe] after the onset of Type Ia supernovae and a high star formation rate during the formation of the high-[α/Fe] sequence as the origin of dual peaks in [α/Fe]. A secondary infall is unnecessary to reproduce the [α/Fe] gap and chemical spread in the disc in our model. We additionally compare the median age for various mono-abundance populations and the age–metallicity relation at different (R, |z|) positions from our fiducial model to observations. We discuss our results in relation to other related work in detail.
Versatile Detection of Diverse Selective Sweeps with Flex-Sweep
Authors: Lauterbur M Elise , Munch Kasper , Enard David 
Published: June 2023

Abstract
Understanding the impacts of selection pressures influencing modern-day genomic diversity is a major goal of evolutionary genomics. In particular, the contribution of selective sweeps to adaptation remains an open question, with persistent statistical limitations on the power and specificity of sweep detection methods. Sweeps with subtle genomic signals have been particularly challenging to detect. Although many existing methods powerfully detect specific types of sweeps and/or those with strong signals, their power comes at the expense of versatility. We present Flex-sweep, a machine learning–based tool designed to detect sweeps with a variety of subtle signals, including those thousands of generations old. It is especially valuable for nonmodel organisms, for which we have neither expectations about the overall characteristics of sweeps nor outgroups with population-level sequencing to otherwise facilitate detecting very old sweeps. We show that Flex-sweep has the power to detect sweeps with subtle signals, even in the face of demographic model misspecification, recombination rate heterogeneity, and background selection. Flex-sweep detects sweeps up to 0.125*4Ne generations old, including those that are weak, soft, and/or incomplete; it can also detect strong, complete sweeps up to 0.25*4Ne generations old. We apply Flex-sweep to the 1000 Genomes Yoruba data set and, in addition to recovering previously identified sweeps, show that sweeps disproportionately occur within genic regions and are close to regulatory regions. In addition, we show that virus-interacting proteins (VIPs) are strongly enriched for selective sweeps, recapitulating previous results that demonstrate the importance of viruses as a driver of adaptive evolution in humans.
ATRT-02. AN INFANTILE PINEAL EMBRYONAL TUMOR SHOWING PATHOLOGICAL FEATURES OF A CNS GANGLIONEUROBLASTOMA IN ADDITION TO SMARCA4 MUTATIONS AND THE METHYLATION PROFILING OF AN ATYPICAL TERATOID/RHABDOID TUMOR
Authors: Fukuoka Kohei , Nakazawa Atsuko , Hirato Junko , Nobusawa Sumihito , Itabashi Toshikazu , Arakawa Yuki , Tanami Yutaka , Ichimura Koichi , Kurihara Jun , Koh Katsuyoshi 
Published: June 2023

Abstract
Embryonal central nervous system tumors require genetic and epigenetic molecular analyses for further classification owing to the pathological, clinical, and molecular heterogeneity among these tumors. Here, we report a case of an infantile pineal tumor showing the pathological features of a CNS ganglioneuroblastoma; however, the specimen also contained SMARCA4 mutations and a methylation signature that is close to an atypical teratoid/rhabdoid tumor. A 2-year-old girl was referred to our hospital because of headache and dizziness presented with a pineal tumor and obstructive hydrocephalus. Radiologically, a large calcification was observed in the mass on head CT. The patient underwent tumor resection, and the pathological diagnosis was CNS ganglioneuroblastoma at that time. The specimen contained a variety of tumor cells, including undifferentiated embryonal cells, neurocytic cells, and ganglion cells embedded in a fibrillary matrix. The patient has been well for 5 years since they received multiagent chemotherapy and local proton irradiation. Subsequent genome-wide DNA methylation analysis revealed that the tumor was molecularly close to a sonic-hedgehog pathway-activated atypical teratoid/rhabdoid tumor. Genetic analysis also revealed SMARCA4 alterations in the splicing region of exons 10 and 34. This report indicates that genetic and epigenetic molecular approaches may facilitate elucidation of the clinical heterogeneity of CNS embryonal tumors, particularly the pathological appearance of CNS ganglioneuroblastomas.
ATRT-17. CAR T CELL THERAPY TARGETING CLAUDIN-6 IS EFFECTIVE IN CELLULAR AND XENOGRAFT MODELS OF ATYPICAL TERATOID/RHABDOID TUMOR
Authors: Madsen Peter , Stern Allison , Dickson Conor , Wilson Cullen , Patterson Luke , Harvey Kyra , Griffin Crystal , Oehm Petra , Rengstl Benjamin , Flemmig Carina , Storm Phillip , Resnick Adam , Foster Jessica 
Published: June 2023

Abstract
Novel therapies are needed to for the treatment of atypical teratoid/rhabdoid tumor (ATRT), an aggressive brain tumor that predominantly affects young children and has an average 5-year survival under 50%. Claudin-6 (CLDN6) is a tight junction protein present during development and is expressed in up to 70% of ATRT specimens but not in normal tissue, making it a promising immunotherapeutic target. CLDN6-targeted chimeric antigen receptor (CAR) T cells in combination with a CAR T cell-amplifying mRNA vaccine have demonstrated antitumor activity against other CLDN6-expressing cancers in pre-clinical and a phase I adult trial (NCT04503278; Haanen J et al AACR, 2022). To assess the effectiveness of CLDN6-targeted CAR T cells against ATRT, we utilized a second-generation mRNA CAR with a 4-1BB costimulatory domain and single-chain variable fragment against CLDN6 (Reinhard et al, 2020). CLDN6 expression in patient-derived ATRT specimens was profiled by RNAseq (mean FPKM 11.4) and immunohistochemistry (positive staining in 53% of specimens). Tumor-derived cell lines were assessed for CLDN6 expression by flow cytometry. Co-culture of CLDN6-directed mRNA CAR T cells resulted in tumor-specific cytotoxicity compared to CD19-directed control CAR T cells in CLDN6-positive ATRT cell lines 7316-2187 (92% versus 15% at 10:1, p &lt; 0.0001; 86% versus 0% at 5:1, p&lt;0.0001) and 7316-2141 (75% versus 7% at 10:1, p&lt;0.0001; 53% versus 0% at 5:1, p&lt; 0.0001). Patient-derived, orthotopic xenograft ATRT models were created through intracranial injection of tumor cells into the cerebellum of NSG mice. Following engraftment with 7316-2141, repeated intratumoral administration of mRNA CLDN6 CAR T cells resulted in significant tumor regression (-1.9x108 vs. +2.4x109 p/sec/cm2/sr, p&lt;0.001) and improved survival compared to mRNA CD19 CAR T cells (median OS not reached vs. 13 days, p=0.002). This work highlights the potential for targeting CLDN6 via CAR T cell therapy in patients with ATRT as a novel therapeutic strategy.