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Queerphobia is defined as society's negative attitude towards LGBTQIA + people, translating into structures that marginalise LGBTQIA + people and contribute to health inequities that cause real harm and can be understood as structural violence. The purpose of this article is to explore what historically marginalised youth in a youth participatory action research (YPAR) project characterise as the big picture issues affecting the lives of LGBTQIA + youth. We used participatory arts-based methods to conduct community and identity building, define research questions and photo prompts, conduct data collection, engage in group thematic analysis, and make recommendations at the state policy level. We also conducted individual semi-structured interviews with participants. Our findings can be grouped into three main themes: LGBTQIA + youth may feel it is safer to remain closeted; queerphobia perpetuates housing instability; and queerphobia functions as a structural barrier to social services. Youth also developed state level policy recommendations to address the structural issues causing harm to LGBTQIA + youth health. Recommendations included increasing access to affordable housing and LGBTQIA + inclusive foster and group homes, and advocating for government-funded LGBTQIA + specific healthcare practices for LGBTQIA + youth. More youth-driven data are needed that centre those directly impacted by structural violence and associated health outcomes.

Huntington's Disease (HD) is an inheritable neurodegenerative condition caused by an expanded CAG trinucleotide repeat in the HTT gene with a direct correlation between CAG repeats expansion and disease severity with earlier onset-of- disease. Previously we have shown that primary skin fibroblasts from HD patients exhibit unique phenotype disease features, including distinct nuclear morphology and perturbed actin cap linked with cell motility, that are correlated with the HD patient disease severity. Here we provide further evidence that mitochondrial fission-fusion morphology balance dynamics, classified using a custom image-based high-content analysis (HCA) machine learning tool, that improved correlation with HD severity status. This mitochondrial phenotype is supported by appropriate changes in fission-fusion biomarkers (Drp1, MFN1, MFN2, VAT1) levels in the HD patients' fibroblasts. These findings collectively point towards a dysregulation in mitochondrial dynamics, where both fission and fusion processes may be disrupted in HD cells compared to healthy controls. This study shows for the first time a methodology that enables identification of HD phenotype before patient's disease onset (Premanifest). Therefore, we believe that this tool holds a potential for improving precision in HD patient's diagnostics bearing the potential to evaluate alterations in mitochondrial dynamics throughout the progression of HD, offering valuable insights into the molecular mechanisms and drug therapy evaluation underlying biological differences in any disease stage., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Similarly to wild poliovirus, vaccine-derived poliovirus (VDPV) strains can cause acute flaccid paralysis, posing a considerable challenge to public health and the eradication of poliovirus. VDPV outbreaks, particularly VDPV type 2 (VDPV2), are increasing worldwide, including in high-income countries with high vaccine coverage. We aimed to conduct a comprehensive analysis of the molecular epidemiology of a widespread VDPV2 outbreak in Israel in 2022-23 using conventional polio identification techniques and whole-genome sequencing., Methods: In this genomic epidemiology study, we monitored and identified poliovirus type 2 (PV2) through the surveillance of stool samples from individuals with acute flaccid paralysis and related contacts, as well as environmental surveillance of sewage samples. Environmental surveillance involved 15 routine surveillance sites and an additional 30 sites dedicated to monitoring this outbreak, covering approximately 70% of Israel's population between April 1, 2022, and June 30, 2023. Additionally, we performed phylogenetic and mutation analyses using whole-genome, next-generation sequencing of PV2 isolates to identify recombination events, characterise VDPV2 lineages according to the capsid region, and establish the geographical distribution and linkage of PV2 isolates., Findings: We detected 256 genetically linked samples from environmental surveillance, as well as one case of acute flaccid paralysis and four positive contacts associated with the Sabin type 2 oral vaccine strain. Most affected locations showed a high-density population of Jewish Ultra-Orthodox communities. Through high-resolution genomic characterisation and phylogenetic analysis of 202 representative sequences with complete capsid coverage, including isolates from both environmental surveillance and the case of acute flaccid paralysis, a conclusive linkage was established among all detections, confirming them to be part of a single VDPV2 outbreak. This strategy enabled the characterisation of three distinct lineages and established connections between different locations in Israel, including linking the case of acute flaccid paralysis and nearby environmental surveillance detections from the northern region with detections in the geographically distant central region., Interpretation: This study highlights the role of environmental surveillance in the early detection and monitoring of poliovirus circulation, enabling a prompt public health response involving enhanced surveillance and a catch-up campaign with inactivated polio vaccine. Whole-genome sequencing offered valuable insights into the origins of the outbreak, linkage across detections, and the geographical distribution of the virus, with higher resolution than would have been possible with the standard analysis of the VP1 gene alone., Funding: None., Competing Interests: Declaration of interests LMS reports consulting for a novel OPV working group and attending related meetings. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Huntington's disease (HD) is a complex neurodegenerative disorder with considerable heterogeneity in clinical manifestations. While CAG repeat length is a known predictor of disease severity, this heterogeneity suggests the involvement of additional genetic and environmental factors. Previously we revealed that HD primary fibroblasts exhibit unique features, including distinct nuclear morphology and perturbed actin cap, resembling characteristics seen in Hutchinson-Gilford Progeria Syndrome (HGPS). This study establishes a link between actin cap deficiency and cell motility in HD, which correlates with the HD patient disease severity. Here, we examined single-cell motility imaging features in HD primary fibroblasts to explore in depth the relationship between cell migration patterns and their respective HD patients' clinical severity status (premanifest, mild and severe). The single-cell analysis revealed a decline in overall cell motility in correlation with HD severity, being most prominent in severe HD subgroup and HGPS. Moreover, we identified seven distinct spatial clusters of cell migration in all groups, which their proportion varies within each group becoming a significant HD severity classifier between HD subgroups. Next, we investigated the relationship between Lamin B1 expression, serving as nuclear envelope morphology marker, and cell motility finding that changes in Lamin B1 levels are associated with specific motility patterns within HD subgroups. Based on these data we present an accurate machine learning classifier offering comprehensive exploration of cellular migration patterns and disease severity markers for future accurate drug evaluation opening new opportunities for personalized treatment approaches in this challenging disorder., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The rewetting of formerly drained peatlands can help to counteract climate change through the reduction of CO 2 emissions. However, this can lead to resuming CH 4 emissions due to changes in the microbiome, favoring CH 4 -producing archaea. How plants, hydrology and microbiomes interact as ultimate determinants of CH 4 dynamics is still poorly understood. Using a mesocosm approach, we studied peat microbiomes, below-ground root biomass and CH 4 fluxes with three different water level regimes (stable high, stable low and fluctuating) and four different plant communities (bare peat, Carex rostrata, Juncus inflexus and their mixture) over the course of one growing season. A significant difference in microbiome composition was found between mesocosms with and without plants, while the difference between plant species identity or water regimes was rather weak. A significant difference was also found between the upper and lower peat, with the difference increasing as plants grew. By the end of the growing season, the methanogen relative abundance was higher in the sub-soil layer, as well as in the bare peat and C. rostrata pots, as compared to J. inflexus or mixture pots. This was inversely linked to the larger root area of J. inflexus. The root area also negatively correlated with CH 4 fluxes which positively correlated with the relative abundance of methanogens. Despite the absence or low abundance of methanotrophs in many samples, the integration of methanotroph abundance improved the quality of the correlation with CH 4 fluxes, and methanogens and methanotrophs together determined CH 4 fluxes in a structural equation model. However, water regime showed no significant impact on plant roots and methanogens, and consequently, on CH 4 fluxes. This study showed that plant roots determined the microbiome composition and, in particular, the relative abundance of methanogens and methanotrophs, which, in interaction, drove the CH 4 fluxes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by Agl , enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. Here, we tested the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model Agl -/- . We used open field, grip strength, and rotarod tests for evaluating GHF-201's effects on locomotion, a biochemistry panel to quantify hematological biomarkers, indirect calorimetry to quantify in vivo metabolism, transmission electron microscopy to quantify glycogen in muscle, and fibroblast image analysis to determine cellular features affected by GHF-201. GHF-201 was able to improve all locomotion parameters and partially reversed hypoglycemia, hyperlipidemia and liver and muscle malfunction in Agl -/- mice. Treated mice burnt carbohydrates more efficiently and showed significant improvement of aberrant ultrastructural muscle features. In GSDIII patient fibroblasts, GHF-201 restored mitochondrial membrane polarization and corrected lysosomal swelling. In conclusion, GHF-201 is a viable candidate for treating GSDIII as it recovered a wide range of its pathologies in vivo, in vitro, and ex vivo.

Our studies toward the total synthesis of the natural product euphosalicin ( 1 ) are presented. Different approaches targeting key intermediates are described, the synthesis of which includes findings on asymmetric dihydroxylations and ring-closing enyne metatheses (RCEYM). Their connection allowed the isolation of highly advanced precursors for studies on macrocyclizations. Our efforts culminated in the preparation of the unique C11/C12 ( Z ) isomer of the C13 nor methyl skeleton of euphosalicin ( 1 ).

Motivated by the scarcity of enantioselective direct intermolecular α-alkylation reactions of ketones with simple alkyl halides, we report a photo-organocatalytic process to access diethyl 2-(2-oxocyclohexyl)malonate and derivatives in good yield and enantioselectivity. The reaction design is based on highly abundant and nature-derived 9-amino-9-deoxy- epi -cinchona alkaloids to activate ketones as transient secondary enamines, which exist unfavorably in equilibrium with imines. These condensed species can serve as powerful photoinitiators via direct photoexcitation. This concept provides access to both enantiomeric antipodes. In addition to introducing an uncomplicated batch-optimized procedure, we investigated the feasibility and limitations of implementing the reaction in continuous flow, thus enabling to obtain diethyl 2-(2-oxocyclohexyl)malonate with a productivity of 47 μmol/h and 84% enantioselectivity.

Na 2 (Fe 2/3 Te 4/3 )O 6 ( Z = 3) or Na 3 (FeTe 2 )O 9 ( Z = 2), tris-odium iron(III) ditellurium(VI) nona-oxide, adopts the ilmenite (FeTiO 3 , Z = 6) structure type with the Ti site (site symmetry 3.) replaced by Na and the Fe site (site symmetry 3.) replaced by a mixed-occupied (Fe III ,Te VI ) site in a Fe:Te ratio of 1:2. Whereas the [(Fe,Te)O 6 ] octa-hedron is only slightly distorted, the [NaO 6 ] octa-hedron shows much stronger distortions, as revealed by a larger spread of the bond lengths and some distortion parameters., (© Eder and Weil 2024.)

Background and Aims: An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections have been suggested as possible triggers. However, the potential etiology is still unclear. We aimed to characterize a cohort of children with HUO in Israel in view of the COVID-19 pandemic., Method: Demographics, clinical data, and laboratory results on the children compatible with the CDC criteria for HUO were collected by the established registry of the Ministry of Health. Available specimens were sent to the Central Virology Laboratory., Results: A total of 39 children were included in the registry. A total of 20 were enrolled prospectively, in which human herpes virus 6 (HHV6) infection or reactivation was identified in 11/19, adenovirus was found in 4/19 of the cases, and AAV2 was detected in 2/16. Past COVID-19 exposure was recorded for 24/39 of the children. A total of 10 children underwent liver biopsy, and 8 were successfully treated with steroids and 2 underwent liver transplantation., Conclusions: The COVID-19 pandemic and the related containment measures combined with reactivation or active infection with other viruses could have been a trigger for the HUO outbreak. In our cohort, HHV6 was the most abundant finding.

The title compound, ammonium trinickel(II) hydrogen arsenate arsenate di-hydroxide, was synthesized under hydro-thermal conditions. Its crystal structure is isotypic with that of K[Cu 3 (HAsO 4 )(AsO 4 )(OH) 2 ] and is characterized by pseudo-hexa-gonal (001) 2 ∞ [Ni 3 As 2 O 18/3 (OH) 6/3 O 1/1 (OH) 1/1 ] - layers formed from vertex- and edge-sharing [NiO 4 (OH) 2 ] octa-hedra and [AsO 3.5 (OH) 0.5 ] tetra-hedra as the building units. The hydrogen atom of the OH group shows occupational disorder and was refined with a site occupation factor of 1/2, indicating the equal presence of [HAsO 4 ] 2- and [AsO 4 ] 3- groups. Strong asymmetric hydrogen bonds between symmetry-related (O,OH) groups of the arsenate units [O⋯O = 2.588 (18) Å] as well as hydrogen bonds accepted by these (O,OH) groups from OH groups bonded to the Ni II atoms [O⋯O = 2.848 (12) Å] link adjacent layers. Additional consolidation of the packing is achieved through N-H⋯O hydrogen bonds from the ammonium ion, which is sandwiched between adjacent layers [N⋯O = 2.930 (7) Å] although the H atoms could not be located in the present study. The presence of the pseudo-hexa-gonal 2 ∞ [Ni 3 As 2 O 18/3 (OH) 6/3 O 1/1 (OH) 1/1 ] - layers may be the reason for the systematic threefold twinning of (NH 4 )[Ni 3 (HAsO 4 )(AsO 4 )(OH) 2 ] crystals. Significant overlaps of the reflections of the respective twin domains complicated the structure solution and refinement., (© Eder and Weil 2024.)

While structural racism has profound impacts on adolescent health, little is known about how youth synthesize racialized experiences and work to dismantle systems of oppression. This article provides an overview of a Youth Participatory Action Research study that used Photovoice and community mapping to explore how structural violence, like racism, impacts the sexual and reproductive health of historically excluded youth as they navigate unjust socio-political landscapes. Youth participants used photography and community maps to identify how the experience of bias, profiling, and tokenism impacted their ability to navigate complex social systems. With youth voices prioritized, participants explored ways to address structural racism in their lives. The importance of co-creating opportunities with and for youth in critical reflection of their lived experience is emphasized. Through an Arts and Cultural in Public Health framework, we provide an analysis of the ways structural racism functions as a gendered racial project and fundamental cause of adolescent sexual and reproductive health inequities, while identifying pathways toward liberation in pursuit of health and well-being.

Single crystals of two basic cadmium phosphates, dicadmium orthophosphate hydroxide, Cd 2 (PO 4 )OH, and penta-cadmium bis-(orthophosphate) tetra-kis-(hydroxide), Cd 5 (PO 4 ) 2 (OH) 4 , were obtained under hydro-thermal conditions. Cd 2 (PO 4 )OH adopts the triplite [(Mn,Fe) 2 (PO 4 )F] structure type. Its asymmetric unit comprises two Cd, one P and five O sites, all situated at the general Wyckoff position 8 f of space group I 2/ a ; two of the O atoms are positionally disordered over two sites, and the H atom could not be localized. Disregarding the disorder, distorted [CdO 6 ] polyhedra form a tri-periodic network by edge-sharing with neighbouring [CdO 6 ] units and by vertex-sharing with [PO 4 ] units. The site associated with the OH group is coordinated by four Cd atoms in a distorted tetra-hedral manner forming 1 ∞ [(OH)Cd 4/2 ] chains parallel to [001]. The oxygen environment around the OH site suggests multiple acceptor atoms for possible O-H⋯O hydrogen-bonding inter-actions and is the putative reason for the disorder. Cd 5 (PO 4 ) 2 (OH) 4 adopts the arsenoclasite [Mn 5 (AsO 4 ) 2 (OH) 4 ] structure type. Its asymmetric unit comprises five Cd, two P, and twelve O sites all located at the general Wyckoff position 4 a of space group P 2 1 2 1 2 1 ; the H atoms could not be localized. The crystal structure of Cd 5 (PO 4 ) 2 (OH) 4 can be subdivided into two main sub-units. One consists of three edge-sharing [CdO 6 ] octa-hedra, and the other of two edge- and vertex-sharing [CdO 6 ] octa-hedra. Each sub-unit forms corrugated ribbons extending parallel to [100]. The two types of ribbons are linked into the tri-periodic arrangement through vertex-sharing and through common [PO 4 ] tetra-hedra. Qu-anti-tative structure comparisons are made with isotypic M 5 ( X O 4 ) 2 (OH) 4 crystal structures ( M = Cd, Mn, Co; X = P, As, V)., (© Eder and Weil 2024.)