bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetric bulges within hairpin RNA transgenes influence small RNA size, secondary siRNA production and viral defence
Authors: Zhang Daai , Jue Dengwei , Smith Neil , Zhong Chengcheng , Finnegan E Jean , de Feyter Robert , Wang Ming-Bo , Greaves Ian 
Published: July 2024

Abstract
Small RNAs (sRNAs) are essential for normal plant development and range in size classes of 21–24 nucleotides. The 22nt small interfering RNAs (siRNAs) and miRNAs are processed by Dicer-like 2 (DCL2) and DCL1 respectively and can initiate secondary siRNA production from the target transcript. 22nt siRNAs are under-represented due to competition between DCL2 and DCL4, while only a small number of 22nt miRNAs exist. Here we produce abundant 22nt siRNAs and other siRNA size classes using long hairpin RNA (hpRNA) transgenes. By introducing asymmetric bulges into the antisense strand of hpRNA, we shifted the dominant siRNA size class from 21nt of the traditional hpRNA to 22, 23 and 24nt of the asymmetric hpRNAs. The asymmetric hpRNAs effectively silenced a β-glucuronidase (GUS) reporter transgene and the endogenous ethylene insensitive-2 (EIN2) and chalcone synthase (CHS) genes. Furthermore, plants containing the asymmetric hpRNA transgenes showed increased amounts of 21nt siRNAs downstream of the hpRNA target site compared to plants with the traditional hpRNA transgenes. This indicates that these asymmetric hpRNAs are more effective at inducing secondary siRNA production to amplify silencing signals. The 22nt asymmetric hpRNA constructs enhanced virus resistance in plants compared to the traditional hpRNA constructs.
The TOPOVIBL meiotic DSB formation protein: new insights from its biochemical and structural characterization
Authors: Diagouraga Boubou , Tambones Izabella , Carivenc Coralie , Bechara Chérine , Nadal Marc , de Massy Bernard , le Maire Albane , Robert Thomas 
Published: July 2024

Abstract
The TOPOVIL complex catalyzes the formation of DNA double strand breaks (DSB) that initiate meiotic homologous recombination, an essential step for chromosome segregation and genetic diversity during gamete production. TOPOVIL is composed of two subunits (SPO11 and TOPOVIBL) and is evolutionarily related to the archaeal TopoVI topoisomerase complex. SPO11 is the TopoVIA subunit orthologue and carries the DSB formation catalytic activity. TOPOVIBL shares homology with the TopoVIB ATPase subunit. TOPOVIBL is essential for meiotic DSB formation, but its molecular function remains elusive, partly due to the lack of biochemical studies. Here, we purified TOPOVIBLΔC25 and characterized its structure and mode of action in vitro. Our structural analysis revealed that TOPOVIBLΔC25 adopts a dynamic conformation in solution and our biochemical study showed that the protein remains monomeric upon incubation with ATP, which correlates with the absence of ATP binding. Moreover, TOPOVIBLΔC25 interacted with DNA, with a preference for some geometries, suggesting that TOPOVIBL senses specific DNA architectures. Altogether, our study identified specific TOPOVIBL features that might help to explain how TOPOVIL function evolved toward a DSB formation activity in meiosis.
O-105 HOW HEALTHY IS YOUR WORKPLACE? OCCUPATIONAL HEALTH PROGRAMS IN GERMAN COMPANIES – CREATION AND VALIDATION OF EFFECTIVE MEASURES*
Authors: Afrahi Jasmin 
Published: July 2024

Abstract

Introduction
Companies are struggling with the costs of absenteeism due to their employees’ physical and increasing psychological illnesses. At the same time, employers should recognize the value of healthy employees in terms of greater productivity and the development of positive organizational attitudes. Many organizations have implemented workplace health promotion (WHP) programs; however, we still have limited knowledge about the effectiveness of various measures. The present study examines 18 WHP activities and their effect on employees’ perceived health support and actual absence rates.

Methods
I organized 112 German companies into four groups based on their subjective (employee perception of health promotion) and objective (absence rate) performance. Applying multinomial regression analysis, I assessed a company’s likelihood of falling into one of the four clusters if a specific measure is not implemented in it.

Results
Five measures were identified that significantly differ between company clusters: healthy food offerings, sports offerings, having fitness rooms, systematically evaluating WHP programs, and smoking cessation courses.

Discussion
Sports courses and fitness rooms not only give employees the chance to improve their physical and mental health but also fulfill social needs by enabling contact with other colleagues. Companies should inform their employees about health topics and make them aware of their own health behavior. Moreover, health managers should carefully implement interventions and follow strategies not only to ensure high participation rates but also to evaluate the interventions systematically.

Conclusion
Investing in occupational health management can be a strategic asset for organizations. It shows that employers can enhance employee well-being by using simple WHP activities. *The full article will be published in the International Journal of Workplace Health Management, DOI 10.1108/IJWHM-08-2023-0118.
P-516 WORKING IN THE TIME OF COVID-19: HOW COVID-19 PUBLIC HEALTH POLICIES AFFECT THE EXPERIENCE OF BULLYING AND HARASSMENT AMONG RESTAURANT WORKERS
Authors: McLeod Christopher , Deering Kathleen , Aguiar Luis , Skourtes Stephanie , Frank Billie 
Published: July 2024

Abstract

Introduction
This study explored how COVID-19 public health policies affected experiences of bullying and harassment among workers in the restaurant industry and the impact of these policies on the health and safety of workers.

Methods
Qualitative interviews were conducted with 47 restaurant workers in the Canadian province of British Columbia. Participants worked in various roles at any kind of restaurant during the first two years of the COVID-19 pandemic. Ethics approval was obtained from the UBC Research Ethics Board. Inductive coding was applied towards the development of themes.

Results
COVID-19 public health restrictions in restaurants contributed to bullying and harassment of workers. A lack of managerial support and implementation guidelines from public health officials led to workers having to enforce restrictions on their own, which resulted in workers routinely experiencing verbal violence and harassment by customers. Workers described unsafe work conditions that put them at risk for contracting COVID-19 as well for bullying and harassment from management, which was exacerbated for women, gender-diverse, and racialized workers. In workplaces with a supportive organizational culture, workers reported feeling safer and buffered from incidents of bullying and harassment from customers.“

Discussion
The COVID-19 pandemic exacerbated existing structural dynamics in the restaurant industry that enabled bullying and harassment of workers, including the hierarchical dynamic of restaurant work as well as discrimination in the industry.

Conclusion
While supportive workplace policies and practices mitigated some of the bullying and harassment experienced by restaurant workers working during the COVID-19 pandemic, broader equity-focused organizational and structural change is needed to protect workers.
Perspectives on U.S. University research reactor policy
Authors: Nienow Sara , Walsh Amanda C , Merker Jonathan 
Published: July 2024

Abstract
Widely promoted by the Atomic Energy Commission in the 1950s and 1960s, university research reactors allowed faculty to experiment with neutron scattering, advancing our understanding of organic and inorganic materials. These advances led to innovations in commercial products, including automobiles, computers, medicine, and batteries. However, since the 1980s, more than half of all the university research reactors have been decommissioned and remaining reactors are ill-suited for modern needs. RTI International assembled a team of economists, neutron scientists, and policy analysts to examine the history of university research reactor policy in the USA, assess barriers to greater usage, and consider how US policy differs from those in other countries. We present three policy options to enhance the role of university research reactors in federal research and the national science infrastructure landscape.
Sustainable application of biocides to promote hygiene and minimize antimicrobial resistance
Authors: Willmott Thomas , Jadaan Layali , Humphreys Gavin J , Lu Jian R , McBain Andrew J , Chapman John 
Published: July 2024

Abstract
Biocidal (microbicidal) products play a critical role in controlling microorganisms in healthcare, industrial, community, and home environments. There is, however, concern that their use and misuse might contribute to the evolution of antimicrobial resistance (AMR). When evaluating the risk associated with biocides, it is important to adopt an objective approach towards the evidence regarding both the benefits of their appropriate deployment as well as potential contribution to AMR. Biocide use should be restricted to applications where there are tangible benefits but also not unnecessarily restricted where genuine benefits can be demonstrated. From the perspective of sustainability, such benefits include the control and prevention of infections in clinical settings with associated reductions in antibiotic use, preservation of a range of products and materials, substantial reduction in infection risk for consumers, hygiene in the community (e.g. in public swimming baths), and microbial control in many facets of industry. Here, we will provide a critical assessment of the contribution of biocides to sustainability based on a critical evaluation of the literature, followed by offering our views on the future management of biocide use across the globe.
Dynamic changes of gut microbiota in mouse models of metabolic dysfunction‐associated steatohepatitis and its transition to hepatocellular carcinoma
Authors: Wang Yu‐Li , Liu Chang , Yang Yong‐Yu , Zhang Li , Guo Xiao , Niu Chen , Zhang Ning‐Ping , Ding Jia , Wu Jian 
Published: July 2024

AbstractDysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction‐associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH‐associated hepatocellular carcinoma (MASH‐HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA‐16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD‐HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH‐HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH‐fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.
Association Among Vitamin D Supplementation, Serum 25(OH)D Concentrations, and Mortality Risk: A Prospective Cohort Study Using NHANES 2007–2018 Data
Authors: Liu Hong , Bai Yu 
Published: July 2024

Background:
To determine the associations among self-reported vitamin D (VD) supplementation, measured serum 25-hydroxyvitamin D (25[OH]D) concentrations, and all-cause and cause-specific mortality risks.

Methods:
Self-reported VD supplementation, serum 25(OH)D concentration, and all-cause and cause-specific mortality data from the National Health and Nutrition Examination Survey 2007–2018 were examined for 10,793 adults ≥20 years from the United States. VD dosage was categorized as <800 or ≥800 IU/d. The mortality status and causes of mortality up to 2019 were determined using the National Death Index. The relationships among VD, 25(OH)D levels, and mortality were analyzed using Cox regression before and after propensity score matching (PSM).

Results:
Over a median of 6.6 years, 915 deaths were recorded, 230 because of cardiovascular disease (CVD), 240 because of cancer, and 445 because of other specific causes. Mortality risk did not differ between VD <800 IU/d and ≥800 IU/d before or after PSM. However, serum 25(OH)D concentrations were statistically different before and after PSM. The upper 2 quartiles of 25(OH)D levels were associated with lower all-cause mortality, and the fourth quartile was associated with reduced other-specific mortality before and after PSM. No correlation was found between the 25(OH)D concentration and CVD- or cancer-specific mortality after PSM. The inverse 25(OH)D–mortality relationship was consistent across subgroups.

Conclusions:
Based on this large cohort study, higher 25(OH)D levels are robustly associated with reduced all-cause and other specific mortality but not CVD- or cancer-specific mortality. These findings support the benefits of maintaining adequate VD status for longevity. Further research is required to elucidate these mechanisms and define the optimal VD concentration to reduce mortality. These results underscore the importance of public health strategies for preventing VD deficiency.
Using Microeconomic Spending Traits to Inform Trends in Utilization of Cosmetic Procedures by Race and Ethnicity
Authors: Rhee Ben S. , Pham John , Tanzer Joshua R. , Charvis Jodi S. , Roussel Lauren O. 
Published: July 2024

Background:
Cosmetic plastic surgery in the United States is underutilized by African American and Hispanic populations compared with their White and Asian counterparts. This study evaluated whether microeconomic spending traits as a representation of financial stability can inform trends in cosmetic procedure volumes by racial group.

Methods:
Annual volumes for the top five cosmetic surgical and cosmetic minimally invasive procedures by racial/ethnic group from 2012 to 2020 were collected from the American Society of Plastic Surgeons’ annual reports. Factor analysis was used to calculate inflexible and flexible consumer spending by racial/ethnic groupings from the US Bureau of Labor Statistics’ consumer expenditure data. All four factors were calculated across US Bureau of Labor Statistics–defined racial/ethnic groupings and standardized so they could be interpreted relative to each other.

Results:
Compared with the other groupings, the White/Asian/other grouping spent significantly more on average for inflexible consumer spending (P = 0.0097), flexible consumer spending (P < 0.0001), cosmetic surgical procedures (P < 0.0001), and cosmetic minimally invasive procedures (P = 0.0006). In contrast, African American people spent significantly less on average for all four factors (all P < 0.01). For Hispanic people, values were significantly less on average for flexible consumer spending (P = 0.0023), cosmetic surgical procedures (P < 0.0001), and cosmetic minimally invasive procedures (P = 0.0002).

Conclusions:
This study demonstrates that inflexible and flexible consumer spending follow trends in utilization of cosmetic surgical and minimally invasive procedures by racial/ethnic groups. These microeconomic spending inequities may help further contextualize the racial/ethnic variation in access to cosmetic surgery.
Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis
Authors: Grimsrud Marit M. , Forster Michael , Goeppert Benjamin , Hemmrich-Stanisak Georg , Sax Irmi , Grzyb Krzysztof , Braadland Peder R. , Charbel Alphonse , Metzger Carmen , Albrecht Thomas , Steiert Tim Alexander , Schlesner Matthias , Manns Michael P. , Vogel Arndt , Yaqub Sheraz , Karlsen Tom H. , Schirmacher Peter , Boberg Kirsten M. , Franke Andre , Roessler Stephanie , Folseraas Trine 
Published: July 2024

Background:
People with primary sclerosing cholangitis (PSC) have a 20% lifetime risk of biliary tract cancer (BTC). Using whole-exome sequencing, we characterized genomic alterations in tissue samples from BTC with underlying PSC.

Methods:
We extracted DNA from formalin-fixed, paraffin-embedded tumor and paired nontumor tissue from 52 resection or biopsy specimens from patients with PSC and BTC and performed whole-exome sequencing. Following copy number analysis, variant calling, and filtering, putative PSC-BTC-associated genes were assessed by pathway analyses and annotated to targeted cancer therapies.

Results:
We identified 53 candidate cancer genes with a total of 123 nonsynonymous alterations passing filtering thresholds in 2 or more samples. Of the identified genes, 19% had not previously been implicated in BTC, including CNGA3, KRT28, and EFCAB5. Another subset comprised genes previously implicated in hepato-pancreato-biliary cancer, such as ARID2, ELF3, and PTPRD. Finally, we identified a subset of genes implicated in a wide range of cancers such as the tumor suppressor genes TP53, CDKN2A, SMAD4, and RNF43 and the oncogenes KRAS, ERBB2, and BRAF. Focal copy number variations were found in 51.9% of the samples. Alterations in potential actionable genes, including ERBB2, MDM2, and FGFR3 were identified and alterations in the RTK/RAS (p = 0.036), TP53 (p = 0.04), and PI3K (p = 0.043) pathways were significantly associated with reduced overall survival.

Conclusions:
In this exome-wide characterization of PSC-associated BTC, we delineated both PSC-specific and universal cancer genes. Our findings provide opportunities for a better understanding of the development of BTC in PSC and could be used as a platform to develop personalized treatment approaches.
A novel case of endophthalmitis secondary to Paenibacillus yonginensis after intravitreal injection of aflibercept
Authors: Ramirez Jose A. , Khurana Rahul N. , Wang Jay C. 
Published: July 2024

Purpose:
To report a case of endophthalmitis after intravitreal injection due to Paenibacillus yonginensis.

Methods:
This is a retrospective case report.

Results:
An 87-year-old man with longstanding neovascular age-related macular degeneration (AMD) in his left eye presented with pain and loss of vision three days after intravitreal injection of aflibercept. Examination revealed a hypopyon and vitreous opacities. A diagnostic anterior chamber paracentesis and intravitreal injections of vancomycin and ceftazidime were performed. One month later, vitrectomy was performed for non-clearing vitreous opacities with a good final visual outcome. The causative bacterium, Paenibacillus yonginensis, was identified with polymerase chain reaction (PCR) sequencing from the aqueous specimen.

Conclusion:
We encountered a rare presentation of endophthalmitis caused by Paenibacillus yonginensis. Paenibacillus species have been implicated in human infection in recent years. DNA sequencing can allow for the identification of uncommon bacteria.
Hydroxyproline Concentration and Associated Factors of Preserved Small Incision Lenticule Extraction–Derived Corneal Stromal Lenticules
Authors: Han Xiaosong , Li Meiyan , Zhao Jing , Sun Bingqing , Zhang Xiaoyu , Xu Haipeng , Zhou Xingtao 
Published: July 2024

Purpose:
To evaluate changes of hydroxyproline concentration and its influencing factors of small incision lenticule extraction (SMILE)-derived corneal stromal lenticules with different preservation methods.

Methods:
A total of 390 corneal stromal lenticules of 195 patients were derived from SMILE surgeries. Thirty of the lenticules were classified as the fresh (control) group, and the rest were randomly and evenly divided and stored in anhydrous glycerol, silicone oil, Optisol, and cryopreservation for 1 day, 1 week, or 1 month. A hydroxyproline assay kit (ab222941, Abcam) was used to measure the hydroxyproline concentration in each preservation method. Concentrations of MMP-2, TIMP-2, TNFα, TGFβ2, and reactive oxygen species were also evaluated.

Results:
In the anhydrous glycerol group, the concentration of hydroxyproline decreased within 1 week (fresh: 1 dΔ = 0.229, P < 0.001*; 1 d − 1 wΔ = 0.055, P < 0.001*) while that in the silicone oil group remained stable in 1 week (1 d − 1 wΔ = −0.005, P = 0.929) and decreased significantly in 1 m (1 m − 1 wΔ = −0.041, P = 0.003*). The sequence of hydroxyproline concentration in the Optisol group was 1 m > 1 day > 1 week. Hydroxyproline concentration in the cryopreservation group decreased within 1 m. Hydroxyproline concentration was highest in the Optisol group and lowest in the anhydrous glycerol group under the same preservation time. Hydroxyproline concentration was negatively correlated with MMP-2 (r = −0.16, P = 0.421) and TIMP-2 (r = −0.56, P = 0.002*) while MMP-2 and TNFα (r = 0.17, P = 0.242), TIMP-2 and TGFβ2 (r = 0.21, P = 0.207), and TNFα and reactive oxygen species (r = 0.52, P = 0.007*) were positively correlated.

Conclusions:
More collagen was retained in SMILE lenticules preserved in Optisol under the same preservation time. The mechanism of the changes of collagen in preserved SMILE-derived lenticules and oxidative stress requires additional investigation.
Phenotyping peripheral neuropathies with and without pruritus: a cross-sectional multicenter study
Authors: Baka Panoraia , Segelcke Daniel , Birklein Frank , Pogatzki-Zahn Esther M. , Bigalke Stephan , Süer Ayşenur , Dugas Martin , Steenken Livia , Sommer Claudia , Papagianni Aikaterini 
Published: July 2024

Abstract
Pruritus often escapes physicians' attention in patients with peripheral neuropathy (PNP). Here we aimed to characterize neuropathic pruritus in a cohort of 191 patients with PNP (large, mixed, or small fiber) and 57 control subjects with deep phenotyping in a multicenter cross-sectional observational study at 3 German sites. All participants underwent thorough neurological examination, nerve conduction studies, quantitative sensory testing, and skin biopsies to assess intraepidermal nerve fiber density. Patients filled in a set of questionnaires assessing the characteristics of pruritus and pain, the presence of depression and anxiety, and quality of life. Based on the severity of pruritus and pain, patients were grouped into 4 groups: “pruritus,” “pain,” “pruritus and pain,” and “no pruritus/no pain.” Although 11% (21/191) of patients reported pruritus as their only symptom, further 34.6% (66/191) reported pruritus and pain. Patients with pain (with or without pruritus) were more affected by anxiety, depression, and reduced quality of life than control subjects. Patients with pruritus (with and without pain) had increases in cold detection threshold, showing Aδ-fiber dysfunction. The pruritus group had lower intraepidermal nerve fiber density at the thigh, concomitant with a more proximal distribution of symptoms compared with the other PNP groups. Stratification of patients with PNP by using cross-sectional datasets and multinominal logistic regression analysis revealed distinct patterns for the patient groups. Together, our study sheds light on the presence of neuropathic pruritus in patients with PNP and its relationship with neuropathic pain, outlines the sensory and structural abnormalities associated with neuropathic pruritus, and highlights its impact on anxiety levels.