bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel, high-performance, low-volume, rapid luciferase immunoprecipitation system (LIPS) assay to detect autoantibodies to zinc transporter 8
Authors: Williams Claire L , Marzinotto Ilaria , Brigatti Cristina , Gillespie Kathleen M ,   The BOX Study Group, Wilson Isabel , Aitken Rachel , Megson Clare , Ballav Chitrabhanu , Dutta Atanu , Russell-Taylor Michelle , Besser Rachel , Bursell James , Chandran Shanthi , Keynes Milton , Patel Sejal , Smith Anne , Kenchaiah Manohara , Margabanthu Gomathi , Kavvoura Foteini , Yaliwal Chandan , Lampasona Vito , Williams Alistair J K , Long Anna E 
Published: December 2023

Abstract

Background
Zinc transporter 8 autoantibodies (ZnT8A) are thought to appear close to type 1 diabetes (T1D) onset and can identify high-risk multiple (≥2) autoantibody positive individuals. Radiobinding assays (RBA) are widely used for ZnT8A measurement but have limited sustainability. We sought to develop a novel, high-performance, non-radioactive luciferase immunoprecipitation system (LIPS) assay to replace RBA.

Methods
A custom dual C-terminal ZnT8 (aa268-369; R325/W325) heterodimeric antigen, tagged with a NanoluciferaseTM (Nluc-ZnT8) reporter, and LIPS assay was developed. Assay performance was evaluated by testing sera from new onset T1D (n = 573), healthy schoolchildren (n = 521), and selected first-degree relatives (FDRs) from the Bart’s Oxford family study (n = 617; 164 progressed to diabetes).

Results
In new-onset T1D, ZnT8A levels by LIPS strongly correlated with RBA (Spearman’s r = 0.89; P &lt; 0.0001), and positivity was highly concordant (94.3%). At a high specificity (95%), LIPS and RBA had comparable assay performance [LIPS pROC-AUC(95) 0.032 (95% CI: 0.029–0.036); RBA pROC-AUC(95) 0.031 (95% CI: 0.028–0.034); P = 0.376]. Overall, FDRs found positive by LIPS or RBA had a comparable 20-year diabetes risk (52.6% and 59.7%, respectively), but LIPS positivity further stratified T1D risk in FDRs positive for at least one other islet autoantibody detected by RBA (P = 0.0346).

Conclusion
This novel, high-performance, cheaper, quicker, higher throughput, low blood volume Nluc-ZnT8 LIPS assay is a safe, non-radioactive alternative to RBA with enhanced sensitivity and ability to discriminate T1D progressors. This method offers an advanced approach to current strategies to screen the general population for T1D risk for immunotherapy trials and to reduce rates of diabetic ketoacidosis at diagnosis.
Grouphood Promotion v. Grouphood Destruction: China’s Regional Ethnic Autonomy as Antithesis to Genocidal Intent
Authors: Yee Sienho 
Published: December 2023

Abstract
China’s ethnic policy is characterized by a strong promotion of ethnic equality and unity and regional ethnic autonomy under the unified multi-ethnic State framework. With regional ethnic autonomy at its core, this is a policy of precision autonomy and grouphood promotion. On the other hand, genocide is a crime of grouphood destruction, committed with the specific intent (dolus specialis) to “destroy, in whole or in part, a national, ethnical, racial or religious group, as such”. An examination of the main tenets of China’s ethnic policy and the specific intent element of the crime of genocide makes it crystal clear that, instead of aiming to “destroy, in whole or in part, a national, ethnical, racial or religious group, as such”, China’s ethnic policy aims to do the opposite, i.e., to promote the perception of the grouphood, the wellbeing and flourishing of every ethnic group. China’s policy of ethnic equality and unity and regional ethnic autonomy under the unified multiethnic State framework is thus the antithesis to genocidal intent of grouphood destruction. The increase of the Uygur population from 2.2 million to 12 million and of the life expectancy of the group from 30 to 74.7 years in Xinjiang over the past 60 years and the idolization of Uygur actors and actresses across China and beyond put on conspicuous display the successful reality of this policy.
ISL-signing mothers’ practices for boosting hearing-signing children’s engagement in shared reading
Authors: Fuks Orit 
Published: December 2023

Abstract
This longitudinal multiple-case study research focused on the scaffolding strategies that two Israeli deaf mothers use to boost their young hearing children’s engagement in reading interactions. Despite being significant to language learning, few studies have examined the dialogic reading practices of deaf-signing mothers. The study shows that until the age of 22 months, the mothers shared picture books with their children. Between the ages of 12 to 24 months, the mothers used mostly low-demand cognitive prompts and responsive utterances. Between the ages of 24 to 36 months, they used more high-demand prompts (including open-ended questions) and expanded their responses. In line with previous studies, this research demonstrated that the Israeli deaf mothers used the books as a foundation for storytelling and reading conversations. The shared reading provided the mothers with opportunities to model the construction of ISL narratives and language functional behaviors, such as asking questions, describing things or expanding on the text.
The cell morphological diversity of Saccharomycotina yeasts
Authors: Chavez Christina M , Groenewald Marizeth , Hulfachor Amanda B , Kpurubu Gideon , Huerta Rene , Hittinger Chris Todd , Rokas Antonis 
Published: December 2023

Abstract
The ∼1 200 known species in subphylum Saccharomycotina are a highly diverse clade of unicellular fungi. During its lifecycle, a typical yeast exhibits multiple cell types with various morphologies; these morphologies vary across Saccharomycotina species. Here, we synthesize the evolutionary dimensions of variation in cellular morphology of yeasts across the subphylum, focusing on variation in cell shape, cell size, type of budding, and filament production. Examination of 332 representative species across the subphylum revealed that the most common budding cell shapes are ovoid, spherical, and ellipsoidal, and that their average length and width is 5.6 µm and 3.6 µm, respectively. 58.4% of yeast species examined can produce filamentous cells, and 87.3% of species reproduce asexually by multilateral budding, which does not require utilization of cell polarity for mitosis. Interestingly, ∼1.8% of species examined have not been observed to produce budding cells, but rather only produce filaments of septate hyphae and/or pseudohyphae. 76.9% of yeast species examined have sexual cycle descriptions, with most producing one to four ascospores that are most commonly hat-shaped (37.4%). Systematic description of yeast cellular morphological diversity and reconstruction of its evolution promises to enrich our understanding of the evolutionary cell biology of this major fungal lineage.
Unveiling the evolutionary history of lingonberry (Vaccinium vitis-idaea L.) through genome sequencing and assembly of European and North American subspecies
Authors: Hirabayashi Kaede , Debnath Samir C , Owens Gregory L 
Published: December 2023

Abstract
Lingonberry (Vaccinium vitis-idaea L.) produces tiny red berries that are tart and nutty in flavor. It grows widely in the circumpolar region, including Scandinavia, northern parts of Eurasia, Alaska, and Canada. Although cultivation is currently limited, the plant has a long history of cultural use among indigenous communities. Given its potential as a food source, genomic resources for lingonberry are significantly lacking. To advance genomic knowledge, the genomes for 2 subspecies of lingonberry (V. vitis-idaea ssp. minus and ssp. vitis-idaea var. ‘Red Candy’) were sequenced and de novo assembled into contig-level assemblies. The assemblies were scaffolded using the bilberry genome (Vaccinium myrtillus) to generate a chromosome-anchored reference genome consisting of 12 chromosomes each with a total length of 548.07 Mb [contig N50 = 1.17 Mb, BUSCO (C%) = 96.5%] for ssp. vitis-idaea and 518.70 Mb [contig N50 = 1.40 Mb, BUSCO (C%) = 96.9%] for ssp. minus. RNA-seq-based gene annotation identified 27,243 and 25,718 genes on the respective assembly, and transposable element detection methods found that 45.82 and 44.58% of the genome were repeats. Phylogenetic analysis confirmed that lingonberry was most closely related to bilberry and was more closely related to blueberries than cranberries. Estimates of past effective population size suggested a continuous decline over the past 1–3 MYA, possibly due to the impacts of repeated glacial cycles during the Pleistocene leading to frequent population fragmentation. The genomic resource created in this study can be used to identify industry-relevant genes (e.g. anthocyanin production), infer phylogeny, and call sequence-level variants (e.g. SNPs) in future research.
Complex epistatic interactions between ELF3, PRR9, and PRR7 regulate the circadian clock and plant physiology
Authors: Yuan Li , Avello Paula , Zhu Zihao , Lock Sarah C L , McCarthy Kayla , Redmond Ethan J , Davis Amanda M , Song Yang , Ezer Daphne , Pitchford Jonathan W , Quint Marcel , Xie Qiguang , Xu Xiaodong , Davis Seth J , Ronald James 
Published: December 2023

Abstract
Circadian clocks are endogenous timekeeping mechanisms that coordinate internal physiological responses with the external environment. EARLY FLOWERING3 (ELF3), PSEUDO RESPONSE REGULATOR (PRR9), and PRR7 are essential components of the plant circadian clock and facilitate entrainment of the clock to internal and external stimuli. Previous studies have highlighted a critical role for ELF3 in repressing the expression of PRR9 and PRR7. However, the functional significance of activity in regulating circadian clock dynamics and plant development is unknown. To explore this regulatory dynamic further, we first employed mathematical modeling to simulate the effect of the prr9/prr7 mutation on the elf3 circadian phenotype. These simulations suggested that simultaneous mutations in prr9/prr7 could rescue the elf3 circadian arrhythmia. Following these simulations, we generated all Arabidopsis elf3/prr9/prr7 mutant combinations and investigated their circadian and developmental phenotypes. Although these assays could not replicate the results from the mathematical modeling, our results have revealed a complex epistatic relationship between ELF3 and PRR9/7 in regulating different aspects of plant development. ELF3 was essential for hypocotyl development under ambient and warm temperatures, while PRR9 was critical for root thermomorphogenesis. Finally, mutations in prr9 and prr7 rescued the photoperiod-insensitive flowering phenotype of the elf3 mutant. Together, our results highlight the importance of investigating the genetic relationship among plant circadian genes.
‘To Live a Peaceful Life’: African American Defectors in the German Democratic Republic
Authors: Klopprogge Nadja 
Published: December 2023

Abstract
In this article I follow the paths of six African Americans who defected from the US Army stationed in West Germany in the early 1950s and applied for political asylum in the German Democratic Republic. Their reasons for moving to and staying in East Germany are my point of departure, in order to gain an understanding of how they made sense of the Cold War divide based on their experiences of racism. The perceptions of the six African Americans are contrasted with the reactions of the Stasi, illustrating how those working to defend the policies and politics of the governing Socialist Unity Party of Germany located race and racism in their conceptualization of political asylum. The article then focuses on the lives of the six defectors in East Germany over a period of roughly four decades. I argue that questions of race/racism were closely linked to questions of (violated) intimacy and settledness, both for the African American defectors and for the Stasi. Zooming in on the intimate allows me to reconfigure the broader context, providing a glimpse into how race and racism shaped the Cold War geography as well as how this geography changed in light of decolonization.
Does a Reduction in Receiving Assistance With Daily Activities Among Older Adults in Mexico Indicate An Increase in Unmet Needs or a Decrease in Needs for Care?
Authors: Downer Brian , Samper-Ternent Rafael , Cantu Philip , Miller Matthew , Wong Rebeca 
Published: December 2023

Abstract

Objectives
The percentage of older adults in Mexico with difficulty completing activities of daily living (ADL) who receive assistance from family appears to be decreasing. We compared 2 birth cohorts of older adults in Mexico to investigate whether this trend reflects an increase in unmet caregiving needs or a decrease in the need for care.

Methods
We selected Mexican Health and Aging Study participants aged 60–76 in 2001 (n = 4,805) and 2018 (n = 6,494). ADL tasks were dressing, walking, bathing, getting in and out of bed, and toileting. Participants who reported difficulty with an ADL were asked if anyone helped them with the task. Logistic regression was used to estimate adjusted odds ratios (aOR) for cohort differences in ≥1 ADL limitations and help with ≥1 ADL. We used a decomposition analysis to identify participant characteristics that mediated cohort differences in receiving help with ≥1 ADL.

Results
The 2018 cohort had higher odds for ≥1 ADL limitations (aOR = 1.85, 95% CI = 1.60–2.14) but lower odds for help with ≥1 ADL (aOR = 0.66, 95% CI = 0.49–0.89). Among participants with ADL disability, the 2018 cohort had fewer living children and a lower prevalence of probable dementia. The lower number of living children and lower prevalence of probable dementia explained 9.34% and 43.7% of the cohort effect on receiving help with ≥1 ADL, respectively.

Discussion
The declining percentage of older adults in Mexico with ADL disability receiving assistance may not reflect increasing unmet needs. However, the increased prevalence of ADL disability will increase the number of older adults needing informal care.
Life Course Risk and Protective Factors of Multimorbidity Resilience Among Older Adults in Rural China: A Longitudinal Study in Anhui Province Before and During COVID-19
Authors: Guo Jin , Wister Andrew , Wang Jie , Li Shuzhuo 
Published: December 2023

Abstract

Objectives
Multimorbidity resilience reflects older adults’ ability to cope with, adapt to, and rebound from its adverse effects through mobilizing resources. This study revised the multidomain Multimorbidity Resilience Index based on the Lifecourse Model of Multimorbidity Resilience referring to the life situations of older adults in rural China to measure the multimorbidity resilience from 2018 to 2021 and to explore factors influencing multimorbidity resilience from the perspective of Life Course theory.

Methods
This study used the seventh and eighth waves of longitudinal data (2018–2021) collected in Anhui, China. Older adults (945) with 2 or more chronic diseases were selected, and 1,201 (person-year) observations were collected and studied. A mixed linear model examined the effects of early- and later-factors on multimorbidity resilience.

Results
Multimorbidity resilience was negatively correlated with age and decreased faster with age after the outbreak of the coronavirus disease-2019 (COVID-19) pandemic. Married older adults have higher multimorbidity resilience. Exposure to hunger was associated with lower multimorbidity resilience when later factors were considered. Self-reported health before age 15, access to medical resources, and multimorbidity resilience were positively correlated. In addition, this study verified the relationship between multimorbidity resilience and the number of chronic diseases, exercise frequency, religious beliefs, self-reported health, and economic satisfaction, among other factors.

Discussion
The associations between life course factors and multimorbidity resilience emphasize the long-term impact of early-life experience and the adverse effects of increasing age, especially after the outbreak of the COVID-19 pandemic. The findings will drive policy development from a life course perspective encompassing prevention and follow-up treatment to promote active aging.
Opinion of GRUR on the European Commission’s Proposal for a Regulation on Standard-Essential Patents (COM (2023) 232)
Authors: Hoffmann Fabian , Altmeyer Stephan , Haertel Alexander , Hufnagel Frank-Erich , Mohsler Gabriele , Nack Ralph , Popp Andreas , Tochtermann Lea 
Published: December 2023

Abstract
The German Association for Intellectual Property Law (GRUR e.V.) has submitted an opinion on the draft SEP Regulation to the German Federal Ministry of Justice and to the EU Commission. The authors, who were substantially involved in the preparation of the opinion, have translated it into English.
In the group of authors, majority decisions were made in some instances for the adoption of the opinion. Therefore, it cannot be assumed that every comment in the opinion is in line with the views of all the authors.
GRUR is a scientific association recognized as a non-profit organization of all members of professional groups and organizations working in the field of industrial property protection and copyright; these are in particular university lecturers, judges, civil servants, lawyers, patent attorneys and representatives of associations and companies.
Total Proctocolectomy vs Subtotal/total Colectomy for Neoplasia in Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
Authors: Dunleavy Katie Ann , Santiago Priscila , Forde Gerard , Harmsen W Scott , McKenna Nicholas P , Coelho-Prabhu Nayantara , Shawki Sherief , Raffals Laura 
Published: December 2023

Abstract

Background
Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) frequently undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for medically refractory disease or colonic dysplasia/neoplasia. Subtotal colectomy with ileosigmoid or ileorectal anastomosis may have improved outcomes but is not well studied. Due to increased risk for colorectal cancer in PSC-IBD, there is hesitancy to perform subtotal colectomy. We aim to describe the frequency of colorectal dysplasia/neoplasia following IPAA vs subtotal colectomy in PSC-IBD patients.

Methods
We completed a retrospective study from 1972 to 2022 of patients with PSC-IBD who had undergone total proctocolectomy with IPAA or subtotal colectomy. We abstracted demographics, disease characteristics, and endoscopic surveillance data from the EMR.

Results
Of 125 patients (99 IPAA; 26 subtotal), the indication for surgery was rectal sparing medically refractory disease (51% vs 42%), dysplasia (37% vs 30%) and neoplasia (11% vs 26%) in IPAA vs subtotal colectomy patients, respectively. On endoscopic surveillance of IPAA patients, 2 (2%) had low-grade dysplasia (LGD) in the ileal pouch and 2 (2%) had LGD in the rectal cuff after an average of 8.4 years and 12.3 years of follow-up, respectively. One (1%) IPAA patient developed neoplasia of the rectal cuff after 17.8 years of surgical continuity. No subtotal colectomy patients had dysplasia/neoplasia in the residual colon or rectum.

Conclusions
In patients with PSC-IBD, there was no dysplasia or neoplasia in those who underwent subtotal colectomy as opposed to the IPAA group. Subtotal colectomy may be considered a viable surgical option in patients with rectal sparing PSC-IBD if adequate endoscopic surveillance is implemented.
Use of Upadacitinib in 16 Tofacitinib-refractory Ulcerative Colitis Patients: A Single-center Case 2Series
Authors: Levine Jake , McKibbin Jey , Ham Rebecca , Cohen-Mekelburg Shirley , Bishu Shrinivas , Tang Kevin , Higgins Peter D R , Berinstein Jeffrey A 
Published: December 2023

Lay Summary
We present a case series of 16 patients with ulcerative colitis who received upadacitinib after failing tofacitinib. Five patients (36%) achieved steroid-free clinical remission. Five (62%) demonstrated endoscopic response, while 2 patients (25%) achieved endoscopic remission. Adverse events were low.
Tofacitinib Affects M1-like and M2-like Polarization and Tissue Factor Expression in Macrophages of Healthy Donors and IBD Patients
Authors: Lethen Isabelle , Lechner-Grimm Kristina , Gabel Michael , Knauss Annkathrin , Atreya Raja , Neurath Markus F , Weigmann Benno 
Published: December 2023

Abstract

Background
Tofacitinib, as inhibitor of Janus kinases (JAK), interrupts the transmission of numerous pro-inflammatory cytokines involved in the pathogenesis of inflammatory bowel diseases (IBD). Therefore, tofacitinib provides a potent option to treat ulcerative colitis (UC). Besides the anti-inflammatory potential, inhibition of widespread JAKs carries the risk of side effects. Macrophages are involved in the form of different subtypes in inflammation, wound healing, and even coagulation. This study aimed to explore the balanced use of tofacitinib in M1-like as well as M2-like macrophages of healthy donors and patients with IBD.

Methods
Monocytes of healthy donors and patients with chronic courses of IBD were obtained from blood samples. Macrophage colony-stimulating factor (M-CSF)-derived macrophages were treated with tofacitinib (1 µM, 5 µM, 10 µM) and polarized with either lipopolysaccharide and interferon (IFN)-γ towards M1-like-phenotype or with interleukin (IL)-4 towards M2-like-phenotype. ELISA and flow cytometry were used to evaluate cytokine levels and surface molecules.

Results
Tofacitinib had a modulating effect on M1-like macrophages whereby the effect on pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12, IL-23) was less pronounced than the induction of anti-inflammatory IL-10. However, during M2-like polarization tofacitinib impaired the development of the corresponding phenotype becoming evident through decreased IL-10 levels and CD206 expression in treated macrophages. In both phenotypes, tofacitinib strongly downregulated the expression of immunostimulatory molecules (CD80, CD86, CD83, CD40). Furthermore, a dose-dependent correlation between treatment with tofacitinib and expressed tissue factor was noticed.

Conclusions
Tofacitinib influences both polarizations (M1/M2) and the expression of tissue factor in a dose-dependent manner.