bluuebunny/crossref_metadata_2025_split huggingface dataset:
An alphacoronavirus polymerase structure reveals conserved replication factor functions
Authors: Anderson Thomas K , Hoferle Peter J , Chojnacki Kennan J , Lee Kenneth W , Coon Joshua J , Kirchdoerfer Robert N 
Published: March 2024

Abstract
Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs.
Trends in Exclusive Non-Cigarette Tobacco Smoking in England: A Population Survey 2013–2023
Authors: Jackson Sarah E , Shahab Lion , Brown Jamie 
Published: March 2024

Abstract

Introduction
The UK Government intends to implement a “smokefree generation” policy prohibiting the sale of all tobacco products to people born after 2008. National surveys provide comprehensive data on cigarette smoking, but little is known about patterns of non-cigarette tobacco smoking across key population groups.

Aims and Methods
Using data from a nationally representative cross-sectional survey of adults in England, collected monthly between September 2013 and September 2023 (n = 196 721), we estimated time trends in exclusive non-cigarette tobacco (eg, cigar/pipe/shisha) smoking prevalence, overall and by age, gender, occupational social grade, region, ethnicity, and vaping status. Interviews were conducted face-to-face until March 2020 and via telephone thereafter.

Results
From September 2013 to September 2023, there was a non-linear increase in exclusive non-cigarette tobacco smoking prevalence (from 0.36% to 1.68%; prevalence ratio = 4.72 [95% CI = 3.43–6.48]). Prevalence was relatively stable up to February 2020 (at an average of 0.46%), then increased sharply at the start of the COVID-19 pandemic (at the same time as survey methods changed), to 0.90% (0.82%–0.99%) in March 2020. This was followed by a steadier rise, peaking at 1.97% in May 2022, before falling slightly to 1.68% by September 2023. In 2022/2023, 1 in 10 smokers (10.8% [9.64%–12.0%]) exclusively used non-cigarette tobacco. The rise in prevalence was observed across all subgroups but was most pronounced among younger adults (eg, reaching 3.21% of 18-year-olds vs. 1.09% of 65-year-olds). Prevalence was consistently higher among men and current vapers.

Conclusions
Although exclusive use of non-cigarette combustible tobacco remains rare among adults in England, it has increased in recent years, particularly among younger ages. As of September 2023, there were approximately 772 800 adult exclusive non-cigarette tobacco smokers in England; around five times more than a decade earlier.

Implications
The proportion of adults in England who do not use cigarettes at all but smoke other combustible tobacco products has increased substantially in recent years, with a particularly pronounced rise among young people. The inclusion of non-cigarette combustible tobacco products under the proposed “smokefree generation” policy is therefore likely to be important for achieving the greatest reduction in youth uptake of tobacco smoking, as it would ensure young people who are unable to legally buy cigarettes do not buy other combustible tobacco products that are similarly harmful to health.
High Myristic Acid in Glycerolipids Enhances the Repair of Photodamaged Photosystem II under Strong Light
Authors: Kurima Kazuki , Jimbo Haruhiko , Fujihara Takashi , Saito Masakazu , Ishikawa Toshiki , Wada Hajime 
Published: March 2024

Abstract
Cyanobacteria inhabit areas with a broad range of light, temperature and nutrient conditions. The robustness of cyanobacterial cells, which can survive under different conditions, may depend on the resilience of photosynthetic activity. Cyanothece sp. PCC 8801 (Cyanothece), a freshwater cyanobacterium isolated from a Taiwanese rice field, had a higher repair activity of photodamaged photosystem II (PSII) under intense light than Synechocystis sp. PCC 6803 (Synechocystis), another freshwater cyanobacterium. Cyanothece contains myristic acid (14:0) as the major fatty acid at the sn-2 position of the glycerolipids. To investigate the role of 14:0 in the repair of photodamaged PSII, we used a Synechocystis transformant expressing a T-1274 encoding a lysophosphatidic acid acyltransferase (LPAAT) from Cyanothece. The wild-type and transformant cells contained 0.2 and 20.1 mol% of 14:0 in glycerolipids, respectively. The higher content of 14:0 in the transformants increased the fluidity of the thylakoid membrane. In the transformants, PSII repair was accelerated due to an enhancement in the de novo synthesis of D1 protein, and the production of singlet oxygen (1O2), which inhibited protein synthesis, was suppressed. The high content of 14:0 increased transfer of light energy received by phycobilisomes to PSI and CP47 in PSII and the content of carotenoids. These results indicated that an increase in 14:0 reduced 1O2 formation and enhanced PSII repair. The higher content of 14:0 in the glycerolipids may be required as a survival strategy for Cyanothece inhabiting a rice field under direct sunlight.
Violence and Democracy
Authors: Cheong Yeilim , Haggard Stephan 
Published: March 2024

Abstract
The relationship between violence and democracy is an enduring theme in political science. We know that civil war, revolution, and state repression are much less likely under democratic rule, but how do we get from such violence to democracy? We draw upon Sarah Zukerman Daly's book, Violent Victors: Why Bloodstained Parties Win Postwar Elections, to explore these questions. Daly addresses the enigma of belligerent parties, often marred by heinous atrocities, emerging victorious in postwar elections. She shows how such violent victors triumph by playing on their capacity to provide security. We broaden out from Daly's focus on postwar democratization to consider the prospects for democracy in the wake of state repression and revolution. Our review finds that voters may be less forgiving of violent state repression compared with civil war violence; political parties emerging from civil wars and state repression face cognate yet distinct challenges; and social revolutionary violence poses more serious and durable threats to democratization than violence from civil wars and state repression. These findings underscore the need for a wider research agenda that investigates the diverse forms of social and political violence and their implications for democracy.
Skin on Trial: Experts and Expertise on ‘Skin Diseases’ in Early Modern Italy
Authors: Savoia Paolo 
Published: March 2024

Summary
By using both static or normative documents (licenses, official regulations, barber-surgeon’s manuals) and more dynamic sources (trials of the Protomedicato), my article asks what was an expert on skin diseases in early modern Italy and how the loose category of “skin diseases” came into being under the influence of medical theory, surgical practice, patient demand, and civic regulation of medical practice. I argue that by the late seventeenth century “skin disease” became an independent category, the surface of the body an independent object, and the empiric surgeon an expert of such surface. As human skin as a surface acquired autonomy as an object of knowledge and practice, a class of experts emerged following a path which is in large measure independent from the transformations of Galenic theoretical medicine and the rise of mechanistic medicine which are typically described as central in this period. I argue that empirical surgeons and barber-surgeons became experts on skin through the licensing system and by inverting the classical path of medical knowledge – not from the inner body to its surface as manifestation of internal humoral imbalances, but rather from the surface to the knowledge and the treatment of the inner body.
Evolutionary trajectory of diverse SARS-CoV-2 variants at the beginning of COVID-19 outbreak
Authors: Lv Jia-Xin , Liu Xiang , Pei Yuan-Yuan , Song Zhi-Gang , Chen Xiao , Hu Shu-Jian , She Jia-Lei , Liu Yi , Chen Yan-Mei , Zhang Yong-Zhen 
Published: March 2024

Abstract
Despite extensive scientific efforts directed toward the evolutionary trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans at the beginning of the COVID-19 epidemic, it remains unclear how the virus jumped into and evolved in humans so far. Herein, we recruited almost all adult coronavirus disease 2019 (COVID-19) cases appeared locally or imported from abroad during the first 8 months of the outbreak in Shanghai. From these patients, SARS-CoV-2 genomes occupying the important phylogenetic positions in the virus phylogeny were recovered. Phylogenetic and mutational landscape analyses of viral genomes recovered here and those collected in and outside of China revealed that all known SARS-CoV-2 variants exhibited the evolutionary continuity despite the co-circulation of multiple lineages during the early period of the epidemic. Various mutations have driven the rapid SARS-CoV-2 diversification, and some of them favor its better adaptation and circulation in humans, which may have determined the waxing and waning of various lineages.
Infectious hepatitis E virus excreted into the vagina
Authors: Cong Chao , Xia Yueping , Gong Shilin , Li Tengyuan , Liu Huichan , Zhong Guo , Chen Dongxue , Zhao Wanqiu , Yu Wenhai , Yao Yinjie , Liu Jiankun , Wei Daqiao , Cao Hongcui , Huang Fen 
Published: March 2024

AbstractHepatitis E virus (HEV) persists in the male genital tract that associates with infertility. However, the presence of HEV in the female genital tract is unreported. Vaginal secretions, cervical smears, and cervix uteri were collected to explore the presence of HEV in the female genital tract. HEV RNA and/or antigens were detected in the vaginal secretions, cervical smears, and the cervix uteri of women. The infectivity of HEV excreted into vaginal secretions was further validated in vitro. In addition, HEV replicates in the female genital tract were identified in HEV‐infected animal models by vaginal injection or vaginal mucosal infection to imitate sexual transmission. Serious genital tract damage and inflammatory responses with significantly elevated mucosal innate immunity were observed in women or animals with HEV vaginal infection. Results demonstrated HEV replicates in the female genital tract and causes serious histopathological damage and inflammatory responses.
InflammamiRs in focus: Delivery strategies and therapeutic approaches
Authors: Akkaya‐Ulum Yeliz Z. , Sen Basak , Akbaba Tayfun Hilmi , Balci‐Peynircioglu Banu 
Published: March 2024

AbstractmicroRNAs (miRNAs) are small non‐protein‐coding RNAs which are essential regulators of host genome expression at the post‐transcriptional level. There is evidence of dysregulated miRNA expression patterns in a wide variety of diseases, such as autoimmune and inflammatory conditions. These miRNAs have been termed “inflammamiRs.” When working with miRNAs, the method followed, the approach to treat or diagnosis, and the selected biological material are very crucial. Demonstration of the role of miRNAs in particular disease phenotypes facilitates their evaluation as potential and effective therapeutic tools. A growing number of reports suggest the significant utility of miRNAs and other small RNA drugs in clinical medicine. Most miRNAs seem promising therapeutic options, but some features associated with miRNA therapy like off‐target effect, effective dosage, or differential delivery methods, mainly caused by the short target's sequence, make miRNA therapies challenging. In this review, we aim to discuss some of the inflammamiRs in diseases associated with inflammatory pathways and the challenge of identifying the most potent therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics. We also discuss the status of inflammamiRs in clinical trials.
The potential roles of antibody-drug conjugates in head and neck squamous cell carcinoma
Authors: Filippini Daria Maria , Le Tourneau Christophe 
Published: March 2024

Purpose of review
To summarize the actual antibody-drug conjugates (ADCs) tested for patients with advanced head and neck squamous cell carcinoma (HNSCC), outlining the results of safety and efficacy through published clinical trials.

Recent findings
ADCs combine the specificity of mAbs with the cytotoxic drug (known as payload) via a chemical linker and it is designed to selectively deliver the ultratoxic payload directly to the target cancer cells. To date, various ADCs have been investigated in multiple solid malignancies and others are in clinical development. In this study, we provide an overview of the structure and biology of ADC and we review recent clinical experience with the ADC in patients with advanced HNSCC, followed by a brief discussion of the evolvement of ADC conception, drug resistance and future perspectives.

Summary
ADC strategy is emerging as a potential active treatment in previously treated patients with advanced HNSCC. However, the recent improvement in the bioengineering of ADC and a better comprehension of sequencing and association strategies could provide more benefit to HNSCC patients in need of innovative therapy.
The prevalence of antiphospholipid antibodies and effects on the outcomes of in vitro fertilization
Authors: Halki Nagham , Khalayli Naram , Haidar Ghina , Al Halaki Waeel , Kudsi Maysoun , Abou Samra Rouaida , Alhalabi Marwan 
Published: March 2024

Introduction:
The problem of infertility is common worldwide. IVF remains the most widely used technique of assisted reproductive technology. Embryo implantation failure is a common cause of unexplained infertility and recurrent miscarriages, thus the relationship between antiphospholipid antibodies and embryo implantation failure after IVF and embryo transfer is an important problem in fertility medicine that must be studied.

Patients and methods:
A retrospective and prospective (bidirectional) cohort study were conducted at the Laboratory Department of the Faculty of Medicine, and Hospital from June 2017 to June 2021. The sample size was 1000 participants, 900 of them were retrospective (2017–2020), and 100 were prospective (2020–2021). Data was collected, including patients’ demographics, type and duration of fertility, and antiphospholipid antibody values. Inclusion criteria-Women <40 years old, undergoing IVF, and in the retrospective study, patients who undergo IVF and who have antibody data, positivity of phospholipids, and/or anticardiolipin, and/or B2 glycoprotein I, and the presence of the gestational sac on ultrasound as a criterion for pregnancy. We performed a PTT LA for the control group in a cohort study (20 healthy women), then a PTT LA test, and the blending test were performed, and the values were considered positive if the correction was not made. The PTT LA test is a screening test.

Results:
The average age of the women was 31.91, the success rate of assisted fertilization in inducing pregnancy in the last trial was 52.8%, the prevalence was 4.4% of anticardiolipin IgG, 2.6% of anticardiolipin IgM, and 4% of Lupus anticoagulant. No relation was found between the antiphospholipid value and the age of the women, the number of times the experiment was conducted, the rate of success and failure, the type of infertility, and the number of oocytes induction, while the duration of sterility was affected by positive values of IgG and lupus coagulant antibodies.

Conclusion:
There is no need for a routine antiphospholipid assay for female candidates for IVF, and when it is confirmed, treatment is required by Anticoagulants.
A Case of Rhegmatogenous Retinal Detachment in Chronic Myeloid Leukemia
Authors: Maganti Nenita , Crabtree Gordon S , Chang Jonathan S , Schildroth Kathleen R 
Published: March 2024

Purpose:
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by uncontrolled proliferation of granulocytes, caused the BCR-ABL1 fusion gene. While ocular manifestations of CML are rare, the presentations can range from asymptomatic to sudden vision loss. CML associated ocular findings that have been reported include retinal hemorrhages, leukemic infiltrates, and optic disc edema, but a rhegmatogenous retinal detachment (RRD) in the setting of CML has not been described.

Methods:
Case report

Results:
A 21-year-old man presented with intermittent vision loss in his right eye, tinnitus in the right ear, and abdominal distension. Work up revealed significant leukocytosis, splenomegaly, and a positive BCR-ABL1 mutation. He was diagnosed with CML and started on systemic therapy. Exam of the right eye revealed a large intraocular mass. After two weeks of systemic treatment, the large elevation in the right eye had improved, allowing visualization of diffuse subretinal whitening. At follow up, an RRD secondary to an atrophic hole in an area of prior subretinal infiltrates were noted. He underwent repair with a scleral buckle. Postoperative course was complicated by redetachment with proliferative vitreoretinopathy, which led to an unrepairable detachment, despite multiple surgeries with silicone oil tamponade.

Conclusions:
Ocular findings related to CML are rare, with the lowest incidence when compared to other leukemias, and are associated with worse outcomes. Posterior segment findings include intraretinal hemorrhages, Roth spots, and retinal infiltrates. This unique case describes an RRD in CML retinopathy with an aggressive course and poor anatomical result.
Inefficient transmission of African swine fever virus to sentinel pigs from
environmental contamination under experimental conditions
Authors: Olesen Ann Sofie , Lohse Louise , Accensi Francesc , Goldswain Hannah , Belsham Graham J. , Bøtner Anette , Netherton Christopher L. , Dixon Linda K. , Portugal Raquel 
Published: March 2024

Abstract
Knowledge about African swine fever virus (ASFV) transmission and its
survival in the environment is mandatory to develop rational control strategies
and combat this serious disease in pigs. In this study, the risk that
environmental contamination poses for infection of naïve pigs was investigated.
Naïve pigs were introduced as sentinels into contaminated pens either on the
same day or up to three days after ASFV-infected pigs were removed. Three
experiments were carried out in which four to six pigs per pen were inoculated
with virulent ASFV isolates OURT88/1 (genotype I), Georgia 2007/1 or
POL/2015/Podlaskie (genotype II), respectively. The majority of the inoculated
pigs developed acute disease but with no evident haemorrhagic lesions or
haemorrhagic diarrhoea and were culled at the predefined humane endpoint. The
levels of ASFV DNA detected in the blood of the infected animals reached
107-9genome copies/ml before euthanasia. Environmental
swabs were taken from different surfaces in the animal rooms, as well as from
faeces and urine, close to the time of introduction of the naïve animals.
Relatively low quantities of virus DNA were detected in the environmental
samples, in the order of 103-7genome copies. Neither
clinical signs nor virus genomes were detected in the blood of any of the
sentinel pigs over a period of two to three weeks after exposure, indicating
that transmission from the ASFV-contaminated environment did not occur.
Interestingly, viral DNA was detected in nasal and oral swabs from some of the
sentinel animals at early days of exposure (ranging between
103.7-5.8genome copies), though none of them developed
ASF. The results indicate a relatively low risk of ASFV transmission from a
contaminated environment in the absence of blood from infected animals.
Neurodevelopmental disorders associated variants inADAT3disrupt the activity of the ADAT2/ADAT3 tRNA deaminase complex and impair neuronal migration
Authors: Del-Pozo-Rodriguez Jordi , Tilly Peggy , Lecat Romain , Vaca Hugo Rolando , Mosser Laureline , Brivio Elena , Balla Till , Gomes Marina Vitoria , Ramos-Morales Elizabeth , Schwaller Noémie , Salinas-Giegé Thalia , VanNoy Grace , England Eleina M. , Lovgren Alysia Kern , O’Leary Melanie , Chopra Maya , Ojeda Naomi Meave , Toosi Mehran Beiraghi , Eslahi Atieh , Alerasool Masoome , Mojarrad Majid , Pais Lynn S. , Yeh Rebecca C. , Gable Dustin L. , Hashem Mais O , Abdulwahab Firdous , Alzaidan Hamad , Aldhalaan Hesham , Tous Ehab , Alsagheir Afaf , Alowain Mohammed , Tamim Abdullah , Alfayez Khowlah , Alhashem Amal , Alnuzha Aisha , Kamel Mona , Al-Awam Bashayer S , Elnaggar Walaa , Almenabawy Nihal , O’Donnell-Luria Anne , Neil Jennifer E. , Gleeson Joseph G. , Walsh Christopher A. , Alkuraya Fowzan S , AlAbdi Lama , Elkhateeb Nour , Selim Laila , Srivastava Siddharth , Nedialkova Danny D. , Drouard Laurence , Romier Christophe , Bayam Efil , Godin Juliette D. 
Published: March 2024

AbstractThe ADAT2/ADAT3 complex catalyzes the adenosine to inosine modification at the wobble position of eukaryotic tRNAs. Mutations inADAT3, the catalytically inactive subunit of the ADAT2/ADAT3 complex, have been identified in patients presenting with severe neurodevelopmental disorders (NDDs). Yet, the physiological function of ADAT2/ADAT3 complex during brain development remains totally unknown. Here we showed that maintaining a proper level of ADAT2/ADAT3 catalytic activity is required for correct radial migration of projection neurons in the developing mouse cortex. In addition, we not only reported 20 new NDD patients carrying biallelic variants inADAT3but also deeply characterized the impact of those variants on ADAT2/ADAT3 structure, biochemical properties, enzymatic activity and tRNAs editing and abundance. We demonstrated that all the identified variants alter both the abundance and the activity of the complex leading to a significant decrease of I34with direct consequence on their steady-state. Usingin vivocomplementation assays, we correlated the severity of the migration phenotype with the degree of the loss of function caused by the variants. Altogether, our results indicate a critical role of ADAT2/ADAT3 during cortical development and provide cellular and molecular insights into the pathogenicity of ADAT3-related neurodevelopmental disorder.