bluuebunny/crossref_metadata_2025 huggingface dataset:
Double longitudinal myotomy in gender-affirming colovaginoplasty: an innovative surgical technique to prevent and treat neovaginal spasms
Authors: Mañero Vazquez Iván , Labanca Trinidad , Herrero Roberto
Published: March 2024

Background

Gender-affirming colovaginoplasty (GACv) presents excellent postoperative results. However, neovaginal spasms, reported as painful cramps, can affect the sexual life of patients.

Aim

The study sought to describe an innovative surgical technique and evaluate its impact on the prevention and treatment of neovaginal spasms.

Methods

This was a single-center prospective observational study with 2 series of patients: (1) patients who underwent GACv with double myotomy (DM) for spasm prevention (series A), in which longitudinal myotomies were performed across the defunctionalized colon, transecting the taenias, and resecting 2 strips of the intestinal muscle layer of approximately 1- to 2-mm wide and tall, leaving intact colonic tissue between strips; and (2) patients who reported neovaginal spasms in whom intravaginal-DM was performed as treatment surgery (series B), in which the posterior wall of the neovagina was dissected from the rectum and transected by longitudinal myotomies, resecting 2 strips of endoluminal mucosa and submucosal muscle of approximately 1- to 2-mm wide and tall, and the colonic mucosa was subsequently closed.

Outcomes

Patient-reported outcomes and neovaginal examination were performed following standardized protocols.

Results

In series A, 177 patients underwent GACv with the DM technique and were prospectively followed for a median time of 18 months (interquartile range, 13-60 months). No patients reported neovaginal spasms. In series B, 18 patients who reported neovaginal spasms after GACv were treated with intravaginal DM. After a median time of 35 months (interquartile range, 26-45 months), 83% (n = 15 of 18) reported remission of symptoms.

Clinical implications

Double longitudinal myotomy performed on the derived portion of the colon in colovaginoplasty is an easy-to-perform and safe technique that may prevent and treat postoperative neovaginal spasms.

Strengths and limitations

Our results presented certain limitations, mainly associated with a low prevalence of neovaginal spasms, which, being of personal perception, can be underdiagnosed. To the same extent, the fact that it is a monocentric experience limits the possibility of extrapolating it to other centers. Moreover, a more trained surgical team may be the cause of fewer postoperative complications. On the other hand, the fact of being a reference center for gender-affirming surgery, having our procedures protocolized, and the prospective nature of the study allowed us to obtain a certain homogeneity and granularity of the results.

Conclusion

DM is a safe procedure and appears to be highly effective for the prevention and treatment of neovaginal spasms after GACv. Routine use of this technique does not increase the operating time or postoperative complications. Multicenter, prospective studies are required to validate our results.
Catholicism as Environmental Protest in Rudolfo Anaya’s Bless Me, Ultima and Ana Castillo’s So Far from God
Authors: Spencer Andrew M
Published: March 2024

The geographical region of the US Southwest now known as New Mexico has been colonized by successive waves of invaders. First, the Spanish arrived carrying with them a militant Catholicism that sought to uproot and replace Native spiritualities. Next, the newly independent Mexican government also used Catholicism as a tool of colonization to counter the threat of Native uprisings and Anglo-American encroachment. Finally, following the Treaty of Guadalupe-Hidalgo in 1848, New Mexico was overrun by Anglo settlers as US policies uprooted Spanish and Mexican landowners from their inherited land grants. While Catholicism remained the dominant religion among the mestiza/o population, Native spiritualities were also able to subvert and influence the direction that this now-distinctive New Mexican Catholicism would take. While scholars have read the decolonial and environmental justice themes at work in these Native spiritualities in both Rudolfo Anaya’s Bless Me, Ultima (1972) and Ana Castillo’s So Far from God (1993), I argue that the Catholic faith of the characters in these novels also plays an important role despite the religion’s use as a tool of colonization in the past. Different from the hybridization process used by the Roman Catholic church to erase/subsume indigenous spiritualities, the iterations of Catholicism in these novels seek a more subtle subversion of the faith’s colonial history. By recognizing the function of guilt within the Catholic church to control behavior, these novels throw this guilt back on the colonizer by redefining the Catholic terminology of sin as harm against people of color and the earth.
Trinity – III. Quasar luminosity functions decomposed by halo, galaxy, and black hole masses as well as Eddington ratios from z = 0–10
Authors: Zhang Haowen , Behroozi Peter , Volonteri Marta , Silk Joseph , Fan Xiaohui , Aird James , Yang Jinyi , Hopkins Philip F
Published: March 2024

We present the redshift evolution of quasar luminosity functions (QLFs) decomposed by halo mass, galaxy mass, supermassive black hole (SMBH) mass, and Eddington ratio, as well as SMBH/radiative energy output ratios from trinity, a flexible empirical model that self-consistently infers the halo–galaxy–SMBH connection that match observational data. Key findings include: (1) The normalization of quasar luminosity function increases by ∼3–4 dex from z ∼ 10 to z ∼ 4, due to the fast mass build-up of different SMBH populations; (2) From z ∼ 4 to z ∼ 1, less massive galaxies and SMBHs make up bigger and bigger fractions of QLFs, due to the active galactic nuclei (AGNs) downsizing effect; (3) At z ∼ 0, massive haloes/galaxies/SMBHs are responsible for most bright quasars due to low Eddington ratios among all SMBHs; (4) The bright ends of QLFs are dominated by SMBHs that are at least 0.3 dex overmassive relative to the median SMBH mass–galaxy mass relation; (5) QLFs at z ∼ 6–7 are dominated by SMBHs accreting at Eddington ratios 0.1 < ηrad < 1, but super-Eddington AGNs contribute more significantly to QLFs towards z ∼ 9–10.
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

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

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

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

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

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

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

Hepatitis 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

microRNAs (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.
Snapping Triceps Syndrome: Surgical Technique
Authors: Chan Fa Yu , Lam Caroline , Butorac Roger , Willemot Laurent
Published: March 2024

Snapping triceps syndrome is a rare cause of medial elbow pain and ulnar neuritis caused by subluxation and triggering of the medial tricipital muscle belly over the medial distal humeral ridge and condyle. The diagnosis and surgical management of snapping triceps syndrome can be challenging due to the subtlety of the symptoms and the infrequent presentation. Despite the diagnosis relying largely on clinical examination, noninvasive dynamic ultrasonography may facilitate detection. Correct recognition of this condition is crucial in the avoidance of surgical misadventure and revision surgery. This paper illustrates our surgical technique for the management of snapping triceps and reviews the available literature on this relatively obscure condition.
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.

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.
Proposals to revise the Statutes of the International Committee on Systematics of Prokaryotes
Authors: Arahal David R. , Göker Markus , Hahnke Richard L. , Manaia Célia M. , Moore Edward R.B. , Oren Aharon , Sutcliffe Iain C. , Ventura Stefano
Published: March 2024

The International Committee on Systematics of Prokaryotes serves to administer the rules of prokaryotic nomenclature via the International Code of Nomenclature of Prokaryotes, ensures the publication of the International Journal of Systematic and Evolutionary Microbiology, and works to represent the interests of the microbiological disciplines regarding prokaryotic nomenclature. The functions and mechanisms of operation of the International Committee on Systematics of Prokaryotes (ICSP) are defined in its Statutes, which were last revised in 2019. As members of the 2020–2023 and the 2023–2026 ICSP Executive Board and the Judicial Commission, we propose here some further revisions to help improve the clarity and functionality of the Statutes.
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

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

The 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.
Novel antibody language model accelerates IgG screening and design for broad-spectrum antiviral therapy
Authors: Almubarak Hannah Faisal , Tan Wuwei , Hoffmann Andrew D. , Sun Yuanfei , Wei Juncheng , El-Shennawy Lamiaa , Squires Joshua R. , Dashzeveg Nurmaa K. , Simonton Brooke , Jia Yuzhi , Iyer Radhika , Xu Yanan , Nicolaescu Vlad , Elli Derek , Randall Glenn C. , Schipma Matthew J. , Swaminathan Suchitra , Ison Michael G. , Liu Huiping , Fang Deyu , Shen Yang
Published: March 2024

Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline AbGen that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains. Our AbGen centers around a novel antibody language model (AbLM) that is pretrained on 12 million generic protein domain sequences and fine-tuned on 4,000+ paired VH-VL sequences, with IgG-specific CDR-masking and VH-VL cross-attention. AbLM provides a latent space of IgG sequence embeddings for AbGen, including (a) landscapes of IgGs’ activities in neutralizing the wild-type virus are analyzed through structure prediction for IgG and IgG-antigen (viral protein spike’s receptor binding domain, RBD) interactions; and (b) landscapes of IgGs’ susceptibility in neutralizing variant viruses are predicted through Gaussian process regression, despite that as few as 14 clinical antibodies’ responses to variants of concern are available. The AbGen pipeline was applied to over 1300 IgG sequences we collected from RBD-binding B cells of convalescent patients. With experimental validations, AbGen efficiently prioritized IgG candidates against a broad spectrum of viral variants (wildtype, Delta, and Omicron), preventing the infection of host cellsin vitroand hACE2 transgenic micein vivo. Compared to other existing protein language models that require 10-100 times more model parameters, AbLM improved the precision from around 50% to 75% to predict IgGs with low variant susceptibility. Furthermore, AbGen enables structure-based computational protein redesign for selected IgG clones with single amino acid substitutions at the RBD-binding interface that doubled the IgG blockade efficacy for one of the severe, therapy-resistant strains - Delta (B.1.617). Our work expedites applications of artificial intelligence in antibody screen and re- design combining data-driven protein language models and Kriging for antibody sequence analysis and activity prediction, in synergy with physics-driven protein docking and design for antibody-antigen interface analyses and functional optimization.
The complement regulator CD55 modulates TLR9 signaling and supports survival in marginal zone B cells
Authors: Lee Iris , Ling Ivana , Verma Sonam , Blanche Wumei , Pham Christine T.N. , Kendall Peggy L.
Published: March 2024

Marginal zone (MZ) B cells bridge innate and adaptive immunity by sensing bloodborne antigens and producing rapid antibody and cytokine responses. CD55 is a membrane-bound complement regulator that interferes with complement activation, an important component of innate immunity. CD55 also regulates adaptive immunity—CD55 downregulation is critical for germinal center reactions. MZ B cells also express low CD55, but its role in MZ B cell function is unknown. Using germline knockout mice, we found that similar numbers of MZ B cells are initially established in 3-week-old CD55-deficient mice compared to wild-type (WT) mice. However, MZ B cells fail to accumulate as mice age and undergo increased apoptosis. Followingex vivostimulation of MZ B cells through Toll-like receptor 9, we observed a proinflammatory phenotype with increased IL-6 expression. These findings demonstrate a critical role for CD55 in supporting MZ B cell survival while also regulating cellular function.
Repeated Exposure Decreases Aesthetic Chills Likelihood but Increases Intensity
Authors: Schoeller F. , Christov-Moore L. , Lynch C. , Jain A. , Diot T. , Reggente N.
Published: March 2024

Aesthetic chills are a peak emotional response to affectively charged stimuli such as music, films, or speech. This study investigates the impact of repeated exposure on the frequency and intensity of aesthetic chills. Through a longitudinal approach, we quantified changes in chill likelihood, intensity, and pleasure across multiple exposures, focusing on audio stimuli. Participants (n = 58) were randomly exposed to 6 chill-evoking stimuli pre-validated on the population of interest, in a counterbalanced order. Our findings revealed a significant decrease in the likelihood of experiencing chills with repeated exposure, suggesting habituation to chills itself or potential fatigue in response to aesthetic stimuli. The study also identified distinct demographic and psychophysiological response patterns across different participant groups, indicating variability in chill responses. These results provide insights into the dynamic nature of aesthetic experiences and their underlying neural mechanisms, with implications for understanding emotional and reward processing in psychophysiology.
A trait-based taxonomic data base for the order Schizomida (Arachnida) with descriptions of a new fossil species from Kachin amber and the female ofSurazomus palenqueVillarreal, Miranda & Giupponi 2016
Authors: Müller Sandro P , Magnussen Ilian De Francesco , Gearty William , Dupérré Nadine , Hammel Jörg U , Kotthoff Ulrich
Published: March 2024

Despite a global distribution throughout the tropics and sub-tropics, the order Schizomida (Arachnida) is heavily understudied and the phylogeny of the group is poorly understood. Identification keys are only available for some regions or genera but not for the entire order. (1) comprehensively reviewed the entire schizomid fauna and established a suite of characters to define all genera known at this time. This suite of characters still depicts the foundation of modern descriptions, supplemented by recently established characters, most of them documenting setation patterns on pedipalps, flagellum and chelicerae. In this paper, we present the Schizomida Trait Data Base (STDB) containing data for 25 characters based on the entire body of schizomid literature. Characters were chosen based on their use for modern taxonomic description and availability of the data. The STDB is a powerful tool that can be used by both amateurs and experienced researchers to categorise newly found specimens, both extant and fossil, down to genus level easily. Analysis using the new database gives insight into biogeographical patterns of characters. Furthermore, we are describing a new species,†Annazomus jamesi,a fossil specimen from Burmese (Kachin) amber and investigate a small collection of extant schizomids from Ecuador, which includes the previously unrecorded female ofSurazomus palenque,herein described for the first time. The taxonomic assignment of both specimens is based on the STDB, highlighting the utility of the new data base approach to schizomid systematics.

Arachnids, biogeography, Cretaceous, data base, fossil, new species, palaeontology, Schizomida, statistics, taxonomy
Localized estimation of event-related neural source activity from simultaneous MEG-EEG with a recurrent neural network
Authors: O’Reilly Jamie A. , Zhu Judy D. , Sowman Paul F.
Published: March 2024

Estimating intracranial current sources underlying the electromagnetic signals observed from extracranial sensors is a perennial challenge in non-invasive neuroimaging. Established solutions to this inverse problem treat time samples independently without considering the temporal dynamics of event-related brain processes. This paper describes current source estimation from simultaneously recorded magneto- and electro-encephalography (MEEG) using a recurrent neural network (RNN) that learns sequential relationships from neural data. The RNN was trained in two phases: (1) pre-training and (2) transfer learning with L1 regularization applied to the source estimation layer. Performance of using scaled labels derived from MEEG, magnetoencephalography (MEG), or electroencephalography (EEG) were compared, as were results from volumetric source space with free dipole orientation and surface source space with fixed dipole orientation. Exact low-resolution electromagnetic tomography (eLORETA) and mixed-norm L1/L2 (MxNE) source estimation methods were also applied to these data for comparison with the RNN method. The RNN approach outperformed other methods in terms of output signal-to-noise ratio, correlation and mean-squared error metrics evaluated against ground-truth event-related field (ERF) and event-related potential (ERP) waveforms. Using MEEG labels with fixed-orientation surface sources produced the most consistent estimates. To estimate sources of ERF and ERP waveforms, the RNN generates temporal dynamics within its internal computational units, driven by sequential structure in neural data used as training labels. It thus provides a data-driven model of computational transformations from psychophysiological events into corresponding event-related neural signals, which is unique among MEG and EEG source reconstruction solutions.
High-fidelity annotated genome of the polyploid and quarantine root-knot nematode,Meloidogyne enterolobii
Authors: Poullet Marine , Gopal Hemanth , Rancurel Corinne , Sallaberry Marine , Lopez-Roques Celine , Lledo Joanna , Kiewnick Sebastian , Danchin Etienne GJ
Published: March 2024

Root-knot nematodes of the genusMeloidogyneare obligatory plant endoparasites that cause substantial economic losses to the agricultural production and impact the global food supply. These plant parasitic nematodes belong to the most widespread and devastating genus worldwide, yet few measures of control are available. The most efficient way to control root-knot nematodes (RKN) is deployment of resistance genes in plants. However, current resistance genes that control otherMeloidogynespecies are mostly inefficient onM. enterolobii. Consequently,M. enterolobiiwas listed as a European Union quarantine pest implementing regulation. To gain insight into the molecular characteristics underlying its parasitic success, exploring the genome ofM. enterolobiiis essential. Here, we report a high-quality genome assembly ofMeloidogyne enterolobiiusing the high-fidelity long-read sequencing technology developed by Pacific Biosciences, combined with a gap-aware sequence transformer, DeepConsensus. The resulting genome assembly spans 273 Mbp with 556 contigs, a GC% of 30 ± 0.042 and an N50 value of 2.11Mb, constituting a useful platform for comparative, population and functional genomics.
Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation
Authors: Sanchez Sarah , Dangi Tanushree , Awakoaiye Bakare , Irani Nahid , Fourati Slim , Richner Justin , Penaloza-MacMaster Pablo
Published: March 2024

mRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines.
Inflammation promotes aging-associated oncogenesis in the lung
Authors: Pham-Danis Catherine , Chia Shi B , Scarborough Hannah A , Danis Etienne , Nemkov Travis , Kleczko Emily K , Navarro Andre , Goodspeed Andrew , Bonney Elizabeth A. , Dinarello Charles A. , Marchetti Carlo , Nemenoff Raphael A. , Hansen Kirk , DeGregori James
Published: March 2024

Background

Lung cancer is the leading cause of cancer death in the world. While cigarette smoking is the major preventable factor for cancers in general and lung cancer in particular, old age is also a major risk factor. Aging-related chronic, low-level inflammation, termed inflammaging, has been widely documented; however, it remains unclear how inflammaging contributes to increased lung cancer incidence.

Aim

To establish connections between aging-associated changes in the lungs and cancer risk.

Methods

We analyzed public databases of gene expression for normal and cancerous human lungs and used mouse models to understand which changes were dependent on inflammation, as well as to assess the impact on oncogenesis.

Results

Analyses of GTEx and TCGA databases comparing gene expression profiles from normal lungs, lung adenocarcinoma, lung squamous cell carcinoma of subjects across age groups revealed upregulated pathways such as inflammatory response, TNFA signaling via NFκB, and interferon-gamma response. Similar pathways were identified comparing the gene expression profiles of young and old mouse lungs. Transgenic expression of alpha 1 antitrypsin (AAT) partially reverses increases in markers of aging-associated inflammation and immune deregulation. Using an orthotopic model of lung cancer using cells derived from EML4-ALK fusion-induced adenomas, we demonstrated an increased tumor outgrowth in lungs of old mice while NLRP3 knockout in old mice decreased tumor volumes, suggesting that inflammation contributes to increased lung cancer development in aging organisms.

Conclusions

These studies reveal how expression of an anti-inflammatory mediator (AAT) can reduce some but not all aging-associated changes in mRNA and protein expression in the lungs. We further show that aging is associated with increased tumor outgrowth in the lungs, which may relate to an increased inflammatory microenvironment.
Chromosome-level genome assembly of the disco clam,Ctenoides ales, a first for the bivalve order Limida
Authors: McElroy Kyle E , Masonbrink Rick , Chudalayandi Sivanandan , Severin Andrew J , Serb Jeanne M
Published: March 2024

The bivalve subclass Pteriomorphia, which includes the economically important scallops, oysters, mussels, and ark clams, exhibits extreme ecological, morphological, and behavioral diversity. Among this diversity are five morphologically distinct eye types, making Pteriomorphia an excellent setting to explore the molecular basis for the evolution of novel traits. Of pteriomorphian bivalves, Limida is the only order lacking genomic resources, greatly limiting the potential phylogenomic analyses related to eyes and phototransduction. Here, we present the first limid genome assembly, the disco clam,Ctenoides ales, which is characterized by invaginated eyes, exceptionally long tentacles, and a flashing light display. This genome assembly was constructed with PacBio long reads and Dovetail Omni-CTMproximity-ligation sequencing. The final assembly is ∼2.3Gb and over 99% of the total length is contained in 18 pseudomolecule scaffolds. We annotated 41,064 protein coding genes and report a BUSCO completeness of 91.9% for metazoa_obd10. Additionally, we report a completely annotated mitochondrial genome, also a first for Limida. The ∼20Kb mitogenome has 12 protein coding genes, 22 tRNAs, 2 rRNA genes, and a 1,589 bp duplicated sequence containing the origin of replication. TheC. alesnuclear genome size is substantially larger than other pteriomorphian genomes, mainly accounted for by transposable element sequences. We inventoried the genome for opsins, the signaling proteins that initiate phototransduction, and found that, unlike its closest eyed-relatives, the scallops,C. aleslacks duplication of the rhabdomeric Gq-protein coupled opsin that is typically used for invertebrate vision. In fact,C. aleshas uncharacteristically few opsins relative to the other pteriomorphian families, all of which have unique expansions of xenopsins, a recently discovered opsin subfamily. This chromosome-level assembly, along with the mitogenome, will be valuable resources for comparative genomics and phylogenetics in bivalves and particularly for the understudied but charismatic limids.

Significance

This high-quality chromosome-level genome assembly forCtenoides ales, the disco clam, is the first genome sequenced from the bivalve order Limida, the only group of Pteriomorphia – a highly diverse and ecologically important clade – lacking genomic resources. The sequence and annotation of theC. alesgenome will be a useful resource for molluscan phylogenetics and comparative genomics.