bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Rapamycin Prevents Surgery-Induced Immune Dysfunction in Patients with Bladder Cancer
Authors: Svatek Robert S. , Ji Niannian , de Leon Essel , Mukherjee Neelam Z. , Kabra Aashish , Hurez Vincent , Nicolas Marlo , Michalek Joel E. , Javors Martin , Wheeler Karen , Sharp Z. Dave , Livi Carolina B. , Shu Zhen-Ju , Henkes David , Curiel Tyler J.
Published: March 2024

Abstract
The mechanistic target of rapamycin (mTOR) integrates environmental inputs to regulate cellular growth and metabolism in tumors. However, mTOR also regulates T-cell differentiation and activation, rendering applications of mTOR inhibitors toward treating cancer complex. Preclinical data support distinct biphasic effects of rapamycin, with higher doses directly suppressing tumor cell growth and lower doses enhancing T-cell immunity. To address the translational relevance of these findings, the effects of the mTOR complex 1 (mTORC1) inhibitor, rapamycin, on tumor and T cells were monitored in patients undergoing cystectomy for bladder cancer. MB49 syngeneic murine bladder cancer models were tested to gain mechanistic insights. Surgery-induced T-cell exhaustion in humans and mice and was associated with increased pulmonary metastasis and decreased PD-L1 antibody efficacy in mouse bladder cancer. At 3 mg orally daily, rapamycin concentrations were 2-fold higher in bladder tissues than in blood. Rapamycin significantly inhibited tumor mTORC1, shown by decreased rpS6 phosphorylation in treated versus control patients (P = 0.008). Rapamycin reduced surgery-induced T-cell exhaustion in patients, evidenced by a significant decrease in the prevalence of dysfunctional programmed death-1 (PD-1)–expressing T cells. Grade 3 to 4 adverse event rates were similar between groups, but rapamycin-treated patients had a higher rate of wound complications versus controls. In conclusion, surgery promoted bladder cancer metastasis and decreased the efficacy of postoperative bladder cancer immunotherapy. Low-dose (3 mg daily) oral rapamycin has favorable pharmacodynamic and immune modulating activity in surgical patients and has the potential to decrease surgery-induced immune dysfunction.
Data from Interleukin 33 Signaling Restrains Sporadic Colon Cancer in an Interferon-γ–Dependent Manner
Authors: Eissmann Moritz F. , Dijkstra Christine , Wouters Merridee A. , Baloyan David , Mouradov Dmitri , Nguyen Paul M. , Davalos-Salas Mercedes , Putoczki Tracy L. , Sieber Oliver M. , Mariadason John M. , Ernst Matthias , Masson Frederick
Published: March 2024

Abstract
Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa. Although IL33 can prevent colon cancer associated with inflammatory colitis, the contribution of IL33 signaling to sporadic colon cancer remains unknown. Here, we utilized a mouse model of sporadic colon cancer to investigate the contribution of IL33 signaling to tumorigenesis in the absence of preexisting inflammation. We demonstrated that genetic ablation of St2 enhanced colon tumor development. Conversely, administration of recombinant IL33 reduced growth of colon cancer cell allografts. In reciprocal bone marrow chimeras, the concurrent loss of IL33 signaling within radioresistant nonhematopoietic, and the radiosensitive hematopoietic, compartments was associated with increased tumor burden. We detected St2 expression within the radioresistant mesenchymal cell compartment of the colon whose stimulation with IL33 induced expression of bona fide NF-κB target genes. Mechanistically, we discovered that St2 deficiency within the nonhematopoietic compartment coincided with increased abundance of regulatory T cells and suppression of an IFNγ gene expression signature, whereas IL33 administration triggered IFNγ expression by tumor allograft-infiltrating T cells. The decrease of this IFNγ gene expression signature was associated with more aggressive disease in human colon cancer patients, suggesting that lack of IL33 signaling impaired the generation of a potent IFNγ-mediated antitumor immune response. Collectively, our data reveal that IL33 functions as a tumor suppressor in sporadic colon cancer. Cancer Immunol Res; 6(4); 409–21. ©2018 AACR.
Supplementary Figure 2 from Ex Vivo Efficacy of SAR442257 Anti-CD38 Trispecific T-cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA-targeted Therapies
Authors: Keller Alana L. , Reiman Lauren T. , Perez de Acha Olivia , Parzych Sarah E. , Forsberg Peter A. , Kim Peter S. , Bisht Kamlesh , Wang Hongfang , van de Velde Helgi , Sherbenou Daniel W.
Published: March 2024

Sensitivity to SAR4422557 across treatment groups
The Association between Lead Exposure and Dental Caries: A Systematic Review
Authors: Lee Gajin , Zhang Yijia , Yang Qiannan , Angley Meghan , Lu Liping , Kahe Ka
Published: March 2024

Introduction: Dental caries has declined over the years, but it remains a major public health issue. This review aimed to investigate the association between lead (Pb) and caries experience in either deciduous or permanent teeth. Methods: A comprehensive search of PubMed, Embase, and Google Scholar was conducted to identify relevant studies published up until December 2022. Included were human observational studies that investigated the association between Pb exposure and dental caries. The review adhered to the PRISMA guideline. Results: Sixteen studies were included in this review, with nine focusing on deciduous teeth, thirteen on permanent teeth, and six examining both types of teeth. Most of the studies (5 of 6) found a positive association between blood lead (PbB) levels and caries in deciduous teeth, while the findings for permanent teeth were less conclusive, with only 3 of 10 studies finding an association. One of the two studies assessing salivary lead levels found a weak association for permanent teeth. All four studies that measured Pb concentration from teeth found a positive association for both deciduous and permanent teeth. Conclusion: Many published studies have indicated a positive association between Pb exposure and caries experience in deciduous dentition. Children with elevated PbB level should be considered having higher caries experience. Due to lack of consensus on measurement and examination technique, there remains insufficient evidence to make any definitive conclusions, especially in permanent dentition, and so more studies are warranted.
Prevalence and Characteristics of Known versus Newly Detected Atrial Fibrillation in Ischemic Stroke: A Population-Based Study
Authors: Mitaine Aurore , Duloquin Gauthier , Pommier Thibaut , Vergely Catherine , Guenancia Charles , Béjot Yannick
Published: March 2024

Background: Atrial fibrillation (AF) is frequently diagnosed during the acute stage of ischemic stroke (IS), and it may reflect undiagnosed AF before stroke, thus representing a missed opportunity for stroke prevention. This population-based study aimed to assess the prevalence of known AF (KAF) and AF diagnosed early after IS (AFDAS) and to compare clinical and brain/arterial imaging characteristics between patients. Methods: Among patients with acute IS recorded in the population-based Dijon Stroke Registry, France (2013–2020), we identified those with KAF or AFDAS. AFDAS was considered when AF was diagnosed during the initial work-up based on electrocardiograms, in-hospital continuous electrocardiographic and/or Holter monitoring. Clinical and imaging characteristics on brain CT scan or angio-CT scan when available including old parenchymal lesions, arterial territory of the index IS, and aortic arch, cervical and intracranial arteries atheroma were compared between groups (KAF vs. AFDAS). Regression logistic models were used to assess factors associated with AFDAS (compared to KAF). Results: Among 1,756 IS patients, 550 (31.3%) had AF (mean age: 83.6 ± 10.3 years old, 60.5% women), of whom 367 (66.7%) presented with KAF and 183 (33.3%) had AFDAS. In multivariable model, hypertension (OR = 0.37; 95% CI: 0.21–0.64, p < 0.001), chronic heart failure (OR = 0.34; 95% CI: 0.18–0.67, p = 0.002), previous stroke (OR = 0.42; 95% CI: 0.26–0.67, p < 0.001), and preexisting dementia (OR = 0.36; 95% CI: 0.21–0.63, p < 0.001) were inversely associated with AFDAS, whereas NIHSS score was associated with AFDAS (OR = 1.02; 95% CI: 1.00–1.05, p = 0.012). Conclusions: Our findings indicate a more advanced stage of the atrial cardiomyopathy in KAF as compared with AFDAS patients and may thus contribute to the fact that in these latter patients AF had not been diagnosed prior to stroke. This group of patients undeniably represents a missed opportunity for stroke prevention.
Cancer-Related Cognitive Dysfunction: A Narrative Review for Clinical Practice
Authors: Rick Oliver , Gerhardt Alexandra , Schilling Georgia
Published: March 2024

Background: Cancer-related cognitive dysfunction (CRCD) is a major functional disorder in patients with cancer. This central nervous dysfunction is found in up to 60% of patients after tumour therapy, often significantly limits the quality of life, and significantly impedes participation in working life. For this reason, diagnosis and treatment of CRCD are of central importance. This narrative review is intended to provide an overview and support for practical clinical care with regard to diagnostics and therapeutic options. Summary: In Germany, CRCD has received insufficient attention in clinical practice due to the lack of guidelines for diagnosis and therapy. The pathophysiology is complex and cannot be explained by chemotherapeutic treatment alone. In addition to the tumour disease as such and the tumour therapy, psychological factors such as anxiety and depression as well as sleep disorders also play a significant role. Today, it is known that in addition to age, molecular genetic changes also have an effect on cognitive function. Morphologically, CRCD can be located in the frontal cortex and hippocampus. In addition to easy-to-use screening instruments such as the visual analogue scale, validated questionnaires such as the Questionnaire of Subjectively Experienced Deficits in Attention (FEDA) developed in Germany are also available. These allow the suspected diagnosis to be substantiated and the patient to be referred to further neurological, neuropsychological, or psycho-oncological diagnostics. Within the framework of further neuropsychological diagnostics, the International Cognition and Cancer Task Force (ICCTF) recommends testing learning, memory, processing speed, and executive functions. From the authors’ point of view, a step-by-step diagnosis is recommended in order to avoid overdiagnosis. In clinical practice, graduation according to the “Common Terminology Criteria for Adversity Events” (CTCAE Version 5.0) is suitable for assessing the degree of severity. Cognitive training should be behaviourally oriented and include regular practice of cognitive skills to restore attention, psychomotor speed, memory, and executive functions. The best evidence is currently found for web-based training programmes that can be used by the patient at home. There is also evidence for mindfulness training and physical exercises. In particular, the combination of these three therapeutic elements currently seems to be the optimal treatment strategy for CRCD. Key Messages: Cognitive dysfunction should be given much more attention in the clinical care of cancer patients. Diagnostic tools for this purpose and evidence-based therapeutic interventions are available. In the future, networks should be created that allow for better care of patients with CRCD.
Experimental Estimates of College Coaching on Postsecondary Reenrollment
Authors: Turner Lesley J. , Gurantz Oded
Published: March 2024

College attendance has increased significantly over the last few decades, but dropout rates remain high, with fewer than half of all adults ultimately obtaining a postsecondary credential. This project investigates whether one-on-one college coaching improves college attendance and completion outcomes for former income state aid recipients identified as low- and middle-income who attended college but left prior to earning a degree. We conducted a randomized control trial with approximately 8,000 former students in their early to mid 20s. Half of the participants assigned to the treatment group were offered the opportunity to receive coaching services from InsideTrack, with all communication done remotely via phone or video. Intent-to-treat analyses based on assignment to coaching show no impacts on college enrollment and we can rule out effects larger than a 2 percentage point (5 percent) increase in subsequent Fall enrollment.
Give Due Consideration …
Authors: Ernst Gisela , Stöger Karl
Published: March 2024

The new EU Regulation on health technology assessment (HTAR) provides for joint clinical assessments (JCA) of health technologies at EU level. When Member States carry out health technology assessments (HTA) at the national level, they shall give due consideration to the results of a JCA and comply with other obligations of the Regulation. This article aims to clarify what these obligations mean for the Member States and whether JCA results have to be considered outside a national health technology assessment as well. In this context, the question of which processes qualify as ‘national HTA’ and which requirements need to be fulfilled to trigger the obligations under Article 13 HTAR are discussed in more detail in this paper.
The Great Kanto Earthquake Ephemera Collection at Princeton University Library
Authors: Noguchi Setsuko
Published: March 2024

The East Asian Library at Princeton contains a substantial collection of books, journals, photographs and ephemera related to the Great Kanto Earthquake of 1923. In this article I introduce the more ephemeral items, including government notifications, posters, maps and flyers. Amongst them are flyers concerning lost children, notices about free accommodation for pregnant woman and exhortations not to believe rumors. Many of these items have now been digitalized and they constitute a valuable research collection.
Assessing the Right to Freedom of Peaceful Assembly in Post-Pandemic, Post-Brexit Britain through the Lens of the 2022–2023 Public Sector Strikes
Authors: Masters Mercedes
Published: March 2024

Britain is currently seeing the most coordinated public sector strike action since the 1970s. In a post-pandemic, post-Brexit Britain, the general public are going through a cost-of-living crisis, with the rate of inflation rising and real-term pay cuts. This, paired with growing restrictions on the right of peaceful assembly through the passing of oppressive policing bills, means that people are increasingly turning to unions and striking to get their voices heard. This article highlights the push-factors leading to the 2022–2023 Public Sector Strikes through a socio-political analysis of democracy and power in post-pandemic, post-Brexit Britain, whilst capturing the voices of those striking and on picket lines.
Taking the Bull by His Horn: Augustus Slays the Mithraic Bull
Authors: Mazhjoo Nina
Published: March 2024

The Mithraic visual language can be read as a hybrid iconography created by the Roman Mithraists to stress the non-Roman provenance of their deity. This note analyses the gesture of Mithras’ slaying the bull and the so-called “Mithraic hold” to reveal the ex-novo nature of the Mithraic visual language and iconography from two vantage points: the first, at the aesthetic level; and the second, from its sources and origin. Additional considerations are also given on the iconographical referent of the Mithraic bull as well as the numismatic symbols traditionally discussed in relation to the Mithraic visual language.
Thoughts on the Iconography of the Sophytos Coinage
Authors: Härtel Stefan
Published: March 2024

The iconography of the coinage issued by Sophytos in early Hellenistic Bactria is analysed. It has long been recognised that the iconography involving a cockerel, winged cheek-guards and an “open 8” caduceus suggests the invocation of the Greek god Hermes. Taking into account the Iranian context of the coinage, the possibility is analysed that the coinage testifies an identification of Hermes with Sraoša. While the evidence is wanting, such an interpretatio seems well possible. Independent of this, the coinage is put into context with the mention of a cockerel used as a field ensign in the Achaemenid period by Plutarch. It suggests that rather than interpret Sophytos as a “rebel” against Macedonian rule in Bactria, he should be considered a governor who derived his legitimacy from an imperial Achaemenid or Macedonian office.
A new species of Eutyphoeus earthworm (Clitellata: Acanthodrilidae) from Mizoram, North-East India
Authors: RODINGPUIA CHRISTOPHER , HMAR LALTHANZARA , JULKA JATINDER , CHAWNGTHU ZOTHANSANGA , MATHIPI VABEIRYUREILAI , LALFELPUII RUTH , KUMAR NACHIMUTHU SENTHIL , GURUSUBRAMANIUN GURUSWAMI , LALCHHANDAMA KHOLHRING , VANLALROVI  , CHHAKCHHUAK LALBIAKZUALA
Published: March 2024

We describe here a new species of terrestrial earthworm Eutyphoeus rihnimensis sp. nov. (family Acanthodrilidae) from specimens collected at Khawrihnim, a village in Mizoram, Northeast India. The new species is distinguished from its congener members in E. gigas group in having an outgrowth that branches into four finger-like projections from the male porophores, five pairs of supra-intestinal glands in 81–88 segments, typhlosole that begins from segment 25, ventral intestinal caeca 10 that covers segments 33-34, a bidiverticulate spermathecae with a short and stout duct, and very short lateral and median diverticula among other characters. Sequence analysis based on mitochondrial cytochrome c oxidase subunit 1 (CO1) gene further warrants its distinction from known species of Eutyphoeus.
New teratological cases in cuckoo wasps, with synonymization of Oligogaster Soliman & Kimsey (Hymenoptera, Chrysididae)
Authors: ROSA PAOLO
Published: March 2024

Aberrations involving the metasoma in Hymenoptera are well-documented, with one notable teratological case being the fusion of metasomal terga, named symphysomery. This aberration, characterized by the fusion of the second and third terga, has been observed in various species groups of Hedychridium, spanning from Southern Africa to Central Asia. Similar aberrations were noted in Prochridium Linsenmaier from Mongolia and Anachrysis Krombein from Southern Africa. The monotypic genus Oligogaster Soliman & Kimsey is distinguished by two visible metasomal terga. However, the sole specimen of Oligogaster kimseyae Soliman, the type species of the genus, is here considered an aberrant specimen affected by symphysomery, exhibiting the fusion of the second and third metasomal terga. Consequently, Oligogaster Soliman & Kimsey is here synonymized with Hedychridium Abeille de Perrin.
Assessing Regional-Scale Heterogeneity in Blue–Green Water Availability under the 1.5°C Global Warming Scenario
Authors: Tyagi Shoobhangi , Sahany Sandeep , Saraswat Dharmendra , Mishra Saroj Kanta , Dubey Amlendu , Niyogi Dev
Published: March 2024

The 2015 Paris Agreement outlined limiting global warming to 1.5°C relative to the preindustrial levels, necessitating the development of regional climate adaptation strategies. This requires a comprehensive understanding of how the 1.5°C rise in global temperature would translate across different regions. However, its implications on critical agricultural components, particularly blue and green water, remains understudied. This study investigates these changes using a rice-growing semiarid region in central India. The aim of this study is to initiate a discussion on the regional response of blue–green water at specific warming levels. Using different global climate models (GCMs) and shared socioeconomic pathways (SSPs), the study estimated the time frame for reaching the 1.5°C warming level and subsequently investigated changes in regional precipitation, temperature, surface runoff, and blue–green water. The results reveal projected reductions in precipitation and surface runoff by approximately 5%–15% and 10%–35%, respectively, along with decrease in green and blue water by approximately 12%–1% and 40%–10%, respectively, across different GCMs and SSPs. These findings highlight 1) the susceptibility of blue–green water to the 1.5°C global warming level, 2) the narrow time frame available for the region to develop the adaptive strategies, 3) the influence of warm semiarid climate on the blue–green water dynamics, and 4) the uncertainty associated with regional assessment of a specific warming level. This study provides new insights for shaping food security strategies over highly vulnerable semiarid regions and is expected to serve as a reference for other regional blue/green water assessment studies.

Significance Statement

This study helps to drive home the message that a global agreement to limit the warming level to 1.5°C does not mean local-scale temperature (and associated hydrological) impacts would be limited to those levels. The regional changes can be more exaggerated and uncertain, and they also depend on the choice of the climate model and region. Therefore, local-scale vulnerability assessments must focus on the multidimensional assessment of a 1.5°C warmer world involving different climate models, climate-sensitive components, and regions. This information is relevant for managing vulnerable agricultural systems. This study is among the first to investigate the critical agricultural components such as the blue–green water over a semiarid Indian region, and the findings and methodology are expected to be transferable for performing regional-scale assessments elsewhere.
Becoming Ecological: The Contribution of Collaborative a/r/tography to Generalist Primary Teachers’ Agency in Arts Education
Authors: Brooke Sarah , MacDonald Abbey , Hunter Mary Ann
Published: March 2024

Internationally, it is widely acknowledged that many generalist primary teachers (GPTs) enter the teaching profession with a paucity of arts practice and pedagogic skills. Many perceive a lack of confidence, competence, and community to change this, particularly in regional and isolated teaching contexts. As a means to address this, this article considers the value of engaging in collaborative a/r/tography as a means of developing more creative ecological approaches to teacher professional development and learning. A multimodal storied assemblage of four primary teachers’ experience of engaging in collaborative a/r/tography is explored, and through diffractive analysis, the authors surface the intra-acting affective agents that enable metho-pedagogic learning possibilities. Specific ways in which collaborative a/r/tography works to foster GPTs’ curricula and metho-pedagogic sensibilities, as well as a sense of creative ecology, are addressed. Speculation as to the ways in which collaborative a/r/tography fosters GPTs “becoming ecological” in relational practices and processes of curriculum enactment and pedagogical engagement is offered thereby contributing to understandings of the generative capacity of a/r/tography as a framework for developing teacher agency and change.
Newtonian laws of motion and conservation principles
Authors: Hill James M
Published: March 2024

Newton’s laws of motion and Newtonian conservation principles such as those for energy and momentum involve the assumption that the vanishing of a certain total time derivative, on integration, yields a fixed constant value as an immediate consequence. While this may ultimately be the case for additional reasons, it is possible to have a properly vanishing total time derivative and yet the individual partial derivates are non-zero. Here, for a particular problem and based only on the requirement that the total time derivative of the quantity vanishes, we investigate the particular mechanism leading to a conventional conservation principle. For the energy and angular momentum totals for planar steady orbiting motion, the partial differential conditions may be formally solved to obtain the general solutions. We determine the general structure for variable energy and angular momentum for which the total time derivatives vanish, and from which it is apparent that the standard expression for constant energy and angular momentum is recovered.
Accuracy of maximal acceleration time of pedal arteries to diagnose critical limb-threatening ischemia
Authors: Trihan Jean-Eudes , Croquette Magali , Hersant Jeanne , Prigent Romain , Fontaine Cedric , Henni Samir , Lanéelle Damien
Published: March 2024

Introduction:

Maximal acceleration time of distal arteries of the foot (ATmax) is correlated to ankle–brachial index (ABI) and toe–brachial index (TBI), and seems very promising in diagnosing severe peripheral artery disease (PAD) and especially critical limb-threatening ischemia (CLTI). Our goal was to confirm the cut-off value of 215 ms to predict a toe pressure (TP) ⩽ 30 mmHg.

Methods:

A 4-month retrospective study was conducted on patients addressed for suspicion of PAD. Demographic data, ABI, TBI, and Doppler ultrasound scanning parameters of the dorsal pedis and lateral plantar arteries (DPA and LPA) were recorded.

Results:

A total of 137 patients with 258 lower limbs were included. ATmax was highly correlated to TBI ( r = −0.89, p < 0.001). With the cut-off value of 215 ms, ATmax was effective to diagnose TP ⩽ 30 mmHg with a sensitivity of 93% [95% CI 77–99], a specificity of 96% [95% CI 92–98], a positive predictive value of 73% [95% CI 56–86], a negative predictive value of 99% [95% CI 97–100], and an area under the receiver operating characteristics curve of 0.99 [95% CI 0.98–1.00]. ATmax also showed promising results to rule out PAD in healthy patients.

Conclusion:

ATmax is a reliable diagnostic tool to diagnose low TP and could be a new easily performed hemodynamic criterion for diagnosis of CLTI.
Combining GWAS and comparative genomics to fine map candidate genes for days to flowering in mung bean
Authors: Chiteri Kevin O. , Rairdin Ashlyn , Sandhu Kulbir , Redsun Sven , Farmer Andrew , O’Rourke Jamie A. , Cannon Steven B. , Singh Arti
Published: March 2024

Background

Mung bean (Vigna radiata (L.) Wilczek), is an important pulse crop in the global south. Early flowering and maturation are advantageous traits for adaptation to northern and southern latitudes. This study investigates the genetic basis of the Days-to-Flowering trait (DTF) in mung bean, combining genome-wide association studies (GWAS) in mung bean and comparisons with orthologous genes involved with control of DTF responses in soybean (Glycine max (L) Merr) and Arabidopsis (Arabidopsis thaliana).

Results

The most significant associations for DTF were on mung bean chromosomes 1, 2, and 4. Only the SNPs on chromosomes 1 and 4 were heavily investigated using downstream analysis. The chromosome 1 DTF association is tightly linked with a cluster of locally duplicated FERONIA (FER) receptor-like protein kinase genes, and the SNP occurs within one of the FERONIA genes. In Arabidopsis, an orthologous FERONIA gene (AT3G51550), has been reported to regulate the expression of the FLOWERING LOCUS C (FLC). For the chromosome 4 DTF locus, the strongest candidates are Vradi04g00002773 and Vradi04g00002778, orthologous to the Arabidopsis PhyA and PIF3 genes, encoding phytochrome A (a photoreceptor protein sensitive to red to far-red light) and phytochrome-interacting factor 3, respectively. The soybean PhyA orthologs include the classical loci E3 and E4 (genes GmPhyA3, Glyma.19G224200, and GmPhyA2, Glyma.20G090000). The mung bean PhyA ortholog has been previously reported as a candidate for DTF in studies conducted in South Korea.

Conclusion

The top two identified SNPs accounted for a significant proportion (~ 65%) of the phenotypic variability in mung bean DTF by the six significant SNPs (39.61%), with a broad-sense heritability of 0.93. The strong associations of DTF with genes that have orthologs with analogous functions in soybean and Arabidopsis provide strong circumstantial evidence that these genes are causal for this trait. The three reported loci and candidate genes provide useful targets for marker-assisted breeding in mung beans.
Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome
Authors: Viel Kenyatta C. M. F. , Parameswaran Sreeja , Donmez Omer A. , Forney Carmy R. , Hass Matthew R. , Yin Cailing , Jones Sydney H. , Prosser Hayley K. , Diouf Arame A. , Gittens Olivia E. , Edsall Lee E. , Chen Xiaoting , Rowden Hope , Dunn Katelyn A. , Guo Rui , VonHandorf Andrew , Leong Merrin Man Long , Ernst Kevin , Kaufman Kenneth M. , Lawson Lucinda P. , Gewurz Ben , Zhao Bo , Kottyan Leah C. , Weirauch Matthew T.
Published: March 2024

Background

There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions.

Results

In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks.

Conclusions

This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.
A road map for the management of a pregnancy complicated by maternal bladder exstrophy
Authors: Hosiani A , Smet M.E. , Nayyar R
Published: March 2024

Bladder exstrophy (BE) is a congenital genito-urinary malformation where there is a defect in the abdominal wall resulting in a protruding open bladder with exposed mucosa (Resnik R.P. et al. Creasy and Resnik’s maternal-fetal medicine: principles and practice. Elsevier, 2019). Several reconstructive procedures are required to correct the anomalies, resulting in an ileal conduit which is an alternate urinary reservoir reconstructed from the terminal ileum (Madersbacher S, et al. J Urol 169(3):985–90, 2003). We describe the care of a pregnant woman with BE and outline the principles of management of her pregnancy with a multidisciplinary team. Timely pre-operative planning is advised to minimise intraoperative complications in the event of a caesarean section. The woman went on to have an uncomplicated classical caesarean section at term by midline laparotomy with a good outcome for both mother and baby.
Rates and determinants of Rotavirus vaccine uptake among children in Italy: a cross-sectional study within the 2022 OBVIOUS* project
Authors: La Fauci Giusy , Soldà Giorgia , Di Valerio Zeno , Salussolia Aurelia , Montalti Marco , Scognamiglio Francesca , Capodici Angelo , Fantini Maria Pia , Larson Heidi J. , Leask Julie , Gori Davide , Lenzi Jacopo
Published: March 2024

Introduction

The World Health Organization defines rotavirus as among the most severe causes of viral gastroenteritis affecting children under 5 year old. Italy and other European countries do not release disaggregated data on rotavirus vaccination coverage. This study aimed to assess the uptake and drivers of rotavirus vaccination in Italy.

Methods

We administered a survey to 10,000 Italian citizens recruited via an online panel and proportionate to key demographic strata. We examined rotavirus vaccine uptake among parents whose youngest child was aged 6 weeks to 4 years, their sociodemographic characteristics, their beliefs about vaccine administration, and who recommended the rotavirus vaccination.

Results

A total of 711 respondents met the inclusion criteria for the rotavirus vaccine questionnaire. The uptake was estimated at 60.3% nationwide (66.4% among mothers and 50.2% among fathers). Being a mother and living in cities/suburbs was significantly associated with a higher likelihood of vaccine uptake, while fathers were more likely to be uncertain of their children’s vaccine status. Living in Central Italy and having friends/relatives opposed to vaccination were found to be significantly associated with a lower likelihood of vaccine uptake, while parents’ education level and children’s demographics were not found to correlate with any outcomes. In 90.3% of cases, the rotavirus vaccination was recalled as being recommended by a paediatrician.

Conclusions

Consistent collection of behavioural preferences and socioeconomic characteristics of recipients of rotavirus vaccine campaigns, their epidemiological information, cost-benefit, and national policy data are crucial for designing effective vaccination strategies in Italy and other European countries with similar social profiles to reach the target uptake.
Clinical study of electroacupuncture on the recovery of gastrointestinal dysfunction after laparoscopic surgery for gastrointestinal cancer - study protocol for a randomized controlled trial
Authors: Chung Shuet Ling , Li Wen , Wang Qiuyue , Qiu Xiaofeng , Tang Yuncheng , Hu Sheng , Wu Huangan , Jin Zhu
Published: March 2024

Background

Gastrointestinal dysfunction is one of the common complaints for patient post-surgery. Acupuncture has been employed to improve gastrointestinal function and sleeping quality and has confirmed clinical efficacy for emotional problems. This study aims to evaluate the clinical effect of electroacupuncture for postoperative rapid recovery.

Methods

This study design is a two-arm, parallel, double-blinded randomized controlled trial. 104 subjects, aged from 40 to 89 years old, diagnosed with gastrointestinal cancer undergoing laparoscopic surgery, will be divided into Interventional Group and Control Group. Patients of both groups receive perioperative care under the guidance of ERAS guidance. The Interventional Group receives electroacupuncture treatment starting from the first day post-surgery for a consecutive 5 days, whereas the Control Group receives placebo electroacupuncture treatment. The primary outcome will be the first flatus time whereas the secondary outcomes will be the first sign of borborygmus, recovery of defecation, laboratory tests and questionnaires including Self-rating anxiety scale, Ford Insomnia Response to Stress Test, TCM rating scale of Gastrointestinal symptoms and Gastrointestinal Symptoms Rating Scales.

Discussion

This study aims to provide timely intervention for post-laparoscopic patients with gastrointestinal tumour using the ERAS concept combined with electroacupuncture, observe the efficacy of this therapy in treating PGID, and contribute reliable scientific evidence for postoperative rapid recovery.

Trial registration

Chictr.org.cn Identifier: ChiCTR2300078710. Registered on 15th December 2023.
Pilot study of the effectiveness of a telehealth group for improving peer relationships for adolescents with neurofibromatosis type 1
Authors: Glad Danielle M. , Pardej Sara K. , Olszewski Ellen , Klein-Tasman Bonita P.
Published: March 2024

Background

Interventions for social difficulties have not been investigated in the neurofibromatosis type 1 (NF1) population despite observations of elevated rates of social difficulties. In this pilot study, the effectiveness of a 14-week telehealth PEERS® intervention with nineteen adolescents with NF1 (Mage=13.79 years, SD = 1.32) with social skills difficulties was examined. Measures of social outcomes were completed at three timepoints (before, immediately after, and at 14-week follow-up).

Results

Caregiver-reported social-emotional skills, social impairment, caregiver-reported number of adolescent get-togethers, and teen social knowledge showed significant improvement following the intervention.

Conclusions

The PEERS® intervention is promising to support the social and friendship skills of adolescents with NF1 who have social difficulties.
Functionally-instructed modifiers of response to ATR inhibition in experimental glioma
Authors: Walter Bianca , Hirsch Sophie , Kuhlburger Laurence , Stahl Aaron , Schnabel Leonard , Wisser Silas , Haeusser Lara A. , Tsiami Foteini , Plöger Sarah , Aghaallaei Narges , Dick Advaita M , Skokowa Julia , Schmees Christian , Templin Markus , Schenke-Layland Katja , Tatagiba Marcos , Nahnsen Sven , Merk Daniel J. , Tabatabai Ghazaleh
Published: March 2024

Background

The DNA damage response (DDR) is a physiological network preventing malignant transformation, e.g. by halting cell cycle progression upon DNA damage detection and promoting DNA repair. Glioblastoma are incurable primary tumors of the nervous system and DDR dysregulation contributes to acquired treatment resistance. Therefore, DDR targeting is a promising therapeutic anti-glioma strategy. Here, we investigated Ataxia telangiectasia and Rad3 related (ATR) inhibition (ATRi) and functionally-instructed combination therapies involving ATRi in experimental glioma.

Methods

We used acute cytotoxicity to identify treatment efficacy as well as RNAseq and DigiWest protein profiling to characterize ATRi-induced modulations within the molecular network in glioma cells. Genome-wide CRISPR/Cas9 functional genomic screens and subsequent validation with functionally-instructed compounds and selected shRNA-based silencing were employed to discover and investigate molecular targets modifying response to ATRi in glioma cell lines in vitro, in primary cultures ex vivo and in zebrafish and murine models in vivo.

Results

ATRi monotherapy displays anti-glioma efficacy in vitro and ex vivo and modulates the molecular network. We discovered molecular targets by genome-wide CRISPR/Cas9 loss-of-function and activation screens that enhance therapeutic ATRi effects. We validated selected druggable targets by a customized drug library and functional assays in vitro, ex vivo and in vivo.

Conclusion

In conclusion, our study leads to the identification of novel combination therapies involving ATRi that could inform future preclinical studies and early phase clinical trials.
Neutrophil lncRNA ZNF100-6:2 is a potential diagnostic marker for active pulmonary tuberculosis
Authors: Huang Shuying , Kang Xiuhua , Zeng Zhenguo , Zhang Qilong , Huang Zikun , Luo Kaihang , Yao Qinqin , Chen Bing , Qing Cheng
Published: March 2024

Active pulmonary tuberculosis (PTB) poses challenges in rapid diagnosis within complex clinical conditions. Given the close association between neutrophils and tuberculosis, we explored differentially expressed long non-coding RNAs (lncRNAs) in neutrophils as potential molecular markers for diagnosing active PTB. We employed a gene microarray to screen for lncRNA alterations in neutrophil samples from three patients with active PTB and three healthy controls. The results revealed differential expression of 1457 lncRNAs between the two groups, with 916 lncRNAs upregulated and 541 lncRNAs down-regulated in tuberculosis patients. Subsequent validation tests demonstrated down-regulation of lncRNA ZNF100-6:2 in patients with active PTB, which was restored following anti-tuberculosis treatment. Our findings further indicated a high diagnostic potential for lncRNA ZNF100-6:2, as evidenced by an area under the receiver operating characteristic (ROC) curve of 0.9796 (95% confidence interval: 0.9479 to 1.000; P < 0.0001). This study proposes lncRNA ZNF100-6:2 as a promising and novel diagnostic biomarker for active PTB.
Association between 3D membranous urethral parameters and urinary continence recovery after RARP
Authors: Wang Ming , Deng Ruiqi , Wang Lei , Li Mingzhao , Zeng Tao , Na Yanqun , Gu Di
Published: March 2024

Objectives

To evaluate whether the urinary continence (UC) recovery after robotic-assisted radical prostatectomy (RARP) relates to the membranous urethral length (MUL) and the membranous urethral complex volume (MUV).

Materials and methods

120 patients who underwent RARP were enrolled according to the different times of UC recovery and examined using prostate magnetic resonance imaging (MRI) before surgery. The membranous urethral (MU) parameters were measured using the three-Dimensional (3D) model reconstructed by holographic technology, such as total MUV (tMUV), exposed MUV (eMUV), full MUL (fMUL) and exposed MUL (eMUL). Statistical software SPSS 26.0 was used to analyze the data and compare the MU parameters and baseline data in different groups.

Results

Patients with larger tMUV (p = 0.038), eMUV (p = 0.003), longer fMUL (p = 0.025), eMUL (p = 0.044) had better UC after removal of the catheter, and eMUV (OR = 1.002, 95%CI = 1.001–1.004, p = 0.004) was a predictor; the patients with younger age (p = 0.021), lower VPSS score (p = 0.004) and larger eMUV (p = 0.012) and longer eMUL (p = 0.049) had better UC recovery one month after RARP while eMUV (OR = 1.002, 95% CI = 1.000–1.003, p = 0.008) and VPSS score (OR = 0.886, 95% CI = 0.806–0.973, p = 0.011) were independent risk factors; The patients with younger age (p = 0.018), larger tMUV (p = 0.029), eMUV (p = 0.016) had better UC recovery three months after RARP. eMUV (OR = 1.002, 95% CI = 1.000–1.004, p = 0.042) and age (OR = 0.904, 95% CI = 0.818–0.998, p = 0.046) were independent risk factors.

Conclusion

This clinical study shows that patients with larger MUV and longer MUL can return to UC earlier after surgery. Among that, eMUV is a better predictor.
Treatment modalities for granulomatous mastitis, seeking the most appropriate treatment with the least recurrence rate: a systematic review and meta-analysis
Authors: Sarmadian Roham , Safi Fatemeh , Sarmadian Hossein , Shokrpour Maryam , Almasi-Hashiani Amir
Published: March 2024

Background

Granulomatous mastitis (GM) is a rare, benign, inflammatory breast disease with an unknown etiology that predominantly affects women of reproductive age. The definitive treatment of GM is currently controversial; an appropriate therapeutic strategy has yet to be identified, and the disease’s high recurrence rate remains. This study aims to determine the recurrence rate for each GM treatment strategy to identify the most appropriate treatment modality.

Methods

The search for relevant articles was undertaken using three international databases, including Medline, Scopus, and Web of Science. Articles published in English until the end of 2021 evaluating the recurrence rate of GM were included. Using Stata 13.0, the pooled incidence and 95% confidence interval (CI) for the recurrence rate were determined.

Results

Sixty-five eligible studies were included in our study. The recurrence rates of systemic steroid use, topical steroid use, antibiotic use, methotrexate use, observation, drainage, excision, antibiotic use and surgery, steroid use and surgery, antibiotic and steroid use, methotrexate and steroid use were 24% (95% CI: 21–27%), 11% (95% CI: 6–21%), 18% (95% CI: 14–22%), 13% (95% CI: 7–22%), 11% (95% CI: 7–17%), 65% (95% CI: 50–78%), 13% (95% CI: 10–16%), 23% (95% CI: 14–36%), 7% (95% CI: 5–11%), 11% (95% CI: 6–18%), and 4% (95% CI: 2–8%), respectively. Drainage had the highest recurrence rate, while combined methotrexate and steroid treatment had the lowest rate.

Conclusion

The optimal treatment strategy for GM depends on the disease’s severity, consequences, and the patient's features. The study results indicate that combination therapy is preferable for minimizing the risk of relapse and reducing treatment complications.
The experience of felt presence in a general population sample
Authors: Brederoo Sanne G. , Alderson-Day Ben , de Boer Janna N. , Linszen Mascha M. J. , Sommer Iris E. C.
Published: March 2024

Felt presence is a widely occurring experience, but remains under-recognised in clinical and research practice. To contribute to a wider recognition of the phenomenon, we aimed to assess the presentation of felt presence in a large population sample (n = 10 447) and explore its relation to key risk factors for psychosis. In our sample 1.6% reported experiencing felt presence in the past month. Felt presence was associated with visual and tactile hallucinations and delusion-like thinking; it was also associated with past occurrence of adverse events, loneliness and poor sleep. The occurrence of felt presence may function as a marker for general hallucination proneness.
Application of Theory of Planned Behavior in Efforts to Increase Community Participation in Vaccination Programs (Study at the Covid-19 Vaccination Program, Pasirwangi District, Garut Regency)
Authors:   President University, Bangkara BMAS Anaconda , Syuryadi Matnur , Marwah Hanny
Published: March 2024

Abstract It should be grateful that the Covid-19 pandemic is getting under control; however, there are still problems related to community participation, especially in the vaccination program. Apart from the Covid-19 vaccination, in Indonesia there are still a number of other vaccinations that, really need the participation of the community. As happened in Pasirwangi District, Garut Regency, out of 53,093 residents who met the requirements to get the Covid-19 vaccine, only 2,492 residents, took advantage of this opportunity. For this reason, this study intends to find alternative ways, through the application of the theory of planned behavior, to increase opportunities for community participation by identifying which variables have the most potential to be used for this purpose. Efforts to collect data through the distribution of questionnaires with an alternative of 5-likert scale answers and involving 650 respondents through purposive sampling technique The analysis tool used was SEM AMOS. The results showed that all exogenous variables were significantly correlated with endogenous variables (behavior), as well as intervening variables that were significantly correlated with endogenous variables. Through the Sobel test, a review of indirect effects was also carried out, and the results showed that all indirect effects were significantly correlated with endogenous variables. Keywords: Vaccination, theory of planned behavior, society participation