bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucin alleviates colonic barrier dysfunction by promoting spermine accumulation through enhanced arginine metabolism in
Limosilactobacillus mucosae
Authors: Zhou Xingjian , Xu Qian , Zhang Xiangyu , Wang Hao , Bai Yu , Wu Yujun , Liu Xiaoyi , Wang Zhenyu , Hu Jie , Huang Mingyi , Pi Yu , Zhao Jinbiao , Wang Junjun , Han Dandan 
Published: April 2024

ABSTRACT

Dietary fiber deprivation is linked to probiotic extinction, mucus barrier dysbiosis, and the overgrowth of mucin-degrading bacteria. However, whether and how mucin could rescue fiber deprivation-induced intestinal barrier defects remains largely unexplored. Here, we sought to investigate the potential role and mechanism by which exogenous mucin maintains the gut barrier function. The results showed that dietary mucin alleviated fiber deprivation-induced disruption of colonic barrier integrity and reduced spermine production
in vivo
. Importantly, we highlighted that microbial-derived spermine production, but not host-produced spermine, increased significantly after mucin supplementation, with a positive association with upgraded colonic
Lactobacillus
abundance. After employing an
in vitro
model, the microbial-derived spermine was consistently dominated by both mucin and
Lactobacillus
spp. Furthermore,
Limosilactobacillus mucosae
was identified as an essential spermine-producing
Lactobacillus
spp., and this isolated strain was responsible for spermine accumulation, especially after adhering to mucin
in vitro
. Specifically, the mucin-supplemented bacterial supernatant of
Limosilactobacillus mucosae
was verified to promote intestinal barrier functions through the increased spermine production with a dependence on enhanced arginine metabolism. Overall, these findings collectively provide evidence that mucin-modulated microbial arginine metabolism bridged the interplay between microbes and gut barrier function, illustrating possible implications for host gut health.

IMPORTANCE

Microbial metabolites like short-chain fatty acids produced by dietary fiber fermentation have been demonstrated to have beneficial effects on intestinal health. However, it is essential to acknowledge that certain amino acids entering the colon can be metabolized by microorganisms to produce polyamines. The polyamines can promote the renewal of intestinal epithelial cell and maintain host-microbe homeostasis. Our study highlighted the specific enrichment by mucin on promoting the arginine metabolism in
Limosilactobacillus mucosae
to produce spermine, suggesting that microbial-derived polyamines support a significant enhancement on the goblet cell proliferation and barrier function.
A novel fast hybrid capture sequencing method for high-efficiency common human coronavirus whole-genome acquisition
Authors: Meng Zixinrong , Wang Shuo , Yu Liping , Zhao Kangchen , Wu Tao , Zhu Xiaojuan , Yang Ning , Qiao Qiao , Ma Junyan , Wu Bin , Ge Yiyue , Cui Lunbiao 
Published: April 2024

ABSTRACT

Rapid and accurate sequencing of the entire viral genome, coupled with continuous monitoring of genetic changes, is crucial for understanding the epidemiology of coronaviruses. We designed a novel method called micro target hybrid capture system (MT-Capture) to enable whole-genome sequencing in a timely manner. The novel design of probes used in target binding exhibits a unique and synergistic “hand-in-hand” conjugation effect. The entire hybrid capture process is within 2.5 hours, overcoming the time-consuming and complex operation characteristics of the traditional liquid-phase hybrid capture (T-Capture) system. By designing specific probes for these coronaviruses, MT-Capture effectively enriched isolated strains and 112 clinical samples of coronaviruses with cycle threshold values below 37. Compared to multiplex PCR sequencing, it does not require frequent primer updates and has higher compatibility. MT-Capture is highly sensitive and capable of tracking variants.

IMPORTANCE
MT-Capture is meticulously designed to enable the efficient acquisition of the target genome of the common human coronavirus. Coronavirus is a kind of virus that people are generally susceptible to and is epidemic and infectious, and it is the virus with the longest genome among known RNA viruses. Therefore, common human coronavirus samples are selected to evaluate the accuracy and sensitivity of MT-Capture. This method utilizes innovative probe designs optimized through probe conjugation techniques, greatly shortening the time and simplifying the handwork compared with traditional hybridization capture processes. Our results demonstrate that MT-Capture surpasses multiplex PCR in terms of sensitivity, exhibiting a thousandfold increase. Moreover, MT-Capture excels in the identification of mutation sites. This method not only is used to target the coronaviruses but also may be used to diagnose other diseases, including various infectious diseases, genetic diseases, or tumors.
Effects of
Klebsiella michiganensis
LDS17 on
Codonopsis pilosula
growth, rhizosphere soil enzyme activities, and microflora, and genome-wide analysis of plant growth-promoting genes
Authors: Jin Tingting , Ren Jiahong , Bai Bianxia , Wu Wei , Cao Yongqing , Meng Jing , Zhang Lihui 
Published: April 2024

ABSTRACT

Codonopsis pilosula
is a perennial herbaceous liana with medicinal value. It is critical to promote
Codonopsis pilosula
growth through effective and sustainable methods, and the use of plant growth-promoting bacteria (PGPB) is a promising candidate. In this study, we isolated a PGPB,
Klebsiella michiganensis
LDS17, that produced a highly active 1-aminocyclopropane-1-carboxylate deaminase from the
Codonopsis pilosula
rhizosphere. The strain exhibited multiple plant growth-promoting properties. The antagonistic activity of strain LDS17 against eight phytopathogenic fungi was investigated, and the results showed that strain LDS17 had obvious antagonistic effects on
Rhizoctonia solani
,
Colletotrichum camelliae
,
Cytospora chrysosperma
, and
Phomopsis macrospore
with growth inhibition rates of 54.22%, 49.41%, 48.89%, and 41.11%, respectively. Inoculation of strain LDS17 not only significantly increased the growth of
Codonopsis pilosula
seedlings but also increased the invertase and urease activities, the number of culturable bacteria, actinomycetes, and fungi, as well as the functional diversity of microbial communities in the rhizosphere soil of the seedlings. Heavy metal (HM) resistance tests showed that LDS17 is resistant to copper, zinc, and nickel. Whole-genome analysis of strain LDS17 revealed the genes involved in IAA production, siderophore synthesis, nitrogen fixation, P solubilization, and HM resistance. We further identified a gene (
koyR
) encoding a plant-responsive LuxR solo in the LDS17 genome.
Klebsiella michiganensis
LDS17 may therefore be useful in microbial fertilizers for
Codonopsis pilosula
. The identification of genes related to plant growth and HM resistance provides an important foundation for future analyses of the molecular mechanisms underlying the plant growth promotion and HM resistance of LDS17.

IMPORTANCE

We comprehensively evaluated the plant growth-promoting characteristics and heavy metal (HM) resistance ability of the LDS17 strain, as well as the effects of strain LDS17 inoculation on the
Codonopsis pilosula
seedling growth and the soil qualities in the
Codonopsis pilosula
rhizosphere. We conducted whole-genome analysis and identified lots of genes and gene clusters contributing to plant-beneficial functions and HM resistance, which is critical for further elucidating the plant growth-promoting mechanism of strain LDS17 and expanding its application in the development of plant growth-promoting agents used in the environment under HM stress.
Severe papilloedema with vision loss secondary to Guillain-Barré syndrome
Authors: Moloney Niamh Bridget , Ong Jessica , Irani Neha 
Published: April 2024

We discuss a patient who presented with bilateral VI and VII cranial nerve palsies, symmetric upper and lower limb weakness and areflexia, 2 weeks following an flu-like illness. At presentation, there was no papilloedema, and her visual function was normal. Cerebrospinal fluid analysis and electrophysiology supported the diagnosis of Guillain-Barré Syndrome (GBS). She received intravenous immunoglobulins. She subsequently developed headaches and vision loss. Funduscopy demonstrated severe papilloedema with visual acuity of 6/18 right eye, 6/12 left eye with bitemporal visual field depression. Lumbar puncture revealed elevated opening pressure with high protein and normal cell count. She received acetazolamide. There was resolution of papilloedema and normal visual function at 3 months. Of note, the patient’s body mass index was 17 kg/m2.Our case highlights the rare occurrence of papilloedema in GBS, reiterating the importance of performing funduscopy on patients with any neurological diagnosis. Early detection and prompt management of papilloedema can prevent permanent vision loss.
4D spherically symmetric time-dependent quantum gravity amplitudes
Authors: Rosabal J. A. 
Published: April 2024

AbstractIn these short notes, we compute non-perturbatively the time-dependent quantum gravity amplitudes for a four-dimensional spherically symmetric space-time with space-like and time-like boundaries. We solve the 4D classical and quantum constraints in a novel way. We identify the classical solution of the constraints as a canonical transformation, where the integration constants are the new variables. We apply this canonical transformation to the path integral representation of the amplitudes we are interested in. We use both, the canonical and the path integral formalism. This procedure allows us to reduce the action to the actual degree of freedom of the theory. In the end, we get the time-dependent amplitudes from the path integral without performing an actual path integration. From these amplitudes, we show that for most of the boundary conditions time evolution in quantum gravity is non-unitary. There is however a special case where unitary evolution could be achieved.
Science as exploration in a knowledge landscape: tracing hotspots or seeking opportunity?
Authors: Liu Feifan , Zhang Shuang , Xia Haoxiang 
Published: April 2024

AbstractThe selection of research topics by scientists can be viewed as an exploration process conducted by individuals with cognitive limitations traversing a complex cognitive landscape influenced by both individual and social factors. While existing theoretical investigations have provided valuable insights, the intricate and multifaceted nature of modern science hinders the implementation of empirical experiments. This study leverages advancements in Geographic Information System (GIS) techniques to investigate the patterns and dynamic mechanisms of topic-transition among scientists. By constructing the knowledge space across 6 large-scale disciplines, we depict the trajectories of scientists’ topic transitions within this space, measuring the flow and distance of research regions across different sub-spaces. Our findings reveal a predominantly conservative pattern of topic transition at the individual level, with scientists primarily exploring local knowledge spaces. Furthermore, simulation modeling analysis identifies research intensity, driven by the concentration of scientists within a specific region, as the key facilitator of topic transition. Conversely, the knowledge distance between fields serves as a significant barrier to exploration. Notably, despite potential opportunities for breakthrough discoveries at the intersection of subfields, empirical evidence suggests that these opportunities do not exert a strong pull on scientists, leading them to favor familiar research areas. Our study provides valuable insights into the exploration dynamics of scientific knowledge production, highlighting the influence of individual cognition, social factors, and the intrinsic structure of the knowledge landscape itself. These findings offer a framework for understanding and potentially shaping the course of scientific progress.
IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Moynihan Kelly D. , Kumar Manu P. , Sultan Hussein , Pappas Danielle C. , Park Terrence , Chin S. Michael , Bessette Paul , Lan Ruth Y. , Nguyen Henry C. , Mathewson Nathan D. , Ni Irene , Chen Wei , Lee Yonghee , Liao-Chan Sindy , Chen Jessie , Schumacher Ton N.M. , Schreiber Robert D. , Yeung Yik A. , Djuretic Ivana M. 
Published: April 2024

Abstract
IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2’s effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells in primates. In mice, an AB248 surrogate demonstrated superior antitumor activity and enhanced tolerability as compared with an untargeted IL2Rβγ agonist. Efficacy was associated with the expansion and phenotypic enhancement of tumor-infiltrating CD8+ T cells, including the emergence of a “better effector” population. These data support the potential utility of AB248 in clinical settings.
Significance: The full potential of IL2 therapy remains to be unlocked. We demonstrate that toxicity can be decoupled from antitumor activity in preclinical models by limiting IL2 signaling to CD8+ T cells, supporting the development of CD8+ T cell–selective IL2 for the treatment of cancer.
See related article by Kaptein et al. p. 1226.
CD4+ Regulatory T Cells in Human Cancer: Subsets, Origin, and Molecular Regulation
Authors: Swatler Julian , De Luca Marco , Rotella Ivano , Lise Veronica , Mazza Emilia Maria Cristina , Lugli Enrico 
Published: April 2024

Abstract
CD4+CD25hiFOXP3+ regulatory T cells (Treg) play major roles in the maintenance of immune tolerance, prevention of inflammation, and tissue homeostasis and repair. In contrast with these beneficial roles, Tregs are abundant in virtually all tumors and have been mechanistically linked to disease progression, metastases development, and therapy resistance. Tregs are thus recognized as a major target for cancer immunotherapy. Compared with other sites in the body, tumors harbor hyperactivated Treg subsets whose molecular characteristics are only beginning to be elucidated. Here, we describe current knowledge of intratumoral Tregs and discuss their potential cellular and tissue origin. Furthermore, we describe currently recognized molecular regulators that drive differentiation and maintenance of Tregs in cancer, with a special focus on those signals regulating their chronic immune activation, with relevant implications for cancer progression and therapy.
Optimal Neoantigen Cancer Vaccines Target CD8+ and CD4+ T Cells with Multiple Antigens
Authors: Slingluff Craig L. 
Published: April 2024

AbstractCancer vaccines targeting mutated neoantigens offer promise for prevention of cancer recurrence and for treatment of established cancers. Questions remain about whether vaccines need to target multiple neoantigens and whether they need to target both CD8+ and CD4+ T cells. In this issue, Garzia and colleagues demonstrate the importance of including multiple antigens to stimulate both CD4+ T cells and CD8+ T cells for treatment of established cancer.See related article by Garzia et al., p. 440 (4).
Allogeneic CAR T Cells: Complex Cellular Therapy Designs Test the Limits of Our Preclinical Models
Authors: Caimi Paolo F. , Melenhorst Jan Joseph 
Published: April 2024

AbstractAll chimeric antigen receptor (CAR) T-cell products currently approved by the FDA are autologous, which poses several challenges for widespread use. In this issue, Degagné and colleagues present their preclinical research on creating off-the-shelf CAR T cells for multiple myeloma. They utilized the CRISPR/Cas12a genome editing platform and gene knock-in techniques to eliminate alloreactivity and decrease susceptibility to natural killer (NK)-cell elimination. This work has led to an ongoing phase I trial of off-the-shelf CAR T cells for multiple myeloma treatment.See related article by Degagné et al., p. 462 (2).
« Penser l’impensé » : traduire Meschonnic
Authors: Ciobaca Carmen-Ecaterina 
Published: April 2024

Le présent travail porte sur les défis qu’engendre la traduction de l’œuvre d’Henri Meschonnic en roumain. La première section est un état de lieux sur la traduction de la traductologie. Les ouvrages traductologiques sont rarement traduits, principalement à cause du manque de projets de traduction. Nous passons en revue dans la seconde section les axes fondamentaux de la pensée de Meschonnic pour examiner dans la dernière section les difficultés de traduction de son discours, partant de l’expérience de traductrice de Pier-Pascale Boulanger. Le texte source choisi dans le cadre de l’étude de cas est l’article « Traduire ce que les mots ne disent pas, mais ce qu’ils font » (Meta, 1995). La traduction est une manière de continuer l’œuvre de Meschonnic et de contribuer au progrès de la traductologie.
Cost‐Effectiveness of a Workplace‐Based Hypertension Management Program in Real‐World Practice in the Kailuan Study
Authors: Zhou Yan‐Feng , Chen Shuohua , Chen Jun‐Xiang , Chen Simiao , Wang Guodong , Pan Xiong‐Fei , Wu Shouling , Pan An 
Published: April 2024

Background
In 2009, a workplace‐based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost‐effectiveness of this program remains unclear.

Methods and Results
This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10‐year follow‐up data, we estimated costs, quality‐adjusted life years (QALYs), life‐years, and incremental cost‐effectiveness ratios (ICERs) for workplace‐based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10‐year follow‐up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life‐years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost‐effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life‐year gained, respectively, when comparing workplace‐based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness‐to‐pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost‐effective in 10 000 samples.

Conclusions
Workplace‐based management, compared with routine care for Chinese men with hypertension, could be cost‐effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.
Quantitative Benefit–Risk Evaluation of Rivaroxaban in Patients After Peripheral Arterial Revascularization: The VOYAGER PAD Trial
Authors: Yuan Zhong , Levitan Bennett , Deng Hsiaowei , Szarek Michael , Bauersachs Rupert M. , Berkowitz Scott D. , Haskell Lloyd , Barnathan Elliot S. , Bonaca Marc P. 
Published: April 2024

Background
The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit–risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit–risk analyses with formal weighting approaches.

Methods and Results
Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi‐criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent‐to‐treat and on‐treatment analyses were conducted. For unweighted intent‐to‐treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, −208 to −32) fewer events of the primary composite end point (per 10 000 patient‐years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8–72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, −85.3 to 52.6) and 68.1 (95% CI, 7.9–135.7) fewer deaths per 10 000 patient‐years (intent‐to‐treat and on‐treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation.

Conclusions
These analyses show a favorable benefit–risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.
Association Between Young Adult Characteristics and Blood Pressure Trajectories
Authors: An Jaejin , Fischer Heidi , Ni Liang , Xia Mengying , Choi Soon Kyu , Morrissette Kerresa L. , Wei Rong , Reynolds Kristi , Muntner Paul , Safford Monika M. , Moran Andrew E. , Bellows Brandon K. , Isasi Carmen R. , Allen Norrina B. , Xanthakis Vanessa , Colantonio Lisandro D. , Zhang Yiyi 
Published: April 2024

Background
Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample.

Methods and Results

We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10‐year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30–39 versus 18–29 years, 1.23 [95% CI, 1.18–1.28]), male sex (13.38 [95% CI, 12.80–13.99]), obesity (body mass index ≥30 versus 18.5–24.9 kg/m
2
, 14.81 [95% CI, 14.03–15.64]), overweight (body mass index 25–29.9 versus 18.5–24.9 kg/m
2
, 3.16 [95% CI, 3.00–3.33]), current smoking (1.58 [95% CI, 1.48–1.67]), prediabetes (1.21 [95% CI, 1.13–1.29]), diabetes (1.60 [95% CI, 1.41–1.81]) and high low‐density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37–1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2).

Conclusions
Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.