bluuebunny/crossref_metadata_2025_split huggingface dataset:
A network of acetyl phosphate-dependent modification modulates c-di-AMP homeostasis in
Actinobacteria
Authors: Fu Yu , Zhao Liu-Chang , Shen Jin-Long , Zhou Shi-Yu , Yin Bin-Cheng , Ye Bang-Ce , You Di 
Published: July 2024

ABSTRACT

Cyclic purine nucleotides are important signal transduction molecules across all domains of life. 3′,5′-cyclic di-adenosine monophosphate (c-di-AMP) has roles in both prokaryotes and eukaryotes, while the signals that adjust intracellular c-di-AMP and the molecular machinery enabling a network-wide homeostatic response remain largely unknown. Here, we present evidence for an acetyl phosphate (AcP)-governed network responsible for c-di-AMP homeostasis through two distinct substrates, the diadenylate cyclase
D
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i
ntegrity
s
canning protein (DisA) and its newly identified transcriptional repressor, DasR. Correspondingly, we found that AcP-induced acetylation exerts these regulatory actions by disrupting protein multimerization, thus impairing c-di-AMP synthesis via K66 acetylation of DisA. Conversely, the transcriptional inhibition of
disA
was relieved during DasR acetylation at K78. These findings establish a pivotal physiological role for AcP as a mediator to balance c-di-AMP homeostasis. Further studies revealed that acetylated DisA and DasR undergo conformational changes that play crucial roles in differentiation. Considering the broad distribution of AcP-induced acetylation in response to environmental stress, as well as the high conservation of the identified key sites, we propose that this unique regulation of c-di-AMP homeostasis may constitute a fundamental property of central circuits in
Actinobacteria
and thus the global control of cellular physiology.

IMPORTANCE

Since the identification of c-di-AMP is required for bacterial growth and cellular physiology, a major challenge is the cell signals and stimuli that feed into the decision-making process of c-di-AMP concentration and how that information is integrated into the regulatory pathways. Using the bacterium
Saccharopolyspora erythraea
as a model, we established that AcP-dependent acetylation of the diadenylate cyclase DisA and its newly identified transcriptional repressor DasR is involved in coordinating environmental and intracellular signals, which are crucial for c-di-AMP homeostasis. Specifically, DisA acetylated at K66 directly inactivates its diadenylate cyclase activity, hence the production of c-di-AMP, whereas DasR acetylation at K78 leads to increased
disA
expression and c-di-AMP levels. Thus, AcP represents an essential molecular switch in c-di-AMP maintenance, responding to environmental changes and possibly hampering efficient development. Therefore, AcP-mediated posttranslational processes constitute a network beyond the usual and well-characterized synthetase/hydrolase governing c-di-AMP homeostasis.
The coding complete genomic sequence of a feline panleukopenia virus detected from a domestic cat (
Felis catus
) in Chattogram, Bangladesh
Authors: Akter Jesmin , Nath Chandan , Hossain Md Saddam , Ahaduzzaman Md 
Published: July 2024

ABSTRACT

The coding complete genome sequence of the feline panleukopenia virus (FPLV), detected from an indigenous cat in Bangladesh, has been determined. The genome spans 4,842 bp and contains four protein-coding genes. The genome will contribute to a comprehensive understanding of the genetic traits and evolutionary trends of FPLV.
Microbiological and functional traits of peri-implant mucositis and correlation with disease severity
Authors: Feng Ziying , Zhu Jinzan , Zhang Limin , Li Chunchun , Su Duyao , Wang Huihui , Yu Youcheng , Song Liang 
Published: July 2024

ABSTRACT

Osseointegrated dental implants replace missing teeth and create an artificial surface for biofilms of complex microbial communities to grow. These biofilms on implants and dental surfaces can trigger infection and inflammation in the surrounding tissue. This study investigated the microbial characteristics of peri-implant mucositis (PM) and explored the correlation between microbial ecological imbalance, community function, and disease severity by comparing the submucosal microflora from PM with those of healthy inter-subject implants and intra-subject gingivitis (G) within a group of 32 individuals. We analyzed submucosal plaques from PM, healthy implant (HI), and G sites using metagenome shotgun sequencing. The bacterial diversity of HIs was higher than that of PM, according to the Simpson index. Beta diversity revealed differences in taxonomic and functional compositions across the groups. Linear discriminant analysis of the effect size identified 15 genera and 37 species as biomarkers that distinguished PM from HIs. Pathways involving cell motility and protein processing in the endoplasmic reticulum were upregulated in PM, while pathways related to the metabolism of cofactors and vitamins were downregulated. Microbial dysbiosis correlated positively with the severity of clinical inflammation measured by the sulcus bleeding index (SBI) in PM.
Prevotella
and protein processing in the endoplasmic reticulum also correlated positively with the SBI. Our study revealed PM’s microbiological and functional traits and suggested the importance of certain functions in disease severity.

IMPORTANCE

Peri-implant mucositis is an early stage in the progression of peri-implantitis. The high prevalence of it has been a threat to the widespread use of implant prosthodontics. The link between the submucosal microbiome and peri-implant mucositis was demonstrated previously. Nevertheless, the taxonomic and functional composition of the peri-implant mucositis microbiome remains controversial. In this study, we comprehensively characterize the microbial signature of peri-implant mucositis and for the first time, we investigate the correlations between microbial dysbiosis, functional potential, and disease severity. With the help of metagenomic sequencing, we find the positive correlations between microbial dysbiosis, genus
Prevotella
, pathway of protein processing in the endoplasmic reticulum, and more severe mucosal bleeding in the peri-implant mucositis. Our studies offer insight into the pathogenesis of peri-implant mucositis by providing information on the relationships between community function and disease severity.
Antibacterial potential of
Stenotrophomonas maltophilia
complex cystic fibrosis isolates
Authors: Crisan Cristian V. , Pettis Morgan L. , Goldberg Joanna B. 
Published: July 2024

ABSTRACT

Over 160,000 people worldwide suffer from cystic fibrosis (CF), a genetic condition that causes mucus to accumulate in internal organs. Lung decline is a significant health burden for people with CF (pwCF), and chronic bacterial pulmonary infections are a major cause of death.
Stenotrophomonas maltophilia
complex (Smc) is an emerging, multidrug-resistant CF pathogen that can cause pulmonary exacerbations and result in higher mortality. However, little is known about the antagonistic interactions that occur between Smc isolates from pwCF and competitor bacteria. We obtained 13 Smc isolates from adult and pediatric pwCF located in the United States or Australia. We co-cultured these isolates with
Pseudomonas aeruginosa
,
Staphylococcus aureus,
and
Escherichia coli
. We also performed whole-genome sequencing of these Smc isolates and compared their genomes using average nucleotide identity analyses. We observed that some Smc CF isolates can engage in antagonistic interactions with
P. aeruginosa
and
S. aureus
but recovered a substantial number of
P. aeruginosa
and
S. aureus
cells following co-cultures with all tested Smc isolates. By contrast, we discovered that most Smc CF isolates display strong antibacterial properties against
E. coli
cells and reduce recovery below detectable limits. Finally, we demonstrate that Smc CF strains from this study belong to diverse phylogenetic lineages.

IMPORTANCE

Antagonism toward competitor bacteria may be important for the survival of
Stenotrophomonas maltophilia
complex (Smc) in external environments, for the elimination of commensal species and colonization of upper respiratory tracts to enable early infections, and for competition against other pathogens after establishing chronic infections. These intermicrobial interactions could facilitate the acquisition of Smc by people with cystic fibrosis from environmental or nosocomial sources. Elucidating the mechanisms used by Smc to eliminate other bacteria could lead to new insights into the development of novel treatments.
A benchmarked comparison of software packages for time-lapse image processing of monolayer bacterial population dynamics
Authors: Ahmadi Atiyeh , Courtney Matthew , Ren Carolyn , Ingalls Brian 
Published: July 2024

ABSTRACT

Time-lapse microscopy offers a powerful approach for analyzing cellular activity. In particular, this technique is valuable for assessing the behavior of bacterial populations, which can exhibit growth and intercellular interactions in a monolayer. Such time-lapse imaging typically generates large quantities of data, limiting the options for manual investigation. Several image-processing software packages have been developed to facilitate analysis. It can thus be a challenge to identify the software package best suited to a particular research goal. Here, we compare four software packages that support the analysis of 2D time-lapse images of cellular populations: CellProfiler, SuperSegger-Omnipose, DeLTA, and FAST. We compare their performance against benchmarked results on time-lapse observations of
Escherichia coli
populations. Performance varies across the packages, with each of the four outperforming the others in at least one aspect of the analysis. Not surprisingly, the packages that have been in development for longer showed the strongest performance. We found that deep learning-based approaches to object segmentation outperformed traditional approaches, but the opposite was true for frame-to-frame object tracking. We offer these comparisons, together with insight into usability, computational efficiency, and feature availability, as a guide to researchers seeking image-processing solutions.

IMPORTANCE
Time-lapse microscopy provides a detailed window into the world of bacterial behavior. However, the vast amount of data produced by these techniques is difficult to analyze manually. We have analyzed four software tools designed to process such data and compared their performance, using populations of commonly studied bacterial species as our test subjects. Our findings offer a roadmap to scientists, helping them choose the right tool for their research. This comparison bridges a gap between microbiology and computational analysis, streamlining research efforts.
Prevalence of therapeutic use exemptions at the Olympic Games and Paralympic Games: an analysis of data from 2016 to 2022
Authors: Vernec Alan , Healy David , Banon Tamar , Petroczi Andrea 
Published: July 2024

ObjectivesThe objectives of this study are to describe the prevalence of therapeutic use exemptions (TUEs) among athletes competing in four Olympic and four Paralympic games. The secondary objective was to present the prohibited substance and methods classes associated with TUEs.MethodsData from the Anti-Doping Administration and Management System were extracted for this cross-sectional observation study. Eight cohorts were created to include athletes with TUEs who competed in the Rio 2016, Pyeongchang 2018, Tokyo 2020 and Beijing 2022 Olympic and Paralympic games. Prevalence of TUEs and proportion of prohibited substance and methods classes were defined as percentages among all athletes competing at each games.Results28 583 athletes competed in four editions of the Olympic games. Total prevalence of athletes with TUEs was 0.90% among all competitors. At the four Paralympic games, a total of 9852 athletes competed and the total TUE prevalence was 2.76%. The most frequently observed substances associated with TUEs at the Summer Olympics were glucocorticoids (0.50% in Rio) and stimulants (0.39% in Tokyo). At the Summer Paralympics, diuretics (0.79% in Rio) and stimulants (0.75% in Tokyo) were the most common. Winter games had somewhat similar trends, although TUE numbers were very low.ConclusionsThe number of athletes competing with valid TUEs at the Olympic and Paralympic games was <1% and <3%, respectively. Variations in substances and methods associated with TUEs for different medical conditions were identified. Nevertheless, numbers were low, further reaffirming that TUEs are not widespread in elite sport.
Oblique subcostal transverse abdominis plane block for postoperative pain control in patients undergoing open sublay mesh hernia repair: a prospective double-blind randomized placebo-controlled clinical trial
Authors: Keller Marius , Dinkel Friederike , Jacoby Johann , Kraft Barbara , Haas Anne , Rosenberger Peter , Meierhenrich Rainer 
Published: July 2024

BackgroundA bilateral oblique subcostal transverse abdominis plane block may help provide perioperative analgesia and reduce opioid use in patients undergoing sublay mesh hernia repair, but its clinical value is unclear.MethodsIn a single-centre, prospective, placebo-controlled, double-blind study, patients scheduled for sublay mesh hernia repair were randomized to receive oblique subcostal transverse abdominis plane blocks with either 60 ml of 0.375% ropivacaine (n=19) or isotonic saline (placebo, n=17). The primary outcome was patient-controlled total morphine consumption at 8:00 p.m. on the second postoperative day (POD), while secondary outcomes included the total morphine consumption during the post-anesthesia care unit stay and the occurrence of adverse events.ResultsTotal morphine consumption at 8:00 p.m. on the second POD was higher in patients receiving ropivacaine (39 mg, IQR 22, 62) compared with placebo (24 mg, IQR 7, 39), p value = 0.04. In contrast, the ropivacaine group received 2 mg less morphine during the post-anesthesia care unit stay (4 mg, IQR: 4, 9 mg vs 2 mg, IQR: 2,6 mg, p = 0.04). Patients receiving ropivacaine used more morphine (8:00 p.m. on the first POD until 8:00 a.m. on the second POD: 8 mg, IQR: 4, 18 mg vs 2 mg, IQR: 0, 9 mg, p = 0.01) and reported higher maximum pain scores since the last assessment (8:00 a.m. on the second POD: 5, IQR: 4, 7 vs 4, IQR: 3, 5, p = 0.03). There were no differences in adverse events between groups.ConclusionsBilateral oblique subcostal transverse abdominis plane blocks in patients undergoing sublay mesh hernia repair were not associated with a prolonged reduction in patient-controlled total morphine consumption in the evening of the second POD in this study. Rebound pain might explain the additional excess opioid required by the ropivacaine group.
Geographic Access to Fertility Counseling among Adolescent and Young Adult Women with Cancer in North Carolina
Authors: Rodriguez-Ormaza Nidia , Anderson Chelsea , Baggett Christopher D. , Delamater Paul L. , Troester Melissa A. , Wheeler Stephanie B. , Wardell Alexis C. , Deal Allison M. , Smitherman Andrew , Mersereau Jennifer , Baker Valerie L. , Nichols Hazel B. 
Published: July 2024

Abstract

Background:
Fertility counseling is recommended for adolescent and young adult women facing gonadotoxic cancer therapy. However, fertility care is subspecialized medical care offered at a limited number of institutions, making geographic access a potential barrier to guideline-concordant care. We assessed the relationship between geographic access and receipt of fertility counseling among adolescent and young adult women with cancer.

Methods:
Using data from the North Carolina Central Cancer Registry, we identified women diagnosed with lymphoma, gynecologic cancer, or breast cancer at ages 15 to 39 years during 2004 to 2015. Eligible women were invited to complete an online survey on various topics, including fertility counseling. Geographic access was measured, using geocoded addresses, as vehicular travel time from residence to the nearest fertility clinic available at diagnosis. Multivariable regression models were used to examine the association between travel time and receipt of fertility counseling by provider type: health care provider versus fertility specialist.

Results:
Analyses included 380 women. The median travel time to a fertility clinic was 31 (IQR: 17–71) minutes. Overall, 75% received fertility counseling from a health care provider and 16% by a fertility specialist. Women who lived ≥30 minutes from a clinic were 13% less likely to receive fertility counseling by a health care provider (prevalence ratio: 0.87; 95% confidence interval, 0.75–1.00) and 49% less likely to receive counseling by a fertility specialist (prevalence ratio: 0.51; 95% confidence interval, 0.28–0.93).

Conclusions:
Women who lived further away from fertility clinics were less likely to receive fertility counseling.

Impact:
Interventions to improve access to fertility counseling should include strategies to alleviate the burden of geographic access.
Tumor-Localized Interleukin-2 and Interleukin-12 Combine with Radiation Therapy to Safely Potentiate Regression of Advanced Malignant Melanoma in Pet Dogs
Authors: Stinson Jordan A. , Barbosa Matheus Moreno P. , Sheen Allison , Momin Noor , Fink Elizabeth , Hampel Jordan , Selting Kim A. , Kamerer Rebecca L. , Bailey Keith L. , Wittrup Karl D. , Fan Timothy M. 
Published: July 2024

AbstractPurpose:Cytokines IL2 and IL12 exhibit potent anticancer activity but suffer a narrow therapeutic window due to off-tumor immune cell activation. Engineering cytokines with the ability to bind and associate with tumor collagen after intratumoral injection potentiated response without toxicity in mice and was previously safe in pet dogs with sarcoma. Here, we sought to test the efficacy of this approach in dogs with advanced melanoma.Patients and Methods:This study examined 15 client-owned dogs with histologically or cytologically confirmed malignant melanoma that received a single 9-Gy fraction of radiotherapy, followed by six cycles of combined collagen-anchored IL2 and IL12 therapy every 2 weeks. Cytokine dosing followed a 3 + 3 dose escalation design, with the initial cytokine dose chosen from prior evaluation in canine sarcomas. No exclusion criteria for tumor stage or metastatic burden, age, weight, or neuter status were applied for this trial.Results:Median survival regardless of the tumor stage or dose level was 256 days, and 10/13 (76.9%) dogs that completed treatment had CT-measured tumor regression at the treated lesion. In dogs with metastatic disease, 8/13 (61.5%) had partial responses across their combined lesions, which is evidence of locoregional response. Profiling by NanoString of treatment-resistant dogs revealed that B2m loss was predictive of poor response to this therapy.Conclusions:Collectively, these results confirm the ability of locally administered tumor-anchored cytokines to potentiate responses at regional disease sites when combined with radiation. This evidence supports the clinical translation of this approach and highlights the utility of comparative investigation in canine cancers.
Rational Protein Engineering to Enhance MHC-Independent T-cell Receptors
Authors: Chang Ju-Fang , Landmann Jack H. , Chang Tien-Ching , Selli Mehmet Emrah , Tenzin Yangdon , Warrington John M. , Ritchey Julie , Hsu Yu-Sung , Slade Michael , Gupta Deepesh Kumar , DiPersio John F. , Holehouse Alex S. , Singh Nathan 
Published: July 2024

Abstract
Chimeric antigen receptor (CAR)–based therapies have pioneered synthetic cellular immunity but remain limited in their long-term efficacy. Emerging data suggest that dysregulated CAR-driven T-cell activation causes T-cell dysfunction and therapeutic failure. To re-engage the precision of the endogenous T-cell response, we designed MHC-independent T-cell receptors (miTCR) by linking antibody variable domains to T-cell receptor constant chains. Using predictive modeling, we observed that this standard “cut and paste” approach to synthetic protein design resulted in myriad biochemical conflicts at the hybrid variable–constant domain interface. Through iterative modeling and sequence modifications, we developed structure-enhanced miTCRs which significantly improved receptor-driven T-cell function across multiple tumor models. We found that 41BB costimulation specifically prolonged miTCR T-cell persistence and enabled improved leukemic control in vivo compared with classic CAR T cells. Collectively, we have identified core features of hybrid receptor structure responsible for regulating function.
Significance: Improving the durability of engineered T-cell immunotherapies is critical to enhancing efficacy. We used a structure-informed design to evolve improved miTCR function across several models. This work underscores the central role of synthetic receptor structure in T-cell function and provides a framework for improved receptor engineering.
Eisenstein's Paris Diary: An Introduction
Authors: Rebecchi Marie , Vogman Elena 
Published: July 2024

Abstract
This introductory text unfolds and interprets some key elements from Eisenstein's Paris Diary, contextualizing his encounters and providing further details for understanding the filmmaker's fragmentary and sometimes cryptic diary as an autotheoretical practice. Written from the perspective of one immersed in the artistic and intellectual Paris of 1929 and 1930—as evidenced by Eisenstein's encounters with Colette, Tristan Tzara, Gertrude Stein, André Malraux, Filippo T. Marinetti, Abel Gance, Jean Cocteau, Louis Aragon, Paul Éluard, Kiki de Montparnasse, Darius Milhaud, and others—the diary highlights the importance of his exchange with the avant-garde micro-cinematographer Jean Painlevé, as well as his theoretical and political kinship with the heterodox Surrealist group around the journal Documents. The introduction investigates the way in which Eisenstein's Paris Diary both documents daily events and serves as an ephemeral depository for the author's theoretical ideas on filmmaking and montage, seeing these in terms of such late works as Method, Montage, and Disney.
The Reflex Republic: Physiologies of Art in the Early Soviet Union
Authors: Vollgraff Matthew 
Published: July 2024

Abstract
In the immediate wake of the Russian Revolution, Pavlovian reflex conditioning was rapidly elevated to a universal materialist model for understanding and manipulating human behavior, including the production and reception of art. This article explores the little-known history of the “reflexology of art,” a movement that applied physiological concepts and techniques to drama, cinema, and literature with the aim of molding atomized individual subjectivities into a corporeal collective. This movement—which involved figures like Vsevolod Meyerhold, Sergei Eisenstein, and Sergei Tret'iakov—formed part of the highly politicized dialogue between science, politics and the arts in the 1920s. By reconstructing the critical discourse around the reflexology of art within the cultural production of the early Soviet state, the article sheds light on the contradictory impulses animating an avant-garde caught between deterministic visions of social engineering and the subversive passions of revolution.