bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemotherapy-associated pneumoperitoneum in cancer patients: a scoping review
Authors: Maina Renee M. , Rader Caroline , Kypa Jeevan , Asahngwa Constantine , Jasmin Hilary M. , Zalamea Nia N. , Nelson John S. , Altomar Jonathan L. , Owens Mary Brinson , Muenyi Clarisse S. , Foretia Denis A.
Published: March 2024

Background:

The presence of air in the peritoneal cavity (pneumoperitoneum) is often secondary to perforated viscus. Emergent operative intervention is typically warranted in non-cancer patients. Cancer patients present a unique challenge as they have an increased risk of pneumoperitoneum due to local tumour invasion, radiation therapy, and frequent endoscopic procedures. There is a paucity of literature on the management of patients undergoing chemotherapy who present with pneumoperitoneum. The authors conducted a scoping review to identify and synthesize preliminary evidence on the presentation, management, and outcomes of this patient population.

Materials and methods:

A scoping review of cases of pneumoperitoneum in cancer patients from 1990 to 2022 was conducted using the Arksey and O’Malley five-stage approach. Inclusion criteria were a known diagnosis of cancer, chemotherapy within 6 months of presentation, and imaging confirmation of pneumoperitoneum. The authors’ exclusion criteria were cancer diagnosis at the time of presentation, perforation secondary to local cancer invasion, and last chemotherapy session greater than 6 months prior to presentation.

Results:

Thirty-four cases (8 paediatric, 26 adults) were identified. The median time from the last chemotherapy treatment to presentation with pneumoperitoneum was 14 days. Twenty-one patients were managed operatively, and 13 were managed non-operatively. The most common source of perforation was multiple sites along the bowel. Thirty-day mortality was 33.3% for the operative cohort and 23.1% for the non-operative group.

Conclusions:

Pneumoperitoneum in cancer patients remains a highly morbid condition with a mortality rate of approximately 30%, regardless of the treatment approach. Non-operative management should be pursued whenever possible.
EFFECT OF MIR-21-3P ON INTESTINAL INJURY IN RATS WITH TRAUMATIC HEMORRHAGIC SHOCK RESUSCITATED WITH THE SODIUM BICARBONATE RINGER'S SOLUTION
Authors: Li Lei , Jiang Hai , Qiu Zhaolei , Wang Zhenjie , Hu Zhansheng
Published: March 2024

Background: This study aims to determine the impact and mechanism of miR-21-3p on intestinal injury and intestinal glycocalyx during fluid resuscitation in traumatic hemorrhagic shock (THS), and the different impacts of sodium lactate Ringer's solution (LRS) and sodium bicarbonate Ringer's solution (BRS) for resuscitation on intestinal damage. Methods: A rat model of THS was induced by hemorrhage from the left femur fracture. The pathological changes of intestinal tissues and glycocalyx structure were observed by hematoxylin-eosin staining and transmission electron microscope. MiR-21-3p expression in intestinal tissues was detected by real-time quantitative polymerase chain reaction. The expression of glycocalyx–, cell junction–, and PI3K/Akt/NF-κB signaling pathway–related proteins was analyzed by western blot. Results: MiR-21-3p expression was increased in THS rats, which was suppressed by resuscitation with BRS. BRS or LRS aggravated the intestinal injury and damaged intestinal glycocalyx in THS rats. The expression of SDC-1, HPA, β-catenin, MMP2, and MMP9 was upregulated, the expression of E-cad was downregulated, and the PI3K/Akt/NF-κB signaling pathway was activated in THS rats, which were further aggravated by BRS or LRS. The adverse effect of LRS was more serious than BRS. MiR-21-3p overexpression deteriorated the injury of intestinal tissues and intestinal glycocalyx; increased the expression of SDC-1, HPA, β-catenin, MMP2, and MMP9 while decreasing E-cad expression; and activated the PI3K/Akt/NF-κB signaling pathway in BRS-resuscitated THS rats. Conclusion: MiR-21-3p aggravated intestinal tissue injury and intestinal glycocalyx damage through activating PI3K/Akt/NF-κB signaling pathway in rats with THS resuscitated with BRS.
REMIMAZOLAM IMPROVES THE MARKERS OF POSTRESUSCITATION CEREBRAL INJURY IN A SWINE MODEL OF CARDIAC ARREST
Authors: Shen Rongrong , Liu Zhilin , Fei Li , Zhang Yixiang , Xu Linwu , Xuan Chaoqi
Published: March 2024

Introduction:Previous studies have manifested that those sedatives acting on γ-aminobutyric acid A (GABAa) receptor could produce effective brain protection against regional and global ischemic stimulation. The present study was designed to investigate the effect of a novel GABAa receptor agonist, remimazolam postconditioning (RP) on cerebral outcome after global ischemic stimulation induced by cardiac arrest and resuscitation in swine.Methods:A total of 24 swine were used in this study, in which the animals were randomly divided into the following three groups: sham group (n = 6), cardiopulmonary resuscitation (CPR) group (n = 9), and CPR + RP group (n = 9). The experimental model was established by the procedure of 10 min of cardiac arrest and 5 min of CPR. Those resuscitated swine in the CPR + RP group received an intravenous infusion of 2.5 mg/kg of remimazolam within 60 min. Postresuscitation cerebral injury biomarkers and neurological function were evaluated for a total of 24 h. At 24 h after resuscitation, brain cortex was harvested to evaluate the severity of pathologic damage, including tissue inflammation, oxidative stress, apoptosis, and necroptosis.Results:Baseline characteristics and CPR outcomes were not significantly different between the CPR and CPR + RP groups. After resuscitation, significantly greater cerebral injury and neurological dysfunction were observed in the CPR and CPR + RP groups than in the sham group. However, remimazolam postconditioning significantly alleviated cerebral injury and improved neurological dysfunction after resuscitation when compared with the CPR group. At 24 h after resuscitation, tissue inflammation, oxidative stress, and cell apoptosis and necroptosis were significantly increased in the CPR and CPR + RP groups when compared with the sham group. Nevertheless, the severity of pathologic damage mentioned previously were significantly milder in those swine treated with the remimazolam when compared with the CPR group.Conclusions:In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of postresuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.
CAUSAL ROLES OF SERUM URIC ACID LEVELS AND GOUT IN SEPSIS: A MENDELIAN RANDOMIZATION STUDY
Authors: Qin Yujun , Yang Xia , Ning Zong
Published: March 2024

Objective: Several epidemiological studies have identified a potential link between serum uric acid (UA), gout, and sepsis. The primary objective of this study is to delve deeper into this connection, investigating the causal effect of UA and gout on sepsis by applying Mendelian randomization (MR). Methods: The causal relationship was analyzed using data from Genome-Wide Association Study (GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Three complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple median method. Horizontal pleiotropy was identified by MR-Egger intercept test. Cochran’s Q statistics were employed to assess the existence of instrument heterogeneity. The leave-one-out method was used as a sensitivity analysis. Results: The IVW results indicated that there was a positive causal relationship between UA and sepsis (critical care) (odds ratio [OR] = 0.24, 95% confidence interval [CI]: 0.04 to 0.43, P = 0.018, F = 4,291.20). There was no significant association between UA and sepsis (28-day death in critical care) (OR = 0.10, 95% CI = −0.29 to 0.50, P = 0.604). There was no significant association between gout and sepsis (critical care) (OR = 0.85, 95% CI = −4.87 to 6.57, P = 0.771), and sepsis (28-day death in critical care) (OR = −6.30, 95% CI = −17.41 to 4.81, P = 0.267). Horizontal pleiotropy was absent in this study. The results were robust under all sensitivity analyses. Conclusion: The study revealed that elevated UA levels were causally linked with sepsis (critical care). No causal relationship had been found between UA and sepsis (28-day death in critical care), as well as between gout and sepsis.
Epidemiological and virological characteristics of people living with HIV on antiretroviral treatment for more than six months in virological failure in Brazzaville, Republic of Congo
Authors: GOT Ferdinand Emaniel Brel , MALONGA Gervillien Arnold , MALANDA-KIMINOU Juthèce Privat , AKOLBOUT Maryse , LOUBANO-MVOUMBI Ghislain , EBOUROMBI Dagene , DIAFOUKA Merlin , ONDZOTTO Gontran
Published: March 2024

Introduction

Virological failure is one of the major causes of treatment failure, and better management of HIV infection requires understanding and controlling the factors that contribute to this phenomenon. The main objective was to characterize the patients of the active file of the Brazzaville Outpatient Treatment Center in virological failure in order to identify predictive factors that lead to virological failure.

Methods

This was a cross-sectional study conducted between June and December 2020. Patients enrolled were HIV-1 infected patients from the Brazzaville Outpatient Treatment Center receiving a potent combination therapy for at least 6 months but experiencing virological failure. Viral load was determined with the automated Abbott Real-time HIV-1 m2000rt System. Sociodemographic and clinical data were collected from a computerized patient record software called Santia. Statistical analysis was performed to identify independent predictors of virological failure.

Results

A total of 109 patients with virological failure were recruited. The median age of the patients was 45 years (IQR: 37-52 years) and women were more represented (74%). More than half of the patients had WHO stage IV HIV and the median duration on ARV treatment was 96 months. The most followed treatment regimen was AZT+3TC+EFV (or NVP) with 48% while the median viral load was 12,985 copies/mL.

Conclusion

In our study, we did not identify any sociodemographic or clinical variables predictive of virological failure. However, we felt that it would be desirable to carry out a study with temporal follow-up and the possibility of sequencing in order to identify the different circulating genotypes and resistance mutations.
First Case Report of Disseminated Gonococcal Arthritis in Newfoundland & Labrador
Authors: Karsenti Nessika , Nelder Matthew , LeMeissurier Jennifer , Bourassa-Blanchette Samuel , Taylor Robert
Published: March 2024

Introduction: Disseminated gonococcal infections (DGIs) are a rare but often debilitating complication of N. gonorrhoeae infections. Often presenting as arthritis-dermatitis syndrome, true suppurative joint infections are an even more rare form of DGI. Here, we present the first known case of DGI in Newfoundland and Labrador in over 10 years.
Case report: A 50-year-old man who is known to inject drugs with multiple housing and social challenges presented to the emergency department with a two-day history of an isolated painful, erythematous knee. After being assessed by orthopedics and undergoing an operative debridement, intraoperative cultures grew N. gonorrhoeae. He was treated with IV ceftriaxone, and his course in hospital was complicated by inadequate pain control and a lack of stable housing.  
Conclusion: DGIs, while rare, need to remain on any clinician’s differential for septic arthritis given the increasing prevalence of gonorrheal infections in Canada, and in Newfoundland and Labrador. In addition, patients who are at risk of delaying accessing care, such as people who inject drugs and unhoused individuals, are at higher risk of complicated hospital stays.
Sequence and origin of the Streptomyces intergenetic-conjugation helper plasmid pUZ8002.
Authors: Larcombe Daniel E , Braes Robyn E , Croxford James T , Wilson James W , Figurski David H , Hoskisson Paul A
Published: March 2024

Conjugation of plasmids from Escherichia coli is essential for the genetic manipulation of Streptomyces spp. To facilitate intergeneric conjugation from E. coli to Streptomyces the conjugative machinery required for genetic transfer is usually provided by the non-transferable helper plasmid, pUZ8002. Here we present the complete nucleotide sequence of pUZ8002, describe the previously undocumented creation process, and provide details of the sequence relative to the parental pUZ8 plasmid and another previously published pUZ8002 sequence.
Modelling SARS-CoV-2 infection in a human alveolus microphysiological system
Authors: Šuligoj Tanja , Coombes Naomi , Booth Catherine , Savva George M. , Bewley Kevin R , Funnell Simon GP , Juge Nathalie
Published: March 2024

The COVID-19 pandemic has highlighted the importance of physiologically relevant in vitro models to assist preclinical research. Here, we describe the adaptation of a human alveolus microphysiological system (MPS) model consisting of primary human alveolar epithelial and lung microvascular endothelial cells to study infection with SARS-CoV-2 at Biosafety Level 3 (BSL3) facility. This infection model recapitulates breathing-like stretch and culture of epithelial cells at the air-liquid interface (ALI) and resulted in clinically relevant cytopathic effects including cell rounding of alveolar type 2 cells (AT2) and disruption of the tight junction protein occludin (OCLN). Viral replication was confirmed by immunocytochemical nucleocapsid staining in the epithelium and increased shedding of SARS-CoV-2 virus within two days post-infection, associated with changes in innate host immune responses. Together, these data demonstrate that, under the experimental conditions used in this work, this human alveolus MPS chip can successfully model SARS-CoV-2 infection of human alveolar lung cells.
Bacteriological profile of community peritonitis operated in a Moroccan Hospital
Authors: BAZHAR SAMIA , Benaissa Elmostafa , Ziad Fatima , Laamara Leila , Ben Lahlou Yassine , Chadli Mariama , Elouennass Mostafa
Published: March 2024

Introduction. Peritonitis is characterized by acute inflammation of the peritoneum, often resulting from digestive organ perforation or intra-abdominal septic focus. It may be either of infectious or noninfectious origin. The germs involved are those of the digestive flora (Enterobacteriaceae and Anaerobic), while gram-positive cocci and yeasts can be isolated in nosocomial infections. Our study aims to isolate and identify the germs involved in community-acquired peritonitis, in order to assess their susceptibility to the antibiotics available in our Country.
 
Methods. This is a retrospective study of bacteriological profile of community peritonitis in Rabat Morocco. A total of 150 adult patients with peritonitis, were admitted and samples were collected intraoperatively for bacteriological examination between July 1, 2022 and April 30, 2023.
 
Results. Among the 150 patients, 101 (67.8%) were males and 48 (32.2%) were females, with sex/ratio of 2.1. The mean age of the patients was 40.5 years +/- 20.12. The distribution of germs was dominated by Escherichia coli (44%). Overall, 70% of Escherichia coli isolated, had a resistance to Ampicillin but no resistance to Ampicillin has been reported by Enterococcus.
 
Discussion. In the present study, we were interested in the bacteriological profile of community peritonitis, in order to adapt the antibiotic therapy to our bacterial ecology. 
Our findings indicate a concerning trend of increasing resistance among Escherichia coli to the commonly used Amoxicillin/Clavulanic Acid combination in our clinical setting.
 
Conclusion. Consequently, there is a need to reassess the empiric antibiotic prescribed for the management of community-acquired peritonitis.
Gene-language models are whole genome representation learners
Authors: Naidenov Bryan , Chen Charles
Published: March 2024

The language of genetic code embodies a complex grammar and rich syntax of interacting molecular elements. Recent advances in self-supervision and feature learning suggest that statistical learning techniques can identify high-quality quantitative representations from inherent semantic structure. We present a gene-based language model that generates whole-genome vector representations from a population of 16 disease-causing bacterial species by leveraging natural contrastive characteristics between individuals. To achieve this, we developed a set-based learning objective, AB learning, that compares the annotated gene content of two population subsets for use in optimization. Using this foundational objective, we trained a Transformer model to backpropagate information into dense genome vector representations. The resulting bacterial representations, or embeddings, captured important population structure characteristics, like delineations across serotypes and host specificity preferences. Their vector quantities encoded the relevant functional information necessary to achieve state-of-the-art genomic supervised prediction accuracy in 11 out of 12 antibiotic resistance phenotypes.

Teaser

Deep transformers capture and encode gene language content to derive versatile latent embeddings of microbial genomes.
Language Abnormalities in Alzheimer’s Disease Arise from Reduced Informativeness: A Cross-Linguistic Study in English and Persian
Authors: Bayat Sabereh , Santai Mahya , Panahi Mehrdad Mohammad , Khodadadi Amirhossein , Ghassimi Mahdieh , Rezaei Sahar , Besharat Sara , Mahboubi Zahra , Almasi Mostafa , Taheri Morteza Sanei , Dickerson Bradford C , Rezaii Neguine
Published: March 2024

INTRODUCTION

This research investigates the psycholinguistic origins of language impairments in Alzheimer’s Disease (AD), questioning if these impairments result from language-specific structural disruptions or from a universal deficit in generating meaningful content.

METHODS

Cross-linguistic analysis was conducted on language samples from 184 English and 52 Persian speakers, comprising both AD patients and healthy controls, to extract various language features. Furthermore, we introduced a machine learning-based metric, Language Informativeness Index (LII), to quantify informativeness.

RESULTS

Indicators of AD in English were found to be highly predictive of AD in Persian, with a 92.3% classification accuracy. Additionally, we found robust correlations between the typical linguistic abnormalities of AD and language emptiness (low LII) across both languages.

DISCUSSION

Findings suggest AD linguistics impairments are attributed to a core universal difficulty in generating informative messages. Our approach underscores the importance of incorporating biocultural diversity into research, fostering the development of inclusive diagnostic tools.
Population scale proteomics enables adaptive digital twin modelling in sepsis
Authors: Scott Aaron M. , Mellhammar Lisa , Malmström Erik , Goch Gustafsson Axel , Bakochi Anahita , Isaksson Marc , Mohanty Tirthankar , Thelaus Louise , Kahn Fredrik , Malmström Lars , Malmström Johan , Linder Adam
Published: March 2024

Sepsis is one of the leading causes of mortality in the world. Currently, the heterogeneity of sepsis makes it challenging to determine the molecular mechanisms that define the syndrome. Here, we leverage population scale proteomics to analyze a well-defined cohort of 1364 blood samples taken at time-of-admission to the emergency department from patients suspected of sepsis. We identified panels of proteins using explainable artificial intelligence that predict clinical outcomes and applied these panels to reduce high-dimensional proteomics data to a low-dimensional interpretable latent space (ILS). Using the ILS, we constructed an adaptive digital twin model that accurately predicted organ dysfunction, mortality, and early-mortality-risk patients using only data available at time-of-admission. In addition to being highly effective for investigating sepsis, this approach supports the flexible incorporation of new data and can generalize to other diseases to aid in translational research and the development of precision medicine.
An objective neurophysiological study of subconcussion in female and male high school student athletes
Authors: D’Arcy Ryan C.N. , McCarthy David , Harrison Derek , Levenberg Zander , Wan Julian , Hepburn Aidan , Kirby Eric D. , Yardley Tanja , Yamada-Bagg Nikita , Fickling Shaun D. , Munce Thayne A. , Dodick David W. , Ahmad Christopher , Stein Ken Shubin
Published: March 2024

Emerging evidence from neurophysiological brain vital sign studies show repeatable sensitivity to cumulative subconcussive impairments over a season of contact sports. The current study addressed the need for a large prospective study comparing a low-contact control group to high-contact group. Importantly, the study also expanded the scope of neurophysiological changes related to repetitive head impacts to include female athletes in addition to male athletes. In total, 89 high school student athletes underwent 231 brain vital sign scans over a full calendar year. The results replicated prior subconcussive cognitive impairments (N400 delays) and sensory impairments (N100 amplitude reductions) in male athletes and demonstrated similar subconcussive impairments for the first time in female athletes. While there was no significant subconcussive difference between female and male athletes, female athletes show overall larger responses in general. The findings demonstrated that subconcussive impairments are detectable in a controlled experimental comparison for both female and male high school athletes. The study highlights the opportunity to monitor subconcussive changes in cognitive processing for both female and male athletes to help advance prevention, mitigation and management efforts aimed at reducing athletes’ risk of potential long-term negative health outcomes related to cumulative exposure to repetitive head impacts.
Artificial Intelligence-Derived Extracellular Volume Fraction for Diagnosis and Prognostication in Patients with Light-Chain Cardiac Amyloidosis
Authors: Hwang In-Chang , Chun Eun Ju , Kim Pan Ki , Kim Myeongju , Park Jiesuck , Choi Hong-Mi , Yoon Yeonyee E. , Cho Goo-Yeong , Choi Byoung Wook
Published: March 2024

Aims

T1 mapping on cardiac magnetic resonance (CMR) imaging is useful for diagnosis and prognostication in patients with light-chain cardiac amyloidosis (AL-CA). We conducted this study to evaluate the performance of T1 mapping parameters for detection of cardiac amyloidosis (CA) in patients with left ventricular hypertrophy (LVH) and their prognostic values in patients with AL-CA, using a semi-automated deep learning algorithm.

Methods and Results

A total of 300 patients who underwent CMR for differential diagnosis of LVH were analyzed. CA was confirmed in 50 patients (39 with AL-CA and 11 with transthyretin amyloidosis), hypertrophic cardiomyopathy in 198, hypertensive heart disease in 47, and Fabry disease in 5. A semi-automated deep learning algorithm (Myomics-Q) was used for the analysis of the CMR images. The optimal cutoff extracellular volume fraction (ECV) for the differentiation of CA from other etiologies was 33.6% (diagnostic accuracy 85.6%). he artificial intelligence (AI)-derived ECV showed a significant prognostic value for a composite of cardiovascular death and heart failure hospitalization in patients with AL-CA (revised Mayo stage III or IV) (adjusted hazard ratio 4.247 for ECV ≥40%, 95% confidence interval 1.215–14.851, p-value=0.024). Incorporation of AI-derived ECV into the revised Mayo staging system resulted in better risk stratification (integrated discrimination index 27.9%, p=0.013; net reclassification index 13.8%, p=0.007).

Conclusions

AI-assisted T1 mapping on CMR imaging allows for improved diagnosis of CA from other etiologies of LVH. Furthermore, AI-derived ECV has significant prognostic value in patients with AL-CA, suggesting its clinical usefulness.

Graphical Abstract
Assessment of Antibiotic Resistance Profiles in Cultivable Coliform Organisms Isolated from Ganga River Waters Across the Upper, Middle, and Lower Ganga Stretch
Authors: Balkrishna Acharya , Singh Shelly , Ghosh Sourav , Arya Ved Priya , Mohini
Published: March 2024

Antibiotic resistance in coliform organisms isolated from the Ganga River waters across its Upper, Middle, and Lower stretches was assessed. The study revealed varying levels of antibiotic resistance among the coliform isolates, with differences observed across the different stretches of the river. In the Upper stretch, sites like Devprayag and Gangotri exhibited high levels of E. coli contamination, with corresponding moderate antibiotic resistance (MAR) values. In the Middle stretch, sites like Farrukhabad and Bithoor showed lower E. coli contamination compared to the Upper stretch but had higher MAR values. The Lower stretch, particularly sites like Revelganj and Bahachoki in Bihar, displayed significantly elevated E. coli contamination levels and MAR values. These findings underscore the presence of antibiotic-resistant coliform organisms in different segments of the Ganga River, emphasizing the need for targeted interventions to mitigate antibiotic resistance spread in this vital water resource. Understanding the antibiotic resistance profiles at specific sites along the Ganga River can inform strategies to preserve water quality and protect public health in regions dependent on this iconic river.
Glyphosate Effects on Growth and Biofilm Formation in Bee Gut Symbionts and Diverse Associated Bacteria
Authors: Motta Erick V. S. , de Jong Tyler K. , Gage Alejandra , Edwards Joseph A. , Moran Nancy A.
Published: March 2024

Biofilm formation is a common adaptation enabling bacteria to thrive in various environments and to withstand external pressures. In the context of host-microbe interactions, biofilms play vital roles in establishing microbiomes associated with animals and plants and are used by opportunistic microbes to facilitate proliferation within hosts. Investigating biofilm dynamics, composition, and responses to environmental stressors is crucial for understanding microbial community assembly and biofilm regulation in health and disease. In this study, we explore the independent gut colonization and in vitro biofilm formation abilities of core members of the honey bee (Apis mellifera) gut microbiota. Additionally, we assess the impact of glyphosate, a widely used herbicide with antimicrobial properties, and a glyphosate-based formulation on growth and biofilm formation in bee gut symbionts as well as in other biofilm-forming bacteria associated with diverse animals and plants. Our results demonstrate that several strains of core bee gut bacterial species can independently colonize the bee gut, which probably depends on their ability to form biofilms. Furthermore, glyphosate exposure has varying effects on bacterial growth and biofilm formation. These findings imply specific impacts of environmental stressors on microbial biofilms with both ecological and host health-related implications.

Importance

Biofilms are essential for microbial communities to establish and thrive in diverse environments. In the honey bee gut, the core microbiota memberSnodgrassella alviforms biofilms, potentially aiding the establishment of other members and promoting interactions with the host. In this study, we show that specific strains of other core members, includingBifidobacterium,Bombilactobacillus,Gilliamella, andLactobacillus, also form biofilms. We then examine the impact of glyphosate, a widely used herbicide that disrupts the bee microbiota, on their growth and biofilm formation. Our findings demonstrate diverse effects of glyphosate on biofilm formation, ranging from inhibition to enhancement, reflecting observations in other beneficial or pathogenic bacteria associated with animals and plants. Thus, glyphosate exposure may influence bacterial growth and biofilm formation, potentially shaping microbial establishment on host surfaces and impacting health outcomes.
Bioinformatic prediction and high throughput in vivo screening to identify cis-regulatory elements for the development of algal synthetic promoters
Authors: Torres-Tiji Y. , Sethuram H. , Gupta A. , McCauley J. , Dutra-Molino J.V. , Pathania R. , Saxton L. , Kang K. , Hillson N. J. , Mayfield S. P.
Published: March 2024

Algae biotechnology holds immense promise for revolutionizing the bioeconomy through the sustainable and scalable production of various bioproducts. However, its development has been hindered by the lack of advanced genetic tools. This study introduces a synthetic biology approach to develop such tools, focusing on the construction and testing of synthetic promoters. By analyzing conserved DNA motifs within the promoter regions of highly expressed genes across six different algal species, we identified cis-regulatory elements (CREs) associated with high transcriptional activity. Combining the algorithms POWRS, STREME and PhyloGibbs, we predicted 1511 CREs and inserted them into a minimal synthetic promoter sequence in 1, 2 or 3 copies, resulting in 4533 distinct synthetic promoters. These promoters were evaluated in vivo for their capacity to drive the expression of a transgene in a high-throughput manner through next-generation sequencing post antibiotic selection and fluorescence-activated cell sorting. To validate our approach, we sequenced hundreds of transgenic lines showing high GFP expression. Further, we individually tested fourteen identified promoters, revealing substantial increases in GFP expression—up to nine times higher than the baseline synthetic promoter, with five matching or even surpassing the performance of the native AR1 promoter. As a result of this study, we identified a catalog of CREs that can now be used to build superior synthetic algal promoters. More importantly, here we present a validated pipeline to generate building blocks for innovative synthetic genetic tools applicable to any algal species with a sequenced genome and transcriptome dataset.

Graphical Abstract
The minimal SUF system can substitute for the canonical iron-sulfur cluster biosynthesis systems by using inorganic sulfide as the sulfur source
Authors: Murata Maya , Murakami Taichi , Yuda Eiki , Mukai Nanami , Zheng Xintong , Kurachi Natsumi , Mori Sachiko , Ogawa Shoko , Kunichika Kouhei , Fujishiro Takashi , Wada Kei , Takahashi Yasuhiro
Published: March 2024

Biosynthesis of iron-sulfur (Fe-S) clusters is indispensable for living cells. Three biosynthesis systems termed NIF, ISC and SUF have been extensively characterized in both bacteria and eukarya. For these L-cysteine is the sulfur source. A bioinformatic survey suggested the presence of a minimal SUF system composed of only two components, SufB* (a putative ancestral form of SufB and SufD) and SufC, in anaerobic archaea and bacteria. Here, we report the successful complementation of anEscherichia colimutant devoid of the usual ISC and SUF systems upon expression of the archaealsufB*Cgenes. Strikingly, this heterologous complementation occurred under anaerobic conditions only when sulfide was supplemented to the culture media. Mutational analysis and structural predictions suggest that the archaeal SufB*C most likely forms a SufB*2C2complex and serves as the scaffold forde novoFe-S cluster assembly using the essential Cys and Glu residues conserved between SufB* and SufB, in conjunction with a His residue shared between SufB* and SufD. We also demonstrate artificial conversion of the SufB*2C2structure to the SufBC2D type by introducing several mutations to the two copies ofsufB*. Our study thus elucidates the molecular function of this minimal SUF system and suggests that it is the evolutionary prototype of the canonical SUF system.
Equivalence of Freeze-dried and Liquid-frozen Formulations of MVA-BN as Smallpox and Mpox Vaccine
Authors: Greenberg Richard N , Schmidt Darja , Reichhardt Daniela , Roesch Siegfried , Vidojkovic Sanja , Maclennan Jane , Chen Liddy M , Gruenert Robert , Kreusel Christian , Weidenthaler Heinz , Meyer Thomas PH , Chaplin Paul
Published: March 2024

Orthopox virus-induced diseases such as smallpox and mpox (also known as monkeypox previously) remain a serious public health concern. Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) has been approved in its liquid-frozen (LF) formulation for prevention of smallpox and mpox in the US, Canada and EU. A freeze-dried (FD) formulation might confer additional benefits such as longer shelf life and less reliance on cold chain storage and transport, thus can better meet the potential challenge of large quantity vaccine deployment in emergency situations.

In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety and reactogenicity.

Strong vaccinia-specific humoral and cellular immune responses were induced by both formulations, with peak humoral responses at Week 6 and peak cellular responses at Week 2. At Week 6, geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At Week 2, geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly higher local reactions in the FD group. No vaccine related serious adverse events (SAEs) or vaccine related AE of special interest were reported.

The FD formulation of MVA-BN was shown to be equivalent to the LF formulation in immunogenicity, and comparable safety findings were observed from both formulations.

Clinical Trial Registration:NCT01668537

Highlights

Equivalence of MVA-BN freeze-dried and liquid-frozen formulations in immunogenicity MVA-BN FD and MVA-BN LF are comparable in clinical safety and reactogenicity Peak T cell responses were observed 2 weeks after the first vaccination
An essential and highly selective protein import pathway encoded by nucleus-forming phage
Authors: Morgan Chase J. , Enustun Eray , Armbruster Emily G. , Birkholz Erica A. , Prichard Amy , Forman Taylor , Aindow Ann , Wannasrichan Wichanan , Peters Sela , Inlow Koe , Shepherd Isabelle L. , Razavilar Alma , Chaikeeratisak Vorrapon , Adler Benjamin A. , Cress Brady F. , Doudna Jennifer A. , Pogliano Kit , Villa Elizabeth , Corbett Kevin D. , Pogliano Joe
Published: March 2024

Targeting proteins to specific subcellular destinations is essential in prokaryotes, eukaryotes, and the viruses that infect them. Chimalliviridae phages encapsulate their genomes in a nucleus-like replication compartment composed of the protein chimallin (ChmA) that excludes ribosomes and decouples transcription from translation. These phages selectively partition proteins between the phage nucleus and the bacterial cytoplasm. Currently, the genes and signals that govern selective protein import into the phage nucleus are unknown. Here we identify two components of this novel protein import pathway: a species-specific surface-exposed region of a phage intranuclear protein required for nuclear entry and a conserved protein, PicA, that facilitates cargo protein trafficking across the phage nuclear shell. We also identify a defective cargo protein that is targeted to PicA on the nuclear periphery but fails to enter the nucleus, providing insight into the mechanism of nuclear protein trafficking. Using CRISPRi-ART protein expression knockdown of PicA, we show that PicA is essential early in the chimallivirus replication cycle. Together our results allow us to propose a multistep model for the Protein Import Chimallivirus (PIC) pathway, where proteins are targeted to PicA by amino acids on their surface, and then licensed by PicA for nuclear entry. The divergence in the selectivity of this pathway between closely-related chimalliviruses implicates its role as a key player in the evolutionary arms race between competing phages and their hosts.

Significance Statement

The phage nucleus is an enclosed replication compartment built by Chimalliviridae phages that, similar to the eukaryotic nucleus, separates transcription from translation and selectively imports certain proteins. This allows the phage to concentrate proteins required for DNA replication and transcription while excluding DNA-targeting host defense proteins. However, the mechanism of selective trafficking into the phage nucleus is currently unknown. Here we determine the region of a phage nuclear protein that targets it for nuclear import and identify a conserved, essential nuclear shell-associated protein that plays a key role in this process. This work provides the first mechanistic model of selective import into the phage nucleus.
Functional Redundancy inCandida aurisCell Surface Adhesins Crucial for Cell-Cell Interaction and Aggregation
Authors: Wang Tristan W. , Sofras Dimitrios , Montelongo-Jauregui Daniel , Paiva Telmo O. , Carolus Hans , Dufrêne Yves F. , Alfaifi Areej A. , McCracken Carrie , Bruno Vincent M. , Van Dijck Patrick , Jabra-Rizk Mary Ann
Published: March 2024

Candida aurisis an emerging nosocomial fungal pathogen associated with life-threatening invasive disease due to its persistent colonization, high level of transmissibility and multi-drug resistance. Aggregative and non-aggregative growth phenotypes forC. aurisstrains with different biofilm forming abilities, drug susceptibilities and virulence characteristics have been described. Using comprehensive transcriptional analysis we identified key cell surface adhesins that were highly upregulated in the aggregative phenotype duringin vitroandin vivogrown biofilms using a mouse model of catheter infection. Phenotypic and functional evaluations of generated null mutants demonstrated crucial roles for the adhesins Als5 and Scf1 in mediating cell-cell adherence, coaggregation and biofilm formation. While individual mutants were largely non-aggregative, in combination cells were able to co-adhere and aggregate, as directly demonstrated by measuring cell adhesion forces using single-cell atomic force spectroscopy. This co-adherence indicates their role as complementary adhesins, which despite their limited similarity, may function redundantly to promote cell-cell interaction and biofilm formation. Functional diversity of cell wall proteins may be a form of regulation that provides the aggregative phenotype ofC. auriswith flexibility and rapid adaptation to the environment, potentially impacting persistence and virulence.
Microbial cancer immunotherapy reprograms hematopoiesis to enhance anti-tumor immunity
Authors: Daman Andrew W. , Antonelli Anthony Claude , Redelman-Sidi Gil , Paddock Lucinda , Cheong Jin Gyu , Jurado Leonardo F. , Benjamin Anna , Jiang Song , Ahimovic Dughan , Khayat Shireen , Bale Michael J. , Loutochin Oleg , McPherson Victor A. , Pe’er Dana , Divangahi Maziar , Pietzak Eugene , Josefowicz Steven Z. , Glickman Michael S.
Published: March 2024

Mycobacterium bovisBCG is the vaccine against tuberculosis and an immunotherapy for bladder cancer. When administered intravenously, BCG reprograms bone marrow hematopoietic stem and progenitor cells (HSPCs), leading to heterologous protection against infections. Whether HSPC-reprogramming contributes to the anti-tumor effects of BCG administered into the bladder is unknown. We demonstrate that BCG administered in the bladder in both mice and humans reprograms HSPCs to amplify myelopoiesis and functionally enhance myeloid cell antigen presentation pathways. Reconstitution of naive mice with HSPCs from bladder BCG-treated mice enhances anti-tumor immunity and tumor control, increases intratumor dendritic cell infiltration, reprograms pro-tumorigenic neutrophils, and synergizes with checkpoint blockade. We conclude that bladder BCG acts systemically, reprogramming HSPC-encoded innate immunity, highlighting the broad potential of modulating HSPC phenotypes to improve tumor immunity.

Graphical Abstract
Space-time dynamics of genome replication studied with super-resolved microscopy
Authors: Gelléri Márton , Sterr Michael , Strickfaden Hilmar , Cremer Christoph , Cremer Thomas , Cremer Marion
Published: March 2024

Genome replication requires duplication of the complete set of DNA sequences together with nucleosomes and epigenetic signatures. Notwithstanding profound knowledge on mechanistic details of DNA replication, major problems of genome replication have remained unresolved. In this perspective article, we consider the accessibility of replication machines to all DNA sequences in due course, the maintenance of functionally important positional and structural features of chromatid domains during replication, and the rapid transition of CTs into prophase chromosomes with two chromatids. We illustrate this problem with EdU pulse-labeling (10 min) and chase experiments (80 min) performed with mouse myeloblast cells. Following light optical serial sectioning of nuclei with 3D structured illumination microscopy (SIM), seven DNA intensity classes were distinguished as proxies for increasing DNA compaction. In nuclei of cells fixed immediately after the pulse-label, we observed a relative under-representation of EdU-labeled DNA in low DNA density classes, representing the active nuclear compartment (ANC), and an over-representation in high density classes representing the inactive nuclear compartment (INC). Cells fixed after the chase revealed an even more pronounced shift to high DNA intensity classes. This finding contrasts with previous studies of the transcriptional topography demonstrating an under-representation of epigenetic signatures for active chromatin and RNAPII in high DNA intensity classes and their over-representation in low density classes. We discuss these findings in the light of current models viewing CDs either as structural chromatin frameworks or as phase-separated droplets, as well as methodological limitations that currently prevent an integration of this contrasting evidence for the spatial nuclear topography of replication and transcription into a common framework of the dynamic nuclear architecture.
Inferring nonequilibrium thermodynamics from tilted equilibrium using information-geometric Legendre transform
Authors: Ohga Naruo , Ito Sosuke
Published: March 2024

Nonstationary thermodynamic quantities depend on the full details of nonstationary probability distributions, making them difficult to measure directly in experiments and numerics. We propose a method to infer thermodynamic quantities in relaxation processes by measuring only a few observables, using additional information obtained from measurements in tilted equilibrium, i.e., equilibrium with external fields applied. Our method is applicable to arbitrary classical stochastic systems, possibly underdamped, that relax to equilibrium. The method allows us to compute the exact value of the minimum entropy production (EP) compatible with the nonstationary observations, giving a tight lower bound on the true EP. Under a certain additional condition, it also allows the inference of the EP rate, thermodynamic forces, and a constraint on relaxation paths. Our method uses a Legendre transform of EP at the level of probability distributions, which we develop based on a similar Legendre transform in information geometry.

Published by the American Physical Society
2024
Training in social intelligence: an augmenter for performance and successful leadership
Authors: Sanwal Tanushree
Published: March 2024

Purpose

The purpose of this study is to investigate the importance of training in social intelligence in the context of effective leadership and enhanced performance. The study investigates how training in social intelligence can assist personnel in enhancing their social and emotional competencies through various methods which in turn can boost their performance and leadership skills.

Design/methodology/approach

This article presents a compilation of interview perspectives from human resources (HR) practitioners and researchers, offering comprehensive training methods that can be implemented in organizations to boost the social intelligence of employees and employers. The views were gathered through telephone and face-to-face interaction with the practitioners.

Findings

Various methods for training in social intelligence for enhancing social intelligence are proposed by the author in this paper, drawing on the perspectives of both practitioners and researchers.

Research limitations/implications

Further studies could test conceptual models by using longitudinal studies’ data, which gives the study more accuracy and supports generalizing the results.

Practical implications

Enhanced performance and Effective leadership can be achieved in the organization if proper training in social intelligence is given to the personnel.

Originality/value

This study is one of the first studies that integrates leadership, performance, and social intelligence and its dimensions in one framework. This study concludes that enhanced employee performance and effective leadership can be achieved by developing social intelligence in personnel through various training methods.
Fact-checking of political information about the Russo-Ukrainian conflict
Authors: Savolainen Reijo
Published: March 2024

Purpose

To elaborate the nature of fact-checking in the domain of political information by examining how fact-checkers assess the validity of claims concerning the Russo-Ukrainian conflict and how they support their assessments by drawing on evidence acquired from diverse sources of information.

Design/methodology/approach

Descriptive quantitative and qualitative content analysis of 128 reports written by the fact-checkers of Snopes – an established fact-checking organisation – during the period of 24 February 2022 – 28 June, 2023. For the analysis, nine evaluation grounds were identified, most of them inductively from the empirical material. It was examined how the fact-checkers employed such grounds while assessing the validity of claims and how the assessments were bolstered by evidence acquired from information sources such as newspapers.

Findings

Of the 128 reports, the share of assessments indicative of the invalidity of the claims was 54.7%, while the share of positive ratings was 26.7%. The share of mixed assessments was 15.6%. In the fact-checking, two evaluation grounds, that is, the correctness of information and verifiability of an event presented in a claim formed the basis for the assessment. Depending on the topic of the claim, grounds such as temporal and spatial compatibility, as well as comparison by similarity and difference occupied a central role. Most popular sources of information offering evidence for the assessments include statements of government representatives, videos and photographs shared in social media, newspapers and television programmes.

Research limitations/implications

As the study concentrated on fact-checking dealing with political information about a specific issue, the findings cannot be extended to concern the fact-checking practices in other contexts.

Originality/value

The study is among the first to characterise how fact-checkers employ evaluation grounds of diverse kind while assessing the validity of political information.