bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing probiotic impact: engineering
Saccharomyces boulardii
for optimal acetic acid production and gastric passage tolerance
Authors: de Carvalho Bruna Trindade , Subotić Ana , Vandecruys Paul , Deleu Sara , Vermeire Séverine , Thevelein Johan M. 
Published: May 2024

ABSTRACT

Saccharomyces boulardii
has been a subject of growing interest due to its potential as a probiotic microorganism with applications in gastrointestinal health, but the molecular cause for its probiotic potency has remained elusive. The recent discovery that
S. boulardii
contains unique mutations causing high acetic acid accumulation and inhibition of bacterial growth provides a possible clue. The natural
S. boulardii
isolates Sb.P and Sb.A are homozygous for the recessive mutation
whi2
S270*
and accumulate unusually high amounts of acetic acid, which strongly inhibit bacterial growth. However, the homozygous
whi2
S270*
mutation also leads to acetic acid sensitivity and acid sensitivity in general. In the present study, we have constructed a new
S. boulardii
strain, derived from the widely therapeutically used CMCN I-745 strain (isolated from the pharmaceutical product Enterol), producing even higher levels of acetic acid while keeping the same tolerance toward low pH as the parent Enterol (ENT) strain. This newly engineered strain, named ENT3, has a homozygous deletion of
ACH1
and strong overexpression of
ALD4
. It is also able to accumulate much higher acetic acid concentrations when growing on low glucose levels, in contrast to the ENT wild-type and Sb.P strains. Moreover, we show the antimicrobial capacity of ENT3 against gut pathogens
in vitro
and observed that higher acetic acid production might correlate with better persistence in the gut in healthy mice. These findings underscore the possible role of the unique acetic acid production and its potential for improvement of the probiotic action of
S. boulardii
.

IMPORTANCE

Superior variants of the probiotic yeast
Saccharomyces boulardii
produce high levels of acetic acid, which inhibit the growth of bacterial pathogens. However, these strains also show increased acid sensitivity, which can compromise the viability of the cells during their passage through the stomach. In this work, we have developed by genetic engineering a variant of
Saccharomyces boulardii
that produces even higher levels of acetic acid and does not show enhanced acid sensitivity. We also show that the
S. boulardii
yeasts with higher acetic acid production persist longer in the gut, in agreement with a previous work indicating competition between probiotic yeast and bacteria for residence in the gut.
On the evolution of chromosomal regions with high gene strand bias in bacteria
Authors: Tomasch Jürgen , Kopejtka Karel , Shivaramu Sahana , Mujakić Izabela , Koblížek Michal 
Published: May 2024

ABSTRACT

On circular bacterial chromosomes, the majority of genes are coded on the leading strand. This gene strand bias (GSB) ranges from up to 85% in some Bacillota to a little more than 50% in other phyla. The factors determining the extent of the strand bias remain to be found. Here, we report that species in the phylum Gemmatimonadota share a unique chromosome architecture, distinct from neighboring phyla: in a conserved 600-kb region around the terminus of replication, almost all genes were located on the leading strands, while on the remaining part of the chromosome, the strand preference was more balanced. The high strand bias (HSB) region harbors the rRNA clusters, core, and highly expressed genes. Selective pressure for reduction of collisions with DNA replication to minimize detrimental mutations can explain the conservation of essential genes in this region. Repetitive and mobile elements are underrepresented, suggesting reduced recombination frequency by structural isolation from other parts of the chromosome. We propose that the HSB region forms a distinct chromosomal domain. Gemmatimonadota chromosomes evolved mainly by expansion through horizontal gene transfer and duplications outside of the ancient high strand bias region. In support of our hypothesis, we could further identify two Spiroplasma strains on a similar evolutionary path.

IMPORTANCE

On bacterial chromosomes, a preferred location of genes on the leading strand has evolved to reduce conflicts between replication and transcription. Despite a vast body of research, the question why bacteria show large differences in their gene strand bias is still not solved. The discovery of “hybrid” chromosomes in different phyla, including Gemmatimonadota, in which a conserved high strand bias is found exclusively in a region at
ter
, points toward a role of nucleoid structure, additional to replication, in the evolution of strand preferences. A fine-grained structural analysis of the ever-increasing number of available bacterial genomes could help to better understand the forces that shape the sequential and spatial organization of the cell’s information content.
Phage protein Gp11 blocks
Staphylococcus aureus
cell division by inhibiting peptidoglycan biosynthesis
Authors: Xu Qi , Tang Li , Liu Weilin , Xu Neng , Hu Yangbo , Zhang Yong , Chen Shiyun 
Published: May 2024

ABSTRACT

Phages and bacteria have a long history of co-evolution. However, these dynamics of phage-host interactions are still largely unknown; identification of phage inhibitors that remodel host metabolism will provide valuable information for target development for antimicrobials. Here, we perform a comprehensive screen for early-gene products of ΦNM1 that inhibit cell growth in
Staphylococcus aureus
. A small membrane protein, Gp11, with inhibitory effects on
S. aureus
cell division was identified. A bacterial two-hybrid library containing 345 essential
S. aureus
genes was constructed to screen for targets of Gp11, and Gp11 was found to interact with MurG and DivIC. Defects in cell growth and division caused by Gp11 were dependent on MurG and DivIC, which was further confirmed using CRISPRi hypersensitivity assay. Gp11 interacts with MurG, the protein essential for cell wall formation, by inhibiting the production of lipid II to regulate peptidoglycan (PG) biosynthesis on the cell membrane. Gp11 also interacts with cell division protein DivIC, an essential part of the division machinery necessary for septal cell wall assembly, to disrupt the recruitment of division protein FtsW. Mutations in Gp11 result in loss of its ability to cause growth defects, whereas infection with phage in which the
gp11
gene has been deleted showed a significant increase in lipid II production in
S. aureus
. Together, our findings reveal that a phage early-gene product interacts with essential host proteins to disrupt PG biosynthesis and block
S. aureus
cell division, suggesting a potential pathway for the development of therapeutic approaches to treat pathogenic bacterial infections.

IMPORTANCE

Understanding the interplay between phages and their hosts is important for the development of novel therapies against pathogenic bacteria. Although phages have been used to control methicillin-resistant
Staphylococcus aureus
infections, our knowledge related to the processes in the early stages of phage infection is still limited. Owing to the fact that most of the phage early proteins have been classified as hypothetical proteins with uncertain functions, we screened phage early-gene products that inhibit cell growth in
S. aureus
, and one protein, Gp11, selectively targets essential host genes to block the synthesis of the peptidoglycan component lipid II, ultimately leading to cell growth arrest in
S. aureus
. Our study provides a novel insight into the strategy by which Gp11 blocks essential host cellular metabolism to influence phage-host interaction. Importantly, dissecting the interactions between phages and host cells will contribute to the development of new and effective therapies to treat bacterial infections.
Geochemical and petrological diversity of a transcrustal magmatic system driven by mushy magma mixing: Insights from the Triassic dike swarms in East Kunlun orogen, northern Tibetan Plateau
Authors: Xiong Fuhao , Yan Dongdong , Ma Changqian , Hou Mingcai , Wang Mingchi , Huang Hu , Wang Wei 
Published: May 2024

Abstract
Geochemical and petrological diversity within transcrustal magmatic systems usually reflects the magma properties and magmatic processes and thus is critical to understanding the origin of magmatic complexes and the evolution of continental crust. Herein, we present an integrated study on the petrology, mineralogy, geochronology, geochemistry, and Sr-Nd-Hf isotopes of Triassic mafic-felsic dikes in the East Kunlun orogenic belt, northern Tibetan Plateau, to elucidate the nature and evolution of the transcrustal magmatic system. The studied dikes intruding into the granodiorite pluton (ca. 235–233 Ma) comprise coeval ca. 220–218 Ma gabbroic diorite porphyry, diorite porphyry, granodiorite porphyry, and alkali-feldspar granite, resembling composite dike swarms. The macrocrysts in these dikes show various zoning patterns, indicating episodic magma recharge and crystal resorption. The compositional gap between the intermediate-mafic dikes (SiO2 = 52.9–67.8 wt%) and the granitic dikes (SiO2 &gt; 75 wt%), as well as their homogeneous whole-rock Sr-Nd isotopes, with (87Sr/86Sr)i = 0.708387–0.710995 and εNd(t) = −5.83 to −4.34, but variable zircon Lu-Hf isotopes, i.e., εHf(t) = −7.67 to −0.36, demonstrates that magma mixing rather than cogenetic fractional crystallization accounts for their origin. In combination with thermobarometric insights, these results suggest that the mafic and felsic parental magmas originating from an enriched lithospheric mantle and ancient continental crust, respectively, were ultimately emplaced and stagnated at varying crustal depths (~22–30 km and 8–17 km). Subsequently, the felsic magma mush was replenished and rejuvenated by the underplated mafic magma, leading to varying degrees of crystal-melt and/or melt-melt mixing. This mush-facilitated crust-mantle magma mixing is an important mechanism accounting for the compositional diversity of the transcrustal magmatic system.
A sea of change: Tracing parasitic dynamics through the past millennia in the northern Adriatic, Italy
Authors: Fitzgerald Erin , Ryan Delaney , Scarponi Daniele , Huntley John Warren 
Published: May 2024

Abstract
Our study uses data from Holocene core samples and modern death assemblages to understand how human-induced environmental change in the northern Adriatic Sea (Italy) may have affected parasite-host dynamics in the economically important bivalve Chamelea gallina. Thirty-one radiocarbon dates confirm temporal distinctness between the periods before and after the onset of significant human influence and confirm that trematode prevalence has decreased by an order of magnitude over the past ~2 k.y. The median number of parasite-induced pits per bivalve host and parasite aggregation has also decreased significantly, signaling a substantial decrease in the effective population size of digenean trematodes. Gaussian finite mixture modeling of pit size does not support the hypothesis of parasite extinction. Combined, these results indicate the (potentially ongoing) collapse of parasite-host interactions in C. gallina in concert with human influence on the Adriatic and its transition to an “urban sea.”
Exploring the value of routinely collected data on EQ-5D-5L and other electronic patient-reported outcome measures as prognostic factors in adults with advanced non-small cell lung cancer receiving immunotherapy
Authors: Liao Kuan , Wong David C , Gomes Fabio , Faivre-Finn Corinne , Moliner Laura , Sperrin Matthew , Yorke Janelle , van der Veer Sabine N 
Published: May 2024

ObjectiveInvestigate whether routinely collected electronic patient-reported outcome measures (ePROMs) add prognostic value to clinical and tumour characteristics for adults with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy.Methods and analysisWe retrospectively analysed data from adults with advanced NSCLC commencing immunotherapy between April 2019 and June 2022. Prognostic factors were ePROMs on quality of life (EuroQoL five-dimension five-level (EQ-5D-5L); EuroQoL Visual Analogue Scale (EQ-VAS)) and symptoms (patient-reported version of the Common Terminology Criteria for Adverse Events v5.0) completed at baseline and the first follow-up. We performed Cox proportional hazard regression for overall survival and time-to-progression as outcomes, and logistic regression for the onset of severe treatment toxicities (grade ≥3).ResultsWe included 379 patients; 161 (42.5%) completed ePROMs at baseline. Median overall survival and time-to-progression were 13.5 months (95% CI 11.3 to 16.7) and 10.5 months (95% CI 8.8 to 13.7), respectively. 36 (9.5%) experienced severe treatment toxicities during follow-up. Patients with lower EQ-5D-5L utility scores (HR per 0.1 unit increase 0.84, 95% CI 0.74 to 0.95) and higher symptom burden (HR 1.11; 95% CI 1.04 to 1.19) had poorer overall survival. This was also true for those with decreased EQ-VAS and increased symptom burden between baseline and the first follow-up. Lastly, only decreased EQ-5D-5L utility scores between baseline and the first follow-up were associated with shorter time-to-progression.ConclusionePROMs may add prognostic value to clinical and tumour characteristics for overall survival in adults with advanced NSCLC receiving immunotherapy.
Serum levels of endothelial glycocalyx constituents in women at 20 weeks' gestation who later develop gestational diabetes mellitus compared to matched controls: a pilot study
Authors: Long David S , Hou Weilin , Taylor Rennae S , McCowan Lesley M E 
Published: May 2024

ObjectivesThe aim of this pilot study was to determine the serum concentration of heparan sulfate, hyaluronan, chondroitin sulfate and syndecan-1 and if these serum concentrations can be used to identify women at 20 weeks' gestation who later develop gestational diabetes mellitus (GDM).DesignNested case–control study from Auckland, New Zealand participants in the prospective cohort Screening for Pregnancy Endpoints study.SettingAuckland, New Zealand.Participants20 pregnant women (70% European, 15% Indian, 10% Asian, 5% Pacific Islander) at 20 weeks' gestation without any hypertensive complications who developed GDM by existing New Zealand criteria defined as a fasting glucose ≥5.5 mmol/L and/or 2 hours ≥9.0 mmol/L after a 75 g Oral Glucose Tolerance Test. Women not meeting these criteria were excluded from this study. The patients with GDM were matched with 20 women who had uncomplicated pregnancies and negative screening for GDM and matched for ethnicity, maternal age and BMI.Primary and secondary outcome measuresThe primary measures were the serum concentrations of syndecan-1, heparan sulfate, hyaluronan and chondroitin sulfate determined by quantitative ELISA. There were no secondary outcome measures.ResultsBinary logistic regression was performed to determine if serum concentrations of endothelial glycocalyx layer constituents in women at 20 weeks' gestation would be useful in predicting the subsequent diagnosis of GDM. The model was not statistically significant χ2=12.5, df=8, p=0.13, which indicates that the model was unable to distinguish between pregnant women at 20 weeks' gestation who later developed GDM and those who did not.ConclusionsSerum concentrations of syndecan-1, heparan sulfate, hyaluronan and chondroitin sulfate in pregnant women at 20 weeks' gestation were not associated with later development of GDM. To further explore whether there is any relationship between endothelial glycocalyx constituents and GDM, the next step is to evaluate serum concentrations at the time diagnosis of GDM.
Trends in activities of daily living disability in a large sample of community-dwelling Chinese older adults in Hong Kong: an age-period-cohort analysis
Authors: Yu Ruby , Wong Moses , Chang Billy , Lai Xin , Lum C M , Auyeung T W , Lee Jenny , Tsoi Kelvin , Lee Ruby , Woo Jean 
Published: May 2024

BackgroundTo examine the trends in activities of daily living (ADL) disability in older Chinese adults in Hong Kong between 2001 and 2012.MethodsUsing data from the Elderly Health Centres (EHCs) of the Department of Health comprising a total of 54 808 community-dwelling Chinese adults aged ≥65 years in 1 early cohort (1904–1917) and 10 3-year birth cohorts (1918–1920, 1921–1923, 1924–1926, 1927–1929, 1930–1932, 1933–1935, 1936–1938, 1939–1941, 1942–1944, 1945–1947), we examined trends in ADL disability by using age-period-cohort (APC) models. ADL disability was defined as being unable to perform at least 1 of 7 ADL activities (bathing, dressing, toileting, transferring, feeding, grooming, walking) independently. Cross-classified random-effects logistic regressions were performed for each of the APC trends with adjustment for age, period, cohort, sociodemographic, lifestyle, comorbidity and self-rated health.ResultsThe mean age of the cohort was 70.9±4.7 (range 65–99) years. The prevalence rate of ADL disability was 1.6%. ADL disability increased with age (p<0.001) and the gradient of the increase was steeper in the older age groups. At the same age, women (1.7%) were more likely to report ADL disability than men (1.4%, p=0.001). For both genders, there was an increase in ADL disability between 2003 and 2012; adjustment for age, cohort and other covariates has diminished the trends observed among men. There was no cohort effect in ADL disability.ConclusionsADL disability in older adults has increased over the last decade. Further study is required to identify possible causes behind the disability trends.
11: AN EVIDENCE BASED APPROACH TO IMPROVEMENT OF TIME VISIT IN THE BIGGEST UNIVERSITY POLICLINIC TABRIZ UNIVERSITY OF MEDICAL SCIENCES EXPERIENCE
Authors: Bakhshian Fariba , Beirami Hossein Jabbari , Beirami Saba Jabbari , Fatollahi Seiied Yaaghoob 
Published: May 2024

Background and aims:Today health systems all around the world have paid more attention to the concept of patient Time visit. This duration is one of the most valuable resources in healthcare and is considered as an important subject in the quality of services. This study has been conducted with evidence based approach in one of the biggest polyclinics of Tabriz University of Medical Sciences (TUMS) aiming in order to increasing patients' visit time.Methods:The first stage of study started with utilization, cost, and satisfaction data review –environmental analysis –problem prioritize - systematically searches- focus groups and intervention selection. In the second stage data of visit time (from time of entering to examination room until exit) were gathered and analyzed using simple method of chronometry by secretaries of wards and under supervision of experts in two time intervals of winter 2015 with sample of 850 patients and spring 2016 with sample of 421 patients.Results:Mean visit duration has increased from 6.04 minutes to more than 14.6 minutes and doubled improvement was observed in most of specialties and even in generalists. On the other hand the number of physicians employed in the center shows 4 times increase, where physicians with benefits of visit promotion have increased from 30% to about 50%, so all subsequences have led to increase in satisfaction of people and the number of service receivers has increased from 15000 to 70000 in month, and the center has reached positive financial balance.Conclusion:Following instructions of evolution plan we witnessed doubling of visit duration and qualitative and quantitative promotion of services comparing with the past, where in previous studies of the country we had 4.7, 7.6, and 8 minutes comparing with numbers above 23 minutes in America. Therefore it would not be surprising to expect significant improvements and reach standards (20 minutes) if there are on-time payments for physicians' receivables as well as managerial efforts with evidence based approach.
112: SITUATION OF RELAPSING FEVER BORRELIOSIS IN BIJAR, IRAN
Authors: Kassiri Hamid , Dostifar Kobra , Karimi Mansor 
Published: May 2024

Background and aims:Tick-Borne Relapsing Fever (TBRF) is a zoonotic disease involving many species of rodents and small mammals in widely distributed areas throughout the world. We describe the epidemiological and demographic characters of found cases of TBRF in the Bijar County, and briefly review it for preventing this illness in the year of 2007–2008.Methods:A confirmed patient was defined as a person who had both febrile illness and detection of spirochetes by Wright-Giemsa or dark-field microscopy in a peripheral blood smear. All patients were asked to complete a questionnaire including demographic characteristics and clinical and epidemiological data of TBRF. Data was analyzed using SPSS. Eleven cases have been reported.Results:There were 5 cases (45.4%) of the patients younger than 10 years. Of the patients, 63.6% occurred in summer. All cases developed during the months of May to October. All of the reported cases were living in rural areas. Fever and chills, the most common symptoms, occurred in all patients. Recurrent fever occurred in 54.5% cases. All of the cases were cured according the national guideline for TBRF treatment. Only 18.2% of the patients were hospitalized. No patients this study died of TBRF. Most (54.5%) of the cases were students. Approximately 72.7% of the patients were keeping cattle and sheep near or inside their homes.Conclusion:As demonstrated, TBRF is a considerable public health concern, especially for children and students living in Bijar County. Considering the epidemiology of the disease, new control measures should be established.