bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histidine kinase NahK regulates pyocyanin production through the PQS system
Authors: Mendoza Alicia G. , Guercio Danielle , Smiley Marina K. , Sharma Gaurav K. , Withorn Jason M. , Hudson-Smith Natalie V. , Ndukwe Chika , Dietrich Lars E. P. , Boon Elizabeth M. 
Published: January 2024

ABSTRACT

Many bacterial histidine kinases work in two-component systems that combine into larger multi-kinase networks. NahK is one of the kinases in the GacS Multi-Kinase Network (MKN), which is the MKN that controls biofilm regulation in the opportunistic pathogen
Pseudomonas aeruginosa
. This network has also been associated with regulating many virulence factors
P. aeruginosa
secretes to cause disease. However, the individual role of each kinase is unknown. In this study, we identify NahK as a novel regulator of the phenazine pyocyanin (PYO). Deletion of
nahK
leads to a fourfold increase in PYO production, almost exclusively through upregulation of phenazine operon two (
phz2
). We determined that this upregulation is due to mis-regulation of all
P. aeruginosa
quorum-sensing (QS) systems, with a large upregulation of the
Pseudomonas
quinolone signal system and a decrease in production of the acyl-homoserine lactone-producing system,
las
. In addition, we see differences in expression of quorum-sensing inhibitor proteins that align with these changes. Together, these data contribute to understanding how the GacS MKN modulates QS and virulence and suggest a mechanism for cell density-independent regulation of quorum sensing.

IMPORTANCE

Pseudomonas aeruginosa
is a Gram-negative bacterium that establishes biofilms as part of its pathogenicity.
P. aeruginosa
infections are associated with nosocomial infections. As the prevalence of multi-drug-resistant
P. aeruginosa
increases, it is essential to understand underlying virulence molecular mechanisms. Histidine kinase NahK is one of several kinases in
P. aeruginosa
implicated in biofilm formation and dispersal. Previous work has shown that the nitric oxide sensor, NosP, triggers biofilm dispersal by inhibiting NahK. The data presented here demonstrate that NahK plays additional important roles in the
P. aeruginosa
lifestyle, including regulating bacterial communication mechanisms such as quorum sensing. These effects have larger implications in infection as they affect toxin production and virulence.
PQS and pyochelin in
Pseudomonas aeruginosa
share inner membrane transporters to mediate iron uptake
Authors: Zhang Heng , Yang Jianshe , Cheng Juanli , Zeng Jing , Ma Xin , Lin Jinshui 
Published: January 2024

ABSTRACT

Bacteria absorb different forms of iron through various channels to meet their needs. Our previous studies have shown that TseF, a type VI secretion system effector for Fe uptake, facilitates the delivery of outer membrane vesicle-associated
Pseudomonas
quinolone signal (PQS)-Fe
3+
to bacterial cells by a process involving the Fe(III) pyochelin receptor FptA and the porin OprF. However, the form in which the PQS-Fe
3+
complex enters the periplasm and how it is moved into the cytoplasm remain unclear. Here, we first demonstrate that the PQS-Fe
3+
complex enters the cell directly through FptA or OprF. Next, we show that inner membrane transporters such as FptX, PchHI, and FepBCDG are not only necessary for
Pseudomonas aeruginosa
to absorb PQS-Fe
3+
and pyochelin (PCH)-Fe
3+
but are also necessary for the virulence of
P. aeruginosa
toward
Galleria mellonella
larvae. Furthermore, we suggest that the function of PQS-Fe
3+
(but not PQS)-mediated quorum-sensing regulation is dependent on FptX, PchHI, and FepBCDG. Additionally, the findings indicate that unlike FptX, neither FepBCDG nor PchHI play roles in the autoregulatory loop involving PchR, but further deletion of
fepBCDG
and
pchHI
can reverse the inactive PchR phenotype caused by
fptX
deletion and reactivate the expression of the PCH pathway genes under iron-limited conditions. Finally, this work identifies the interaction between FptX, PchHI, and FepBCDG, indicating that a larger complex could be formed to mediate the uptake of PQS-Fe
3+
and PCH-Fe
3+
. These results pave the way for a better understanding of the PQS and PCH iron absorption pathways and provide future directions for research on tackling
P. aeruginosa
infections.

IMPORTANCE

Pseudomonas aeruginosa
has evolved a number of strategies to acquire the iron it needs from its host, with the most common being the synthesis, secretion, and uptake of siderophores such as pyoverdine, pyochelin, and the quorum-sensing signaling molecule
Pseudomonas
quinolone signal (PQS). However, despite intensive studies of the siderophore uptake pathways of
P. aeruginosa
, our understanding of how siderophores transport iron across the inner membrane into the cytoplasm is still incomplete. Herein, we reveal that PQS and pyochelin in
P. aeruginosa
share inner membrane transporters such as FptX, PchHI, and FepBCDG to mediate iron uptake. Meanwhile, PQS and pyochelin-mediated signaling operate to a large extent via these inner membrane transporters. Our study revealed the existence of shared uptake pathways between PQS and pyochelin, which could lead us to reexamine the role of these two molecules in the iron uptake and virulence of
P. aeruginosa
.
Major urinary protein (
Mup
) gene family deletion drives sex-specific alterations in the house-mouse gut microbiota
Authors: Real Madalena V. F. , Colvin Melanie S. , Sheehan Michael J. , Moeller Andrew H. 
Published: January 2024

ABSTRACT

The gut microbiota is shaped by host metabolism. In house mice (
Mus musculus
), major urinary protein (MUP) pheromone production represents a considerable energy investment, particularly in sexually mature males. Deletion of the
Mup
gene family shifts mouse metabolism toward an anabolic state, marked by lipogenesis, lipid accumulation, and body mass increases. Given the metabolic implications of MUPs, they may also influence the gut microbiota. Here, we investigated the effect of a deletion of the
Mup
gene family on the gut microbiota of sexually mature mice. Shotgun metagenomics revealed distinct taxonomic and functional profiles between wild-type and knockout males but not females. Deletion of the
Mup
gene cluster significantly reduced diversity in microbial families and functions in male mice. Additionally, a species of
Ruminococcaceae
and several microbial functions, such as transporters involved in vitamin B
5
acquisition, were significantly depleted in the microbiota of
Mup
knockout males. Altogether, these results show that MUPs significantly affect the gut microbiota of house mouse in a sex-specific manner.

IMPORTANCE

The community of microorganisms that inhabits the gastrointestinal tract can have profound effects on host phenotypes. The gut microbiota is in turn shaped by host genes, including those involved with host metabolism. In adult male house mice, expression of the major urinary protein (
Mup
) gene cluster represents a substantial energy investment, and deletion of the
Mup
gene family leads to fat accumulation and weight gain in males. We show that deleting
Mup
genes also alters the gut microbiota of male, but not female, mice in terms of both taxonomic and functional compositions. Male mice without
Mup
genes harbored fewer gut bacterial families and reduced abundance of a species of
Ruminococcaceae
, a family that has been previously shown to reduce obesity risk. Studying the impact of the
Mup
gene family on the gut microbiota has the potential to reveal the ways in which these genes affect host phenotypes.
Analysis of ‘One in a Million’ primary care consultation conversations using natural language processing
Authors: Pyne Yvette , Wong Yik Ming , Fang Haishuo , Simpson Edwin 
Published: January 2024

BackgroundModern patient electronic health records form a core part of primary care; they contain both clinical codes and free text entered by the clinician. Natural language processing (NLP) could be employed to generate these records through ‘listening’ to a consultation conversation.ObjectivesThis study develops and assesses several text classifiers for identifying clinical codes for primary care consultations based on the doctor–patient conversation. We evaluate the possibility of training classifiers using medical code descriptions, and the benefits of processing transcribed speech from patients as well as doctors. The study also highlights steps for improving future classifiers.MethodsUsing verbatim transcripts of 239 primary care consultation conversations (the ‘One in a Million’ dataset) and novel additional datasets for distant supervision, we trained NLP classifiers (naïve Bayes, support vector machine, nearest centroid, a conventional BERT classifier and few-shot BERT approaches) to identify the International Classification of Primary Care-2 clinical codes associated with each consultation.ResultsOf all models tested, a fine-tuned BERT classifier was the best performer. Distant supervision improved the model’s performance (F1 score over 16 classes) from 0.45 with conventional supervision with 191 labelled transcripts to 0.51. Incorporating patients’ speech in addition to clinician’s speech increased the BERT classifier’s performance from 0.45 to 0.55 F1 (p=0.01, paired bootstrap test).ConclusionsOur findings demonstrate that NLP classifiers can be trained to identify clinical area(s) being discussed in a primary care consultation from audio transcriptions; this could represent an important step towards a smart digital assistant in the consultation room.
ChatGPT in glioma adjuvant therapy decision making: ready to assume the role of a doctor in the tumour board?
Authors: Haemmerli Julien , Sveikata Lukas , Nouri Aria , May Adrien , Egervari Kristof , Freyschlag Christian , Lobrinus Johannes A , Migliorini Denis , Momjian Shahan , Sanda Nicolae , Schaller Karl , Tran Sebastien , Yeung Jacky , Bijlenga Philippe 
Published: January 2024

ObjectiveTo evaluate ChatGPT‘s performance in brain glioma adjuvant therapy decision-making.MethodsWe randomly selected 10 patients with brain gliomas discussed at our institution’s central nervous system tumour board (CNS TB). Patients’ clinical status, surgical outcome, textual imaging information and immuno-pathology results were provided to ChatGPT V.3.5 and seven CNS tumour experts. The chatbot was asked to give the adjuvant treatment choice, and the regimen while considering the patient’s functional status. The experts rated the artificial intelligence-based recommendations from 0 (complete disagreement) to 10 (complete agreement). An intraclass correlation coefficient agreement (ICC) was used to measure the inter-rater agreement.ResultsEight patients (80%) met the criteria for glioblastoma and two (20%) were low-grade gliomas. The experts rated the quality of ChatGPT recommendations as poor for diagnosis (median 3, IQR 1–7.8, ICC 0.9, 95% CI 0.7 to 1.0), good for treatment recommendation (7, IQR 6–8, ICC 0.8, 95% CI 0.4 to 0.9), good for therapy regimen (7, IQR 4–8, ICC 0.8, 95% CI 0.5 to 0.9), moderate for functional status consideration (6, IQR 1–7, ICC 0.7, 95% CI 0.3 to 0.9) and moderate for overall agreement with the recommendations (5, IQR 3–7, ICC 0.7, 95% CI 0.3 to 0.9). No differences were observed between the glioblastomas and low-grade glioma ratings.ConclusionsChatGPT performed poorly in classifying glioma types but was good for adjuvant treatment recommendations as evaluated by CNS TB experts. Even though the ChatGPT lacks the precision to replace expert opinion, it may serve as a promising supplemental tool within a human-in-the-loop approach.
Differences in College Lecturers’ Ratings of Principals Instructional Leadership: A Jamaican Perspective.
Authors: Nevins-Bennett Cerease 
Published: January 2024

The purpose of this quantitative study is to determine how lecturers rated their principals as instructional leaders and to examine the differences in lecturers’ ratings of principals’ instructional leadership based on the demographic characteristics of gender, age range, lecturing status, number of years current principals have been employed to the colleges. and the highest level of educational attainment of the current principals. A survey that adopted the Principal Instructional Management Rating Scale (PIMRS) was used to collect data from 170 participants purposively. Overall, lecturers had moderately high ratings of principals’ instructional leadership within the colleges. There were no statistically significant differences in the ratings of lecturers based on age range and the number of years the current principal has been employed within the colleges. Male lecturers rated their principal higher than female lecturers on the dimension of creating a positive college climate. Adjunct lecturers gave their principals a higher rating than full-time lecturers on the dimension of managing instructional programs. Principals that had a master’s degree as their highest educational attainment were rated higher by the lecturers on the dimension of defining the college mission. This study contributes to the body of knowledge by filling the gap at the college level.
Exploring Socio-Economics and Its Role in the Oral Health Care of Patients in A Philippine Government Hospital
Authors: Alas Carmi Angeline , Candelaria Emilio Paul , Canlas Jocelyn , Patacsil Jaya Grace , Malang Bernandino P. 
Published: January 2024

Despite the availability of dental services and educational programs, as well as, established national health system responses, and oral health interventions and procedures, oral health problems (dental caries, gum diseases and unmet dental needs) persist in the Philippines. The aim of this study was to investigate the socioeconomic factors in terms of sex, age, marital status, educational attainment, occupation, and monthly income and their effect on the oral health awareness in terms of benefit and practices. A total of 100 patients from a selected government hospital were surveyed. The respondents were asked to answer a standardized questionnaire about their socioeconomic status, awareness on the benefits of oral health care, and awareness on the practices for oral health care. Chi-Square Test for Independence was used to identify which demographic and socioeconomic indicators determined the level of awareness of the respondents on the benefits of and practices for good oral health. The Chi-Square Test showed that only sex had a significant relationship with the awareness on the benefits of good oral health (p-value = 0.05). All the other indicators had insignificant effects; Age group (p-value = 0.435), Civil Status (p-value = 0.443), Education (p-value = 0.244), Employment status (p-value = 0.722), Income (p-value = 0.986). For the awareness on good oral practice, both sex and civil status showed a significant relationship (p-values 0.028 and 0.01). For the other indicators, null hypothesis was accepted; Age group (p-value = 0.61), education (p-value = 0.914), employment status (p-value = 0.334), income (p-value = 0.64). The results of this study are in line with the Andersen Healthcare Utilization Model, which holds that people's use of healthcare services is influenced by several predisposing, enabling, and need-related factors. The knowledge of, and observance of, good oral health is essential in determining the need for oral healthcare. Moreover, a variety of socioeconomic and personal factors (enabling and predisposing) are crucial in facilitating or impeding people's ability to access and make use of oral healthcare services. Addressing these issues and promoting education and knowledge about the value of excellent oral health practices are crucial for good oral health.
Safety, Security, and Disaster Preparedness Plan of AIMS as Perceived by Internal Stakeholders: Towards the Enhancement of Institutional Safety and Security Plan
Authors: Cabasal Maria Celia C. , Lusiniara Manolito T. , Alumia Amador B. 
Published: January 2024

Employing descriptive-comparative design, the perception towards the safety, security and disaster preparedness of AIMS was taken from 167 employees and 343 students and strategically compared using T-test and analysis of variance (ANOVA). A standardized questionnaire adapted from the School Safety and Security Checklist by the New York State Police and the Virginia State Education Department was used as instrument during the data gathering period held last 1st Trimester of school year 2022-2023. Demographic profile and mean perception were also statistically treated using frequency, percentage and weighted mean. Based on the results, most of the employee respondents are newly-hired, single, not over 30 years old, physically fit and majority are females. They agreed that AIMS management have a safety and security management plan for its internal stakeholders. However, there are significant differences on their perception when grouped by Department, Position, and Years of Service at AIMS. Specifically, employees who are older and more mature seek improvement and enhancement on the services, facilities, and policies pertaining to safety.
On the other hand, majority of the student respondents are male, BSMT first year students and claimed to be physically fit. Their perception towards the safety and security management of AIMS were higher compared to the employees. However, no significant difference was shown on their perception towards the safety and security management plan of AIMS when grouped according to their profile. For the school grounds, both respondents imply the need for parking facility improvement while on the school interior, it is recommended to conduct a psychological capability training and access to conflict resolution under the initiative of the Regiment Department.
ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban
Authors: Ren An-Jing , Wei Chunchun , Liu Ya-Jin , Liu Mengna , Wang Ping , Fan Juan , Wang Kai , Zhang Sha , Qin Zhenbang , Ren Qiu-Xiao , Zheng Yanjun , Chen Yu-Xia , Xie Zhifang , Gao Ling , Zhu Yi , Zhang Youyi , Yang Huang-Tian , Zhang Weiping J. 
Published: January 2024

BACKGROUND:

Intracellular Ca
2+
cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca
2+
-ATPase 2a) is responsible for the sequestration of cytosolic Ca
2+
into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear.

METHODS:

Cardiomyocyte-specific ZBTB20 knockout mice were generated by crossing ZBTB20
flox
mice with Myh6-Cre mice. Echocardiography, blood pressure measurements, Langendorff perfusion, histological analysis and immunohistochemistry, quantitative reverse transcription-PCR, Western blot analysis, electrophysiological measurements, and chromatin immunoprecipitation assay were performed to clarify the phenotype and elucidate the molecular mechanisms.

RESULTS:

Specific ablation of ZBTB20 in cardiomyocyte led to a significant increase in basal myocardial contractile parameters both in vivo and in vitro, accompanied by an impairment in cardiac reserve and exercise capacity. Moreover, the cardiomyocytes lacking ZBTB20 showed an increase in sarcoplasmic reticular Ca
2+
content and exhibited a remarkable enhancement in both SERCA2a activity and electrically stimulated contraction. Mechanistically, PLN expression was dramatically reduced in cardiomyocytes at the mRNA and protein levels by ZBTB20 deletion or silencing, and PLN overexpression could largely restore the basal contractility in ZBTB20-deficient cardiomyocytes.

CONCLUSIONS:
These data point to ZBTB20 as a fine-tuning modulator of PLN expression and SERCA2a activity, thereby offering new perspective on the regulation of basal contractility in the mammalian heart.
Radiographic Investigation of Differences in Static Anterior Tibial Translation With Axial Load Between Isolated ACL Injury and Controls
Authors: Cance Nicolas , Dan Michael J. , Pineda Tomas , Demey Guillaume , Dejour David H. 
Published: January 2024

Background: Static anterior tibial translation (SATT) is radiographically measured to show the amount of tibial translation during the single-leg stance, and thus it is representative of the physiological axial load subjected to the anterior cruciate ligament (ACL) during the stance. Increased SATT has been associated with increased posterior tibial slope (PTS) and is also associated with increased graft failure. Purpose: To compare the SATT value in a control population with that in a population with an isolated ACL injury, as well as to compare the effect of tibial slope on SATT between the 2 groups. Study Design: Cohort study; Level of evidence, 3. Methods: A consecutive series of patients without ligamentous or meniscal injuries between 2019 and 2022 was reviewed. A matched consecutive cohort of patients with nonacute ACL injuries (surgery between 6 and 12 weeks after injury) without concomitant pathology was reviewed. Preoperative SATT and PTS were measured with a previously validated technique on lateral weightbearing knee radiographs. The SATT value was determined, and regression analysis was performed to investigate the relationship between SATT and PTS. Results: In total, 101 controls and 115 patients with an ACL injury were included in this study. The mean SATT was 1.31 mm (SD, 2.44 mm) and the mean PTS was 10.61° (SD, 3.28°) in the control cohort. The SATT was larger (mean, 2.27 mm; SD, 3.36 mm) in the ACL-injured cohort despite the tibial slope measurement being less in the ACL-injured cohort (mean, 9.46°; SD, 2.85°; P = .016). Linear regression analysis showed that for every 1° of increase in PTS, there was a 0.34-mm increase in SATT in the control cohort; however, there was a greater increase of 0.5 mm for every 1° of increase in PTS in the ACL-injured cohort. We found no significant differences in SATT when the cohorts were compared by age ( P = .26) or sex ( P = .10). Conclusion: The present study reports a reference SATT value of 1.31 mm (SD, 2.44 mm) in a non–ACL-injured cohort, which was lower than in the ACL-injured cohort (mean, 2.27 mm; SD, 3.36 mm). The effect of slope on weightbearing anterior tibial translation was greater in the ACL-injured population than in the control cohort.
A Study on Attitude Towards Social Networking Among Adolescents and Parents
Authors: Mathur Tripti , Sharma Ratna Dixit 
Published: January 2024

The purpose of this study is to know how students in school and parents perceive social networks. A random sample of 50 adolescents aged 17–21 and 50 parents aged 45–48 irrespective of gender were selected randomly from students in the eleventh and twelfth grades with their parents in Ambala, Haryana, India. A self-developed questionnaire consisting of 60 items about social networking was used, of which half of the items were in favour and half not in favour of social networking. The scoring of the questionnaire was done using scores 1 to 7 correlating to the options from ‘strongly disagree’ to ‘strongly agree’. Descriptive analysis and part–whole correlations and t-ratios were used to analyse the obtained data. The difference in opinion between parents and adolescents about social networking is more evident when one considers the generation gap, income group and rural and urban groups. The attitude of parents, teachers and adolescents towards social networking sites is neutral. Social networking sites are both a boon and a curse, depending upon the level of awareness pertaining to the different aspects such as privacy, accessibility and the purpose for which they are being used.