bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing teacher leader efficacy to address attrition
Authors: Lin Joyce , Galosy Jodie , Ross Carolyn , Watts Jessica , Wilson Gina 
Published: February 2025

AbstractResearch shows that 44% of new teachers quit teaching within the first 5 years. This study aims to explore the link between teacher leadership and the retention of science and math teachers and contributes to the increasing body of research suggesting that teacher leadership could be a promising way to tackle the problem of retaining teachers in our country. Drawing on survey data from a 5‐year teaching fellowship program serving beginning high school math and science teachers, we propose that teacher leader efficacy, or the extent to which a teacher believes they have the capacity to improve education beyond their own classroom, can be a promising mediator that supports retention. We investigate how expanding teachers' views of leadership and developing and sharing practitioner knowledge can enhance teacher leader efficacy and improve teacher retention. Our findings shed light on the connection between teacher leadership efficacy and retention, emphasizing the importance of leadership models and practitioner inquiry in developing teacher leadership efficacy. We end by discussing implications for others supporting teacher leadership and teacher retention or conducting research in these areas.
Identification of the Novel HLA‐DRB3*02:213 Allele by Next‐Generation Sequencing
Authors: Bouthemy Charlène , Milhès Jean , Congy‐Jolivet Nicolas 
Published: February 2025

ABSTRACTHLA‐DRB3*02:213 differs from DRB3*02:02 by one nucleotide substitution in codon 6 in exon 2.
Discovery of the Novel HLA‐DQB1*04:104 Allele Using Short‐ and Long‐Read Sequencing Technologies
Authors: Santos Angela , Mendes‐Oliveira Victoria , Vianna Romulo , Porto Luís Cristóvão , Secco Danielle 
Published: February 2025

ABSTRACTThe novel HLA‐DQB1*04:104 allele, first described in an individual from Brazil.
Next Generation Sequencing Reveals A Novel HLA‐C Allele, HLA‐C*07:1172
Authors: Rakhmanov Mirzokhid , Bernheiden Martin , Verboom Murielle , Hallensleben Michael , Emmerich Florian 
Published: February 2025

ABSTRACTHLA‐C*07:1172 differs from HLA‐C*07:01:01:01 by a single nucleotide substitution in Codon 7 in Exon 2.
Implementing an Escape Room for Clinical Skills Practice in a Paediatrics Clerkship
Authors: Khera Sofia , Wai Andrew , Ford Christine , Yoo Andrew , Joe Daniel , Oyoyo Udochukwu 
Published: February 2025

ABSTRACTBackgroundEscape rooms include the same experiential learning methods that make traditional simulation practices effective while adding gamification which improves learner engagement. Our existing simulation curriculum lacked active experimentation, an essential component of Kolb's experiential learning cycle. The goal of this curriculum innovation was to determine the feasibility of adding an escape room immediately following the simulation to provide an effective independent learning experience for learners.ApproachWe created a 40‐min escape room activity using principles of self‐determination theory. All students in the paediatric clerkship participated once over one academic year. Students were presented with an unstable child with seizures and worked in teams of 3–5 to open locks and solve puzzles as they applied nine clinical skills learned from the preceding simulation session.EvaluationStudents (N = 66) reported increases in knowledge after both the simulation and the escape room and an increase in confidence after completing the escape room, indicating we were successful in adding active experimentation to our curriculum. They also commented on the value of applying and practising new skills and of engaging in teamwork, which reinforced the utilization of self‐determination theory as a guiding principle for escape room design.ImplicationsOur escape room is novel in that it takes place in a paediatric clerkship setting and builds upon existing curricular elements to provide students with independent practice of clinical skills in a gamified and fun approach early in their clinical training years. Escape rooms are a feasible and an effective method to provide hands‐on experience to clinical learning.
Inhibition of BK channels by GABAb receptors enhances intrinsic excitability of layer 2/3 vasoactive intestinal polypeptide‐expressing interneurons in mouse neocortex
Authors: Bogaj Karolina , Urban‐Ciecko Joanna 
Published: February 2025

AbstractGABAb receptors (GABAbRs) affect many signalling pathways, and hence the net effect of the activity of these receptors depends upon the specific ion channels that they are linked to, leading to different effects on specific neuronal populations. Typically, GABAbRs suppress neuronal activity in the cerebral cortex. Previously, we found that neocortical parvalbumin‐expressing cells are strongly inhibited through GABAbRs, whereas somatostatin interneurons are immune to this modulation. Here, we employed in vitro whole‐cell patch‐clamp recordings to study whether GABAbRs modulate the activity of vasoactive intestinal polypeptide‐expressing interneurons (VIP‐INs) in layer (L) 2/3 of the mouse primary somatosensory cortex. Utilizing machine learning algorithms (hierarchical clustering and principal component analysis), we revealed that one VIP‐IN cluster (about 68% of all VIP‐INs) was sensitive to GABAbR activation. Paradoxically, when recordings were performed in standard conditions with high extracellular Ca2+ level, GABAbRs indirectly inhibited the activity of large conductance voltage‐ and calcium‐activated potassium (BK) channels and reduced GABAaR‐mediated inhibition, leading to an increase in intrinsic excitability of these interneurons. However, a classical inhibitory effect of GABAbRs on L2/3 VIP‐INs was observed in modified artificial cerebrospinal fluid with physiological (low) Ca2+ concentration. Our results are essential for a deeper understanding of mechanisms underlying the modulation of cortical networks.
imageKey points
Layer 2/3 vasoactive intestinal polypeptide‐expressing interneurons (VIP‐INs) in the mouse somatosensory cortex cluster into three electrophysiological types differentially sensitive to GABAb receptors (GABAbRs).
The majority of VIP‐INs (type 1, about 68% of all VIP‐INs) are regulated through pre‐ and postsynaptic GABAbRs, while a subset of these interneurons (types 2 and 3) is controlled only presynaptically.
The net effect of GABAbR activation on VIP‐IN excitability depends on [Ca2+] in artificial cerebrospinal fluid.
When [Ca2+] is high (2.5 mM), GABAbRs indirectly inhibit BK channels and reduce GABAaR inhibition leading to increased intrinsic excitability of type 1 VIP‐INs.
When [Ca2+] is low (1 mM), which is more physiological, BK channels do not regulate the intrinsic excitability of VIP‐INs and thus postsynaptic GABAbRs canonically decrease the intrinsic excitability of type 1 VIP‐INs.
Surface Modification of LPBF Ti6Al4V Through In Situ Nitrogen-Assisted Laser Surface Remelting
Authors: Porwal Ankit , Dhara Santanu , Kumar Cheruvu Siva 
Published: February 2025

Abstract
Laser surface remelting is a widely used method for surface modification of titanium and related alloys, particularly to enhance its workability in the biomedical industry through surface nitriding. The present work aims to develop the nitride surface over the laser powder bed fusion (LPBF)-processed Ti6Al4V substrate by introducing the nitrogen environment in the build chamber during the remelting. The effects of different laser power and laser scan speeds were studied over the surface topography and elemental changes of the remelted surface. The result shows an increase in surface roughness with selective laser remelting, which could enhance cell proliferation or osseointegration, which is advantageous for biomedical applications. Energy-dispersive X-ray (EDX) results show a significant increase in nitrogen content in terms of weight percentage for the in situ remelted surface. X-ray diffraction (XRD) phase analysis shows the presence of titanium (Ti) and aluminum (Al) nitride peaks, and X-ray photon-electron spectrometry (XPS) also indicates the formation of nitrogen bonds with Ti and Al, which were initially missing in the substrate. The results reported here confirm the nitride surface formation over the substrate due to the in situ remelting under the nitrogen environment for the LPBF-processed Ti6Al4V, which could be used for improved biomedical applications.
Efficacy and safety of switching from entecavir to tenofovir alafenamide in chronic hepatitis B patients with low-level viremia: a real-world 48-week extension study
Authors: He Meng-Wen , Cui Li , Chen Dan-Dan , Zhao Yun , Luo Wen-Zhao , Jia Yun-Fei , Zhou Jie , He Qing-Juan , Dai Ying , Zhang Wei-Hua , Yu Zhao-Xia , Wang Wen-Chang , Guo Chang , Fu Yi-Ming , Yang Wu-Cai , Li Xu-Yang , Guo Yi-Fan , Wang Chun-Yan , Wang Jian-Jun , Li Ping , Qiao Bing , Ji Dong , Li Zhong-Bin 
Published: February 2025

ABSTRACT

Chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment might develop low-level viremia (LLV), which is proven to be associated with worse clinical outcomes, such as risk of drug-related mutations, progression to cirrhosis, and even hepatocellular carcinoma. This real-world prospective study evaluated the efficacy and safety of switching from ETV to tenofovir alafenamide fumarate (TAF) in CHB patients with LLV. From August 2020 to August 2023, 351 ETV-experienced CHB patients with LLV were enrolled from eight hospitals. Patients either continued ETV or switched to TAF. The primary efficacy endpoint was the complete virological response (CVR) at week 48; the safety endpoint was the first occurrence of any clinical adverse event during the treatment; and the renal safety and change in blood lipids were also assessed. Inverse probability treatment weighting (IPTW) generated 350.9 cases in the ETV group and 351.4 cases in the TAF group. After the 48-week treatment, the CVR and ALT normalization rates in the TAF group were 75.3% and 67.8%, which were significantly higher than 11.4% and 17.1% in the ETV group (
P
< 0.001). The two strategies showed comparable impact on renal function and lipid profiles, regarding low-density lipoprotein (LDL) cholesterol and the total cholesterol to high-density lipoprotein (TC/HDL) ratio. Therefore, for ETV-treated patients with LLV, switching to TAF is superior compared with continuing ETV treatment in terms of virological and biochemical response, with non-inferior renal safety and lipid profiles.

CLINICAL TRIALS

This study is registered with the Chinese Clinial Trial Registry as
ChiCTR2400089257
.
Contribution of the gonococcal
NEIS1446-ispD
gene conversion to the pathobiology of the
Neisseria meningitidis
urethritis clade,
Nm
UC
Authors: Rodriguez Emilio I. , Tzeng Yih-Ling , Sannigrahi Soma , Stephens David S. 
Published: February 2025

ABSTRACT

Over the last decade, a
Neisseria meningitidis
(
Nm
) urethritis-causing clade (
Nm
UC) has emerged to cause clusters of meningococcal urethritis in the United States and globally. One genomic signature of
Nm
UC is the integration of
Neisseria gonorrhoeae
(
Ng
) DNA in an operon,
NEIS1446-NEIS1438
, which partially replaced the
Nm ispD
gene. IspD is the 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase of the terpenoid precursor synthesis pathway, required for the production of ubiquinones of the electron transfer chain. IspD is essential in several gram-negative bacteria. The biological importance of the
NEIS1446-ispD
gene conversion event for
Nm
UC was investigated. The
ispD
gene was found to be essential in
Nm
UC (CNM3) and non-clade
Nm
(MC58), and a mutation at the native locus can only be made with the insertion of a second
ispD
copy in the genome. The IspD
MC58
variant was more efficient at promoting aerobic growth at a low level than IspD
CNM3
; the two proteins differ by 15 residues. Maximal aerobic growth densities of strains with an
Nm
UC background resembled
Ng
(FA19), and both were significantly lower than
Nm
. In contrast to non-clade
Nm
, all
Nm
UC strains survived well anaerobically. Increasing
ispD
expression by titrating IPTG in non-clade
Nm
enhanced anaerobic survival. Translational reporters of the
Nm
UC and
Ng
promoters demonstrated similar expression levels, and both were significantly higher than non-clade
Nm
, under aerobic and microaerobic conditions. Our findings suggest that the integration of gonococcal DNA into the
NEIS1446-NEIS1438
operon of
Nm
UC has increased
ispD
expression
,
contributing to
Nm
UC’s adaptation to the oxygen-limited environment of the human urogenital tract.
Genome-wide analysis of
Enterococcus faecalis
genes that facilitate interspecies competition with
Lactobacillus crispatus
Authors: Lam Ling Ning , Savage Kathryn E. , Shakir Camille N. , Lemos José A. 
Published: February 2025

ABSTRACT

Enterococci are opportunistic pathogens notorious for causing a variety of infections. While both
Enterococcus faecalis
and
Lactobacillus crispatus
are commensal residents of the vaginal tract, the molecular mechanisms that enable
E. faecalis
to take advantage of a vaginal biome with lower counts of lactobacilli to colonize the vaginal tract and induce aerobic vaginitis remain unknown. Here, we show that
L. crispatus
eradicates
E. faecalis
in a contact-independent manner. Using transposon sequencing to identify
E. faecalis
OG1RF transposon (Tn) mutants that are either under-represented or over-represented when co-cultured with
L. crispatus
, we found that Tn mutants with disruption in the
dltABCD
operon, that encodes the proteins responsible for the D-alanylation of teichoic acids, and
OG1RF_11697
encoding for an uncharacterized hypothetical protein are more susceptible to killing by
L. crispatus
. Inversely, Tn mutants with disruption in
ldh1,
which encodes for L-lactate dehydrogenase, are more resistant to
L. crispatu
s killing. Using the
Galleria mellonella
infection model, we show that co-injection of
L. crispatus
with
E. faecalis
OG1RF enhances larvae survival while this
L. crispatus
-mediated protection was lost in larvae co-infected with either
L. crispatus
and
E. faecalis
Δ
ldh1
or Δ
ldh1
Δ
ldh2
strains. Last, using RNA sequencing to identify
E. faecalis
genes that are differently expressed in the presence of
L. crispatus
, we found major changes in the expression of genes associated with glycerophospholipid metabolism, central metabolism, and general stress responses. The findings in this study provide insights into how
E. faecalis
mitigate assaults by
L. crispatus
.

IMPORTANCE

Enterococcus faecalis
is an opportunistic pathogen notorious for causing a multitude of infections. As vaginal commensals,
E. faecalis
must interact with
Lactobacillus crispatus
, but how
E. faecalis
overcomes or mitigate assaults by
L. crispatus
killing remains unknown. We show that
L. crispatus
eradicates
E. faecalis
temporally in a contact-independent manner. Using high-throughput molecular approaches, we identified genetic determinants that enable
E. faecalis
to compete with
L. crispatus
. This study represents an important first step for the identification of adaptive genetic traits required for enterococci to tolerate assaults by lactobacilli.
Targeting Ikaros and Aiolos with pomalidomide fails to reactivate or induce apoptosis of the latent HIV reservoir
Authors: Pascoe Rachel D. , Kim Youry , Rhodes Ajantha , Ong Jesslyn , Tumpach Carolin , Gubser Celine , Chang J. Judy , McMahon James H. , Lewin Sharon R. , Rasmussen Thomas A. 
Published: February 2025

ABSTRACT

HIV persists in people living with HIV (PLHIV) on antiretroviral therapy (ART) in long-lived and proliferating latently infected CD4+ T cells that selectively express pro-survival proteins, including the zinc finger proteins, Ikaros and Aiolos. In this study, we investigated whether pomalidomide, an immunomodulatory agent that induces degradation of Ikaros and Aiolos, could increase the death of HIV-infected cells and/or reverse HIV latency. Using an
in vitro
model of CD4+ T cells infected with a green fluorescent protein (GFP) reporter virus, pomalidomide increased the expression of the pro-survival protein B cell lymphoma (Bcl)-2 and did not increase apoptosis of GFP+ HIV productively infected CD4+ T cells. Pomalidomide also increased the expression of CD155 and UL16-binding protein (ULBP) stress proteins on GFP+ HIV productively infected CD4+ T cells, but this did not translate to enhanced clearance following co-culture with a natural killer (NK) cell line. Using CD4+ T cells from PLHIV on ART, pomalidomide
ex vivo
activated memory CD4+ T cells resulting in elevated HLA-DR expression and induced CD4+ T cell proliferation but only in the presence of T cell receptor stimulation with anti-CD3 and anti-CD28. There was no effect on cell-associated HIV RNA or the frequency of intact HIV DNA. In conclusion, despite an increase in stress protein expression, promoting Ikaros and Aiolos degradation in CD4+ T cells using pomalidomide did not directly induce apoptosis of HIV-infected cells or induce HIV latency reversal.

IMPORTANCE

People living with HIV (PLHIV) require lifelong antiretroviral therapy (ART) due to the persistence of latently infected cells. The zinc finger proteins, Ikaros and Aiolos, have recently been implicated in promoting the persistence of latently infected cells. In this study, we investigated the effects of pomalidomide, an immunomodulatory imide drug that induces the degradation of Ikaros and Aiolos, on HIV latency reversal and death of infected cells. Using CD4+ T cells from people living with HIV on suppressive antiretroviral therapy, as well as an
in vitro
model of productive HIV infection, we found that pomalidomide induced T cell activation and expression of stress proteins but no evidence of latency reversal or selective death of infected cells.
RAF1 promotes successful human cytomegalovirus replication and is regulated by AMPK-mediated phosphorylation during infection
Authors: Dunn Diana M. , Pack Ludia J. , Munger Joshua C. 
Published: February 2025

ABSTRACT

RAF1 is a key player in growth factor receptor signaling, which has been linked to multiple viral infections, including human cytomegalovirus (HCMV) infection. Although HCMV remains latent in most individuals, it can cause acute infection in immunocompromised populations, such as transplant recipients, neonates, and cancer patients. Current treatments are suboptimal, highlighting the need for novel therapies. Multiple points in the growth factor signaling pathway are important for HCMV infection, but the relationship between HCMV and RAF1, a component of the mitogen-activated protein kinase (MAPK) cascade, is not well understood. The AMP-activated protein kinase (AMPK) is a known regulator of RAF1, and AMPK activity is induced by HCMV infection, which is important for productive HCMV replication. Our data indicate that HCMV infection induces AMPK-specific changes in RAF1 protein phosphorylation, including increasing phosphorylation at RAF1-Ser621, a known AMPK phospho-site, which results in increased binding to the 14-3-3 scaffolding protein, an important aspect of RAF1 protein activation. Inhibition of RAF1, either pharmacologically or via shRNA or CRISPR-mediated targeting, inhibits viral replication and spread in both fibroblasts and epithelial cells. Collectively, our data indicate that HCMV infection and AMPK activation modulate RAF1 activity, which is important for viral replication.

IMPORTANCE
Human cytomegalovirus (HCMV) infection is a widespread infection impacting approximately 60–90% of the global population. Although latent in healthy individuals, acute infection in immunocompromised populations, such as neonates, transplant recipients, and cancer patients, can result in retinal and gastrointestinal problems, hearing loss, and even death. Current antivirals are suboptimal due to the development of viral resistance or toxicity in patients, highlighting the need for novel treatments. Our research suggests a new potential target, RAF1, which is a regulator of cellular growth and proliferation. We find that RAF1 is phosphorylated by AMP-activated protein kinase, and that inhibition of RAF1 negatively impacts viral infection. Furthermore, drugs currently used to treat certain cancers also inhibit RAF1 and may have an additional anti-HCMV therapeutic effect in HCMV-susceptible cancer patients.
Regulation of IL-10 production in dendritic cells is controlled by the co-activation of TLR2 and Mincle by
Lactiplantibacillus plantarum
OLL2712
Authors: Sakabe Ryuhei , Onishi Kazumasa , Mochizuki Junko , Toshimitsu Takayuki , Shimazu Tomoyuki , Kishino Shigenobu , Ogawa Jun , Yamasaki Sho , Sashihara Toshihiro 
Published: February 2025

ABSTRACT

We showed that
Lactiplantibacillus plantarum
OLL2712 (OLL2712) strongly induces interleukin (IL)-10 production in immune cells. Although beneficial effects of this strain have been observed in both mice and humans, the mechanisms underlying IL-10 induction remain unclear. In this study, we found that OLL2712 co-activates two pattern recognition receptors, leading to IL-10 production in the mouse-derived thermosensitive dendritic cell line, tsDC. We first revealed the involvement of the Toll-like receptor (TLR)2-Myeloid differentiation primary response gene (MYD) 88 pathway in OLL2712-induced IL-10 production in tsDCs. However, stimulation with the TLR2 agonist alone was insufficient to induce IL-10 production. Consequently, we explored additional signaling pathways and found that the phosphorylation of spleen tyrosine kinase (Syk) was important in response to OLL2712, which was not triggered by a TLR2 agonist alone. Notably, the activation of Syk was found to depend on macrophage-inducible C-type lectin receptor (Mincle), one of the C-type lectin receptors. However, the surface-expressed Mincle is not responsible for the IL-10 production by OLL2712. Instead, it depends on the incorporation of OLL2712 into tsDCs, suggesting that Mincle recognizes incorporated OLL2712 intracellularly. In summary, OLL2712 is initially recognized by TLR2, which subsequently induces the expression of Mincle to recognize incorporated OLL2712, ultimately inducing IL-10 production.

IMPORTANCE

The objective of this study is to elucidate the mechanism by which
Lactiplantibacillus plantarum
OLL2712 (OLL2712), previously identified by our research group as a potent stimulator of interleukin-10 production in immune cells, exerts its immunomodulatory effects. Our findings indicate that OLL2712 acts in synergy with two pattern-recognition receptors: Toll-like receptor 2 and Macrophage inducible C-type lectin receptor (Mincle). Additionally, we observed that OLL2712 needs to be internalized intracellularly to be recognized by Mincle. These findings represent the first insights into the detailed mechanism underlying the anti-inflammatory effects of OLL2712.