bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community‐Engaged Insights: Understanding the Housing Needs of Rural Caregivers During Hospital Treatment
Authors: Owens Jennifer A. , Bush Angie , Campbell Peter , Ward Roger J. , Lilly Flavius R. W. 
Published: December 2024

ABSTRACTPurposeThis study explored the experiences of rural caregivers who require temporary housing during hospital treatment when healthcare is not available in their home communities. Understanding these experiences can identify challenges and inform solutions for improving rural access to healthcare.MethodsWe conducted a community‐engaged qualitative study using semi‐structured interviews with caregivers who stayed at a healthcare hospitality house in Charlotte, NC. Data were collected through virtual interviews in the fall of 2023 and analyzed by three independent reviewers using thematic analysis.FindingsCaregivers faced significant financial, logistical, and emotional challenges associated with accessing healthcare far from home. Financial burdens were notable, with substantial out‐of‐pocket expenses despite reduced costs from the hospitality house. Proximity to hospitals was crucial, with participants favoring hospitality houses over hotels for their convenience and security. Emotional support from peers provided meaningful social bonds and alleviated feelings of isolation. Practical amenities, such as laundry facilities and kitchens, eased the daily living obligations. Participants also highlighted the need for advocacy and coordination in navigating care logistics.ConclusionOur findings highlight key themes showcasing the challenges faced by rural caregivers experiencing a health crisis and who must travel to access healthcare outside their home communities. Medical housing can serve multifaceted social needs during a health crisis and support the interconnectedness of financial, emotional, and practical aspects of healthcare access. Future research should explore broader and more diverse samples and continue to consider community‐engaged approaches to deepen the understanding of health‐related social needs needed to access healthcare.
“I Say I'm Kind of Out”: An Insider Qualitative Study of Queer Medical Students
Authors: Breheny Cate Goldwater , Lee Dominic , Ly Daniel , Oliver Holly , Bi Anbreen , Bull Stephanie 
Published: December 2024

ABSTRACTBackgroundUnited Kingdom Queer medical students' experiences have only been explored in depth in one previous study, despite longstanding calls to address National Health Service queerphobia. The study aims to combine our participants' data with personal insights from the Queer medical student research team to both record Queer medical students' experiences and provide practical actions that can promote support, inclusivity and celebration for Queer medical students.MethodsIndividual semi‐structured interviews were conducted with 12 participants across three medical schools in England and Scotland. Inductive thematic analysis was conducted. Insider insights were combined with analysis to generate practical advice for educators.ResultsParticipants had a broad range of Queer identities, including non‐binary, bisexual and asexual identities. Four themes were identified, as well as a table of practical advice:

Developing a unified Queer medical student identity: the cognitive and emotional process of aligning Queer and medical student identities;
A culture of discrimination: actions occurring at cultural, system and individual levels that result in negative queerphobic experiences;
A counterculture of support: representation and support provided by Queer faculty and doctors and Queer friends, and in curriculum material;
Belonging and not belonging: thoughts and feelings of acceptance and value within academic, clinical and social environments.
DiscussionQueer medical students continue to experience discrimination despite calls for change. We suggest a deeper cultural reimagination of belonging as a Queer medical student, alongside practical support from educators to create this, is needed to improve Queer medical students' experiences.
Prioritising Competencies in Clinician Educator Training in Residency Programmes
Authors: Ratan Bani M. , Appelbaum Nital P. , Boedeker Peter J. , McNeil Sara G. , Hausmann Robert C. , Turner Teri L. 
Published: December 2024

ABSTRACTIntroductionAlthough Clinician Educator Tracks (CETs) have been developed for postgraduate trainees, more clarity is needed regarding which competencies are most relevant to resident and fellow physicians (housestaff) seeking to become Clinician Educators (CEs).MethodsWe used the Clinician Educator Milestones, an established framework for competencies at the faculty level, to perform a targeted needs assessment at a large academic institution from April–May 2023. Educational leaders in undergraduate (UME), graduate (GME) and senior medical education (SME) leadership roles were asked to prioritise the Clinician Educator Milestones subcompetencies for a 1‐year track. Descriptive statistics and logistic regression analysis were performed; text comments underwent content analysis.ResultsOf the 285 leaders, 118 (41%) completed the survey. The average length in educational leadership was 6.9 ± 5.6 years, with 33% having formal education training, 23% representing surgical specialities and 17% in SME roles. The subcompetencies of learner assessment and feedback were prioritised highest (86%), while change management was prioritised lowest (23%). Respondents in SME roles compared to UME and GME roles or those in educational leadership ≥ 6 years compared to < 6 years prioritised professionalism. Respondents without formal education training prioritised medical education scholarship more often than those with training. Surgical respondents more often prioritised administrative skills than nonsurgical respondents. Open‐ended comments were generally positive towards a CET for housestaff, suggesting a hybrid format with flexible scheduling.ConclusionsTeaching‐oriented subcompetencies were highly prioritised for a CET targeted at housestaff. The prioritisation choices offer guidance for a CE's progression through the subcompetencies.
Internal Medicine Student Chief Elective
Authors: Newman Jessica R. , Rouse Michael , Davies Gage , Bisarya Roshan , Nguyen Emma , Fink Jennifer 
Published: December 2024

ABSTRACTBackgroundWith increasing patient care responsibilities, administrative work and education demands, physicians may find it challenging to provide high‐quality and engaging clinical education to third‐year medical students on clerkships. Fourth‐year students in the role of near‐peer teachers can help fill this role, but they often also have competing responsibilities.ApproachA 4‐week Internal Medicine Student Chief (Student Chief) elective was created, designed such that fourth‐year students would apply for dedicated time to serve as student leaders, coaches and educators for the third‐year students on the Internal Medicine clerkship. They were provided an asynchronous medical education curriculum and conducted their own Medicine subject exam reviews, case conferences and feedback sessions.EvaluationCourse evaluations by clerkship students did not detect a significant difference between the “quality” of the Internal Medicine clerkship and the “amount of formative feedback” from pre−post Student Chief elective introduction. Clerkship students' feedback regarding their interactions with and the ratings of the Student Chief, however, were excellent. Evaluations by the Student Chief suggested that the course provided rich opportunities for students interested in medical education to learn and practice skills in teaching, mentoring and coaching of Internal Medicine clerkship students.ImplicationsGiven overwhelmingly positive feedback, the Student Chief elective has continued. Student Chief responsibilities evolved based on feedback, and the Student Chiefs themselves develop their own learning goals for their experience. Future studies could include a more longitudinal evaluation of the program, expanding the scope of the Student Chief experience to other specialties and publication of an implementation toolkit.
The Family Anesthesia Experience (FAX): Implementing a Social Support–Focused Wellness Programme Across Multiple Residency Programmes
Authors: Martinelli Susan M. , Tran Thanh N. , Canter Courtney , Isaak Robert S. , Afroze Farzana , Mulaikal Teresa A. , Ladlie Beth , Jain Ankit , Willie Chelsea , Stahl David L. , Blanchard Erin , Zisblatt Lara , Hoefnagel Amie L. , Marshall Julie M. , Collins Stephen , Keneally Ryan J. , Martin Timothy W. , Chen Fei 
Published: December 2024

ABSTRACTIntroductionLack of social support negatively impacts medical trainees' wellness. Programmes to educate medical trainees and their support persons (SPs) have been developed to improve resident wellness, but implementation of these programmes at other institutions remains unclear. We aimed to demonstrate the feasibility of implementing the Family Anesthesia Experience (FAX) programme across multiple institutions and to assess the programme's utility.MethodsFAX includes didactics on wellness, burnout, substance use disorder and institutional resources; a panel of senior residents and their SPs; and small‐group simulations of airway management, common procedures and a high‐fidelity intraoperative code. We assessed the programme qualitatively using semistructured interviews of 20 first year anaesthesiology residents and 20 SPs. Data analysis was performed via a content analysis approach.ResultsTwelve anaesthesiology programmes of varying size and geographic locations implemented FAX with minor adaptations. Minimal direct costs were incurred for the virtual programme. Participants enjoyed the event overall. Content analysis showed that FAX improved SPs' understanding of residency and communication between SPs and residents, had minimal impact on SPs' stress, reduced residents' interpersonal stress with SPs and modified perceptions on wellness and burnout. We developed a conceptual model in which we propose SPs' understanding and empathy for their residents would improve through FAX, which may improve communication with and support for residents.ConclusionWe demonstrated that FAX can be implemented at varying anaesthesiology residency programmes. Family‐oriented educational events like FAX may be an effective approach to improve SPs' understanding of a resident's role, thereby increasing social support for residents.
Groups acting on veering pairs and Kleinian groups
Authors: Baik Hyungryul , Jung Hongtaek , Kim KyeongRo 
Published: December 2024

AbstractWe show that some subgroups of the orientation‐preserving circle homeomorphism group with invariant veering pairs of laminations are hyperbolic 3‐orbifold groups. On the way, we show that from a veering pair of laminations, one can construct a loom space (in the sense of Schleimer–Segerman) as a quotient. Our approach does not assume the existence of any 3‐manifold to begin with, so this is a geometrization‐type result, and supersedes some of the results regarding the relation among veering triangulations, pseudo‐Anosov flows, taut foliations in the literature.
Durlobactam in combination with β-lactams to combat
Mycobacterium abscessus
Authors: Shin Eunjeong , Dousa Khalid M. , Taracila Magdalena A. , Bethel Christopher R. , Nantongo Mary , Nguyen David C. , Akusobi Chidiebere , Kurz Sebastian G. , Plummer Mark S. , Daley Charles L. , Holland Steven M. , Rubin Eric J. , Bulitta Jürgen B. , Boom W. Henry , Kreiswirth Barry N. , Bonomo Robert A. 
Published: December 2024

ABSTRACT

Mycobacterium abscessus
(
Mab
) presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against
Mab
and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1–5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies. Thermal stability and morphological changes were determined. Imipenem demonstrated high binding affinity to LDTs and PBPs, with extremely low inhibition constants (

K
i

,
app

; ≤0.002 mg/L for LDT1−2, ≤0.6 mg/L for PBPs), while cephalosporins, sulopenem, tebipenem, and amoxicillin exhibited moderate to low binding affinity. Durlobactam inactivated Bla
Mab
and LDT/PBPs more potently than avibactam. The

K
i,app

s of durlobactam for PBP B, PBP-lipo, and LDT2 were below clinically achievable unbound concentrations, while avibactam’s

K
i,app

for LDT/PBPs exceeded the clinical concentrations. Single β-lactam treatments resulted in minimal killing (~1 log
10
reduction). Although avibactam yielded no effect, combinations with avibactam showed a significant reduction (~4 log
10
CFU/mL). Durlobactam alone showed ~2 log
10
reduction, and when combined with imipenem or two β-lactams, durlobactam achieved near-eradication of
Mab
, surpassing the current therapy (amikacin + clarithromycin + imipenem/cefoxitin). Inactivation of PBP-lipo by sulopenem, imipenem, durlobactam, and amoxicillin (with avibactam) led to morphological changes, showing filaments. This study demonstrates the mechanistic basis of combinations therapy, particularly imipenem + durlobactam, in overcoming β-lactam resistance in
Mab
.
Patterns of spontaneous and induced genomic alterations in
Yarrowia lipolytica
Authors: Xiong Yuan-Ru , Fang Yuan-Chun , He Min , Li Ke-Jing , Qi Lei , Sui Yang , Zhang Ke , Wu Xue-Chang , Meng Liang , Li Ou , Zheng Dao-Qiong 
Published: December 2024

ABSTRACT

This study explored the genomic alterations in
Yarrowia lipolytica
, a key yeast in industrial biotechnology, under both spontaneous and mutagen-induced conditions. Our findings reveal that spontaneous mutations occur at a rate of approximately 4 × 10
−10
events per base pair per cell division, primarily manifesting as single-nucleotide variations (SNVs) and small insertions and deletions (InDels). Notably, C-to-T/G-to-A transitions and C-to-A/G-to-T transversions dominate the spontaneous SNVs, while 1 bp deletions, likely resulting from template slippage, are the most frequent InDels. Furthermore, chromosomal aneuploidy and rearrangements occur, albeit at a lower frequency. Exposure to ultraviolet (UV) light, methylmethane sulfonate (MMS), and Zeocin significantly enhances the rates of SNVs and alters their mutational spectra in distinct patterns. Notably, Zeocin-induced SNVs are predominantly T-to-A and T-to-G substitutions, often occurring within the 5′-TGT
*
−3′ motif (
*
denotes the mutated base). Additionally, Zeocin exhibits a higher potency in stimulating InDels compared to UV and MMS. Translesion DNA synthesis is implicated as the primary mechanism behind most Zeocin-induced SNVs and some InDels, whereas non-homologous end joining serves as the main pathway for Zeocin-mediated InDels. Intriguingly, the study identifies the gene
YALI1_E21053g
, encoding a protein kinase, as negatively associated with Zeocin resistance. Overall, our results not only deepened our knowledge about the genome evolution in
Y. lipolytica
but also provided reference to develop innovative strategies to harness its genetic potential.

IMPORTANCE

Yarrowia lipolytica
exhibits high environmental stress tolerance and lipid metabolism capabilities, making it a microorganism with significant industrial application potential. In this study, we investigated the genomic variation and evolutionary patterns of this yeast under both spontaneous and induced mutation conditions. Our results reveal distinctive mutation spectra induced by different mutagenic conditions and elucidate the underlying genetic mechanisms. We further highlight the roles of non-homologous end joining and translesion synthesis pathways in Zeocin-induced mutations, demonstrating that such treatments can rapidly confer drug resistance to the cells. Overall, our research enhances the understanding of how yeast genomes evolve under various conditions and provides guidance for developing more effective mutagenesis and breeding techniques.
Identification of an antibiotic from an HTS targeting EF-Tu:tRNA interaction: a prospective topical treatment for MRSA skin infections
Authors: Mandecki Wlodek , Chudaev Maxim , Ye Wenjuan , Wang Amy Q. , Wilson Kenneth J. , Xu Xin , Kim Jisun , Parker Dane , Alland David , Kumar Pradeep , Li Barry , Yang Jason H. , Kreiswirth Barry , Mediavilla Jose R. , Marugan Juan J. , Henderson Mark J. , Goldman Emanuel 
Published: December 2024

ABSTRACT

Because of the urgent need for new antibiotics to treat drug-resistant bacterial pathogens, we employed an assay that rapidly screens large quantities of compounds for their ability to interfere with bacterial protein synthesis, in particular, the delivery of amino acids to the ribosome via tRNA and elongation factor Tu (EF-Tu). We have identified a drug lead, named MGC-10, which kills Gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus
(MRSA), with a MIC of 6 µM, while being harmless to mammalian cells
in vitro
in that concentration range. The antibacterial activity of MGC-10 was broad against over 50 strains of antibiotic-resistant samples obtained from hospital infections, where MGC-10 inhibited all tested strains of MRSA. Extensive selection and screening with MGC-10 did not yield any resistant strains, indicating it may have universal antibacterial activity against
S. aureus
. Pharmacokinetics performed in mice suggested that MGC-10 was too toxic for systemic use; however, it appears to have potential as a topical treatment for difficult-to-treat wounds or skin infections by Gram-positive pathogens such as MRSA. In a mouse skin-infection model with MRSA, MGC-10 performed as well or better than the present topical drug of choice, mupirocin. MGC-10 showed little, if any, accumulation in the livers of topically treated mice. These results bode well for the future use of MGC-10 in clinical application as it could be used to treat a broad range of
S. aureus
skin infections that are resistant to known antibiotics.

IMPORTANCE

There is a critical need for new antibiotics to treat bacterial infections caused by pathogens resistant to many if not all currently available antibiotics. We describe here the identification of a prospective new antibiotic from high-throughput screening of a chemical library. The screening was designed to detect the inhibition of formation of a complex required for bacterial protein synthesis in all bacteria, the “ternary complex,” comprised of elongation factor Tu (EF-Tu), aminoacyl-tRNA, and GTP. The inhibitory compound, renamed MGC-10, was effective against all Gram-positive bacteria, including a wide variety of methicillin-resistant
Staphylococcus aureus
(MRSA) strains. Although apparently too toxic for systemic use, the compound was safe and effective for topical use for treating skin infections in a mouse model. No resistance to the compound has been detected thus far, suggesting the potential to develop this compound for topical use to treat infections, especially those caused by pathogens resistant to existing antibiotics.
Evolutionary and functional divergence of Sfx, a plasmid-encoded H-NS homolog, underlies the regulation of IncX plasmid conjugation
Authors: Wang Avril , Cordova Martha , Navarre William Wiley 
Published: December 2024

ABSTRACT

Conjugative plasmids are widespread among prokaryotes, highlighting their evolutionary success. Conjugation systems on most natural plasmids are repressed by default. The negative regulation of F-plasmid conjugation is partially mediated by the chromosomal nucleoid-structuring protein (H-NS). Recent bioinformatic analyses have revealed that plasmid-encoded H-NS homologs are widespread and exhibit high sequence diversity. However, the functional roles of most of these homologs and the selective forces driving their phylogenetic diversification remain unclear. In this study, we characterized the functionality and evolution of Sfx, a H-NS homolog encoded by the model IncX2 plasmid R6K. We demonstrate that Sfx, but not chromosomal H-NS, can repress R6K conjugation. Notably, we find evidence of positive selection acting on the ancestral Sfx lineage. Positively selected sites are located in the dimerization, oligomerization, and DNA-binding interfaces, many of which contribute to R6K repression activity—indicating that adaptive evolution drove the functional divergence of Sfx. We additionally show that Sfx can physically interact with various chromosomally encoded proteins, including H-NS, StpA, and Hha. Hha enhances the ability of Sfx to regulate R6K conjugation, suggesting that Sfx retained functionally important interactions with chromosomal silencing proteins. Surprisingly, the loss of Sfx does not negatively affect the stability or dissemination of R6K in laboratory conditions, reflecting the complexity of selective pressures favoring conjugation repression. Overall, our study sheds light on the functional and evolutionary divergence of a plasmid-borne H-NS-like protein, highlighting how these loosely specific DNA-binding proteins evolved to specifically regulate different plasmid functions.

IMPORTANCE
Conjugative plasmids play a crucial role in spreading antimicrobial resistance and virulence genes. Most natural conjugative plasmids conjugate only under specific conditions. Therefore, studying the molecular mechanisms underlying conjugation regulation is essential for understanding antimicrobial resistance and pathogen evolution. In this study, we characterized the conjugation regulation of the model IncX plasmid R6K. We discovered that Sfx, a H-NS homolog carried by the plasmid, represses conjugation. Molecular evolutionary analyses combined with gain-of-function experiments indicate that positive selection underlies the conjugation repression activity of Sfx. Additionally, we demonstrate that the loss of Sfx does not adversely affect R6K maintenance under laboratory conditions, suggesting additional selective forces favoring Sfx carriage. Overall, this work underscores the impact of protein diversification on plasmid biology, enhancing our understanding of how molecular evolution affects broader plasmid ecology.