bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies to reduce 28-day mortality in adult patients with bacteremia in the emergency department
Authors: Laurier Noémie , Karellis Angela , Xue Xiaoqing , Afilalo Marc , Weiss Karl 
Published: December 2024

Abstract
Background
Bacteremia, a common emergency department presentation, has a high burden of mortality, cost and morbidity. We aimed to identify areas for potential improvement in emergency department bacteremia management.

Methods
This retrospective cohort study included adults with bacteremia in an emergency department in 2019 and 2022. The primary outcome was 28-day mortality. Descriptive analyses evaluated demographics, comorbidities and clinical characteristics. Univariate and multivariate analyses identified mortality predictors.

Results
Overall, 433 patients were included [217 males (50.1%), mean ± SD age: 74.1 ± 15.2 years]. The 28-day mortality rate was 15.2% (n = 66). In univariate analysis, age ≥ 70 years, arrival by ambulance, arrhythmia, congestive heart failure, recent steroid use, hypotension (< 90/60 mmHg), mechanical ventilation, cardiac arrest, intensive care unit (ICU) admission, intravenous antibiotics, pneumonia as bacteremia source, non-urinary tract infections, no infectious disease consultation, no antibiotic adjustment and no control blood cultures were significantly associated with 28-day mortality (p < 0.05). Malignancy showed a statistical trend (0.05 < p < 0.15). The above-stated sixteen variables, identified in univariate analysis, were assessed via multivariate analysis. Primarily, clinical relevance and, secondarily, statistical significance were used for multivariate model creation to prioritize pertinent variables. Five risk factors, significantly associated with mortality (p < 0.05), were included in the model: ICU admission [adjusted OR (95% CI): 6.03 (3.08–11.81)], pneumonia as bacteremia source [4.94 (2.62–9.32)], age ≥ 70 [3.16 (1.39–7.17)], hypotension [2.12 (1.02–4.40)], and no infectious disease consultation [2.02 (1.08–3.78)]). Surprisingly, initial antibiotic administration within 6 h, inappropriate initial antibiotic regimen and type of bacteria (Gram-negative, Gram-positive) were non-significant (p > 0.05).

Conclusions
We identified significant mortality predictors among emergency department patients presenting with bacteremia. Referral to an infectious disease physician is the only modifiable strategy to decrease 28-day mortality with long-term effect and should be prioritized.
Diet and Immune Effects Trial (DIET)- a randomized, double-blinded dietary intervention study in patients with melanoma receiving immunotherapy
Authors: Farias Rachel M. , Jiang Yan , Levy Erma J. , Hwang Cindy , Wang Jian , Burton Elizabeth M. , Cohen Lorenzo , Ajami Nadim , Wargo Jennifer A. , Daniel Carrie R. , McQuade Jennifer L. 
Published: December 2024

Abstract
Background
Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.

Methods
This is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50 g/day from whole foods) or healthy control diet (target fiber 20 g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.

Discussion
This DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.

Trial registration
This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.
Care coordinator delivered Method of Levels therapy for people reporting first-episode psychosis: Experiences and views of service user, care coordinator, and team manager participants of the CAMEO trial
Authors: Griffiths Robert , Tai Sara , Ormrod Susan , Welsh Natalie , Jones Adam , Palmier-Claus Jasper , Dixon James , Dawber Alison , Lovell Karina 
Published: December 2024

Abstract
Background
Without effective and timely support, psychosis can lead to negative personal, economic, and societal outcomes. Care coordinators play a key role in the delivery of early intervention in psychosis services, which aim to improve outcomes and promote recovery for people experiencing first-episode psychosis. Enhancing the support offered by care coordinators could improve outcomes and reduce levels of service user disengagement. This study aimed to understand participants’ views on the acceptability of a transdiagnostic talking therapy, called Method of Levels (MOL), delivered by care coordinators in early intervention in psychosis services. It also sought to understand participants’ experiences of the MOL training and supervision programme, and to identify any barriers that might impact on the implementation of the approach in routine practice.

Methods
Semi-structured interviews and focus groups were conducted with service users (n = 14), care coordinators (n = 6), and team managers (n = 6) from early intervention in psychosis services. Interviews and focus groups were transcribed and reflexive thematic analysis was used to analyse the data.

Results
Three themes were identified: ‘Digging deeper to find my own solutions’; (2) ‘Prepared for practice?’; and (3) ‘Levels of implementation’. Participants described how the use of MOL enabled service users to explore problems in greater depth and generate their own solutions to these. Care coordinators generally reported feeling ready to deliver the intervention after attending MOL training and were able to integrate the approach into their practice in a flexible way. High workloads limited care coordinators’ capacity to attend MOL supervision regularly, reducing their overall confidence in delivering the approach. This impacted on the degree to which care coordinators used MOL in their practice.

Conclusions
Findings suggest that MOL delivered by care coordinators could be a helpful approach for people experiencing first-episode psychosis. Care coordinators found it difficult to attend clinical supervision, however, which represents a barrier to implementation. This issue will need to be addressed before care coordinator delivered-MOL for first-episode psychosis can be evaluated in a larger study or implemented in practice.
Quality of cognitive-behavioural therapy in routine psychiatric care: therapist adherence and competence, and patient outcomes for depression and anxiety disorders
Authors: Bergvall Hillevi , Linde Johanna , Alfonsson Sven , Sunnhed Rikard , Barber Jacques P. , Lundgren Tobias , Andersson Gerhard , Bohman Benjamin 
Published: December 2024

Abstract
Background
Quality of care is essential for the dissemination of evidence-based practices, yet therapist adherence and competence are seldom assessed. We examined the quality of delivery of cognitive-behavioural therapy (CBT) in routine psychiatric care for depression and anxiety disorders, considering therapist adherence and competence, and therapy effectiveness, as well as their associations.

Methods
Twenty-nine therapists recruited 85 patients with a principal diagnosis of depression or anxiety disorder from two routine psychiatric outpatient clinics in Stockholm, Sweden. Therapist adherence was assessed mid-CBT by observers and post-CBT by patients and therapists, respectively, using an instrument developed as part of the present study. Therapist competence was assessed using role-plays with a standardised patient. Patients rated symptoms, functional impairment, and global health pre- and post-CBT. Linear mixed models were used to analyse associations.

Results
Therapist adherence was high according to patients, moderate to high according to therapists, and moderate according to observers. Most therapists demonstrated competence in CBT, as assessed using the Cognitive Therapy Scale-Revised (M = 40.5, SD = 6.5; 76% passed the ≥ 36 points competence threshold). Patients improved significantly from pre- to post-CBT across outcome measures (Cohen’s ds = 0.80 – 1.36). Neither therapist adherence nor competence was associated with patient outcomes.

Conclusions
In routine psychiatric care, therapists delivered CBT with adherence, competence, and improvements for patients with depression and anxiety disorders, on par with previous research results in controlled settings. The implications for quality assessment and improvement are discussed.

Trial registration
ClinicalTrials.gov NCT03625024 10/08/2018.
Overdiagnosis of dental caries in South Korea: a pseudo-patient study
Authors: Son Ji-Young , Park Yuyi , Park Ji-Yeon , Kim Min-Ji , Han Dong-Hun 
Published: December 2024

Abstract
Background
To evaluates the tendency of South Korean dentists to over-diagnose clinically healthy teeth in pseudo-patients.

Methods
We conducted a pseudo-patient, cross-sectional study in 196 private dental clinics with 58 pseudo-patients in South Korea between August and December 2018. Trained pseudo-patients with no previous oral diseases, including dental caries, diagnosed by two experienced dentists, were sent to each dental clinic. Before visiting each private dental clinic, participants were instructed to state, “I have no symptoms, but I would like to have a dental caries examination”. The oral examination was performed using visual and tactile inspection methods only. The interactions between the dental clinic staff and the pseudo-patient were documented on a data collection form shortly after each visit.

Results
In 33.2% (65/196) of these interactions, the pseudo-patients were diagnosed as having no dental caries. 11.7% (23/196), 12.8% (25/196), 10.7% (21/196), and 10.7% (21/196) of the sample were diagnosed with dental caries in one, two, three, and four teeth, respectively. Dentists diagnosed five or more dental caries in 20.9% (41/196) of the sample. 196 dental clinics diagnosed a total of 503 dental caries. Of these, 392 were in molars. Small solo practice dentists diagnosed 3.54 dental caries and large group practice dentists 1.57, but the difference was not significant (p = 0.07). The recommendation rate for dental caries treatment was highest among 43 (55.1%) large solo practices, and lowest in 7 (33.3%) large group practices. However, small solo practices had the lowest rate of preventive care recommendations at 12 (30.8%) and 10 (47.6%) in large group practices. The data shows that preventive care recommendations increased as the practice size increased.

Conclusion
The study findings indicate that Korean dentists tend to over-diagnose dental caries, which could pose a threat to public health both in Korea and worldwide. Therefore, it is important to carefully consider strategies to improve the correct diagnosis and standard of care for dental caries by private dentists.
Lost in translation: a qualitative study of medical students’ experiences of theoretical and practical teaching of empathy
Authors: von Knorring Johanna , Salmi Johanna , Lehti Arja , Semb Olof 
Published: December 2024

Abstract
Background
Empathy has proven to be a fundamental component in the patient-doctor relationship and correlates to several positive outcomes in patient care. Despite this, research suggests that empathy decreases during medical education. To increase the understanding of empathy development during medical education, this study explores medical students’ experiences of learning empathy in the transition from theoretical to practical context.

Methods
Eleven semi-structured interviews with students at a medical school in Sweden. The interviews were transcribed verbatim and analysed using grounded theory.

Results
The analysis resulted in three categories and a core category “Lost in translation”. Early on, students regard empathy as a valued and necessary skill. While students generally encounter high expectations of being empathic, they also met gendered expectations. There is a mismatch between the theoretical and the practical teaching of empathy. The core category refers both to the students feeling lost in their own professional development and empathy becoming lost in the translation from theory to clinical practice.

Conclusion
The results describe clashes between theory and clinical reality and the efforts of the students to develop and maintain empathy in this context. To encourage students to develop empathy it is necessary for both educators and practitioners to acknowledge, and attempt to bridge, the gap between the theoretical and the practical curriculum regarding empathy.
Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases
Authors: Urban Oliver Y. , Driedger Jan H. , Garbade Sven F. , Hoffmann Georg F. , Kölker Stefan , Ries Markus , Syrbe Steffen 
Published: December 2024

Abstract
Purpose
Aicardi syndrome is a rare epileptic encephalopathy, almost exclusively affecting girls. It was first described as a triad of infantile spasms, chorioretinal defects and agenesis of the corpus callosum. The etiology remains unknown and there is uncertainty on best practice therapy and outcome. We aimed at defining quantitative clinical endpoints that will inform future research and clinical trials.

Methods
Quantitative natural history modeling of cases with Aicardi syndrome from published clinical reports. Main outcome measures were age at disease onset, survival and diagnostic delay. Phenotypic features of affected individuals as well as neuroradiological and ophthalmological features were descriptively stated. STROBE criteria were respected.

Results
Two hundred forty-five cases were available for analysis. Median age at disease onset was 2.2 months. Median diagnostic delay was 1 month. Mortality was estimated with 6% at 1 and 17% at 5 years of age. 60% of children showed the classic clinical features, while 40% met the revised diagnostic criteria. We delineate possible predictors of disease severity and of seizure control.

Conclusion
We provide natural history data including geographical localization of 245 published patients with Aicardi syndrome. Quantitative history modeling in rare epileptic encephalopathies will help to raise disease awareness and facilitate future clinical trials as one core element of quantitative systems pharmacology.
Revisiting mutational resistance to ampicillin and cefotaxime in Haemophilus influenzae
Authors: Diricks Margo , Petersen Sabine , Bartels Lennart , Lâm Thiên-Trí , Claus Heike , Bajanca-Lavado Maria Paula , Hauswaldt Susanne , Stolze Ricardo , Vázquez Omar Jiménez , Utpatel Christian , Niemann Stefan , Rupp Jan , Wohlers Inken , Merker Matthias 
Published: December 2024

Abstract
Background
Haemophilus influenzae is an opportunistic bacterial pathogen that can cause severe respiratory tract and invasive infections. The emergence of β-lactamase-negative ampicillin-resistant (BLNAR) strains and unclear correlations between genotypic (i.e., gBLNAR) and phenotypic resistance are challenging empirical treatments and patient management. Thus, we sought to revisit molecular resistance mechanisms and to identify new resistance determinants of H. influenzae.

Methods
We performed a systematic meta-analysis of H. influenzae isolates (n = 291) to quantify the association of phenotypic ampicillin and cefotaxime resistance with previously defined resistance groups, i.e., specific substitution patterns of the penicillin binding protein PBP3, encoded by ftsI. Using phylogenomics and a genome-wide association study (GWAS), we investigated evolutionary trajectories and novel resistance determinants in a public global cohort (n = 555) and a new clinical cohort from three European centers (n = 298), respectively.

Results
Our meta-analysis confirmed that PBP3 group II- and group III-related isolates were significantly associated with phenotypic resistance to ampicillin (p < 0.001), while only group III-related isolates were associated with resistance to cefotaxime (p = 0.02). The vast majority of H. influenzae isolates not classified into a PBP3 resistance group were ampicillin and cefotaxime susceptible. However, particularly group II isolates had low specificities (< 16%) to rule in ampicillin resistance due to clinical breakpoints classifying many of them as phenotypically susceptible. We found indications for positive selection of multiple PBP3 substitutions, which evolved independently and often step-wise in different phylogenetic clades. Beyond ftsI, other possible candidate genes (e.g., oppA, ridA, and ompP2) were moderately associated with ampicillin resistance in the GWAS. The PBP3 substitutions M377I, A502V, N526K, V547I, and N569S were most strongly related to ampicillin resistance and occurred in combination in the most prevalent resistant haplotype H1 in our clinical cohort.

Conclusions
Gradient agar diffusion strips and broth microdilution assays do not consistently classify isolates from PBP3 groups as phenotypically resistant. Consequently, when the minimum inhibitory concentration is close to the clinical breakpoints, and genotypic data is available, PBP3 resistance groups should be prioritized over susceptible phenotypic results for ampicillin. The implications on treatment outcome and bacterial fitness of other extended PBP3 substitution patterns and novel candidate genes need to be determined.
Behavioral decline in Shank3Δex4–22 mice during early adulthood parallels cerebellar granule cell glutamatergic synaptic changes
Authors: Kshetri Rajaram , Beavers James O. , Hyde Romana , Ewa Roseline , Schwertman Amber , Porcayo Sarahi , Richardson Ben D. 
Published: December 2024

Abstract
Background
SHANK3, a gene encoding a synaptic scaffolding protein, is implicated in autism spectrum disorder (ASD) and is disrupted in Phelan-McDermid syndrome (PMS). Despite evidence of regression or worsening of ASD-like symptoms in individuals with PMS, the underlying mechanisms remain unclear. Although Shank3 is highly expressed in the cerebellar cortical granule cells, its role in cerebellar function and contribution to behavioral deficits in ASD models are unknown. This study investigates behavioral changes and cerebellar synaptic alterations in Shank3Δex4–22 mice at two developmental stages.

Methods
Shank3Δex4–22 wildtype, heterozygous, and homozygous knockout mice lacking exons 4–22 (all functional isoforms) were subjected to a behavioral battery in both juvenile (5–7 weeks old) and adult (3–5 months old) mouse cohorts of both sexes. Immunostaining was used to show the expression of Shank3 in the cerebellar cortex. Spontaneous excitatory postsynaptic currents (sEPSCs) from cerebellar granule cells (CGCs) were recorded by whole-cell patch-clamp electrophysiology.

Results
Deletion of Shank3 caused deficits in motor function, heightened anxiety, and repetitive behaviors. These genotype-dependent behavioral alterations were more prominent in adult mice than in juveniles. Reduced social preference was only identified in adult Shank3Δex4–22 knockout male mice, while self-grooming was uniquely elevated in males across both age groups. Heterozygous mice showed little to no changes in behavioral phenotypes in most behavioral tests. Immunofluorescence staining indicated the presence of Shank3 predominantly in the dendrite-containing rosette-like structures in CGCs, colocalizing with presynaptic markers of glutamatergic mossy fiber. Electrophysiological findings identified a parallel relationship between the age-related exacerbation of behavioral impairments and the enhancement of sEPSC amplitude in CGCs.

Limitations
Other behavioral tests of muscle strength (grip strength test), memory (Barnes/water maze), and communication (ultrasonic vocalization), were not performed. Further study is necessary to elucidate how Shank3 modulates synaptic function at the mossy fiber-granule cell synapse in the cerebellum and whether these changes shape the behavioral phenotype.

Conclusions
Our findings reveal an age-related exacerbation of behavioral impairments in Shank3Δex4–22 mutant mice. These results suggest that Shank3 may alter the function of glutamatergic receptors at the mossy fiber-cerebellar granule cell synapse as a potential mechanism causing cerebellar disruption in ASD.