bluuebunny/crossref_metadata_2025_split huggingface dataset:
Needs assessment for enhancing pediatric clerkship readiness
Authors: Weinstein Adam , MacPherson Peter , Schmidt Suzanne , Van Opstal Elizabeth , Chou Erica , Pogemiller Mark , Gibbs Kathleen , Held Melissa 
Published: March 2023

AbstractBackgroundMany students report feeling inadequately prepared for their clinical experiences in pediatrics. There is striking variability on how pediatric clinical skills are taught in pre-clerkship curricula.MethodsWe asked students who completed their clerkships in pediatrics, family medicine, surgery, obstetrics-gynecology and internal medicine to rate their pre-clinical training in preparing them for each clerkship, specifically asking about medical knowledge, communication, and physical exam skills. Based on these results, we surveyed pediatric clerkship and clinical skills course directors at North American medical schools to describe the competence students should have in the pediatric physical exam prior to their pediatric clerkship.ResultsClose to 1/3 of students reported not feeling adequately prepared for their pediatrics, obstetrics-gynecology, or surgery clerkship. Students felt less prepared to perform pediatric physical exam skills compared to physical exam skills in all other clerkships. Pediatric clerkship directors and clinical skills course directors felt students should have knowledge of and some ability to perform a wide spectrum of physical exam skills on children. There were no differences between the two groups except that clinical skills educators identified a slightly higher expected competence for development assessment skills compared to pediatric clerkship directors.ConclusionsAs medical schools undergo cycles of curricular reform, it may be beneficial to integrate more pre-clerkship exposure to pediatric topics and skills. Further exploration and collaboration establishing how and when to incorporate this learning could serve as a starting point for curricular improvements, with evaluation of effects on student experience and performance. A challenge is identifying infants and children for physical exam skills practice.
Improving heart failure care with an Experience-Based Co-Design approach: what matters to persons with heart failure and their family members?
Authors: Suutari Anne-Marie , Thor Johan , Nordin Annika , Josefsson Kristina Areskoug 
Published: March 2023

Abstract
Background
Heart failure is a chronic heart condition. Persons with heart failure often have limited physical capability, cognitive impairments, and low health literacy. These challenges can be barriers to healthcare service co-design with family members and professionals. Experience-Based Co-Design is a participatory healthcare quality improvement approach drawing on patients’, family members’ and professionals’ experiences to improve healthcare. The overall aim of this study was to use Experience-Based Co-Design to identify experiences of heart failure and its care in a Swedish cardiac care setting, and to understand how these experiences can translate into heart failure care improvements for persons with heart failure and their families.

Methods
A convenience sample of 17 persons with heart failure and four family members participated in this single case study as a part of an improvement initiative within cardiac care. In line with Experienced-Based Co-Design methodology, field notes from observations of healthcare consultations, individual interviews and meeting minutes from stakeholders’ feedback events, were used to gather participants’ experiences of heart failure and its care. Reflexive thematic analysis was used to develop themes from data.

Results
Twelve service touchpoints, organized within five overarching themes emerged. The themes told a story about persons with heart failure and family members struggling in everyday life due to a poor quality of life, lack of support networks, and difficulties understanding and applying information about heart failure and its care. To be recognized by professionals was reported to be a key to good quality care. Opportunities to be involved in healthcare varied, Further, participants’ experiences translated into proposed changes to heart failure care such as improved information about heart failure, continuity of care, improved relations, and communication, and being invited to be involved in healthcare.

Conclusions
Our study findings offer knowledge about experiences of life with heart failure and its care, translated into heart failure service touchpoints. Further research is warranted to explore how these touchpoints can be addressed to improve life and care for persons with heart failure and other chronic conditions.
Physicians’ views on optimal use and payment system for telemedicine: a qualitative study
Authors: Raes Sarah , Annemans Lieven , Willems Ruben , Trybou Jeroen 
Published: March 2023

Abstract
Background
Telemedicine is already in use in daily practice, but appropriate reimbursement and physician payment is falling behind in many countries. One reason is the limited availability of research on the matter. This research therefore examined physicians’ views on the optimal use and payment modalities for telemedicine.

Methods
Sixty-one semi-structured interviews were conducted with physicians from 19 medical disciplines. Interviews were encoded using thematic analysis.

Results
Telephone and video televisits tend not to be used as a first patient contact, except for triage of patients in urgency situations. Several minimum required modalities for the payment system of televisits and telemonitoring were identified. For televisits these were: (i) remuneration of both telephone- and videovisits to increase healthcare equity, (ii) little or no differentiation between videovisit and in-person visit fee to make videovisits financially attractive and sustainable for physicians, (iii) differentiation of televisit fee per medical discipline, and (iv) quality requirements such as mandatory reporting in the patient’s medical file. The identified minimum required modalities for telemonitoring were: (i) an alternative payment scheme than fee-for-service, (ii) remunerating not only physicians but also other involved health professionals, (iii) designating and remunerating a coordinator, and (iv) distinguishing sporadic vs. continuously follow-up.

Conclusions
This research investigated the telemedicine usage behavior of physicians. Moreover, several minimum required modalities were identified for a physician-supported payment system of telemedicine, as these innovations necessitate challenging and innovation of the healthcare payment systems as well.
Differences in drug use behaviors that impact overdose risk among individuals who do and do not use fentanyl test strips for drug checking
Authors: Tilhou Alyssa Shell , Zaborek Jen , Baltes Amelia , Salisbury-Afshar Elizabeth , Malicki Julia , Brown Randall 
Published: March 2023

Abstract
Background
Opioid-involved overdose continues to rise, largely explained by fentanyl adulteration of the illicit opioid supply. Fentanyl test strips are a novel drug checking tool that can be used by people who use drugs to detect the presence of fentanyl in drug products. However, it is unclear whether fentanyl test strip use can prompt behavior changes that impact risk of overdose.

Methods
In this mixed-methods study involving a structured survey (n = 341) of syringe service program clients in southern Wisconsin, we examined the association between fentanyl test strip use and overdose risk behaviors in scenarios where the presence of fentanyl is confirmed and unknown. Individual items were transformed into summary scales representing the performance of riskier and safer behaviors. Linear regression examined the association of behaviors with FTS use. Models are adjusted for study site, race/ethnicity, age, gender, drug of choice, indicator of polysubstance use, times used per day, and lifetime overdose count.

Results
In response to survey questions before prompting about fentanyl risk, people who used fentanyl test strips reported an increased number of safer (p = 0.001) as well as riskier behaviors (p = 0.018) relative to people who did not use fentanyl test strips. The same held true in situations when fentanyl adulteration was suspected, though fentanyl test strip use lost significance in the fully adjusted model examining safer behaviors (safer: p = 0.143; riskier: p = 0.004). Among people who use fentanyl test strips, in unadjusted models, a positive test result was associated with more safer behaviors and fewer riskier behaviors, but these associations became nonsignificant in fully adjusted models (safer: p = 0.998; riskier: p = 0.171). Loss of significance was largely due to the addition of either polysubstance use or age to the model.

Conclusions
Fentanyl test strip use is associated with behaviors that may impact overdose risk, including safer and riskier behaviors. Specifically, a positive test result may promote more risk reducing behaviors and fewer risk enhancing behaviors than a negative test result. Results suggest that while FTS may promote safer drug use behaviors, outreach and education should emphasize the need for multiple harm reduction techniques in all scenarios.
Diagnostic performance of Idylla MSI test in colorectal cancer biopsies
Authors: Ukkola Iiris , Nummela Pirjo , Kero Mia , Ristimäki Ari 
Published: March 2023

AbstractUniversal testing for microsatellite instability (MSI) is recommended in colorectal cancer (CRC) to screen for Lynch syndrome and to guide optimal treatment and follow-up of the patients. Especially in neoadjuvant setting, where immuno-oncological treatments have recently shown excellent responses, identification of MSI status at biopsy is a prerequisite. Idylla MSI test offers a rapid and automated test to assess MSI-status from formalin-fixed paraffin-embedded tumor tissue sections. In this study, we compared the performance of the Idylla MSI test to mismatch repair (MMR) protein immunohistochemistry (IHC) using 117 CRC biopsies with previously known deficient MMR status. The concordance between Idylla and IHC was 99.0% (95/96) for biopsies with the recommended ≥ 20% tumor cell content. Further, 85.7% (18/21) of suboptimal CRC biopsy specimens (tumor cell content 5–15%) were diagnosed as MSI. Overall, we identified four discrepant cases of which three had tumor cell content less than 20%, explaining the discordant result. Our study shows that the Idylla MSI test offers a competent tool for MSI screening in CRC biopsy specimens.
Targeted gene deletion with SpCas9 and multiple guide RNAs in Arabidopsis thaliana: four are better than two
Authors: Ordon Jana , Kiel Niklas , Becker Dieter , Kretschmer Carola , Schulze-Lefert Paul , Stuttmann Johannes 
Published: March 2023

Abstract
Background
In plant genome editing, RNA-guided nucleases such as Cas9 from Streptococcus pyogenes (SpCas9) predominantly induce small insertions or deletions at target sites. This can be used for inactivation of protein-coding genes by frame shift mutations. However, in some cases, it may be advantageous to delete larger chromosomal segments. This is achieved by simultaneously inducing double strand breaks upstream and downstream of the segment to be deleted. Experimental approaches for the deletion of larger chromosomal segments have not been systematically evaluated.

Results
We designed three pairs of guide RNAs for deletion of a ~ 2.2 kb chromosomal segment containing the Arabidopsis WRKY30 locus. We tested how the combination of guide RNA pairs and co-expression of the exonuclease TREX2 affect the frequency of wrky30 deletions in editing experiments. Our data demonstrate that compared to one pair of guide RNAs, two pairs increase the frequency of chromosomal deletions. The exonuclease TREX2 enhanced mutation frequency at individual target sites and shifted the mutation profile towards larger deletions. However, TREX2 did not elevate the frequency of chromosomal segment deletions.

Conclusions
Multiplex editing with at least two pairs of guide RNAs (four guide RNAs in total) elevates the frequency of chromosomal segment deletions at least at the AtWRKY30 locus, and thus simplifies the selection of corresponding mutants. Co-expression of the TREX2 exonuclease can be used as a general strategy to increase editing efficiency in Arabidopsis without obvious negative effects.
Tumor-to-bone distance and radiomic features on MRI distinguish intramuscular lipomas from well-differentiated liposarcomas
Authors: Sudjai Narumol , Siriwanarangsun Palanan , Lektrakul Nittaya , Saiviroonporn Pairash , Maungsomboon Sorranart , Phimolsarnti Rapin , Asavamongkolkul Apichat , Chandhanayingyong Chandhanarat 
Published: March 2023

AbstractBackgroundTo develop a machine learning model based on tumor-to-bone distance and radiomic features derived from preoperative MRI images to distinguish intramuscular (IM) lipomas and atypical lipomatous tumors/well-differentiated liposarcomas (ALTs/WDLSs) and compared with radiologists.MethodsThe study included patients with IM lipomas and ALTs/WDLSs diagnosed between 2010 and 2022, and with MRI scans (sequence/field strength: T1-weighted (T1W) imaging at 1.5 or 3.0 Tesla MRI). Manual segmentation of tumors based on the three-dimensional T1W images was performed by two observers to appraise the intra- and interobserver variability. After radiomic features and tumor-to-bone distance were extracted, it was used to train a machine learning model to distinguish IM lipomas and ALTs/WDLSs. Both feature selection and classification steps were performed using Least Absolute Shrinkage and Selection Operator logistic regression. The performance of the classification model was assessed using a tenfold cross-validation strategy and subsequently evaluated using the receiver operating characteristic curve (ROC) analysis. The classification agreement of two experienced musculoskeletal (MSK) radiologists was assessed using the kappa statistics. The diagnosis accuracy of each radiologist was evaluated using the final pathological results as the gold standard. Additionally, we compared the performance of the model and two radiologists in terms of the area under the receiver operator characteristic curves (AUCs) using the Delong’s test.ResultsThere were 68 tumors (38 IM lipomas and 30 ALTs/WDLSs). The AUC of the machine learning model was 0.88 [95% CI 0.72–1] (sensitivity, 91.6%; specificity, 85.7%; and accuracy, 89.0%). For Radiologist 1, the AUC was 0.94 [95% CI 0.87–1] (sensitivity, 97.4%; specificity, 90.9%; and accuracy, 95.0%), and as to Radiologist 2, the AUC was 0.91 [95% CI 0.83–0.99] (sensitivity, 100%; specificity, 81.8%; and accuracy, 93.3%). The classification agreement of the radiologists was 0.89 of kappa value (95% CI 0.76–1). Although the AUC of the model was lower than of two experienced MSK radiologists, there was no statistically significant difference between the model and two radiologists (allP > 0.05).ConclusionsThe novel machine learning model based on tumor-to-bone distance and radiomic features is a noninvasive procedure that has the potential for distinguishing IM lipomas from ALTs/WDLSs. The predictive features that suggested malignancy were size, shape, depth, texture, histogram, and tumor-to-bone distance.
Relationship between preoperative red blood cell distribution width and postoperative pneumonia in elderly patients with hip fracture: a retrospective cohort study
Authors: Zhang Daxue , Zhang Yu , Yang Shiwei , Sun Lixin , Zhang Ning , Huang Shaocai 
Published: March 2023

Abstract
Objective
The relationship between the preoperative red blood cell distribution width and postoperative pneumonia in elderly patients with hip fractures remains unclear. This study investigated whether the preoperative red blood cell distribution width was associated with postoperative pneumonia in elderly patients with hip fractures.

Methods
Clinical data of patients with hip fractures in the Department of orthopedics of a hospital from January 2012 to December 2021 were retrospectively analyzed. A generalized additive model was used to identify both linear and nonlinear relationships between red blood cell distribution width and postoperative pneumonia. A two-piecewise linear regression model was used to calculate the saturation effect. Subgroup analyses were performed using stratified logistic regression.

Results
This study included a total of 1444 patients. The incidence of postoperative pneumonia was 6.30% (91/1444), the mean age of the patients was 77.55 ± 8.75 years, and 73.06% of them (1055/1444) were female. After full adjustment for covariates, the preoperative red blood cell distribution width showed a nonlinear relationship with postoperative pneumonia. The two-piecewise regression model showed an inflection point at 14.3%. On the left side of the inflection point, the incidence of postoperative pneumonia increased by 61% for every 1% increase in red blood cell distribution width (OR: 1.61, 95% CI 1.13–2.31, P = 0.0089). The effect size was not statistically significant on the right side of the inflection point (OR: 0.83, 95% CI 0.61–1.12, P = 0.2171).

Conclusion
The relationship between preoperative red blood cell distribution width and incidence or postoperative pneumonia was nonlinear in elderly patients with hip fractures. The incidence of postoperative pneumonia was positively correlated with red blood cell distribution width when it was < 14.3%. A saturation effect was observed when the red blood cell distribution width reached 14.3%.
Alzheimer’s disease genetic risk and cognitive reserve in relationship to long-term cognitive trajectories among cognitively normal individuals
Authors: Pettigrew Corinne , Nazarovs Jurijs , Soldan Anja , Singh Vikas , Wang Jiangxia , Hohman Timothy , Dumitrescu Logan , Libby Julia , Kunkle Brian , Gross Alden L. , Johnson Sterling , Lu Qiongshi , Engelman Corinne , Masters Colin L. , Maruff Paul , Laws Simon M. , Morris John C. , Hassenstab Jason , Cruchaga Carlos , Resnick Susan M. , Kitner-Triolo Melissa H. , An Yang , Albert Marilyn 
Published: March 2023

Abstract
Background
Both Alzheimer’s disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition.

Methods
Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by (i) apolipoprotein-E (APOE) genetic status (APOE-ε2 and APOE-ε4 vs. APOE-ε3; N = 1819) and (ii) AD polygenic risk scores (AD-PRS; N = 1175). A CR index was calculated by combining years of education and literacy scores. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, episodic memory, and executive function.

Results
In mixed-effects models, higher CR index scores were associated with better baseline cognitive performance for all cognitive outcomes. APOE-ε4 genotype and AD-PRS that included the APOE region (AD-PRSAPOE) were associated with declines in all cognitive domains, whereas AD-PRS that excluded the APOE region (AD-PRSw/oAPOE) was associated with declines in executive function and global cognition, but not memory. There were significant 3-way CR index score × APOE-ε4 × time interactions for the global (p = 0.04, effect size = 0.16) and memory scores (p = 0.01, effect size = 0.22), indicating the negative effect of APOE-ε4 genotype on global and episodic memory score change was attenuated among individuals with higher CR index scores. In contrast, levels of CR did not attenuate APOE-ε4-related declines in executive function or declines associated with higher AD-PRS. APOE-ε2 genotype was unrelated to cognition.

Conclusions
These results suggest that APOE-ε4 and non-APOE-ε4 AD polygenic risk are independently associated with global cognitive and executive function declines among individuals with normal cognition at baseline, but only APOE-ε4 is associated with declines in episodic memory. Importantly, higher levels of CR may mitigate APOE-ε4-related declines in some cognitive domains. Future research is needed to address study limitations, including generalizability due to cohort demographic characteristics.
The microbial dark matter and “wanted list” in worldwide wastewater treatment plants
Authors: Zhang Yulin , Wang Yulin , Tang Mingxi , Zhou Jizhong , Zhang Tong 
Published: March 2023

Abstract
Background
Wastewater treatment plants (WWTPs) are one of the largest biotechnology applications in the world and are of critical importance to modern urban societies. An accurate evaluation of the microbial dark matter (MDM, microorganisms whose genomes remain uncharacterized) proportions in WWTPs is of great value, while there is no such research yet. This study conducted a global meta-analysis of MDM in WWTPs with 317,542 prokaryotic genomes from the Genome Taxonomy Database and proposed a “wanted list” for priority targets in further investigations of activated sludge.

Results
Compared with the Earth Microbiome Project data, WWTPs had relatively lower genome-sequenced proportions of prokaryotes than other ecosystems, such as the animal related environments. Analysis showed that the median proportions of the genome-sequenced cells and taxa (100% identity and 100% coverage in 16S rRNA gene region) in WWTPs reached 56.3% and 34.5% for activated sludge, 48.6% and 28.5% for aerobic biofilm, and 48.3% and 28.5% for anaerobic digestion sludge, respectively. This result meant MDM had high proportions in WWTPs. Besides, all of the samples were occupied by a few predominant taxa, and the majority of the sequenced genomes were from pure cultures. The global-scale “wanted list” for activated sludge contained four phyla that have few representatives and 71 operational taxonomic units with the majority of them having no genome or isolate yet. Finally, several genome mining methods were verified to successfully recover genomes from activated sludge such as hybrid assembly of the second- and third-generation sequencing.

Conclusions
This work elucidated the proportion of MDM in WWTPs, defined the “wanted list” of activated sludge for future investigations, and certified potential genome recovery methods. The proposed methodology of this study can be applied to other ecosystems and improve understanding of ecosystem structure across diverse habitats.