bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mean Delta Method: Quantifying Assessor Stringency and Leniency and Identifying Outliers in Workplace-Based Assessments
Authors: Dewhirst Sebastian , Cheung Warren J. , Wood Timothy , Szabo Nora D. , Frank Jason R. 
Published: July 2024

Abstract
Assessor stringency and leniency (ASL)—an assessor’s tendency to award low or high scores—has a significant effect on workplace-based assessments. Outliers on this spectrum have a disproportionate effect. However, no method has been published for quantifying ASL or identifying outlier stringent or lenient assessors using workplace-based assessment data. The authors propose the mean delta method, which compares the scores that an assessor awards to trainees with those trainees’ mean scores. This novel, simple method can be used to quantify ASL and identify outlier assessors without requiring specialized statistical knowledge or software. As a worked example, the mean delta method was applied to a set of end-of-shift assessments completed in a large Canadian academic emergency department from July 1, 2017, to May 31, 2018, and used to examine the net effect of ASL on learners’ assessment scores. A total of 3,908 assessments were completed by 99 assessors for 151 trainees, with a median (interquartile range) of 37 (12–39) completed assessments per trainee. Using cutoff values of 1.5 and 2 standard deviations, a total of 11 and 3 outlier assessors were identified, respectively. Moreover, ASL changed overall scores by more than the mean difference between years of training for nearly 1 in 4 learners. The mean delta method was able to quantify ASL and identify outlier lenient and stringent assessors. It was also used to quantify the net effect of ASL on individual trainees. This method could be used to further study outlier assessors, to identify assessors who may benefit most from targeted coaching and feedback, and to measure changes in assessors’ tendencies over time or with specific intervention.
Procedures for a Transpyloric Feeding Tube Inserted Into Newborns and Infants
Authors: Quinteiro Norma Mejias , Fioravanti Dos Santos Josilene , de Siqueira Caldas Jamil Pedro , Carmona Elenice Valentim 
Published: July 2024

Background:
Enteral feeding by a transpyloric tube in critically ill infants is indicated when there is a failure in gastric feeding. However, there is a wide variability regarding the insertion technique.

Purpose:
To perform a systematic review of the methods for inserting a transpyloric feeding tube in newborns and infants.

Data Sources:
Nine databases, without date or language restrictions, accessed in September 2021.

Study Selection:
A systematic review of experimental and nonexperimental studies, according to the “Patient/problem; Intervention; Comparison; Outcome” strategy and the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” guidelines. The clinical question was about the measurement and insertion techniques, as well as the success rates of properly placing a transpyloric tube in newborns and infants.

Data Extraction:
Two authors (N.M.Q. and J.F.S.) analyzed 6 observational descriptive prospective studies, all of them published in peer-reviewed indexed medical journals and one in the official journal of the National Association of Neonatal Nurses.

Results:
The success rate varied between 70% and 100%. There was an important variability in the type of tube, measurement method, and insertion techniques. It was found that the most common strategies to achieve proper positioning were glabella-calcaneal measurements, gastric air insufflation, and right lateral decubitus.

Implications for Practice:
A transpyloric catheter insertion protocol needs to be established in each neonatal unit, according to the literature findings.

Implications for Research:
Randomized controlled studies that evaluate the gastric air insufflation technique and other adjuvant measures could elucidate the knowledge gap concerning the correct positioning of transpyloric tubing in newborns and infants.
New Predictive Equation for the Estimation of Plasma Concentrations of Formed Colistin in Patients Treated With Colistimethate Sodium for Multidrug-Resistant Gram-Negative Bacterial Infections
Authors: Luque Sonia , Sorlí Luisa , Li Jian , Fernández-Sala Xènia , Berenguer Nuria , Colominas-González Elena , Benítez-Cano Adela , Montero María Milagro , Subirana Isaac , Prim Nuria , García-Paricio Ramón , Horcajada Juan Pablo , Grau Santiago 
Published: July 2024

Background:The clinical use of colistin methanesulphonate (CMS) is limited by potential nephrotoxicity. The selection of an efficient and safe CMS dose for individual patients is complicated by the narrow therapeutic window and high interpatient pharmacokinetic variability. In this study, a simple predictive equation for estimating the plasma concentration of formed colistin in patients with multidrug and extremely drug-resistant gram-negative bacterial infections was developed.Methods:The equation was derived from the largest clinical cohort of patients undergoing therapeutic drug monitoring (TDM) of colistin for over 8 years in a tertiary Spanish hospital. All variables associated with Css,avgwere selected in a multiple linear regression model that was validated in a second cohort of 40 patients. Measured Css,avgvalues were compared with those predicted by our model and a previous published algorithm for critically ill patients.Results:In total, 276 patients were enrolled [the mean age was 67.2 (13.7) years, 203 (73.6%)] were male, and the mean (SD) Css,avgwas 1.12 (0.98) mg/L. Age, gender, estimated glomerular filtration rate, CMS dose and frequency, and concomitant drugs were included in the model. In the external validation, the previous algorithm appeared to yield more optimized colistin plasma concentrations when all types of Css,avgvalues (high and low) were considered, while our equation yielded a more optimized prediction in the subgroup of patients with low colistin plasma concentrations (Css,avg<1.5 mg/L).Conclusions:The proposed equation may help clinicians to better use CMS among a wide variety of patients, to maximize efficacy and prevent nephrotoxicity. A further prospective PK study is warranted to externally validate this algorithm.
Vulvar Reconstruction with Keystone Flaps after Radical Vulvectomy
Authors: Páez López Germán , Martínez Gil Sofia , Zannin Ferrero Andreina , Ramos Hernández Daniel , Caicedo Páez Lina M. 
Published: July 2024

Summary:
Vulvar cancer is a rare oncologic pathology, accounting for only 3%–5% of all gynecologic neoplasms, with squamous cell carcinoma responsible for more than 90% of these cases; the remaining 10% includes Paget disease, lichen sclerosus, and vulvar melanoma. Radical vulvectomy has become the gold standard treatment due to the high recurrence rate and effective local control in patients with squamous cell carcinoma stages IB to IVA. To address these needs, various reconstructive options have been reported in the literature, each potentially offering different results due to their diverse nature. We present a series of patients who underwent vulvar reconstruction with the keystone flap, describing the surgical technique, complication rate, advantages over other techniques, and long-term follow-up.
Establishing a Collaborative Orthoplastic Approach for the Management of Primary Musculoskeletal Neoplasms: An 8-year Case Series
Authors: Byrnes Yasmeen M. , Makar Gabriel , Madera Joshua D. , Ruffino Amanda E. , Frank Katie , Bowen Thomas R. , Devitt Sean M. 
Published: July 2024

Summary:
Orthoplastic surgery is a multidisciplinary approach that is well-studied for extremity trauma, but not for musculoskeletal oncologic reconstruction. Here, the authors describe the application of a collaborative orthoplastic approach for the management of primary musculoskeletal neoplasms and evaluate its impact. The collaboration protocol, implemented in July 2019, comprises specific checkpoints of interdisciplinary co-management, which span the pre-, intra-, and postoperative treatment period. This involves direct communication between attending surgeons and their respective clinical teams. Patients who underwent resection of a primary musculoskeletal neoplasm between March 2014 and April 2022 were retrospectively categorized into conventional or collaboration groups. Of the 136 total patients, there were 63.2% (n = 86) conventional and 36.8% (n = 50) collaboration; 31.6% (n = 43) had reconstruction and 68.4% (n = 93) did not. Compared with the conventional group, the collaboration group had significantly higher rates of diabetes (18% versus 7%, P = 0.048) and radiation treatment (68% versus 43%, P = 0.005). The collaboration group was significantly more likely to have plastic surgery involvement in their care than the conventional group (38% versus 14%, P = 0.001), and to undergo reconstruction (42% versus 26%, P = 0.047). The groups showed no difference in rates of hematoma, seroma, delayed healing, infection, 30- or 90-day reoperation, or partial or complete flap/graft failure. The collaborative approach described here is feasible and associated with increased plastic surgery involvement and reconstructive surgery. Complications were equivalent despite evidence suggesting increased case complexity in the collaboration group. These early results are promising and could inspire wider adoption of structured orthoplastic protocols for care of these patients.
Labor Market Participation Among Working-Age Heart Failure Patients With a Cardiac Resynchronization Therapy Device
Authors: Bjerre Henrik Laurits , Mols Rikke Elmose , Bakos Istvan , Frausing Maria Hee Jung Park , Horváth-Puhó Erzsébet , Witt Christoffer Tobias , Eiskjær Hans , Løgstrup Brian Bridal , Kronborg Mads Brix , Nielsen Jens Cosedis 
Published: July 2024

Purpose:
Labor market participation is an important rehabilitation goal for working-age patients living with heart failure (HF). Cardiac resynchronization therapy (CRT) reduces mortality and HF hospitalizations and improves quality of life, but no studies have investigated labor market participation following CRT. We therefore aimed to describe labor market participation in patients with HF before and after CRT implantation.

Methods:
This region-wide register-based cohort study comprised patients with HF aged 40 to 63 yr, with ejection fraction ≤35% and QRS duration >130 milliseconds, who received a CRT system from 2000 to 2017 in the Central Denmark Region. Using unambiguous, individual-level linkage in Danish medical and administrative registries, we assessed weekly employment status from 1 yr prior to CRT implantation until 2 to 5 yr of follow-up and conducted stratified analyses by sociodemographic and disease-related risk factors.

Results:
We identified 546 patients, of whom 42% were in early retirement 1 yr prior to implantation. Active employment decreased from 45% to 19% from 1 yr before until implantation, declining primarily in the last 8 wk before implantation. The proportion of patients in active employment increased in the first 8 wk after CRT implantation and then stabilized, reaching 31% at 1-yr follow-up. We observed lower labor market participation in patients with older age, multimorbidity, lower educational level, and upgrade procedures, but higher in later calendar year.

Conclusions:
In working-age patients with HF, labor market participation increased after CRT implantation, despite many patients being retired prior to implantation. We observed differences in active employment related to several sociodemographic and disease-related factors.
Intestinal IL-33 promotes microbiota-derived trimethylamine N-oxide synthesis and drives metabolic dysfunction–associated steatotic liver disease progression by exerting dual regulation on HIF-1α
Authors: Hai Suping , Li Xitang , Xie Erliang , Wu Wenhui , Gao Qiang , Yu Binghui , Hu Junjian , Xu Feiyang , Zheng Xizhe , Zhang Bin-hao , Wu Di , Yan Weiming , Ning Qin , Wang Xiaojing 
Published: July 2024

Background and Aims:
Gut microbiota plays a prominent role in the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD). IL-33 is highly expressed at mucosal barrier sites and regulates intestinal homeostasis. Herein, we aimed to investigate the role and mechanism of intestinal IL-33 in MASLD.

Approach and Results:
In both humans and mice with MASLD, hepatic expression of IL-33 and its receptor suppression of tumorigenicity 2 (ST2) showed no significant change compared to controls, while serum soluble ST2 levels in humans, as well as intestinal IL-33 and ST2 expression in mice were significantly increased in MASLD. Deletion of global or intestinal IL-33 in mice alleviated metabolic disorders, inflammation, and fibrosis associated with MASLD by reducing intestinal barrier permeability and rectifying gut microbiota dysbiosis. Transplantation of gut microbiota from IL-33 deficiency mice prevented MASLD progression in wild-type mice. Moreover, IL-33 deficiency resulted in a decrease in the abundance of trimethylamine N-oxide–producing bacteria. Inhibition of trimethylamine N-oxide synthesis by 3,3-dimethyl-1-butanol mitigated hepatic oxidative stress in mice with MASLD. Nuclear IL-33 bound to hypoxia-inducible factor-1α and suppressed its activation, directly damaging the integrity of the intestinal barrier. Extracellular IL-33 destroyed the balance of intestinal Th1/Th17 and facilitated Th1 differentiation through the ST2-Hif1a-Tbx21 axis. Knockout of ST2 resulted in a diminished MASLD phenotype resembling that observed in IL-33 deficiency mice.

Conclusions:
Intestinal IL-33 enhanced gut microbiota–derived trimethylamine N-oxide synthesis and aggravated MASLD progression through dual regulation on hypoxia-inducible factor-1α. Targeting IL-33 and its associated microbiota may provide a potential therapeutic strategy for managing MASLD.
SLC10A5 deficiency causes hypercholanemia
Authors: Xu Yuqing , Qian Yeqing , Yu Ying , Zhan Xin , Jin Pengzhen , Hong Jiawei , Dong Minyue 
Published: July 2024

Background and Aims:
Solute Carrier Family 10 Member 5 (SLC10A5) is a member of SLC10, comprising transporters of bile acids, steroidal hormones, and other substrates, but its function remains unclear. The aim of the current investigation was to clarify its function in the metabolism of bile acid and hypercholanemia.

Approach and Results:
Whole-exome sequencing and Sanger sequencing were used to identify and confirm the variant in the subjects of hypercholanemia. CRISPR/Cas9-mediated genome engineering was used to establish the knockout and point mutation mice. Primary mouse hepatocytes were isolated, and cell lines were cultured. SLC10A5 was silenced by siRNA and overexpressed by wild-type and mutant plasmids. The fluorescent bile acid derivative was used for the bile acid uptake assay. Bile acids were assessed with ultra-performance liquid chromatography tandem mass spectrometry. A heterozygous variant SLC10A5: c.994_995del (p.D332X) was identified in subjects with elevated total bile acid or altered bile acid profiles. Bile acids were increased in the serum and liver of knockout and point mutation mice. The expressions of FXR and SHP, regulators involved in the negative feedback of bile acid synthesis, were downregulated, while the bile acid synthesis genes CYP7A1 and CYP8B1 were upregulated in both gene-edited mice. Both the wild and mutant SLC10A5 proteins were localized on the plasma membrane. Knockdown, knockout, or targeted mutation of SLC10A5 led to the inhibition of bile acid uptake by cell lines and primary mouse hepatocytes.

Conclusion:

SLC10A5 is involved in the uptake of bile acid, and its deficiency causes hypercholanemia.
Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver
Authors: Huang Yeping , Yu Fan , Ding Yue , Zhang Hong , Li Xinyue , Wang Xiao , Wu Xiaoshan , Xu Jie , Wang Liang , Tian Chenxu , Jiang Min , Zhang Rong , Yan Chenyan , Song Yingxiang , Huang Haijun , Xu Guangzhong , Ding Qiurong , Ye Xiao , Lu Yan , Hu Cheng 
Published: July 2024

Background and Aims:
An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain.

Approach and Results:
This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3β HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3β HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3β HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3β HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice.

Conclusions:
These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3β HCA and hepatic lipid homeostasis.
Temporary Pupil Scaffolding Technique for Managing Positive Vitreous Pressure and Impending Intraocular Lens and Vitreous Extrusion During Penetrating Keratoplasty
Authors: Jacob Soosan , Parashar Parnika , Assaf Jad , Knyazer Boris , Agarwal Amar , Kumar Arun 
Published: July 2024

Purpose:
Positive vitreous pressure (PVP) secondary to intraoperative acute hypotony during penetrating keratoplasty can result in extrusion of the intraocular lens and vitreous. Currently described techniques are difficult or impossible to apply intraoperatively when positive vitreous pressure is noticed in an “open sky” situation after excision of the host corneal button.

Methods:
We describe a technique where pupil scaffolding is used to prevent intraocular lens or crystalline lens extrusion by simply closing the pupil with a temporary suture that holds the retropupillary contents back. Once the eye is thus stabilized, the donor cornea is sutured rapidly after which the pupillary knot is cut and removed using microscissors and microforceps.

Results:
Five patients undergoing penetrating keratoplasty under peribulbar anesthesia underwent this technique after experiencing PVP after host corneal button excision. PVP was successfully controlled in all 5 patients, and the optical grafts remained clear in the postoperative period.

Conclusions:
Temporary pupillary scaffolding can help control PVP and prevent ocular content extrusion during PKP surgeries.
Human Herpesvirus 6 Infection Complicated by Viral Encephalitis Following Liver Transplantation: A Case Report
Authors: Kou Kai , Huang Heyu , Qiu Wei , Chen Yuguo , Sun Xiaodong , Lv Guoyue 
Published: July 2024

Abstract
Human herpesvirus 6 (HHV-6) is a significant pathogen following solid organ transplantation. Here, we report a 64-year-old female with cirrhosis related to nonalcoholic fatty liver disease who underwent orthotopic allogeneic liver transplantation and was ultimately diagnosed with HHV-6 encephalitis through cerebrospinal fluid analysis and MRI. Empirical treatment with daily ganciclovir was initiated according to characteristics indicative of viral encephalitis 3 days before confirmed diagnosis. Subsequent improvement in symptoms was observed, with clearance of HHV-6 from the blood. The complex diagnosis and management of this case accentuate the possibility of serious consequences of HHV-6 infection in postoperative liver transplant patients. Clinicians must maintain a high index of suspicion for HHV-6 reactivation, especially given its association with immunosuppressive drug regimens. Prompt recognition and initiation of antiviral therapy are paramount, particularly when patients present with fever or psychiatric symptoms, as these may indicate HHV-6 encephalitis.
Predictors of Neurologic Disability at Hospital Discharge for Acyclovir-treated Pediatric Herpes Simplex Virus Encephalitis
Authors: Tran Xuan Ngoc , Pham Son Thai , Trinh Tung Huu , Liu Jason J. 
Published: July 2024

Background:
Herpes simplex virus encephalitis (HSE) is a rare but serious neurological infection that causes neurological dysfunction. Research is lacking on the clinical predictors of neurological outcomes and the optimal duration of therapy for pediatric HSE patients. In this study of pediatric HSE patients, we identified factors predicting neurological disability at hospital discharge and examined associations of acyclovir therapy duration with neurological outcomes.

Methods:
This was a retrospective cohort study on 37 children diagnosed with HSE confirmed by polymerase chain reaction at age 1 month to 16 years from 2015 to 2021 in Ho Chi Minh City’s Children’s Hospital No. 2, Vietnam. For the acyclovir duration analysis, we examined 22 children with negative polymerase chain reaction on day 14 of treatment. Poisson regression was used to obtain the risk ratio and 95% confidence interval.

Results:
The study population consisted of 73% males, with a median age of 14 months (interquartile range: 9–35). Coma at acyclovir treatment, hypotension and the need for mechanical ventilation ≥48 hours significantly predicted neurological disability in the bivariate analysis. There were no significant associations between acyclovir duration (14 vs. 21 days) and neurological outcomes, adjusting for age at diagnosis and pediatric Glasgow Coma Scale score at acyclovir initiation.

Conclusion:
We identified significant predictors of neurological disability unaffected by postacyclovir treatment factors. Among patients with negative HSE polymerase chain reaction on day 14, 14 days of acyclovir treatment may be as effective as 21 days. Additional studies on the effects of acyclovir duration are needed.