bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the costs and consequences of computerized clinical decision support systems in hospitals: a scoping review and recommendations for future practice
Authors: White Nicole M , Carter Hannah E , Kularatna Sanjeewa , Borg David N , Brain David C , Tariq Amina , Abell Bridget , Blythe Robin , McPhail Steven M 
Published: March 2023

Abstract

Objective
Sustainable investment in computerized decision support systems (CDSS) requires robust evaluation of their economic impacts compared with current clinical workflows. We reviewed current approaches used to evaluate the costs and consequences of CDSS in hospital settings and presented recommendations to improve the generalizability of future evaluations.

Materials and Methods
A scoping review of peer-reviewed research articles published since 2010. Searches were completed in the PubMed, Ovid Medline, Embase, and Scopus databases (last searched February 14, 2023). All studies reported the costs and consequences of a CDSS-based intervention compared with current hospital workflows. Findings were summarized using narrative synthesis. Individual studies were further appraised against the Consolidated Health Economic Evaluation and Reporting (CHEERS) 2022 checklist.

Results
Twenty-nine studies published since 2010 were included. Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences. We recommend future studies follow guidance from the CHEERS checklist; use study designs that adjust for confounders; consider both the costs of CDSS implementation and adherence; evaluate consequences that are directly or indirectly affected by CDSS-initiated behavior change; examine the impacts of uncertainty and differences in outcomes across patient subgroups.

Discussion and Conclusion
Improving consistency in the conduct and reporting of evaluations will enable detailed comparisons between promising initiatives, and their subsequent uptake by decision-makers.
Estimating and improving dynamic treatment regimes with a time-varying instrumental variable
Authors: Chen Shuxiao , Zhang Bo 
Published: March 2023

Abstract
Estimating dynamic treatment regimes (DTRs) from retrospective observational data is challenging as some degree of unmeasured confounding is often expected. In this work, we develop a framework of estimating properly defined ‘optimal’ DTRs with a time-varying instrumental variable (IV) when unmeasured covariates confound the treatment and outcome, rendering the potential outcome distributions only partially identified. We derive a novel Bellman equation under partial identification, use it to define a generic class of estimands (termed IV-optimal DTRs) and study the associated estimation problem. We then extend the IV-optimality framework to tackle the policy improvement problem, delivering IV-improved DTRs that are guaranteed to perform no worse and potentially better than a prespecified baseline DTR. Importantly, this IV-improvement framework opens up the possibility of strictly improving upon DTRs that are optimal under the no unmeasured confounding assumption (NUCA). We demonstrate via extensive simulations the superior performance of IV-optimal and IV-improved DTRs over the DTRs that are optimal only under the NUCA. In a real data example, we embed retrospective observational registry data into a natural, two-stage experiment with noncompliance using a differential-distance-based, time-varying IV and estimate useful IV-optimal DTRs that assign mothers to a high-level or low-level neonatal intensive care unit based on their prognostic variables.
UV-DDB stimulates the activity of SMUG1 during base excision repair of 5-hydroxymethyl-2'-deoxyuridine moieties
Authors: Jang Sunbok , Raja Sripriya J , Roginskaya Vera , Schaich Matthew A , Watkins Simon C , Van Houten Bennett 
Published: March 2023

Abstract
UV-damaged DNA-binding protein (UV-DDB) is a heterodimeric protein, consisting of DDB1 and DDB2 subunits, that works to recognize DNA lesions induced by UV damage during global genome nucleotide excision repair (GG-NER). Our laboratory previously discovered a non-canonical role for UV-DDB in the processing of 8-oxoG, by stimulating 8-oxoG glycosylase, OGG1, activity 3-fold, MUTYH activity 4-5-fold, and APE1 (apurinic/apyrimidinic endonuclease 1) activity 8-fold. 5-hydroxymethyl-deoxyuridine (5-hmdU) is an important oxidation product of thymidine which is removed by single-strand selective monofunctional DNA glycosylase (SMUG1). Biochemical experiments with purified proteins indicated that UV-DDB stimulates the excision activity of SMUG1 on several substrates by 4-5-fold. Electrophoretic mobility shift assays indicated that UV-DDB displaced SMUG1 from abasic site products. Single-molecule analysis revealed that UV-DDB decreases the half-life of SMUG1 on DNA by ∼8-fold. Immunofluorescence experiments demonstrated that cellular treatment with 5-hmdU (5 μM for 15 min), which is incorporated into DNA during replication, produces discrete foci of DDB2-mCherry, which co-localize with SMUG1-GFP. Proximity ligation assays supported a transient interaction between SMUG1 and DDB2 in cells. Poly(ADP)-ribose accumulated after 5-hmdU treatment, which was abrogated with SMUG1 and DDB2 knockdown. These data support a novel role for UV-DDB in the processing of the oxidized base, 5-hmdU.
Association Between Candidemia and Noninfectious Interstitial Pneumonia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group
Authors: Kimura Shun-ichi , Akahoshi Yu , Shiratori Souichi , Okinaka Keiji , Harada Kaito , Uchida Naoyuki , Doki Noriko , Ikegame Kazuhiro , Nakamae Hirohisa , Tanaka Masatsugu , Takada Satoru , Kawakita Toshiro , Matsuoka Ken-ichi , Ara Takahide , Ota Shuichi , Sawa Masashi , Onizuka Makoto , Fukuda Takahiro , Atsuta Yoshiko , Kanda Yoshinobu , Nakasone Hideki 
Published: March 2023

Abstract

Background
α-mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in mouse models. This study aimed to evaluate the association between candidemia and noninfectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients.

Methods
Using a Japanese transplant registry database, we analyzed 9143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7531) or second (n = 1612) allogeneic HCT between 2009 and 2019.

Results
Noninfectious IP was observed in 694 patients at a median (range) of 63 (0–1292) days after HCT. Candidemia occurred in 358 patients at a median (range) of 31 (0–903) days after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of noninfectious IP (hazard ratio [HR], 2.51; 95% CI, 1.48–4.25), along with total body irradiation (&gt;8 Gy; HR, 1.57; 95% CI, 1.18–2.10) and malignant lymphoma (vs acute myeloid leukemia; HR, 1.30; 95% CI, 1.004–1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95% CI, 0.45–0.75) and acute lymphoblastic leukemia (vs acute myeloid leukemia; HR, 0.68; 95% CI, 0.49–0.94) were associated with reduced incidence of noninfectious IP. The median survival after the development of noninfectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs 59 days; P &lt; .001).

Conclusions
Candidemia was associated with an increased incidence of noninfectious IP. The prognosis of noninfectious IP after candidemia was extremely poor.
Lamivudine induced pure red cell aplasia and HIV-1 drug resistance-associated mutations: a case report
Authors: Kakubu Mireille A M , Bikinesi Tarisai , Katoto Patrick D M C 
Published: March 2023

ABSTRACTAdverse effects linked to antiretroviral therapy (ART) may contribute to poor adherence on the patient’s side. Consequently, human immunodeficiency virus (HIV) drug resistance mutations could emerge, negatively impacting the body’s immune system. Meanwhile, severe immunosuppression can lead to several conditions, including anemia. The cause of anemia in HIV infection is multifactorial, and can be mainly explained by deleterious direct effects of the virus on the bone marrow, and opportunistic infections such as Parvovirus B19. Other causes include blood loss resulting from neoplasms and gastrointestinal lesions. Moreover, anemia can also be caused by antiretroviral drugs. We report a case of persistent anemia after ART initiation, kidney injury and treatment failure following a lengthy period of non-adherence to ART. The anemia was classified as Pure Red Cell Aplasia (PRCA). With treatment modification, the anemia resolved and the patient attained virologic suppression. Lamivudine (3TC) was pointed out as the cause of PRCA, which resolved after its withdrawal from the ART regimen. This rare side effect should be investigated in patients on 3TC who present with recurrent anemia.
Ruptured pulmonary hydatid cyst and lophomoniasis comorbidity in a young man: a rare case
Authors: Jalayeri Mohammad H T , Zakariaei Zakaria , Fakhar Mahdi , Sharifpour Ali , Banimostafavi Elham S , Soleymani Mostafa 
Published: March 2023

ABSTRACTHydatidosis is a parasitic and zoonotic infection caused by the larval stage of Echinococcus granulosus. Cysts of this parasite involve almost all the organs of the human body, especially the liver and lungs. Asymptomatic cases may develop into symptomatic pulmonary hydatidosis due to the rupture of hydatid cysts. Lophomonas, as causative agents of pulmonary lophomoniasis, is an emerging protozoan that mostly infects the lower respiratory airways. Clinical symptoms of these two diseases can mostly be overlapped. Herein, we describe the rare case of comorbidity of a ruptured cystic echinococcosis and lophomoniasis in a 38-year-old male farmer with a history of opium addiction from northern Iran.
Cognitive heterogeneity reveals molecular signatures of age-related impairment
Authors: Logan Sreemathi , Baier Matthew P , Owen Daniel B , Peasari John , Jones Kenneth L , Ranjit Rojina , Yarbrough Hannah P , Masingale Anthony M , Bhandari Suyesha , Rice Heather C , Kinter Michael T , Sonntag William E 
Published: March 2023

AbstractThe greatest risk factor for cognitive decline is aging. The biological mechanisms for this decline remain enigmatic due, in part, to the confounding of normal aging mechanisms and those that contribute to cognitive impairment. Importantly, many individuals exhibit impaired cognition in age, while some retain functionality despite their age. Here, we establish a behavioral testing paradigm to characterize age-related cognitive heterogeneity in inbred aged C57BL/6 mice and reliably separate animals into cognitively “intact” (resilient) and “impaired” subgroups using a high-resolution home-cage testing paradigm for spatial discrimination. RNA sequencing and subsequent pathway analyses of cognitively stratified mice revealed molecular signatures unique to cognitively impaired animals, including transcriptional down-regulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) and sirtuin (Sirt1 and Sirt3) expression in the hippocampus. Mitochondrial function assessed using high-resolution respirometry indicated a reduced OXPHOS coupling efficiency in cognitively impaired animals with subsequent hippocampal analyses revealing an increase in the oxidative damage marker (3-nitrotyrosine) and an up-regulation of antioxidant enzymes (Sod2, Sod1, Prdx6, etc.). Aged–impaired animals also showed increased levels of IL-6 and TNF-α gene expression in the hippocampus and increased serum levels of proinflammatory cytokines, including IL-6. These results provide critical insight into the diversity of brain aging in inbred animals and reveal the unique mechanisms that separate cognitive resilience from cognitive impairment. Our data indicate the importance of cognitive stratification of aging animals to delineate the mechanisms underlying cognitive impairment and test the efficacy of therapeutic interventions.
Optimal synchronization in pulse-coupled oscillator networks using reinforcement learning
Authors: Chen Ziqin , Anglea Timothy , Zhang Yuanzhao , Wang Yongqiang 
Published: March 2023

Abstract
Spontaneous synchronization is ubiquitous in natural and man-made systems. It underlies emergent behaviors such as neuronal response modulation and is fundamental to the coordination of robot swarms and autonomous vehicle fleets. Due to its simplicity and physical interpretability, pulse-coupled oscillators has emerged as one of the standard models for synchronization. However, existing analytical results for this model assume ideal conditions, including homogeneous oscillator frequencies and negligible coupling delays, as well as strict requirements on the initial phase distribution and the network topology. Using reinforcement learning, we obtain an optimal pulse-interaction mechanism (encoded in phase response function) that optimizes the probability of synchronization even in the presence of nonideal conditions. For small oscillator heterogeneities and propagation delays, we propose a heuristic formula for highly effective phase response functions that can be applied to general networks and unrestricted initial phase distributions. This allows us to bypass the need to relearn the phase response function for every new network.
68Ga-labeled amphiphilic polymer nanoparticles for PET imaging of sentinel lymph node metastasis
Authors: Chen Qin , Fu Xiaomin , Cai Huawei , Fu Shengxiang , Cai Zhongyuan , Li Mufeng , Wu Xiaoai , Tian Rong , Ai Hua 
Published: March 2023

Abstract
Precise diagnosis of lymph node metastasis is important for therapeutic regimen planning, prognosis analysis and probably better outcomes for cancer patients. In this work, 68Ga-labeled amphiphilic alternating copolymers nanoparticles with different rigid ligands were synthesized as positron emission tomography (PET) probes for lymph node metastasis imaging. The labeling efficiency and stability of nanoparticles was improved with increased rigidity of coordination unit. PU(68Ga-L-MDI-PEG) nanoparticles (PU(68Ga-L-MDI-PEG) NPs) with the strongest rigidity of coordination unit exhibited the lowest critical micelle concentration, the best 68Ga labeling efficiency and stability. During in vivo lymph node metastasis imaging, PU(68Ga-L-MDI-PEG) NPs led to different accumulations in normal lymph nodes (N-LN) and tumor metastasized sentinel lymph nodes (T-SLN), which resulted in different PET signal presentation, making it feasible to differentiate N-LN from T-SLN. In comparison, small molecule probe 68GaL had poor lymph node accumulation, not only making it difficult to find lymph nodes on PET/computed tomography scan, but also tough to distinguish N-LN from metastatic ones. Overall, this work provides a reference for design of 68Ga labeled polymeric nanoparticles with high chelation efficiency and stability, as sensitive PET probes for lymph node imaging.
Metabolic disturbances in children with narcolepsy: a retrospective study
Authors: Zhang Min , Thieux Marine , Arvis Laura , Lin Jian-Sheng , Guyon Aurore , Plancoulaine Sabine , Villanueva Carine , Franco Patricia 
Published: March 2023

Abstract

Study objectives
To determine the prevalence of metabolic syndrome (MS) in children with narcolepsy and to evaluate their clinical and sleep characteristics according to the different components of MS.

Methods
This retrospective study consisted of 58 de novo children with narcolepsy (median age: 12.7 years, 48.3% of boys). The recently published MS criteria in a French population of children were used. Clinical and sleep characteristics were compared between groups with different components of MS.

Results
MS was present in 17.2% of children with narcolepsy, among whom 79.3% presented with high homeostasis model assessment for insulin resistance (HOMA-IR), 25.9% with high body mass index, 24.1% with low high-density lipoprotein cholesterol (HDL-C), and 12.1% with high triglycerides. Patients with at least two MS components had more night eating behaviors and tended to have lower percentage of slow-wave sleep and more fragmented sleep. On multiple sleep latency test, they had shorter mean sleep latencies to rapid eye movement (REM), non-REM sleep and tended to have more sleep onset REM periods (SOREMPs) than those with less than two MS components.

Conclusions
Insulin resistance was found to be the core metabolic disturbance in obese as well as in nonobese children with narcolepsy. Children with narcolepsy with at least two MS components presented a more severe daytime sleepiness and a higher prevalence of night-eating behaviors than those with less than two MS components. Such children might benefit from early evaluation and management in order to prevent future complications.
OpNotes and Clinical Exercises: Activities to Enhance the Clinical Context of the Preclerkship Anatomy Dissection Laboratory
Authors: Meredith M. Alex , Harrell Kelly M. , Foster Kenneth W. , Edwards Cherie , Puche Adam C. 
Published: March 2023

ProblemDespite numerous pedagogical approaches and technologies now available for medical gross anatomy, students can find it difficult to translate what occurs in a dissection laboratory into the context of clinical practice.ApproachUsing complementary and collaborative approaches at 2 different medical schools, Virginia Commonwealth University (VCU) and University of Maryland (UM), we designed and implemented a series of clinical activities in the preclerkship medical gross anatomy laboratory that directly link dissected structures to clinical procedures. These activities specifically direct students to perform simulated clinically related procedures on anatomic donors during laboratory dissection sessions. The activities are called OpNotes at VCU and Clinical Exercises at UM. Each activity in the VCU OpNotes requires about 15 minutes of group activity at the end of a scheduled laboratory and involves faculty to grade the student responses submitted via a web-based-assessment form. Each exercise in UM Clinical Exercises also requires about 15 minutes of group activity during the schedule laboratory but does not involve faculty to complete grading.OutcomesCumulatively, the activities in OpNotes and Clinical Exercises both brought clinical context directly to anatomical dissections. These activities began in 2012 at UM and 2020 at VCU, allowing a multiyear and multi-institute development and testing of this innovative approach. Student participation was high, and perception of its effectiveness was almost uniformly positive.Next StepsFuture iterations of the program will work to assess the efficacy of the program as well as to streamline the scoring and delivery of the formative components. Collectively, we propose that the concept of executing clinic-like procedures on donors in anatomy courses is an effective means of enhancing learning in the anatomy laboratory while concurrently underscoring the relevance of basic anatomy to future clinical practice.
Are all Cages Created Equal? Analysis of Cervical Cage Malfunctions Using FDA MAUDE Database
Authors: Ungurean Victor , Piple Amit S. , Raji Oluwatodimu Richard , Rowland Andrea , Schlauch Adam , Kondrashov Dimitriy G. , Hsu Ken Y. , Zucherman James F. 
Published: March 2023

Study Design.
Retrospective case series.

Objective.
To characterize failure rates of cervical cages based on manufacturer and design characteristics using the nationwide database of reported malfunctions.

Background.
The Food and Drug Administration (FDA) aims to ensure the safety and efficacy of cervical interbody implants postimplantation; however, intraoperative malfunctions may be overlooked.

Materials and Methods.
The FDA’s Manufacturer and User Facility Device Experience database was queried for reports of cervical cage device malfunctions from 2012 to 2021. Each report was categorized based on the failure type, implant design, and manufacturer. Two market analyses were performed. First, “failure-to-market share indices” were generated by dividing the number of failures per year for each implant material by its yearly US market share in cervical spine fusion. Second, “failure-to-revenue indices” were calculated by dividing the total number of failures per year for each manufacturer by their approximate yearly revenue from spinal implants in the US. Outlier analysis was performed to generate a threshold value above which failure rates were defined as greater than the normal index.

Results.
In total, 1336 entries were identified, and 1225 met the inclusion criteria. Of these, 354 (28.9%) were cage breakages, 54 (4.4%) were cage migrations, 321 (26.2%) were instrumentation-related failures, 301 (24.6%) were assembly failures, and 195 (15.9%) were screw failures. Poly-ether-ether-ketone implants had higher failure by market share indices for both migration and breakage compared with titanium. Upon manufacturer market analysis, Seaspine, Zimmer-Biomet, K2M, and LDR exceeded the failure threshold.

Conclusion.
The most common cause of implant malfunction was breakage. Poly-ether-ether-ketone cages were more likely to break and migrate compared with titanium ones. Many of these implant failures occurred intraoperatively during instrumentation, which underscores the need for FDA evaluation of these implants and their accompanying instrumentation under the appropriate loading conditions before commercial approval.
The Utility of 18F-NaF-Positron Emission Tomography/Computed Tomography in Measuring the Metabolic Activity of the Aging Spine
Authors: Park Peter Sang Uk , Resto David A. , Khurana Navpreet , Raynor William Y. , Werner Thomas J. , Høilund-Carlsen Poul Flemming , Alavi Abass 
Published: March 2023

Study Design.
Cross-sectional; observational.

Objectives.
To determine whether sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) can be used to monitor decreased bone turnover with aging in the spine.

Background.
Osteoporosis is characterized by structural changes in the bone such as decreased bone mineral density leading to an increased risk for fractures. An imaging modality capable of identifying molecular changes that precede these structural changes could be critical for the early diagnosis and monitoring of osteoporosis and other metabolic bone disorders.

Materials and Methods.
The potential of 18F-sodium fluoride (NaF)–PET/CT in detecting changes in bone turnover associated with aging was examined in the lumbar spine of 88 healthy volunteers (43 females, 45 males; mean age 44.6 yr). Regions of interest equal to the trabecular body of the L1 to L4 vertebrae were used to calculate the mean standardized uptake value (SUVmean) and average Hounsfield unit (HU) values. Receiver-operating characteristic curve analysis with an area under the curve using the Wilson/Brown method was generated to assess the value of NaF uptake (SUVmean) in predicting osteoporosis as defined by HU-threshold values. To determine the correlation among global SUVmean, mean HU values, and age, the Spearman correlation test was performed on images acquired at 90 minutes postinjection.

Results.
There was a significant negative correlation between NaF SUVmean and age in females (P < 0.0001, r = −0.59), and a weaker, but also significant correlation in males (P = 0.03, r = −0.32). In females only, there was a significant correlation between NaF uptake and age at all acquisition time points. Measured NaF uptake increased by 10% to 15% with acquisition time in both sexes, from 45 to 90 minutes and from 90 to 180 minutes.

Conclusions.
NaF-PET/CT detects decreased vertebral bone turnover with aging, particularly in females. Measured NaF uptake increased with PET acquisition time after tracer injection, which must be considered in follow-up studies monitoring disease development and treatment effects.