bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of nuclear RAGE–Mcm2 axis in diabetes or cancer-associated replication stress
Authors: Han Zhe , Andrš Martin , Madhavan Bindhu K , Kaymak Serap , Sulaj Alba , Kender Zoltan , Kopf Stefan , Kihm Lars , Pepperkok Rainer , Janscak Pavel , Nawroth Peter , Kumar Varun 
Published: March 2023

AbstractAn elevated frequency of DNA replication defects is associated with diabetes and cancer. However, data linking these nuclear perturbations to the onset or progression of organ complications remained unexplored. Here, we report that RAGE (Receptor for Advanced Glycated Endproducts), previously believed to be an extracellular receptor, upon metabolic stress localizes to the damaged forks. There it interacts and stabilizes the minichromosome-maintenance (Mcm2–7) complex. Accordingly, RAGE deficiency leads to slowed fork progression, premature fork collapse, hypersensitivity to replication stress agents and reduction of viability, which was reversed by the reconstitution of RAGE. This was marked by the 53BP1/OPT-domain expression and the presence of micronuclei, premature loss-of-ciliated zones, increased incidences of tubular-karyomegaly, and finally, interstitial fibrosis. More importantly, the RAGE–Mcm2 axis was selectively compromised in cells expressing micronuclei in human biopsies and mouse models of diabetic nephropathy and cancer. Thus, the functional RAGE–Mcm2/7 axis is critical in handling replication stress in vitro and human disease.
Automated tumor segmentation and brain tissue extraction from multiparametric MRI of pediatric brain tumors: A multi-institutional study
Authors: Fathi Kazerooni Anahita , Arif Sherjeel , Madhogarhia Rachel , Khalili Nastaran , Haldar Debanjan , Bagheri Sina , Familiar Ariana M , Anderson Hannah , Haldar Shuvanjan , Tu Wenxin , Chul Kim Meen , Viswanathan Karthik , Muller Sabine , Prados Michael , Kline Cassie , Vidal Lorenna , Aboian Mariam , Storm Phillip B , Resnick Adam C , Ware Jeffrey B , Vossough Arastoo , Davatzikos Christos , Nabavizadeh Ali 
Published: March 2023

AbstractBackgroundBrain tumors are the most common solid tumors and the leading cause of cancer-related death among all childhood cancers. Tumor segmentation is essential in surgical and treatment planning, and response assessment and monitoring. However, manual segmentation is time-consuming and has high interoperator variability. We present a multi-institutional deep learning-based method for automated brain extraction and segmentation of pediatric brain tumors based on multi-parametric MRI scans.MethodsMulti-parametric scans (T1w, T1w-CE, T2, and T2-FLAIR) of 244 pediatric patients (n = 215 internal and n = 29 external cohorts) with de novo brain tumors, including a variety of tumor subtypes, were preprocessed and manually segmented to identify the brain tissue and tumor subregions into four tumor subregions, i.e., enhancing tumor (ET), non-enhancing tumor (NET), cystic components (CC), and peritumoral edema (ED). The internal cohort was split into training (n = 151), validation (n = 43), and withheld internal test (n = 21) subsets. DeepMedic, a three-dimensional convolutional neural network, was trained and the model parameters were tuned. Finally, the network was evaluated on the withheld internal and external test cohorts.ResultsDice similarity score (median ± SD) was 0.91 ± 0.10/0.88 ± 0.16 for the whole tumor, 0.73 ± 0.27/0.84 ± 0.29 for ET, 0.79 ± 19/0.74 ± 0.27 for union of all non-enhancing components (i.e., NET, CC, ED), and 0.98 ± 0.02 for brain tissue in both internal/external test sets.ConclusionsOur proposed automated brain extraction and tumor subregion segmentation models demonstrated accurate performance on segmentation of the brain tissue and whole tumor regions in pediatric brain tumors and can facilitate detection of abnormal regions for further clinical measurements.
With power comes responsibility: Mazzoleni v Summerhill
Authors: Rimmer John 
Published: March 2023

Abstract
The exercise of a power held in a fiduciary capacity can be open to challenge in court. In Mazzoleni v Summerhill Trust Company (Isle of Man) Limited (2021) 2DS 2021/3 the Isle of Man High Court tackled the decision by a conflicted trustee not to appoint a protector who might have overseen its decisions. Was a trustee bound to appoint a protector in any case? And could a trustee be compelled to exercise a power to appoint a protector—even if the terms of the power were not mandatory?
Stable isotopes in tree rings record physiological trends inLarix gmeliniiafter fires
Authors: Zhang Yujian , Qin Qianqian , Zhu Qiang , Sun Xingyue , Bai Yansong , Liu Yanhong 
Published: March 2023

AbstractFire is an important regulator of ecosystem dynamics in boreal forests, and in particular has a complicated association with growth and physiological processes of fire-tolerant tree species. Stable isotope ratios in tree rings are used extensively in eco-physiological studies for evaluating the impact of past environmental (e.g., drought and air pollution) factors on tree growth and physiological processes. Yet, such studies based on carbon (δ13C) and oxygen (δ18O) isotope ratios in tree rings are rarely conducted on fire effect, and are especially not well explored for fire-tolerant trees. In this study, we investigated variations in basal area increment and isotopes of Larix gmelinii (Rupr.) Rupr. before and after three moderate fires (different fire years) at three sites across the Great Xing’an Mountains, Northeastern China. We found that the radial growth of L. gmelinii trees has significantly declined after the fires across study sites. Following the fires, a simultaneous increase in δ13C and δ18O has strengthened the link between the two isotopes. Further, fires have significantly enhanced the 13C-derived intrinsic water-use efficiency (iWUE) and largely altered the relationships between δ13C, δ18O, iWUE and climate (temperature and precipitation). A dual-isotope conceptual model revealed that an initial co-increase in δ13C and δ18O in the fire year can be mainly attributed to a reduction in stomatal conductance with a constant photosynthetic rate. However, this physiological response would shift to different patterns over post-fire time between sites, which might be partly related to spring temperature. This study is beneficial to better understand, from a physiological perspective, how fire-tolerant tree species adapt to a fire-prone environment. It should also be remembered that the limitation of model assumptions and constraints may challenge model applicability and further inferred physiological response.
The Collateral Effect of Enhanced Recovery After Surgery Protocols on Spine Patients With Neuromuscular Scoliosis
Authors: Tøndevold Niklas , Bari Tanvir Johanning , Andersen Thomas Borbjerg , Gehrchen Martin 
Published: March 2023

Introduction:
Enhanced recovery after surgery (ERAS) protocols are often specific to a specific type of surgery without assessing the overall effect on the ward. Previous studies have demonstrated reduced length of stay (LOS) with ERAS protocols in patients with adolescent idiopathic scoliosis (AIS), although the patients are often healthy and with few or no comorbidities. In 2018, we used ERAS principles for patients undergoing AIS surgery with a subsequent 40% reduced LOS. The current study aims to assess the potential collateral effect of LOS in patients surgically treated for neuromuscular scoliosis admitted to the same ward and treated by the same staff but without a standardized ERAS protocol.

Methods:
All patients undergoing neuromuscular surgery 2 years before and after ERAS introduction (AIS patients) with a gross motor function classification score of 4 to 5 were included. LOS, intensive care stay, and postoperative complications were recorded. After discharge, all complications leading to readmission and mortality were noted with a minimum of 2 years of follow-up using a nationwide registry.

Results:
Forty-six patients were included; 20 pre-ERAS and 26 post-ERAS. Cross groups, there were no differences in diagnosis, preoperative curve size, pulmonary or cardiac comorbidities, weight, sex, or age. Postoperative care in the intensive care unit was unchanged between the two groups (1.2 vs 1.1; P = 0.298). When comparing LOS, we found a 41% reduction in the post-ERAS group (11 vs 6.5; P < 0.001) whereas the 90-day readmission rates were without any significant difference (45% vs 34% P = 0.22) We found no difference in the 2-year mortality in either group.

Conclusion:
The employment of ERAS principles in a relatively uncomplicated patient group had a positive, collateral effect on more complex patients treated in the same ward. We believe that training involving the caregiving staff is equally important as pharmacological protocols.
A Novel Utility of Bilobed Flap for Amputation Stump Coverage
Authors: Hasan Meirizal , Aprilya Dina , Surya Arian 
Published: March 2023

Summary:
Preparing a good amputation stump with a well-padded, stable, sensate, and painless soft tissue coverage is of utmost importance to achieve early ambulation and return the patient to the daily activity level. When the primary closure is impossible or fails to achieve a good closure, secondary closure must be considered. To date, no literature reported the use of bilobed flaps for stump defect closure. We aimed to utilize this technically easy procedure for better management of defect closure on amputated limb stumps that often cause complex clinical problems. This is a retrospective observational study in limb amputation patients with various etiologies: crush injury, chronic limb necrosis, and amniotic band syndrome. All patients had stump defect closure with bilobed flap and were observed with a minimum of 6-months follow-up to evaluate the wound healing, the use of prosthesis, and the complications. A bilobed flap was performed in 11 amputation cases as the final closure (64% trans-femoral, 18% trans-tibial, 9% trans-humeral, and 9% trans-radial). The mean follow-up time was 8.5 ± 2.21 months. Most of the patients healed uneventfully with the optimal use of prosthesis in a mean healing time of 29.64 ± 7.49 days. The bilobed flap potentially provides a good amputation stump coverage that is ideal for prosthesis fitting. This simple procedure can be done without the necessity of special microsurgery settings. Thus, when the neighboring tissue is available and mobile enough to be transposed to the stump defect, a bilobed flap can be considered.
Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes
Authors: Pennisi Grazia , Enea Marco , Falco Vincenzo , Aithal Guruprasad P. , Palaniyappan Naaventhan , Yilmaz Yusuf , Boursier Jerome , Cassinotto Christophe , de Lédinghen Victor , Chan Wah Kheong , Mahadeva Sanjiv , Eddowes Peter , Newsome Philip , Karlas Thomas , Wiegand Johannes , Wong Vincent Wai-Sun , Schattenberg Jörn M. , Labenz Christian , Kim Won , Lee Myoung Seok , Lupsor-Platon Monica , Cobbold Jeremy F. L. , Fan Jian-Gao , Shen Feng , Staufer Katharina , Trauner Michael , Stauber Rudolf , Nakajima Atsushi , Yoneda Masato , Bugianesi Elisabetta , Younes Ramy , Gaia Silvia , Zheng Ming-Hua , Cammà Calogero , Anstee Quentin M. , Mózes Ferenc E. , Pavlides Michael , Petta Salvatore 
Published: March 2023

Background and Aims:
We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D).

Methods and Results:
This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%–20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%–60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%–10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH.

Conclusions:
LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.
Plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer
Authors: Liu Zixu , Wang Ling , Gao Shugeng , Xue Qi , Tan Fengwei , Li Zhili , Gao Yushun 
Published: March 2023

Background:
Multiple primary lung cancer (MPLC) is becoming increasingly common in clinical practice. Imaging examination is sometimes difficult to differentiate from intrapulmonary metastasis (IM) or single primary lung cancer (SPLC) before surgery. There is a lack of effective blood biomarkers as an auxiliary diagnostic method.

Participants and Methods
A total of 179 patients who were hospitalized and operated in our department from January to June 2019 were collected, and they were divided into SPLC with 136 patients, MPLC with 24 patients, and IM with 19 patients. In total, 96 healthy people without lung cancer were enrolled. Medical history, imaging, and pathology data were assembled from all participants. Plasma metabolomics analysis was performed by quadrupole time-of-flight tandem mass spectrometry, and data were analyzed using SPSS19.0/Simca 14.1/MetaboAnalyst5.0 software. Significant metabolites were selected by variable importance in projection, P value, and fold change. The area under the receiver operating characteristic curve was used to evaluate their diagnostic ability.

Results
There were significant differences in plasma metabolite profiles between IM and MPLC. Seven metabolites were screened out. Two metabolites had higher levels in IM, and five metabolites had higher levels in MPLC. All had favorable discriminating capacity. Phosphatidyl ethanolamine (38:5) showed the highest sensitivity (0.95) and specificity (0.92). It was followed by l-histidine with sensitivity 0.92 and specificity 0.84. l-tyrosine can be used to identify SPLC and MPLC. The panel composed of related metabolites exhibited higher diagnostic ability. Eight principal metabolites caused remarkable differences between healthy people and MPLC, and five of them had area under the curves greater than 0.85, showing good discriminating power.

Conclusion
Through the study of plasma metabolomics, it was found that there were obvious differences in the metabolite profiles of MPLC, IM, SPLC, and the healthy population. Some discovered metabolites possessed excellent diagnostic competence with high sensitivity and specificity. They had the potential to act as biomarkers for the screening and differential diagnosis of MPLCs.
Magnetic Resonance Imaging Findings in Idiopathic Intracranial Hypertension With and Without Pulsatile Tinnitus: An Age-Matched Cohort Study
Authors: Widmeyer Jonathan R. , Sismanis Aristides , Felton Warren , Haines Scott , Tang Yang , Gharavi Mohammed , Miller Nathaniel , Coelho Daniel H. 
Published: March 2023

Objective
Many but not all patients with idiopathic intracranial hypertension (IIH) have pulsatile tinnitus (PT). However, little is known about why some patients with IIH develop PT and others do not. The purpose of this study was to determine if any of the classic magnetic resonance imaging (MRI)–detectable markers of IIH differ between patients with and without PT, thereby shedding light on potential pathophysiology.

Methods
A retrospective age-matched cohort study of patients with documented IIH (diagnosed by neuro-ophthalmologist) was performed. All patients had MRI performed around the time of diagnosis. MRIs were assessed for 16 variables known to be associated with IIH (e.g., pituitary displacement/empty sella, optic nerve tortuosity, transverse sinus stenosis, inferior cerebellar tonsils, arachnoid granulations, slit-like ventricles) by two blinded neuroradiologists. All binary variables were analyzed via χ
2 test with Yates correction, or Fisher exact when appropriate. Continuous variables were analyzed via Student t test. Inter-rater reliability for binary variables was assessed by Cohen κ. For continuous variables, intraclass correlation coefficient was calculated.

Results
Forty age-matched patients with IIH met the inclusion criteria (20 with PT, 20 without PT). For all known binary MRI findings associated with IIH, there were no statistically significant differences between groups. Likewise, there were no statistically significant differences for continuous variables.

Conclusions
The classic MRI findings associated with IIH do not differ between patients with and without PT, suggesting that systemic (rather than localized intrinsic or extrinsic) factors may play a critical role in the pathophysiology.
Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure
Authors: McCluskey Suzanne M. , Govender Katya , Adamson John , Gandhi Monica , Spinelli Matthew A. , Moosa Mahomed-Yunus , Muyindike Winnie , Moodley Pravi , Pillay Melendhran , Masette Godfrey , Sunpath Henry , Pillay Selvan , Chen Geoffrey , Hedt-Gauthier Bethany , Marconi Vincent C. , Siedner Mark J. 
Published: March 2023

Objective:
We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART).

Design:
We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa.

Methods:
Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen.

Results:
Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% (n = 243/283). Of those with TFV detected on the POC assay, 91% (n = 204/224) had HIVDR, vs. only 66% (n = 39/59) among those with no TFV detected (P-value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively.

Conclusions:
In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.
Estimated cost-effectiveness of point-of-care testing in community pharmacies vs. self-testing and standard laboratory testing for HIV
Authors: Mital Shweta , Kelly Deborah , Hughes Christine , Nosyk Bohdan , Thavorn Kednapa , Nguyen Hai V. 
Published: March 2023

Objective:
Point-of-care-testing (POCT) for HIV at community pharmacies can enhance care linkage compared with self-tests and increase testing uptake relative to standard lab testing. While the higher test uptake may increase testing costs, timely diagnosis and treatment can reduce downstream HIV treatment costs and improve health outcomes. This study provides the first evidence on the cost-effectiveness of pharmacist-led POCT vs. HIV self-testing and standard lab testing.

Design:
Dynamic transmission model

Methods:
We compared three HIV testing strategies: POCT at community pharmacies; self-testing using HIV self-test kits; and standard lab testing. Analyses were conducted from the Canadian health system perspective over a 30-year time horizon for all individuals aged 15–64 years in Canada. Costs were measured in 2021 Canadian dollars and effectiveness was captured using quality-adjusted life-years (QALYs).

Results:
Compared with standard lab testing, POCT at community pharmacies would save $885 million in testing costs over 30 years. Though antiretroviral treatment costs would increase by $190 million with POCT as more persons living with HIV are identified and treated, these additional costs would be partly offset by their lower downstream healthcare utilization (savings of $150 million). POCT at community pharmacies would also yield over 5000 additional QALYs. Compared with HIV self-testing, POCT at community pharmacies would generate both higher costs and higher QALYs and would be cost-effective with an incremental cost-effectiveness ratio of $47 475 per QALY gained.

Conclusions:
Offering POCT at community pharmacies can generate substantial cost savings and improve health outcomes compared with standard lab testing. It would also be cost-effective vs. HIV self-testing.
Preliteracy assessment in children living with HIV in Tanzania: comparison to results from children living without HIV in Tanzania and the United States
Authors: Bonacina Silvia , Niemczak Christopher , Lichtenstein Jonathan D. , Magohe Albert , Fellows Abigail , Nicol Trent , Massawe Enica , Buckey Jay C. , Kraus Nina 
Published: March 2023

Objective:
Children with HIV (CWH) are at increased risk for cognitive and developmental delays. Whether HIV affects literacy development, however, remains unknown. Rapid automatized naming (RAN) tasks offer the simplest preliteracy assessment a child can perform that predicts future reading skills across languages.

Design and Methods:
RAN performance was analyzed cross-sectionally on 473 children (249 children without HIV and 217 CWH; ages 3–9) drawn from a longitudinal study in Tanzania. These data were compared to results from 341 normally developing children without HIV (ages 3–8) from the United States. Participants performed two RAN subtests: colors and objects.

Results:
RAN object completion was greater than for the RAN color in Tanzanian children. CWH were less likely to complete either subtest and performed worse on the object subtest compared to Tanzanian children without HIV. Compared to the US cohort, the Tanzanian cohort was less likely to complete both subtests - in particular the colors subtest - and showed more variability in responses at younger ages. After approximately age 6, however, the trajectory of improvement between the United States and Tanzania was similar.

Conclusions:
CWH performed worse on this per-literacy test, indicating literacy skill development in CWH needs further study. The differences between US and Tanzanian results likely reflect variability in when children learn to name colors and objects. The trajectory of improvement between countries became more similar as the children aged. This study motivates further longitudinal analyses aimed at assessing the developmental trajectory of the RAN, its predictive ability for reading skills, and its link with other preliteracy and cognitive skills.