bluuebunny/crossref_metadata_2025_split huggingface dataset:
Useful or merely convenient: can enzymatic antioxidant activity be used as a proxy for abiotic stress tolerance?
Authors: Xu Le , Liu Huaqiong , Mittler Ron , Shabala Sergey 
Published: December 2024

Abstract
During their lifespan, plants are often exposed to a broad range of stresses that change their redox balance and lead to accumulation of reactive oxygen species (ROS). The traditional view is that this comes with negative consequences to cells structural integrity and metabolism and, to prevent this, plants evolved a complex and well-coordinated antioxidant defence system that relies on the operation of a range of enzymatic and non-enzymatic antioxidants (AO). Due to the simplicity of measuring their activity, and in light of the persistent dogma that stress-induced ROS accumulation is detrimental for plants, it is not surprising that enzymatic AOs have often been advocated as suitable proxies for stress tolerance as well as potential targets for improving tolerance traits. However, there are a growing number of reports showing either no changes or even down-regulation of AO systems in stressed plants. Moreover, ROS are recognized now as important second messengers operating in both local and systemic signalling, synergistically interacting with the primary stressor, to regulate gene expression needed for optimal acclimatization. This work critically assesses the suitability of using enzymatic AOs as a proxy for stress tolerance or as a target for crop genetic improvement. It is concluded that constitutively higher AO activity may interfere with stress-induced ROS signalling and be a disadvantage for plant stress tolerance.
TangoSIDM Project: is the stellar mass Tully–Fisher relation consistent with SIDM?
Authors: Correa Camila A , Schaller Matthieu , Schaye Joop , Ploeckinger Sylvia , Borrow Josh , Bahé Yannick 
Published: December 2024

ABSTRACT
Self-interacting dark matter (SIDM) has the potential to significantly influence galaxy formation in comparison to the cold, collisionless dark matter paradigm (CDM), resulting in observable effects. This study aims to elucidate this influence and to demonstrate that the stellar mass Tully–Fisher relation imposes robust constraints on the parameter space of velocity-dependent SIDM models. We present a new set of cosmological hydrodynamical simulations that include the SIDM scheme from the TangoSIDM project and the SWIFT-EAGLE galaxy formation model. Two cosmological simulations suites were generated: one (Reference model) which yields good agreement with the observed $z=0$ galaxy stellar mass function, galaxy mass–size relation, and stellar-to-halo mass relation; and another (WeakStellarFB model) in which the stellar feedback is less efficient, particularly for Milky Way-like systems. Both galaxy formation models were simulated under four dark matter cosmologies: CDM, SIDM with two different velocity-dependent cross-sections, and SIDM with a constant cross-section. While SIDM does not modify global galaxy properties such as stellar masses and star formation rates, it does make the galaxies more extended. In Milky Way-like galaxies, where baryons dominate the central gravitational potential, SIDM thermalizes, causing dark matter to accumulate in the central regions. This accumulation results in density profiles that are steeper than those produced in CDM from adiabatic contraction. The enhanced dark matter density in the central regions of galaxies causes a deviation in the slope of the Tully–Fisher relation, which significantly diverges from the observational data. In contrast, the Tully–Fisher relation derived from CDM models aligns well with observations.
A NICU Postoperative Pain Management Improvement Project to Reduce Uncontrolled Pain and Improve Staff Satisfaction
Authors: Sprecher Alicia , Roeloffs Kimberly , Czarnecki Michelle L. , Labovsky Kristen , Kissell Anna , Hornung Genesee , Uhing Michael 
Published: December 2024

Background:
Postoperative pain management in the neonatal period is an area of high variability and a source of staff dissatisfaction. Pain management is a key component of high-quality care; however, pain assessment in infants is difficult and analgesics can negatively impact the developing brain.

Purpose:
We aimed to improve postoperative pain control for infants in our neonatal intensive care unit (NICU), limit variability in the approach to pain management, and increase staff satisfaction.

Methods:
This project was completed between April 2019 and March 2022 with sustainment tracked through December 2023. Interventions took place in a 70-bed level IV NICU using quality improvement methodology. Interventions included efforts aimed at improving pain assessment as well as development and implementation of a pain management guideline. Outcome measures included frequency of uncontrolled postoperative pain and measures of staff satisfaction. Process measures included compliance with pain assessment cadence and guideline recommendations. Opioid exposure within 24 hours of surgery was included as a balancing measure.

Results:
Pain management was assessed in 811 infants: 392 prior to guideline implementation, 273 during implementation, and 146 during sustainment period. Uncontrolled postoperative pain decreased from 26% pre-implementation to 18% post implementation and into the sustainment period. Staff satisfaction improved from 67% to 83%. These improvements were associated with decreased variability in postoperative pain management and a decrease in postoperative opioid exposure.

Implications for Practice and Research:
The use of a postoperative pain management guideline can improve pain control, decrease drug regimen variability, decrease opioid exposure, and increase staff satisfaction.
A Case of Leukemia Cutis (Acute Myeloid Leukemia) With Epidermotropism
Authors: Aran Brenna M. , Duran Juanita , Gru Alejandro A. 
Published: December 2024

Abstract:
Acute myeloid leukemia is a cancer involving uncontrolled proliferation of hematopoietic cells. Cutaneous involvement is referred to as leukemia cutis (LC). The histopathologic presentation of LC is variable, and may present with perivascular, periadnexal, dermal, or subcutaneous infiltrate. Epidermotropism is notably absent. We report an unusual case of acute myeloid LC with epidermotropism in a 68-year-old man. A punch biopsy revealed a mononuclear myeloblast infiltrate involving the dermis and subcutaneous tissue. The epidermis was focally acanthotic, with several vesicles and atypical epidermotropic cells. Mitotic figures and apoptotic cells were present. Immunohistochemistry showed the blasts to be positive for CD56, CD123, and lysozyme, and weakly positive for CD4 and CD163. Negative immunostaining included CD3, CD20, CD34, TdT, and CD117. Epstein–Barr virus in situ hybridization was negative. A bone marrow biopsy revealed the same myeloblast population with identical phenotype to the skin. The blasts were negative for CD34, CD117, CD3, CD19, CD163, CD68, CD61, myeloperoxidase, pankeratin, E-cadherin, CD4, and transcription factor 4. A diagnosis of acute myeloid leukemia with monocytic differentiation and leukemia cutis was established. These findings suggest that the differential diagnosis for conditions with epidermotropism may be even broader than previously thought.
A review of validated techniques and tools for tumor intensity-modulated radiation therapy
Authors: Yao Xiao , Chuan Chen 
Published: December 2024

Intensity-modulated radiation therapy (IMRT) is an advanced tumor treatment technique that enables precise three-dimensional dose distribution. However, factors such as field design, data algorithms, and machine errors may lead to deviations between the actual dose and the planned dose, potentially resulting in irradiation errors.
Common dose verification methods include point dose verification, two-dimensional dose verification, and three-dimensional dose verification. This paper reviews various verification methods and focuses on the errors and limitations of each method to improve the safety and effectiveness of IMRT treatment.
Accuracy of ICD-10 Codes for Suicidal Ideation and Action in Pediatric Emergency Department Encounters
Authors: Xu Rena , Bode Louisa , Geva Alon , Mandl Kenneth D. , McMurry Andrew J. 
Published: December 2024

Objectives
According to the ideation-to-action framework of suicidality, suicidal ideation and suicidal action arise via distinct trajectories. Studying suicidality under this framework requires accurate identification of both ideation and action. We sought to assess the accuracy of International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes for suicidal ideation and action in emergency department encounters.

Methods
Accuracy of ICD-10-CM coding for suicidality was assessed through chart review of clinical notes for 205 emergency department encounters among patients 6–18 years old at a large academic pediatric hospital between June 1, 2016 and June 1, 2022. Physician notes were reviewed for documentation of past or present suicidal ideation, suicidal action, or both. The study cohort consisted of 103 randomly selected “cases,” or encounters assigned at least 1 ICD-10-CM code for suicidality, and 102 propensity-matched “noncases” lacking ICD-10-CM codes. Accuracy of ICD-10-CM codes was assessed using sensitivity, specificity, positive predictive value, and negative predictive value.

Results
Against a gold standard chart review, the positive predictive value for ICD-10-CM suicidality codes was 86.9% (95% confidence interval [CI]: 84.5%–89.3%), and the negative predictive value was 76.2% (95% CI: 73.2%–79.2%). Nearly half of encounters involving suicidality were not captured by ICD-10-CM coding (sensitivity = 53.4%; 95% CI: 49.9%–56.9%). Sensitivity was higher for ideation-present (82.4%, 95% CI: 77.7%–87.1%) than for action-present (33.7%, 95% CI: 27.9%–39.5%) or action-past (20.4%, 95% CI: 15.5%–25.3%).

Conclusions
Many cases of suicidality may be missed by relying on only ICD-10-CM codes. Accuracy of ICD-10-CM codes is high for suicidal ideation but low for action. To scale the ideation-to-action model for use in large populations, better data sources are needed to identify cases of suicidal action.
Immediate Implant Placement in a Hypothyroid Geriatric Patient: Aesthetic Excellence, Secondary Stability, and Successful Outcome—A Case Report
Authors: Srinivas Sowmya , Aradya Anupama , Somashekarachar Ganesh , Doddawad Vidya G. 
Published: December 2024

Placing an implant immediately into extraction sockets provides a distinct advantage over delayed placement, eliminating the need for a 4 to 6 months waiting period for bone formation. However, when patients present with hypothyroidism, the feasibility of immediate placement of dental implants becomes uncertain. This case involved a hypothyroid woman in her late 60s with loose lower anterior teeth. We performed atraumatic extractions. Immediately after extraction, we implanted tilted implants into her lower posterior arch, which is an area with limited vertical bone height. In the anterior arch, which is characterized by thick, soft tissue, we implanted vertical implants. We used multiunit abutments in the anterior region to address hygiene and angulation issues. The final prosthesis comprised a porcelain-fused-to-metal screw-retained bridge with group function occlusion. These prostheses offer advantages compared with cement-retained prostheses, particularly with multiunit abutments that allow passive prosthetic fitting despite implant axis deviation. This approach strengthens the hemidesmosomal connection, reduces the need for repeated screwing and unscrewing, and promotes stability in the peri-implant tissues. This case underscores the clinical benefits of immediate implant placement and the advantages of using screw-retained prostheses in patients with hypothyroidism. Although extensive research has been conducted to analyze factors influencing the success of dental implants in individuals with hypothyroidism, ongoing debates persist in the literature. This case demonstrates successful implantation of dental implants in a patient with hypothyroidism.
99mTc-Labeled Blood Pool Scintigraphy and SPECT/CT Findings in a Rare Case of Blue Rubber Bleb Nevus Syndrome
Authors: Wakankar Ritwik , Dharmashaktu Yamini , Kumar Rakesh 
Published: December 2024

Abstract
Blue rubber bleb nevus syndrome or Bean syndrome is a rare genetic disorder characterized by the presence of multiple venous hemangiomas, most commonly involving the skin and gastrointestinal tract, but which can also involve other organs as well. We present an interesting case of a 21-year-old woman with blue rubber bleb nevus syndrome and describe the findings of her 99mTc-labeled whole-body blood pool scintigraphy and SPECT/CT.
Rising to the Ultrasensitive Rapid Diagnostic Challenge with Buoyant-Analyte-Magnetic (BAM) Assays
Authors: Wang Chuanlei , Satterfield Emory , Livi Carolina B. , Dean Delphine , Anker Jeffrey N. 
Published: December 2024

AbstractUltrasensitive, inexpensive, rapid, and portable assays are needed to detect infectious diseases at early stages to improve treatment and prevent transmission, especially to vulnerable patients. Unfortunately, most ultrasensitive assays require rinsing and development steps which increase their complexity, cost, and read time. We address these issues in a novel assay that uses a combination of buoyant microbubbles and magnetic microspheres to doubly label an analyte (SARS-CoV-2 N-protein from surfactant-lysed viruses) and form buoyant-analyte-magnetic (BAM) sandwich complexes. A permanent magnet pulls down the BAM complexes, while unbound microbubbles float towards the surface and separate without rinsing. Removing the magnet releases the buoyant BAM complexes allowing them to float upwards. Under flashlight illumination, they appear as bright rising dots. A simple digital camera (or even cell phone camera) counts the BAM complexes. Remarkably, the analytical detection limit is ∼50 N-protein molecules in 5 µL of saliva. The assay gave positive results for all PCR-positive saliva specimens tested, with concentrations ranging from 0.7 to 2.51×105RNA copies/µL. We also discuss assay limitations and ways to address them in the future.
Detecting SARS-CoV-2 Cryptic Lineages using Publicly Available Whole Genome Wastewater Sequencing Data
Authors: Suarez Reinier , Gregory Devon A. , Baker David A. , Rushford Clayton , Hunter Torin , Minor Nicholas R. , Russ Clayton , Copen Emma , O’Connor David H. , Johnson Marc C. 
Published: December 2024

AbstractBeginning in early 2021, unique and highly divergent lineages of SARS-CoV-2 were sporadically found in wastewater sewersheds using a sequencing strategy focused on the most mutagenic region of SARS-CoV-2, the receptor binding domain (RBD). Because these RBD sequences did not match known circulating strains and their source was not known, we termed them “cryptic lineages”. To date, more than 20 cryptic lineages have been identified using the RBD-focused sequencing strategy. Here, we identified and characterized additional cryptic lineages from SARS-CoV-2 wastewater sequences submitted to NCBI’s Sequence Read Archives (SRA). Wastewater sequence datasets were screened for individual sequence reads that contained combinations of mutations frequently found in cryptic lineages but not contemporary circulating lineages. Using this method, we identified 18 cryptic lineages that appeared in multiple samples from the same sewershed, including 12 that were not previously reported. Partial consensus sequences were generated for each cryptic lineage by extracting and mapping sequences containing cryptic-specific mutations. Surprisingly, seven of the mutations that appeared convergently in cryptic lineages were reversions to sequences that were highly conserved in SARS- CoV-2-related bat Sarbecoviruses. The apparent reversion to bat Sarbecovirus sequences suggests that SARS- CoV-2 adaptation to replicate efficiently in respiratory tissues preceded the COVID-19 pandemic.Author SummaryWastewater surveillance has been used during the SARS-CoV-2 pandemic to monitor viral activity and the spread of viral lineages. Occasionally, SARS-CoV-2 sequences from wastewater reveal unique evolutionary advanced lineages of SARS-CoV-2 from an unknown source, which are termed cryptic lineages. Many groups nationwide also use wastewater surveillance to track the virus and upload that information to NCBI’s SRA database. That sequence data was screened to identify 18 cryptic lineages worldwide and identify convergent mutations throughout the genome of multiple cryptic lineages that suggest reversion to residues common in SARS-CoV-2-related Sarbecoviruses.
Advantages to interspace-level analyses over person-level analyses when studying relationships between lumbar spinal degeneration findings : a cross-sectional study
Authors: Suri Pradeep , Elgaeva Elizaveta E. , Jarvik Jeffrey G. , Rundell Sean D. , Tsepilov Yakov A. , Williams Frances M.K. , Heagerty Patrick J. 
Published: December 2024

ABSTRACTPurposeTo examine associations between lumbar intervertebral disc degeneration (LDD) and type II Modic changes (MC) when retaining information at each interspace (“interspace-level analysis”), as compared to aggregating information across interspaces as is typically done in spine research (“person-level analysis”). The study compared results from (1) interspace-level analyses assuming a common relationship across interspaces (the “interspace-level, common-relationship” approach), (2) interspace-level analyses allowing for interspace-specific associations (an “interspace-level, interspace-specific” approach), and (3) a conventional person-level analytic approach.MethodsAdults in primary care (n=147) received lumbar spine magnetic resonance imaging (MRI) and neuroradiologist-evaluated assessments of prevalent disc height narrowing (DHN), type II MC, and other LDD parameters. Analyses examined associations between DHN and type II MC in interspace-level, commonrelationship analyses, interspace-level, interspace-specific analyses, and conventional person-level analyses.ResultsCross-sectional, interspace-level, common-relationship analyses found large-magnitude DHN-type II MC associations (adjusted OR [aOR]=6.5, 95% confidence intervals (CIs) 3.3-13; p<0.001). The magnitude of this association was larger and more precise than that yielded by person-level analyses (aOR=2.9 [95% CI 1.2-7]), and substantially more precise than interspace-level, interspace-specific analyses which allowed the association between DHN and type II MC to vary across levels. Across exploratory analyses of disc signal intensity and other MC types, interspace-level, common-relationship analyses produced larger-magnitude and more precise associations than person-level analyses in most situations, and were more precise than interspace-level, interspace-specific analyses.ConclusionsInterspace-level analytic approaches offer some advantages to person-level analyses that may be useful in understanding relationships between spinal degeneration findings.
Lysosomal reduced thiols are essential for mouse embryonic development
Authors: Adelmann Charles H. , Venkatachalam Avanthika , Huang Lingjuan , Liu Michelle , Germana Sharon , Sabatini David M. , Fisher David E. 
Published: December 2024

AbstractWhile it has been appreciated for decades that lysosomes can import cysteine, its for organismal physiology is unclear. Recently, the MFSD12 transmembrane protein was shown to be necessary to import cysteine into lysosomes (and melanosomes), enabling the study of these processes using genetic tools. Here, we find that mice lackingMfsd12die between embryonic days 10.5-12.5, suggesting that MFSD12 is essential for organogenesis. Within lysosomes, it is well known that a significant fraction of the cysteine is converted into cystine (oxidized cysteine), which accumulates and can be released into the cytosol via the CTNS (cystinosin) transporter. However, in contrast toMfsd12, loss ofCtnsresults in live animals, indicating that it is not an essential gene. This suggests that the essential function of MFSD12 is not to enable cystine storage for use in the cytosol but rather to supply reduced cysteine to the lysosomal lumen itself. Consistent with this idea, the treatment of breeding heterozygous mice with cysteamine, a lysosome-penetrant thiol, rescued the development ofMfsd12knockout mice and resulted in live births. Our work implicates lysosomal thiol import as an essential metabolic pathway and provides tools for deciphering its complex genetic and metabolic interactions.
The Efficacy and Safety of Sodium-Glucose Cotransporter Protein 2 Inhibitors (SGLT2Is) in Liver Cirrhosis: A Systematic Review and Meta-Analysis
Authors: Dhoop Sudheer , Shehada Mohammed , Sawaf Bisher , Patel Manthan , Roberts Luke , Smith Wade-Lee , Hart Benjamin 
Published: December 2024

SummaryBackgroundSodium-Glucose Cotransporter Protein 2 Inhibitors (SGLT2Is) are known for their cardiovascular and renoprotective benefits and are efficacious in managing Metabolic-Associated Steatotic Liver Disease (MASLD). However, limited data exist on their use in advanced liver disease, particularly liver cirrhosis.AimsTo synthesize existing evidence on the efficacy and safety of SGLT2Is in patients with liver cirrhosis and to provide clinical guidance.MethodsA systematic review and meta-analysis were conducted following the PRISMA 2020 Statement. Searches in major health databases identified studies where SGLT2Is were used in patients with cirrhosis. The analysis focused on prospective trials in decompensated cirrhosis and retrospective studies in compensated cirrhosis. Primary outcomes included the need for large-volume paracentesis (LVP) and mortality. Secondary outcomes assessed weight loss, loop diuretic dose reduction, residual ascites, acute kidney injury (AKI), hyponatremia, hepatic encephalopathy (HE), and urinary tract infections (UTIs).ResultsTen studies (8 peer-reviewed) from 2020-2024 were included: 2 randomized controlled trials, 4 single-arm prospective trials, and 4 retrospective studies. SGLT2I use was associated with reduced LVP (RR 0.45, CI 0.31-0.66, p<0.001) and mortality (aHR 0.46, CI 0.38-0.55, p<0.001). Benefits included a 39 mg reduction in loop diuretic dose, 7 kg weight loss, and no significant increase in residual ascites, AKI, hyponatremia, HE, or UTIs.ConclusionsSGLT2Is show promise in managing diuretic-resistant ascites and reducing mortality in liver cirrhosis without causing significant adverse events. Larger, randomized controlled trials are needed to validate these findings.
3D Structure-based Generative Small Molecule Drug Design: Are We There Yet?
Authors: Yang Bo , Xiang Chijian , Li Jianing 
Published: December 2024

AbstractStructure-based drug design (SBDD) plays a crucial role in pre-clinical drug discovery. Recently developed structure-based 3D generative algorithms have the potential to streamline the SBDD process by enabling the generation of novel, druglike molecules based on the structure of a target protein’s binding pocket. However, no effective metric currently exists to assess the chemical plausibility of molecules generated by these algorithms, which hampers further advancements in their development. In this study, we propose two novel metrics for evaluating the chemical plausibility of generated molecules. Combined with additional analyses, we demonstrate that existing algorithms could generate chemically implausible structures with some property distributions that deviate from those of known drug-like molecules. The metrics and analytical methods presented here offer model developers and user valuable tools to quantify the chemical plausibility of molecules they generate, ultimately facilitating the application of these algorithms in drug discovery.