bluuebunny/crossref_metadata_2025 huggingface dataset:
The periaxonal space as a conduit for cerebrospinal fluid flow to peripheral organs
Authors: Li Xinyu , Wang Siman , Zhang Dianjun , Feng Yuliang , Liu Yingyu , Yu Weiyang , Cui Lulu , Harkany Tibor , Verkhratsky Alexei , Xia Maosheng , Li Baoman
Published: November 2024

Mechanisms controlling the movement of the cerebrospinal fluid (CSF) toward peripheral nerves are poorly characterized. We found that, in addition to the foramina Magendie and Luschka for CSF flow toward the subarachnoid space and glymphatic system, CSF outflow could also occur along periaxonal spaces (termed “PAS pathway”) from the spinal cord to peripheral organs, such as the liver and pancreas. When interrogating the latter route, we found that serotonin, acting through 5-HT
2B
receptors expressed in ependymocytes that line the central canal, triggered Ca
2+
signals to induce polymerization of F-actin, a cytoskeletal protein, to reduce the volume of ependymal cells. This paralleled an increased rate of PAS-mediated CSF redistribution toward peripheral organs. In the liver, CSF was received by hepatic stellate cells. CSF efflux toward peripheral organs through the PAS pathway represents a mechanism dynamically connecting the nervous system with the periphery. Our findings are compatible with the traditional theory of CSF efflux into the glymphatic system to clear metabolic waste from the cerebral parenchyma. Thus, we extend the knowledge of CSF flow and expand the understanding of connectivity between the CNS and peripheral organs.
Transmission of societal stereotypes to individual-level prejudice through instrumental learning
Authors: Schultner David T. , Stillerman Benjamin S. , Lindström Björn R. , Hackel Leor M. , Hagen Damaris R. , Jostmann Nils B. , Amodio David M.
Published: November 2024

How are societal stereotypes transmitted to individual-level group preferences? We propose that exposure to a stereotype, regardless of whether one agrees with it, can shape how one experiences and learns from interactions with members of the stereotyped group, such that it induces individual-level prejudice—a process involving the interplay of semantic knowledge and instrumental learning. In a series of experiments, participants interacted with players from two groups, described with either positive or negative stereotypes, in a reinforcement learning (RL) task presented as a money-sharing game. Although players’ actual sharing rates were equated between groups, participants formed more positive reward associations with players from positively stereotyped than negatively stereotyped groups. This effect persisted even when stereotypes were described as unreliable and participants were instructed to ignore them. Computational modeling revealed that this preference was due to stereotype effects on priors regarding group members’ behavior as well as the learning rates through which reward associations were updated in response to player feedback. We then show that these stereotype-induced preferences, once formed, spread unwittingly to others who observe these interactions, illustrating a pathway through which stereotypes may be transmitted and propagated between society and individuals. By identifying a mechanism through which stereotype knowledge can bypass explicit beliefs to induce prejudice, via the interplay of semantic and instrumental learning processes, these findings illuminate the impact of stereotype messages on the formation and propagation of individual-level prejudice.
Fermionic Critical Fluctuations: Potential Driver of Strange Metallicity and Violation of the Wiedemann–Franz Law in YbRh2Si2
Authors: Steglich Frank
Published: November 2024

Results of combined thermal and electrical transport measurements through the magnetic field-induced quantum critical point (QCP) in the heavy-fermion compound YbRh2Si2 were revisited to explore the relationship between the strange-metal behavior observed in electrical and electronic thermal resistivities and the violation of the Wiedemann–Franz (WF) law in the zero-temperature limit. A new type of inelastic scattering center for the charge and heat carriers was detected, attributed to small-to-large Fermi surface fluctuations operating near the Kondo-destroying QCP. These fermionic quantum critical fluctuations are considered the primary driver of the strange-metal behavior and the violation of the WF law.
Enhancement of impact synchronous modal analysis with brain-computer interface
Authors: Zahid Fahad Bin , Ong Zhi Chao , Khoo Shin Yee , Mohd Salleh Mohd Fairuz , Akram Naveed
Published: November 2024

Novel Impact Synchronous Modal Analysis (ISMA) suffers from inefficient operation. The Automated Phase Controlled Impact Device (APCID), a fully automated device, was developed to efficiently perform ISMA, however, the actuator, support structure and power supply of the APCID make it large, heavy, and unsuitable for commercial applications. The APCID can be replaced with manual operation while still using its controls but by nature there is randomness in human behaviour, which can greatly reduce the effectiveness of the APCID control scheme. A smart semi-automated device for imparting impacts is developed in this study, which uses Brain-Computer Interface (BCI) to predict impact time prior to impact. Brainwaves are measured using a portable, wireless and low-cost Electroencephalogram (EEG) device. Using brainwaves, a Machine Learning (ML) model is developed to predict the impact time. The ML model gave a Mean Absolute Percentage Error (MAPE) of 7.5% and 8% in evaluation (offline testing) and in real-time testing, respectively, while predicting impact time prior to impact using brainwaves. When integrated with the control of APCID to perform ISMA, the ML model gave a MAPE of 8.3% in real-time ISMA while predicting impact time prior to impact and adjusting the APCID control for the upcoming impact accordingly. To demonstrate the effectiveness of the EEG ML model in performing ISMA, modal testing was performed at 2 different operating speeds. The study concludes by comparing the developed ISMA method with other ISMA methods. The BCI based device developed in this study for performing ISMA outranks other ISMA methods due to its performance, efficiency and practicality.
Searching for an absolutely maximally five-level entangled state
Authors: Zha Xinwei
Published: November 2024

Entangled states play an important role in quantum computation and information. In this paper, for a five-level entangled state, we define some unitary operations and give an operator multiplication. With the help of the unitary operation, we obtain some local unitary equivalent bipartite and tripartite five-level absolutely maximally entangled states (AMES). Furthermore, by using recurrence relations, some four-partite and five-partite five-level AMES can be constructed.
Effects of introducing astigmatism aberration to spiral elements of diverse geometrical shapes
Authors: Javidi B , Sabatyan A
Published: November 2024

In this study, we explore the impact of astigmatism on the focusing characteristics of various spiral zone plates with different geometries. We examine four types of spiral zone plates: spiral circular, spiral square, spiral orthogonal, and spiral checkerboard. Our theoretical analysis of the spiral circular zone plate indicates that introducing astigmatism aberration changes the focused vortex into Hermite beams, producing a series of interference lines. The quantity of dark fringes reflects the topological charge of the vortex beam and the orientation reveals determines whether the vorticity is clockwise or counterclockwise. This phenomenon is consistent across the other spiral zone plates as well, as astigmatism modifies the resulting beam into an interference pattern that indicates both the magnitude and direction of the topological charge.
Dependence of divertor turbulence on plasma density and current in TCV
Authors: Wüthrich C. , Theiler C. , Oliveira D.S. , Wang Y. , Ducker R. , Durr-Legoupil-Nicoud G. , Duval B.P. , Galassi D. , Golfinopolus T. , Lee K. , Offeddu N. , Tsui C.K. ,   the TCV team
Published: November 2024

To reliably predict the distribution of heat and particle fluxes at the target plates of tokamaks, a comprehensive understanding of turbulence throughout the entire Scrape-Off-Layer (SOL) is imperative. This study examines divertor turbulence systematically across a broad parameter range on the TCV tokamak, including variations in magnetic field direction, plasma current

I

p

∈
[
140
,
320
]

 kA, edge safety factor

q

95

∈
[
2.6
,
4.7
]

and Greenwald fraction

f

G

∈
[
0.18
,
0.6
]

. The TCV X-point Gas Puff Imaging (GPI) system is used to measure 2D filament properties in the inner and outer divertor region. The fluctuation levels in the divertor are found to strongly increase with density (to 80% over most of the SOL) while remaining insensitive to

I

p

. The previously identified divertor-localized filaments (DLF), located on the bad curvature side of the outer divertor leg, are found to be a common feature on TCV, while no filaments are observed in the PFR. DLFs are present over most of the parameter space and in both field directions. However, they are absent, or appear only closer to the target, for sufficiently large

Λ

div

≳
10

or

q

95

≳
3.7

. Across both

I

p

and

f

G

scans, some clear trends with

Λ

div

are found for divertor filament sizes and velocities, and with target fall-off lengths of density and heat flux profiles at the outer target. This study provides important experimental insights to turbulent transport in the divertor also for comparison with self-consistent, turbulence simulations and extrapolation to future reactor conditions.
Additive manufacturing of a strong and ductile oxygen-doped NbTiZr medium-entropy alloy
Authors: An Yaqiong , Liu Yijie , Liu Shujie , Zhang Bozhao , Yang Guanghui , Zhang Cheng , Tan Xipeng , Ding Jun , Ma En
Published: November 2024

Refractory multi-principal element alloys (RMPEAs) have garnered attention for their potential in high-temperature applications. Additive manufacturing (AM) provides opportunities to tailor RMPEAs’ microstructures to enhance these properties. However, controlling defects and addressing the challenges posed by the complex thermal history during the AM process are crucial for optimizing RMPEAs’ performance. This study aims to fabricate a high-quality oxygen-doped NbTiZr alloys using laser powder bed fusion and investigate their microstructure and mechanical properties. Our analysis reveals refined grain sizes and a periodic combination of fine near-equiaxed and columnar grain morphologies in the AM-fabricated alloy. Its substructure is characterized by the coexistence of loosely defined cellular dislocation networks and elemental segregation. Compared to its cast counterpart, the additively manufactured alloy exhibits a combination of high yield strength, excellent tensile ductility, and enhanced work hardening. These attributes make the AM-fabricated oxygen-doped NbTiZr alloy a promising candidate for applications required balanced mechanical properties. Understanding the specific effects of different crystal structures and deformation mechanisms is essential for optimizing AM processes to tailor the microstructure and achieve the desired mechanical performance in various engineering applications.
A Woman’s Machine
Authors: Chen Eva
Published: November 2024

This chapter discusses speed’s role as coercive regimentation of women’s typewriting body in the Taylorite office. It examines journalistic and literary responses to the faster body of the typewriter girl, who is variously viewed as a sexy but dumb machine woman; an emancipated, energized feminist activist; or a fatigued, lonely, and stultified urban worker tackling poverty and the grinding costs of coercive industrial speed. This last image echoes similar concerns in the mid-century industrial novel, but foregrounds for the first time the working female body. The chapter analyses stories and comments from the popular masculine press, women’s press, as well as novels like Gissing’s The Odd Women and Mitton’s A Bachelor Girl in London.
Leaf temperatures exceed thermal heat tolerances for a community of eastern North America hardwood trees
Authors: Endris Joe , Rehm Evan
Published: November 2024

Changing climates are creating more intense and frequent high temperature events that could disrupt forest communities. In temperate forests, we have a relatively limited understanding of how trees are impacted by heat events, hindering our ability to predict impacts of future heat waves. We conducted a community-level assessment of thermal safety margins in 11 hardwood tree species native to eastern North America. We used chlorophyll fluorescence to determine the critical heat tolerance of photosystem II (PSII) across two years in central Tennessee, USA. We focus on the temperature at which PSII first starts to decline (Tcrit) as this is the temperature where membranes become unstable, resulting in permanent damage to these tissues. Tcrit varied within season and between years, being higher in July than June and in 2022 than 2023. Tcrit also varied among species with species like Ulmus rubra and Ostrya virginiana showing consistently lower heat tolerances. When compared to the record high temperature for our study site, 10 of 11 species would have experienced heat stress during at least one sample period. When compared to current year high temperatures, the risk was variable and lower across all species and sample periods. However we found that leaf temperatures often exceeded air temperatures, therefore many species were likely heat stressed as heat tolerances were often below species-specific leaf temperatures. Indeed, four species were potentially heat stressed during every sample period. Our data highlights the importance of using leaf temperature, not air temperature to assess thermal safety margins and that community wide stress may already occur under extreme heat conditions. As climate change intensifies, leaf temperatures will likely approach critical thresholds that lead to damage across the tree community. Understanding species-specific responses to heat stress is essential to predicting future forest dynamics and ecosystem functioning.
Clinical pharmacist-led antifungal drug utilization reviews in cancer care hospital: a prospective audit and feedback
Authors: Akbar Zunaira , Aamir Muhammad , Saleem Zikria , Khan Muhammad Rehan , Bhutta Omar Akhlaq
Published: November 2024

Background and objective

The global rise in systemic fungal infections and increased antifungal use underscores the need for pharmacist-led antifungal stewardship in oncology but data on such interventions are scarce. This study aimed to evaluate the clinical pharmacist-led antifungal drug utilization reviews for optimizing antifungal therapy in a specialized cancer care hospital.

Patients and Method

This pharmacist-led prospective audit and feedback study evaluated 350 admitted patients with cancer who were prescribed systemic antifungals. Electronic medical records of the included patients were reviewed to evaluate pharmacist interventions. Data were entered and analysed through SPSS version 21.

Result

Most of the patients were prescribed antifungals for suspected fungal infections (41.7%). Febrile neutropenia was present in 55.4% of patients. The most frequently isolated fungus was C. albicans (15.4%) followed by C. tropicalis (8.6%) and A. flavus (7.7%). The most frequently prescribed antifungal drug was voriconazole (38.8%) and amphotericin B (31.7%). Major pharmacist-led interventions were a change of IV antifungal therapy to an oral drug (18%), choice of drug therapy (17.4%) and dose reduction (16.9%). All the interventions made by the pharmacist were accepted by the AFS team (100%).

Conclusion

Pharmacists play a crucial role in optimizing antifungal therapy by conducting drug utilization reviews and implementing targeted interventions. These interventions are beneficial for overall management of patients with cancer and improving the quality of antifungal prescribing.
Developing personas to inform the design of digital interventions for perinatal mental health
Authors: Zimmermann Martha , Yonkers Kimberly A , Tabb Karen M , Schaefer Ana , Peacock-Chambers Elizabeth , Clare Camille A , Boudreaux Edwin D , Lemon Stephenie C , Byatt Nancy , Tulu Bengisu
Published: November 2024

Objectives

Digital interventions are increasingly in demand to address mental health concerns, with significant potential to reach populations that disproportionately face barriers to accessing mental health care. Challenges with user engagement, however, persist. The goal of this study was to develop user personas to inform the development of a digital mental health intervention (DMHI) for a perinatal population.

Materials and Methods

We used participatory User-Centered Design (UCD) methods to generate and validate personas (ie, representative profiles of potential users). We applied this methodology to a case example of an Anxiety Sensitivity Intervention. Phases included (1) Characteristic identification, (2) Persona generation, (3) Persona consolidation, (4) Persona validation, and (5) Persona refinement. Advisory Council members with lived expertise of perinatal mental health conditions generated 6 personas. We used cluster analysis and qualitative analysis to consolidate personas. We used participant interviews with perinatal individuals experiencing depression or anxiety and economic marginalization (n = 12) to qualitatively validate and refine these personas.

Results

We identified 4 user personas with potentially unique design needs that we characterized as being “Resilient,” “Lonely,” “Overwhelmed,” and “Aware.”

Discussion

Personas generated through this process had distinct characteristics and design implications including the need to prioritize (1) content personalization, (2) additional content describing support options and resources (eg, doulas, midwives), (3) careful consideration of the type of information provided by users, and (4) transparent options for information and data sharing.

Conclusion

DMHIs will need to be adapted for relevance for a perinatal population. The personas we developed are suggestive of the need for design considerations specific to distinct potential user groups within this population.
Natural product mitigation of ferroptosis in platinum-based chemotherapy toxicity: targeting the underpinning oxidative signaling pathways
Authors: Famurewa Ademola C , Prabhune Nupura Manish , Prabhu Sudharshan
Published: November 2024

Objectives

Platinum-based anticancer chemotherapy (PAC) represents a cornerstone in cancer treatment, retaining its status as the gold standard therapy. However, PAC’s efficacy is countered by significant toxicities, such as nephrotoxicity, ototoxicity, and neurotoxicity. Recent studies have linked these toxicities to ferroptosis, characterized by iron accumulation, reactive oxygen species generation, and lipid peroxidation. This review explores the mechanisms underlying PAC-induced toxicities, focusing on the involvement of ferroptosis with three major PAC drugs—cisplatin, carboplatin, and oxaliplatin. Further, we provide a comprehensive analysis of the natural product mitigation of PAC-induced ferroptotic toxicity.

Key findings

The mechanistic role of ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, while studies on carboplatin-induced ferroptotic toxicities are lacking. Natural compounds targeting molecular pathways of ferroptosis have been explored to mitigate PAC-induced ferroptotic toxicity.

Conclusion

While ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, there remains a notable dearth of studies examining its involvement in carboplatin-induced toxicities. Hence, further exploration is warranted to define the role of ferroptosis in carboplatin-induced toxicities, and its further mitigation. Moreover, in-depth mechanistic evaluation is necessary to establish natural products evaluated against PAC-induced ferroptosis, as PAC adjuvants.
Urgent call for cross-border approach to control rabies in India and Nepal
Authors: Acharya Krishna Prasad , Phuyal Sarita
Published: November 2024

Given the high possibility of rabies spread across borders a collaborative cross-border disease control partnership is necessary.
Ordering Effects versus Cognitive Burden: How Should We Structure Attributes in Conjoint Experiments?
Authors: Rudolph Lukas , Freitag Markus , Thurner Paul W
Published: November 2024

Conjoint experiments offer a flexible way to elicit population preferences on complex decision tasks. We investigate whether we can improve respondents’ survey experience and, ultimately, choice quality by departing from the current recommendation of completely randomized conjoint attribute ordering. Such random ordering guarantees that potential bias from attribute order cancels out on average. However, in situations with many attributes, this may unnecessarily increase cognitive burden, as attributes belonging together conceptually are presented scattered across the choice table. Hence, we study experimentally whether purposeful ordering (“theoretically important” attributes first) or block randomized ordering (attributes belonging to the same theoretical concept displayed in randomized bundles) affects survey experience, response time, and choice itself, as compared to completely randomized ordering. Drawing on a complex preregistered choice design with nine attributes (N = 6,617), we find that ordering type affects neither self-reported survey experience, choice task timing, nor attribute weighting. Potentially, block randomization reduces cognitive burden for some subgroups. To our knowledge, we thereby provide the first systematic empirical evidence that ordering effects are likely of low relevance in conjoint choice experiments and that the trade-off between cognitive burden and ordering effects is minimal from the perspective of respondents, at least for our substantive application.
Conductive hydrogels: intelligent dressings for monitoring and healing chronic wounds
Authors: Fang Ying , Han Yiran , Yang Lu , Kankala Ranjith Kumar , Wang Shibin , Chen Aizheng , Fu Chaoping
Published: November 2024

Conductive hydrogels (CHs) represent a burgeoning class of intelligent wound dressings, providing innovative strategies for chronic wound repair and monitoring. Notably, CHs excel in promoting cell migration and proliferation, exhibit powerful antibacterial and anti-inflammatory properties, and enhance collagen deposition and angiogenesis. These capabilities, combined with real-time monitoring functions, play a pivotal role in accelerating collagen synthesis, angiogenesis and continuous wound surveillance. This review delves into the preparation, mechanisms and applications of CHs in wound management, highlighting their diverse and significant advantages. It emphasizes the effectiveness of CHs in treating various chronic wounds, such as diabetic ulcers, infected wounds, temperature-related injuries and athletic joint wounds. Additionally, it explores the diverse applications of multifunctional intelligent CHs in advanced wound care technologies, encompassing self-powered dressings, electrically-triggered drug delivery, comprehensive diagnostics and therapeutics and scar-free healing. Furthermore, the review highlights the challenges to their broader implementation, explores the future of intelligent wound dressings and discusses the transformative role of CHs in chronic wound management, particularly in the context of the anticipated integration of artificial intelligence (AI). Additionally, this review underscores the challenges hindering the widespread adoption of CHs, delves into the prospects of intelligent wound dressings and elucidates the transformative impact of CHs in managing chronic wounds, especially with the forthcoming integration of AI. This integration promises to facilitate predictive analytics and tailor personalized treatment plans, thereby further refining the healing process and elevating patient satisfaction. Addressing these challenges and harnessing emerging technologies, we postulate, will establish CHs as a cornerstone in revolutionizing chronic wound care, significantly improving patient outcomes.
A clinical study to detect COVID-19 infection from a non-invasive breath sample
Authors: Winchester Stephen , Rowles Jonathan , Pomeroy Linda , Chapovsky Alexander , Gorbunov Boris , John Joshua , Jabbar Kashif , John Isaac
Published: November 2024

Objectives

Rapid diagnosis of coronavirus disease 2019 (COVID-19) is important to the control of SARS-CoV-2. The objective of this study was to assess the feasibility of diagnosing COVID-19 infection from a breath sample using a rapid, non-invasive point-of-care breath test that does not require off-site analysis. This could increase the accessibility of testing and reduce the discomfort of current swabbing techniques.

Methods

In this prospective observational study, samples of expired air from adults diagnosed with COVID-19 and controls were collected and analyzed with gas chromatography combined with ion mobility spectrometry (BreathSpec© GC-IMS, G.A.S mbH) and also with machine learning (ML) biomarker analysis (MLBA, Ancon Technologies Ltd.).

Key findings

A total of 330 participants, who tested negative or positive for COVID-19 through RT-PCR, were enrolled in the study. In an ML analysis of data collected, the MLBA algorithms enable distinction between COVID-19 and non-COVID-19 subjects with an accuracy of 94.1%.

Conclusions

This study indicates that patients with COVID-19 can be quickly identified at the point of use. The development and validation of this method may allow for a rapid, circa 10-min diagnosis of COVID-19 both now and in future seasons. It may also offer an alternative tool for the detection of other viral and microbial infections.
Early NRS Leg and Back Thresholds Predict Clinical Recovery after MIS Transforaminal Lumbar Interbody Fusion for Degenerative Spine Disease
Authors: DiSilvestro Kevin J. , Bay Annika , Kwas Cole T. , Asada Tomoyuki , Hirase Takashi , Zhang Joshua , Doran William G. , Singh Nishtha , Durbas Atahan , Araghi Kasra , Tuma Olivia C. , Korsun Maximillian K. , Kim Eric T. , Simon Chad Z. , Zhao Eric R. , Allen Myles RJ , Mai Eric , Subramanian Tejas , Iyer Sravisht , Qureshi Sheeraz A.
Published: November 2024

Study Design.

This retrospective study included patients who underwent primary one-level minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) for degenerative lumbar spine conditions.

Objective.

To identify early predictors of failing to achieve the Oswestry Disability Index (ODI) minimum clinically important difference (MCID) one-year post-surgery.

Summary of Background Data.

Early identification of patients at risk of failing to achieve ODI-MCID is crucial for early intervention and improved postoperative counseling. Currently, no specific thresholds guide patient follow-up for optimal recovery.

Methods.

The assessment included demographic information, surgical details, and patient-reported outcome measures (PROMs). PROMs were collected postoperatively at 2-, 6-, and 12-week time points, as well as at 6- and 12-months.

Results.

The study included 166 patients, with 34% failing to achieve ODI-MCID at one year. Early VAS back and leg scores were found to be significant predictors of ODI-MCID achievement. The optimal thresholds identified were 2.25 for early VAS back and 4.25 for early VAS leg. A rerun regression identified the thresholds as independent predictors of ODI-MCID, with odds ratios of 0.31 for both measures.

Conclusion.

VAS back and leg score thresholds at 6-12 weeks can predict ODI-MCID achievement one year after MIS TLIF. Patients exceeding the identified thresholds may be at risk of failing ODI-MCID and should be monitored closely.

Level of Evidence.

Level 3
Is Frailty Discouraging Surgeons from Performing Thoracolumbar Fusion? A Retrospective Study
Authors: Linden Benjamin M. , Willging Abbygale M. , Chainani Masoom , Koch Kelsey , Galet Colette , McGonagill Patrick W.
Published: November 2024

Study Design.

Retrospective cohort study.

Objective.

To evaluate whether frailty scoring is associated with adverse outcomes and management of thoracolumbar fractures (TLF) patients.

Summary of background data.

Trauma patients with TLF often face longer recovery. The Canadian Study of Health and Aging clinical frailty scale (CSHA-CFS) predicts outcomes in older trauma patients.

Methods.

Adult trauma patients admitted from 2017 to 2021 who presented with TLF were included. Frailty was scored using CSHA-CFS. Endpoints were in-hospital mortality, hospital length of stay, surgery, complications, and discharge disposition. Multivariate analyses adjusting for baseline characteristics were performed. P<0.05 was considered significant.

Results.

Overall, 1456 patients were included; 1013 fit, 240 pre-frail, and 203 frail. Frail patients underwent fewer surgeries (OR=0.5 [0.32-0.77], P=0.002). TL fusion was associated with lower mortality (OR=0.31 [0.11-0.85], P=0.024). Pre-frailty and frailty were associated with increased risk of pneumonia (OR=2.522 [1.428-4.456], P=0.001; OR=2.93 [1.32-6.54], P=0.008, respectively) and death (OR=3.581 [1.853-6.921], P<0.001; OR=2.46 [1.07-5.67], P=0.035). Pre-frail and frail patients were more likely to discharge to skilled nursing facilities (OR=1.687 [1.024-2.780], P=0.04; OR=4.89 [2.66-9.0]), P<0.001).

Conclusions.

Pre-frailty and frailty were associated with poor outcomes and higher level of care at discharge. Frail patients were less likely to undergo TL fusion, despite its association with improved survival. This suggests frailty should not discourage surgeons from performing thoracolumbar fusion. Frailty scoring upon admission may help guide management and set realistic expectations for patients and their families.
Severe metabolic alkalosis with fludrocortisone therapy—a case report
Authors: Williams Grace , Hinxman Honor
Published: November 2024

Background

We present an atypical case of severe metabolic alkalosis, not reported in the literature to date.

Case Presentation

Owing to concerns of apneas and desaturation, a 75-year-old man presented to the emergency department with significantly deranged physiology: bicarbonate level of 63.6 mmol/L, a base excess of 40.6, and a potassium concentration of 1.9 mmol/L.

Primary diagnoses included metabolic alkalosis secondary to fludrocortisone therapy with respiratory compensation, hypokalemia, and hypochloremia. He initially received potassium replacement with cardiac monitoring, followed by permissive hypercapnia in the intensive care unit. He received acetazolamide to further improve his acid-base status. The patient had a good outcome with gradual return of his pH and bicarbonate levels to baseline. He was then discharged.

Conclusion

Iatrogenic mineralocorticoid excess should be considered when the patient presents with significantly raised bicarbonate levels. When starting fludrocortisone, renal function needs to be diligently monitored due to risk of hypokalemia metabolic alkalosis.
MELAS syndrome and risk of infection
Authors: Saleem Muskaan , Sohail Myra , Akhtar Ahmad
Published: November 2024

This perspective explores the relationship between mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and an increased risk of infections. Mitochondrial dysfunction impairs immune cell function, impacting the body’s defense against pathogens. Additional effects on the immune system may manifest through altered B-cell function and disruptions in the gut microbiota balance. The complex connection between infections, MELAS symptoms, and treatment complicates patient management. We propose greater focus on genetic abnormalities and their immunologic impacts, indicating a possible path for targeted pharmaceutical therapies to improve overall illness management.
The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation
Authors: Cavallari Larisa H. , Hicks J. Kevin , Patel Jai N. , Elchynski Amanda L. , Smith D. Max , Bargal Salma A. , Fleck Ashley , Aquilante Christina L. , Killam Shayna R. , Lemke Lauren , Ochi Taichi , Ramsey Laura B. , Haidar Cyrine E. , Ho Teresa , El Rouby Nihal , Monte Andrew A. , Allen Josiah D. , Beitelshees Amber L. , Bishop Jeffrey R. , Bousman Chad , Campbell Ronald , Cicali Emily J. , Cook Kelsey J. , Duong Benjamin , Tsermpini Evangelia Eirini , Girdwood Sonya Tang , Gregornik David B. , Grimsrud Kristin N. , Lamb Nathan , Lee James C. , Lopez Rocio Ortiz , Mazhindu Tinashe Adrian , Morris Sarah A. , Nagy Mohamed , Nguyen Jenny , Pasternak Amy L. , Petry Natasha , van Schaik Ron H.N. , Schultz April , Skaar Todd C. , Al Alshaykh Hana , Stevenson James M. , Stone Rachael M. , Tran Nam K. , Tuteja Sony , Woodahl Erica L. , Yuan Li-Chi , Lee Craig R.
Published: November 2024

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual’s genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice. The Pharmacogenomics Global Research Network Implementation Working Group seeks to engage institutions globally that have implemented pharmacogenetic testing into clinical practice or are in the process or planning stages of implementing testing to collectively disseminate data on implementation strategies, metrics, and health-related outcomes with the use of genotype-guided drug therapy to ultimately help advance pharmacogenetic implementation. This paper describes the goals, structure, and initial projects of the group in addition to implementation priorities across sites and future collaborative opportunities.
Decrements in Morning and Evening Energy Are Associated With a Higher Symptom Burden in Patients With Gynecologic Cancers Receiving Chemotherapy
Authors: Asakitogum David Ayangba , Nutor Jerry J. , Hammer Marilyn J. , Pozzar Rachel , Paul Steven M. , Cooper Bruce A. , Conley Yvette P. , Levine Jon , Miaskowski Christine
Published: November 2024

Background

Decrements in energy are a significant problem associated with chemotherapy. To date, no study examined the variability of energy in patients with gynecologic cancers.

Objective

To identify distinct morning and evening energy profiles in patients with gynecologic cancers and evaluate for differences in demographic and clinical characteristics, other common symptoms, and quality-of-life (QOL) outcomes.

Methods

A sample of 232 patients with gynecologic cancers completed questionnaires 6 times over 2 cycles of chemotherapy. Latent profile analysis was used to identify distinct morning and evening energy profiles. Differences in demographic and clinical characteristics, other common symptoms, and QOL outcomes were evaluated using parametric and nonparametric tests.

Results

Three distinct morning (ie, high [9.2%], low [63.1%], very low [27.1%]) and 2 distinct evening (moderate [30.6%], very low [69.4%]) energy classes were identified. Clinical risk factors associated with the worst morning energy profiles included lower functional status and a higher comorbidity burden. Less likely to exercise on a regular basis was the only characteristic associated with the worst evening energy profile. For both symptoms, the worst profiles were associated with higher levels of depression and sleep disturbance, lower levels of cognitive function, and poorer QOL.

Conclusions

Approximately 70% of patients with gynecologic cancers experienced decrements in morning and evening energy. The study identified modifiable risk factors associated with more decrements in morning and evening energy.

Implications for Practice

Clinicians can use these findings to identify higher-risk patients and develop individualized energy conservation interventions for these vulnerable patients.
Laryngectomy Margin Assessment: A Little Help From a Template
Authors: Zaccarini Daniel J. , Thompson Lester D.R.
Published: November 2024

Laryngectomy margin assessment is an important part of patient care and can affect outcomes. There is no standard approach to grossing laryngectomy specimens, with variations in the published guidelines. A uniform approach to margin assessment may be helpful to improve patient care and future research. At the very least, sampling of all mucosal margins (arytenoid area, hypopharyngeal, and anterior epiglottis) and tracheal margin should be performed. Sampling of soft tissue margins may be delegated to the pathologist, and contingent on the tumor extent into soft tissue. If a tracheostomy is present, skin and soft tissue margins should be sampled from the stoma. This review provides a template for laryngectomy margin assessment and can be used as a guideline as to which margins should be assessed.
99mTc-PSMA and 99mTc-FAPI-46 Uptake in Pulmonary Lymphangitic Carcinomatosis
Authors: Raeisi Nasrin , Aghaee Atena , Aryana Kamran , Soltani Salman , Ghorbani Hamidreza
Published: November 2024

This case report presents a rare instance of pulmonary lymphangitic carcinomatosis (PLC) in a prostate cancer patient, showcasing uptake of 99mTc–prostate-specific membrane antigen and 99mTc-fibroblast activation protein inhibitor-46 on imaging scans. A 70-year-old man with elevated serum prostate-specific antigen (PSA) levels exhibited respiratory symptoms and was diagnosed with widespread skeletal and pulmonary metastases. Following taxane-based chemotherapy and androgen deprivation therapy, imaging revealed decreased uptake and improvement in clinical symptoms, indicating treatment response. PLC in prostate cancer is exceptionally rare, with only limited documented cases. This report highlights the diagnostic value of 99mTc–prostate-specific membrane antigen and 99mTc–fibroblast activation protein inhibitor scans in identifying PLC and monitoring treatment response, offering insights into the management of this challenging condition.
Facial Nerve Reanimation Using Free-functioning Gracilis Muscle Transfer in Adolescent Patients. Long-term Follow-up With Outcome Assessment Using House-Brackmann Facial Nerve Grading System
Authors: Opyrchał Jakub , Bula Daniel , Krakowczyk Dominika , Walczak Dominik , Krakowczyk Łukasz
Published: November 2024

Objective:

Facial nerve palsy is a condition that carries significant consequences, especially when it occurs during adolescence. It represents a considerable clinical problem due to limited treatment options, as well as the fact that it has significant cosmetic and functional implications. In adolescents with persistent facial palsy, microsurgical procedures for dynamic facial reanimation may effectively restore facial symmetry. A commonly performed intervention is free-functioning muscle transfer.

Methods:

The study group includes 10 pediatric patients aged 11 to 17 with diagnosed persistent facial nerve palsy, surgically treated for the restoration of mimic muscle function between 2018 and 2022. All patients included in the study underwent surgical treatment using free-functioning muscle transfer. The average observation period was 38 months (range: 21–54 mo). To objectively assess the return of function of the transferred innervated muscle flap during treatment and postoperative recovery, the House-Brackmann Facial Nerve Grading System was used.

Results:

At an average observation period of 38 months, at least grade 3 according to the HBGS scoring system was demonstrated in all cases. Twelve months after the procedure, 6 patients (60%) were classified as grade 3, and in 4 cases (40%), the achieved symmetry was sufficient to obtain grade 2. No patient reported limitations in the adduction of the lower limb resulting from the harvest of the gracillis muscle.

Conclusions:

Further research should focus on patient-reported outcomes, conducting studies on a large study group could lead to the development of a clinical algorithm that could facilitate the assessment and effectively assist in the treatment of facial palsy.
Limited Availability and Readability of Spanish Language Patient Educational Material: A Review of the Nation’s Top Children’s Hospitals
Authors: Yu Nina , Saldana Golddy M. , Firriolo Joseph M. , Wong Granger
Published: November 2024

Cleft lip with or without cleft palate (CL/P) is a common congenital facial pathology that occurs at higher incidences in Hispanic communities. The authors analyzed the availability and readability of Spanish-written patient education materials (PEMs) on CL/P from top-ranking U.S. children’s hospitals to determine the presence of health literacy barriers. Availability of PEM was evaluated by 2 methods: (1) Google search and (2) evaluation of the official hospital websites. For each institution, a Google search was conducted using the phrase, “labio leporino y/o paladar hendido (translation: CL/P) + (hospital name).” In addition, each hospital website was assessed for Spanish PEM availability. Spanish PEMs were then categorized by whether they had been generated by an automated translation function or if they were independently written Spanish text. English PEM readability was assessed using the Simple Measure of Gobbledygook (SMOG). Spanish PEM readability was assessed using spanish orthgraphic length (Spanish Orthographic Length), the SMOG converted for the Spanish language. Unpaired 2-tailed t tests were used to compare readability. Of a total of 85 pediatric hospitals, 28 (37.3%) had Spanish PEM. Five (6.7%) hospitals created their own Spanish-language document. The average spanish orthgraphic length reading level was 9.49 compared with an average SMOG of 11.38 (P < 0.001). Institutions that did not provide Spanish PEM in any format had a significantly higher SMOG for English PEM of 12.13 compared with 11.38 of those that had SMOG with English PEM (P = 0.04). Health literacy barriers not only exist for Spanish PEM but also for English PEM, indicating an opportunity to improve communication.
Tenascin-C from the tissue microenvironment promotes muscle stem cell self-renewal through Annexin A2
Authors: Loreti Mafalda , Cecchini Alessandra , Kaufman Collin D. , Stamenkovic Cedomir , Renero Alma , Nicoletti Chiara , Kervadec Anais , Guarnaccia Gabriele , Mayer Daphne , Colas Alexandre , Puri Pier Lorenzo , Sacco Alessandra
Published: November 2024

Skeletal muscle tissue self-repair occurs through the finely timed activation of resident muscle stem cells (MuSC). Following perturbation, MuSC exit quiescence, undergo myogenic commitment, and differentiate to regenerate the injured muscle. This process is coordinated by signals present in the tissue microenvironment, however the precise mechanisms by which the microenvironment regulates MuSC activation are still poorly understood. Here, we identified Tenascin-C (TnC), an extracellular matrix (ECM) glycoprotein, as a key player in promoting of MuSC self-renewal and function. We show that fibro-adipogenic progenitors (FAPs) are the primary cellular source of TnC during muscle repair, and that MuSC sense TnC signaling through cell the surface receptor Annexin A2. We provide in vivo evidence that TnC is required for efficient muscle repair, as mice lacking TnC exhibit a regeneration phenotype of premature aging. We propose that the decline of TnC in physiological aging contributes to inefficient muscle regeneration in aged muscle. Taken together, our results highlight the pivotal role of TnC signaling during muscle repair in healthy and aging skeletal muscle.
5-methylcytosine and 5-hydroxymethylcytosine are synergistic biomarkers for early detection of colorectal cancer
Authors: Puddu Fabio , Johansson Annelie , Modat Aurelie , Scotcher Jamie , Sethi Riccha , Harding Nick , Hill Mark , Lleshi Ermira , Teyssandier Jean , Crawford Robert , Charlesworth Tom , Osborne Robert J , Balasubramanian Shankar , Creed Paidi , Yu Shirong , Lumby Casper , Wilson Michael
Published: November 2024

Early cancer detection has the potential to significantly improve treatment outcomes and survival rates. This study investigates the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA). Using whole genome sequencing, we analyzed cfDNA from 37 treatment-naive CRC patients and 32 healthy controls. Our findings indicate that combining measurements of 5mC and 5hmC significantly enhances diagnostic accuracy (AUC = 0.95) compared to traditional approaches that conflate these markers (modified C, AUC = 0.66). Notably, 71.7% of differentially methylated regions (DMRs) exhibiting an increase in 5hmC in stage I cfDNA also showed a corresponding decrease in 5mC in stage IV, suggesting that 5hmC can effectively track regions undergoing demethylation during tumor development. These results support the hypothesis that distinguishing between 5mC and 5hmC can improve the sensitivity of liquid biopsy tests for early cancer detection.
Exploring fractal dimensions on ultrasound of gonadal images for sex determination in shortnose sturgeon (Acipenser brevirostrum)
Authors: Balazadeh Keyvan , Litvak Matthew K.
Published: November 2024

Sturgeon are often viewed as monomorphic species because they often lack external features that allow differentiation between sexes. Current practices for sexing sturgeon rely heavily on surgical invasive procedures to visually examine gonadal tissues. An alternative which is widely used in different species of Acipenserids is the use of ultrasound to sex them. The challenge with ultrasound is that it requires an experienced operator to successfully sex the fish by recognizing relevant patterns in the structures of gonads. The objective of this study is to attempt to lay the groundwork for potential systematization of sexing techniques using a portable ultrasound as a medium. We used texture analysis software based on lacunarity measurements and fractal dimensions to determine whether male gonads, female granular tissue (GT) and female pinheads were significantly different from each other using two different resolutions on the ultrasound machine. Male gonads and GT were significantly different from pinheads in lacunarity measurements (p=0.001) using 10-12Mhz general resolution imaging. Fractal dimensions did not result in any significant differences. Lacunarity has the potential to determine sex based on gray level-co-occurrence matrices and the software is freely available. We have also developed a relative probability table based on the data gathered on lacunarity in this study available as supplementary material for quick reference.
Tailor-Designed Models for the Turbulent Velocity Gradient through Normalizing Flow
Authors: Carbone M. , Peterhans V. J. , Ecker A. S. , Wilczek M.
Published: November 2024

Small-scale turbulence can be comprehensively described in terms of velocity gradients, which makes them an appealing starting point for low-dimensional modeling. Typical models consist of stochastic equations based on closures for nonlocal pressure and viscous contributions. The fidelity of the resulting models depends on the accuracy of the underlying modeling assumptions. Here, we discuss an alternative data-driven approach leveraging machine learning to derive a velocity gradient model which captures its statistics by construction. We use a normalizing flow to learn the velocity gradient probability density function (PDF) from direct numerical simulation (DNS) of incompressible turbulence. Then, by using the equation for the single-time PDF of the velocity gradient, we construct a deterministic, yet chaotic, dynamical system featuring the learned steady-state PDF by design. Finally, utilizing gauge terms for the velocity gradient single-time statistics, we optimize the time correlations as obtained from our model against the DNS data. As a result, the model time realizations resemble the time series from DNS statistically closely.

Published by the American Physical Society
2024