bluuebunny/crossref_metadata_2025 huggingface dataset:
Entanglement in cosmology
Authors: Boutivas K. , Katsinis D. , Pastras G. , Tetradis N.
Published: April 2024

We compute the evolution of the entanglement entropy for a massless field within a
spherical region throughout the inflationary period and the subsequent era of radiation
domination, starting from the Bunch-Davies vacuum. In order to focus on the entanglement of modes
that are directly accessible to observations, we impose an ultraviolet cutoff set by the
wavelength of the last mode that exited the horizon at the end of inflation. The transition of
each mode towards a squeezed state upon horizon exit during inflation and the additional squeezing
when radiation domination sets in enhance the entanglement entropy. Shortly after the transition
to the radiation-dominated era, a volume term develops and becomes the leading contribution to the
entropy at late times, as is common for systems lying in squeezed states. We estimate the
magnitude of the entropy and discuss its interpretation in the light of the quantum to classical
transition for modes exiting the horizon during inflation. Our results raise the possibility that
the quantum nature of weakly interacting fields, such as gravitational waves resulting from tensor
modes during inflation, may be detectable in today's universe. On the other hand, an observer with
no knowledge of the degrees of freedom beyond the horizon would interpret the entropy as
thermal. From this point of view, the reheating after inflation would be a result of
quantum entanglement.
Radial acceleration relation of galaxies with joint kinematic and weak-lensing data
Authors: Mistele T. , McGaugh S. , Lelli F. , Schombert J. , Li P.
Published: April 2024

We combine kinematic and gravitational lensing data to construct the Radial Acceleration Relation (RAR) of galaxies over a large dynamic range.
We improve on previous weak-lensing studies in two ways.
First, we compute stellar masses using the same stellar population model as for the kinematic data.
Second, we introduce a new method for converting excess surface density profiles to radial accelerations.
This method is based on a new deprojection formula which is exact, computationally efficient, and gives smaller systematic uncertainties than previous methods.
We find that the RAR inferred from weak-lensing data smoothly continues that inferred from kinematic data by about 2.5 dex in acceleration.
Contrary to previous studies, we find that early- and late-type galaxies lie on the same joint RAR when a sufficiently strict isolation criterion is adopted and their stellar and gas masses are estimated consistently with the kinematic RAR.
Mechanical compression regulates tumor spheroid invasion into a 3D collagen matrix
Authors: Pandey Mrinal , Suh Young Joon , Kim Minha , Davis Hannah Jane , Segall Jeffrey E , Wu Mingming
Published: April 2024

Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stress within the tumor. Although the effects of tension within 3D extracellular matrices (ECMs) on tumor growth and invasion are well established, the role of compression in tumor mechanics and invasion is largely unexplored. In this study, we modified a Transwell assay such that it provides constant compressive loads to spheroids embedded within a collagen matrix. We used microscopic imaging to follow the single cell dynamics of the cells within the spheroids, as well as invasion into the 3D ECMs. Our experimental results showed that malignant breast tumor (MDA-MB-231) and non-tumorigenic epithelial (MCF10A) spheroids responded differently to a constant compression. Cells within the malignant spheroids became more motile within the spheroids and invaded more into the ECM under compression; whereas cells within non-tumorigenic MCF10A spheroids became less motile within the spheroids and did not display apparent detachment from the spheroids under compression. These findings suggest that compression may play differential roles in healthy and pathogenic epithelial tissues and highlight the importance of tumor mechanics and invasion.
Optimizing dynamic aperture studies with active learning
Authors: Di Croce D. , Giovannozzi M. , Krymova E. , Pieloni T. , Redaelli S. , Seidel M. , Tomás R. , Van der Veken F.F.
Published: April 2024

Dynamic aperture is an important concept for the study of
non-linear beam dynamics in circular accelerators. It describes the
extent of the phase-space region where a particle's motion remains
bounded over a given number of turns. Understanding the features of
dynamic aperture is crucial for the design and operation of such
accelerators, as it provides insights into nonlinear effects and the
possibility of optimising beam lifetime. The standard approach to
calculate the dynamic aperture requires numerical simulations of
several initial conditions densely distributed in phase space for a
sufficient number of turns to probe the time scale corresponding to
machine operations. This process is very computationally intensive
and practically outside the range of today's computers. In our
study, we introduced a novel method to estimate dynamic aperture
rapidly and accurately by utilising a Deep Neural Network
model. This model was trained with simulated tracking data from the
CERN Large Hadron Collider and takes into account variations in
accelerator parameters such as betatron tune, chromaticity, and the
strength of the Landau octupoles. To enhance its performance, we
integrate the model into an innovative Active Learning
framework. This framework not only enables retraining and updating
of the computed model, but also facilitates efficient data
generation through smart sampling. Since chaotic motion cannot be
predicted, traditional tracking simulations are incorporated into
the Active Learning framework to deal with the chaotic nature of
some initial conditions. The results demonstrate that the use of the
Active Learning framework allows faster scanning of the
configuration parameters without compromising the accuracy of the
dynamic aperture estimates.
All-aqueous droplets-templated tailorable core-shell alginate microspheres for constructing vascularized intestinal mucosa in vitro models
Authors: Hao Xin , Du Ting , Yang Feng , Wang Yilan , He Huatao , Yang Menghan , Hong Meiying , Wang Guanxiong , Huang Deqing , Wang Yaolei
Published: April 2024

Recently, in vitro models of intestinal mucosa have become important tools for drug screening and studying the physiology and pathology of the intestine. These models enable the examination of cellular behavior in diseased states or in reaction to alterations in the microenvironment, potentially serving as alternatives to animal models. One of the major challenges in constructing physiologically relevant in vitro models of intestinal mucosa is the creation of three-dimensional microstructures that accurately mimic the integration of intestinal epithelium and vascularized stroma. Here, core–shell alginate (Alg) microspheres were generated to create the compartmentalized extracellular matrix microenvironment needed to simulate the epithelial and vascularized stromal compartments of the intestinal mucosa. We demonstrated that NIH-3T3 and human umbilical vein endothelial cells embedded in the core of the microspheres can proliferate and develop a vascular network, while human colorectal adenocarcinoma cells (Caco-2) can form an epithelial monolayer in the shell. Compared to Caco-2 monolayer encapsulated within the shell, the presence of the vascularized stroma enhances their proliferation and functionality. As such, our core–shell Alg microspheres provide a valuable method for generating in vitro models of vascularized intestinal mucosa with epithelial and vascularized stroma arranged in a spatially relevant manner and demonstrating near-physiological functionality.
Emergent constraint on the projected central equatorial Pacific warming and northwestern Pacific monsoon trough change
Authors: Tang Tao , Qi Li , Tozuka Tomoki , Luo Jing-Jia , Ling Fenghua , Luo Ling , He Jin-Hai
Published: April 2024

The northwestern Pacific monsoon trough (NWPMT) deeply impacts socio-economic development and human security over East Asia by supplying moisture to the summer monsoon rainfall and modulating tropical cyclone activities. However, considerable inter-model spreads in the coupled model inter-comparison project phase 6 models make the future projection of the NWPMT less reliable. Here, we find that the inter-model spread of the NWPMT change is significantly correlated with the central equatorial Pacific sea surface temperature change, and mainly determined by the equatorial thermocline sharpness in the historical simulations. According to the emergent constraint method, the central equatorial Pacific SST would warm up about 6% slower than the multi-model mean with 56% uncertainty reduced. Correspondingly, the NWPMT would slacken westward with 36% uncertainty reduced. Results here emphasize the importance of examining and reducing systematic model biases in simulating thermocline sharpness that have been overlooked in past literatures, before achieving more reliable future projections.
Stochastic quantum trajectories demonstrate the quantum Zeno effect in open spin 1/2, spin 1 and spin 3/2 systems
Authors: Walls Sophia M , Schachter Julien M , Qian Haocheng , Ford Ian J
Published: April 2024

We investigate the quantum Zeno effect (QZE) in spin 1/2, spin 1 and spin 3/2 open quantum systems undergoing Rabi oscillations, revealing unexplored features for the spin 1 and spin 3/2 systems. The systems interact with an environment designed to perform continuous measurements of an observable, driving the systems stochastically towards one of the eigenstates of the corresponding operator. The system-environment coupling constant represents the strength of the measurement. Stochastic quantum trajectories are generated by unravelling a Markovian Lindblad master equation using the quantum state diffusion formalism. These are regarded as a more appropriate representation of system behaviour than consideration of the averaged evolution since the latter can mask the effect of measurement. Complete positivity is maintained and thus the trajectories can be considered as physically meaningful. The QZE is investigated over a range of measurement strengths. Increasing the strength leads to greater system dwell in the vicinity of the eigenstates of the measured observable and lengthens the time taken by the system to return to that eigenstate, thus the QZE emerges. For very strong measurement, the Rabi oscillations resemble randomly occurring near-instantaneous jumps between eigenstates. The trajectories followed by the quantum system are heavily dependent on the measurement strength which other than slowing down and adding noise to the Rabi oscillations, changes the paths taken in spin phase space from a circular precession into elaborate figures-of-eight. For spin 1 and spin 3/2 systems, the measurement strength determines which eigenstates are explored and the QZE is stronger when the system dwells in the vicinity of certain eigenstates compared to others.
Towers and the First-order Theories of Hyperbolic Groups
Authors: Guirardel Vincent , Levitt Gilbert , Sklinos Rizos
Published: April 2024

This paper is devoted to the first-order theories of torsion-free hyperbolic groups. One of its purposes is to review some results and to provide precise and correct statements and definitions, as well as some proofs and new results.

A key concept is that of a tower (Sela) or NTQ system (Kharlampovich-Myasnikov). We discuss them thoroughly.

We state and prove a new general theorem which unifies several results in the literature: elementarily equivalent torsion-free hyperbolic groups have isomorphic cores (Sela); if

H
H

is elementarily embedded in a torsion-free hyperbolic group

G
G

, then

G
G

is a tower over

H
H

relative to

H
H

(Perin); free groups (Perin-Sklinos, Ould-Houcine), and more generally free products of prototypes and free groups, are homogeneous.

The converse to Sela and Perin’s results just mentioned is true. This follows from the solution to Tarski’s problem on elementary equivalence of free groups, due independently to Sela and Kharlampovich-Myasnikov, which we treat as a black box throughout the paper.

We present many examples and counterexamples, and we prove some new model-theoretic results. We characterize prime models among torsion-free hyperbolic groups, and minimal models among elementarily free groups. Using Fraïssé’s method, we associate to every torsion-free hyperbolic group

H
H

a unique homogeneous countable group

M

{\mathcal {M}}

in which any hyperbolic group

H
′

H’

elementarily equivalent to

H
H

has an elementary embedding.

In an appendix we give a complete proof of the fact, due to Sela, that towers over a torsion-free hyperbolic group

H
H

are

H
H

-limit groups.
Trends in the Prevalence of Multiple Chronic Conditions Among US Adults With Hypertension From 1999–2000 Through 2017–2020
Authors: Alanaeme Chibuike J , Ghazi Lama , Akinyelure Oluwasegun P , Wen Ying , Christenson Ashley , Poudel Bharat , Dooley Erin E , Chen Ligong , Hardy Shakia T , Foti Kathryn , Bowling C Barrett , Long Michelle T , Colantonio Lisandro D , Muntner Paul
Published: April 2024

BACKGROUND

The prevalence of many chronic conditions has increased among US adults. Many adults with hypertension have other chronic conditions.

METHODS

We estimated changes in the age-adjusted prevalence of multiple (≥3) chronic conditions, not including hypertension, using data from the National Health and Nutrition Examination Survey, from 1999–2000 to 2017–2020, among US adults with (n = 24,851) and without (n = 24,337 hypertension. Hypertension included systolic blood pressure (BP) ≥130 mm Hg, diastolic BP ≥80 mm Hg, or antihypertensive medication use. We studied 14 chronic conditions: arthritis, asthma, cancer, coronary heart disease, chronic kidney disease, depression, diabetes, dyslipidemia, hepatitis B, hepatitis C, heart failure, lung disease, obesity, and stroke.

RESULTS

From 1999–2000 to 2017–2020, the age-adjusted mean number of chronic conditions increased more among US adults with vs. without hypertension (2.2 to 2.8 vs. 1.7 to 2.0; P-interaction <0.001). Also, the age-adjusted prevalence of multiple chronic conditions increased from 39.0% to 52.0% among US adults with hypertension and from 26.0% to 30.0% among US adults without hypertension (P-interaction = 0.022). In 2017–2020, after age, gender, and race/ethnicity adjustment, US adults with hypertension were 1.94 (95% confidence interval: 1.72–2.18) times as likely to have multiple chronic conditions compared to those without hypertension. In 2017–2020, dyslipidemia, obesity, and arthritis were the most common 3 co-occurring chronic conditions among US adults with and without hypertension (age-adjusted prevalence 16.5% and 3.1%, respectively).

CONCLUSIONS

In 2017–2020, more than half of US adults with hypertension had ≥3 additional chronic conditions, a substantial increase from 20 years ago.
New Surgery and Hospital-diagnosed Infections in Elderly Patients with Inflammatory Bowel Disease Undergoing Surgery: A Nationwide Cohort Study
Authors: Nørgård Bente Mertz , Garvik Olav Sivertsen , Zegers Floor Dijkstra , Nielsen Jan , Lund Ken , Knudsen Torben , Kjeldsen Jens
Published: April 2024

Background

Elderly patients with inflammatory bowel disease [IBD] are fragile in many respects. Therefore, in these patients, we studied postoperative complications [new abdominal surgery and serious infections after the first IBD surgery].

Methods

This is a nationwide cohort study based on Danish health registries and included patients with IBD undergoing surgery. The study population was split into ulcerative colitis [UC] and Crohn’s disease [CD]. The exposed cohort [elderly] constituted those at an age of ≥60 years at first IBD surgery, and the unexposed [adults] those with surgery at the age of 18–59 years. We estimated adjusted hazard ratios [aHRs] of: a] new abdominal surgery within 2 years; and b] serious [hospital-diagnosed] infections within 6 and 12 months. We adjusted for several confounders including type of index surgery [laparoscopic or open].

Results

The aHR for a new surgery among elderly with UC and CD were 0.69 [95% CI 0.58-0.83] and 0.98 [95% CI 0.83-1.15], respectively. In elderly with UC, the aHRs of infections within 6 and 12 months after surgery were 1.07 [95% CI 0.81-1.40] and 0.85 [95% CI 0.67-1.08], respectively. In the elderly with CD, the aHRs of infections within 6 and 12 months were 1.45 [95% CI 1.12-1.88] and 1.26 [95% CI 1.00-1.59], respectively.

Conclusion

The elderly with IBD did not have an increased risk of new abdominal surgery within 2 years of the first surgery. Elderly with CD, but not UC, had an increased risk of serious infections within 6 months of surgery.
Seasonal shifts in gut microbiota and cold tolerance metrics in a northern population of Reticulitermes flavipes (Blattodea: Rhinotermitidae)
Authors: Arango Rachel A , Bishell Amy B , Ohno Katie M , Shelton Thomas G , Schoville Sean D , Carlos-Shanley Camila
Published: April 2024

Eastern subterranean termites, Reticulitermes flavipes (Kollar), are widely distributed across North America where they are exposed to a broad range of environmental conditions. However, mechanisms for overwintering are not well understood. Wisconsin is a unique location to study mechanisms of cold tolerance as it represents the northern boundary for persistent R. flavipes populations. In this study, we evaluated seasonal shifts in cold tolerance using critical thermal minimum (CTmin) and supercooling point (SCP) and examined how these measurements correlate to changes in the microbial community of the termite gut. Results showed seasonal acclimatization to cold, which is consistent with the use of behavioral freeze-avoidant mechanisms. However, these insects also demonstrated an increased susceptibility to freezing later in the season, which may be tied to changes in gut microbiota. Our results found shifts in the composition of the gut microbiome in R. flavipes between mid- to late summer and early to late fall. These differences may be suggestive of a change in metabolism to adjust to a period of reduced feeding and increased metabolic stress during overwintering. Specifically, results showed an increased abundance of Methanobrevibacter sp. (Euryarchaeota) associated with cold, which may be indicative of a metabolic shift from acetogenesis to methanogenesis associated with overwintering. Further work is needed focusing on specific contributions of certain gut microbes, particularly their role in metabolic adaptability and in providing protection from oxidative stress associated with changes in environmental conditions.
Efficacy and residual toxicity of chitosan for Rhagoletis pomonella (Diptera: Tephritidae)
Authors: Tohline Logan I , Stoffolano John G , Piñero Jaime C
Published: April 2024

Chitosan is a naturally derived polymer that has significant potential for use as a bioinsecticide. Despite this, there is a lack of research as to the efficacy of chitosan for many insect pest species. The apple maggot fly, Rhagoletis pomonella (Walsh) (Diptera: Tephritidae), is one such pest for which chitosan toxicity has not been explored. In this study, the toxicity of chitosan for R. pomonella adults was tested via no-choice feeding assays. An aging trial was further used to test the mortality of flies provided dried chitosan-sucrose treatments (CST), which were aged for 0 or 3 days in greenhouse conditions. This study found that the CST is toxic for R. pomonella adults when ingested, leading to a significant increase in the rate of mortality compared to control groups. The use of dried chitosan, however, did not change the mortality of flies, suggesting this will not be an effective delivery mechanism. Effective biopesticide delivery systems have not been defined for chitosan use outside of a laboratory, indicating the need for further research testing delivery mechanisms. It is suggested that an effective method of delivery can be as a food-based bait in attract-and-kill traps, as chitosan must be ingested to kill flies. Forming a viscous solution, chitosan may be best suited to these lure systems.
Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3
Authors: Wang Miao , Li Xiao-Wei , Yuan Sen-Chao , Pan Jie , Guo Zeng-Lin , Sun Li-Ming , Jiang Shao-Zhen , Zhao Ming , Xue Wen , Cai Hong , Gu Lin , Luo Dan , Chen Ling , Zhou Xue-Qing , Han Qiu-Ying , Li Jin , Zhou Tao , Xia Tian , Li Tao
Published: April 2024

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor–IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi–Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.
fastDFE: Fast and Flexible Inference of the Distribution of Fitness Effects
Authors: Sendrowski Janek , Bataillon Thomas
Published: April 2024

Estimating the distribution of fitness effects (DFE) of new mutations is of fundamental importance in evolutionary biology, ecology, and conservation. However, existing methods for DFE estimation suffer from limitations, such as slow computation speed and limited scalability. To address these issues, we introduce fastDFE, a Python-based software package, offering fast, and flexible DFE inference from site-frequency spectrum (SFS) data. Apart from providing efficient joint inference of multiple DFEs that share parameters, it offers the feature of introducing genomic covariates that influence the DFEs and testing their significance. To further simplify usage, fastDFE is equipped with comprehensive VCF-to-SFS parsing utilities. These include options for site filtering and stratification, as well as site-degeneracy annotation and probabilistic ancestral-allele inference. fastDFE thereby covers the entire workflow of DFE inference from the moment of acquiring a raw VCF file. Despite its Python foundation, fastDFE incorporates a full R interface, including native R visualization capabilities. The package is comprehensively tested and documented at fastdfe.readthedocs.io.
Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance
Authors: Chen Meiting , Huang Riqing , Chen Rishang , Pan Fei , Shen Xiujiao , Li Haifeng , Rong Qixiang , An Xin , Xue Cong , Shi Yanxia
Published: April 2024

Background

The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC.

Methods

This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023. Outcomes included the objective response rate (ORR) for ADC1 and ADC2, progression free survival 2 (PFS2), defined as the time from initiation of ADC2 to progression, and overall survival (OS).

Results

Seventy-nine female patients were included, 64 of whom had HER2-positive disease. The ORR for ADC2 with similar payload of ADC1 was found to be 5.3%. When switching to a different payload, the ORR of ADC2 increased to 22.6%. The PFS2 for ADC2 remained similar regardless of whether the payload was similar or different. Switching to different payload showed a higher ORR in patients with rapid progression and a durable response longer than 6 months (41.2% vs 15.0%). Specifically, significantly longer PFS2 and OS were seen in patients treated with trastuzumab deruxtecan (T-Dxd) compared to those treated with disitamab vedotin (RC48) after progression from trastuzumab emtansine (T-DM1; median PFS2 5.37 months vs 3.30 months, HR = 0.40, 95% CI 0.17-0.93, P = .034; median OS 50.6 months vs 20.2 months, HR = 0.27, 95% CI 0.08-0.91, P = .034). For patients who progressed after T-Dxd, the median PFS2 was 6.05 months for those treated with RC48 versus 0.93 months for those treated with T-DM1 (HR = 0.03, 95% CI 0.002-0.353, P = .0093). Genomic analysis revealed that alternation of retinoblastoma1 was significantly associated with superior PFS.

Conclusion

The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.
Perioperative pain optimization in the age of the opioid epidemic
Authors: Patel Janki , Snyder Kyle , Brooks Amber K.
Published: April 2024

Purpose of review

The opioid epidemic remains a constant and increasing threat to our society with overdoses and overdose deaths rising significantly during the COVID-19 pandemic. Growing evidence suggests a link between perioperative opioid use, postoperative opioid prescribing, and the development of opioid use disorder (OUD). As a result, strategies to better optimize pain management during the perioperative period are urgently needed. The purpose of this review is to summarize the most recent multimodal analgesia (MMA) recommendations, summarize evidence for efficacy surrounding the increased utilization of Enhanced Recovery After Surgery (ERAS) protocols, and discuss the implications for rising use of buprenorphine for OUD patients who present for surgery. In addition, this review will explore opportunities to expand our treatment of complex patients via transitional pain services.

Recent findings

There is ample evidence to support the benefits of MMA. However, optimal drug combinations remain understudied, presenting a target area for future research. ERAS protocols provide a more systematic and targeted approach for implementing MMA. ERAS protocols also allow for a more comprehensive approach to perioperative pain management by necessitating the involvement of surgical specialists. Increasingly, OUD patients taking buprenorphine are presenting for surgery. Recent guidance from a multisociety OUD working group recommends that buprenorphine not be routinely discontinued or tapered perioperatively. Lastly, there is emerging evidence to justify the use of transitional pain services for more comprehensive treatment of complex patients, like those with chronic pain, preoperative opioid tolerance, or substance use disorder.

Perioperative physicians must be aware of the impact of the opioid epidemic and explore methods like MMA techniques, ERAS protocols, and transitional pain services to improve the perioperative pain experience and decrease the risks of opioid-related harm.
A Case of CD4+ T-Cell Lymphoma With Gamma–Delta Phenotype, Incidentally Manifesting in a Wound Debridement Sample
Authors: Adams Paige E. , Ehyayee Vida , Ahmed Aadil
Published: April 2024

We report an 85-year-old male patient with a medical history significant for psoriasis who presented with a thigh wound that expanded slowly over the course of 9 months. The patient was previously treated with amputation of hand digits for osteomyelitis. Histologic examination of the tissue sample revealed a broad ulceration with large areas of necrosis extending into the subcutis. The edge of the specimen also revealed a nodular lymphoid infiltrate in the subcutaneous adipose tissue composed of atypical cells. These cells were only positive for CD3, CD4, and T-cell receptor (TCR) delta stains . The Ki-67 proliferation index of tumor cells was about 70%. The tumor cells were negative for CD30, CD8, CD56, TCR BF1, granzyme, TIA1, CD123, and Epstein-Barr encoding region (EBER)-ish stains. A diagnosis of gamma–delta T-cell lymphoma was made. Further imaging showed regional lymphadenopathy. The patient was started on mini-CHOP and filgrastim; however, the patient died within 1 month after the diagnosis. This is an interesting case of gamma–delta T-cell lymphoma that was incidentally diagnosed on a chronic wound. In addition, it showed a CD4+, CD8− phenotype that is exceedingly rare for T-cell lymphomas with gamma–delta phenotype.
Nail Telocytes: Identification, Potential Physiological Function, and Role in Pathology: A Reappraisal of the So-Called Onychofibroblasts/Onychodermis
Authors: Perrin Christophe
Published: April 2024

Some authors have suggested that the fibroblasts of the nail mesenchyme (onychofibroblasts) can be distinguished from skin fibroblasts by their high expression of CD10. My 2015 study documented the presence of a relatively sparse CD34+/CD10+ dendritic subpopulation in the dermis and hypodermis of the matrix. For some time now, my hypothesis has been that these interstitial dendritic mesenchymal cells of the matrix correspond to telocytes. Telocytes have been described as peculiar interstitial dendritic cells present in the mesenchymal tissue of numerous organs, including the skin, but their presence and characteristics in the nail unit have not been explored. This study was undertaken to more comprehensively investigate the existence and characteristics of nail telocytes. A series of 20 normal adult nail units were examined with a combination of morphological and immunohistochemical analyses. The matrix dermis contained a sparse subpopulation of CD34+/CD10+ elongated telocytes with a higher density in the lunular region and, at this distal level, a change in their immunohistochemical profile, resulting in a progressive loss of CD34 expression. The matrix hypodermis showed CD34+/CD10+ telocytes in their classical elongated aspect, which acquired, especially in the distal fibromyxoid area of the thumb, an oval to round morphology with multiple intracytoplasmic vacuoles. The characteristic dynamic immunophenotypic profile of the dermal telocytes with a progressive distal loss of the defining molecule CD34 was equally observed in the distal hypodermis. The nail bed dermis was thick with a dense fibrous connective tissue. A reticular network of CD34−/CD10+ telocytes was present in the superficial dermis of the proximal nail bed. The mesenchymal cells of the deep part of the proximal nail bed dermis and the entire distal nail bed dermis were CD34−/CD10−. The adult nail mesenchyme is composed of 3 microanatomically distinct regions. Only the thumb has a distal hypodermis rich in mucinous material. The population of telocytes is relatively sparse compared with the fibroblastic population of the entire nail mesenchyme. The concept of onychodermis/onychofibroblasts is not valid. Nail telocytes have a dynamic immunohistochemical profile depending on whether they are located proximally or distally. The CD34+/CD10+ profile correlates with the onychogenic epithelial region, while the CD34−/CD10+ profile correlates with a spatial rearrangement of the nail epidermal bed.
Fosfomycin Susceptibility Among Multidrug-Resistant Extended-Spectrum β-Lactamase and Metallo-β-Lactamase–Producing Uropathogens in a Tertiary Care Hospital
Authors: Kothari Aditi , Chaturvedi Parul , Bhumbla Upasana
Published: April 2024

Background

Urinary tract infections (UTIs) affect an estimated 150 million people each year worldwide involving women more than men. Because of unrestricted use of antimicrobials and accelerating antimicrobial resistance, therapeutic options for treatment of UTIs are becoming limited. Fosfomycin, a broad-spectrum, rapidly absorbable, antimicrobial agent with good bioavailability and substantial activity against multidrug-resistant (MDR) isolates has antimicrobial activity against a substantial percentage of these MDR isolates.

Methods

A cross-sectional study over a period of 20 months on urine samples of all patients of all age groups clinically suspected of UTI was conducted in a tertiary care center of southern Rajasthan. Samples were processed immediately as per standard microbiological techniques, followed by culture by a semiquantitative method and antimicrobial susceptibility testing using the Kirby-Bauer disk diffusion method. All gram-negative pathogens were screened for extended-spectrum β-lactamase and further metallo-β-lactamase production using standard disk diffusion tests.

Results

Of the 1858 positive samples isolated, the most common uropathogen was Escherichia coli (59.96%), with 8.97% confirmed extended-spectrum β-lactamase–producing isolates. Fosfomycin had susceptibility of 96.69%, with its sensitivity and specificity being 98.15% and 6.98% more than nitrofurantoin, respectively. Among the metallo-β-lactamase producers, fosfomycin had susceptibility of 78.58%, with sensitivity and specificity being 91.67% and 25% more than nitrofurantoin, respectively.

Conclusion

With an increasing threat due to MDR uropathogens in both hospitals and in the community, fosfomycin, with its unique mechanism of action, appears to be a better oral, effective, and safe therapeutic option and a viable potential alternative over other drugs for treatment of UTIs.
On the Difficulty Predicting Word Recognition Performance After Cochlear Implantation
Authors: Bartholomew Ryan A. , Hoffman Samantha E. , Juliano Amy F. , Wu Pei-zhe , Zhao Yan , de Gruttola Victor , Liberman M. Charles , Maison Stéphane F.
Published: April 2024

Hypothesis

Preimplantation word scores cannot reliably predict postimplantation outcomes.

Background

To date, there is no model based on preoperative data that can reliably predict the postoperative outcomes of cochlear implantation in the postlingually deafened adult patient.

Methods

In a group of 228 patients who received a cochlear implant between 2002 and 2021, we tested the predictive power of nine variables (age, etiology, sex, laterality of implantation, preimplantation thresholds and word scores, as well as the design, insertion approach, and angular insertion depth of the electrode array) on postimplantation outcomes. Results of multivariable linear regression analyses were then interpreted in light of data obtained from histopathological analyses of human temporal bones.

Results

Age and etiology were the only significant predictors of postimplantation outcomes. In agreement with many investigations, preimplantation word scores failed to significantly predict postimplantation outcomes. Analysis of temporal bone histopathology suggests that neuronal survival must fall below 40% before word scores in quiet begin to drop. Scores fall steeply with further neurodegeneration, such that only 20% survival can support acoustically driven word scores of 50%. Because almost all cochlear implant implantees have at least 20% of their spiral ganglion neurons (SGNs) surviving, it is expected that most cochlear implant users on average should improve to at least 50% word recognition score, as we observed, even if their preimplantation score was near zero as a result of widespread hair cell damage and the fact that ~50% of their SGNs have likely lost their peripheral axons. These “disconnected” SGNs would not contribute to acoustic hearing but likely remain electrically excitable.

Conclusion

The relationship between preimplantation word scores and data describing the survival of SGNs in humans can explain why preimplantation word scores obtained in unaided conditions fail to predict postimplantation outcomes.
Temporal Swelling Following Cochlear Implantation: Frequency, Treatment, and Outcomes
Authors: Kasuga Mariko , Yoshimura Hidekane , Takumi Yutaka
Published: April 2024

Objective

To investigate the frequency, treatment, and outcomes of postoperative delayed-onset swelling around cochlear implants.

Study Design

Retrospective, observational, nonrandomized group study.

Setting

Academic medical center.

Patients/Interventions

Among 354 patients (516 ears) who underwent cochlear implantation (CI) at our hospital between May 2009 and October 2022, 329 (472 ears: 138 children [246 ears] and 191 adults [226 ears]) with a follow-up period of >3 months were included.

Main Outcome Measures

Physical examination and computed tomography of the head were performed.

Results

In total, 5.5% (26/472 ears) had a history of delayed-onset swelling around the implant. This complication occurred in 9.8% (24/246 ears) of children and 0.9% (2/226 ears) of adults. The mean time to onset of swelling was 50 (range, 5.5–147) months following CI. In 60% (21/35) of the cases, the cause was unknown, whereas in 25.7% (9/35) and 11.5% (4/35) of cases, it was head trauma and acute inflammation, respectively. Conservative treatment (observation, antibiotics, and/or strong magnetic compression) was adapted in 91.4% (32/35) of cases. After conservative treatment, revision CI surgery was performed in one ear. Additionally, recurrent swelling was observed in 23.1% (6/26 ears) of swelling cases.

Conclusions

The results suggest that delayed-onset swelling around implants occurs more frequently in children than in adults because of the higher incidence rates of head trauma and acute otitis media in children. In most cases, conservative treatment was adequate; however, careful follow-up is necessary. Our findings can serve as a reference for optimizing care and intervention options after CI.
Very Long-Term Survivorship in Pediatric DIPG: Case Report and Review of the Literature
Authors: Dimentberg Evan , Marceau Marie-Pier , Lachance Alexandre , Bergeron-Gravel Samuel , Saikali Stephan , Crevier Louis , Bourget Catherine , Hawkins Cynthia , Jabado Nada , Giannakouros Panagiota , Renzi Samuele , Larouche Valérie
Published: April 2024

Diffuse intrinsic pontine gliomas are lethal tumors with a prognosis generally less than 1 year. Few cases of survivors of 5 years or more have been reported. This case report highlights the journey of a 9.5-year survivor who underwent 3 rounds of focal radiotherapy; she experienced 6 years of progression-free survival following the first round but ultimately succumbed to her disease. An autopsy revealed a favorable IDH1 mutation and the absence of H3K27M. This case reiterates the importance of extensive molecular analyses in diffuse intrinsic pontine gliomas and explores the potential benefit of re-irradiation in patients with positive responses and long periods of remission.
FDG PET/CT in the Diagnosis and After Sunitinib Follow-up of Synchronous Base of Tongue and Thyroid Metastases From Renal Cell Carcinoma
Authors: Kumar Srinivas Ananth , Mittal Bhagwant Rai , Kumar Suraj , Singh Harmandeep , Kumar Rajender , Bal Amanjit
Published: April 2024

Renal cell carcinoma (RCC) is a leading cause of mortality among genitourinary malignancies with limited therapeutic options. The hematogenous route, lymphatic spread, and direct invasion have been documented in RCC. Usually, metastases are regional lymph nodes, lungs, bone, liver, adrenal glands, contralateral kidney, and brain. Metastases to the rare sites such as skin, breast, head and neck were documented in the literature. In the present case, we describe the synchronous metastases to the base of the tongue and thyroid gland in RCC and the response to sunitinib therapy on 18F-FDG PET/CT.
Bacterial etiologies, antimicrobial susceptibility profiles and associated factors among patients with otitis media referred to Nekemte Public Health Research and Referral Laboratory Center, Western Ethiopia: A prospective cross-sectional study
Authors: Guteta Endalu Tesfaye , Abdi Fedassan Alemu , Feyisa Seifu Gizaw , Zewudie Belay Merkeb , Kinfu Betrearon Sileshi , Geleta Hunduma Feyisa , Tafesse Tadesse Bekele
Published: April 2024

Background

Otitis media is among the leading causes of illnesses responsible for causing hearing problems and adding significant costs to the public health system. Bacteria are the most common causative agents for otitis media. Currently, there is little information on the prevalence and antimicrobial susceptibility patterns of pathogenic bacterial isolates from patients with otitis media in Ethiopia.

Methodology

A laboratory – based cross-sectional study was conducted from June to September 2023 among 242 patients with otitis media referred to Nekemte Public Health Research and Referral Laboratory Center. Sociodemographic and clinical data were obtained by trained nurses and/or health officers in face-to-face interviews using structured questionnaires. Middle ear discharge samples were collected by trained clinical microbiology experts following all aseptic techniques. Conventional culture, different biochemical tests and antimicrobial susceptibility testing were performed for all the isolated bacteria. Reference strains were used as a positive and negative controls. The data were checked for completeness and consistency, entered into EpiData version 4.6.06 and analyzed by SPSS version 25. Logistic regression analysis was performed to determine the associated factors of otitis media. Adjusted odds ratio was used to determine strength of association. Statistical significance was obtained at p-value of below 0.05. The data were interpreted using graphs, tables, and results statements.

Results

A total of 242 middle ear discharge samples were collected and cultured from which 212 (87.6%) were culture positive. A total of 228 pathogenic bacterial isolates were recovered. The predominant bacterial isolates wereS. aureus92 (40.4%) followed byP. aeruginosa33 (14.5%) andE. coli24 (10.5%). One hundred fifty-one (66.2%) bacterial pathogens were multidrug resistant. Piperacillin-tazobactam and tobramycin are relatively common drugs to which most of the isolates were susceptible while ampicillin and tetracycline were the most resistant. Purulent discharge (p-value = 0.001), middle ear discharge ≥14 days (P-value = 0.000) and a history of active/passive smoking (P-value = 0.043) were significantly associated with otitis media.

Conclusion

The prevalence of bacterial pathogens, most of which were multidrug-resistant, was high among patients with otitis media. A significant association was observed with purulent ear discharge, chronic otitis media, and passive or active smoking. Choosing the proper antibiotic for the treatment of bacterial infection is crucial.
Dynamic land-plant carbon sources in marine sediments inferred from ancient DNA
Authors: Herzschuh Ulrike , Weiss Josefine Friederike , Stoof-Leichsenring Kathleen Friederike , Harms Lars , Nuernberg Dirk , Mueller Juliane
Published: April 2024

Terrigenous organic matter in marine sediments is considered a significant long-term carbon sink, yet our knowledge regarding its source taxa is severely limited. Here, we leverage land-plant ancient DNA from six globally distributed marine sediment cores covering the Last Glacial-Holocene transition as a proxy for the share, accumulation rate, preservation, and composition of terrigenous organic matter. We show that the spatial and temporal plant composition as revealed by sedaDNA records reflects mainly the vegetation dynamics of nearby continents as revealed by comparison with pollen from land archives. However, we also find indications of a global north-to-south translocation of sedaDNA. The plant composition shows that upland vegetation is strongly underrepresented in the record compared to riverine and coastal sources. We also find that plant sedaDNA has a higher accumulation rate in samples from the Late Glacial, which is characterized by high runoff and mineral load. Thus plant DNA in marine sediments allows for new perspectives on the global linkages between the terrestrial and marine carbon cycle which would benefit from a more quantitative understanding of DNA preservation and dispersal. This represents the basis of how climate change and land-use change translate into carbon-sink dynamics and also informs about natural carbon-capture solutions.
Cryo-EM Structures Reveal Tau Filaments from Down Syndrome Adopt Alzheimer’s Disease Fold
Authors: Ghosh Ujjayini , Tse Eric , Yang Hyunjun , Shi Marie , Caro Christoffer D. , Wang Feng , Merz Gregory E. , Prusiner Stanley B. , Southworth Daniel R. , Condello Carlo
Published: April 2024

Down syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among their complex clinical features, including musculoskeletal, neurological, and cardiovascular disabilities, individuals with DS have an increased risk of developing progressive dementia and early-onset Alzheimer’s disease (AD). This dementia is attributed to the increased gene dosage of the amyloid-β (Aβ) precursor protein gene, the formation of self-propagating Aβ and tau prion conformers, and the deposition of neurotoxic Aβ plaques and tau neurofibrillary tangles. Tau amyloid fibrils have previously been established to adopt many distinct conformations across different neurodegenerative conditions. Here, we report the characterization of brain samples from four DS cases spanning 36 to 63 years of age by spectral confocal imaging with conformation-specific dyes and cryo–electron microscopy (cryo-EM) to determine structures of isolated tau fibrils. High-resolution structures revealed paired helical filament (PHF) and straight filament (SF) conformations of tau that were identical to those determined from AD cases. The PHFs and SFs are made of twoC-shaped protofilaments, each containing a cross-β/β-helix motif. Similar to filaments from AD cases, most filaments from the DS cases adopted the PHF form, while a minority (approximately 20%) formed SFs. Samples from the youngest individual with no documented dementia had sparse tau deposits. To isolate tau for cryo-EM from this challenging sample we used a novel affinity-grid method involving a graphene oxide surface derivatized with anti-tau antibodies. This method improved isolation and revealed that primarily tau PHFs and a minor population of chronic traumatic encephalopathy type II–like filaments were present in this youngest case. These findings expand the similarities between AD and DS to the molecular level, providing insight into their related pathologies and the potential for targeting common tau filament folds by small-molecule therapeutics and diagnostics.
Radiation of pain: Psychophysical evidence for a population coding mechanism in humans
Authors: Adamczyk Wacław M. , Ramu Vishwanath , Jackson Catherine , Schulze Geraldine , Goldschneider Kenneth R. , Kashikar-Zuck Susmita , King Christopher D. , Coghill Robert C.
Published: April 2024

The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers (27 females, 23 males, ages 14-44) participated in this study wherein noxious stimuli (43, 45, 47 and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s durations. Also, visual stimuli displayed on the target bodily area were utilized as a control. Participants provided pain (and light) spatial extent ratings as well as pain (and light) intensity ratings. In the extent rating procedure, participants adjusted the extent of the square displayed on the screen with the extent of pain (or light) which they experienced. Pain extent ratings showed statistically significant radiation of pain indicated by 12.42× greater spatial spread of pain (pain extent) than the area of the stimulation with 49°C (p<0.001), in contrast to visual ratings which closely approximated the size of the stimulus (1.22×). Pain radiation was more pronounced in hairy than glabrous skin (p<0.05) and was more pronounced with longer stimulus duration (p<0.001). Pain intensity explained only 14% of the pain radiation variability. The relative independence of the pain radiation from pain intensity indicates that distinct components of population coding mechanisms may be involved in the spatial representation of pain versus intensity coding.