bluuebunny/crossref_metadata_2025 huggingface dataset:
Dramatic changes in mitochondrial subcellular location and morphology accompany activation of the CO
2
concentrating mechanism
Authors: Findinier Justin , Joubert Lydia-Marie , Fakhimi Neda , Schmid Michael F. , Malkovskiy Andrey V. , Chiu Wah , Burlacot Adrien , Grossman Arthur R.
Published: October 2024

Dynamic changes in intracellular ultrastructure can be critical for the ability of organisms to acclimate to environmental conditions. Microalgae, which are responsible for ~50% of global photosynthesis, compartmentalize their Ribulose 1,5 Bisphosphate Carboxylase/Oxygenase (Rubisco) into a specialized structure known as the pyrenoid when the cells experience limiting CO
2
conditions; this compartmentalization is a component of the CO
2
Concentrating Mechanism (CCM), which facilitates photosynthetic CO
2
fixation as environmental levels of inorganic carbon (Ci) decline. Changes in the spatial distribution of mitochondria in green algae have also been observed under CO
2
limitation, although a role for this reorganization in CCM function remains unclear. We used the green microalga
Chlamydomonas reinhardtii
to monitor changes in mitochondrial position and ultrastructure as cells transition between high CO
2
and Low/Very Low CO
2
(LC/VLC). Upon transferring cells to VLC, the mitochondria move from a central to a peripheral cell location and orient in parallel tubular arrays that extend along the cell’s apico-basal axis. We show that these ultrastructural changes correlate with CCM induction and are regulated by the CCM master regulator CIA5. The apico-basal orientation of the mitochondrial membranes, but not the movement of the mitochondrion to the cell periphery, is dependent on microtubules and the MIRO1 protein, with the latter involved in membrane–microtubule interactions. Furthermore, blocking mitochondrial respiration in VLC-acclimated cells reduces the affinity of the cells for Ci. Overall, our results suggest that mitochondrial repositioning functions in integrating cellular architecture and energetics with CCM activities and invite further exploration of how intracellular architecture can impact fitness under dynamic environmental conditions.
Dramatic recent declines in the size of monarch butterfly (
Danaus plexippus
) roosts during fall migration
Authors: Davis Andrew K. , Croy Jordan R. , Snyder William E.
Published: October 2024

The conservation status of monarch butterflies in North America is a topic of intense scrutiny and debate. It is clear that winter colonies in Mexico are declining, yet some recent studies suggest that summer breeding populations are relatively stable and similar to historical abundances. One possible explanation for these discordant patterns is that fall migration success has been recently disrupted. Here, we use a relatively unexplored citizen-scientist dataset on the size of monarch “roosts,” which are resting aggregations on vegetation, to infer changes in monarch abundance along the fall migration route over the last 17 y. We found that the timing of migration remained relatively unchanged while the flyway has generally become warmer and greener. Warmer and greener conditions were associated with larger roosts, yet we found steady, dramatic declines in roost sizes through time that were independent of climate and landscape factors. Roost sizes have declined as much as 80%, with losses increasing from north to south along the migration route. These findings suggest that failure during the fall migration could explain the apparent drop in monarch numbers from summer breeding to overwintering populations. This in turn suggests that conservation efforts that support fall migration success are most needed, such as providing high quality nectar plants along the migration route or limiting the planting of nonnative milkweeds that enhance monarch parasite loads. Overall, it appears the fall migration of monarch butterflies is under imminent threat, even if the species’ overall survival is not.
Eye closures in spoken Hebrew
Authors: Shor Leon
Published: October 2024

The present study focuses on eye closure (EC) as a communicative facial gesture in Israeli Hebrew
media talk and pays particular attention to its coordination with co-expressive verbal, prosodic, and embodied resources. Drawing
on the interactional approach to language and embodied action, the study demonstrates that EC can convey four contextual meanings
— concentration, hedging, negation, and totality — depending on the context in which it occurs and the verbal
material with which it is co-produced. The paper proposes that these contextual meanings are derived from the more general meaning
of disengagement conveyed by EC. Moreover, the present paper suggests several potential semiotic connections between the
basic physiological use of EC as a reflex of self-protection and evasion and its observed contextual meanings. This provides
evidence for the co-optation of the basic functions of facial gestures for communicative purposes via metaphorical-metonymical
extensions.
Effects of TMIn flow rate during quantum barrier growth on multi-quantum well material properties and device performance of GaN-based laser diodes
Authors: Chen 陈 Zhenyu 振宇 , Zhao 赵 Degang 德刚 , Liang 梁 Feng 锋 , Liu 刘 Zongshun 宗顺 , Yang 杨 Jing 静 , Chen 陈 Ping 平
Published: October 2024

Multidimensional influences of indium composition in barrier layers on GaN-based blue laser diodes (LDs) are discussed from both material quality and device physics perspectives. LDs with higher indium content in the barriers demonstrate a notably lower threshold current and shorter lasing wavelength compared to those with lower indium content. Our experiments reveal that higher indium content in the barrier layers can partially reduce indium composition in the quantum wells, a novel discovery. Employing higher indium content barrier layers leads to improved luminescence properties of the MQW region. Detailed analysis reveals that this improvement can be attributed to better homogeneity in the indium composition of the well layers along the epitaxy direction. InGaN barrier layers suppress the lattice mismatch between barrier and well layers, thus mitigating the indium content pulling effect in the well layers. In supplement to experimental analysis, theoretical computations are performed, showing that InGaN barrier structures can effectively enhance carrier recombination efficiency and optical confinement of LD structure, thus improving the output efficiency of GaN-based blue LDs. Combining these theoretical insights with our experimental data, we propose that higher indium content barriers effectively enhance carrier recombination efficiency and indium content homogeneity in quantum well layers, thereby improving the output performance of GaN-based blue LDs.
The Viola in My Life II
Authors: DeLio Thomas
Published: October 2024

Chapter 3 constitutes a detailed analysis of The Viola in My Life II, scored for viola soloist and chamber ensemble, though it is an ensemble different from that of The Viola in My Life I in several significant ways. As a result of these differences, the composer develops a rather different structural evolution than that of the previous work, one based on the sonic qualities of this new timbral group. Moreover, in Viola II Feldman introduces verbatim quotations from the first work in the set, a procedure that will be amplified as the set of four compositions evolves.
The Viola in My Life IV
Authors: DeLio Thomas
Published: October 2024

Chapter 5 presents a detailed analysis of The Viola in My Life IV, which departs from its predecessors in numerous ways, most notably in that it is scored for viola soloist and full orchestra. As such, the oppositions encountered in the earlier works in Feldman’s set are amplified in manifold ways. In addition, the process of drawing material from his preceding works and quoting himself is also amplified, as a large portion of this composition is borrowed from its predecessors.
Influence of intergenerational social mobility on brain structure and global cognition: findings from the Whitehall II study across 20 years
Authors: Liu Yingxu , Thyreau Benjamin , Cui Yuehua , Zhang Ye , Tatewaki Yasuko , Taki Yasuyuki
Published: October 2024

Background

Whether changes in socioeconomic position (SEP) across generations, i.e. intergenerational social mobility, influence brain degeneration and cognition in later life is unclear.

Objective

To examine the association of social mobility, brain grey matter structure and global cognition.

Methods

We analysed T1 brain MRI data of 771 old adults (69.8 ± 5.2 years) from the Whitehall II MRI substudy, with MRI data collected between 2012 and 2016. Social mobility was defined by SEP changes from their fathers’ generation to mid-life status. Brain structural outcomes include grey matter (GM) volume and cortical thickness (CT) covering whole brain. Global cognition was measured by the Mini Mental State Examination. We firstly conducted analysis of covariance to identify regional difference of GM volume and cortical thickness across stable high/low and upward/downward mobility groups, followed with diagonal reference models studying the relationship between mobility and brain cognitive outcomes, apart from SEP origin and destination. We additionally conducted linear mixed models to check mobility interaction over time, where global cognition was derived from three phases across 2002 to 2017.

Results

Social mobility related to 48 out of the 136 GM volume regions and 4 out of the 68 CT regions. Declined volume was particularly seen in response to downward mobility, whereas no independent association of mobility with global cognition was observed.

Conclusion

Despite no strong evidence supporting direct influence of mobility on global cognition in later life, imaging findings warranted a severe level of neurodegeneration due to downward mobility from their father’s generation.
Sclerosing Extramedullary Hematopoietic Tumor of the Breast
Authors: Bamdad S , Ozkizilkaya H I , Greenwald J , Wang T
Published: October 2024

Introduction/Objective

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare tumor that occurs in patients with chronic myeloproliferative conditions. SEMHT can be seen in abdominal organs, retroperitoneum and mesentery. It can also be regarded as an advanced manifestation of myelofibrosis. SEMHT can occur singly or as multiple masses and manifests later in the disease course of CMPD. The differential diagnosis includes breast cancer, soft tissue tumor, and extramedullary hematopoiesis. Here we present a case of SEMHT in the breast.

Methods/Case Report

This is a 80-year-old female, who has a history of left breast ductal carcinoma in situ who underwent lumpectomy and received radiation in 2020. The patient also has Polycythemia Vera and MF. Bone marrow aspiration, Trephine biopsy imprints and Trephine and clot biopsies showed persistent myelofibrotic myeloid neoplasm involving a cellular bone marrow with marked fibrosis (MF Grade 3), megakaryoblastic hyperplasia, atypical megakaryocytes. In 3/2023, there were two small masses found in upper outer right breast by ultrasound measuring 4 mm and 3 mm in diameter. Breast biopsy sections showed scattered rare atypical cells within fibrotic stroma. They were only positive for Vimentin and Androgen Receptor (rare) within the performed immunohostochemistry panel.

Ki67 proliferation index was 20%. The biopsy report was signed out as aytpical mesenchymal tumor. Resection was recommended. The resection showed same atypical cells within large sclerotic stroma. These atypical cells were scattered in the breast tissue along with sinusoidal capillarization. The atypical cells were atypical megakaryocytes highlighted with CD61. Erythrocyte precursors are highlighted with glycophorin a. Based on the clinical history and histologic features, SEMHT diagnosis was made.

Results (if a Case Study enter NA)

NA due to being a case study.

Conclusion

SEMHT is a rare tumor, that can occur in patients with CMPD. It can occur within different locations in the body, including breast. SEHMT should be kept in mind for an accurate diagnosis of the tumor and correct management of the patients.
Solid-basaloid Variant of Mammary Adenoid Cystic Carcinoma – Report of an Unusual Case with Literature Review
Authors: Yang L , Wang H , Jolly A L , Fu Z
Published: October 2024

Introduction/Objective

Adenoid cystic carcinoma (AdCC) of breast is a rare subtype of malignancy, constituting approximately 0.1% of all breast carcinomas. The solid-basaloid variant (SB-AdCC) is exceedingly uncommon. Here, we present such an unusual case of SB-AdCC.

Methods/Case Report

A 64-year-old woman who underwent screening mammography presented with abnormal findings, revealing a hypoechoic ovoid, lobulated nodule at 7:00 of the left breast, which prompted an ultrasound- guided biopsy. Histologically, the biopsy cores demonstrated a 9 mm infiltrative round, solid nests with focal “cribriforming” areas. It was composed of monomorphic basaloid epithelial cells with marked nuclear atypia and high mitotic count. High-grade ductal carcinoma in situ, solid papillary carcinoma, and nonspecific invasive carcinoma were in differentials. Immunohistochemical (IHC) staining expressed positivity for CD117 and CK 5/6, while p63, SMMHC, and synaptophysin were negative. MYB gene rearrangement confirmed by fluorescence in situ hybridization. As expected, the tumor lacked ER, PR, and HER2 expression by IHC. Left breast mastectomy and axillary lymph node dissection have been scheduled.

Results (if a Case Study enter NA)

NA

Conclusion

Per literature review, the mean age of SB-AdCC at diagnosis was 68 years (33-84 years) with an average tumor size of 25 mm (12-70 mm). It had more aggressive behavior, with a higher propensity for lymph node metastasis, locally recurrence, and distant metastasis. The median disease-free survival was 46.5 months versus 151.8 months in those with class AdCC. Notably, neovascularization has emerged as a strong independent predictor of outcome in SB-AdCC. Most patients were treated with surgical excision, axillary lymph node dissection, and/or adjuvant chemotherapy. Limited studies demonstrated that neoadjuvant chemotherapy may induce an excellent response. Furthermore, a distinct molecular mutation enriched in NOTCH and CREBBP genes has been identified, which could be novel potential therapeutic target. Thus, awareness of this extremely rare breast cancer subtype and accurate differentiation from other entities are paramount for appropriate management strategies.
A Complex Case of Extrahepatic Biliary Obstruction: Syphilitic abdominal lymphadenitis
Authors: Muzaffar S , siddiqui F , Jameel R
Published: October 2024

Introduction/Objective

Syphilis, a sexually transmitted disease that is caused by spirochete Treponema pallidum, can vary widely in presentation. Infective lymphadenitis due to syphilis have been reported before in cervical and inguinal lymph nodes.Here we present an interesting case of syphilitic lymphadenitis with unusual presentation and location.

Methods/Case Report

A 30-year-old male with no past medical history presented with epigastric pain, fever, jaundice, weight loss, and night sweats. Computed tomography imaging revealed a 4.1 cm solid mass at the porta hepatis with involvement of perihepatic lymph nodes, raising suspicion of malignancy. All serological tumor markers were negative. The patient underwent ERCP with biliary drainage to relieve obstructive jaundice. Bile duct brushing and liver biopsy at that time were non-diagnostic. Later the patient underwent laparoscopic lymph node excision.

Histological examination of the lymph node showed intact follicular architecture with an increase in plasma cells and sinus histiocytes, without evidence of carcinoma or lymphoma cells. Flow cytometry on the lymph node showed polytypic B-cells and antigenically normal T-cells with CD4: CD8 ratio of 0.5 showing relatively excess of CD8 positive cytotoxic cells. Positive staining for Treponema pallidum with appropriate control highlighted micro-organisms suggestive of secondary syphilitic infection. This evidence was later supported by positive rapid plasma reagin (RPR) test. He subsequently tested positive for Human immunodeficiency virus (HIV-1).

Results (if a Case Study enter NA)

NA

Conclusion

In summary, appropriate histologic and serological testing lead to timely diagnosis in this case. This case contributes to the limited literature on syphilitic lymphadenitis and reports the first documented case of isolated intra- abdominal lymph node involvement.
PFAS-mediated disruptions on thyroid histology
Authors: Hartmann H , Weiss V , Loberg M , Lee E
Published: October 2024

Introduction/Objective

Per-and polyfluroalkyl substances (PFAS), are environmental contaminants of emerging concern due to their abundance in the environment and potential adverse health impacts. PFAS are used in waterproof clothing, makeup, carpets, upholstery, cookware, and fast-food containers. These organic pollutants have been found in the blood of 98% of Americans and have been linked to disruption in thyroid hormones. During fetal life, thyroid hormones are crucial for brain development and alterations in these hormones can induce long-term impacts on intellectual and brain impairments. T3 and T4 are known to be altered by PFAS exposure, but the mechanism by which this is done remains unclear.

Methods/Case Report

Normal thyroid cells were treated for 72 hours with 1000 nM solution containing either GEnX, PFOA, PFOS, or 1% DMSO control. Immunofluorescence for actin, tubulin, and DAPI was performed using a Nikon spinning disk. In vivo studies where 8-week-old mice are gavaged with 7.5 mg/kg of PFOS, PFOA, and GenX or PBS control for 8 weeks.

Results (if a Case Study enter NA)

We hypothesized the PFAS treatment alters thyroid cells morphology and histology. Immunofluorescence staining of normal thyroid cells treated with PFAS show a decrease in actin stress fibers compared to control cells. PFAS treated mice show a decrease in follicle size compared to control (average 1017 um2 size, p=0.0483).

Conclusion

This is the first study to show changes in thyroid histology after 8 weeks of PFAS exposure. As structure and function are closely linked, it is likely that this reduction in follicle size and actin reorganization contribute to alterations in thyroid function. Future studies are needed to illuminate the mechanism by which PFAS alter thyroid function in vivo. Understanding the role of PFAS-mediated thyroid dysregulation will have far reaching implications on environmental regulations and considerations for limiting PFAS in our environment.
SNaPshot minisequencing for SARS CoV 2 Variant Genotyping
Authors: Moon J J
Published: October 2024

Introduction/Objective

The SNaPshot Multiplex System (Thermo Fisher) can investigate up to fifty SNP markers simultaneously by using PCR amplification and subsequent dideoxy single base extension of an unlabeled primer and capillary electrophoresis. After electrophoresis and fluorescence detection, the alleles of a single marker appear as different colored peaks at roughly the same size in the electropherogram plot. The size of the different allele peaks vary slightly due to differences in molecular weight of the dyes. We propose a new set of primers and probes to use this system to differentiate variants of SARs Cov 2 variants.

Methods/Case Report

SNAPSHOT analysis was performed using the primers designed internally and analysis was done of up to 7 mutation hot spots, which were 417, 4511, 478, 484, 501, 614, and 681. By implementing the algorithm of systems and methods herein with the traces depicted in Figures, true positive and true negative outcomes for the different COVID variants can be performed, based on the highlighted peaks, which are not necessarily the most intense peaks. 10 Positive controls achieved from in stro transcript plasmid was tested then 10 viral RNA obtained through BEI Resources, NIAID was tested after mixed into 30 pooled negative PCR-swab specimens.

Genmapper was used for analysis of results. 40 Korean patient samples were tested as well.

Results (if a Case Study enter NA)

Both In vitro transcript and derived specimens of wild type, alpha, beta, delta, gamma, kappa, omicron, and pirola showed expected results in 78/80 of the specimens. For example,delta B.1.617.2 variant showed 1 = A (green) at Primer 452R-F, 2 = G (blue): Primer 484Q-F, and 3 = A (green) at Primer 614-F. Of note, hetero type was noted in a few of the patient strains but none of the BEI strains and this may be due to a transfromation of the virus and worth investigation.

Conclusion

The SNaPshot® Multiplex System is a accurate system that may be applied to multiple applications including viral strain anylsis and here we can show how it may be effectively used for SARS-Cov-2 gentotyping. Using this technique, it is possible to analyze more than 50 SNPs distributed throughout the genome in a single multiplex reaction, making it an advantage when compared with traditional sequencing reaction. This is a important study that shows that this technique may be used in multiple field applictions.
Development of an 18-color flow cytometry panel for B-lymphoblastic leukemia minimal residual disease detection
Authors: Sy Chandler , Gulgar Kameisha , Chiu Steven , Murray Angela , Inghirami Giorgio , Simonson Paul
Published: October 2024

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by a neoplastic proliferation of precursor B cells that have blast cytomorphology and immature immunophenotype. Following treatment of B-ALL, flow cytometry is utilized to detect minimal residual disease (MRD), which aids in monitoring therapeutic response and informing prognosis. In our institution, the BD FACSCanto cytometer is used in conjunction with two standardized 8-antibody EuroFlow panels to detect MRD in B-ALL patients. The objective of this study was to validate a new 18-color B-ALL MRD panel for bone marrow aspirate specimens to be run on a BD LSRFortessa cytometer, with the intention of improving sensitivity and consolidating the testing into one antibody panel. The proposed panel consisted of 22 antibodies, some of which were stacked within the same fluorescence channel, in addition to a viability stain. Twelve bone marrow aspirate specimens collected in 2023 (five positive and seven negative B-ALL MRD specimens) were stained with the new antibody panel and analyzed on the Fortessa cytometer. CD45 dim, CD19-positive blasts were analyzed using BD FACSDiva Software. For the five specimens previously reported as B-ALL MRD-positive using the EuroFlow panels, we were able to detect phenotypically identical B-ALL cells with the 18-color panel. A paired t-test done on the five MRD-positive specimens showed no significant difference in the percentage of residual B-ALL cells (out of total viable cells) measured by the 18-color panel when compared to the EuroFlow panels (EuroFlow/18-color: 0.0096%/0.0097%, 0.024%/0.012%, 0.94%/0.99%, 0.85%/0.85%, 0.022%/0.017%; p=0.58). All seven specimens that were previously reported as B-ALL MRD-negative using the EuroFlow panels were also negative for residual B-ALL cells when stained with the 18-color panel and analyzed on the Fortessa cytometer. The antibody cost per test of the EuroFlow panels ($20-$25, ~$44 for both panels) and new 18-color panel ($63) were calculated based on the unit cost of each antibody aliquot and the required volume of reagent per test. In summary, the new 18-color B-ALL MRD panel run on the BD LSRFortessa cytometer appears to provide similar results as the EuroFlow panels run on the BD FACSCanto cytometer. Although compared to the two EuroFlow panels, the single 18-color panel is more expensive per test in terms of antibodies, it may be preferable when there is scant tissue (such as cerebrospinal fluid) as there may not be enough material to run both EuroFlow panels.
Extragenital self-collection testing for gonorrhea and chlamydia: A feasibility study for expanding STI screening in the Veterans Health Administration
Authors: Navas Maria E , Musoke Lewis , Van Epps Puja , Allen Kristen , Coffey KC , Appleby-Sigler Andrea , Peralta Karla , Del Pilar Mark , DuBois Marie , Kapadia Iqbal , Tash Kaley , Vallone John , Barrera Aurelio , Adams Jill , Rajagopalan Chitra , Rexroth Karen , Benator Debra , Melton Shelby D , Wachsmann Megan B , Wais Jennifer , Catania Jelena , Ho Minh Q , Benitez Espinosa Ruben , Wigton Bradley , Kaka Anjum S , Niehans Gloria , Wang-Rodriguez Jessica , Klutts J Stacey
Published: October 2024

Objectives

Rectal and pharyngeal infections with gonorrhea and chlamydia are of concern because they are associated with higher risk of HIV acquisition. Extragenital screening in asymptomatic persons at high risk may have the potential to reduce the incidence of these sexually transmitted infections (STIs). Several testing platforms are available for the testing of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using nucleic acid amplification tests (NAATs). Self-collected extragenital samples are currently not approved by the US Food and Drug Administration in any NAAT platform. This study compares the analytical performance of self-collected extragenital specimens to that of clinician-collected specimens.

Methods

We performed a multicenter/multiplatform validation study as a National Veterans Health Administration Pathology and Laboratory Medicine quality improvement project, with 9 different participating sites. Self-collected specimens were obtained at the same time as clinician-collected specimens. Clinician-collected specimens were used as the gold standard to evaluate the sensitivity and specificity of self-collection.

Results

A total of 2324 individual tests were analyzed (501 rectal and 661 oropharyngeal). The sensitivity was 94.44% for CT and 100% for NG for rectal specimens, whereas it was 100% for CT and 97.22% for NG for oral specimens. Specificity for oral specimens was 99.85% for CT and 99.36% for NG, whereas for rectal specimens, it was 99% for CT and NG.

Conclusions

Self-collected specimens for extragenital CT/NG testing are highly sensitive and specific, with negative predictive values of 100%. Self-collection has the potential to overcome a major barrier for STI screening by providing an accessible, convenient, and patient-centered alternative.
Design of a Location-Based Case-Control Study of Built Environment Risk Factors for Pedestrian Fatalities in the U.S.
Authors: Rundle Andrew G , Uong Stephen P , Bader Michael D M , Kinsey Eliza W , Kinsey Dirk , Lovasi Gina S , Mooney Stephen J , Neckerman Kathryn M , Quinn James W
Published: October 2024

The location-based case-control design is a useful approach for studies where the exposures of interest are aspects of the environment around the location of a health event such as a pedestrian fatality. In this design locations are the unit of analysis and an enumerated cohort of locations are followed through time for the health events of interest and a case-control study of locations is nested within the cohort. Locations where events occurred (case-locations) are compared to matched locations where these events did not occur (control-locations). We describe the application of this design to the issue of pedestrian fatalities using a cohort of 9,612,698 intersections, 17,737,728 road segments, and 222,318 entrance/exit ramp segments that existed in 2017 across all 384 U.S. Metropolitan Statistical Areas. This cohort of locations was followed up from Jan 1, 2017 to Dec 31, 2018 for pedestrian fatalities using the National Highway Traffic Safety Administration Fatality Analysis Reporting System. In total, 10,587 fatalities were identified as having occurred on cohort locations and 21,174 matched control locations were selected using incidence density sampling. Geographic information systems, spatially linked administrative data sets and virtual neighborhood audits via Google Street View are underway to characterize study locations.
An unusual cause of erythroderma
Authors: Wei Qiang Chng , Wen Yang Benjamin Ho , Shi Wang , Kok Hing Lim , Hui Li Yao Laura
Published: October 2024

This clinicopathological case describes a patient who had erythroderma with an unusual cause. We also provide guidance for the diagnosis of such cases.
Mechanisms and consequences of myeloid adhesome dysfunction in atherogenesis
Authors: Zhevlakova Irina , Liu Huan , Dudiki Tejasvi , Gao Detao , Yakubenko Valentin , Tkachenko Svyatoslav , Cherepanova Olga , Podrez Eugene A , Byzova Tatiana V
Published: October 2024

Aims

In the context of atherosclerosis, macrophages exposed to oxidized low-density lipoproteins (oxLDLs) exhibit cellular abnormalities, specifically in adhesome functions, yet the mechanisms and implications of these adhesive dysfunctions remain largely unexplored.

Methods and results

This study reveals a significant depletion of Kindlin3 (K3) or Fermt3, an essential component of the adhesome regulating integrin functions, in macrophages located within atherosclerotic plaques in vivo and following oxLDL exposure in vitro. To examine the effects of K3 deficiency, the study utilized hyperlipidaemic bone marrow chimeras devoid of myeloid Kindlin3 expression. The absence of myeloid K3 increased atherosclerotic plaque burden in the aortas in vivo and enhanced lipid accumulation and lipoprotein uptake in macrophages from Kindlin3-null chimeric mice in vitro. Importantly, re-expression of K3 in macrophages ameliorated these abnormalities. RNA sequencing of bone marrow-derived macrophages (BMDM) from K3-deficient mice revealed extensive deregulation in adhesion-related pathways, echoing changes observed in wild-type cells treated with oxLDL. Notably, there was an increase in Olr1 expression [encoding the lectin-like oxidized LDL receptor-1 (LOX1)], a gene implicated in atherogenesis. The disrupted K3–integrin axis in macrophages led to a significant elevation in the LOX1 receptor, contributing to increased oxLDL uptake and foam cell formation. Inhibition of LOX1 normalized lipid uptake in Kindlin3-null macrophages. A similar proatherogenic phenotype, marked by increased macrophage LOX1 expression and foam cell formation, was observed in myeloid-specific Itgβ1-deficient mice but not in Itgβ2-deficient mice, underscoring the critical role of K3/Itgβ1 interaction.

Conclusion

This study shows that the loss of Kindlin3 in macrophages upon exposure to oxLDL leads to adhesome dysfunction in atherosclerosis and reveals the pivotal role of Kindlin3 in macrophage function and its contribution to the progression of atherosclerosis, providing valuable insights into the molecular mechanisms that could be targeted for therapeutic interventions.
Disease management program in patients with type 2 diabetes
Authors: Bender Mette , Glümer Charlotte , Brønnum-Hansen Henrik , Andersen Ingelise , Vrangbæk Karsten
Published: October 2024

The aim of this paper was to study ethnic and socioeconomic (SEP) factors’ association with provision and participation in a type 2 diabetes disease-management program. In 2016–21, 3464 persons were referred to type 2 diabetes management in Copenhagen municipality. Personalized plans included a mix of activities; program consultations, dietary education, telephone conversations, patient education, and physical training. We estimated the association between education, income, civic status, employment, and country of origin with the number of booked and participated activities using Poisson regression models. A total of 55 394 program sessions were scheduled. Small differences in booked dietary education, program consultations, telephone conversations, and patient education were seen between SEP groupings. In situations where groups with lower SEP had booked more sessions (e.g. unemployed bookings of dietary education), these were predominantly translated into equal or more participated sessions among persons with high SEP. Regarding physical training, considerably more booked and participated sessions were delivered to women with lower SEP and ethnic minorities. This study is unique, in the sense that it is the first of its kind to analyze data on diabetes-management programs, systematically collected by primary healthcare workers. Our results suggest that specific elements of the program together with a higher number of booked sessions promoted vulnerable women to participate in more physical training sessions. In closing, these findings have the potential to provide motivation and ideas for policymakers and health professionals in how to design equitable type 2 diabetes management activities.
Control strategies for mitigating torsional and axial vibrations in rotary oilwell drilling systems
Authors: Toumi Samir , Mlayeh Rhouma
Published: October 2024

This paper examines a nonlinear dynamics model to explore the significant factors influencing the coupled torsional-axial vibrations of a drill string. The primary focus lies in effectively modelling, analysing and controlling both torsional and axial vibrations occurring in a rotary oil well drilling system. The model employed incorporates a wave equation with a damping term (PDE) connected to an ordinary differential equation (ODE) through a nonlinear function representing the interaction between the drill bit and the rock. We proceed to establish the well-posedness of the coupled PDE-ODE in an appropriate functional space. As a PDE-ODE coupled system, we specifically investigate the stability problem concerning the velocity at the bottom extremity, considering both the presence and absence of the damping term in the wave PDE. To address this, we propose a systematic method based on a Lyapunov approach for designing feedback controllers. These controllers ensure system stability and effectively suppress harmful vibrations.
Genesis of intimal thickening due to hemodynamical shear stresses
Authors: Mukherjee Avishek , Mohammad Mirzaei Navid , Fok Pak-Wing
Published: October 2024

This paper investigates intimal growth in arteries, induced by hemodynamical shear stress, through finite element simulation using the FEniCS computational environment. In our model, the growth of the intima depends on cross-section geometry and shear stress. In this work, the arterial wall is modeled as three distinct layers: the intima, the media and the adventitia, each with different mechanical properties. We assume that the cross-section of the vessel does not change in the axial direction. We further assume that the blood flow is steady, non-turbulent and unidirectional. Blood flow induces shear stress on the endothelium and stimulates the release of platelet derived growth factor (PDGF) which drives the growth. We simulate intimal growth for three distinct arterial cross section geometries. We show that the qualitative nature of intimal thickening varies depending on arterial geometry. For cross section geometries that are annular, the growth of the intima is uniform in the angular direction, and the endothelium stays circular as the intima grows. For non-annular cross section geometries, the intima grows more quickly where it is thicker, and shear stress and intimal thickening are negatively correlated with the distance from the flow center, where the flow velocity is maximal. Over time, the maxima and minima of the curvature increase and decrease, respectively, the PDGF concentration increases and the lumen becomes more polygonal. The model provides a framework for coupling hemodynamics simulations to mathematical descriptions of atherosclerosis, both of which have been modeled separately in great detail.
Revealing the impact of social circumstances on the selection of cancer therapy through natural language processing of social work notes
Authors: Sun Shenghuan , Zack Travis , Williams Christopher Y K , Butte Atul J , Sushil Madhumita
Published: October 2024

Objective

We aimed to investigate the impact of social circumstances on cancer therapy selection using natural language processing to derive insights from social worker documentation.

Materials and Methods

We developed and employed a Bidirectional Encoder Representations from Transformers (BERT) based approach, using a hierarchical multi-step BERT model (BERT-MS), to predict the prescription of targeted cancer therapy to patients based solely on documentation by clinical social workers. Our corpus included free-text clinical social work notes, combined with medication prescription information, for all patients treated for breast cancer at UCSF between 2012 and 2021. We conducted a feature importance analysis to identify the specific social circumstances that impact cancer therapy regimen.

Results

Using only social work notes, we consistently predicted the administration of targeted therapies, suggesting systematic differences in treatment selection exist due to non-clinical factors. The findings were confirmed by several language models, with GatorTron achieving the best performance with an area under the receiver operating characteristic curve (AUROC) of 0.721 and a Macro F1 score of 0.616. The UCSF BERT-MS model, capable of leveraging multiple pieces of notes, surpassed the UCSF-BERT model in both AUROC and Macro-F1. Our feature importance analysis identified several clinically intuitive social determinants of health that potentially contribute to disparities in treatment.

Discussion

Leveraging social work notes can be instrumental in identifying disparities in clinical decision-making. Hypotheses generated in an automated way could be used to guide patient-specific quality improvement interventions. Further validation with diverse clinical outcomes and prospective studies is essential.

Conclusions

Our findings indicate that significant disparities exist among breast cancer patients receiving different types of therapies based on social determinants of health. Social work reports play a crucial role in understanding these disparities in clinical decision-making.
Effects of chicken slurry inclusion on apparent total tract macronutrient digestibility, palatability, and fecal characteristics, microbiota, and metabolites of healthy adult dogs
Authors: Geary Elizabeth L , Vogel Christina L , Oba Patrícia M , Mioto Julio C , de Godoy Maria R C , Swanson Kelly S
Published: October 2024

“Premium” pet foods are often formulated with meat slurries. Meat slurries are believed to be of higher quality than rendered meals, but inadequate research has been performed to test how their inclusion affects palatability, digestibility, or indicators of gastrointestinal health. Therefore, the objectives of this study were to determine how chicken slurry inclusion affected the palatability and apparent total tract digestibility (ATTD) of dog foods and to assess their effects on the fecal characteristics, metabolites, and microbiota of dogs. A replicated 3 × 3 Latin square design digestibility study was conducted using 9 healthy adult dogs (age = 5.44 ± 0.53 yr) to test diets containing 0% (control; CON), 8% (low inclusion; LOW), and 16% (high inclusion; HIGH) chicken slurry. The experiment comprised three 21-d experimental periods (14 d of adaptation, 5 d of total fecal collection (used for ATTD calculations), and 2 d of blood collection). On the first day of fecal collections, one fresh sample was collected for measurement of pH, dry matter (DM) content, fermentative metabolite concentrations, and microbiota populations. A 2-d palatability study (n = 20 dogs) was also conducted to compare CON vs. HIGH. Data were analyzed statistically by Mixed Models using SAS 9.4, with P < 0.05 being significant. In the palatability study, dogs were shown to prefer (P < 0.05) the HIGH diet by a ratio of 2:1. In the digestibility study, fecal output, scores, pH, and DM percentage were not different among diets. The ATTD of protein was higher (P < 0.05) for the HIGH diet (84.6%) than for the LOW (82.7%) or CON (82.6%) diets. The ATTD of other nutrients and energy were not different among diets (all over 80%). Fecal propionate, butyrate, and total short-chain fatty acid concentrations were higher (P < 0.05) in dogs fed the LOW diet (122.0, 67.4, and 408.2 μmol/g, respectively) than those fed the HIGH diet (89.0, 46.9, and 338.2 μmol/g, respectively). The other fecal metabolites (acetate, branched-chain fatty acids, ammonia, phenol, and indole) were not different among treatments. Few changes to the fecal microbiota were noted. However, the relative abundance of fecal Fusobacterium was higher (P < 0.05) in dogs fed the CON diet than those fed the HIGH diet (25.7% vs. 20.0% relative abundance). In summary, chicken slurry inclusion improved palatability but had minimal effects on nutrient digestibility and fecal characteristics, metabolites, and microbiota.
Diagnosis of invasive aspergillosis in haemato-oncology patients in a routine diagnostic setting
Authors: Solaimalai Dhanalakshmi , Varghese Rosemol , Karumathil Sujith , Kulkarni Uday , George Biju , Michael Joy Sarojini
Published: October 2024

Invasive Aspergillosis (IA) is a potentially lethal infection in high-risk haemato-oncology patients. Since traditional diagnostic methods have many inherent challenges, Polymerase Chain Reaction (PCR) has been used to diagnose IA. This prospective study evaluated a commercial AsperGenius multiplex real-time PCR for its clinical utility in diagnosing IA compared with galactomannan (GM) testing serum samples from haemato-oncology patients with clinically suspected IA. A total of 107 patients were recruited between April 2022 and March 2023. Serum samples (n = 113) collected from those patients for the routine diagnosis by GM Enzyme Linked Immuno-Sorbent Assay (ELISA) were subjected to PCR. The patients were categorised into probable, possible, and no IA based on revised (2020) and previous (2008) European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) criteria. The performance characteristics of PCR and GM were calculated against the EORTC criteria by combining probable and possible cases as diseased groups. Among the 107 recruited patients, 93 were categorised into probable/possible IA (diseased group) and 14 into no IA group. The PCR was positive in 53 samples from 49 patients. The sensitivity and specificity of single positive PCR and GM were 51.61% [95% confidence interval, 41–62], 92.86% (66.1–99.8) and 26.88% (18.2–37.1), 92.86% (66.1–99.8), respectively. The combination-based strategy (GM and/or PCR positive) exhibited a moderate sensitivity of 62.37% (51–72.2) and a specificity of 85.71% (57.2–98.2). To conclude, the combined strategy of serum GM and/or PCR positivity, along with radiological findings that fulfilled the EORTC/MSG criteria, has improved the diagnosis of probable IA among high-risk haematological patients with clinically suspected IA.
One stream or two – exploring Andromeda’s North West stream
Authors: Preston Janet , Erkal Denis , Collins Michelle L M , Rich R Michael , Ibata Rodrigo , Delorme Maxime
Published: October 2024

We present results of our dynamical stream modelling for the North West Stream in the outer halo of the Andromeda galaxy (M31). Comprising two main segments, the North West Stream was thought to be a single structured arching around M31. However, recent evidence suggests that it is two separate, unrelated, streams. To test this hypothesis, we use observational data from six fields associated with the upper segment of the North West Stream together with eight fields and five globular clusters associated with the lower segment to constrain model orbits. We fit both segments of the stream using a fixed potential model for M31 and an orbit integrator to compare orbits with the observed streams. We measure the central tracks and predict proper motions for the upper segment (lower segment) finding ${\mu ^{*}_{\alpha }}$  = 0.078$^{+0.015}_{-0.012}$ (0.085$^{+0.001}_{-0.002}$) mas yr−1 and ${\mu _{\delta }}$  = $-0.05^{+0.008}_{-0.009}$ ($-0.095^{+0.003}_{-0.005}$) mas yr−1. Our results support the hypothesis that the dwarf spheroidal galaxy Andromeda XXVII is the progenitor of the upper segment of the North West Stream and that the upper and lower segments do not comprise a single structure. We propose that the upper segment, which appears to be on an infall trajectory with M31, be renamed the ‘Andromeda XXVII Stream’ and the lower segment, also apparently infalling towards M31, retain the name ‘North West Stream’.
Magnetic coupling through flux branching of adjacent type-I and -II superconductors in a neutron star
Authors: Thong K H , Melatos A
Published: October 2024

The inner and outer cores of neutron stars are believed to contain type-I and -II proton superconductors, respectively. The type-I superconductor exists in an intermediate state, comprising macroscopic flux-free and flux-containing regions, while the type-II superconductor is flux-free, except for microscopic, quantized flux tubes. Here, we show that the inner and outer cores are coupled magnetically, when the macroscopic flux tubes subdivide dendritically into quantized flux tubes, a phenomenon called flux branching. An important implication is that up to ${\sim} 10^{12} (r_1/10^6 \, {\rm cm}) \, {\rm erg}$ of energy are required to separate a quantized flux tube from its progenitor macroscopic flux tube, where $r_1$ is the length of the macroscopic flux tube. Approximating the normal-superconducting boundary as sharp, we calculate the magnetic coupling energy between a quantized and macroscopic flux tube due to flux branching as a function of, $f_1$, the radius of the type-I inner core divided by the radius of the type-II outer core. Strong coupling delays magnetic field decay in the type-II superconductor. For an idealized inner core containing only a type-I proton superconductor and poloidal flux, and in the absence of ambipolar diffusion and diamagnetic screening, the low magnetic moments (${\lesssim} 10^{27} \, {\rm G \, cm^3}$) of recycled pulsars imply $f_1 \lesssim 10^{-1.5}$.
A regularization technique to precisely infer limb darkening using transit measurements: can we estimate stellar surface magnetic fields?
Authors: Verma Kuldeep , Maxted Pierre F L , Singh Anjali , Ludwig H -G , Sable Yashwardhan
Published: October 2024

The high-precision measurements of exoplanet transit light curves that are now available contain information about the planet properties, their orbital parameters, and stellar limb darkening (LD). Recent 3D magnetohydrodynamical (MHD) simulations of stellar atmospheres have shown that LD depends on the photospheric magnetic field, and hence its precise determination can be used to estimate the field strength. Among existing LD laws, the uses of the simplest ones may lead to biased inferences, whereas the uses of complex laws typically lead to a large degeneracy among the LD parameters. We have developed a novel approach in which we use a complex LD model but with second derivative regularization during the fitting process. Regularization controls the complexity of the model appropriately and reduces the degeneracy among LD parameters, thus resulting in precise inferences. The tests on simulated data suggest that our inferences are not only precise but also accurate. This technique is used to re-analyse 43 transit light curves measured by the NASA Kepler and Transiting Exoplanet Survey Satellite missions. Comparisons of our LD inferences with the corresponding literature values show good agreement, while the precisions of our measurements are better by up to a factor of 2. We find that 1D non-magnetic model atmospheres fail to reproduce the observations while 3D MHD simulations are qualitatively consistent. The LD measurements, together with MHD simulations, confirm that Kepler-17, WASP-18, and KELT-24 have relatively high magnetic fields ($\gt 200$ G). This study paves the way for estimating the stellar surface magnetic field using the LD measurements.