bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of netrin‐1 in uterine serous carcinoma and its association with prognosis
Authors: Ucuncu Kefeli Aysegul , Yaprak Bayrak Busra , Betul Tunce Esra , Vural Cigdem , Suyusal Ibrahim Halil , Kefeli Umut , Aksu Maksut Gorkem
Published: April 2024

Background/Objectives

At present, there are few biomarkers used to predict the prognosis of uterine serous carcinoma (USC). Netrin‐1 may be a promising biomarker candidate. We investigated netrin‐1 expression in USC tissues and healthy endometrial tissues to determine its relevance to disease prognosis.

Materials and Methods

Netrin‐1 expression was examined in the tissues of 48 patients with USC and 30 patients with healthy benign endometrial tissues via immunohistochemistry.

Results

None of the healthy tissues were stained with netrin‐1. In tumor tissues, the overall positivity rate of netrin‐1 was 75%, detected as high expression in 17 patients (35%) and low in 19 (40%). Patients who had tumors with no netrin‐1 expression (n = 12) had a median overall survival (OS) of 60.0 months (95% confidence interval [CI], 47–98), whereas patients who had tumors with low to strong netrin‐1 expression (n = 33) had a lower median OS of 50 months, but the difference was not statistically significant (95% CI, 58–108; P = 0.531). Disease‐free survival (DFS) was not statistically significant between the groups (95% CI, 67.7–115.9; P = 0.566). Patients with a tumor diameter ≥2 cm had higher netrin‐1 expression than those with a tumor diameter of 2 cm (P = 0.027). We did not find any difference in overall and DFS when age, tumor stage, histology, tumor diameter, p53 status, lymphovascular space invasion, myometrial invasion, and lymph node metastasis were compared according to netrin‐1 expression (P > 0.05).

Conclusion

Netrin‐1 was expressed in USC but not in healthy tissues. Its expression was not associated with OS or DFS.
Setting hinge position distal to the proximal margin of the distal lateral femur reduces the maximum principal strains of the hinge area and risk of hinge fractures
Authors: Tanaka Atsuki , Matsushita Takehiko , Nakatsuji Tatsuya , Katsui Yosuke , Nagai Kanto , Nishida Kyohei , Mukai Toshiji , Kuroda Ryosuke
Published: April 2024

Purpose

The optimal hinge position to prevent hinge fractures in medial closing wedge distal femoral osteotomy (MCWDFO) based on the biomechanical background has not yet been well examined. This study aimed to examine the appropriate hinge position in MCWDFO using finite element (FE) analysis to prevent hinge fractures.

Methods

Computer‐aided design (CAD) models were created using composite replicate femurs. FE models of the MCWDFO with a 5° wedge were created with three different hinge positions: (A) 5 mm proximal to the proximal margin of the lateral epicondylar region, (B) proximal margin level and (C) 5 mm distal to the proximal margin level. The maximum and minimum principal strains in the cortical bone were calculated for each model. To validate the FE analysis, biomechanical tests were performed using composite replicate femurs with the same hinge position models as those in the FE analysis.

Results

In the FE analysis, the maximum principal strains were in the order of Models A > B > C. The highest value of maximum principal strain was observed in the area proximal to the hinge. In the biomechanical test, hinge fractures occurred in the area proximal to the hinge in Models A and B, whereas the gap closed completely without hinge fractures in Model C. Fractures occurred in an area similar to where the highest maximal principal strain was observed in the FE analysis.

Conclusion

Distal to the proximal margin of the lateral epicondylar region is an appropriate hinge position in MCWDFO to prevent hinge fractures.

Level of Evidence

Level V.
Vascular Aging in the Choroid Plexus: A 7T Ultrasmall Superparamagnetic Iron Oxide (USPIO)‐MRI Study
Authors: Sun Zhe , Li Chenyang , Muccio Marco , Jiang Li , Masurkar Arjun , Buch Sagar , Chen Yongsheng , Zhang Jiangyang , Haacke E. Mark , Wisniewski Thomas , Ge Yulin
Published: April 2024

Background

The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP.

Purpose

To investigate the sub‐structural characteristics of the ChP, particularly the vascular compartment using high‐resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super‐paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels.

Study Type

Prospective.

Subjects

Forty‐nine subjects without neurological disorders (age: 21–80 years; 42 ± 17 years; 20 females).

Field Strength/Sequence

7‐T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR.

Assessment

The vascular and stromal compartments of the ChP were segmented using K‐means clustering on post‐contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Volvessel/VolChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE‐derived susceptibility‐weighted imaging and quantitative susceptibility mapping, respectively.

Statistical Tests

Independent t‐test, Mann–Whitney U test, and Chi‐square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra‐class coefficient was calculated for inter‐observer agreement. A P value <0.05 was considered statistically significant.

Results

2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = −0.48, and r = −0.45).

Data Conclusion

Ferumoxytol‐enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment.

Evidence Level

1

Technical Efficacy

Stage 2
Second‐Order Motion‐Compensated Echo‐Planar Cardiac Diffusion‐Weighted MRI: Usefulness of Compressed Sensitivity Encoding
Authors: Chen Rui , Luo Ruohong , Xu Yongzhou , Ou Jiehao , Li Xiaodan , Yang Yuelong , Cao Liqi , Wu Zhigang , Luo Wei , Liu Hui
Published: April 2024

Background

Cardiac diffusion‐weighted imaging (DWI) using second‐order motion‐compensated spin echo (M2C) can provide noninvasive in‐vivo microstructural assessment, but limited by relatively low signal‐to‐noise ratio (SNR). Echo‐planar imaging (EPI) with compressed sensitivity encoding (EPICS) could address these issues.

Purpose

To combine M2C DWI and EPCIS (M2C EPICS DWI), and compare image quality for M2C DWI.

Study Type

Prospective.

Population

Ten ex‐vivo hearts, 10 healthy volunteers (females, 5 [50%]; mean ± SD of age, 25 ± 4 years), and 12 patients with diseased hearts (female, 1 [8.3%]; mean ± SD of age, 44 ± 16 years; including coronary artery heart disease, congenital heart disease, dilated cardiomyopathy, amyloidosis, and myocarditis).

Field Strength/Sequence

3‐T, M2C EPICS DWI, and M2C DWI.

Assessment

The apparent SNR (aSNR) and the rating scores were used to evaluate and compared image quality of all three groups. The aSNR was calculated using , and the myocardium was segmented manually. Three observers independently rated subjective image quality using a 5‐point Likert scale.

Statistical Tests

Bland–Altman analysis and paired t‐tests. The threshold for statistical significance was set at P < 0.05.

Results

In healthy volunteers, the aSNR with a b‐value of 450 s/mm2 acquired by M2C EPICS DWI was significantly higher than M2C DWI at in‐plane resolutions of 3.0 × 3.0, 2.5 × 2.5, and 2.0 × 2.0 mm2. In patients with diseased hearts, the aSNR ofM2C EPICS DWI was also significantly higher than that for M2C DWI (bias of M2C EPICS‐M2C = 1.999, 95% limits of agreement, 0.362 to 3.636; mean ± SD, 7.80 ± 1.37 vs. 5.80 ± 0.81). The ADC values of M2C EPICS was significantly higher than M2C DWI in in‐vivo hearts. Over 80% of the images with rating scores for M2C EPICS DWI were higher than M2C DWI in in‐vivo hearts.

Data Conclusion

Cardiac imaging by M2C EPICS DWI may demonstrate better overall image quality and higher aSNR than M2C DWI.

Evidence Level

2

Technical Efficacy

Stage 1
Obesity fosters severe disease outcomes in a mouse model of coronavirus infection associated with transcriptomic abnormalities
Authors: Rai Pallavi , Marano Jeffrey M. , Kang Lin , Coutermarsh‐Ott Sheryl , Daamen Andrea R. , Lipsky Peter E. , Weger‐Lucarelli James
Published: April 2024

Obesity has been identified as an independent risk factor for severe outcomes in humans with coronavirus disease 2019 (COVID‐19) and other infectious diseases. Here, we established a mouse model of COVID‐19 using the murine betacoronavirus, mouse hepatitis virus 1 (MHV‐1). C57BL/6 and C3H/HeJ mice exposed to MHV‐1 developed mild and severe disease, respectively. Obese C57BL/6 mice developed clinical manifestations similar to those of lean controls. In contrast, all obese C3H/HeJ mice succumbed by 8 days postinfection, compared to a 50% mortality rate in lean controls. Notably, both lean and obese C3H/HeJ mice exposed to MHV‐1 developed lung lesions consistent with severe human COVID‐19, with marked evidence of diffuse alveolar damage (DAD). To identify early predictive biomarkers of worsened disease outcomes in obese C3H/HeJ mice, we sequenced RNA from whole blood 2 days postinfection and assessed changes in gene and pathway expression. Many pathways uniquely altered in obese C3H/HeJ mice postinfection aligned with those found in humans with severe COVID‐19. Furthermore, we observed altered gene expression related to the unfolded protein response and lipid metabolism in infected obese mice compared to their lean counterparts, suggesting a role in the severity of disease outcomes. This study presents a novel model for studying COVID‐19 and elucidating the mechanisms underlying severe disease outcomes in obese and other hosts.
The abortive SARS‐CoV‐2 infection of osteoclast precursors promotes their differentiation into osteoclasts
Authors: Sviercz Franco , Jarmoluk Patricio , Godoy Coto Joshua , Cevallos Cintia , Freiberger Rosa Nicole , López Cinthya Alicia Marcela , Ennis Irene Lucia , Delpino M. Victoria , Quarleri Jorge
Published: April 2024

The Coronavirus Disease 2019 (COVID‐19) pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the respiratory system, the impact of COVID‐19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS‐CoV‐2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte‐derived macrophages, which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased postinfection, with no significant impact on cellular viability and redox balance. Both SARS‐CoV‐2 strains heightened osteoclast formation in a dose‐dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS‐CoV‐2 induced early pro‐inflammatory M1 macrophage polarization, shifting toward an M2‐like profile. Osteoclastogenesis‐related genes (RANK, NFATc1, DC‐STAMP, MMP9) were upregulated, and surprisingly, SARS‐CoV‐2 variants promoted RANKL‐independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS‐CoV‐2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID‐19.
Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review
Authors: El Hajj Rojine , Al Sagheer Tareq , Ballout Nissrine
Published: April 2024

Neurodegenerative diseases are progressive disorders characterized by synaptic loss and neuronal death. Optogenetics combines optical and genetic methods to control the activity of specific cell types. The efficacy of this approach in neurodegenerative diseases has been investigated in many reviews, however, none of them tackled it systematically. Our study aimed to review systematically the findings of optogenetics and its potential applications in animal models of chronic neurodegenerative diseases and compare it with deep brain stimulation and designer receptors exclusively activated by designer drugs techniques. The search strategy was performed based on the PRISMA guidelines and the risk of bias was assessed following the Systematic Review Centre for Laboratory Animal Experimentation tool. A total of 247 articles were found, of which 53 were suitable for the qualitative analysis. Our data revealed that optogenetic manipulation of distinct neurons in the brain is efficient in rescuing memory impairment, alleviating neuroinflammation, and reducing plaque pathology in Alzheimer's disease. Similarly, this technique shows an advanced understanding of the contribution of various neurons involved in the basal ganglia pathways with Parkinson's disease motor symptoms and pathology. However, the optogenetic application using animal models of Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis was limited. Optogenetics is a promising technique that enhanced our knowledge in the research of neurodegenerative diseases and addressed potential therapeutic solutions for managing these diseases' symptoms and delaying their progression. Nevertheless, advanced investigations should be considered to improve optogenetic tools' efficacy and safety to pave the way for their translatability to the clinic.
Dupilumab in adolescent eosinophilic esophagitis: Experience with fibrostenosis and eosinophilic gastrointestinal disease with esophageal involvement
Authors: Becker Robert , Rigsby Mariah , Suchi Mariko , Lerner Diana G. , Chugh Ankur
Published: April 2024

We evaluated patients aged 12–20 on dupilumab 300 mg weekly for treatment of eosinophilic esophagitis (EoE) who had ≥1 follow‐up endoscopy at a tertiary care pediatric hospital (n = 18). Fifty percent had inflammatory EoE (n = 9), 22% had fibrostenotic EoE (n = 4), and 28% had non‐EoE eosinophilic gastrointestinal disease (EGID) with esophageal involvement (n = 5). Ninety‐four percent discontinued topical corticosteroids (TCS) 2–4 weeks after starting dupilumab. Eighty‐nine percent of inflammatory EoE patients had histological response (<15 eosinophils/high‐powered field) after an average of 19.1 weeks. One hundred percent of patients with fibrostenotic disease exhibited histological response after 16.8 weeks. Of patients with non‐EoE EGID, 60% achieved esophageal histological response after an average of 40.1 weeks. In a small cohort, dupilumab was very effective for adolescent inflammatory and fibrostenotic EoE despite rapid weaning of TCS. Dupilumab was also somewhat effective for non‐EoE EGID with esophageal involvement; however, a longer duration of therapy was required.
Both arthroscopic one‐step Broström–Gould and Lasso‐loop stitch techniques achieved favourable clinical outcomes for chronic lateral ankle instability
Authors: Liu Zhuo‐fan , Su Tong , Wang Zhen‐yu , Hu Yue‐lin , Guo Qin‐wei , Yang Jie , Zhang Zhu , Liu Ning‐jing , Jiao Chen , Jiang Dong
Published: April 2024

Purpose

Both the arthroscopic Broström–Gould and Lasso‐loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one‐step outside‐in Broström–Gould (AOBG) technique and compare the mid‐term outcomes of the AOBG technique and Lasso‐loop stitch technique.

Methods

All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso‐loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson–Peterson score were evaluated preoperatively and during the follow‐up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared.

Results

A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow‐up of 39 months. No statistically significant differences were observed in demographic parameters or follow‐up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference.

Conclusion

Both the AOBG and Lasso‐loop stitch techniques yielded comparable favourable mid‐term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients.

Level of Evidence

Level III.
Assessment of Variability in Free Flap Color Match to Facial Skin by Donor Site and Race
Authors: Plonowska‐Hirschfeld Karolina A. , Eltawil Yasmin , Soroudi Daniel , Patel Neil N. , Park Andrea M. , Knott P. Daniel
Published: April 2024

Objectives

To use portable colorimetry to quantify color differences between facial skin and potential three head and neck microvascular free tissue transfer (MFTT) donor sites—radial forearm (RF), anterolateral thigh (ALT), and fibula (FF)—and compare these differences by pigmentation of the donor site skin and self‐identified race.

Methods

In this cross‐sectional cohort study, healthy volunteers consented to handheld colorimeter measurements at the three potential MFTT donor sites (RF, ALT, FF) to quantify color match to the facial skin using the CIE color space (DeltaE). The comparison of ipsilateral to contralateral cheek served as control for measurements. Cross‐sectional measurements in healthy volunteers were then compared to measurements obtained in postoperative head and neck MFTT patients.

Results

DeltaE measurements were obtained for 128 healthy controls and 24 postoperative patients (N = 152). With increasing lightness (decreased pigmentation) of the skin at the donor site, the color match significantly worsened (higher DeltaE) across all potential MFTT donor sites (all p < 0.05). DeltaE from healthy controls closely approximated postoperative color match measurements in patients who underwent cervicofacial MFTT (DeltaE RF: 5.3 vs. 6.0, p = 0.432; DeltaE ALT: 6.2 vs. 6.4, p = 0.822; DeltaE FF: 6.0 vs. 6.4, p = 0.806).

Conclusion

Patients with decreased skin pigmentation who are undergoing head and neck MFTT may experience worse color discrepancy between cervicofacial skin and the transferred skin paddle than those with more pigmented skin. Portable colorimetry may identify patients who could benefit from interventions such as dermis‐resected free tissue reconstruction with skin grafting to improve postoperative appearance.

Level of Evidence

3 Laryngoscope, 134:3581–3586, 2024
Validation of daily 0.35 T diffusion‐weighted MRI for MRI‐guided glioblastoma radiotherapy
Authors: Lutsik Natalia , Nejad‐Davarani Siamak P. , Valderrama Alessandro , Herr Janette , Maziero Danilo , Cullison Kaylie , Azzam Gregory A. , Kubicek Gregory J , Meshman Jessica , de la Fuente Macarena I. , Armstrong Tess , Mellon Eric A.
Published: April 2024

Background

MRI‐Linac systems enable daily diffusion‐weighed imaging (DWI) MRI scans for assessing glioblastoma tumor changes with radiotherapy treatment.

Purpose

Our study assessed the image quality of echoplanar imaging (EPI)‐DWI scans compared with turbo spin echo (TSE)‐DWI scans at 0.35 Tesla (T) and compared the apparent diffusion coefficient (ADC) values and distortion of EPI‐DWI on 0.35 T MRI‐Linac compared to high‐field diagnostic MRI scanners.

Methods

The calibrated National Institute of Standards and Technology (NIST)/Quantitative Imaging Biomarkers Alliance (QIBA) Diffusion Phantom was scanned on a 0.35 T MRI‐Linac, and 1.5 T and 3 T MRI with EPI‐DWI. Five patients were scanned on a 0.35 T MRI‐Linac with a TSE‐DWI sequence, and five other patients were scanned with EPI‐DWI on a 0.35 T MRI‐Linac and a 3 T MRI. The quality of images was compared between the TSE‐DWI and EPI‐DWI on the 0.35 T MRI‐Linac assessing signal‐to‐noise ratios and presence of artifacts. EPI‐DWI ADC values and distortion magnitude were measured and compared between 0.35 T MRI‐Linac and high‐field MRI for both phantom and patient studies.

Results

The average ADC differences between EPI‐DWI acquired on the 0.35 T MRI‐Linac, 1.5 T and 3 T MRI scanners and published references in the phantom study were 1.7%, 0.4% and 1.0%, respectively. Comparing the ADC values based on EPI‐DWI in glioblastoma tumors, there was a 3.36% difference between 0.35 and 3 T measurements. Susceptibility‐induced distortions in the EPI‐DWI phantoms were 0.46 ± 1.51 mm for 0.35 MRI‐Linac, 0.98 ± 0.51 mm for 1.5 T MRI and 1.14 ± 1.88 mm for 3 T MRI; for patients ‐0.47 ± 0.78 mm for 0.35 T and 1.73 ± 2.11 mm for 3 T MRIs. The mean deformable registration distortion for a phantom was 1.1 ± 0.22 mm, 3.5 ± 0.39 mm and 4.7 ± 0.37 mm for the 0.35 T MRI‐Linac, 1.5 T MRI, and 3 T MRI scanners, respectively; for patients this distortion was –0.46 ± 0.57 mm for 0.35 T and 4.2 ± 0.41 mm for 3 T. EPI‐DWI 0.35 T MRI‐Linac images showed higher SNR and lack of artifacts compared with TSE‐DWI, especially at higher b‐values up to 1000 s/mm2.

Conclusion

EPI‐DWI on a 0.35 T MRI‐Linac showed superior image quality compared with TSE‐DWI, minor and less distortions than high‐field diagnostic scanners, and comparable ADC values in phantoms and glioblastoma tumors. EPI‐DWI should be investigated on the 0.35 T MRI‐Linac for prediction of early response in patients with glioblastoma.
Client and clinician perspectives about a virtual education and exercise chronic disease management programme for people with hip and knee osteoarthritis
Authors: Van Damme Jill , Dal Bello‐Haas Vanina , Strachan Patricia , Kuspinar Ayse , Kalu Michael , Zaide Mashal
Published: April 2024

Introduction

Osteoarthritis (OA) is one of the most prevalent chronic conditions in Canada. Despite the established benefits of non‐pharmacological management (education, exercise) for people with OA, many do not receive treatment, resulting in pain, decreased physical function, and poorer quality of life. Virtual programme options grew significantly during the recent pandemic and may provide longer‐term opportunities for increased uptake by reaching individuals otherwise unable to participate. This study explored the experiences and perspectives of clients participating in and clinicians providing the Good Life with osteoArthritis: Denmark (GLA:DTM) Canada remote programme.

Methods

This qualitative descriptive study recruited 10 clients with hip and/or knee OA and 11 clinicians across Canada using purposive sampling. An online pre‐interview survey was completed, and individual interviews were conducted, audio‐recorded, transcribed verbatim and analysed independently by two researchers using inductive thematic analysis. Coding and analyses were initially conducted separately by group and then compared and combined.

Results

Four overarching themes (and 11 subthemes) were identified: (1) Expected and unexpected benefits of virtual programs; (2) Drawbacks to virtual programs; (3) Programme delivery in a virtual world; (4) Shifting and non‐shifting perspectives. Although initially sceptical, after completion of the programme, clients were in favour of virtual delivery with many benefits described. Clinicians' perspectives varied about feedback aimed to correct client movement patterns.

Conclusions

Clients and clinicians identified important experiential and procedural elements for virtual chronic disease management programs that include education and exercise. Additional work is needed to understand if the GLA:DTM remote outcomes are equivalent to the in‐person programme.
Percutaneous tibial neuromodulation initial therapy compliance and subsequent third‐line treatment patterns
Authors: Padmanabhan Priya , Zwaans Bernadette M. M. , Wu Charlotte , Boldt Ryan J.
Published: April 2024

Purpose

Percutaneous Tibial Neuromodulation (PTNM) is used to treat Overactive Bladder (OAB). This analysis summarizes patient adherence to PTNM treatment and examines trends of other third‐line therapy use during and after PTNM.

Methods

Optum's deidentified Clinformatics® Data Mart Database (CDM) and CMS Research Identifiable Files were queried for adults with OAB symptoms and who underwent PTNM treatment (2019–2020). We evaluated the proportion of patients who completed 12 visits within 1 year, and defined patients as treatment compliant if 12 PTNM visits were completed within 12 weeks. We then identified the proportion of patients who used other third‐line therapies after PTNM and stratified these patients based on their PTNM therapy compliance status.

Results

2302 patients met selection criteria from CDM and 16,473 patients from CMS. The proportion of patients completing a full PTNM treatment course increased over time; from 16% at week 12% to 42% by week 52 (CDM) and 24% to 38% (CMS). Other third‐line therapy use increased over time and was higher for PTNM noncompliant versus compliant patients at 52 weeks: onabotulinumtoxinA was 6.5% versus 5.7% for noncompliant versus compliant (CMS, p = 0.0661) and 6.4% versus 4.9% (CDM, p = 0.035), SNM trial procedure was 6.5% versus 2.5% (CDM, p = 0.002) and 4.2% versus 2.0% (CMS, p = 0.010).

Conclusions

Most patients are noncompliant with recommended PTNM treatment regimen. Albeit low, third‐line therapy was pursued more frequently by noncompliant patients. Given low compliance, the effectiveness of PTNM may be compromised. Alternative implantable technologies may be needed to assure effectiveness of neuromodulation.
Understanding central nervous system fluid networks: Historical perspectives and a revised model for clinical neurofluid imaging
Authors: Mehta Rupal I. , Mehta Rashi I.
Published: April 2024

The central nervous system (CNS) lacks traditionally defined lymphatic vasculature. However, CNS tissues and barriers compartmentalize the brain, spinal cord, and adjacent spaces, facilitating the transmittal of fluids, metabolic wastes, immune cells, and vital signals, while more conventional lymphatic pathways in the meninges, cervicofacial and paraspinal regions transmit efflux fluid and molecules to peripheral lymph and lymph nodes. Thus, a unique and highly organized fluid circulation network encompassing intraparenchymal, subarachnoid, dural, and extradural segments functions in unison to maintain CNS homeostasis. Pathways involved in this system have been under investigation for centuries and continue to be the source of considerable interest and debate. Modern imaging and microscopy technologies have led to important breakthroughs pertaining to various elements of CNS fluid circuitry and exchange over the past decade, thus enhancing knowledge on mechanisms of mammalian CNS maintenance and disease. Yet, to better understand precise anatomical routes, the physiology and clinical significance of these CNS pathways, and potential therapeutic targets in humans, fluid conduits, flow‐regulating factors, and tissue effects must be analyzed systematically and in a global manner in persons across age, demographical factors, and disease states. Here, we illustrate the system‐wide nature of intermixing CNS fluid networks, summarize historical and clinical studies, and discuss anatomical and physiological similarities and differences that are relevant for translation of evidence from mice to humans. We also review Cushing's classical model of cerebrospinal fluid flow and present a new framework of this “third circulation” that emphasizes previously unexplained complexities of CNS fluid circulation in humans. Finally, we review future directions in the field, including emerging theranostic techniques and MRI studies required in humans.
Over 132 Years Ago, the Inaugural Immunotherapy Treated Its First Head and Neck Cancer Patient
Authors: Martin Joey , Hans Stéphane , Ferris Robert L. , Baudouin Robin
Published: April 2024

Immunotherapy in oncology has a more extensive history than is commonly perceived. Rooted in the observations and experiences of multiple physicians in the late 19th century, immunological interventions are currently integral to the oncological therapeutic repertoire. This article seeks to delineate the evolution of cancer immunotherapy, tracing its inception in 1891 with the pioneering work of an American surgeon, William B. Coley, who achieved the first documented cure of a cancer case involving a malignant head and neck tumor. The narrative extends to encompass successive historical breakthroughs and prospective developments in this dynamic field.
Preparation and properties of novolac epoxy resins containing polycyclic aromatic hydrocarbons
Authors: Chen Xinyu , Jin Chaoen , Wang Fan , Zhu Yaping , Qi Huimin
Published: April 2024

To meet the demands of high‐density and miniaturized integrated circuits, electronic packaging materials need to have excellent properties. One approach to enhance the performance is to design novel structures. In this study, two novolac oligomers containing naphthalene Naphthalene novolac oligomer (NPF) and biphenyl Biphenyl novolac oligomer (LPF) were synthesized and then reacted with epichlorohydrin to synthesize novel novolac epoxy resins containing polycyclic aromatic hydrocarbons (NPF‐EP and LPF‐EP). Their chemical structures were characterized by Fourier transform infrared and 1H nuclear magnetic resonance spectra. Tetrahydromethyl‐1,3‐isobenzofurandione (MeTHPA) was used as curing agent to prepare cured NPF‐EP/MeTHPA and LPF‐EP/MeTHPA thermosets. Both NPF‐EP/MeTHPA and LPF‐EP/MeTHPA exhibited better thermal and mechanical properties compared with novolac epoxy resin (PF‐EP/MeTHPA). In particular, NPF‐EP/MeTHPA presented the highest glass transition temperature of 193°C and LPF‐EP/MeTHPA had excellent mechanical properties, with tensile and flexural strengths of 94 and 151 MPa, respectively. Additionally, the cured NPF‐EP/MeTHPA and LPF‐EP/MeTHPA also exhibit a lower dielectric constant and dielectric loss, and low coefficient of thermal expansion compared with cured PF‐EP/MeTHPA. This investigation provides valuable insights for the manufacturing of high‐performance novolac epoxy resins for application in electronic packaging materials.
Ballistic impact resistance and flexural performance of natural basalt fiber with carbon and glass fibers in inter‐ply hybrid composites
Authors: Doğru Mehmet Hanifi , Yeter Eyüp , Göv İbrahim , Göv Kürşad
Published: April 2024

The ballistic and flexural behaviors of basalt (natural fabric), carbon, glass fiber, and their hybrid composites, were investigated in this study. The main objective of the paper was the addition of natural basalt fiber to the carbon and glass fibers with inter‐ply hybrid sequences to search for possible usage to the ballistic loads carrying structures. The composite and hybrid composite plates produced nine layers with cross‐ply stacking sequences ([0/90]9). The ballistic impact tests were conducted using a specially designed ballistic test setup and the flexural tests were performed through the standard three‐point bending test. The results showed that basalt/epoxy absorbed the most energy under ballistic loading among all models. It was observed that the basalt‐glass‐basalt/epoxy (BGB) hybrid composite had an energy absorption capacity very close to the basalt/epoxy composite. When BGB and carbon‐glass‐carbon/epoxy (CGC) hybrid models were compared, the energy absorption capacity of CGC was 62.7% less than BGB. Unlike the ballistic test result, basalt/epoxy had the lowest flexural strength, while carbon/epoxy had the highest flexural strength. Among the hybrid models, it was seen that BGB had the lowest flexural strength, while CGC had the highest flexural strength. The flexural strength of the CGC is 38% higher than BGB. The study found that basalt fiber has high ballistic resistance, whether alone or when combined with commonly used fibers. It also suggests that basalt fiber is a promising candidate for future research and development in the field of protective materials.

Highlights

Basalt (natural fabric) composite materials behavior.

Hybridization of basalt with carbon and glass.

Target plates damage resistance according to applied ballistic loads.

Target plates damage resistance according to applied flexural loads.

Non‐hybrid and hybrid composites plates comparisons.
Biological and physiological effects in Bemisia tabaci feeding on tomatoes endophytically colonized by Beauveria bassiana
Authors: Wang Xian , Yuan Qian , He Liqiang , Wang Zhou , Li Guangyun , Wang Ziying , Liu Huai
Published: April 2024

BACKGROUND

Entomopathogenic fungi (EPF) treatment of plants may affect the survival and feeding preferences of herbivorous pests. However, comprehensive studies on the fitness across their entire life cycle, feeding behavior, and physiological changes in herbivores consuming EPF‐treated plants within the tripartite interactions of EPF, plants, and pests are still limited. In this study, we utilized life tables, electrical penetration graph (EPG), and metabolomics to uncover the biological and physiological characteristics of Bemisia tabaci on tomato plants inoculated with Beauveria bassiana through root irrigation.

RESULTS

Our study indicated that Beauveria bassiana Bb252 can penetrate the entire tissue from the point of inoculation, primarily colonizing the intercellular spaces and vascular tissue. However, this colonization is temporary, lasting no more than 35 days. Moreover, the population fitness and feeding behavior of Bemisia tabaci on tomato plants treated with Beauveria bassiana via root irrigation were significantly affected, showing a substantial 41.4% decrease in net reproductive rate (R0), a notable reduction in watery salivation, and shortened phloem ingestion. Lastly, we observed a significant decrease in hormones and amino acids of whiteflies that fed on Beauveria bassiana‐treated tomato plants by root irrigation.

CONCLUSIONS

Our results indicated that the endophyte, Beauveria bassiana Bb252, reduced demographic fitness of Bemisia tabaci by altering its hormones and amino acids levels. These findings enhance our understanding of multitrophic interactions in integrated pest management. © 2024 Society of Chemical Industry.
Information‐based group sequential design for post‐market safety monitoring of medical products using real world data
Authors: Zhang Zhiwei , Nielson Carrie , Chuo Ching‐Yi , Ye Zhishen
Published: April 2024

Real world healthcare data are commonly used in post‐market safety monitoring studies to address potential safety issues related to newly approved medical products. Such studies typically involve repeated evaluations of accumulating safety data with respect to pre‐defined hypotheses, for which the group sequential design provides a rigorous and flexible statistical framework. A major challenge in designing a group sequential safety monitoring study is the uncertainty associated with product uptake, which makes it difficult to specify the final sample size or maximum duration of the study. To deal with this challenge, we propose an information‐based group sequential design which specifies a target amount of information that would produce adequate power for detecting a clinically significant effect size. At each interim analysis, the variance estimate for the treatment effect of interest is used to compute the current information time, and a pre‐specified alpha spending function is used to determine the stopping boundary. The proposed design can be applied to regression models that adjust for potential confounders and/or heterogeneous treatment exposure. Simulation results demonstrate that the proposed design performs reasonably well in realistic settings
Local identification of equatorial Kelvin waves in real‐time operational forecasts
Authors: Cruz João B. , Castanheira José M. , DaCamara Carlos C.
Published: April 2024

Equatorial Kelvin waves (KWs) are associated with a variety of equatorial atmospheric phenomena, namely, tropical convection, cloud and precipitation variability, tropical cyclogenesis, the onset of monsoon season over Africa and India, and even the quasi‐biennial oscillation and the Madden–Julian oscillation. As such, if operational forecasts are to improve near the Tropics, it is important that they correctly represent KWs. This article aims at developing a novel methodology for identifying KWs in real‐time operational forecasts at specific longitudes using only the meridional structures of the solutions to the free Laplace tidal equations, known as Hough vector functions. The main advantages of this newly proposed methodology are that (a) it can identify KWs at a specific longitude and (b) very low computational cost is needed to apply it to real‐time operational forecasts. The application of the method to 2015–2017 European Centre for Medium‐range Weather Forecasts (ECMWF) analysis and operational forecast data reveals a systematic bias in the representation of KWs by the ECMWF operational forecast model.
High‐resolution multi‐reflection time‐of‐flight mass spectrometer with atmospheric pressure interface
Authors: Yan Shuxiong , Ren Yi , Huang Qi , Hong Yi , Chen Zhengge , Li Mei , Hu Bin , Huang Zhengxu
Published: April 2024

Rationale

Atmospheric pressure interface multi‐reflection time‐of‐flight mass spectrometry (API‐MRTOF‐MS) has the potential to be a rapid and high‐resolution analytical tool for versatile applications in chemistry, biology, environmental science, and medicine.

Methods

The ions were reflected in a mass analyzer via electrostatic mirrors and folded flight path. Therefore, flight distances were significantly increased. The ion flight path of the API‐MRTOF‐MS was extended from meters to over 1 km, and the mass resolution was increased. Furthermore, the mass analysis could be completed at around 10 ms due to the rapid response of TOF‐MS.

Results

A high‐resolution API‐MRTOF‐MS approach is successfully developed in this study. The mass resolution could achieve 116 050 (full widths at half maximum [FWHM]) for Cs+ ions using an atmospheric pressure electrospray ionization within a total TOF of only 18 ms. An ion transmission efficiency of over 50% was achieved after 600 cycles.

Conclusions

The analytical performance of the newly developed API‐MRTOF‐MS demonstrated that it is suitable for high resolution and rapid analysis in many fields.
Unravelling the triad of neuroinvasion, neurodissemination, and neuroinflammation of human immunodeficiency virus type 1 in the central nervous system
Authors: Calado Marta , Ferreira Rita , Pires David , Santos‐Costa Quirina , Anes Elsa , Brites Dora , Azevedo‐Pereira José Miguel
Published: April 2024

Since the identification of human immunodeficiency virus type 1 (HIV‐1) in 1983, many improvements have been made to control viral replication in the peripheral blood and to treat opportunistic infections. This has increased life expectancy but also the incidence of age‐related central nervous system (CNS) disorders and HIV‐associated neurodegeneration/neurocognitive impairment and depression collectively referred to as HIV‐associated neurocognitive disorders (HAND). HAND encompasses a spectrum of different clinical presentations ranging from milder forms such as asymptomatic neurocognitive impairment or mild neurocognitive disorder to a severe HIV‐associated dementia (HAD). Although control of viral replication and suppression of plasma viral load with combination antiretroviral therapy has reduced the incidence of HAD, it has not reversed milder forms of HAND. The objective of this review, is to describe the mechanisms by which HIV‐1 invades and disseminates in the CNS, a crucial event leading to HAND. The review will present the evidence that underlies the relationship between HIV infection and HAND. Additionally, recent findings explaining the role of neuroinflammation in the pathogenesis of HAND will be discussed, along with prospects for treatment and control.
In Situ Engineering Multifunctional Active Sites of Ruthenium–Nickel Alloys for pH‐Universal Ampere‐Level Current‐Density Hydrogen Evolution
Authors: Liu Yang , Shi Hang , Dai Tian‐Yi , Zeng Shu‐Pei , Han Gao‐Feng , Wang Tong‐Hui , Wen Zi , Lang Xing‐You , Jiang Qing
Published: April 2024

Developing robust non‐platinum electrocatalysts with multifunctional active sites for pH‐universal hydrogen evolution reaction (HER) is crucial for scalable hydrogen production through electrochemical water splitting. Here ultra‐small ruthenium‐nickel alloy nanoparticles steadily anchored on reduced graphene oxide papers (Ru‐Ni/rGOPs) as versatile electrocatalytic materials for acidic and alkaline HER are reported. These Ru–Ni alloy nanoparticles serve as pH self‐adaptive electroactive species by making use of in situ surface reconstruction, where surface Ni atoms are hydroxylated to produce bifunctional active sites of Ru‐Ni(OH)2 for alkaline HER, and selectively etched to form monometallic Ru active sites for acidic HER, respectively. Owing to the presence of Ru‐Ni(OH)2 multi‐site surface, which not only accelerates water dissociation to generate reactive hydrogen intermediates but also facilitates their recombination into hydrogen molecules, the self‐supported Ru90Ni10/rGOP hybrid electrode only takes overpotential of as low as ≈106 mV to deliver current density of 1000 mA cm−2, and maintains exceptional stability for over 1000 h in 1 m KOH. While in 0.5 m H2SO4, the Ru90Ni10/rGOP hybrid electrode exhibits acidic HER catalytic behavior comparable to commercially available Pt/C catalyst due to the formation of monometallic Ru shell. These electrochemical behaviors outperform some of the best Ru‐based catalysts and make it attractive alternative to Pt‐based catalysts toward highly efficient HER.
Improved Performance of High‐Entropy Disordered Rocksalt Oxyfluoride Cathode by Atomic Layer Deposition Coating for Li‐Ion Batteries
Authors: Zhou Bei , An Siyu , Kitsche David , Dreyer Sören L. , Wang Kai , Huang Xiaohui , Thanner Jannik , Bianchini Matteo , Brezesinski Torsten , Breitung Ben , Hahn Horst , Wang Qingsong
Published: April 2024

Lithium‐excess cation‐disordered rocksalt materials are a promising class of transition metal‐based cathodes that exhibit high specific capacity and energy density. The exceptional performance is achieved through participation of anionic redox in addition to cationic redox reactions in the electrochemistry. However, anionic redox reactions accompanied by oxygen evolution, accelerated electrolyte breakdown, and structural evolution lead to voltage hysteresis and low initial Coulombic efficiency. Herein, an Al2O3 layer with varying thickness has been coated onto a high‐entropy disordered rocksalt oxyfluoride cathode through atomic layer deposition to enhance battery performance. The results indicate that the utilization of a uniform Al2O3 coating improves the capacity retention and rate capability of the cathode, with the performance being strongly dependent on the layer thickness. Further investigation into cathode–electrolyte interfacial reactions reveals that the thin protecting Al2O3 coating can reduce the decomposition of electrolyte on the cathode surface but cannot prevent bulk phase degradation during prolonged cycling. These findings highlight the need for optimized coating design on the disordered rocksalt cathode to improve battery performance.
Theme‐Driven Social Analysis: Three Approaches
Authors: DeGloma Thomas
Published: April 2024

In this article, I present three strategies for building cultural and historical analyses that are driven by broadly relevant social themes rather than particular cases. Each of these strategies represents a different way to approach “concept‐driven sociology,” focusing the researcher on robust and deep‐seated social and cultural forces that underly and shape various actions, events, and experiences occurring at different times and places. Such a thematic analysis requires bringing together multiple cases that illustrate a common social phenomenon despite their substantive differences, while also highlighting those differences and interpreting each case to reinforce the analysis of the general theme at hand. After discussing the relevance of form, process, and culture to thematic analysis, I draw on previous and ongoing research to outline three strategies: (1) formal analytic abstraction, (2) the configuration of analytic subtypes from a master theme, and (3) transcendent historical analysis. While thematic analysis involves illustrating how several otherwise different cases cohere around a common theme, and thus highlighting important similarities among them, I conclude by discussing why we must also take deep analytic dives into the cases we study in order to enhance our understanding of the theme that ties them together.
Cavitation assisted intensification of biogas production: A review
Authors: Gharat Sandip H. , Gogate Parag R.
Published: April 2024

Intensified cavitation‐assisted biogas production from sustainable feedstock has been discussed describing the working principles and governing mechanisms for intensification. Various methods of biogas production discussed in the work include activated sludge processes, membrane bioreactor (MBR), and processes involving methanogenic and sulfate‐reducing microorganisms. Design aspects of cavitational reactors (sonochemical and hydrodynamic cavitation) have been presented with detailed understanding into effect of several operational parameters, such as the biomass‐to‐water ratio, operating pressure, treatment duration, operating temperature, power dissipation, and so on. Selection of optimum parameters is crucial to improve the performance and observed intensification from such processes. The possible benefits in terms of applicability to various types of biomass, efficiency, higher yields, and energy‐saving as compared to the conventional production processes have been demonstrated. Overall, cavitation‐assisted techniques are very effective in increasing biogas production and have significant potential for commercial applications, which would result in significant cost savings.
Prostate cancer characteristics in Black septuagenarian men
Authors: Shah Navin , Ioffe Vladimir
Published: April 2024

Prostate cancer is the most common (non‐cutaneous) cancer and the second leading cause of cancer death in US men. Both Black men and men 70–80 years old are at high risk for high‐grade prostate cancer. Despite that some groups recommend against PSA‐ and DRE‐based prostate cancer screening in men 70 years of age and older without regard to high‐risk factors. The authors present results of a study of prostate biopsy characteristics of men 70–80 years of age to determine whether they harbor a concerning incidence of high‐grade prostate cancer and should be offered screening.