bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of 3-(1,3-oxazol-5-yl)aniline as a highly efficient corrosion inhibitor for mild steel in 1 M HCl solution
Authors: Alamiery Ahmed , Al-Azzawi Waleed K
Published: August 2023

Mild steel corrosion in acidic environments presents a significant challenge with detrimental consequences for both industrial infrastructure and the environment. Effective corrosion control measures are crucial to prolonging the lifespan of equipment. Inhibition techniques have proven to be an efficient method for protecting mild steel from corrosion, particularly in acidic conditions. This study investigates the efficacy of 3-(1,3-oxazol-5-yl)aniline (3-OYA) as a corrosion inhibitor for mild steel in a hydrochloric acid (HCl) solution. Traditional weight-loss tests, as well as electrochemical techniques, such as potentiodynamic polarization and electrochemical impedance spectroscopy, were employed to evaluate the corrosion inhibition performance. The results reveal that 3-OYA, at a concentration of 0.05 mM, exhibits an outstanding protection efficacy of 93.5%. This remarkable performance can be attributed to the formation of a protective adsorption layer on the mild steel surface, effectively inhibiting the corrosion rate and enhancing inhibitory efficacy. The inhibition efficiency was found to increase with increasing inhibitor concentration, while it decreased with rising temperature. Langmuir adsorption isotherm analysis confirmed the high adsorption–inhibition activity of 3-OYA. The $\Delta {G}_{ads}^o$ value indicated the occurrence of both physical and chemical adsorption mechanisms on the mild steel surface. Furthermore, density functional theory (DFT) calculations were utilized to determine the quantum chemical parameters and establish a correlation between the inhibition activity and the molecular structure. The consistency between the experimental and theoretical analyses reinforces the robustness of our findings.
Subordination Theory in Practice: An Empirical Analysis of Chinese Courts’ Approaches to Classifying Labour Relationships in Platform Cases
Authors: Zheng Qi , Su Jianning
Published: August 2023

Determining the juridical nature of the work relationship is key to understanding the capacity of labour law to protect the rights and interests of gig workers. How to apply the traditional ‘subordination’ test and its constituent elements to platform work remains controversial in both theory and practice. In this article we examine the approaches of courts to this question using a sample of 71 Chinese judgments. We construct a binary probit model to conduct an empirical test of the degree of correlation between eight factors which serve to identify protected worker status, on the one hand, and courts’ rulings on the presence or absence of subordination, on the other. We find that, among the factors relevant to the subordination test, ‘control’ and ‘integration’ strongly predict a finding of worker status. We conclude that the subordination test is still being widely used to determine the status of gig workers in China, and that an approach to classification based on the ‘primacy of the facts’ of the case continues to be feasible in the context of platform work.
A Call to Action: Current Challenges and Considerations for COVID-19 Vaccination in Immunocompromised Populations
Authors: Bonanni Paolo , Ceddia Francesca , Dawson Rachel
Published: August 2023

The heightened risk of infection and complexities of preventing disease in immunocompromised individuals are at the forefront of public health strategies. The COVID-19 pandemic highlighted the increased vulnerability and susceptibility to serious outcomes in this population. COVID-19 prevention efforts led to the development of vaccines, including mRNA-based options, which were initially recommended as a 2-dose primary schedule for both immunocompromised and immunocompetent individuals. However, post-rollout assessments led to updated recommendations specific to immunocompromised populations. As COVID-19 potentially transitions to become endemic disease, immunocompromised individuals will remain at high risk of severe disease; thus, the evaluation of current vaccination challenges remains crucial for guiding effective public health efforts. This article summarizes key findings from the previous articles of this supplement, highlighting current vaccination challenges for at-risk immunocompromised groups and exploring solutions to ensure protection against COVID-19 for these vulnerable populations.
Omega-3 meat enrichment and L-FABP, PPARA, and LPL genes expression are modified by the level and period of tuna oil supplementation in slow-growing chickens
Authors: Khosinklang Wichuta , Kubota Satoshi , Riou Cindy , Kaewsatuan Pramin , Molee Amonrat , Molee Wittawat
Published: August 2023

This study proposes a strategy to manipulate the fatty acid (FA) content in slow-growing Korat chicken (KRC) meat using tuna oil (TO). To determine the optimal level and feeding period of TO supplementation, we conducted a study investigating the effects of dietary TO levels and feeding periods on meat quality, omega-3 polyunsaturated fatty acid (n-3 PUFA) composition, and gene expression related to FA metabolism in KRC breast meat. At 3 wk of age, 700 mixed-sex KRC were assigned to seven augmented factorial treatments with a completely randomized design, each consisting of four replicate pens containing 25 chickens per pen. The control group received a corn-soybean-based diet with 4.5% rice bran oil (RBO), while varying amounts of TO (1.5%, 3.0%, or 4.5%) replaced a portion of the RBO content in the experimental diets. The chickens were fed these diets for 3 and 6 wk, respectively, before being slaughtered at 9 wk. Our results indicated no significant interactions between TO levels and feeding periods on the growth performance or meat quality of KRC (P > 0.05). However, the liver fatty acid-binding protein gene (L-FABP, also known as FABP1), responsible for FA transport and accumulation, showed significantly higher expression in the chickens supplemented with 4.5% TO (P < 0.05). The chickens supplemented with 4.5% TO for a longer period (3 to 9 wk of age) exhibited the lowest levels of n-6 PUFA and n-6 to n-3 ratio, along with the highest levels of eicosapentaenoic acid, docosahexaenoic acid, and n-3 PUFA in the breast meat (P < 0.05). However, even a short period of supplementation with 4.5% TO (6 to 9 wk of age) was adequate to enrich slow-growing chicken meat with high levels of n-3 PUFA, as recommended previously.

Our findings indicated that even a short period of tuna oil supplementation could lead to desirable levels of omega-3 enrichment in slow-growing chicken meat. This finding has practical implications for the poultry industry, providing insights into optimal supplementation strategies for achieving desired FA profiles without adversely affecting growth performance or meat quality.
Community-based integrated tick management programs: cost and feasibility scenarios
Authors: Schulze Terry L , Eisen Lars , Russell Katie , Jordan Robert A
Published: August 2023

Numerous studies have assessed the efficacy of environmentally based control methods to suppress populations of the blacklegged tick (Ixodes scapularis Say), but few of these estimated the cost of control. We estimated costs for a range of tick control methods (including habitat management, deer exclusion or population reduction, broadcast of acaricides, and use of host-targeted acaricides) implemented singly or in combination and applied to a model community comprising 320 residential properties and parklands. Using the high end for cost ranges, tick control based on a single method was estimated to have mean annual costs per household in the model community ranging from $132 for treating only forest ecotone with a broadcast synthetic acaricide to kill host-seeking ticks (or $404 for treating all residential forested habitat) to >$2,000 for deployment of bait boxes (SELECT TCS) across all residential tick habitat to treat rodents topically with acaricide to kill infesting ticks. Combining different sets of multiple methods in an integrated tick management program placed the annual cost between $508 and 3,192 annually per household in the model community, underscoring the disconnect between what people in Lyme disease endemic areas say they are willing to pay for tick control (not more than $100–150 annually) and the actual costs for tick control. Additional barriers to implementing community-based tick management programs within residential communities are discussed.
Appendiceal cancer showing a submucosal tumor-like morphology in the ascending colon on colonoscopy: a case report
Authors: Koshino Kurodo , Nakagawa Ryosuke , Tani Kimitaka , Ogawa Shimpei , Yamamoto Tomoko , Inoue Yuji , Yamaguchi Shigeki
Published: August 2023

Few reports have described a submucosal tumor (SMT)-like colon tumor together with appendiceal cancer. Moreover, some appendiceal tumors may exhibit a cecal protuberance. Here, we report an uncommon case of appendiceal cancer with an SMT-like tumor, which was a protuberant lesion in the ascending colon. To our knowledge, this is the first report in Japan. Our case was a 50-year-old man with an ascending colon tumor presented at our hospital for further evaluation of this lesion. This was discovered as a cystic lesion near the ascending colon on colonoscopy. Our initial diagnosis was an ascending colon SMT-like tumor, and our treatment strategy was laparoscopic resection. The differential diagnosis was appendiceal cancer or mucocele. Postoperative pathological findings led to a diagnosis of adenocarcinoma of the appendix. The postoperative course was uneventful, and the patient was followed up with computed tomography and blood sampling on an outpatient basis.
Primary leiomyosarcoma of the uterine cervix: an unusual case and critical appraisal
Authors: Lebbe Ines , De Cuypere Eveline , Claes Nele , Loccufier Anne , Ghysel Christophe , Van Trappen Philippe
Published: August 2023

Leiomyosarcomas of the uterine cervix are rare, mostly occurring in perimenopausal women. Diagnosis is based on pathology and immunohistochemistry. Surgery with a total abdominal hysterectomy and bilateral salpingo-oophorectomy remains the standard. A female patient in her 60s presented with heavy postmenopausal bleeding. Vaginal ultrasound scan and magnetic resonance imaging showed a large strongly vascularized cervical mass with features suspicious of sarcomatous degeneration. Positron Emission Tomography-Computed Tomography (PET-CT) did not reveal any evidence of metastases nor lymphadenopathy, but presence of right hydronephrosis. An abdominal hysterectomy with bilateral salpingo-oophorectomy, and end-to-end anastomosis of the right ureter, was performed. Pathology showed an International Federation of Gynecology and Obstetrics (FIGO)-stage 1B leiomyosarcoma of the uterine cervix. No adjuvant treatment was given. Adjuvant radiotherapy reduces the risk of recurrence but no survival impact. The benefit of adjuvant chemotherapy is questionable given the lack of randomized trials. Multidisciplinary research concerning molecular alterations of the disease is required to determine optimal management strategies with potential novel molecular therapies.
History of infertility and sexual dysfunction in midlife women: Is there a link?
Authors: Saadedine Mariam , Faubion Stephanie S , Kling Juliana M , Kuhle Carol , Shufelt Chrisandra L , Mara Kristin , Enders Felicity , Kapoor Ekta
Published: August 2023

Background

Infertility has been linked with an increased risk of sexual dysfunction in reproductive-aged women, with longer periods of infertility associated with a greater risk.

Aim

The study’s aim was to examine whether a history of infertility treatment in women is linked to sexual dysfunction during midlife.

Methods

The cross-sectional study was conducted among sexually active women, between the ages of 45 and 65 years, who sought consultation at the women’s health clinics at a US tertiary care center. History of infertility treatment was assessed with a single question that asked participants if they were treated for infertility in the past. The association between a history of infertility treatment and sexual dysfunction—which was diagnosed by a combination of Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale–Revised score ≥11—was assessed in a multivariable logistic regression model that adjusted for multiple confounders.

Outcomes

The primary outcome was sexual dysfunction in midlife women.

Results

The analysis included 5912 women, with a mean age of 54.1 years. Nearly 16% of women reported receiving treatment for infertility. More than half the women (55%) had sexual dysfunction: 56.3% of those with previous fertility treatments and 54.4% of those without any fertility treatment (P = .3). Receiving treatment for infertility in the younger years did not significantly increase the odds of sexual dysfunction in midlife in univariate (odds ratio, 1.08; 95% CI, 0.94-1.24; P = .3) and multivariable analyses (odds ratio, 1.11; 95% CI, 0.96-1.29; P = .17).

Clinical Implications

While infertility is known to be predictive of sexual dysfunction in women during their reproductive years, there was no association between a history of infertility treatment and sexual dysfunction in midlife women in the current study.

Strengths and Limitations

The study used validated questionnaires accounting for sexual complaints and distress and adjusted for multiple confounding factors. Limitations include the selection bias introduced by the study of women presenting for evaluation of sexual dysfunction, which may have been a result of factors stronger than the influence of infertility. Other limitations include the study’s cross-sectional nature with suboptimal racial and ethnic representation.

Conclusion

Although infertility is commonly associated with female sexual dysfunction in women of reproductive age, the association was not present in midlife women in the current study.
A Case of Whipple’s Disease With Concomitant Esophageal Candidiasis
Authors: Choi Ryan , Pazevic Alexander , Pak Kevin , Skaret Michael , Bachmann Angela , Wilkerson Rashad
Published: August 2023

Whipple’s Disease (WD) is a rare disease caused by the infection of Tropheryma whipplei. It can lead to immunosuppression and a multitude of effects on different organ systems, resulting in a constellation of seemingly unrelated findings. Although treatment may appear straightforward, T. whipplei can be difficult to eradicate. We present the case of a 36-year-old male with months of progressively worsening watery diarrhea, migratory arthralgias, and weight loss. He had undergone an extensive evaluation for rheumatologic, oncologic, and infectious disorders without positive findings. Esophagogastroduodenoscopy and colonoscopy revealed esophageal candidiasis, Helicobacter pylori infection, and foamy macrophages in the lamina propria of the duodenum and ileum with positive polymerase chain reaction for T. whipplei. There were no other risk factors for esophageal candidiasis. He received treatment for his esophageal candidiasis and H. pylori infection and was treated for WD with ceftriaxone for 2 weeks, followed by hydroxychloroquine and doxycycline for 1 year. Symptoms resolved after 3 months of therapy. One year later, repeat bidirectional endoscopy was performed. Biopsies were negative for T. whipplei, although there were persistent foamy macrophages. There have been previously reported cases of patients with WD with concomitant esophageal candidiasis, and this association implies a likely state of relative immunosuppression associated with WD, which is thought to be the result of impaired T helper cell 1 activity. This impairment likely contributes to the high rate of relapse. Having a low threshold for repeat evaluation is advisable for recurrent symptoms, but long-term surveillance strategies are not clearly defined.
The loneliest galaxies in the Universe: a GAMA and Galaxy Zoo study on void galaxy morphology
Authors: Porter Lori E , Holwerda Benne W , Kruk Sandor , Lara-López Maritza , Pimbblet Kevin A , Henry Christopher P A , Casura Sarah , Kelvin Lee S
Published: August 2023

The large-scale structure of the Universe is comprised of galaxy filaments, tendrils, and voids. The majority of the Universe’s volume is taken up by these voids, which exist as underdense, but not empty, regions. The galaxies found inside these voids are expected to be some of the most isolated objects in the Universe. This study, using the Galaxy and Mass Assembly (GAMA) and Galaxy Zoo surveys, aims to investigate basic physical properties and morphology of void galaxies versus field (filament and tendril) galaxies. We use void galaxies with stellar masses ($M_*$) of 109.35 M⊙ < M* < 1011.25 M⊙, and this sample is split by identifying two redshift-limited regions, 0 < z < 0.075 and 0.075 < z < 0.15. To find comparable objects in the sample of field galaxies from GAMA and Galaxy Zoo, we identify ‘twins’ of void galaxies as field galaxies within ±0.05 and ±0.15 dex of $M_*$ and specific star formation rate. We determine the statistical significance of our results using the Kolmogorov–Smirnov test. We see that void galaxies, in contrast with field galaxies, seem to be disc-dominated and have predominantly round bulges (with >50 per cent of the Galaxy Zoo citizen scientists agreeing that bulges are present).
Measuring mass transfer of AM CVn binaries with a space-based gravitational wave detector
Authors: Wang Zijian , Cao Zhoujian , Zhang Xian-Fei
Published: August 2023

The formation mechanism of AM CVn binary has not been well understood yet. Accurate measurements of the mass transfer rate can help us to determine the formation mechanism. But unfortunately such observation by electromagnetic means is quite challenging. One possible formation channel of AM CVn binary is a semidetached white dwarf binary. Such system emits strong gravitational wave radiation which could be measured by the future space-based detectors. We can simultaneously extract the mass transfer rate and the orbital period from the gravitational wave signal. We employ a post-Keplerian waveform model of gravitational wave and carry out a Fisher analysis to estimate the measurement accuracy of mass transfer rate through gravitational wave detection. Special attention is paid to the observed sources in Gaia Data Release 2. We found that we can accurately measure the mass transfer rate for those systems. Comparing to electromagnetic observations, gravitational wave detection improves the accuracy more than two orders of magnitude. Our results imply that the gravitational wave detection will help much in understanding the formation mechanism of AM CVn binaries.
Influences of dynamical disruptions on the evolution of pulsars in globular clusters
Authors: Oh Kwangmin , Hui C Y , Hong Jongsuk , Takata J , Kong A K H , Tam Pak-Hin Thomas , Li Kwan-Lok , Cheng K S
Published: August 2023

By comparing the physical properties of pulsars hosted by core-collapsed (CCed) and non-core-collapsed (non-CCed) globular clusters (GCs), we find that pulsars in CCed GCs rotate significantly slower than their counterparts in non-CCed GCs. Additionally, radio luminosities at 1.4 GHz in CCed GCs are higher. These findings are consistent with the scenario that dynamical interactions in GCs can interrupt angular momentum transfer processes and surface magnetic field decay during the recycling phase. Our results suggest that such effects in CCed GCs are stronger due to more frequent disruptions of compact binaries. This is further supported by the observation that both estimated disruption rates and the fraction of isolated pulsars are predominantly higher in CCed GCs.
NEIM-05 PURSUE: RESULTS FROM A PROSPECTIVE, PHASE 2B TRIAL TO DEFINE IMAGE INTERPRETATION CRITERIA FOR18F-FLUCICLOVINE-PET FOR DETECTION OF RECURRENT BRAIN METASTASES AFTER RADIATION THERAPY
Authors: Kotecha Rupesh , Chiang Veronica , Tom Martin C , Nabavizadeh Ali , Zan Elcin , Peddi Srinivas , Sulman Erik P , Siegel Barry A , Huang Jiayi , Brem Steven , Ware Marcus , Kesari Santosh , Parent Ephraim E , Pope Whitney B , Holmes Robin , Chau Albert , Teoh Eugene J , Chao Samuel T , Aboian Mariam
Published: August 2023

BACKGROUND

After radiation therapy (RT) for brain metastases (BM), differentiating radiation necrosis from tumor recurrence remains challenging. PURSUE (NCT04410367) evaluated various measures of lesion 18F-fluciclovine uptake to establish image interpretation criteria (IIC) for 18F-fluciclovine-PET to accurately diagnose recurrent BM.

METHODS

Patients with solid tumor BM and a previously irradiated ‘reference’ lesion equivocal for recurrence on MRI who were scheduled for craniotomy underwent 18F-fluciclovine-PET (185 MBq) <42 days post-MRI and 1-21 days pre-craniotomy. Lesion 18F-fluciclovine uptake was qualitatively rated as ‘mild’ (up to blood pool), ‘moderate’ (above blood pool to parotid gland), or ‘marked’ (above parotid gland) by three independent blinded readers. The primary endpoint was diagnostic performance of different uptake thresholds on qualitative reads vs central histopathology. Secondary endpoints included diagnostic performance, based on different thresholds, of quantitative (e.g., lesion standardized uptake value [SUV]) and dynamic measures. IIC were determined by committee and subsequently used to assess the diagnostic performance of 18F-fluciclovine.

RESULTS

All 23 reference lesions from 23 enrolled patients underwent histopathological analysis; 10 (43%) were pathologically-confirmed BM recurrence. The highest performing qualitative measure was ‘marked’, rendering 92-100% sensitivity and 40-80% specificity across readers. SUVmax was a reader-independent, high-performing quantitative metric (AUC 0.87, SUVmax threshold 4.8, 80% sensitivity, 85% specificity). Dynamic measures did not add diagnostic value. Thus, IIC was established as: “Lesions with 18F-fluciclovine uptake of SUVmax equal to or greater than 4.8, or visually greater than the parotid gland, should be considered suspicious for recurrence. Otherwise, recurrence should be considered unlikely.” Application of the IIC resulted in 80% sensitivity, 77-85% specificity, 73-80% PPV, and 83-85% NPV across the readers.

CONCLUSIONS

PURSUE is the first prospective, multicenter trial to establish IIC for 18F-fluciclovine-PET for suspected recurrent BM after RT, verified by histopathology. Finalized IIC demonstrated excellent diagnostic performance for 18F-fluciclovine and will help evaluate 18F-fluciclovine-PET in future studies.
NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
Authors: Kim Lauren , De Feyter Henk , de Graaf Robin , Fulbright Robert , Liu Yanning , Rothman Douglas , Baehring Joachim , Blondin Nicholas , Kim Peter , Antonio Omuro , Chiang Veronica , Moliterno Jennifer , Omay Sacit Bulent , Piepmeier Joseph , Corbin Zachary
Published: August 2023

BACKGROUND

The Warburg Effect (WE) is a metabolic change in which tumors favor glycolysis over oxidative phosphorylation and has been linked to cancer aggressiveness. Mutations in the isocitrate dehydrogenase (IDH) genes in gliomas are associated with improved outcomes. We deployed a magnetic resonance (MR) spectroscopic imaging technique coined Deuterium Metabolic Imaging (DMI) to measure the WE in multiple brain tumor types.

METHODS

Twenty-one patients underwent DMI, acquired on a Bruker 4T MR scanner after oral administration of 0.75g/kg of deuterated glucose. The WE was defined as the ratio of deuterated lactate, representing glycolysis, over deuterated glutamate and glutamine, representing oxidative phosphorylation. We devised an interval scale from 0 to 2 for the WE

RESULTS

The Wilcoxon rank sum test was performed to detect differences between groups.

RESULTS

The WE measurements for the largest groups, by diagnosis, showed: glioblastoma (n=9, mean=1.67); astrocytoma, IDH-mutant, WHO grade 3 (n=2, mean=0.25); oligodendroglioma, WHO grade 3 (n=3, mean=0.5); low grade glioma, IDH-mutant (n=2, mean=0); and meningioma, WHO grade 2 (n=2, mean=0). The WE for high-grade tumors (n=15, mean=1.27) was significantly different from the WE for low-grade tumors (n=5, mean=0), with a p=0.010. The WE for IDH wild type gliomas (n=9, mean=1.67) was significantly different from the WE for IDH-mutant gliomas (n=9, mean=0.44), with a p=0.007. Analysis is ongoing.

CONCLUSIONS

DMI successfully and non-invasively detects the WE in many types of brain tumors. The WE was larger in high-grade tumors as compared to low-grade tumors, and the WE was larger in IDH wild type gliomas as compared to IDH-mutant gliomas. If validated with future studies, our results suggest that DMI is a useful tool to measure differences in the metabolism of brain tumors with different clinical behaviors.
SDPS-20 THE HER2 FLIP: HER2 AMPLIFICATION OF TUMOR CELLS IN THE CEREBROSPINAL FLUID (CSF-TCS) OF PATIENTS WITH LEPTOMENINGEAL METASTASIS HAVING SOLID TUMORS; IMPLICATIONS FOR TREATING THE LM TUMOR WITH ANTI-HER2 THERAPY
Authors: Kumthekar Priya , Youssef Michael , Blondin Nicholas , Azadi Amir , Piccioni David , Glantz Michael , Carillo Jose , Avgeropoulos Nicholas , Makar Sherif , Blouw Barbara , Natasha Anna , Fisher Deanna , Huynh Lan , Peters John , Sweed Nathan , Dugan Michael , Kesari Santosh
Published: August 2023

INTRODUCTION

Patients diagnosed with Leptomeningeal Metastasis (LM) have limited treatment options. However, they may benefit from targetable therapy. LM breast cancer patients with HER2 positive primary tumors treated with IT Trastuzumab experienced clinical benefit (Malani, 2020), and improved craniospinal PFS (Figura, 2019). HER2 amplification of the primary and metastatic tumors can be heterogeneous. Biocept’s CNSideTM is a CLIA validated Laboratory Developed Test and is used commercially at the discretion of Physicians to detect CSF tumor cells (CSF-TCs). We analyzed HER2 amplification on CSF-TCs in LM patients with breast-, upper GI cancer as well as Non-Small Cell Lung Cancer (NSCLC).

METHODS

CSF was collected from patients with suspected or confirmed LM having Breast Cancer (N=334 patients, N=181 evaluable), NSCLC (N=28 patients) or upper GI cancer (N=4 patients, N=2 evaluable). CSF TCs were tested for HER2 amplification by FISH using CNSide.

RESULTS

For the breast cancer patients, 38% (68/181) had HER2 FISH detected on CSF TCs, 60% (109/181) had a HER2 negative primary tumor of which 35% (38/109) had HER2 positive CSF-TCs. Furthermore, 8% (14/181) had an equivocal HER2 primary tumor, 21% (3/14) of which had HER2 positive CSF-TCs. For the NSCLC patients, 50% (14/28) showed HER2 amplification on the CSF-TCs. For the upper GI cancer patients, one patient had an equivocal HER2 primary tumor, and HER2 positive CSF-TCs.

CONCLUSION

HER2 amplification is detected on CSF-TCs of patients with LM having breast cancer, upper GI cancer or NSCLC cancer. For NSCLC patients, HER2 positivity in the LM can be associated with drug resistance. Patients who have a HER2 negative primary tumor can develop HER2 positive LM, allowing for an anti-HER2 targetable treatment. Additional studies are needed to establish the clinical utility of CNSide in the detection of HER2 on the CSF-TCs to direct treatment of anti-HER2 therapy in patients with LM.
TIPS-08 ACTION: A RANDOMIZED PHASE 3 STUDY OF DORDAVIPRONE (ONC201) IN PATIENTS WITH NEWLY DIAGNOSED H3 K27M-MUTANT DIFFUSE GLIOMA
Authors: Arrillaga-Romany Isabel , Lassman Andrew , McGovern Susan , Mueller Sabine , Nabors Louis Burt , van den Bent Martin , Vogelbaum Michael , Allen Joshua E , Melemed Allen S , Tarapore Rohinton , Wen Patrick , Cloughsey Timothy
Published: August 2023

BACKGROUND

H3 K27M-mutant diffuse midline glioma is a universally fatal malignancy primarily affecting children and young adults. While radiotherapy (RT) provides transient benefit, no effective systemic therapy is currently available and current standard of care is RT followed by monitoring. Dordaviprone (ONC201), a first-in-class imipridone, is an oral, blood-brain barrier penetrating, selective small molecule antagonist of dopamine receptor D2/3 (DRD2) and agonist of the mitochondrial protease ClpP. An integrated pooled analysis of five open-label trials previously demonstrated efficacy in dordaviprone-treated patients with recurrent disease. This phase 3 trial will be the first randomized, controlled study evaluating ONC201 in patients with H3 K27M-mutant disease.

METHODS

ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international Phase 3 study of ONC201 in patients with newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy will be randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on two consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS) in all participants; PFS will be assessed by response assessment in neuro-oncology-high grade glioma by blind independent central review. Other objectives include assessments of safety, additional efficacy endpoints, clinical benefit, quality of life, pharmacokinetics, biomarkers, and healthcare resource utilization. Eligible patients will have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility will not be restricted based on age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in the United States, with international sites opening imminently.
TIPS-17 A FIRST-IN-HUMAN FEASIBILITY STUDY TO EVALUATE THE SAFETY OF SELECTIVE INTRA-ARTERIAL YTTRIUM-90 MICROSPHERE TREATMENT IN PATIENTS WITH RECURRENT GLIOBLASTOMA (THE FRONTIER TRIAL)
Authors: Mouli Samdeep , Goyal Piyush , Tate Matthew , Dixit Karan , Primdahl Ditte , Boockvar John , Quinones-Hinojosa, Alfredo , Weiss Cliffword , Butowski Nicholas , Dreher Matthew , Stupp Roger , Salem Riad
Published: August 2023

BACKGROUND: Glioblastoma (GBM) is the most aggressive primary brain tumor that virtually always recurs with no established standard therapy at recurrence. Median survival after recurrence is 7-12 months. Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) glass microspheres (TheraSphere™, Boston Scientific, Marlborough, MA) is an FDA approved standard treatment for hepatocellular carcinoma, and represents a novel strategy to treat regionally localized brain tumors. We are conducting a first-in-human clinical trial (under IDE) using Y90 microspheres modified to treat tumors in the brain. The goal of selectively delivering Y90 intra-arterially is to achieve higher tumoral absorbed doses while limiting non-target exposure. DESIGN: The primary objective is to evaluate the safety of Y90 microspheres treatment. Target enrollment is 12 patients at 5 participating medical centers. Key inclusion criteria include: 1st or 2nd recurrence of GBM , size 1-5cm, located in the non-dominant hemisphere in a non-eloquent region, accessible neurovascular anatomy for single intra-arterial treatment based on a diagnostic cerebral angiogram. After consent, patients will undergo screening angiography and imaging that be reviewed by the trial steering committee to determine treatment suitability. Treatment consists of Y90 microspheres administered intra-arterially to deliver 40Gy ± 10% to the treatment volume. Post-administration Y90 PET and MRI images allow assessment of dose distribution and acute safety. Following overnight admission, patients will be followed as outpatients weekly x 4, and then monthly up to month 6. Primary endpoints include treatment-related limiting toxicities, dose limiting toxicity defined as non-hematological toxicities ≥ grade 3, CNS toxicity ≥ grade 3 (eg. symptomatic ischemia or edema) related to non-target embolization, occurring through 30 days post procedure. Secondary endpoints include: treatment-related serious adverse events, change in post-treatment neurological function, technical success, objective response rate, progression-free survival, and overall survival.

The study is registered with clinicaltrials.gov, number: NCT05303467.
Zoonotic Transmission of Vaccine-Derived Bordetella bronchiseptica
Authors: Kraai Imke , Knoester Marjolein , Bathoorn Erik , Bakker Martijn , Nijland Marcel
Published: August 2023

We describe a unique case of a 43-year-old-female with a Bordetella bronchiseptica infection caused by zoonotic transmission following vaccination of her dog. With this report, we want to raise awareness of potential zoonotic transmission of live attenuated vaccines from animals to patients with impaired immunity.
Reproductive roles as likely drivers of sexual dimorphism in New Zealand’s endangered mountain parrot, the Kea
Authors: McLean Lydia R W , Horton Travis W , Robertson Bruce C , Robertson Fiona , Greer Amanda L , Nelson Ximena J
Published: August 2023

New Zealand’s endangered mountain parrot, the Kea (Nestor notabilis), exhibits moderate male-biased sexual size dimorphism in linear body measurements (~5%) and a pronounced dimorphism in bill size (12–14%). Using stable isotope analyses of carbon and nitrogen in Kea feathers and blood sampled from a significant portion (~10%) of the extant population, we determined that Kea bill dimorphism may be an ecologically selected trait that enhances male Kea’s ability to forage at a higher trophic level in order to provision females and offspring during nesting. Sexual dimorphism can arise through sexual selection, ecological drivers, or a combination of both. Ecological selection is associated with foraging niche divergence between the sexes to reduce inter-sexual competition or due to differing dietary needs associated with reproductive role. Despite the widespread occurrence of sexual dimorphism throughout the animal kingdom, empirical evidence for ecological causation is rare. We conducted the first molecular confirmation of sexual size dimorphism in Kea. We then employed Bayesian mixing models to explore potential correlations between diet and bill size to determine whether the dimorphism is linked to diet partitioning throughout all age classes (fledgling, juvenile, subadult, and adult). Female Kea foraged at a consistent, relatively low, trophic level throughout their lifetime, whereas male trophic level increased with age to a maximum at subadult stage, prior to breeding for the first time—a time in which males may have been actively learning extractive foraging techniques associated with a high protein diet. Adult males foraged at a high trophic level relative to all groups except subadult males. As males provision females on the nest, which in turn provision young, these results highlight that the evolution of morphology and reproductive output may be linked in circuitous ways.
PINOID and PIN-FORMED Paralogous Genes Are Required for Leaf Morphogenesis in Rice
Authors: Liu Jiajun , Shi Xi’an , Zhong Tianhui , Jie Wanrong , Xu Ruihan , Ding Yanfeng , Ding Chengqiang
Published: August 2023

Auxin plays an essential role in modulating leaf development. However, its role in leaf development in rice (Oryza sativa L.) remains largely unknown. In this study, we found that PINOID (OsPID) and two Sister-of-PIN1s, termed PIN-FORMED1c (OsPIN1c) and OsPIN1d, are necessary for rice leaf development. The ospin1c ospin1d null mutant lines presented severe defects in leaf morphogenesis, including drooping and semi-drooping blades, an abnormally thickened sheath and lamina joint, and fused leaves with absent ligules and auricles. Loss-of-function ospid mutants displayed generally similar leaf morphology but lacked leaf fusion. Interestingly, misshaped leaf genesis displayed a preference for being ipsilateral. In addition, OsPIN1c and OsPID were commonly localized in the initiating leaf primordia. Furthermore, accompanied by the more severe organ morphogenesis in the ospin1c ospin1d ospid triple mutant, RNA sequencing analysis revealed that many genes essential for leaf development have an altered expression level. Together, this study furthers our understanding of the role auxin transport plays during leaf development in monocot rice.
Social Media Effects on Public Trust in the European Union
Authors: Kiratli Osman Sabri
Published: August 2023

This paper scrutinizes the effect of social media use on institutional trust in the European Union (EU) among European citizens. Fixed-effects regression models on data from the Eurobarometer survey conducted in 2019, the year of the most recent European Parliament (EP) elections, demonstrate that higher social media use is associated with lower trust in the EU. More importantly, social media usage habits exert particularly detrimental effects in regions with wider and faster internet connections. In such high-information environments, those who more frequently use online social networks, tend to trust those networks, and receive information on EU affairs from these networks have less faith in the EU compared to those in regions with lower-quality internet access. In contrast, in regions with lower broadband access, receiving EU information from social media fosters political trust.
Evolution of monoclonal gammopathy of undetermined significance in patients treated with JAK inhibitors for rheumatic diseases: data from the MAJIK-SFR registry
Authors: Faganello Déborah , Bertrand Anne , Meunier Pauline , Avouac Jérôme , Toussirot Eric , Coury Fabienne , Seror Raphaele , Le Mélédo Guillaume , Germain Vincent , Dellal Azedinne , Shima Ditmar , Hulin Cyrille , Prati Clément , Schaeverbeke Thierry , Richez Christophe , Truchetet Marie-Elise , Kostine Marie
Published: August 2023

Objective

Monoclonal gammopathy of undetermined significance (MGUS) is common, but there are scarce data regarding the effect of DMARDs on this premalignant condition. We aimed to evaluate the impact of JAK inhibitors (JAKis) on MGUS when initiated for an active rheumatic disease.

Methods

Patients with monoclonal abnormality prior to JAKi initiation for an active rheumatic disease were identified through the MAJIK-SFR Registry, a French multicentre prospective study. Clinical and biological data were collected using a standardized case report form.

Results

Twenty patients were identified with a mean age of 65 years and a diagnosis of RA (n = 15), PsA (n = 3), and axial SpA (n = 2). The JAKi prescribed was baricitinib (n = 9), tofacitinib (n = 6) or upadacitinib (n = 5), with a mean duration of 15.5 months. Seventeen patients had individualized serum monoclonal protein (IgG kappa n = 9; IgG lambda n = 4; IgM kappa n = 3; IgA lambda n = 1) ranging from 0.16 to 2.3 g/dl, and three patients did not have an initial measurable spike but they had a positive serum immunofixation. With a follow-up of 4–28 months, the serum monoclonal protein level decreased in 8 of 17 patients (47%), remained stable in 8 patients (47%) and increased in 1 patient (6%). The maximal decrease observed was an initial IgG kappa of 2.3 g/dl, decreasing to 0.2 g/dl at month 14.

Conclusion

This study provides reassuring and promising data on MGUS evolution in patients treated with JAKis for rheumatic diseases, which may guide the choice of treatment in patients with both conditions.
Uncovering the Heterogeneity of Cardiac Lin−KIT+ Cells: A scRNA-seq Study on the Identification of Subpopulations
Authors: Shen Yan , Kim Il-Man , Tang Yaoliang
Published: August 2023

The reparative potential of cardiac Lin–KIT+ (KIT) cells is influenced by their population, but identifying their markers is challenging due to changes in phenotype during in vitro culture. Resolving this issue requires uncovering cell heterogeneity and discovering new subpopulations. Single-cell RNA sequencing (scRNA-seq) can identify KIT cell subpopulations, their markers, and signaling pathways. We used 10× genomic scRNA-seq to analyze cardiac-derived cells from adult mice and found 3 primary KIT cell populations: KIT1, characterized by high-KIT expression (KITHI), represents a population of cardiac endothelial cells; KIT2, which has low-KIT expression (KITLO), expresses transcription factors such as KLF4, MYC, and GATA6, as well as genes involved in the regulation of angiogenic cytokines; KIT3, with moderate KIT expression (KITMOD), expresses the cardiac transcription factor MEF2C and mesenchymal cell markers such as ENG. Cell-cell communication network analysis predicted the presence of the 3 KIT clusters as signal senders and receivers, including VEGF, CXCL, and BMP signaling. Metabolic analysis showed that KIT1 has the low activity of glycolysis and oxidative phosphorylation (OXPHOS), KIT2 has high glycolytic activity, and KIT3 has high OXPHOS and fatty acid degradation activity, indicating distinct metabolic adaptations of the 3 KIT populations. Through the systemic infusion of KIT1 cells in a mouse model of myocardial infarction, we observed their involvement in promoting the formation of new micro-vessels. In addition, in vitro spheroid culture experiments demonstrated the cardiac differentiation capacity of KIT2 cells.
Disability Justice and the Americans with Disabilities Act: An Opportunity for Social Work
Authors: Muster Caroline L
Published: August 2023

According to the Centers for Disease Control and Prevention, over 61 million Americans have a disability, which translates to about 26 percent of the national population. The most common types of disability are physical (13.7 percent), or those that impact mobility, and intellectual (10.8 percent), or those related to cognitive processing. The Bureau of Justice Statistics has reported that 32 percent of people in state prisons and 40 percent of people in county jails have at least one disability, rates that demonstrate alarming disproportionality. Yet the history of the disability rights movement, the impact of the Americans with Disabilities Act for people with disabilities who are involved with the criminal justice system, and the implications of disability justice and critical disability theory for the field of social work are not well understood. The purpose of this article is to review these under-recognized topics and offer recommendations for addressing this neglected area of social work education, research, policy, and practice.
Interleukin-17A Promotes Proliferation and Osteogenic Differentiation of Human Ligamentum Flavum Cells Through Regulation of β-Catenin Signaling
Authors: Lin Jialiang , Jiang Shuai , Xiang Qian , Zhao Yongzhao , Wang Longjie , Fan Dongwei , Zhong Woquan , Sun Chuiguo , Chen Zhongqiang , Li Weishi
Published: August 2023

Study Design.

A basic experimental study.

Objective.

To elucidate the role and mechanism of interleukin (IL)-17A in thoracic ossification of the ligamentum flavum (TOLF).

Summary of Background Data.

TOLF is characterized by the replacement of the thoracic ligamentum flavum with ossified tissue and is one of the leading causes of thoracic spinal stenosis. IL-17A is an important member of the IL-17 family that has received widespread attention for its key contributions to the regulation of bone metabolism and heterotopic ossification. However, it is unclear whether IL-17A is involved in TOLF.

Materials and Methods.

Cell counting kit‐8 assay and 5-ethynyl-2’-deoxyuridine staining were performed to assess the proliferation of ligamentum flavum cells (LFCs). Alkaline phosphatase activity assay, Alizarin red staining, and protein level expression of osteogenic-related genes were used to evaluate the osteogenic differentiation potential of LFCs. The effect of IL-17A on the proliferation and osteogenic differentiation of LFCs was further assessed after silencing β-catenin by transfection with small interfering RNA. In addition, the possible source of IL-17A was further demonstrated by coculture assays of T helper 17 (Th17) cells with LFCs. Student t test was used for comparisons between groups, and the one-way analysis of variance, followed by the Tukey post hoc test, was used for comparison of more than two groups.

Results.

IL-17A was elevated in TOLF tissue compared with normal ligamentum flavum. IL-17A stimulation promoted the proliferation and osteogenic differentiation of LFCs derived from patients with TOLF. We found that IL-17A promoted the proliferation and osteogenic differentiation of LFCs by regulating the β-catenin signaling. Coculture of Th17 cells with LFCs enhanced β-catenin signaling-mediated proliferation and osteogenic differentiation of LFCs. However, these effects were markedly attenuated after the neutralization of IL-17A.

Conclusions.

This is the first work we are aware of to highlight the importance of IL-17A in TOLF. IL-17A secreted by Th17 cells in the ligamentum flavum may be involved in the ossification of the microenvironment by regulating β-catenin signaling to promote the proliferation and osteogenic differentiation of LFCs.
The Plastic Surgery In-service Training Examination: An In-depth Reference Analysis
Authors: Meaike Jesse D. , Asaad Malke , Cantwell Sean , Elmorsi Rami , Jabal Mohamed Sobhi , Moran Steven L.
Published: August 2023

Background:

The goal of this study was to characterize the references provided as supporting evidence of the Plastic Surgery In-service Training Examination (PSITE) syllabi, including those on the novel “core surgical principles” section.

Methods:

We analyzed the references from five consecutive PSITE Examination syllabi (2016–2020). We collected the following information from each question: question section, total number of references, and source of publication of each reference.

Results:

We analyzed 1250 questions and 3436 references. Plastic and Reconstruction Surgery was overall the most frequently referenced journal followed by Journal of Hand Surgery (American Volume) and Annals of Plastic Surgery. The most commonly referenced textbooks were Plastic Surgery (by Neligan), Green’s Operative Hand Surgery, and Grabb and Smith’s Plastic Surgery. Regarding the “core surgical principles” section, Plastic and Reconstruction Surgery remained the most frequently cited journal, followed by the Journal of the American Medical Association, New England Journal of Medicine, Annals, and Aesthetic Surgery Journal. “Core surgical principles” contained the largest number of unique journals (n = 209) among all test sections. Within the “core” section, Statistics in Medicine was the most frequently referenced textbook followed by Grabb and Smith’s Plastic Surgery.

Conclusions:

The main plastic surgery texts and literature were used to support approximately half of the answers within the “core surgical principles” section. The references within this section originated from the largest number of different journals, thus highlighting the breadth and variety of this content and the challenges in preparing for this section.