bluuebunny/crossref_metadata_2025 huggingface dataset:
The temporal and spatial variations of lithium abundance in the Galactic disc
Authors: Sun Tiancheng , Bi Shaolan , Chen Xunzhou , Lu Yuxi (Lucy) , Chen Yuqin , Ding Ming-Yi , Shi Jianrong , Yan Hongliang , Ge Zhishuai
Published: November 2024

This study investigates the temporal and spatial variations in lithium abundance within the Milky Way using a sample of 22 034 main-sequence turn-off (MSTO) stars and subgiants, characterized by precise stellar ages, 3D non-local thermodynamic equilibrium lithium abundances, and birth radii. Our results reveal a complex variation in lithium abundance with stellar age: a gradual increase from 14 to 6 Gyr, followed by a decline between 6 and 4.5 Gyr, and a rapid increase thereafter. We find that young Li-rich stars (ages $\lt $ 4 Gyr, A(Li) $\gt $ 2.7 dex) predominantly originate from the outer disc. By binning the sample according to guiding centre radius and z$_{\rm max}$, we observe that these young Li-rich stars migrate radially to the local and inner discs. In addition, the stars originating from the inner disc experienced a rapid Li enrichment process between 8 and 6 Gyr. Our analysis suggests that the age range of Li-dip stars is 4–5 Gyr, encompassing evolution stages from MSTO stars to subgiants. The Galactic radial profile of A(Li) (with respect to birth radius), as a function of age, reveals three distinct periods: 14–6 Gyr ago, 6–4 Gyr ago, and 4–1 Gyr ago. Initially, the lithium abundance gradient is positive, indicating increasing Li abundance with birth radius. During the second period, it transitions to a negative and broken gradient, mainly affected by Li-dip stars. In the final period, the gradient reverts to a positive trend.
Portraits of Galeommatoidea
Authors: Bouchet Philippe , Strong E E
Published: November 2024

Galeommatoidea are bivalves with small (usually 1–15 mm), fragile, sometimes vestigial, shells, occurring free-living or in association with other benthic invertebrates from the intertidal to depths in excess of 7,000 m. They are the most diverse but least studied and most underrepresented group of bivalves in biodiversity surveys and museum collections. The majority of commensal species of Galeommatoidea have dull, frequently uncoloured, unsculptured shells, but free-living species have papillate, sometimes coloured, mantles; they can be gregarious, and superficially resemble crawling gastropods. Many species of Galeommatoidea remain to be discovered, and we argue that future descriptions of free-living new species should ideally include photos of living animals, while many of the historically known species described based on their shells will probably be best treated as nomina dubia.
Metals in the gut: microbial strategies to overcome nutritional immunity in the intestinal tract
Authors: Egan Marisa S , de Macedo Raquel , Zackular Joseph P
Published: November 2024

Trace metals are indispensable nutritional factors for all living organisms. During host-pathogen interactions, they serve as crucial resources that dictate infection outcomes. Accordingly, the host uses a defense strategy known as nutritional immunity, which relies on coordinated metal chelation to mitigate bacterial advances. In response, pathogens employ complex strategies to secure these resources at sites of infection. In the gastrointestinal (GI) tract, the microbiota must also acquire metals for survival, making metals a central line of competition in this complex ecosystem. In this minireview, we outline how bacteria secure iron, zinc, and manganese from the host with a focus on the GI tract. We also reflect on how host dietary changes impact disease outcomes and discuss therapeutic opportunities to target bacterial metal uptake systems. Ultimately, we find that recent discoveries on the dynamics of transition metals at the host-pathogen-microbiota interface have reshaped our understanding of enteric infections and provided insights into virulence strategies, microbial cooperation, and antibacterial strategies.
European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection
Authors: Sahm Felix , Bertero Luca , Brandner Sebastian , Capper David , Goldbrunner Roland , Jenkinson Michael D , Kalamarides Michel , Lamszus Katrin , Albert Nathalie L , Mair Maximilian J , Berghoff Anna S , Mawrin Christian , Wirsching Hans-Georg , Maas Sybren L N , Raleigh David R , Reifenberger Guido , Schweizer Leonille , Suwala Abigail K , Tabatabai Ghazaleh , Tabouret Emeline , Short Susan , Wen Patrick Y , Weller Michael , Le Rhun Emilie , Wesseling Pieter , van den Bent Martin , Preusser Matthias
Published: November 2024

Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4,  ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I (“ready for clinical use”) classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II (“investigational”) classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.
Stratification economics: historical origins and theoretical foundations
Authors: Davis John B
Published: November 2024

Stratification economics (SE) investigates how economies are organized around group inequalities, especially by race and gender but also by ethnicity, national origin, religion, sexual orientation, etc. Its historical origins and theoretical foundations have both a structural strand that addresses how and a social behavioural strand. SE’s structural strand goes back to Ricardo and Marx regarding the relationship between growth and distribution, and then draws on recent economic theory of noncompeting groups and dual economy models of labour market segmentation. SE’s structural strand produces an inequality-based understanding of economics’ standard goods taxonomy. The social behavioural strand builds on Du Bois’s psychological wage concept, Veblen’s social ladders theory of emulation, Blumer’s theory of prejudice and stereotyping, and current social identity theory. SE’s social behavioural strand makes it possible to explain how discrimination selectively stigmatizes people’s social identities in order to reinforce existing intergroup inequalities.
Sixty years of the Voting Rights Act: progress and pitfalls
Authors: Bernini Andrea , Facchini Giovanni , Tabellini Marco , Testa Cecilia
Published: November 2024

We review the literature on the effects of the 1965 Voting Rights Act (VRA), which removed formal restrictions to Black political participation. After a brief description of racial discrimination suffered by Black Americans since Reconstruction, we introduce the goals that the VRA was meant to achieve. Next, we discuss the local level impact of the law on political participation and representation, on public goods provision and policing practices, and on labour market outcomes. We then turn to Whites’ reactions, from political realignment to electoral counter-mobilization to changes in voting rules and arrests patterns. We conclude by discussing how the evidence reviewed in this article can inform policy-making and the design of legislation aimed at reducing racial discrimination and inequality.
The continuing significance of Oliver Cox’s Caste, Class, and Race
Authors: McAuley Christopher
Published: November 2024

Despite being a major study that compares India’s caste system to the system of racial stratification in the United States, Oliver C. Cox’s Caste, Class, and Race continues to be largely under-appreciated and under-explored by scholars of both systems. This article re-evaluates Cox’s contributions to social theory by putting him into conversation with Isabel Wilkerson, Bhimrao Ambedkar, and Gunnar Myrdal. Cox, like Ambedkar, concluded that, despite occasional similarities, caste and racial systems were products of two distinct pasts with distinct objectives. Whereas the caste system emerged from a variant of an estate society akin to European feudalism, the modern racial system is an outgrowth of capitalism, according to Cox. However, what Cox failed to consider in his theory of the caste system is the degree to which its expansion and institutionalization over the Indian subcontinent were also modern phenomena.
Ethnic minority and migrant pay gaps over the life-cycle
Authors: Hall Tessa , Manning Alan , Rose Rebecca
Published: November 2024

It is well-known that ethnic minority and migrant workers have lower average pay than the White UK-born workforce. However, we know much less about how these gaps vary over the life-cycle because of data limitations. We use new data that combine a 1999–2018 panel from the Annual Survey of Hours and Earnings (ASHE) with individual characteristics from the 2011 Census in England and Wales. We investigate pay gaps on labour market entry and differences in pay growth. We find that differences in entry pay gaps are more important than differences in pay growth. The entry pay gaps are large, though vary across groups. The pay penalties on labour market entry can, to a considerable degree, be explained by over-representation in lower-paying firms and, within firms, in lower-paying occupations. For most groups, the pay gaps at entry seem to be largely preserved over the life-cycle, neither narrowing nor widening. For migrants, we find that the extra pay penalty is concentrated almost exclusively in those who arrived in the UK at later ages.
The long-run impacts of banning affirmative action in US higher education
Authors: Antman Francisca M , Duncan Brian , Lovenheim Michael
Published: November 2024

This paper estimates the long-run impacts of banning affirmative action on men and women from under-represented minority (URM) racial and ethnic groups in the United States. Using data from the US Census and American Community Survey, we use a difference-in-differences framework to compare the college degree completion, graduate degree completion, earnings, and employment of URM individuals to non-URM individuals before and after affirmative action bans went into effect across several US states. We also employ event study analyses and alternative estimators to confirm the validity of our approach and discuss the generalizability of the findings. Results suggest that banning affirmative action results in a decline in URM women’s college degree completion, earnings, and employment relative to non-Hispanic White women, driven largely by impacts on Hispanic women. Thus, affirmative action bans resulted in an increase in racial/ethnic disparities in both college degree completion and earnings among women. Effects on URM men are more ambiguous and indicate significant heterogeneity across states, with some estimates pointing to a possible positive impact on labour market outcomes of Black men. These results suggest that the relative magnitude of college quality versus mismatch effects vary for URM men and women and highlight the importance of disaggregating results by gender, race, and ethnicity. We conclude by discussing how our results compare with others in the literature and directions for future research.
The colour-blind approach to discrimination and inequality: the case of France
Authors: Govind Yajna , Santini Paolo
Published: November 2024

The colour-blind approach to data collection has long been debated. The lack of ethno-racial information in surveys and administrative data impedes researchers from studying the level of inequality and discrimination against minorities. As an alternative to ethno-racial information, the use of factual information such as parents’ place of birth has been proposed. In this paper, we discuss the colour-blind approach in France and review the evidence of discrimination based on origins. Using the Trajectories and Origins survey, we propose a novel index capturing the degree of individuals’ alterity, and we present evidence that it is associated with a penalty in the labour market. Exploiting this index, we further investigate whether information on parents’ place of birth is valuable and adequate to measure population diversity.
Caste, class, race, and inequality: insights for economic policy
Authors: Darity William A , Ruiz Isabel
Published: November 2024

Disparities across social identity groups (such as race, caste, and ethnicity) are a global phenomenon, where significant differences in wealth and other socioeconomic outcomes are observed. Although the contexts and historical roots of these differences vary by country, there are common factors—particularly arising at the intersection of social identity and social class—that help explain the persistence of these inequalities. This issue of the Oxford Review of Economic Policy examines various dimensions of inequality tied to intergroup disparities and social hierarchy, drawing insights from policy responses across different contexts, countries, and regions. The article introduces stratification economics as a framework to understand these shared global patterns. It further reviews the papers published in the issue that explore topics such as social mobility, labour market discrimination, social exclusion, the role of artificial intelligence, the challenges associated with the interpretation and application of the law, the importance of data collection, and the role of existing and potential policy interventions (e.g. affirmative action and reparations) to address these persistent inequalities.
Modeling protoplanetary disk heating by planet-induced spiral shocks
Authors: Ono Tomohiro , Okamura Tatsuki , Okuzumi Satoshi , Muto Takayuki
Published: November 2024

We investigate the heating of protoplanetary disks caused by shocks associated with spiral density waves induced by an embedded planet. Using two-dimensional hydrodynamical simulations, we explore the dependence of shock heating rates on various disk and planetary parameters. Our results show that the shock heating rates are primarily influenced by the planet’s mass and the disk’s viscosity, while being insensitive to the thermal relaxation rate and the radial profiles of the disk’s surface density and sound speed. We provide universal empirical formulas for the shock heating rates produced by the primary and secondary spiral arms as a function of orbital radius, viscosity parameter $\alpha$, and planet-to-star mass ratio $q$. The obtained formulas are accurate within a factor of a few for a moderately viscous and adiabatic disk with a planet massive enough that its spiral arms are strongly nonlinear. Using these universal relations, we show that shock heating can overwhelm viscous heating when the disk viscosity is low ($\alpha \lesssim 10^{-3}$) and the planet is massive ($q \gtrsim 10^{-3}$). Our empirical relations for the shock heating rates are simple and can be easily implemented into radially one-dimensional models of gas and dust evolution in protoplanetary disks.
Viscoelastic hydrogel combined with dynamic compression promotes osteogenic differentiation of bone marrow mesenchymal stem cells and bone repair in rats
Authors: Yang Chao , Cai Wenbin , Xiang Pan , Liu Yu , Xu Hao , Zhang Wen , Han Fengxuan , Luo Zongping , Liang Ting
Published: November 2024

A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour. Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair. However, the detailed mechanism of the mechanical regulation remains ambiguous. In addition, TRPV4 is involved in bone development. Therefore, this study aims to construct a viscoelastic hydrogel combined with dynamic compressive loading and investigate the effect of the dynamic mechanical environment on the osteogenic differentiation of stem cells and bone repair in vivo. The role of TRPV4 in the mechanobiology process was also assessed. A sodium alginate–gelatine hydrogel with adjustable viscoelasticity and good cell adhesion ability was obtained. The osteogenic differentiation of BMSCs was obtained using the fast stress relaxation hydrogel and a smaller compression strain of 1.5%. TRPV4 was activated in the hydrogel with fast stress relaxation time, followed by the increase in intracellular Ca2+ level and the activation of the Wnt/β-catenin pathway. The inhibition of TRPV4 induced a decrease in the intracellular Ca2+ level, down-regulation of β-catenin and reduced osteogenesis differentiation of BMSCs, suggesting that TRPV4 might be the key mechanism in the regulation of BMSC osteogenic differentiation in the viscoelastic dynamic mechanical environment. The fast stress relaxation hydrogel also showed a good osteogenic promotion effect in the rat femoral defect model. The dynamic viscoelastic mechanical environment significantly induced the osteogenic differentiation of BMSCs and bone regeneration, which TRPV4 being involved in this mechanobiological process. Our study not only provided important guidance for the mechanical design of new biomaterials, but also provided a new perspective for the understanding of the interaction between cells and materials, the role of mechanical loading in tissue regeneration and the use of mechanical regulation in tissue engineering.
Endostatin-expressing endometrial mesenchymal stem cells inhibit angiogenesis in endometriosis through the miRNA-21-5p/TIMP3/PI3K/Akt/mTOR pathway
Authors: Cheng Yan , Guo Qiuyan , Cheng Yulei , Wang Dejun , Sun Liyuan , Liang Tian , Wang Jing , Wu Han , Peng Zhibin , Zhang Guangmei
Published: November 2024

Endometriosis is a chronic inflammatory and neoangiogenic disease. Endostatin is one of the most effective inhibitors of angiogenesis. Mesenchymal stem cells (MSCs) have been investigated as compelling options for cell therapy. However, the effect and mechanism of action of endostatin-expressing endometrial MSCs (EMSCs) in endometriosis are unclear. Here, EMSCs were genetically modified to overexpress endostatin (EMSCs-Endo). A reduction in the angiogenic capacity of HUVECs was observed in vitro after treatment with EMSCs-Endo. EMSCs-Endo significantly suppressed endometriotic lesion growth in vivo. The limited efficacy was associated with suppressed angiogenesis. The miRNA-21-5p level and the levels of p-PI3K, p-mTOR, and p-Akt in HUVECs and mouse endometriotic lesions significantly decreased after treatment with EMSCs-Endo, whereas TIMP3 expression significantly increased. In summary, targeted gene therapy with EMSCs-Endo is feasible, and its efficacy in regulating endometriosis can be attributed to the inhibition of angiogenesis, suggesting that EMSCs could be used as promising vehicles for targeted gene therapy.
What Perioperative Factors Are Associated With High-risk Daily Morphine Milligram Equivalent Totals in Spinal Decompressions?
Authors: Truumees Eeric , Duncan Ashley , Singh Devender , Geck Matthew J. , Adindu Ebubechi , Stokes John K.
Published: November 2024

Study Design/Setting:

Retrospective cohort analysis.

Objective:

To determine what factors are associated with high-risk daily morphine milligram equivalent (MME) totals in patients undergoing spinal decompression.

Background:

Daily dosages of ≥100 MME/d are associated with an almost 9-fold increased risk of overdose. Current general recommendations endorse the lowest effective dose and ≤50 MME/d.

Materials and Methods:

Retrospective analysis was conducted on 260 patients who underwent spinal decompressive surgery. Average MME/d was calculated as the sum of qualifying inpatient MMEs administered divided by the sum of inpatient length of stay. Independent variables across demographic, clinical, and surgical domains were subject to comparative and logistic regression analysis.

Results:

Overall MME per day was 54.19 ± 39.37, with a range of 1.67–218.34 MME/d. Sixty-six patients were determined to have “high-risk MME.” These patients were significantly younger (58.8 ± 13.1 vs 70.53 ± 11.5; P < 0.001) and reported higher preoperative pain visual analog scale (VAS; 4.8 ± 3 vs 2.8 ± 3.3; P = 0.0021) than the patients at low risk. In addition, high-risk patients had significantly higher body mass indexes (BMIs; P < 0.05) and received ketamine as part of anesthesia (P < 0.05). Patients who consumed high-risk dosages of MMEs in the perioperative period were more likely to have been on opioids before surgery and to report higher pain scores at 4–6 week follow-ups (P < 0.05). The final logistics regression model identified independent risk factors to be younger age, higher BMIs and preoperative VAS, and prior use of opioids and intraoperative ketamine.

Conclusions:

Patients with high MME per day who underwent spinal decompression were significantly younger with higher BMIs and preoperative VAS with an increased incidence of preoperative opioid use and intraoperative ketamine. A closer look at interaction models revealed that a combination of high preoperative pain and intraoperative ketamine usage were at a significantly increased risk of higher MME consumption. Preoperative opioid risk education and mitigation strategies should be considered in patients with high MME risk, especially in younger patients already utilizing opioids before surgery.
Induction of neuronal differentiation in glioma cells by histone deacetylase inhibitors based on Connectivity Map discovery
Authors: Tang Zhao-Qi , Xu Hong-Bin , Cao Chang , Liu Yue-Jin , Ye Yan-Rong , Shen Yun
Published: November 2024

Neuron conversion leads to proliferation inhibition of glioma cells and may be an effective strategy to combat glioma and prevent recurrence. In this study, drug repositioning based on Connectivity Map (CMap) was conducted to discover drugs that could induce the differentiation of glioma cells into neuron-like cells, complemented by in vitro experimental validation. Downregulated neuronal genes in glioma were identified by the Human Protein Atlas database and the GeneCards database, and enrichment analysis and Gene Expression Profiling Interactive Analysis (GEPIA) were performed to ensure their reliability before they were uploaded to CMap for drug screening. The potential drug targets were screened through GEPIA and validated by the Chinese Glioma Genome Atlas database. Cell morphology, proliferation, and neuronal marker expression were detected to evaluate the differentiation-inducing effect of the selected drugs. The bioinformatics analysis identified histone deacetylase (HDAC) inhibitors as potential drugs. HDAC1/3/7 showed the relationship with neuronal genes, and HDAC1 showed the highest level of inverse correlation with neuronal gene expression and had the highest hazard ratio. In vitro study showed that both the pan-HDAC inhibitor belinostat, class I and class IIa HDAC inhibitor valproic acid, and selective HDAC1 inhibitor parthenolide induce morphology alteration, proliferation inhibition, expression of neuronal markers including microtubule-associated protein 2, neuronal nuclei antigen, and synaptophysin in U87 cells. This study suggests that the HDAC inhibitors belinostat, valproic acid, and parthenolide can induce glioma cells to differentiate into neuron-like cells, with HDAC1/3/7 being the likely drug targets and HDAC1 potentially playing an important role in this.
Sorafenib as maintenance therapy in FLT3+ acute myeloid leukemia post allogeneic transplantation: a case report
Authors: Martín Roldán Alicia , Alarcón-Payer Carolina , Sánchez Suárez María Del Mar , Jiménez Morales Alberto
Published: November 2024

This case report highlights sorafenib as maintenance therapy postallogeneic hematopoietic stem cell transplantation (allo-HSCT) in a young patient with acute myeloid leukemia (AML) with FMS-like tirosine kinase-3 (FLT3)-internal tandem duplication (ITD) mutation. Given the high relapse risk in FLT3-ITD–positive AML, the tyrosine kinase inhibitor sorafenib was administered. Several studies have shown that sorafenib improves survival in younger AML patients when combined with chemotherapy, though side effects can limit use in older patients. Sorafenib is increasingly significant after allo-HSCT maintenance, offering a promising option for high-risk AML cases. In this case, the patient achieved long-term remission with minimal side effects.
Association of the number of pregnancies and births with cognitive performance in older postmenopausal women: a cross-sectional study
Authors: Zhao Yue , Li Kaixin , Peng Junge , Xiao Jiang , Zhang Mengying , Mo Hongfei , Wang Guirong , Li Yan
Published: November 2024

Objective

Cognitive impairment in the elderly is a serious public health problem. However, the effect of the number of pregnancies and births in the early years of life on cognitive function in postmenopausal women remains controversial. This study aims to investigate the relationship between these two factors.

Methods

We used the National Health and Nutrition Examination Survey 2011-2014 data on women aged ≥60 years. This study included sociodemographic data, history of estrogen use, and contraceptive use as confounding variables. The combined scores of the Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL), delayed word recall (CERAD-DR), the Animal Fluency test (AF), and the Digit Symbol Substitution Test (DSST) were used to assess the cognitive performance of participants. Hierarchical multiple regression analysis explored the relationship between the number of pregnancies and births and cognitive function.

Results

The study screened 1,259 postmenopausal women and found that 24.3% had low cognitive performance. The study found a significant increase in low cognitive performance among older adults, Mexican Americans, those with a lower education level and poverty-income ratio, those who were widowed, and those with diabetes and hypertension (P < 0.001). In the multiple regression analysis, the number of pregnancies remained a significant determinant of cognitive performance (B = −0.188, P < 0.001).

Conclusions

The number of pregnancies was associated with cognitive performance in a population of postmenopausal women in the United States. A lower number of pregnancies is associated with better cognitive performance.
Identifying Preferences for Exercise and Sport in Australians With Mild Multiple Sclerosis: Looking Beyond Clinical Characteristics when Implementing Exercise Interventions
Authors: Baynton Shavaughn L. , Mavropalias Georgios , Inderpreet Kaur , van Rens Fleur , Learmonth Yvonne C.
Published: November 2024

Objective:

Exercise is a salient component in delaying disability progression in multiple sclerosis (MS). This study considers personal preferences regarding exercise program prescription and the resources needed to facilitate exercise.

Design:

Cross-sectional study.

Setting:

Community online, Australia.

Participants:

Adults with MS.

Independent variables:

Participants completed online questionnaires on current exercise and sport, and preferences toward exercise prescription variables, facilitative resource needs, and delivery method.

Main outcomes:

We established preference responses for the entire sample, and separately, we used logistic regression and analysis of variance to compare preferences between participants stratified according to (1) geographical rurality (ie, metro vs rural and remote) and (2) current exercise engagement (ie, active, moderately active, and insufficiently active).

Results:

Fifty people with a diagnosis of MS completed the survey. Participants had mild disability; most were metro-dwelling (74%) and physically active (58%). Preferences included a program of at least 6 months (70%), where exercise sessions are performed 5 d/wk (38%) at a moderate intensity (50%). Half (50%) of responders wanted to participate in sports for exercise. There was a significant difference in the preference toward higher-intensity exercise in active persons compared with inactive persons. Facilitative resources selected included a behavioral exercise coach (80%) who provides MS-specific information (46%) and behavioral change strategies (41%).

Conclusions:

Persons with mild MS are interested in participating in various exercises and sports. Encouraging participation will have long-term benefits. We recommend that HCPs and researchers consider individual social factors, in addition to patient symptoms and disability, when designing exercise programs for an Australian MS population.
Atypical Teratoid Rhabdoid Tumor of the Brain in a Young Adult With Down Syndrome: Case Report and Literature Review
Authors: Judd Dallin , Almefty Kaith K. , Vern-Gross Tamara Z. , Hoffman Lindsey M. , Abdullaev Zied Kh. , Quezado Martha M. , Aldape Kenneth D. , Tiwari Nishant , Vaughn Jennifer A. , Mangum Ross
Published: November 2024

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive, malignant embryonal tumor with dismal long-term survival despite aggressive multimodal therapy. While this tumor typically presents in infancy or early childhood, there are published case reports of adult-onset ATRT. Making prognostic conclusions or therapeutic decisions for this older patient population remains challenging due to the paucity of these reports. A 25-year-old female with Down syndrome presented with dysphagia and facial droop and was found to have an avidly enhancing, cerebellopontine angle mass. Histology demonstrated sheets of rhabdoid cells with loss of INI1 expression, pathognomonic for ATRT. Further sequencing detected a frameshift SMARCB1 mutation and methylation profiling matched with high confidence to the MYC subclass of ATRT. The patient was treated with subtotal surgical resection and focal proton beam irradiation, followed by chemotherapy on a modified regimen due to concern for heightened risk of treatment-related toxicity. On most recent follow-up 22 months from diagnosis, the patient remains without evidence of disease. This report represents the first known case of ATRT in a young adult patient with Down syndrome, offering unique mechanistic insight into the tumorigenesis of ATRT. Further studies are needed to define an appropriate risk-adapted and standardized therapeutic approach for this patient population.
Neonatal Mastitis
Authors: Kaplan Ron L.
Published: November 2024

Mastitis is an uncommon but potentially serious infection in neonates. Characteristic findings include erythema, induration, and tenderness around the breast bud. Fluctuance and purulent drainage may be present with abscess formation. Fever and signs of systemic illness may occur, or there may only be signs of localized soft tissue infection. Until recently, there have been very few cohort studies of neonatal mastitis in high-income countries, and no literature available regarding the incidence of concurrent serious bacterial infection such as meningitis or urinary tract infection. A recent large, multicenter study suggests that most neonatal mastitis presents as localized soft tissue infection, with very low rates of concurrent serious bacterial infection or adverse outcomes. Treatment of neonatal mastitis consists primarily of antibiotic administration. Surgical intervention, such as incision and drainage or intraoperative debridement, may be needed for frank abscesses. While antibiotics are typically administered intravenously, there may be a role for oral antibiotics in some lower risk infants with mastitis.
18F-FDG PET/CT Incidental Finding of Rare Extrapulmonary Presentation of Mycobacterium tuberculosis
Authors: Ranes Jennifer M. C. , Ormaza Ana J. , Desai Charismas , Tewari Sanjit O. , Flynt Lesley
Published: November 2024

A 41-year-old woman presented with a left breast mass for which mammography was performed. Mammogram revealed a suspicious BI-RADS 4, palpable left breast mass with associated nipple retraction. As malignancy was suspected, the patient underwent breast MRI and 18F-FDG PET/CT for staging. Multiple ultrasound guided biopsies were then performed of the left breast, left axillary lymph nodes, and left cervical lymph nodes. Final pathology was negative for malignancy, but final cultures grew Mycobacterium tuberculosis (Tb). The patient was initially intolerant to frontline medications, but eventually successfully treated with isoniazid, ethambutol, pyrazinamide, and moxifloxacin, as demonstrated by posttreatment mammography.
Diffuse Peritoneal Carcinomatosis of Prostate Cancer Unveiled by [89Zr]Zr-PSMA-617 PET/CT
Authors: Bastian Moritz B. , Burgard Caroline , Blickle Arne , Ezziddin Samer , Rosar Florian
Published: November 2024

We report an interesting case of a 64-year-old man with a history of radical prostatectomy for prostate cancer. The patient presented with steady increasing prostate-specific antigen levels, but with negative findings on previous multiple conventional prostate-specific membrane antigen (PSMA) PET/CT (with [68Ga]Ga-PSMA-11) and [18F]FDG PET/CT. A recently introduced PSMA tracer using long-lived 89Zr (half-life 3.3 days), [89Zr]Zr-PSMA-617, was administered in attempt to localize potential local recurrence or metastasis. [89Zr]Zr-PSMA-617 PET/CT clearly revealed diffuse peritoneal carcinomatosis and local recurrence of the prostate cancer, which were unidentified on previous conventional PET/CT scans. This case highly demonstrates the potential of PET imaging with the novel PSMA tracer [89Zr]Zr-PSMA-617.
Validity of Presurgery cTNM- and UICC-status in Patients With Oral Squamous Cell Carcinoma (OSCC)
Authors: Thoenissen Philipp , Burck Iris , Winkelmann Ria , Sader Robert , Ghanaati Shahram
Published: November 2024

Aim:

In treating patients with oral squamous cell carcinoma (OSCC), therapy decisions are regularly made in interdisciplinary oncologic board meetings that rely on the synopsis of clinical examinations and structured clinical imaging modalities. In many cases, postsurgical results differed from those of the initial assessment. Therefore, this study compared presurgical and postsurgical tumor stages according to tumor, node, metastasis (TNM), and Union Contre le Cancer (UICC) classifications to find a better assessment of the real tumor stage.

Materials and Methods:

In a retrospective analysis from January 2014 to December 2020, patients who underwent primary tumor resection of OSCC and bilateral neck dissection (ND) according to the recommendations of an interdisciplinary oncologic board meeting at a university head and neck tumor center were included. Patients underwent local and cervical clinical examinations, computed tomography (CT), and magnetic resonance imaging (MRI) of the head and neck, followed by surgery and pathological examination.

Results:

: The cTNM/UICC classification of 168 patients were compared against their postsurgical pTNM and subsequent UICC classifications. In 51.19% of all cases, intra- individual differences in the comparison of the pre- and postsurgery TNM/UICC-classification were found. Testing between cUICC and pUICC shows moderate concordance according to Cohen’s Kappa (95% CI) with 0.42 (0.30-0.55; p<0.001).

Conclusion:

Concordance between pretherapeutic staging and the exact postsurgical status in patients with OSCC is lacking. Therefore, the further development of improved staging modalities is required. The opinion of the surgeon must be considered in the correct therapy proposal.
Next-generation Robotics in Otology: The HEARO Procedure
Authors: Tekin Ahmet M. , Bleys Ronald L. A. W. , Matulic Marco , Assadi Masoud Zoka , van de Heyning Paul , Bahşi İlhan , Topsakal Vedat
Published: November 2024

Background:

In a world that is globalizing and centered on rapid communication, hearing impairment is one of the most common disabilities. The most effective and successful neural prosthesis in humans for treating the dysfunction of a sensory organ is cochlear implantation. The minimally invasive placement of the array in the cochlea should warrant the rehabilitation of profound hearing loss over all frequencies. Some key factors for structure and hearing preservation consist of minimal invasive drilling in the temporal bone and tailored inner ear access. Next-generation Robotically Assisted Cochlear Implantation Surgery (RACIS) focuses on robotic inner ear access. The purpose of this cadaveric preclinical study was to assess the viability and precision of a novel technology (the HEARO method) for RACIS, or more particularly, personalized robotic inner ear access.

Methods:

The external auditory canal, chorda tympani, ossicles, facial nerve, and other pertinent anatomical components were all 3-dimensional (3D)-reconstructed by the surgeon. The mean intended distance and drilling trajectory to the chorda tympani and facial nerve were, respectively, 0.44±0.13 and 0.35±0.27 mm.

Results:

With a mean insertion percentage of 94%, the surgeon was able to complete the HEARO method in 9 out of 10 procedures. There was no evidence of a collision or damage to vital structures.

Conclusion:

Future iterations of RACIS will prioritize haptic feedback, automated segmentation and trajectory, robotic insertion with adjustable speed, and imaging mobile cone beam computed tomography.
Asymmetrical 5’RACE RNA-based immunoglobulins repertoire sequencing is an accurate and specific tool for diagnosis of POEMS syndrome
Authors: Roussel Murielle , Pascal Virginie , Jaccard Arnaud , Bridoux Frank , Bender Sebastien , Sirac Christophe
Published: November 2024

POEMS syndrome is a rare form of plasma cell dyscrasia with multiple clinical features including polyneuropathy and sclerotic bone lesions. As various signs and symptoms can be observed, diagnosis is often delayed and we need an accurate diagnosis tool for these patients. Vascular endothelial growth factor (VEGF) is known to play a major role in the pathology and is frequently increased in sera of the patients but is not specific. This condition is also associated with the presence of a monoclonal immunoglobulin light chain composed of highly restricted variable domains (IGLV1-40, IGLV1-44, IGLV1-36 and IGJV3*02 genes). Using RNA-based high-throughput sequencing (5’ RACE RepSeq), we previously showed mutated consensus stretches in the CDR1/FR2 regions of the variable domains of the light chains: (P/A)VNWYQ and (D/G)VNWYQ. We have now added 70 light chain sequences to our cohort and confirmed the variable domain restriction, the consensus stretches and found a new YSVNWYQ pattern on IGLV1-44 light chains. When correlated with our clinical database of POEMS patients, these mutation patterns had an accuracy of 89% and a specificity of 100%. 5’RACE RepSeq is an important tool to ensure the diagnosis of patients suspected of having POEMS syndrome, even with a small secretory clone. Samples from an involved organ are mandatory in the case of localized disease.
Physiology Guided Machine Learning Approach to Predict Short and Long Term Outcomes of Obstructive Sleep Apnea
Authors: Wickramaratne Sajila D. , Kam Korey , Tolbert Thomas M. , Varga Andrew , Ayappa Indu , Rapoport David M. , Parekh Ankit
Published: November 2024

Obstructive Sleep Apnea(OSA) is a chronic condition that affects 1 billion people worldwide. Apnea Hypopnea Index(AHI) is the clinical gold standard to measure the severity of OSA. This study highlights limitations in the apnea-hypopnea index as a predictor for obstructive sleep apnea (OSA) outcomes. Instead, a physiology-guided machine learning (ML) approach was developed using features from ventilatory, hypoxic, and arousal domains, based on polysomnography data from the Sleep Heart Health Study (SHHS). The ML model demonstrated superior predictive performance for all-cause mortality (AUROC-0.93) and daytime sleepiness (AUROC-0.81) compared to AHI. Explainable AI techniques, such as SHAP analysis, provided insights into feature importance, offering a clinically interpretable and scalable tool for OSA outcome prediction.
A network regularized linear model to infer spatial expression pattern for single cell
Authors: Gu Chaohao , Chen Hu , Liu Zhandong
Published: November 2024

Spatial transcriptomics, situated at the intersection of genomics and spatial biology, offers profound insights into the spatial organization of gene expression within tissues. However, its potential has been constrained by either limited resolution or throughput. While single-cell RNA-seq allows for in-depth profiling of cellular gene expression, the crucial spatial information is often sacrificed during sample collection. In a groundbreaking fusion of these two techniques, our research introduces the glmSMA computational algorithm. This innovative approach aims to predict cell locations by integrating scRNA-seq data with spatial-omics reference atlases. The essence of glmSMA lies in formulating cell mapping as a convex problem, strategically minimizing differences between cellular expression profiles and location expression profiles through L1 and Generalized L2 regularization. Our algorithm has undergone rigorous testing across diverse tissues, including mouse brain, drosophila embryo, and human PDAC samples. The compelling results validate glmSMA’s efficacy, demonstrating its capability to faithfully recapitulate spatial gene expression and anatomical structures. This marks a significant stride forward in overcoming the limitations of existing spatial transcriptomic techniques.
Improving antibody-mediated protection against HSV infection by eliminating interactions with the viral Fc receptor gE/gI
Authors: Slein Matthew D. , Backes Iara M. , Kelkar Natasha S. , Garland Callaghan R. , Khanwalkar Urjeet S. , Sholukh Anton M. , Johnston Christine M. , Leib David A. , Ackerman Margaret E.
Published: November 2024

Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules, allowing the virus to escape immune clearance. In addition to their role in neuropathogenesis and cell-cell spread, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG and promote evasion of humoral immune responses. While monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of the vFcR on mAb-mediated protection by binding to IgG is unknown. Using HSV-1 with intact and ablated gE-mediated IgG Fc binding, and Fc-engineered antibodies with modified ability to interact with gE/gI, we investigated the role of the vFcR in viral pathogenesis and mAb-mediated protection from nHSV. The gD-specific human mAb HSV8 modified to lack binding to gE exhibited enhanced neutralization andin vivoprotection compared to its native IgG1 form. This improved protection by the engineered mAbs was dependent on the presence of the vFcR. Human IgG3 allotypes lacking vFcR binding also exhibited enhanced antiviral activityin vivo, suggesting that vaccines that robustly induce IgG3 responses could show enhanced protection. suggesting the value of vaccination strategies that robustly induce this subclass. Lastly, analysis of longitudinal responses to acute primary genital infection in humans raised the possibility that unlike most viruses, HSV may exhibited slow induction of IgG3. In summary, this study demonstrates that mAbs lacking the ability to interact with the vFcR can exhibit improved protection from HSV—offering new prospects for antibody-based interventions.

One Sentence Summary:The herpes simplex virus neutralizing antibody HSV8 demonstrates improved activityin vitroandin vivowhen its IgG Fc domain lacks the ability to bind the viral Fc receptor glycoprotein E/I complex through either Fc engineering or natural human IgG3 allotypes.
Extended-spectrum beta-lactamase-producingEscherichia coliandKlebsiella pneumoniaefrom human carriage, the human-polluted environment, and food: molecular epidemiology of two prospective cohorts in five European metropolitan areas
Authors: Verschuuren TD , Guther J , Riccio ME , Martak D , Salamanca E , Göpel S , Conzelmann N , Scharringa J , Musicha P , Autenrieth IB , Cooper BS , Hocquet D , Tacconelli E , Rodríguez-Baño J , Harbarth S , Fluit AC , Peter S , Kluytmans JAJW
Published: November 2024

Objectives

For 475 ESBL-producingEscherichia coli(ESBL-Ec), and 171 ESBL-producingKlebsiella pneumoniae(ESBL-Kp) collected from human carriers, the human-polluted (hp)-environment, and food: (i) to compare the antimicrobial resistance gene (ARG) content, and (ii) to assess clonal relationships between human and non-human isolates.

Methods

Two prospective multicentre cohorts were assessed: colonised hospitalised index-subjects and household contacts, and long-term care facility (LTCF) residents. Additionally, linked hp-environment and food samples were collected. Presence of ARGs were assessed using pairwise comparisons and proportional similarity index (PSI). Clonal relationships were assessed using cgMLST distance visualisations and maximum likelihood phylogeny.

Results

ESBL-Ec and ESBL-Kp co-occurred in 14/65 households, 3/6 LTCFs, and in 33/202 of ESBL-positive participants. Thirty-nine percent of detected ARG types were found in both species (36/93). Frequencies of beta-lactamase, ESBL, aminoglycoside, and sulfonamide ARG types from human ESBL-Ec and ESBL-Kp overlapped considerably: PSIs 0.59-0.75, and were equal or higher compared to the overlap between ESBL-Ec from humans and food isolates: PSIs 0.33-0.72. Isolates from humans and the hp-environment were frequently clonally related, indicating human contamination of the environment. Links with food isolates were observed less frequently. For ESBL-Ec both interregional and regional clonal dissemination were observed, while for ESBL-Kp clonal dissemination was mainly regional.

Conclusions

ESBL-Ec and ESBL-Kp from human carriage showed considerable overlap in ARG content. Furthermore, clonal links were observed frequently between humans and hp-environment, and with lower frequency between humans and food. These findings are consistent with human-to-human transmission as an important driver of ARG spread in humans.