bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S3 from Allogeneic CAR Invariant Natural Killer T Cells Exert Potent Antitumor Effects through Host CD8 T-Cell Cross-Priming
Authors: Simonetta Federico , Lohmeyer Juliane K. , Hirai Toshihito , Maas-Bauer Kristina , Alvarez Maite , Wenokur Arielle S. , Baker Jeanette , Aalipour Amin , Ji Xuhuai , Haile Samuel , Mackall Crystal L. , Negrin Robert S.
Published: November 2024

Supplemental Figure 3
Figure S2 from Allogeneic CAR Invariant Natural Killer T Cells Exert Potent Antitumor Effects through Host CD8 T-Cell Cross-Priming
Authors: Simonetta Federico , Lohmeyer Juliane K. , Hirai Toshihito , Maas-Bauer Kristina , Alvarez Maite , Wenokur Arielle S. , Baker Jeanette , Aalipour Amin , Ji Xuhuai , Haile Samuel , Mackall Crystal L. , Negrin Robert S.
Published: November 2024

Supplemental Figure 2
Supplementary Figure 4 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAFV600E-Mutant Human Glioma
Authors: Schreck Karisa C. , Morin Andrew , Zhao Guisheng , Allen Amy N. , Flannery Patrick , Glantz Michael , Green Adam L. , Jones Chris , Jones Kenneth L. , Kilburn Lindsay B. , Nazemi Kellie J. , Samuel David , Sanford Bridget , Solomon David A. , Wang Jiawan , Pratilas Christine A. , Nicolaides Theodore , Mulcahy Levy Jean M.
Published: November 2024

GSEA comparing paired pre-/post- treatment glioma with BRAF V600E mutations (n=10) against BRAF wild type (n = 4) specimens. Highlighted are selected groups of similar differentially expressed gene sets. WT = wild type
Supplemental Table 3 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAFV600E-Mutant Human Glioma
Authors: Schreck Karisa C. , Morin Andrew , Zhao Guisheng , Allen Amy N. , Flannery Patrick , Glantz Michael , Green Adam L. , Jones Chris , Jones Kenneth L. , Kilburn Lindsay B. , Nazemi Kellie J. , Samuel David , Sanford Bridget , Solomon David A. , Wang Jiawan , Pratilas Christine A. , Nicolaides Theodore , Mulcahy Levy Jean M.
Published: November 2024

GSEA subgroup analysis of paired RNA samples. Subgroups were analyzed based on the presence (Enriched in post-txt mutant) or absence (Enriched in post-txt non-mutant) of a genomic alteration at time of recurrence. Subgroup analysis was also conducted on tumors with identified RTK, cell cycle, or RAS-ERK alterations in tumor at time of progression.
Supplemental Table 1 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAFV600E-Mutant Human Glioma
Authors: Schreck Karisa C. , Morin Andrew , Zhao Guisheng , Allen Amy N. , Flannery Patrick , Glantz Michael , Green Adam L. , Jones Chris , Jones Kenneth L. , Kilburn Lindsay B. , Nazemi Kellie J. , Samuel David , Sanford Bridget , Solomon David A. , Wang Jiawan , Pratilas Christine A. , Nicolaides Theodore , Mulcahy Levy Jean M.
Published: November 2024

Upstream regulators predicted in Ingenuity Pathway Analysis. All significant p<0.01) patient sample and cell line upstream regulators predicted to have changed after exposure to BRAFi, organized by tab. Analysis was conducted per-patient, comparing pre- and post-BRAFi RNA sequencing.
Supplementary Figure 3 from IL13Rα2 Promotes Proliferation and Outgrowth of Breast Cancer Brain Metastases
Authors: Márquez-Ortiz R. Alejandro , Contreras-Zárate Maria J. , Tesic Vesna , Alvarez-Eraso Karen L.F. , Kwak Gina , Littrell Zachary , Costello James C. , Sreekanth Varsha , Ormond D. Ryan , Karam Sana D. , Kabos Peter , Cittelly Diana M.
Published: November 2024

Supplementary Figure 3. Predictive value of IL13RA2 or EFNB1 mRNA levels in primary tumors known to metastasize to brain. Dataset contains 21 matched breast cancer primary and brain metastasis samples, reported in (https://pubmed.ncbi.nlm.nih.gov/29961873/). A. Kaplanmeier plots for IL13RA2 mRNA expression in primary tumors. B. Kaplan-Meier plots to EFNB1 mRNA in primary tumors. C. Kaplan-meier plots for primary tumors with low-IL13RA2/highEFNB1 compared to samples with high-IL13RA2/low-EFNB1. For all plots, average mRNA expression was determined for each target and expression ranked as low (below mean) or high (above mean). Survival curves comparisons were made using Log-rank (Mantel-Cox) test. p<0.05 was considered significant (italic bold). OS: overall survival; DFS: disease free survival; BMFS: brain metastasis free survival; SPBM: survival post brain metastasis.
Supplementary Figure 1 from IL13Rα2 Promotes Proliferation and Outgrowth of Breast Cancer Brain Metastases
Authors: Márquez-Ortiz R. Alejandro , Contreras-Zárate Maria J. , Tesic Vesna , Alvarez-Eraso Karen L.F. , Kwak Gina , Littrell Zachary , Costello James C. , Sreekanth Varsha , Ormond D. Ryan , Karam Sana D. , Kabos Peter , Cittelly Diana M.
Published: November 2024

Supplementary Figure 1. A. 231BR cells were transfected with an empty vector (gEV) or using sgRNAs targeting IL13Rα2 (gIL13Ra2). Cells were selected for clonal populations and IL13Rα2 protein expression assessed by western blot. α-tubulin was used as loading control. B. 231BR and JmT1BR3 cells transfected with a DOXY inducible system were assessed to determine any possible side proliferation effect after DOXY induction. Cells harboring the EV were treated with DOXY at 1 µg/mL or 2 µg/mL and % of confluence was measured over time using Incucyte live imaging. (n=4 treatment). There were no significant changes in proliferation.
Data from Circulating and Intratumoral Adrenal Androgens Correlate with Response to Abiraterone in Men with Castration-Resistant Prostate Cancer
Authors: Mostaghel Elahe A. , Marck Brett T. , Kolokythas Orpheus , Chew Felix , Yu Evan Y. , Schweizer Michael T. , Cheng Heather H. , Kantoff Phillip W. , Balk Steven P. , Taplin Mary-Ellen , Sharifi Nima , Matsumoto Alvin M. , Nelson Peter S. , Montgomery R. Bruce
Published: November 2024

AbstractPurpose:
In metastatic castration-resistant prostate cancer (mCRPC) low serum androgens prior to starting abiraterone acetate (AA) is associated with more rapid progression. We evaluated the effect of AA on androgens in castration-resistant prostate cancer (CRPC) metastases and associations of intratumoral androgens with response.
Experimental Design:
We performed a phase II study of AA plus prednisone in mCRPC. The primary outcome was tissue testosterone at 4 weeks. Exploratory outcomes were association of steroid levels and genomic alterations with response, and escalating AA to 2,000 mg at progression.
Results:
Twenty-nine of 30 men were evaluable. Testosterone in metastatic biopsies became undetectable at 4 weeks (P < 0.001). Serum and tissue dehydroepiandrosterone sulfate (DHEAS) remained detectable in many patients and was not increased at progression. Serum and tissue DHEAS in the lowest quartile (pretreatment), serum DHEAS in the lowest quartile (4 weeks), and undetectable tissue DHEAS (on-therapy) associated with rapid progression (20 vs. 48 weeks, P = 0.0018; 20 vs. 52 weeks, P = 0.0003; 14 vs. 40 weeks, P = 0.0001; 20 vs. 56 weeks, P = 0.02, respectively). One of 16 men escalating to 2,000 mg had a 30% PSA decline; 13 developed radiographic progression by 12 weeks. Among patients with high serum DHEAS at baseline, wild-type (WT) PTEN status associated with longer response (61 vs. 33 weeks, P = 0.02).
Conclusions:
Low-circulating adrenal androgen levels are strongly associated with an androgen-poor tumor microenvironment and with poor response to AA. Patients with CRPC with higher serum DHEAS levels may benefit from dual androgen receptor (AR)-pathway inhibition, while those in the lowest quartile may require combinations with non–AR-directed therapy.
Data from Allogeneic CAR Invariant Natural Killer T Cells Exert Potent Antitumor Effects through Host CD8 T-Cell Cross-Priming
Authors: Simonetta Federico , Lohmeyer Juliane K. , Hirai Toshihito , Maas-Bauer Kristina , Alvarez Maite , Wenokur Arielle S. , Baker Jeanette , Aalipour Amin , Ji Xuhuai , Haile Samuel , Mackall Crystal L. , Negrin Robert S.
Published: November 2024

AbstractPurpose:
The development of allogeneic chimeric antigen receptor (CAR) T-cell therapies for off-the-shelf use is a major goal that faces two main immunologic challenges, namely the risk of graft-versus-host disease (GvHD) induction by the transferred cells and the rejection by the host immune system limiting their persistence. In this work we assessed the direct and indirect antitumor effect of allogeneic CAR-engineered invariant natural killer T (iNKT) cells, a cell population without GvHD-induction potential that displays immunomodulatory properties.
Experimental Design:
After assessing murine CAR iNKT cells direct antitumor effects in vitro and in vivo, we employed an immunocompetent mouse model of B-cell lymphoma to assess the interaction between allogeneic CAR iNKT cells and endogenous immune cells.
Results:
We demonstrate that allogeneic CAR iNKT cells exerted potent direct and indirect antitumor activity when administered across major MHC barriers by inducing tumor-specific antitumor immunity through host CD8 T-cell cross-priming.
Conclusions:
In addition to their known direct cytotoxic effect, allogeneic CAR iNKT cells induce host CD8 T-cell antitumor responses, resulting in a potent antitumor effect lasting longer than the physical persistence of the allogeneic cells. The utilization of off-the-shelf allogeneic CAR iNKT cells could meet significant unmet needs in the clinic.
Data from Diagnostic Accuracy of FEC-PET/CT, FDG-PET/CT, and Diffusion-Weighted MRI in Detection of Nodal Metastases in Surgically Treated Endometrial and Cervical Carcinoma
Authors: Rockall Andrea G. , Barwick Tara D. , Wilson William , Singh Naveena , Bharwani Nishat , Sohaib Aslam , Nobbenhuis Marielle , Warbey Victoria , Miquel Marc , Koh Dow-Mu , De Paepe Katja N. , Martin-Hirsch Pierre , Ghaem-Maghami Sadaf , Fotopoulou Christina , Stringfellow Helen , Sundar Sudha , Manchanda Ranjit , Sahdev Anju , Hackshaw Allan , Cook Gary J. , Stewart Victoria , Farthing Alan , Kyrgiou Maria , Yazbek Joseph , Dina Roberto , Ind Thomas , Barton Desmond , Butler John , Attygalle Ayoma , Hazell Steve , Taylor Alexandra , Lalondrelle Susan , Zerizer Imene , Rosof-Williams Diana , Dobson Mike , Hill Jonathan , Brockbank Elly , Lawrence Alexandra , Jeyarajah Arjun , Oram David , Ganesan Raji , Guest Peter , Davies Mark , Vosper Laura , Coetzee Carike
Published: November 2024

AbstractPurpose:
Preoperative nodal staging is important for planning treatment in cervical cancer and endometrial cancer, but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-fluoro-deoxy-glucose-(FDG)-PET/CT, and diffusion-weighted-MRI (DW-MRI) with conventional morphologic MRI.
Experimental Design:
A prospective, multicenter observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centers. FEC-PET/CT, FDG-PET/CT, and DW-MRI were compared with nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable cervical cancer stage ≥ 1B1 or endometrial cancer (grade 3 any stage with myometrial invasion or grade 1–2 stage ≥ II).
Results:
Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT and 60 underwent FEC-PET/CT. In 118 patients, 267 nodal regions were strictly correlated at histology (nodal positivity rate, 25%). Sensitivity per patient (n = 118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT was 40%*, 53%, 53%, 63%*, and 67% for all cases (*, P = 0.016); 10%, 10%, 20%, 30%, and 25% in cervical cancer (n = 40); 65%, 75%, 70%, 80% and 88% in endometrial cancer (n = 78). FDG-PET/CT outperformed nodal size (P = 0.006) and size ratio (P = 0.04) for per-region sensitivity. False positive rates were all <10%.
Conclusions:
All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different from other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions.
Figure S2 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells
Authors: Schaaf Zachary A. , Ning Shu , Leslie Amy R. , Sharifi Masuda , Gao Richard Y. , Maine James P. , Lou Wei , Lombard Alan P. , Liu Chengfei , Yu Ai-Ming , Mitsiades Nicholas , Gao Allen C.
Published: November 2024

supplementary data
Figure 6 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells
Authors: Schaaf Zachary A. , Ning Shu , Leslie Amy R. , Sharifi Masuda , Gao Richard Y. , Maine James P. , Lou Wei , Lombard Alan P. , Liu Chengfei , Yu Ai-Ming , Mitsiades Nicholas , Gao Allen C.
Published: November 2024

Inhibiting PINK1 expression decreases relative active mitochondria and lowers ETCC1 activity. A, Left, 2B-OlapR cells treated with siPINK1 show lower relative positive MitoTracker staining. 10× images shown, with 20× crops within. Right, MitoTracker to DAPI TCF ratio is reduced in the siPINK1 group. B, Left, Decreased PINK1 expression results in lower ETCC1 activity. Right, siPINK1-dosed 2B-OlapR cells report decreased the ETCC1 activity rate. **, P≤0.01; ****, P≤0.0001.
Figure 4 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells
Authors: Schaaf Zachary A. , Ning Shu , Leslie Amy R. , Sharifi Masuda , Gao Richard Y. , Maine James P. , Lou Wei , Lombard Alan P. , Liu Chengfei , Yu Ai-Ming , Mitsiades Nicholas , Gao Allen C.
Published: November 2024

PINK1 expression is increased in 2B-OlapR cells and associated with negative patient prognosis. Treating 2B-OlapR cells with siPINK1 ASOs decreases PINK1 expression and protein level, as well as cell growth, and improves olaparib efficacy. A, Transcriptomic data reveal increased expression of PINK1 in the 2b-OlapR subline. B, qRT-PCR verification of increased PINK1 gene expression in 2b-OlapR cells. C, Western immunoblot analysis showing increased cellular PINK1 protein in 2b-OlapR cells. D, Deceased patients with prostate cancer have higher amounts of tumor PINK1 expression (Abida 2019). E, High-PINK1–expressing striated patients with prostate cancer show lower survival over time (GSE21032). F, 2B-OlapR cells treated with siPINK1 show lower mRNA expression through qRT-PCR (left) and decrease in cellular protein (right). G, siPINK1 treatment decreases growth of 2B-OlapR cells and increases relative olaparib efficacy at 5 μmol/L. *, P≤0.05; **, P≤0.01; ***, P≤0.001; ****, P≤0.0001.
Figure 2 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells
Authors: Schaaf Zachary A. , Ning Shu , Leslie Amy R. , Sharifi Masuda , Gao Richard Y. , Maine James P. , Lou Wei , Lombard Alan P. , Liu Chengfei , Yu Ai-Ming , Mitsiades Nicholas , Gao Allen C.
Published: November 2024

Seahorse Mito Stress Test assay results comparing C4-2B and 2B-OlapR cells at basal state and with mitochondrial inhibitor supplementation to deduce relative function. A and B, Mito Stress Test summary graphic representing differential OCR and extracellular acidification rate between naïve and resistant cell lines under normal conditions and with the addition of mitochondrial inhibitors. C, Cellular OCR at basal state is increased in the olaparib-resistant cell line. D, Amount of oxygen consumption utilized for ATP production, derived through OCR difference before and after oligomycin (ETC complex V inhibitor) is added. 2B-OlapR displays increased oxygen consumption related to ATP production. E, Change in the OCR between basal readings and maximal readings after FCCP (mitochondrial membrane uncoupler) is added. 2B-OlapR cells exhibit greater ability to increase respiration under mitochondrial insult. F, Difference in cellular OCR reading after rotenone and antimycin A (complex I and III inhibitors) are added, eliminating all ETC-based oxygen consumption. 2B-OlapR cells show amplified maximal respiration compared with parental C4-2B. G, Difference between readings after oligomycin addition and the readings after antimycin A/rotenone addition, inferring oxygen consumption not ultimately utilized for ATP production. The rate in 2B-OlapR cells is almost twice that in C4-2B. ECAR, extracellular acidification rate. **, P≤0.01; ***, P≤0.001; ****, P≤0.0001.
Migrants & Minorities into Citizens: Education & Membership Regimes Since the Early Modern Period
Authors: Lucassen Leo
Published: November 2024

Schools are one of the institutions that determine the possibilities to participate in society. Therefore, access to education is crucial to the settlement process of immigrants, minorities, and their offspring. Newcomers who join a community have always faced different membership regimes, long before the emergence of the nation-state in the nineteenth century. Such regimes determine whether, to what extent, and under what conditions children of migrants and minorities have access to schools. They also determine whether schools are segregated along religious, racial, or socioeconomic lines. These conditions are not limited to international migrants, but may also apply to internal migrants, such as low-income Chinese people who have moved from the countryside to large cities since the early 1980s and have limited access to (more expensive) urban schools. In this essay, I compare different parts of the world over the past five centuries to understand how polities allow or restrict access to education, and to what extent schools function as gateways to full participation in societies for children of migrants and minorities.
From Girls' Education to Gender-Transformative Education: Lessons from Different Nations
Authors: Murphy-Graham Erin
Published: November 2024

The examination of gender inequality in education around the globe reveals a multifaceted issue deeply intertwined with persistent challenges within education systems and society at large. Over the past three decades, girls' education has often been portrayed as a panacea, touted as the solution to a wide array of societal problems, including issues as diverse as high fertility rates and global warming. This essay explores gender disparities in education, employing case studies from Latin America to elucidate the intricate dynamics of this global phenomenon and to illustrate the potential of gender-transformative approaches. Drawing upon two decades of empirical research and theoretical insights from the capability approach, I discuss the linkages between gender, education, and social transformation.
Agricultural by-products as functional substrates modulate the growth, the cytoprotective mechanisms and the antioxidant potential of Tenebrio molitor (Coleoptera: Tenebrionidae)
Authors: Chatzimpalasis Dimitrios , Paia Christos , Panteli Nikolas , Padovani Marianthi , Feidantsis Konstantinos , Krigas Nikos , Andreadis Stefanos S. , Antonopoulou Efthimia
Published: November 2024

The emergence of insects as a nutrient source in the human diet and animal feed propels the urgent development of a viable mass production sector. The objective of the present study was to evaluate the suitability of rice and corn by-products as substrates for mealworm rearing namely Tenebrio molitor L. (Coleoptera: Tenebrionidae) in terms of growth, stress response, and antioxidant defence. In this context, mealworm larvae were reared on wheat bran (WB) as the control substrate, rice bran (RB) and corncob (CC), both enriched with post-distillation residues of Mediterranean medicinal-aromatic plants (MMAPs; 0, 10 or 20% w/w). Cell signaling components including Heat shock proteins (Hsps), Mitogen-activated protein kinases (MAPKs), and apoptotic proteins (Bax and Bcl-2) were assessed through immunoblot analysis, while the spectrophotometric technique was employed to determine the activities of the antioxidant enzymes (superoxide dismutase, catalase, and glutathione reductase). Regardless of the MMAPs supplementation level, a weight reduction was apparent in larvae reared on RB substrate, while 20% MMAPs supplementation in WB substrate seemed to trigger an apoptosis-associated weight loss as demonstrated by the elevated Bax/Bcl-2 ratio. In contrast, corncob was regarded as a nutritionally adequate substrate considering that the efficient larvae growth was accompanied by suppression of Hsps expression and MAPKs activation. The elevated antioxidant activity in T. molitor of the 10% MMAPs-enriched RB and CC substrates may underline the attention that must be given in the utilization of MMAPs in insects’ production processes due to the potential insecticidal and repellent effects. Collectively, the effective valorization of agricultural-by-products and MMAPs supplementation in T. molitor feed varies depending on the source of the substrate and the potential interactions among the bioactive compounds.
Remote Justice and Civil Proceedings
Authors: Mancuso Carolina
Published: November 2024

The paper explores the evolving implications of the principle of orality in civil proceedings in the context of remote justice. It begins with a historical overview to contextualize the contemporary implications of digital justice in the information era. Then it focuses on the impact of digital orality on the principle of a fair trial, as interpreted by the ECtHR. It examines the right to be heard under Article 6(1) echr and Article 47 cfr and scrutinizes whether videoconferencing aligns with these provisions. The paper also compares orality in physical versus virtual hearings, discussing the need to rethink the traditional principles of immediacy, publicity, and concentration. It concludes by assessing the potential of eli/unidroit model rules to harmonize the reinterpretation of the principle of orality across jurisdictions, providing preliminary conclusions on this harmonization effort.
Salvia gibbosa, S. gracilicaulis and S. ruizii (Lamiaceae), three new species from Peru
Authors: GONZÁLEZ-GALLEGOS JESÚS GUADALUPE , URÍA ROLANDO , RODRÍGUEZ-RODRÍGUEZ ERIC FRANK
Published: November 2024

Peru is the second American country in terms of species richness of the genus Salvia but such diversity seems to be stabilized when compared with that in other American countries with continuous findings of new Salvia species. This is probably an artifact reflecting the need to intensify the study of the genus in the country and several taxonomic novelties are predicted. In fact, recent botanical explorations in northern Peru have led to the discovery of three new species unmatched with any of the known salvias, which are here consequently supported as new additions to the Peruvian Flora: Salvia gibbosa, S. gracilicaulis and S. ruizii. Descriptions, diagnostic characters, photographs and a distribution map are presented to support the proposal of these new species.
The nomenclature associated with the name Kalanchoe arborescens (Crassulaceae subfam. Cotyledonoideae), the type of which is the type of K. subg. Calophygia
Authors: SMITH GIDEON F.
Published: November 2024

Although the vast majority of kalanchoes are low-growing herbs or medium-sized shrubs, in terms of growth form a small group of four Malagasy kalanchoes (Crassulaceae subfam. Cotyledonoideae) attain arborescent dimensions. These are Kalanchoe arborescens, K. beharensis, K. dinklagei, and K. grandidieri. All four species are endemic to southern Madagascar. The type of the name of one of these, the aptly named K. arborescens, is the type of the recently reinstated K. subg. Calophygia. The nomenclature of K. arborescens is revisited and corrected. The second-step lectotype of the name K. arborescens designated here is illustrated.
A replacement name for Magnolia multinervia (Magnoliaceae)
Authors: KOTTAIMUTHU RAMALINGAM , MAHESH YALATOOR , SWAIN HAREKRUSHNA
Published: November 2024

N/A
Trends in Cutaneous Melanoma in Nova Scotia With a Focus on 2007 to 2019
Authors: Dorey Rachel A. , Walsh Gordon , Dewar Ron , Hull Peter R.
Published: November 2024

Background:

Melanoma represents a significant public health challenge in Canada, contributing to the deaths of over 1000 individuals each year. Prince Edward Island and Nova Scotia were previously noted to have the highest incidence rates of melanoma in Canada.

Methods:

Data from patients diagnosed with or dying from melanoma was extracted from the Nova Scotia Cancer Registry. TNM stage was available for cases diagnosed 2007 to 2017. Incidence (1992-2019) and mortality (1992-2021) rates were examined using Join Point Trend Analysis Software.

Results:

Between 2007 and 2019, 2450 cases of in situ and 4063 cases of invasive melanoma were documented, of which 52.8% were male. The largest number of cases was from the 60- to 79-year age group. The most common site in females was upper limbs (in situ) and lower limbs (invasive), and for males, face, and neck (in situ), and trunk (invasive). The majority of invasive cases (71.5%) were diagnosed at stage I. Invasive melanoma incidence has been increasing by 2.7% per year since 1992, while in situ disease has increased at a greater rate (4.9% per year). The current estimate of 92% for 5 years of net survival has not changed appreciably over the same period. Survival for late-stage melanoma has shown a modest improvement for patients diagnosed over the period.

Conclusion:

With increasing rates of melanoma in Nova Scotia, there is a need for informed education, directed at the public and physicians, around pigmented skin lesions. This would allow the patient to detect atypical melanocytic lesions at an early stage. Sun safety practices in Nova Scotia should continue to be encouraged.
Digital storytelling within a community-based mental health improvement programme (ARCLIGHT) in Guyana
Authors: Mitchell Helena A , Waights Verina , Hart Tania
Published: November 2024

Over one billion people globally struggle with mental ill-health, including depression, and self-harm. Mental ill-health is prevalent in lower income nations, where lack of research in implementation and policy change is further impeded by stigma and fragmented service delivery. This British Academy funded project (ARCLIGHT) developed from a ‘pre-bid stage’ in partnership with key Guyanese stakeholders. The project was a participatory action research study (PAR) across three differing Guyanese communities. Its objective was to co-create a community-based mental health improvement programme. A key component included supporting participants recording their digital stories of successful practices using mobile phones linked to local Wi-Fi systems. The study contributed to the United Nations Sustainable Development Goals of improving wellbeing and health, enhancing gender equality, and reducing social and economic inequalities and meeting the World Health Organisation’s strategic priorities for Guyana regarding mental health and violence. This interdisciplinary project considered the cultural, professional, and political barriers to mental health recovery, provided new conceptual understandings and policy-relevant evidence that addressed the global challenge of mental health, in multi-ethnic and resource-poor countries. Our collaborative approach, underpinned by PAR, encouraged behavioural change, economic independence, and enhanced local services provision.
Contextualised Processing of Stimuli Modulates Auditory Mismatch Responses in the Rat
Authors: Jalewa Jaishree , Todd Juanita , Michie Patricia T. , Hodgson Deborah M. , Harms Lauren
Published: November 2024

Mismatch negativity (MMN), an auditory prediction error signal, is an enhanced response to unexpected (deviant) stimuli compared to expected (standard) stimuli. There is strong interest in MMN due to reliable findings of reduced MMN in schizophrenia. To interpret reduced MMN in schizophrenia, an enhanced understanding of the factors that influence MMN amplitude could lead to a better understanding of neural mechanisms underpinning the reduction. While several laboratories have observed mismatch responses (MMRs) in rodents, this study assesses how MMR is altered in more complex auditory sequences in rats. Prediction-errors are elicited in relation to “predictive” internal models of regularities. These internal models are updated dynamically when a regularity changes, but human MMN exhibits order effects when two regularities alternate; while deviants in both regularities elicit MMN (ie, the model updates) there is a slower build-up in MMN amplitude over time in the second encountered regularity type. We investigate whether order effects occur in rat MMRs. MMRs were studied to rare ascending and descending frequency deviations in awake, freely moving Wistar rats using wireless telemetry in both separate sequences (one regularity at a time) and in alternating sequences where regularities changed back and forth. The rat MMR did not show order effects, however, substantial MMRs occurred in response to both ascending and descending deviants in the alternating context but to the ascending deviant only when the same regularities were presented separately. The longer-term sequence structure altered prediction-error signalling in rat auditory system revealing a long term context sensitivity in internal models.
Examining Complex Program Adoption Decision-Making in a Health Pilot for U.S. Women Military Veterans: A Single Revelatory Case Study
Authors: Sanders Kelly , Jarpe-Ratner Elizabeth , Ahmadi-Montecalvo Halima , Welter Christina
Published: November 2024

A single retrospective, qualitative case study was conducted to examine the decision-making factors that impacted the adoption of a women-specific health transition pilot as a permanent program. The pilot was adopted as a permanent program prior to completing all expected pilot sessions and before the final pilot evaluation report was produced. This study examined factors affecting the program adoption decision at the societal, organizational, interpersonal, and individual levels. To examine this research question, the socioecological model was used as a theoretical framework to identify and understand the decision-making factors and their interactions at the various socio-ecological levels. Semi-structured interviews were conducted with 15 Veterans Health Administration (VHA) Transition Training pilot stakeholders. The study identified 12 predominant factors that facilitated the pilot’s adoption as a permanent program. The paper discusses implications and considerations for practitioners for making evidence-based decisions in highly complex contexts.
Andy Horne: A Memorial Tribute to a Pillar of Prevention in Counseling Psychology
Authors: Conyne Robert K. , Hage Sally , Kenny Maureen , Orpinas Pamela , Romano John , Schwartz Jonathon
Published: November 2024

Arthur (Andy) M. Horne, PhD, Research Emeritus Professor and Dean at the University of Georgia, was born on November 26, 1942 and passed away unexpectedly of complications from open heart surgery, on August 26, 2024. We will mourn his passing forever but also want to celebrate his life and accomplishments. For a fuller commentary on Andy’s life and work, please locate his obituary, beautifully written by his daughter, Sharon Horne (herself a well-known psychologist), at: https://www.lordandstephens.com/. The present tribute focuses on Andy’s contributions to prevention in counseling psychology. It was Maureen Kenny who termed him a “Pillar of Prevention,” a moniker that fits like a good glove.
Breaking new ground or business as usual? Urban village redevelopment under China’s new normal
Authors: Li Zhigang , Ye Yumin , Tong De
Published: November 2024

This special issue explores the redevelopment of urban villages in China. Drawing on top-down and bottom-up approaches, this article interrogates the work of six articles within it examining the diverse strategies employed in urban village redevelopment. The top-down approach highlights the state’s central role in managing large-scale transformations and the collaboration between government, developers, and village collectives; the bottom-up strategies reveal the potential for local actors to shape the redevelopment through grassroots initiatives. The convergence of the two approaches demonstrates how top-down and bottom-up methods can complement each other, creating inclusive and sustained transformations. Above all, we articulate the importance of integrated governance models in ensuring that urban village redevelopment enhances economic growth and promotes social equity.
Disentangling mechanisms by which microplastic films affect plant-soil systems: physical effects of particles can override toxic effects of additives
Authors: Lozano Y. M. , Perlenfein C. , Bernal M. G. , Rillig M. C.
Published: November 2024

Background

Microplastics, polymer-based particles < 5 mm, affect plant–soil systems positively or negatively, suggesting there are different modes of action. Microplastics, as particles, have physical effects but the leaching of additives likely contributes chemical mechanisms, both of which may be dependent on microplastic size. To disentangle such mechanisms, we established a controlled experiment involving polypropylene and polyethylene films of small, medium and large size, and we evaluated the individual and combined effect of plastic particles and additives (leachates from plastic particles) on soil properties and plant performance of the phytometer Daucus carota and on bare soils.

Results

We find that additives better explained variation in soil properties (e.g., 44.6% vs 1.3%). Soil respiration and aggregation were negatively affected for additives, likely due to the presence of toxic substances. Overall, such effects increased as plastic size decreased. By contrast, plastic particles better explained plant biomass responses. The positive effect of particles on aeration which may promote root penetration and nutrient uptake, and microplastics itself as a source of carbon potentially promoting soil microbial activity, help explain the positive effect of particles on plant biomass. Plants mitigated the negative effects of additives on bare soils while enhancing the positive effects of particles. This improvement was likely linked to an increase in root activity and rhizodeposition, as plastic particles improved soil aeration. The combined effect of additives and particles, which mimics the microplastic found in the soil, mitigated their individual negative effects on plant–soil systems. As the negative effect of additives could have been masked by the positive effects of particles, simply reporting net positive effects would capture only part of the response.

Conclusions

Additives and plastic particles differently affect soil properties and plant biomass. Additives primarily negatively affect soil properties due to toxic substances, while plastic particles enhance plant biomass likely by improving soil aeration. When examining microplastics effects on terrestrial systems (i.e., the combined effect of additives and particles), the negative effect of additives may be masked by the positive effects of plastic particles. Reporting only net positive effects risks overlooking these underlying negative effects. Plants can mitigate the negative impacts of additives and amplify the positive effects of plastic particles. Our study emphasizes the importance of investigating both the individual and combined effects of additives and particles to fully understand and address the impacts of microplastics on terrestrial ecosystems.
Optimizing identification of Lyme disease diagnoses in commercial insurance claims data, United States, 2016–2019
Authors: Nawrocki Courtney C. , Earley Austin R. , Hook Sarah A. , Hinckley Alison F. , Kugeler Kiersten J.
Published: November 2024

Background

Commercial insurance claims data are a stable and consistent source of information on Lyme disease diagnoses in the United States and can contribute to our understanding of overall disease burden and the tracking of epidemiological trends. Algorithms consisting of diagnosis codes and antimicrobial treatment information have been used to identify Lyme disease diagnoses in claims data, but there might be opportunity to improve their accuracy.

Methods

We developed three modified versions of our existing claims-based Lyme disease algorithm; each reflected refined criteria regarding antimicrobials prescribed and/or maximum days between diagnosis code and qualifying prescription claim. We applied each to a large national commercial claims database to identify Lyme disease diagnoses during 2016–2019. We then compared characteristics of Lyme disease diagnoses identified by each of the modified algorithms to those identified by our original algorithm to assess differences from expected trends in demographics, seasonality, and geography.

Results

Observed differences in characteristics of patients with diagnoses identified by the three modified algorithms and our original algorithm were minimal, and differences in age and sex, in particular, were small enough that they could have been due to chance. However, one modified algorithm resulted in proportionally more diagnoses in men, during peak summer months, and in high-incidence jurisdictions, more closely reflecting epidemiological trends documented through public health surveillance. This algorithm limited treatment to only first-line recommended antimicrobials and shortened the timeframe between a Lyme disease diagnosis code and qualifying prescription claim.

Conclusions

As compared to our original algorithm, a modified algorithm that limits the antimicrobials prescribed and shortens the timeframe between a diagnosis code and a qualifying prescription claim might more accurately identify Lyme disease diagnoses when utilizing insurance claims data for supplementary, routine identification and monitoring of Lyme disease diagnoses.
Timing matters: diurnal spine length variation in pediatric patients during radiotherapy
Authors: Meijer Karin M. , van Dijk Irma W.E.M. , Schonk Tamara J. , Balgobind Brian V. , Loginova Anna , van Wieringen Niek , Bel Arjan
Published: November 2024

Background

During the day-night cycle, gravity and applied stress to the body mass and spine causes a decrease in body height, which is restored overnight. This diurnal spine length variation has not yet been quantified during radiotherapy. Therefore, we aimed to quantify diurnal spine length variation on cone beam CTs (CBCTs) of pediatric patients (< 18 years) who underwent radiotherapy.

Methods

For this retrospective study, we included 32 patients (mean age 10.0, range 2.7–16.1 years) who received image guided radiotherapy between 2012 and 2018 in two institutes. Patients were included when they had two fractions per day, or when fractions were scheduled on varying time slots over the course of treatment. Daily CBCTs were registered to the planning CTs using two automatic registrations relative to the bony anatomy; one to vertebra T11 and one to vertebra L4. For each CBCT, the differences between the cranial-caudal (CC) position of the T11 and L4 vertebrae were calculated. To determine the diurnal spine length variation, the difference in vertebrae position between the morning and afternoon CBCTs was calculated. Furthermore, we investigated the possible correlation of diurnal spine length variation with the time slot differences (time interval) between CBCTs (Spearman’s ρ).

Results

Overall, the median spine length variation was -1.0 (range -3.9–0.1) mm, and we found a significant reduction in spine length over the day (p < 0.001) with substantial variations between patients. Time intervals between CBCTs ranging from 4.0 to 9.5 h were not correlated with spine length reduction (ρ=-0.01; p = 0.95).

Conclusions

We found a small but significant reduction in spine length (vertebrae T11 to L4) over the course of day in pediatric patients undergoing radiotherapy, measured on CBCT imaging. Spine length reduction did not correlate with CBCT time intervals. However, our results indicate that diurnal spine length reduction could induce a setup error during treatment, and therefore should be considered in pediatric radiotherapy.
Potential of natural products and gut microbiome in tumor immunotherapy
Authors: Cao Luchang , Wang Xinmiao , Ma Xinyi , Xu Manman , Li Jie
Published: November 2024

Immunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies.
Dual inhibition of HERs and PD-1 counteract resistance in KRASG12C-mutant head and neck cancer
Authors: Novoplansky Ofra , Jagadeeshan Sankar , Prasad Manu , Yegodayev Ksenia M. , Marripati Divyasree , Shareb Raghda Abu , Greenshpan Yariv , Mathukkada Sooraj , Ben-Lulu Talal , Bhattacharya Baisali , Porgador Angel , Kong Dexin , Brägelmann Johannes , Gutkind J. Silvio , Elkabets Moshe
Published: November 2024

Background

Basket clinical trials targeting the KRASG12C-mutation in solid tumors have shown initial promise, including in orphan KRASG12C head and neck cancer (HNC). However, development of resistance to KRASG12C-mutant-specific inhibitors (KRASG12Ci) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRASG12Ci—MRTX849 and AMG510 in a unique syngenic murine KRASG12C-mutated HNC cell line.

Methods

Western-blotting was used for protein abundance and activation, overexpression, and ligand activation studies to verify the intrinsic mechanism of resistance to KRASG12Ci in KRASG12C-mutated HNC cell line, 4NQO-L. In vitro KRASG12C-acquired-resistant cells were developed from 4NQO-L (4NQO-L-AcR). MRTX849/lapatinib combination efficacy, and CD8+ T-cells depletion, were assessed in C57BL/6 J mice and supplementation of anti-PD-1 (αPD-1) to MRTX849/lapatinib was also performed in 4NQO-L– KRASG12Ci-senisitve and 4NQO-L-AcR tumors. Immunohistochemistry (IHC) and Immunoflourescence (IF) analyses were performed to profile the TME and programmed death-ligand 1 (PD-L1) expression in tumors.

Results

Activation and upregulation of EGFR and HER2/3 (pan-HERs) are the intrinsic mechanism of resistance to KRASG12Ci in 4NQO-L cells, and blocking pan-HERs signaling with lapatinib enhanced MRTX849 efficacy in vitro by inhibiting the MAPK and AKT/mTOR pathways. 4NQO-L-AcR upregulated the expression of pan-HERs, and lapatinib treatment re-sensitized 4NQO-L-AcR to MRTX849. In mice, MRTX849 showed a slight anti-tumor effect, but in combination with lapatinib a significant tumor growth delay was observed, but all tumors progressed over time. Histopathology analysis of the TME revealed infiltration of CD8+ T-cells after treatment combination, and these CD8+ T-cells play a key role in MRTX849/lapatinib efficacy. MRTX849/lapatinib treatment upregulated PD-L1 overexpression in both stromal and tumor cells, which presumably suppressed CD8+ T-cells and enabled immune escape and tumor progression. Supplementation of αPD-1 prolonged the progression-free survival of 4NQO-L-bearing mice treated with MRTX849/lapatinib. MRTX849/lapatinib treatment delayed tumor growth of 4NQO-L-AcR in mice; however, the percentages of CD8+ T-cells in 4NQO-L-AcR were low, and supplementation of MRTX849/lapatinib with αPD-1 did not improve the outcome.

Conclusions

Our study highlights the critical need for blocking both intrinsic and extrinsic mechanisms of resistance for the prolonged response and shows that such treatment is ineffective in KRASG12Ci-AcR tumors.
Interventions to modify the habituation of biological responses to repeated stress in healthy adults: a randomized controlled trial
Authors: Janson-Schmitt Johanna , Rohleder Nicolas
Published: November 2024

Background

Changes in response patterns of biological stress systems, including responses of the sympathetic nervous system (SNS) and the hypothalamus–pituitary–adrenal (HPA) axis to repeated stress, can promote the development and progression of chronic diseases via changes in downstream inflammatory processes. The aim of this project is thus to investigate, whether habituation of biological stress system activity including responses of the inflammatory system can be modified. Aiming to test for possible paths of action, a randomized controlled study with two intervention programs designed to manipulate cognitive coping strategies will be carried out. By increasing either ruminative or self-compassionate thoughts among healthy young adults, the intervention programs are expected to affect the regulation of occurring emotions as expressed by the responsiveness of biological systems during repeated stress exposure.

Methods

In this study, a total of 120 healthy adults will complete the Trier Social Stress Test (TSST) on two consecutive days. Immediately after the first stress induction, participants will be randomly assigned to two experimental conditions designed to manipulate cognitive coping strategies (rumination vs. self-compassion) or a control condition. Measures of HPA axis (salivary cortisol) and autonomic activity (salivary alpha amylase, heart rate, heart rate variability) as well as inflammatory markers (plasma interleukin(IL)-6, expression rates of pro- and anti-inflammatory cytokine genes) will be repeatedly assessed throughout the experimental sessions. Response and habituation indices of these measures will be calculated and compared between the experimental conditions and the control condition.

Discussion

The results should provide insight into whether modifying response patterns of biological stress systems could reverse a significant biological mechanism in the development of stress-related diseases.

Trial registration

German Clinical Trials Register (DKRS), DRKS00034790. Registered on August 12, 2024, https://www.drks.de/DRKS00034790.