bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA–Associated Pancreatic Cancer in the Clinical and Preclinical Setting
Authors: Stossel Chani , Raitses-Gurevich Maria , Atias Dikla , Beller Tamar , Glick Gorman Yulia , Halperin Sharon , Peer Eyal , Denroche Robert E. , Zhang Amy , Notta Faiyaz , Wilson Julie M. , O'Kane Grainne M. , Haimov Talmoud Elina , Amison Nora , Schvimer Michael , Salpeter Seth J. , Bar Vered , Zundelevich Adi , Tirosh Itay , Tal Rotem , Dinstag Gal , Kinar Yaron , Eliezer Yonatan , Ben-David Uri , Gavert Nancy S. , Straussman Ravid , Gallinger Steven J. , Berger Raanan , Golan Talia
Published: July 2023

Abstract
Germline BRCA–associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum of response to platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable response followed by acquired resistance (OS <36 months), and (iii) long-term responders (OS >36 months). Patient-derived xenografts (PDX) were generated from 25 patients with glBRCA PDAC at different clinical time points. Response to platinum/PARP inhibition in vivo and ex vivo culture (EVOC) correlated with clinical response. We deciphered the mechanisms of resistance in glBRCA PDAC and identified homologous recombination (HR) proficiency and secondary mutations restoring partial functionality as the most dominant resistant mechanism. Yet, a subset of HR-deficient (HRD) patients demonstrated clinical resistance. Their tumors displayed basal-like molecular subtype and were more aneuploid. Tumor mutational burden was high in HRD PDAC and significantly higher in tumors with secondary mutations. Anti–PD-1 attenuated tumor growth in a novel humanized glBRCA PDAC PDX model. This work demonstrates the utility of preclinical models, including EVOC, to predict the response of glBRCA PDAC to treatment, which has the potential to inform time-sensitive medical decisions.
Significance:
glBRCA PDAC has a favorable response to platinum/PARP inhibition. However, most patients develop resistance. Additional treatment options for this unique subpopulation are needed. We generated model systems in PDXs and an ex vivo system (EVOC) that faithfully recapitulate these specific clinical scenarios as a platform to investigate the mechanisms of resistance for further drug development.

This article is highlighted in the In This Issue feature, p. 1749
Data from Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA–Associated Pancreatic Cancer in the Clinical and Preclinical Setting
Authors: Stossel Chani , Raitses-Gurevich Maria , Atias Dikla , Beller Tamar , Glick Gorman Yulia , Halperin Sharon , Peer Eyal , Denroche Robert E. , Zhang Amy , Notta Faiyaz , Wilson Julie M. , O'Kane Grainne M. , Haimov Talmoud Elina , Amison Nora , Schvimer Michael , Salpeter Seth J. , Bar Vered , Zundelevich Adi , Tirosh Itay , Tal Rotem , Dinstag Gal , Kinar Yaron , Eliezer Yonatan , Ben-David Uri , Gavert Nancy S. , Straussman Ravid , Gallinger Steven J. , Berger Raanan , Golan Talia
Published: July 2023

Abstract
Germline BRCA–associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum of response to platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable response followed by acquired resistance (OS <36 months), and (iii) long-term responders (OS >36 months). Patient-derived xenografts (PDX) were generated from 25 patients with glBRCA PDAC at different clinical time points. Response to platinum/PARP inhibition in vivo and ex vivo culture (EVOC) correlated with clinical response. We deciphered the mechanisms of resistance in glBRCA PDAC and identified homologous recombination (HR) proficiency and secondary mutations restoring partial functionality as the most dominant resistant mechanism. Yet, a subset of HR-deficient (HRD) patients demonstrated clinical resistance. Their tumors displayed basal-like molecular subtype and were more aneuploid. Tumor mutational burden was high in HRD PDAC and significantly higher in tumors with secondary mutations. Anti–PD-1 attenuated tumor growth in a novel humanized glBRCA PDAC PDX model. This work demonstrates the utility of preclinical models, including EVOC, to predict the response of glBRCA PDAC to treatment, which has the potential to inform time-sensitive medical decisions.
Significance:
glBRCA PDAC has a favorable response to platinum/PARP inhibition. However, most patients develop resistance. Additional treatment options for this unique subpopulation are needed. We generated model systems in PDXs and an ex vivo system (EVOC) that faithfully recapitulate these specific clinical scenarios as a platform to investigate the mechanisms of resistance for further drug development.
Supplementary Figure 1 from Major histocompatibility complex-class II is induced by Interferon-gamma and follows three distinct patterns of expression in colorectal cancer organoids
Authors: Pickles Oliver J , Wanigasooriya Kasun , Ptasinska Anetta , Patel Akshay J. , Robbins Helen L , Bryer Claire , Whalley Celina M , Tee Louise , Lal Neeraj , Pinna Maria , Elzefzafy Nahla , Taniere Philippe , Beggs Andrew D , Middleton Gary M.
Published: July 2023

Full flow cytometry results from all fifteen organoid lines for Class I and Class II expression +/- IFNγ stimulation (24 hours). Histogram overlay representing change in Class II expression with stimulation with control (red) and treated (blue). See also Figure 1 a-c.
Data from MHC Class II is Induced by IFNγ and Follows Three Distinct Patterns of Expression in Colorectal Cancer Organoids
Authors: Pickles Oliver J. , Wanigasooriya Kasun , Ptasinska Anetta , Patel Akshay J. , Robbins Helen L. , Bryer Claire , Whalley Celina M. , Tee Louise , Lal Neeraj , Pinna Claudia M.A. , Elzefzafy Nahla , Taniere Philippe , Beggs Andrew D. , Middleton Gary M.
Published: July 2023

Tumor-specific MHC class II (tsMHC-II) expression impacts tumor microenvironmental immunity. tsMHC-II positive cancer cells may act as surrogate antigen-presenting cells and targets for CD4+ T cell–mediated lysis. In colorectal cancer, tsMHC-II negativity is common, in cell lines due to CIITA promoter methylation. To clarify mechanisms of tsMHC-II repression in colorectal cancer, we analyzed colorectal cancer organoids which are epigenetically faithful to tissue of origin. 15 primary colorectal cancer organoids were treated with IFNγ ± epigenetic modifiers: flow cytometry was used for tsMHC-II expression. qRT-PCR, total RNA sequencing, nanopore sequencing, bisulfite conversion/pyrosequencing, and Western blotting was used to quantitate CIITA, STAT1, IRF1, and JAK1 expression, mutations and promoter methylation and chromatin immunoprecipitation to quantitate H3K9ac, H3K9Me2, and EZH2 occupancy at CIITA.

We define three types of response to IFNγ in colorectal cancer: strong, weak, and noninducibility. Delayed and restricted expression even with prolonged IFNγ exposure was due to IFNγ-mediated EZH2 occupancy at CIITA. tsMHC-II expression was enhanced by EZH2 and histone deacetylase inhibition in the weakly inducible organoids. Noninducibility is seen in three consensus molecular subtype 1 (CMS1) organoids due to JAK1 mutation. No organoid demonstrates CIITA promoter methylation.

Providing IFNγ signaling is intact, most colorectal cancer organoids are class II inducible. Upregulation of tsMHC-II through targeted epigenetic therapy is seen in one of fifteen organoids. Our approach can serve as a blueprint for investigating the heterogeneity of specific epigenetic mechanisms of immune suppression across individual patients in other cancers and how these might be targeted to inform the conduct of future trials of epigenetic therapies as immune adjuvants more strategically in cancer.
Significance:
Cancer cell expression of MHC class II significantly impacts tumor microenvironmental immunity. Previous studies investigating mechanisms of repression of IFNγ-inducible class II expression using cell lines demonstrate epigenetic silencing of IFN pathway genes as a frequent immune evasion strategy. Unlike cell lines, patient-derived organoids maintain epigenetic fidelity to tissue of origin. In the first such study, we analyze patterns, dynamics, and epigenetic control of IFNγ-induced class II expression in a series of colorectal cancer organoids.
Behavioural Activation versus Treatment as Usual for Depressed Older Adults in Primary Care: A Pragmatic Cluster-Randomised Controlled Trial
Authors: Janssen Noortje P , Lucassen Peter , Huibers Marcus J H , Ekers David , Broekman Theo , Bosmans Judith E , Van Marwijk Harm , Spijker Jan , Oude Voshaar Richard , Hendriks Gert-Jan
Published: July 2023

Introduction: Effective non-pharmacological treatment options for depression in older adults are lacking. Objective: The effectiveness of behavioural activation (BA) by mental health nurses (MHNs) for depressed older adults in primary care compared with treatment as usual (TAU) was evaluated. Methods: In this multicentre cluster-randomised controlled trial, 59 primary care centres (PCCs) were randomised to BA and TAU. Consenting older (≥65 years) adults (n = 161) with clinically relevant symptoms of depression (PHQ-9 ≥ 10) participated. Interventions were an 8-week individual MHN-led BA programme and unrestricted TAU in which general practitioners followed national guidelines. The primary outcome was self-reported depression (QIDS-SR16) at 9 weeks and 3, 6, 9, and 12-month follow-up. Results: Data of 96 participants from 21 PCCs in BA and 65 participants from 16 PCCs in TAU, recruited between July 4, 2016, and September 21, 2020, were included in the intention-to-treat analyses. At post-treatment, BA participants reported significantly lower severity of depressive symptoms than TAU participants (QIDS-SR16 difference = −2.77, 95% CI = −4.19 to −1.35), p < 0.001; between-group effect size = 0.90; 95% CI = 0.42–1.38). This difference persisted up to the 3-month follow-up (QIDS-SR16 difference = −1.53, 95% CI = −2.81 to −0.26, p = 0.02; between-group effect size = 0.50; 95% CI = 0.07–0.92) but not up to the 12-month follow-up [QIDS-SR16 difference = −0.89 (−2.49 to 0.71)], p = 0.28; between-group effect size = 0.29 (95% CI = −0.82 to 0.24). Conclusions: BA led to a greater symptom reduction of depressive symptoms in older adults, compared to TAU in primary care, at post-treatment and 3-month follow-up, but not at 6- to 12-month follow-up.
Immunvermittelte entzündliche Erkrankungen: Spezialisten aus Klinik und Praxis sollten sich austauschen
Authors: Adler Sabine
Published: July 2023

Hintergrund: Chronische Entzündungserkrankungen (engl. «immune-mediated inflammatory diseases» [IMID]) sind mit einer erheblichen Krankheitslast verbunden. Diese ist umso ausgeprägter, sofern diese gleichzeitig bei Patienten auftreten oder z. B. weitere Komorbiditäten bestehen. Die Versorgung der IMID ist komplex und involviert diverse medizinische Fachdisziplinen. Ziel der Arbeit: Die Beschreibung der Krankheitslast und der aktuellen Arzneimittelversorgung der Patienten mit IMID. Material und Methoden: Die retrospektive Querschnittanalyse erfolgte unter Nutzung von Abrechnungsdaten der gesetzlichen Krankenversicherung der InGef-Datenbank. Unter 3.988.695 Versicherten wurden im Jahr 2018 anhand dokumentierter Diagnosen (ICD-10-GM) prävalente Patienten mit Psoriasis (Pso), Psoriasisarthritis (PsA), Spondyloarthritiden (SpA), rheumatoider Arthritis (RA), Morbus Crohn (MC), Colitis ulcerosa (CU) oder Kollagenosen identifiziert. Das gemeinsame Auftreten verschiedener IMID sowie weiterer Begleiterkrankungen wurde im Vergleich zur Referenzpopulation untersucht. Die medikamentöse Versorgung wurde basierend auf vordefinierten Therapieformen beschrieben. Ergebnisse: Im Jahr 2018 wurden 188.440 Patienten mit IMID (4,7%) identifiziert. Im Vergleich zur Referenzpopulation war die Prävalenz von depressiven Episoden und kardiovaskulären Risikoerkrankungen bei Patienten mit IMID höher. Bei MC, CU, RA, und PsA wurden DMARDs (engl. «disease-modifying antirheumatic drugs») und klassische systemische Therapien am häufigsten eingesetzt. Bei Pso, SpA und Kollagenosen waren NSAR (nichtsteroidale Antirheumatika) die häufigsten Therapieformen oft in Kombination mit anderen Wirkstoffen.
Teledermatologie: Was den Erfolg in der Breitenversorgung von Patienten mit Akne bremst
Authors: Kirsten Natalia
Published: July 2023

Background: Acne vulgaris is one of the most common dermatological diseases, especially in adolescents and young adults. Objective: The current study aimed to compare teledermatology versus face-to-face consultation in the follow-up of patients with mild-to-moderate acne. Methods: In this investigator-initiated, parallel arms, open-label, randomized clinical trial, after screening, participants were randomly assigned in a 1:1 ratio to be followed up through teledermatology or standard face-to-face consultations for a period of 6 months. The primary endpoint was the cumulative time spent by physician for consultations or online assessments. Results: Out of 24 patients (21 females and 3 males; mean age 23.0 ± 3.3 years) underwent randomization in the two study groups. In intention-to-treat analysis, the cumulative time spent by physician was higher in the teledermatology group compared to face-to-face consultations with an average difference of 8:24 mm:ss (95% CI: 1:17-15:31). However, the cumulative time spent by the patient was significantly lower in the teledermatology group (mean difference 1:21:39 hh:mm:ss; 95% CI: 41:51-2:01:27). An optimal reduction of acne-severity was observed in both groups, without significant differences between them. The patient's satisfaction did not change significantly over time and between groups, and was generally quite high. AEs were reported by one patient in the teledermatology group and four patients in the consultation group.
Akupunktur bei saisonaler allergischer Rhinitis: Studie zeigt positive Effekte auf Entzündungsparameter
Authors: Lang Anna , Luschkova Daria , Traidl-Hoffmann Claudia
Published: July 2023

Purpose: Numerous studies have demonstrated effectiveness for acupuncture in the treatment of seasonal allergic rhinitis (SAR). However, the underlying mechanism remains still unclear. Methods: 29 SAR patients were recruited from a large randomized, controlled trial investigating the efficacy of acupuncture in SAR. 16 patients were treated by acupuncture plus rescue medication (RM, cetirizine), 6 patients received sham acupuncture plus RM and 8 patients RM alone over 8 weeks. Patients were blinded to the allocation to real or sham acupuncture. At baseline and different time-points during intervention, plasma and nasal concentration of mediators of various biological functions were determined in addition to validated disease-specific questionnaires. Results: The concentration of biomarkers related to the Th1-, Th2-, and Treg-cluster was not changed in patients who received acupuncture, in neither plasma nor nasal fluid. However, with respect to eotaxin and some unspecific pro-inflammatory cytokines (IL-1b, IL-8, IP-10, MIP-1b, MCP-1), acupuncture led to a, partially significantly, lower nasal concentration than sham acupuncture or RM. Furthermore, the nasal symptom score was significantly reduced in patients only after real acupuncture.
Redes sociotécnicas, ação social e democracia na Ciberpólis: reflexões sobre a hibridização do espaço, o desenvolvimento do capitalismo de vigilância e as subjetividades
Authors: Nasser Ricardo Massao Nakamura , Egler Tamara Tania Cohen
Published: July 2023

O escrito tem como desígnio discutir, em âmbito sociológico, político e econômico, o processo de ascensão da sociabilidade mediada pelas tecnologias da informação e comunicação baseadas nas redes sociotécnicas, os efeitos desse tipo de interação sobre a subjetividade humana e sobre as relações espaço-temporais e corpo-espaciais. Estabelece como esteio epistemológico a formulação de um espaço híbrido e vivo, existente na interface entre o virtual e o concreto denominado Ciberpólis. Elenca as etapas de consolidação dos estudos sociais em tecnologia e inovação e o processo de reconhecimento da realidade que se conecta com os intensos fluxos de dados e informação, abordando a consolidação do capitalismo de vigilância, apontado como nova faceta do sistema econômico e cultural vigente, que se estabelece pelas bases do monopólio, do controle e da manipulação. Por fim, lança questionamentos específicos acerca da questão da democracia na conjuntura do sul global inserido na Ciberpólis e os caminhos societários possíveis para transformação do espaço das redes em locus inclusivo, plural e equitativo.
A formação da sociologia digital: emergência de uma nova especialidade na sociologia ou um campo para repensar a própria sociologia?
Authors: Cordeiro Veridiana Domingos , Gomes Letícia Pereira Simões , Waizbort Leopoldo Garcia Pinto
Published: July 2023

Apresentação do dossiê
101 anos de Darcy Ribeiro
Authors: Varjão João Victtor Gomes
Published: July 2023

Em seu centenário, como uma forma de reconhecer e rememorar seu engajamento político, social e intelectual, a Revista Cadernos de Campo propôs o dossiê especial “O centenário de Darcy Ribeiro” organizado pelo editor João Victtor Gomes Varjão. Este dossiê tematiza sua obra, sua luta e seu engajamento político, bem como, sua influência decisiva ao pensamento social brasileiro contemporâneo. O objetivo central do dossiê foi o de apresentar e analisar a obra desse importante intelectual brasileiro, sem deixar de lado sua atuação política. Nesse sentido, junto com a Comissão e o Comitê Editorial da Revista Cadernos de Campo, propomos convites a antropólogos que possuem relações com Darcy Riberio – desde pesquisadores que trabalharam diretamente com o antropólogo a pesquisadores que debruçaram-se sobre sua obra. Foram convidados os antropólogos e as antropólogas André Borges de Mattos, Delcides Marques, Gisele Jacon de Araujo Moreira e Lux Vidal, que, em diferentes abordagens, apresentaram facetas de Darcy Riberio.
O conto vence por nocaute: resenha de Valise de cronópio
Authors: Sousa Saulo Lopes de
Published: July 2023

Resenha do livro Valise de cronópio (2018), de Julio Cortázar, especialmente, os capítulos “Alguns aspectos do conto” e “Do conto breve e seus arredores”.
A Sabiá
Authors: Silva Mateus Roque da
Published: July 2023

Conto de Mateus Roque da Silva.
A solidão
Authors: Parma Diego Cestari
Published: July 2023

Poema de Diego Parma.
O Filho do vento
Authors: Araújo Manoel Matias Medeiros de
Published: July 2023

Conto de Manoel Matias Medeiros de Araújo.
Amor, desespero e o pior das probabilidades
Authors: Izzo Jeison
Published: July 2023

Conto de Jeison Izzo.
Uma Canção Indigesta: o teatro dos trabalhadores do Engenho Teatral
Authors: Bustamante Fernando
Published: July 2023

Por meio de uma breve discussão sobre a história, a filiação artística e os pressupostos teóricos e estéticos da obra do Engenho Teatral, cuja trajetória se inicia em 1979, seguida por uma análise sucinta de sua última peça Canção Indigesta (2019), o artigo aborda a trajetória e a produção de um grupo teatral que há mais de quatro décadas tem abordado, por meio de suas peças, as questões da classe trabalhadora, tanto em seus aspectos objetivos como subjetivos, fazendo delas o seu tema fundamental.
A representação do professor nos romances de Jeferson Tenório
Authors: Lengert Hugo Ricardo
Published: July 2023

Este artigo tem o intuito de investigar como ocorre a representação do professor como personagem nos romances O beijo na parede (2013), Estela sem Deus (2018) e O avesso da pele (2020b), do escritor Jeferson Tenório. Aspectos do enredo, do narrador e de outros personagens foram abordados neste estudo para compor a representação do professor como figura social e comportamental nos romances deste autor. A análise deste estudo ocorreu por meio de pesquisa bibliográfica baseada em estudos literários de Brasil (2019), Dalcastagnè (2005), Polesso (2018) e Spalding (2018), além de estudos sobre educação na escola de Alves (2010), Moysés (1994, 1998) e Zatti (2007). O escritor leciona Português na cidade de Porto Alegre e, por essa razão, constrói um retrato desses profissionais que trabalham com a educação básica num contexto de representação, pelo qual se analisa a figura do professor. Logo, a prosa de Tenório convida o leitor à reflexão sobre o papel dos educadores e, em especial, chama a atenção para o trabalho dos docentes nas escolas públicas.
Marias
Authors: Alves Daniel Cardoso
Published: July 2023

Poema de Daniel Cardoso Alves.
Sobre a política do Partido no terreno da arte e da filosofia
Authors: Trótski Leon , Canary Henrique
Published: July 2023

Tradução da resposta de Leon Trótski aos camaradas americanos Glee, Ross e Morris sobre as políticas do Partido quanto às artes e a filosofia.
Maria e os ventos caídos
Authors: Munizo Raeltom Santos
Published: July 2023

Conto de Raeltom Santos Munizo.
“Uma excelente estreia”: a chegada do romance proletário ao Brasil
Authors: Chareyre Antoine
Published: July 2023

Com Parque industrial, lançado em São Paulo no começo de 1933 sob o pseudônimo de Mara Lobo, a jovem Patrícia Galvão (1910-1962), então conhecida pelo nome de Pagu, assinava, sem nenhuma pretensão à carreira literária, o primeiro “romance proletário” publicado no Brasil. Mesmo que ele tenha permanecido muito tempo relegado a segundo plano, para não dizer ocultado na história literária até sua primeira reedição em 1981 – e a redescoberta da escritora data da mesma época –, o romance foi objeto de uma recepção diligente e bastante atenta, antes que Cacau de Jorge Amado viesse alguns meses mais tarde capturar o debate entorno do romance proletário. O exame dessa fortuna crítica, acompanhado por uma recontextualização da obra por meio da biografia da autora, permite hoje compreender melhor qual era a imagem pública e o lugar de Pagu no campo literário e cultural. A partir daí é possível também reavaliar a singularidade e as potencialidades de um texto que conjuga, de maneira surpreendente, os critérios da literatura engajada ao serviço do combate comunista, e os da literatura de vanguarda, assimilando a herança formal e estilística do movimento modernista no seio do qual a autora havia feito seus primeiros passos.
Prehospital Activation of the Cardiac Catheterization Laboratory in ST‐Segment–Elevation Myocardial Infarction for Primary Percutaneous Coronary Intervention
Authors: Savage Michael L. , Hay Karen , Vollbon William , Doan Tan , Murdoch Dale J. , Hammett Christopher , Poulter Rohan , Walters Darren L. , Denman Russell , Ranasinghe Isuru , Raffel Owen Christopher
Published: July 2023

Background

Prehospital activation of the cardiac catheter laboratory is associated with significant improvements in ST‐segment–elevation myocardial infarction (STEMI) performance measures. However, there are equivocal data, particularly within Australia, regarding its influence on mortality. We assessed the association of prehospital activation on performance measures and mortality in patients with STEMI treated with primary percutaneous coronary intervention from the Queensland Cardiac Outcomes Registry (QCOR).

Methods and Results

Consecutive ambulance‐transported patients with STEMI treated with primary percutaneous coronary intervention were analyzed from January 1, 2017 to December 31, 2020 from the QCOR. The total and direct effects of prehospital activation on the primary outcomes (30‐day and 1‐year cardiovascular mortality) were estimated using logistic regression analyses. Secondary outcomes were STEMI performance measures. Among 2498 patients (mean age: 62.2±12.4 years; 79.2% male), 73% underwent prehospital activation. Median door‐to‐balloon time (34 minutes [26–46] versus 86 minutes [68–113];
P
<0.001), first‐electrocardiograph‐to‐balloon time (83.5 minutes [72–98] versus 109 minutes [81–139];
P
<0.001), and proportion of patients meeting STEMI targets (door‐to‐balloon <60 minutes 90% versus 16%;
P
<0.001), electrocardiograph‐to‐balloon time <90 minutes (62% versus 33%;
P
<0.001) were significantly improved with prehospital activation. Prehospital activation was associated with significantly lower 30‐day (1.6% versus 6.6%;
P
<0.001) and 1‐year cardiovascular mortality (2.9% versus 9.5%;
P
<0.001). After adjustment, no prehospital activation was strongly associated with increased 30‐day (odds ratio [OR], 3.6 [95% CI, 2.2–6.0],
P
<0.001) and 1‐year cardiovascular mortality (OR, 3.0 [95% CI, 2.0–4.6];
P
<0.001).

Conclusions

Prehospital activation of cardiac catheterization laboratory for primary percutaneous coronary intervention was associated with significantly shorter time to reperfusion, achievement of STEMI performance measures, and lower 30‐day and 1‐year cardiovascular mortality.
Role of ST‐Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST‐Segment–Elevation Myocardial Infarction
Authors: Wu Chao , Gao Xiaojin , Li Ling , Jing Quanmin , Li Weimin , Xu Haiyan , Zhang Wenbo , Li Sidong , Zhao Yanyan , Wang Yang , Li Wei , Wu Yongjian , Hu Fenghuan , Jin Chen , Qiao Shubin , Yang Jingang , Yang Yuejin ,   the CAMI (China Acute Myocardial Infarction) Registry Study Group
Published: July 2023

Background

To evaluate the role of ST‐segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST‐segment–elevation myocardial infarction by investigating the long‐term prognostic impact.

Methods and Results

From January 2013 through September 2014, we studied 5966 patients with ST‐segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST‐segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2‐year all‐cause mortality. STR < 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2‐year mortality than STR <50% (11.7%). Successful STR was an independent predictor of 2‐year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2‐year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.

Conclusions

Post‐PPCI STR is a robust long‐term prognosticator for ST‐segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, supporting it as a convenient and reliable surrogate end point for defining successful PPCI.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01874691.
COVID-19, Meaning and Mental Health in Higher Education: An International Comparison
Authors: Schilderman Hans , Kregting Joris , Scherer-Rath Michael , Riegel Ulrich , Unser Alexander
Published: July 2023

The impact of the COVID-19 pandemic is studied among Dutch and German university students and staff, at the inception of the pandemic in April 2020. The effects of conditions of study and work are studied on mental health, while taking into account the adaptive function of meaning and controlling for relevant demographic characteristics. Results indicate that negative experiences of study and work affect various dimensions of mental health and differ for Dutch and German university contexts. Meaning acts as a resource for mental health, especially regarding dimensions of meaningfulness and trust. Programs for university care are called for in which the insights of this study are taken into account.
Domestic Courts’ Reliance on International Law to Interpret the Charter of Rights and Freedoms and/or other Domestic Law in the Seychelles
Authors: Ddamulira Mujuzi Jamil
Published: July 2023

Unlike the Constitutions of some African States such as Kenya, South Africa, Zimbabwe and Comoros, the Constitution of Seychelles is silent on the status of international law (both treaty law and customary international law) in the Seychelles legal system. However, Article 48 of the Constitution requires courts to, inter alia, ensure that the Charter of Rights and Freedoms (the Charter) is ‘interpreted in such a way so as not to be inconsistent with any international obligations of Seychelles relating to human rights and freedoms.’ Article 64(4) of the Constitution provides that for Seychelles to be bound by a treaty, such a treaty has to be ratified by Parliament. In this article, the author illustrates how Seychelles courts (the Supreme Court, the Constitutional Court and the Court of Appeal) have applied or interpreted Articles 48 and 64 of the Constitution. The author submits, inter alia, that there is room for the argument that Seychelles courts may also refer to treaties which have not been ratified by Seychelles when interpreting the Charter of Rights. It is also argued that for courts to refer to a treaty when interpreting the Charter, there is no requirement for such a treaty to have been domesticated in Seychelles. It is argued further that in the absence of a constitutional provision to the contrary, customary international law is part of Seychelles law.
3. Separate Careers, Separate Lives
Authors: Auspos Patricia
Published: July 2023

Elsie Clews Parsons (1874-1941) and her husband Herbert Parsons (1869-1925) present a very different pattern of conflict and accommodation in a marriage shaped by the wife’s determination to work. Both Elsie and Herbert came from wealthy and prominent New York families. When they married in 1900, after a six-year courtship, Elsie was an atheist, a feminist, and a social rebel who openly challenged female stereotypes and traditional roles. A Ph.D. in sociology, she was teaching at Barnard College and insisted on keeping her job. Herbert, a deeply religious and rather staid man, was a successful lawyer and politician.

Although Elsie and Herbert seemed mismatched, I argue, in contrast to other of Elsie’s biographers, that their marriage was a love match. Their troubles began after Herbert was elected to Congress in 1904. Elsie gave up her teaching job, moved to Washington with their two children, and had four more children (two died shortly after birth). When the controversial views she espoused in her first book set off a public furor that offended and embarrassed Herbert, she stopped publishing under her own name. A few years later, she was wracked with jealousy when she thought he had fallen in love with another woman.

Elsie and Herbert did not divorce, but they led increasingly separate lives after they returned to New York in 1911. Elsie organized her personal and domestic life around two new careers. After establishing a foothold in the feminist, bohemian intellectual world in Greenwich Village, she became a sought-after, influential social critic, writing for The Masses and The New Republic. Then she connected with Franz Boas’s professional circle and became a highly respected anthropologist, studying indigenous peoples in the American Southwest, the Caribbean, and South America.

Elsie had two lengthy love affairs, with the architect Grant LaFarge, and the novelist Robert Herrick. She deliberately chose lovers who – unlike Herbert – were adventurous, interested in her work, and eager to travel with her. In the late teens and twenties, her relationship with Herbert gradually improved, in part because he took on more responsibility for their four surviving children. His unexpected death in 1925, while she was involved with Herrick, was a blow for Elsie.

Deeply in love with Elsie, Herrick wrote about her in several novels and short stories in the 1920s. Initially supportive of her work, he became increasingly jealous of her success and deeply angry at being reduced to what he thought was a subordinate role in her life. His last book about her, published in 1932, several years after their affair ended, cruelly disparaged her and her work.

Elsie was repeatedly disappointed by the men in her life, but she never stopped trying to implement her feminist vision of a more equitable and intimate relationship grounded in work rather than domestic life.
Understanding the Driving Forces of the North Pacific Victoria Mode
Authors: Li Zongrong , Ding Ruiqiang , Mao Jiangyu , Ren Zhengyi
Published: July 2023

The Victoria Mode (VM) is defined as the second empirical orthogonal function (EOF) of sea surface temperature anomalies (SSTAs) in the North Pacific. It is independent of the Pacific decadal oscillation (PDO) and represents the second climate mode of North Pacific variability. Using a first-order autoregressive model and forcing indices that track the Aleutian low, the North Pacific Oscillation (NPO), anomalous ocean circulation in the Kuroshio–Oyashio Extension (KOE), and the cold tongue (CT) and warm pool (WP) El Niño–Southern Oscillation (ENSO), this study reconstructs the North Pacific SSTAs and examines the relative contributions of different forcing mechanisms to the VM variance. It is found that the NPO and ENSO, especially the WP ENSO, are the dominant sources of VM variability, whereas the contributions of the Aleutian low and zonal advection in the KOE region are relatively small. Further analysis shows that the forcing mechanisms acting on the VM are frequency dependent. At decadal and longer time scales, the VM variance comes mainly from the WP ENSO, whereas at interannual-time-scale contributions from the NPO and CT ENSO are important. This study suggests that the VM is an oceanic response to the NPO forcing and atmospheric teleconnections excited by ENSO events.
Management Experiences of Post-Gastrectomy Severe Alkaline Reflux Esophagitis
Authors: Temperley Hugo C. , Phoenix Eimear , Waters Caitlin , Hanna Joseph , Fanning Michelle , Donlon Noel E. , Reynolds John V. , Donohoe Claire L.
Published: July 2023

Alkaline reflux esophagitis is a recognized complication of procedures that compromise the lower esophageal sphincter (LES), including gastrectomy. Incidence of reflux is dependent on the reconstructive procedure, with Roux-en-Y (RY) esophagojejunostomy commonly accepted as the optimal method. The authors report their experience of 5 patients who underwent remedial intervention for severe alkaline reflux esophagitis following gastric cancer surgery, over a 6-year period (2014-2020). Primary diagnoses encompassed 4 gastric adenocarcinomas and 1 gastric neuroendocrine tumor. Four patients previously underwent total gastrectomy and 1 subtotal gastrectomy with RY reconstruction. Onset of postoperative reflux symptoms ranged from 2 weeks to 3 years. Failing medical management, all patients underwent jejunojejunal anastomosis and Roux limb length revision with surgical jejunostomy. At follow-up, 4 out of 5 patients had some degree of symptom resolution and one with unresolved symptoms. The authors report our experience of managing this complication following gastrectomy with jejunojejunal anastomosis and Roux limb length revision.
When international rituals go wrong: How ritual failure undermines peaceful change in NATO
Authors: Koschut Simon
Published: July 2023

Recent International Relations scholarship has emphasized the significance of ritual and emotion in international politics. Much less attention has been paid to instances of ritual failure. Ritual failure refers to the occurrence of deliberate mistakes, errors or sabotage to contest the sociocultural boundaries, hierarchies and structures underlying international rituals. In this article, I argue that ritual is an emotion transformer that generates a sense of community among North Atlantic Treaty Organization (NATO) members. Successful ritual makes community members experience ‘we-feeling’, which underpins peaceful change in a security community. NATO members carry the group-aroused emotions for a time and come out of the ritual encounter feeling strong and confident. Conversely, a failed ritual lowers the confidence of community members because they do not experience ‘we-feeling’. I suggest that this explains the internal divisions and anxieties when rituals go wrong, such as during Trump’s infamous speech in front of the new NATO headquarters in 2017.
Understanding social responsibility and relational pressures in nonprofit organisations
Authors: Azmat Fara , Rentschler Ruth , Lee Boram , Fujimoto Yuka
Published: July 2023

Relational pressures across multiple levels push organisations to behave socially responsibly or sometimes irresponsibly. But how do relational pressures across multiple levels influence social responsibility of small nonprofit organisations working with marginalised groups? Nonprofit organisations are increasing in importance owing to their role in development and representation of marginalised groups’ interests, yet their social responsibility is little understood. Using the lens of standpoint theory, we explore social responsibility of small disability arts organisations in the nonprofit sector in Australia drawing on 53 interviews involving actors at multiple levels, supplemented by site visits and observations. We find small nonprofit organisations’ social responsibility in a state of flux, influenced by differing priorities, expectations, and demands from various actors across levels. We provide insights into organisational social responsibility dynamics, identifying three major tensions that small arts organisations face – formality versus informality, agency versus representation, and access versus excellence – in seeking to be socially responsible. Our findings have relevance for organisations in the wider nonprofit sector, underscoring the need to explore their social responsibility from a relational perspective. Further, the resultant tensions from relational pressures, as identified in our study, provide important implications for organisational social responsibility advancing theoretical and practical knowledge in this emerging field.
Co-occurrence of Periodontitis and Diabetes-Related Complications
Authors: Bitencourt F.V. , Nascimento G.G. , Costa S.A. , Andersen A. , Sandbæk A. , Leite F.R.M.
Published: July 2023

Periodontitis is a common finding among people with diabetes mellitus (DM) and has been cited as a DM complication. Whether and how periodontitis relates to other diabetes-related complications has yet to be explored. This study aims to examine the clustering of periodontitis with other diabetes-related complications and explore pathways linking diabetes-related complications with common risk factors. Using data from participants with DM across 3 cycles of the National Health and Nutrition Examination Survey (NHANES) ( n = 2,429), we modeled direct and indirect pathways from risk factors to diabetes-related complications, a latent construct comprising periodontitis, cardiovascular diseases, proteinuria, and hypertension. Covariates included age, sex, socioeconomic status (SES), smoking, physical activity, healthy diet, alcohol consumption, hemoglobin A1c (HbA1c), dyslipidemia, and body mass index (BMI). Sensitivity analyses were performed considering participants with overweight/obesity and restricting the sample to individuals without DM. Periodontitis clustered with other diabetes complications, forming a latent construct dubbed diabetes-related complications. In NHANES III, higher HbA1c levels and BMI, older age, healthy diet, and regular physical activity were directly associated with the latent variable diabetes-related complications. In addition, a healthy diet and BMI had a total effect on diabetes-related complications. Although sex, smoking, dyslipidemia, and SES demonstrated no direct effect on diabetes-related complications in NHANES III, a direct effect was observed using NHANES 2011–2014 cycles. Sensitivity analysis considering participants with overweight/obesity and without DM showed consistent results. Periodontal tissue breakdown seems to co-occur with multiple diabetes-related complications and may therefore serve as a valuable screening tool for other well-known diabetes-related complications.
Tmem2 Deficiency Leads to Enamel Hypoplasia and Soft Enamel in Mouse
Authors: Nag P. , Inubushi T. , Sasaki J.I. , Murotani T. , Kusano S. , Nakanishi Y. , Shiraishi Y. , Kurosaka H. , Imazato S. , Yamaguchi Y. , Yamashiro T.
Published: July 2023

Teeth consist of 3 mineralized tissues: enamel, dentin, and cementum. Tooth malformation, the most common craniofacial anomaly, arises from complex genetic and environmental factors affecting enamel structure, size, shape, and tooth eruption. Hyaluronic acid (HA), a primary extracellular matrix component, contributes to structural and physiological functions in periodontal tissue. Transmembrane protein 2 (TMEM2), a novel cell surface hyaluronidase, has been shown to play a critical role during embryogenesis. In this study, we demonstrate Tmem2 messenger RNA expression in inner enamel epithelium and presecretory, secretory, and mature ameloblasts. Tmem2 knock-in reporter mice reveal TMEM2 protein localization at the apical and basal ends of secretory ameloblasts. Micro–computed tomography analysis of epithelial-specific Tmem2 conditional knockout ( Tmem2- CKO) mice shows a significant reduction in enamel layer thickness and severe enamel deficiency. Enamel matrix protein expression was remarkably downregulated in Tmem2- CKO mice. Scanning electron microscopy of enamel from Tmem2- CKO mice revealed an irregular enamel prism structure, while the microhardness and density of enamel were significantly reduced, indicating impaired ameloblast differentiation and enamel matrix mineralization. Histological evaluation indicated weak adhesion between cells and the basement membrane in Tmem2- CKO mice. The reduced and irregular expressions of vinculin and integrin β1 suggest that Tmem2 deficiency attenuated focal adhesion formation. In addition, abnormal HA accumulation in the ameloblast layer and weak claudin 1 immunoreactivity in Tmem2- CKO mice indicate impaired tight junction gate function. Irregular actin filament assembly was also observed at the apical and basal ends of secretory ameloblasts. Last, we demonstrated that Tmem2-deficient mHAT9d mouse ameloblasts exhibit defective adhesion to HA-containing substrates in vitro. Collectively, our data highlight the importance of TMEM2 in adhesion to HA-rich extracellular matrix, cell-to-cell adhesion, ameloblast differentiation, and enamel matrix mineralization.
Leading Through Loss: Experiences of Nursing Home Administrators-in-Training During the COVID-19 Pandemic
Authors: Hawes Frances M.
Published: July 2023

End-of-life care is a critical aspect of long-term care, yet there is limited understanding of nursing home staff’s experiences and preparation in this area, particularly among facility administrators. To address this gap, two cohorts of Administrators-in-Training (2021 & 2022) were interviewed about their knowledge and practices regarding end-of-life care in skilled nursing facilities. Interviews focused on involvement in end-of-life discussions, coping strategies, grief support, and personal perspectives on death. The findings revealed a significant lack of training on death management and end-of-life care for Administrators-in-Training (AITs), with limited grief support mechanisms in place within skilled nursing facilities. Personal experiences with death influenced AITs' approach to end-of-life care, and various coping strategies were observed. The results highlight the need for comprehensive training programs and improved support for AITs to enhance end-of-life care delivery.
An Updated Review on Atrophic Rhinitis and Empty Nose Syndrome
Authors: Sumaily Ibrahim Ali , Hakami Nouf Adel , Almutairi Anwar Dhawi , Alsudays Abdulrahman Abdullah , Abulqusim Ebrahim Mohammed , Abualgasem Mohammed Maki , Alghulikah Abdulrahman Ahmad , Alserhani Abdulrahman Awad
Published: July 2023

Objective: Atrophic rhinitis (AR) is a rare clinical condition affecting the nasal mucosa. It is characterized by progressive nasal congestion and thick, bothersome nasal secretions. In this narrative review, pathogenesis, differences between the 2 types of AR, new management modalities, and the impact of management on lifestyle have been highlighted. Materials and Methods: An extensive literature search was conducted using PubMed, Web of Science, Google Scholar, and Saudi Digital Library databases. The articles were investigated to extract information on the pathogenesis, types, new treatment modalities, and the impact of management on lifestyle. Results: AR has primary and secondary types that affect different populations and have specific clinical presentations. Primary AR is common in women and countries with long, warm seasons. Secondary AR is the most common disease in the industrialized world. It is more common among adults who have systemic disease, have undergone extensive nasal surgery, and have experienced nasal trauma. Certain infections, autoimmune disorders, chronic sinusitis, hormonal imbalance, poor nutritional condition, and iron deficiency anemia have been suggested as etiological factors. Conservative treatment is safe, inexpensive, and effective. Hygiene, a well-balanced diet, smoking cessation, and early detection and treatment of nasal pathology can help prevent AR. Some interventions shown to improve quality of life was explained in detail. Conclusions: This paper reviewed published relevant literature on AR related to pathogenesis, types, new treatment modalities, and the impact of treatment on lifestyle, thus, providing a comprehensive view of the management and prevention of AR.
A Case Study of Threats Against a University-Based Labor Education Program: A Personal Remembrance
Authors: Nissen Bruce
Published: July 2023

University- and college-based labor education programs historically have had a precarious existence. In the early and mid-twentieth century, suspicion by American Federation of Labor leaders and indifference from higher education institutions were the main threats to health and stability. By the 1980s, these dangers lessened considerably, but new menaces emerged. This article relates a personal history wherein the author experienced a series of assaults on his university-based labor education program with the author frequently being at the center of the controversy. The case is analyzed in the context of corporatization of the university and political and labor-related trends.
European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development
Authors: Monné Rodríguez Josep M. , Frisk Anna-Lena , Kreutzer Robert , Lemarchand Thomas , Lezmi Stephane , Saravanan Chandrassegar , Stierstorfer Birgit , Thuilliez Céline , Vezzali Enrico , Wieczorek Grazyna , Yun Seong-Wook , Schaudien Dirk
Published: July 2023

In situ hybridization (ISH) is used for the localization of specific nucleic acid sequences in cells or tissues by complementary binding of a nucleotide probe to a specific target nucleic acid sequence. In the last years, the specificity and sensitivity of ISH assays were improved by innovative techniques like synthetic nucleic acids and tandem oligonucleotide probes combined with signal amplification methods like branched DNA, hybridization chain reaction and tyramide signal amplification. These improvements increased the application spectrum for ISH on formalin-fixed paraffin-embedded tissues. ISH is a powerful tool to investigate DNA, mRNA transcripts, regulatory noncoding RNA, and therapeutic oligonucleotides. ISH can be used to obtain spatial information of a cell type, subcellular localization, or expression levels of targets. Since immunohistochemistry and ISH share similar workflows, their combination can address simultaneous transcriptomics and proteomics questions. The goal of this review paper is to revisit the current state of the scientific approaches in ISH and its application in drug research and development.