bluuebunny/crossref_metadata_2025 huggingface dataset:
LIG1 Is a Synthetic Lethal Target in BRCA1 Mutant Cancers
Authors: Martires Lauren Catherine M. , Ahronian Leanne G. , Pratt Charlotte B. , Das Nikitha M. , Zhang Xiaobin , Whittington Douglas A. , Zhang Hongxiang , Shen Binzhang , Come Jon , McCarren Patrick , Liu Mu-Sen , Min Chengyin , Feng Tianshu , Jahic Haris , Ali Janid A. , Aird Daniel R. , Li Fang , Andersen Jannik N. , Huang Alan , Mallender William D. , Nicholson Hilary E.
Published: January 2025

Synthetic lethality approaches in BRCA1/2-mutated cancers have focused on PARP inhibitors, which are subject to high rates of innate or acquired resistance in patients. In this study, we used CRISPR/Cas9-based screening to identify DNA ligase I (LIG1) as a novel target for synthetic lethality in BRCA1-mutated cancers. Publicly available data supported LIG1 hyperdependence of BRCA1 mutant cells across a variety of breast and ovarian cancer cell lines. We used CRISPRn, CRISPRi, RNAi, and protein degradation to confirm the lethal effect of LIG1 inactivation at the DNA, RNA, and protein level in BRCA1 mutant cells in vitro. LIG1 inactivation resulted in viability loss across multiple BRCA1-mutated cell lines, whereas no effect was observed in BRCA1/2 wild-type cell lines, demonstrating target selectivity for the BRCA1 mutant context. On-target nature of the phenotype was demonstrated through rescue of viability with exogenous wild-type LIG1 cDNA. Next, we demonstrated a concentration-dependent relationship of LIG1 protein expression and BRCA1 mutant cell viability using a titratable, degradable LIG1 fusion protein. BRCA1 mutant viability required LIG1 catalytic activity, as catalytically dead mutant LIG1K568A failed to rescue viability loss caused by endogenous LIG1 depletion. LIG1 perturbation produced proportional increases in PAR staining in BRCA1 mutant cells, indicating a mechanism consistent with the function of LIG1 in sealing ssDNA nicks. Finally, we confirmed LIG1 hyperdependence in vivo using a xenograft model in which LIG1 loss resulted in tumor stasis in all mice. Our cumulative findings demonstrate that LIG1 is a promising synthetic lethal target for development in patients with BRCA1-mutant cancers.
Table 2 from Deep Learning Predicts Subtype Heterogeneity and Outcomes in Luminal A Breast Cancer Using Routinely Stained Whole-Slide Images
Authors: Kurian Nikhil Cherian , Gann Peter H. , Kumar Neeraj , McGregor Stephanie M. , Verma Ruchika , Sethi Amit
Published: January 2025

PFS for the test cohort of PAM50-assigned LumA breast cancer, comparing pure vs. admixed cases based on the proportion of the tumor image classified as LumA by the deep learning model
Supplementary Table S2 from Deep Learning Predicts Subtype Heterogeneity and Outcomes in Luminal A Breast Cancer Using Routinely Stained Whole-Slide Images
Authors: Kurian Nikhil Cherian , Gann Peter H. , Kumar Neeraj , McGregor Stephanie M. , Verma Ruchika , Sethi Amit
Published: January 2025

Supplementary Table S2. Clinical and molecular features of PAM50 Luminal A breast cancers in the independent test set (n = 230) according to degree of adherence of transcriptomic profile to the LumA subtype by semi-supervised noon-negative matrix factorization (ssNMF).
COMPARING DIRECTIONAL AND OMNIDIRECTIONAL DEEP BRAIN STIMULATION IN PARKINSON’S DISEASE PATIENTS
Authors: Kallel Mazen , De Schlichting Emmanuel , Fraix Valerie , Castrioto Anna , Moro Elena , Cordier Louise , Seigneuret Eric , Chabardes Stephan
Published: January 2025

Introduction: In 2015, directional leads have been released in Europe for deep brain stimulation (DBS) and have been particularly used for subthalamic nucleus (STN) DBS for Parkinson’s disease (PD). In this study we aimed to compare an omnidirectional and directional leads cohort of PD patients when it comes to clinical effectiveness and to assess the correlation with volume of tissue activated - target overlap (VTA-target).
Methods: A total of 60 consecutive patients were retrospectively included. 27 patients with bilateral directional leads were compared to 33 patients with bilateral omnidirectional leads. MDS-UPDRS part III scores, levodopa equivalent daily dose (LEDD), and VTA overlaps using both motor STN region and motor improvement sweetspot volume were compared at 12 months after surgery.
Results: There is a significantly higher LEDD reduction in the directional leads group (51.3 % reduction vs 42.7% reduction, p= 0.042) when compared to the omnidirectional group, with similar MDS-UPDRS III motor scores at 12 months. Omnidirectional leads patients had a significantly superior VTA-motor STN overlap volume than directional leads patients (32.01 mm3 vs 20.38 mm2, p = 0.0226). In directional leads patients, LEDD reduction was correlated to VTA overlap with the overall motor improvement mean map sweetspot (R = 0.36, p = 0.036), which was not the case for omnidirectional leads patients (R = 0.11, p = 0.276). Forty one percent of patients implanted with directional leads had a directional stimulation setting at 12 months, compared to thirty three percent at 3 months follow up. In directional leads patient’s subgroup analysis, there was no significant difference in MDS UPDRS III scores, LEDD reduction, VTA overlaps with motor STN or overall motor improvement mean map sweetspot between patients stimulated omnidirectionally and directionally at 12 months.
Conclusion: At 12 months, when compared to omnidirectional leads, directional leads manage with smaller VTA-target overlaps to obtain comparable MDS-UPDRS III scores with greater LEDD reduction in STN DBS for PD patients.
The Problems with Genetic Essentialism, Determinism, and Reductionism
Authors: Moore David S. , Kampourakis Kostas , Gericke Niklas
Published: January 2025

In this article, we address misunderstandings about genetic essentialism, genetic determinism, and genetic reductionism. There are good reasons to carefully consider the meanings and relationships that characterize genetic essentialism, genetic determinism, and genetic reductionism; these are different (if related) concepts, despite their superficial resemblances. Although a recent Nature Reviews Genetics article addressed these issues, problems intrinsic to them remained unexplored, problems that we address here by adopting a developmental systems perspective. Discussions of these concepts should explicitly communicate that genetic essentialism fails because individuals are as they are in part due to the contexts in which they develop, that genetic determinism fails because all phenotypes depend on co-acting genomic and non-genomic factors for their development, and that genetic reductionism fails because emergent properties above the level of the genome can feed back and influence the subsequent functioning of that genome. Elucidating the meaning of these concepts without providing arguments for rejecting them is problematic. Developmental science offers the required arguments.
Quality of Life After Alloplastic vs. Autologous Breast Reconstruction: 'The Influence of Patient Characteristics on Outcomes'
Authors: Holt-Kedde Iris L. , Sadok Nadia , Krabbe-Timmerman Irene S. , de Bock Geertruida H. , Sidorenkov Grigory , Werker Paul M. N.
Published: January 2025

Objective: Quality of life (QoL) following autologous breast reconstruction has been found to be higher compared to alloplastic breast reconstruction. However, evaluating QoL is complex, as it is influenced by various factors, including patient characteristics and treatment types. Previous studies comparing QoL between reconstruction techniques have not sufficiently addressed baseline differences between patient groups, some of which contribute to indication bias. Using an alternative approach to identify the confounders, this study aims to evaluate which factors affect the patient satisfaction and QoL after alloplastic or autologous reconstruction, with follow-up extending up to three years post-surgery. Method: QoL and satisfaction were measured using the Breast-Q preoperatively, and after breast reconstruction( post-BR) at six weeks, six months, one year, and three years. General and mental health were measured using the SF-36 and the HADS. A generalized linear mixed model was utilized to assess which factors confound the relationship between reconstruction technique and Breast-Q scores. Results: Factors contributing to the disparity in Breast-Q scores between autologous and alloplastic breast reconstruction varied across Breast-Q subscales. Autologous breast reconstruction patients consistently reported higher “Satisfaction with Breasts” and “Physical Well-being”, while the minimal important differences in “Psychosocial” and “Sexual Well-being” were lost after adjustment for confounding factors. Conclusion: This study confirms that even when adjusted for confounders, scores on two QoL sub-scales autologous breast reconstruction patients score significantly higher over time. Although autologous reconstruction remained superior regarding “Satisfaction with Breasts”, scores decreased in autologous reconstruction patients when they were depressed at baseline, underwent radiotherapy, had a history of breast cancer, or faced major complications.
Relationship Between Podocyte Injury and Renal Outcomes in Patients with Acute Kidney Injury: A Report From a Retrospective Study in China
Authors: Wu Shun , Guo Mengling , Wang Yudan , Zhou Yilun , Zhang Liyuan , Zhou Yun , Xing Yuanyuan , Sun Dong , Hu Xueqing , Ruan Zhenmin , He John Cijiang , Ren Hongqi
Published: January 2025

Introduction: Podocyte injury has been proven to be a major cause for poor renal outcomes after acute kidney injury (AKI). However, clinical trial data are still limited. This study aimed to explore the clinical correlations between podocyte injury and renal outcomes in hospitalized AKI patients. Method: This retrospective study analyzed data on 52 AKI patients who were histologically diagnosed with acute tubular necrosis (ATN) or acute interstitial nephritis (AIN) from six centers throughout China between January 2012 and June 2023. Patients were classified into two groups based on the degree of foot process fusion: ≤50% (mild podocyte injury group), and ＞50% (severe podocyte injury group). The outcomes were post-AKI new-onset proteinuria and incident CKD. Results: Among 52 AKI patients (14 male; median age, 49 [30, 56] years), 28 (53.8%) had mild podocyte injury, 24 (46.2%) had severe podocyte injury. After 12-month follow-up, 16(57.1%) had post-AKI proteinuria, and 5(17.9%) had post-AKI incident CKD in mild podocyte injury group. 20 (83.3%) had post-AKI new-onset proteinuria, and 14 (58.3%) had post-AKI incident CKD in severe podocyte injury group. Patients with more severe foot process fusion exhibited significantly higher incidences of post-AKI new-onset proteinuria (83.3% vs. 57.1%, P = 0.041) and incident CKD (58.3% vs. 17.9%, P = 0.003) at 12 months following AKI. The degree of foot process fusion (95%CI 1.013～3.88, P=0.048) and proteinuria at 3 months (95%CI 1.309～5.443, P=0.015) were identified as independent risk factors for post-AKI new-onset proteinuria at 12 months. The degree of foot process fusion (95%CI 1.026～14.196, P=0.048), and the presence of partial renal pathological features, including tubular atrophy (95%CI 1.012～5.958, P=0.030), interstitial inflammation (95%CI 1.005～6.846, P=0.039), interstitial fibrosis (95%CI 1.110～6.075, P=0.043) were independent risk factors for post-AKI incident CKD at 12month. Kaplan-Meier analysis shows severe podocyte injury group had worst renal survival, including post-AKI new-onset proteinuria (P=0.0066) and incident CKD (P=0.0455). Conclusion: The degree of podocyte injury is an independent risk factor for post-AKI new-onset proteinuria and incident CKD in patients, and patients with more severe podocyte injury exhibit a higher incidence of post-AKI new-onset proteinuria and incident CKD.
High expression of tetraspanin CD63 predicts poor prognosis in esophageal squamous cell carcinoma
Authors: Matsumoto Yasunori , Otsuka Ryota , Nishioka Yuri , Toyozumi Takeshi , Sekino Nobufumi , Shiraishi Tadashi , Okada Koichiro , Kamata Toshiki , Iida Shinichiro , Morishita Hiroki , Makiyama Tenshi , Yamada Masanari , Matsubara Hisahiro
Published: January 2025

Introduction: Esophageal squamous cell carcinoma (ESCC) has one of the poorest cancer prognosis rates; there is an urgent need to develop new drug therapies and biomarkers. CD63, a tetraspanin protein and well-known exosomal marker, is implicated in cancer progression; however, the significance of CD63 expression in ESCC remains unclear. Herein, we report the significance of CD63 expression by analyzing ESCC patient samples and ESCC cell lines.

Methods: ESCC patient samples (n=86) were evaluated for CD63 expression by immunostaining; univariate and multivariate analysis using Cox proportional hazards were used to evaluate CD63 expression and clinicopathological features as prognostic factors for survival. For in vitro analysis, CD63 knockdown was performed in human ESCC cell lines (TE2 and TE15) using siRNA, and changes in proliferative potential. The gene expression change were also analyzed by microarray and gene set enrichment analysis.

Results: Overall survival was significantly worse in the CD63 high group (P=0.031, log-rank test). Five-year overall survival univariate analysis identified positive lymph nodes, pStage 3 or higher, and CD63 high expression as poor prognostic factors, while multivariate analysis showed that CD63 high expression was an independent poor prognostic factor (P=0.009, HR 2.56, 95%CI 1.269–5.167). CD63 knockdown in ESCC cell lines resulted in a phenotype of decreased proliferative potential. CD63 knockdown increased the expression of genes involved in cell adhesion and suppressed the expression of genes involved in granule secretion. CD63 also shown to affect nuclear import, protein complex localization, and ERBB-signaling pathways. In conclusion, CD63 affects gene expression in ESCC, and high tissue expression of CD63 predicts poor prognosis in ESCC patients.
A New Case of Nager Syndrome as a Rare Cause of Acrofacial Dysostosis
Authors: Aglamis Senel Ozge , Kilic Esra
Published: January 2025

Introduction: Nager acrofacial dysostosis (#154400) is a rare and mostly sporadic malformation syndrome characterized by craniofacial and extremity findings. In the study, a new case diagnosed in the neonatal period will be presented.

Case presentation: The neonatal intensive care unit consulted to our pediatrics genetic clinic for a 2-week-old male patient, who was being followed up in their unit, due to his dysmorphic findings and extremity defects. In the physical examination, downward palpebral fissures, zygomatic bone hypoplasia, mandibular hypoplasia, retromicrognathia, bilateral microtia, bilateral external auditory canal atresia, and bilateral thumb agenesis were observed. Direct radiographs showed left radius hypoplasia and bilateral thumb agenesis. Nager syndrome was considered in the presence of typical craniofacial findings, preaxial extremity deformities, and radiological findings. In the SF3B4 sequence analysis, c.737dupC p.(V247Sfs*239) heterozygous variant was detected.

Conclusion: As a result of the segregation analysis, it was demonstrated that the variant was de novo. Nager acrofacial dysostosis should be considered in the patients with craniofacial malformations and radial ray findings.
Validation of a New Classification for Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants: Insights from a Large Japanese Cohort
Authors: Nakanishi Hidehiko , Ito Masato , Kato Shin , Saito Makoto , Miyahara Naoyuki , Arai Hirokazu , Ota Erika , Namba Fumihiko ,   on behalf of Neonatal Research Network
Published: January 2025

Introduction: A recent scoping review identified histological chorioamnionitis (HCA), small for gestational age (SGA), and bubbly/cystic appearance on chest X-ray (bubbly/cystic CXR) as risk factors for severe bronchopulmonary dysplasia (BPD). To further validate these results, a large-scale database was analyzed.
Methods: This retrospective multicenter cohort study included infants born at <28 weeks' gestational age between 2003 and 2016. The validated risk factors identified from the scoping review were analyzed for independent associations with severe BPD using multivariable logistic regression. Additionally, the association of these factors with long-term outcomes at 3 years, including home oxygen therapy (HOT) and neurodevelopmental impairments (NDIs), were analyzed.
Results: Among 15,834 extremely preterm infants, HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were significantly and independently associated with severe BPD (adjusted odds ratio, 1.20; 95% confidence interval, 1.06–1.36) (1.73; 1.51–1.98) (1.79; 1.60–2.01), respectively. These three factors were also linked to HOT at 3 years (1.54; 1.14–2.08) (1.70; 1.21–2.39) (2.63; 1.94–3.56), respectively. Their combination significantly increased the prevalence of severe BPD and HOT at 3 years, particularly with bubbly/cystic CXR. Only SGA was independently associated with NDIs in BPD infants (1.55; 1.32–1.83).
Conclusions: HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were identified as important risk factors for severe BPD and long-term respiratory outcomes. While further research is needed to validate their role in endotype-specific classification of BPD, these findings may contribute to early prognostic strategies and targeted interventions before 36 weeks' postmenstrual age.
“Cartas serviçais e amigas”: A epistolografia em Correio da Roça, de Júlia Lopes de Almeida
Authors: Modolo Verônica dos Santos
Published: January 2025

Júlia Lopes de Almeida foi uma figura de grande relevância na história literária brasileira, uma mulher escritora de sucesso no início do século XX. Nos últimos 20 anos, a fortuna crítica busca compreender o estilo de escrita de Lopes de Almeida e seus posicionamentos no contexto da belle époque brasileira. Especificamente sobre a obra Correio da Roça (1913), objeto deste artigo, enquanto suas temáticas foram discutidas ao longo dos anos, sua estrutura recebeu menor foco. É sobre este aspecto crítico que este artigo propõe se debruçar, ao colocar em questão a denominação de ‘cartilha’ para o livro e, como alternativa, enfatizar a centralidade do gênero epistolar para a composição da obra e para a coesão dos diversos temas que a perpassam. Como base desta análise, valemo-nos de pesquisadores do gênero epistolar em sua especificidade literária como Altman (1985), Sussekind (2003), Diaz (2016), Haroche-Bouzinac (2016). Nesta leitura, propomos que estas missivas, inseridas na dinâmica epistolar deste romance, têm uma função para além da informativa, na medida em que fomentam nas correspondentes a busca pelo conhecimento pela observação do mundo e a autonomia de ação.
O meu amor é melhor que o teu: uma análise discursivo-pragmática de declarações de amor em publicações no Instagram
Authors: Ninitas Mariana Silva
Published: January 2025

Social media allow, among other aspects, to simulate a level of interpersonal closeness, achieved through the exposure of an individual's intimacy to a group of people who, under other circumstances, would not have access to such information. Among the different strategies for sharing privacy on social media, the love confession may perhaps be one of the most frequent, constituting a text in which the author confesses their feelings, ideally paying tribute to the person they are involved with. In this sequence, in the present work, we aim to understand whether these texts are a new way of expressing love in writing, constituting updated examples of the epistolary genre, even if it wasn’t the only way of doing it in the past. To do so, we analyze a corpus of seven Instagram captions from different authors, seeking to understand, from a discursive-pragmatic perspective, the convergences between these examples and the genre in question. Focusing this goal, we analyze some typical features of the epistolary genre, such as opening and closing formulas, and treatment and courtesy forms, relating them to the notion of ethos, but also of implicit. In general terms, we conclude that the common points are evident, not only regarding verbal routines but also concerning the construction of the authors' ethos, the dialogical nature of the discourse, as well as the choice of speech acts.
O repetível de um gênero do discurso e o repetível da história: centralização e universalização
Authors: Correa Manoel Luiz Gonçalves
Published: January 2025

Neste trabalho, assumimos o repetível dos gêneros do discurso para estabelecer um paralelo entre duas cartas emblemáticas na história da produção literária (e documental) do Brasil: a Carta pras Icamiabas (capítulo do romance Macunaíma, de Mário de Andrade) e a Carta de Caminha. No repetível dos gêneros habita também o repetível da história e é essa a leitura que, neste trabalho, orienta a exploração da imanência do dado histórico no dado linguístico. Ambas as cartas apresentam um deslocamento no espaço, uma viagem. Como resultado, temos: a) no caso da Carta de Caminha, um dado de centralização do poder por um estado e um soberano, linguisticamente presente na busca de exatidão para as descrições e cálculos, como elementos universalizáveis; b) no caso da Carta pras Icamiabas, a centralização do poder é pura quimera e a universalização não passa de contenção, apesar do anúncio hiperbólico – fora de qualquer pretensão de exatidão – de um poder que gira em falso; c) as aproximações entre as duas cartas, marcadamente por um pedido de ajuda, põem o aspecto lendário do herói mítico na ordem da personagem histórica, ao mesmo tempo em que permite observar o ser histórico encarnado no escrivão oficial em seu aspecto lendário.
“Carta aos leitores e leitoras”: o dialogismo interdiscursivo bakhtiniano na escrita epistolar freireana
Authors: Cunha Simone
Published: January 2025

This research addresses the interdiscursive dialogicity of the ‘Letter to readers,’ written by Paulo Freire and published as a ‘presentation’ for his book Literacy: reading the world, reading the word. This material shows the educator's handwriting and was digitally made available by the platform that bears his name on the web. Under the methodology of qualitative research, of a bibliographical and documentary nature, the investigation analyzes the linguistic-discursive resources used by Freire to address his readership through epistolary discourse. To this end, we draw on Marcuschi (2008) and Seara (1998), regarding the discursive genre ‘letter;’ Bakhtin (1997[1979]) and Volóchinov (2018[1929]) on interdiscursive dialogism; Bhatia (1997, 2010) on interdiscursivity in professional discursive practices; and Freire (1996) and Gadotti (1996) in relation to Freire’s writing. With this, we can see the dialogical nature of the letter, present in its textual and interdiscursive fabric, immortalized as digital heritage, in which is inscribed the persuasive and dialectical intention of this Brazilian thinker in favor of an education that liberates minds and men.
Uma cartografia do sujeito autoral de mulheres negras em cartas
Authors: Santos Tainara Cecília Pereira , Duarte Rosinês de Jesus
Published: January 2025

This article aims to analyze some contemporary epistolary texts by black women, understanding them as important instruments for reconstructing the collective and cultural memory of the black population through writing, a diasporic and universal phenomenon that permeates the writing of the black women who will be analyzed, from the constitution of the authorial subject of the text. We will analyze how the writing present in the epistolary texts of black women is an exercise in memory and transgression and rupture with a racist, oppressive and violent system. These subject-authors find in writing a place of emancipation and empowerment that, in the letters, is shared with recipient-readers.
As pesquisas acadêmicas sobre cartas de autore(a)s da Literatura Brasileira – O Estado da Arte
Authors: Feitosa Conceição de Maria Corrêa
Published: January 2025

In the past few years, readers' interest on intimate genres has significantly increased: diaries, autobiographies, confessions, memoirs and letters, mainly because they provide information more related to the life of a real character in history, an artist, a writer. Researchers and literary critics have used this instrument as support for various analyses. Considering this recent trend in Brazilian literary criticism, the present work aims to make a survey, a State of the Art, of the last 10 years (2014 to 2024), of research involving the letters of author(s) of Brazilian literature, in an attempt to show whether these studies are viable and whether they are being carried out in academia and published in journals; what are the most recurring themes, which authors are most accessed, what are the most found results, how important is this research for the general public. With this State of the Art, it is also intended to provide a general overview that contributes to the advancement and development of themes that may arise from a letter.
A correspondência entre Gonçalves Dias e Teófilo Leal: uma obra à parte
Authors: Lima Renata Ribeiro
Published: January 2025

O presente artigo tem como objetivo examinar uma amostra do epistolário gonçalvino, no seu diálogo com o melhor amigo, Alexandre Teófilo de Carvalho Leal (1822-1879), durante o período em que Gonçalves Dias era recém-chegado à Corte. Analisa-se nessas cartas o modo como o autor ultrapassa os lugares-comuns do gênero, por meio de um grande cuidado com a linguagem e da inserção de elementos próprios de outros textos, como o lírico, o dramático e o romanesco. Ademais, verifica-se que as expansões do poeta maranhense com esse correspondente eleito indicam o desenvolvimento de uma espécie de personagem, de um perfil de poeta romântico que o autor desejava transmitir ao leitor – não só ao amigo íntimo, mas também à posteridade que o aguardava como “Primeiro Poeta do Brasil”.
Amuletos da criação: a correspondência entre Lygia Fagundes Telles e Rachel de Queiroz e seu papel na inserção das mulheres na literatura brasileira
Authors: Neves Angela das
Published: January 2025

A correspondência das escritoras Lygia Fagundes Telles (1923-2022) e de Rachel de Queiroz (1910-2003), hoje preservada no acervo literário do Instituto Moreira Salles e pouco conhecida no meio acadêmico, apresenta um interesse particular para seus estudiosos e para o estudo da carta enquanto manuscrito literário. Os documentos aqui transcritos e analisados propiciam uma abordagem profunda no pensamento íntimo de Lygia Fagundes Telles e suas reflexões sobre a criação e a vida literária. Seu diálogo com Rachel de Queiroz, que pode ser lido em bilhetes, cartões-postais e telegrama, enviados entre os anos 1980 e 2000, revela em filigrana as escolhas lygianas e permite ver a mensagem constante, trocada entre as duas autoras: a necessidade de inserção e afirmação da mulher de letras, num espaço majoritariamente ocupado e orquestrado por homens. O papel das duas autoras no cenário modernista brasileiro e questões que envolvem sua iniciação na literatura e na Academia são alguns dos assuntos discutidos neste artigo.
Assessing Knowledge Claims in Scientific Controversies: On the Origins of COVID-19
Authors: Panagiotou Aristeidis
Published: January 2025

In the field of Science and Technology Studies (STS), scientific controversies (SCs) are often viewed as essential steps in the development of knowledge and technoscientific artifacts. This paper addresses the lack of an orchestrated epistemological effort to assess the quality of knowledge claims (KCs) articulated during SCs. This study proposes a framework that bridges ontology with appropriate methodological techniques to evaluate KCs, considering them as ontological hybrids in which the social and epistemic are interwoven. This paper argues for the rehabilitation of the existential autonomy of the natural world, which has been overshadowed by an overreaction to positivism. By employing methodological bracketing, specifically that of positive and normative analyses, this study aims to assess KCs in terms of their proximity to intransitive reality and the socio-political dynamics that influence their emergence respectively. The second part of the paper applies this framework to the SC on the origins of the COVID-19 pandemic, suggesting a nuanced understanding that goes beyond the dichotomy of zoonosis and genetic engineering. This study highlights the impact of social factors on scientists’ epistemic stances, and the importance of public deliberation in policy formation. The contributions of this study are both epistemological and policy-oriented.
A new species of catfish, Pterocryptis vorax (Actinopterygii: Siluridae), from northern Borneo
Authors: NG HEOK HEE , KAHAR RAFHIAH , TAN HEOK HUI
Published: January 2025

This study describes Pterocryptis vorax, a new species of silurid catfish from the upper reaches of the Temburong River drainage in Brunei Darussalam, northern Borneo. Pterocryptis vorax is distinguished from congeners in having a unique combination of the following characters: rictal lobe ending at vertical posterior to posterior orbital margin, deep lower jaw with a more gently curved anteroventral margin, a color pattern of densely distributed dark brown patches on the flanks that coalesce to form a reticulate pattern, a dark vertical band at the caudal-fin base, 46–57 anal-fin rays and 48–49 vertebrae. Sexual dichromatism in Pterocryptis is also reported for the first time here.
Processes Linking Shared Spiritual Practices, Spiritual Intimacy, and Sanctification of Marriage to Attachment to Spouse and Relationship Satisfaction
Authors: Klausli Julia , Gross Christopher , Leedom Emily
Published: January 2025

The goal of the current study was to examine processes by which shared spiritual practices, such as denominational homogamy, praying together, discussing spiritual topics, and serving in a Church setting together, are associated with attachment to spouse and relationship satisfaction. Sanctification of marriage and spiritual intimacy were included as possible mediators of the associations. The results suggested that proximal spiritual practices (e.g., praying together, discussing spiritual topics together) were more closely associated with relationship functioning than distal practices (e.g., denominational homogamy). In addition, serial mediation models indicated that sanctification of marriage and spiritual intimacy mediated the link between shared spiritual practices and relationship satisfaction. Sanctification of marriage was directly associated with relationship satisfaction, while spiritual intimacy was additionally mediated by attachment to spouse in its association with satisfaction. The results are discussed in light of future research needs and implications for practitioners and individuals working in faith communities.
Three-Plane Calcaneal Osteotomy With Joint Preservation vs Subtalar Arthrodesis to Treat Painful Calcaneal Fracture Malunions
Authors: Feng Hui , Ji Dong-Dong , Yang Xin-Quan , Yue Yang , Wang Zhe , Zhang Yan , Liu Pei-Long , Liang Jing-Qi , Zhao Hong-Mou
Published: January 2025

Background:

Calcaneal fracture malunion (CFM) commonly occurs with multiple pathologic changes and progressive pain and difficulty walking. The purpose of this study was to propose a modified 3-plane joint-preserving osteotomy for the treatment of CFM with subtalar joint incongruence, and to compare its efficacy to subtalar arthrodesis.

Methods:

A retrospective comparative analysis of the data of 56 patients with CFM admitted from January 2017 to December 2022 was performed. Twenty-six patients were in the osteotomy group and 30 in the arthrodesis group. Computed tomographic (CT) scans were used for measurement of the intraarticular steps. Radiologic parameters, visual analog scale (VAS) score for pain, 12-Item Short Form Health Survey (SF-12) mental component summary (MCS) and physical component summary (PCS) scores were compared between the 2 groups of patients to assess the outcome preoperatively and at last follow-up, which averaged 22.6 ± 3.6 months and 27.6 ± 3.6 months for the osteotomy and arthrodesis groups, respectively.

Results:

Improvements in pain, function, and overall quality of life were obtained in both groups compared with the preoperative values at last follow-up. The VAS and SF-12 scores were similar between the groups at the last follow-up. In the osteotomy group, the average CT scan–measured intraarticular step-offs were significantly reduced from 3.7 ± 1.2 mm to 0.9 ± 0.3 mm. The osteotomy group showed improvement in pronation and supination range of motion (ROM) of the feet ( P < .01). The correction of the ankle height and Meary angle were slightly better in the osteotomy group.

Conclusion:

In this short-term follow-up study, good results were achieved in both joint-preserving osteotomy and subtalar arthrodesis groups for the treatment of CFM with subtalar joint incongruence. The osteotomy group preserved the subtalar joint and achieved improvements in pronation and supination ROM.
Reducing undesirable effects of revolute joint clearances on the dynamic performance of spatial parallel mechanism
Authors: Chen Xiulong , Zhang Lianzhen , Jia Yonghao
Published: January 2025

To mitigate the adverse effects of joint clearances on the dynamic performance of mechanisms, it is essential to investigate the dynamic optimization design of spatial parallel mechanisms with clearances. Currently, there are many studies on the dynamic characteristics of mechanisms with clearances, but there are few studies on dynamic optimization design of mechanisms with clearances, especially on the optimization design of parallel mechanisms with clearances. Therefore, the dynamic optimization design of 3-RRPaR (R stands for revolute joint, Pa stands for quadrilateral structure) parallel mechanism with dry friction clearance of revolute joints is studied. The dynamic model of the parallel mechanism with revolute joint clearance is derived. On these grounds, the dynamic response of the end actuator, the contact collision force at the clearance joint, and their weighted combination are defined as objective functions, respectively. The mass and moment of inertia of the end actuator are taken as optimization variables. A mathematical model for the dynamic optimization design of the parallel mechanism considering dry friction clearances is developed, and the optimal mass and moment of inertia of the end actuator are obtained by G-MSRS method. This study comparatively analyzes the dynamic characteristics of parallel mechanisms with clearances before and after optimization. The results indicate that dynamic optimization significantly enhances the dynamic characteristics of the mechanism. This study lays a theoretical foundation for dynamic optimization design of parallel mechanisms with clearances.
Neonatal inpatient stays longer than one year: Who was admitted, what happened, and how much did it cost?
Authors: Shah Nihaal , Sunny Angel , Dapaah-Siakwan Fredrick
Published: January 2025

Background

Anecdotal evidence suggests that some preterm infants remain hospitalized for more than a year, but little is known about this population. We aimed to describe the characteristics, the hospital course, and the hospital costs for preterm hospitalizations with length of stay (LOS) ≥365 days.

Methods

This was a retrospective, descriptive cohort study of the 2016 and 2019 Kids Inpatient Database. ICD-10 codes were used to identify preterm infants, their comorbidities, and surgical interventions. The study population was dichotomized into LOS ≤364 days (PT364) and LOS ≥365 days (PT365) and compared using Chi-square or Mann-Whitney U test as appropriate. The exposure was PT365, and the outcomes were the characteristics, comorbidities, discharge disposition, and inflation-adjusted hospital costs.

Results

Among 688,995 preterm infants, 111 had LOS ≥365 days (0.016%). Compared to PT364, PT365 were more likely to be males (74.6% vs 53.2%), of gestational age ≤27 weeks (71.5% vs 4.7%), and <1000 gm birthweight (64.2% vs 4.0%). PT365 were more likely to have a higher prevalence of comorbidities in each organ system, surgical and procedural interventions, and neonatal chronic complex conditions (872% vs 13.3%). PT365 were less likely to be discharged home (45.7% vs 93.4%) and more likely to be discharged to home healthcare (28.0% vs 5.7%) or to a skilled nursing facility (16.0% vs 0.8). The median hospital cost per surviving PT365 was $1,616,336.

Conclusion

PT365 was rare but was associated with complex chronic conditions, increased morbidity and surgical burden, and high inflation-adjusted hospital costs.
Long-term sublingual bacterial immunotherapy prevents ear, nose and throat infections: A real-life study
Authors: Aarestrup Paula F , Aarestrup Matheus F , JV Aarestrup Beatriz , Cheloni Edir P , Aarestrup Fernando M
Published: January 2025

Objective:

Bacterial extracts have been used for many years to prevent airway infections. Recent findings suggest that immunity can be trained by inducing an immunological memory in both the innate and acquired immune response. This real-life observational study investigated the potential of sublingual bacterial immunotherapy in the prevention of ear, nose, and throat infections.

Methods:

Patients received sublingual bacterial immunotherapy for 12 months and were followed for 24 months. The number of ear, nose, and throat infection episodes from the previous year was recorded during the initial visit based on the patient’s clinical history. Patients were then followed up with visits every 2 months, and the occurrence of ear, nose, and throat infection episodes was documented at 6, 12, 18, and 24 months after the start of the study.

Results:

The results demonstrated a strong potential for preventing ear, nose, and throat infections, with a reduction in the number of episodes by 75.68%, 82.27%, 82.78%, and 89.88% at 6, 12, 18, and 24 months, respectively. No adverse effects related to sublingual bacterial immunotherapy administration were reported.

Conclusion:

The results suggested that long-term sublingual bacterial immunotherapy is safe and effectively prevents ear, nose, and throat infections, even after treatment ends.
Standardizing Sonography Pre-clinical Instruction Utilizing Peyton’s 4-Step Approach
Authors: Wampler Kathryn , Sundberg Brandy , Ridenour Angela , Michael Kimberly
Published: January 2025

Objective:

The aim of this quality improvement project was to use Peyton’s 4-step approach to standardize sonography pre-clinical lab instruction between diagnostic medical sonography (DMS) educational sites and instructors.

Materials and Methods:

The participants included DMS students (n = 26) enrolled at a Midwestern university during academic years of 2020–2022. Pre-survey and post-survey were used to collect and analyze data related to sonography lab instruction with Peyton’s 4-step approach.

Results:

Pre-survey data found no students were familiar with Peyton’s approach. Semester end post-surveys showed students found all steps of Peyton’s approach helpful in learning sonography skills, but results varied by semester.

Conclusion:

Peyton’s approach with modifications was used to standardized pre-clinical lab instruction in a DMS program across multiple educational sites and all lab sessions. While the approach required more initial planning and preparatory time than a traditional teaching method, the approach provided a structured sequence and order to the learning process, which most students found helpful.
Advances in RNA editing in hematopoiesis and associated malignancies
Authors: Pu Shuangshuang , Cheng Tao , Cheng Hui
Published: January 2025

Adenosine-to-inosine (A-to-I) RNA editing is a prevalent RNA modification essential for cell survival. The process is catalyzed by the Adenosine Deaminase Acting on RNA (ADAR) enzyme family that converts adenosines in double-stranded RNAs (dsRNAs) into inosines, which are read as guanosines during translation. Deep sequencing has helped to reveal that A-to-I editing occurs across various types of RNAs to affect their functions. RNA editing detection is now so sophisticated that we can achieve a high level of accuracy and sensitivity to identify low abundance edited events. Consequently, A-to-I editing has been implicated in various biological processes, including immune and stress responses, cancer progression and stem cell fate determination. In particular, a crucial role for this process has been recently reported in hematopoietic cell development and hematologic malignancy progression. Results from genetic mouse models have demonstrated the impact of ADARs' catalytic activity on hematopoietic cells, complemented by insights from human cell studies. Meanwhile clinical studies have implicated ADAR enzymes and RNA editing events in hematologic malignancies and highlighted their potential as prognostic indicators. In this review, we outline the regulatory mechanisms of RNA editing in both normal hematopoiesis and hematologic malignancies. We then speculate on how targeting ADAR expression and site-specific RNA substrates might serve as a therapeutic avenue for affected patients.
Masquelet’s induced membrane technique in the upper limb: a systematic review of the current outcomes
Authors: Pederiva Davide , De Luca Lapo , Faldini Cesare , Vergano Luigi Branca
Published: January 2025

Background

The Masquelet induced membrane technique is a surgical procedure that allows the reconstruction of segmental bone defects using a relatively simple approach that requires minimal resources from both the healthcare facility and the patient. Historically applied to the lower limb, this technique is gaining increasing attention in the literature for its use in the upper limb.

Methods

A systematic review of the literature was conducted using the PubMed and Google Scholar databases to identify all studies reporting the outcomes of the Masquelet induced membrane technique in the long bones of the upper limb (humerus, radius, and ulna) with a sample size of at least 3 patients. The papers had to include the length of the bone defect, a description of the protocol used for treatment, the complications of each case, and the anatomical location of the defect. The studies that did not meet the above inclusion criteria were excluded.

Results

The search identified 1044 studies, of which 15 met the inclusion criteria. These studies described a total of 156 patients with a mean age of 42 years. The affected bone segments included the humerus in 22 cases and the forearm in 134 cases. In 108 cases, the bone defect was septic. The average defect length was 4.5 cm. PMMA was used as a spacer in all cases, with antibiotics added in 77% of them. The average time interval between the first and second phases of the procedure was 9.5 weeks, and bone union took an average of 5.5 months. The mean follow-up duration was 48 months, and the complication rate was 21%, ranging from 0% to 75%.

Conclusions

The Masquelet induced membrane technique is a viable surgical option for managing segmental bone defects of the upper limb. However, the complication rate remains significant. Further research is needed to identify strategies to improve the outcomes of this technique.

Level of Evidence: Level 2.
Prevalence and dynamics of antimicrobial resistance in pioneer and developing Arctic soils
Authors: Roy Shamik , Dawson Robin A. , Bradley James A. , Hernández Marcela
Published: January 2025

Antimicrobial resistance (AMR) in soil is an ancient phenomenon with widespread spatial presence in terrestrial ecosystems. However, the natural processes shaping the temporal dissemination of AMR in soils are not well understood. We aimed to determine whether, how, and why AMR varies with soil age in recently deglaciated pioneer and developing Arctic soils using a space-for-time approach. Specifically, we assess how the magnitude and spread of AMR changes with soil development stages, including antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and antibiotic-resistant bacteria (ARB). We showed that ARGs, MGEs, and ARB are present, and exhibit a non-uniform distribution in the developing soils. Their abundance generally increases with soil age but at different rates overall and across different glacier forefields. Our analyses suggest a strong positive relationship between soil age and ARGs and ARB, which we attribute to increased competition between microbes in older soils. We also observed a strong negative relationship between soil age and ARG diversity mediated by soil organic matter – suggesting facilitation due to the alleviation of nutrient limitation. These contrasting results suggest that both competition and facilitation can regulate AMR spread through time in the Arctic, but competition might be the stronger determinant of AMR spread.
Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study)
Authors: Glöckner Annemarie , Schönland Stefan , Einsele Hermann , Kröger Nicolaus
Published: January 2025

Background

Even though major improvements have been made in the treatment of myeloma, the majority of patients eventually relapse or progress. Patients with multiple myeloma who relapse after initial high-dose chemotherapy with autologous stem cells have a median progression free survival up to 2–3 years, depending on risk factors such as previous remission duration. In recent years, growing evidence has suggested that allogeneic stem cell transplantation could be a promising treatment option for patients with relapsed or progressed multiple myeloma. However, prospective randomized trials including allogeneic stem cell transplantation as second-line therapy do not exist to date and therefore urgently needed to demonstrate the value of this therapy in the overall setting of patients with multiple myeloma.

Methods

This clinical trial is a national, multicenter, randomized, open labeled phase III study conducted in 30 hospitals spread all over Germany. After study inclusion, all patients will receive 3 cycles of salvage therapy with one of the currently approved triplet regimens for first relapse. After 3 cycles of salvage therapy, remission status will be assessed. If the patient achieves at least stable disease, partial or complete remission and an HLA compatible stem cell donor could be identified, he/she will be randomized (1:1) to the control or interventional study arm. Approximately 400 patients will be enrolled to enable a randomization of 280 patients. The primary endpoint is overall survival at five years after randomization. The main secondary objectives and endpoints are progression-free survival rate, time-to first occurrence of an infection with CTCAE grade 3–5, non-relapse mortality rate and incidence of acute and chronic graft-versus-host disease after allogeneic stem cell transplantation.

Discussion

The present clinical study is designed to evaluate the superiority of allogeneic stem cell transplantation compared to conventional therapy (triplet chemotherapy) for the difference in overall survival at 5 years, toxicity and quality of life in patients with multiple myeloma who have relapsed or progressed after first-line autologous stem cell therapy.

Trial registration

ClinicalTrials.gov (NCT05675319) registered on January 9, 2023.