bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline
Authors: Iwama Shintaro , Kobayashi Tomoko , Yasuda Yoshinori , Okuji Takayuki , Ito Masaaki , Ando Masahiko , Zhou Xin , Yamagami Ayana , Onoue Takeshi , Kawaguchi Yohei , Miyata Takashi , Sugiyama Mariko , Takagi Hiroshi , Hagiwara Daisuke , Suga Hidetaka , Banno Ryoichi , Hase Tetsunari , Morise Masahiro , Wakahara Keiko , Yokota Kenji , Kato Masashi , Nishio Naoki , Tanaka Chie , Miyata Kazushi , Ogura Atsushi , Ito Takanori , Sawada Tsunaki , Shimokata Tomoya , Niimi Kaoru , Ohka Fumiharu , Ishigami Masatoshi , Gotoh Momokazu , Hashimoto Naozumi , Saito Ryuta , Kiyoi Hitoshi , Kajiyama Hiroaki , Ando Yuichi , Hibi Hideharu , Sone Michihiko , Akiyama Masashi , Kodera Yasuhiro , Arima Hiroshi 
Published: November 2021

Abstract

Background
Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for anti-thyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown.

Methods
A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit.

Results
Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P &lt; 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P &lt; 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline.

Conclusions
This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.
Lack of GNAS Remethylation During Oogenesis May Be a Cause of Sporadic Pseudohypoparathyroidism Type Ib
Authors: Milioto Angelo , Reyes Monica , Hanna Patrick , Kiuchi Zentaro , Turan Serap , Zeve Daniel , Agarwal Chhavi , Grigelioniene Giedre , Chen Ang , Mericq Veronica , Frangos Myrto , Ten Svetlana , Mantovani Giovanna , Salusky Isidro B , Tebben Peter , Jüppner Harald 
Published: November 2021

Abstract

Context
Pseudohypoparathyroidism type Ib (PHP1B) is characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone resistance in the proximal renal tubules. Maternal pathogenic STX16/GNAS variants leading to maternal epigenetic GNAS changes impair expression of the stimulatory G protein alpha-subunit (Gsα) thereby causing autosomal dominant PHP1B. In contrast, genetic defects responsible for sporadic PHP1B (sporPHP1B) remain mostly unknown.

Objective
Determine whether PHP1B encountered after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) causes GNAS remethylation defects similar to those in sporPHP1B.

Design
Retrospective analysis.

Results
Nine among 36 sporPHP1B patients investigated since 2000, all with loss of methylation (LOM) at the 3 maternal GNAS differentially methylated regions (DMRs) and gain of methylation at the paternal NESP DMR, had been conceived through IVF or ICSI. Besides abnormal GNAS methylation, IVF/ICSI PHP1B cases revealed no additional imprinting defects. Three of these PHP1B patients have dizygotic twins, and 4 have IVF/ICSI-conceived siblings, all with normal GNAS methylation; 2 unaffected younger siblings were conceived naturally.

Conclusion
Sporadic and IVF/ICSI-conceived PHP1B patients revealed indistinguishable epigenetic changes at all 4 GNAS DMRs, thus suggesting a similar underlying disease mechanism. Given that remethylation at the 3 maternal DMRs occurs during oogenesis, male factors are unlikely to cause LOM postfertilization. Instead, at least some of the sporPHP1B variants could be caused by a defect or defects in an oocyte-expressed gene that is required for fertility and for re-establishing maternal GNAS methylation imprints. It remains uncertain, however, whether the lack of GNAS remethylation alone and the resulting reduction in Gsα expression is sufficient to impair oocyte maturation.
Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function
Authors: Shi Fang-Hong , Li Hao , Shen Long , Xu Li , Ge Heng , Gu Zhi-Chun , Lin Hou-Wen , Pu Jun 
Published: November 2021

Abstract

Background
Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients.

Methods
A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included.

Results
Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e’ ratio, E/e’ and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: −6.319 g, −10.850 to −1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: −9.134 mL, −15.808 to −2.460; LVESV: −8.440 mL, −15.093 to −1.787; LAVI: −2.791 mL/m2, −.554 to −1.027; E/e’: −1.567, −2.440 to −0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment.

Conclusions
Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).
The Role of Iodine for Thyroid Function in Lactating Women and Infants
Authors: Andersson Maria , Braegger Christian P 
Published: November 2021

AbstractIodine is a micronutrient needed for the production of thyroid hormones, which regulate metabolism, growth, and development. Iodine deficiency or excess may alter the thyroid hormone synthesis. The potential effects on infant development depend on the degree, timing, and duration of exposure. The iodine requirement is particularly high during infancy because of elevated thyroid hormone turnover. Breastfed infants rely on iodine provided by human milk, but the iodine concentration in breast milk is determined by the maternal iodine intake. Diets in many countries cannot provide sufficient iodine, and deficiency is prevented by iodine fortification of salt. However, the coverage of iodized salt varies between countries. Epidemiological data suggest large differences in the iodine intake in lactating women, infants, and toddlers worldwide, ranging from deficient to excessive intake. In this review, we provide an overview of the current knowledge and recent advances in the understanding of iodine nutrition and its association with thyroid function in lactating women, infants, and toddlers. We discuss risk factors for iodine malnutrition and the impact of targeted intervention strategies on these vulnerable population groups. We highlight the importance of appropriate definitions of optimal iodine nutrition and the need for more data assessing the risk of mild iodine deficiency for thyroid disorders during the first 2 years in life.
Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease
Authors: Mauvais-Jarvis Franck , Lange Carol A , Levin Ellis R 
Published: November 2021

Abstract
Rapid effects of steroid hormones were discovered in the early 1950s, but the subject was dominated in the 1970s by discoveries of estradiol and progesterone stimulating protein synthesis. This led to the paradigm that steroid hormones regulate growth, differentiation, and metabolism via binding a receptor in the nucleus. It took 30 years to appreciate not only that some cellular functions arise solely from membrane-localized steroid receptor (SR) actions, but that rapid sex steroid signaling from membrane-localized SRs is a prerequisite for the phosphorylation, nuclear import, and potentiation of the transcriptional activity of nuclear SR counterparts. Here, we provide a review and update on the current state of knowledge of membrane-initiated estrogen (ER), androgen (AR) and progesterone (PR) receptor signaling, the mechanisms of membrane-associated SR potentiation of their nuclear SR homologues, and the importance of this membrane-nuclear SR collaboration in physiology and disease. We also highlight potential clinical implications of pathway-selective modulation of membrane-associated SR.
From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective
Authors: Gao Xiao-Bing , Horvath Tamas L 
Published: November 2021

AbstractThe hypocretin/orexin (Hcrt/Orx) system in the perifornical lateral hypothalamus has been recognized as a critical node in a complex network of neuronal systems controlling both physiology and behavior in vertebrates. Our understanding of the Hcrt/Orx system and its array of functions and actions has grown exponentially in merely 2 decades. This review will examine the latest progress in discerning the roles played by the Hcrt/Orx system in regulating homeostatic functions and in executing instinctive and learned behaviors. Furthermore, the gaps that currently exist in our knowledge of sex-related differences in this field of study are discussed.
Congenital Micropenis: Etiology And Management
Authors: Stancampiano Marianna Rita , Suzuki Kentaro , O’Toole Stuart , Russo Gianni , Yamada Gen , Faisal Ahmed Syed 
Published: November 2021

AbstractIn the newborn, penile length is determined by a number of androgen dependent and independent factors. The current literature suggests that there are interracial differences in stretched penile length in the newborn and although congenital micropenis should be defined as a stretched penile length of less than 2.5 SDS of the mean for the corresponding population and gestation, a pragmatic approach would be to evaluate all boys with a stretched penile length below 2 cm, as congenital micropenis can be a marker for a wide range of endocrine conditions. However, it remains unclear as to whether the state of micropenis, itself, is associated with any long-term consequences. There is a lack of systematic studies comparing the impact of different therapeutic options on long-term outcomes, in terms of genital appearance, quality of life, and sexual satisfaction. To date, research has been hampered by a small sample size and inclusion of a wide range of heterogeneous diagnoses; for these reasons, condition-specific outcomes have been difficult to compare between studies. Lastly, there is a need for a greater collaborative effort in collecting standardized data so that all real-world or experimental interventions performed at an early age can be studied systematically into adulthood.
Microsimulation of Household and Marital Transitions Leading to Childlessness Among Dutch Women Born Between 1971 and 2000
Authors: Boissonneault Michaël , de Beer Joop 
Published: November 2021

AbstractAfter reaching historically low levels among the women born in the early 1940s, childlessness has been increasing in most Western countries among women born in the 1950s and 1960s. This increase took place as patterns of transition to adulthood have become increasingly late, protracted, and complex. Yet, it is precisely those women who enter a first relationship late, spend more time as single, and experience union instability who more often remain childless. This suggests that levels of childlessness will continue to increase as younger cohorts complete their childbearing histories. In this study, we use microsimulation to project the household and union formation histories of cohorts of Dutch women born between 1971 and 2000. Results suggest that childlessness will actually decrease among cohorts born between 1971 and 1983 and then increase among those born between 1984 and 2000. The decrease occurs as pathways of household and union formation become later, more protracted, and more complex, but also as cohabiting women start to exhibit a higher propensity to become mothers. The increase, on the other hand, occurs as pathways become somewhat less protracted and complex, but also as the propensity of cohabiting women to become mothers returns to previous levels and as age at leaving the parental home strongly rises. Childlessness levels appear to increasingly depend on the childbearing decisions of cohabiting couples and on age at leaving the parental home.
Hybridization chain reaction enables a unified approach to multiplexed, quantitative, high-resolution immunohistochemistry and in situ hybridization
Authors: Schwarzkopf Maayan , Liu Mike C. , Schulte Samuel J. , Ives Rachel , Husain Naeem , Choi Harry M. T. , Pierce Niles A. 
Published: November 2021

ABSTRACT
RNA in situ hybridization based on the mechanism of the hybridization chain reaction (HCR) enables multiplexed, quantitative, high-resolution RNA imaging in highly autofluorescent samples, including whole-mount vertebrate embryos, thick brain slices and formalin-fixed paraffin-embedded tissue sections. Here, we extend the benefits of one-step, multiplexed, quantitative, isothermal, enzyme-free HCR signal amplification to immunohistochemistry, enabling accurate and precise protein relative quantitation with subcellular resolution in an anatomical context. Moreover, we provide a unified framework for simultaneous quantitative protein and RNA imaging with one-step HCR signal amplification performed for all target proteins and RNAs simultaneously.
It takes time to heal a broken heart: ventricular plasticity improves heart performance after myocardial infarction in rainbow trout, Oncorhynchus mykiss
Authors: Zena Lucas A. , Ekström Andreas , Gräns Albin , Olsson Catharina , Axelsson Michael , Sundh Henrik , Sandblom Erik 
Published: November 2021

ABSTRACT
Coronary arteriosclerosis is a common feature of both wild and farmed salmonid fishes and may be linked to stress-induced cardiac pathologies. Yet, the plasticity and capacity for long-term myocardial restructuring and recovery following a restriction in coronary blood supply are unknown. Here, we analyzed the consequences of acute (3 days) and chronic (from 33 to 62 days) coronary occlusion (i.e. coronary artery ligation) on cardiac morphological characteristics and in vivo function in juvenile rainbow trout, Oncorhynchus mykiss. Acute coronary artery occlusion resulted in elevated resting heart rate and decreased inter-beat variability, which are both markers of autonomic dysfunction following acute myocardial ischemia, along with severely reduced heart rate scope (maximum−resting heart rate) relative to sham-operated trout. We also observed a loss of myocardial interstitial collagen and compact myocardium. Following long-term coronary artery ligation, resting heart rate and heart rate scope normalized relative to sham-operated trout. Moreover, a distinct fibrous collagen layer separating the compact myocardium into two layers had formed. This may contribute to maintain ventricular integrity across the cardiac cycle or, alternatively, demark a region of the compact myocardium that continues to receive oxygen from the luminal venous blood. Taken together, we demonstrate that rainbow trout may cope with the aversive effects caused by coronary artery obstruction through plastic ventricular remodeling, which, at least in part, restores cardiac performance and myocardium oxygenation.
Miejsce hasła i sloganu w komunikowaniu politycznym
Authors: Śleziak Marta 
Published: November 2021

The Place of Catchwords and Slogans in Political Communication
The paper discusses the function of catchwords and slogans, as well as the role that these forms play in political communication. Not only are they short and catchy sayings, but they also carry important meanings – from the point of view of both the government and the society. Political slogans and catchwords are a significant part of political campaigns, politicians’ presentations and election programs, as well as social movements and protests. As multimodal carries, they can be examined with the use of systemic functional linguistics methods. The analysis and conclusions are based on the collection of more than 3100 items: political catchwords from Polish political discourse, excerpted from written (ephemera, press) and oral texts (protests, demonstrations, live presentations) published in 1918–2018. The collection is the part of the project which aims at publishing A Dictionary of Political Catchwords.
Zaprzedać duszę diabłu – reprodukowalność mitu we frazematyce z polskiego obszaru gwarowego i języka potocznego w kontekście kultury tradycyjnej
Authors: Masłowska Ewa 
Published: November 2021

Selling One’s Soul to the Devil – Reproducibility of the Mythical Motif in Phrasematics of the Polish Colloquial Language in the Context of Traditional Culture
The author of the article discussed reproducibility of the mythical motif of “Adam’s pact with the devil” in Polish traditional culture and in dialectal and colloquial phrasematics. The adoption of the concept of “language narrativeness” in the description of a small piece of reality such as the act of selling one’s soul to the devil, makes it possible to present this piece in a form of a structured image within the frames of a great narrative about the world (based on the Christian belief concerning the soul) which contains small narratives (referring to myths and folk demonology included in stereotypical text motifs) and micro-narratives that are hidden in lexis and broadly understood phrasematics and that reflect a whole range of interpretations and evaluations related to a person’s pact with a demonic being.
Krystyna Pisarkowa – ta, która inspiruje
Authors: Tyrpa Anna 
Published: November 2021

Krystyna Pisarkowa – The One Who Inspires
The article consists of three parts. In the first one: Krystyna Pisarkowa as a Supervisor, the author shares her memories from the times when she wrote the doctoral thesis supervised by Pisarkowa. In the second part: Krystyna Pisarkowa – the Author of an Article, the author discusses how the text by Pisarkowa entitled Semantic Connotation of Nationalities provided inspiration to fourteen authors of twenty-three monographs and one lexicon. Most of those scholars are experts in Polish language and linguists, but the thoughts included in Pisarkowa’s article also influenced two experts in Russian studies: one sociologist and one anthropologist of culture. Those books were published within 40 years (1980–2020). Five of them were published after the death of Krystyna Pisarkowa. This proves the power of her article’s influence. The third part of the article is entitled Supplement. It describes the history of the book by Ogden and Richards: The Meaning of Meaning. A Study of The Influence of Language upon Thought and of The Science of Symbolism with Supplementary Essays by B. Malinowski and F. G. Crookshank, which followed a strange route from London and reached Pisarkowa who used it while writing: Linguistics by Bronisław Malinowski, vol. 1: Bonds of Shared Language (2000).
Historia składni języka polskiego Krystyny Pisarkowej – świadectwo zmiany i źródło inspiracji
Authors: Słoboda Agnieszka 
Published: November 2021

Krystyna Pisarkowa’s The History of Polish Syntax – The Testimony of Change and the Source of Inspiration
The author of the article shows Krystyna Pisarkowa’s monograph as a text which presents a diachronic approach to Polish syntax in a new and modern way, taking into account the times and the Polish linguistic tradition. Focusing on discontinuous phenomena in the history of the Polish language, Pisarkowa separates tendencies and processes typical of each syntactic level. Not only does she discuss traditionally described elements of simple and complex utterances, but she also takes into account the semantic structure of sentences and their pragmatic aspect. Therefore, Historia składni języka polskiego [The History of Polish Syntax] is a testimony of a methodological change and a quest for adequate solutions, as well as a source of inspiration for further generations of researchers.
SMITH, KEYNES, HAYEK E A PRODUÇÃO DO ESPAÇO COMO FUNCIONALIDADE HISTÓRICA
Authors: Gesteira Luiz André Maia Guimarães , Conceição Alexandrina Luz 
Published: November 2021

Dentre as distintas funcionalidades do Estado ao modo de produção capitalista, sua instrumentalização no processo de produção do espaço tem revelado ao longo da história utilidade fundamental. Mesmo no período de ascensão do mainstream smithiano, onde defendeu-se o esvaziamento do ente suprassocial de algumas de suas funções históricas na economia e na sociedade, a construção das infraestruturas necessárias aos investimentos da classe burguesa sempre foi mantida como função primordial do Estado. No período keynesiano essa funcionalidade assume ainda novas facetas, incrementando sobremodo a ação do Estado na produção do espaço. A partir da hegemonia do modelo neoliberal uma convergência de mediações passa a caracterizar a atuação do Estado para produzir o espaço, elevando essa função estatal à níveis de instrumentalização inéditos. Dessa forma, a produção do espaço é compreendida como funcionalidade histórica contínua e fundamental do Estado ao capital, reiteradamente ampliada de acordo com as demandas do modo de produção.
A experiência estética na prática docente da educação básica
Authors: Dos Santos Maurício Inácio , Betlinski Carlos 
Published: November 2021

Este artigo aborda o tema da experiência estética na prática docente. O condutor da investigação foi: Como os docentes da Educação Básica percebem a experiência estética em suas práticas? O objetivo foi caracterizar as experiências estéticas realizadas pelos docentes em suas práticas pedagógicas, para identificar elementos que geram o empobrecimento dessa experiência nessas práticas. A partir da análise de dados e à luz das teorias de Theodor Adorno e Max Horkheimer, afirma-se que a redescoberta do lugar da experiência estética cria sentidos e potencializa o trabalho docente, superando a tendência reducionista da racionalidade instrumental e o desencanto pela profissão.