bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Assessment of Outcome Measurement Instruments in Cauda Equina Syndrome: A Systematic Review
Authors: Richardson George E. , Millward Christopher P. , Mitchell James W. , Clark Simon , Wilby Martin , Marson Anthony G. , Williamson Paula R. , Srikandarajah Nisaharan
Published: January 2024

Study Design

This was a systematic review of surgically managed Cauda Equina Syndrome (CES) Outcome Measurement Instruments (OMI).

Objective

A core outcome set (COS) defines agreed outcomes which should be reported as a minimum in any research study for a specific condition. This study identified OMIs used in the wider CES literature and compare these to the established CESCOS.

Methods

To identify measurement methods and instruments in the CES surgical outcome evidence base, a systematic review was performed. Medline, Embase and CINAHL plus databases were queried. In addition, a secondary search for validation studies of measurement instruments in CES was undertaken. Identified studies from this search were subject to the COSMIN risk of bias assessment.

Results

In total, 112 studies were identified investigating surgical outcomes for CES. The majority (80%, n = 90) of these OMI studies were retrospective in nature and only 55% (n = 62) utilised a measurement method or instrument. The remaining 50 studies used study specific definitions for surgical outcomes defined within their methods. Of the 59 measurement instruments identified, 60% (n = 38 instruments) were patient reported outcome measures. Only one validated instrument was identified, which was a patient reported outcome measure. The validated instrument was not used in any study identified in the initial search (to identify measurement instruments).

Conclusions

This review highlights the wide heterogeneity of measurement instruments used in surgically managed CES research. Subsequently, there is need for consensus agreement on which instrument or instruments should be used to measure each core outcome for CES surgical outcomes.
Team Presentation Theory I: The Five Formats
Authors: Usera Daniel , Fuller Alex
Published: January 2024

Team presentations are prevalent in education and business, yet there is a notable scarcity of scholarly research and discussion on effective delivery practices. The authors bridge this gap by introducing a theoretical foundation for team presentations, enabling further exploration. They first establish prerequisites that a team must address regarding the speech outline, member roles, and transition techniques. They then categorize five distinct team presentation formats and explore each one’s strategic advantages, disadvantages, and application contexts. Lastly, the authors offer strategic implications for practitioners and proposals for future academic inquiries into the realm of team presentation theory.
A Dakota Cultural Intervention’s Influence on Native Students’ Sense of Belonging: A CBPR Case Study
Authors: Peters Heather J. , Peterson Teresa R. , Community The Dakota Wicoḣaƞ
Published: January 2024

This community-based participatory research case study demonstrates how Dakota Wicoḣaƞ utilized Indigenous and feminist epistemologies to create, implement, and evaluate a cultural intervention, the Mni Sota Makoce: Dakota Homelands Curriculum, to increase Native 6th- and 10th-grade social studies students’ peoplehood sense of belonging (Tachine et al., 2017). Findings demonstrate Native students liked the curriculum and reported an increase in support and a decrease in invalidation of their sense of belonging. While the curriculum provided a source of racial-ethnic socialization, some European American students criticized the curriculum, which likely negatively impacted 6th-grade students psychological sense of school membership (Goodenow, 1993). Results indicate Indigenous culture, epistemologies, and pedagogies should be infused throughout all curricula, teachers need to be prepared to effectively deal with racist and discriminatory behavior, and Indian education is important to Native students’ belonging. Implications and recommendations for funders, schools, researchers, teacher education programs, and Native communities are discussed.
Arab World in Hergé’s The Adventures of Tintin: Making Visible the Idea of Terra Nullius
Authors: Chatterjee Nilanjana , Chatterjee Anindita
Published: January 2024

The nineteenth- and twentieth-century European texts on “unfamiliar” parts of the world were injected with the idea of terra nullius (more pernicious than its legal and military implications) to justify European imperialism. It is a projection of “diffusionism,” which intends to theorize how the “outside” world lacks indigenous geography, history, or culture. In this context, this article takes up Georges Remi Hergé’s representations of the Arab world in The Crab with the Golden Claws, The Red Sea Sharks, Cigars of the Pharaoh, and Land of Black Gold to identify traces of the idea of terra nullius albeit it was not legally applied on the land and its people.
If Students Don’t Feel it, They Won’t Learn it: Early Career Secondary Social Studies Educators Plan for Emotional Engagement
Authors: Reidel Michelle , Salinas Cinthia
Published: January 2024

This qualitative case study examines early career social studies educators’ knowledge of the role of emotion in teaching and learning. More specifically, we examine how our efforts to expand social studies educators’ understanding of emotion, shifted their perception of the role of emotion in learning social studies content and how they can use this knowledge to plan instruction. Prior to beginning their “emotion education,” all participants described the role of emotion in teaching and learning as important for relationship-building and as something to be carefully managed. They focused their efforts in the classroom on creating a welcoming environment for their students and managing their students’ emotions. Though they described their classrooms as emotional spaces, none had explicitly considered the role of emotion in learning content .As they learned about the role of emotion in cognitive processes like memory and problem-solving, participants began to recognize the need to rethink their pedagogical choices. However, none of the participants embraced or accepted an expanded view of emotions as social and political forces. Reluctant to consider how emotions shape our identities, our communities and our politics, these social studies educators did not meaningfully engage in a critical examination of how social studies curriculum can contribute to “schooling” students’ emotions. Findings from this initial study suggest it is important to engage social studies educators in critical awareness of their own emotions and critical examination of what emotions “do” in the world and how the social studies content we teach can contribute to the “schooling” of our students’ emotions.
Who Represents Asian American in Mainstream Newspapers
Authors: Lin Hao
Published: January 2024

Who counts as Asian Americans? Previous research with survey data shows that South Asian Americans are less likely to be recognized as Asian Americans compared with East Asian Americans. Using a national news dataset, this visualization presents annual trends in the mentions of three subethnicities (East Asian, South Asian, and Southeast Asian) when discussing Asian Americans from 1977 to 2022. East Asians are the most likely to be mentioned when discussing Asian Americans compared with South Asians and Southeast Asians. The patterns are consistent over time. This suggests that such disparity among Asian subethnic groups is institutionalized in news media.
Impact of leukoaraiosis on the infarct growth rate and clinical outcome in acute large vessel occlusion stroke after endovascular thrombectomy
Authors: He Guangchen , Fang Hui , Xue Bo , Wei Liming , Lu Haitao , Deng Jiangshan , Zhu Yueqi
Published: January 2024

Introduction:

As a marker of chronic cerebral small vessel disease, leukoaraiosis (LA) was reported to impact the recruitment of collaterals in acute ischemic stroke (AIS). We intended to explore the impact of LA on the infarct growth rate (IGR) and clinical outcome by impaired collateral development in AIS patients with large vessel occlusion (LVO) who underwent endovascular thrombectomy (EVT).

Patients and methods:

Two hundred thirty-six AIS patients who underwent EVT were retrospectively reviewed. The severity of LA was graded using the Fazekas scale with non-contrast CT. IGR was calculated by the acute core volume on CT perfusion divided by the time from stroke onset to imaging. The collateral status after LVO was assessed using the ASITN/SIR collateral scale. The clinical outcomes after EVT were evaluated using a modified Rankin Scale ( mRS). The Alberta stroke program early CT score ( ASPECTS), the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the modified treatment in cerebral infarction ( mTICI) score after EVT were also included. Correlations between those factors were analyzed.

Results:

Patients with severe LA had significantly larger core volume on CTP ( p = 0.022) and lower collateral grade ( p < 0.001). Faster IGR was significantly associated with higher LA severity (adjusted odds ratio [aOR]: 1.53; 95% CI: 1.02–2.33; p = 0.046), higher NIHSS (aOR: 1.04; 95% CI: 1.00–1.09; p = 0.032) and impaired collaterals (aOR: 2.26; 95% CI: 1.27–4.03; p = 0.005). In mediation analysis, collaterals explained 33% of the effect of LA on fast IGR. There was correlation between the severity of LA and mRS ( p = 0.007).

Discussion and Conclusion:

The increasing severity of LA is associated with impaired collateral status and fast infarct growth. These findings suggest that LA may become a predictive imaging biomarker for the likelihood of progression of tissue injury and clinical outcome after EVT in acute large vessel occlusion stroke.
Entrepreneurs as Architects: Design (ing) Focus in Entrepreneurship Education
Authors: Mansoori Yashar , Dimov Dimo
Published: January 2024

Designing requires skills that are different from making and is an integral part of venture creation. To encourage considerations of design in entrepreneurship education, this paper elaborates how designing can be embedded in entrepreneurship education as a distinct composite capability to be developed. It outlines a perspective of entrepreneurial action as design, whereby activities of framing, modeling, and performing give a concrete action its entrepreneurial meaning of concerning a future venture. We discuss how the underpinning capabilities can be developed in educational settings, using principles, methods, and examples as distinct types of instructions to be deployed by entrepreneurship educators in different combinations and for different purposes. We develop the implications of our work by offering a set of design principles tailored for entrepreneurship education.
Buddhism-based Intentional Communities Becoming Ecovillages: A Case of Sisa Asoke in Thailand
Authors: Suh Jungho
Published: January 2024

The primary aim of spiritual or religious intentional communities is that their members live their lives based on spiritual or religious principles and precepts. This article presents a case study of Sisa Asoke in Thailand as a contemporary example of a Buddhism-based intentional community. The article tracks down how Sisa Asoke has evolved into an ecovillage, which was not its primary intention. This study employs ethnographic methods, including participant observations, to gain insights into the community’s day-to-day activities, and interviews to provide an understanding of the community from the community’s perspective. The study categorises observation and interview data into the cultural, ecological, social and economic dimensions of sustainability, aligning with the definition of an ecovillage. The study finds that Sisa Asoke has collectively committed to organic agriculture, relying on local resources. Daily activities at Sisa Asoke are interrelated, showcasing the holistic integration of the four dimensions of sustainability. Furthermore, this study concludes that their shared belief in and practice of the Buddha’s teachings have catalysed the development of regenerative social and natural environments. Therefore, it can be inferred that Sisa Asoke has come very close to being classified as an ecovillage.
A Rare Case Report of Takotsubo Cardiomyopathy in a Patient with Hashimoto’s Encephalopathy and Autoimmune Thyroiditis
Authors: Kumar Abhishek , Gupta Manisha
Published: January 2024

Takotsubo cardiomyopathy (TCMP), also called as stress cardiomyopathy, is a transient left ventricular (LV) dysfunction. TCMP’s association with endocrine and thyroid diseases has been recently described, but TCMP in a patient of Hashimoto’s thyroiditis with encephalopathy is rarely reported. 1 Here, we present a recent case of TCMP in a patient with Hashimoto’s encephalopathy who was treated with steroids and responded well. Our case here highlights about having a lower threshold for screening of thyroid and other endocrine disorders in patients with TCMP.
The constantly expanding goal fields: Turning the discourse of goals into fields
Authors: Campill Marc Antoine
Published: January 2024

The human being as an individual has unique ways of perceiving the dynamic interrelation between self-environments. The shift in the irreversible time interrelates with the organic notion of development. Still, change does not simply mean that we are physically changing, but it also implies that our way of seeing the changing reality-construct is constantly in change. But how do we actually see the world and what goal does the concept of goals/dreams play in all of that? In the following article the construct “goal” is redefined into a more phenomenological-based understanding in which goals are transformed into fields that inhabit our vision field and flourish in the deep spheres of imagination.
Quantum Uncertainty and the Black-Scholes Formula
Authors: Orrell David
Published: January 2024

The publication of the Black-Scholes formula in 1973 appeared for the first time to put the pricing of financial options onto a rational and objective basis. Its adoption transformed the perception of option pricing from a form of gambling to scientific risk management, and led to a huge increase in options trading. However while the formula revolutionised the world of finance, and remains the industry-standard pricing model today, its proof relies on a number of assumptions about price behaviour which are often contested, such as that log prices follow a random walk with constant volatility, and that one can constantly buy or sell stocks and options without incurring transaction fees. This paper presents an alternative approach to option pricing, based on a quantum oscillator model of stock prices. In the quantum model, the bid/ask spread between buy and sell prices is treated as a fundamental measure of uncertainty, and volatility is not constant but exhibits a smile-like dependence on strike. We show how the Black-Scholes model and its assumptions lead to a systematic mispricing of commonly-traded options, while results can be improved by adopting the quantum model.
Bank Deposits as Money Quanta
Authors: Bagarello Fabio , Bossone Biagio
Published: January 2024

According to the Accounting View of Money (AVM), the money issued by commercial banks in the form of demand deposits features a hybrid nature, since deposits can be shown to consist of a share of deposits bearing the characteristics of debt (debt-deposits) and a share of deposits bearing the characteristics of equity (equity-deposits), in a mix that depends on factors that relate to the issuing banks and the environment where they operate and interact, which may change over time. Following this important finding of the AVM, it is only consequential to associate the hybrid nature of bank deposits with the dual nature of the objects which is typical in quantum physics, and to investigate whether and how the application of quantum analytical methods and ideas to a form of money showing dualistic features could be used to extract valuable economic information. This article studies demand deposits (which represents the prevailing form of money in all contemporary economies) as a possible form of “money quanta”, that is, quantities reflecting some aspects tipical of quantum physics, and analyzes it using a quantum model to describe some relevant aspects of it, including for instance how banks’ power to create money (i.e., issue deposits typically via the credit channel) is affected by the interactions taking place between the banks and between the banks and their environments, and how system efficiency and stability change in relation to changes in bank behaviors. This article lays the foundations of money quanta and is the first step towards a better understanding of the relevance of quantum mechanical tools and ideas in connection with the study of economics and finance.
Quantum Financial Modeling on Noisy Intermediate-Scale Quantum Hardware: Random Walks Using Approximate Quantum Counting
Authors: Widdows Dominic , Bhattacharyya Amit
Published: January 2024

Quantum computers are expected to contribute more efficient and accurate ways of modeling economic processes. Quantum hardware is currently available at a relatively small scale, but effective algorithms are limited by the number of logic gates that can be used, before noise from gate inaccuracies tends to dominate results. Some theoretical algorithms that have been proposed and studied for years do not perform well yet on quantum hardware in practice. This encourages the development of suitable alternative algorithms that play similar roles in limited contexts. This paper implements this strategy in the case of quantum counting, which is used as a component for keeping track of position in a quantum walk, which is used as a model for simulating asset prices over time. We introduce quantum approximate counting circuits that use far fewer 2-qubit entangling gates than traditional quantum counting that relies on binary positional encoding. The robustness of these circuits to noise is demonstrated. While this paper is mainly about robust simplified quantum circuit designs, we compare some aspects of the results with price change distributions from stock indices, and compare the behavior of circuits with and without mid-measurement to trends in the housing market.
Co-Teaching: A Review of the Literature
Authors: Nápoles Jessica
Published: January 2024

In this literature review, I explore the research centered on co-teaching, including its history and evolution, labels and definitions, benefits and drawbacks, and working models, with the goal of making transfers to music teaching contexts. Established initially within an inclusive teaching framework as a result of governmental reforms, co-teaching expanded into professional development for teachers. Benefits to students include varied viewpoints, differentiation of instruction, more feedback, and extra attention. Co-teaching also offers teachers opportunities for collaboration, reduced professional isolation, and mentorship. Some researchers have identified drawbacks of co-teaching: potential confusion for students and inequitable distribution of work for teachers, leading one teacher to play a subordinate role to another. Multiple researchers have emphasized that administrative support and common planning time were essential for successful co-teaching.
Mechanical properties of short oxide fibre-kaolin clay matrix composites
Authors: Papargyri S.A. , Cooke R.G. , Papargyris D.A. , Botis A. , Papapolymerou G. , Papargyris A.D.
Published: January 2024

A series of short fibre ceramic composites was produced by mixing, slip casting, and sintering kaolin clay with Al2O3 or mullite fibres at various volume contents. Sintering was conducted in air at various temperatures. The resulting composites were characterised with respect to chemical and mineralogical composition, microstructure, and mechanical properties. Sintering above 1200 °C changed the microstructure of kaolin from a weak point bonded structure to a strong dense glass ceramic structure, and changed δ-Al2O3 to α-Al2O3. The addition of oxide fibres to kaolin clay resulted in the formation of ceramic matrix composites, the properties of which depended on sintering temperature, matrix and fibre structures and relative volumes, the properties of the fibre/matrix interface, and fibre length. A relative increase in strength and toughness with incorporation of fibres is achieved with limited additions of fibres, and mainly in the weak point bonded structures. The application of linear elastic fracture mechanics to the examined ceramic matrix composites is also discussed.
The hepatokine FGL1 regulates hepcidin and iron metabolism during anemia in mice by antagonizing BMP signaling
Authors: Sardo Ugo , Perrier Prunelle , Cormier Kevin , Sotin Manon , Personnaz Jean , Medjbeur Thanina , Desquesnes Aurore , Cannizzo Lisa , Ruiz-Martinez Marc , Thevenin Julie , Billoré Benjamin , Jung Grace , Abboud Elise , Peyssonnaux Carole , Nemeth Elizabeta , Ginzburg Yelena Z. , Ganz Tomas , Kautz Léon
Published: January 2024

As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure the adequate supply of iron to the bone marrow for red blood cell production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine fibrinogen-like 1 (FGL1) as a previously undescribed suppressor of hepcidin that is induced in the liver in response to hypoxia during the recovery from anemia, and in thalassemic mice. We demonstrated that FGL1 is a potent suppressor of hepcidin in vitro and in vivo. Deletion of Fgl1 in mice results in higher hepcidin levels at baseline and after bleeding. FGL1 exerts its activity by directly binding to bone morphogenetic protein 6 (BMP6), thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription.
Prednisone vs high-dose dexamethasone in newly diagnosed adult primary immune thrombocytopenia: a randomized trial
Authors: Mazzucconi Maria Gabriella , Rodeghiero Francesco , Avvisati Giuseppe , De Stefano Valerio , Gugliotta Luigi , Ruggeri Marco , Vianelli Nicola , Fazi Paola , Paoloni Francesca , Sargentini Valeria , Baldacci Erminia , Ferretti Antonietta , Martino Bruno , Vincelli Iolanda Donatella , Carli Giuseppe , Fortuna Stefania , Di Ianni Mauro , Ranalli Paola , Palandri Francesca , Polverelli Nicola , Lugli Elisabetta , Rivolti Elena , Patriarca Andrea , Rago Angela , D’Adda Mariella , Gentile Massimo , Siragusa Sergio , Sibilla Silvia , Carella Angelo Michele , Rossi Elena , Battistini Roberta , Zaja Francesco , Bocchia Monica , Di Renzo Nicola , Musto Pellegrino , Crugnola Monica , Giuffrida Anna Chiara , Krampera Mauro , Tafuri Agostino , Santoro Cristina
Published: January 2024

A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410.
The evolution ofin vitromodels of lung fibrosis: promising prospects for drug discovery
Authors: Kolanko Emanuel , Cargnoni Anna , Papait Andrea , Silini Antonietta Rosa , Czekaj Piotr , Parolini Ornella
Published: January 2024

Lung fibrosis is a complex process, with unknown underlying mechanisms, involving various triggers, diseases and stimuli. Different cell types (epithelial cells, endothelial cells, fibroblasts and macrophages) interact dynamically through multiple signalling pathways, including biochemical/molecular and mechanical signals, such as stiffness, affecting cell function and differentiation. Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing interstitial lung disease (fILD), characterised by a notably high mortality. Unfortunately, effective treatments for advanced fILD, and especially IPF and non-IPF progressive fibrosing phenotype ILD, are still lacking. The development of pharmacological therapies faces challenges due to limited knowledge of fibrosis pathogenesis and the absence of pre-clinical models accurately representing the complex features of the disease. To address these challenges, new model systems have been developed to enhance the translatability of preclinical drug testing and bridge the gap to human clinical trials. The use of two- and three-dimensionalin vitrocultures derived from healthy or diseased individuals allows for a better understanding of the underlying mechanisms responsible for lung fibrosis. Additionally, microfluidics systems, which replicate the respiratory system's physiologyex vivo, offer promising opportunities for the development of effective therapies, especially for IPF.
From treatable traits to GETomics in airway disease: moving towards clinical practice
Authors: Papi Alberto , Faner Rosa , Pavord Ian , Baraldi Federico , McDonald Vanessa M. , Thomas Mike , Miravitlles Marc , Roche Nicholas , Agustí Alvar
Published: January 2024

The treatable traits approach represents a strategy for patient management. It is based on the identification of characteristics susceptible to treatments or predictive of treatment response in each individual patient. With the objective of accelerating progress in research and clinical practice relating to such a treatable traits approach, the Portraits event was convened in Barcelona, Spain, in November 2022. Here, while reporting the key concepts that emerged from the discussions during the meeting, we review the current state of the art related to treatable traits and chronic respiratory diseases management, and we describe the possible actions that clinicians can take in clinical practice to implement the treatable traits framework. Furthermore, we explore the new concept of GETomics and the new models of research in the field of COPD.
Pulmonary veno-occlusive disease: illustrative cases and literature review
Authors: Lechartier Benoit , Boucly Athénaïs , Solinas Sabina , Gopalan Deepa , Dorfmüller Peter , Radonic Teodora , Sitbon Olivier , Montani David
Published: January 2024

Pulmonary veno-occlusive disease (PVOD), also known as “pulmonary arterial hypertension (PAH) with overt features of venous/capillary involvement”, is a rare cause of PAH characterised by substantial small pulmonary vein and capillary involvement, leading to increased pulmonary vascular resistance and right ventricular failure. Environmental risk factors have been associated with the development of PVOD, such as occupational exposure to organic solvents and chemotherapy, notably mitomycin. PVOD may also be associated with a mutation in theEIF2AK4gene in heritable forms of disease. Distinguishing PVOD from PAH is critical for guiding appropriate management. Chest computed tomography typically displays interlobular septal thickening, ground-glass opacities and mediastinal lymphadenopathy. Life-threatening pulmonary oedema is a complication of pulmonary vasodilator therapy that can occur with any class of PAH drugs in PVOD. Early referral to a lung transplant centre is essential due to the poor response to therapy when compared with other forms of PAH. Histopathological analysis of lung explants reveals microvascular remodelling with typical fibrous veno-occlusive lesions. This review covers the main features distinguishing PVOD from PAH and two clinical cases that illustrate the challenges of PVOD management.
Next-generation sequencing reveals genetic heterogeneity and resistance mechanisms in patients withEGFR-mutated non-small cell lung cancer treated with afatinib
Authors: Liang Sheng-Kai , Wei Pin-Fei , Hsieh Min-Shu , Wu Chia-Ling , Shih Jin-Yuan
Published: January 2024

Background

Afatinib, an irreversible ErbB family inhibitor, is widely used as first-line treatment in advanced lung adenocarcinoma patients harbouring mutant epidermal growth factor receptor (EGFR). With the advancements in next-generation sequencing (NGS), comprehensive research into the clinical impact of co-occurring genetic mutations and the molecular mechanisms of acquired resistance is required for afatinib users.

Materials

From January 2010 to December 2019, we enrolled patients with advanced lung adenocarcinoma withEGFRmutations using afatinib as first-line treatment, and we retrospectively collected pre- and post-afatinib treatment specimens from these patients for NGS testing.

Results

Of the 362 enrolled patients, 73 samples (68.9%) from 56 patients successfully returned complete NGS reports. In pre-afatinib treatment specimens, the most frequent co-occurring alterations wereTP53,MUC16,USH2A,SNYE1,RECQL4andFAT1; however, they were not related to progression-free survival. Small cell lung cancer transformation,EGFRp.T790M, amplification ofMET,ERBB2,KRAS,EGFR, cell cycle-regulated genes andMDM2, andPTENalterations were identified as acquired resistance mechanisms.EGFRp.T790M (p=0.0304) andAPCalterations (p=0.0311) in post-afatinib specimens were significantly associated with longer overall survival, whileMETamplification was significantly associated with poor overall survival (p=0.0324). The co-occurrence ofTP53alterations was significantly associated with shorter overall survival (p=0.0298).

Conclusions

Our results show that the frequent co-occurring alterations in advancedEGFR-mutated lung adenocarcinoma did not influence the effectiveness of afatinib.EGFRp.T790M is not only the major resistance mechanism to afatinib but also related to favourable survival outcomes.METamplification andTP53mutations were associated with poorer overall survival.
YGL3 Encoding an IPP and DMAPP Synthase Interacts with OsPIL11 to Regulate Chloroplast Development in Rice
Authors: Chen Wei , Tang Liqun , Li Qianlong , Cai Yicong , Ahmad Shakeel , Wang Yakun , Tang Shengjia , Guo Naihui , Wei Xiangjin , Tang Shaoqing , Shao Gaoneng , Jiao Guiai , Xie Lihong , Hu Shikai , Sheng Zhonghua , Hu Peisong
Published: January 2024

As the source of isoprenoid precursors, the plastidial methylerythritol phosphate (MEP) pathway plays an essential role in plant development. Here, we report a novel rice (Oryza sativa L.) mutant ygl3 (yellow-green leaf3) that exhibits yellow-green leaves and lower photosynthetic efficiency compared to the wild type due to abnormal chloroplast ultrastructure and reduced chlorophyll content. Map-based cloning showed that YGL3, one of the major genes involved in the MEP pathway, encodes 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, which is localized in the thylakoid membrane. A single base substitution in ygl3 plants resulted in lower 4-hydroxy-3-methylbut-2-enyl diphosphate reductase activity and lower contents of isopentenyl diphosphate (IPP) compared to the wild type. The transcript levels of genes involved in the syntheses of chlorophyll and thylakoid membrane proteins were significantly reduced in the ygl3 mutant compared to the wild type. The phytochrome interacting factor-like gene OsPIL11 regulated chlorophyll synthesis during the de-etiolation process by directly binding to the promoter of YGL3 to activate its expression. The findings provides a theoretical basis for understanding the molecular mechanisms by which the MEP pathway regulate chloroplast development in rice.
Combined transcriptome and metabolome analysis reveals breed-specific regulatory mechanisms in Dorper and Tan sheep
Authors: Ma Yuhao , Cai Ganxian , Chen Jianfei , Yang Xue , Hua Guoying , Han Deping , Li Xinhai , Feng Dengzhen , Deng Xuemei
Published: January 2024

Background

Dorper and Tan sheep are renowned for their rapid growth and exceptional meat quality, respectively. Previous research has provided evidence of the impact of gut microbiota on breed characteristics. The precise correlation between the gastrointestinal tract and peripheral organs in each breed is still unclear. Investigating the metabolic network of the intestinal organ has the potential to improve animal growth performance and enhance economic benefits through the regulation of intestinal metabolites.

Results

In this study, we identified the growth advantage of Dorper sheep and the high fat content of Tan sheep. A transcriptome study of the brain, liver, skeletal muscle, and intestinal tissues of both breeds revealed 3,750 differentially expressed genes (DEGs). The genes PPARGC1A, LPL, and PHGDH were found to be highly expressed in Doper, resulting in the up-regulation of pathways related to lipid oxidation, glycerophospholipid metabolism, and amino acid anabolism. Tan sheep highly express the BSEP, LDLR, and ACHE genes, which up-regulate the pathways involved in bile transport and cholesterol homeostasis. Hindgut content analysis identified 200 differentially accumulated metabolites (DAMs). Purines, pyrimidines, bile acids, and fatty acid substances were more abundant in Dorper sheep. Based on combined gene and metabolite analyses, we have identified glycine, serine, and threonine metabolism, tryptophan metabolism, bile secretion, cholesterol metabolism, and neuroactive ligand-receptor interaction as key factors contributing to the differences among the breeds.

Conclusions

This study indicates that different breeds of sheep exhibit unique breed characteristics through various physiological regulatory methods. Dorper sheep upregulate metabolic signals related to glycine, serine, and threonine, resulting in an increase in purine and pyrimidine substances. This, in turn, promotes the synthesis of amino acids and facilitates body development, resulting in a faster rate of weight gain. Tan sheep accelerate bile transport, reduce bile accumulation in the intestine, and upregulate cholesterol homeostasis signals in skeletal muscles. This promotes the accumulation of peripheral and intramuscular fat, resulting in improved meat quality. This work adopts a joint analysis method of multi-tissue transcriptome and gut metabolome, providing a successful case for analyzing the mechanisms underlying the formation of various traits.
Identification of transient receptor potential channel genes from the swimming crab, Portunus Trituberculatus, and their expression profiles under acute temperature stress
Authors: Qian Yichen , Yu Qiaoling , Zhang Jun , Han Yaoyao , Xie Xi , Zhu Dongfa
Published: January 2024

Background

Temperature is an important environment factor that is critical to the survival and growth of crustaceans. However, the mechanisms by which crustaceans detect changes in temperature are still unclear. The transient receptor potential (TRP) channels are non-selective cation channels well known for properties in temperature sensation. However, comprehensive understandings on TRP channels as well as their temperature sensing functions are still lacking in crustaceans.

Results

In this study, a total of 26 TRP genes were identified in the swimming crab, Portunus trituberculatus, which can be classified into TRPA, TRPC, TRPP, TRPM, TRPML, TRPN and TRPV. Tissue expression analysis revealed a wide distribution of these TRP genes in P. trituberculatus, and antennules, neural tissues, and ovaries were the most commonly expressed tissues. To investigate the responsiveness of TRP genes to the temperature change, 18 TRPs were selected to detect their expression after high and low temperature stress. The results showed that 12 TRPs showed induced gene expression in both high and low temperature groups, while 3 were down-regulated in the low temperature group, and 3 showed no change in expression in either group.

Conclusions

This study characterized the TRP family genes in P. trituberculatus, and explored their involvement in response to temperature stress. Our results will enhance overall understanding of crustacean TRP channels and their possible functions.
Effects of resistance training and nutritional support on osteosarcopenia in older, community-dwelling postmenopausal Korean females (ERTO-K study): a study protocol
Authors: Lee Byung Chan , Kim Kyung Il , Cho Kang Hee , Moon Chang-Won
Published: January 2024

Background

Osteosarcopenia is geriatric syndrome defined as the concomitant occurrence of osteopenia/osteoporosis, and sarcopenia. Osteosarcopenia is a relatively new concept in geriatric medicine; however, it may increase the risk of fragility fractures, several morbidities and mortalities, and socioeconomic costs. Although resistance exercises and nutritional support—including protein, calcium, and vitamin D—are potential non-pharmacological management procedures, evidence is still lacking. The objective of this study was therefore to evaluate the effect of combined resistance exercise and nutritional support on the quality and quantity of bone and muscle in postmenopausal females with osteosarcopenia.

Methods

This research proposal presents the protocol for a prospective, single-center, single-blinded, two-armed randomized controlled trial. Thirty-four participants with osteosarcopenia will be recruited and randomly divided into intervention and control groups; both groups will receive nutritional supplements (protein, 40 g; vitamin D, 1600 IU; calcium, 600 mg) daily. The intervention group will undergo 24 weeks of resistance exercise of increasing intensity, achieved through a three-phase step-up process. The primary outcomes will be the changes in skeletal muscle index and bone marrow density of the lumbar spine and femoral neck between the baseline and end of intervention (24 weeks). The secondary outcomes will be the body composition, whole body phase angle, physical function assessment, quality of life, psychological assessment, and bone turnover markers of participants, surveyed at multiple time points.

Discussion

This randomized controlled trial may reveal the effect of resistance exercise and nutritional support on older postmenopausal women with osteosarcopenia. The results will provide evidence for developing proper non-pharmacological management guidelines for postmenopausal women.

Trial registration

Clinical Research Information Service of Republic of Korea, KCT0008291, Registered on 16 March 2023, https://cris.nih.go.kr/cris/search/detailSearch.do/25262.
Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers
Authors: Kameda Takuro , Utsunomiya Atae , Otsuka Nobuaki , Kubuki Yoko , Uchida Taisuke , Shide Kotaro , Kamiunten Ayako , Nakano Nobuaki , Tokunaga Masahito , Miyazono Takayoshi , Ito Yoshikiyo , Yonekura Kentaro , Kawakita Toshiro , Akizuki Keiichi , Tahira Yuki , Karasawa Masayoshi , Hidaka Tomonori , Konagata Ayaka , Taniguchi Norifumi , Nagatomo Yuma , Kogo Fumiko , Shimizu Koichiro , Ueno Hiroaki , Ishizaki Junzo , Takahashi Naoya , Ikei Yoshihiko , Hidaka Michihiro , Yamaguchi Hideki , Shimoda Kazuya
Published: January 2024

Background

Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown.

Methods

To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors.

Results

We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers.

Conclusions

The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
Single-cell analysis of the cellular landscape of vulvar melanoma provides new insight for immunotherapy administration
Authors: Wang Xinqi , Li Jiahui , Li Yifei , Lv Mingyi , Dong Xue , Fan Zhenxin , Guo Tao
Published: January 2024

Background

Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM.

Methods

At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment.

Results

This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis.

Conclusion

This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.
Systemic inflammatory biomarkers in Schizophrenia are changed by ECT administration and related to the treatment efficacy
Authors: Wang Yu , Wang Guangfa , Gong Muxin , Yang Yujing , Ling Yuru , Fang Xinyu , Zhu Tingting , Wang Zixu , Zhang Xiangrong , Zhang Caiyi
Published: January 2024

Immune inflammation has long been implicated in the pathogenesis of schizophrenia. Despite as a rapid and effective physical therapy, the role of immune inflammation in electroconvulsive therapy (ECT) for schizophrenia remains elusive. The neutrophils to lymphocytes (NLR), platelets to monocytes (PLR) and monocytes to lymphocytes (MLR) are inexpensive and accessible biomarkers of systemic inflammation. In this study, 70 schizophrenia patients and 70 age- and sex-matched healthy controls were recruited. The systemic inflammatory biomarkers were measured before and after ECT. Our results indicated schizophrenia had significantly higher peripheral NLR, PLR and MLR compared to health controls at baseline, while lymphocytes did not differ. After 6 ECT, the psychiatric symptoms were significantly improved, as demonstrated by the Positive and Negative Syndrome Scale (PANSS). However, there was a decline in cognitive function scores, as indicated by the Mini-Mental State Examination (MMSE). Notably, the neutrophils and NLR were significantly reduced following ECT. Although lymphocytes remained unchanged following ECT, responders had significantly higher lymphocytes compared to non-responders. Moreover, the linear regression analyses revealed that higher lymphocytes served as a predictor of larger improvement in positive symptom following ECT. Overall, our findings further highlighted the presence of systemic inflammation in schizophrenia patients, and that ECT may exert a therapeutic effect in part by attenuating systemic inflammation. Further research may therefore lead to new treatment strategies for schizophrenia targeting the immune system.
Investigation of carotid intima-media thickness in patients with schizophrenia
Authors: Kapıcı Yaşar , Kapıcı Olga Bayar , Abuş Sabri , Örüm Mehmet Hamdi , Ayhan Selçuk , Bozkurt Mehmet , Özer Bilal , Tekin Atilla
Published: January 2024

Background

Patients with schizophrenia (SCZ) have a higher risk of cardiovascular diseases than the average population. Early diagnosis of SCZ patients with subclinical atherosclerosis is great importance in reducing cardiovascular morbidity and mortality. The aim of this study was to investigate some clinical risk factors for atherosclerosis in patients with SCZ.

Methods

Fifty-one SCZ patients (20 females, 31 males) and 55 healthy controls (HCs) (25 females, 30 males) were included in the study. Electrocardiography (ECG), lipid parameters, hemogram, and biochemistry values of the participants were taken. Low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting triglycerides, and total cholesterol were measured. The arrhythmogenic index of plasma (AIP) was analyzed. The recorded right and left carotid intima-media thickness (CIMT) measurements by carotid ultrasonography were scanned.

Results

QT interval (p = 0.035), CIMT-left (p = 0.008), CIMT-right (p = 0.002), fasting triglyceride (p = 0.005), AIP (p = 0.005) in the SCZ group compared to HCs (< 0.001) was statistically higher, while HDL (p = 0.003) was statistically lower. Smoking rates, QT interval (p = 0.035), CIMT-left (p = 0.008), and CIMT-right (p = 0.002) were significantly higher in the the SCZ group than in the HCs. According to odds ratios, individuals with SCZ have a 6.3-fold higher smoking rate. According to Pearson correlation analysis, CIMT-left was positively correlated with age and QT interval (r = 0.568, p < 0.001 and r = 0.589, p < 0.001, respectively). CIMT-right value was also positively correlated with age and QT interval (r = 0.533, p < 0.001 and r = 0.555, p < 0.001, respectively). QT interval positively and significantly predicted CIMT-left and CIMT-right (p < 0.001, β = 0.549 and p = 0.001 and β = 0.506 accordingly).

Conclusion

In this study, a close relationship was found between the QT interval and CIMT in SCZ patients. This finding could be valuable for using an easy-to-calculate data such as QT in place of a laborious test such as CIMT.