bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a Questionnaire on Sexual and Reproductive Health Among Immigrant Vocational Education Students in Portugal from São Tomé and Príncipe
Authors: Brazete Cátia , Caveiro Diogo , Neto Marisa Lopes , Dinis João Pedro , Rocha Luís Castro , Sá Lígia , Carvalhido Ricardo
Published: May 2023

Sexual and reproductive health interventions’ effectiveness should be evaluated using a valid instrument. This study aimed to validate a questionnaire on sexual and reproductive health in adolescents and young adults from São Tomé and Príncipe who voluntarily enrolled in a vocational school in Portugal to complete their 12th school year and obtain a professional card.

A questionnaire consisting of perception and knowledge sections was adapted from previous questionnaires. We followed the steps of psychometric analysis. Firstly, we assessed face validity and content validity. We used factorial analysis to validate the perceptions section (which included Likert-type questions). For the knowledge section (which consisted of multiple-choice questions), we used the key check, discrimination index, and difficulty index. We evaluated internal consistency through Cronbach’s alpha for the perceptions section and the Kuder-Richardson score for the knowledge section.

Out of 105 invited students, a total of ninety students were enrolled in this study, of whom 88 completed most of the questions. The exploratory analysis showed that most students agreed with the right to refuse intercourse. However, while approximately 23% disagreed that consensual sex among adult women or men is always wrong, around the same proportion agreed. A considerable number of students recognized condoms and pills as effective methods of contraception. However, most students were unfamiliar with other methods. Most knowledge questions showed acceptable difficulty levels, and the discrimination index varied among questions. The knowledge questions demonstrated good consistency levels. This study enabled us to develop an appropriate instrument for evaluating the effectiveness of public health interventions and identifying specific knowledge gaps in migrant populations from low-income countries. This will help prioritise topics to be addressed in sexual health education sessions.
Two-Year Results of the Banded Versus Non-banded Re-sleeve Gastrectomy as a Secondary Weight Loss Procedure After the Failure of Primary Sleeve Gastrectomy: a Randomized Controlled Trial
Authors: Hany Mohamed , Ibrahim Mohamed , Zidan Ahmed , Agayaby Ann Samy Shafiq , Aboelsoud Moustafa R. , Gaballah Muhammad , Torensma Bart
Published: May 2023

Background

Insufficient weight loss or weight regain has been reported in up to 30% of patients after laparoscopic sleeve gastrectomy (LSG). Approximately 4.5% of patients who undergo LSG need revisional surgery for a dilated sleeve.

Methods

This randomized controlled trial compared the outcomes between banded (BLSG) and non-banded re-LSG (NBLSG) after weight regain. Percentage excess body weight loss (%EWL), percentage total weight loss (%TWL), associated medical problems, gastric volume measurement, and endoscopy were measured preoperatively and 1 and 2 years postoperatively.

Results

Both groups (25 patients each) achieved similar % EWL and %TWL at six months, one year, and two years postoperatively (%EWL 46.9 vs. 43.6, 83.7 vs. 86.3, and 85.7 vs. 83.9) (p= > 0.151) (%TWL 23.9 vs. 21.8, 43.1 vs .43.3, 44.2 vs. 42.2) (p=>0.342), respectively. However, the body mass index was significantly lower with BLSG (24.9 vs. NBLSG, 26.9). Both groups showed a significant reduction in stomach volume after two years (BLSG -248.4 mL vs. NBLSG -215.8 mL). Food tolerance (FT) scores were significantly reduced in both groups, whereby BSLG had significantly lower FT with an average of -1.1 point. No significant differences were observed regarding improvement of the associated medical problems after the first and two years after revisional LSG or the postoperative complications between both groups.

Conclusion

Laparoscopic re-LSG is feasible and safe with satisfactory outcomes in patients with weight regain after LSG who have gastric dilatation without reflux esophagitis. Both groups had comparable significant weight loss effects and improvement of associated medical problems. The BLSG tends to have a more stable weight loss after two years with a significantly lower BMI, lower stomach volume, and less weight regain. Food tolerance decreased in both groups but reduced more in the BLSG group. After a 2-year follow-up, we may regard both procedures are safe, with no significant differences in the occurrence of complications and nutritional deficits.

Graphical Abstract
Cardiology Encounters for Underrepresented Racial and Ethnic Groups with Human Immunodeficiency Virus and Borderline Cardiovascular Disease Risk
Authors: Bloomfield Gerald S. , Hill C. Larry , Chiswell Karen , Cooper Linda , Gray Shamea , Longenecker Chris T. , Louzao Darcy , Marsolo Keith , Meissner Eric G. , Morse Caryn G. , Muiruri Charles , Thomas Kevin L. , Velazquez Eric J. , Vicini Joseph , Pettit April C. , Sanders Gretchen , Okeke Nwora Lance
Published: May 2023

Background

Underrepresented racial and ethnic groups (UREGs) with HIV have a higher risk of cardiovascular disease (CVD) compared with the general population. Referral to a cardiovascular specialist improves CVD risk factor management in high-risk individuals. However, patient and provider factors impacting the likelihood of UREGs with HIV to have an encounter with a cardiologist are unknown.

Methods

We evaluated a cohort of UREGs with HIV and borderline CVD risk (10-year risk ≥ 5% by the pooled cohort equations or ≥ 7.5% by Framingham risk score). Participants received HIV-related care from 2014–2020 at four academic medical centers in the United States (U.S.). Adjusted Cox proportional hazards regression was used to estimate the association of patient and provider characteristics with time to first ambulatory cardiology encounter.

Results

A total of 2,039 people with HIV (PWH) and borderline CVD risk were identified. The median age was 45 years (IQR: 36–50); 52% were female; and 94% were Black. Of these participants, 283 (14%) had an ambulatory visit with a cardiologist (17% of women vs. 11% of men, p < .001). In fully adjusted models, older age, higher body mass index (BMI), atrial fibrillation, multimorbidity, urban residence, and no recent insurance were associated with a greater likelihood of an encounter with a cardiologist.

Conclusion

In UREGs with HIV and borderline CVD risk, the strongest determinants of a cardiology encounter were diagnosed CVD, insurance type, and urban residence. Future research is needed to determine the extent to which these encounters impact CVD care practices and outcomes in this population.

Trial Registration

ClinicalTrials.gov Identifier: NCT04025125.
Formation control of unmanned rotorcraft systems with state constraints and inter-agent collision avoidance
Authors: Zhou Panpan , Lai Shupeng , Cui Jinqiang , Chen Ben M.
Published: May 2023

We present in this paper a novel framework and distributed control laws for the formation of multiple unmanned rotorcraft systems, be it single-rotor helicopters or multi-copters, with physical constraints and with inter-agent collision avoidance, in cluttered environments. The proposed technique is composed of an analytical distributed consensus control solution in the free space and an optimization based motion planning algorithm for inter-agent and obstacle collision avoidance. More specifically, we design a distributed consensus control law to tackle a series of state constraints that include but not limited to the physical limitations of velocity, acceleration and jerk, and an optimization-based motion planning technique is utilized to generate numerical solutions when the consensus control fails to provide a collision-free trajectory. Besides, a sufficiency condition is given to guarantee the stability of the switching process between the consensus control and motion planning. Finally, both simulation and real flight experiments successfully demonstrate the effectiveness of the proposed technique.
Investigation of metabolic pathways from gut microbiome analyses regarding type 2 diabetes mellitus using artificial neural networks
Authors: Siptroth Julienne , Moskalenko Olga , Krumbiegel Carsten , Ackermann Jörg , Koch Ina , Pospisil Heike
Published: May 2023

Background

Type 2 diabetes mellitus is a prevalent disease that contributes to the development of various health issues, including kidney failure and strokes. As a result, it poses a significant challenge to the worldwide healthcare system. Research into the gut microbiome has enabled the identification and description of various diseases, with bacterial pathways playing a critical role in this context. These pathways link individual bacteria based on their biological functions. This study deals with the classification of microbiome pathway profiles of type 2 diabetes mellitus patients.

Methods

Pathway profiles were determined by next-generation sequencing of 16S rDNA from stool samples, which were subsequently assigned to bacteria. Then, the involved pathways were assigned by the identified gene families. The classification of type 2 diabetes mellitus is enabled by a constructed neural network. Furthermore, a feature importance analysis was performed via a game theoretic approach (SHapley Additive exPlanations). The study not only focuses on the classification using neural networks, but also on identifying crucial bacterial pathways.

Results

It could be shown that a neural network classification of type 2 diabetes mellitus and a healthy comparison group is possible with an excellent prediction accuracy. It was possible to create a ranking to identify the pathways that have a high impact on the model prediction accuracy. In this way, new associations between the alteration of, e.g. a biosynthetic pathway and the presence of diabetes mellitus type 2 disease can also be discovered. The basis is formed by 946 microbiome pathway profiles from diabetes mellitus type 2 patients (272) and healthy comparison persons (674).

Conclusion

With this study of the gut microbiome, we present an approach using a neural network to obtain a classification of healthy and type 2 diabetes mellitus and to identify the critical features. Intestinal bacteria pathway profiles form the basis.
Key Technologies of Financial Digital Industry Innovation and Green Development Driven by Information Technology
Authors: Li Yueru
Published: May 2023

With the development and application of Internet technology, the world has entered a new era of the Internet economy. Information resources worldwide are no longer limited by time or space, which significantly improves the operational efficiency of production and commerce. As an essential part of the digital economy, digital finance is developing rapidly. Compared with traditional finance, Internet finance and digital finance have the advantages of low informational and transactional costs, and efficient services, which bring more benefits to consumers and investors. In the traditional small and fragmented long-tail market, the availability of finance has been effectively improved through technology-driven development. However, the sound development of the financial digital industry is inseparable from the self-generated sense of innovation and the exploration of green and sustainable development within the industry. This paper shows the evolution of the innovation and development of the financial digital industry driven by information technology in recent years, summarizes and discusses the key technologies emerging in it, and analyzes its limitations and shortcomings. This work will provide some references for the green development of the current industry.
From Privacy-Enhancing to Health Data Utilisation: The Traces of Anonymisation and Pseudonymisation in EU Data Protection Law
Authors: He Zhicheng
Published: May 2023

The proliferation of digital technologies in healthcare creates two conflicting needs: protection of health data and the free flow of such data. Anonymisation and pseudonymisation hold the potential to play important roles in reconciling these two conflicting needs by enabling the processing of health data in a less privacy-intrusive manner. Taking a forward-looking perspective, this paper aims to contribute to the scholarly debate around anonymisation and pseudonymisation by extending the discussion to the contexts of forthcoming EU data laws, with a focus on the draft European Health Data Space (EHDS) Regulation. It does so by digging into the past, present and future of anonymisation and pseudonymisation in EU data laws. Starting with a positivist enquiry, the paper investigates the traces and evolution of anonymisation and pseudonymisation in EU data protection instruments from both before and after the entry into force of the General Data Protection Regulation. It then shifts focus to future EU data laws and examines the roles of anonymisation and pseudonymisation in these instruments, including the draft EHDS Regulation, the newly adopted EU Data Governance Act and the draft EU Data Act. Ultimately, the paper makes preliminary remarks and recommendations on the draft EHDS Regulation and questions to what extent its current incorporation of anonymisation and pseudonymisation can be reconciled with the health data sharing arrangements proposed in this Regulation.
Public voices on tie-breaking criteria and underlying values in COVID-19 triage protocols to access critical care: a scoping review
Authors: Ramirez Claudia Calderon , Farmer Yanick , Bouthillier Marie-Eve
Published: May 2023

Background

To reduce the arbitrariness in the allocation of rare resources in intensive care units (ICU) in the context of the pandemic, tiebreakers were considered in some COVID-19 triage algorithms. They were also contemplated to facilitate the tragic decisions of healthcare workers when faced with two patients with similar prognosis and only one ICU bed available. Little is known about the public's perspective on tiebreakers.

Objectives

To consolidate the available scientific literature on public consultations, particularly on tiebreakers and their underlying values. Also, to obtain an overview of the key arguments presented by the participating public and to identify potential gaps related to this topic.

Methods

The steps described by Arksey and O’Malley was the preferred method to our approach. Seven electronic databases were searched from January 2020 to April 2022, using keywords for each database: PubMed, Medline, EMBASE, Web of Science, PsycINFO, EBM reviews, CINAHL complete. We also searched in Google and Google Scholar, and in the references of the articles found. Our analysis was mainly qualitative. A thematic analysis was performed to consider the public’s perspectives on tiebreakers and their underlying values, according to these studies.

Results

Of 477 publications found, 20 were selected. They carried out public consultations through various methods: surveys (80%), interviews (20%), deliberative processes (15%) and others (5%) in various countries: Australia, Brazil, Canada, China, France, Germany, India, Iran, Italy, Japan, Korea, Netherlands, Portugal, Spain, Switzerland, Thailand, United Kingdom, and United States. Five themes emerged from our analysis. The public favored the life cycle (50%) and absolute age (45%) as a tiebreaker. Other values considered important were reciprocity, solidarity, equality, instrumental value, patient merit, efficiency, and stewardship. Among the new findings were a preference for patient nationality and those affected by COVID-19.

Conclusions

There is a preference for favoring younger patients over older patients when there is a tie between similar patients, with a slight tendency to favor intergenerational equity. Variability was found in the public’s perspectives on tiebreakers and their values. This variability was related to socio-cultural and religious factors. More studies are needed to understand the public's perspective on tiebreakers.
The Temporal Asymmetry of Causation
Authors: Fernandes Alison
Published: May 2023

Causes always seem to come prior to their effects. What might explain this asymmetry? Causation's temporal asymmetry isn't straightforwardly due to a temporal asymmetry in the laws of nature—the laws are, by and large, temporally symmetric. Nor does the asymmetry appear due to an asymmetry in time itself. This Element examines recent empirical attempts to explain the temporal asymmetry of causation: statistical mechanical accounts, agency accounts and fork asymmetry accounts. None of these accounts are complete yet and a full explanation of the temporal asymmetry of causation will likely require contributions from all three programs.
Design and implementation of a digital site-less clinical study of serial rapid antigen testing to identify asymptomatic SARS-CoV-2 infection
Authors: Soni Apurv , Herbert Carly , Pretz Caitlin , Stamegna Pamela , Filippaios Andreas , Shi Qiming , Suvarna Thejas , Harman Emma , Schrader Summer , Nowak Chris , Schramm Eric , Kheterpal Vik , Behar Stephanie , Tarrant Seanan , Ferranto Julia , Hafer Nathaniel , Robinson Matthew , Achenbach Chad , Murphy Robert L. , Manabe Yukari C. , Gibson Laura , Barton Bruce , O’Connor Laurel , Fahey Nisha , Orvek Elizabeth , Lazar Peter , Ayturk Didem , Wong Steven , Zai Adrian , Cashman Lisa , Rao Lokinendi V. , Luzuriaga Katherine , Lemon Stephenie , Blodgett Allison , Trippe Elizabeth , Barcus Mary , Goldberg Brittany , Roth Kristian , Stenzel Timothy , Heetderks William , Broach John , McManus David
Published: May 2023

Background:

Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.

Methods:

This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.

Key Results:

A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.

Conclusions:

The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.
Determinantes de la eficiencia del gasto público sanitario en Latinoamérica: Una evaluación de frontera estocástica
Authors: Pinilla-Rodríguez Diego E. , Jiménez-Aguilera Juan de Dios , Montero-Granados Roberto
Published: May 2023

El objetivo de este artículo es establecer el nivel de eficiencia del gasto público sanitario en América Latina y comprobar su relación con determinadas características institucionales como calidad regulatoria, participación del sector privado, descentralización o tamaño de la burocracia. Se estima una frontera estocástica de verdaderos efectos aleatorios que relaciona el gasto público en salud per cápita frente a la tasa de mortalidad neonatal e infantil y la esperanza de vida después de los sesenta años. Se regresan las ineficiencias resultantes respecto del conjunto de variables institucionales explicativas. Se evidencia el importante papel del gasto público sanitario en la obtención de determinados niveles de realización sanitaria. Sin embargo, su eficiencia es mejorable, especialmente a partir de optimizar la calidad regulatoria del Estado. Latinoamérica ha configurados sistemas sanitarios complejos, pero no han logrado mejorar la coordinación entre sus actores, lo que explica su ineficiencia. La rectoría del gobierno es esencial.
John Henry Newman's National Monument: an Oxford Controversy
Authors: ATHERSTONE ANDREW
Published: May 2023

According to the standard narrative, although John Henry Newman was driven away from Oxford in the 1840s by the dominant Protestant consensus, by the end of his life in the 1890s he was back in favour, fêted in Oxford as a Roman Catholic celebrity and as an esteemed alumnus. This article challenges that interpretation by examining the forgotten controversy over Newman's national monument, a significant aspect of his reception history. It shows how Newman's memory and reputation remained hotly contested, provoking resistance by the dons and citizens of late Victorian Oxford, even in this recently secularised and professedly tolerant university city.
Methodological issues in social cognition research in autism spectrum disorder and schizophrenia spectrum disorder: a systematic review
Authors: Konstantin Grace E. , Nordgaard Julie , Henriksen Mads Gram
Published: May 2023

Recent systematic reviews and meta-analyses conclude that similar social cognitive impairments are found in autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD). While methodological issues have been mentioned as a limitation, no study has yet explored the magnitude of methodological heterogeneity across these studies and its potential impact for their conclusion. The purpose of this study was to systematically review studies comparing social cognitive impairments in ASD and SSD with a focus on methodology. Following the PRISMA guidelines, we searched all publications on PubMed, PsycINFO, and Embase. Of the 765 studies identified in our data base searches, 21 cross-sectional studies were included in the review. We found significant methodological heterogeneity across the studies. In the 21 studies, a total of 37 different measures of social cognition were used, 25 of which were only used in 1 study. Across studies, the same measure was often said to be assessing different constructs of social cognition – a confusion that seems to reflect the ambiguous definitions of what these measures test in the studies that introduced them. Moreover, inadequate differential diagnostic assessment of ASD samples was found in 81% of the studies, and sample characteristics were markedly varied. The ASD and SSD groups were also often unmatched in terms of medication usage and substance use disorder history. Future studies must address these methodological issues before a definite conclusion can be drawn about the potential similarity of social cognitive impairments in ASD and SSD.
Tracing the origins of midlife despair: association of psychopathology during adolescence with a syndrome of despair-related maladies at midlife
Authors: Brennan Grace M. , Moffitt Terrie E. , Ambler Antony , Harrington HonaLee , Hogan Sean , Houts Renate M. , Mani Ramakrishnan , Poulton Richie , Ramrakha Sandhya , Caspi Avshalom
Published: May 2023

Background

Midlife adults are experiencing a crisis of deaths of despair (i.e. deaths from suicide, drug overdose, and alcohol-related liver disease). We tested the hypothesis that a syndrome of despair-related maladies at midlife is preceded by psychopathology during adolescence.

Methods

Participants are members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972–73 and followed to age 45 years, with 94% retention. Adolescent mental disorders were assessed in three diagnostic assessments at ages 11, 13, and 15 years. Indicators of despair-related maladies across four domains – suicidality, substance misuse, sleep problems, and pain – were assessed at age 45 using multi-modal measures including self-report, informant-report, and national register data.

Results

We identified and validated a syndrome of despair-related maladies at midlife involving suicidality, substance misuse, sleep problems, and pain. Adults who exhibited a more severe syndrome of despair-related maladies at midlife tended to have had early-onset emotional and behavioral disorders [β = 0.23, 95% CI (0.16–0.30), p < 0.001], even after adjusting for sex, childhood SES, and childhood IQ. A more pronounced midlife despair syndrome was observed among adults who, as adolescents, were diagnosed with a greater number of mental disorders [β = 0.26, 95% CI (0.19–0.33), p < 0.001]. Tests of diagnostic specificity revealed that associations generalized across different adolescent mental disorders.

Conclusions

Midlife adults who exhibited a more severe syndrome of despair-related maladies tended to have had psychopathology as adolescents. Prevention and treatment of adolescent psychopathology may mitigate despair-related maladies at midlife and ultimately reduce deaths of despair.
Work and Identity in Early Modern England
Authors: Hailwood Mark , Waddell Brodie
Published: May 2023

How did work shape people's identity before industrial capitalism? It is a question that early modernists have never really got to grips with. Thanks to decades of research by social and cultural historians, we now have a much better understanding of how people in the past saw themselves and labelled those around them. But until recently scholars of early modern England have had surprisingly little to say about how a person's working life – their occupation, trade, vocation or livelihood – influenced their social identity. This essay is therefore an attempt to synthesise recent research on the subject into a more explicit historiographical intervention. Early modernists need to broaden their research to consider ‘working identities’ as a whole, rather than merely the narrower concept of ‘occupational identities’. By exploring how work influenced a person's self-image and social role, we can reshape our understanding of broader social relations in this period and challenge some of the ‘grand narratives’ of early modern social and economic change.
The Politics of Printing and Knowledge Production in Latin America and the Caribbean
Authors: Samur Daniela
Published: May 2023

In this review essay I examine how recent books about print culture and knowledge production in Latin America and the Caribbean have addressed the relationship between printing and power, and in doing so have contributed to global discussions about the hierarchies of knowledge production. The study of print culture in a broader social framework shows how printed materials matter beyond the realm of culture. I explore how these new works have understood printing as political and have unravelled its contentious politics; how they have grappled with the global circulation and mobility of printers, prints, and paper; and how they have examined the relation between printing, reading, and writing and the production of urban space.
Legal Pluralism from History to Theory and Back: Otto von Gierke, Santi Romano, and Francesco Calasso on Medieval Institutions
Authors: Conte Emanuele
Published: May 2023

This paper considers the historical contexts in which theories of legal pluralism grew and developed between the final third of the nineteenth century and the first half of the twentieth century. Theories of the state as a pluralistic system, as opposed to the absolute supremacy of state-made law, were the focus of German legal historical scholarship in the late nineteenth century, represented by the towering figure of Otto von Gierke. Gierke's image of a pluralist German Middle Ages largely influenced legal scholarship in Europe, even affecting the Italian scholar Santi Romano, whose book on the “legal order” has been considered a milestone in the construction of pluralist legal theories. Once passed from a legal historian like Gierke to a theorist like Romano, the model of a pluralist legal order returned to legal historiography, inspiring the innovative historical interpretation of medieval law proposed by Francesco Calasso. Gierke was a conservative, right-wing socialist, and Romano was a fascist and counselor of the fascist Italian government. Calasso, on the contrary, was a liberal opponent of the fascist regime. The three versions of legal pluralism, then, decline the same basic vision in three different ways, being influenced by the political contexts in which the three authors operated.
Cerebral Organoid Research Ethics and Pinning the Tail on the Donkey
Authors: McKeown Alex
Published: May 2023

The risk of creating cerebral organoids/assembloids conscious enough to suffer is a recurrent concern in organoid research ethics. On one hand, we should, apparently, avoid discovering how to distinguish between organoids that it would be permissible (non-conscious) and impermissible (conscious) to use in research, since if successful we would create organoids that suffer. On the other, if we do not, the risk persists that research might inadvertently continue to cause organoids to suffer. Moreover, since modeling some brain disorders may require inducing stress in organoids, it is unclear how to eliminate the risk, if we want to develop effective therapies. We are committed to harm avoidance but hamstrung by a presumption that we should avoid research that might tell us clearly when suffering occurs. How can we negotiate this challenge and maximize the therapeutic benefits of cerebral organoid research? The author interrogates the challenge, suggesting a tentative way forward.
Instrumented insoles for assessment of gait in patients with vestibular schwannoma
Authors: Leong Stephen , Teh Bing M. , Duong Ton , Hu Diane , Chui Alexander , Chen Jocelyn S. , Sisti Michael B. , Wang Tony J.C. , Zanotto Damiano , Lalwani Anil K.
Published: May 2023

Background

Imbalance and gait disturbances are common in patients with vestibular schwannoma (VS) and can result in significant morbidity. Current methods for quantitative gait analysis are cumbersome and difficult to implement. Here, we use custom-engineered instrumented insoles to evaluate the gait of patients diagnosed with VS.

Methods

Twenty patients with VS were recruited from otology, neurosurgery, and radiation oncology clinics at a tertiary referral center. Functional gait assessment (FGA), 2-minute walk test (2MWT), and uneven surface walk test (USWT) were performed. Custom-engineered instrumented insoles, equipped with an 8-cell force sensitive resistor (FSR) and a 9-degree-of-freedom inertial measurement unit (IMU), were used to collect stride-by-stride spatiotemporal gait parameters, from which mean values and coefficients of variation (CV) were determined for each patient.

Results

FGA scores were significantly correlated with gait metrics obtained from the 2MWT and USWT, including stride length, stride velocity, normalized stride length, normalized stride velocity, stride length CV, and stride velocity CV. Tumor diameter was negatively associated with stride time and swing time on the 2MWT; no such association existed between tumor diameter and FGA or DHI.

Conclusions

Instrumented insoles may unveil associations between VS tumor size and gait dysfunction that cannot be captured by standardized clinical assessments and self-reported questionnaires.
Modeling the Recent Changes of Phytoplankton Blooms Dynamics in the Arctic Ocean
Authors: Manizza Manfredi , Carroll Dustin , Menemenlis Dimitris , Zhang Hong , Miller Charles E.
Published: May 2023

In recent decades, Arctic Ocean (AO) sea ice has experienced intense climate‐related modifications, which coincide with earlier melting in spring and delayed formation in the fall. In this study, we use the ECCO2‐Darwin ocean biogeochemistry model to gain a mechanistic understanding of how changes in sea‐ice seasonality impact the phenology of AO phytoplankton blooms. We use a 2006–2013 simulation to show that early sea‐ice melt in 2007 and 2012 triggers earlier phytoplankton blooms (∼1 month earlier compared to other years) and that the blooms dissipate earlier due to more rapid nutrient depletion in the surface AO. Our simulation also confirms that delayed formation of sea ice during fall triggers second fall blooms, in agreement with observations. These results suggest that in a warmer and changing climate, further changes to sea‐ice extent could drastically impact AO phytoplankton, with important consequences for Arctic marine ecosystems.
Depth Distribution of Chlorine at Gale Crater, Mars, as Derived From the DAN and APXS Experiments Onboard the Curiosity Rover
Authors: Litvak M. L. , Mitrofanov I. G. , Gellert R. , Djachkova M. V. , Lisov D. I. , Vasavada A. R. , Czarnecki S.
Published: May 2023

The subsurface chlorine depth distribution at Gale crater has been studied using measurements from the Alpha Particle X‐ray Spectrometer (APXS) and Dynamic Albedo of Neutrons (DAN) instruments onboard NASA's Curiosity Mars rover. These measurements have been acquired at or near ∼30 drill holes made by Curiosity along its 30 km drive. APXS measured a ∼15 micron surface layer of bedrock and shallow depth of ∼5 cm of drill tailings. DAN is sensitive to the bulk (∼50 cm depth) chlorine abundance and that of other neutron absorbing elements. Joint analysis of APXS and DAN data shows that the chlorine distribution at Gale crater consists of two components: surficial chlorine with concentrations >1 wt.%, possibly controlled by aeolian deposition of Cl‐rich dust and surface alteration, and subsurface chlorine with concentrations <1 wt.%, likely a result of groundwater activity in the past.
Modeling Bankfull Channel Geometry Based on Watershed and Precipitation Characteristics Using Dimensionless Parameters
Authors: Bastola Hridaya , Diplas Panayiotis
Published: May 2023

Regression models have consistently identified discharge as a suitable variable for capturing the systematic trends in channel geometry. Using a discharge‐based relation, however, does not reflect the more fundamental dependence of channel geometry on basic watershed properties and precipitation characteristics. To explore relations between bankfull channel geometry and watershed properties, we consider two sets of dimensionless regression models: (a) with bankfull discharge as an independent variable, and (b) with bankfull discharge as a dependent variable. While bankfull discharge is used as an input variable in the first set of regression analyses, average annual precipitation has been used in the second set. Other watershed and channel variables considered include drainage area, median sediment grain size, and valley slope. A data set of 538 sandy and gravel channel reaches from UK, and various physiographic provinces of the USA is considered. By representing bankfull discharge, width, depth and watershed variables in the form of dimensionless parameters, we specify the relationship between channel morphology and watershed and precipitation characteristics using an approach that is applicable to sandy and gravel streams from a range of climatic and physiographic regions. The formulation presented here is an effort toward the development of models that will be capable of predicting bankfull channel dimensions and discharge under modified average annual precipitation due to change in climate.
Evaluating the efficacy and cardiotoxicity of EGFR-TKI AC0010 with a novel multifunctional biosensor
Authors: Jiang Deming , Wei Xinwei , Zhu Yuxuan , Qiu Yong , Liu Xin , Kong Liubing , Li Fengheng , Liu Jingwen , Zhuang Liujing , Wan Hao , Ying Kejing , Wang Ping
Published: May 2023

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically improved the life expectancy of patients with NSCLC, concerns about TKI-induced cardiotoxicities have increased. AC0010, a novel third-generation TKI, was developed to overcome drug resistance induced by EGFR-T790M mutation. However, the cardiotoxicity of AC0010 remains unclear. To evaluate the efficacy and cardiotoxicity of AC0010, we designed a novel multifunctional biosensor by integrating microelectrodes (MEs) and interdigital electrodes (IDEs) to comprehensively evaluate cell viability, electrophysiological activity, and morphological changes (beating of cardiomyocytes). The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative, label-free, noninvasive, and real-time manner. AC0010 was found to significantly inhibit NCI-H1975 (EGFR-L858R/T790M mutation), while weak inhibition was found for A549 (wild-type EGFR). Negligible inhibition was found in the viabilities of HFF-1 (normal fibroblasts) and cardiomyocytes. With the multifunctional biosensor, we found that 10 μM AC0010 significantly affected the extracellular field potential (EFP) and mechanical beating of cardiomyocytes. The amplitude of EFP continuously decreased after AC0010 treatment, while the interval decreased first and then increased. We analyzed the change in the systole time (ST) and diastole time (DT) within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment. This result probably indicated that the relaxation of cardiomyocytes was insufficient, which may further aggravate the dysfunction. Here, we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations (10 μM). This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated. In addition, novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.
Vimentin is required for tumor progression and metastasis in a mouse model of non–small cell lung cancer
Authors: Berr Alexandra L. , Wiese Kristin , dos Santos Gimena , Koch Clarissa M. , Anekalla Kishore R. , Kidd Martha , Davis Jennifer M. , Cheng Yuan , Hu Yuan-Shih , Ridge Karen M.
Published: May 2023

Vimentin is highly expressed in metastatic cancers, and its expression correlates with poor patient prognoses. However, no causal in vivo studies linking vimentin and non–small cell lung cancer (NSCLC) progression existed until now. We use three complementary in vivo models to show that vimentin is required for the progression of NSCLC. First, we crossed LSL-KrasG12D; Tp53fl/fl mice (KPV+/+) with vimentin knockout mice (KPV−/−) to demonstrate that KPV−/− mice have attenuated tumor growth and improved survival compared with KPV+/+ mice. Next, we therapeutically treated KPV+/+ mice with withaferin A (WFA), an agent that disrupts vimentin intermediate filaments (IFs). We show that WFA suppresses tumor growth and reduces tumor burden in the lung. Finally, luciferase-expressing KPV+/+, KPV−/−, or KPVY117L cells were implanted into the flanks of athymic mice to track cancer metastasis to the lung. In KPVY117L cells, vimentin forms oligomers called unit-length filaments but cannot assemble into mature vimentin IFs. KPV–/– and KPVY117L cells fail to metastasize, suggesting that cell-autonomous metastasis requires mature vimentin IFs. Integrative metabolomic and transcriptomic analysis reveals that KPV–/– cells upregulate genes associated with ferroptosis, an iron-dependent form of regulated cell death. KPV–/– cells have reduced glutathione peroxidase 4 (GPX4) levels, resulting in the accumulation of toxic lipid peroxides and increased ferroptosis. Together, our results demonstrate that vimentin is required for rapid tumor growth, metastasis, and protection from ferroptosis in NSCLC.
A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors
Authors: Zhang Chao , Guo Qiang , Chen Lifeng , Wu Zheming , Yan Xiao-Jian , Zou Chengyang , Zhang Qiuxue , Tan Jiahong , Fang Tian , Rao Qunxian , Li Yang , Shen Shizhen , Deng Min , Wang Liewei , Gao Huanyao , Yu Jia , Li Hu , Zhang Cheng , Nowsheen Somaira , Kloeber Jake , Zhao Fei , Yin Ping , Teng Chunbo , Lin Zhongqiu , Song Kun , Yao Shuzhong , Yao Liangqing , Wu Lingying , Zhang Yong , Cheng Xiaodong , Gao Qinglei , Yuan Jian , Lou Zhenkun , Zhang Jin-San
Published: May 2023

Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination (HR) deficiency. However, many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin. The biomarker responsible for this mechanism remains unclear. Here, we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients. PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage (ATM) signaling-induced pro-apoptotic ribosomal stress, which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage. Therefore, the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin. The gene panel as an independent biomarker was validated by multiple published clinical datasets, as well as by an ovarian cancer organoids library we established. More importantly, its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data. Furthermore, we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines. These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance. Together, our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.
SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication
Authors: Pan Pan , Ge Weiwei , Lei Zhiwei , luo Wei , Liu Yuqing , Guan Zhanwen , Chen Lumiao , Yu Zhenyang , Shen Miaomiao , Hu Dingwen , Xiang Qi , Wang Wenbiao , Wan Pin , Tian Mingfu , Yu Yang , Luo Zhen , Chen Xulin , Xiao Heng , Zhang Qiwei , Liang Xujing , Chen Xin , Li Yongkui , Wu Jianguo
Published: May 2023

Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.
Inhibition of extranodal NK/T-cell lymphoma by Chiauranib through an AIF-dependent pathway and its synergy with L-asparaginase
Authors: Gao Tianxiao , Huang Jieye , Yin Haofan , Huang Jiajia , Xie Jinye , Zhou Ti , Fan Wei , Yang Xia , Gao Guoquan , Li Zhiming
Published: May 2023

Extranodal NK/T-cell lymphoma (NKTL) is a rare and aggressive form of extranodal lymphoma with a poor prognosis. Currently, there are very limited treatment options for patients with advanced-stage disease or those with relapsed/recurrent disease. Here we show that Chiauranib, an orally small molecule inhibitor of select serine-threonine kinases (aurora B, VEGFRs, PDGFR, CSF1R, c-Kit), inhibited NKTL cell proliferation, induced cell cycle arrest, as well as suppressed the microvessel density in vitro and in vivo similar as in other types of cancer cells. Surprisingly, Chiauranib unfolded a new effect to induce apoptosis of NKTL cells by triggering AIF-dependent apoptosis other than the traditional cyt-c/caspase mitochondrial apoptosis pathway. The knockdown of AIF in vitro and in vivo dramatically blocked the efficacy of Chiauranib on NKTL. Mechanistically, the release of AIF from mitochondria is due to the upregulation of VDAC1 by the AKT-GSK3β pathway and activation of calcium-dependent m-calpain, which promotes the cleavage of VDAC1 and therefore permits the release of AIF. Notably, the low expression of Bax in both NKTL cells and patient tissues restrained the cyt-c release. It resulted in the inhibition of cyt-c/caspase mitochondrial pathway, suggesting that drugs targeting this traditional pathway may not be effective in NKTL. Furthermore, we found that L-asparaginase triggered CD95 (Fas/Apo-1)-caspase 8-caspase 3 apoptotic pathway in NKTL cells, and combination of Chiauranib and L-asparaginase exhibited a synergistic effect, suggesting a feasibility to combine these two drugs for effective treatment of NKTL. This study demonstrates Chiauranib’s positive efficacy toward NKTL through the activation of the AIF-dependent apoptosis pathway for the first time. The novel and multi-targets of Chiauranib and the synergistic effect with L-asparaginase may provide a promising therapy for NKTL patients.
Serum amyloid protein A in inflammatory bowel disease: from bench to bedside
Authors: Chen Rirong , Chen Qia , Zheng Jieqi , Zeng Zhirong , Chen Minhu , Li Li , Zhang Shenghong
Published: May 2023

Inflammatory bowel diseases (IBD) is featured by gastrointestinal inflammation and a disease course with alternating recurrence and remission. The global burden caused by IBD has significantly boosted in recent years, necessitating treatment optimization. Serum amyloid A (SAA) is a class of 104 amino acid conservative acute-phase proteins, which is essential in immune-mediated inflammatory processes, like IBD. The SAA monomeric structure is composed of four α-helical regions and a C-terminal amorphous tail. Its disordered structure enables multiple bindings to different ligands and permits multiple functions. It has been proven that SAA has dual roles in the inflammatory process. SAA stimulates the pro-inflammatory cytokine expression and promotes the pathogenic differentiation of TH17 cells. In addition, SAA can remove toxic lipids produced during inflammatory responses and membrane debris from dead cells, redirect HDL, and recycle cholesterol for tissue repair. In IBD, SAA acts on gut epithelium barriers, induces T-cell differentiation, and promotes phagocytosis of Gram-negative bacteria. Owing to the tight connection between SAA and IBD, several clinical studies have taken SAA for a biomarker for diagnosis, assessing disease activity, and predicting prognosis in IBD. Furthermore, 5-MER peptide, a drug specifically targeting SAA, has shown anti-inflammatory effects in some SAA-dependent animal models, providing novel insights into the therapeutic targets of IBD.