bluuebunny/crossref_metadata_2025 huggingface dataset:
Down syndrome and Alzheimer's disease: A scoping review of functional performance and fall risk
Authors: Washington Selena E. , Cler Emily , Lowery Cameron , Stark Susan L.
Published: May 2023

Introduction

Alzheimer's disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer's disease and related dementias (ADRD) in adults with DS.

Methods

This scoping review included six electronic databases (e.g., PsycInfo, Academic Search Complete, CINAHL, COCHRANE Library, MEDLINE, and PubMed). Eligible studies included participants with DS ≥25 years of age, studies with functional measures and/or outcomes (e.g., activities of daily living, balance, gait, motor control, speech, behavior, and cognition; falls; and fall risks), and studies that investigated AD pathology and implications.

Results

Fourteen eligible studies were included and categorized through a thematic analysis into the following themes: (1) physical activity and motor coordination (PAMC), (2) cognition, (3) behavior, and (4) sleep. The studies indicated how functional activity performance and engagement may contribute to early identification of those at risk of cognitive decline and AD development and/or progression.

Discussion

There is a need to expand the research regarding ADRD pathology relative to functional outcomes in adults with DS. Functional measures related to disease staging and cognitive impairment are essential to understanding how AD progression is characterized within real‐world settings. This scoping review identified the need for additional mixed‐methods research to examine the use of assessment and intervention related to function and its detection of cognitive decline and AD progression.
Causes of thrombocytopenia in dogs in the United Kingdom: A retrospective study of 762 cases
Authors: Martín‐Ambrosio Francés Marina , Seth Mayank , Sharman Mellora , Pollard Danica , Ortiz Ana Liza , Miller Rachel , Natsiopoulos Thomas , Walker David , Jones Bryn , Hardwick Joshua , Glanemann Barbara , Garcia Andrés Salas , Bacon Jessica , Selgas Aida Gómez
Published: May 2023

Background

Thrombocytopenia is a common laboratory abnormality in dogs, and numerous diseases have been associated with its development. Estimates for the sensitivity and specificity of the degree of reduction of platelet concentration for the diagnosis of primary immune‐mediated thrombocytopenia (pITP) have not been reported.

Objectives

To report the prevalence of different causes of thrombocytopenia in dogs in the United Kingdom and to investigate the utility of platelet concentration to differentiate causes of thrombocytopenia.

Methods

Medical records of 762 dogs with thrombocytopenia presented to seven referral hospitals from January 2017 to December 2018 were retrospectively reviewed. Cases were assigned into the following categories: pITP, infectious diseases, neoplasia, inflammatory/other immune‐mediated disorders and miscellaneous causes. The prevalence of the different categories was estimated, and platelet concentrations were compared. Receiver‐operating characteristic (ROC) curves were used to investigate the utility of platelet concentration to differentiate between causes of thrombocytopenia.

Results

The most common disease category associated with thrombocytopenia was neoplasia (27.3%), followed by miscellaneous causes (26.9%), pITP (18.8%), inflammatory/immune‐mediated disorders (14.4%) and infectious diseases (12.6%). Dogs with pITP had significantly lower platelet concentrations (median 8 × 109/L, range: 0–70 × 109/L) than dogs in the other four categories. Platelet concentration was useful for distinguishing pITP from other causes of thrombocytopenia (area under ROC curve = 0.89, 95% confidence interval 0.87, 0.92), with a platelet concentration ≤12 × 109/L being 60% sensitive and 90% specific.

Conclusions

Severe thrombocytopenia was highly specific for a diagnosis of pITP, which was more prevalent in this UK population of thrombocytopenic dogs compared with previous epidemiological studies. Conversely, the proportion of dogs with infectious diseases was lower than in previous reports from other locations.
Combining surveys in small area estimation using area‐level models
Authors: Franco Carolina , Maitra Poulami
Published: May 2023

For many sample surveys, researchers, policymakers, and other stakeholders are interested in obtaining estimates for various domains, such as for geographic levels, for demographic groups, or a cross‐classification of both. Often, the demand for estimates at a disaggregated level exceeds what the sample size and survey design can support when estimation is done by traditional design‐based estimation methods. Small area estimation involves exploiting relationships among domains and borrowing strength from multiple sources of information to improve inference relative to direct survey methods. This typically involves the use of models whose success depends heavily on the quality and predictive ability of the sources of information used. Possible sources of auxiliary information include administrative records, Censuses, big data such as traffic or cell phone data, or previous vintages of the same survey. One rich source of information is that of other surveys, especially in countries like the United States, where multiple surveys exist that cover related topics. We will provide an introduction to the topic of combining information from multiple surveys in small area estimation using area‐level models, including practical advice and a technical introduction, and illustrating with applications. We will discuss reasons to combine surveys and give an overview of some of the most common types of models.

This article is categorized under:

Statistical Models > Multivariate Models
Research on mining software repositories to facilitate refactoring
Authors: Nyamawe Ally S.
Published: May 2023

Software refactoring focuses on improving software quality by applying changes to the internal structure that do not alter the observable behavior. Determining which refactorings should be applied and presented to developers the most relevant and optimal refactorings is often challenging. Existing literature suggests that one of the potential sources to identify and recommend required refactorings is the past software development and evolution histories which are often archived in software repositories. In this article, we review a selection of existing literature that has attempted to propose approaches that facilitate refactoring by exploiting information mined from software repositories. Based on the reviewed papers, existing works leverage software history mining to support analysis of code smells, refactoring, and guiding software changes. First, past history information is used to detect design flaws in source code commonly referred to as code smells. Moreover, other studies analyze the evolution of code smells to establish how and when they are introduced into the code base and get resolved. Second, software repositories mining provides useful insights that can be used in predicting the need for refactoring and what specific refactoring operations are required. In addition, past history can be used in detecting and analyzing previously applied refactorings to establish software change facts, for instance, how developers refactor code and the motivation behind it. Finally, change patterns are used to predict further changes that might be required and recommend a set of files for change during a given modification task. The paper further suggests other exciting possibilities that can be pursued in the future in this research direction.

This article is categorized under:

Algorithmic Development > Text Mining

Application Areas > Data Mining Software Tools
Flow of two immiscible uniformly rotating micropolar and viscous fluid layers
Authors: Bashir Sammar , Sajid Muhammad
Published: May 2023

The interfacial flow of two immiscible uniformly rotating micropolar and viscous fluid layers is investigated in this article. The top layer contains a micropolar fluid of having velocity components ), micro‐rotation components , density ρ1, viscosity μ1 and pressure p1 that is rotating with angular velocity ω1. A viscous fluid layer exists in the lower region with velocity components , density ρ2, viscosity μ2 and pressure p2 rotating with constant angular velocity ω2. The flow similarity solutions exist under the constraint , where (angular velocities ratio) and (densities ratio). The flow shows a co‐rotating case for and a counter‐rotating case for . A strong numerical technique known as the Keller‐box approach is utilized to obtain the solution of the resultant set of an ordinary differential equation. Similarity solutions can be found for (co‐rotating flows) but for (counter‐rotating flows), the similarity solution occurs up to the certain critical value of σ (i.e., ). Due to the coupling type of the flow near the liquid‐liquid interface, the micro polarity parameter K1 has an impact on both fluid's layer, even though the micropolar fluid exists just in the upper layer. The key objective of the current article is to analyze how these two different fluid layers will behave under the weak and strong concertation of microelements that can be fruitful in the engineering and scientific disciplines.
The Experience (and Constitution) of Society in Postwar and Post-Industrial Finland, 1960–2020
Authors: Haapala Pertti
Published: May 2023

This chapter asks how experiences of society, societal structures, and ideas of society are related; how they produce actions (like politics); and how these factors explain the change of society. A particular focus is on the explanatory power of experience. The case studied here is the rapid societal change in Finland after World War II. This was the period when a version of the Nordic Model was built in Finland. The modernization of society and the birth of the redistributive state was a success story but not without problems. A crucial element in making the change legitimate among citizens was the fulfilled expectations people had in a relatively poor society in the 1950s. Wide commitment to the idea of social equality was the major political driving force behind the reforms from the years of reconstruction until the challenges of globalization and information revolution.
The Challenges of Narrating the Welfare State in the Age of Social Media: A Narrative-Theoretical Approach
Authors: Mäkelä Maria
Published: May 2023

The chapter presents narrative-theoretical methods for the analysis of the narrativization of the welfare state as shared experience. The focus is on early twenty-first-century narrative environments, particularly on the written forms of social media, journalism, institutional communication and fiction. The methods are derived from theories of narrative complexity, cognitive narratology, master and counter-narratives, narrative agency and viral social media storytelling. The chapter argues for the ultimate untellability of a well-functioning welfare system and shows how this resistance to narrativization fosters counter-narratives of the failure of the system. In the digital era, the most tellable counter-narrative contesting the master narrative of the foolproof welfare system is a viral social media story of personal experience, which is prone to transform into the representative and normative through sharing.
Pre-trained Language Models
Authors: Paaß Gerhard , Giesselbach Sven
Published: May 2023

This chapter presents the main architecture types of attention-based language models, which describe the distribution of tokens in texts: Autoencoders similar to BERT receive an input text and produce a contextual embedding for each token. Autoregressive language models similar to GPT receive a subsequence of tokens as input. They produce a contextual embedding for each token and predict the next token. In this way, all tokens of a text can successively be generated. Transformer Encoder-Decoders have the task to translate an input sequence to another sequence, e.g. for language translation. First they generate a contextual embedding for each input token by an autoencoder. Then these embeddings are used as input to an autoregressive language model, which sequentially generates the output sequence tokens. These models are usually pre-trained on a large general training set and often fine-tuned for a specific task. Therefore, they are collectively called Pre-trained Language Models (PLM). When the number of parameters of these models gets large, they often can be instructed by prompts and are called Foundation Models. In further sections we described details on optimization and regularization methods used for training. Finally, we analyze the uncertainty of model predictions and how predictions may be explained.
Knowledge Acquired by Foundation Models
Authors: Paaß Gerhard , Giesselbach Sven
Published: May 2023

During pre-training, a Foundation Model is trained on an extensive collection of documents and learns the distribution of words in correct and fluent language. In this chapter, we investigate the knowledge acquired by PLMs and the larger Foundation Models. We first discuss the application of Foundation Models to specific benchmarks to test knowledge in a large number of areas and examine if the models are able to derive correct conclusions from the content. Another group of tests assesses Foundation Models by completing text and by applying specific probing classifiers that consider syntactic knowledge, semantic knowledge, and logical reasoning separately. Finally, we investigate if the benchmarks are reliable and reproducible, i.e. whether they actually test the targeted properties and yield the same performance values when repeated by other researchers.
Framing Green and Blue Infrastructure
Authors: Giudice Benedetta , Novarina Gilles , Voghera Angioletta
Published: May 2023

Green and blue infrastructure (GBI) is increasingly popular in international literature and cultural debates. Indeed, international opinion agrees that GBI is a strategic planning and design tool to face current and upcoming societal challenges. However, goals and practical applications are not fixed and differ based on disciplinary approaches and geographical areas. Thus, the chapter attempts to provide a systematic frame on the current cultural debate on GBI, presenting the diverse contributions deriving from planning and design practices, from vast scale strategies to local projects.
A Multi-Scalar Green Infrastructure Project for the Landscape Enhancement and Regional Regeneration of Media and Alta Valtellina
Authors: Arcidiacono Andrea , Ronchi Silvia , di Martino Viviana , Pristeri Guglielmo
Published: May 2023

In the process of updating the Lombardy Region’s territorial and landscape planning tools, the Green Infrastructure has been defined as a strategic landscape infrastructure built based on the interpretation, assessment, and mapping of Ecosystem Services, with the aim of increasing their relative performance and, consequently, their Natural capital. The Regional Green Infrastructure is inspired by the European Commission’s principles, defined as a network of natural, rural, and anthropic landscape elements planned at a strategic level to improve human well-being. The Green Infrastructure design is multi-scale in that it allows both for the analysis of Ecosystem Services using the most appropriate functional and ecological scale and for the formulation of strategies and objectives that can be taken up and systematised by the most appropriate planning and programming tools with respect to the scale of implementation. This paper describes the procedure for downscaling the project contents and design of the Lombardy Region’s Green Infrastructure in the pilot area of Media and Alta Valtellina, as a fragile landscape context subjected to significant planning projects scheduled for the coming years. The Green Infrastructure downscaling procedure also becomes an opportunity to systematise and highlight the synergies among the various strategic and design-related components developed in support of the Lombard landscape planning tools.
NLO quark self-energy and dispersion relation using the hard thermal loop resummation
Authors: Sumit  , Haque Najmul , Patra Binoy Krishna
Published: May 2023

Abstract

Using the hard-thermal-loop (HTL) resummation in real-time formalism, we study the next-to-leading order (NLO) quark self-energy and corresponding NLO dispersion laws. In NLO, we have replaced all the propagators and vertices with the HTL-effective ones in the usual quark self-energy diagram. Additionally, a four-point vertex diagram also contributes to the quark NLO self-energy. We calculate the usual quark self-energy diagram and the four-point vertex diagram separately. Using those, we express the NLO quark self-energy in terms of the three- and four-point HTL-effective vertex functions. Using the Feynman parametrization, we express the integrals containing the three- and four-point HTL effective vertex functions in terms of the solid angles. After completing the solid angle integrals, we numerically calculate the momentum integrals in the NLO quark self-energy and plot them as a function of the ratio of momentum and energy. Using the NLO quark self-energy, we plot the NLO correction to dispersion laws.
Third-family quark-lepton Unification and electroweak precision tests
Authors: Allwicher Lukas , Isidori Gino , Lizana Javier M. , Selimović Nudžeim , Stefanek Ben A.
Published: May 2023

Abstract

We analyze the compatibility of the hypothesis of third-family quark-lepton unification at the TeV scale with electroweak precision data, lepton flavor universality tests, and high-pT constraints. We work within the framework of the UV complete flavor non-universal 4321 gauge model, which is matched at one loop to the Standard Model Effective Field Theory. For consistency, all electroweak precision observables are also computed at one loop within the effective field theory. At tree level, the most sizeable corrections are to W → τντ and Z → ντντ due to integrating out a pseudo-Dirac singlet fermion required by the model for neutrino mass generation. At loop level, the new colored states of the model generate large flavor-universal contributions to the electroweak precision observables via leading- and next-to-leading log running effects, yielding a significant improvement in the electroweak fit (including an increase in the W-boson mass). These effects cannot be decoupled if the model addresses the charged-current B-meson anomalies. Overall, we find good compatibility between the data sets, while simultaneously satisfying all low- and high-energy constraints.
The Loop Momentum Amplituhedron
Authors: Ferro Livia , Łukowski Tomasz
Published: May 2023

Abstract

In this paper we focus on scattering amplitudes in maximally supersymmetric Yang-Mills theory and define a long sought-after geometry, the loop momentum amplituhedron, which we conjecture to encode tree and (the integrands of) loop amplitudes in spinor helicity variables. Motivated by the structure of amplitude singularities, we define an extended positive space, which enhances the Grassmannian space featuring at tree level, and a map which associates to each of its points tree-level kinematic variables and loop momenta. The image of this map is the loop momentum amplituhedron. Importantly, our formulation provides a global definition of the loop momenta. We conjecture that for all multiplicities and helicity sectors, there exists a canonical logarithmic differential form defined on this space, and provide its explicit form in a few examples.
Mental fatigue does not affect static balance under both single and dual task conditions in young adults
Authors: Salihu Abubakar Tijjani , Usman Jibrin Sammani , Hill Keith D. , Zoghi Maryam , Jaberzadeh Shapour
Published: May 2023

The ability to control balance and prevent falls while carrying out daily life activities may require a predominantly controlled (cognitive) or automatic processing depending on the balance challenge, age, or other factors. Consequently, this process may be affected by mental fatigue which has been shown to impair cognitive abilities. Controlling static balance in young adults is a relatively easy task that may proceed automatically with minimal cognitive input making it insusceptible to mental fatigue. To investigate this hypothesis, static single and dual task (while concurrently counting backward by seven) balance was assessed in 60 young adults (25.2 ± 2.4 years) before and after 45 min of Stroop task (mental fatigue condition) and watching documentary (control), presented in a randomized counterbalanced order on separate days. Moreover, because mental fatigue can occur due to task underload or overload, participants carried out two different Stroop tasks (i.e., all congruent, and mainly incongruent trials) on separate days in the mental fatigue condition. Results of the study revealed a significantly higher feeling of mental fatigue after the mental fatigue conditions compared to control (p < 0.001). Similarly, the performance on congruent Stroop trials decreases with time indicating objective mental fatigue (p < 0.01). However, there was no difference in balance or concurrent task performance under both single and dual task assessments between the three conditions (p > 0.05) indicating lack of effect of mental fatigue on static balance in this population. Therefore, future studies investigating this phenomenon in occupational or sport settings in similar population should consider using more challenging balance tasks.
Tuberculosis revisted: classic imaging findings in childhood
Authors: Mahomed Nasreen , Kilborn Tracy , Smit Elsabe Jacoba , Chu Winnie Chiu Wing , Young Catherine Yee Man , Koranteng Nonceba , Kasznia-Brown Joanna , Winant Abbey J. , Lee Edward Y. , Sodhi Kushaljit Singh
Published: May 2023

Tuberculosis (TB) remains one of the major public health threats worldwide, despite improved diagnostic and therapeutic methods. Tuberculosis is one of the main causes of infectious disease in the chest and is associated with substantial morbidity and mortality in paediatric populations, particularly in low- and middle-income countries. Due to the difficulty in obtaining microbiological confirmation of pulmonary TB in children, diagnosis often relies on a combination of clinical and radiological findings. The early diagnosis of central nervous system TB is challenging with presumptive diagnosis heavily reliant on imaging. Brain infection can present as a diffuse exudative basal leptomeningitis or as localised disease (tuberculoma, abscess, cerebritis). Spinal TB may present as radiculomyelitis, spinal tuberculoma or abscess or epidural phlegmon. Musculoskeletal manifestation accounts for 10% of extrapulmonary presentations but is easily overlooked with its insidious clinical course and non-specific imaging findings. Common musculoskeletal manifestations of TB include spondylitis, arthritis and osteomyelitis, while tenosynovitis and bursitis are less common. Abdominal TB presents with a triad of pain, fever and weight loss. Abdominal TB may occur in various forms, as tuberculous lymphadenopathy or peritoneal, gastrointestinal or visceral TB. Chest radiographs should be performed, as approximately 15% to 25% of children with abdominal TB have concomitant pulmonary infection. Urogenital TB is rare in children. This article will review the classic radiological findings in childhood TB in each of the major systems in order of clinical prevalence, namely chest, central nervous system, spine, musculoskeletal, abdomen and genitourinary system.

Graphical Abstract
Phase 1 study of the pan-RAF inhibitor tovorafenib in patients with advanced solid tumors followed by dose expansion in patients with metastatic melanoma
Authors: Rasco Drew W. , Medina Theresa , Corrie Pippa , Pavlick Anna C. , Middleton Mark R. , Lorigan Paul , Hebert Chris , Plummer Ruth , Larkin James , Agarwala Sanjiv S. , Daud Adil I. , Qiu Jiaheng , Bozon Viviana , Kneissl Michelle , Barry Elly , Olszanski Anthony J.
Published: May 2023

Purpose

Genomic alterations of BRAF and NRAS are oncogenic drivers in malignant melanoma and other solid tumors. Tovorafenib is an investigational, oral, selective, CNS-penetrant, small molecule, type II pan‑RAF inhibitor. This first-in-human phase 1 study explored the safety and antitumor activity of tovorafenib.

Methods

This two-part study in adult patients with relapsed or refractory advanced solid tumors included a dose escalation phase and a dose expansion phase including molecularly defined cohorts of patients with melanoma. Primary objectives were to evaluate the safety of tovorafenib administered once every other day (Q2D) or once weekly (QW), and to determine the maximum-tolerated and recommended phase 2 dose (RP2D) on these schedules. Secondary objectives included evaluation of antitumor activity and tovorafenib pharmacokinetics.

Results

Tovorafenib was administered to 149 patients (Q2D n = 110, QW n = 39). The RP2D of tovorafenib was defined as 200 mg Q2D or 600 mg QW. In the dose expansion phase, 58 (73%) of 80 patients in Q2D cohorts and 9 (47%) of 19 in the QW cohort had grade ≥ 3 adverse events. The most common of these overall were anemia (14 patients, 14%) and maculo-papular rash (8 patients, 8%). Responses were seen in 10 (15%) of 68 evaluable patients in the Q2D expansion phase, including in 8 of 16 (50%) patients with BRAF mutation-positive melanoma naïve to RAF and MEK inhibitors. In the QW dose expansion phase, there were no responses in 17 evaluable patients with NRAS mutation-positive melanoma naïve to RAF and MEK inhibitors; 9 patients (53%) had a best response of stable disease. QW dose administration was associated with minimal accumulation of tovorafenib in systemic circulation in the dose range of 400–800 mg.

Conclusions

The safety profile of both schedules was acceptable, with QW dosing at the RP2D of 600 mg QW preferred for future clinical studies. Antitumor activity of tovorafenib in BRAF-mutated melanoma was promising and justifies continued clinical development across multiple settings.

ClinicalTrials.gov identifier

NCT01425008.
AI-assisted compressed sensing and parallel imaging sequences for MRI of patients with nasopharyngeal carcinoma: comparison of their capabilities in terms of examination time and image quality
Authors: Liu Haibin , Deng Dele , Zeng Weilong , Huang Yingyi , Zheng Chunling , Li Xinyang , Li Hui , Xie Chuanmiao , He Haoqiang , Xu Guixiao
Published: May 2023

Objective

To compare examination time and image quality between artificial intelligence (AI)–assisted compressed sensing (ACS) technique and parallel imaging (PI) technique in MRI of patients with nasopharyngeal carcinoma (NPC).

Methods

Sixty-six patients with pathologically confirmed NPC underwent nasopharynx and neck examination using a 3.0-T MRI system. Transverse T2-weighted fast spin-echo (FSE) sequence, transverse T1-weighted FSE sequence, post-contrast transverse T1-weighted FSE sequence, and post-contrast coronal T1-weighted FSE were obtained by both ACS and PI techniques, respectively. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and duration of scanning of both sets of images analyzed by ACS and PI techniques were compared. The images from the ACS and PI techniques were scored for lesion detection, margin sharpness of lesions, artifacts, and overall image quality using the 5-point Likert scale.

Results

The examination time with ACS technique was significantly shorter than that with PI technique (p < 0.0001). The comparison of SNR and CNR showed that ACS technique was significantly superior with PI technique (p < 0.005). Qualitative image analysis showed that the scores of lesion detection, margin sharpness of lesions, artifacts, and overall image quality were higher in the ACS sequences than those in the PI sequences (p < 0.0001). Inter-observer agreement was evaluated for all qualitative indicators for each method, in which the results showed satisfactory-to-excellent agreement (p < 0.0001).

Conclusion

Compared with the PI technique, the ACS technique for MR examination of NPC can not only shorten scanning time but also improve image quality.

Clinical relevance statement

The artificial intelligence (AI)–assisted compressed sensing (ACS) technique shortens examination time for patients with nasopharyngeal carcinoma, while improving the image quality and examination success rate, which will benefit more patients.

Key Points

• Compared with the parallel imaging (PI) technique, the artificial intelligence (AI)–assisted compressed sensing (ACS) technique not only reduced examination time, but also improved image quality.

• Artificial intelligence (AI)–assisted compressed sensing (ACS) pulls the state-of-the-art deep learning technique into the reconstruction procedure and helps find an optimal balance of imaging speed and image quality.
Echo2Pheno: a deep-learning application to uncover echocardiographic phenotypes in conscious mice
Authors: Bukas Christina , Galter Isabella , da Silva-Buttkus Patricia , Fuchs Helmut , Maier Holger , Gailus-Durner Valerie , Müller Christian L. , Hrabě de Angelis Martin , Piraud Marie , Spielmann Nadine
Published: May 2023

Echocardiography, a rapid and cost-effective imaging technique, assesses cardiac function and structure. Despite its popularity in cardiovascular medicine and clinical research, image-derived phenotypic measurements are manually performed, requiring expert knowledge and training. Notwithstanding great progress in deep-learning applications in small animal echocardiography, the focus has so far only been on images of anesthetized rodents. We present here a new algorithm specifically designed for echocardiograms acquired in conscious mice called Echo2Pheno, an automatic statistical learning workflow for analyzing and interpreting high-throughput non-anesthetized transthoracic murine echocardiographic images in the presence of genetic knockouts. Echo2Pheno comprises a neural network module for echocardiographic image analysis and phenotypic measurements, including a statistical hypothesis-testing framework for assessing phenotypic differences between populations. Using 2159 images of 16 different knockout mouse strains of the German Mouse Clinic, Echo2Pheno accurately confirms known cardiovascular genotype–phenotype relationships (e.g., Dystrophin) and discovers novel genes (e.g., CCR4-NOT transcription complex subunit 6-like, Cnot6l, and synaptotagmin-like protein 4, Sytl4), which cause altered cardiovascular phenotypes, as verified by H&E-stained histological images. Echo2Pheno provides an important step toward automatic end-to-end learning for linking echocardiographic readouts to cardiovascular phenotypes of interest in conscious mice.

Graphical abstract
Long-term spatial variations in turbidity and temperature provide new insights into coral-algal states on extreme/marginal reefs
Authors: Cartwright Paula J. , Browne Nicola K. , Belton David , Parnum Iain , O’Leary Michael , Valckenaere Jurgen , Fearns Peter , Lowe Ryan
Published: May 2023

Globally, coral reefs are under threat, with many exhibiting degradation or a shift towards algal-dominated regimes following marine heat waves, and other disturbance events. Marginal coral reefs existing under naturally extreme conditions, such as turbid water reefs, may be more resilient than their clear water counterparts as well as offer some insight into how reefs could look in the future under climate change. Here, we surveyed 27 benthic habitats across an environmental stress gradient in the Exmouth Gulf region of north Western Australia immediately following a marine heatwave event. We used multidecadal remotely sensed turbidity (from an in-situ validated dataset) and temperature, to assess how these environmental drivers influence variability in benthic communities and coral morphology. Long-term turbidity and temperature variability were associated with macroalgal colonisation when exceeding a combined threshold. Coral cover was strongly negatively associated with temperature variability, and positively associated with depth, and wave power, while coral morphology diversity was positively associated with turbidity. While moderate turbidity (long-term average ~ 2 mg/L suspended matter) appeared to raise the threshold for coral bleaching and macroalgal dominance, regions with higher temperature variability (> 3.5 °C) appeared to have already reached this threshold. The region with the least turbidity and temperature variability had the highest amount of coral bleaching from a recent heatwave event and moderate levels of both these variables may confer resilience to coral reefs.
Impact of processing-latency induced interaural delay and level discrepancy on sensitivity to interaural level differences in cochlear implant users
Authors: Körtje Monika , Stöver Timo , Baumann Uwe , Weissgerber Tobias
Published: May 2023

Purpose

This study investigated whether an interaural delay, e.g. caused by the processing latency of a hearing device, can affect sensitivity to interaural level differences (ILDs) in normal hearing subjects or cochlear implant (CI) users with contralateral normal hearing (SSD-CI).

Methods

Sensitivity to ILD was measured in 10 SSD-CI subjects and in 24 normal hearing subjects. The stimulus was a noise burst presented via headphones and via a direct cable connection (CI). ILD sensitivity was measured for different interaural delays in the range induced by hearing devices. ILD sensitivity was correlated with results obtained in a sound localization task using seven loudspeakers in the frontal horizontal plane.

Results

In the normal hearing subjects the sensitivity to interaural level differences deteriorated significantly with increasing interaural delays. In the CI group, no significant effect of interaural delays on ILD sensitivity was found. The NH subjects were significantly more sensitive to ILDs. The mean localization error in the CI group was 10.8° higher than in the normal hearing group. No correlation between sound localization ability and ILD sensitivity was found.

Conclusion

Interaural delays influence the perception of ILDs. For normal hearing subjects a significant decrement in sensitivity to ILD was measured. The effect could not be confirmed in the tested SSD-CI group, probably due to a small subject group with large variations. The temporal matching of the two sides may be beneficial for ILD processing and thus sound localization for CI patients. However, further studies are needed for verification.
Normative data for certain vocal fold biomarkers among young normophonic adults using ultrasonography
Authors: Rai Santosh , Ramdas Divya , Jacob Nidhi Lalu , Bajaj Gagan , Balasubramanium Radish Kumar , Bhat Jayashree S.
Published: May 2023

Purpose

The current study aimed to profile vocal fold morphology, vocal fold symmetry, gender and task-specific data for vocal fold length (VFL) and vocal fold displacement velocity (VFDV) in young normophonic adults in the age range of 18–30 years using ultrasonography (USG).

Methods

Participants underwent USG across quiet breathing, /a/ phonation and /i/ phonation tasks, and acoustic analysis was conducted to explore the relationship between USG and acoustic measures.

Results

The study found that males have longer vocal folds than females, and overall greater velocities were observed in /a/ phonation, followed by /i/ phonation, with the lowest velocity observed in the quiet breathing task.

Conclusions

The obtained norms can be used as a quantitative benchmark for analyzing the vocal fold behavior in young adults.
Escaping the enemy’s bullets: an update on how malaria parasites evade host immune response
Authors: Ezema Chinonso Anthony , Okagu Innocent Uzochukwu , Ezeorba Timothy Prince Chidike
Published: May 2023

Malaria continues to cause untold hardship to inhabitants of malaria-endemic regions, causing significant morbidity and mortality that severely impact global health and the economy. Considering the complex life cycle of malaria parasites (MPs) and malaria biology, continued research efforts are ongoing to improve our understanding of the pathogenesis of the diseases. Female Anopheles mosquito injects MPs into its hosts during a blood meal, and MPs invade the host skin and the hepatocytes without causing any serious symptoms. Symptomatic infections occur only during the erythrocytic stage. In most cases, the host’s innate immunity (for malaria-naïve individuals) and adaptive immunity (for pre-exposed individuals) mount severe attacks and destroy most MPs. It is increasingly understood that MPs have developed several mechanisms to escape from the host’s immune destruction. This review presents recent knowledge on how the host’s immune system destroys invading MPs as well as MPs survival or host immune evasion mechanisms. On the invasion of host cells, MPs release molecules that bind to cell surface receptors to reprogram the host in a way to lose the capacity to destroy them. MPs also hide from the host immune cells by inducing the clustering of both infected and uninfected erythrocytes (rosettes), as well as inducing endothelial activation. We hope this review will inspire more research to provide a complete understanding of malaria biology and promote interventions to eradicate the notorious disease.
Amniotic fluid content in children with kidney and urinary tract anomalies determines pre- and postnatal development
Authors: Schulz Anne Mareike , Lauten Angela , Lehmann Thomas , Proquitté Hans , Eckoldt Felicitas , Weigel Friederike , Mentzel Hans-Joachim , Schneider Uwe , John-Kroegel Ulrike
Published: May 2023

Background

Renal oligohydramnios (ROH) describes an abnormally low volume of amniotic fluid (AF) during pregnancy. ROH is mostly caused by congenital fetal kidney anomalies. The ROH diagnosis frequently implies an increased risk of peri- and postnatal fetal mortality and morbidity. The present study aimed to evaluate the impact of ROH on pre-and postnatal development in children with congenital kidney anomalies.

Methods

This retrospective study included 168 fetuses with anomalies in the kidney and urinary tract. Based on the amount of AF measured by ultrasound, patients were divided into three groups: normal amniotic fluid (NAF), amniotic fluid in the lower normal range (LAF), and ROH. These groups were compared with respect to prenatal sonographic parameters, perinatal outcomes, and postnatal outcomes.

Results

Among the 168 patients with congenital kidney anomalies, 26 (15%) had ROH, 132 (79%) had NAF, and 10 (6%) had LAF. Of the 26 families affected by ROH, 14 (54%) decided to terminate pregnancy. Of 10 live-born children in the ROH group, 6 (60%) survived the observation time; of these, 5/6 presented with chronic kidney disease, stages I–III, at their last examination. The main differences in postnatal development between the ROH group and the NAF and LAF groups were: restricted height and weight gain, respiratory issues, complicated feeding, and the presence of extrarenal malformations.

Conclusions

ROH is not a mandatory indicator of severe postnatal kidney function impairment. However, children with ROH have complicated peri-and postnatal periods, due to the presence of concomitant malformations, which must be considered in prenatal care.

Graphical abstract
A novel model associated with tumor microenvironment on predicting prognosis and immunotherapy in triple negative breast cancer
Authors: Zhang Juan , Zhang Mi , Tian Qi , Yang Jin
Published: May 2023

Triple negative breast cancer (TNBC) is the most aggressive and malignant subtype in breast cancer. Immunotherapy is a currently promising and effective treatment for TNBC, while not all patients are responsive. Therefore, it is necessary to explore novel biomarkers to screen sensitive populations for immunotherapy. All mRNA expression profiles of TNBC from The Cancer Genome Atlas (TCGA) database were clustered into two subgroups by analyzing tumor immune microenvironment (TIME) with single sample gene set enrichment analysis (ssGSEA). A risk score model was constructed based on differently expressed genes (DEGs) identified from two subgroups using Cox and Least Absolute Shrinkage and Selector Operation (LASSO) regression model. And it was validated by Kaplan–Meier analysis and Receiver Operating Characteristic (ROC) analysis in Gene Expression Omnibus (GEO) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Multiplex immunofluorescence (mIF) and Immunohistochemical (IHC) staining were performed on clinical TNBC tissue samples. The relationship between risk score and immune checkpoint blockades (ICB) related signatures was further investigated, as well as the biological processes were performed by gene set enrichment analysis (GSEA). We obtained three DEGs positively related to prognosis and infiltrating immune cells in TNBC. Our risk score model could be an independent prognostic factor and the low risk group exhibited a prolonged overall survival (OS). Patients in low risk group were more likely to present a higher immune infiltration and stronger response to immunotherapy. GSEA revealed the model was associated with immune-related pathways. We constructed and validated a novel model based on three prognostic genes related to TIME in TNBC. The model contributed a robust signature that could predict the prognosis in TNBC, especially for the efficacy of immunotherapy.
Root aphid (Aploneura lentisci) population size on perennial ryegrass is determined by drought and endophyte strain
Authors: Hewitt Katrin G. , Hofmann Rainer W. , Ball Oliver J. , Cox Neil , Bryant Racheal H. , Finch Sarah C. , Popay Alison J.
Published: May 2023

Climate change is anticipated to lead to an increase in the occurrence and intensity of drought and fluctuations in insect cycles that will challenge modern pasture systems. Feeding by root aphids such as Aploneura lentisci Pass. can be a significant challenge to pastures. These below-ground living aphids are commonly found in New Zealand and Australia, feeding year-round on the roots of graminaceous plants such as perennial ryegrass (Lolium perenne L.). Some strains of the fungal endophyte Epichloë festucae var. lolii in perennial ryegrass can provide protection against root aphids and greater resilience under drought, contributing to higher persistency and growth than endophyte-free plants. However, the interaction between insect pressure and drought is not understood. This study examined the effect of drought on root aphid populations and plant performance in perennial ryegrass plants relative to endophyte status (±) and endophyte strain (AR37, NZCT) in a glasshouse experiment. Plants were cloned across the drought and well-watered treatments, and half of the plants were inoculated with root aphids, whilst half of the plants were treated with insecticide. Endophyte infection with strain NZCT and AR37 reduced root aphid numbers. Aphid populations were significantly higher in drought-stressed than in well-watered plants in both endophyte-infected and endophyte-free treatments. Under drought conditions, root aphid populations were increased 4-fold in NZCT and 8-fold in AR37 and endophyte-free plants in comparison with their well-watered counterparts. Root aphids reduced shoot dry weight by 16% in drought-exposed and 26% in well-watered plants in comparison with their insecticide-treated counterparts whilst reducing root biomass by 49%. Our results suggest that root aphids are likely able to exploit the higher availability of amino acids in the plant sap of drought-exposed plants. This study provides evidence that climate change-mediated impacts of root aphids could reduce production in perennial ryegrass-dominant pastures. However, field trials would be necessary to determine whether this effect is seen in situ, where numerous additional factors will be operating at the same time.
The Conley–Zehnder indices of the spatial Hill three-body problem
Authors: Aydin Cengiz
Published: May 2023

We explore the interaction between the Conley–Zehnder index and bifurcation points of symmetric planar as well as spatial periodic orbits in the spatial Hill three-body problem. We start with the fundamental families of planar periodic orbits which are those of direct (familyg) and retrograde periodic orbits (familyf). Since the spatial system is invariant under a symplectic involution, whose fixed point set corresponds to the planar problem, planar orbits have planar and spatial Floquet multipliers, and planar and spatial Conley–Zehnder indices. When the Floquet multipliers move through a root of unity, new families of periodic orbits bifurcate and the index jumps. For very low energies, the familiesgand farise dynamically from the rotating Kepler problem, and in a recent work (Aydin From Babylonian lunar observations to Floquet multipliers and Conley-Zehnder Indices) we determined analytically their indices. By their numerical continuations for higher energies, we determine the index of various families of planar and spatial periodic orbits bifurcating fromgandf. Since these families can bifurcate again and meet each other, this procedure can get complicated. This index leads to a grading on local Floer homology. Since the local Floer homology and its Euler characteristic stay invariant under bifurcation, the index provides important information about the interconnectedness of such families, which we illustrate in form of bifurcation graphs. Since the solutions of Hill’s system may serve as orbits for space mission design or astronomical observations, our results promote the interaction between Symplectic Geometry and practical problems.
Clinical characteristics, treatment, and long-term outcome of patients with brain metastases from thyroid cancer
Authors: Wolff Ladislaia , Steindl Ariane , Popov Petar , Dieckmann Karin , Gatterbauer Brigitte , Widhalm Georg , Berghoff Anna Sophie , Preusser Matthias , Raderer Markus , Kiesewetter Barbara
Published: May 2023

Brain metastases (BM) in patients with thyroid cancer (TC) are rare with an incidence of 1% for papillary and follicular, 3% for medullary and up to 10% for anaplastic TC (PTC, FTC, MTC and ATC). Little is known about the characteristics and management of BM from TC. Thus, we retrospectively analyzed patients with histologically verified TC and radiologically verified BM identified from the Vienna Brain Metastasis Registry. A total of 20/6074 patients included in the database since 1986 had BM from TC and 13/20 were female. Ten patients had FTC, 8 PTC, one MTC and one ATC. The median age at diagnosis of BM was 68 years. All but one had symptomatic BM and 13/20 patients had a singular BM. Synchronous BM at primary diagnosis were found in 6 patients, while the median time to BM diagnosis was 13 years for PTC (range 1.9–24), 4 years for FTC (range 2.1–41) and 22 years for the MTC patient. The overall survival from diagnosis of BM was 13 months for PTC (range 1.8–57), 26 months for FTC (range 3.9–188), 12 years for the MTC and 3 months for the ATC patient. In conclusion, development of BM from TC is exceedingly rare and the most common presentation is a symptomatic single lesion. While BM generally constitute a poor prognostic factor, individual patients experience long-term survival following local therapy.