bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacious application of laboratory testing in internal medicine
Authors:   , Vrijsen Bram Evert Luciën
Published: September 2023

Laboratory testing plays a major role in internal medicine, especially in diagnosing diseases. In order to use laboratory testing most effectively, several conditions need to be met.
Firstly, only tests that contribute to patient management should be performed. Otherwise, overtesting occurs. It leads to unnecessary costs and can be a burden on patients. In this thesis, several examples of overtesting were investigated. We found a high rate of unnecessary repetitions of laboratory tests when patients are referred to the outpatient clinic. We also found that when patients are admitted on the ward, laboratory testing is performed far more often than recommended.
Secondly, test results need to be available when required. In this thesis, we found that in the emergency department, a shorter turnaround time, defined as the time from ordering of the tests and the results’ becoming available, is associated with a shorter length of stay. Shorter turnaround times also allow laboratory testing to be performed directly before visits to the outpatient clinic. We found that pre-visit testing lead to more patients receiving a diagnosis on their first visit.
Thirdly, test results need to be interpreted correctly. We found that in the setting of patients receiving checkpoint inhibitors for cancer, routinely measured hematological tests can aid in the diagnosis of auto-immune toxicity.
Increased automation and decision support systems using artificial intelligence may be able to help increase the efficacy of laboratory testing.
An Analysis of the Meaning in the Satisfaction with Lecture Consulting of Newly Appointed Professors at the University: Focusing on the Network Analysis of the Case of University A
Authors:   The Korean Society of Culture and Convergence, Seo Yonghee , Lee Jeeyoung
Published: September 2023

This study conducted a network analysis on the keywords presented in the class consulting satisfaction survey to investigate the perception of class consulting among newly appointed professor at University A. The primary findings, analyzed using Textome and UCINET, are as follows. First, the key terms associated with satisfaction in lecture consulting included lecture, lecture consulting, student, thoughts, class, assistance, and gratitude. Second, the CONCOR analysis revealed four clusters: 'willingness to change through lecture consulting,' 'importance of lecture consulting,' 'collaboration with consultants,' and 'recommendations for lecture consulting.' The newly appointed professor at University A perceived lecture consulting as a beneficial experience that contributed to the enhancement of their classes. They also suggested conducting more detailed consultations that take into account the instructor's characteristics and contextual factors. Based on the research findings, suggestions for follow-up studies were made.
Properties and Lightfastness of Natural and Artificial Azurite Used As Painting Pigment
Authors: Park Ju-Hyun , Kim Myoung-Nam , Park Se-Rin , Lee Sun-Myung
Published: September 2023

Azurite is an inorganic pigment commonly used in traditional painting arts and even today. This pigment has two types: natural azurite and synthetic artificial azurite, called blue verditer or blue bice. Because they have the same structure and similar appearance they are difficult to distinguish. The purpose of this study is to compare these two types pigments, focusing on material properties and accelerated weathering behavior. Natural azurite consist of copper carbonate and mineral compounds like quartz, kaolinite. On the other hand, artificial azurites are synthesized using azurite and calcite. As a result of thermal analysis, unlike natural azurite, the calcite in artificial azurite resulted in weight loss at three temperatures, at approximately 350 ℃, 650 ℃, and 840 ℃. According to the microscope analysis results, natural azurites have clearly blue angular particles with sharp edges, produced by crushing. Artificial azurite showed spherules and aggregates with tiny rounded or fibrous particles. After accelerated weathering tests, the natural azurites had no change in color, particle shape or original components, but the artificial azurites noticeably changed color and shape. The color changes of artificial azurites occurred due to the growth of calcite crystallite, a slight new product formation, and change in particle shape. Even though natural azurites are more expensive pigments, they provide superior color durability and particle shape stability compared to artificial azurites.
MEMBANGUN PENGETAHUAN TEORI PERSAMAAN DIFERENSIAL TINGKAT I MELALUI TUGAS TERSTRUKTUR
Authors: Mudjiono  , Wiwaha Sigit Setya , Imron Aly
Published: September 2023

The research aims to describe how the structured task needs to be formulated and the extent to which it has an impact on improving student achievement. This research is based on Vygotsky's view which states that the potential of students will develop effectively if in the learning carried out, external factors, especially teachers/lecturers and students' friends are involved in learning. Cooperative learning is a learning system that contains various interrelated elements, including: (1) positive interdependence, (2) faceto-face interaction, (3) individual accountability, and (4) skills to establish interpersonal relationships. Structured task-based learning as a form of cooperative learning consists of 4 principles, namely: (1) Making assignments meaningful, clear, and challenging, (2) Diversifying assignments, (3) Paying attention to the level of difficulty, (4) Monitoring student progress. The method in this study uses two approaches, namely a qualitative approach and a quantitative approach. The effect of the action on the group given the task was calculated through the statistical tool of analysis of variance. After two actions were taken, it was found that the students who were given the task got a higher academic score. The key is that on every assignment given, the lecturer needs to provide feedback, especially on difficult questions.
MODEL PENGAUDITAN BERBANTUAN KOMPUTER TERHADAP LAPORAN KEUANGAN PERGURUAN TINGGI NEGERI VOKASI BADAN LAYANAN UMUM
Authors: Haris Zainal Abdul , Sumiadji  , Widiastuti Retno
Published: September 2023

The availability of databases resulting from the use of financial planning, management and reporting applications from vocational public tertiary institutions (polytechnics) of public service agencies is a resource that can be utilized for the purpose of achieving the effectiveness of auditing the resulting financial reports. However, the existence of these resources has never been exploited. Referring to these conditions, research was carried out which aims to develop a computer-assisted audit model of the financial reports of vocational colleges (polytechnics) of public service bodies through the use of database files generated by applications used in the financial administration of work units such as SAS, SIMAK BMN, and Inventory Application. The research method used is applied research. The object of research is the work unit of a vocational tertiary institution that applies the Public Service Agency Management Pattern. The results of the research are in the form of a computer-assisted auditing narrative model that describes the steps that must be carried out in computer-assisted auditing of the financial statements of vocational colleges that apply the Public Service Agency Financial Management Pattern.
The Relationship between Smartphone Addiction and Functional Neck Disability among University Students during COVID-19 Pandemic
Authors: ABDEL-AZİEM Amr , DEWİR Ibrahim , ALOTİBİ Mosab , MORSHED Hamzh , ALKHAMMASH Ziyad , ALSHAHRANİ Muqren
Published: September 2023

Objective: This study aimed to determine the prevalence of smartphones addiction, and to investigate the relationship between smartphones addiction and functional neck disability among the students of Taif University during a Covid-19 pandemic.

Methods: A 1060 students from Taif University participated in this study. The smartphones addiction was evaluated by using the short version of the smartphone’s addiction scale (SAS-SV) and functional neck disability was measured by the neck disability index (NDI).

Results: About 83 % of the students reported smartphones addiction, 50% were suffering from mild neck disability, and 84% used their smartphones for more than 4 hours/day. Female students represented one and half times more than male to develop a smartphones addiction (p< 0.05). There was a significant association between smartphones addition and neck disability (p< 0.05). Moreover, female students had a functional neck disability significantly greater than male students (p= 0.001). Students with smartphones addiction represented three times more than students without addiction to develop functional neck disability (p= 0.001), and female students represented two times more than male students to develop functional neck disability (p= 0.001).

Conclusion: During a COVID-19 pandemic, more than four-fifth of the students showed smartphones addiction. The female students are more predictive to smartphones addiction than male. The smartphones addiction and female students were found to be the predictors for functional neck disability.
Three-dimensional architecture and assembly mechanism of the egg-shaped shell in testate amoeba Paulinella micropora
Authors: Nomura Mami , Ohta Keisuke , Nishigami Yukinori , Nakayama Takuro , Nakamura Kei-Ichiro , Tadakuma Kenjiro , Galipon Josephine
Published: September 2023

Unicellular euglyphid testate amoeba Paulinella micropora with filose pseudopodia secrete approximately 50 siliceous scales into the extracellular template-free space to construct a shell isomorphic to that of its mother cell. This shell-constructing behavior is analogous to building a house with bricks, and a complex mechanism is expected to be involved for a single-celled amoeba to achieve such a phenomenon; however, the three-dimensional (3D) structure of the shell and its assembly in P. micropora are still unknown. In this study, we aimed to clarify the positional relationship between the cytoplasmic and extracellular scales and the structure of the egg-shaped shell in P. micropora during shell construction using focused ion beam scanning electron microscopy (FIB-SEM). 3D reconstruction revealed an extensive invasion of the electron-dense cytoplasm between the long sides of the positioned and stacked scales, which was predicted to be mediated by actin filament extension. To investigate the architecture of the shell of P. micropora, each scale was individually segmented, and the position of its centroid was plotted. The scales were arranged in a left-handed, single-circular ellipse in a twisted arrangement. In addition, we 3D printed individual scales and assembled them, revealing new features of the shell assembly mechanism of P. micropora. Our results indicate that the shell of P. micropora forms an egg shape by the regular stacking of precisely designed scales, and that the cytoskeleton is involved in the construction process.
Grounding perceptions: the value of otoendoscopy images in strengthening parents and children's understanding and decision making in a pediatric ENT clinic
Authors: Carter Bernie , Hampton Thomas , Sharma Sunil , De Sujata
Published: September 2023

Introduction

In recent years, there has been an increasing use of otoendoscopy in middle ear surgery. There is also increasing evidence of its usefulness as a diagnostic tool for clinicians. However, there is limited evidence on whether understanding their ear condition is of benefit to patients. This novel study sought to explore the perceptions, perspectives, and satisfaction of parents, children, and young people regarding the use of otoendoscope images in outpatient ENT consultations in relation to their understanding of ear symptoms, disease, and subsequent treatment. The framework for the study is child (and parent) health literacy and how visual images can play in scaffolding understanding, communication, and decision-making.

Methods

This qualitative descriptive exploratory study used semi-structured observation, a survey, short conversational interviews, and child activities.

Results

Purposive sampling of 16 children (aged 4–15 yrs, various diagnoses) and parents/carers attending an outpatient ENT clinic at a tertiary pediatric hospital. One overarching theme, “Grounding perceptions and deepening engagement,” and two sub-themes, “Strengthening understanding” and “Supporting decision-making,” were identified. The children and parents valued the opportunity to see the images and gain insight and knowledge of their child's pathology.

Discussion

The images appeared to promote child (and parent) health literacy and interaction between the child-parent-clinician and informed shared decision-making. This study suggests that the use of otoendoscopy in an out-patient setting and sharing of the images with parents, children, and young people have a largely positive impact on understanding, relationship building, and decision making in pediatric ENT consultations.
Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin
Authors: Di Conza Giusy , Barbaro Fulvio , Zini Nicoletta , Spaletta Giulia , Remaggi Giulia , Elviri Lisa , Mosca Salvatore , Caravelli Silvio , Mosca Massimiliano , Toni Roberto
Published: September 2023

Background

Disordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine –metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentiation, woven bone formation, and mineralization by MSCs we looked at the intermediate filament desmin (DES) during the skeletogenic commitment of rat bone marrow MSCs (rBMSCs), where its bone-related action remains elusive.

Results

Monolayer cultures of immunophenotypically- and morphologically - characterized, adult male rBMSCs showed co-localization of desmin (DES) with vimentin, F-actin, and runx2 in all cell morphotypes, each contributing to sparse and dense colonies. Proteomic analysis of these cells revealed a topologically-relevant interactome, focused on cytoskeletal and related enzymes//chaperone/signalling molecules linking DES to runx2 and alkaline phosphatase (ALP). Osteogenic differentiation led to mineralized woven bone nodules confined to dense colonies, significantly smaller and more circular with respect to controls. It significantly increased also colony-forming efficiency and the number of DES-immunoreactive dense colonies, and immunostaining of co-localized DES/runx-2 and DES/ALP. These data confirmed pre-osteoblastic and osteoblastic differentiation, woven bone formation, and mineralization, supporting DES as a player in the molecular pathway leading to the osteogenic fate of rBMSCs.

Conclusion

Immunocytochemical and morphometric studies coupled with proteomic and bioinformatic analysis support the concept that DES may act as an upstream signal for the skeletogenic commitment of rBMSCs. Thus, we suggest that altered metabolism of osteoblasts, woven bone, and mineralization by dysfunctional BMSCs might early be revealed by changes in DES expression//levels. Non-union fractures and endocrine – metabolic bone disorders like fibrous dysplasia and Paget disease of bone might take advantage of this molecular evidence for their early diagnosis and follow-up.
Investigation of the usability of industrial mining wastes in agriculture
Authors: Eker Hasan
Published: September 2023

In this study, the usability of the mixtures consisting of lignite coal taken from Tekirdag region and marble and travertine wastes taken from the marble factory in Gumushane region in local bean (Kelkit) cultivation was researched. First, control samples were created using only humus soil without coal, marble, or travertine dust. Then, for each coal or coal waste, coal/coal waste—waste marble dust and coal/coal waste—travertine dust mixtures were formed. These mixtures were obtained by mixing 25%, 50%, 75%, and 100% by weight of coal and 25%, 50%, and 75% by weight of marble and travertine dust. Afterwards, local beans were planted in these mixtures and their development was followed under laboratory conditions. Additionally, temperature and humidity values were recorded at certain intervals, pH and heavy metal analysis measurements were made on the mixtures before and after bean planting, the height and leaf measurement of the beans grown and the number of beans grown in these beans were also followed, and chlorophyll analysis was performed on the bean plants grown in these mixtures. As a result, 50% Coal-3D + 50% Travertine mixture had the maximum length increase, that 25% Coal Waste (Powder)-K3 + 75% Marble mixture had the highest number of beans, and that 50% Coal Waste -AK + 50% Marble mixture had the maximum leaf formation. In these mixtures, maximum 12 beans were grown and maximum 93 leaves were formed. Also, the bean plant was grown in all mixtures. The chlorophyll contents were at least as much as the values of the beans grown only in soil. However, heavy metal values do not exceed the permissible limit values in soil.
Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer
Authors: Bugoye Fidelis Charles , Torrorey-Sawe Rispah , Biegon Richard , Dharsee Nazima , Mafumiko Fidelice M. S. , Patel Kirtika , Mining Simeon K.
Published: September 2023

Over the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. Certain of these modifications, notably gene alterations known as homologous recombination (HRR) genes; PALB2, CHEK2 BRCA1, BRCA2, ATM, and genes for DNA mismatch repair (MMR); MLH1, MSH2, MSH6, and PMS2 are connected to a higher risk of prostate cancer and more severe types of the disease. The DNA damage repair (DDR) is essential for constructing and diversifying the antigen receptor genes required for T and B cell development. But this DDR imbalance results in stress on DNA replication and transcription, accumulation of mutations, and even cell death, which compromises tissue homeostasis. Due to these impacts of DDR anomalies, tumor immunity may be impacted, which may encourage the growth of tumors, the release of inflammatory cytokines, and aberrant immune reactions. In a similar vein, people who have altered MMR gene may benefit greatly from immunotherapy. Therefore, for these treatments, mutational genetic testing is indicated. Mismatch repair gene (MMR) defects are also more prevalent than previously thought, especially in patients with metastatic disease, high Gleason scores, and diverse histologies. This review summarizes the current information on the mutation spectrum and clinical significance of DDR mechanisms, such as HRR and MMR abnormalities in prostate cancer, and explains how patient management is evolving as a result of this understanding.
Lenticel hydration alters the susceptibility of apple fruit to infection by Phlyctema vagabunda
Authors: Everett Kerry R. , Hasna Luna , Pushparajah Irene P. S. , Vergara Michelle J. , Wood Peter N. , Fisher Brent M. , Sutherland Paul S. , Richards Kate K. , Husheer Sean W.
Published: September 2023

Bull’s eye rot, caused by Phlyctema vagabunda, is an important postharvest rot of apples. A combination of laboratory and field trials were conducted to examine the relationship between infection and status of apple lenticels. Fruit were hydrated and then inoculated, and climatic factors were compared with inoculations and natural infections in the field. In laboratory trials it was shown that increased lenticel density and size led to more infections. Hydration distended lenticel diameter, and dehydration contracted lenticels. A strong relationship with wind run, leaf wetness and temperature were shown to be important for laboratory inoculations of monthly harvested fruit, natural infections in trap fruit experiments, and monthly field inoculations. It was hypothesised that high wind run (> c. 240 km/day) reduced fruit susceptibility by promoting lenticel closure, and when lenticels were open, temperature limited the formation of an infection stroma. If the stroma did not form, postharvest expression of disease was negligible. Leaf wetness over 28 days was also an important factor for infection, probably because of the effect on micro-crack formation and resealing of lenticels during maturation by components of the cuticle. From these results, pre-harvest application of compounds that close lenticels could provide some control of bull’s eye rot without the need for fungicides.
Cyclone: an accessible pipeline to analyze, evaluate, and optimize multiparametric cytometry data
Authors: Patel Ravi K. , Jaszczak Rebecca G. , Im Kwok , Carey Nicholas D. , Courau Tristan , Bunis Daniel G. , Samad Bushra , Avanesyan Lia , Chew Nayvin W. , Stenske Sarah , Jespersen Jillian M. , Publicover Jean , Edwards Austin W. , Naser Mohammad , Rao Arjun A. , Lupin-Jimenez Leonard , Krummel Matthew F. , Cooper Stewart , Baron Jody L. , Combes Alexis J. , Fragiadakis Gabriela K.
Published: September 2023

In the past decade, high-dimensional single-cell technologies have revolutionized basic and translational immunology research and are now a key element of the toolbox used by scientists to study the immune system. However, analysis of the data generated by these approaches often requires clustering algorithms and dimensionality reduction representation, which are computationally intense and difficult to evaluate and optimize. Here, we present Cytometry Clustering Optimization and Evaluation (Cyclone), an analysis pipeline integrating dimensionality reduction, clustering, evaluation, and optimization of clustering resolution, and downstream visualization tools facilitating the analysis of a wide range of cytometry data. We benchmarked and validated Cyclone on mass cytometry (CyTOF), full-spectrum fluorescence-based cytometry, and multiplexed immunofluorescence (IF) in a variety of biological contexts, including infectious diseases and cancer. In each instance, Cyclone not only recapitulates gold standard immune cell identification but also enables the unsupervised identification of lymphocytes and mononuclear phagocyte subsets that are associated with distinct biological features. Altogether, the Cyclone pipeline is a versatile and accessible pipeline for performing, optimizing, and evaluating clustering on a variety of cytometry datasets, which will further power immunology research and provide a scaffold for biological discovery.
Relationship between serum iron and blood eosinophil counts in asthmatic adults: data from NHANES 2011-2018
Authors: Wen Jun , Wang Changfen , Xia Jing , Giri Mohan , Guo Shuliang
Published: September 2023

Background

So far, quite a few studies have revealed that systemic iron levels are related to asthmatic inflammatory reactions. And most studies have focused on the correlation between systemic iron levels and asthma, with inconsistent findings. Yet, few studies have investigated the connection between serum iron and blood eosinophil counts. Hence, we have explored the connection between serum iron and blood eosinophil counts in asthmatics by utilizing data from NHANES.

Methods

A total of 2549 individuals were included in our study after screening NHANES participants from 2011 to 2018. The linear regression model and XGBoost model were used to discuss the potential connection. Linear or nonlinear association was further confirmed by the generalized additive model and the piecewise linear regression model. And we also performed stratified analyses to figure out specific populations.

Results

In the multivariable linear regression models, we discovered that serum iron levels were inversely related to blood eosinophil counts in asthmatic adults. Simultaneously, we found that for every unit increase in serum iron (umol/L), blood eosinophil counts reduced by 1.41/uL in model 3, which adjusted for all variables excluding the analyzed variables. Furthermore, the XGBoost model of machine learning was applied to assess the relative importance of chosen variables, and it was determined that vitamin C intake, age, vitamin B12 intake, iron intake, and serum iron were the five most important variables on blood eosinophil counts. And the generalized additive model and piecewise linear regression model further verify this linear and inverse association.

Conclusion

Our investigation discovered that the linear and inverse association of serum iron with blood eosinophil counts in asthmatic adults, indicating that serum iron might be related to changes in the immunological state of asthmatics. Our work offers some new thoughts for next research on asthma management and therapy. Ultimately, we hope that more individuals become aware of the role of iron in the onset, development, and treatment of asthma.
Relatively preserved functional immune capacity with standard COVID-19 vaccine regimen in people living with HIV
Authors: Hung Chen-Yiu , Hsiao Sung-Han , Huang Chung-Guei , Chang Chia-Shiang , Chen Guan-Yan , Huang Yu-Lin , Dutta Avijit , Huang Ching-Tai
Published: September 2023

Introduction

People living with HIV (PLWH) are at a higher risk of severe disease with SARS-CoV-2 virus infection. COVID-19 vaccines are effective in most PLWH. However, suboptimal immune responses to the standard two-shot regimen are a concern, especially for those with moderate to severe immunodeficiency. An additional dose is recommended as part of the extended primary series in Taiwan. Herein, we study the efficacy of this additional shot in PLWH with mild immunodeficiency compared to that in healthy non-HIV people.

Methods

In total, 72 PLWH that were asymptomatic or with mild immunodeficiency (CD4 counts ≥200/mm3) and suppressed virology, and 362 healthcare workers of our hospital were enrolled. None of the participants had a history of SARS-CoV-2 infection. They received mRNA-1273 and ChAdOx1 vaccines. Anti-SARS-CoV-2 neutralizing and anti-Spike IgG antibodies, and SARS-CoV-2-specific T cell responses were evaluated.

Results

The standard two-shot regimen elicited lower responses in PLWH than the healthcare workers without HIV infection, although the difference was statistically insignificant. They had comparable levels of neutralizing and anti-Spike antibodies and comparable effector CD4+ and CD8+ T cell responses. The third shot boosted the SARS-CoV-2 immunity significantly more with better antibody responses and higher IFN-γ and IL-2 responses of the CD4+ and CD8+ T cells in PLWH compared to those without HIV. Upon in vitro stimulation with extracted Wuhan strain SARS-CoV-2 proteins, CD8+ T cells from PLWH after 3 shots had more durable effector responses than the non-HIV controls with extended time of stimulation.

Conclusion

This subtle difference between PLWH and non-HIV people implied immune exhaustion with two shots in non-HIV people. Slightly compromised immunity in PLWH indeed preserved the functional capacity for further response to the third shot or natural infection.
Reactive oxidative species (ROS)-based nanomedicine for BBB crossing and glioma treatment: current status and future directions
Authors: Wu Dandan , Chen Xuehui , Zhou Shuqiu , Li Bin
Published: September 2023

Glioma is the most common primary intracranial tumor in adults with poor prognosis. Current clinical treatment for glioma includes surgical resection along with chemoradiotherapy. However, the therapeutic efficacy is still unsatisfactory. The invasive nature of the glioma makes it impossible to completely resect it. The presence of blood-brain barrier (BBB) blocks chemotherapeutic drugs access to brain parenchyma for glioma treatment. Besides, tumor heterogeneity and hypoxic tumor microenvironment remarkably limit the efficacy of radiotherapy. With rapid advances of nanotechnology, the emergence of a new treatment approach, namely, reactive oxygen species (ROS)-based nanotherapy, provides an effective approach for eliminating glioma via generating large amounts of ROS in glioma cells. In addition, the emerging nanotechnology also provides BBB-crossing strategies, which allows effective ROS-based nanotherapy of glioma. In this review, we summarized ROS-based nanomedicine and their application in glioma treatment, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiation therapy, etc. Moreover, the current challenges and future prospects of ROS-based nanomedicine are also elucidated with the intention to accelerate its clinical translation.
Discovering immunoreceptor coupling and organization motifs
Authors: Reth Michael
Published: September 2023

The recently determined cryo-EM structures of the T cell antigen receptor (TCR) and B cell antigen receptor (BCR) show in molecular details the interactions of the ligand-binding part with the signaling subunits but they do not reveal the signaling mechanism of these antigen receptors. Without knowing the molecular basis of antigen sensing by these receptors, a rational design of optimal vaccines is not possible. The existence of conserved amino acids (AAs) that are not involved in the subunit interaction suggests that antigen receptors form higher complexes and/or have lateral interactors that control their activity. Here, I describe evolutionary conserved leucine zipper (LZ) motifs within the transmembrane domains (TMD) of antigen and coreceptor components that are likely to be involved in the oligomerization and lateral interaction of antigen receptor complexes on T and B cells. These immunoreceptor coupling and organization motifs (ICOMs) are also found within the TMDs of other important receptor types and viral envelope proteins. This discovery suggests that antigen receptors do not function as isolated entities but rather as part of an ICOM-based interactome that controls their nanoscale organization on resting cells and their dynamic remodeling on activated lymphocytes.
An evaluation of survey designs and model-based inferences of fish aggregations using active acoustics
Authors: White Allison L. , Sullivan Patrick J. , Binder Benjamin M. , Boswell Kevin M.
Published: September 2023

“Star” survey designs have become an increasingly popular alternative to parallel line designs in fisheries-independent sampling of areas with isolated fish aggregations, such as artificial reefs, seamounts, fish aggregating devices, and spawning aggregation sites. In this study, we simulated three scenarios of fish aggregating around a feature of interest with variations in the size and complexity of aggregations as well as their location relative to the habitat feature. Simulated and empirical data representing goliath grouper (Epinephalus itajara) spawning aggregations at artificial reefs were utilized as a case study, and scenarios were generated in relation to both a single habitat feature and a reef complex with multiple structures. Seven variations of survey design using both star and parallel transects were examined and compared by geostatistical and generalized additive models (GAMs) to identify the most robust approach to quantify fish aggregations in each scenario. In most scenarios, precision in the mean and variability of backscatter estimates is not significantly affected by the number of transects passing over the habitat feature as long as at least one pass is made. Estimation error is minimized using the GAM approach, and is further reduced when sampling variance is high, which was better accomplished by parallel designs overall. These results will help inform surveyors on the best overall approach to improve precision in quantifying fish aggregations given basic knowledge of their behavior around an established habitat feature and help them to adapt their survey designs based on common difficulties in sampling these populations simulated below.
Navigating the depths: a stratification-aware coarse-to-fine received signal strength-based localization for internet of underwater things
Authors: Mei Xiaojun , Han Dezhi , Saeed Nasir , Wu Huafeng , Miao Fahui , Xian Jiangfeng , Chen Xinqiang , Han Bing
Published: September 2023

Underwater wireless sensor networks (UWSNs) are the primary enabling technology for the Internet of underwater things (IoUT), with which all underwater objects can interact and communicate. In UWSNs, localization is vital for military or civilized applications since data collected without location are meaningless. However, accurate localization using acoustic signals in UWSNs is challenging, especially for received signal strength (RSS)-based techniques. The adverse effect of hybrid loss (path and absorption loss) and stratified propagation may severely impact localization accuracy. Even though some schemes have been proposed in the literature, the accuracy is unsatisfactory. To this end, this study proposes a coarse-to-fine localization method (CFLM). The problem is reformed into an alternating nonnegative constrained least squares (ANCLS) framework, where a constrained ellipse adjustment (CEA) using block principal pivoting is proposed to obtain the coarse estimation. A refined step using a Taylor series expansion is then further presented, in which a corrected solution is acquired by iteration. Additionally, this study derives the Cramér-Rao lower bound (CRLB) to evaluate the proposed method. Simulation results show that the proposed CFLM improves the localization accuracy by up to 66 percent compared with weighted least squares (WLS), privacy-preserving localization (PPSL), two-step linearization localization approach (TLLA), particle swarm optimization-based (PSO) localization, and differential evolution-based (DE) localization under different scenarios.
Ultrastructure of the organ of Corti in harbor seals (Phoca vitulina)
Authors: Rojas Laura , Haulena Martin , Reichmuth Colleen , Busse Björn , Ramos-Garduño L. Aurora , Rico-Chávez Oscar , Siebert Ursula , Morell Maria
Published: September 2023

Ultrastructural descriptions of the inner ear of highly sound-dependent mammalian species are lacking and needed to gain a better understanding of the hearing sense. Here, we present the first morphometric descriptions of the sensory cells of the inner ear in the harbor seal (Phoca vitulina), a mammal with broadly sensitive amphibious hearing. Scanning electron micrographs of the apical surface of the outer hair cells (OHCs) and inner hair cells (IHCs) within the organ of Corti were obtained from five individuals and analyzed by linear and geometric morphometrics. Measurements were taken at regular locations along the cochlea. The spiral shape of the seal cochlea contained two and a half turns. The organ of Corti had an average length of 27.7 mm with 12,628 OHCs (12,400-12,900). Six linear morphometric parameters showed significant patterns of change associated with their location within the cochlear spiral. Likewise, these trends were similarly expressed in cell configuration (cell blocks with 57 landmarks in 12 representative cells) revealed by geometric morphometry. Cell configuration varied predictably with position in the cochlea according to clustering analyses and Procrustes ANOVA (F= 25.936, p<0001). Changes associated with OHCs were primarily responsible for observed changes in cell configuration. An integration trend in cell shape change was also observed in which IHCs and OHCs share features in their morphological variation by the two-block partial least squares analysis (CR=0.987, p<0.001) and the modularity hypothesis (CV=0.99, p=0.05). These descriptive and quantitative findings provide a baseline for the morphology and morphometry of the sensory cells of the organ of Corti in harbor seals, allowing for comparisons between normal and pathological features. This initial morphological description should enable the correlation between position, morphometric features, and frequency coding along the spiral of the inner ear in this species, whose hearing ability is well studied.
What makes joint assessment procedures attractive to the innovative industry: successes, challenges, and proposed improvements
Authors: Miletic Nevena , Adam Sarah , Acquah Jacqueline , Aziz Zainab , Joos Angelika , Mwangi John M.
Published: September 2023

Regulatory harmonization and convergence have been identified as the key driver in promoting efficient evaluation of medicines, reducing workload, and supporting earlier access to medicines on the African continent. There has been great progress to date in enhancing regulatory harmonization and convergence on the African continent via the Regional Economic Communities (RECs) and with the establishment of the Africa Medicines Agency (AMA). In this article, the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Africa Regulatory Network (ARN) presents its perspective based on the available literature review and results from a survey conducted with innovative biopharmaceutical companies to gather experiences using regional joint assessment procedures (JAPs) in Africa, such as the East African Community Medicines Regulatory Harmonization (EAC-MRH), the West African Medicines Regulatory Harmonization (WA-MRH), and the Southern African Development Community Medicines Regulatory Harmonization (SADC-MRH) initiative through the ZAZIBONA Collaborative Procedure for Medicines Registration (ZaZiBoNa), and provides best practices in this evolving landscape. The article also assesses other collaborative registration pathways available to facilitating registration of pharmaceutical products in African countries, such as WHO Collaborative Registration Procedures (CRP), Swissmedic’s Marketing Authorisation for Global Health Products (MAGHP) and EU Medicines for All (EU-M4ALL). Benefits and challenges of each of the existing pathways are discussed in this article. Main benefits include building more expert capacity and improved collaboration amongst experts, as well as shorter review timelines in some cases. Key challenges include the lack of predictability in the adherence to procedural timelines as defined per guidelines, lengthy timeline to achieve national marketing authorization following joint assessment, the lack of dedicated personnel, administrative issues during the submission process as well as additional country-specific requirements on top of JAP-specific requirements. Our recommendations for improvements include harmonization of requirements across countries and regions and with international standards, appropriate resource allocation for JAP activities to ensure adherence to timelines, use of JAPs throughout the entire product lifecycle and all product categories, adequate use of digital technologies, and improved communication and transparency with applicants. These improvements will allow industry to better plan their filing strategies for the region which will lead to overall improved usability of the JAPs in Africa and enable faster patient access.
mTOR signaling in hair follicle and hair diseases: recent progress
Authors: Tu Wei , Cao Yu-Wei , Sun Mang , Liu Qian , Zhao Heng-Guang
Published: September 2023

Mammalian target of rapamycin (mTOR) signaling pathway is a major regulator of cell proliferation and metabolism, playing significant roles in proliferation, apoptosis, inflammation, and illness. More and more evidences showed that the mTOR signaling pathway affects hair follicle circulation and maintains the stability of hair follicle stem cells. mTOR signaling may be a critical cog in Vitamin D receptor (VDR) deficiency-mediated hair follicle damage and degeneration and related alopecia disorders. This review examines the function of mTOR signaling in hair follicles and hair diseases, and talks about the underlying molecular mechanisms that mTOR signaling regulates.
Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study
Authors: Bichet Daniel G. , Hopkin Robert J. , Aguiar Patrício , Allam Sridhar R. , Chien Yin-Hsiu , Giugliani Roberto , Kallish Staci , Kineen Sabina , Lidove Olivier , Niu Dau-Ming , Olivotto Iacopo , Politei Juan , Rakoski Paul , Torra Roser , Tøndel Camilla , Hughes Derralynn A.
Published: September 2023

Objective

Fabry disease is a progressive disorder caused by deficiency of the α-galactosidase A enzyme (α-Gal A), leading to multisystemic organ damage with heterogenous clinical presentation. The addition of the oral chaperone therapy migalastat to the available treatment options for Fabry disease is not yet universally reflected in all treatment guidelines. These consensus recommendations are intended to provide guidance for the treatment and monitoring of patients with Fabry disease receiving migalastat.

Methods

A modified Delphi process was conducted to determine consensus on treatment decisions and monitoring of patients with Fabry disease receiving migalastat. The multidisciplinary panel comprised 14 expert physicians across nine specialties and two patients with Fabry disease. Two rounds of Delphi surveys were completed and recommendations on the use of biomarkers, multidisciplinary monitoring, and treatment decisions were generated based on statements that reached consensus.

Results

The expert panel reached consensus agreement on 49 of 54 statements, including 16 that reached consensus in round 1. Statements that reached consensus agreement are summarized in recommendations for migalastat treatment and monitoring, including baseline and follow-up assessments and frequency. All patients with Fabry disease and an amenable mutation may initiate migalastat treatment if they have evidence of Fabry-related symptoms and/or organ involvement. Treatment decisions should include holistic assessment of the patient, considering clinical symptoms and organ involvement as well as patient-reported outcomes and patient preference. The reliability of α-Gal A and globotriaosylsphingosine as pharmacodynamic response biomarkers remains unclear.

Conclusion

These recommendations build on previously published guidelines to highlight the importance of holistic, multidisciplinary monitoring for patients with Fabry disease receiving migalastat, in addition to shared decision-making regarding treatments and monitoring throughout the patient journey.
Clinical trials of antibody drugs in the treatments of atopic dermatitis
Authors: Zhou Guihao , Huang Yueyao , Chu Ming
Published: September 2023

Atopic dermatitis (AD) is one of the most common, relapsing, chronic inflammatory skin disease, being regarded as a global health issue. Recent studies have shown that Th2 cell-mediated type 2 immunity plays a central role in AD. The type 2 inflammatory cytokines such as IL-4, IL-13, IL-22, IL-31, IL-17 and IL-5 mediate the pathogenesis of AD. A variety of antibody drugs targeting these cytokines have been developed to treat AD in clinics. Notably, several antibody drugs have exhibited high efficacy in treating atopic dermatitis in previous studies, demonstrating that they could be therapeutic methods for AD patients. Herein, we reviewed the clinical trials of antibody drugs in the treatment of AD, which provides a useful guideline for clinicians to treat patients with AD in clinics.
Evolutionary conservation of Zinc-Activated Channel (ZAC) functionality in mammals: a range of mammalian ZACs assemble into cell surface-expressed functional receptors
Authors: Jensen Anders A.
Published: September 2023

In contrast to the other pentameric ligand-gated ion channels in the Cys-loop receptor superfamily, the ZACN gene encoding for the Zinc-Activated Channel (ZAC) is exclusively found in the mammalian genome. Human ZAC assembles into homomeric cation-selective channels gated by Zn2+, Cu2+ and H+, but the function of the receptor in human physiology is presently poorly understood. In this study, the degree of evolutionary conservation of a functional ZAC in mammals was probed by investigating the abilities of a selection of ZACs from 10 other mammalian species than human to be expressed at the protein level and assemble into cell surface-expressed functional receptors in mammalian cells and in Xenopus oocytes. In an enzyme-linked immunosorbent assay, transient transfections of tsA201 cells with cDNAs of hemagglutinin (HA)-epitope-tagged versions of these 10 ZACs resulted in robust total expression and cell surface expression levels of all proteins. Moreover, injection of cRNAs for 6 of these ZACs in oocytes resulted in the formation of functional receptors in two-electrode voltage-clamp recordings. The ZACs exhibited robust current amplitudes in response to Zn2+ (10 mM) and H+ (pH 4.0), and the concentration-response relationships displayed by Zn2+ at these channels were largely comparable to that at human ZAC. In conclusion, the findings suggest that the functionality of ZAC at the molecular level may be conserved throughout mammalian species, and that the channel thus may govern physiological functions in mammals, including humans.
Differential effects of ageing on the neural processing of speech and singing production
Authors: Moisseinen Nella , Särkämö Teppo , Kauramäki Jaakko , Kleber Boris , Sihvonen Aleksi J. , Martínez-Molina Noelia
Published: September 2023

Background

Understanding healthy brain ageing has become vital as populations are ageing rapidly and age-related brain diseases are becoming more common. In normal brain ageing, speech processing undergoes functional reorganisation involving reductions of hemispheric asymmetry and overactivation in the prefrontal regions. However, little is known about how these changes generalise to other vocal production, such as singing, and how they are affected by associated cognitive demands.

Methods

The present cross-sectional fMRI study systematically maps the neural correlates of vocal production across adulthood (N=100, age 21–88 years) using a balanced 2x3 design where tasks varied in modality (speech: proverbs / singing: song phrases) and cognitive demand (repetition / completion from memory / improvisation).

Results

In speech production, ageing was associated with decreased left pre- and postcentral activation across tasks and increased bilateral angular and right inferior temporal and fusiform activation in the improvisation task. In singing production, ageing was associated with increased activation in medial and bilateral prefrontal and parietal regions in the completion task, whereas other tasks showed no ageing effects. Direct comparisons between the modalities showed larger age-related activation changes in speech than singing across tasks, including a larger left-to-right shift in lateral prefrontal regions in the improvisation task.

Conclusion

The present results suggest that the brains’ singing network undergoes differential functional reorganisation in normal ageing compared to the speech network, particularly during a task with high executive demand. These findings are relevant for understanding the effects of ageing on vocal production as well as how singing can support communication in healthy ageing and neurological rehabilitation.