bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of insomnia and its correction on quality of life of persons with disabilities
Authors: Akavov A. N. , Korabel'nikova E. A. , Baranov M. L.
Published: November 2023

Aim. To study the effect of insomnia on the severity of the condition and on the quality of life in patients with disabilities.Materials and methods. A prospective cohort study was conducted from 2019 to 2022, in which 100 patients took part. Patients with acute cerebrovascular accident (ACV) were selected as a clinical model of persons with disabilities. Two groups were formed from the total number of patients included in the study. 50 patients with acute cerebrovascular accident and suffering from insomnia constituted the main group, which was divided into 2 subgroups by a simple choice according to the random sampling rule in the Statistica 12 program. MG1 – the main subgroup 1–26 people who received, as part of complex therapy, a course of short-term (five sessions) cognitive-behavioral therapy for insomnia in combination with doxylamine at a dose of 15 mg 15–30 minutes before bedtime for 10 days. The second subgroup of the main group of patients (MG2) – 24 people who received only standard treatment. The comparison group (GS) (50 people) and a part (48 %) of the patients of the main group (24 people) also received only standard treatment for the underlying disease. All patients were assessed using the SF-36 Quality of Life Questionnaire, the Perrudet-Badoux, Mendelsohn, Chiche Subjective Wellbeing Scale (PSS), sleep quality questionnaires (Pittsburgh Sleep Quality Questionnaire and the Insomnia Severity Scale).Results and conclusions. Against the background of the treatment in the main group 1, there was a reduction in insomnia, as well as an improvement in the quality of life on all scales of the quality of life questionnaire and more pronounced than in the comparison group and the main group 2. Thus, the correction of insomnia in addition to the basic therapy of post-stroke patients with limited opportunities allows you to achieve a more significant result of treatment than the use of only basic therapy for patients.
Diagnosis and treatment of dizziness and vertigo in clinical practice
Authors: Makarov S. A. , Guseva A. L.
Published: November 2023

The article describes vertigo diagnostic algorithm. Acute, paroxysmal, and chronic vestibular syndromes determination, attacks duration assessment, provoking factors and comorbid diseases are described. The otoneurologic examination main tests and their interpretation in assessing of spontaneous nystagmus, the results of stato-coordination tests, the head rotation test and positional tests are presented. Diagnostic criteria and basic approach to the most common disorders manifested by vertigo treatment are discussed, including benign paroxysmal positional vertigo, vestibular neuronitis, Meniere's disease, vestibular migraine, persistent postural-perceptual vertigo, bilateral vestibulopathy and others.
Point stimulation with essential oils in complex effect on lumbosacral dorsopathies
Authors: Agasarov L. G. , Bazarova B. S. , Konchugova T. V. , Apkhanova T. V.
Published: November 2023

The work is devoted to the analysis of the mechanisms and evaluation of the effectiveness of various methods of topical use of essential oils in dorsopathies.Materials and methods. 90 patients (38 women and 52 men aged 40 to 75 years with exacerbation of dorsopathy at the lumbosacral level) were under observation. Along with neurological, psychological (using questionnaire methods) and electrophysiological analysis was performed, including thermography, rheovasography and ultrasound Doppler sonography of the vessels of the legs and feet. Three groups of 30 patients each were formed, in which standard treatment was performed. In addition to this, a mixture of essential oils was used in the first two groups. In the 1st group, with the use of this composition, massage of the lumbosacral zone was performed, in the 2nd group, the method of biopuncture was used, i. e., applying minimal doses of the mixture to the projection of reflexology points. In the 3rd control group, sesame oil was applied to the point area as a placebo.Results. In the course of the work, the effectiveness of both types of true use of essential oils was confirmed, significantly exceeding the control indicators in this regard. However, stable analgesia was achieved in the 2nd group significantly earlier than in the 1st: in a proportion close to this, the final intensity of pain sensations also decreased. On the other hand, in both groups of oil use, there was a comparable improvement in zonal vascular provision, confirmed electrophysiologically.Conclusions. During the follow-up evaluation, recurrences of dorsopathy in the control group were noted in a third of patients, whereas in the case of the use of essential oils, there were comparably fewer doses. Nevertheless, in these groups there are differences in the severity of recurring algias: in the 2nd group they increased slightly, while in others they increased to a greater extent. In addition, the data of rheovasograms testified in favor of greater stability of the results in the 2nd group. These differences can be explained by the cumulative effect inherent in the methods of reflexology and, in particular, biopuncture with essential oils.
Cerebrorenal connections in patients with chronic cerebral ischemia living in Republic of Sakha (Yakutia)
Authors: Kudrina P. I. , Bogolepova A. N. , Ariev A. L. , Shadrina S. S.
Published: November 2023

Purpose of the study. Identification of cerebrorenal relationships in patients with chronic cerebral ischemia (CCI) of elderly and senile age.Material and methods. We studied 522 elderly and senile patients with stage I and II CCI living in the Republic of Sakha (Yakutia). Doppler ultrasound was the main method for studying cerebral hemodynamics in this work. Glomerular filtration rate (GFR), which is the most reliable integral measure of the functional state of the kidneys, was calculated using the CKD-EPI formula, which takes into account race, gender, age, and serum creatinine levels.Results. Between the value of the glomerular filtration rate and almost all ultrasonic indicators included in the analysis (except for the diameter of the right and left vertebral arteries and the linear velocity of blood flow in the vertebral artery on the right), weak and moderate negative correlations were found. A univariate analysis confirmed the existence of relationships between GFR, age, duration of CCI, and blood lipid parameters.Conclusions. The study revealed a statistical relationship between GFR and age, duration of CCI, lipid spectrum parameters, as well as with all 12 ultrasound parameters characterizing cerebral hemodynamics.
Interpretation of results of automated analysis of pleural effusion (clinical cases)
Authors: Baranovskaya I. B. , Kotivets K. A. , Sysoeva I. P.
Published: November 2023

Automated analysis of effusion fluids, providing a large amount of objective information about a biological sample, has significantly expanded the diagnostic capabilities of the cytological service. At the same time, there are currently no unified algorithms for interpreting the obtained data.

   The aim of the work was to develop, based on the results of automated analysis of pleural fluids, alternative predictions of the genesis of the effusion (benign / malignant).

   The study was carried out on the basis of the Clinical Regional Hospital No. 2 in Krasnodar (Russia). The results of automated analysis of biological fluids obtained using the Sysmex XN analyzer were compared with the data of cytological, laboratory and instrumental studies. The article presents some of our own developments that can serve as indicative criteria for interpreting the results of automated analysis of biological fluids. It has been established that in terms of differential diagnosis of the genesis of effusion, the indicators of total cytosis (TC-BF) and the absolute content of highly fluorescent mononuclear cells (HF-BF#) are the most informative. Accounting for clinical data, results of laboratory and instrumental studies increases the informative value of automated analysis of biological fluids.
Genetic testing in clinical laboratory diagnostics: Present and future
Authors: Shcherbo S. N. , Shcherbo D. S. , Novikov A. A. , Savina M. I. , Turkina T. I.
Published: November 2023

Authors discuss the current state and prospects for the development of genetic testing in clinical laboratory diagnostics, recent nucleic acids sequencing technologies, their advantages and applications. Although genome-wide association studies (GWAS) have become a standard practice in identifying SNPs to determine disease susceptibility, this approach has limitations. A novel approach is proposed: integrative genome-wide association analysis (iGWAS), which relies on gene expression information to investigate the associations between SNPs and disease phenotype. Numerous studies have shown that iGWAS can significantly facilitate the search for genetic correlations and is superior to a method that relies only on the search for SNPs. Genetic testing will facilitate the molecular-based reclassification of human diseases. Authors describe the technical aspects of nanopore sequencing, the development of an iPhone app to complement miniature sequencing devices, and the world’s first mobile genomic sequence analyzer, iGenomics.
Advanced lung organoids and lung-on-a-chip for cancer research and drug evaluation: a review
Authors: Zhu Leqing , Zhang Jianhua , Guo Quanwei , Kuang Jun , Li Dongfang , Wu Mengxi , Mo Yijun , Zhang Tao , Gao Xinghua , Tan Jianfeng
Published: November 2023

Lung cancer has become the primary cause of cancer-related deaths because of its high recurrence rate, ability to metastasise easily, and propensity to develop drug resistance. The wide-ranging heterogeneity of lung cancer subtypes increases the complexity of developing effective therapeutic interventions. Therefore, personalised diagnostic and treatment strategies are required to guide clinical practice. The advent of innovative three-dimensional (3D) culture systems such as organoid and organ-on-a-chip models provides opportunities to address these challenges and revolutionise lung cancer research and drug evaluation. In this review, we introduce the advancements in lung-related 3D culture systems, with a particular focus on lung organoids and lung-on-a-chip, and their latest contributions to lung cancer research and drug evaluation. These developments include various aspects, from authentic simulations and mechanistic enquiries into lung cancer to assessing chemotherapeutic agents and targeted therapeutic interventions. The new 3D culture system can mimic the pathological and physiological microenvironment of the lung, enabling it to supplement or replace existing two-dimensional culture models and animal experimental models and realize the potential for personalised lung cancer treatment.
NG2/CSPG4 attenuates motility in mandibular fibrochondrocytes under serum starvation conditions
Authors: Ahn Shin Young , Bagheri Varzaneh Mina , Zhao Yan , Rozynek Jacob , Ravindran Sriram , Banks Jonathan , Chaudhry Minahil , Reed David A.
Published: November 2023

The migration of mandibular fibrochondrocytes is important for the development of the mandible, the homeostasis of the mandibular cartilage, and for the capacity of the tissue to respond to injury. Mandibular fibrochondrocytes have to overcome formidable obstacles during migration including a dense and heterogeneous three-dimensional matrix. Guiding the direction of cell migration and commitment to a migratory phenotype in this microenvironment necessitates a multivalent response to chemotactic and extracellular matrix-mediated stimuli. One of the key matrix components in the cartilage of the temporomandibular joint is type VI collagen. Neuron/glial antigen 2 (NG2/CSPG4) is a transmembrane proteoglycan that binds with collagen VI and has been implicated in a wide range of cell behaviors including cell migration, motility, adhesion, and proliferation. While NG2/CSPG4 has been shown to be a key regulator of mandibular cartilage homeostasis, its role in the migration of mandibular fibrochondrocytes during normal and cell stress conditions has yet to be resolved. Here, we address this gap in knowledge by characterizing NG2/CSPG4-dependent migration in mandibular fibrochondrocytes using primary mandibular fibrochondrocytes isolated from control and full length NG2/CSPG4 knockout mice, in primary mandibular fibrochondrocytes isolated from NG2|DsRed reporter mice and in an immortalized mandibular fibrochondrocyte cell line with a mutated NG2/CSPG4 ectodomain. All three cells demonstrate similar results, with loss of the full length or truncated NG2/CSPG4 increasing the rate of cell migration in serum starvation/cell stress conditions. These findings clearly implicate NG2/CSPG4 as a key molecule in the regulation of cell migration in mandibular fibrochondrocytes in normal and cell stress conditions, underscoring the role of NG2/CSPG4 as a mechanosensitive signaling hub in the mandibular cartilage.
A systematic review on the efficacy of virtual reality and gamification interventions for managing anxiety and depression
Authors: Jingili Nuru , Oyelere Solomon Sunday , Nyström Markus B. T. , Anyshchenko Lina
Published: November 2023

This systematic review aims to assess the effectiveness of virtual reality (VR) and gamification interventions in addressing anxiety and depression. The review also seeks to identify gaps in the current VR treatment landscape and provide guidelines for future research and development. A systematic literature search was conducted using Scopus, Web of Science, and PubMed databases, focusing on studies that utilized VR and gamification technology to address anxiety and depression disorders. A total of 2,664 studies were initially identified, 15 of those studies fulfilled the inclusion criteria for this systematic review. The efficacy of VR in addressing anxiety and depression was evident across all included studies. However, the diversity among VR interventions highlights the need for further investigation. It is advised to incorporate more diverse participant samples and larger cohorts and explore a broader spectrum of therapeutic approaches within VR interventions for addressing anxiety and depression to enhance the credibility of future research. Additionally, conducting studies in varying socioeconomic contexts would contribute to a more comprehensive understanding of their real-world applicability.
Promising treatment biomarkers in asthma
Authors: Bonnesen Barbara , Jensen Jens-Ulrik S. , Mathioudakis Alexander G. , Corlateanu Alexandru , Sivapalan Pradeesh
Published: November 2023

Asthma is a highly heterogenous disease which researchers over time have attempted to classify into different phenotypes and endotypes to improve diagnosis, prognosis and treatment. Earlier classifications based on reaction to environmental allergens, age, sex and lung function have evolved, and today, the use of precision medicine guided by biomarkers offers new perspectives on asthma management. Identifying biomarkers that may reveal the underlying pathophysiology of the disease will help to select the patients who will benefit most from specific treatments. This review explores the classification of asthma phenotypes and focuses on the most recent advances in using biomarkers to guide treatment.
The landscape of global research on diabetic neuropathy
Authors: Tavakoli Mitra , Klingelhöfer Doris , Fadavi Hassan , Groneberg David A.
Published: November 2023

Introduction

Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes, imposing a significant burden on individuals and healthcare systems worldwide. This study presents a comprehensive analysis of the global research landscape in DN, aiming to provide scientists, funders, and decision-makers with valuable insights into the current state of research and future directions.

Methods

Through a systematic review of published articles, key trends in DN research, including epidemiology, diagnosis, treatment strategies, and gaps in knowledge, are identified and discussed.

Results

The analysis reveals an increasing prevalence of DN alongside the rising incidence of diabetes, emphasizing the urgent need for effective prevention and management strategies. Furthermore, the study highlights the geographical imbalance in research activity, with a majority of studies originating from high-income countries.

Discussion

This study underscores the importance of fostering international collaboration to address the global impact of DN. Key challenges and limitations in DN research are also discussed, including the need for standardized diagnostic criteria, reliable biomarkers, and innovative treatment approaches. By addressing these gaps, promoting collaboration, and increasing research funding, we can pave the way for advancements in DN research and ultimately improve the lives of individuals affected by this debilitating condition.
Research progress on branched-chain amino acid aminotransferases
Authors: Chen Can , Naveed Hassan , Chen Keping
Published: November 2023

Branched-chain amino acid aminotransferases, widely present in natural organisms, catalyze bidirectional amino transfer between branched-chain amino acids and branched-chain α-ketoacids in cells. Branched-chain amino acid aminotransferases play an important role in the metabolism of branched-chain amino acids. In this paper, the interspecific evolution and biological characteristics of branched-chain amino acid aminotransferases are introduced, the related research of branched-chain amino acid aminotransferases in animals, plants, microorganisms and humans is summarized and the molecular mechanism of branched-chain amino acid aminotransferase is analyzed. It has been found that branched-chain amino acid metabolism disorders are closely related to various diseases in humans and animals and plants, such as diabetes, cardiovascular diseases, brain diseases, neurological diseases and cancer. In particular, branched-chain amino acid aminotransferases play an important role in the development of various tumors. Branched-chain amino acid aminotransferases have been used as potential targets for various cancers. This article reviews the research on branched-chain amino acid aminotransferases, aiming to provide a reference for clinical research on targeted therapy for various diseases and different cancers.
Comparative analysis of classification techniques for topic-based biomedical literature categorisation
Authors: Stepanov Ihor , Ivasiuk Arsentii , Yavorskyi Oleksandr , Frolova Alina
Published: November 2023

Introduction: Scientific articles serve as vital sources of biomedical information, but with the yearly growth in publication volume, processing such vast amounts of information has become increasingly challenging. This difficulty is particularly pronounced when it requires the expertise of highly qualified professionals. Our research focused on the domain-specific articles classification to determine whether they contain information about drug-induced liver injury (DILI). DILI is a clinically significant condition and one of the reasons for drug registration failures. The rapid and accurate identification of drugs that may cause such conditions can prevent side effects in millions of patients.

Methods: Developing a text classification method can help regulators, such as the FDA, much faster at a massive scale identify facts of potential DILI of concrete drugs. In our study, we compared several text classification methodologies, including transformers, LSTMs, information theory, and statistics-based methods. We devised a simple and interpretable text classification method that is as fast as Naïve Bayes while delivering superior performance for topic-oriented text categorisation. Moreover, we revisited techniques and methodologies to handle the imbalance of the data.

Results: Transformers achieve the best results in cases if the distribution of classes and semantics of test data matches the training set. But in cases of imbalanced data, simple statistical-information theory-based models can surpass complex transformers, bringing more interpretable results that are so important for the biomedical domain. As our results show, neural networks can achieve better results if they are pre-trained on domain-specific data, and the loss function was designed to reflect the class distribution.

Discussion: Overall, transformers are powerful architecture, however, in certain cases, such as topic classification, its usage can be redundant and simple statistical approaches can achieve compatible results while being much faster and explainable. However, we see potential in combining results from both worlds. Development of new neural network architectures, loss functions and training procedures that bring stability to unbalanced data is a promising topic of development.
Differential larval growth strategies and trophodynamics of larval Atlantic bluefin tuna (Thunnus thynnus) from two discrete spawning grounds
Authors: Malca Estrella , Quintanilla José M. , Gerard Trika , Alemany Francisco , Sutton Tracey , García Alberto , Lamkin John T. , Laiz-Carrión Raúl
Published: November 2023

Atlantic bluefin tuna (ABT), Thunnus thynnus, is a globally important fishery resource. This oceanic top predator undertakes long-distance migrations from its nutrient-rich feeding grounds in the north Atlantic to oligotrophic spawning grounds. Larvae are born mainly in the corresponding ecosystems of its two well-established spawning areas: the Gulf of Mexico (GoM) and the Mediterranean Sea (MED). Stable isotopes analyses (SIA) of δ15N and δ13C have proven useful for understanding marine food webs and have evaluated larval ABT signatures in their respective spawning areas. This study is among the first to use larvae collected during the same spawning season (2014) from the GoM and one of the main spawning areas within the MED (the Balearic Sea) to standardize methodologies, compare larval growth, and relate SIA with larval postflexion growth using GAMs for the two spawning areas. The main findings identify significant population differences, with comparatively faster growth in GoM larvae. The GoM population had larger otoliths with wider increments, as well as higher δ15N values and higher trophic position for postflexion stages. Collectively, these findings highlight the importance of not only developing well-calibrated growth curves, but also integrating the distinct early life history dynamics for each spawning area to properly support ABT’s ongoing management efforts.
Surface microplastics in the Kara Sea: from the Kara Gate to the 83°N
Authors: Berezina Anfisa , Pakhomova Svetlana , Zhdanov Igor , Mekhova Olga , Polivanova Tatiana , Novikov Matvei , Pogojeva Maria , Osadchiev Alexander , Stepanova Natalia , Yakushev Evgeniy
Published: November 2023

Despite ongoing research into microplastics pollution in the Arctic Ocean, the region remains underexplored. In the Eurasian Arctic studies mainly focus on the Barents Sea, while there are only limited and variable data from few stations in the Kara Sea. The study aims to perform an extensive survey of microplastics floating on the sea surface in the Kara Sea. The sampling throughout the Kara Sea was carried out using a neuston net in the August 2021 starting from the Kara Gate strait, reaching 83N latitude and ending in the north-eastern part of the Barents Sea along the border with the Kara Sea. Average abundance of microplastics was 0.124 ± 0.383 items/m3 in the Kara Sea. The Kara Gate exhibited the highest abundance of microplastics (0.93 ± 0.73 items/m3), suggesting that it is an important source of the microplastics pollution of the Kara Sea. The results suggest that the Ob and Yenisey rivers do not substantially contribute to the microplastic pollution of the Kara Sea due to significantly lower concentrations in the river plume water (0.008 ± 0.009 items/m3) compared to the other regions of the Kara Sea. Further, the river plume differs in chemical composition of microplastics dominated by expanded polystyrene (EPS) particles (52%) in contrast to other regions where the predominant polymer is polyethylene (PE) (64-77%). The study highlights the potential of the Kara Sea to accumulate the microplastics due to its semi-enclosed nature and complex interaction between inflow of waters originating from the North Atlantic and Ob-Yenisey river plume.
Experimental study into the propagation and attenuation of blasting vibration waves in porous rock-like materials
Authors: Lu Ge , Tao Yuhang
Published: November 2023

Rock blasting vibration can cause harm to the surrounding environment. This article aims to investigate the propagation and attenuation of vibration waves in the blasting excavation of porous rock. Similar materials were used to simulate porous rock media and indoor blasting experiments were conducted on 12 porous rock-like models poured to estimate influences of the media material, porosity, moisture conditions, and decoupling coefficient of blast holes on the propagation of blasting stress waves. The results show that: 1) the crack propagation path of vibration waves in foam ceramics similar materials (FC) is not a completely straight line: cracks tend to produce a large deflection during the development process; 2) damage modes of low-porosity similar materials are mainly dominated by crack development, while damage and failure of high-porosity similar materials involve crack expansion and crushed fragments; 3) the peak vibration acceleration presents exponential decay with the distance, which will not vary with changes in the media material, porosity, moisture conditions, and the decoupling coefficient of blast holes; 4) the peak vibration acceleration of cement-based similar materials (SM) demonstrates the exponential decay coefficient of −1.4 ∼ −1.0, the exponential decay coefficient of the peak vibration acceleration for FC is −0.8 ∼ −0.4. The peak vibration acceleration of high-porosity similar material shows a faster decay rate, which is generally 0.3 less than that of the low-porosity similar material; 5) the type of material exerts the most significant controlling effect on the decay coefficient of peak vibration acceleration, followed by the effects of porosity and degree of water saturation; the decoupling coefficient of blast holes does not exert any significant influence on the decay of peak vibration acceleration.
Prevalence and molecular characterization of Salmonella isolated from wild birds in fresh produce environments
Authors: Smith Jared C. , Varriano Sofia , Roach Kerrie , Snipes Zach , Dawson Joshua L. , Shealy Justin , Dunn Laurel L. , Snyder William E. , Shariat Nikki W.
Published: November 2023

Wild birds pose a difficult food safety risk to manage because they can avoid traditional wildlife mitigation strategies, such as fences. Birds often use agricultural fields and structures as foraging and nesting areas, which can lead to defecation on crops and subsequent transfer of foodborne pathogens. To assess the food safety risk associated with these events, wild bird feces were collected from produce fields across the southeastern United States during the 2021 and 2022 growing seasons. In total 773 fecal samples were collected from 45 farms across Florida, Georgia, South Carolina, and Tennessee, and 2.1% (n = 16) of samples were Salmonella-positive. Importantly, 75% of Salmonella were isolated from moist feces, showing reduced Salmonella viability when feces dry out. 16S microbiome analysis showed that presence of culturable Salmonella in moist feces correlated to a higher proportion of the Enterobacteriaceae family. From the Salmonella-positive samples, 62.5% (10/16) contained multi-serovar Salmonella populations. Overall, 13 serovars were detected, including six most commonly attributed to human illness (Enteriditis, Newport, Typhimurium, Infantis, Saintpaul, and Muenchen). PCR screening identified an additional 59 Salmonella-positive fecal samples, which were distributed across moist (n = 44) and dried feces (n = 15). On-farm point counts and molecular identification from fecal samples identified 57 bird species, including for 10 Salmonella-positive fecal samples. Overall, there was a low prevalence of Salmonella in fecal samples, especially in dried feces, and we found no evidence of Salmonella transmission to proximal foliage or produce. Fecal samples collected in farms close together shared highly related isolates by whole genome sequencing and also had highly similar Salmonella populations with comparable relative frequencies of the same serovars, suggesting the birds acquired Salmonella from a common source.
Analysis of predictive factors of unforeseen nodal metastases in resected clinical stage I NSCLC
Authors: Gallina Filippo Tommaso , Marinelli Daniele , Tajè Riccardo , Forcella Daniele , Alessandrini Gabriele , Cecere Fabiana Letizia , Fusco Francesca , Visca Paolo , Sperduti Isabella , Ambrogi Vincenzo , Cappuzzo Federico , Melis Enrico , Facciolo Francesco
Published: November 2023

Background

Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy.

Methods

Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines.

Results

A total of 297 patients were included in the study. 159 patients were female, and the median age was 68 (61 - 73). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the number of resected lymph nodes and micropapillar/solid adenocar-cinoma subtype. This result was confirmed in the multivariate analysis with a OR= 2.545 (95%CI 1.136-5.701; p=0.02) for the number of resected lymph nodes and a OR=2.717 (95%CI 1.256-5.875; p=0.01) for the high-grade pattern of adenocarcinoma.

Conclusion

Our results showed that in a homogeneous cohort of patients with clinical stage I NSCLC, the number of resected lymph nodes and the histological subtype of adenocarcinoma can significantly be associated with nodal metastasis.
Case Report: Progressive disease of BRCA2-mutant colon adenocarcinoma following talazoparib therapy
Authors: Polyanskaya Elizaveta , Lebedeva Alexandra , Kuznetsova Olesya , Belova Ekaterina , Kavun Alexandra , Ivanov Maxim , Fedyanin Mikhail , Tryakin Alexey , Mileyko Vladislav , Nosov Dmitry
Published: November 2023

Colorectal cancer (CRC) is currently one of the most common tumor types diagnosed worldwide. In the early stages, the disease responds well to surgical and chemotherapeutic treatment, but in the later stages when therapeutic options are exhausted, comprehensive genomic profiling can guide further treatment decisions. We present the case of a 46-year-old man of Ashkenazi Jewish ancestry who was diagnosed with KRAS-mutated metastatic colorectal cancer. After surgery and progression on standard FOLFOX/FOLFIRI + bevacizumab therapy, as well as on Trifluridine/Tipiracil, comprehensive genomic profiling was performed with the hope of expanding therapeutic options. Following comprehensive tumor molecular profiling via NGS, a discussion of the case was discussed at the local molecular tumor board in order to determine further treatment strategy. An activating variant of KRAS and PIK3CA, FLT3 and SRC amplification and damaging TP53 and APC variants were discarded by MTB as potential targetable biomarkers. The BRCA2 p.S1415fs*4 founder frameshift variant was of interest and the patient was included in the clinical trial investigating the efficacy of a PARP inhibitor talazoparib. Unfortunately, the disease progression was detected within one month of talazoparib treatment and the patient died during the 8th cycle of FOLFIRI + bevacizumab therapy rechallenge.
Long-term experience in treatment of acute promyelocytic leukemia in Mexican children in a tertiary care hospital
Authors: Murillo-Maldonado Marco Antonio , Galván Paulina González , Ortega Israel Parra , Morales Félix Gaytán , Villegas Luis Juárez , Acosta Elisa Dorantes
Published: November 2023

Introduction

Acute promyelocytic leukemia (APL) is a rare myeloid leukemia subtype affecting adult and pediatric populations. APL constitutes 15-20% of all childhood AML in Latin America, compared to 7% in the non-Latino population. This leukemia has unique characteristics, such as its association with chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. In addition, APL is also distinct from other AML subtypes due to its response to all-trans-retinoic acid (ATRA), which induces terminal granulocytic differentiation of blasts. Overall 5-year survival rates are generally reported to be greater than 80%.

Materials and methods

A study was conducted from January 2008 to December 2022 applying the IC-APL 2006 treatment protocol. This case series reports the clinical results of 22 children with APL. In all cases, the diagnosis was made by bone marrow aspiration and evaluation of the t(15:17) or t(11:17) transcripts.

Results

We identified 22 patients with APL, of whom 10 were female and 12 were male. Twelve patients debuted with coagulation abnormalities. The doses of anthracyclines varied according to the risk, with an average of 496.8 mgm2. The cardiological assessment was performed before and after chemotherapy, finding 2/22 patients with moderate sisto-diastolic dysfunction and one with mild pulmonary insufficiency at the end of treatment. There were 6/22 patients with complications related to ATRA treatment, the most frequent being pseudotumor cerebri. All complications were transitory and treated immediately without complications. In this series of cases, an overall survival of 90.6% and a relapse-free survival of 90.6% were recorded. The follow-up mean was 9.1 ± 3.8 years.

Conclusion

APL is a highly curable disease when combined with ATRA and anthracyclines. In this series of cases, good long-term results were observed with the IC-APL 2006 protocol. However, in Latin America, the availability of drugs such as arsenic trioxide as the first line of treatment is an unresolved challenge.
Applications of machine and deep learning to thyroid cytology and histopathology: a review
Authors: Slabaugh Greg , Beltran Luis , Rizvi Hasan , Deloukas Panos , Marouli Eirini
Published: November 2023

This review synthesises past research into how machine and deep learning can improve the cyto- and histopathology processing pipelines for thyroid cancer diagnosis. The current gold-standard preoperative technique of fine-needle aspiration cytology has high interobserver variability, often returns indeterminate samples and cannot reliably identify some pathologies; histopathology analysis addresses these issues to an extent, but it requires surgical resection of the suspicious lesions so cannot influence preoperative decisions. Motivated by these issues, as well as by the chronic shortage of trained pathologists, much research has been conducted into how artificial intelligence could improve current pipelines and reduce the pressure on clinicians. Many past studies have indicated the significant potential of automated image analysis in classifying thyroid lesions, particularly for those of papillary thyroid carcinoma, but these have generally been retrospective, so questions remain about both the practical efficacy of these automated tools and the realities of integrating them into clinical workflows. Furthermore, the nature of thyroid lesion classification is significantly more nuanced in practice than many current studies have addressed, and this, along with the heterogeneous nature of processing pipelines in different laboratories, means that no solution has proven itself robust enough for clinical adoption. There are, therefore, multiple avenues for future research: examine the practical implementation of these algorithms as pathologist decision-support systems; improve interpretability, which is necessary for developing trust with clinicians and regulators; and investigate multiclassification on diverse multicentre datasets, aiming for methods that demonstrate high performance in a process- and equipment-agnostic manner.
ClickArr: a novel, high-throughput assay for evaluating β-arrestin isoform recruitment
Authors: French Alexander R. , Meqbil Yazan J. , van Rijn Richard M.
Published: November 2023

Background: Modern methods for quantifying signaling bias at G protein–coupled receptors (GPCRs) rely on using a single β-arrestin isoform. However, it is increasingly appreciated that the two β-arrestin isoforms have unique roles, requiring the ability to assess β-arrestin isoform preference. Thus, methods are needed to efficiently screen the recruitment of both β-arrestin isoforms as they compete for a target GPCR in cells.

Methods: We used molecular cloning to develop fusion proteins of the δ-opioid receptor (δOR), β-arrestin 1, and β-arrestin 2 to fragments of click beetle green and click beetle red luciferases. In this assay architecture, recruitment of either β-arrestin 1 or 2 to the δOR generates a spectrally distinct bioluminescent signal, allowing us to co-transfect all three constructs into cells prior to agonist challenge.

Results: We demonstrate that our new assay, named “ClickArr,” is a live-cell assay that simultaneously reports the recruitment of both β-arrestin isoforms as they compete for interaction with the δOR. We further find that the partial δOR agonist TAN67 has a significant efficacy bias for β-arrestin 2 over β-arrestin 1 when recruitment is normalized to the reference agonist leu-enkephalin. We confirm that ClickArr reports this bias when run either as a high-throughput endpoint or high-throughput kinetic assay, and cross-validate this result using the PathHunter assay, an orthogonal commercial assay for reporting β-arrestin recruitment to the δOR.

Conclusion: Our results suggest that agonist:GPCR complexes can have relative β-arrestin isoform bias, a novel signaling bias that may potentially open up a new dimension for drug development.
Comparison of bioelectrical body and visceral fat indices and anthropometric measures in relation to type 2 diabetes by sex among Chinese adults, a cross-sectional study
Authors: He Jiangshan , Zhang Binbin , Fan Yaqi , Wang Yuxue , Zhang Mianzhi , Li Chunjun , Zhang Li , Guo Pei , Zhang Minying
Published: November 2023

Objectives

We aim to compare the efficacies of the bioelectrical indices (percentage of body fat, PBF; visceral fat area, VFA) with the conventional anthropometric measures (body mass index, BMI; waist-hip ratio, WHR) for predicting type 2 diabetes (T2D) risk by sex and to determine the sex-specific optimal adiposity indices to predict the T2D risk.

Design

Cross-sectional design.

Setting

Tianjin First Central Hospital and Tianjin Union Medical Center, Tianjin, China.

Participants

A total of 9,332 adults (41.35% men) undergoing physical examination.

Primary and secondary outcome measures

T2D was defined using the WHO’s criteria: fasting blood glucose (FBG) ≥7.0 mmol/L and/or previous diagnosis of T2D. Height, weight, waist, hip, PBF, VFA, and fasting plasma glucose were measured.

Results

All studied adiposity indices were associated with T2D among both males and females, and the observed associations differed by sex. The standardized aORs of BMI, WHR, PBF and VFA for T2D were 1.60 (95% CI 1.42–1.81), 1.43 (95% CI 1.25–1.64), 1.42 (95% CI 1.23–1.62) and 1.53 (95% CI 1.35–1.75) for females, and 1.47 (95% CI 1.31–1.66), 1.40 (95% CI 1.25–1.58), 1.54 (95% CI 1.36–1.74) and 1.47 (95% CI 1.31–1.65) for males, respectively. The AUCs of VFA, WHR and BMI were 0.743, 0.742 and 0.717 in women, respectively, whereas none of the indices had AUC larger than 0.70 in men. The AUCs were not significantly different between VFA and WHR, while both demonstrate larger AUCs than BMI and PBF in females (all p < 0.05). The optimal cutoff values of VFA, WHR, and BMI for T2D in women were 103.55 cm2, 0.905, and 24.15 kg/m2, respectively.

Conclusion

Although BMI, WHR, and PBF and VFA as measured by bioelectrical impedance analysis (BIA) were all positively associated with T2D, their efficacy for predicting the risk of T2D differed by sex. VFA, WHR and BMI could be used as biomarkers to predict T2D risk in women, however none of the study indicators demonstrated favorable efficacy of predicting T2D risk in men.
Perinatal tuberculosis—An approach to an under-recognized diagnosis
Authors: Schaaf H. Simon , Bekker Adrie , Rabie Helena
Published: November 2023

Tuberculosis (TB) in young infants (<3 months of age), often referred to as perinatal TB, is underdiagnosed, leading to severe morbidity and high mortality. Perinatal TB includes both congenital and postnatal transmission of Mycobacterium tuberculosis. We aimed to increase an awareness of TB in neonates and young infants and to provide guidance on the assessment and management when in contact with mothers with TB during or soon after pregnancy. Approximately 217,000 pregnant women develop TB annually; if they are not diagnosed and treated during pregnancy, their infants are at high risk of adverse birth outcomes and TB disease. Although safe and effective antituberculosis treatment regimens are available during pregnancy, the diagnosis of TB is challenging. Infants born to mothers newly diagnosed with TB, not receiving any effective treatment or with cultures not yet negative, should be assessed for TB disease or M. tuberculosis infection. TB preventive therapy should be instituted if the infant is clinically well but exposed to TB, while prompt initiation of TB treatment is essential if TB disease is presumed. HIV status of mother and infant should be considered as this will affect the management. Further research is needed for the diagnosis and prevention of TB during pregnancy, an early diagnosis of TB in infants, and antituberculosis drug pharmacokinetics in young infants.
Host ecology drives frog skin microbiome diversity across ecotone in South-Central North America
Authors: Smith Sierra N. , Watters Jessa L. , Siler Cameron D.
Published: November 2023

Anurans (frogs and toads) are an ecologically diverse group of vertebrate organisms that display a myriad of reproductive modes and life history traits. To persist in such an expansive array of habitats, these organisms have evolved specialized skin that is used for respiration while also protecting against moisture loss, pathogens, and environmental contaminants. Anuran skin is also colonized by communities of symbiotic microorganisms, and these skin microbiota serve critical roles in numerous processes associated with anuran host health and persistence such as pathogen resistance and immunity. However, gaps remain in our understanding of the environmental and evolutionary processes that shape frog skin microbial communities. Here, we combined existing anuran disease data with 16S rRNA skin microbial inventories to elucidate the roles that geographic location, host evolutionary history, host ecology, and pathogen presence play in the microbial community assemblage of five co-distributed frog host species in Oklahoma. These focal species possess distinct ecological preferences: aquatic, semi-aquatic, and arboreal, and our results indicate that host ecology is the primary driver of frog skin microbial community structure. Additionally, compositional differences were observed among select host species based on geographic location, but this was not consistent among all five frog species. We did not find evidence of phylogenetic signal among our samples and results from the Classification and Regression Tree Analysis revealed that the presence of the amphibian pathogenBatrachochytrium dendrobatidisand the severity of infection were not drivers of skin microbiome differences among our focal host species. Results from this comparative study contribute to our growing understanding of the environmental and host-associated drivers of skin microbial community assemblage and represents one of the first studies on landscape-level variation in skin microbial communities among North American frogs.
Do robots outperform humans in human-centered domains?
Authors: Riener Robert , Rabezzana Luca , Zimmermann Yves
Published: November 2023

The incessant progress of robotic technology and rationalization of human manpower induces high expectations in society, but also resentment and even fear. In this paper, we present a quantitative normalized comparison of performance, to shine a light onto the pressing question, “How close is the current state of humanoid robotics to outperforming humans in their typical functions (e.g., locomotion, manipulation), and their underlying structures (e.g., actuators/muscles) in human-centered domains?” This is the most comprehensive comparison of the literature so far. Most state-of-the-art robotic structures required for visual, tactile, or vestibular perception outperform human structures at the cost of slightly higher mass and volume. Electromagnetic and fluidic actuation outperform human muscles w.r.t. speed, endurance, force density, and power density, excluding components for energy storage and conversion. Artificial joints and links can compete with the human skeleton. In contrast, the comparison of locomotion functions shows that robots are trailing behind in energy efficiency, operational time, and transportation costs. Robots are capable of obstacle negotiation, object manipulation, swimming, playing soccer, or vehicle operation. Despite the impressive advances of humanoid robots in the last two decades, current robots are not yet reaching the dexterity and versatility to cope with more complex manipulation and locomotion tasks (e.g., in confined spaces). We conclude that state-of-the-art humanoid robotics is far from matching the dexterity and versatility of human beings. Despite the outperforming technical structures, robot functions are inferior to human ones, even with tethered robots that could place heavy auxiliary components off-board. The persistent advances in robotics let us anticipate the diminishing of the gap.