bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Diversity and Selective Signature in Dabieshan Cattle Revealed by Whole-Genome Resequencing
Authors: Guan Xiwen , Zhao Shuanping , Xiang Weixuan , Jin Hai , Chen Ningbo , Lei Chuzhao , Jia Yutang , Xu Lei
Published: September 2022

Dabieshan cattle are a typical breed of southern Chinese cattle that have the characteristics of muscularity, excellent meat quality and tolerance to temperature and humidity. Based on 148 whole-genome data, our analysis disclosed the ancestry components of Dabieshan cattle with Chinese indicine (0.857) and East Asian taurine (0.139). The Dabieshan genome demonstrated a higher genomic diversity compared with the other eight populations, supported by the observed nucleotide diversity, linkage disequilibrium decay and runs of homozygosity. The candidate genes were detected by a selective sweep, which might relate to the fertility (GPX5, GPX6), feed efficiency (SLC2A5), immune response (IGLL1, BOLA-DQA2, BOLA-DQB), heat resistance (DnaJC1, DnaJC13, HSPA4), fat deposition (MLLT10) and the coat color (ASIP). We also identified the “East Asian taurine-like” segments in Dabieshan cattle, which might contribute to meat quality traits. The results revealed by the unique and valuable genomic data can build a foundation for the genetic improvement and conservation of genetic resources for indigenous cattle breeds.
Trophism and Homeostasis of Liver Sinusoidal Endothelial Graft Cells during Preservation, with and without Hypothermic Oxygenated Perfusion
Authors: Vasuri Francesco , Germinario Giuliana , Ciavarella Carmen , Carroli Michele , Motta Ilenia , Valente Sabrina , Cescon Matteo , D’Errico Antonia , Pasquinelli Gianandrea , Ravaioli Matteo
Published: September 2022

The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in liver grafts. Special attention was paid to grafts that underwent hypothermic oxygenated perfusion (HOPE). Forty-seven donors were prospectively enrolled, and two distinct biopsies were performed in each case: one allocation biopsy (at the stage of organ allocation) and one post-perfusion biopsy, performed after graft implant in the recipients. In all biopsies, immunohistochemistry and RT-PCR analyses were carried out for the endothelial markers CD34, ERG, Nestin, and VEGFR-2. We observed an increase in CD34 immunoreactivity in LSEC during the whole preservation/perfusion period (p < 0.001). Nestin and ERG expression was low in allocation biopsies, but increased in post-perfusion biopsies, in both immunohistochemistry and RT-PCR (p < 0.001). An inverse correlation was observed between ERG positivity and donor age. Our results indicate that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this machine perfusion technique in restoring endothelial functions.
Elevated CO2 and Water Stress in Combination in Plants: Brothers in Arms or Partners in Crime?
Authors: Shanker Arun Kumar , Gunnapaneni Deepika , Bhanu Divya , Vanaja Maddi , Lakshmi Narayana Jyothi , Yadav Sushil Kumar , Prabhakar Mathyam , Singh Vinod Kumar
Published: September 2022

The changing dynamics in the climate are the primary and important determinants of agriculture productivity. The effects of this changing climate on overall productivity in agriculture can be understood when we study the effects of individual components contributing to the changing climate on plants and crops. Elevated CO2 (eCO2) and drought due to high variability in rainfall is one of the important manifestations of the changing climate. There is a considerable amount of literature that addresses climate effects on plant systems from molecules to ecosystems. Of particular interest is the effect of increased CO2 on plants in relation to drought and water stress. As it is known that one of the consistent effects of increased CO2 in the atmosphere is increased photosynthesis, especially in C3 plants, it will be interesting to know the effect of drought in relation to elevated CO2. The potential of elevated CO2 ameliorating the effects of water deficit stress is evident from literature, which suggests that these two agents are brothers in arms protecting the plant from stress rather than partners in crime, specifically for water deficit when in isolation. The possible mechanisms by which this occurs will be discussed in this minireview. Interpreting the effects of short-term and long-term exposure of plants to elevated CO2 in the context of ameliorating the negative impacts of drought will show us the possible ways by which there can be effective adaption to crops in the changing climate scenario.
Where Electrostatics Matter: Bacterial Surface Neutralization and Membrane Disruption by Antimicrobial Peptides SAAP-148 and OP-145
Authors: Vejzovic Djenana , Piller Paulina , Cordfunke Robert A. , Drijfhout Jan W. , Eisenberg Tobias , Lohner Karl , Malanovic Nermina
Published: September 2022

The need for alternative treatment of multi-drug-resistant bacteria led to the increased design of antimicrobial peptides (AMPs). AMPs exhibit a broad antimicrobial spectrum without a distinct preference for a specific species. Thus, their mechanism, disruption of fundamental barrier function by permeabilization of the bacterial cytoplasmic membrane is considered to be rather general and less likely related to antimicrobial resistance. Of all physico-chemical properties of AMPs, their positive charge seems to be crucial for their interaction with negatively charged bacterial membranes. Therefore, we elucidate the role of electrostatic interaction on bacterial surface neutralization and on membrane disruption potential of two potent antimicrobial peptides, namely, OP-145 and SAAP-148. Experiments were performed on Escherichia coli, a Gram-negative bacterium, and Enterococcus hirae, a Gram-positive bacterium, as well as on their model membranes. Zeta potential measurements demonstrated that both peptides neutralized the surface charge of E. coli immediately after their exposure, but not of E. hirae. Second, peptides neutralized all model membranes, but failed to efficiently disrupt model membranes mimicking Gram-negative bacteria. This was further confirmed by flow cytometry showing reduced membrane permeability for SAAP-148 and the lack of OP-145 to permeabilize the E. coli membrane. As neutralization of E. coli surface charges was achieved before the cells were killed, we conclude that electrostatic forces are more important for actions on the surface of Gram-negative bacteria than on their cytoplasmic membranes.
The Allopregnanolone Response to Acute Stress in Females: Preclinical and Clinical Studies
Authors: Pisu Maria Giuseppina , Concas Luca , Siddi Carlotta , Serra Mariangela , Porcu Patrizia
Published: September 2022

The neuroactive steroid allopregnanolone ((3α,5α)-3-hydroxypregnan-20-one or 3α,5α-THP) plays a key role in the response to stress, by normalizing hypothalamic-pituitary-adrenal (HPA) axis function to restore homeostasis. Most studies have been conducted on male rats, and little is known about the allopregnanolone response to stress in females, despite that women are more susceptible than men to develop emotional and stress-related disorders. Here, we provide an overview of animal and human studies examining the allopregnanolone responses to acute stress in females in the context of stress-related neuropsychiatric diseases and under the different conditions that characterize the female lifespan associated with the reproductive function. The blunted allopregnanolone response to acute stress, often observed in female rats and women, may represent one of the mechanisms that contribute to the increased vulnerability to stress and affective disorders in women under the different hormonal fluctuations that occur throughout their lifespan. These studies highlight the importance of targeting neuroactive steroids as a therapeutic approach for stress-related disorders in women.
Hepatitis B x (HBx) as a Component of a Functional Cure for Chronic Hepatitis B
Authors: Feitelson Mark A. , Arzumanyan Alla , Spector Ira , Medhat Arvin
Published: September 2022

Patients who are carriers of the hepatitis B virus (HBV) are at high risk of chronic liver disease (CLD) which proceeds from hepatitis, to fibrosis, cirrhosis and to hepatocellular carcinoma (HCC). The hepatitis B-encoded X antigen, HBx, promotes virus gene expression and replication, protects infected hepatocytes from immunological destruction, and promotes the development of CLD and HCC. For virus replication, HBx regulates covalently closed circular (ccc) HBV DNA transcription, while for CLD, HBx triggers cellular oxidative stress, in part, by triggering mitochondrial damage that stimulates innate immunity. Constitutive activation of NF-κB by HBx transcriptionally activates pro-inflammatory genes, resulting in hepatocellular destruction, regeneration, and increased integration of the HBx gene into the host genome. NF-κB is also hepatoprotective, which sustains the survival of infected cells. Multiple therapeutic approaches include direct-acting anti-viral compounds and immune-stimulating drugs, but functional cures were not achieved, in part, because none were yet devised to target HBx. In addition, many patients with cirrhosis or HCC have little or no virus replication, but continue to express HBx from integrated templates, suggesting that HBx contributes to the pathogenesis of CLD. Blocking HBx activity will, therefore, impact multiple aspects of the host–virus relationship that are relevant to achieving a functional cure.
Treatment of Brain Metastases: The Synergy of Radiotherapy and Immune Checkpoint Inhibitors
Authors: Matsui Jennifer K. , Perlow Haley K. , Raj Rohit K. , Nalin Ansel P. , Lehrer Eric J. , Kotecha Rupesh , Trifiletti Daniel M. , McClelland Shearwood , Kendra Kari , Williams Nicole , Owen Dwight H. , Presley Carolyn J. , Thomas Evan M. , Beyer Sasha J. , Blakaj Dukagjin M. , Ahluwalia Manmeet S. , Raval Raju R. , Palmer Joshua D.
Published: September 2022

Brain metastases are a devastating sequela of common primary cancers (e.g., lung, breast, and skin) and have limited effective therapeutic options. Previously, systemic chemotherapy failed to demonstrate significant benefit in patients with brain metastases, but in recent decades, targeted therapies and more recently immune checkpoint inhibitors (ICIs) have yielded promising results in preclinical and clinical studies. Furthermore, there is significant interest in harnessing the immunomodulatory effects of radiotherapy (RT) to synergize with ICIs. Herein, we discuss studies evaluating the impact of RT dose and fractionation on the immune response, early studies supporting the synergistic interaction between RT and ICIs, and ongoing clinical trials assessing the benefit of combination therapy in patients with brain metastases.
Alveolar Nitric Oxide in Chronic Obstructive Pulmonary Disease—A Two-Year Follow-Up
Authors: Högman Marieann , Palm Andreas , Sulku Johanna , Ställberg Björn , Lisspers Karin , Bröms Kristina , Janson Christer , Malinovschi Andrei
Published: September 2022

Chronic obstructive pulmonary disease (COPD) affects the airways and gas exchange areas. Nitric oxide (NO) production from the airways is presented as FENO50 and from the gas exchange areas as alveolar NO (CANO). We aimed to evaluate, over two years, the consistency of the CANO estimations in subjects with COPD. A total of 110 subjects (45 men) who completed the study were included from primary and secondary care settings. CANO was estimated using the two-compartment model. CANO increased slightly during the two-year follow-up (p = 0.01), but FENO50 remained unchanged (p = 0.24). Among the subjects with a low CANO (<1 ppb) at inclusion, only 2% remained at a low level. For those at a high level (>2 ppb), 29% remained so. The modified Medical Research Council dyspnoea scale (mMRC) score increased at least one point in 29% of the subjects, and those subjects also increased in CANO from 0.9 (0.5, 2.1) ppb to 1.8 (1.1, 2.3) ppb, p = 0.015. We conclude that alveolar NO increased slightly over two years, together with a small decline in lung function. The increase in CANO was found especially in those whose levels of dyspnoea increased over time.
Freezing of Gait in Parkinson’s Disease Patients Treated with Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Long-Term Overview
Authors: Di Rauso Giulia , Cavallieri Francesco , Campanini Isabella , Gessani Annalisa , Fioravanti Valentina , Feletti Alberto , Damiano Benedetta , Scaltriti Sara , Bardi Elisa , Corni Maria Giulia , Antonelli Francesca , Rispoli Vittorio , Cavalleri Francesca , Molinari Maria Angela , Contardi Sara , Menozzi Elisa , Puzzolante Annette , Rossi Jessica , Meletti Stefano , Biagini Giuseppe , Pavesi Giacomo , Fraix Valerie , Lusuardi Mirco , Fraternali Alessandro , Versari Annibale , Budriesi Carla , Moro Elena , Merlo Andrea , Valzania Franco
Published: September 2022

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (≥5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twenty STN-DBS treated PD patients were included. Each patient was assessed before surgery through a detailed neurological evaluation, including FOG score, and revaluated in the long-term (median follow-up: 5-years) in different stimulation and drug conditions. In the long term follow-up, FOG score significantly worsened in the off-stimulation/off-medication condition compared with the pre-operative off-medication assessment (z = −1.930; p = 0.05) but not in the on-stimulation/off-medication (z = −0.357; p = 0.721). There was also a significant improvement of FOG at long-term assessment by comparing on-stimulation/off-medication and off-stimulation/off-medication conditions (z = −2.944; p = 0.003). These results highlight the possible beneficial long-term effects of STN-DBS on FOG.
Chagas Disease Megaesophagus Patients Carrying Variant MRPS18B P260A Display Nitro-Oxidative Stress and Mitochondrial Dysfunction in Response to IFN-γ Stimulus
Authors: Silva Karla Deysiree Alcântara , Nunes João Paulo Silva , Andrieux Pauline , Brochet Pauline , Almeida Rafael Ribeiro , Kuramoto Takara Andréia Cristina Kazue , Pereira Natalia Bueno , Abel Laurent , Cobat Aurelie , Zaniratto Ricardo Costa Fernandes , Levy Débora , Bydlowski Sergio Paulo , Cecconello Ivan , Seguro Francisco Carlos Bernal da Costa , Kalil Jorge , Chevillard Christophe , Cunha-Neto Edecio
Published: September 2022

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, affects 8 million people, and around 1/3 develop chronic cardiac (CCC) or digestive disease (megaesophagus/megacolon), while the majority remain asymptomatic, in the indeterminate form of Chagas disease (ASY). Most CCC cases in families with multiple Chagas disease patients carry damaging mutations in mitochondrial genes. We searched for exonic mutations associated to chagasic megaesophagus (CME) in genes essential to mitochondrial processes. We performed whole exome sequencing of 13 CME and 45 ASY patients. We found the damaging variant MRPS18B 688C > G P230A, in five out of the 13 CME patients (one of them being homozygous; 38.4%), while the variant appeared in one out of 45 ASY patients (2.2%). We analyzed the interferon (IFN)-γ-induced nitro-oxidative stress and mitochondrial function of EBV-transformed lymphoblastoid cell lines. We found the CME carriers of the mutation displayed increased levels of nitrite and nitrated proteins; in addition, the homozygous (G/G) CME patient also showed increased mitochondrial superoxide and reduced levels of ATP production. The results suggest that pathogenic mitochondrial mutations may contribute to cytokine-induced nitro-oxidative stress and mitochondrial dysfunction. We hypothesize that, in mutation carriers, IFN-γ produced in the esophageal myenteric plexus might cause nitro-oxidative stress and mitochondrial dysfunction in neurons, contributing to megaesophagus.
Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer
Authors: Deshet-Unger Naamit , Horn Galit , Rawet-Slobodkin Moran , Waks Tova , Laskov Ido , Michaan Nadav , Raz Yael , Bar Vered , Zundelevich Adi , Aharon Sara , Turovsky Lubov , Mallel Giuseppe , Salpeter Seth , Neev Guy , Hollander Kenneth Samuel , Katz Ben-Zion , Grisaru Dan , Globerson Levin Anat
Published: September 2022

High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial ovarian cancer. The majority of cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over the past decades, survival rates with HGSOC have only modestly improved. Chimeric antigen receptor (CAR)-T cells enable T cells to directly bind to tumor-associated antigens in a major histocompatibility complex-independent manner, thereby inducing tumor rejection. While CAR-T cell therapy shows great promise in hematological malignancies, its use in solid tumors is limited. Therefore, innovative approaches are needed to increase the specificity of CAR-modified T cells against solid tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal (IP) versus intravenous (IV) CAR-T cell therapy in the treatment of HGSOC. We constructed a CAR that targets the ErbB2/HER2 protein (ErbB2CAR), which is overexpressed in HGSOC, and evaluated the functionality of ErbB2CAR on ovarian cancer cell lines (OVCAR8, SKOV3, and NAR). Our findings show that an IP injection of ErbB2CAR-T cells to tumor-bearing mice led to disease remission and increased survival compared to the IV route. Moreover, we found that IP-injected ErbB2CART cells circulate to a lesser extent, making them safer for non-tumor tissues than IV-injected cells. Further supporting our findings, we show that the effect of ErbB2CAR-T cells on primary HGSOC tumors is correlated with ErbB2 expression. Together, these data demonstrate the advantages of an IP administration of CAR-T cells over IV administration, offering not only a safer strategy but also the potential for counteracting the effect of ErbB2CAR in HGSOC. Significance: IP-injected ErbB2CAR-T cells led to disease remission and increased survival compared to the IV route. These findings demonstrate the advantages of IP administration, offering a safe treatment strategy with the potential for counteracting the effect of ErbB2CAR in HGSOC.
An Update on In Vitro Folliculogenesis: A New Technique for Post-Cancer Fertility
Authors: Labrune Elsa , Salle Bruno , Lornage Jacqueline
Published: September 2022

Introduction: Obtaining in vitro mature oocytes from ovarian tissue to preserve women’s fertility is still a challenge. At present, there is a therapeutic deadlock for girls and women who need emergency fertility preservation in case of a high risk of ovary invasion by malignant cells. In such a case, ovarian tissue cannot be engrafted; an alternative could be in vitro folliculogenesis. Methods: This review focuses on the progress of in vitro folliculogenesis in humans. PubMed and Embase databases were used to search for original English-language articles. Results: The first phase of in vitro folliculogenesis is carried out in the original ovarian tissue. The addition of one (or more) initiation activator(s) is not essential but allows better yields and the use of a 3D culture system at this stage provides no added value. The second stage requires a mechanical and/or enzymatic isolation of the secondary follicles. The use of an activator and/or a 3D culture system is then necessary. Conclusion: The current results are promising but there is still a long way to go. Obtaining live births in large animals is an essential step in validating this in vitro folliculogenesis technique.
DNA Methylation Profiling in Rare Sellar Tumors
Authors: Wright Kyla , Galbraith Kristyn , Snuderl Matija , Agrawal Nidhi
Published: September 2022

The histologic diagnosis of sellar masses can be challenging, particularly in rare neoplasms and tumors without definitive biomarkers. Moreover, there is significant inter-observer variability in the histopathological diagnosis of many tumors of the CNS, and some rare tumors risk being misclassified. DNA methylation has recently emerged as a useful diagnostic tool. To illustrate the clinical utility of machine-learning-based DNA methylation classifiers, we report a rare case of primary sellar esthesioneuroblastoma histologically mimicking a non-functioning pituitary adenoma. The patient had multiple recurrences, and the resected specimens had unusual histopathology. A portion of the resected sellar lesion was profiled using clinically validated whole-genome DNA methylation and classification. DNA was extracted from the tissue, hybridized on DNA methylation chips, and analyzed using a clinically validated classifier. DNA methylation profiling of the lesion showed that the tumor classified best with the esthesioneuroblastoma reference cohort. This case highlights the difficulty in diagnosing atypical sellar lesions by standard histopathological methods. However, when phenotypic analyses were nonconclusive, DNA methylation profiling resulted in a change in diagnosis. We discuss the growing role of DNA methylation profiling in the classification and diagnosis of CNS tumors, finding that utilization of DNA methylation studies in cases of atypical presentation or diagnostic uncertainty may improve diagnostic accuracy with therapeutic and prognostic implications.
Adipose Tissue Development Relies on Coordinated Extracellular Matrix Remodeling, Angiogenesis, and Adipogenesis
Authors: Johnston Elizabeth K. , Abbott Rosalyn D.
Published: September 2022

Despite developing prenatally, the adipose tissue is unique in its ability to undergo drastic growth even after reaching its mature size. This development and subsequent maintenance rely on the proper coordination between the vascular niche and the adipose compartment. In this review, the process of adipose tissue development is broken down to explain (1) the ultrastructural matrix remodeling that is undertaken during simultaneous adipogenesis and angiogenesis, (2) the paracrine crosstalk involved during adipose development, (3) the mechanical regulators involved in adipose growth, and (4) the proteolytic and paracrine oversight for matrix remodeling during adipose development. It is crucial to gain a better understanding of the complex relationships that exist between adipose tissue and the vasculature during tissue development to provide insights into the pathological tissue expansion of obesity and to develop improved soft-tissue reconstruction techniques.
Multimodular Bio-Inspired Organized Structures Guiding Long-Distance Axonal Regeneration
Authors: Doblado Laura Rodríguez , Martínez-Ramos Cristina , Pradas Manuel Monleón
Published: September 2022

Axonal bundles or axonal tracts have an aligned and unidirectional architecture present in many neural structures with different lengths. When peripheral nerve injury (PNI), spinal cord injury (SCI), traumatic brain injury (TBI), or neurodegenerative disease occur, the intricate architecture undergoes alterations leading to growth inhibition and loss of guidance through large distance. In order to overcome the limitations of long-distance axonal regeneration, here we combine a poly-L-lactide acid (PLA) fiber bundle in the common lumen of a sequence of hyaluronic acid (HA) conduits or modules and pre-cultured Schwann cells (SC) as cells supportive of axon extension. This multimodular preseeded conduit is then used to induce axon growth from a dorsal root ganglion (DRG) explant placed at one of its ends and left for 21 days to follow axon outgrowth. The multimodular conduit proved effective in promoting directed axon growth, and the results may thus be of interest for the regeneration of long tissue defects in the nervous system. Furthermore, the hybrid structure grown within the HA modules consisting in the PLA fibers and the SC can be extracted from the conduit and cultured independently. This “neural cord” proved to be viable outside its scaffold and opens the door to the generation of ex vivo living nerve in vitro for transplantation.
The Anti-Aggregative Peptide KLVFF Mimics Aβ1-40 in the Modulation of Nicotinic Receptors: Implications for Peptide-Based Therapy
Authors: Trebesova Hanna , Olivero Guendalina , Marchi Mario , Grilli Massimo
Published: September 2022

In recent years, the inhibition of beta-amyloid (Aβ) aggregation has emerged as a potential strategy for Alzheimer’s disease. KLVFF, a small peptide corresponding to the aminoacidic sequence 16-20 of Aβ, reduces Aβ fibrillation dose dependently. Therefore, the toxic and functional characterization of its brain activity is fundamental for clarifying its potential therapeutic role. Accordingly, we studied the modulatory role of KLVFF on the cholinergic receptors regulating dopamine and noradrenaline release in rat synaptosomes. Nicotinic receptors on dopaminergic nerve terminals in the nucleus acccumbens are inhibited by KLVFF, which closely resembles full-length Aβ1-40. Moreover, KLVFF entrapped in synaptosomes does not modify the nicotinic receptor’s function, suggesting that external binding to the receptor is required for its activity. The cholinergic agent desformylflustrabromine counteracts the KLVFF effect. Remarkably, muscarinic receptors on dopaminergic terminals and nicotinic receptors regulating noradrenaline release in the hippocampus are completely insensitive to KLVFF. Based on our findings, KLVFF mimics Aβ1-40 as a negative modulator of specific nicotinic receptor subtypes affecting dopamine transmission in the rat brain. Therefore, new pharmacological strategies using the anti-aggregative properties of KLVFF need to be evaluated for potential interference with nicotinic receptor-mediated transmission.
Role of Paper-Based Sensors in Fight against Cancer for the Developing World
Authors: Dukle Amey , Nathanael Arputharaj Joseph , Panchapakesan Balaji , Oh Tae-Hwan
Published: September 2022

Cancer is one of the major killers across the globe. According to the WHO, more than 10 million people succumbed to cancer in the year 2020 alone. The early detection of cancer is key to reducing the mortality rate. In low- and medium-income countries, the screening facilities are limited due to a scarcity of resources and equipment. Paper-based microfluidics provide a platform for a low-cost, biodegradable micro-total analysis system (µTAS) that can be used for the detection of critical biomarkers for cancer screening. This work aims to review and provide a perspective on various available paper-based methods for cancer screening. The work includes an overview of paper-based sensors, the analytes that can be detected and the detection, and readout methods used.
The Influence of Emotion Regulation on Estimation Strategy Execution in Individuals with Trait Anxiety
Authors: Song Huan , Tan Chenghui , Zhu Chuanlin , Liu Dianzhi , Peng Wenbo
Published: September 2022

Previous studies have shown that some negative emotions hinder estimation strategy execution. However, these studies rarely investigate the influence of negative emotions on the estimation strategy execution in individuals with trait anxiety. The present study examines the relationship between negative emotions and trait anxiety in individuals’ estimation strategy execution. Moreover, it looks into the influence of different emotion regulation strategies on their estimation strategy execution. In October 2010, 803 college students were evaluated using the Trait Anxiety Scale. From these participants, individuals with high and low trait anxiety were selected to complete the double-digit multiplication estimation task. The results showed that the estimation strategy’s execution speed in individuals with high trait anxiety was slower than those with low trait anxiety under negative emotions (t (113) = −2.269, p = 0.025, d = 0.427). Both expression inhibition and cognitive reappraisal could significantly improve the execution speed of the estimation strategy in low trait anxiety (p < 0.001). For individuals with high trait anxiety, cognitive reappraisal regulating negative emotions can promote the estimation strategy’s execution speed (p = 0.031). However, the use of expression inhibition has no significant effect on estimation strategy execution (p = 0.101). In summary, the present study revealed that different emotion regulation strategies moderated the arithmetic strategy execution of individuals with trait anxiety, and cognitive reappraisal had a better effect in individuals with high trait anxiety.
Eye Movement Control in Tibetan Reading: The Roles of Word Length and Frequency
Authors: Li Xiao-Wei , Li Shan , Gao Lei , Niu Zi-Bei , Wang Dan-Hui , Zeng Man , Li Tian-Zhi , Bai Xue-Jun , Gao Xiao-Lei
Published: September 2022

We investigated the effects of word length and frequency on eye movement control during Tibetan reading through two experiments. A preliminary experiment examined the predictive effect of word length and frequency on fixation duration and landing position using multiple linear regression analysis. In the formal experiment, we manipulated the length and frequency of target words simultaneously to investigate the effects of word length and frequency on fixation duration and landing position in Tibetan reading. In this study, we found that: (1) there were significant word-length and word-frequency effects affecting all lexical processing in Tibetan reading; (2) there are preferred viewing locations in Tibetan reading; specifically, for short words, it is the end, whereas for long words, it spans from the center to the beginning of the word; (3) word frequency does not affect preferred viewing location in Tibetan reading; (4) the preferred viewing position and the interaction of word length and viewing position found in this study supported the “strategy-tactics” approach.
Corpus Callosum Microstructural Tract Integrity Relates to Longer Emotion Recognition Reaction Time in People with Schizophrenia
Authors: Burke Tom , Gleeson Christina , Holleran Laurena , Mothersill David , Holland Jessica , Costello Laura , Kane Ruán , McKernan Declan P. , Morris Derek W. , Kelly John P. , Corvin Aiden P. , Hallahan Brian P. , McDonald Colm , Donohoe Gary
Published: September 2022

Objective: Schizophrenia is a complex functionally debilitating neurodevelopmental disorder, with associated social cognitive impairment. Corpus Callosum (CC) white matter tracts deficits are reported for people with schizophrenia; however, few studies focus on interhemispheric processing relative to social cognition tasks. This study aimed to determine if a relationship between the CC and social cognition exists. Method: In this cross-section study, a sample of n = 178 typical controls and n = 58 people with schizophrenia completed measures of mentalising (Reading the Mind in the Eyes), emotion recognition outcome and reaction time (Emotion Recognition Test), and clinical symptoms (Positive and Negative Symptom Scale), alongside diffusion-based tract imaging. The CC and its subregions, i.e., the genu, body, and splenium were the regions of interest (ROI). Results: Reduced white matter tract integrity was observed in the CC for patients when compared to controls. Patients performed slower, and less accurately on emotion recognition tasks, which significantly and negatively correlated to the structural integrity of the CC genu. Tract integrity further significantly and negatively related to clinical symptomatology. Conclusions: People with schizophrenia have altered white matter integrity in the genu of the CC, compared to controls, which relates to cognitive deficits associated with recognising emotional stimuli accurately and quickly, and severity of clinical symptoms.
Does Non-Immersive Virtual Reality Improve Attention Processes in Severe Traumatic Brain Injury? Encouraging Data from a Pilot Study
Authors: De Luca Rosaria , Bonanno Mirjam , Rifici Carmela , Pollicino Patrizia , Caminiti Angelo , Morone Giovanni , Calabrò Rocco Salvatore
Published: September 2022

Traumatic brain injury (TBI) is a sudden injury that causes damage to the brain. Rehabilitation therapies include specific training, such as attention process training (APT) programs using either standard or innovative approaches. The aim of this study is to evaluate the effects of a non-immersive virtual reality-based attention training to stimulate attention processes and mood in TBI patients. Thirty subjects with TBI were enrolled at the Neurorehabilitation Unit of the IRCCS Neurolesi Center and divided into either the Conventional Attention Process Training Group (C_APT: n = 15) or the Virtual-Based Attention Processes Training Group (VB_APT: n = 15), treated with the Virtual Reality Rehabilitation System (VRRS-Evo). All of the patients were evaluated with a specific psychometric battery before (T0) and after the end (T1) of each program. We found statistically significant differences between the two groups, in particular concerning global cognitive status (p < 0.02), attention processes (p < 0.03), depression symptoms (p < 0.04) and visual attention (p < 0.01). Experimental intragroup analysis showed great statistical significances in all psychometric tests, i.e., the Montreal Cognitive Assessment (p < 0.0006), Attention Matrices (p < 0.0007), the Hamilton Rating Scale-Depression (p < 0.004), the Trail Making Test-A (p < 0.0007), the Trail Making Test-B (p < 0.0007), and the Trail Making test-BA (p < 0.007). Our results suggest that non-immersive virtual reality may be a useful and effective approach for the attention processes recovery and mood of TBI patients, leading to better cognitive and behavioral outcomes.
Finite Element Analysis of Precast Concrete Deck-Steel Beam-Connection Concrete (PCSC) Connectors Using Ultra-High Performance Concrete (UHPC) for the Composite Beam
Authors: Guo Jincen , Zhou Zhixiang , Zou Yang , Zhang Zhongya , Jiang Jinlong
Published: September 2022

A precast concrete deck-steel beam-connection concrete (PCSC) connector using ultra-high-performance concrete (UHPC) as post-cast concrete has been proposed to enable rapid on-site construction of assembled composite bridges. This paper aims to optimize the structure of PCSC connectors using the finite element (FE) model to maximize material utilization and economic efficiency. A refined FE model comprising the bond degradation at the steel–UHPC interface was developed based on the push-out experimental results of PCSC connectors. The shear mechanism of the PCSC connectors was analyzed. Subsequently, parametric analyses were performed to investigate the effects of stud diameter, height, spacing, and concrete strength on the mechanical properties of PCSC connectors. The results indicate that the bond at the steel–connection concrete interface positively affects the shear bearing capacity and stiffness of the PCSC connectors. When UHPC was used as connection concrete, it improved the bearing capacity by about 20% and the shear stiffness of the stud by about 16% compared with normal concrete, but the ductility was 38% lower. It was also found that increasing the compressive strength of the connection concrete increased the shear strength of specimens. However, when the compressive strength of UHPC exceeded 130 MPa, the additional UHPC strength did not significantly enhance the shear performance of specimens. In order to ensure the effective restraint of the connection concrete to studs, it is recommended that the minimum width and height of the connection concrete (UHPC) be determined based on the minimum horizontal spacing and height of the studs. Specifically, the length-to-diameter ratio of studs is greater than or equal to 3.18, the horizontal spacing of studs can be at least 2.82 d, and the clear distance between the outer stud shank and the edge of the UHPC cannot be less than 30 mm. The results are expected to provide a reference for the engineering design of PCSC connectors and a reference for conventional stud connectors with UHPC.
Circulating Cell-Free DNA in Renal Cell Carcinoma: The New Era of Precision Medicine
Authors: Francini Edoardo , Fanelli Giuseppe Nicolò , Pederzoli Filippo , Spisak Sandor , Minonne Erika , Raffo Massimiliano , Pakula Hubert , Tisza Viktoria , Scatena Cristian , Naccarato Antonio Giuseppe , Loda Massimo , Nuzzo Pier Vitale
Published: September 2022

Tumor biopsy is still the gold standard for diagnosing and prognosis renal cell carcinoma (RCC). However, its invasiveness, costs, and inability to accurately picture tumor heterogeneity represent major limitations to this procedure. Analysis of circulating cell-free DNA (cfDNA) is a non-invasive cost-effective technique that has the potential to ease cancer detection and prognosis. In particular, a growing body of evidence suggests that cfDNA could be a complementary tool to identify and prognosticate RCC while providing contemporary mutational profiling of the tumor. Further, recent research highlighted the role of cfDNA methylation profiling as a novel method for cancer detection and tissue-origin identification. This review synthesizes current knowledge on the diagnostic, prognostic, and predictive applications of cfDNA in RCC, with a specific focus on the potential role of cell-free methylated DNA (cfMeDNA).
Benefits from Adjuvant Chemotherapy in Patients with Resected Non-Small Cell Lung Cancer: Possibility of Stratification by Gene Amplification of ACTN4 According to Evaluation of Metastatic Ability
Authors: Tozuka Takehiro , Noro Rintaro , Seike Masahiro , Honda Kazufumi
Published: September 2022

Surgical treatment is the best curative treatment option for patients with non-small cell lung cancer (NSCLC), but some patients have recurrence beyond the surgical margin even after receiving curative surgery. Therefore, therapies with anti-cancer agents also play an important role perioperatively. In this paper, we review the current status of adjuvant chemotherapy in NSCLC and describe promising perioperative therapies, including molecularly targeted therapies and immune checkpoint inhibitors. Previously reported biomarkers of adjuvant chemotherapy for NSCLC are discussed along with their limitations. Adjuvant chemotherapy after resective surgery was most effective in patients with metastatic lesions located just outside the surgical margin; in addition, these metastatic lesions were the most sensitive to adjuvant chemotherapy. Thus, the first step in predicting patients who have sensitivity to adjuvant therapies is to perform a qualified evaluation of metastatic ability using markers such as actinin-4 (ACTN4). In this review, we discuss the potential use of biomarkers in patient stratification for effective adjuvant chemotherapy and, in particular, the use of ACTN4 as a possible biomarker for NSCLC.
Assessment of a Large-Scale Unbiased Malignant Pleural Effusion Proteomics Study of a Real-Life Cohort
Authors: Zahedi Sara , Carvalho Ana Sofia , Ejtehadifar Mostafa , Beck Hans C. , Rei Nádia , Luis Ana , Borralho Paula , Bugalho António , Matthiesen Rune
Published: September 2022

Background: Pleural effusion (PE) is common in advanced-stage lung cancer patients and is related to poor prognosis. Identification of cancer cells is the standard method for the diagnosis of a malignant PE (MPE). However, it only has moderate sensitivity. Thus, more sensitive diagnostic tools are urgently needed. Methods: The present study aimed to discover potential protein targets to distinguish malignant pleural effusion (MPE) from other non-malignant pathologies. We have collected PE from 97 patients to explore PE proteomes by applying state-of-the-art liquid chromatography-mass spectrometry (LC-MS) to identify potential biomarkers that correlate with immunohistochemistry assessment of tumor biopsy or with survival data. Functional analyses were performed to elucidate functional differences in PE proteins in malignant and benign samples. Results were integrated into a clinical risk prediction model to identify likely malignant cases. Sensitivity, specificity, and negative predictive value were calculated. Results: In total, 1689 individual proteins were identified by MS-based proteomics analysis of the 97 PE samples, of which 35 were diagnosed as malignant. A comparison between MPE and benign PE (BPE) identified 58 differential regulated proteins after correction of the p-values for multiple testing. Furthermore, functional analysis revealed an up-regulation of matrix intermediate filaments and cellular movement-related proteins. Additionally, gene ontology analysis identified the involvement of metabolic pathways such as glycolysis/gluconeogenesis, pyruvate metabolism and cysteine and methionine metabolism. Conclusion: This study demonstrated a partial least squares regression model with an area under the curve of 98 and an accuracy of 0.92 when evaluated on the holdout test data set. Furthermore, highly significant survival markers were identified (e.g., PSME1 with a log-rank of 1.68 × 10−6).
Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications
Authors: Agnarelli Alessandro , Vella Viviana , Samuels Mark , Papanastasopoulos Panagiotis , Giamas Georgios
Published: September 2022

Gastric cancer has a median survival of 11 months, and this poor prognosis has not improved over the last 30 years. Recent pre-clinical data suggest that there is high tumour-related neoantigen expression in gastric cancer cells, suggesting that a clinical strategy that enhances the host’s immune system against cancer cells may be a successful approach to improve clinical outcomes. Additionally, there has been an increasing amount of translational evidence highlighting the relevance of PD-L1 expression in gastric cancer cells, indicating that PD-1/PD-L1 inhibitors may be useful. Several molecular subgroups of gastric cancer have been identified to respond with excellent outcomes to immunotherapy, including microsatellite instable tumours, tumours bearing a high tumour mutational burden, and tumours related to a chronic EBV infection. In gastric cancer, immunotherapy has produced durable responses in chemo-refractory patients; however, most recently there has been a lot of enthusiasm as several large-scale clinical trials highlight the improved survival noted from the incorporation of immunotherapy in the first line setting for advanced gastric cancer. Our review aims to discuss current pre-clinical and clinical data supporting the innovative role of immunotherapy in gastric cancer.
Dendritic-Cell-Vaccine-Based Immunotherapy for Hepatocellular Carcinoma: Clinical Trials and Recent Preclinical Studies
Authors: Jeng Long-Bin , Liao Li-Ying , Shih Fu-Ying , Teng Chiao-Fang
Published: September 2022

Although many surgical and nonsurgical therapeutic options have been well-established, hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related death worldwide. Therefore, the discovery of novel potential therapeutic strategies is still urgently required for improving survival and prognosis of HCC patients. As the most potent antigen-presenting cells in the human immune system, dendritic cells (DCs) play an important role in activating not only innate but also adaptive immune responses to specifically destroy tumor cells. As a result, DC-based vaccines, which are prepared by different tumor-antigen-pulsing strategies or maturation-stimulating reagents, either alone or in combination with various anticancer therapies and/or immune effector cells, have been developed as a promising personalized cancer immunotherapy. This review provides a comprehensive summary of the evidence from clinical trials evaluating the safety, feasibility, and efficacy of DC-based vaccines in treating HCC patients and highlights the data from recent preclinical studies regarding the development of promising strategies for optimizing the efficacy of DC-vaccine-based immunotherapy for HCC.
Evaluation of ·OH Production Potential of Particulate Matter (PM2.5) Collected on TiO2-Supporting Quartz Filters
Authors: Sohara Koki , Yamauchi Katsuya , Sekine Yoshika
Published: September 2022

Oxidative stress induced by fine particulate matter 2.5 (PM2.5) is a potential cause of adverse health effects owing to the production of reactive oxygen species (ROS). Air filtration is a key technology for preventing exposure to particulate contaminations; however, particulate matter trapped by filters has the potential risk of human contact with condensed PM2.5. Thus, this study aims to reduce the hydroxyl radical (·OH) production potential of PM2.5 collected on such TiO2-supporting quartz filters. The ·OH production potential was evaluated for PM2.5, which was collected in Kanagawa, Japan, using a terephthalate assay coupled with flow injection analysis. Although the PM2.5 levels at the sampling site were not severe, the PM2.5 samples exhibited ·OH production potential, which was mostly attributed to organic aerosols. The effect was verified using a TiO2-supporting quartz filter for the collection and subsequent degradation of PM2.5. The ·OH production potential was significantly reduced from 0.58 ± 0.40 pmol/(min m3) to 0.22 ± 0.13 pmol/(min m3) through ultraviolet irradiation for 24 h. This suggests that the photocatalytic reaction of the TiO2 filter is effective in reducing the ·OH production potential of PM2.5.
Structure-Based Study to Overcome Cross-Reactivity of Novel Androgen Receptor Inhibitors
Authors: Radaeva Mariia , Li Huifang , LeBlanc Eric , Dalal Kush , Ban Fuqiang , Ciesielski Fabrice , Chow Bonny , Morin Helene , Awrey Shannon , Singh Kriti , Rennie Paul S. , Lallous Nada , Cherkasov Artem
Published: September 2022

The mutation-driven transformation of clinical anti-androgen drugs into agonists of the human androgen receptor (AR) represents a major challenge for the treatment of prostate cancer patients. To address this challenge, we have developed a novel class of inhibitors targeting the DNA-binding domain (DBD) of the receptor, which is distanced from the androgen binding site (ABS) targeted by all conventional anti-AR drugs and prone to resistant mutations. While many members of the developed 4-(4-phenylthiazol-2-yl)morpholine series of AR-DBD inhibitors demonstrated the effective suppression of wild-type AR, a few represented by 4-(4-(3-fluoro-2-methoxyphenyl)thiazol-2-yl)morpholine (VPC14368) exhibited a partial agonistic effect toward the mutated T878A form of the receptor, implying their cross-interaction with the AR ABS. To study the molecular basis of the observed cross-reactivity, we co-crystallized the T878A mutated form of the AR ligand binding domain (LBD) with a bound VPC14368 molecule. Computational modelling revealed that helix 12 of AR undergoes a characteristic shift upon VPC14368 binding causing the agonistic behaviour. Based on the obtained structural data we then designed derivatives of VPC14368 to successfully eliminate the cross-reactivity towards the AR ABS, while maintaining significant anti-AR DBD potency.