bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovalbumin-Induced Allergic Inflammation Diminishes Cross-Linked Collagen Structures in an Experimental Rabbit Model of Corneal Cross-Linking
Authors: Zhao Zhongyang , Liang Minghui , He Huan , Wang Xuemei , Zhu Chengfang , Li Lan , Liu Bin , Zong Rongrong , Jin Qifang , Wu Huping , Li Wei , Lin Zhirong
Published: May 2022

Background

Allergic conjunctivitis (AC) is one of the reported potential risk factors of progression in keratoconus patients after corneal cross-linking surgery; however, the causal relationship is still inconclusive. Recent studies have indicated that various inflammatory cytokines play a vital role in the development of primary keratoconus. It is still unclear whether these inflammatory mediators also trigger CXL failures. This study aimed to investigate the impact of AC on the rabbit corneas after trans-epithelial corneal cross-linking (TCXL).

Methods

A total of six rabbits were kept untreated as the normal control (NC) group. A total of 18 rabbits were treated by TCXL and divided into three groups (six in each group), namely, no treatment (TCXL group); induction of AC (TCXL + AC group); and induction of AC plus topical prednisolone acetate (TCXL + AC + PA group), according to additional treatment. AC was induced by topical application of ovalbumin after intraperitoneal pre-sensitization with ovalbumin. Rabbits were evaluated by slit lamp, in vivo laser scanning confocal microscopy, anterior segment optical coherence tomography, and measurement of corneal biomechanics. The cornea specimens were collected for the transmission electron microscope, the collagenase I digestion test, and PCR assay for TNF-α, IL-6, IL-1β, matrix metalloproteinase 9 (MMP-9), lysyl oxidase (LOX), and tissue inhibitor of metalloproteinases 1 (TIMP-1) on the day (D) 28.

Results

On D28, the TNF-α, IL-6, IL-1β, MMP-9, and LOX levels were significantly increased while the TIMP-1 was decreased in the TCXL + AC group when compared with the TCXL and TCXL + AC + PA groups. In vivo confocal microscopy revealed that at a depth of 150–210 μm, a trabecular patterned hyperdense structure surrounded by elongated needle-like processes could be observed in the TCXL and TCXL + AC + PA groups, but hardly seen in the TCXL + AC group. The demarcation lines were indistinct and blurred in the TCXL + AC group. An electron microscope demonstrated less interlacing fibril lamellae and higher interfibrillar spacing in the TCXL + AC group. The stability of corneal biomechanics and resistance to collagenase were decreased in the TCXL + AC group.

Conclusion

The corneal microstructures induced by TCXL and biomechanical stability were diminished in rabbits with AC but could be maintained by topical anti-inflammatory treatment. Our results supported the causal relationship between altered cytokine profiles and corneal microstructure after primary corneal cross-linking.
Peritoneal Protein Loss, Inflammation, and Nutrition: Refuting Myths
Authors: Malho Guedes Anabela , Calças Marques Roberto , Ribeiro Brigitte , Fernandes Mónica T. , Faísca Marília , Silva Ana Paula , Bragança José , Rodrigues Anabela
Published: May 2022

Peritoneal protein loss (PPL) has been correlated with mortality, malnutrition and inflammation. More recently overhydration was brought to the equation. This study aims to review classic and recent factors associated with PPL. Prevalent and incident peritoneal dialysis (PD) patients were included. Dialysate and serum IL-6 was obtained during PET. Hydration and nutritional status were assessed by bio-impedance. Linear regression and Cox regression were performed. The 78 included patients presented median values of PPL 4.8 g/24 h, serum IL-6: 5.1 pg/mL, and IL-6 appearance rate 153.5 pg/min. Mean extracellular water excess (EWexc) was 0.88 ± 0.94 L, and lean body mass index (LBMI) 17.3 ± 2.4 kg/m2. After mean follow-up of 33.9 ± 29.3 months, 12 patients died. Linear univariable analysis showed positive associations between PPL and small solute transport, body composition (LBMI and EWexc), comorbidities and performing CAPD (vs. cycler). PPL correlated positively with dialysate appearance rate of IL-6, but not with serum IL-6. Linear multivariable analysis confirmed positive association between PPL and EWexc (p = 0.012; 95%CI: 4.162–31.854), LBMI (p = 0.008; 95%CI: 1.720–11.219) and performing CAPD (p = 0.023; 95%CI: 4.375–54.190). In survival analysis, no relationship was found between mortality and PPL. Multivariable Cox regression showed Charlson Comorbidity Index (HR: 1.896, 95%CI: 1.235–2.913), overhydration (HR: 10.034, 95%CI: 1.426–70.587) and lower PPL (HR: 0.576, 95%CI: 0.339–0.978) were predictors for mortality. Overhydration, was a strong predictor of PPL, overpowering variables previously reported as determinants of PPL, namely clinical correlates of endothelial dysfunction or local inflammation. PPL were not associated with malnutrition or higher mortality, emphasizing the importance of volume overload control in PD patients.
Catching a Walker in the Act—DNA Partitioning by ParA Family of Proteins
Authors: Mishra Dipika , Srinivasan Ramanujam
Published: May 2022

Partitioning the replicated genetic material is a crucial process in the cell cycle program of any life form. In bacteria, many plasmids utilize cytoskeletal proteins that include ParM and TubZ, the ancestors of the eukaryotic actin and tubulin, respectively, to segregate the plasmids into the daughter cells. Another distinct class of cytoskeletal proteins, known as the Walker A type Cytoskeletal ATPases (WACA), is unique to Bacteria and Archaea. ParA, a WACA family protein, is involved in DNA partitioning and is more widespread. A centromere-like sequence parS, in the DNA is bound by ParB, an adaptor protein with CTPase activity to form the segregation complex. The ParA ATPase, interacts with the segregation complex and partitions the DNA into the daughter cells. Furthermore, the Walker A motif-containing ParA superfamily of proteins is associated with a diverse set of functions ranging from DNA segregation to cell division, cell polarity, chemotaxis cluster assembly, cellulose biosynthesis and carboxysome maintenance. Unifying principles underlying the varied range of cellular roles in which the ParA superfamily of proteins function are outlined. Here, we provide an overview of the recent findings on the structure and function of the ParB adaptor protein and review the current models and mechanisms by which the ParA family of proteins function in the partitioning of the replicated DNA into the newly born daughter cells.
Seed-Borne Erwinia persicina Affects the Growth and Physiology of Alfalfa (Medicago sativa L.)
Authors: Yao Bo , Huang Rong , Zhang Zhenfen , Shi Shangli
Published: May 2022

Seed-borne Erwinia persicina can be transmitted globally via alfalfa (Medicago sativa L.) seed trade, but there is limited information about the impact of this plant-pathogenic bacterium on alfalfa plants. In this study, strain Cp2, isolated from alfalfa seeds, was confirmed by whole-genome sequencing to belong to E. persicina. Subsequently, the effects of Cp2 on alfalfa growth and physiology were evaluated by constructing a rhizosphere infection model. Strain Cp2 had a strong inhibitory effect on the elongation and growth of alfalfa roots, which was very unfavorable to these perennial plants. Furthermore, an increased number of leaf spots and yellowing symptoms were observed in plants of the Cp2 group from day 10 to day 21 and the strain Cp2 was re-isolated from these leaves. Correlation between growth and photosynthetic parameters was analyzed and the significant decreases in fresh weight and root and plant lengths in the Cp2 group were related to the marked reduction of chlorophyll b, carotenoid, transpiration rate, and stomatal conductance of leaves (r > 0.75). In addition, nine physiological indicators of root, stem, and leaf were measured in the plants 21 days after treatment with Cp2. The physiological response of root and leaf to Cp2 treatment was stronger than that of stem. The physiological indicators with the greatest response to Cp2 infection were further explored through principal component analysis, and superoxide dismutase, peroxidase, ascorbate peroxidase, and soluble protein showed the greatest changes in roots, stems, and leaves (P < 0.001). Among tissues, the commonality was the change of soluble protein. Therefore, soluble protein is speculated to be a physiological marker during alfalfa–E. persicina interactions. These findings indicate that once E. persicina spreads from alfalfa seeds to the rhizosphere, it can invade alfalfa roots and cause disease. This study demonstrates that this plant pathogenic bacterium may be a potential threat to new environment when they spread via seed trade and these “dangerous hitchhikers” warrant further attention, especially in the study of bacterial diseases in pasture-based production systems.
Functional and Phenotypic Diversity of Microglia: Implication for Microglia-Based Therapies for Alzheimer’s Disease
Authors: Xu Yi-Jun , Au Ngan Pan Bennett , Ma Chi Him Eddie
Published: May 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and is closely associated with the accumulation of β-amyloid (Aβ) and neurofibrillary tangles (NFTs). Apart from Aβ and NFT pathologies, AD patients also exhibit a widespread microglial activation in various brain regions with elevated production of pro-inflammatory cytokines, a phenomenon known as neuroinflammation. In healthy central nervous system, microglia adopt ramified, “surveying” phenotype with compact cell bodies and elongated processes. In AD, the presence of pathogenic proteins such as extracellular Aβ plaques and hyperphosphorylated tau, induce the transformation of ramified microglia into amoeboid microglia. Ameboid microglia are highly phagocytic immune cells and actively secrete a cascade of pro-inflammatory cytokines and chemokines. However, the phagocytic ability of microglia gradually declines with age, and thus the clearance of pathogenic proteins becomes highly ineffective, leading to the accumulation of Aβ plaques and hyperphosphorylated tau in the aging brain. The accumulation of pathogenic proteins further augments the neuroinflammatory responses and sustains the activation of microglia. The excessive production of pro-inflammatory cytokines induces a massive loss of functional synapses and neurons, further worsening the disease condition of AD. More recently, the identification of a subset of microglia by transcriptomic studies, namely disease-associated microglia (DAM), the progressive transition from homeostatic microglia to DAM is TREM2-dependent and the homeostatic microglia gradually acquire the state of DAM during the disease progression of AD. Recent in-depth transcriptomic analysis identifies ApoE and Trem2 from microglia as the major risk factors for AD pathogenesis. In this review, we summarize current understandings of the functional roles of age-dependent microglial activation and neuroinflammation in the pathogenesis of AD. To this end, the exponential growth in transcriptomic data provides a solid foundation for in silico drug screening and gains further insight into the development of microglia-based therapeutic interventions for AD.
Precise Quantification of Behavioral Individuality From 80 Million Decisions Across 183,000 Flies
Authors: de Bivort Benjamin , Buchanan Sean , Skutt-Kakaria Kyobi , Gajda Erika , Ayroles Julien , O’Leary Chelsea , Reimers Pablo , Akhund-Zade Jamilla , Senft Rebecca , Maloney Ryan , Ho Sandra , Werkhoven Zach , Smith Matthew A.-Y.
Published: May 2022

Individual animals behave differently from each other. This variability is a component of personality and arises even when genetics and environment are held constant. Discovering the biological mechanisms underlying behavioral variability depends on efficiently measuring individual behavioral bias, a requirement that is facilitated by automated, high-throughput experiments. We compiled a large data set of individual locomotor behavior measures, acquired from over 183,000 fruit flies walking in Y-shaped mazes. With this data set we first conducted a “computational ethology natural history” study to quantify the distribution of individual behavioral biases with unprecedented precision and examine correlations between behavioral measures with high power. We discovered a slight, but highly significant, left-bias in spontaneous locomotor decision-making. We then used the data to evaluate standing hypotheses about biological mechanisms affecting behavioral variability, specifically: the neuromodulator serotonin and its precursor transporter, heterogametic sex, and temperature. We found a variety of significant effects associated with each of these mechanisms that were behavior-dependent. This indicates that the relationship between biological mechanisms and behavioral variability may be highly context dependent. Going forward, automation of behavioral experiments will likely be essential in teasing out the complex causality of individuality.
Case Report: Novel Biallelic Variants in the COL18A1 Gene in a Chinese Family With Knobloch Syndrome
Authors: Chong Shuk Ching , Yuen Yuet-Ping , Cao Ye , Fan Sze-Shing , Leung Tak Yeung , Chan Emily K. Y. , Zhu Xian Lun
Published: May 2022

Knobloch syndrome is a rare collagenopathy characterized by severe early onset myopia, retinal detachment, and occipital encephalocele with various additional manifestations due to biallelic changes in the COL18A1 gene. Here we reported a Chinese family with two affected siblings presented with antenatal occipital encephalocele, infantile onset retinal detachment, and pronounced high myopia at early childhood. Quartet whole exome sequencing was performed in this family and identified that both siblings carried novel compound heterozygous variants in the COL18A1 gene (NM_001379500.1): the maternally inherited variant c.1222-1G>A at the consensus acceptor splice site of intron 8, and the paternally inherited frameshift variant c.3931_3932delinsT p.(Gly1311Serfs*25) in the last exon. Both patients had successful surgical treatment for the occipital encephalocele soon after birth. They had normal neurocognitive outcome and good general conditions examined at the age of 7 years old for the elder sister and 4 years old for the younger brother. The younger brother developed infantile onset retinal detachment at 7 months of age while the sister had high myopia without signs of retinal detachment until 7 years old. This report expands the phenotype and genotype spectrum of Knobloch syndrome with antenatal and postnatal findings.
Correlation of Phenotype–Genotype and Protein Structure in RYR1-Related Myopathy
Authors: Chang Xingzhi , Wei Risheng , Wei Cuijie , Liu Jieyu , Qin Lun , Yan Hui , Ma Yinan , Wang Zhaoxia , Xiong Hui
Published: May 2022

Introduction

Next generation sequencing results in an explosive identification of rare variants of RYR1, making the correlation between phenotype and genotype complicated. We analyzed the data of 33 patients with RYR1-related myopathy, attempting to elucidate correlations between phenotype, genotype, and protein structure of RyR1.

Methods

Clinical, histopathologic, and genetic data were evaluated, and variants were mapped to the cryo-EM RyR1 structure. The three-dimensional structure of the variant on RyR1 was analyzed.

Results

The clinical spectrum was highly variable regardless of the mode of inheritance. Recessive variations were associated with more severe feeding problems and respiratory insufficiency in infancy (p < 0.05). Forty pathogenic and likely pathogenic variations were identified, and 14 of them were novel. Missense was the most common variation type regardless of inheritance mode. Arginine (15/45) was the most frequently involved residue. All but one dominant variation clustered in Pore forming and pVSD domains, while recessive variations enriched in Bsol (7/25) and SPRYs (6/25) domains. Analysis of the spatial structure of variants showed that dominant variants may impact RyR1 mainly by breaking down hydrogen or electrovalent bonds (10/21); recessive variants located in different domains may impact the function of RyR1 through different pathways. Variants located in RyR1 coupling sites (PY1&2 and the outermost of Bsol) may cause the most severe clinical manifestation.

Conclusion

Clinical diversity of RYR1-related myopathy was impacted by the inheritance mode, variation type, and variant location. Dominant and recessive variants have different sensitive domains impacting the function of RyR1 through different pathways.
Neural Correlates of Executive Functioning in Anorexia Nervosa and Obsessive–Compulsive Disorder
Authors: Thomas Kai S. , Birch Rosalind E. , Jones Catherine R. G. , Vanderwert Ross E.
Published: May 2022

Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are commonly reported to co-occur and present with overlapping symptomatology. Executive functioning difficulties have been implicated in both mental health conditions. However, studies directly comparing these functions in AN and OCD are extremely limited. This review provides a synthesis of behavioral and neuroimaging research examining executive functioning in AN and OCD to bridge this gap in knowledge. We outline the similarities and differences in behavioral and neuroimaging findings between AN and OCD, focusing on set shifting, working memory, response inhibition, and response monitoring. This review aims to facilitate understanding of transdiagnostic correlates of executive functioning and highlights important considerations for future research. We also discuss the importance of examining both behavioral and neural markers when studying transdiagnostic correlates of executive functions.
Effects of Transcranial Direct Current Stimulation Over the Left Primary Motor Cortex on Verbal Intelligence
Authors: Huang Yifan , Zhang Yinling , Zhang Yizhe , Mai Xiaoqin
Published: May 2022

Previous studies have shown that changes in gray matter density and volume in the left primary motor cortex are significantly associated with changes in individuals’ verbal intelligence quotient (VIQ), but not with their performance intelligence quotient (PIQ). In the present study, we examined the effects of transcranial direct current stimulation (tDCS) over the left primary motor cortex on performance in intelligence tests. We chose four subtests (two each for VIQ and PIQ) of the Wechsler Adult Intelligence Scale-Chinese Revised version and randomized participants into anodal, cathodal, and sham groups. We found that anodal stimulation significantly improved performance in verbal intelligence subtests compared to cathodal and sham stimulation, while performance intelligence subtest scores did not change in any stimulation condition. These findings suggest that the excitation level of the left primary motor cortex has a unique effect on verbal intelligence.
Non-invasive Brain Stimulation for Chronic Pain: State of the Art and Future Directions
Authors: Xiong Huan-Yu , Zheng Jie-Jiao , Wang Xue-Qiang
Published: May 2022

As a technique that can guide brain plasticity, non-invasive brain stimulation (NIBS) has the potential to improve the treatment of chronic pain (CP) because it can interfere with ongoing brain neural activity to regulate specific neural networks related to pain management. Treatments of CP with various forms of NIBS, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), using new parameters of stimulation have achieved encouraging results. Evidence of moderate quality indicates that high-frequency rTMS of the primary motor cortex has a clear effect on neuropathic pain (NP) and fibromyalgia. However, evidence on its effectiveness regarding pain relief in other CP conditions is conflicting. Concerning tDCS, evidence of low quality supports its benefit for CP treatment. However, evidence suggesting that it exerts a small treatment effect on NP and headaches is also conflicting. In this paper, we describe the underlying principles behind these commonly used stimulation techniques; and summarize the results of randomized controlled trials, systematic reviews, and meta-analyses. Future research should focus on a better evaluation of the short-term and long-term effectiveness of all NIBS techniques and whether they decrease healthcare use, as well as on the refinement of selection criteria.
Zolpidem Profoundly Augments Spared Tonic GABAAR Signaling in Dentate Granule Cells Ipsilateral to Controlled Cortical Impact Brain Injury in Mice
Authors: Boychuk Jeffery A. , Butler Corwin R. , Smith Katalin Cs. , Halmos Miklos B. , Smith Bret N.
Published: May 2022

Type A GABA receptors (GABAARs) are pentameric combinations of protein subunits that give rise to tonic (ITonicGABA) and phasic (i.e., synaptic; ISynapticGABA) forms of inhibitory GABAAR signaling in the central nervous system. Remodeling and regulation of GABAAR protein subunits are implicated in a wide variety of healthy and injury-dependent states, including epilepsy. The present study undertook a detailed analysis of GABAAR signaling using whole-cell patch clamp recordings from mouse dentate granule cells (DGCs) in coronal slices containing dorsal hippocampus at 1–2 or 8–13 weeks after a focal, controlled cortical impact (CCI) or sham brain injury. Zolpidem, a benzodiazepine-like positive modulator of GABAARs, was used to test for changes in GABAAR signaling of DGCs due to its selectivity for α1 subunit-containing GABAARs. Electric charge transfer and statistical percent change were analyzed in order to directly compare tonic and phasic GABAAR signaling and to account for zolpidem’s ability to modify multiple parameters of GABAAR kinetics. We observed that baseline ITonicGABA is preserved at both time-points tested in DGCs ipsilateral to injury (Ipsi-DGCs) compared to DGCs contralateral to injury (Contra-DGCs) or after sham injury (Sham-DGCs). Interestingly, application of zolpidem resulted in modulation of ITonicGABA across groups, with Ipsi-DGCs exhibiting the greatest responsiveness to zolpidem. We also report that the combination of CCI and acute application of zolpidem profoundly augments the proportion of GABAAR charge transfer mediated by tonic vs. synaptic currents at both time-points tested, whereas gene expression of GABAAR α1, α2, α3, and γ2 subunits is unchanged at 8–13 weeks post-injury. Overall, this work highlights the shift toward elevated influence of tonic inhibition in Ipsi-DGCs, the impact of zolpidem on all components of inhibitory control of DGCs, and the sustained nature of these changes in inhibitory tone after CCI injury.
Adaptation of Threat Responses Within the Negative Valence Framework
Authors: Smith Nancy J. , Markowitz Sara Y. , Hoffman Ann N. , Fanselow Michael S.
Published: May 2022

External threats are a major source of our experience of negatively valanced emotion. As a threat becomes closer and more real, our specific behavior patterns and our experiences of negative affect change in response to the perceived imminence of threat. Recognizing this, the National Institute of Mental Health’s Research Domain Criteria (RDoC) Negative Valence system is largely based around different levels of threat imminence. This perspective describes the correspondence between the RDoC Negative Valence System and a particular neurobiological/neuroecological model of reactions to threat, the Predatory Imminence Continuum (PIC) Theory. Using the COVID-19 pandemic as an illustration, we describe both adaptive and maladaptive behavior patterns from this perspective to illustrate how behavior in response to a crisis may get shaped. We end with suggestions on how further consideration of the PIC suggests potential modifications of the negative valence systems RDoC.
Conventional and Novel Technologies in the Production of Dairy Bioactive Peptides
Authors: Murtaza Mian Anjum , Irfan Shafeeqa , Hafiz Iram , Ranjha Muhammad Modassar A. N. , Rahaman Abdul , Murtaza Mian Shamas , Ibrahim Salam A. , Siddiqui Shahida Anusha
Published: May 2022

Background

In recent years, researchers have focused on functional ingredients, functional foods, and nutraceuticals due to the rapidly increasing interest in bioactive components, especially in bioactive peptides. Dairy proteins are a rich and balanced source of amino acids and their derived bioactive peptides, which possess biological and physiological properties. In the dairy industry, microbial fermentation and enzymatic hydrolysis are promising methods for producing bioactive peptides because of their rapid efficiency, and mild reaction conditions. However, these methods utilize less raw material, take long reaction time, result in low yields, and low activity products when used alone, which pose industry to seek for novel methods as pretreatments to increase the yield of bioactive peptides.

Scope and Approach

This review emphasizes the production of peptides from the dairy proteins and discusses the potential use of novel technologies as pretreatments to conventional methods of bioactive peptides production from dairy proteins, including the mechanisms of novel technologies along with respective examples of use, advantages, limitations, and challenges to each technology.

Key Findings and Conclusion

Noteworthily, hydrolysis of dairy proteins liberate wide-range of peptides that possess remarkable biological functions to maintain human health. Novel technologies in the dairy industry such as ultrasound-assisted processing (UAP), microwave-assisted processing (MAP), and high pressure processing (HPP) are innovative and environmentally friendly. Generally, novel technologies are less effectual compared to conventional methods, therefore used in combination with fermentation and enzymatic hydrolysis, and are promising pretreatments to modify peptides’ profile, improve the yields, and high liberation of bioactive peptides as compared to conventional technologies. UAP is an innovative and most efficient technology as its mechanical effects and cavitation change the protein conformation, increase the biological activities of enzymes, and enhance enzymatic hydrolysis reaction rate.
Impact of Intermittent Fasting Combined With High-Intensity Interval Training on Body Composition, Metabolic Biomarkers, and Physical Fitness in Women With Obesity
Authors: Batitucci Gabriela , Faria Junior Eli V. , Nogueira Jonatas E. , Brandão Camila F. C. , Abud Gabriela F. , Ortiz Gabriela U. , Marchini Julio S. , Freitas Ellen C.
Published: May 2022

Background

Intermittent fasting (IF) is a dietary approach that is widely popular due to its effects on weight and body fat loss, but it does not appear to ensure muscle mass preservation. Incorporating high-intensity interval training (HIIT) into an individual’s routine could be an attractive and viable therapeutic option for improving body composition, lifestyle and health promotion. Problematizing the emerging situation of fighting obesity, led us to clarify gaps about IF and hypothesize that IF and HIIT in conjunction may protect against muscle mass decline without impairing nitrogen balance (NB), in addition to improving the physical fitness of women with obesity.

Objectives

To evaluate the effects of IF alone and combined with HIIT on body composition, NB and strength and physical fitness in women with obesity.

Methods

Thirty-six women (BMI 34.0 ± 3.2; 32.2 ± 4.4 years) participated and were randomly distributed into three groups: (1) Intermittent fasting combined with exercise group (IF + EX); (2) Exercise group (EX); and (3) Intermittent fasting group (IF). The interventions took place over 8 weeks and all evaluations were performed pre and post-intervention. The HIIT circuit was performed 3x/week, for 25 mins/session, at 70–85% of the maximum heart rate. The intermittent fasting protocol was a 5:2 diet with two meals within 6 h on fasting days, being 25% of total energy intake, plus 18 h of complete fasting. The protocol was performed 2x/week and 5 days of ad libitum ingestion. Resting metabolic rate (RMR) was measured by indirect calorimetry, body composition by BodPod®, NB from urinary nitrogen, food consumption by food records and physical and strength performance were measured by physical tests. ANOVA two-way repeated measures mixed model was performed followed by Sidak post hoc (p < 0.05). This project was registered in ClinicalTrials.gov, NCT05237154.

Results

There were a reduction in body weight (P = 0.012) and BMI (P = 0.031) only in the IF + EX group. There was body fat loss in the IF + EX group (−4%, P < 0.001) and in the EX group (−2.3%, P = 0.043), an increase in fat-free mass in the IF + EX group (+3.3%, P < 0.001) and also in the EX group (+2%, P = 0.043), without differences between groups and the IF group showed no changes. The NB was equilibrium in all groups. All parameters of aerobic capacity and strength improved.

Conclusion

Combining IF with HIIT can promote increments in fat-free mass, NB equilibrium and improve physical fitness and strength.
Three-Dimensional 3D Culture Models in Gynecological and Breast Cancer Research
Authors: Salinas-Vera Yarely M. , Valdés Jesús , Pérez-Navarro Yussel , Mandujano-Lazaro Gilberto , Marchat Laurence A. , Ramos-Payán Rosalio , Nuñez-Olvera Stephanie I. , Pérez-Plascencia Carlos , López-Camarillo César
Published: May 2022

Traditional two-dimensional (2D) monolayer cell cultures have long been the gold standard for cancer biology research. However, their ability to accurately reflect the molecular mechanisms of tumors occurring in vivo is limited. Recent development of three-dimensional (3D) cell culture models facilitate the possibility to better recapitulate several of the biological and molecular characteristics of tumors in vivo, such as cancer cells heterogeneity, cell-extracellular matrix interactions, development of a hypoxic microenvironment, signaling pathway activities depending on contacts with extracellular matrix, differential growth kinetics, more accurate drugs response, and specific gene expression and epigenetic patterns. In this review, we discuss the utilization of different types of 3D culture models including spheroids, organotypic models and patient-derived organoids in gynecologic cancers research, as well as its potential applications in oncological research mainly for screening drugs with major physiological and clinical relevance. Moreover, microRNAs regulation of cancer hallmarks in 3D cell cultures from different types of cancers is discussed.
Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma: A Systemic Review and Meta-Analysis
Authors: Jang Jong Keon , Pyo Junhee , Suh Chong Hyun , Park Hye Sun , Chae Young Kwang , Kim Kyung Won
Published: May 2022

Background

Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma.

Methods

The PubMed, EMBASE, and Cochrane databases were searched to identify articles published before June 30, 2021 describing the use of CAR T-cell therapy in glioblastoma. Information on the toxicity of CAR T-cell therapy was summarized. The pooled objective response rate (ORR) and overall survival (OS) of patients who underwent CAR T-cell therapy were estimated using a random-effects model with an inverse-variance weighting model and quantile estimation method, respectively.

Results

Of 397 articles identified, eight studies including 63 patients with recurrent glioblastoma treated with various CAR T-cell regimens were included in the analysis. Six (9.5%) patients developed cytokine release syndrome (grade ≤2), and 16 (25.4%) experienced non-critical neurological events. The pooled ORR was 5.1% (95% confidence interval [CI], 0.0–10.4; I2 = 0.05%), and the pooled median OS was 8.1 months (95% CI, 6.7–9.5; I2 = 0.00%).

Conclusion

Although CAR T-cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research is necessary for its translation into clinical practice for the treatment of recurrent glioblastoma.
Takotsubo Syndrome (TTS) in Onco-Hematologic Patients: Retrospective Analysis and Focus on the Correlation or Not With Anticancer Drugs. Case Reports and Review of the Literature
Authors: Monti Manlio , Cortesi Pietro , Vespignani Roberto , Bronico Ilaria , Gallio Chiara , Flospergher Michele , Matteucci Laura , Frassineti Giovanni Luca
Published: May 2022

Takotsubo syndrome (TTS) is an uncommon cardiovascular condition also known as stress-induced cardiomyopathy or broken heart disease. The syndrome, characterized by acute non-coronary segmental ventricular dysfunction, commonly occurs as a reaction to severe emotional or physical stress and can cause significant problems. Several classes of chemotherapeutic agents that are known to be cardiotoxic have been shown to be associated with TTS in cancer patients. Describing a case of TTS from chemotherapy and/or monoclonal antibody is important because these drugs are widely used and their temporary or permanent suspension could compromise the success of treatment. The detection and reporting of suspected adverse drug reactions in clinical practice are the foundations of postmarketing surveillance. We performed a retrospective analysis of a large number of patients followed at our cancer centre to identify drugs that could lead to the onset of TTS, focusing our attention on 2 monoclonal antibodies, bevacizumab and rituximab plus chemotherapy. A search was carried out for the word “Takotsubo” in database sources such as in PubMed, in medical oncology, radiology and cardiology electronic clinical records. From October 2007 to March 2021, of the 79,005 patients seen or treated for any kind of malignancy at our institute, 9 had a diagnosis of TTS (4 before and 5 after the diagnosis of malignancy). Only 2 patients had TTS after treatment with the anticancer drugs, bevacizumab and rituximab plus chemotherapy. These two patients were hospitalised, one for subocclusion while the other for pulmonary embolism (PE) with a life threatening condition and in need of intravenous catecholamines. For both patients, an ECG, echocardiography and coronary angiography were performed as well as blood tests with a subsequent diagnosis of TTS and both received cardiological treatment with resolution of the clinical picture. A reassessment of the two cases found that a subocclusion and intravenous catecholamines appeared to be the most likely triggers. In conclusion, TTS is rare in cancer patients. Identifying TTS triggers could be useful because it could induce therapeutic changes.
Comparison Between Modified Lateral Arm Free Flap and Traditional Lateral Arm Free Flap for the Reconstruction of Oral and Maxillofacial Soft Tissue Defects
Authors: Wang Wei-Ming , Sun Lu , Yang Si-Si , Hu Shu-Jun , Zuo Yi-Jie , Min An-Jie
Published: May 2022

Objective

The traditional lateral arm free flap (tLAFF) has the disadvantages of short vascular pedicle, small vascular diameter, and non-perforator flap. We used a new method to prepare modified LAFF (mLAFF) and evaluate its application value in the repair of oral and maxillofacial soft tissue defects.

Methods

The anatomical features of the flap were recorded and compared between the tLAFF group and the mLAFF group. All the flaps in the modified group were perforator flaps. Statistical analysis was performed on the data using ANOVA on SPSS 22.0 statistical software package.

Results

Forty-five mLAFFs were prepared as eccentric design rotation repair perforated flap, or multi-lobed or chimeric perforator flaps. Compared with the tLAFF, the vascular pedicle length of the mLAFF was increased, and the outer diameter of the anastomosis was thickened. The damage to the donor site was less. The difference was statistically significant.

Conclusion

The mLAFF can effectively lengthen the vascular pedicle length and increase the anastomosis diameter. Perforator LAFFs in the repair of oral and maxillofacial defects have good application value.
Impact and Treatment of Sarcopenia in Patients Undergoing Radiotherapy: A Multidisciplinary, AMSTAR-2 Compliant Review of Systematic Reviews and Metanalyses
Authors: Medici Federica , Bazzocchi Alberto , Buwenge Milly , Zamagni Alice , Macchia Gabriella , Deodato Francesco , Cilla Savino , De Iaco Pierandrea , Perrone Anna Myriam , Strigari Lidia , Rizzo Stefania , Morganti Alessio G.
Published: May 2022

Background

Sarcopenia (SP) is defined as the quantitative and functional impairment of skeletal muscles. SP is commonly related to older age and is frequent in patients with cancer. To provide an overview of SP in patients treated with radiotherapy (RT) and to evaluate the current evidence, we analyzed the available systematic reviews and meta-analyses.

Methods

Reviews were identified using PubMed, Scopus, and Cochrane library databases, without date restriction. Only systematic reviews and meta-analyses on the prognostic impact of SP and on any treatments aimed at reducing SP effect, in patients undergoing RT, were included in this review. The analyses not separately reporting the results in patients treated with RT were excluded. The quality assessment was performed using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews).

Results

From the 84 papers identified, five reviews met the inclusion criteria with four reports mainly including non-randomized trials. Three reviews on the effect of SP showed a significantly negative impact on overall survival in patients undergoing RT and/or chemoradiation for H&N cancers (HR: 1.63-2.07). Two reviews on interventional studies showed the possibility of 1) improving physical functions through nutritional and physical interventions and 2) avoiding muscle wasting by means of sufficient protein intake. The quality assessment of the included review showed that two and three analyses are classifiable as having low and moderate overall confidence rating, respectively.

Conclusions

The analyzed reviews uniformly confirmed the negative impact of SP in patients with H&N tumors undergoing RT and the possibility of improving muscle mass and function through nutritional and physical interventions. These results justify further research on this topic based on a more uniform SP definition and on a complete evaluation of the potentially confounding parameters.
Research Progress of Antibody–Drug Conjugate Therapy for Advanced Gastric Cancer
Authors: Wang Na , Mei Qingyun , Wang Ziwei , Zhao Lu , Zhang Dou , Liao Dongying , Zuo Jinhui , Xie Hongxia , Jia Yingjie , Kong Fanming
Published: May 2022

Gastric cancer is an intractable malignant tumor that has the fifth highest morbidity and the third highest mortality in the world. Even though various treatment options did much to ameliorate the prognosis of advanced gastric cancer, the survival time remained unsatisfactory. It is significant to develop new therapeutic agents to improve the long-term outcome. Antibody–drug conjugate is an innovative and potent antineoplastic drug composed of a specifically targeted monoclonal antibody, a chemical linker, and a small molecule cytotoxic payload. Powerful therapeutic efficacy and moderate toxicity are its preponderant advantages, which imply the inevitable pharmaceutical developments to meet the demand for individualized precision therapy. Nevertheless, it is unavoidable that there is a phenomenon of drug resistance in this agent. This article systematically reviewed the recent progress of antibody–drug conjugates in advanced gastric cancer therapy.
The Role of LncRNAs in the Regulation of Radiotherapy Sensitivity in Cervical Cancer
Authors: Zhang Hanqun , Fang Chunju , Feng Zhiyu , Xia Tingting , Lu Liang , Luo Min , Chen Yanping , Liu Yuncong , Li Yong
Published: May 2022

Cervical cancer (CC) is one of the three majors gynecological malignancies, which seriously threatens women’s health and life. Radiotherapy (RT) is one of the most common treatments for cervical cancer, which can reduce local recurrence and prolong survival in patients with cervical cancer. However, the resistance of cancer cells to Radiotherapy are the main cause of treatment failure in patients with cervical cancer. Long non-coding RNAs (LncRNAs) are a group of non-protein-coding RNAs with a length of more than 200 nucleotides, which play an important role in regulating the biological behavior of cervical cancer. Recent studies have shown that LncRNAs play a key role in regulating the sensitivity of radiotherapy for cervical cancer. In this review, we summarize the structure and function of LncRNAs and the molecular mechanism of radiosensitivity in cervical cancer, list the LncRNAs associated with radiosensitivity in cervical cancer, analyze their potential mechanisms, and discuss the potential clinical application of these LncRNAs in regulating radiosensitivity in cervical cancer.
Surgical Management of Malignant Glioma in the Elderly
Authors: Klingenschmid Julia , Krigers Aleksandrs , Kerschbaumer Johannes , Thomé Claudius , Pinggera Daniel , Freyschlag Christian F.
Published: May 2022

Background

The median age for diagnosis of glioblastoma is 64 years and the incidence rises with increasing age to a peak at 75-84 years. As the total number of high-grade glioma patients is expected to increase with an aging population, neuro-oncological surgery faces new treatment challenges, especially regarding aggressiveness of the surgical approach and extent of resection. In the elderly, aspects like frailty and functional recovery time have to be taken into account before performing surgery.

Material & Methods

Patients undergoing surgery for malignant glioma (WHO grade III and IV) at our institution between 2015 and 2020 were compiled in a centralized tumor database and analyzed retrospectively. Karnofsky Performance Scale (KPS) and Clinical Frailty Scale (CFS) were used to determine functional performance pre- and postoperatively. Overall survival (OS) was compared between age groups of 65-69 years, 70-74 years, 75-79 years, 80-84 years and >85 years in view of extent of resection (EOR). Furthermore, we performed a literature evaluation focusing on surgical treatment of newly diagnosed malignant glioma in the elderly.

Results

We analyzed 121 patients aged 65 years and above (range 65 to 88, mean 74 years). Mean overall survival (OS) was 10.35 months (SD = 11.38). Of all patients, only a minority (22.3%) received tumor biopsy instead of gross total resection (GTR, 61.2%) or subtotal resection (STR, 16.5%). Postoperatively, 52.9% of patients were treated according to the Stupp protocol. OS differed significantly between extent of resection (EOR) groups (4.0 months after biopsy vs. 8.3 after STR vs. 13.8 after GTR, p < 0.05 and p < 0.001 correspondingly). No significant difference was observed regarding EOR across different age groups.

Conclusion

GTR should be the treatment of choice also in elderly patients with malignant glioma as functional outcome and survival after surgery are remarkably better compared to less aggressive treatment. Elderly patients who received GTR of high-grade gliomas survived significantly longer compared to patients who underwent biopsy and STR. Age seems to have little influence on overall survival in selected surgically extensive treated patients, but high preoperative functional performance is mandatory.
Individualized Treatment for Advanced Non-Small Cell Lung Cancer: A Case Report and Literature Review
Authors: Sun Qianqian , Li Weiqing , Liu Taorui , Guo Huiqin
Published: May 2022

The incidence of lung cancer is high and about 75% of the patients with lung cancer are found in the middle and advanced stage, which has a limited treatment strategy. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. In this article, we delineate the treatment process of a middle-aged male patient with advanced-stage lung cancer to explain the significance of individualized chemotherapy combined with immunotherapy and surgery. This patient has extensive bone metastasis with PS scores of 2. After nine cycles of preoperative neoadjuvant chemotherapy, surgery, and two cycles of postoperative adjuvant chemotherapy, the patient achieved complete response (CR) and his PS score was 0. Although there is a standard chemotherapy regimen for lung adenocarcinoma, the treatment effect varies because of individual differences. Comprehensive analysis of the characteristics of patients through a variety of means to develop a precise individualized chemotherapy plan will be a major direction of lung cancer treatment in the future. Additionally, surgical treatment for advanced lung cancer patients after chemotherapy can effectively reduce the primary lesion and prolong the survival time of patients.
Total Flavonoids of Rhizoma Drynariae Ameliorate Bone Growth in Experimentally Induced Tibial Dyschondroplasia in Chickens via Regulation of OPG/RANKL Axis
Authors: Xu Tingting , Zheng Jingjing , Jin WeiXing , Li Lu , Lin Luxi , Shaukat Aftab , Zhang Chaodong , Cao Qinqin , Ashraf Muhammad , Huang Shucheng
Published: May 2022

Background:Rhizoma Drynariae, traditional Chinese herb, is widely used to treat and prevent bone disorders. However, experimental evidence on the use of Rhizoma Drynariae extract, total flavonoids of Rhizoma Drynariae (TFRD) to treat tibial dyschondroplasia (TD) in chickens and its underlying mechanisms have not been investigated.

Purpose: To evaluate the therapeutic effect of TFRD on leg disease caused by TD and elucidate its mechanisms in modulating the bone status.

Methods: Thiram-induced chicken TD model has been established. The tibia status was evaluated by analyzing tibia-related parameters including tibial weight, tibial length and its growth plate width and by performing histopathological examination. The expression of tibial bone development-related genes and proteins was confirmed by western blotting and qRT-PCR.

Results: The results showed that administration of TFRD mitigated lameness, increased body weight, recuperated growth plate width in broilers affected by TD and the increase of tibia weight and tibia length is significantly positively correlated with body weight. Compared with the TD group broilers, 500 mg/kg TFRD evidently reduced the damage width of the growth plate and improved its blood vessel distribution by elevating the gene expression levels of BMP-2 and Runx2 and OPG/RANKL ratio. Furthermore, correlation analysis found that the damage width of the growth plate was negatively correlated with the expression levels of BMP-2 and OPG.

Conclusion: The present study revealed that TFRD could promote the bone growth via upregulating OPG/RANKL ratio, suggesting that TFRD might be a potential novel drug in the treatment of TD in chickens.
The Imaging Performance of Preclinical Ultrasound Scanners Using the Edinburgh Pipe Phantom
Authors: Moran Carmel M , McLeod Christopher , McBride Karne , Inglis Scott , Thomson Adrian JW , Pye Stephen D
Published: May 2022

The greyscale imaging performance of a total of 17 preclinical transducer/scanner combinations were measured over a period of 10 years. These comprised nine single element transducers and eight array transducers with nominal central frequencies ranging between 15 and 55 MHz, and were from four commercially-available preclinical ultrasound scanners. Performance was assessed using a single figure of merit, the resolution integral, using measurements acquired from images of a test-object, the Edinburgh Pipe Phantom. Two further parameters were derived from the resolution integral: characteristic resolution and depth-of-field. Our results demonstrate that 1) resolution integral values of the array transducers were greater than single-element transducers, and 2) the array transducers demonstrated greater depths of field than the single-element transducers of the same nominal frequency. Moreover we demonstrate that use of this single figure-of-merit enabled identification and quantification of changes in imaging performance of preclinical transducers over a 10-years period.