bluuebunny/crossref_metadata_2025 huggingface dataset:
The Power of Microbiome Studies: Some Considerations on Which Alpha and Beta Metrics to Use and How to Report Results
Authors: Kers Jannigje Gerdien , Saccenti Edoardo
Published: March 2022

Background

Since sequencing techniques have become less expensive, larger sample sizes are applicable for microbiota studies. The aim of this study is to show how, and to what extent, different diversity metrics and different compositions of the microbiota influence the needed sample size to observe dissimilar groups. Empirical 16S rRNA amplicon sequence data obtained from animal experiments, observational human data, and simulated data were used to perform retrospective power calculations. A wide variation of alpha diversity and beta diversity metrics were used to compare the different microbiota datasets and the effect on the sample size.

Results

Our data showed that beta diversity metrics are the most sensitive to observe differences as compared with alpha diversity metrics. The structure of the data influenced which alpha metrics are the most sensitive. Regarding beta diversity, the Bray–Curtis metric is in general the most sensitive to observe differences between groups, resulting in lower sample size and potential publication bias.

Conclusion

We recommend performing power calculations and to use multiple diversity metrics as an outcome measure. To improve microbiota studies, awareness needs to be raised on the sensitivity and bias for microbiota research outcomes created by the used metrics rather than biological differences. We have seen that different alpha and beta diversity metrics lead to different study power: because of this, one could be naturally tempted to try all possible metrics until one or more are found that give a statistically significant test result, i.e., p-value < α. This way of proceeding is one of the many forms of the so-called p-value hacking. To this end, in our opinion, the only way to protect ourselves from (the temptation of) p-hacking would be to publish a statistical plan before experiments are initiated, describing the outcomes of interest and the corresponding statistical analyses to be performed.
Prevalence of Wheat Associated Bacillus spp. and Their Bio-Control Efficacy Against Fusarium Root Rot
Authors: Mulk Shah , Wahab Abdul , Yasmin Humaira , Mumtaz Saqib , El-Serehy Hamed A. , Khan Naeem , Hassan Muhammad Nadeem
Published: March 2022

Bacillus spp. are the most prevalent group of bacteria in nature. Their prevalence depends upon multiple factors, namely, sporulation, antagonism, and production of secondary metabolites. The development of an eco-friendly approach to cope with edible crops diseases is very substantial for humans. In the present study, 658 isolates were obtained from wheat grown in the wheat rice cropping system and tested for their antagonistic activity against four wheat root rot pathogens, namely, Fusarium oxysporum, Fusarium moniliforme, Macrophomina phaseolina, and Rhizoctonia solani. Out of 658, 106 isolates were found antagonistic to either single or multiple fungi. Out of 106 antagonistic bacteria, 62 (23%) were rhizospheric, 28 (14%) were root endospheric, and 16 (9%) were leaf endospheric. Based on mean inhibition against all fungi, the bacterial strains SM-39 and SM-93 showed maximum antagonistic activity. The 16S rRNA gene analysis revealed that most of the antagonistic bacteria exhibiting ≥48% antagonism were Bacillus spp. (98%), except two were Klebsiella spp. (2%). The bacterial strains exhibited phylogenetic lineage with the type strains of the respective genus based on the 16S rRNA gene sequences. In the net house experiment, Bacillus velezensis (SM-39) and Bacillus cabrialesii (SM-93) significantly suppressed Fusarium root rot severity in wheat (42–62%). Plants treated with these strains had lower electrolytic leakage (29–36%), as compared to untreated (44%). Relative water content was much higher (46–58%) for plants inoculated with these strains. These antagonistic strains also considerably colonized the wheat rhizosphere with a cell population of 5.8–6.9.log CFU/g of soil. The rhizosphere of wheat grown in the wheat-rice cropping system could be the potential habitat of effective biocontrol agents.
Endophytic Bacterium Serratia plymuthica From Chinese Leek Suppressed Apple Ring Rot on Postharvest Apple Fruit
Authors: Sun Meng , Liu Junping , Li Jinghui , Huang Yonghong
Published: March 2022

Apple ring rot caused by Botryosphaeria dothidea is an economically significant plant disease that spreads across the apple production areas in China. The pathogen infects apple fruits during the growing season and results in postharvest fruits rot during storage, which brings about a huge loss to plant growers. The study demonstrated that an endophytic bacterium Serratia plymuthica isolated from Chinese leek (Allium tuberosum) significantly suppressed the mycelial growth, severely damaging the typical morphology of B. dothidea, and exerted a high inhibition of 84.64% against apple ring rot on postharvest apple fruit. Furthermore, S. plymuthica significantly reduced the titratable acidity (TA) content, enhanced the soluble sugar (SS) content, vitamin C content, and SS/TA ratio, and maintained the firmness of the fruits. Furthermore, comparing the transcriptomes of the control and the S. plymuthica treated mycelia revealed that S. plymuthica significantly altered the expressions of genes related to membrane (GO:0016020), catalytic activity (GO:0003824), oxidation-reduction process (GO:0055114), and metabolism pathways, including tyrosine metabolism (ko00280), glycolysis/gluconeogenesis (ko00010), and glycerolipid metabolism (ko00561). The present study provided a possible way to control apple ring rot on postharvest fruit and a solid foundation for further exploring the underlying molecular mechanism.
A C∧S-Cyclometallated Gold(III) Complex as a Novel Antibacterial Candidate Against Drug-Resistant Bacteria
Authors: Ratia Carlos , Cepas Virginio , Soengas Raquel , Navarro Yolanda , Velasco-de Andrés María , Iglesias María José , Lozano Francisco , López-Ortiz Fernando , Soto Sara M.
Published: March 2022

The worldwide emergence and spread of infections caused by multidrug-resistant bacteria endangers the efficacy of current antibiotics in the clinical setting. The lack of new antibiotics in the pipeline points to the need of developing new strategies. Recently, gold-based drugs are being repurposed for antibacterial applications. Among them, gold(III) complexes have received increasing attention as metal-based anticancer agents. However, reports on their antibacterial activity are scarce due to stability issues. The present work demonstrates the antibacterial activity of the gold(III) complex 2 stabilized as C∧S-cycloaurated containing a diphenylphosphinothioic amide moiety, showing minimum inhibitory concentration (MIC) values that ranged from 4 to 8 and from 16 to 32 mg/L among Gram-positive and Gram-negative multidrug-resistant (MDR) pathogens, respectively. Complex 2 has a biofilm inhibitory activity of only two to four times than its MIC. We also describe for the first time a potent antibacterial synergistic effect of a gold(III) complex combined with colistin, showing a bactericidal effect in less than 2 h; confirming the role of the outer membrane as a permeability barrier. Complex 2 shows a low rate of internalization in Staphylococcus aureus and Acinetobacter baumannii; it does not interact with replication enzymes or efflux pumps, causes ultrastructural damages in both membrane and cytoplasmic levels, and permeabilizes the bacterial membrane. Unlike control antibiotics, complex 2 did not generate resistant mutants in 30-day sequential cultures. We detected lower cytotoxicity in a non-tumoral THLE-2 cell line (IC50 = 25.5 μM) and no acute toxicity signs in vivo after an i.v. 1-mg/kg dose. The characterization presented here reassures the potential of complex 2 as a new chemical class of antimicrobial agents.
NADPH Oxidase Gene, FgNoxD, Plays a Critical Role in Development and Virulence in Fusarium graminearum
Authors: Li Taiying , Kim Dohyun , Lee Jungkwan
Published: March 2022

NADPH oxidase is an enzyme that generates reactive oxygen species from oxygen and NADPH and is highly conserved in eukaryotes. In Fusarium graminearum, a series of different Nox enzymes have been identified. NoxA is involved in sexual development and ascospore production and, like NoxB, also contributes to pathogenicity. Both NoxA and NoxB are regulated by the subunit NoxR, whereas NoxC is usually self-regulated by EF-hand motifs found on the enzyme. In this study, we characterized another NADPH oxidase in F. graminearum, FgNoxD. In the FgNoxD deletion mutant, vegetative growth and conidia production were reduced, while sexual development was totally abolished. The FgNoxD deletion mutant also showed reduced resistance to cell wall perturbing agents; cell membrane inhibitors; and osmotic, fungicide, cold, and extracellular oxidative stress, when compared to the wild type. Moreover, in comparison to the wild type, the FgNoxD deletion mutant exhibited reduced virulence against the host plant. The FgNoxD deletion mutant produced less deoxynivalenol than the wild type, and the Tri5 and Tri6 gene expression was also downregulated. In conclusion, our findings show that FgNoxD is involved in the survival against various stresses, conidiation, sexual development, and virulence, highlighting this enzyme as a new target to control the disease caused by F. graminearum.
High Affinity Iron Acquisition Systems Facilitate but Are Not Essential for Colonization of Chickens by Salmonella Enteritidis
Authors: Wellawa Dinesh H. , Lam Po-King S. , White Aaron P. , Gomis Susantha , Allan Brenda , Köster Wolfgang
Published: March 2022

The roles of TonB mediated Fe3+(ferric iron) uptake via enterobactin (involving biosynthesis genesentABCDEF) and Fe2+(ferrous iron) uptake through the FeoABC transporter are poorly defined in the context of chicken-Salmonellainteractions. Both uptake systems are believed to be the major contributors of iron supply in theSalmonellalife cycle. Current evidence suggests that these iron uptake systems play a major role in pathogenesis in mammals and as such, they represent promising antibacterial targets with therapeutic potential. We investigated the role of these iron uptake mechanisms regarding the ability ofSalmonellaEnteritidis (SEn) strains to colonize in a chicken infection model. Further we constructed a bioluminescent reporter to sense iron limitation during gastrointestinal colonization ofSalmonellain chicken viaex vivoimaging. Our data indicated that there is some redundancy between the ferric and ferrous iron uptake mechanisms regarding iron acquisition during SEn pathogenesis in chicken. We believe that this redundancy of iron acquisition in the host reservoir may be the consequence of adaptation to unique avian environments, and thus warrants further investigation. To our knowledge, this the first report providing direct evidence that both enterobactin synthesis and FeoABC mediated iron uptake contribute to the virulence of SEn in chickens.
Recent Developments in Isothermal Amplification Methods for the Detection of Foodborne Viruses
Authors: Suther Cassandra , Stoufer Sloane , Zhou Yanjiao , Moore Matthew D.
Published: March 2022

Foodborne and enteric viruses continue to impose a significant public health and economic burden globally. As many of these viruses are highly transmissible, the ability to detect them portably, sensitively, and rapidly is critical to reduce their spread. Although still considered a gold standard for detection of these viruses, real time polymerase chain reaction (PCR)-based technologies have limitations such as limited portability, need for extensive sample processing/extraction, and long time to result. In particular, the limitations related to the susceptibility of real time PCR methods to potential inhibitory substances present in food and environmental samples is a continuing challenge, as the need for extensive nucleic acid purification prior to their use compromises the portability and rapidity of such methods. Isothermal amplification methods have been the subject of much investigation for these viruses, as these techniques have been found to be comparable to or better than established PCR-based methods in portability, sensitivity, specificity, rapidity, and simplicity of sample processing. The purpose of this review is to survey and compare reports of these isothermal amplification methods developed for foodborne and enteric viruses, with a special focus on the performance of these methods in the presence of complex matrices.
Direct Lytic Agents: Novel, Rapidly Acting Potential Antimicrobial Treatment Modalities for Systemic Use in the Era of Rising Antibiotic Resistance
Authors: Schuch Raymond , Cassino Cara , Vila-Farres Xavier
Published: March 2022

Direct lytic agents (DLAs) are novel antimicrobial compounds with unique mechanisms of action based on rapid cell wall destabilization and bacteriolysis. DLAs include two classes of purified polypeptides—lysins (peptidoglycan hydrolase enzymes) and amurins (outer membrane targeting peptides). Their intended use is to kill bacteria in a manner that is complimentary to and synergistic with traditional antibiotics without selection for DLA resistance. Lysins were originally described as having activity against Gram-positive pathogens and of those, exebacase, is the first to have advanced into Phase 3 of clinical development. Recently, both engineered and native DLAs have now been described with potent bactericidal activity against a range of Gram-negative pathogens, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Importantly, novel DLAs targeting Gram-negatives, including the lysin CF-370 and the amurin peptides, are active in biological matrices (blood/serum) and, as such, offer promise for therapeutic use as systemically administered agents for the treatment of life-threatening invasive infections. In this review, DLAs are discussed as potential new classes of antimicrobial biologics that can be used to treat serious systemic infections.
Let’s Get Physical: Flavivirus-Host Protein–Protein Interactions in Replication and Pathogenesis
Authors: Fishburn Adam T. , Pham Oanh H. , Kenaston Matthew W. , Beesabathuni Nitin S. , Shah Priya S.
Published: March 2022

Flaviviruses comprise a genus of viruses that pose a significant burden on human health worldwide. Transmission by both mosquito and tick vectors, and broad host tropism contribute to the presence of flaviviruses globally. Like all viruses, they require utilization of host molecular machinery to facilitate their replication through physical interactions. Their RNA genomes are translated using host ribosomes, synthesizing viral proteins that cooperate with each other and host proteins to reshape the host cell into a factory for virus replication. Thus, dissecting the physical interactions between viral proteins and their host protein targets is essential in our comprehension of how flaviviruses replicate and how they alter host cell behavior. Beyond replication, even single interactions can contribute to immune evasion and pathogenesis, providing potential avenues for therapeutic intervention. Here, we review protein interactions between flavivirus and host proteins that contribute to virus replication, immune evasion, and disease.
Globally-Optimal Inlier Maximization for Relative Pose Estimation Under Planar Motion
Authors: Liu Haotian , Chen Guang , Liu Yinlong , Liang Zichen , Zhang Ruiqi , Knoll Alois
Published: March 2022

Planar motion constraint occurs in visual odometry (VO) and SLAM for Automated Guided Vehicles (AGVs) or mobile robots in general. Conventionally, two-point solvers can be nested to RANdom SAmple Consensus to reject outliers in real data, but the performance descends when the ratio of outliers goes high. This study proposes a globally-optimal Branch-and-Bound (BnB) solver for relative pose estimation under general planar motion, which aims to figure out the globally-optimal solution even under a quite noisy environment. Through reasonable modification of the motion equation, we decouple the relative pose into relative rotation and translation so that a simplified bounding strategy can be applied. It enhances the efficiency of the BnB technique. Experimental results support the global optimality and demonstrate that the proposed method performs more robustly than existing approaches. In addition, the proposed algorithm outperforms state-of-art methods in global optimality under the varying level of outliers.
The Mind After Midnight: Nocturnal Wakefulness, Behavioral Dysregulation, and Psychopathology
Authors: Tubbs Andrew S. , Fernandez Fabian-Xosé , Grandner Michael A. , Perlis Michael L. , Klerman Elizabeth B.
Published: March 2022

Sufficient sleep with minimal interruption during the circadian/biological night supports daytime cognition and emotional regulation. Conversely, disrupted sleep involving significant nocturnal wakefulness leads to cognitive and behavioral dysregulation. Most studies to-date have examined how fragmented or insufficient sleep affects next-day functioning, but recent work highlights changes in cognition and behavior that occur when someone is awake during the night. This review summarizes the evidence for day-night alterations in maladaptive behaviors, including suicide, violent crime, and substance use, and examines how mood, reward processing, and executive function differ during nocturnal wakefulness. Based on this evidence, we propose theMind after Midnighthypothesis in which attentional biases, negative affect, altered reward processing, and prefrontal disinhibition interact to promote behavioral dysregulation and psychiatric disorders.
Imprecise Predictive Coding Is at the Core of Classical Schizophrenia
Authors: Liddle Peter F. , Liddle Elizabeth B.
Published: March 2022

Current diagnostic criteria for schizophrenia place emphasis on delusions and hallucinations, whereas the classical descriptions of schizophrenia by Kraepelin and Bleuler emphasized disorganization and impoverishment of mental activity. Despite the availability of antipsychotic medication for treating delusions and hallucinations, many patients continue to experience persisting disability. Improving treatment requires a better understanding of the processes leading to persisting disability. We recently introduced the term classical schizophrenia to describe cases with disorganized and impoverished mental activity, cognitive impairment and predisposition to persisting disability. Recent evidence reveals that a polygenic score indicating risk for schizophrenia predicts severity of the features of classical schizophrenia: disorganization, and to a lesser extent, impoverishment of mental activity and cognitive impairment. Current understanding of brain function attributes a cardinal role to predictive coding: the process of generating models of the world that are successively updated in light of confirmation or contradiction by subsequent sensory information. It has been proposed that abnormalities of these predictive processes account for delusions and hallucinations. Here we examine the evidence provided by electrophysiology and fMRI indicating that imprecise predictive coding is the core pathological process in classical schizophrenia, accounting for disorganization, psychomotor poverty and cognitive impairment. Functional imaging reveals aberrant brain activity at network hubs engaged during encoding of predictions. We discuss the possibility that frequent prediction errors might promote excess release of the neurotransmitter, dopamine, thereby accounting for the occurrence of episodes of florid psychotic symptoms including delusions and hallucinations in classical schizophrenia. While the predictive coding hypotheses partially accounts for the time-course of classical schizophrenia, the overall body of evidence indicates that environmental factors also contribute. We discuss the evidence that chronic inflammation is a mechanism that might link diverse genetic and environmental etiological factors, and contribute to the proposed imprecision of predictive coding.
Electrodermal Activity Biofeedback Alters Evolving Functional Brain Networks in People With Epilepsy, but in a Non-specific Manner
Authors: Schach Sophia , Rings Thorsten , Bregulla Madeleine , Witt Juri-Alexander , Bröhl Timo , Surges Rainer , von Wrede Randi , Lehnertz Klaus , Helmstaedter Christoph
Published: March 2022

There is evidence that biofeedback of electrodermal activity (EDA) can reduce seizure frequency in people with epilepsy. Prior studies have linked EDA biofeedback to a diffuse brain activation as a potential functional mechanism. Here, we investigated whether short-term EDA biofeedback alters EEG-derived large-scale functional brain networks in people with epilepsy. In this prospective controlled trial, thirty participants were quasi-randomly assigned to one of three biofeedback conditions (arousal, sham, or relaxation) and performed a single, 30-min biofeedback training while undergoing continuous EEG recordings. Based on the EEG, we derived evolving functional brain networks and examined their topological, robustness, and stability properties over time. Potential effects on attentional-executive functions and mood were monitored via a neuropsychological assessment and subjective self-ratings. Participants assigned to the relaxation group seemed to be most successful in meeting the task requirements for this specific control condition (i.e., decreasing EDA). Participants in the sham group were more successful in increasing EDA than participants in the arousal group. However, only the arousal biofeedback training was associated with a prolonged robustness-enhancing effect on networks. Effects on other network properties were mostly unspecific for the different groups. None of the biofeedback conditions affected attentional-executive functions or subjective behavioral measures. Our results suggest that global characteristics of evolving functional brain networks are modified by EDA biofeedback. Some alterations persisted after the single training session; however, the effects were largely unspecific across the different biofeedback protocols. Further research should address changes of local network characteristics and whether multiple training sessions will result in more specific network modifications.
Expression of Circ_Satb1 Is Decreased in Mesial Temporal Lobe Epilepsy and Regulates Dendritic Spine Morphology
Authors: Gomes-Duarte Andreia , Venø Morten T. , de Wit Marina , Senthilkumar Ketharini , Broekhoven Mark H. , van den Herik Joëlle , Heeres Fleur R. , van Rossum Daniëlle , Rybiczka-Tesulov Mateja , Legnini Ivano , van Rijen Peter C. , van Eijsden Pieter , Gosselaar Peter H. , Rajewsky Nikolaus , Kjems Jørgen , Vangoor Vamshidhar R. , Pasterkamp R. Jeroen
Published: March 2022

Mesial temporal lobe epilepsy (mTLE) is a chronic disease characterized by recurrent seizures that originate in the temporal lobes of the brain. Anti-epileptic drugs (AEDs) are the standard treatment for managing seizures in mTLE patients, but are frequently ineffective. Resective surgery is an option for some patients, but does not guarantee a postoperative seizure-free period. Therefore, further insight is needed into the pathogenesis of mTLE to enable the design of new therapeutic strategies. Circular RNAs (circRNAs) have been identified as important regulators of neuronal function and have been implicated in epilepsy. However, the mechanisms through which circRNAs contribute to epileptogenesis remain unknown. Here, we determine the circRNA transcriptome of the hippocampus and cortex of mTLE patients by using RNA-seq. We report 333 differentially expressed (DE) circRNAs between healthy individuals and mTLE patients, of which 23 circRNAs displayed significant adjusted p-values following multiple testing correction. Interestingly, hippocampal expression of circ_Satb1, a circRNA derived from special AT-rich sequence binding protein 1 (SATB1), is decreased in both mTLE patients and in experimental epilepsy. Our work shows that circ_Satb1 displays dynamic patterns of neuronal expression in vitro and in vivo. Further, circ_Satb1-specific knockdown using CRISPR/CasRx approaches in hippocampal cultures leads to defects in dendritic spine morphology, a cellular hallmark of mTLE. Overall, our results identify a novel epilepsy-associated circRNA with disease-specific expression and previously unidentified cellular effects that are relevant for epileptogenesis.
Dietary Patterns in the Argentinian Population and Their Association With Sociodemographic Characteristics: Results From the ELANS Study (2014–2015)
Authors: Mendez Ignacio , Fasano Maria Victoria , Guajardo Viviana , Zonis Luciana , Kovalskys Irina
Published: March 2022

Aim

To describe dietary patterns in the Argentinian population and their association with sociodemographic characteristics.

Methods

Cross-sectional analysis of Argentina's food consumption and sociodemographic data of 1,266 men and women between 15 and 65 years from the Latin American Study of Nutrition and Health carried out between March 2014 and December 2015. Dietary patterns were identified by using factor analysis and median factor scores were calculated for gender, age, region, body mass index (BMI), socioeconomic, education, and physical activity categories.

Results

Five dietary patterns were identified. Western, Local Western, and Rural were generally characterized by high consumptions of animal fats, sugar-sweetened beverages, meats or processed meats, pizza and empanadas, sweets, pastries, and low consumption of fruits and vegetables. Traditional pattern was mainly characterized by consumption of oils, starchy vegetables, and red meat and Sweet Prudent by milk and yogurt, vegetables, fruit, artificially sweetened beverages, sweets, and cookies. Higher adherence to the Sweet Prudent pattern was observed in women, in people who meet physical activity guidelines and higher socioeconomic and educational levels. Higher adherence to traditional pattern was only observed for men. Higher adherence to the rest of the patterns was observed mostly by men, young, leaner, lower socioeconomic, and educational levels, not meeting physical activity guidelines, from the metropolitan area of Buenos Aires or northern regions.

Conclusion

Food consumption in Argentina is expressed in a diversity of dietary patterns. Men, younger, and sedentary individuals, with lower socioeconomic and educational level, from the metropolitan area of Buenos Aires and northern regions, seem to have higher adherence to least healthy dietary patterns.
Perspective: Are Online Food Delivery Services Emerging as Another Obstacle to Achieving the 2030 United Nations Sustainable Development Goals?
Authors: Jia Si Si , Gibson Alice A. , Ding Ding , Allman-Farinelli Margaret , Phongsavan Philayrath , Redfern Julie , Partridge Stephanie R.
Published: March 2022

Online food delivery usage has soared during the 2019 novel coronavirus (COVID-19) pandemic which has seen increased demand for home-delivery during government mandated stay-at-home periods. Resulting implications from COVID-19 may threaten decades of development gains. It is becoming increasingly more important for the global community to progress toward sustainable development and improve the wellbeing of people, economies, societies, and the planet. In this perspective article, we discuss how the rising use of these platform-to-consumer delivery operations may impede advances toward the United Nations 2030 Sustainable Development Goals (SDGs). Specifically, online food delivery services may disrupt SDGs that address good health and wellbeing, responsible consumption and production, climate action and decent work and economic growth. To mitigate potential negative impacts of these meal delivery apps, we have proposed a research and policy agenda that is aligned with entry points within a systems approach identified by the World Health Organization. Food industry reforms, synergised public health messaging and continuous monitoring of the growing impact of online food delivery should be considered for further investigation by researchers, food industry, governments, and policy makers.
Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia
Authors: Zhang Jiaqiang , Chang Chia-Lun , Lu Chang-Yun , Chen Ho-Min , Wu Szu-Yuan
Published: March 2022

Purpose

We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.

Patients and Methods

Patients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28–0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3–4, pathological nodal (pN) stage 1, and pN stage 2–3 were 1.16 (1.04–2.08), 1.28 (1.07–2.12), 3.71 (1.82–7.59), 4.67 (1.65–13.18), 1.09 (1.02–1.21), 1.17 (1.03–2.16), 1.10 (1.03–1.33), and 1.22 (1.06–2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64–0.94) compared with that for no adjuvant RT.

Conclusion

PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.
The Least Nodal Disease Burden Defines the Minimum Number of Nodes Retrieved for Esophageal Squamous Cell Carcinoma
Authors: Zhang Hanlu , Yan Xiuji , Yang Yu-Shang , Yang Hong , Yuan Yong , Tian Dong , Li Yin , Wu Zhi-Yong , Wang Yun , Fu Jian-Hua , Chen Long-Qi
Published: March 2022

Background

Clinically, a single positive lymph node (SPLN) should indicate the least nodal disease burden in node-positive patients with esophageal squamous cell carcinoma (ESCC) and may also be used to define the minimum number of examined lymph nodes (NELNs) in ESCC patients.

Methods

Data from three Chinese cohorts of 2448 ESCC patients who underwent esophagectomy between 2008 and 2012 were retrospectively analyzed. Based on lymph node status, patients were divided into two groups: N0 ESCC and SPLN ESCC. A Cox proportional hazards regression model was used to determine the minimum NELNs retrieved to maximize survival for ESCC patients with localized lymph node involvement. The results were then validated externally in the SEER database.

Results

A total of 1866 patients were pathologically diagnosed with N0 ESCC, and 582 patients were diagnosed with SPLN ESCC. The overall survival rate of patients with N0 ESCC was significantly better than that of patients with SPLN ESCC (HR 1.88, 95% CI 1.64-2.13, P<0.001), but no significant difference was found between SPLN ESCC patients with ≥ 20 lymph nodes harvested and N0 ESCC patients (HR 1.20, 95% CI 0.95-1.52, P=0.13). Analysis of patients selected from the SEER database showed the same trend, and no significant difference was observed between N0 ESCC patients and SPLN ESCC patients with ≥ 20 lymph nodes retrieved (HR: 1.02, 95% CI 0.72-1.43, P=0.92).

Conclusions

A minimum of 20 lymph nodes retrieved should be introduced as a quality indicator for ESCC patients with localized lymph node involvement.
Identification of N6-Methyladenosine-Related lncRNAs as a Prognostic Signature in Glioma
Authors: Chen Yujia , Guo Yuduo , Li Shenglun , Xu Jiacheng , Wang Xiang , Ning Weihai , Ma Lixin , Qu Yanming , Zhang Mingshan , Zhang Hongwei
Published: March 2022

N6-methyladenosine (m6A) modification is the most abundant modification in long noncoding RNAs (lncRNAs). Current studies have shown that the abnormal expression of m6A-related genes is closely associated with the tumorigenesis and progression of glioma. However, the role of m6A-related lncRNAs in glioma development is still unclear. Herein, we screened 566 m6A-related lncRNAs in glioma from The Cancer Genome Atlas (TCGA) database. The expression pattern of these lncRNAs could cluster samples into two groups, in which various classical tumor-related functions and the tumor immune microenvironment were significantly different. Subsequently, a nine-factor m6A-related lncRNA prognostic signature (MLPS) was constructed by using a LASSO regression analysis in the training set and was validated in the test set and independent datasets. The AUC values of the MLPS were 0.881, 0.918 and 0.887 for 1-, 3- and 5-year survival in the training set, respectively, and 0.856, 0.916 and 0.909 for 1-, 3-, and 5-year survival in the test set, respectively. Stratification analyses of the MLPS illustrated its prognostic performance in gliomas with different characteristics. Correlation analyses showed that the infiltrations of monocytes and tumor-associated macrophages (TAMs) were significantly relevant to the risk score in the MLPS. Moreover, we detected the expression of four MLPS factors with defined sequences in glioma and normal cells by using RT–PCR. Afterwards, we investigated the functions of LNCTAM34A (one of the MLPS factors) in glioma cells, which have rarely been reported. Via in vitro experiments, LNCTAM34A was demonstrated to promote the proliferation, migration and epithelial-mesenchymal transition (EMT) of glioma cells. Overall, our study revealed the critical role of m6A-related lncRNAs in glioma and elucidated that LNCTAM34A could promote glioma proliferation, migration and EMT.
The Potential of Photoacoustic Imaging in Radiation Oncology
Authors: Lefebvre Thierry L. , Brown Emma , Hacker Lina , Else Thomas , Oraiopoulou Mariam-Eleni , Tomaszewski Michal R. , Jena Rajesh , Bohndiek Sarah E.
Published: March 2022

Radiotherapy is recognized globally as a mainstay of treatment in most solid tumors and is essential in both curative and palliative settings. Ionizing radiation is frequently combined with surgery, either preoperatively or postoperatively, and with systemic chemotherapy. Recent advances in imaging have enabled precise targeting of solid lesions yet substantial intratumoral heterogeneity means that treatment planning and monitoring remains a clinical challenge as therapy response can take weeks to manifest on conventional imaging and early indications of progression can be misleading. Photoacoustic imaging (PAI) is an emerging modality for molecular imaging of cancer, enabling non-invasive assessment of endogenous tissue chromophores with optical contrast at unprecedented spatio-temporal resolution. Preclinical studies in mouse models have shown that PAI could be used to assess response to radiotherapy and chemoradiotherapy based on changes in the tumor vascular architecture and blood oxygen saturation, which are closely linked to tumor hypoxia. Given the strong relationship between hypoxia and radio-resistance, PAI assessment of the tumor microenvironment has the potential to be applied longitudinally during radiotherapy to detect resistance at much earlier time-points than currently achieved by size measurements and tailor treatments based on tumor oxygen availability and vascular heterogeneity. Here, we review the current state-of-the-art in PAI in the context of radiotherapy research. Based on these studies, we identify promising applications of PAI in radiation oncology and discuss the future potential and outstanding challenges in the development of translational PAI biomarkers of early response to radiotherapy.
Case Report: Complete Remission With Anti−PD−1 and Anti−VEGF Combined Therapy of a Patient With Metastatic Primary Splenic Angiosarcoma
Authors: Xu Weiran , Wang Kai , Gu Wenguang , Nie Xinxin , Zhang Hao , Tang Chuanhao , Lin Li , Liang Jun
Published: March 2022

Primary splenic angiosarcoma (PSA) is a rare malignancy with poor prognosis. At present, little study is available on immunotherapy in PSA. Here, we report a case of a patient with metastatic PSA who was treated with programmed death-1 (PD-1) inhibitors and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors combined therapy and achieved complete response (CR). The patient was a 57−year−old woman with three liver metastases. She was treated with seven cycles of toripalimab plus anlotinib. Programmed death-ligand 1 (PD-L1) immunohistochemistry and next-generation sequencing was performed, and the PD-L1 tumor proportion score was 75%. Finally, she achieved CR after six cycles of the combined therapy regimen. No serious adverse events were detected. To the best of our knowledge, this is the first clinical evidence that anti-PD-1 plus anti-VEGF therapy might be a promising option for patients with metastatic PSA. However, more clinical trials are needed to verify this conclusion.
Empirical Relative Biological Effectiveness (RBE) for Mandible Osteoradionecrosis (ORN) in Head and Neck Cancer Patients Treated With Pencil-Beam-Scanning Proton Therapy (PBSPT): A Retrospective, Case-Matched Cohort Study
Authors: Yang Yunze , Muller Olivia M. , Shiraishi Satomi , Harper Matthew , Amundson Adam C. , Wong William W. , McGee Lisa A. , Rwigema Jean-Claude M. , Schild Steven E. , Bues Martin , Fatyga Mirek , Anderson Justin D. , Patel Samir H. , Foote Robert L. , Liu Wei
Published: March 2022

Purpose

To retrospectively investigate empirical relative biological effectiveness (RBE) for mandible osteoradionecrosis (ORN) in head and neck (H&N) cancer patients treated with pencil-beam-scanning proton therapy (PBSPT).

Methods

We included 1,266 H&N cancer patients, of which, 931 patients were treated with volumetric-modulated arc therapy (VMAT) and 335 were treated with PBSPT. Among them, 26 VMAT and 9 PBSPT patients experienced mandible ORN (ORN group), while all others were included in the control group. To minimize the impact of the possible imbalance in clinical factors between VMAT and PBSPT patients in the dosimetric comparison between these two modalities and the resulting RBE quantification, we formed a 1:1 case-matched patient cohort (335 VMAT patients and 335 PBSPT patients including both the ORN and control groups) using the greedy nearest neighbor matching of propensity scores. Mandible dosimetric metrics were extracted from the case-matched patient cohort and statistically tested to evaluate the association with mandibular ORN to derive dose volume constraints (DVCs) for VMAT and PBSPT, respectively. We sought the equivalent constraint doses for VMAT so that the critical volumes of VMAT were equal to those of PBSPT at different physical doses. Empirical RBEs of PBSPT for ORN were obtained by calculating the ratio between the derived equivalent constraint doses and physical doses of PBSPT. Bootstrapping was further used to get the confidence intervals.

Results

Clinical variables of age, gender, tumor stage, prescription dose, chemotherapy, hypertension or diabetes, dental extraction, smoking history, or current smoker were not statistically related to the incidence of ORN in the overall patient cohort. Smoking history was found to be significantly associated with the ORN incidence in PBSPT patients only. V40Gy[RBE], V50Gy[RBE], and V60Gy[RBE] were statistically different (p<0.05) between the ORN and control group for VMAT and PBSPT. Empirical RBEs of 1.58(95%CI: 1.34-1.64), 1.34(95%CI: 1.23-1.40), and 1.24(95%: 1.15-1.26) were obtained for proton dose at 40 Gy[RBE=1.1], 50 Gy[RBE=1.1] and 60 Gy[RBE=1.1], respectively.

Conclusions

Our study suggested that RBEs were larger than 1.1 at moderate doses (between 40 and 60 Gy[RBE=1.1]) with high LET for mandible ORN. RBEs are underestimated in current clinical practice in PBSPT. The derived DVCs can be used for PBSPT plan evaluation and optimization to minimize the incidence rate of mandible ORN.
5-HT1F Receptor Agonist Ameliorates Mechanical Allodynia in Neuropathic Pain via Induction of Mitochondrial Biogenesis and Suppression of Neuroinflammation
Authors: Zhang Long-Qing , Zhou Ya-Qun , Li Jia-Yan , Sun Jia , Zhang Shuang , Wu Jia-Yi , Gao Shao-Jie , Tian Xue-Bi , Mei Wei
Published: March 2022

Neuropathic pain is a devastating disease that affects millions of people worldwide. Serotonin (5-hydroxytryptamine, 5-HT) is involved in pain modulation. Several lines of evidence have indicated that 5-HT1F receptor agonists are potent inducers of mitochondrial biogenesis. In this study, we tested the hypothesis that 5-HT1F receptor agonists ameliorate mechanical allodynia in neuropathic pain via the induction of mitochondrial biogenesis and suppression of neuroinflammation. Male Sprague–Dawley rats were used to establish a neuropathic pain model via spared nerve injury (SNI). The paw withdrawal threshold (PWT) was used to evaluate mechanical allodynia. Real-time polymerase chain reaction was used to examine the mitochondrial DNA (mtDNA) copy number. Western blotting and immunofluorescence were used to examine the expression of target proteins. Our results showed that mitochondrial biogenesis was impaired in the spinal cord of rats with SNI. Moreover, activation of PGC-1α, the master regulator of mitochondrial biogenesis, attenuates established mechanical allodynia in rats with neuropathic pain. In addition, the neuronal 5-HT1F receptor is significantly downregulated in the spinal cord of rats with neuropathic pain. Furthermore, the selective 5-HT1F receptor agonist lasmiditan attenuated established mechanical allodynia in rats with neuropathic pain. Finally, lasmiditan (Las) treatment restored mitochondrial biogenesis and suppressed neuroinflammation in the spinal cord of rats with SNI. These results provide the first evidence that lasmiditan ameliorates mechanical allodynia in neuropathic pain by inducing mitochondrial biogenesis and suppressing neuroinflammation in the spinal cord. Inducers of mitochondrial biogenesis may be an encouraging therapeutic option for the management of neuropathic pain.
Infinite-Layer Nickelate Superconductors: A Current Experimental Perspective of the Crystal and Electronic Structures
Authors: Chow L. E. , Ariando A.
Published: March 2022

After the reward of more than 2 decades of pursuit on the high-Tc cuprate analog with the hope to obtain a better understanding of the mechanism of high-Tc superconductivity, the discovery of superconductivity in the infinite-layer nickelate brings more mystery to the picture than expected. Tops in the list of questions are perhaps 1) absence of superconductivity in the bulk nickelate and limited thickness of the infinite-layer phase in thin film, 2) absence of superconductivity in the La-nickelate despite it being the earliest studied rare-earth nickelate, and the role of 4 f orbital in the recipe of superconductivity, 3) absence of Meissner effect and suspect of the origin of superconductivity from the interface, 4) whether nickelate hosts similar pairing symmetry to the single-band high-Tc cuprates or multiband iron-based superconductor. In this perspective article, we will discuss the following aspects: 1) stabilization of the infinite-layer phase on the SrTiO3(001) substrate and the thickness dependency of observables; 2) rare-earth dependence of the superconducting dome and phase diagram of the (La/Pr/Nd)- infinite-layer nickelate thin film; 3) experimental aspects of the measurement of Meissner effect; 4) theoretical framework and experimental study of the pairing symmetry of infinite-layer nickelate superconductor.
Preparing Excitable Cardiac Papillary Muscle and Cardiac Slices for Functional Analyses
Authors: Palmer Bradley M. , Bell Stephen P.
Published: March 2022

While the reductionist approach has been fruitful in understanding the molecular basis of muscle function, intact excitable muscle preparations are still important as experimental model systems. We present here methods that are useful for preparing cardiac papillary muscle and cardiac slices, which represent macroscopic experimental model systems with fully intact intercellular and intracellular structures. The maintenance of these in vivo structures for experimentation in vitro have made these model systems especially useful for testing the functional effects of protein mutations and pharmaceutical candidates. We provide solutions recipes for dissection and recording, instructions for removing and preparing the cardiac papillary muscles, as well as instruction for preparing cardiac slices. These instructions are suitable for beginning experimentalists but may be useful for veteran muscle physiologists hoping to reacquaint themselves with macroscopic functional analyses.
Effect of the Number of Micro-Osteoperforations on the Rate of Tooth Movement and Periodontal Response in Mice
Authors: Erdenebat Tselmuun , Lee Dong-Joon , Kim Su-Jung , Choi Yoon Jeong , Kim Eun-Jung , Choi Eun-Hack , Liu Jing , Hwang Chung-Ju , Jung Han-Sung , Cha Jung-Yul
Published: March 2022

Accelerated tooth movement can be achieved using micro-osteoperforations (MOPs) to stimulate regeneration of the alveolar bone during minimally invasive surgical trauma. However, there is currently no standardized protocol and limited reports regarding the side effects of MOPs based on biological evidence. This study sought to evaluate the biological effects of the number of MOPs on orthodontic tooth movement (OTM) and the potential risk for root resorption. Male CD1 mice were divided into 4 groups based on the number of MOPs, as follows: Sham; 0MOP+OTM; 2MOP+OTM; and 4MOP+OTM groups. Tooth movement distance and the number of osteoclasts were higher whereas bone volume and trabecular number were lower in the 4MOP+OTM group compared to those of the 0MOP+OTM group. Immunofluorescent assay analysis indicated that the 4MOP+OTM group was positively associated with rapid cementum regeneration and periodontal ligament tissue formation. Our findings revealed that the MOP procedure affected tooth movement and did not significantly contribute to root resorption, whereas it may promote constitutive activation of cementogenesis.
Microcytosis in Erythropoietic Protoporphyria
Authors: Graziadei Giovanna , Duca Lorena , Granata Francesca , De Luca Giacomo , De Giovanni Anna , Brancaleoni Valentina , Nava Isabella , Di Pierro Elena
Published: March 2022

Partial deficiency of the last enzyme of the heme biosynthetic pathway, namely, ferrochelatase (FECH), is responsible for erythropoietic protoporphyria (EPP) in humans. This disorder is characterized by painful skin photosensitivity, due to excessive protoporphyrin IX (PPIX) production in erythrocytes. Although several papers report the presence of iron deficiency anemia in about 50% of EPP patients, there is still no a conclusive explanation of the why this occurs. In the present work, we explored hematological indices and iron status in 20 unrelated Italian EPP patients in order to propose a new hypothesis. Our data show that microcytosis is present in EPP patients also in the absence of anemia and iron deficiency with a link between PPIX accumulation and reduced MCV, probably indicating an indirect condition of heme deficiency. Patients studied had a downward shift of iron parameters due to increased hepcidin concentrations only in a state of repleted iron stores. Interestingly, hemoglobin synthesis was not limited by iron supply except in cases with further iron loss, in which concomitantly increased soluble transferrin (Tf) receptor (sTfR) levels were detected. The mechanisms involved in the iron uptake downregulation in EPP remain unclear, and the role of PPIX accumulation in microcytosis.