bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Media Use, Psychological Distress and Knowledge, Attitude, and Practices Regarding the COVID-19 Among a Sample of the Population of Pakistan
Authors: Rizwan Muhammad , Ahmad Tauseef , Qi Xuehong , Murad Manal Abdulaziz , Baig Mukhtiar , Sagga Abdullah Khalid , Tariq Saba , Baig Fizzah , Naz Rozina , Hui Jin
Published: October 2021

This study was conducted to assess social media (SM) use, psychological distress, and knowledge, attitude, and practices (KAP) regarding the coronavirus disease 2019 (COVID-19) among a sample of the population of Pakistan. A cross-sectional study was conducted in Multan, Pakistan between April and May 2020. Demographics details, SM use, psychological distress, and KAP on the COVID-19 were investigated. A total of 800 respondents were analyzed out of which 33.5% (n = 268) were women. No gender-wise difference was found in the terms of SM use and duration of SM use. Women were prone to have psychological disorders such as anxiety, depression, and stress than men in the current COVID-19 pandemic. The mean knowledge score of men was significantly higher compared to women (18.69 ± 4.20 vs. 16.89 ± 3.04, p < 0.001), while the mean score of the attitude and practices on the COVID-19 prevention measures was significantly better in women (p = 0.012 and p < 0.001, respectively). The psychological problems such as anxiety (p < 0.001) and depression scores (p = 0.033) were higher among women than men. The stress score was also higher in women but not significantly higher (p = 0.079). The knowledge was significantly correlated with attitude, anxiety, depression, and stress. The regression analysis showed that the COVID-19-related KAPs are the predictors of psychological suffering of an individual. The female gender was positively associated with anxiety and depression. The SM use was the predictor of the stress. Male respondents had significantly more knowledge of the COVID-19 than female respondents, but women had significantly better attitudes and practiced the COVID-19 prevention measures. Gender is a significant determinant of psychological distress and KAP about the COVID-19. The government has already taken significant steps to limit the spread of the disease; however, much more effort is required to tackle this COVID-19 pandemic.
Lactobacilli as Anti-biofilm Strategy in Oral Infectious Diseases: A Mini-Review
Authors: Giordani Barbara , Parolin Carola , Vitali Beatrice
Published: October 2021

The spread of biofilm-related diseases in developed countries has led to increased mortality rates and high health care costs. A biofilm is a community of microorganisms that is irreversibly attached to a surface, behaving very differently from planktonic cells and providing resistance to antimicrobials and immune response. Oral diseases are an excellent example of infection associated with the formation of highly pathogenic biofilms. It is generally accepted that, when the oral homeostasis is broken, the overgrowth of pathogens is facilitated. Among them, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are the main etiological agents of periodontitis, while Streptococcus mutans is strongly associated with the onset of dental caries. Other microorganisms, such as the fungus Candida albicans, may also be present and contribute to the severity of infections. Since the common antibiotic therapies usually fail to completely eradicate biofilm-related oral diseases, alternative approaches are highly required. In this regard, the topical administration of probiotics has recently gained interest in treating oral diseases. Thus, the present mini-review focuses on the possibility of using Lactobacillus spp. as probiotics to counteract biofilm-mediated oral infections. Many evidence highlight that Lactobacillus living cells can impede the biofilm formation and eradicate mature biofilms of different oral pathogens, by acting through different mechanisms. Even more interestingly, lactobacilli derivatives, namely postbiotics (soluble secreted products) and paraprobiotics (cell structural components) are able to trigger anti-biofilm effects too, suggesting that they can represent a novel and safer alternative to the use of viable cells in the management of biofilm-related oral diseases.
The Capacity to Produce Hydrogen Sulfide (H2S) via Cysteine Degradation Is Ubiquitous in the Human Gut Microbiome
Authors: Braccia Domenick J. , Jiang Xiaofang , Pop Mihai , Hall A. Brantley
Published: October 2021

As one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such asDesulfovibrioandBilophilaspecies. However, an alternative source for H2S production, cysteine degradation, is present in some gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in all known gut microbes. We classify mechanisms of cysteine degradation into primary, secondary, and erroneous levels of H2S production and perform a comprehensive search for primary, secondary, and erroneous cysteine-degrading enzymes in 4,644 non-redundant bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalog. Of the 4,644 genomes we have putatively identified 2,046 primary, 1,951 secondary, and 5 erroneous cysteine-degrading species. We identified the presence of at least one putative cysteine-degrading bacteria in metagenomic data of 100% of 6,623 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomic data of 100% of 736 samples taken from 318 individuals. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate-reducing bacteria across healthy controls, IBD patients and CRC patients (p< 2.2e-16, Wilcoxon rank sum test). Although we have linked many taxa with the potential for cysteine degradation, experimental validation is required to establish the H2S production potential of the gut microbiome. Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.
Wild Halophytic Phragmites karka Biomass Saccharification by Bacterial Enzyme Cocktail
Authors: Ansari Immad , Ejaz Uroosa , Abideen Zainul , Gulzar Salman , Syed Muhammad Noman , Liu Jing , Li Wang , Fu Pengcheng , Sohail Muhammad
Published: October 2021

Graphical Abstract

Saccharification of phragmites karka.
The Comparative Abilities of a Small Laccase and a Dye-Decoloring Peroxidase From the Same Bacterium to Transform Natural and Technical Lignins
Authors: Vuong Thu V. , Singh Rahul , Eltis Lindsay D. , Master Emma R.
Published: October 2021

The relative ability of the small laccase (sLac) and dye-decoloring peroxidase (DyP2) from Amycolatopsis sp. 75iv2 to transform a variety of lignins was investigated using time-of-flight secondary ion mass spectrometry (ToF-SIMS). The enzymes modified organosolv hardwood lignin to different extents even in the absence of an added mediator. More particularly, sLac decreased the lignin modification metric S (S-lignin)/Ar (total aromatics) by 58% over 16h, while DyP2 lowered this ratio by 31% in the absence of exogenous H2O2. When used on their own, both sLac and DyP2 also modified native lignin present in aspen wood powder, albeit to lesser extents than in the organosolv lignin. The addition of ABTS for sLac and Mn2+ as well as H2O2 for DyP2 led to increased lignin modification in aspen wood powder as reflected by a decrease in the G/Ar metric by up to a further 13%. This highlights the importance of exogenous mediators for transforming lignin within its native matrix. Furthermore, the addition of ABTS reduced the selectivity of sLac for S-lignin over G-lignin, indicating that the mediator also altered the product profiles. Finally, when sLac was included in reactions containing DyP2, in part to generate H2O2in situ, the relative abundance of lignin products differed from individual enzymatic treatments. Overall, these results identify possible routes to tuning lignin modification or delignification through choice of enzyme and mediator. Moreover, the current study expands the application of ToF-SIMS to evaluating enzyme action on technical lignins, which can accelerate the discovery and engineering of industrially relevant enzymes for lignin valorization.
Disentangling the Effects of Ocean Carbonation and Acidification on Elemental Contents and Macromolecules of the Coccolithophore Emiliania huxleyi
Authors: Xie Emei , Xu Kui , Li Zhengke , Li Wei , Yi Xiangqi , Li Hongzhou , Han Yonghe , Zhang Hong , Zhang Yong
Published: October 2021

Elemental contents change with shifts in macromolecular composition of marine phytoplankton. Recent studies focus on the responses of elemental contents of coccolithophores, a major calcifying phytoplankton group, to changing carbonate chemistry, caused by the dissolution of anthropogenically derived CO2 into the surface ocean. However, the effects of changing carbonate chemistry on biomacromolecules, such as protein and carbohydrate of coccolithophores, are less documented. Here, we disentangled the effects of elevated dissolved inorganic carbon (DIC) concentration (900 to 4,930μmolkg−1) and reduced pH value (8.04 to 7.70) on physiological rates, elemental contents, and macromolecules of the coccolithophore Emiliania huxleyi. Compared to present DIC concentration and pH value, combinations of high DIC concentration and low pH value (ocean acidification) significantly increased pigments content, particulate organic carbon (POC), and carbohydrate content and had less impact on growth rate, maximal relative electron transport rate (rETRmax), particulate organic nitrogen (PON), and protein content. In high pH treatments, elevated DIC concentration significantly increased growth rate, pigments content, rETRmax, POC, particulate inorganic carbon (PIC), protein, and carbohydrate contents. In low pH treatments, the extents of the increase in growth rate, pigments and carbohydrate content were reduced. Compared to high pH value, under low DIC concentration, low pH value significantly increased POC and PON contents and showed less impact on protein and carbohydrate contents; however, under high DIC concentration, low pH value significantly reduced POC, PON, protein, and carbohydrate contents. These results showed that reduced pH counteracted the positive effects of elevated DIC concentration on growth rate, rETRmax, POC, PON, carbohydrate, and protein contents. Elevated DIC concentration and reduced pH acted synergistically to increase the contribution of carbohydrate–carbon to POC, and antagonistically to affect the contribution of protein–nitrogen to PON, which further shifted the carbon/nitrogen ratio of E. huxleyi.
Eradication of Porphyromonas gingivalis Persisters Through Colloidal Bismuth Subcitrate Synergistically Combined With Metronidazole
Authors: Wang Chuan , Li Xuan , Cheng Tianfan , Sun Hongzhe , Jin Lijian
Published: October 2021

Microbial persisters enable the development of certain intrinsic strategies for survival with extreme tolerance to multiple antimicrobials. Porphyromonas gingivalis is considered to be the “keystone” periodontopathogen. Indeed, periodontitis, as a highly common inflammatory disease, is the major cause of severe tooth loss and edentulism in adults globally, and yet it is crucially involved in various systemic comorbidities like diabetes. We have recently revealed P. gingivalis persisters-induced perturbation of immuno-inflammatory responses and effective suppression of this key pathogen by bismuth drugs. This study further explored novel approaches to eradicating P. gingivalis persisters through synergistic combination of colloidal bismuth subcitrate (CBS) with traditional antibiotics. P. gingivalis (ATCC 33277) cells in planktonic and biofilm states were cultured to stationary phase, and then treated with metronidazole (100 mg/L), amoxicillin (100 mg/L), CBS, (100 μM) and combinations of these medications, respectively. Persister survival rate was calculated by colony-forming unit. Cell viability and cytotoxicity of CBS were assessed in human gingival epithelial cells (HGECs). Notably, CBS combined with metronidazole enabled the effective eradication of P. gingivalis persisters in planktonic mode, and nearly eliminated their existence in biofilm mode. Importantly, CBS exhibited no effects on the viability of HGECs, along with minimal cytotoxicity (<5%) even at a high concentration (400 μM). This pioneering study shows that P. gingivalis persisters could be well eliminated via the synergistic combination of CBS with metronidazole. Our findings may contribute to developing novel approaches to tackling periodontitis and inflammatory systemic comorbidities.
Daptomycin Resistance Occurs Predominantly in vanA-Type Vancomycin-Resistant Enterococcus faecium in Australasia and Is Associated With Heterogeneous and Novel Mutations
Authors: Li Lucy , Higgs Charlie , Turner Adrianna M. , Nong Yi , Gorrie Claire L. , Sherry Norelle L. , Dyet Kristin H. , Seemann Torsten , Williamson Deborah A. , Stinear Timothy P. , Howden Benjamin P. , Carter Glen P.
Published: October 2021

Healthcare associated infections caused by vancomycin-resistant Enterococcus faecium (VREfm) have a major impact on health outcomes. VREfm is difficult to treat because of intrinsic and acquired resistance to many clinically used antimicrobials, with daptomycin being one of the few last line therapeutic options for treating multidrug-resistant VREfm. The emergence of daptomycin-resistant VREfm is therefore of serious clinical concern. Despite this, the impact that daptomycin-resistant VREfm have on patient health outcomes is not clearly defined and knowledge on the mechanisms and genetic signatures linked with daptomycin resistance in VREfm remains incomplete. To address these knowledge gaps, phenotypic daptomycin susceptibility testing was undertaken on 324 E. faecium isolates from Australia and New Zealand. Approximately 15% of study isolates were phenotypically resistant to daptomycin. Whole genome sequencing revealed a strong association between vanA-VREfm and daptomycin resistance, with 95% of daptomycin-resistant study isolates harbouring vanA. Genomic analyses showed that daptomycin-resistant VREfm isolates were polyclonal and carried several previously characterised mutations in the liaR and liaS genes as well as several novel mutations within the rpoB, rpoC, and dltC genes. Overall, 70% of daptomycin-resistant study isolates were found to carry mutations within the liaR, rpoB, rpoC, or dltC genes. Finally, in a mouse model of VREfm bacteraemia, infection with the locally dominant daptomycin-resistant clone led to reduced daptomycin treatment efficacy in comparison to daptomycin-susceptible E. faecium. These findings have important implications for ongoing VREfm surveillance activities and the treatment of VREfm infections.
The Kinocidin Interleukin-26 Shows Immediate Antimicrobial Effects Even to Multi-resistant Isolates
Authors: Hansen Bjoern-Thore , Maschkowitz Gregor , Podschun Rainer , Fickenscher Helmut
Published: October 2021

The cationic proinflammatory cytokine Interleukin 26 (IL-26) shows antibacterial activity and inhibits the replication of cytomegalovirus and hepatitis C virus. This study evaluates the early microbicidal activities of IL-26 against major bacterial species including multi-resistant variants and Candida albicans. Recombinant IL-26 was bacterially expressed and studied for its microbicidal effects in culture. We show that IL-26 has strong 90% bactericidal activities against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Similarly, IL-26 sensitivity was also detectable in vancomycin-resistant Enterococcus species, methicillin-resistant S. aureus, and carbapenem-resistant A. baumannii clinical isolates. Additionally, a significant, albeit weak fungicidal effect against Candida albicans was observed. Activities against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were not detectable. The proinflammatory cytokine and kinocidin IL-26 shows strong bactericidal activities against A. baumannii and, almost selectively, against Gram-positive bacteria.
Blood Pressure After Endovascular Thrombectomy and Malignant Cerebral Edema in Large Vessel Occlusion Stroke
Authors: Huang Xianjun , Xu Junfeng , Yang Ke , Xu Youqing , Yuan Lili , Cai Qiankun , Xu Xiangjun , Yang Qian , Zhou Zhiming , Zhu Shuanggen , Liu Xinfeng
Published: October 2021

Background: Elevated blood pressure (BP) can cause blood–brain barrier disruption and facilitates brain edema formation. We aimed to investigate the association of BP level after thrombectomy with the development of malignant cerebral edema (MCE) in patients treated with endovascular thrombectomy (EVT).

Methods: Consecutive patients who underwent EVT for an anterior circulation ischemic stroke were enrolled from three comprehensive stroke centers. BP was measured hourly during the first 24 h after thrombectomy. MCE was defined as swelling causing a midline shift on the follow-up imaging within 5 days after EVT. Associations of various BP parameters, including mean BP, maximum BP (BPmax), and BP variability (BPV), with the development of MCE were analyzed.

Results: Of the 498 patients (mean age 66.9 ± 11.7 years, male 58.2%), 97 (19.5%) patients developed MCE. Elevated mean systolic BP (SBP) (OR, 1.035; 95% CI, 1.006–1.065; P = 0.017) was associated with a higher likelihood of MCE. The best SBPmax threshold that predicted the development of MCE was 165 mmHg. Additionally, increases in BPV, as evaluated by SBP standard deviation (OR, 1.061; 95% CI, 1.003–1.123; P = 0.039), were associated with higher likelihood of MCE.

Interpretation: Elevated mean SBP and BPV were associated with a higher likelihood of MCE. Having a SBPmax > 165 mm Hg was the best threshold to discriminate the development of MCE. These results suggest that continuous BP monitoring after EVT could be used as a non-invasive predictor for clinical deterioration due to MCE. Randomized clinical studies are warranted to address BP goal after thrombectomy.
Radiological Manifestation of Neurological Complications in the Course of SARS-CoV-2 Infection
Authors: Sklinda Katarzyna , Dorobek Małgorzata , Wasilewski Piotr G. , Dreżewski Karol , Dȩbicka Marta , Walecki Jerzy , Mruk Bartosz
Published: October 2021

Many reports suggest the SARS-CoV-2 infection may result in neurological complications. A wide spectrum of clinical syndromes have been reported, including both central and peripheral nervous system. Such symptoms may be a consequence of a direct viral injury, secondary to systemic inflammatory response, autoimmune processes, ischemic lesions or combination of these. Anosmia and dysgeusia are highly prevalent in the early stage of infection. Cerebrovascular events in patients with COVID-19 have also been documented with increasing frequency. Some cases of parainfectious autoimmune neurologic manifestations concurrent with active SARS-CoV-2 infection have been described, including hemorrhagic necrotizing encephalopathy, Guillain-Barré and Miller-Fisher syndromes. There are also a few reports documenting encephalitis and acute demyelinating encephalomyelitis (ADEM) in the course of COVID-19. There is also a growing number of cases of patients after recovery from COVID-19 with psychosomatic disorders, manifesting with memory disfunction, cognitive functions disorders, depression or other affective disorders, which may lead to a decrease of intellectual functions. Many of these neurological manifestations of the infection are possible to distinguish using radiological imaging techniques. It plays a very important role in evaluating the course of COVID-19 as well as diagnosing respiratory complications and choosing a proper management of infected patients. Similarly, radiological techniques play crucial role in identifying the cause of neurological symptoms connected to SARS-CoV-2 infection, being one of the most important elements of diagnostics. Especially in case of the presence of nervous system implication, using radiological imaging techniques to monitor the emerging onset of various symptoms is crucial to assess the severity and scope of involvement. Quick diagnostic process and identifying complications as fast as possible in order to implement specific treatment can be crucial to avoid long-term secondary conditions and accelerate the recovery period. In this review, we present the most important neurological complications that may occur in the course of SARS-CoV-2 infection and summarize their radiological manifestations.
Nitric Oxide Synthase Type 1 Methylation Is Associated With White Matter Microstructure in the Corpus Callosum and Greater Panic Disorder Severity Among Panic Disorder Patients
Authors: Xu Huazhen , Zhong Yuan , Yuan Shiting , Wu Yun , Ma Zijuan , Hao Ziyu , Ding Huachen , Wu Huiqing , Liu Gang , Pang Manlong , Liu Na , Wang Chun , Zhang Ning
Published: October 2021

Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding.

Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD.

Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = −1.731 to −0.034).

Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.
Interlimb Coordination Performance in Seated Position in Persons With Multiple Sclerosis: Reduced Amplitude Over 6 min and Higher Coordination Variability in Persons With Walking Fatigability
Authors: Goetschalckx Mieke , Van Geel Fanny , Meesen Raf , Triccas Lisa Tedesco , Geraerts Marc , Moumdjian Lousin , Feys Peter
Published: October 2021

Background: Walking fatigability is prevalent in MS and can be measured by a percentage distance decline during a 6-min walking test. Walking is characterized by an accurate and consistent interlimb antiphase coordination pattern. A decline in coordination each minute during a 6-min walking test is observed in persons with MS (pwMS). Measuring coordination during a 6-min seated coordination task with minimized balance and strength requirements, is assumed to examine a more fundamental interlimb antiphase coordination pattern in pwMS. This research aimed to answer the following research question: How does interlimb antiphase coordination pattern change during a seated coordination task in pwMS with walking fatigability (WF), non-walking fatigability (NWF) and Healthy Controls (HC)?

Methods: Thirty-five pwMS and 13 HC participated. Interlimb coordination was assessed by a seated 6-min coordination task (6MCT) with the instruction to perform antiphase lower leg movements as fast as possible. Outcomes were Phase Coordination Index (PCI) and movement parameters (amplitude, frequency).

Results: Mixed models revealed a significant effect of time for the the variability of generating interlimb movements, with a difference in mean values between WF and HC. A significant group∗time interaction effect was found for movement amplitude, represented by a significant decrease in movement amplitude in the WF group from minute 1 to the end of the task.

Conclusion: The higher variability in interlimb coordination and decrease in movement amplitude over time during the 6MCT in the WF group could be an indicator of decreased control of fundamental antiphase coordination pattern in pwMS with walking fatigability.

Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT04142853 (registration date: October 29, 2019) and NCT03938558 (registration date: May 6, 2019).
Sleep-Aware Adaptive Deep Brain Stimulation Control: Chronic Use at Home With Dual Independent Linear Discriminate Detectors
Authors: Gilron Ro’ee , Little Simon , Wilt Robert , Perrone Randy , Anso Juan , Starr Philip A.
Published: October 2021

Adaptive deep brain stimulation (aDBS) is a promising new technology with increasing use in experimental trials to treat a diverse array of indications such as movement disorders (Parkinson’s disease, essential tremor), psychiatric disorders (depression, OCD), chronic pain and epilepsy. In many aDBS trials, a neural biomarker of interest is compared with a predefined threshold and stimulation amplitude is adjusted accordingly. Across indications and implant locations, potential biomarkers are greatly influenced by sleep. Successful chronic embedded adaptive detectors must incorporate a strategy to account for sleep, to avoid unwanted or unexpected algorithm behavior. Here, we show a dual algorithm design with two independent detectors, one used to track sleep state (wake/sleep) and the other used to track parkinsonian motor state (medication-induced fluctuations). Across six hemispheres (four patients) and 47 days, our detector successfully transitioned to sleep mode while patients were sleeping, and resumed motor state tracking when patients were awake. Designing “sleep aware” aDBS algorithms may prove crucial for deployment of clinically effective fully embedded aDBS algorithms.
Functional and Neuropathological Evidence for a Role of the Brainstem in Autism
Authors: Baizer Joan S.
Published: October 2021

The brainstem includes many nuclei and fiber tracts that mediate a wide range of functions. Data from two parallel approaches to the study of autistic spectrum disorder (ASD) implicate many brainstem structures. The first approach is to identify the functions affected in ASD and then trace the neural systems mediating those functions. While not included as core symptoms, three areas of function are frequently impaired in ASD: (1) Motor control both of the limbs and body and the control of eye movements; (2) Sensory information processing in vestibular and auditory systems; (3) Control of affect. There are critical brainstem nuclei mediating each of those functions. There are many nuclei critical for eye movement control including the superior colliculus. Vestibular information is first processed in the four nuclei of the vestibular nuclear complex. Auditory information is relayed to the dorsal and ventral cochlear nuclei and subsequently processed in multiple other brainstem nuclei. Critical structures in affect regulation are the brainstem sources of serotonin and norepinephrine, the raphe nuclei and the locus ceruleus. The second approach is the analysis of abnormalities from direct study of ASD brains. The structure most commonly identified as abnormal in neuropathological studies is the cerebellum. It is classically a major component of the motor system, critical for coordination. It has also been implicated in cognitive and language functions, among the core symptoms of ASD. This structure works very closely with the cerebral cortex; the cortex and the cerebellum show parallel enlargement over evolution. The cerebellum receives input from cortex via relays in the pontine nuclei. In addition, climbing fiber input to cerebellum comes from the inferior olive of the medulla. Mossy fiber input comes from the arcuate nucleus of the medulla as well as the pontine nuclei. The cerebellum projects to several brainstem nuclei including the vestibular nuclear complex and the red nucleus. There are thus multiple brainstem nuclei distributed at all levels of the brainstem, medulla, pons, and midbrain, that participate in functions affected in ASD. There is direct evidence that the cerebellum may be abnormal in ASD. The evidence strongly indicates that analysis of these structures could add to our understanding of the neural basis of ASD.
Quantitative Expression of Key Cancer Markers in the AS-30D Hepatocarcinoma Model
Authors: Briones-Orta Marco A. , Delgado-Coello Blanca , Gutiérrez-Vidal Roxana , Sosa-Garrocho Marcela , Macías-Silva Marina , Mas-Oliva Jaime
Published: October 2021

Hepatocellular carcinoma is one of the cancers with the highest mortality rate worldwide. HCC is often diagnosed when the disease is already in an advanced stage, making the discovery and implementation of biomarkers for the disease a critical aim in cancer research. In this study, we aim to quantify the transcript levels of key signaling molecules relevant to different pathways known to participate in tumorigenesis, with special emphasis on those related to cancer hallmarks and epithelial-mesenchymal transition, using as a model the murine transplantable hepatocarcinoma AS-30D. Using qPCR to quantify the mRNA levels of genes involved in tumorigenesis, we found elevated levels for Tgfb1 and Spp1, two master regulators of EMT. A mesenchymal signature profile for AS-30D cells is also supported by the overexpression of genes encoding for molecules known to be associated to aggressiveness and metastatic phenotypes such as Foxm1, C-met, and Inppl1. This study supports the use of the AS-30D cells as an efficient and cost-effective model to study gene expression changes in HCC, especially those associated with the EMT process.
Rapid Response to the Combination of Lenvatinib and Sintilimab in a Pancreatic Acinar Cell Carcinoma Patient With Elevated Alpha-Fetoprotein: A Case Report
Authors: Qin Lanqun , Shen Jie , Yang Yueling , Zou Zhengyun
Published: October 2021

A 48-year old woman was diagnosed with metastatic pancreatic acinar cell carcinoma (PACC) and with a marked elevation in alpha-fetoprotein (AFP), this being a recognized but uncommon feature of PACC. As she refused chemotherapy, the combined therapy of lenvatinib and sintilimab (lenvatinib 8 mg, orally, qd; and sintilimab 100 mg, intravenous glucose tolerance test, q21d) was given, which conferred significant tumor shrinkage and long progression-free survival (>21 months). This study is the first report and description of a PACC demonstrating favorable response to the combination therapy of an antiangiogenic agent and immunotherapy.
Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B
Authors: Shi Shupeng , Fan Zhihua , Liu Yang , Huang Chengyu , Zhou Jianda
Published: October 2021

Melanoma has gradually entered the public view because of its high morbidity and rising prevalence rate, which is a serious threat to human life and health. Recently, N6-methyladenine (m6A) modification has been increasingly confirmed as a potential role in the development of tumogenesis. The purpose of this study is to explore the role and function of m6a-related regulators in the development of melanoma disease at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. We screened and validated differential expression genes (DEGs) in m6A regulators via the GEO, GTEx, TCGA database. The biological processes and signaling pathway involved by DEGs were improved by constructing bioinformational methods such as PPI, GO enrichment, KEGG enrichment, GSEA enrichment, and immune infiltration analysis. And then, we explored the biological function of the key gene, SPRR1B, through cell invasion, migration, infiltration, and tissue chips. The gene IGF2BP3 which was differentially expressed in m6A regulatory factor gene was screened. The results of the enrichment analysis are significantly enriched in the biological processes and pathways of the skin barrier, epidermal differentiation, cytoskeleton, lymphocyte migration and other pathways, pointing to the direction of tumor immunity and tumor metastasis. Tumor immune-related genes YTHDC1, YTHDC2 and ALKBH5 were found. Knock SPRR1B reduction group had a significantly lower invasive ability, the ability to migrate. Nomogram prediction model shows that SPRR1B increased, expressing a worse prognosis. For this purpose, the relationship between m6A regulatory factor and melanoma progression was explored. At the same time, it was found that the abnormal up-regulated expression of SPRR1B before metastasis would lead to poor prognosis of melanoma. SPRR1B promotes the proliferation, invasion and migration of human melanoma cells.
Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer
Authors: Lan Sheng-Hui , Lin Shu-Ching , Wang Wei-Chen , Yang Yu-Chan , Lee Jenq-Chang , Lin Pei-Wen , Chu Man-Ling , Lan Kai-Ying , Zuchini Roberto , Liu Hsiao-Sheng , Wu Shan-Ying
Published: October 2021

Many studies reported that microRNAs (miRNAs) target autophagy-related genes to affect carcinogenesis, however, autophagy-deficiency-related miRNA dysfunction in cancer development remains poorly explored. During autophagic progression, we identified miR-449a as the most up-regulated miRNA. MiR-449a expression was low in the tumor parts of CRC patient specimens and inversely correlated with tumor stage and metastasis with the AUC (area under the curve) of 0.899 and 0.736 as well as poor overall survival rate, indicating that miR-449a has the potential to be a prognostic biomarker. In the same group of CRC specimens, low autophagic activity (low Beclin 1 expression and high p62 accumulation) was detected, which was significantly associated with miR-449a expression. Mechanistic studies disclosed that autophagy upregulates miR-449a expression through degradation of the coactivator p300 protein which acetylates the transcription factor Forkhead Box O1 (FoxO1). Unacetylated FoxO1 translocated to the nucleus and bound to the miR-449a promoter to drive gene expression. Either activation of autophagy by the inducer or overexpression of exogenous miR-449a decreases the expression of target gene LEF-1 and cyclin D1, which lead to decreased proliferation, colony formation, migration, and invasion of CRC cells. Autophagy-miR-449a-tartet genes mediated suppression of tumor formation was further confirmed in the xenograft mouse model. In conclusion, this study reveals a novel mechanism wherein autophagy utilizes miR-449a-LEF1-cyclin D1 axis to suppress CRC tumorigenesis. Our findings open a new avenue toward prognosis and treatment of CRC patients by manipulating autophagy-miR-449a axis.
Conditionally Reprogrammed Cells and Robotic High-Throughput Screening for Precision Cancer Therapy
Authors: Alkhilaiwi Faris
Published: October 2021

Cancer is a devastating disease that takes the lives of millions of people globally every year. Precision cancer therapy is based on a patient’s tumor histopathology, expression analyses, and/or tumor RNA or DNA analysis. Only 2%–20% of patients with solid tumors benefit from genomics-based precision oncology. Therefore, functional diagnostics and patient-derived cancer models are needed for precision cancer therapy. In this review, we will summarize the potential use of conditional cell reprogramming (CR) and robotic high-throughput screening in precision cancer medicine. Briefly, the CR method includes the co-culturing of irradiated Swiss-3T3-J2 mouse fibroblast cells alongside digested primary non-pathogenic or pathogenic cells with the existence of Rho-associated serine–threonine protein kinase inhibitor called Y-27632, creating an exterior culture environment, allowing the cells to have the ability to gain partial properties of stem cells. On the other hand, quantitative high-throughput screening (qHTS) assays screen thousands of compounds that use cells in a short period of time. The combination of both technologies has the potential to become a driving force for precision cancer therapy.
FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis
Authors: Kim Jung Han , Jeong Soo Young , Jang Hyun Joo , Park Sung Taek , Kim Hyeong Su
Published: October 2021

The fibroblast growth factor-4 receptor (FGFR4) is a member of receptor tyrosine kinase. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor has been shown to increase genetic susceptibility to cancers. However, its prognostic impact in cancer patients still remains controversial. Herein, we performed this meta-analysis to evaluate the clinicopathological and prognostic impacts of the FGFR4 Gly388Arg polymorphism in patients with cancer. We carried out a computerized extensive search using PubMed, Medline, and Ovid Medline databases up to July 2021. From 44 studies, 11,574 patients were included in the current meta-analysis. Regardless of the genetic models, there was no significant correlation of the FGFR4 Gly388Arg polymorphism with disease stage 3/4. In the homozygous model (Arg/Arg vs. Gly/Gly), the Arg/Arg genotype tended to show higher rate of lymph node metastasis compared with the Gly/Gly genotype (odds ratio = 1.21, 95% confidence interval (CI): 0.99-1.49, p = 0.06). Compared to patients with the Arg/Gly or Arg/Arg genotype, those with the Gly/Gly genotype had significantly better overall survival (hazard ratios (HR) = 1.19, 95% CI: 1.05-1.35, p = 0.006) and disease-free survival (HR = 1.25, 95% CI: 1.03-1.53, p = 0.02). In conclusion, this meta-analysis showed that the FGFR4 Gly388Arg polymorphism was significantly associated with worse prognosis in cancer patients. Our results suggest that this polymorphism may be a valuable genetic marker to identify patients at higher risk of recurrence or mortality.
Survival in Metastatic Renal Cell Carcinoma Patients Treated With Sunitinib With or Without Cryoablation
Authors: Gu Cheng-Yuan , Wang Jun-jie , Zhang Hai-Liang , Shi Guo-Hai , Ye Ding-Wei
Published: October 2021

Background

Percutaneous cryoablation (PCA) has emerged as an alternative to extirpative management of small renal masses in select patients. In recent years, the use of targeted therapies has become mainstream, while the role of PCA in treating primary tumor is not well established among patients with metastatic renal cell carcinoma (mRCC). We sought to evaluate how mRCC patients react to PCA in combination with sunitinib.

Methods

We retrospectively identified patients with mRCC (primary tumor diameter ≤ 7 cm) treated with sunitinib between 2013 and 2019. These patients were categorized by initial treatment (cryoablation followed by sunitinib versus sunitinib only). Oncological outcomes and rate of adverse events were compared.

Results

Of the 178 patients analyzed, 65 underwent PCA prior to sunitinib. The median overall survival (OS) in the PCA-sunitinib group was 31.7 months (95% CI; 26.1-37.3), better than the sunitinib-only group, which reported a median OS of 19.8 months (95% CI; 17.1-22.4) (p < 0.001). The median progression-free survival (PFS) in patients treated with PCA-sunitinib versus sunitinib alone was 13.8 months (95% CI; 10.0-17.6) versus 7.2 months (95% CI: 6.1-8.3) (p < 0.005). No significant differences in adverse events were observed (p > 0.05).

Conclusions

PCA combined with sunitinib is associated with better survival outcomes than sunitinib alone in patients with mRCC. Careful patient selection remains warranted. These results should inform future prospective trials.
Albumin-To-Alkaline Phosphatase Ratio as a Novel and Promising Prognostic Biomarker in Patients Undergoing Esophagectomy for Carcinoma: A Propensity Score Matching Study
Authors: Zhu Xianying , Chen Dongni , Li Shuangjiang , Zhang Wenbiao , Li Yongjiang , Wang Xiaoyu , Zhou Jian , Wen Zhesheng
Published: October 2021

Background

Albumin-to-alkaline phosphatase ratio (AAPR) has been reported as a novel prognostic predictor for numerous solid tumors. We aimed to assess the prognostic role of preoperative AAPR in surgically resectable esophageal squamous cell carcinoma (ESCC) by a propensity score matching (PSM) analysis with predictive nomograms.

Methods

Our study was conducted in a single-center prospective database between June 2009 and December 2012. Kaplan-Meier analysis was used to distinguish the difference in survival outcomes between patients stratified by an AAPR threshold. Multivariable Cox proportional hazards regression model was finally generated to specify independent prognostic markers for the entire and PSM cohorts.

Results

A total of 497 patients with ESCC were included in this study. An AAPR of 0.50 was determined as the optimal cutoff point for prognostic outcome stratification. Patients with AAPR<0.50 had significantly worse overall survival (OS), and progression-free survival (PFS) compared to those with AAPR≥0.50 (Log-rank P<0.001). This significant difference remained stable in the PSM analysis. Multivariable analyses based on the entire and PSM cohorts consistently showed that AAPR<0.50 might be one of the most predominant prognostic factors resulting in unfavorable OS and PFS of ESCC patients undergoing esophagectomy (P<0.001). The nomograms consisting of AAPR and other independent prognostic factors further demonstrated a plausible predictive accuracy of postoperative OS and PFS.

Conclusion

AAPR can be considered as a simple, convenient and noninvasive biomarker with a significant prognostic effect in surgically resected ESCC.
Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes?
Authors: Ma Haiyan , Tang Zezhong , Xiao Feifan , Li Long , Li Yangfang , Tang Wenyan , Chen Liping , Kang Wenqing , Lu Yulan , Dong Xinran , Cheng Guoqiang , Wang Laishuan , Lu Wei , Yang Lin , Ni Qi , Peng Xiaomin , Wang Yao , Cao Yun , Wu Bingbing , Zhou Wenhao , Zhuang Deyi , Lin Guang , Wang Huijun
Published: October 2021

Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disorder-specific therapies. Our study aims to provide an overview of the genetic causes of NMA in patients from NICUs. We performed next-generation sequencing (NGS) on neonates with NMA from January 2016 to December 2019. Clinical features, genetic diagnoses, and their effects on clinical interventions were collected for analysis. In the 354 enrolled patients, 131 (37%) received genetic diagnoses; 95 (72.5%) of them were autosomal recessively inherited diseases. Two hundred and fifteen variants spanning 57 genes were classified as pathogenic (P) or likely pathogenic (LP) in 131 patients. The leading cause was metabolic disorders due to 35 genes found in 89 patients (68%). The other 42 NMA patients (32%) with 22 genes had malformations and renal, neuromuscular, and immune-hematological disorders. Seven genes (MMUT, MMACHC, CHD7, NPHS1, OTC, IVD, and PHOX2B) were noted in more than four patients, accounting for 48.9% (64/131) of the identified P/LP variants. Forty-six diagnosed patients with uncorrected NMA died or gave up. In conclusion, 37% of neonates with metabolic acidosis had genetic disorders. Next-generation sequencing should be considered when investigating the etiology of NMA in NICUs. Based on early molecular diagnoses, valuable treatment options can be provided for some genetic diseases to achieve better outcomes.
Respiratory Infections in Children During a Covid-19 Pandemic Winter
Authors: Diesner-Treiber Susanne C. , Voitl Peter , Voitl Julian J. M. , Langer Klara , Kuzio Ulrike , Riepl Angela , Patel Pia , Mühl-Riegler Alexandra , Mühl Bernhard
Published: October 2021

Background: The Covid-19 pandemic compelled the implementation of measures to curb the SARS CoV-2 spread, such as social distancing, wearing FFP2 masks, and frequent hand hygiene. One anticipated ramification of these measures was the containment of other pathogens. This prospective, longitudinal study aimed to investigate the spread of 22 common seasonal non-SARS-CoV-2 pathogens, such as RSV and influenza, among children with an acute respiratory infection during a pandemic.

Methods: Three hundred ninety children (0-24 months) admitted to Vienna's largest pediatric center with acute respiratory infection (November 2020-April 2021) were included in this study. The researchers tested nasal swabs for 22 respiratory pathogens by Multiplex PCR, documented clinical features and treatment, and evaluated data for a potential connection with the lockdown measures then in force.

Results: The 448 smears revealed the most common pathogens to be rhino-/enterovirus (41.4%), adenovirus (2.2%), and coronavirus NL63 (13.6%). While the first two were active throughout the entire season, coronaviruses peaked in the first trimester of 2021 in conjunction with the lift of the lockdown period (OR 4.371, 95%CI 2.34-8.136, P < 0.001). RSV, metapneumovirus, and influenza were absent.

Conclusion: This prospective, longitudinal study shows that Covid-19 measures suppressed the seasonal activity of influenza, RSV, and metapneumovirus among very young children, but not of rhino-/enterovirus and adenovirus. The 0-24 month-olds are considered the lowest risk group and were only indirectly affected by the public health measures. Lockdowns were negatively associated with coronaviruses infections.
Prevention of Cyclophosphamide-Induced Immunosuppression in Mice With Traditional Chinese Medicine Xuanfei Baidu Decoction
Authors: Yan Huimin , Lu Jia , Wang Jiabao , Chen Lu , Wang Yu , Li Lin , Miao Lin , Zhang Han
Published: October 2021

Background and aims: Xuanfei Baidu decoction (XFBD), a traditional Chinese medicine formulation, was designed and successfully applied for COVID-19 disease treatment in China, while the mechanism is still not clear.

Methods: To evaluate the protective effect of XFBD on immunosuppression in cyclophosphamide (CY)-treated mice, XFBD was orally administrated, the body weight was measured, and the immune organ index was calculated. HE staining was performed to analyze the pathological structures of the liver, spleen, and thymus. The levels of cytokines and immunoglobulin in the serum and spleen were evaluated by ELISA and RT-PCR. Splenic lymphocytes were isolated, and LPS-stimulated cell proliferation and the number of CD4+ and CD8+ T lymphocytes were evaluated.

Results: XFBD significantly suppressed body weight loss and increased the indices of spleen and thymus. The pathological alteration was much improved after XFBD administration. The reductions of TNF-α, IFN-γ, IgG, and IgM levels in serum and IL-2, IL-4, and IL-6 expressions in the spleen were all significantly alleviated by XFBD. Splenic lymphocyte proliferation in response to LPS was further enhanced after treatment with XFBD. The reduction of CD4+ and CD8+ T lymphocytes in CY-treated mice was also highly increased in XFBD groups.

Conclusion: Our findings suggested that XFBD played a crucial role in protection against immunosuppression in CY-treated mice and could be a potential candidate for immune modification and therapy.