bluuebunny/crossref_metadata_2025 huggingface dataset:
U-Shaped Association Between Serum Uric Acid and Short-Term Mortality in Patients With Infective Endocarditis
Authors: Wei Xuebiao , Fu Bingqi , Chen Xiaolan , Chen WeiTao , Wang Zhenqian , Yu Danqing , Jiang Guozhi , Chen Jiyan
Published: November 2021

Background

Increased uric acid (UA) levels have been reported to be associated with poor clinical outcomes in several conditions. However, the prognostic value of UA in patients with infective endocarditis (IE) is yet unknown.

Methods

A total of 1,117 patients with IE were included and divided into two groups according to the current definition of hyperuricemia (UA>420 μmol/L in men and >360 μmol/L in women): hyperuricemia group (n=336) and normouricemia group (n=781). The association between the UA level and short-term outcomes were examined.

Results

The in-hospital mortality was 6.2% (69/1117). Patients with hyperuricemia carried a higher risk of in-hospital death (9.8% vs. 4.6%, p=0.001). Hyperuricemia was not an independent risk factor for in-hospital death (adjusted odds ratio [aOR]=1.92, 95% confidence interval [CI]: 0.92-4.02, p=0.084). A U-shaped relationship was found between the UA level and in-hospital death (p<0.001). The in-hospital mortality was lower in patients with UA in the range 250–400 μmol/L. The aOR of in-hospital death in patients with UA>400 and <250 μmol/L was 3.48 (95% CI: 1.38-8.80, p=0.008) and 3.28 (95%CI: 1.27-8.51, p=0.015), respectively. Furthermore, UA>400 μmol/L (adjusted hazard ratio [aHR]=3.54, 95%CI: 1.77-7.07, p<0.001) and <250 μmol/L (aHR=2.23, 95%CI: 1.03-4.80, p=0.041) were independent risk factors for the 6-month mortality.

Conclusion

The previous definition of hyperuricemia was not suitable for risk assessment in patients with IE because of the U-shaped relationship between UA levels and in-hospital death. Low and high levels of UA were predictive of increased short-term mortality in IE patients.
Ketogenic Diets and Cardio-Metabolic Diseases
Authors: Zhang Weiyue , Guo Xin , Chen Lulu , Chen Ting , Yu Jiayu , Wu Chaodong , Zheng Juan
Published: November 2021

While the prevalence of cardio-metabolic diseases (CMDs) has become a worldwide epidemic, much attention is paid to managing CMDs effectively. A ketogenic diet (KD) constitutes a high-fat and low-carbohydrate diet with appropriate protein content and calories. KD has drawn the interests of clinicians and scientists regarding its application in the management of metabolic diseases and related disorders; thus, the current review aimed to examine the evidences surrounding KD and the CMDs to draw the clinical implications. Overall, KD appears to play a significant role in the therapy of various CMDs, which is manifested by the effects of KDs on cardio-metabolic outcomes. KD therapy is generally promising in obesity, heart failure, and hypertension, though different voices still exist. In diabetes and dyslipidemia, the performance of KD remains controversial. As for cardiovascular complications of metabolic diseases, current evidence suggests that KD is generally protective to obese related cardiovascular disease (CVD), while remaining contradictory to diabetes and other metabolic disorder related CVDs. Various factors might account for the controversies, including genetic background, duration of therapy, food composition, quality, and sources of KDs. Therefore, it’s crucial to perform more rigorous researches to focus on clinical safety and appropriate treatment duration and plan of KDs.
Impact of Different Modules of 21-Gene Assay in Early Breast Cancer Patients
Authors: Chen Mengdi , Liu Deyue , Chen Weilin , Chen Weiguo , Shen Kunwei , Wu Jiayi , Zhu Li
Published: November 2021

Background

The 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages.

Methods

A total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, >40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules.

Results

In patients >40 years, RS had a strong negative correlation with its estrogen module (ρ = −0.76 and −0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients.

Conclusions

RS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.
Process Simulation and Optimization of Anaerobic Co-Digestion
Authors: Inayat Abrar , Ahmed Shams Forruque , Djavanroodi F. , Al-Ali Fatima , Alsallani Mira , Mangoosh Shama
Published: November 2021

Anaerobic digestion (AD) is an established method that has been extensively utilized for waste management, waste treatment, and biogas production. Anaerobic co-digestion (AcoD) is regarded as a practical approach to address substrate characteristics and system optimization issues. The distinction between AcoD and mono-digestion is that AcoD has a higher organic loading and significant substrate composition variation. There are many factors involved in AcoD which affect the biogas plant’s production ability and performance. Using response surface methodology (RSM) to forecast the optimal conditions for maximum biogas output, this article provides an overview of the different operational parameters in the AcoD process, modeling of the AcoD process, and overall process optimization. Standard software used for AcoD process simulation are Aspen Plus, SuperPro Designer, BioWin, CFD, and MATLAB. Review addresses design, development, and optimization frameworks for biogas production systems that take numerous aspects into account. The most significant AcoD optimization parameters include temperature, co-substrate concentration, inoculum ratio (percent), and C/N ratio.
Early Life Stress Alters Gene Expression and Cytoarchitecture in the Prefrontal Cortex Leading to Social Impairment and Increased Anxiety
Authors: Usui Noriyoshi , Ono Yuta , Aramaki Ryoko , Berto Stefano , Konopka Genevieve , Matsuzaki Hideo , Shimada Shoichi
Published: November 2021

Early life stress (ELS), such as abuse, neglect, and maltreatment, exhibits a strong impact on the brain and mental development of children. However, it is not fully understood how ELS affects social behaviors and social-associated behaviors as well as developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice until adolescence and investigated these behaviors and PFC characteristics in adolescent mice. We found the ELS induced social impairments in social novelty, social interaction, and social preference in adolescent mice. We also observed increases of anxiety-like behaviors in ELS mice. In histological analysis, we found a reduced number of neurons and an increased number of microglia in the PFC of ELS mice. To identify the gene associated with behavioral and histological features, we analyzed transcriptome in the PFC of ELS mice and identified 15 differentially expressed genes involved in transcriptional regulation, stress, and synaptic signaling. Our study demonstrates that ELS influences social behaviors, anxiety-like behaviors through cytoarchitectural and transcriptomic alterations in the PFC of adolescent mice.
Rapid Identification of Secondary Structure and Binding Site Residues in an Intrinsically Disordered Protein Segment
Authors: Chandra Soumyanetra , Chattopadhyay Gopinath , Varadarajan Raghavan
Published: November 2021

Mycobacterium tuberculosis harbours nine toxin-antitoxin (TA) systems of the MazEF family. MazEF TA modules are of immense importance due to the perceived role of the MazF toxin in M. tuberculosis persistence and disease. The MazE antitoxin has a disordered C-terminal domain that binds the toxin, MazF and neutralizes its endoribonuclease activity. However, the structure of most MazEF TA complexes remains unsolved till date, obscuring structural and functional information about the antitoxins. We present a facile method to identify toxin binding residues on the disordered antitoxin. Charged residue scanning mutagenesis was used to screen a yeast surface displayed MazE6 antitoxin library against its purified cognate partner, the MazF6 toxin. Binding residues were deciphered by probing the relative reduction in binding to the ligand by flow cytometry. We have used this to identify putative antitoxin interface residues and local structure attained by the antitoxin upon interaction in the MazEF6 TA system and the same methodology is readily applicable to other intrinsically disordered protein regions.
Comprehensive Multi-Omics Identification of Interferon-γ Response Characteristics Reveals That RBCK1 Regulates the Immunosuppressive Microenvironment of Renal Cell Carcinoma
Authors: Xu Wenhao , Tao Juli , Zhu Wenkai , Liu Wangrui , Anwaier Aihetaimujiang , Tian Xi , Su Jiaqi , Shi Guohai , Huang Haineng , Wei Gaomeng , Li Chuanyu , Qu Yuanyuan , Zhang Hailiang , Ye Dingwei
Published: November 2021

Interferon-gamma (IFN-γ) has a complex role in modulating the tumor microenvironment (TME) during renal cell carcinoma (RCC) development. To define the role of IFN-γ response genes in RCC progression, we characterized the differential gene expression, prognostic implications, and DNA variation profiles of selected IFN-γ response signatures, which exhibited a significant hazard ratio for the overall survival (OS) and progression-free survival (PFS) of papillary, chromophobia, and clear cell RCC (ccRCC) patients (n = 944). Prognostic nomograms were constructed to predict the outcomes for ccRCC patients, highlighting the prognostic implications of RANBP2-type and C3HC4-type zinc finger containing 1 (RBCK1). Interestingly, large-scale pan-cancer samples (n = 12,521) and three single-cell RNA datasets revealed that RBCK1 showed markedly differential expression between cancer and normal tissues and significantly correlated with tumor-infiltrating immune cells, tumor purity, and immune checkpoint molecules, such as PD-L1, CTLA-4, LAG-3, and TIGIT in pan-cancer samples. Notably, the TIDE score was significantly higher in the RBCK1high group compared with the RBCK1low group in both ccRCC and RCC cohorts. Besides, immunohistochemistry staining showed significantly elevated RBCK1 expression in tumors (n = 50) compared with kidney samples (n = 40) from a real-world cohort, Fudan University Shanghai Cancer Center (FUSCC, Shanghai). After RBCK1 expression was confirmed in ccRCC, we found a significantly decreased number of infiltrating CD4+ T cells, CD4+ FOXP3+ Treg cells, M1 macrophages, and CD56bight/dim NK cells in the immune-cold RBCK1high group. In addition to the distinct heterogeneous immune microenvironment, the increased expression of RBCK1 predicted a prominently worse prognosis than the RBCK1low group for 232 ccRCC patients in the FUSCC proteomic cohort. Furthermore, after transfected with siRNA in human ccRCC cells, extraordinarily decreased cell proliferation, migration capacities, and prominently elevated apoptosis tumor cell proportion were found in the siRNA groups compared with the negative control group. In conclusion, this study identified IFN-γ response clusters, which might be used to improve the prognostic accuracy of immune contexture in the ccRCC microenvironment. Immune-cold RBCK1high patients have pro-tumorigenic immune infiltration and significantly worse outcomes than RBCK1low patients based on results from multi-omics to real-world data. Our discovery of novel independent prognostic indicators for RCC highlights the association between tumor alterations and immune phenotype.
Dissecting Host-Pathogen Interactions in TB Using Systems-Based Omic Approaches
Authors: Borah Khushboo , Xu Ye , McFadden Johnjoe
Published: November 2021

Tuberculosis (TB) is a devastating infectious disease that kills over a million people every year. There is an increasing burden of multi drug resistance (MDR) and extensively drug resistance (XDR) TB. New and improved therapies are urgently needed to overcome the limitations of current treatment. The causative agent, Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens that can manipulate host cell environment for adaptation, evading immune defences, virulence, and pathogenesis of TB infection. Host-pathogen interaction is important to establish infection and it involves a complex set of processes. Metabolic cross talk between the host and pathogen is a facet of TB infection and has been an important topic of research where there is growing interest in developing therapies and drugs that target these interactions and metabolism of the pathogen in the host. Mtb scavenges multiple nutrient sources from the host and has adapted its metabolism to survive in the intracellular niche. Advancements in systems-based omic technologies have been successful to unravel host-pathogen interactions in TB. In this review we discuss the application and usefulness of omics in TB research that provides promising interventions for developing anti-TB therapies.
Dendritic Cell Vaccination of Glioblastoma: Road to Success or Dead End
Authors: Datsi Angeliki , Sorg Rüdiger V.
Published: November 2021

Glioblastomas (GBM) are the most frequent and aggressive malignant primary brain tumor and remains a therapeutic challenge: even after multimodal therapy, median survival of patients is only 15 months. Dendritic cell vaccination (DCV) is an active immunotherapy that aims at inducing an antitumoral immune response. Numerous DCV trials have been performed, vaccinating hundreds of GBM patients and confirming feasibility and safety. Many of these studies reported induction of an antitumoral immune response and indicated improved survival after DCV. However, two controlled randomized trials failed to detect a survival benefit. This raises the question of whether the promising concept of DCV may not hold true or whether we are not yet realizing the full potential of this therapeutic approach. Here, we discuss the results of recent vaccination trials, relevant parameters of the vaccines themselves and of their application, and possible synergies between DCV and other therapeutic approaches targeting the immunosuppressive microenvironment of GBM.
HIV-1 Env Does Not Enable the Development of Protective Broadly Neutralizing Antibodies in an Experimental Autoimmune Encephalomyelitis Mouse Model
Authors: Siracusano Gabriel , Finardi Annamaria , Pastori Claudia , Martinelli Vittorio , Furlan Roberto , Lopalco Lucia
Published: November 2021

Recent studies showed that immunological tolerance may restrict the development of Env-specific autoreactive broadly neutralizing antibodies. This evidence is consistent with the finding that Env immunization of a systemic lupus erythematosus (SLE) murine model produced antibodies that neutralize tier 2 HIV-1 strains. In this study, we address the possibility of eliciting neutralizing anti-Env antibodies in other autoimmune diseases such as multiple sclerosis (MS). While, as reported for SLE, we showed for the first time that a small number of HIV-1 negative, relapsing remitting MS patients exhibited antibodies with neutralizing properties, our attempts at inducing those antibodies in a EAE mouse model of MS failed. The success in eliciting Env-specific neutralizing antibodies might be related to the specific characteristics of the autoimmune disease, or it might rely in improving the vaccination design. Studies using mouse models are useful to gain insight in how HIV-specific neutralizing antibody responses are regulated in order to develop a protective HIV-1 vaccine.
Blockade of CC Chemokine Receptor Type 3 Diminishes Pain and Enhances Opioid Analgesic Potency in a Model of Neuropathic Pain
Authors: Pawlik Katarzyna , Ciechanowska Agata , Ciapała Katarzyna , Rojewska Ewelina , Makuch Wioletta , Mika Joanna
Published: November 2021

Neuropathic pain is a serious clinical issue, and its treatment remains a challenge in contemporary medicine. Thus, dynamic development in the area of animal and clinical studies has been observed. The mechanisms of neuropathic pain are still not fully understood; therefore, studies investigating these mechanisms are extremely important. However, much evidence indicates that changes in the activation and infiltration of immune cells cause the release of pronociceptive cytokines and contribute to neuropathic pain development and maintenance. Moreover, these changes are associated with low efficacy of opioids used to treat neuropathy. To date, the role of CC chemokine receptor type 3 (CCR3) in nociception has not been studied. Similarly, little is known about its endogenous ligands (C-C motif ligand; CCL), namely, CCL5, CCL7, CCL11, CCL24, CCL26, and CCL28. Our research showed that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with upregulation of CCL7 and CCL11 in the spinal cord and dorsal root ganglia (DRG). Moreover, our results provide the first evidence that single and repeated intrathecal administration of the CCR3 antagonist SB328437 diminishes mechanical and thermal hypersensitivity. Additionally, repeated administration enhances the analgesic properties of morphine and buprenorphine following nerve injury. Simultaneously, the injection of SB328437 reduces the protein levels of some pronociceptive cytokines, such as IL-6, CCL7, and CCL11, in parallel with a reduction in the activation and influx of GFAP-, CD4- and MPO-positive cells in the spinal cord and/or DRG. Moreover, we have shown for the first time that an inhibitor of myeloperoxidase-4-aminobenzoic hydrazide may relieve pain and simultaneously enhance morphine and buprenorphine efficacy. The obtained results indicate the important role of CCR3 and its modulation in neuropathic pain treatment and suggest that it represents an interesting target for future investigations.
Paleo-Typhoon Events as Indicated by Coral Reef Boulder Deposits on the Southern Coast of Hainan Island, China
Authors: Zhou Liang , Gao Shu , Jia Jianjun , Yang Yang , Tong Changliang , Wang Aijun
Published: November 2021

The southern coast of Hainan Island, China, is one of the most frequently hit areas of tropical cyclones in the Northwest Pacific regions. Although some of the extreme typhoon events were known in historical times, quantitative information on the timing and magnitude of paleo-typhoon events in this coastal area remains rare. In the present study, a large number of coral reef boulders were found on the Xiaodonghai reef platform, on the south coast of Hainan Island. Morphometric analysis of the boulders shows an exponentially fining landward trend, indicating a storm origin; a wave-induced current velocity of 2.41–5.71 m/s during the storm events is required to transport the boulders that were originally situated outside the reef edge. Based on the U/Th and 14C dating for the age-indicating samples taken from the boulders, seven major periods with intense typhoon activities were identified for the last 4,000 years, i.e., 1800–1500 BCE, 1200–900 BCE, 50–120 CE, 550–800 CE, 900–1000 CE, 1350–1900 CE, and 1910–2000 CE. A comparison with the regional typhoon records in terms of climatic parameters in the northwestern Pacific and the South China Sea regions indicates that the longitudinal variations of intense typhoon frequency were mainly controlled by El Niño-Southern Oscillation (ENSO), dominantly modulated by the Intertropical Convergence Zone. Because of the future warming climate, there will be a trend of enhanced typhoon risk for the southern Hainan Island coasts.
Synthesis and Photocatalytic Degradation of Water to Produce Hydrogen from Novel Cerium Dioxide and Silver-Doped Cerium Dioxide Fiber Membranes by the Electrospinning Method
Authors: Pu Xingyu , Wang Chencheng , Chen Xingwang , Jin Jing , Li Wanfei , Chen Feng
Published: November 2021

The sol-gel method combined with the electrospinning technique were used to synthesize CeO2 nanofiber membranes and CeO2 fiber membranes doped with different contents of nano-silver. The thermal degradation behavior, phase structure, morphology, and optical and photocatalytic hydrogen production efficiency of CeO2 nanofiber membranes and CeO2 fiber membranes doped with different contents of nano-silver were studied. X-ray diffraction (XRD) results indicate that the increase of silver concentration can inhibit the formation of CeO2 crystal. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations show that in the prepared CeO2 with a diameter of about 100 nm and fiber membrane material doped with nano-silver, the fiber is made of a large number of accumulating grains. Analysis of optical properties found that the doped nano–silver CeO2 fiber membranes enhance the absorption of visible light and reduce the band gap of the material. Photocatalytic experiments show that the cerium dioxide nanofibers doped with nano-silver can greatly improve the photocatalytic performance of materials than that of pure CeO2. The Ag/CeO2 fiber membrane with the Ag/CeO2 molar ratio of 3:50 possesses the highest photocatalytic hydrogen production efficiency because of its high electron hole transfer and separation efficiency. This novel synthesis strategy can be used to prepare other broad band gap semiconductor oxides and enhance their photocatalytic activity.
Raman Microspectroscopy Goes Viral: Infection Dynamics in the Cosmopolitan Microalga, Emiliania huxleyi
Authors: Yakubovskaya Elena , Zaliznyak Tatiana , Martínez Joaquín Martínez , Taylor Gordon T.
Published: November 2021

Emiliania huxleyi is a cosmopolitan member of the marine phytoplankton. This species’ capacities for carbon sequestration and sulfur mobilization make it a key player in oceanic biogeochemical cycles that influence climate on a planetary scale. Seasonal E. huxleyi blooms are abruptly terminated by viral epidemics caused by a clade of large DNA viruses collectively known as coccolithoviruses (EhVs). EhVs thereby mediate a significant part of material and energy fluxes associated with E. huxleyi population dynamics. In this study, we use spontaneous Raman microspectroscopy to perform label-free and non-invasive measurements of the macromolecular composition of individual virions and E. huxleyi host cells. Our novel autofluorescence suppression protocol enabled spectroscopic visualization of evolving macromolecular redistributions in individual E. huxleyi cells at different stages of EhV infection. Material transfer from E. huxleyi hosts to single EhV-163 virions was confirmed by combining stable isotope probing (SIP) experiments with Raman microspectroscopy. Inheritance of the host cells’ 13C-enriched isotopic signature was quantified based on red shifts of Raman peaks characteristic of phenylalanine’s phenyl ring. Two-dimensional Raman mapping of EhV-infected E. huxleyi cells revealed that the compact region producing an intense Raman DNA signal (i.e., the nucleus) in healthy E. huxleyi cells becomes diffuse during the first hours of infection. Raman DNA emissions integrated throughout individual cells decreased during the infection cycle. Our observations are consistent with EhV-163 degrading the host’s nuclear DNA, scavenging released nucleotides for its own genome replication, and shedding newly-produced virions prior to host lysis via budding.
Optimizing Bioremediation: Elucidating Copper Accumulation Mechanisms of Acinetobacter sp. IrC2 Isolated From an Industrial Waste Treatment Center
Authors: Irawati Wahyu , Djojo Eric Santoso , Kusumawati Lucia , Yuwono Triwibowo , Pinontoan Reinhard
Published: November 2021

Acinetobacter sp. IrC2 is a copper-resistant bacterium isolated from an industrial waste treatment center in Rungkut, Surabaya. Copper-resistant bacteria are known to accumulate copper inside the cells as a mechanism to adapt to a copper-contaminated environment. Periplasmic and membrane proteins CopA and CopB have been known to incorporate copper as a mechanism of copper resistance. In the present study, protein profile changes in Acinetobacter sp. IrC2 following exposure to copper stress were analyzed to elucidate the copper resistance mechanism. Bacteria were grown in a Luria Bertani agar medium with and without CuSO4 supplementation. Intracellular copper ion accumulation was quantified using atomic absorption spectrophotometry. Changes in protein profile were assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results showed that 6 mM CuSO4 was toxic for Acinetobacter sp. IrC2, and as a response to this copper-stress condition, the lag phase was prolonged to 18 h. It was also found that the bacteria accumulated copper to a level of 508.01 mg/g of cells’ dry weight, marked by a change in colony color to green. The protein profile under copper stress was altered as evidenced by the appearance of five specific protein bands with molecular weights of 68.0, 60.5, 38.5, 24.0, and 20.5 kDa, suggesting the presence of CopA, multicopper oxidase (MCO), CopB, universal stress protein (Usp), and superoxide dismutase (SOD) and/or DNA-binding protein from starved cells, respectively. We proposed that the mechanism of bacterial resistance to copper involves CopA and CopB membrane proteins in binding Cu ions in the periplasm and excreting excess Cu ions as well as involving enzymes that play a role in the detoxification process, namely, SOD, MCO, and Usp to avoid cell damage under copper stress.
Identification, Characterization, and Antioxidant Potential of Bifidobacterium longum subsp. longum Strains Isolated From Feces of Healthy Infants
Authors: Zhao Li , Wang Song , Dong Jiahuan , Shi Jialu , Guan Jiaqi , Liu Deyu , Liu Fei , Li Bailiang , Huo Guicheng
Published: November 2021

Increasing evidence has indicated that oxidative stress is associated with the health of infants. Bifidobacterium, especially B. longum subsp. longum strains, are abundant in the gut microbiota of infants, which may have the potential to ameliorate oxidative damage. Thus, this study aimed to isolate and screen B. longum subsp. longum strains with probiotic characters and antioxidant properties as infants’ dietary supplements. In this study, 24 B. longum subsp. longum strains were isolated from 15 healthy infants identified via 16S rRNA and heat shock protein 60 (hsp60) sequences. B. longum subsp. longum B13, F2, K4, K5, K10, K13, and K15 strains were selected based on high values obtained from autoaggregation, hydrophobicity, and adhesion assays to HT-29 cells. Among these seven strains, B. longum subsp. longum F2, K5, K10, and K15 were selected according to the high tolerance of gastrointestinal tract conditions compared to Bifidobacterium animalis subsp. lactis BB-12. Among these four strains, B. longum subsp. longum K5 was susceptible to common antibiotics and showed the highest intestinal epithelial cell proliferation of CCD 841 CoN. Additionally, B. longum subsp. longum K5 showed a strong antioxidant capacity, and its supernatant exhibited better activity of reducing power, hydroxyl radical scavenging, and DPPH radical scavenging than that of the intact cells with cell-free extracts. The findings indicated that B. longum subsp. longum K5 could be used as a probiotic candidate in infant nutrition.
Whole Genome Sequencing Analysis of Bacillus thuringiensis GR007 Reveals Multiple Pesticidal Protein Genes
Authors: Pacheco Sabino , Gómez Isabel , Chiñas Marcos , Sánchez Jorge , Soberón Mario , Bravo Alejandra
Published: November 2021

Bacillus thuringiensis (Bt) are soil ubiquitous bacteria. They produce a great variability of insecticidal proteins, where certain of these toxins are used worldwide for pest control. Through their adaptation to diverse ecosystems, certain Bt strains have acquired genetic mobile elements by horizontal transfer, harboring genes that encode for different virulent factors and pesticidal proteins (PP). Genomic characterization of Bt strains provides a valuable source of PP with potential biotechnological applications for pest control. In this work, we have sequenced the complete genome of the bacterium Bt GR007 strain that is toxic to Spodoptera frugiperda and Manduca sexta larvae. Four replicons (one circular chromosome and three megaplasmids) were identified. The two largest megaplasmids (pGR340 and pGR157) contain multiple genes that codify for pesticidal proteins: 10 cry genes (cry1Ab, cry1Bb, cry1Da, cry1Fb, cry1Hb, cry1Id, cry1Ja, cry1Ka, cry1Nb, and cry2Ad), two vip genes (vip3Af and vip3Ag), two binary toxin genes (vpa2Ac and vpb1Ca), five genes that codify for insecticidal toxin components (Tc’s), and a truncated cry1Bd-like gene. In addition, genes that codify for several virulent factors were also found in this strain. Proteomic analysis of the parasporal crystals of GR007 revealed that they are composed of eight Cry proteins. Further cloning of these genes for their individual expression in Bt acrystalliferous strain, by means of their own intrinsic promoter showed expression of seven Cry proteins. These proteins display differential toxicity against M. sexta and S. frugiperda larvae, where Cry1Bb showed to be the most active protein against S. frugiperda larvae and Cry1Ka the most active protein against M. sexta larvae.
Demyelination of the Optic Nerve: An Underlying Factor in Glaucoma?
Authors: Xue Jingfei , Zhu Yingting , Liu Zhe , Lin Jicheng , Li Yangjiani , Li Yiqing , Zhuo Yehong
Published: November 2021

Neurodegenerative disorders are characterized by typical neuronal degeneration and axonal loss in the central nervous system (CNS). Demyelination occurs when myelin or oligodendrocytes experience damage. Pathological changes in demyelination contribute to neurodegenerative diseases and worsen clinical symptoms during disease progression. Glaucoma is a neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the optic nerve. Since it is not yet well understood, we hypothesized that demyelination could play a significant role in glaucoma. Therefore, this study started with the morphological and functional manifestations of demyelination in the CNS. Then, we discussed the main mechanisms of demyelination in terms of oxidative stress, mitochondrial damage, and immuno-inflammatory responses. Finally, we summarized the existing research on the relationship between optic nerve demyelination and glaucoma, aiming to inspire effective treatment plans for glaucoma in the future.
The Effect of Virtual Reality-Based Therapy on Improving Upper Limb Functions in Individuals With Stroke: A Randomized Control Trial
Authors: El-Kafy Ehab Mohamed Abd , Alshehri Mansour Abdullah , El-Fiky Amir Abdel-Raouf , Guermazi Mohamad Abdelhamid
Published: November 2021

Background: Stroke is a common cause of motor disability. The recovery of upper limb after stroke is poor, with few stroke survivors regaining some functional use of the affected upper limb. This is further complicated by the fact that the prolonged rehabilitation is accompanied by multiple challenges in using and identifying meaningful and motivated treatment tasks that may be adapted and graded to facilitate the rehabilitation program. Virtual reality-based therapy is one of the most innovative approaches in rehabilitation technology and virtual reality systems can provide enhanced feedback to promote motor learning in individuals with neurological or musculoskeletal diseases.

Purpose: This study investigated the effect of virtual reality-based therapy on improving upper limb functions in individuals with chronic stroke.

Methods: Forty Saudi individuals with chronic stroke (6–24 months following stroke incidence) and degree of spasticity ranged between 1, 1 + and 2 according to Modified Ashworth Scale were included in this study. Participants were randomly assigned into two groups, experimental and control, with the experimental group undertaking a conventional 1-h functional training program, followed by another hour of virtual reality-based therapy using Armeo Spring equipment and the control group received 2 h of a conventional functional training program. The treatment program was conducted three times per week for three successive months. The change in the scores of Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), WMFT-Time (time required to complete the test) and Hand Grip Strength (HGS) were recorded at baseline and after completion of the treatment. Parametric (paired and unpaired t-tests) non-parametric (Wilcoxon and Mann–Whitney tests) statistical tests were used to identify the differences within and between groups (experimental group and control group) and evaluation times (pre- and immediately post-treatment).

Results: Both groups showed significant differences (all, P < 0.05) in all measured variables after 3 months of the treatment. Individuals with stoke in the experimental group had a better improvement in ARAT (P < 0.01), WMFT (P < 0.01) and WMFT-Time (P < 0.01) scores after completion of the treatment compared to the control group. No significant difference in HGS scores was detected between groups after completion of the treatment (P = 0.252).

Conclusion: The use of combined treatment of virtual reality-based therapy and conventional functional training program is more effective for improving upper limb functions in individuals with chronic stroke than the use of the conventional program alone.
Theoretical Rationale for Design of Tasks in a Virtual Reality-Based Exergame for Rehabilitation Purposes
Authors: Bovim Lars Peder Vatshelle , Valved Lauritz , Bleikli Bendik , Geitung Atle Birger , Soleim Harald , Bogen Bård
Published: November 2021

Virtual reality games are playing a greater role in rehabilitation settings. Previously, commercial games have dominated, but increasingly, bespoke games for specific rehabilitation contexts are emerging. Choice and design of tasks for VR-games are still not always clear, however; some games are designed to motivate and engage players, not necessarily with the facilitation of specific movements as a goal. Other games are designed specifically for the facilitation of specific movements. A theoretical background for the choice of tasks seems warranted. As an example, we use a game that was designed in our lab: VR Walk. Here, the player walks on a treadmill while wearing a head-mounted display showing a custom-made virtual environment. Tasks include walking on a glass bridge across a drop, obstacle avoidance, narrowing path, walking in virtual footsteps, memory, and selection tasks, and throwing and catching objects. Each task is designed according to research and theory from movement science, exercise science, and cognitive science. In this article, we discuss how for example walking across a glass bridge gives perceptual challenges that may be suitable for certain medical conditions, such as hearing loss, when perceptual abilities are strained to compensate for the hearing loss. In another example, walking in virtual footsteps may be seen as a motor and biomechanical constraint, where the double support phase and base of support can be manipulated, making the task beneficial for falls prevention. In a third example, memory and selection tasks may challenge individuals that have cognitive impairments. We posit that these theoretical considerations may be helpful for the choice of tasks and for the design of virtual reality games.
Experiences of Stroke Survivors and Clinicians With a Fully Immersive Virtual Reality Treadmill Exergame for Stroke Rehabilitation: A Qualitative Pilot Study
Authors: Moan Merete Endresen , Vonstad Elise Klæbo , Su Xiaomeng , Vereijken Beatrix , Solbjør Marit , Skjæret-Maroni Nina
Published: November 2021

Use of VR-games is considered a promising treatment approach in stroke rehabilitation. However, there is little knowledge on the use and expectations of patients and health professionals regarding the use of treadmill walking in a fully immersive virtual environment as a rehabilitation tool for gait training for stroke survivors. The objectives of the current study were to determine whether stroke survivors can use fully immersive VR utilizing modern HMDs while walking on a treadmill without adverse effects, and to investigate the experiences of stroke survivors and clinicians after testing with focus on acceptability and potential utilization in rehabilitation. A qualitative research design with semi-structured interviews was used to collect data. Five stroke survivors and five clinicians participated in the study and tested a custom-made VR-game on the treadmill before participating in individual semi-structured interview. Data were analyzed through thematic analysis. The analysis of the interview data identified two main categories: (1) experiencing acceptability through safety and motivation, and (2) implementing fully immersive VR in rehabilitation. Both stroke survivors' and clinicians enjoyed the treadmill-based VR-game and felt safe when using it. The stroke survivors experienced motivation for exercising and achievement by fulfilling tasks during the gaming session as the VR-game was engaging. The clinicians found additional motivation by competing in the game. Both groups saw a potential for use in gait rehabilitation after stroke, on the premise of individual adaptation to each patient's needs, and the technology being easy to use. The findings from this qualitative study suggest that a fully immersive treadmill-based VR-game is acceptable and potentially useful as part of gait rehabilitation after stroke, as it was positively received by both stroke survivors and clinicians working within stroke rehabilitation. The participants reported that they experienced motivation in the game through safety, engagement and achievement. They also saw the potential of implementing such a setup in their own rehabilitation setting. Elements that enable safety and engaging experience are important to maintain when using a fully immersive VR-game in stroke rehabilitation.
Visualizing Oscillations in Brain Slices With Genetically Encoded Voltage Indicators
Authors: Rhee Jun Kyu , Iwamoto Yayoi , Baker Bradley J.
Published: November 2021

Genetically encoded voltage indicators (GEVIs) expressed pan-neuronally were able to optically resolve bicuculline induced spontaneous oscillations in brain slices of the mouse motor cortex. Three GEVIs were used that differ in their timing of response to voltage transients as well as in their voltage ranges. The duration, number of cycles, and frequency of the recorded oscillations reflected the characteristics of each GEVI used. Multiple oscillations imaged in the same slice never originated at the same location, indicating the lack of a “hot spot” for induction of the voltage changes. Comparison of pan-neuronal, Ca2+/calmodulin-dependent protein kinase II α restricted, and parvalbumin restricted GEVI expression revealed distinct profiles for the excitatory and inhibitory cells in the spontaneous oscillations of the motor cortex. Resolving voltage fluctuations across space, time, and cell types with GEVIs represent a powerful approach to dissecting neuronal circuit activity.
Whole-Brain Afferent Inputs to the Caudate Nucleus, Putamen, and Accumbens Nucleus in the Tree Shrew Striatum
Authors: Ni Rong-Jun , Shu Yu-Mian , Li Tao , Zhou Jiang-Ning
Published: November 2021

Day-active tree shrews have a well-developed internal capsule (ic) that clearly separates the caudate nucleus (Cd) and putamen (Pu). The striatum consists of the Cd, ic, Pu, and accumbens nucleus (Acb). Here, we characterized the cytoarchitecture of the striatum and the whole-brain inputs to the Cd, Pu, and Acb in tree shrews by using immunohistochemistry and the retrograde tracer Fluoro-Gold (FG). Our data show the distribution patterns of parvalbumin (PV), nitric oxide synthase (NOS), calretinin (CR), and tyrosine hydroxylase (TH) immunoreactivity in the striatum of tree shrews, which were different from those observed in rats. The Cd and Pu mainly received inputs from the thalamus, motor cortex, somatosensory cortex, subthalamic nucleus, substantia nigra, and other cortical and subcortical regions, whereas the Acb primarily received inputs from the anterior olfactory nucleus, claustrum, infralimbic cortex, thalamus, raphe nucleus, parabrachial nucleus, ventral tegmental area, and so on. The Cd, Pu, and Acb received inputs from different neuronal populations in the ipsilateral (60, 67, and 63 brain regions, respectively) and contralateral (23, 20, and 36 brain regions, respectively) brain hemispheres. Overall, we demonstrate that there are species differences between tree shrews and rats in the density of PV, NOS, CR, and TH immunoreactivity in the striatum. Additionally, we mapped for the first time the distribution of whole-brain input neurons projecting to the striatum of tree shrews with FG injected into the Cd, Pu, and Acb. The similarities and differences in their brain-wide input patterns may provide new insights into the diverse functions of the striatal subregions.
Predictive Factors of Surgical Site Infection Following Cranioplasty: A Study Including 3D Printed Implants
Authors: Kim Myung Ji , Lee Hae-Bin , Ha Sung-Kon , Lim Dong-Jun , Kim Sang-Dae
Published: November 2021

In patients who have undergone decompressive craniectomy (DC), subsequent cranioplasty is required to reconstruct cranial defects. Surgical site infection (SSI) following cranioplasty is a devastating complication that can lead to cranioplasty failure. The aim of the present study, therefore, was to identify predictive factors for SSI following cranioplasty by reviewing procedures performed over a 10-year period. A retrospective analysis was performed for all patients who underwent cranioplasty following DC between 2010 and 2020 at a single institution. The patients were divided into two groups, non-SSI and SSI, in order to identify clinical variables that are significantly correlated with SSI following cranioplasty. Cox proportional hazards regression analyses were then performed to identify predictive factors associated with SSI following cranioplasty. A total of 172 patients who underwent cranioplasty, including 48 who received customized three-dimensional (3D) printed implants, were enrolled in the present study. SSI occurred in 17 patients (9.9%). Statistically significant differences were detected between the non-SSI and SSI groups with respect to presence of fluid collections on CT scans before and after cranioplasty. Presence of fluid collections on computed tomography (CT) scan before (p = 0.0114) and after cranioplasty (p < 0.0000) showed significant association with event-free survival rate for SSI. In a univariate analysis, significant predictors for SSI were fluid collection before (p = 0.0172) and after (p < 0.0001) cranioplasty. In a multivariate analysis, only the presence of fluid collection after cranioplasty was significantly associated with the occurrence of SSI (p < 0.0001). The present study investigated predictive factors that may help identify patients at risk of SSI following cranioplasty and provide guidelines associated with the procedure. Based on the results of the present study, only the presence of fluid collection on CT scan after cranioplasty was significantly associated with the occurrence of SSI. Further investigation with long-term follow-up and large-scale prospective studies are needed to confirm our conclusions.
Therapeutic Hypothermia Modulates the Relationships Between Indicators of Severity of Neonatal Hypoxic Ischemic Encephalopathy and Serum Biomarkers
Authors: Chavez-Valdez Raul , Miller Sarah , Spahic Harisa , Vaidya Dhananjay , Parkinson Charlamaine , Dietrick Barbara , Brooks Sandra , Gerner Gwendolyn J. , Tekes Aylin , Graham Ernest M. , Northington Frances J. , Everett Allen D.
Published: November 2021

Objective: To determine the changes due to therapeutic hypothermia (TH) exposure in the strength of association between traditional clinical and biochemical indicators of severity of neonatal hypoxic-ischemic encephalopathy (HIE) and serum biomarkers. We hypothesized that culmination of TH changes the strength of the relationships between traditional indicators of severity of HIE and serum biomarkers.

Methods: This was a single-center observational cohort study of 178 neonates with HIE treated with TH and followed with serum biomarkers: (i) brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) (neurotrophins); (ii) tau and glial fibrillary acidic protein (GFAP) (neural cell injury); and (iii) interleukin 6 (IL-6), IL-8, and IL-10 (cytokines), during their first week of life. Adjusted mixed-effect models tested associations with HIE indicators in relation to TH exposure.

Results: At admission, lower Apgar scores and base excess (BE) and higher lactate and nucleated red blood cell (NRBC) count correlated with higher Sarnat scores. These indicators of worse HIE severity, including higher Sarnat score, correlated with lower VEGF and higher tau, GFAP, and IL-10 levels at different time points. Within the first 24 h of life, patients with a Sarnat score >2 had lower VEGF levels, whereas only those with score of 3 also had higher GFAP and IL-10 levels. Tau levels increased during TH in patients with Sarnat score of 3, whereas tau and GFAP increased after TH in those with scores of 2. After adjustments, lower VEGF levels during TH and higher tau, GFAP, and IL-10 levels during and after TH were associated with worse Sarnat scores. Tau and GFAP relationship with Sarnat score became stronger after TH.

Conclusion: Therapeutic hypothermia exerts an independent modulatory effect in the relationships between traditional indicators of severity of HIE and serum biomarkers after adjustments. Thus, the timing of biomarker testing in relation to TH exposure must be carefully considered if biomarkers are proposed for patient stratification in novel clinical trials.