bluuebunny/crossref_metadata_2025 huggingface dataset:
High Serum Levels of Otolin-1 in Patients With Benign Paroxysmal Positional Vertigo Predict Recurrence
Authors: Fan Zhenyi , Hu Zhizhou , Han Weiwei , Lu Xiaoxiong , Liu Xiaoxia , Zhou Min , Yan Wang , Wu Yunqin
Published: March 2022

Background

Otolin-1 is an inner ear-specific protein that is exclusively expressed in otoconia and vestibule and cochlea cells. Recent investigations reported that otolin-1 can cross the blood-labyrinthine barrier and that the levels in serum well-reflected otolith status. Serum otolin-1 levels in patients with benign paroxysmal positional vertigo (BPPV) are significantly elevated compared with healthy controls. We aimed to explore whether otolin-1 can also serve as a biomarker for predicting BPPV recurrence.

Method

Patients at our institution with new-onset of idiopathic BPPV between May, 2017 and May, 2018 were recruited and followed up for 2 years. All demographic data of the patients were collected, and serum levels of otolin-1 and other laboratory indicators were measured and compared according to the recurrence status.

Results

A total of 74 patients, who met the inclusion criteria were enrolled in this study, of which 27 (36.5%) patients had suffered one or more episodes of recurrence after undergoing canal repositioning treatments during the study. The serum levels of otolin-1 in patients with recurrent BPPV were significantly higher than those in patients without recurrent BPPV (363.9 vs. 309.8 pg/ml, p = 0.001). In multivariate analysis comparing the second to fourth quartiles (Q2–Q4) against the first quartile (Q1) of otolin-1, the level of otolin-1 in Q4 could significantly predict BPPV recurrence, and the odds ratio (OR) was elevated by approximately 812% (OR = 9.12; 95% confidence interval [CI]: 1.44–57.9; p = 0.019).

Conclusion

High serum levels of otolin-1 were associated with an increased risk of BPPV recurrence, and further investigation is required to confirm this association and clarify the exact mechanism.
Factors Associated With Early and Late Post-stroke Fatigue in Patients With Mild Impairment. Results From the Stroke Cohort Study Augsburg
Authors: Kirchberger Inge , Wallner Florian , Linseisen Jakob , Zickler Philipp , Ertl Michael , Naumann Markus , Meisinger Christine
Published: March 2022

Background

Post-stroke fatigue is a common symptom after stroke. However, studies on the factors associated with early and late fatigue are scarce. The objective of this study was to identify variables associated with early and late fatigue.

Methods

In the German Stroke Cohort Augsburg (SCHANA) study, participants were interviewed during their hospital stay and completed a postal questionnaire 3 and 12 months post-stroke. Fatigue was assessed using the Fatigue Assessement Scale (FAS). In addition, depression was measured by the Patient Health Questionnaire (PHQ-9), general health status by the EQ-5D visual analog scale, and physical activity by the International Physical Activity Questionnaire (IPAQ). Multivariable regression models were used to determine the associations between FAS scores at 3 and 12 months post-stroke and demographic, psychosocial and health-related covariables.

Results

Among 505 participants, the frequency of fatigue was 31.1% 3 months and 29.1% 12 months post-stroke. Prior stroke (ß = 2.37, p = 0.0076), prior diagnosis of depression (ß = 5.04, p = 0.0001), higher NIHSS (ß = 0.25, p = 0.0360) and higher PHQ-9 scores (ß = 0.55, p < 0.0001) were significantly associated with higher fatigue levels 3 months post-stroke. Additionally, younger age (ß = −0.07, p = 0.0219), a worse rating of general health at baseline (ß = −0.04, p = 0.0287) and low pre-stroke physical activity (ß = −0.0004, p = 0.0089) were significantly associated with higher fatigue levels 12 months after stroke.

Conclusions

Fatigue is a common and persisting symptom even in patients with mild impairment. Prior depressive disorder and early depressive symptoms were the most relevant predictors of both early and late fatigue.
Liquid State Machine on SpiNNaker for Spatio-Temporal Classification Tasks
Authors: Patiño-Saucedo Alberto , Rostro-González Horacio , Serrano-Gotarredona Teresa , Linares-Barranco Bernabé
Published: March 2022

Liquid State Machines (LSMs) are computing reservoirs composed of recurrently connected Spiking Neural Networks which have attracted research interest for their modeling capacity of biological structures and as promising pattern recognition tools suitable for their implementation in neuromorphic processors, benefited from the modest use of computing resources in their training process. However, it has been difficult to optimize LSMs for solving complex tasks such as event-based computer vision and few implementations in large-scale neuromorphic processors have been attempted. In this work, we show that offline-trained LSMs implemented in the SpiNNaker neuromorphic processor are able to classify visual events, achieving state-of-the-art performance in the event-based N-MNIST dataset. The training of the readout layer is performed using a recent adaptation of back-propagation-through-time (BPTT) for SNNs, while the internal weights of the reservoir are kept static. Results show that mapping our LSM from a Deep Learning framework to SpiNNaker does not affect the performance of the classification task. Additionally, we show that weight quantization, which substantially reduces the memory footprint of the LSM, has a small impact on its performance.
Interleukin-17a Induces Neuronal Differentiation of Induced-Pluripotent Stem Cell-Derived Neural Progenitors From Autistic and Control Subjects
Authors: Gomes Ana Karolyne Santos , Dantas Rafaelly Mayara , Yokota Bruno Yukio , Silva André Luiz Teles e , Griesi-Oliveira Karina , Passos-Bueno Maria Rita , Sertié Andréa Laurato
Published: March 2022

Prenatal exposure to maternal immune activation (MIA) has been suggested to increase the probability of autism spectrum disorder (ASD). Recent evidence from animal studies indicates a key role for interleukin-17a (IL-17a) in promoting MIA-induced behavioral and brain abnormalities reminiscent of ASD. However, it is still unclear how IL-17a acts on the human developing brain and the cell types directly affected by IL-17a signaling. In this study, we used iPSC-derived neural progenitor cells (NPCs) from individuals with ASD of known and unknown genetic cause as well as from neurotypical controls to examine the effects of exogenous IL-17a on NPC proliferation, migration and neuronal differentiation, and whether IL-17a and genetic risk factors for ASD interact exacerbating alterations in NPC function. We observed that ASD and control NPCs endogenously express IL-17a receptor (IL17RA), and that IL-17a/IL17RA activation modulates downstream ERK1/2 and mTORC1 signaling pathways. Exogenous IL-17a did not induce abnormal proliferation and migration of ASD and control NPCs but, on the other hand, it significantly increased the expression of synaptic (Synaptophysin-1, Synapsin-1) and neuronal polarity (MAP2) proteins in these cells. Also, as we observed that ASD and control NPCs exhibited similar responses to exogenous IL-17a, it is possible that a more inflammatory environment containing other immune molecules besides IL-17a may be needed to trigger gene-environment interactions during neurodevelopment. In conclusion, our results suggest that exogenous IL-17a positively regulates the neuronal differentiation of human NPCs, which may disturb normal neuronal and synaptic development and contribute to MIA-related changes in brain function and behavior.
Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities
Authors: Gabriele Rebecca M. C. , Abel Emily , Fox Nick C. , Wray Selina , Arber Charles
Published: March 2022

Amyloid precursor protein (APP) and its cleavage fragment Amyloid-β (Aβ) have fundamental roles in Alzheimer’s disease (AD). Genetic alterations that either increase the overall dosage of APP or alter its processing to favour the generation of longer, more aggregation prone Aβ species, are directly causative of the disease. People living with one copy of APP are asymptomatic and reducing APP has been shown to lower the relative production of aggregation-prone Aβ species in vitro. For these reasons, reducing APP expression is an attractive approach for AD treatment and prevention. In this review, we will describe the structure and the known functions of APP and go on to discuss the biological consequences of APP knockdown and knockout in model systems. We highlight progress in therapeutic strategies to reverse AD pathology via reducing APP expression. We conclude that new technologies that reduce the dosage of APP expression may allow disease modification and slow clinical progression, delaying or even preventing onset.
Clinical and Functional Features of Epilepsy-Associated In-Frame Deletion Variants in SCN1A
Authors: Wang Jing-Yang , Tang Bin , Sheng Wen-Xiang , Hua Li-Dong , Zeng Yang , Fan Cui-Xia , Deng Wei-Yi , Gao Mei-Mei , Zhu Wei-Wen , He Na , Su Tao
Published: March 2022

Objective

Naturally occurring in-frame deletion is a unique type of genetic variations, causing the loss of one or more amino acids of proteins. A number of in-frame deletion variants in an epilepsy-associated gene SCN1A, encoding voltage gated sodium channel alpha unit 1.1 (Nav1.1), have been reported in public database. In contrast to the missense and truncation variants, the in-frame deletions in SCN1A remains largely uncharacterized.

Methods

We summarized the basic information of forty-four SCN1A in-frame deletion variants and performed further analysis on six variants identified in our cases with epilepsy. Mutants of the six in-frame deletions and one truncating variant used as comparison were generated and co-transfected with beta-1 and -2 subunits in tsA201 cells, followed by patch clamp recordings.

Results

Reviewing all the in-frame deletions showed that they spread over the entire Nav1.1 protein, without obvious “hot spots.” The dominant type (54%) was single residue loss. There was no obvious relationship between the length or locations of deletions and their clinical phenotypes. The six in-frame deletions were two single residue deletions (p.M400del and p.I1772del), one microdeletion (p.S128_F130del) and three macrodeletions (p.T303_R322del, p.T160_Y202del, and p.V1335_V1428del). They scatter and affect different functional domains, including transmembrane helices, pore region, and P-loop. Electrophysiological recordings revealed no measurable sodium current in all of the six mutants. In contrast, the truncating mutant p.M1619Ifs*7 that loses a long stretch of peptides retains partial function.

Significance

The complete loss-of-function in these shortened, abnormal mutants indicates that Nav1.1 protein is a highly accurate structure, and many of the residues have no redundancy to ion conductance. In-frame deletions caused particularly deleterious effect on protein function possibly due to the disruption of ordered residues.
The 14-3-3 Protein Family and Schizophrenia
Authors: Navarrete Meaghan , Zhou Yi
Published: March 2022

Schizophrenia is a debilitating mental disorder that affects approximately 1% of the world population, yet the disorder is not very well understood. The genetics of schizophrenia is very heterogenous, making it hard to pinpoint specific alterations that may cause the disorder. However, there is growing evidence from human studies suggesting a link between alterations in the 14-3-3 family and schizophrenia. The 14-3-3 proteins are abundantly expressed in the brain and are involved in many important cellular processes. Knockout of 14-3-3 proteins in mice has been shown to cause molecular, structural, and behavioral alterations associated with schizophrenia. Thus, 14-3-3 animal models allow for further exploration of the relationship between 14-3-3 and schizophrenia as well as the study of schizophrenia pathology. This review considers evidence from both human and animal model studies that implicate the 14-3-3 family in schizophrenia. In addition, possible mechanisms by which alterations in 14-3-3 proteins may contribute to schizophrenia-like phenotypes such as dopaminergic, glutamatergic, and cytoskeletal dysregulations are discussed.
Water and Beverages Intake Among Workers Amid the COVID-19 Pandemic in Indonesia
Authors: Sunardi Diana , Chandra Dian Novita , Medise Bernie Endyarni , Manikam Nurul Ratna Mutu , Friska Dewi , Lestari Wiji , Insani Putri Novia Choiri
Published: March 2022

As the COVID-19 pandemic hit worldwide in the early 2020, people were urged to alter their behavior to prevent disease spread, thus, led to change water intake. This study aimed to analyze water and beverage intake among health workers and general workers during COVID-19 pandemic in Indonesia. This study was a comparative descriptive study where the participants were 20–45-year-old health workers and general workers in Indonesia. Data collected included demographic, water and beverage intake, physical activity, nutrient intake, and body weight and height. All data collection was obtained online using self-reported questionnaire. Water intake data was collected for 7 days consecutively using a 7-day fluid record. There were 246 participants comprised of 102 (41.5%) general workers and 144 (58.5%) health workers who were analyzed in this study. All participants showed barely adequate intake of daily total fluid 1,882 (1,473–2,433) ml/day. Total fluid intake among general workers was 1,759 (1,447–2,396) ml/day, whereas in health workers it was slightly higher 1,939 (1,516–2,446) ml/day (p-value = 0.378). Among health workers who were highly exposed to patients with COVID-19 showed the highest percentage in drinking water adequately (20 participants, 60.6%) compared to health workers who worked under moderate (29 participants, 48.3%) and low (24 participants, 47.2%) level of exposure to patients with COVID-19. In conclusion, workers need to improve their daily fluid intake. This study also showed better behavior of water consumption among health workers compared to general workers despite of their strict personal protection equipment during working hour.
Green Banana Flour Contributes to Gut Microbiota Recovery and Improves Colonic Barrier Integrity in Mice Following Antibiotic Perturbation
Authors: Li Ping , Li Ming , Song Ying , Huang Xiaochang , Wu Tao , Xu Zhenjiang Zech , Lu Hui
Published: March 2022

Green banana flour (GBF) is rich in resistant starch that has been used as a prebiotic to exert beneficial effects on gut microbiota. In this study, GBF was evaluated for its capacity to restore gut microbiota and intestinal barrier integrity from antibiotics (Abx) perturbation by comparing it to natural recovery (NR) treatment. C57B/L 6 J mice were exposed to 3 mg ciprofloxacin and 3.5 mg metronidazole once a day for 2 weeks to induce gut microbiota dysbiosis model. Then, GBF intervention at the dose of 400 mg/kg body weight was conducted for 2 weeks. The results showed that mice treated with Abx displayed increased gut permeability and intestinal barrier disruption, which were restored more quickly with GBF than NR treatment by increasing the secretion of mucin. Moreover, GBF treatment enriched beneficial Bacteroidales S24-7, Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae that accelerated the imbalanced gut microbiota restoration to its original state. This study puts forward novel insights into the application of GBF as a functional food ingredient to repair gut microbiota from Abx perturbation.
Dietary Fiber Intake and Femoral Bone Mineral Density in Middle-Aged and Older US Adults: A Cross-Sectional Study of National Health and Nutrition Examination Survey 2013–2014
Authors: Tang Yuchen , Liu Jinmin , Zhang Xiaohui , Geng Bin
Published: March 2022

Sufficient dietary fiber intake (DFI) is considered necessary for human health. However, the association between DFI and bone mineral density (BMD) remains unclear. Therefore, this study aimed to investigate the association between DFI and BMD and to determine whether sex modifies the association between DFI and BMD. Participants aged ≥ 40 years from the 2013–2014 National Health and Nutrition Examination Survey were included in the final analysis. The association between DFI and BMD was evaluated using a multivariate linear regression model. The non-linear relationship between DFI and BMD was characterized by smooth curve fittings and generalized additive models. Finally, 1,935 participants with a mean age of 58.12 ± 11.84 years were included in the final analysis. The results revealed that DFI was positively associated with femoral BMD in the unadjusted model. However, no correlation was observed between DFI and femoral BMD after adjusting for covariates. Moreover, the results showed an inverted U-shaped association between total DFI and femoral BMD among men but not women for the nonlinear relationship between DFI and femoral BMD. In conclusion, our results indicate that DFI might not follow a linear relationship with femoral BMD, and sex factors might modify the association between DFI and BMD. Particularly, high total DFI might contribute to lower femoral neck BMD. However, more studies are needed to investigate whether the negative effect of high DFI on femoral BMD does exist and whether high DFI has clear biological effects on bone metabolism, such as increasing the risk of osteoporosis.
MicroRNAs/LncRNAs Modulate MDSCs in Tumor Microenvironment
Authors: Liu Xiaocui , Zhao Shang , Sui Hongshu , Liu Hui , Yao Minhua , Su Yanping , Qu Peng
Published: March 2022

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells derived from bone marrow that play critical immunosuppressive functions in the tumor microenvironment (TME), promoting cancer progression. According to base length, Non-coding RNAs (ncRNAs) are mainly divided into: microRNAs (miRNAs), lncRNAs, snRNAs and CircRNAs. Both miRNA and lncRNA are transcribed by RNA polymerase II, and they play an important role in gene expression under both physiological and pathological conditions. The increasing data have shown that MiRNAs/LncRNAs regulate MDSCs within TME, becoming one of potential breakthrough points at the investigation and treatment of cancer. Therefore, we summarize how miRNAs/lncRNAs mediate the differentiation, expansion and immunosuppressive function of tumor MDSCs in TME. We will then focus on the regulatory mechanisms of exosomal MicroRNAs/LncRNAs on tumor MDSCs. Finally, we will discuss how the interaction of miRNAs/lncRNAs modulates tumor MDSCs.
Transcriptomics Reveals the Mevalonate and Cholesterol Pathways Blocking as Part of the Bacterial Cyclodipeptides Cytotoxic Effects in HeLa Cells of Human Cervix Adenocarcinoma
Authors: Lázaro-Mixteco Pedro E. , González-Coronel José M. , Hernández-Padilla Laura , Martínez-Alcantar Lorena , Martínez-Carranza Enrique , López-Bucio Jesús Salvador , Guevara-García Ángel A. , Campos-García Jesús
Published: March 2022

The incidence of human cervix adenocarcinoma (CC) caused by papillomavirus genome integration into the host chromosome is the third most common cancer among women. Bacterial cyclodipeptides (CDPs) exert cytotoxic effects in human cervical cancer HeLa cells, primarily by blocking the PI3K/Akt/mTOR pathway, but downstream responses comprising gene expression remain unstudied. Seeking to understand the cytotoxic and anti-proliferative effects of CDPs in HeLa cells, a global RNA-Seq analysis was performed. This strategy permitted the identification of 151 differentially expressed genes (DEGs), which were either up- or down-regulated in response to CDPs exposure. Database analysis, including Gene Ontology (COG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed differential gene expression on cancer transduction signals, and metabolic pathways, for which, expression profiles were modified by the CDPs exposure. Bioinformatics confirmed the impact of CDPs in the differential expression of genes from signal transduction pathways such as PI3K-Akt, mTOR, FoxO, Wnt, MAPK, P53, TGF-β, Notch, apoptosis, EMT, and CSC. Additionally, the CDPs exposure modified the expression of cancer-related transcription factors involved in the regulation of processes such as epigenetics, DNA splicing, and damage response. Interestingly, transcriptomic analysis revealed the participation of genes of the mevalonate and cholesterol biosynthesis pathways; in agreement with this observation, total cholesterol diminished, confirming the blockage of the cholesterol synthesis by the exposure of HeLa cells to CDPs. Interestingly, the expression of some genes of the mevalonate and cholesterol synthesis such as HMGS1, HMGCR, IDI1, SQLE, MSMO1, SREBF1, and SOAT1 was up-regulated by CDPs exposure. Accordingly, metabolites of the mevalonate pathway were accumulated in cultures treated with CDPs. This finding further suggests that the metabolism of cholesterol is crucial for the occurrence of CC, and the blockade of the sterol synthesis as an anti-proliferative mechanism of the bacterial CDPs, represents a reasonable chemotherapeutic drug target to explore. Our transcriptomic study supports the anti-neoplastic effects of bacterial CDPs in HeLa cells shown previously, providing new insights into the transduction signals, transcription factors and metabolic pathways, such as mevalonate and cholesterol that are impacted by the CDPs and highlights its potential as anti-neoplastic drugs.
Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship
Authors: Slominski Radomir M. , Sarna Tadeusz , Płonka Przemysław M. , Raman Chander , Brożyna Anna A. , Slominski Andrzej T.
Published: March 2022

Melanin pigment plays a critical role in the protection against the harmful effects of ultraviolet radiation and other environmental stressors. It is produced by the enzymatic transformation of L-tyrosine to dopaquinone and subsequent chemical and biochemical reactions resulting in the formation of various 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) oligomers—main constituents of eumelanin, and benzothiazine and benzothiazole units of pheomelanin. The biosynthesis of melanin is regulated by sun exposure and by many hormonal factors at the tissue, cellular, and subcellular levels. While the presence of melanin protects against the development of skin cancers including cutaneous melanoma, its presence may be necessary for the malignant transformation of melanocytes. This shows a complex role of melanogenesis in melanoma development defined by chemical properties of melanin and the nature of generating pathways such as eu- and pheomelanogenesis. While eumelanin is believed to provide radioprotection and photoprotection by acting as an efficient antioxidant and sunscreen, pheomelanin, being less photostable, can generate mutagenic environment after exposure to the short-wavelength UVR. Melanogenesis by itself and its highly reactive intermediates show cytotoxic, genotoxic, and mutagenic activities, and it can stimulate glycolysis and hypoxia-inducible factor 1-alpha (HIF-1α) activation, which, combined with their immunosuppressive effects, can lead to melanoma progression and resistance to immunotherapy. On the other hand, melanogenesis-related proteins can be a target for immunotherapy. Interestingly, clinicopathological analyses on advanced melanomas have shown a negative correlation between tumor pigmentation and diseases outcome as defined by overall survival and disease-free time. This indicates a “Yin and Yang” role for melanin and active melanogenesis in melanoma development, progression, and therapy. Furthermore, based on the clinical, experimental data and diverse effects of melanogenesis, we propose that inhibition of melanogenesis in advanced melanotic melanoma represents a realistic adjuvant strategy to enhance immuno-, radio-, and chemotherapy.
Exosomes Regulate the Epithelial–Mesenchymal Transition in Cancer
Authors: Jiang Jingwen , Li Jiayu , Zhou Xiumei , Zhao Xueqin , Huang Biao , Qin Yuan
Published: March 2022

Exosomes are important mediators of intercellular communication and participate in complex biological processes by transferring a variety of bioactive molecules between cells. Epithelial–mesenchymal transition (EMT) is a process in which the cell phenotype changes from epithelioid to mesenchymal-like. EMT is also an important process for cancer cells by which they acquire invasive and metastatic capabilities, which aggravates the degree of tumor malignancy. Numerous studies have demonstrated that exosomes encapsulate various components, such as microRNAs and proteins, and transfer information between tumor cells or between tumor cells and the tumor microenvironment, thereby regulating the EMT process. Exosomes can also be used for cancer diagnosis and treatment or as a drug delivery platform. Thus, they can be used as a therapeutic tool to control the occurrence of EMT and affect cancer progression. In this review, we summarize the latest research advancements in the regulation of the EMT process in tumor cells by the contents of exosomes. Furthermore, we discuss the potential and challenges of using exosomes as a tool for cancer treatment.
The Correlation Between Mechanical Ventilation Duration, Pediatric Sequential Organ Failure Assessment Score, and Blood Lactate Level in Children in Pediatric Intensive Care
Authors: Lu Fang , Qin Hua , Li Ai-Min
Published: March 2022

Objective

This study aimed to investigate whether the ventilation duration for children undergoing invasive mechanical ventilation (IMV) in pediatric intensive care unit (PICU) is correlated with pediatric sequential organ failure (pSOFA) score, white blood cell (WBC) count, blood lactate level, and duration of fever.

Methods

Retrospectively reviewed that the medical records of patients who received IMV in the PICU of Jingzhou Central Hospital between January 2018 and December 2020. According to the duration of IMV in diagnosis-related groups, these patients were divided into two groups: group A, ventilation duration <96 h, and group B, ventilation duration ≥96 h. Each group's pSOFA scores, WBC counts, blood lactate levels, and durations of fever were compared. Logistic regression analysis was used to analyze the clinical risk factors of ventilation duration ≥96 h, and the receiver operator characteristic (ROC) curve was drawn.

Results

A total of 42 patients were included, including 23 in group A and 19 in group B. The difference in pSOFA score between group A and group B was statistically significant (P < 0.05), while the differences in blood lactate level, duration of fever, and WBC count between the two groups were not statistically significant (P > 0.05). Logistic regression analysis was conducted to analyze the influencing factors of mechanical ventilation duration ≥96 h. An ROC curve was drawn with pSOFA score as a test variable and duration of mechanical ventilation ≥96 h as a state variable, revealing that the area under the curve was 0.76 (SE = 0.075, 95% CI: 0.614–0.906, P = 0.005). The sensitivity and specificity were 68.4 and 73.9%, respectively, and the corresponding pSOFA score was 7.5.

Conclusion

When the pSOFA score ≥8, the risk of mechanical ventilation duration ≥96 h increases.
Cardiac MRI and Echocardiography for Early Diagnosis of Cardiomyopathy Among Boys With Duchenne Muscular Dystrophy: A Cross-Sectional Study
Authors: Prakash Nidhi , Suthar Renu , Sihag Bhupendra Kumar , Debi Uma , Kumar Rohit Manoj , Sankhyan Naveen
Published: March 2022

Background

Cardiomyopathy is an important cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). Early diagnosis is a prerequisite for timely institution of cardioprotective therapies.

Objective

We compared cardiac MRI (CMRI) with transthoracic echocardiography (TTE) including tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) for diagnosis of cardiomyopathy in early ambulatory boys with DMD.

Methodology

This cross-sectional study was conducted between June 2018 and December 2020. Consecutive boys between 7 and 15 years of age with DMD were enrolled. Percentage ejection fraction (EF), fractional shortening, wall motion abnormalities, early diastolic mitral annulus velocity (Ea), medial mitral annulus ratio (E/Ea), and global strain were measured with STE. CMRI-derived EF, segmental hypokinesia, and late gadolinium enhancement (LGE) were studied and compared.

Results

A total of 38 ambulatory boys with DMD were enrolled. The mean age was 8.8 ± 1.6 years, and none had clinical features suggestive of cardiac dysfunction. In the TTE, EF was ≤55% in 5 (15%), FS was ≤28% in 3 (9%), and one each had left ventricular wall thinning and wall hypokinesia. In TDI, none had diastolic dysfunction, and STE showed reduced global strain of < 18% in 3 (9%) boys. CMRI-derived EF was ≤55% in 20 (53%) boys and CMRI showed the presence of left ventricular wall hypokinesia in 9 (24%) and LGE in 4 (11%) boys.

Conclusion

Cardiomyopathy remains clinically asymptomatic among early ambulatory boys with DMD. A significantly higher percentage of boys revealed early features of DMD-related cardiomyopathy in CMRI in comparison with echocardiography.
Case Report: Novel CA12 Homozygous Variant Causing Isolated Hyperchloridrosis in a Chinese Child With Hyponatremia
Authors: Han Meigui , Peng Min , Han Ziming , Zhu Xiaojuan , Huang Qian , Gu Weiyue , Guo Yong
Published: March 2022

Isolated hyperchloridrosis (HYCHL; OMIM 143860) is a rare autosomal recessive disorder caused by biallelic mutations in the carbonic anhydrase 12 (CA12; OMIM 603263) gene, which is characterized by abnormally high levels of salt in sweat that can lead to dehydration associated with low levels of sodium in the blood. To date, only four variants of the CA12 gene have been identified to be associated with HYCHL. Here, we presented a rare Chinese case of HYCHL in an infant with decreased food intake, mild diarrhea, severe dehydration, and hypovolemic shock who was hospitalized in our department three times. Laboratory tests showed hyponatremia and hypochloremia. Because of recurrent attacks, whole-exome sequencing (WES) was performed and revealed a novel homozygous missense variant c.763A>C (p.Thr255Pro) in the CA12 gene (NM_001218.5). In total 0.9% sodium chloride (NaCl) solution was orally administered until 1 year and 6 months of age. Followed up to 3 years of age, the patient showed good growth and development without similar manifestations. This study reported a novel CA12 gene mutation leading to HYCHL for the first time in China, which enriched the genotype of HYCHL and emphasized the early suspicion and identification of the rare condition to adequate treatment.
Traditional Knowledge to Contemporary Medication in the Treatment of Infectious Disease Dengue: A Review
Authors: Dhiman Mamta , Sharma Lakshika , Dadhich Abhishek , Dhawan Poonam , Sharma M. M.
Published: March 2022

Dengue has become a worldwide affliction despite incessant efforts to search for a cure for this long-lived disease. Optimistic consequences for dengue vaccine are implausible as the efficiency is tied to previous dengue virus (DENV) exposure and a very high cost is required for large-scale production of vaccine. Medicinal plants are idyllic substitutes to fight DENV infection since they constitute important components of traditional medicine and show antiviral properties, although the mechanism behind the action of bioactive compounds to obstruct viral replication is less explored and yet to be discovered. This review includes the existing traditional knowledge on how DENV infects and multiplies in the host cells, conscripting different medicinal plants that obtained bioactive compounds with anti-dengue properties, and the probable mechanism on how bioactive compounds modulate the host immune system during DENV infection. Moreover, different plant species having such bioactive compounds reported for anti-DENV efficiency should be validated scientificallyviadifferentin vitroandin vivostudies.
Proton Pump Inhibitors and Cancer: Current State of Play
Authors: Bridoux Marie , Simon Nicolas , Turpin Anthony
Published: March 2022

Background: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are overprescribed in patients with cancer; there is increasing evidence of their effects on cancer development and survival. The objective of this narrative review is to comprehensively identify cancer medications that have clinically meaningful drug–drug interactions (DDIs) with PPIs, including loss of efficacy or adverse effects, and to explore the association between PPIs and cancer.

Methods: A PubMed search of English language studies published from 1 January 2016, to 1 June 2021 was conducted. The search terms included “proton pump inhibitors,” “cancer,” “chemotherapy,” “immunotherapy,” “hormonotherapies,” “targeted therapies,” “tyrosine kinase inhibitors,” and “gut microbiome”. Recent and relevant clinical trials, meta-analyses, and reviews were included.

Results: PPIs may have pro-tumor activity by increasing plasma gastrin levels or anti-tumor activity by inhibiting V-ATPases. However, their impact on cancer survival remains unclear. PPIs may decrease the efficacy of some antineoplastic agents through direct DDIs (e.g., some tyrosine kinase inhibitors, capecitabine, irinotecan, methotrexate). More complex DDIs seem to exist for immunotherapies with indirect interactions through the microbiome. PPIs worsen hypomagnesemia, bone loss, iron, and vitamin B12 deficiencies but may have a protective effect on the renal system.

Discussion/Conclusions: PPIs may interact with the cancer microbiome and the efficacy of various antineoplastic agents, although only a few DDIs involving PPIs are clinically significant. Further pharmaco-epidemiological studies are warranted, but physicians should be aware of the potential consequences of PPI use, which should be dose appropriate and prescribed according to guidelines.
Design and Characterization of Paclitaxel-Loaded Polymeric Nanoparticles Decorated With Trastuzumab for the Effective Treatment of Breast Cancer
Authors: Sakhi Mirina , Khan Abad , Iqbal Zafar , Khan Ismail , Raza Abida , Ullah Asmat , Nasir Fazli , Khan Saeed Ahmad
Published: March 2022

The aim of the study was to design and formulate an antibody-mediated targeted, biodegradable polymeric drug delivery system releasing drug in a controlled manner to achieve a therapeutic goal for the effective treatment of breast cancer. Antibody-mediated paclitaxel-loaded PLGA polymeric nanoformulations were prepared by the solvent evaporation method using different experimental parameters and compatibility studies. The optimized formulations were selected for in vitro and in vivo evaluation and cytotoxicity studies. The in vitro drug release studies show a biphasic release pattern for the paclitaxel-loaded PLGA nanoparticles showing a burst release for 24 h followed by an extended release for 14 days; however, a more controlled and sustained release was observed for antibody-conjugated polymeric nanoparticles. The cytotoxicity of reference drug and paclitaxel-loaded PLGA nanoparticles with and without antibody was determined by performing MTT assay against MCF-7 cells. Rabbits were used as experimental animals for the assessment of various in vivo pharmacokinetic parameters of selected formulations. The pharmacokinetic parameters such as Cmax (1.18–1.33 folds), AUC0-t (39.38–46.55 folds), MRT (10.04–12.79 folds), t1/2 (3.06–4.6 folds), and Vd (6.96–8.38 folds) have been increased significantly while clearance (4.34–4.61 folds) has been decreased significantly for the selected nanoformulations as compared to commercially available paclitaxel formulation (Paclixil®). The surface conjugation of nanoparticles with trastuzumab resulted in an increase in in vitro cytotoxicity as compared to plain nanoformulations and commercially available conventional brand (Paclixil®). The developed PLGA-paclitaxel nanoformulations conjugated with trastuzumab have the desired physiochemical characteristics, surface morphology, sustained release kinetics, and enhanced targeting.
Capsaicin, a Phytochemical From Chili Pepper, Alleviates the Ultraviolet Irradiation-Induced Decline of Collagen in Dermal Fibroblast via Blocking the Generation of Reactive Oxygen Species
Authors: Wu Qiyun , Bai Panzhu , Guo Hongsheng , Guo Maggie S. S. , Xia Yingjie , Xia Yiteng , Gao Xiong , Wang Xiaoyang , Wu Jiahui , Dong Tina T. X. , Tsim Karl W. K.
Published: March 2022

Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.
Experimental Study of Imbibition Within Core Chips of Shale in Ordos Basin
Authors: Wu Jiang , Mu Lijun , Ren Dazhong , Liu Jin , Hui Honggang , Wang Zhenze
Published: March 2022

The main exploring technology of No.7 Yanchang Formation of the Triassic reservoir in the Ordos Basin adopts quasi-natural downhole energy driven by volume fracturing, and the region production thus cannot be improved by an injection well network. Enhanced oil recovery (EOR) has been carried out through an enhanced imbibition process during reservoir stimulation work. To further understand the oil-water displacement mechanism, a thin-cut chips of shale imbibition experimental study was carried out. Simultaneously, nuclear magnetic resonance (NMR) changes of the fluid within the pores of chips were measured. This method was used to evaluate the application effect of imbibition surfactant in use, and the field practice was compared and analyzed by means of a chemical tracer among dozens of clusters in the same horizontal well.
Investigation of Hydrogen Incorporations in Bulk Infinite-Layer Nickelates
Authors: Puphal P. , Pomjakushin V. , Ortiz R. A. , Hammoud S. , Isobe M. , Keimer B. , Hepting M.
Published: March 2022

Infinite-layer (IL) nickelates are an emerging class of superconductors, where the Ni1+ valence state in a square planar NiO2 coordination can only be reached via topotactic reduction of the perovskite phase. However, this topotactic soft chemistry with hydrogenous reagents is still at a stage of rapid development, and there are a number of open issues, especially considering the possibility of hydrogen incorporation. Here, we study the time dependence of the topotactic transformation of LaNiO3 to LaNiO2 for powder samples with x-ray diffraction and gas extraction techniques. While the hydrogen content of the powder increases with time, neutron diffraction shows no negative scattering of hydrogen in the LaNiO2 crystal lattice. The extra hydrogen appears to be confined to grain boundaries or secondary-phase precipitates. The average crystal structure, and possibly also the physical properties, of the primary LaNiO2 phase are, therefore, not noticeably affected by hydrogen residues created by the topotactic transformation.
Polarization-Entangled Two-Photon Absorption in Inhomogeneously Broadened Ensembles
Authors: Schlawin Frank
Published: March 2022

Entangled photons are promising candidates for a variety of novel spectroscopic applications. In this paper, we simulate two-photon absorption (TPA) of entangled photons in a molecular ensemble with inhomogeneous broadening. We compare our results with a homogeneously broadened case and comment on the consequences for the possible quantum enhancement of TPA cross sections. We find that, while there are differences in the TPA cross section, this difference always remains small and of the order unity. We further consider the impact of the polarization degrees of freedom and carry out the orientational average of a model system Hamiltonian. We find that certain molecular geometries can give rise to a substantial polarization dependence of the entangled TPA rate. This effect can increase the TPA cross section by up to a factor of five.
Rapid Prediction of Fig Phenolic Acids and Flavonoids Using Mid-Infrared Spectroscopy Combined With Partial Least Square Regression
Authors: Hssaini Lahcen , Razouk Rachid , Bouslihim Yassine
Published: March 2022

Graphical Abstract

Scheme diagram showing the research methodology and analytical approaches.
Melatonin Induced Cold Tolerance in Plants: Physiological and Molecular Responses
Authors: Qari Sameer H. , Hassan Muhammad Umair , Chattha Muhammad Umer , Mahmood Athar , Naqve Maria , Nawaz Muhammad , Barbanti Lorenzo , Alahdal Maryam A. , Aljabri Maha
Published: March 2022

Cold stress is one of the most limiting factors for plant growth and development. Cold stress adversely affects plant physiology, molecular and biochemical processes by determining oxidative stress, poor nutrient and water uptake, disorganization of cellular membranes and reduced photosynthetic efficiency. Therefore, to recover impaired plant functions under cold stress, the application of bio-stimulants can be considered a suitable approach. Melatonin (MT) is a critical bio-stimulant that has often shown to enhance plant performance under cold stress. Melatonin application improved plant growth and tolerance to cold stress by maintaining membrane integrity, plant water content, stomatal opening, photosynthetic efficiency, nutrient and water uptake, redox homeostasis, accumulation of osmolytes, hormones and secondary metabolites, and the scavenging of reactive oxygen species (ROS) through improved antioxidant activities and increase in expression of stress-responsive genes. Thus, it is essential to understand the mechanisms of MT induced cold tolerance and identify the diverse research gaps necessitating to be addressed in future research programs. This review discusses MT involvement in the control of various physiological and molecular responses for inducing cold tolerance. We also shed light on engineering MT biosynthesis for improving the cold tolerance in plants. Moreover, we highlighted areas where future research is needed to make MT a vital antioxidant conferring cold tolerance to plants.
Patterns of Volatile Diversity Yield Insights Into the Genetics and Biochemistry of the Date Palm Fruit Volatilome
Authors: Flowers Jonathan M. , Hazzouri Khaled M. , Lemansour Alain , Capote Tiago , Gros-Balthazard Muriel , Ferrand Sylvie , Lebrun Marc , Amiri Khaled M. A. , Purugganan Michael D.
Published: March 2022

Volatile organic compounds are key components of the fruit metabolome that contribute to traits such as aroma and taste. Here we report on the diversity of 90 flavor-related fruit traits in date palms (Phoenix dactylifera L.) including 80 volatile organic compounds, which collectively represent the fruit volatilome, as well as 6 organic acids, and 4 sugars in tree-ripened fruits. We characterize these traits in 148 date palms representing 135 varieties using headspace solid-phase microextraction gas chromatography. We discovered new volatile compounds unknown in date palm including 2-methoxy-4-vinylphenol, an attractant of the red palm weevil (Rhynchophorus ferrugineus Olivier), a key pest that threatens the date palm crop. Associations between volatile composition and sugar and moisture content suggest that differences among fruits in these traits may be characterized by system-wide differences in fruit metabolism. Correlations between volatiles indicate medium chain and long chain fatty acid ester volatiles are regulated independently, possibly reflecting differences in the biochemistry of fatty acid precursors. Finally, we took advantage of date palm clones in our analysis to estimate broad-sense heritabilities of volatiles and demonstrate that at least some of volatile diversity has a genetic basis.
Loss of Plastid Developmental Genes Coincides With a Reversion to Monoplastidy in Hornworts
Authors: MacLeod Alexander I. , Raval Parth K. , Stockhorst Simon , Knopp Michael R. , Frangedakis Eftychios , Gould Sven B.
Published: March 2022

The first plastid evolved from an endosymbiotic cyanobacterium in the common ancestor of the Archaeplastida. The transformative steps from cyanobacterium to organelle included the transfer of control over developmental processes, a necessity for the host to orchestrate, for example, the fission of the organelle. The plastids of almost all embryophytes divide independently from nuclear division, leading to cells housing multiple plastids. Hornworts, however, are monoplastidic (or near-monoplastidic), and their photosynthetic organelles are a curious exception among embryophytes for reasons such as the occasional presence of pyrenoids. In this study, we screened genomic and transcriptomic data of eleven hornworts for components of plastid developmental pathways. We found intriguing differences among hornworts and specifically highlight that pathway components involved in regulating plastid development and biogenesis were differentially lost in this group of bryophytes. Our results also confirmed that hornworts underwent significant instances of gene loss, underpinning that the gene content of this group is significantly lower than other bryophytes and tracheophytes. In combination with ancestral state reconstruction, our data suggest that hornworts have reverted back to a monoplastidic phenotype due to the combined loss of two plastid division-associated genes, namely, ARC3 and FtsZ2.
The Nexus Between Human Resource Management Practices and Service Recovery Performance in Takaful Insurance Industry in Pakistan: The Mediating Role of Employee Commitment
Authors: Mao Jie , Siyal Saeed , Javed Ahmed Munawer , Ahmad Riaz , Xin Chunlin , Qasim Samina
Published: March 2022

Service recovery performance (SRP) is very important for the takaful insurance industry for maintaining and attracting new clients, which in turn serves as a competitive advantage for the survival and continued future of the businesses. If the insurance sector could not maintain SRP, then the competitive advantage of the organizations could be decayed. Therefore, under the theoretical foundation of equity theory and resource-based theory, this research has investigated the link between human resources management practices (HRMP) (such as human capital, training, job description, teamwork, empowerment, and rewards) and SRP directly and indirectly through the employee commitment. By using a convenient sampling technique data was collected from the employees working in the Takaful industry in Pakistan to empirically test the proposed hypotheses and validate the findings. Using cross research design and quantitative research approach. The Structural Equation Modeling (SEM) had presented the positive relationship between HRM practices and SRP. On the other hand, employee commitment had also mediated this relationship. As employee commitment is significantly mediated among most of the HRMP, this aspect is therefore considered to be a big contribution of the study in the context of Pakistan. Based on these findings, the current study has several important implications the practitioners and readers.