bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulation and Senso-Chemical Evaluation of Aloe Vera (Aloe Barbadensis Miller) Based Value Added Beverages
Authors: Alam S , Ahiduzzaman M , Islam MN , Haque MA , Akanda MAM
Published: March 2022

The aloe vera pulp contains more than 98% water and less than 1% total soluble solids (TSS). Blending of pineapple juice and roselle extract with aloe vera may not only increases the TSS level but also add other nutritional properties in the final mixed products. The current study was carried out to investigate the different formulations and the quality of various types of mixed beverages prepared from aloe vera, roselle herb and pineapple juice. Developed products were evaluated for their chemical properties as well as sensory attributes. In addition, selected products were tested for shelf-life potentials. Formulated drinks and juices were found as highly nutritious (maximum of 6.86 mg/100 ml ascorbic acid, 0.045% Ca, 0.26% Mg, 0.154% K, 0.034%Na, and 12.09 ppm Fe). Sensory evaluation revealed that products with 20% and 40% aloe vera pulp with pineapple and roselle extract were highly liked by the consumers. With the storage time, pH and ascorbic acid content decreased (maximum around 40% for pH and around 10% for ascorbic acid respectively) in all the formulated beverages, while TSS increased regardless of the formulations. In addition, aloe vera with pineapple and sugar blend exhibited an acceptable level of microbial load during the shelf-life study. Results from this study suggest that it could be possible to commercially produce aloe vera based value added products, which in turn could play an important role in addressing socioeconomic as well as health conditions.
Ann. Bangladesh Agric. (2021) 25 (1) : 43-54
PENGARUH PENDIDIKAN KESEHATAN METODE DEMONSTRASI TERHADAP HAND HYGIENE 6 LANGKAH 5 MOMEN KELUARGA PASIEN
Authors: Rosidah Binti
Published: March 2022

Hospital arrangement is a place that has a high risk of Healthcare Associated Infection (HAIs). Family behavior and patients undergoing treatment at the hospital greatly influence the emergence of HAIs, one of which is applying handwashing. Health education is one way to improve the accuracy of hand washing 6 steps the first moment. The purpose of this study was to determine the difference in the accuracy of the implementation of hand washing in the patient's family with and without the provision of health education using the hand hygiene demonstration method in Irna 2 Surgery Room, RSUD Dr. Saiful Anwar Malang. Method: The design of this study was a quasi-experimental study with a non-equivalent control group design. The treatment group was given an intervention in the form of demonstration method handwashing education, while the control group was not given an intervention. 26 respondents as the control group and 26 respondents as the treatment group. Result and analysis: The results obtained 14 respondents (53.85%) in the control group did not wash their hands properly. 17 respondents (65.38%) in the intervention group washed their hands properly. There is a difference in the accuracy of hand washing in the patient's family in IRNA 2 Surgical Class  3 of RSUD Dr. Saiful Anwar Malang between control and intervention groups (p<0.05). Health education demonstration method increases the accuracy of handwashing in the patient's family. It is hoped that education about 6 steps of hand washing will continue.
HUBUNGAN ANTARA MOTIVASI PERAWAT DENGAN SIKAP PENDOKUMENTASIAN ASUHAN KEPERAWATAN
Authors: Andreas Andreas Aditya Noviawan
Published: March 2022

Tujuan Studi: Tujuan penelitian ini untuk mengetahui hubungan antara motivasi perawat dengan sikap pendokumentasian asuhan keperawatan.

Metodologi: Penelitian ini merupakan penelitian Kuantitatif dengan pendekatan Cross Sectional. Dalam penelitian ini populasinya adalah seluruh perawat IRNA 1 yang berjumlah 171 responden dengan teknik sampel Probability Sampling. Sampel diambil secara Simple Random Sampling yang memenuhi kriteri inklusi eksklusi didapatkan 120 responden. Pengumpulan data dilakukan selama 8 hari menggunakan kuesioner.

Hasil: Dari hasil penelitian didapatkan sebagian besar responden menunjukan motivasi sedang sebanyak 105 responden (87.50%), sedangkan sikap pendokumentasian asuhan keperawatan sebagian besar  responden menunjukan sikap yang negative sebanyak 63 responden (52.5%). Hasil uji korelasi Rank Spearman menunjukkan hubungan yang signifikan dengan nilai p< 0.05 (p= 0.000< 0.05) antara motivasi perawat dengan sikap pendokumentasian asuhan keperawatan di IRNA 1 RSUD DR Saiful Anwar Malang, dengan tingkat korelasi lemah r=  0.391 serta korelasi bernilai positif maka hubungan bersifat searah, artinya semakin tinggi motivasi perawat maka semakin positif sikap pendokumentasian asuhan keperawatan.

Manfaat: Penelitian ini dapat digunakan untuk meningkatkan kualitas motivasi perawat dengan  sikap pendokumentasian asuhan keperawatan di IRNA 1 RSUD. DR Saiful Anwar Malang.
Loop stoma as a risk factor of postoperative ileus in colorectal cancer surgery (review), Dmitry A. Khubezov, Ivan S. Ignatov, Alexander Yu. Ogoreltsev, Yuliya B. Li, Alyona B. Piksina
Authors: Editorial Article
Published: March 2022

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Computed Tomography-Based Machine Learning Differentiates Adrenal Pheochromocytoma From Lipid-Poor Adenoma
Authors: Liu Haipeng , Guan Xiao , Xu Beibei , Zeng Feiyue , Chen Changyong , Yin Hong ling , Yi Xiaoping , Peng Yousong , Chen Bihong T.
Published: March 2022

Objectives

To assess the accuracy of computed tomography (CT)-based machine learning models for differentiating subclinical pheochromocytoma (sPHEO) from lipid-poor adenoma (LPA) in patients with adrenal incidentalomas.

Patients and Methods

The study included 188 tumors in the 183 patients with LPA and 92 tumors in 86 patients with sPHEO. Pre-enhanced CT imaging features of the tumors were evaluated. Machine learning prediction models and scoring systems for differentiating sPHEO from LPA were built using logistic regression (LR), support vector machine (SVM) and random forest (RF) approaches.

Results

The LR model performed better than other models. The LR model (M1) including three CT features: CTpre value, shape, and necrosis/cystic changes had an area under the receiver operating characteristic curve (AUC) of 0.917 and an accuracy of 0.864. The LR model (M2) including three CT features: CTpre value, shape and homogeneity had an AUC of 0.888 and an accuracy of 0.832. The S2 scoring system (sensitivity: 0.859, specificity: 0.824) had comparable diagnostic value to S1 (sensitivity: 0.815; specificity: 0.910).

Conclusions

Our results indicated the potential of using a non-invasive imaging method such as CT-based machine learning models and scoring systems for predicting histology of adrenal incidentalomas. This approach may assist the diagnosis and personalized care of patients with adrenal tumors.
Effects of Different Cropland Reclamation Periods on Soil Particle Size and Nutrients From the Perspective of Wind Erosion in the Mu Us Sandy Land
Authors: Liu Xiufan , Du Heqiang , Li Sen , Wang Tao , Fan Yawei
Published: March 2022

Land use changes could notably influence the magnitude and distribution of wind erosion. In recent decades, land reclamation flourished in the Mu Us Sandy Land (MUSL) to supplement cultivated lands (CLs) occupied by urbanization. To analyze the effects of land reclamation on wind erosion, the soil texture and soil nutrients in arable and uncultivated lands should be evaluated. In this study, we collected 54 paired soil samples from CLs and nearby uncultivated lands (NULs) in the MUSL considering land use data pertaining to different phases. Then, the soil particle distribution (PSD) and contents of soil organic carbon (SOC) and total nitrogen (TN) were measured in the laboratory. The results indicated that after 1–15 years (Yr) of cultivation, compared to the NULs, particles ranging from 60 to 400 μm obviously decreased. With increasing number of cultivation years, the wind sorting effects accumulated, and the content of erodible particles susceptible to wind erosion decreased. Among the CLs with different cultivation years, new CLs exhibited the highest erodible particle content, and medium CLs exhibited the lowest erodible particle fraction content. The SOC contents in the medium and fine sand groups among the new CLs was significantly influenced by wind erosion, whereas the TN content was primarily controlled by nitrogenous fertilizer application. After cultivation for longer than 40 years, the total SOC and TN contents in the CLs were significantly higher than those in the NULs. Among the CLs, the wind sorting effects and number of cultivation years obviously influenced the SOC content, whereas the TN content in the CLs was mainly influenced by nitrogenous fertilizer utilization. Rapid urbanization of Shaanxi Province, a new round of national ecological policy adjustments and altered wind environments are the main reasons for the development of new CLs, and a superior location and soil physicochemical properties contribute to the occurrence of old CLs. Based on the above analysis, we propose that conservative cultivation is the key to the protection of new CLs from wind erosion hazards.
Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer
Authors: Niu Mengke , Liu Yiming , Yi Ming , Jiao Dechao , Wu Kongming
Published: March 2022

The immune checkpoint pathway consisting of the cell membrane-bound molecule programmed death protein 1 (PD-1) and its ligand PD-L1 has been found to mediate negative regulatory signals that effectively inhibit T-cell proliferation and function and impair antitumor immune responses. Considerable evidence suggests that the PD-1/PD-L1 pathway is responsible for tumor immune tolerance and immune escape. Blockage of this pathway has been found to reverse T lymphocyte depletion and restore antitumor immunity. Antagonists targeting this pathway have shown significant clinical activity in specific cancer types. Although originally identified as membrane-type molecules, several other forms of PD-1/PD-L1 have been detected in the blood of cancer patients, including soluble PD-1/PD-L1 (sPD-1/sPD-L1) and exosomal PD-L1 (exoPD-L1), increasing the composition and functional complications of the PD-1/PD-L1 signaling pathway. For example, sPD-1 has been shown to block the PD-1/PD-L immunosuppressive pathway by binding to PD-L1 and PD-L2, whereas the role of sPD-L1 and its mechanism of action in cancer remain unclear. In addition, many studies have investigated the roles of exoPD-L1 in immunosuppression, as a biomarker for tumor progression and as a predictive biomarker for response to immunotherapy. This review describes the molecular mechanisms underlying the generation of sPD-1/sPD-L1 and exoPD-L1, along with their biological activities and methods of detection. In addition, this review discusses the clinical importance of sPD-1/sPD-L1 and exoPD-L1 in cancer, including their predictive and prognostic roles and the effects of treatments that target these molecules.
CD8+ T-Cell Exhaustion Phenotype in Chronic Hepatitis C Virus Infection Is Associated With Epitope Sequence Variation
Authors: Osuch Sylwia , Laskus Tomasz , Perlejewski Karol , Berak Hanna , Bukowska-Ośko Iwona , Pollak Agnieszka , Zielenkiewicz Magdalena , Radkowski Marek , Caraballo Cortés Kamila
Published: March 2022

Background and Aims

During chronic hepatitis C virus (HCV) infection, CD8+ T-cells become functionally exhausted, undergoing progressive phenotypic changes, i.e., overexpression of “inhibitory” molecules such as PD-1 (programmed cell death protein 1) and/or Tim-3 (T-cell immunoglobulin and mucin domain-containing molecule-3). The extreme intrahost genetic diversity of HCV is a major mechanism of immune system evasion, facilitating epitope escape. The aim of the present study was to determine whether T-cell exhaustion phenotype in chronic HCV infection is related to the sequence repertoire of NS3 viral immunodominant epitopes.

Methods

The study population was ninety prospective patients with chronic HCV genotype 1b infection. Populations of peripheral blood CD8+ T-cells expressing PD-1/Tim-3 were assessed by multiparametric flow cytometry, including HCV-specific T-cells after magnetic-based enrichment using MHC-pentamer. Autologous epitope sequences were inferred from next-generation sequencing. The correction of sequencing errors and genetic variants reconstruction was performed using Quasirecomb.

Results

There was an interplay between the analyzed epitopes sequences and exhaustion phenotype of CD8+ T-cells. A predominance of NS31406 epitope sequence, representing neither prototype KLSGLGLNAV nor cross-reactive variants (KLSSLGLNAV, KLSGLGINAV or KLSALGLNAV), was associated with higher percentage of HCV-specific CD8+PD-1+Tim-3+ T-cells, P=0.0102. Variability (at least two variants) of NS31406 epitope sequence was associated with increased frequencies of global CD8+PD-1+Tim-3+ T-cells (P=0.0197) and lower frequencies of CD8+PD-1−Tim-3− T-cells (P=0.0079). In contrast, infection with NS31073 dominant variant epitope (other than prototype CVNGVCWTV) was associated with lower frequency of global CD8+PD-1+Tim-3+ T-cells (P=0.0054).

Conclusions

Our results indicate that PD-1/Tim-3 receptor expression is largely determined by viral epitope sequence and is evident for both HCV-specific and global CD8+ T-cells, pointing to the importance of evaluating autologous viral epitope sequences in the investigation of CD8+ T-cell exhaustion in HCV infection.
Adenosine-A2A Receptor Pathway in Cancer Immunotherapy
Authors: Sun Changfa , Wang Bochu , Hao Shilei
Published: March 2022

A2A receptors (A2AR), a typical GPCR with a high affinity for adenosine, was expressed in many immune cells, such as regulatory T cells, cytotoxic T cells, macrophages, etc. Adenosine binding to the A2AR receptor activates the typical G protein and triggers the cAMP/PKA/CREB pathway. The adenosine-A2AR pathway plays an important role in protecting normal organs and tissues from the autoimmune response of immune cells. However, many solid tumors hijack the adenosine-A2AR pathway by promoting adenosine accumulation. The activation of the A2AR pathway inhibited the immune response of immune cells and then promotes the immune escape of tumor cells in the tumor microenvironment. Recently, both animal experiments and clinical trials indicated that blocking the adenosine pathway can inhibit the progression of a variety of solid tumors. In addition, it is encouraging that A2AR blockade combined with CAR T cells therapy showed better anti-tumor efficacy. Therefore, this review will discuss the role of the adenosine-A2AR pathway in the tumor microenvironment and summarize recent advances of A2AR-cancer related studies.
Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging
Authors: Cao Dehong , Sun Ruonan , Peng Lei , Li Jinze , Huang Yin , Chen Zeyu , Chen Bo , Li Jin , Ai Jianzhong , Yang Lu , Liu Liangren , Wei Qiang
Published: March 2022

To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to February 2021 using the following key words: “benign prostatic hyperplasia”, “inflammation”, “pathogenesis” and “disease development”. Articles were obtained and reviewed to provide a systematic review of the current progress of the role of inflammation in the pathogenesis and progression of BPH. Inflammation contributes to the initiation and maintenance of unregulated cell proliferation and is closely related to the occurrence and development of BPH. Its action pathways include tissue damage and subsequent chronic healing, autoimmunity, and coaction with androgens. During the progression of inflammation, macrophages, interleukin-8 (IL-8), interleukin-1 (IL-1) and other inflammatory-related substances aggregate locally and cause BPH through various biochemical pathways. At the same time, BPH can also counteract inflammation to expand its scope and aggravate the situation. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. In the course of treatment, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.
SARS-COV-2 Infection, Vaccination, and Immune-Mediated Diseases: Results of a Single-Center Retrospective Study
Authors: Luchetti Gentiloni Michele Maria , Paci Valentino , Marconi Valentina , Gigli Marco , Benfaremo Devis , Sordillo Raffaella , Macchini Cristina , Massaccesi Leonardo , Perna Gian Piero , Offidani Anna Maria , Moroncini Gianluca
Published: March 2022

Objectives

The relationship between infections or vaccine antigens and exacerbations or new onset of immune-mediated diseases (IMDs) has long been known. In this observational study, conducted during the COVID-19 pandemic, we evaluated the onset of clinical and laboratory immune manifestations related to COVID-19 or SARS-CoV-2 vaccination.

Methods

Four groups of patients were evaluated: A) 584 COVID-19 inpatients hospitalized from March 2020 to June 2020 and from November 2020 to May 2021; B) 135 outpatients with previous SARS-CoV-2 infection, assessed within 6 months of recovery; C) outpatients with IMDs in remission and flared after SARS-COV-2 infection; D) outpatients with symptoms of probable immune-mediated origin after SARS-CoV-2 vaccination.

Results

In cohort A we observed n. 28 (4.8%) arthralgia/myalgia, n. 2 (0.3%) arthritis, n. 3 (0.5%) pericarditis, n. 1 (0.2%) myocarditis, n. 11 (1.9%) thrombocytopenia or pancytopenia, and in the follow up cohort B we identified 9 (6.7%) cases of newly diagnosed IMDs after the recovery from COVID-19. In all cases, serological alterations were not observed.

In cohort C we observed n.5 flares of pre-existing IMD after SARS-COV2 infection, and in the cohort D n. 13 IMD temporally close with SARS-CoV-2 vaccination in 8 healthy subjects (with clinical classifiable IMD-like presentation) and in 5 patients affected by an anamnestic IMD. Also in these latter cases, except in 2 healthy subjects, there were not found serological alterations specific of a classifiable IMD.

Conclusions

This study suggests that the interplay between SARS-CoV-2 and the host may induce complex immune-mediated reactions, probably induced by the anti-spike antibodies, in healthy people and IMD patients without specific serological autoimmunity. Moreover, our data suggest that the anti-SARS-CoV-2 antibodies generated by the vaccination may cause in healthy subjects’ clinical manifestations similar to well-definite IMDs. These findings support the hypothesis that SARS-Cov2 infection in COVID-19 induce an innate and adaptive immune response that may be both responsible of the symptoms correlated with the occurrence of the IMDs described in our study. And, in this context, the IMDs observed in healthy people in close temporal correlation with the vaccination suggest that the anti-Spike antibodies may play a key role in the induction of an abnormal and deregulated immune response.
Supplementation of Dietary Quercetin and Vitamin E Promotes the Intestinal Structure and Immune Barrier Integrity in Aged Breeder Hens
Authors: Amevor Felix Kwame , Cui Zhifu , Du Xiaxia , Ning Zifan , Deng Xun , Xu Dan , Shu Gang , Wu Youhao , Cao Xueqing , Shuo Wei , Tian Yaofu , Li Diyan , Wang Yan , Zhang Yao , Du Xiaohui , Zhu Qing , Han Xue , Zhao Xiaoling
Published: March 2022

In aged animals, the physiological functions of the gastrointestinal tract (GIT) are reduced. Dietary intervention is necessary to re-activate GIT functions. The objective of this study was to investigate the impacts of dietary combination of quercetin (Q) and vitamin E (VE) on the intestinal structure and barrier integrity in aged breeder chickens. A sum of 400 (65-wks-old) Tianfu breeder hens were randomly allotted into four (4) groups with four (4) replicates, and fed with basal diet; basal diet supplemented with 0.4g/kg of Q; basal diet supplemented with 0.2g/kg of VE; and basal diet supplemented with the combination of Q (0.4 g/kg) and VE (0.2 g/kg) for 14 weeks. At the end of the 14th week, serum and gut segments were collected from eight hens per group for analyses. The results showed that Q+VE exerted synergistic effects on intestinal morphology by promoting villi height and crypt depth (P < 0.05), as well as mitigated the intestinal inflammatory damage of the aged hens, but decreased the concentration of serum D-lactate and diamine oxidase; and increased the levels of secretory immunoglobulin A (sIgA) and Mucin-2 mRNA (P < 0.05). Furthermore, the mRNA expression of intestinal tight junction proteins including occludin, ZO1, and claudin-1 was increased by Q+VE (P < 0.05). Moreover, Q+VE decreased the mRNA expression of the pro-inflammatory genes (TNF-α, IL-6, and IL-1β), and increased the expression of anti-inflammatory genes (IL-10 and IL-4) (P < 0.05). These results were consistent with the mRNA expression of Bax and Bcl-2. In addition, Q+VE protected the small intestinal tract from oxidative damage by increasing the levels of superoxide dismutase, total antioxidant capacity, glutathione peroxidase, catalase (P < 0.05), and the mRNA expression of SOD1 and GPx-2. However, Q+VE decreased malondialdehyde levels in the intestine compared to the control (P < 0.05). These results indicated that dietary Q+VE improved intestinal function in aged breeder hens, by protecting the intestinal structure and integrity. Therefore, Q+VE could act as an anti-aging agent to elevate the physiological functions of the small intestine in chickens.
Value of FDG-PET/MR in Oral Focus Assessment in Head and Neck Cancer Patients—A Feasibility Study
Authors: Valdec Silvio , Bosshard Fabienne A. , Hüllner Martin , Schwaninger Dominic R. , Stocker Larissa , Giacomelli-Hiestand Barbara , Stadlinger Bernd
Published: March 2022

FDG-PET/MR is a hybrid imaging modality used for the staging and restaging of advanced head & neck cancer (HNC) patients. Their treatment typically involves radiation therapy, which requires previous dental focus assessment. The aim of this study was to analyze if staging FDG-PET/MR is a valuable tool for oral focus assessment. For this purpose, FDG-PET/MR findings, such as metabolic activity of periapical radiolucencies and marginal periodontitis, were retrospectively compared with conventional standardized dental focus assessment, including dental radiographs and clinical assessment of 124 teeth in seven patients. Increased FDG uptake of periapical lesions was found in one out of 23 lesions. Increased FDG uptake of the marginal periodontium was recorded in one out of 34 lesions. In summary, standardized dental focus assessment by panoramic radiography and periapical radiographs may be enriched by information from FDG-PET/MR, showing active inflammation in dental foci. However, many dental foci have no correlate in FDG-PET/MR. The treatment decision for oral foci may benefit from the visualized presence or absence of metabolic activity on FDG-PET/MR.
Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.
Authors: Palmieri Fabio , Koutsokera Angela , Bernasconi Eric , Junier Pilar , von Garnier Christophe , Ubags Niki
Published: March 2022

Fungal infections are estimated to be the main cause of death for more than 1.5 million people worldwide annually. However, fungal pathogenicity has been largely neglected. This is notably the case for pulmonary fungal infections, which are difficult to diagnose and to treat. We are currently facing a global emergence of antifungal resistance, which decreases the chances of survival for affected patients. New therapeutic approaches are therefore needed to face these life-threatening fungal infections. In this review, we will provide a general overview on respiratory fungal infections, with a focus on fungi of the genus Aspergillus. Next, the immunological and microbiological mechanisms of fungal pathogenesis will be discussed. The role of the respiratory mycobiota and its interactions with the bacterial microbiota on lung fungal infections will be presented from an ecological perspective. Finally, we will focus on existing and future innovative approaches for the treatment of respiratory fungal infections.
Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials
Authors: Ling Hai-Qian , Chen Zi-Hao , He Lei , Feng Feng , Weng Chuang-Gui , Cheng Si-Jin , Rong Li-Min , Xie Pei-Gen
Published: March 2022

Objective

To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network analysis.

Methods

A Bayesian network meta-analysis of literature searches within PubMed, Cochrane Library, Embase, and Web of Science databases from their inception to February 21 2021 was conducted without language restrictions. Paired and network meta-analyses of random effects were used to estimate the total standardized mean deviations (SMDs) and odds ratios (ORs).

Results

A total of 1,133 citations were identified and 20 RCTs (including 1,198 patients) involving 11 drugs and placebos for post-SCI NP selected. The 5 outcomes from all 11 drugs and placebos had no inconsistencies after Bayesian network analysis. BTX-A gave the most effective pain relief for the 4 weeks, following a primary outcome. No significant differences were found among drugs with regard to adverse events of the primary outcome. Gabapentin, BTX-A, and pregabalin were found to be the most helpful in relieving secondary outcomes of mental or sleep-related symptoms with differences in SMDs, ranging from −0.63 to −0.86. Tramadol triggered more serious adverse events than any of the other drugs with differences in ORs ranging from 0.09 to 0.11.

Conclusion

BTX-A, gabapentin, pregabalin, amitriptyline, ketamine, lamotrigine, and duloxetine were all effective for NP management following SCI. Lamotrigine and gabapentin caused fewer side effects and had better efficacy in relieving mental or sleep-related symptoms caused by SCI-related NP. Tramadol, levetiracetam, carbamazepine, and cannabinoids could not be recommended due to inferior safety or efficacy.

Systematic Review Registration

[https://inplasy.com/inplasy-2020-7-0061/], identifier [INPLASY202070061].
Neural Correlates of Non-ordinary States of Consciousness in Pranayama Practitioners: The Role of Slow Nasal Breathing
Authors: Zaccaro Andrea , Piarulli Andrea , Melosini Lorenza , Menicucci Danilo , Gemignani Angelo
Published: March 2022

The modulatory effect of nasal respiration on integrative brain functions and hence consciousness has recently been unambiguously demonstrated. This effect is sustained by the olfactory epithelium mechanical sensitivity complemented by the existence of massive projections between the olfactory bulb and the prefrontal cortex. However, studies on slow nasal breathing (SNB) in the context of contemplative practices have sustained the fundamental role of respiratory vagal stimulation, with little attention to the contribution of the olfactory epithelium mechanical stimulation. This study aims at disentangling the effects of olfactory epithelium stimulation (proper of nasal breathing) from those related to respiratory vagal stimulation (common to slow nasal and mouth breathing). We investigated the psychophysiological (cardio-respiratory and electroencephalographic parameters) and phenomenological (perceived state of consciousness) aftereffects of SNB (epithelium mechanical – 2.5 breaths/min) in 12 experienced meditators. We compared the nasal breathing aftereffects with those observed after a session of mouth breathing at the same respiratory rate and with those related to a resting state condition. SNB induced (1) slowing of electroencephalography (EEG) activities (delta-theta bands) in prefrontal regions, (2) a widespread increase of theta and high-beta connectivity complemented by an increase of phase-amplitude coupling between the two bands in prefrontal and posterior regions belonging to the Default Mode Network, (3) an increase of high-beta networks small-worldness. (4) a higher perception of being in a non-ordinary state of consciousness. The emerging scenario strongly suggests that the effects of SNB, beyond the relative contribution of vagal stimulation, are mainly ascribable to olfactory epithelium stimulation. In conclusion, slow Pranayama breathing modulates brain activity and hence subjective experience up to the point of inducing a non-ordinary state of consciousness.
Focal Serous Tubal Intra-Epithelial Carcinoma Lesions Are Associated With Global Changes in the Fallopian Tube Epithelia and Stroma
Authors: Wu Jingni , Raz Yael , Recouvreux Maria Sol , Diniz Márcio Augusto , Lester Jenny , Karlan Beth Y. , Walts Ann E. , Gertych Arkadiusz , Orsulic Sandra
Published: March 2022

Objective

Serous tubal intra-epithelial carcinoma (STIC) lesions are thought to be precursors to high-grade serous ovarian cancer (HGSOC), but HGSOC is not always accompanied by STIC. Our study was designed to determine if there are global visual and subvisual microenvironmental differences between fallopian tubes with and without STIC lesions.

Methods

Computational image analyses were used to identify potential morphometric and topologic differences in stromal and epithelial cells in samples from three age-matched groups of fallopian tubes. The Benign group comprised normal fallopian tubes from women with benign conditions while the STIC and NoSTIC groups consisted of fallopian tubes from women with HGSOC, with and without STIC lesions, respectively. For the morphometric feature extraction and analysis of the stromal architecture, the image tiles in the STIC group were further divided into the stroma away from the STIC (AwaySTIC) and the stroma near the STIC (NearSTIC). QuPath software was used to identify and quantitate secretory and ciliated epithelial cells. A secretory cell expansion (SCE) or a ciliated cell expansion (CCE) was defined as a monolayered contiguous run of >10 secretory or ciliated cells uninterrupted by the other cell type.

Results

Image analyses of the tubal stroma revealed gradual architectural differences from the Benign to NoSTIC to AwaySTIC to NearSTIC groups. In the epithelial topology analysis, the relative number of SCE and the average number of cells within SCE were higher in the STIC group than in the Benign and NoSTIC groups. In addition, aging was associated with an increased relative number of SCE and a decreased relative number of CCE. ROC analysis determined that an average of 15 cells within SCE was the optimal cutoff value indicating the presence of a STIC lesion in the tubal epithelium.

Conclusions

Our findings suggest that global stromal alterations and age-associated reorganization of tubal secretory and ciliated cells are associated with STIC lesions. Further studies will need to determine if these alterations precede STIC lesions and provide permissible conditions for the formation of STIC.
Point Mutations in the FLT3-ITD Region Are Rare but Recurrent Alterations in Adult AML and Associated With Concomitant KMT2A-PTD
Authors: Stasik Sebastian , Kramer Michael , Zukunft Sven , Röllig Christoph , Baldus Claudia D. , Platzbecker Uwe , Serve Hubert , Müller-Tidow Carsten , Schäfer-Eckart Kerstin , Kaufmann Martin , Krause Stefan , Sauer Tim , Hänel Mathias , Neubauer Andreas , Ehninger Gerhard , Bornhäuser Martin , Schetelig Johannes , Middeke Jan M. , Thiede Christian
Published: March 2022

FLT3-ITD mutations are common druggable alterations in patients with acute myeloid leukemia (AML) and associated with poor prognosis. Beside typical ITD mutations, point mutations and deletions in the juxtamembrane domain (JMD) have been observed. However, due to the low frequency of these alterations, there is only limited information on molecular and clinical associations. To evaluate the prognostic impact of non-ITD mutations in the FLT3 JMD region, we analyzed a large cohort of 1,539 adult AML patients treated in different protocols of the Study Alliance Leukemia, using next-generation sequencing. Non-ITD point mutations and deletions within the FLT3 JMD were identified with a prevalence of ~1.23% (n = 19). Both FLT3-ITD and non-ITD mutations were associated with a higher rate of NPM1 (42%–61%; p < 0.001) and DNMT3A mutations (37%–43%; p < 0.001), as well as an increased percentage of peripheral blood (54%–65%) and bone marrow blast cells (74%; p < 0.001), compared to FLT3-wild-type patients. Most significantly, AML patients with FLT3 non-ITD mutations had a higher rate of concomitant KMT2A-PTD mutations (37.5%; p < 0.001) as compared to FLT3-ITD (7%) or FLT3-wild-type cases (4.5%). In a multivariable analysis, FLT3 non-ITD mutations were not an independent prognostic factor. However, patients with dual FLT3 non-ITD and KMT2A-PTD mutations showed a trend for inferior outcome, which points at a functional interaction in this subset of AML.
HAAO rs3816183 Polymorphisms [T] Increase Anterior/Middle Hypospadias Risk in Southern Han Chinese Population
Authors: Liu Yanqing , Fu Wen , Fu Kai , Zuo Xiaoyu , Jia Wei , Wang Ning , Zhang Yan , Liu Guochang , Deng Fuming
Published: March 2022

Hypospadias is one of the most common congenital external genital malformations, which is characterized by abnormal urethral meatus. However, the etiology remains to be incompletely understood. HAAO is a gene that encodes a protein, which catalyzes the synthesis of quinolinic acid, and has been identified as a risk gene for hypospadias. Thus, this study was conducted to elaborate the association between HAAO gene polymorphism rs3816183 T>C and hypospadias in the largest hypospadias cohort from Asia, including 577 patients and 654 healthy controls in China. The strength of interrelation was evaluated using 95% confidence intervals (CIs) and odds ratios (ORs). Based on the stratified analysis of hypospadias subtypes, it was found that the HAAO risk allele rs386183[T] enhances the susceptibility for hypospadias among patients with anterior/middle hypospadias subtypes (adjusted OR = 1.31, 95% CI = 1.05–1.64, p = 0.017). Enhanced risk of hypospadias in the entirety could not be demonstrated (OR = 1.20, 95% CI = 1.00–1.47, p = 0.054). In summary, our study found that the rs3816183[T] polymorphism is associated with increased risk of anterior/middle hypospadias among Southern Han Chinese children. The mechanisms by which the variations in the HAAO gene require further research.
Potential Therapeutic Targets of Rehmannia Formulations on Diabetic Nephropathy: A Comparative Network Pharmacology Analysis
Authors: Chan Kam Wa , Yu Kam Yan , Yiu Wai Han , Xue Rui , Lok Sarah Wing-yan , Li Hongyu , Zou Yixin , Ma Jinyuan , Lai Kar Neng , Tang Sydney Chi-wai
Published: March 2022

Background: Previous retrospective cohorts showed that Rehmannia-6 (R-6, Liu-wei-di-huang-wan) formulations were associated with significant kidney function preservation and mortality reduction among chronic kidney disease patients with diabetes. This study aimed to investigate the potential mechanism of action of common R-6 variations in a clinical protocol for diabetic nephropathy (DN) from a system pharmacology approach.

Study Design and Methods: Disease-related genes were retrieved from GeneCards and OMIM by searching “Diabetic Nephropathy” and “Macroalbuminuria”. Variations of R-6 were identified from a published existing clinical practice guideline developed from expert consensus and pilot clinical service program. The chemical compound IDs of each herb were retrieved from TCM-Mesh and PubChem. Drug targets were subsequently revealed via PharmaMapper and UniProtKB. The disease gene interactions were assessed through STRING, and disease–drug protein–protein interaction network was integrated and visualized by Cytoscape. Clusters of disease–drug protein–protein interaction were constructed by Molecular Complex Detection (MCODE) extension. Functional annotation of clusters was analyzed by DAVID and KEGG pathway enrichment. Differences among variations of R-6 were compared. Binding was verified by molecular docking with AutoDock.

Results: Three hundred fifty-eight genes related to DN were identified, forming 11 clusters which corresponded to complement and coagulation cascades and signaling pathways of adipocytokine, TNF, HIF-1, and AMPK. Five variations of R-6 were analyzed. Common putative targets of the R-6 variations on DN included ACE, APOE, CCL2, CRP, EDN1, FN1, HGF, ICAM1, IL10, IL1B, IL6, INS, LEP, MMP9, PTGS2, SERPINE1, and TNF, which are related to regulation of nitric oxide biosynthesis, lipid storage, cellular response to lipopolysaccharide, inflammatory response, NF-kappa B transcription factor activity, smooth muscle cell proliferation, blood pressure, cellular response to interleukin-1, angiogenesis, cell proliferation, peptidyl-tyrosine phosphorylation, and protein kinase B signaling. TNF was identified as the seed for the most significant cluster of all R-6 variations. Targets specific to each formulation were identified. The key chemical compounds of R-6 have good binding ability to the putative protein targets.

Conclusion: The mechanism of action of R-6 on DN is mostly related to the TNF signaling pathway as a core mechanism, involving amelioration of angiogenesis, fibrosis, inflammation, disease susceptibility, and oxidative stress. The putative targets identified could be validated through clinical trials.
Pitavastatin Induces Cancer Cell Apoptosis by Blocking Autophagy Flux
Authors: Tilija Pun Nirmala , Lee Naeun , Song Sang-Hoon , Jeong Chul-Ho
Published: March 2022

Statins, a class of lipid-lowering drugs, are used in drug repositioning for treatment of human cancer. However, the molecular mechanisms underlying statin-induced cancer cell death and autophagy are not clearly defined. In the present study, we showed that pitavastatin could increase apoptosis in a FOXO3a-dependent manner in the oral cancer cell line, SCC15, and the colon cancer cell line, SW480, along with the blockade of autophagy flux. The inhibition of autophagy by silencing the LC3B gene reduced apoptosis, while blockade of autophagy flux using its inhibitor, Bafilomycin A1, further induced apoptosis upon pitavastatin treatment, which suggested that autophagy flux blockage was the cause of apoptosis by pitavastatin. Further, the FOXO3a protein accumulated due to the blockade of autophagy flux which in turn was associated with the induction of ER stress by transcriptional upregulation of PERK-CHOP pathway, subsequently causing apoptosis due to pitavastatin treatment. Taken together, pitavastatin-mediated blockade of autophagy flux caused an accumulation of FOXO3a protein, thereby leading to the induction of PERK, ultimately causing CHOP-mediated apoptosis in cancer cells. Thus, the present study highlighted the additional molecular mechanism underlying the role of autophagy flux blockade in inducing ER stress, eventually leading to apoptosis by pitavastatin.
Psychological Impact in Healthcare Workers During Emergencies: The Italian Experience With COVID-19 First Wave
Authors: Pisanu Elisabetta , Di Benedetto Annalisa , Infurna Maria Rita , Rumiati Raffaella I.
Published: March 2022

Background

The COVID-19 outbreak imposed an overwhelming workload as well as emotional burdens on Healthcare workers (HCWs). In May 2020, an online survey was administered to HCWs in Italy to assess the pandemic's psychological impact and to investigate possible predictive factors that led to individual differences.

Methods

The psychological experience was measured based on the prevalence of self-reported feelings during the pandemic, including negative and positive emotional states. We analyzed the relationship between factors of gender, age, geographic region, professional role, and operational unit, and the four-point scale used to rate the frequency of each emotional state experienced by performing several multinomial logistic regressions, one for each emotion.

Results

Our findings suggest that more than half of HCWs experienced psychological distress during the first COVID-19 outbreak in Italy. Female and younger respondents, especially those operating in northern Italy experienced more frequently negative emotional states such as irritability, anxiety, loneliness, and insecurity. However, positive feelings, first of all solidarity, were also reported especially by female and older workers. The majority of the negative as well as positive emotional states were experienced almost equally by both doctors and nurses, and independently of the operational unit in which they operated.

Conclusions

This study can be very useful as a contribution to the current literature on the psychological effects of this pandemic on health workers. Moreover, our findings can provide useful information in planning more tailored psychological interventions to support this category of workers in the ongoing and future emergencies.
The Effects of Plasma Homocysteine Level on the Risk of Three Major Psychiatric Disorders: A Mendelian Randomization Study
Authors: Yu Jing , Xue Ranran , Wang Qiuling , Yu Hao , Liu Xia
Published: March 2022

Background

Higher homocysteine (Hcy) level has been suggested to be associated with major psychiatric disorders (MPDs), such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). We investigated the causal relationships between plasma Hcy level and MPDs risks using the Mendelian randomization (MR) method.

Methods

We selected 18 loci associated with plasma Hcy level from a large-scale genome-wide association study (GWAS) as genetic instruments. Genetic associations with SCZ, MDD, BD and BD subtypes (BD-I and BD-II) were extracted from several GWAS datasets from the Psychiatric Genomics Consortium. We used the Generalized Summary-data-based Mendelian Randomization (GSMR) method to estimate the associations of genetically predicted plasma Hcy levels with MPDs risks. We also performed inverse variance-weighted (IVW) analysis to verify the GSMR results and used MR-Egger regression and leave-one-out analysis to test the assumptions for a valid MR analysis.

Results

Genetically predicted plasma Hcy levels were associated with risks of SCZ (odds ratio [OR] = 1.12,PGSMR= 1.73 × 10−3) and BD-I (OR = 1.14,PIVW= 5.23 × 10−3) after Bonferroni correction. These associations were statistically significant when using IVW analysis (SCZ: OR = 1.11,PIVW= 2.74 × 10−3; BD-I: OR = 1.13,PIVW= 9.44 × 10−3). Furthermore, no significant horizontal pleiotropy was found by sensitivity analysis, and leave-one-out analyses showed no specific SNP affected the overall estimate. However, genetically determined plasma Hcy levels were not causally associated with MDD, BD, or BD-II risks.

Conclusion

Our results suggest that elevated plasma Hcy levels may increase the risk of SCZ or BD-I. Further randomized clinical trials are warranted to validate the MR findings in our study.
Evaluating Electromyography and Sonomyography Sensor Fusion to Estimate Lower-Limb Kinematics Using Gaussian Process Regression
Authors: Rabe Kaitlin G. , Fey Nicholas P.
Published: March 2022

Research on robotic lower-limb assistive devices over the past decade has generated autonomous, multiple degree-of-freedom devices to augment human performance during a variety of scenarios. However, the increase in capabilities of these devices is met with an increase in the complexity of the overall control problem and requirement for an accurate and robust sensing modality for intent recognition. Due to its ability to precede changes in motion, surface electromyography (EMG) is widely studied as a peripheral sensing modality for capturing features of muscle activity as an input for control of powered assistive devices. In order to capture features that contribute to muscle contraction and joint motion beyond muscle activity of superficial muscles, researchers have introduced sonomyography, or real-time dynamic ultrasound imaging of skeletal muscle. However, the ability of these sonomyography features to continuously predict multiple lower-limb joint kinematics during widely varying ambulation tasks, and their potential as an input for powered multiple degree-of-freedom lower-limb assistive devices is unknown. The objective of this research is to evaluate surface EMG and sonomyography, as well as the fusion of features from both sensing modalities, as inputs to Gaussian process regression models for the continuous estimation of hip, knee and ankle angle and velocity during level walking, stair ascent/descent and ramp ascent/descent ambulation. Gaussian process regression is a Bayesian nonlinear regression model that has been introduced as an alternative to musculoskeletal model-based techniques. In this study, time-intensity features of sonomyography on both the anterior and posterior thigh along with time-domain features of surface EMG from eight muscles on the lower-limb were used to train and test subject-dependent and task-invariant Gaussian process regression models for the continuous estimation of hip, knee and ankle motion. Overall, anterior sonomyography sensor fusion with surface EMG significantly improved estimation of hip, knee and ankle motion for all ambulation tasks (level ground, stair and ramp ambulation) in comparison to surface EMG alone. Additionally, anterior sonomyography alone significantly improved errors at the hip and knee for most tasks compared to surface EMG. These findings help inform the implementation and integration of volitional control strategies for robotic assistive technologies.
Establishment of a Dynamic Nomogram for Predicting the Risk of Lymph Node Metastasis in T1 Stage Colorectal Cancer
Authors: Liu Zitao , Huang Chao , Tian Huakai , Liu Yu , Huang Yongshan , Zhu Zhengming
Published: March 2022

Background

Accurate prediction of the risk of lymph node metastasis in patients with stage T1 colorectal cancer is crucial for the formulation of treatment plans for additional surgery and lymph node dissection after endoscopic resection. The purpose of this study was to establish a predictive model for evaluating the risk of LNM in patients with stage T1 colorectal cancer.

Methods

The clinicopathological and imaging data of 179 patients with T1 stage colorectal cancer who underwent radical resection of colorectal cancer were collected. LASSO regression and a random forest algorithm were used to screen the important risk factors for LNM, and a multivariate logistic regression equation and dynamic nomogram were constructed. The C index, Calibration curve, and area under the ROC curve were used to evaluate the discriminant and prediction ability of the nomogram. The net reclassification index (NRI), comprehensive discriminant improvement index (IDI), and clinical decision curve (DCA) were compared with traditional ESMO criteria to evaluate the accuracy, net benefit, and clinical practicability of the model.

Results

The probability of lymph node metastasis in patients with T1 colorectal cancer was 11.17% (20/179). Multivariate analysis showed that the independent risk factors for LNM in T1 colorectal cancer were submucosal invasion depth, histological grade, CEA, lymphovascular invasion, and imaging results. The dynamic nomogram model constructed with independent risk factors has good discrimination and prediction capabilities. The C index was 0.914, the corrected C index was 0.890, the area under the ROC curve was 0.914, and the accuracy, sensitivity, and specificity were 93.3, 80.0, and 91.8%, respectively. The NRI, IDI, and DCA show that this model is superior to the ESMO standard.

Conclusion

This study establishes a dynamic nomogram that can effectively predict the risk of lymph node metastasis in patients with stage T1 colorectal cancer, which will provide certain help for the formulation of subsequent treatment plans for patients with stage T1 CRC after endoscopic resection.