bluuebunny/crossref_metadata_2025 huggingface dataset:
A tungsten enzyme using hydrogen as an electron donor to reduce carboxylic acids and NAD+
Authors: Winiarska Agnieszka , Hege Dominik , Gemmecker Yvonne , Kryściak-Czerwenka Joanna , Seubert Andreas , Heider Johann , Szaleniec Maciej
Published: April 2022

Tungsten-dependent aldehyde oxidoreductases (AOR) catalyse the oxidation of aldehydes to acids and are the only known enzymes reducing non-activated acids using electron donors with low redox potentials. We report here that AOR from Aromatoleum aromaticum (AORAa) catalyses the reduction of organic acids not only with low-potential Eu(II) or Ti(III) complexes but also with H2 as an electron donor. Additionally, AORAa catalyzes the H2-dependent reduction of NAD+ or benzyl viologen. The rate of H2 dependent NAD+ reduction equals to 10% of that of aldehyde oxidation, representing the highest H2 turnover rate observed among the Mo/W enzymes. As AORAa simultaneously catalyzes the reduction of acids and NAD+ we designed a cascade reaction utilizing a NAD(P)H-dependent alcohol dehydrogenase to reduce organic acids to the corresponding alcohols with H2 as the only reductant. The newly discovered W-hydrogenase side-activity of AORAa may find applications in either NADH-recycling or conversion of carboxylic acids to more useful biochemicals.
Effects of postural education on daily habits in children. Intervention effects from the PEPE study.
Authors: Maria Galmes-Panades Aina , Josep Vidal-Conti
Published: April 2022

Purpose. Reducing the disease burden of unspecific low back pain (LBP) in children is of major public health relevance, due to children with episodes of LBP tend to experience chronic back pain in adulthood. Methods. The aim of the current randomised controlled trial was to investigate the effects of a 4.5 months postural education program on daily life habits related to LBP in children aged between 10 and 12 years. The study was performed in Majorca (Spain), with 253 primary schoolchildren. The overall strategy for developing the project was based on 1) intervention on classroom teachers, physical education teachers, and school management team; 2) awareness of the educational community (teachers, students, families); 3) teacher training; 4) a continuous intervention throughout the academic year. Results. Lifetime LBP prevalence rate was 54.9% in the whole study sample. Neither single postural items nor postural habits score mostly did improved after the intervention in experimental group, and also in control group. Conclusion. This telematic intervention has not managed to improve postural habits in children. Nevertheless, there is a lack of evidence to determine whether it is feasible to carry out telematics intervention that promotes lifestyle changes in children.
Reliability and validity of Foot Posture Index (FPI-6) for evaluating foot posture in participants with low back pain
Authors: Yang Jiaman , Ou Zhiwen , Mao Zhitao , Wang Yi , Zhong Yiheng , Chen Zehua , Dong Wei , Shen Zhen
Published: April 2022

Background: Previous studies have demonstrated that Foot Posture Index (FPI-6) is a valid and moderately reliable tool to evaluate foot posture. However, data about reliability and validity of FPI-6 in the assessment of foot posture in people with low back pain (LBP) is lacking.Objectives: To investigate reliability and validity of FPI-6 in the assessment of foot posture in people with LBP.Methods: Thirty volunteers with LBP, aged 20 - 64 years, were recruited for the research and assessed by two raters. The data measured by different raters on the same day were used to calculate the inter-rater reliability. The data measured by the same rater on different dates were used to calculate the test-retest reliability. The reliability of FPI-6 was tested with intraclass correlation coefficient (ICC), and absolute reliability with standard error of measurement (SEM), minimal detectable change (MDC) and Bland–Altman analysis. The validity of FPI-6 was tested with Exploratory Factor Analysis (EFA) and Spearman's correlation coefficients. Results: The FPI-6 indicated excellent inter-rater and test-retest reliability in the evaluation of foot posture in people with LBP (ICC = 0.97 and 0.95). The agreement for inter-rater and test-retest was excellent based on the SEM (SEM = 0.12) and MDC value (MDC = 0.33). Bland–Altman plots showed that there was no significant systematic bias for the agreement on the ground of low mean difference (< 1). The EFA suggested that the fit indices were considered acceptable according to the Kaiser-Meyer-Olkin (KMO) value (KMO = 0.620) and Bartlett's sphericity test (P < 0.01). There was a statistically significant positive correlation between each item and total score of FPI-6 because the Spearman’s correlation coefficient of six items were all > 0.3 (P < 0.01).Conclusions: The inter-rater and test-retest reliability and validity of FPI-6 on people with LBP were proved reliable. It might be considered a reliable and valid adjunctive tool to detect possible changes of foot posture after interventions in patients with LBP.
Care patterns and TCM constitution as factors of depression and anxiety in systemic scleroderma: a cross- sectional study during the COVID-19 pandemic
Authors: Kong Qi , Chen Li-Ming , Dai Zong-Hao , Tang Yun-Zhe , Zhou Yu-Yang , Tu Wen-Zhen , Zhao Yin-Huan , Zhang Jia-Qian
Published: April 2022

Background: Care patterns and TCM constitution affects systemic scleroderma (SSc) patients’ emotion and health while the prevalence of covid-19 may aggravate this situation. Thus, we investigated depression and anxiety level in SSc patients during the COVID-19 pandemic to identify the correlation between care patterns, TCM constitution and patients' emotion. Methods: This was a cross-sectional study. SSc patients and healthy individuals were surveyed through the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, the Constitution in Chinese Medicine Questionnaire and a modified care pattern questionnaire. Factors correlated with depression and anxiety were screened by univariate and multivariate logistic regression. Results: A total of 273 SSc patients and 111 healthy individuals were included. The median age was 45 years in both patient and healthy groups. 74.36% of SSc patients were in depression and 51.65% were in anxiety. 69.60% worked remotely and 50.92% experienced a decrease in income, which were both higher than in the healthy group (38.74%, 29.73%). The proportion of income reduction in the online group (56.19%) was higher than that in the hospital group (33.33%) (P = 0.001). 36.99% of SSc patients had disease progression during the pandemic. Yang-deficiency constitution (82.05%) was the TCM constitution characteristic of SSc patients, while Qi-deficiency(73.63%) and Blood-stasis constitution (57.14%) were also more common. TCM constitution of patients from different sources distributed roughly similar. Qi-deficiency (adjusted OR=2.250) and Qi-stagnation (adjusted OR= 3.824) constitution were significantly associated with depression. The major constitution of dampness-heat was associated with a decrease in depression (adjusted OR=0.160). Remote work during the outbreak (adjusted OR= 1.920), decreasing in income (adjusted OR=3.556), and disease progression (P=0.030) were associated with the occurrence of depression. Conclusion: Chinese SSc patients have a high prevalence of depression and anxiety. The COVID-19 pandemic has changed the care patterns of Chinese SSc patients in terms of work, income, and ways of getting medical support. Within the care patterns, work, income, disease and change of medications were correlates of depression or anxiety in SSc patients. Qi-stagnation and Qi-deficiency constitution were associated with depression, and Qi-stagnation constitution was associated with anxiety in SSc patients. Further research is needed. Trial registration: ChiCTR, ChiCTR2000038796, Registered 02 October 2020, http://www.chictr.org.cn/showproj.aspx?proj=62301
Accurate prediction of molecular targets using a self-supervised image representation learning framework
Authors: Zeng Xiangxiang , Xiang Hongxin , Yu Linhui , Wang Jianmin , Li Kenli , Nussinov Ruth , Cheng Feixiong
Published: April 2022

The clinical efficacy and safety of a drug is determined by its molecular targets in the human proteome. However, proteome-wide evaluation of all compounds in human, or even animal models, is challenging. In this study, we present an unsupervised pre-training deep learning framework, termed ImageMol, from 8.5 million unlabeled drug-like molecules to predict molecular targets of candidate compounds. The ImageMol framework is designed to pretrain chemical representations from unlabeled molecular images based on local- and global-structural characteristics of molecules from pixels. We demonstrate high performance of ImageMol in evaluation of molecular properties (i.e., drug’s metabolism, brain penetration and toxicity) and molecular target profiles (i.e., human immunodeficiency virus) across 10 benchmark datasets. ImageMol shows high accuracy in identifying anti-SARS-CoV-2 molecules across 13 high-throughput experimental datasets from the National Center for Advancing Translational Sciences (NCATS) and we re-prioritized candidate clinical 3CL inhibitors for potential treatment of COVID-19. In summary, ImageMol is an active self-supervised image processing-based strategy that offers a powerful toolbox for computational drug discovery in a variety of human diseases, including COVID-19.
A patient with hepatitis B virus infection had hepatic epithelioid angiomyolipoma scattered in the liver which was not suitable for surgical resection: A case report
Authors: Cai Xiangren , Sun Shuchuan , Deng Yuxin , Pan Siyuan
Published: April 2022

Hepatic epithelioid angiomyolipoma (HEAML) is a rare tumor of mesenchymal tissue with a malignant tendency. It most frequently occurs in women. According to incomplete statistics, the incidence in men and women is approximately 1:5. Most HEAML lesions are single, and the lesions are generally located in the right lobe of the liver. In rare cases, the occurrence and development of the disease is hidden, the lesions are generally found by chance by patients, there are no special signs, and imaging has no specificity in the diagnosis of the disease. In addition, the misdiagnosis rate is very high with an accuracy rate of < 32%. Therefore, it has led to great difficulties in our diagnosis and treatment. This patient was a middle-aged female with a history of hepatitis B and no other special symptoms. She is a patient with multiple intrahepatic angiomyolipoma. Due to the small and scattered foci, complete resection was impossible, and due to her history of hepatitis B, conservative treatment was taken, and regular follow-up was performed. There was no tumor neogenesis or metastasis at the one-year follow-up.
Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion
Authors: Giroux Nicholas S. , Ding Shengli , McClain Micah T. , Burke Thomas W. , Petzold Elizabeth , Chung Hong A. , Rivera Grecia O. , Wang Ergang , Xi Rui , Bose Shree , Rotstein Tomer , Nicholson Bradly P. , Chen Tianyi , Henao Ricardo , Sempowski Gregory D. , Denny Thomas N. , De Ussel Maria Iglesias , Satterwhite Lisa L. , Ko Emily R. , Ginsburg Geoffrey S. , Kraft Bryan D. , Tsalik Ephraim L. , Shen Xiling , Woods Christopher
Published: April 2022

SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associate with mild or moderate symptoms are already robust and include severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity is marked by upregulation classical antiviral pathways including those regulating IRF1 and IRF7, whereas in moderate disease these classical antiviral signals diminish suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19.
Appreciation of the personalized BETER lifestyle intervention for overweight: a case series design
Authors: Kanera Iris Maria , Kleynen Melanie , Schroën Yan , Luxzenburg Tanja Johanna Jacques de Jong van , Braun Susy Michelle
Published: April 2022

Background: Obesity is an epidemic affecting many citizens worldwide. Behavior change through lifestyle interventions can be effective, but success rates vary. Personalized interventions based on a systems biology approach might represent the individual variety of characteristics and underlying pathways in this target population better. Five subtypes of overweight were used for a personalized lifestyle program called BETER. This pilot study aimed to assess the degree of appreciation for the BETER program and to observe changes in vitality, lifestyle and body mass index (BMI).Methods: A case series design was applied. In a sample of people with overweight an evaluation of the appreciation of the program and a comparison of vitality, lifestyle, and BMI were performed. Data collection through questionnaires and clinical measurements were performed at baseline, after three and six months. The data were analyzed descriptively. Results: Seventy-nine adults (31 males, range average BMI: 28.4-31.3, range age: 19-65 years) reported promising results: a high degree of appreciation (8 out of 10), low dropout rates (9%), short term self-reported positive changes in lifestyle behaviors (adoption of lifestyle recommendations: physical activity: range 50-100%; nutrition: range 50-90%), increased perceived vitality (range participants ‘positive’ 67-81%) and a positive trend was seen in BMI reduction. Decline in adherence at follow-up was observed.Conclusion: The BETER lifestyle program was greatly appreciated and contributed to self-reported positive lifestyle changes and weight loss. Further research is needed to investigate whether the use of subtypes from a systems biology approach can provide key elements to increase the success rate of lifestyle interventions for obesity and chronic diseases, also on the long term.
P66Shc-mediated reactive oxygen species and autophagy disrupts brain microvascular endothelial cell function in response to hyperglycemia
Authors: Wang Lin , Yang Mengzhen , Wu Chao , Hu Hanyang , Ji Lulu , Lai Rujie , Peng Min , Huang Shenghe
Published: April 2022

Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can lead to serious central nervous system complications. The blood-brain barrier(BBB) is essential for maintaining the environmental stability of the central nervous system. Hyperglycemia may cause blood-brain barrier dysfunction and lead to central nervous system complications, but the mechanism is not clear. To explore the molecular mechanism of BBB injury caused by high glucose (HG), we hypothesize that p66Shc damaged BBB by promoting ROS production and autophagy. Human brain microvascular endothelial cells (HBMEC) were treated with different concentrations of glucose, Mito-tempo (MT), autophagy inhibitor (3-MA), autophagy inducer rapamycin (RAP), and P66Shc siRNA. Western blot was used to detect the expression of LC3, P62, ZO-1, claudin-5, and P66Shc in HBMEC. Autophagosomes were observed by transmission electron microscopy (TEM). Immunofluorescence staining was used to observe the expression of ZO-1, occludin, and ROS. The autophagy level was enhanced by HG. HG decreased the expression of ZO-1 and increased the expression of P66Shc and ROS. Inhibition of ROS levels under HG reversed the high level of autophagy induced by HG and increased the expression of ZO-1. The autophagy level was negatively correlated with the ZO-1 expression in HG. In HG, inhibit the expression of P66Shc reduced the ROS and autophagy levels and increased the ZO-1 expression. HG increased the autophagy level and destroyed the integrity of the tight junctions between HBMEC. Silencing P66Shc repaired HG damaged-HBMEC by inhibiting ROS production and reducing autophagy. To explore the molecular mechanism of BBB injury caused by high glucose (HG), we hypothesize that p66Shc damaged BBB by promoting ROS production and autophagy.
Importance of urodynamic evaluation of bladder function after untethering in spina bifida patients – Single center experience of 30 years
Authors: Lingnau Anja , Ciesla Luise , Schneider Joanna , Marco Beatriz Bañuelos , Schulz Matthias , Thomale Ulrich-Wilhelm , Geppert Tamara , Trojan Katharina C. , Kaindl Angela M.
Published: April 2022

Introduction: A TCS after primary closure of meningomyeloceles is a known complication of the spina bifida disease. Data on the outcome after SSCU surgery is heterogeneous and lacking standardization. Thus we aimed to find a reliable system for assessment of the bladder function before and after SSCU surgery and document postoperative outcome.Methods: A retrospective study was performed on a cohort of 306 patients with spina bifida diagnosis. In total, 130 patients underwent 182 SSCU surgeries, 56 of those met our inclusion criteria. A classification system, including two different methods, was used. The AC system used baseline pressure and detrusor over activity to define three levels of bladder dysfunction, the second method ranked the severity of bladder dysfunction by awarding points from 0 to 2 for bladder capacity, maximal detrusor pressure during autonomous contractions, leak point pressure and vesicoureteral reflux A high score is correlated with a severe bladder dysfunction.Results: Gender distribution was equally (male: n=29; 51,8%; female: n=27; 48,2%). The median age at SSCU was 9,02 years (range 0,5 – 22,8 years).After SSCU, the stage improved in 11 patients (19.6%), worsened in 11 (19.6%) patients and remained the same in 34 patients (60.7%) after intervention (AC score). Non-worsening was observed in a total of 45 cases (80.4%) (p<0.001).MHS score (n=27, 48,2%) improved, remained unchanged (n=12, 21.4%), 17 patients worsened (30.4%). Non-worsening in postoperative bladder functional outcome was demonstrated in 39 cases (69,6%) over all (p<0.005).Regardless of whether bladder function is categorized by AC or MHS, postoperative outcome worsened significantly when SSCU was performed due to increasing deterioration in motor function alone (p<0.05). Of the 24 cases with NOD as indication, 22 (91,7%) had an unchanged (n=10; 41,7%) or improved (n=12; 50,0%), meaning positive neuro-orthopedic outcome, only 2 (8,3%) deteriorated (p<0,001).Conclusion: Our study presents reliable evaluation systems for bladder function in spina bifida patients. Since indications for SSCU surgery differ, it is important to know the possible effects on bladder function after this surgical procedure. Even a mild impairment of bladder function has a risk to deteriorate after SSCU surgery. Particularly interesting becomes this with regard to the fact that the prevalence of TCS might become more frequent with the rising numbers of prenatal closures of meningomyeloceles.
Successful salvage urethroplasty with pedicled soft tissue reinforcement for failed hypospadias repair.
Authors: Seo Shogo , Miyake Yuichiro , Takeda Masahiro , Yazaki Yuta , Ochi Takanori , Miyano Go , Koga Hiroyuki , Lane Geoffrey J. , Yamataka Atsuyuki
Published: April 2022

Purpose: The high incidence of scarring and vascular compromise after failed hypospadias repair greatly compromises salvage urethroplasty. Pedicled soft tissue reinforcement (STR) is presented for enhancing the potential for success.Methods: The impact of lateral reinforcement of the scarred urethral plate to boost thickness and perfusion at the time of curvature correction (called CHARGE by the authors) and covering the neourethra at the time of urethroplasty (NUC) used as STR during salvage tubularized incised plate urethroplasty performed between 2003 and 2019 were assessed by retrospective review of the medical records of 8 cases of failed hypospadias repair. Results: Types of hypospadias were perineal/penoscrotal (n=7), and mid-shaft (n=1). Indications for salvage surgery included residual penile curvature (n=5), urethral diverticulum >15mm (n=3), urethral dehiscence (n=1), and urethral stricture (n=1). Salvage surgery was single-stage (urethroplasty at the same of curvature correction; n=1) or multi-stage (n=7; two-stage: n=4, three-stage: n=3). All cases had NUC and 4/8 had CHARGE. All salvage repairs were successful with no incidence of postoperative complications after mean follow-up of 3.9 years (range: 1.6-6.4 years) after the last procedure.Conclusion: STR most likely enhanced tissue perfusion/pliability which ensured the success of salvage urethroplasty for failed hypospadias repair.
Hypoxic microenvironment as a crucial factor triggering events leading to rupture of intracranial aneurysm
Authors: Aoki Tomohiro , Ono Isao , Kayahara Tomomichi , Kawashima Akitsugu , Okada Akihiro , Miyamoto Susumu , Kataoka Hiroharu , Kurita Hiroki , Ishii Akira
Published: April 2022

Background: Subarachnoid hemorrhage being the rupture of intracranial aneurysm (IA) as a major cause has a high mortality rate in spite of technical advancement in treatment interventions. Thereby, it is mandatory for social health to clarify mechanisms regulating rupture of IAs and to develop a novel therapeutic strategy to prevent rupture. Following the recent experimental studies, we and others have clarified the formation of vasa vasorum in IA lesions presumably for inflammatory cells to infiltrate in lesions as the potential histopathological alternation leading to rupture. Main Body: We first clarified the origin of vasa vasorum as arteries located at the brain surface in 3D-immunohistochemistry with tissue transparency. We then found the presence of hypoxic microenvironment mainly at the adventitia of intracranial arteries where IA is induced by using the Pimonidazole-based probe in vivo. Among angiogenic factors potentially responsible for the formation of vasa vasorum, the production of vascular endothelial growth factor (VEGF) from cultured macrophages in such a hypoxic condition was identified in vitro and in vivo experiment using rupture-prone IA lesions induced in a rat model reproduced the production of VEGF from infiltrating macrophages. We further examined VEGF production in human unruptured IA lesions and found the accumulation of VEGF in the lesions, supporting the production of VEGF in situ. Finally, the VEGF-dependent induction of neovessels from arteries on brain surface was confirmed in experiments placing the sheet for the slow-release of VEGF on brain surface. Here, because intracranial arteries histologically lack vasa vasorum and are surrounded by cerebrospinal fluid space, the formation of the hypoxic microenvironment could be a character of intracranial arteries and inflammatory responses there could further facilitate such a condition to induce vasa vasorum. In addition, the enlargement of the lesions and the disruption of physical barrier like arachnoid might be a necessary factor for the migration of vasa vasorum into subarachnoid space from arteries on brain surface.Conclusions: The findings from the present study have revealed the potential role of hypoxic microenvironment and hypoxia-induced VEGF production as a machinery triggering rupture of IAs via providing root for inflammatory cells in lesions to exacerbate inflammation.
The density of Crown-Like Structures in epicardial adipose tissue could play a role in cardiovascular diseases
Authors: Malavazos Alexis Elias , Vincenzo Angelica Di , Iacobellis Gianluca , Basilico Sara , Dubini Carola , Morricone Lelio , Menicanti Lorenzo , Luca Tonia , Giordano Antonio , Castorina Sergio , Carruba Michele , Nisoli Enzo , Prato Stefano Del , Cinti Saverio
Published: April 2022

Purpose The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. Methods We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n=5) or valvular replacement (VR) (n=5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. Results Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/104 adipocytes vs. 0,0 CLS/104 adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. Conclusion CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain.Level of evidence: No level of evidence; this is a basic science study.
Emicizumab in children: bleeding episodes and outcome before and after transition to Emicizumab
Authors: Glonnegger Hannah , Andresen Felicia , Kapp Friedrich , Malvestiti Stefano , Büchsel Martin , Zieger Barbara
Published: April 2022

Purpose: Real-world data and study data regarding therapy with Emicizumab in pediatric cohorts with haemophilia A is scarce. Especially, data on previously untreated pediatric patients (PUPs) and minimally treated patients (MTPs) are missing.Methods: 14 pediatric patients with haemophilia A and treatment with Emicizumab were retrospectively evaluated for Annual Bleeding Rates (ABR) pre-and post-Emicizumab treatment. Safety data and data on management of minor surgery as well as laboratory results were collected. Additionally, we describe the clinical features of two PUPs and one MTP that are included in our cohort.Results: Median age at initiation of Emicizumab was 5.9 (0.26-21.34) years, three patients were younger than one year at initiation of treatment with Emicizumab. Median follow-up time on Emicizumab was 24 (0.7-40) months. Total ABR (p=0.006) as well as spontaneous (p=0.018), traumatic (p=0.012), and joint (p=0.018) ABR reduced significantly post-Emicizumab transition. Safety profile was favourable as only one local site reaction occurred; no cessation of treatment was necessary. Surgery was successfully performed in three patients receiving rFVlla pre- and post-surgery. Emicizumab trough levels showed a median of 43.4 mg/ml (23.9-72.1) after three doses of 3 mg/kg and 53.9 mg/ml (30.4-75) at first follow-up with 1.5 mg/kg. Conclusion: Emicizumab is safe and efficient in pediatric patients with and without inhibitors. More data on larger multicenter cohorts and especially on PUPs/MTPs are still needed.
Preoperative computed tomography-guided localization for multiple pulmonary nodules: comparison of methylene blue and coil
Authors: Zhang Sheng-Feng , Liu Hai-Ri , Ma Ai-Li , Li Er-Liang
Published: April 2022

Background
Preoperative computed tomography (CT)-guided localization has been used to guide the video-assisted thoracoscopic surgery (VATS) sublobar (wedge or segmental) resection for pulmonary nodules (PNs). We aimed to assess the relative efficacy and safety of CT-guided methylene blue (MB)- and coil-based approaches to the preoperative localization of multiple PNs (MPNs).
Methods
Between January 2015 and December 2020, 31 total cases suffering from MPNs at our hospital underwent CT-guided localization and subsequent VATS resection in our hospital, of whom 15 and 16 respectively underwent MB localization (MBL) and coil localization (CL). The clinical effectiveness and complication rates were compared between 2 groups.
Results
The PN- and patient-based technical success rates in the MBL group were both 100%, whereas in the CL group they were 97.2% (35/36) and 93.8% (15/16), respectively, with no substantial discrepancies between groups. Patients in the MBL group illustrated a substantially shorter CT-guided localization duration compared with the CL group (20.1 min vs. 32.5 min, P < 0.001). Pneumothorax rates (P = 1.000) and lung hemorrhage (P = 1.000) were comparable in both groups. In the MBL and CL groups, the mean interval between localization and VATS was 1.2 h and 11.7 h, respectively (P < 0.001). One-stage VATS sublobar resection of the target nodules was successfully performed in all patients from both groups.
Conclusion
Both CT-guided MBL and CL can be readily and safely utilized for preoperative localization in individuals who had MPNs, with MBL being correlated with a shorter localization duration compared with CL.
Post COVID-19 hyperinflammatory acute kidney injury and background ovarian insufficiency: Renal functional restoration after combined angiotensin-converting enzyme inhibitor with estrogen replacement
Authors: Sills E Scott , Wood Samuel H , Walsh Anthony P H
Published: April 2022

Adolescents with COVID-19 and subsequent multisystem inflammatory injury share key features with Kawasaki disease and toxic shock syndrome. As referenced in a United Nations WHO brief from May 2020, findings from North America and Europe drew notice to an acute illness accompanied by severe, diffuse hyperinflammation leading to multiorgan failure. While females diagnosed with COVID-19 generally have more favorable outcomes than males, this protective effect is negated by any low/absent estrogen state. Our research focuses on secondary amenorrhea from pre-adulthood ovarian insufficiency where RUNX2, SALL1 and SAMD9 variants were identified by exon sequencing in a healthy, phenotypically normal 46,XX adolescent. Against this background, COVID-19 infection occurred necessitating hospital admission where multisystem inflammatory syndrome in children (MIS-C) was diagnosed. Although renal function was compromised secondary to COVID-19 infection, this damage was transient and apparently reversed by angiotensin-converting enzyme inhibitor plus transdermal estrogen replacement therapy. This research is the first to study the intersection of multigene variants, ovarian insufficiency, COVID-19, and acute kidney injury as a component of MIS-C. The background transition from adolescence to adulthood is also considered, where successful recovery of renal function was attained using combined enalapril and supplemental estrogen.
Leishmanicidal and Antimicrobial Activities of 4-Quinolone Alkaloids from Stems of the Medicinal Plant Waltheria indica (Malvaceae) and their Chemotaxonomic Significance
Authors: Silva Raquel , Domingos Levy , de Castro Gabriellen , Laport Marinella , Ferreira-Pereira Antônio , Lima Murilo , Cotinguiba Fernando
Published: April 2022

A chemical investigation of the stem of Waltheria indica (Malvaceae) yielded twelve 4-quinolone alkaloids, which were primarily waltheriones. These were waltherione A (1), waltherione B (2), waltherione C (3), waltherione G (4), waltherione H (5), waltherione J (6), waltherione L (7), waltherione P (8), chamaedrone (9), 8-deoxy-antidesmone (10), antidesmone (11), and the previously unreported alkaloid N-methoxy-waltherione A (12). These alkaloids belong to an unusual class of 4-quinolones and therefore, have chemosystematic significance for distinguishing the Waltheria and Melochia genera from the rest of the Malvaceae family. The ability of the alkaloid isolates to reverse the phenotypic expression of fluconazole-resistance was tested by using a mutant strain of Saccharomyces cerevisiae that expressed a Candida albicans transporter. Of the isolates tested, waltherione G afforded a positive result. Leishmanicidal activity and bactericidal tests were also performed using the isolated alkaloids, which showed promising results.
Bioassay of oxidative properties and toxic side effects of apple juice
Authors: Samoylov Artem , Suraeva Natal’ya , Zaytseva Mariya , Petrov Andrey
Published: April 2022

Introduction. Apple juice owes its beneficial properties to various biologically active compounds, e.g. antioxidants. Therefore, food science needs effective methods that would cover all the mechanisms of their effect on human metabolism. However, fruit juice production raises certain safety issues that are associated not only with production risks, but also with some natural components in the raw material. The Allium cepa test seems to be an effective solution to the problem. This plant bioassay has a good correlation tested on mammalian cell cultures.

Study objects and methods. Onion roots (A. cepa) were treated with aqueous solutions of juices and sorbic acid to assess their antioxidant profile. The toxic effects on root tissues were described according to biomass growth, malondialdehyde (MDA) concentration, and proliferative and cytogenetic disorders.

Results and discussion. The study revealed the optimal conditions for the A. cepa assay of the antioxidant properties of apple juice. The antioxidant activity was at its highest when the juice was diluted with water 1:9 and the onion roots were treated with sorbic acid. The lipid oxidation of the A. cepa roots decreased by 43%. A comparative analysis of three different juice brands showed that the difference in their antioxidant profiles was ≤ 3%. As for toxic side effects, the chromosome aberrations increased by six times in all samples.

Conclusion. The research offers a new in vivo method for determining the antioxidant profile of apple juice. Three juice brands proved to have irreversible cytotoxic and genotoxic effects.
Mengembangkan dan Mempertahankan Bisnis UMKM Di Tengah Wabah Korona Dengan Memanfaatkan Bisnis Digital
Authors:   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Sekar Putri Alifia , Hijriansyah Daffa ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Sonofal Darell ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Nathanael Edward ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Gratiana Hironima ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Tejakusuma Kevin ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Nurhayati Nurhayati ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339
Published: April 2022

Kegiatan Kuliah Kerja Nyata (KKN) yang dilakukan di Desa Pajambon, Kuningan ini bertujuan untuk membantu Ibu Eha selaku mitra dalam mengembangkan dan mempertahankan bisnisnya, ditambah dengan keadaan yang sedang sulit akibat wabah covid-19 yang membatasi kegiatan di luar rumah termasuk kegiatan jual beli di pasar. Setelah melakukan identifikasi masalah ditemukan beberapa kekurangan dan kelebihan mitra baik secara internal maupun eksternal. Sehingga solusi yang diambil kelompok adalah membuat logo merek untuk mitra, kartu nama, brosur, akun media sosial Instagram dan Facebook, dan akun e-commerce di Shopee. . Hasil yang didapatkan berupa adanya pemesanan secara online melalui media sosial setelah pemasangan merek pada produk dan penyebaran kartu nama disertai juga dengan brosur yang dilengkapi dengan kontak info mitra, meningkatnya pengikut media sosial mitra akibat adanya aktivitas promosi yang menunjukan peningkatan brand awareness dan efektifitas penggunaan media sosial sebagai sarana promosi, produk mitra juga sudah terjual hingga keluar Pajambon dengan bantuan Shopee dan Instagram. Dengan bantuan dan bimbingan kelompok Ibu Eha tetap dapat melanjutkan bisnisnya di tengah pandemi dengan memanfaatkan bisnis online melalui media sosial dan juga e-commerce sebagai media bisnis digital.
ANALISA PENGEMBANGAN BISNIS SEKTOR PARIWISATA DI DESA CIPUTRI
Authors:   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Putri Yuditama Avifa , Go Calvin ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Rachman Fathur ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Saliman Karen ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Ziyan Agrily Muhammad ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, suryandaru reinardus ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339
Published: April 2022

Industri pariwisata di Indonesia adalah salah satu pendorong ekonomi utama di Indonesia. Sektor bisnis khusus ini telah meningkat lebih dari dua kali lipat selama dekade terakhir. Industri pariwisata telah berkembang dan menjadi pendorong utama ekonomi dan fitur utama dari strategi pertumbuhan ekonomi pemerintah. Meskipun terdapat perkembangan pesat terkait sektor pariwisata, namun tidak seluruh potensi wisata di Indonesia telah berkembang dan dikenal masyarakat. Mengingat fakta tersebut, tim memutuskan untuk menganalisis dan mengembangkan salah satu potensi wisata di Daerah Cianjur, tepatnya Saung Sarongge yang berlokasi di lereng Gunung Gede dan menawarkan berbagai jasa wisata dari empat aspek, yaitu : operasional, pemasaran, keuangan dan juga sumber daya manusia.
Pendampingan UMKM Stick Yummy di Sukatani terhadap Efisiensi Produksi dan Penjualan
Authors:   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Soh Brigitta , Rusli Darren ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Evano Wihardjo Joshua ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Josia Michael ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Elsha Riani Stefany ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Randy Suryajaya William ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339, Ariawan Eko ,   School of Business and Economics Universitas Prasetiya Mulya, BSD City Kavling Edutown I.1, Jl. BSD Raya Utama No.1, BSD City, Kec. Pagedangan, Kabupaten Tangerang, Banten 15339
Published: April 2022

Setiap tahun Universitas Prasetiya Mulya selalu menyelenggarakan Kegiatan Pengabdian Kepada Masyarakat (KPM), dengan tujuan pengembangan UMKM yang dimiliki oleh mitra agar menjadi mandiri. Ada banyak kesempatan dan ruang untuk perubahan ke arah yang lebih baik bagi mitra dari seluruh aspek proses bisnis. Manfaat dari program yang dilakukan tidak hanya tertuju pada bisnis mitra melainkan peningkatan pemahaman serta pengetahuan mitra akan strategi bisnis yang tepat. Dari hasil analisis situasi yang sempat dilakukan, kelompok melihat diperlukannya perubahan dari aspek operasional, aspek pemasaran, aspek keuangan, aspek penelitian dan pengembangan. Selama 30 hari, kelompok telah tinggal bersama mitra dan membantu usaha Stick Yummy untuk meningkatkan efisiensi produksi serta peningkatan penjualan yang terukur secara jelas. Penulisan dari artikel ini menggambarkan akan permasalahan yang dihadapi oleh usaha mitra, Stick Yummy, dan langkah-langkah yang dibentuk oleh kelompok demi menanggulangi permasalahan tersebut.
The fate and risk of nontuberculous mycobacteria in the water supply system: a review
Authors: Gan Yalan , Rahmatika Iftita , Kurisu Futoshi , Furumai Hiroaki , Simazaki Dai , Fukano Hanako , Hoshino Yoshihiko , Kasuga Ikuro
Published: April 2022

Nontuberculous mycobacteria (NTM) infection is estimated as the most serious waterborne infectious disease. NTM are ubiquitous in drinking water supply systems, which could be one of the possible exposure pathways for NTM disease, posing a serious concern to human health. Characteristics of NTM, such as exposure via inhalation, disinfectant resistance, survival in oligotrophic conditions, and association with amoebae, are largely different from those of Escherichia coli (E. coli) which has been traditionally regarded as a model bacterium causing gastrointestinal diseases in water safety. However, the fate of NTM in water supply systems from source water to the point of use has not been systematically revealed yet. Thus, this review proposes that NTM should be regarded as alternative model bacteria in water use by updating the current knowledge on the occurrence, removal efficiency, and regrowth of NTM in water supply systems. Moreover, we demonstrate the need to establish a comprehensive quantitative microbial risk assessment to identify the critical control point, which is indispensable to mitigate NTM risk in water use.
Synthesis and Structure of Hetaryl Substituted 2,5-dioxo-1,2,3,4,5,6,7,8- Octahydroquinolines
Authors: Ozokan Kadri Gokhan , Kaban Seniz
Published: April 2022

Aims and Objective:

Condensation of 5-hetarylidene-2,2-dimethyl-1,3-dioxane-4,6-diones with 5,5-dimethyl-3-arylamino-2-cyclohexanones yields 1-aryl-4-hetaryl-7,7-dimethyl-2,5-dioxo-l,2,3,4,5,5,7,8-octahydro-quinolines. The structures of all the synthesized compounds have been verified by IR, 1H-NMR, 13C-NMR, and mass spectral methods. The 13C-NMR assignments were supported by HSQC and HMBC experiments. Moreover, spin decoupling and NOE experiments have been carried out in order to elucidate stereoisomeric configurations of the compounds. It has been established that the N-phenyl ring, which projects from the plane of the octahydroquinolinedione ring, has a shielding effect on the magnetic field of the protons at 7- and 8-positions of the ring in the molecules of the compounds synthesized.

Materials and Methods:

The NMR spectra were recorded on a Varian Gemini spectrometer [400 MHz (1H) and 100 MHz (13C)]. EI mass spectra were obtained with a Hewlett Packard GC/MS 6890/5973 machine. MALDI-TOF mass measurements were recorded on a Bruker auto-flex III smart beam.

Results:

Various reaction conditions were applied in order to find an optimum and convenient procedure for the formation of octahydroquinoline derivates having hetaryl group. The highest yields (40-50 %) were achieved using acetic acid as solvent, p-toluenesulphonic acid as acidic catalyst, and excess enaminone (1.5 equiv).

Conclusion:

We synthesized eight new 1-aryl-7,7-dimethyl-4-hetaryl-1,2,3,4,5,6,7,8-octahydro-quinoline-2,5-dione compounds containing thienyl core as a result of Michael addition reaction of Knoevenagel products of Meldrum’s acid with dimedone enaminone compounds. Optimum circumstances were established using various reaction conditions and catalyzers throughout the research. The structures of all the synthesized compounds were analyzed by IR, 1H-NMR, 13C-NMR, and mass spectral methods. Furthermore, the structures were verified with the help of 2D (HSQC and HMBC), spin decoupling, and NOE NMR techniques.
Characteristics, Biological Activities, Synthesis, and Methods for the
Determination of Brexpiprazole in Different Matrices
Authors: Shrivastava Alankar , Mittal Ashu , Khabiya Rakhi , Choudhary GP , Darwhekar Gajanan N.
Published: April 2022

Background:

Brexpiprazole (BRZ) is a "third-generation" antipsychotic dopaminergic
(D2) and 5HT1A (serotonin) partial agonist, approved in July 2015 by the US Food and Drug Administration
for the treatment of the major depressive disorder (MDD) other than schizophrenia in
adults. Antipsychotics are known to produce extrapyramidal effects as side effects. The recent development
in this segment is of piperazine-based antipsychotic BRZ, which is more specific towards
indented indications (depression) and has fewer side effects.

Objective:

To critically review the different analytical methods available in the literature.

Methods:

Eight spectrophotometry-based studies, nineteen chromatography-based studies, and
two other method-based studies were found in the literature search. A brief discussion on pharmacokinetics
and the mechanism of action is also included.

Conclutions:

This review can be used for the development of more robust and suitable analytical
methods for the determination of drugs in different matrices. A brief discussion concerning the
approach towards the advancement of green analytical methods is likewise one of the points of
this review.
COVID-19 and Coinfections: A Serious Health Threat Requires Combination
of Diagnosis and Therapy
Authors: Nawaz Shahid , Saleem Maira
Published: April 2022

Since the advent of the COVID-19 pandemic in 2019, a mammoth research activity targeting
the etiological features of COVID-19 has commenced. Many aspects of the disease have been studied,
and various others are under consideration. The secondary microbial coinfections with COVID-19
have generated some serious concerns across the globe. This review mainly focuses on the notable
secondary coinfections. The coinfection of influenza, tuberculosis, and typhoid may mimic the original
COVID-19 symptoms. Physicians and clinicians must focus on the secondary coinfections which may
aggravate the disease progression towards acute respiratory disorder syndrome (ARDS). Diagnostic
strategies must also be redefined to determine the actual underlying secondary coinfection. There is a
need for combination therapy and diagnostic approaches to minimize the risks associated with the
COVID-19 pandemic effectively.