bluuebunny/crossref_metadata_2025 huggingface dataset:
Radioactive 125I Seed Implantation for Recurrent Cervical Carcinoma After Surgery and Radiotherapy: A Case Report
Authors: Qiao Shiqi , Zhang Hongtao , Di Xuemin , Zhao JinXin , Wang Juan
Published: December 2021

Background: The prognosis of cervical cancer is remarkable, but there are still instances of pelvic and/or extrapelvic recurrence after radical hysterectomy with platinum-based chemoradiotherapy. Sixty percent of the patients with radiotherapy (RT) failure have pelvic recurrence, and 80% of them relapse within two years after treatment. Recurrent cervical cancer seriously affects the prognosis and survival rate of patients. Due to the dose limitation for normal tissue, it is difficult to deliver a sufficient number of doses to recurrent lesions through reirradiation. With the rapid development of brachytherapy technologies such as three-dimensional afterloading brachytherapy, interstitial brachytherapy and radioactive 125I seed implantation, the overall survival (OS) of patients with recurrent cervical cancer has been improving. In the present study, a case in which the patient was successfully treated with radioactive 125I seed implantation is reported.Case presentation: The patient, a 47-year-old woman, was initially diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer and received preoperative radiotherapy, radical hysterectomy, pelvic lymph node dissection and postoperative radiotherapy. After 95 months of follow-up, retroperitoneal lymph node metastasis and edema of the left lower limb . The size of the retroperitoneal lesion was 2.3 × 2.0 cm, and the size of the left supraclavicle lesion was 2.0 × 1.5 cm. Radioactive 125I seed implantation was performed for retroperitoneal lymph node metastasis and left supraclavicular metastasis. Paclitaxel and cisplatin chemotherapy were given after the operation. Three months after implantation, the size of the retroperitoneal focus was 1.5 × 1.1 cm, and the size of the left supraclavicular lesion was 1.0 × 0.6 cm. Thirteen months after implantation, according to the RECIST standard, the therapeutic effect reached CR. At the time of submission, the patient's progression-free survival was 6 years and 4 months.Conclusions: CT-guided 125I seed implantation is a safe, effective, and minimally invasive method for treating patients with recurrent cervical cancer after radiotherapy. The response of this patient indicates that 125I seed implantation can be used as a complementary treatment for recurrent cervical cancer after chemoradiotherapy and may also prove to be reliable for comprehensive treatment of cervical cancer.
The Effect of SBAR Communication on Nurse Attitude and Behavior in Increasing Patient Safety in KRMT Wongsonegoro Hospital, Semarang
Authors: Girsang Ermi , Nasution Sri Lestari Ramadhani , Fatmah Annisya Ul , Cristy Melyala
Published: December 2021

Introduction: WHO officially published the Nine Life Saving Patient Safety, which one is correct communication during handover using the SBAR method. SBAR is considered a clear sign and secure method of communication for problem solving among various disciplines in the medical environment and a simple way of sharing patient information with other medical professionals. Methods: This research is a quasi-experimental study with a pretest-posttest design with control group design, the results of the research were processed using paired sample t-test. The data collection of this research uses a checklist of observation sheets to assess the ability of nurses to communicate SBAR, attitudes and behavior of nurses using a questionnaire. Result and discussion: this study showed a significant difference in the attitudes and behavior of nurses in improving patient safety after being given SBAR communication materials with p-value < 0.05. Conclusion: This study showed significant differences in the attitudes and behavior of nurses after being given SBAR communication training in the intervention group. Meanwhile, the control group showed a non-significant difference This showed that SBAR communication materials affect the attitudes and behavior of nurses in improving patient safety.
Comorbid Symptoms of Internet Addiction Among Adolescents with and Without Autism Spectrum Disorder: A Comparative Study
Authors: Kawabe Kentaro , Horiuchi Fumie , Hosokawa Rie , Nakachi Kiwamu , Soga Junya , Ueno Shu-ichi
Published: December 2021

Over the last decade, research into the characteristics of problematic internet use among individuals with autism spectrum disorder (ASD) has greatly increased. We investigated Internet addiction’s prevalence and compared its related factors, among adolescents with and without ASD. Outpatients (n = 102) aged 12–15 years, completed the Basic Information Questionnaire, Internet Addiction Test, and Quick Inventory of Depressive Symptomatology Self-Report Japanese version. Their parents completed the Social Responsiveness Scale-2 and Attention Deficit Hyperactivity Disorder Rating Scale-IV. Scores of both (ASD and without ASD) groups were analyzed. Prevalence of Internet addiction was 40.0% in ASD group and 23.9% in without ASD group. Statistically related factors of Internet addiction were not found in the ASD group. However, factors of Internet addiction were related to the QIDS and ADHD-RS scores in the without ASD group. In conclusion, factors related to Internet addiction differed for ASD patients and without ASD patients.
A Qualitative Study Exploring Barriers and Facilitators to Establishing Nurse-led, Multidisciplinary Psychological Care for Trauma Patients: Experiences From Doctors and Nurses
Authors: Leng Yanan , Wu Ying , Wang Zonghua , Zhou Xiaoping , Liao Jianmei
Published: December 2021

BackgroundTrauma patients are often in a state of psychological stress, experiencing helplessness, sadness, frustration, irritation, avoidance, irritability and other adverse emotions. Doctors and nurses are at the forefront of caring trauma patients and they play a crucial role in psychological supports and mental health care. However, few qualitative studies had based on the framework of the Theory of Planned Behavior (TPB) to explore the experiences in providing psychological care for trauma patients. We examined attitudinal, normative, and control beliefs underpinning medical staffs’ decisions to perform psychological care.MethodA qualitative study of in-depth semi-structured interviews was conducted among 14 doctors and nurses engaging in trauma care. The participants came from six tertiary hospitals in Chongqing, China. Data analysis was performed using the approach of Colaizzi. According to the framework of TPB, the researchers identified and summarized the themes.ResultsImportant advantages (mutual trust, patients' adherence and recovery), disadvantages (workload, short-term ineffective, practice unconfidently), referents (supportive: managers, patients, kinsfolk, nursing culture; unsupportive: some colleagues and patients), barriers (insufficient time or energy, resources situations), and facilitators (access to psychologist, training/education, reminders) were identified. Some demands, such as training diversity, multidisciplinary cooperation and families' support, reflected by doctors and nurses were important for them to carry out psychological care.ConclusionAccording to the TPB, this article explored the internal and external promotion and hindrance factors that affecting the intentions and behaviors of doctors and nurses in implementing psychological care for trauma patients. We also focused on the experience and demands of health professionals in conducting psychological care, which could provide references for managers to formulate corresponding psychological care procedures and norms.
Network Analysis Reveals Dysregulated Functional Patterns in Type II Diabetic Skin
Authors: Liu Chunan , Ram Sudha , Hurwitz Bonnie L.
Published: December 2021

Skin disorders are one of the most common complications of type II diabetes (T2DM). Long-term effects of high blood glucose leave individuals with T2DM more susceptible to cutaneous diseases, but its underlying molecular mechanisms are unclear. Network-based methods consider the complex interactions between genes which can complement the analysis of single genes in previous research. Here, we use network analysis and topological properties to systematically investigate dysregulated gene co-expression patterns in type II diabetic skin with skin samples from the Genotype-Tissue Expression database. Our final network consisted of 8,812 genes from 73 subjects with T2DM and 147 non-T2DM subjects matched for age, sex, and race. Two gene modules significantly related to T2DM were functionally enriched in the pathway lipid metabolism, activated by PPARA and SREBF (SREBP). Transcription factors KLF10, KLF4, SP1, and microRNA-21 were predicted to be important regulators of gene expression in these modules. Intramodular analysis and betweenness centrality identified NCOA6 as the hub gene while KHSRP and SIN3B are key coordinators that influence molecular activities differently between T2DM and non-T2DM populations. We built a TF-miRNA-mRNA regulatory network to reveal the novel mechanism (miR-21-PPARA-NCOA6) of dysregulated keratinocyte proliferation, differentiation, and migration in diabetic skin, which may provide new insights into the susceptibility of skin disorders in T2DM patients. Hub genes and key coordinators may serve as therapeutic targets to improve diabetic skincare.
Simultaneous determination of gross alpha/beta activities in water by liquid scintillation counting and its applications in the environmental monitoring
Authors: Li Xiaoyun , Wang Shaolin , Lou Hailin , Pan Jingshun , Dong Qian , Zheng Yifan , Chen Ling
Published: December 2021

Based on the standards of ISO11704-2018 and ASTM D7283-17, a method for simultaneous determination of gross alpha and gross beta activity concentrations in water by liquid scintillation counting (LSC) was established, which can be applied to various types of water samples in routine monitoring, such as drinking water, groundwater, geothermal water, seawater, and radioactive wastewater. The sample’s pH value and concentrated volume must be controlled to avoid quenching as much as possible. The validation tests show that the deviations of gross alpha and gross beta activities can satisfy quality control requirements in a wide range of activity ratios. For the actual samples, the measurement results of the LSC method are in good agreement with those of the thick source method. Moreover, the LSC method performs better in detection limit and a simpler pretreatment process than the thick source method.
Valorization of Oil Waste for Biodetergent Production Using Serratia Marcescens N2 and Gamma Irradiation Assisted Biorecovery
Authors: Elkenawy Nora M. , Gomaa Ola M.
Published: December 2021

The aim of the present work is to valorize previously used frying oil and use it as biodetergent. Serratia marscens N2 valorized 20% used oil and 8% cell concentration, the biosurfactant produced was a negatively charged lipopeptide with surface tension of 26.8 mN/m. Gamma radiation was used to obtain the higher yield of the biosurfactant by exposing the cells after growth under optimal conditions to low dose gamma radiation. The results showed that the use of radiation led to an increase in the amount of biosurfactant, and the biorecovery took place in a shorter time than usual. The chemical or functional form of the substance did not change at doses of 500 and 1000 gray, while there was a change in production and chemical and functional form at the dose of 2000 gray. The produced biosurfactant was used before and after irradiation to wash oil soiled cloths, the results showed 87% removal at 60oC under stirring conditions. Skin irritation tests performed on experimental mice showed that the surfactant does not cause any inflammation or red spots. Optical images of cloth patches showed no effect on fabric threads post washing the oil soiled cloth patches with biosurfactant. This study proved that 1) previously used oil can be bioconverted into biosurfactant and 2) the use of low doses gamma radiation results in an increase in biosurfactant yield by creating holes in the bacterial cell wall, which helps to recover more quantities of the biosurfactant without change in its chemical or functional form.
Fenton Reaction Facilitates The Fungal Infection On The Unicellular Alga Haematococcus Pluvialis and Discovery of a Biosafe and Environment-Friendly Chemical That Blocks The Infection
Authors: Yan Hailong , Ma Haiyan , Li Yanhua , Zhao Liang , Lin Juan , Jia Qikun , Hu Qiang , Han Danxiang
Published: December 2021

Background

The green microalga Haematococcus pluvialis is used as cell factories for producing astaxanthin, the high-value natural compound with multiple biological functions. However, H. pluvialis is prone to the infection by a parasitic fungus Paraphysoderma sedebokerense, which is the most devastating threat to the mass culture of H. pluvialis all over the world. Little is known for the mechanisms underlying the infection process, though it is of great essential for developing effective measures to mitigate the pathogen threatening for the natural astaxanthin industry.
Results

We observed that there were heat-stable substances with small molecular weight produced during the infection process, which significantly stimulated the parasitism process and enhanced the susceptibility of H. pluvialis cells to the pathogen. Systematic approaches including multi-omics, biochemical and imaging analysis were deployed to uncover the identity of the metabolites and the underlying mechanisms. Two metabolites, 3-hydroxyanthranilic acid and hordenine were identified and proved to stimulate the infection via driving fenton reaction mediated oxidative stress to H. pluvialis. The reaction generated hydroxyl radicals to disrupt the subcellular components of the algal cells and to make the algal cells more susceptible to the infection. Based on these findings, a biosafe and environment-friendly antioxidant butylated hydroxyanisole was selected to inhibit the fungal infection, which completely abolished the infection at 12 ppm.
Conclusions

This study provide for the first time, a framework to dissect the functions of secondary metabolites in the interaction between the unicellular algal H. pluvialis and its fungi parasite, indicating that oxidative degradation is a strategy used for the fungal infest. Eliminating the oxidative burst through adding antioxidant butylated hydroxyanisole could be an effective measure to reduce parasitic infection in H. pluvialis mass culture.
Interaction Between Caveolin-1 Polymorphism with Dietary Fat Quality Indices and the Relationship with Visceral Adiposity Index (VAI) and Body Adiposity Index (BAI) Among Overweight and Obese Women: A Cross-Sectional Study
Authors: Ensaf Rasool Ghaffarian , Shiraseb Farideh , Mirzababaei Atieh , Clark Cain , Mirzaei Khadijeh
Published: December 2021

Background & Aims:

Caveolin-1(CAV-1) in adipocyte tissue, and other parts of body, possess numerous biological functions. In the present study, we sought to investigate the interaction between CAV-1 polymorphism with dietary fat quality indices and the relationship with visceral adiposity index (VAI) and body adiposity index (BAI) among overweight and obese women.
Methods

This study was conducted on 386 women, aged 18-48 years old. Biochemical measurements were measured by standard protocols. We used a food frequency questionnaire (FFQ) to calculate the dietary intake and the indices of dietary fat quality intake. Anthropometric values and body composition were measured by standard methods. Finally, the CAV-1 genotype was measured using PCR-RFLP method.
Results

We found a marginally significant difference in waist-to-hip ratio (WHR) (P=0.06) and BAI (P=0.06) of participants, after adjusting with potential cofounders. For dietary intakes, after adjusting with the energy intake, mean differences in biotin (P=0.04) and total fiber (P=0.06) were significant and marginally significant, respectively. The interaction between two risk allele genotype group (AA) with omega-6 to omega-3 ratio (W6/W3) on BAI, after adjustment with potential cofounders (age, physical activity, energy intake, education), was marginally positive (β = 14.08, 95%CI= -18.65,46.81, P= 0.07). In comparison to the reference group (GG), there was a positive interaction between the two risk allele (AA) with W6/W3 ratio on VAI (β = 2.81, 95%CI= 1.20,8.84, P= 0.06) in the adjusted model.
Conclusions

We found that there may be an interaction between CAV-1 genotypes with dietary quality fat indices on VAI and BAI among overweight and obese women.
Loss of Tau Expression Attenuates Neurodegeneration Associated with α-Synucleinopathy
Authors: Vermilyea Scott C. , Christensen Anne , Meints Joyce , Singh Balvindar , Martell-Martínez Héctor , Karim Md. Razaul , Lee Michael K
Published: December 2021

Background: Neuronal dysfunction and degeneration linked to a-synuclein (aS) pathology is thought to be responsible for the progressive nature of Parkinson’s Disease and related Dementia with Lewy Bodies. Studies indicate to bidirectional pathological relationships between aS pathology and tau abnormalities. We recently showed that A53T mutant human aS (HuaS) can cause post-synaptic and cognitive deficits that require microtubule-associated protein tau expression. However, the role of tau in development of aS pathology and subsequent neuronal dysfunction has been controversial. Herein, we set to determine the role of tau in the onset and progression of aS pathology (a-synucleinopathy) using a transgenic mouse model of a-synucleinopathy lacking mouse tau expression. Methods: Transgenic mice expressing A53T mutant HuaS (TgA53T) were crossed with mTau-/- mice to generate TgA53T/mTau-/-. To achieve uniform induction of a-synucleinopathy in mice, we used intramuscular injections of aS preformed fibrils (PFF) to non-transgenic (nTg), TgA53T, TgA53T/mTau-/-, and mTau-/- mice. Motor behavior was analyzed at 70 days post inoculation (dpi) of PFF and tissues for biochemical and neuropathological analysis were collected at 40 dpi, 70 dpi, and end stage. Results: Loss of tau expression significantly delayed onset of motor deficits in the TgA53T model and delayed a-synucleinopathy disease progression, as evidenced by a significant reduction in histopathological and behavioral markers of neurodegeneration and disease, and a significant improvement in survival. In vitro application of PFF to primary mouse hippocampal neurons demonstrated no changes in PFF uptake and processing or pS129 aS aggregation as a function of tau expression. However, PFF-induced neurotoxicity, including morphological deficits in nTg neurons, were prevented with tau removal. Conclusions: Collectively, our data suggest that tau is likely acting downstream of aS pathology to affect neuronal homeostasis and survival. This work further supports the investigation of tau in a-synucleinopathies to identify novel disease-modifying therapeutic strategies.
Prognostic Significance of Globulin/Low-Density Lipoprotein Ratio In Patients With Hepatocellular Carcinoma After Local Ablative Therapy
Authors: Qiao Wenying , Wang Qi , Li Jianjun , Yuan Chunwang , Guo Dandan , Zhu Tong , Zang Chaoran , Liu Biyu , Wang Qi , Wang Wen , Zhang Yonghong
Published: December 2021

Background: Low-density lipoprotein (LDL) and globulin have been found to be predictors for some malignant tumors, but their predictive value in hepatocellular carcinoma (HCC) has hardly to be elucidated. This study assessed the prognostic significance of globulin to low-density lipoprotein ratio (GLR) in HCC patients before ablation.Materials and methods: This study analyzed 312 HCC patients hospitalized and underwent ablative treatment in Beijing You 'an Hospital, Capital Medical University, from January 1, 2012 to January 1, 2017. Cox regression analysis was used to assess the factors independently associated with recurrence and survival. The optimal cut-off value and prognostic role of GLR and other markers were evaluated via the receiver operating characteristic-ROC curves and the Youden index. Overall survival (OS) and recurrence-free survival (RFS) were calculated by Kaplan-Meier analysis, and compared between groups using the log-rank.Result: Univariate and multivariate analysis found that the tumor number (HR: 1.676;95%CI: 1.113-2.526), tumor size (HR: 1.967;95%CI: 1.251-3.092), GLR (HR: 1.028;95%CI: 1.004-1.052) were independent risk factors of relapse; while etiology (HR: 1.328;95%CI: 1.052-1.677), tumor number (HR: 1.615;95%CI: 1.015-2.570), tumor size (HR: 2.061; 95%CI: 1.243-3.418), Fib (HR: 0.73; 95%CI: 0.535-0.996) and GLR (HR: 1.031;95%CI: 1.003-1.06) were related to overall survival. We classified the patients into groups with high and low levels of GLR based on the optimal cut-off value of GLR identified by generating receiver operating characteristics (ROC) curve. The cumulative 1-, 3-, and 5-year RFS rates in the low GLR group were 76.4%, 53.8% and 43.4%, while those in the high GLR group were 71%, 31% and 22%, respectively (P <0.001). Concerning OS, the low GLR group showed a 1-, 3- and 5-year OS of 99.5%, 92.0% and 80.2% versus 98%, 73% and 63% for the high GLR group (P <0.001). Finally, patients were stratified by GLR and tumor size. The outcomes revealed that patients in group A (GLR<16.54 and tumor size ≤30mm) showed better prognosis than group B (GLR≥16.54 and tumor size≤30mm or GLR<16.54 and tumor size >30mm) and group C (GLR≥16.54 and tumor size >30mm) (P <0.001). Conclusions: Preoperative GLR ratio could serve as a biomarker to predict prognosis in HCC patients who underwent complete ablation.
Advantages and Challenges of Fostering Cognitive Integration Through Virtual Collaborative Learning: a Qualitative Study
Authors: Ignacio Jeanette , Chen Hui-Chen , Roy Tanushri
Published: December 2021

BackgroundThe drastic shift from face-to-face classes to online learning due to the COVID-19 pandemic has enabled educators to ensure the continuity of learning for health professions students in higher education. Collaborative learning, a pedagogy used to facilitate knowledge integration by helping students translate theory from basic sciences to clinical application and practice, has thus been transformed from a face-to-face to a virtual strategy to achieve the learning objectives of a multi-disciplinary and integrated module.ObjectivesThis study aimed to describe and evaluate, through focus group discussions, a virtual collaborative learning activity implemented to assist first year undergraduate nursing students to develop cognitive integration in a module consisting of pathophysiology, pharmacology and nursing practice.MethodsFourteen first year undergraduate students and four faculty involved in facilitating the virtual collaboration participated in the study. Focus group discussions were conducted to elicit the perceptions of students and staff on the virtual collaborative learning session conducted at the end of the semester.ResultsThree themes were generated from the thematic analysis of the students’ focus group scripts. These were: (1) achieving engagement and interaction, (2) supporting the collaborative process, and (3) considering practical nuances. The three themes were further subdivided into subthemes to highlight noteworthy elements captured during focus group discussions. Three themes also emerged from the focus group discussion scripts of faculty participants: (1) learning to effectively manage, (2) facing engagement constraints, and (3) achieving integration. These themes were further sectioned into salient subthemes.ConclusionThe virtual collaborative learning pedagogy is valuable in fostering cognitive integration. However, meticulous planning considering various variables prior to implementation is needed. With better planning directed at addressing the learners’ needs and the faculty’s capabilities and readiness for online learning pedagogies, and with a strong institutional support to help mitigate the identified constraints of virtual collaborative learning, students and faculty will benefit.
Phenotyping of boro rice (Oryza sativa L.) cultivars in Assam based on its potential yield and variable component traits
Authors: Pradhan Amit Kumar , Tanti Bhaben
Published: December 2021

The current environmental scenario and increased average yield rate has marked boro rice cultivars as a potent rice cultivar during rabi season. It serves to be an alternative to traditional sali rice and an escape to flood problems. The selection and development of potent boro rice cultivar among its diverse types has been an issue. In this study, 117 traditionally grown boro rice cultivars in different low-lying areas and newly developed irrigated areas of Assam were analyzed. The cultivars were analyzed based on yield and related component traits as per the standard evaluation system for rice. Grain yield and its related component traits showed a significant relationship among the cultivars. All the traits analyzed showed positive relationship with grain yield and harvest index except to time taken for flowering and maturity. Based on total yield, principal component and cluster analysis, Bahurupi, PSB 68, Mandhya Vijaya, Bahunipi, Pathariya showed to be best performing cultivars, with high yield and higher component traits performance. This study marks the significant association of grain yield with its component traits and further provides an insight to the selection of rice cultivars for breeding programmes.
High Neutrophil-lymphocyte Ratio Is a Prognostic Marker for Mortality in Severe Covid-19 and Is Associated With Elevated Age and Kidney Failure
Authors: Santos Heitor , Delpino Felipe , Veloso Octavio , Freire Juliana , Gomes Erlaine , Pereira Cristina
Published: December 2021

Neutrophil and lymphocyte ratio (NLR) has emerged as a prognostic marker in intensive care. This study aimed to associate high NLR values with COVID-19-associated diseases and mortality among critically ill patients. A cross-sectional study encompassing 189 critically ill patients with COVID-19 was performed. Crude model and adjusted (1- age; 2- sex; 3- kidney failure, diabetes, obesity, hypertension, sex, and age) modes were used. Participants with NLR ≥10.6 were older than those with NLR <10.6 (p < 0.001). The number of deaths (37 vs. 18, p = 0.001) and patients with kidney failure (30 vs. 20, p = 0.045) were higher for NLR ≥10.6 than NLR <10.6. NLR ≥10.6 was associated with higher number of deaths for the crude model (OR: 3.10 [95%CI:1.60-6.01], p = 0.001), age-adjusted (OR: 2.62 [95%CI:1.32-5.20], p = 0.006) and sex-adjusted (OR: 2.97 [95%CI:1.52-5.78], p = 0.031), as well as in the fully-adjusted model (OR: 2.48 [95%CI:1.21-5.08], p = 0.013), when compared to NLR <10.6. Older adults (≥60y) had an OR of 2.61 (95%CI:1.26-5.39, p = 0.010) for mortality compared to adults (≤59y), and the same value was found for the model adjusted for sex (OR: 2.61 [95%CI:1.26-5.42], p = 0.010). Kidney failure was associated with mortality for the crude model (OR: 2.58 [95%CI:1.30-5.11], p = 0.007), age-adjusted (OR: 2.09 [95%CI:1.02-4.27], p = 0.044), and sex-adjusted (OR: 2.45 [95%CI:1.23-4.89], p = 0.011). In conclusion, high NLR is a prognostic marker for mortality in severe COVID-19 and is associated with advanced age and kidney failure.
Reduction of The Pyruvate Decarboxylase Activity Improves Isobutanol Production By Klebsiella Pneumoniae
Authors: Shu Lin , Gu Jinjie , Wang Qinghui , Sun Shaoqi , Cui Youtian , Fell Jason , Mak Wai Shun , Siegel Justin B. , Shi Jiping , Lye Gary J. , Baganz Frank , Hao Jian
Published: December 2021

Background

Klebsiella pneumoniae contains an endogenous isobutanol synthesis pathway. ipdC, annotated as an indole-3-pyruvate decarboxylase (Kp-IpdC), was identified to catalyze the formation of isobutyraldehyde from 2-ketoisovalerate.
Results

Compared with 2-ketoisovalerate decarboxylase from Lactococcus lactis (KivD), a decarboxylase commonly used in artificial isobutanol synthesis, Kp-IpdC has an 2.8-fold lower Km for 2-ketoisovalerate, leading to higher isobutanol production without induction. However, high level expression of ipdC by induction resulted in a low isobutanol titer. In vitro enzymatic reactions showed that Kp-IpdC exhibits promiscuous pyruvate decarboxylase activity, which adversely consume the available pyruvate precursor for isobutanol synthesis. To address this we have engineered Kp-IpdC to reduce pyruvate decarboxylase activity. From computational modeling we identified 10 residues surrounding the active site for mutagenesis. Ten designs consisting of eight single-point mutants and two double-mutants were selected for exploration. Mutants L546W and T290L showed 5.1% and 22.1% of catalytic efficiency on pyruvate, which were then expressed in K. pneumoniae for in vivo test. Isobutanol production by K. pneumoniae T290L was 25% higher than the control strain, and a final titer of 5.5 g/L isobutanol was obtained with a substrate conversion ratio of 0.16 mol/mol glucose.
Conclusions

This research provides a new way to improve the efficiency of the biological route of isobutanol production.
A New Prognostic and Therapeutic Immune-related Risk Signature of Colorectal Cancer
Authors: Li Yuan , Huang Hao , Feng Jun , Zhu Yulan , Jiang Tianwei , Xu Bin , Zheng Xiao , Chen Lujun
Published: December 2021

BackgroundAlthough some advanced colorectal cancer (CRC) patients could select immunotherapy, but still most microsatellite stability (MSS) CRC patients did not respond. Our present study aims to set up a novel system for prognostic prediction and immunotherapeutic responsiveness for MSS CRC patients.MethodsUnivariable Cox regression survival analysis and least absolute shrinkage and selector operation (LASSO) regression analysis were performed to identify prognostic genes and establish immune risk signatures. Multivariate Cox regression analysis was performed to verify whether these clinical features could predict prognosis. R package was used to analyze the relationship between the immune-related risk model and these immune cells, effector molecules, and immune checkpoints.ResultsWe constructed an immune-related signature and verified its predictive capability. Immune-related signature included 12 differentially expressed IRGs (12 DE IR MSSGs), including CXCL1, CD36, FABP4, MS4A2, NRG1, VGF, GRP, HDC, XCL1, NGF, MAGEA1, and IL13. The signature consisting of 12 DE IR MSSGs was an independent and effective prognostic factor for the overall survival of CRC patients. In addition, the signature consisting of 12 DE IR MSSGs reflected the infiltration characteristics of different immunocytes in tumor immune microenvironment. The signature consisting of 12 DE IR MSSGs also had a significant correlation with immune checkpoint molecules.
From Theory to Experiment: Transformer-based Generation Enables Rapid Discovery of Novel Reactions
Authors: Wang Xinqiao , Yao Chuansheng , Zhang Yun , Yu Jiahui , Qiao Haoran , Zhang Chengyun , Wu Yejian , Bai Renren , Duan Hongliang
Published: December 2021

Deep learning methods have been proven their potential roles in the chemical field, such as reaction prediction and retrosynthesis analysis. However, the de novo generation of unreported reactions using artificial intelligence technology remains not be completely explored. Inspired by molecular generation, we proposed the task of novel reaction generation. In this work, we applied the Heck reactions to train the transformer model, state-of-art natural language process model and obtained 4717 generated reactions after sampling and processing. We then confirmed that 2253 novel Heck reactions by organizing chemists to judge the generated reactions, and adopted organic synthesis experiment to verify the feasibility of unreported reactions. In this process, it only took 15 days from Heck reaction generation to experimental verification, proving that our model learns reaction rules in-depth and can make great contributions in the novel reaction discovery.
Effects of Ketoconazole On Clinical Recovery In Central Serous Chorioretinopathy
Authors: Chantarasorn Yodpong , Rasmidatta Kochapong , Pokawattana Itsara , Silpa-archa Sukhum
Published: December 2021

Background: Hypercortisolism has long been correlated with choroidal vasorelaxation in central serous chorioretinopathy (CSCR). This may explain the inconsistency of therapeutic responses of the mineralocorticoid receptor (MR) antagonist since hyperaldosteronism has rarely been detected in such cases. Hence, an early treatment using ketoconazole, the first line cortisol inhibitor that also blocks the MR ligand, appears to be rational. This study aimed to evaluate the effects of ketoconazole on CSCR, and to analyze correlations between choroidal thickness and steroid hormones.Method: In this three-center retrospective cohort, forty-one naïve CSCR eyes of 41 patients were categorized into control (20 eyes) and treatment group (21 eyes). Patients in the treatment group were given oral ketoconazole at a daily dose of 400 or 600 mg for three to six weeks. At week 12, rescue laser therapy was applied to patients exhibiting persistent subretinal fluid (SRF). We performed a survival analysis to determine the time interval from presentation to clinical resolution of SRF. The secondary outcomes consisted of proportion of eyes with persistent SRF, and factors affecting therapeutic response.Results: Mean 24-hour urinary free cortisol (UFC) were elevated at 181 ± 70 and 150 ± 68 µg/day (range = 20-150) in the treatment and control group (p = 0.21). After controlling for age and gender, baseline UFC levels demonstrated a positive correlation with choroidal thickness in both eyes (p < 0.05). Ketoconazole significantly accelerated the resolution of CSCR with the median time to resolution of 7 versus 16 weeks (p < 0.01), and reduced the proportion of eyes receiving rescue therapy at 12 weeks (23.8% versus 50%, p = 0.01). Prolonged CSCR durations were likely found in elderly patients who had thick choroid in fellow eyes.Conclusions: Elevated glucocorticoids are likely responsible for the pathogenesis of CSCR. Therefore, a temporary decrease in choroidal hyperpermeability using the cortisol blocker could reduce the persistency of CSCR.
Gene Expression Variation Explains Maize Seed Germination Heterosis
Authors: Wan Jiong , Wang Qiyue , Zhao Jiawen , Dang Kuntai , Guo Zhanyong , Hu Desheng , Meng Shujun , Lin Yuan , Qiu Xiaoqian , Mu Liqin , Ding Dong , Tang Jihua
Published: December 2021

BackgroundHeterosis has been extensively utilization in plant breeding, however, the underlying molecular mechanism remain largely elusive. Maize (Zea mays), which exhibits strong heterosis, is an ideal material for studying heterosis.ResultsIn this study, there is a faster imbibition and development in reciprocal crossing Zhengdan958 hybrids than in their parent lines during seed germination. To investigate the mechanism of heterosis of maize germination, comparative transcriptomic analyses was conducted between reciprocal crossing hybrids and their parental lines. The gene expression patterns showed that 1324 (47.27%) and 1592 (66.44%) of the different expression genes between hybrids and either parental line display parental dominance up or higher levels in Zhengdan958 and Zhengdan958 reciprocal-cross, respectively. Notably, these genes were mainly enriched in metabolic pathways, including carbon metabolism, glycolysis/gluconeogenesis, protein processing in endoplasmic reticulum, etc.ConclusionOur results provide evidence for the higher expression level genes in hybrid involved in metabolic pathways acting as main contributors to maize seed germinating heterosis. These findings provide new insights into the gene expression variation of maize embryo and improve the understanding of maize seed germination heterosis.
Determinants of knowledge, attitudes, and practices of front-line health workers during the first wave of COVID-19 in Africa: a multi-center online cross-sectional study
Authors: Kamabu Larrey Kasereka , Lekuya Hervé Monka , Iranya Richard Newton , Kasusula Bienvenu Muhindo , Sikakulya Franck Katembo , Kicaber Saviour , Valimungighe Moise Muhindo , Nganza Sifa Katungu , Butala Eric Sadiki , Sikiminya Zacharie Muhindo , Kathaka Louange Maha , Munyambalu Dalton Kambale , Katsioto Agnès Kavira , Longombe Thérèse Yenyi Ahuka , Mumbere Bienfait , Nzanzu Adelard Kalima , Kavughe Frederic , Kambere Thaddée Katembo , Robinson Ssebuufu
Published: December 2021

Background: During its first wave of COVID-19 infection in sub-Saharan Africa, there was insufficient understanding of the pandemic among front-line health care professionals that has led to a misidentification, and mistreatment of affected patients, with a potential risk of contracting and spreading the disease. This study was carried out to determine the Knowledge, attitude, and practices (KAP) of front-line health workers (HWs) towards COVID-19 in Africa and their related factors.Methods: This was a multi-centers online cross-sectional study conducted over a 3-months study-period using a google survey link among front lines HWs involved in the COVID-19 response in 26 African countries. Chi-square test & logistic regression were used in the bivariate and multivariate analysis respectively to assess determinants of KAP. Statistical analysis was done using STATA version 16; all tests were two-sided with 95% confidence interval. Results: Five hundred and seventeen (517, 96.3%) consented to participate in this study from 26 African countries; 289 (55.9%) were male and 228 (44.1%) female. Overall, most of HWs, 379 (73.3%) showed poor knowledge about COVID-19 infection and preventive measures. In contrast, majority of them showed good attitude (89%) and practice (90.3%) towards prevention of COVID-19 infections. Knowledge varied among countries; Uganda had the greatest number of HWs with good knowledge. (OR = 28.09, p <0.0001) followed by Ghana (OR=10.92, p=0.001) and DRC (OR: 4.59, p=0.015). The cadre of HWs also influenced knowledge; doctors were the most knowledgeable as compared to other cadres (OR: 3.4, p= 0.005). Additionally, knowledge increased with increasing HWs’ education level (p=0.011).Attitude and practice were both influenced by HWs country of workplace (p=0.05 & p< 0.0001 respectively) and their cadre (p = 0.025 & p < 0.0001 respectively).Conclusions: Majority of the front-line HWs in the African region had an overall good attitude and practice towards COVID-19 infection and practice measures despite relatively poor Knowledge. The KAP is influenced by HWs country of workplace, their cadre and level of education.
Integrated rupture mechanics for slow slip events and earthquakes
Authors: Weng Huihui
Published: December 2021

Slow slip events usually occur downdip of seismogenic zones in subduction megathrusts and crustal faults, with rupture speeds much slower than earthquakes. The empirical moment-duration scaling relation can help constrain the physical mechanism of slow slip events, yet it is still debated whether this scaling is linear or cubic and a fundamental model unifying slow slip events and earthquakes is still lacking. Here I present numerical simulations that show that slow slip events are regular earthquakes with negligible dynamic-wave effects. A continuum of rupture speeds, from arbitrarily-slow speeds up to the S-wave speed, is primarily controlled by the stress drop and a transition slip rate above which the fault friction transitions from rate-weakening behaviour to rate-strengthening behaviour. This continuum includes tsunami earthquakes, whose rupture speeds are about one-third of the S-wave speed. These numerical simulation results are predicted by the three-dimensional theory of dynamic fracture mechanics of elongated ruptures. This fundamental model unifies slow slip events and earthquakes, reconciles the observed moment-duration scaling relations, and opens new avenues for understanding earthquakes through investigations of the kinematics and dynamics of frequently occurring slow slip events.
Tb-practecal: Study Protocol for a Randomised, Controlled, Open-label, Phase II-III Trial to Evaluate the Safety and Efficacy of Regimens Containing Bedaquiline and Pretomanid for the Treatment of Adult Patients With Pulmonary Multidrug Resistant Tuberculosis
Authors: Berry Catherine , du Cros Philipp , Fielding Katherine , Gajewski Suzanne , Kazounis Emil , McHugh Timothy D , Merle Corinne , Motta Ilaria , Moore David AJ , Nyang'wa Bern-Thomas
Published: December 2021

BackgroundGlobally rifampicin-resistant tuberculosis disease affects around 460 000 people each year. Current recommended regimens are 9-24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. MethodsTB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24 week regimens containing bedaquiline and pretomanid to treat rifampicin resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin resistant pulmonary tuberculosis and requiring a new course of therapy are eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients are randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also include moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment is administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study is equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome is the percentage of unfavourable outcomes at 72 weeks post randomisation. This is a composite of early treatment discontinuation, treatment failure, recurrence, lost to follow up and death. The study is conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. DiscussionTB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel regimens that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to end of recruitment and additionally, the planned final analysis at 72 weeks after end of recruitment. Trial registrationClinicaltrials.gov registration number NCT02589782
AM/GM-based optimization : gheometry and generalizations
Authors:   , Naumann Helen
Published: December 2021

The problem of unconstrained or constrained optimization occurs in many branches of mathematics and various fields of application. It is, however, an NP-hard problem in general. In this thesis, we examine an approximation approach based on the class of SAGE exponentials, which are nonnegative exponential sums. We examine this SAGE-cone, its geometry, and generalizations. The thesis consists of three main parts: 1. In the first part, we focus purely on the cone of sums of globally nonnegative exponential sums with at most one negative term, the SAGE-cone. We ex- amine the duality theory, extreme rays of the cone, and provide two efficient optimization approaches over the SAGE-cone and its dual. 2. In the second part, we introduce and study the so-called S-cone, which pro- vides a uniform framework for SAGE exponentials and SONC polynomials. In particular, we focus on second-order representations of the S-cone and its dual using extremality results from the first part. 3. In the third and last part of this thesis, we turn towards examining the con- ditional SAGE-cone. We develop a notion of sublinear circuits leading to new duality results and a partial characterization of extremality. In the case of poly- hedral constraint sets, this examination is simplified and allows us to classify sublinear circuits and extremality for some cases completely. For constraint sets with certain conditions such as sets with symmetries, conic, or polyhedral sets, various optimization and representation results from the unconstrained setting can be applied to the constrained case.
Modeling the Effect of Temperature on the Flower Development Rate of Hybrid Impatiens
Authors: Vargo Mary , Faust James E.
Published: December 2021

The effect of average daily temperature (ADT) on flower bud development and subsequent time to flower was investigated on hybrid impatiens (Impatiens ×hybrida) cultivars Compact Electric Orange, Compact Hot Coral, and Compact Orchid Blush. Plants with a visible flower bud measuring 2 mm in width were placed in one of the four greenhouses with temperature setpoints ranging from 16 to 28 °C. Flower bud width was measured every 3 days in each ADT treatment until flowering. The subsequent days to flower (DTF) from the onset of a visible bud decreased from 36 to 27 days as the ADT increased from 17 to 28 °C. The DTF from visible bud varied by <3 days among the three cultivars across all temperatures; therefore, cultivar data were pooled to create a stronger prediction model. A logistic formula was used to predict the remaining DTF as a function of flower bud width and ADT. The model accurately described the effect of bud width and ADT on flowering time within ±3 days for 87% of the actual DTF across all three cultivars. The resulting flower development model provides greenhouse growers with a guide for manipulating temperature to produce flowering plants for specific market dates based on flower bud width measurements.
Low Temperature Is Critical for Jujube Grafting Success in Frost-prone Northern New Mexico
Authors: Yao Shengrui
Published: December 2021

The increased popularity of jujube (Ziziphus jujuba) combined with the difficulty of grafting have limited supplies of grafted trees in the United States. From 2011 to 2020, grafting was practiced for cultivar amplification after importation and cultivar trials in frost-prone northern New Mexico. Grafting success was related to not only grafting techniques but also climate factors. Bark grafting, whip/tongue grafting, and cleft grafting were commonly used in nurseries. Low temperatures had a critical role in jujube grafting success in marginal regions and were more important than the grafting technique. If frost occurs before or near the leafing time, then grafting should be delayed until the rootstocks are determined to be healthy and alive. If frost occurs after grafting, then grafting failure and/or thin and small plant percentages increased. If only branchlets appear after grafting, then pinching branchlets could stimulate new shoot growth.