bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainty-Aware Mixed-Variable Machine Learning for Materials Design
Authors: Zhang Hengrui , Chen Wei (Wayne) , Iyer Akshay , Apley Daniel W. , Chen Wei
Published: August 2022

Data-driven design shows the promise of accelerating materials discovery but is challenging due to the prohibitive cost of searching the vast design space of chemistry, structure, and synthesis methods. Bayesian Optimization (BO) employs uncertainty-aware machine learning models to select promising designs to evaluate, hence reducing the cost. However, BO with mixed numerical and categorical variables, which is of particular interest in materials design, has not been well studied. In this work, we survey frequentist and Bayesian approaches to uncertainty quantification of machine learning with mixed variables. We then conduct a systematic comparative study of their performances in BO using a popular representative model from each group, the random forest-based Lolo model (frequentist) and the latent variable Gaussian process model (Bayesian). We examine the efficacy of the two models in the optimization of mathematical functions, as well as properties of structural and functional materials, where we observe performance differences as related to problem dimensionality and complexity. By investigating the machine learning models' predictive and uncertainty estimation capabilities, we provide interpretations of the observed performance differences. Our results provide practical guidance on choosing between frequentist and Bayesian uncertainty-aware machine learning models for mixed-variable BO in materials design.
Biocompatible Amino-modificated Tantalum Nanoparticles with Catalase Activity for Sustained Intra-articular Reactive Oxygen Species Scavenging and Alleviation of MIA induced Osteoarthritis
Authors: Jiang Yunsheng , Li Tao , Yang Junjun , Wang Xin , Song Xiongbo , Chen GuangXing , Dai Gang , Li Rong , Yao Chunyan , Chen Jiajia , Gong Xiaoyuan , Yang Liu
Published: August 2022

Background
Osteoarthritis (OA), which involves the dysfunction of articular cartilage, is the most common form of joint disease that results in arthralgia, joint deformation and limited mobility in patients. Recent studies highlighted the vital role of oxidative stress and reactive oxygen species (ROS) during progression of OA. Therefore, attenuating oxidative stress and reducing ROS generation in articular joints represent reasonable strategies for the treatment of OA. However, in addition to instability of current antioxidants caused by fluctuation in osteoarthritic physicochemical microenvironment, poor biocompatibility and short articular joint retention also seriously hindered their clinical application.
Results
Considering the above-mentioned, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH2 NPs) with sustained intra-articular catalase activity. Our in vitro results showed that Ta-NH2 NPs had good biocompatibility and stability, and could protect viability and hyaline-like phenotype in chondrocyte under H2O2 challenge. In addition, the in vivo biodistribution data demonstrated sustained retention of Ta-NH2 NPs in the joint cavity, particularly in articular cartilage with unnoticed organ toxicity and abnormity in hemogram and blood biochemistry analyses. Finally, compared with catalase (CAT), Ta-NH2 NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced OA model.
Conclusion
This study explored the potential of Ta-NH2 NPs as effective ROS scavenging agent for intra-articular injection, and offered a novel strategy to achieve sustained ROS suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.
Psychosocial and individual factors affecting Quality of Life (QoL) in patients suffering from Achilles tendinopathy: A Systematic Review
Authors: Vergés Josep , Martínez Nina , Pascual Aina , Bibas Marco , Santiña Manel , Rodas Gil
Published: August 2022

Background: Achilles tendinopathy (AT) is a joint condition that causes functional restrictions and pain. This condition negatively impacts patients' social connectedness and psychological well-being, reducing their quality of life (QoL). This review aims to summarise the current information on QoL in patients suffering from AT and share the reported individual factors that influence it.Methods: A systematic review was conducted at PubMed, Cochrane, Google Scholar, and PsycINFO using tendinopathy and QoL-related keywords up to November 2021. Articles were included if they compared QoL to demographic factors such as age or gender, lifestyle factors (physical activity levels), comorbidity factors (diabetes, obesity), and/or a control group.Results: 327 articles were reviewed; 21 met inclusion criteria. SF-36, EQ-5D, and VISA-A were the most common instrument used. All studies reported worse QoL in AT patients compared to a control group. When women were compared to men, women reported worse QoL. Education delivered by health care professionals improved QoL in patients with AT. Surgical AT interventions generally resulted in good to excellent outcomes, although results varied by age.Conclusion: AT has a substantial impact on QoL. In AT patients, QoL is also influenced by specific individual factors, including gender and physical activity. To better comprehend AT, QoL data is a valuable tool that allows health care professionals to implement the most effective treatment plan.
The traditional Chinese medicine monomer Ailanthone improves the therapeutic efficacy of anti-PD-L1 in melanoma cells by targeting c-Jun
Authors: Yu Pian , Wei Hui , Zhu Shiguo , Li Jie , Chen Chao , Zhang Detian , Li Yayun , Zhu Lei , Yi Xiaoqing , Liu Nian , Liu Panpan , Zhao Shuang , Chen Xiang , Peng Cong
Published: August 2022

Background: C-Jun, a critical component of AP-1, exerts essential functions in various tumors, including melanoma, and is believed to be a druggable target for cancer therapy. Unfortunately, no effective c-Jun inhibitors are currently approved for clinical use. The advent of immune checkpoint inhibitor (ICI) has brought a paradigm shift in melanoma therapy, but more than half of patients fail to exhibit clinical responses. The exploration of new combination therapies has become the current pursuit of melanoma treatment strategy. This study aims to screen out Chinese herbal monomers that can target c-Jun, explore the combined effect of c--Jun inhibitor and ICI, and further clarify the related molecular mechanism.Methods: We adopted a combinatorial screening strategy, including molecular docking, ligand-based online approaches and consensus quantitative structure-activity relationship (QSAR) model, to filter out c-Jun inhibitors from a traditional Chinese medicine (TCM) library. A mouse melanoma model was used to evaluate the therapeutic efficacy of monotherapy and combination therapy. Multicolor flow cytometry was employed to assess the tumor microenvironment (TME). Multiple in vitro assays were performed to verify down-streaming signaling pathway. CD4+ T-cell differentiation assay was applied to investigate Treg differentiation in vitro.Results: Ailanthone (AIL) was screened out as a c-Jun inhibitor, and inhibited melanoma cell growth by directly targeting c-Jun and promoting its degradation. Surprisingly, AIL also facilitated the therapeutic efficacy of anti-programmed death ligand-1 (PD-L1) in melanoma cells by reducing the infiltration of Tregs in TME. Additionally, AIL treatment inhibited c-Jun-induced PD-L1 expression and secretion. As a consequence, Treg differentiation was attenuated after treatment with AIL through the c-Jun/PD-L1 axis.Conclusions: Our findings identified AIL as a novel c-Jun inhibitor, and revealed its previously unrecognized anti-melanoma effects and the vital role in regulating TME by Treg suppression, which provides a novel combination therapeutic strategy of c-Jun inhibition by AIL with ICI.
A case of psoriasis treated by TCM for 20 years
Authors: LuJingjing  , Luyiqian
Published: August 2022

Chronic plaque psoriasis is an inflammatory disease. Due to the complex interaction of genetic and environmental factors, immune-related cytokine imbalance leads to abnormal epidermal proliferation. A 73-year-old female patient had intractable psoriasis for 20 years, whose condition improved significantly after 2 weeks of treatment with traditional Zhuang medicine. Moxibustion with medicinal thread combined with pricking and bloodletting may be a good choice for the treatment of psoriasis in the future.
Preclinical study of Therapeutic application of Sertoli Cells transplantation for treatment of Neurodegenerative Diseases: A Systematic Review
Authors: Ahmadi Houssein , Mehboudi Leila , Vatandoust Dorsa , Asadi Robabeh , Amini Abdollah
Published: August 2022

Progressive loss of neuronal function, brain atrophy, and abnormal protein deposition are the hallmarks of neurodegenerative diseases (NDs). NDs affect various parts of the brain and have various etiologies. Despite massive attempts to discover treatments for NDs during the past decades, there is still a need for effective therapeutic agents. Sertoli Cells (SCs), whether transplanted as allogeneic or xenogeneic cells, could offer a feasible opportunity for improving graft persistence by secreting immunomodulatory and trophic substances which shield replaced cells and tissues from the immune system. To date, there is no coherent information about the neuroprotective effects of SCs transplantation on NDs. Hence, this review tried to evaluate and report coherent information on the neuroprotective effects of these cells on NDs in preclinical settings. In this systematic review, the databases including, Scopus, PubMed, and ISI WEB of science were considered as a motor engine to search and get the relevant scientific articles and full text published between 2000 to 2022. Our search revealed 9 related articles on the effectiveness of SCs transplantation on NDs. Here, most of the evidence shows that SCs transplantation has promising effects on improving the symptoms of neurological diseases in rats. most of these relevant studies emphasize that many standardized preclinical trials should be conducted to provide reliable statistical evidence to confirm the application of SCs transplantation and the improvement of symptoms of neurodegenerative diseases.
Internalizing problems and engagement among preschool children predict the trajectories of several functional outcomes’ in a Swedish longitudinal study
Authors: Markkula Andrea , Gustafsson Berit
Published: August 2022

Mental health problems among children are prevalent, often found within the socioemotional domains, and tend to persist over time. Early detection could predict the need for interventions for children at risk. This study aimed to study the role of internalizing problems and engagement in a preschool setting with respect to the trajectory of several functional outcomes. Using preschool teacher estimations of a representative cohort of 845 Swedish preschool children (438 boys and 407 girls, age range 13–71 months), this study constructed risk groups based on the emotional subscale of the Strengths and Difficulties Questionnaire (SDQ) and the engagement scale derived from the Children’s Engagement Questionnaire (CEQ) at baseline. These risk groups were associated with the trajectory of WHO International Classification of Functioning, Disability and Health (ICF) (p < 0.001) SDQ (p < 0.001) SDQ-emotional subscale (p < 0.001), and CEQ (p < 0.001) over three years. Concise assessments of these risk factors in children could help predict the need for targeted interventions to ensure a positive development for children at risk.
Healthcare- Seeking Behaviours and the Impact of Covid-19 preventive Measures on Anxiety and Depression among Survivors of Covid-19 at the Buea Regional Hospital Cameroon: A Case Control Study
Authors: Yusinyu Dinayen Dieudonne , Cyrile Nkouonlack Duquesne , Georges Teuwafeu Denis , Ngwayi Shifu Ismaila , Tanue Elvis Asangbeng , Shey Nsagha Dickson , Kongnyu Njamnshi Alfred
Published: August 2022

BackgroundThe outbreak of the COVID-19 Pandemic led to the implementation of preventive measures to curb the spread of the virus. The fear of contracting the virus and some infection prevention and control measures have been associated with poor mental and brain health outcomes .We therefore assessed the health care- seeking behaviours and the impact of COVID-19 preventive measures on depression and anxiety among survivors of COVID-19 at the Buea Regional Hospital. Materials and MethodsThe study design was an unmatched case control study. Cases were identified from health facility records and the controls were patients who are inhabitants of same community. Data was collected using an online google questionnaire and a physical questionnaire which was self-administered .We used the Hospital Anxiety and Depression Scale to assess anxiety and depression. Data was analyzed using SPSS version 25.0 and a P-value of <0.05 was considered to be statistically significant.ResultsWe recruited 245 participants with the mean age for our participants being 32.89±13.17years. With regards to Health care -seeking behaviours 78.9 vs 75.1% (OR 1.24, CI: 0.65-2.38) sought care from the hospital among the cases and controls respectively. Survivors of COVID-19 were about 12 times more likely to seek for conventional medication as a treatment for their disease (OR 11.96, 95% CI: 6.25-22.90, p=0.000) compared to the controls. Survivors of COVID-19 presented with higher mean scores for depression and anxiety compared to the controls respectively (7.74±3.93 vs. 4.01±4.48, p=0.000), (6.84±3.87 vs. 3.10±3.75, p=0.000). Participants who wore face mask were 3 times more likely to be anxious and depressed than those who did not. Factors associated with adverse mental health outcomes were losing a love one due to COVID-19, quarantine and social isolation among the casesConclusions Health care seeking behaviour was more appropriate in the cases than the controls. COVID-19 preventive measures were associated with a negative psychosocial impact among COVID-19 survivors; thus public health officials should implement measures targeting psychosocial support of the population
Risk factors of central area lymph nodes metastasis for guiding optimal right colon cancer surgery: A retrospective multicenter study
Authors: Feng Xiaochuang , Wang Hao , Feng Bo , Chen Xinlin , Yi Xiaojiang , Zhang Qing , Li En , Zhuang Yezhong , Li Hongming , Lu Xinquan , Chen Zhaoyu , Wan Jin , Liao Weilin , Wang Jiahao , Deng Haijun , Chen Chuangqi , Diao Dechang
Published: August 2022

Background: D3 or CME lymphadenectomy for right colon cancer (RCC) with lymph nodes metastasis (LNM) is strongly recommended but the anatomical landmark remains controversial. Central LNM predicted poor prognosis in RCC and determined the extent of lymphadenectomy. Methods: Data for 1712 RCC patients treated with D3/CME lymphadenectomy were reviewed. These patients had been treated in 9 centers. A total of 1023 RCC patients were enrolled in the derivation cohort while 689 patients were enrolled in the validation cohort. Results: The overall central LNM incidence was 12.58% (215/1712). In the derivation cohort, univariate and multivariate cox regression analyses revealed that preoperative N staging based on CT scan (OR=7.85, 95% CI, 4.53-14.51, p<0.001), tumor differentiation (OR=0.53, 95% CI, 0.33-0.86, p=0.01) and intraoperative view of tumor movability (OR=0.53, 95% CI, 0.33-0.86, p=0.02) were significant independent factors. Areas under receiver-operating characteristic curves (AUC) for assessing central LNM in the derivation and validation cohorts were 0.802 and 0.750, respectively. The risk-scoring system for patients with RCC was also established. A score of 0 points was the optimal cut-off value for central LNM. Compared to patients in the low-risk group, patients in the high-risk group exhibited worse overall survival outcomes (p<0.001).Conclusions: The established model can be used for preoperative assessment of the risk of central LNM in RCC patients, and for determining the landmark for D3/CME lymphadenectomy, therefore might contribute to decreased therapeutic complications and improved clinical outcomes.
CuSeO4 and Cu(SeO3OH)2 ·6H2O, two novel copper– selenium(VI) oxysalts
Authors: Effenberger Herta S. , Giester Gerald , Wildner Manfred
Published: August 2022

The two new copper(II) salts Cu(SeO 4) and Cu(SeO 3 OH) 2 ·6H 2 O were synthesized at low-temperature hydrothermal conditions (220 °C), and room temperature, respectively. Their atomic arrangements were studied based on single-crystal X-ray investigations [P2 1 /n, a = 4.823(1), b = 8.957(2), c = 6.953(1) Å, β = 94.82(1)° Z = 4; P – 1, a = 6.133(1), b = 6.303(1), c = 8.648(2) Å, α = 70.45(1), β = 84.60(1), γ = 73.44(1)°, Z = 1]. Cu(SeO 4) adopts the MnAsO 4 structure type. It exhibits structural as well as topological relations with two formerly known isochemical compounds. They crystallize in the structure type ZnSO 4 (mineral name zincosite, Pnma) respectively NiSO 4 (Cmcm). The two minerals dravertite, CuMg(SO 4) 2 , and hermannjahnite, CuZn(SO 4) 2 , are isotypic with CuSeO 4-P2 1 /n; interestingly, also α-NaCu(PO 4) belongs to this structure type: some rotation of the XO 4 group allows a supplementary position for the Na atom. ― Cu(SeO 3 OH) 2 ·6H 2 O represents a new structure type. The protonated selenate group shows an extended Se―O h bond distance (1.695 Å) as compared to the other Se―O bonds (1.614 to 1.626 Å). One OH dipole of the three independent H 2 O molecules represents a rather free hydrogen bond. For the other H atoms, the O―H···O lengths vary from 2.585 to 2.799 Å. Interestingly, the distance O w 7···O w 7 of only 2.791 Å does not represent an edge in a coordination polyhedron and it is not preliminary involved in the hydrogen bond scheme. All Cu 2+ ions in the two title compounds are in a pronounced [4+2] coordination. The Cu 2+[4+2] atoms in Cu(SeO 4) are linked to chains along [100]; in Cu(SeO 3 OH) 2 ·6H 2 O they are not connected among each other.
Is musical engagement enough to keep the brain young?
Authors: Matziorinis Anna Maria , Gaser Christian , Koelsch Stefan
Published: August 2022

Music-making and engagement in music-related activities have shown procognitive benefits for healthy and pathological populations, suggesting reductions in brain aging. A previous brain aging study, using Brain Age Gap Estimation (BrainAGE), showed that professional and amateur-musicians had younger appearing brains than non-musicians. Our study sought to replicate those findings and analyze if musical training or active musical engagement was necessary to produce an age decelerating effect in a cohort of healthy individuals. We scanned 125 healthy controls and investigated if musician status, and if musical behaviours, namely Active Musical Engagement (AME) and Musical Training (MT) (as measured using the Goldsmiths Musical Sophistication Index (Gold-MSI)), had effects on brain aging. Our findings suggest that musician status is not related to BrainAGE score, although involvement in current physical activity is. Although neither MT or AME subscales of the Gold-MSI are predictive for BrainAGE scores, dispositional resilience, namely the ability to deal with challenge is related to both musical behaviours and sensitivity to musical pleasure. While the study failed to replicate the previous brain aging study, musical training and active musical engagement are related to the resilience factor of challenge. This finding may reveal how such musical behaviours can potentially strengthen the brain’s resilience to age, possibly revealing a type of neurocognitive reserve.
Chondrule-like objects and CAIs in asteroid Ryugu: earlier generations of chondrules
Authors: Nakashima Daisuke , Nakamura Tomoki , Zhang Mingming , Kita Noriko , Mikouchi Takashi , Yoshida Hideto , Enokido Yuma , Morita Tomoyo , Kikuiri Mizuha , Amano Kana , Kagawa Eiichi , Yada Toru , Nishimura Masahiro , Nakato Aiko , Miyazaki Akiko , Yogata Kasumi , Abe Masanao , Okada Tatsuaki , Usui Tomohiro , Yoshikawa Makoto , Saiki Takanao , Tanaka Satoshi , Nakazawa Satoru , Terui Fuyuto , Yurimoto Hisayoshi , Noguchi Takaaki , Yabuta Hikaru , Naraoka Hiroshi , Okazaki Ryuji , Sakamoto Kanako , Watanabe Sei-ichiro , Tachibana Shogo , Tsuda Yuichi
Published: August 2022

Chondrule-like objects and Ca-Al-rich inclusions (CAIs) are discovered in the retuned samples from asteroid Ryugu. Three chondrule-like objects, which are 16O-rich and -poor with D17O (= d17O – 0.52 × d18O) values of ~ − 23‰ and ~ − 3‰, are dominated by Mg-rich olivine, resembling what proposed as earlier generations of chondrules. The 16O-rich objects are likely to be melted amoeboid olivine aggregates that escaped from incorporation into 16O-poor chondrule precursor dust. Two CAIs composed of spinel, hibonite, and perovskite are 16O-rich with D17O of ~ − 23‰ and possibly as old as the oldest CAIs. The chondrule-like objects and CAIs (< 30 µm) are as small as those from comets, suggesting radial transport favoring smaller objects from the inner solar nebula to the formation location of the Ryugu original parent body, which is farther from the Sun and scarce in chondrules. The transported objects may have been mostly destroyed during aqueous alteration.
Haploinsufficiencies of FOXF1, FOXC2 and FOXL1 genes originated from deleted 16q24.1q24.2 fragment related with alveolar capillary dysplasia with misalignment of pulmonary veins and lymphedema–distichiasis syndrome: relationship to phenotype
Authors: Wang Xuezhen , Guo Lili , Zhang Bei , Wu Jiebin , Sun Yu , Tao Huimin , Sha Jing , Zhai Jingfang , Liu Min
Published: August 2022

Objective:We describe a fetus with a 2.12-Mb in 16q terminal deletion which associated with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) and lymphedema–distichiasis syndrome (LDS); we also review other similar published studies and discuss the genetype-phenotype correlation.Methods:Amniotic fluid of the fetus was collected for karyotype analysis and copy number variation sequencing (CNV-seq) after informed consent.Results:The fetal karyotype was 46,XX; the result of CNV-seq showed that there was an approximately 2.12-Mb deletion in 16q24.1-q24.2 (85220000-87340000) indicating pathogenicity.Conclusion:Molecular genetic testing should be recommend as a first line diagnostic tool for suspected ACD/MPV and / or LDS or other genetic syndromes for the fetuses with structural abnormalities in clinical practice.
A key axis of the N-WASP signaling pathway promotes distant metastasis in pancreatic cancer: LOXL2-FAK-N-WASP
Authors: Kim Hyung Sun , Lee Yun Sun , Dong Seung Myung , Kim Hyo Jung , Lee Da Eun , Kang Hyeon Woong , Kim Myeong Jin , Park Joon Seong
Published: August 2022

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies. A specific mechanism of its metastasis is not established. In our present study, we investigated whether Neural Wiskott-Aldrich Syndrome Protein (N-WASP) plays a role in distant metastasis of PDAC.MethodsPancreatic cancer cell lines MIA PaCa-2, PANC-1, AsPC-1, and BxPC-3 were used for in vitro and in vivo study. To evaluate the endogenous expression level of N-WASP, we purified the whole RNA and protein to perform the qPCR, RT-PCR and Western blot. And we confirmed the motility and invasiveness and the RNA-seq assays. By using of pancreatic cancer cell lines, orthotopic mouse model of pancreatic cancer was established.ResultsWe found that N-WASP is markedly expressed in clinical patients with PDAC. Through the analysis of clinical patient samples, N-WASP positive group had a much more distant metastatic-pattern than N-WASP negative group. Moreover, it was turned out that N-WASP is a novel mediator of epithelial–mesenchymal transition (EMT) via gene expression profile studies. In addition, knockdown of N-WASP in pancreatic cancer cells had significantly inhibited cell invasion, migration, and EMT. We also observed that the lysyl oxidase-like 2 (LOXL2) and focal adhesion kinase (FAK) are positively associated with the N-WASP-mediated response, thereby modulating EMT and invadopodia. Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.ConclusionsThese results clarify a new role for N-WASP signaling associated with LOXL2 in EMT and invadopodia that regulates intercellular communication in tumor cells to promote pancreatic cancer metastasis. These findings may aid in the development of therapeutic strategies against pancreatic cancer.
Sex difference on neurological outcomes and post-cardiac arrest care in out-of-hospital cardiac arrest patients treated with targeted temperature management
Authors: Park Seon Yeong , Oh Sang Hoon , Park Sang Hyun , Oh Jae Hun , Kim Soo Hyun
Published: August 2022

Background: Conflicting results regarding sex-based differences in the outcomes of out-of-hospital cardiac arrest (OHCA) patients have been reported. Furthermore, no study has examined whether differences in in-hospital interventions and courses are driven by sex. This study evaluated the effect of sex on the in-hospital course as well as the survival rates and long-term neurological outcomes of OHCA patients treated with targeted temperature management.Methods: We retrospectively analyzed the Korean Hypothermia Network Prospective Registry composed of data collected from 22 hospitals in Korea between October 2015 and December 2018. To evaluate the effect of sex on patient outcomes, we created various multivariate logistic regression models. Regarding the difference in in-hospital courses, we compared daily total and SOFA sub-scores between the sexes and analyzed whether the decision regarding early cardiac interventions and limitations in in-hospital care were associated with sex.Results: The rate of good neurological outcomes after 6 months was higher in men (OR = 1.66, 95% CI: 1.26 2.17). However, when the results were adjusted using resuscitation variables and in-hospital variables were added, there was no significant difference between the two sexes (OR =1.22, 95% CI: 0.85 – 1.74; OR = 1.13, 95 CI: 0.76 – 1.68, respectively). There was no association between sex and outcome in patients of reproductive age and no interaction between age and sex. Regarding the in-hospital course, the daily total SOFA score was similar in both sexes whereas cardiovascular scores were higher in women on 2 and 3 days (on day 2, p = 0.006; on day 3, p = 0.017). The adjusted effect of sex was not associated with the clinician’s decision to perform early cardiac interventions except that men had more extracorporeal membrane oxygenation (ECMO) (OR=2.51, 95% CI: 1.11-5.66). The decision to discontinue life-sustaining treatment was determined by poor prognostic factors, not by sex. Conclusions: The findings suggested that men had more favorable 6-month neurological outcomes. However, after adjusting for confounders, there was no difference between the sexes. The results regarding in-hospital course were similar in men and women.
Prevalence of substandard quality artemether-lumefantrine antimalarial agents in Uganda
Authors: Ocan Moses , Nakalembe Loyce , Otike Caroline , Nambatya Winnie , Omali Denis , Buzibye Allan , Nsobya Sam
Published: August 2022

Background: Substandard antimalarial agents are a key challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of antimalarial agents in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, we assessed the pharmacopeial quality of Artemether-Lumefantrine (AL) in low and high malaria transmission settings in Uganda. Methods: This was a cross-sectional study conducted among randomly selected drug outlets (pharmacies/drug shops). The AL antimalarial agents available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity and content assay tests. The assay test was done using Liquid chromatography-mass spectrometry (LC-MS) following International and Unites States Pharmacopoeia (USP) method. The samples were considered substandard if the Active Pharmaceutical Ingredient (API) content was outside 90-110% range of the label claim. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using fisher’s exact test of independence at 95% level of significance.Results: A total of 74 AL antimalarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) having a ‘Green leaf logo’. Overall, prevalence of substandard quality artemether-lumefantrine was 18.9% (14/74; 95%CI: 11.4-29.7). Substandard quality AL was significantly associated with setting (p=0.002). A total of 10 samples (13.5%) failed artemether content assay while, 4 samples (5.4%, 4/74) had substandard lumefantrine content. One sample from a high malaria transmission setting failed both Artemether and Lumefantrine assay test. Of the samples that failed artemether assay test, majority, 90% had low (<90%) artemether content. Conclusion: Substandard quality AL, the recommended first-line antimalarial agent in treatment of uncomplicated malaria is common especially in high malaria transmission settings. There is need for regular surveillance and monitoring of the quality of artemisinin based antimalarial agents across the country.
Biofloc meal as a supplementary feed ingredient replacing fish meal in the diets of rohu (Labeo rohita) (Hamilton, 1822)
Authors: Padhan Bhenkatesh , Athithan S.
Published: August 2022

The authors have requested that this preprint be removed from Research Square.
Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population
Authors: Rando Maria Margherita , Biscetti Federico , Cecchini Andrea Leonardo , Nardella Elisabetta , Nicolazzi Maria Anna , Angelini Flavia , Iezzi Roberto , Eraso Luis H , Dimuzio Paul J , Pitocco Dario , Gasbarrini Antonio , Massetti Massimo , Flex Andrea
Published: August 2022

Background: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients.The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI).Methods: we conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. Results: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariate analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75).Conclusions: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI.
Spike generation governed by the stochasticion adsorption-desorption process
Authors: Tamagawa Hirohisa , Ikeda Kota , Delalande Bernard , Mulembo Titus
Published: August 2022

There is a deep conviction that the generation of the action potentialis one of the most fundamental biological activities. According to themembrane theory, active ion transport and its flow variations across theplasma membrane are responsible for generating the action potential.However, in contrast to the living model, an in vitro model based on theadsorption-desorption process of ions could equally well explain the gen-eration of the action potential. The authors constructed such a modeland mathematically related it using the stochastic differential equation(SDE). This SDE model is consistent with the kinetics of the reactionand explains the generation of the action potential. Therefore, it is phys-iologically important to re-examine the mechanism of action potentialgeneration from the perspective of the ion adsorption-desorption model.
Is pulmonary hypertension a risk factor for severe bronchiolitis?
Authors: Rossi Maria Lucia , Escobar-Diaz Maria Clara , Hadley Stephanie Marie , Randanne Paula Cecilia , Sanchez-de-Toledo Joan , Jordán Iolanda
Published: August 2022

Background and ObjectivesPulmonary hypertension has been reported as a crucial factor in the pathophysiology of severe bronchiolitis. The aim of this study was to evaluate pulmonary artery pressure (PAP) and cardiac function in patients with bronchiolitis and to analyze their correlation with clinical outcomes. MethodsThis prospective cohort study examined children admitted for bronchiolitis. PAP was assessed by right ventricle (RV) acceleration/ejection time ratio (AT/ET), isovolumic relaxation time, eccentricity index and the presence of a pulmonary systolic notch. Pulmonary hypertension (PH) was defined if at least two altered parameters were present. Severity of clinical course was established by cardiac dysfunction, higher N-terminal (NT)-pro hormone BNP (NT-proBNP) values, the need for positive pressure respiratory support (PPRS) and the duration of hospital admission.Results169 children were included in analysis. Median age was 2 months. 68 patients (40%) required PPRS and showed increased NT-proBNP values and worse RV systolic function compared to mild cases (p=0.007 and p<0.001, respectively).Twenty-three (13.5%) cases had at least two altered parameters of PAP and met criteria for PH, with no difference in NT-proBNP values, cardiac function, need for PPRS or hospital length of stay with normal PAP group (p=1, p=0.18, p=0.56 and p= 0.67, respectively). We found no correlation between altered RV AT/ET and worse cardiac function, NT-proBNP values or hospital length of stay.Conclusions In our cohort, the presence of PH was not a determinant of worse clinical outcomes. Patients with severe bronchiolitis had higher values ​​of NT-proBNP and worse RV systolic function but, interestingly, no clear association with PH.
Association between Triglyceride-glucose index and carotid artery plaque in young and middle-aged occupational population
Authors: Pan Jia , Yang Bo , Wang Zihang , Tang Lei , Jia Peng , Yang Shujuan , Zeng Honglian
Published: August 2022

Background:China has the world’s highest rail transportation density, and the health of railway workers, therefore, deserves public attention. The triglyceride glucose (TyG) index has been proposed as a surrogate indicator of insulin resistance. However, there are limited studies on the association between the TyG index and carotid artery plaque (CAP) in railway workers.Methods:This cross-sectional study was conducted among southwest China railway workers. 3,169 workers were divided into four groups according to TyG index quartiles. The CAP was assessed by carotid doppler ultrasound. Logistic regression and restricted cubic spline were used to estimate the association between TyG index and CAP, and subgroup analysis was performed by age, blood pressure, metabolic dysfunction-associated fatty liver disease (MAFLD), smoking, drinking, and physical activity.Results:Compared with participants in the lowest quartile, those with high TyG index quartiles were more likely to have a higher prevalence of CAP, with 11.63%, 14.11%, 20.20% and 18.56% from quartile 1st[Q1] to quartile 4th[Q4]. When the TyG index was treated as a continuous variable, the multi-adjusted logistic regression models showed that the TyG index was positively associated with the risk of CAP (OR: 1.26, 95% CI: 1.08,1.47). With increasing TyG index tertiles, TyG index as a categorical variable, the risk of CAP increased substantially with ORs (95% CIs) of 1.24 (0.92,1.69) for Q2, 1.78 (1.32,2.41) for Q3, 1.56 (1.14,2.15) for Q4 compared with the lowest quartile of TyG index.Conclusion:The TyG index, especially in high quartiles, was associated with CAP in the railway workers. Monitoring the TyG index was a good risk management strategy of CAP.
A Fractal ARIMA and Fractal IGARCH model of the RMB Exchange Rate
Authors: hongqiangzhao
Published: August 2022

Classical economics uses normal distribution as the basic assumption of economicresearch. With the improvement of econometric methods, it is found that the assumption of normaldistribution is not correct in economics. First, we tested RMB exchange rate’s fractal characters.Then, w e consider GARCH, f ractal ARIMA ARFIMA and f ractal IGARCH FIGARCH modelof RMB exchange rate to correct this normal distribution fault . Last, we find that thoseuntraditional model s is useful and favorable in RMB exchange rate analysis.
Cyclophosphamide combined with methylprednisolone ameliorates bleomycin-induced pulmonary fibrosis in rats through immunomodulatory mechanisms
Authors: Xu Qingjie , Chen Yan , Tang Ming , Zhang Manka , Liu Yin , Li Zhouping , Ma Runlin , Xue Xiaoyan
Published: August 2022

Background Idiopathic pulmonary fibrosis(IPF) is a distressing lung disorder with poor prognosis and high mortality rates.Immune factors are currently recognized as pathogenic agents throughout the onset of IPF.In clinical studies,the combination of methylprednisolone (MP) and cyclophosphamide (CTX) has great benefits for patients with IPF,but the immune mechanism of improving IPF is not clear. Results The lung inflammation and fibrosis model was established by intratracheal instillation of bleomycin (BLM).Pulmonary fibrosis was observed in rats on day 7 after BLM injection. With prolonged fibrosis,we can see that the expression of neutrophils and T lymphocytes was out of control.Our data suggests that immune disorders run through the whole process of pulmonary fibrosis both in the early stage(day 14)and in the advanced stage(day 28).The inflammation and immune disorders were better than before after intervention with medication. Conclusions The combination of MP and CTX can alleviate IPF by reducing inflammation,and improving T cell immunity.So CTX combined with MP can modulate immune disorders,which may be an effective anti-fibrosis drug in the treatment of clinical IPF patients.But we should pay attention to dosage and use course of the treatment,in order to prevent the occurrence of toxic side effects.
Multimorbidity and health-related quality of life amongst Indigenous Australians: A longitudinal analysis
Authors: Keramat Syed Afroz , Perales Francisco , Alam Khorshed , Monasi Nahid , Ali Mohammad Afshar , Sathi Nusrat Jahan , Haque Rezwanul , Hashmi Rubayyat
Published: August 2022

Background
The burden of multimorbidity has been observed worldwide, and it has significant consequences on health outcomes. In Australia, health-related quality of life (HRQoL) is comparatively low amongst Aboriginal and/or Torres Strait Islanders. Yet no studies have examined the association between multimorbidity and HRQoL within this at-risk population. This is the aim of the present study.
Methods
Longitudinal data were derived from three waves (9, 13 and 17) of the Household, Income and Labour Dynamics in Australia Survey. A total of 1,007 person-year observations from 592 Aboriginal and/or Torres Strait Islanders aged 15 years and above were included. HRQoL was captured using the 36-item Short-Form Health Survey (SF-36), and multimorbidity was defined as having two or more chronic health conditions. A random effects tobit model was used to assess the associations between multimorbidity and HRQoL.
Results
Approximately 21% of Indigenous Australians were classified as experiencing multimorbidity. Respondents with multimorbidity reported lower scores than their counterparts without multimorbidity on the SF-36 sub-scales, summary measures and health utility index. Multimorbidity had pronounced adverse effects on overall HRQoL, including on the SF-36 physical component scale (β = −3.232; 95% CI: −4.734 to − 1.730), mental component scale (β = −5.625; 95% CI: −7.435 to − 3.815) and short-form six-dimension scale (β = −0.061; 95% CI: −0.082 to − 0.041).
Conclusion
This study demonstrated that having two or more chronic diseases is significantly associated with lower HRQoL amongst Indigenous Australians. Advanced health strategies addressing foreseeable challenges imposed on multimorbid adults should be implemented to improve the HRQoL of Indigenous Australians.
Percutaneous Transforaminal Endoscopic Surgery (PTES) and OLIF with Self-lock Cage through mini-incision for Surgical Treatment of L5 Spondylolisthesis
Authors: Zhou Tianyao , Zhang Yingkai , Ma Tianle , Che Wu , Zhang Liang , Wang Yichao , Gu Yutong
Published: August 2022

Purpose: We designed Percutaneous Transforaminal Endoscopic Surgery (PTES) technique and OLIF with self-lock cage through mini-incision for the treatment of L5 spondylolisthesis. The purpose of study is to evaluate the feasibility, efficacy and safety of this method.Methods: Thirteen cases of L5 spondylolisthesis with nerve root symptoms were included in this study. PTES under local anesthesia, and then OLIF with self-lock cage and allograft under general anesthesia was performed. Back and leg pain were preoperatively and postoperatively evaluated using VAS, and the clinical outcomes were evaluated with ODI before surgery and at 2-year follow-up. Anterior and posterior intervertebral space height, lumbar lordotic angle, and operative segmental lordotic angle were measured on lumbar spine X-rays preoperatively and postoperatively. The fusion status was assessed according to the Bridwell’s fusion grades.Results: The VAS significantly dropped after surgery and the ODI decreased from 64.7±7.8% to 12.9±4.3% 2 years after surgery (p<0.001). Anterior and posterior intervertebral space height, and operative segmental lordotic angle significantly improved after surgery (p<0.05). Fusion grades based on the Bridwell grading system at 2-year follow-up were grade I in 9 segments (69.2%), grade II in 4 segments (30.8%). No patients had any form of permanent iatrogenic nerve damage and a major complication. No failure of instruments was observed.Conclusion: PTES and OLIF with self-lock cage is a good choice of minimally invasive surgery for L5 spondylolisthesis, which can get direct neurologic decompression and satisfying fusion, and hardly destroy the rectus abdominis and its sheath, paraspinal muscles and bone structures.
Optimal emerald ash borer (Agrilus planipennis) control across the United States
Authors: Hudgins Emma , Hanson Jeffrey , MacQuarrie Chris , Yemshanov Denys , Baker Christopher , Chades iadine , Holden Matthew , McDonald-Madden Eve , Bennett Joseph
Published: August 2022

The invasive emerald ash borer (Agrilus planipennis) causes damages to street trees estimated at US$ 900 million in the next 30 years. Although millions of dollars are spent annually to control this species, such approaches are often based on rules-of-thumb. Here, we reveal an optimal management strategy to protect urban trees in North America from A. planipennis. To achieve this, we embedded a pest dispersal model within a mixed integer programming framework. We discovered that optimized strategies consistently outperformed those based on rules-of-thumb, potentially resulting in the protection of an additional one million street trees and savings of $585 million. Critically, the best management strategies always relied on quarantines and biological control (constituting 74-89% and 11-26% of the project budget, respectively), in contrast with current practices, which have abandoned quarantines. Our findings serve to inform future pest control efforts, and can potentially protect many more trees from this invasive species.
The prophylactic role of tamsulosin in preventing of postoperative urinary retention in rectal cancer patients
Authors: Abtahi Setareh , Ahmadi-Amoli Hadi , Abedi-kichi Raziyeh , Rahimpour Ehsan
Published: August 2022

Purpose
We designed a prospective study to evaluate the efficiency of tamsulosin, a selective alpha adrenergic antagonist, on development of postoperative urinary retention.
Methods
A total of 100 rectal cancer patients who underwent elective surgery in Department of Surgery of Tehran university Hospital, were included in this study. Patients were classified into one of two groups. In control group, the patients were not received tamsulosin. Patients in tamsulosin group were prescribed 0.4 mg of tamsulosin orally, 14 hours and 2 hours before surgery and postoperatively until patient is discharged orally.
Results
47 patients were included in control group and 53 in tamsulosin group. Although the incidence of postoperative urinary retention was lower in the tamsulosin group than other (11.32% vs 17.02%), but no significant difference was found (p = 0.24).
Conclusions
This prospective study showed that tamsulosin at 0.4 mg/day does not prevent postoperative urinary retention in rectal cancer patients.
Trait driven or neutral: understanding the change in functional trait diversity during early plant succession using Price partitions
Authors: Ulrich Werner , Zaplata Markus Klemens
Published: August 2022

Habitat filtering, species interactions, and neutral colonisation and extinction dynamics govern the sequence of community assembly and functional diversity during primary plant succession. For an understanding we need to disentangle the underlying abiotic and biotic drivers behind these processes. Here we use data on plant seed size, number and specific leaf area from 107 initially homogeneous study plots along a seven year sequence of primary succession (2005–2011) in a 6 ha German artificial catchment and show that an additive partition of the temporal change in functional diversity (FD) into trait, richness, and abundance effects can according to a recently developed new Price partitioning provide insights into the relative importance of these drivers. Average FD steadily increased during the first four years of succession and reached a plateau in 2009. The annual change in FD was plot specific manifest in a highly positively skewed distribution. Average change in FD were comparatively low up to 2008 and later high. Initial soil characteristics and plant demand traits did not significantly influence the change in functional diversity. We observed trade-offs in the influence of species and abundance effects that tended to decrease the change in FD. We conclude that the high plot specific spatial variability of the annual changes in FD transform an initially homogeneous distribution of plants into a mosaic of very different local plant communities. Our partitioning results also indicate that the successional sequences in FD are in accordance with a hidden Markov series.