bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial
Authors: Boesing Maria , Abig Kristin , Brändle Michael , Brutsche Martin , Burri Emanuel , Frye Björn C. , Giezendanner Stéphanie , Grutters Jan C. , Haas Philippe , Heisler Justian , Jaun Fabienne , Leuppi-Taegtmeyer Anne B. , Lüthi-Corridori Giorgia , Müller-Quernheim Joachim , Nüesch Reto , Pohl Wolfgang , Rassouli Frank , Leuppi Jörg D.
Published: September 2022

Background

Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS.

Methods

This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization.

Discussion

Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19.

Trial registration

ClinicalTrials.gov,NCT04536350. Registered 02 September 2020.
Regional gain and global loss of 5-hydroxymethylcytosine coexist in genitourinary cancers and regulate different oncogenic pathways
Authors: Qi Jie , Shi Yue , Tan Yezhen , Zhang Qi , Zhang Jianye , Wang Jilu , Huang Cong , Ci Weimin
Published: September 2022

Background

DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. However, 5hmC is also cell-type specific, and its variability may exist between differentiated tumor cells and cancer stem cells. Thus, cancer-associated changes in 5hmC may be contributed by distinct sets of tumor cells within the tumor tissues.

Results

Here, we applied a sensitive immunoprecipitation-based method (hMeDIP-seq) to analyze 5hmC changes during genitourinary carcinogenesis (including prostate, urothelial and kidney). We confirmed the tissue-specific distribution of 5hmC in genitourinary tissues and identified regional gain and global loss of 5hmC coexisting in genitourinary cancers. The genes with gain of 5hmC during tumorigenesis were functionally enriched in regulating stemness and hypoxia, whereas were associated with poor clinical prognosis irrespective of their differences in tumor type. We identified that gain of 5hmC occurred in soft fibrin gel-induced 3D tumor spheres with a tumor-repopulating phenotype in two prostate cancer cell lines, 22RV1 and PC3, compared with conventional two-dimensional (2D) rigid dishes. Then, we defined a malignant signature derived from the differentially hydroxymethylated regions affected genes of cancer stem-like cells, which could predict a worse clinical outcome and identified phenotypically malignant populations of cells from prostate cancer tumors. Notably, an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, restored 5hmC and killed the cancer stem cell-like cells leading to apoptosis in prostate cancer cell lines.

Conclusions

Collectively, our study dissects the regional gain of 5hmC in maintaining cancer stem-like cells and related to poor prognosis, which provides proof of concept for an epigenetic differentiation therapy with vitamin C by 5hmC reprogramming.

Graphic Abstract
Identification of reindeer fine-scale foraging behaviour using tri-axial accelerometer data
Authors: Rautiainen Heidi , Alam Moudud , Blackwell Paul G. , Skarin Anna
Published: September 2022

Animal behavioural responses to the environment ultimately affect their survival. Monitoring animal fine-scale behaviour may improve understanding of animal functional response to the environment and provide an important indicator of the welfare of both wild and domesticated species. In this study, we illustrate the application of collar-attached acceleration sensors for investigating reindeer fine-scale behaviour. Using data from 19 reindeer, we tested the supervised machine learning algorithms Random forests, Support vector machines, and hidden Markov models to classify reindeer behaviour into seven classes: grazing, browsing low from shrubs or browsing high from trees, inactivity, walking, trotting, and other behaviours. We implemented leave-one-subject-out cross-validation to assess generalizable results on new individuals. Our main results illustrated that hidden Markov models were able to classify collar-attached accelerometer data into all our pre-defined behaviours of reindeer with reasonable accuracy while Random forests and Support vector machines were biased towards dominant classes. Random forests using 5-s windows had the highest overall accuracy (85%), while hidden Markov models were able to best predict individual behaviours and handle rare behaviours such as trotting and browsing high. We conclude that hidden Markov models provide a useful tool to remotely monitor reindeer and potentially other large herbivore species behaviour. These methods will allow us to quantify fine-scale behavioural processes in relation to environmental events.
Research on copper production of the Bohai Kingdom in Northeast China
Authors: Li Chenyuan , Wu Song , Li Qiang , Song Yubin , Jia Ying , Li Yanxiang
Published: September 2022

The systematic investment and rearrangement of the unearthed artefacts of Longtoushan Royal Cemetery of the Bohai Kingdom have provided a bunch of new information for the archaeometallurgy research on non-ferrous metal production. We have synthesised the latest discoveries of several related mining/smelting sites and urban relics for making a direct approach to the chain of copper production in this research. SEM-EDS and p-XRF unveiled the distinction between copper and bronze artefacts. The yield gap between the scale of smelting and the number of artefacts was also discussed based on historical records. The evidence and detail of indigenous copper production could help the researcher comprehend the technology and material exchange and geopolitical relationship development of the Bohai Kingdom.
Seismic analysis, design, and retrofit of built-environments: a procedural review of current practices and case studies
Authors: Kim Ju-Hyung , Hessek Christopher J. , Kim Yail J. , Park Hong-Gun
Published: September 2022

This paper presents a synthesis of current practices in regard to the seismic analysis, design, and retrofit of built-environments. Background information on the behavior of existing buildings subjected to earthquake loadings is gathered and rehabilitation methodologies are elaborated. The first part of the review examines design standards and guidelines that are used in the structural engineering community. These documents are mandatory for the legal adoption of a model code by the governing jurisdiction where the building in question is to be located. The second part discusses retrofit procedures alongside specific provisions dominating the requirements and techniques appertaining to ground motions. The third part handles case studies emphasizing an upgrade of school buildings that are non-conforming to contemporary specifications and guidelines. For substantiating the performance of proposed methodologies, laboratory tests are conducted in conjunction with finite element analysis, which form the technical foundation of site implementations.
Aging Impairs Adaptive Unfolded Protein Response and Drives Beta Cell Dedifferentiation in Humans
Authors: Song Jiaxi , Ni Qicheng , Sun Jiajun , Xie Jing , Liu Jianmin , Ning Guang , Wang Weiqing , Wang Qidi
Published: September 2022

Context

Diabetes is an age-related disease; however, the mechanism underlying senescent beta cell failure is still unknown.

Objective

The present study was designed to investigate whether and how the differentiated state was altered in senescent human beta cells by excluding the effects of impaired glucose tolerance.

Methods

We calculated the percentage of hormone-negative/chromogranin A–positive endocrine cells and evaluated the expressions of forkhead box O1 (FoxO1) and Urocortin 3 (UCN3) in islets from 31 nondiabetic individuals, divided into young (<40 years), middle-aged (40-60 years) and elderly (>60 years) groups. We also assessed adaptive unfolded protein response markers glucose-regulated protein 94 (GRP94), and spliced X-box binding protein 1 (XBP1s) in senescent beta cells and their possible contributions to maintaining beta cell identity and differentiation state.

Results

We found an almost 2-fold increase in the proportion of dedifferentiated cells in elderly and middle-aged groups compared with the young group (3.1 ± 1.0% and 3.0 ± 0.9% vs 1.7 ± 0.5%, P < .001). This was accompanied by inactivation of FoxO1 and loss of UCN3 expression in senescent human beta cells. In addition, we demonstrated that the expression levels of adaptive unfolded protein response (UPR) components GRP94 and XBP1s declined with age. In vitro data showed knockdown GRP94 in Min6-triggered cells to dedifferentiate and acquire progenitor features, while restored GRP94 levels in H2O2-induced senescent Min6 cells rescued beta cell identity.

Conclusion

Our finding highlights that the failure to establish proper adaptive UPR in senescent human beta cells shifts their differentiated states, possibly representing a crucial step in the pathogenesis of age-related beta cell failure.
Idiopathic Hirsutism and Metabolic Status: A Population-based Prospective Cohort Study
Authors: Mahmoudieh Leila , Amiri Mina , Rahmati Maryam , Habibi Moeini Ali Siamak , Sarvghadi Farzaneh , Azizi Fereidoun , Ramezani Tehrani Fahimeh
Published: September 2022

Background

A limited number of studies have investigated the impact of idiopathic hirsutism (IH) on cardiometabolic parameters with contradictory and inconclusive results. This study aimed to explore the effect of IH on metabolic outcomes.

Method

In this population-based prospective study, 334 women with IH and 1226 women as healthy controls were selected from Tehran Lipid and Glucose Study. The generalized estimation equations method was applied to investigate the secular longitudinal trends of metabolic indices, including fasting blood sugar (FBS), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL), non-HDL, triglyceride (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist circumference (WC) in both groups. Unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% CIs for the association between IH and metabolic disorders. Potential confounding factors such as age, body mass index, smoking, physical activity, history of hypertension (HTN), and family history of diabetes were included in the adjusted model.

Results

This study showed that compared with healthy controls, women with IH had lower SHBG and higher total testosterone (median [interquartile ratio; IQR]: 0.37 [0.16-0.70] vs 0.33 [0.14-0.58]; P = 0.01), free androgen index (median [IQR]: 0.85 [0.38-1.54] vs 0.54 [0.26-0.97]; P = 0.001), androstenedione (median [IQR]: 1.60 [1.00-2.25] vs 1.10 [0.90-1.70]; P = 0.001), and dehydroepiandrosterone sulfate (median [IQR]: 168.5 [91.1-227.8] vs 125.2 [66.3-181]; P = 0.001). Over time, mean changes of FBS, HDL-C, LDL-C, non-HDL-C, TG, SBP, DBP, and WC were not significantly different in women with IH, compared with healthy controls. According to the unadjusted Cox regression model, except for type 2 diabetes mellitus (T2DM) (HR [95% CI]: 1.45 [1.00-2.11]) P = 0.05; there was no statistically significant difference in hazard of metabolic disorders (ie, HTN, pre-HTN, pre-T2DM, and metabolic syndrome) in IH, compared with healthy controls. Besides, the adjusted Cox regression model showed no significant differences in the hazard of these outcomes.

Conclusion

This study showed no significant difference in overtime mean changes of metabolic risk factors and cardiometabolic outcomes in women with IH, compared with the healthy control group, except marginally significant difference on T2DM, which disappeared after further adjustment for potential confounders. Accordingly, routine screening of women for these metabolic outcomes should not recommend.
Circulating Plasma Concentrations of ACE2 in Primary Aldosteronism and Cardiovascular Outcomes
Authors: Wu Vin-Cent , Peng Kang-Yung , Hu Ya-Hui , Chang Chin-Chen , Chan Chieh-Kai , Lai Tai-Shuan , Lin Yen-Hung , Wang Shuo-Meng , Lu Ching-Chu , Liu Yu-Chun , Tsai Yao-Chou , Chueh Jeff S
Published: September 2022

Context

The plasma concentrations of angiotensin-converting enzyme 2 (pACE2) has been independently associated with cardiovascular diseases.

Objective

Higher pACE2 concentrations may be found in patients with primary aldosteronism (PA) and might lead to increased cardiovascular events.

Methods

Using an inception observational cohort, we examined pACE2 among 168 incident patients with PA. The expression of ACE2, serine protease 2 (TMPRSS2), and metalloprotease 17 (ADAM17) were assessed in peripheral blood mononuclear cells.

Results

Incident PA and essential hypertension (EH) patients had similarly elevated pACE2 (47.04 ± 22.06 vs 46.73 ± 21.06 ng/mL; P = .937). Age was negatively (β = −2.15; P = .033) and higher serum potassium level (β = 2.29; P = .024) was positively correlated with higher pACE2 in PA patients. Clinical complete hypertension remission after adrenalectomy (Primary Aldosteronism Surgery Outcome criteria) was achieved in 36 (50%) of 72 surgically treated unilateral PA (uPA) patients. At follow-up, pACE2 decreased in surgically treated patients who had (P < .001) or had no (P = .006) hypertension remission, but the pACE2 attenuation was not statistically significant in uPA (P = .085) and bilateral PA (P = .409) administered with mineralocorticoid receptor antagonist (MRA). Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was related to all-cause mortality and cardiovascular events among PA patients (hazard ratio = 8.8; P = .04); with a mean follow-up of 3.29 years. TMPRSS2 messenger RNA (mRNA) expression was higher in uPA (P = .018) and EH (P = .038) patients than in normotensive controls; it was also decreased after adrenalectomy (P < .001).

Conclusion

PA and EH patients had elevated pACE2 and higher expression of TMPRSS2 mRNA compared to those of normotensive population. Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was associated risk of mortality and incident cardiovascular events.
Methylation guide RNAs without box C/D motifs
Authors: Wang Jiayin , Yang Zuxiao , Ye Keqiong
Published: September 2022

Box C/D RNAs guide site-specific 2'-O-methylation of RNAs in archaea and eukaryotes. The defining feature of methylation guide RNAs is two sets of box C and D motifs that form kink-turn structures specifically recognized by L7Ae family proteins. Here, we engineered a new type of methylation guides that lack C/D motifs and require no L7Ae for assembly and function. We determined a crystal structure of a bipartite C/D-free guide RNA in complex with Nop5, fibrillarin and substrate in the active form at 2.2 Å resolution. The stems of new guide RNAs functionally replace C/D motifs in Nop5 binding, precisely placing the substrate for site-specific modification. We also found that the bipartite architecture and association of L7Ae with C/D motifs enhance modification when association of guide RNAs or substrates is weak. Our study provides insights into the variations, robustness and possible evolutionary path of methylation guide RNAs.
Risk factors for postoperative infectious complications after RIRS treatment of kidney and ureteral stones
Authors: Stachura Tomasz , Bąk Sebastian , Budzeń Kamil , Wesołowski Paweł , Gładysz Konrad , Marzęda Magdalena , Blicharz Agnieszka , Sygacz Oliwer
Published: September 2022

Abstract

Introduction and aim of the study: Urolithiasis is a disease involving the formation of deposits in the lumen of the urinary tract. The continued development of minimally invasive treatment methods allows for more effective treatment with greater operator comfort and less risk to the patient. It has been concluded that retrograde intrarenal surgery (RIRS) is superior to other therapeutic methods in many respects. The aim of this study is to review the available studies and publications and to identify potential complications following treatment of kidney and ureteral stones by RIRS, with a particular focus on infectious complications and their risk factors.

 

Method and materials: We reviewed the literature available on PubMed and Google Scholar, using the words 'urolithiasis'; 'urolithiasis treatment'; 'retrograde intrarenal surgery'; 'infectious complications of retrograde intrarenal surgery'.

 

Results: Among the risk factors associated with infectious complications after RIRS, long duration of surgery, recent positive urine culture, urinary tract infections or antibiotic use, purulent urine, urinary nitrites, obstructed access through the ureter, struvite stones, co-morbidities play a special role.

 

Conclusions: Among the complications of surgical treatment of nephrolithiasis and ureteral stones by RIRS, infectious complications are of particular concern. In view of the knowledge of their risk factors, preventive measures should include limiting the duration of surgery, possible antibiotic therapy and considering the use of a larger diameter UAS. This is especially true for patients with abnormal urine results, struvite stones, a history of urinary tract infection or predisposing comorbidities.

 

Key words: Urolithiasis; Kidney Calculi; Retrograde Intrarenal Surgery; Urolithiasis infection;
Adaptations to a cohort study in response to the COVID-19 pandemic: insights from Growing Up in Ireland
Authors: Kelly Lisa , Murray Aisling , Quail Amanda , McNamara Eoin
Published: September 2022

Growing Up in Ireland (GUI) is the national longitudinal study of children and young people in the Republic of Ireland and has followed two cohorts for over ten years to date: Cohort ’98 who were recruited into the study at age nine years and Cohort ’08, recruited at age nine months. The study aims to describe the lives of Irish children and young people in terms of their development, with a view to positively affecting policies and services available for them. Traditionally, data collection involved in-home visits from an interviewer who conducted face-to-face interviews, recorded physical measurements of study participants and administered cognitive assessments. However, with the onset of the COVID-19 pandemic and the associated restrictions, significant adaptations were required to these methods to ensure data collection for the pilot and main fieldwork for Cohort ’08 at age 13 could continue to the expected timeline. Face-to-face interviews with participants were replaced with telephone and web-based modes, interviewer training was conducted online, online resources were made available for interviewers and participants and COVID-19 related items were added to questionnaires. In addition to the scheduled data collection, a special COVID-19 survey was also conducted on both GUI cohorts in December 2020 to explore the impact of the pandemic on participants’ lives. This paper outlines the adaptations made to traditional data collection methods in GUI, highlighting the challenges that were met, but also the benefits of some changes that may be worth incorporating into future waves of GUI.
VDE-Net: a two-stage deep learning method for phase unwrapping
Authors: Zhao Jiaxi , Liu Lin , Wang Tianhe , Wang Xiangzhou , Du Xiaohui , Hao Ruqian , Liu Juanxiu , Liu Yong , Zhang Jing
Published: September 2022

Phase unwrapping is a critical step to obtaining a continuous phase distribution in optical phase measurements and coherent imaging techniques. Traditional phase-unwrapping methods are generally low performance due to significant noise or undersampling. This paper proposes a deep convolutional neural network (DCNN) with a weighted jump-edge attention mechanism, namely, VDE-Net, to realize effective and robust phase unwrapping. Experimental results revealed that the weighted jump-edge attention mechanism, which is first proposed and simple to calculate, is useful for phase unwrapping. The proposed algorithm outperformed other networks or common attention mechanisms. In addition, an unseen wrapped phase image of a living red blood cell (RBC) was successfully unwrapped by the trained VDE-Net, thereby demonstrating its strong generalization capability.
Descattering for transmissive inspection in production line using slanted linear image sensors
Authors: Kushida Takahiro , Tahara Komei , Chiba Hayato , Kagawa Yukihiro , Tanaka Kenichiro , Funatomi Takuya , Mukaigawa Yasuhiro
Published: September 2022

We propose a descattering method that can be easily applied to food production lines. The system consists of several sets of linear image sensors and linear light sources slanted at different angles. The images captured by these sensors are partially clear along the direction perpendicular to the sensors. We computationally integrate these images on the frequency domain into a single clear image. The effectiveness of the proposed method is assessed by simulation and real-world experiments. The results show that our method recovers clear images. We demonstrate the applicability of the proposed method to a real production line by a prototype system.
Research on detection of different metallographic structures of high speed wheel steel based on laser-induced breakdown spectroscopy
Authors: Jun Hu , Liang Yang , Tongzheng Lin , Hongyang Shi , Peng Qiao , Yong He , Yande Liu
Published: September 2022

The laser-induced breakdown spectroscopy (LIBS) experimental platform was applied to obtain LIBS spectral the data of 10 CL60 wheel steel samples. The principle component analysis (PCA) was used to preliminarily analyze the macroscopic characteristics of LIBS spectral data. With the spectral intensity and spectral intensity combined with spectral intensity ratio as variables, three spectral correction methods including median filtering, baseline correction and multiple scattering correction (MSC) were used for pretreatment. And the support vector machine (SVM) qualitative model was established to determine the metallographic structure. It was found that the SVM model established by using the pre-processed data of MSC as the input variable has the best effect. The accuracy rate of calibration set is 100%, and the accuracy rate of prediction set is 98.4%. The research has shown that LIBS combined with SVM model can be used for discriminant analysis of different metallographic structures of train wheel steel.
Accurate unsupervised estimation of aberrations in digital holographic microscopy for improved quantitative reconstruction
Authors: Brault Dylan , Olivier Thomas , Soulez Ferréol , Joshi Sachin , Faure Nicolas , Fournier Corinne
Published: September 2022

In the context of digital in-line holographic microscopy, we describe an unsupervised methodology to estimate the aberrations of an optical microscopy system from a single hologram. The method is based on the Inverse Problems Approach reconstructions of holograms of spherical objects. The forward model is based on a Lorenz-Mie model distorted by optical aberrations described by Zernike polynomials. This methodology is thus able to characterize most varying aberrations in the field of view in order to take them into account to improve the reconstruction of any sample. We show that this approach increases the repeatability and quantitativity of the reconstructions in both simulations and experimental data. We use the Cramér-Rao lower bounds to study the accuracy of the reconstructions. Finally, we demonstrate the efficiency of this aberration calibration with image reconstructions using a phase retrieval algorithm as well as a regularized inverse problems algorithm.
Capability and convergence of linearized invariant-imbedding T-matrix and physical-geometric optics methods for light scattering
Authors: Sun Bingqiang , Gao Chenxu , Liang Dongbin , Liu Zhaoyuan , Liu Jian
Published: September 2022

The linearized invariant-imbedding T-matrix method (LIITM) and linearized physical-geometric optics method (LPGOM) were applied on regular hexagonal prisms from small to large sizes to obtain the scattering properties and their partial derivatives. T-matrices and their derivatives from the LIITM are presented and discussed in the expansion order, where the minor diagonal elements are dominant. The simulation results of single-scattering properties and their corresponding linearization from both methods are compared. The mutual agreements can be treated as further verification of both linearized methods. Using extinction efficiency as the criterion, the LPGOM are convergent at the LIITM for the particle size parameter larger than 130 with a relative difference of less than 1%, with errors of about 3% and 5% for particle sizes of 50 and 30, respectively. The capability and convergence of the LIITM and LPGOM are discussed in detail based on linearized properties.
SERS enhancement induced by the Se vacancy defects in ultra-thin hybrid phase SnSex nanosheets
Authors: Chen Chuansong , Zhang Wenjie , Duan Pengyi , Liu Wenying , Shafi Muhammad , Hu Xiaoxuan , Zhang Can , Zhang Chao , Man Baoyuan , Liu Mei
Published: September 2022

Improving the photo-induced charge transfer (PICT) efficiency by adjusting the energy levels difference between adsorbed probe molecules and substrate materials is a key factor for boosting the surface enhanced Raman scattering (SERS) based on the chemical mechanism (CM). Herein, a new route to improve the SERS activity of two-dimensional (2D) selenium and tin compounds (SnSex, 1 ≤ x ≤ 2) by the hybrid phase materials is researched. The physical properties and the energy band structure of SnSex were analyzed. The enhanced SERS activity of 2D SnSex can be attribute to the coupling of the PICT resonance caused by the defect energy levels induced by Se vacancy and the molecular resonance Raman scattering (RRS). This established a relationship between the physical properties and SERS activity of 2D layered materials. The resonance probe molecule, rhodamine (R6G), which is used to detect the SERS performance of SnSex nanosheets. The enhancement factor (EF) of R6G on the optimized SnSe1.35 nanosheets can be as high as 2.6 × 106, with a detection limit of 10−10 M. The SERS result of the environmental pollution, thiram, shows that the SnSex nanosheets have a practical application in trace SERS detection, without the participation of metal particles. These results demonstrate that, through hybrid phase materials, the SERS sensitivity of 2D layered nanomaterials can be improved. It provides a kind of foreground non-metal SERS substrate in monitoring or detecting and provide a deep insight into the chemical SERS mechanism based on 2D layered materials.
Nearly degenerate two-color impulsive coherent Raman hyperspectral imaging
Authors: Smith David R. , Shivkumar Siddarth , Field Jeff , Wilson Jesse W. , Rigneault Hervé , Bartels Randy A.
Published: September 2022

Impulsive stimulated Raman scattering (ISRS) is a robust technique for studying low frequency (<300 cm−1) Raman vibrational modes, but ISRS has faced difficulty in translation to an imaging modality. A primary challenge is the separation of the pump and probe pulses. Here we introduce and demonstrate a simple strategy for ISRS spectroscopy and hyperspectral imaging that uses complementary steep edge spectral filters to separate the probe beam detection from the pump and enables simple ISRS microscopy with a single-color ultrafast laser source. ISRS spectra are obtained that span from the fingerprint region down to <50 cm−1 vibrational modes. Hyperspectral imaging and polarization-dependent Raman spectra are also demonstrated.
Oocyte mitophagy is critical for extended reproductive longevity
Authors: Cota Vanessa , Sohrabi Salman , Kaletsky Rachel , Murphy Coleen T.
Published: September 2022

Women’s reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans’ reproduction declines in mid-adulthood and is caused by oocyte quality decline. Aberrant mitochondrial morphology is a hallmark of age-related dysfunction, but the role of mitochondrial morphology and dynamics in reproductive aging is unclear. We examined the requirements for mitochondrial fusion and fission in oocytes of both wild-type worms and the long-lived, long-reproducing insulin-like receptor mutant daf-2. We find that normal reproduction requires both fusion and fission, but that daf-2 mutants utilize a shift towards fission, but not fusion, to extend their reproductive span and oocyte health. daf-2 mutant oocytes’ mitochondria are punctate (fissioned) and this morphology is primed for mitophagy, as loss of the mitophagy regulator PINK-1 shortens daf-2’s reproductive span. daf-2 mutants maintain oocyte mitochondria quality with age at least in part through a shift toward punctate mitochondrial morphology and subsequent mitophagy. Supporting this model, Urolithin A, a metabolite that promotes mitophagy, extends reproductive span in wild-type mothers–even in mid-reproduction—by maintaining youthful oocytes with age. Our data suggest that promotion of mitophagy may be an effective strategy to maintain oocyte health with age.
Factors influencing the sustainability of homestead vegetable production intervention in Rufiji, Tanzania: A cross-sectional mixed methods study
Authors: Mlalama Killian N. , Matemu Athanasia , Kosia Efraim , Canavan Chelsey R. , Bellows Alexandra L. , Blakstad Mia , Noor Ramadhani A. , Kinabo Joyce , Fawzi Wafaie W. , Masanja Honorati , Mosha Dominic
Published: September 2022

There is growing evidence that home vegetable gardening interventions improve food security and nutrition outcomes at the family level. Sustainability of many of these community interventions remain a challenge. This study assessed factors influencing the sustainability of homestead vegetable production intervention in Rufiji district, Tanzania, one year after the cessation of external support. This was a community based cross-sectional study using both quantitative and qualitative data collection methods. A total of 247 randomly selected women from households who participated in the homestead vegetable intervention were interviewed using a structured questionnaire. The study held four focus group discussions with women from households that participated in the intervention, and four In-Depth interviews with two extension workers, one community health worker, and one agriculture district officer. Multiple logistic regression for quantitative data and thematic analysis for qualitative data was conducted. About 20.24% (50/247) of households sustained homestead vegetable production for one year after the intervention phased out. Shortage of seeds (adjusted odds ratio = 0.65: CI = 0.46–0.93, p-value 0.018) and either manure or fertilizers (adjusted odds ratio = 1.62: CI = 1.04–2.46, p-value 0.031) were significant factors influencing the sustainability of homesteads vegetable production. In the Focus Group discussions (FGDs) and In-Depth Interview (IDIs), all participating women and extension workers reported high cost of water, destruction from free-grazing animals, agriculture pests and diseases, poor soil fertility, shortage of seeds, and lack of capital affected homestead vegetable production sustainability. Existing individual, community, and system challenges influence the sustainability of external-funded agriculture and nutrition interventions. The study findings underscore the importance of community authorities, scientists, and policymakers in having a well-thought sustainability plan in all promising external-funded interventions.
Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population
Authors: Bhandari Sushil , Dolma Padma , Mukerji Mitali , Prasher Bhavana , Montgomery Hugh , Kular Dalvir , Jain Vandana , Dadhwal Vatsla , Williams David J. , Bhattacharyaa Aniket , Gilbert Edmund , Cavalleri Gianpiero L. , Hillman Sara L.
Published: September 2022

Pathological low birth weight due to fetal growth restriction (FGR) is an important predictor of adverse obstetric and neonatal outcomes. It is more common amongst native lowlanders when gestating in the hypoxic environment of high altitude, whilst populations who have resided at high altitude for many generations are relatively protected. Genetic study of pregnant populations at high altitude permits exploration of the role of hypoxia in FGR pathogenesis, and perhaps of FGR pathogenesis more broadly. We studied the umbilical cord blood DNA of 316 neonates born to pregnant women managed at the Sonam Norboo Memorial Hospital, Ladakh (altitude 3540m) between February 2017 and January 2019. Principal component, admixture and genome wide association studies (GWAS) were applied to dense single nucleotide polymorphism (SNP) genetic data, to explore ancestry and genetic predictors of low birth weight. Our findings support Tibetan ancestry in the Ladakhi population, with subsequent admixture with neighboring Indo-Aryan populations. Fetal growth protection was evident in Ladakhi neonates. Although no variants achieved genome wide significance, we observed nominal association of seven variants across genes (ZBTB38, ZFP36L2, HMGA2, CDKAL1, PLCG1) previously associated with birthweight.
The histone deacetylase inhibitor M344 as a multifaceted therapy for pancreatic cancer
Authors: Knoche Shelby M. , Brumfield Gabrielle L. , Goetz Benjamin T. , Sliker Bailee H. , Larson Alaina C. , Olson Madeline T. , Poelaert Brittany J. , Bavari Audrey , Yan Ying , Black Jennifer D. , Solheim Joyce C.
Published: September 2022

The histone deacetylase (HDAC) inhibitor vorinostat, used with gemcitabine and other therapies, has been effective in treatment of experimental models of pancreatic cancer. In this study, we demonstrated that M344, an HDAC inhibitor, is efficacious against pancreatic cancerin vitroandin vivo, alone or with gemcitabine. By 24 hours post-treatment, M344 augments the population of pancreatic cancer cells in G1, and at a later time point (48 hours) it increases apoptosis. M344 inhibits histone H3 deacetylation and slows pancreatic cancer cell proliferation better than vorinostat, and it does not decrease the viability of a non-malignant cell line more than vorinostat. M344 also elevates pancreatic cancer cell major histocompatibility complex (MHC) class I molecule expression, potentially increasing the susceptibility of pancreatic cancer cells to T cell lysis. Taken together, our findings support further investigation of M344 as a pancreatic cancer treatment.
Decontamination of Geobacillus Stearothermophilus using the Arca Aerosolized Hydrogen Peroxide decontamination system
Authors: Mead Loren Benjamin , Mathison Tanner , Osborne Garry , Richards Anne Marie
Published: September 2022

Introduction

In response to the limited supply of personal protective equipment during the pandemic caused by SARS-CoV-2, recent studies demonstrate that gaseous H2O2 is an effective decontaminant of N95 filtering facepiece respirators to enable reuse of these items in a clinical setting. This paper evaluates the efficacy of the Arca Aerosolized Hydrogen Peroxide Decontamination System (Arca), a novel aerosolized H2O2 decontamination system, using biologic indicator testing.

Materials and methods

The Arca produces and circulates H2O2 aerosol inside of a sealed stainless steel chamber. The Arca’s decontamination efficacy was evaluated in 8 decontamination trials with 2 H2O2 concentrations (3% and 12%) and 4 decontamination cycle durations (45, 60, 90, and 120 minutes). Efficacy was evaluated by testing: 1) the concentration in parts per million (ppm) of H2O2 produced inside the chamber and the concentration in ppm of H2O2 vented from the chamber, and 2) the decontamination of Mesa Biologic Indicator filter strips (BI) inoculated with Geobacillus Stearothermophilus. Control tests were conducted by submerging BI strips in 3mL of 3% and 12% H2O2 for 120 minutes (negative controls) and by not exposing one BI strip to H2O2 (positive control).

Results

Greater than 5000 ppm of H2O2 was detected on the concentration strips inside the chamber for each of the eight decontamination trials. No vented H2O2 was detected on the external concentration strips after any decontamination trial. No growth was observed for any of the negative controls after seven days. The positive control was positive for growth.

Conclusion

The Arca Aerosolized Hydrogen Peroxide Decontamination System is effective at decontaminating bacterial G. Stearothermophilus at a cycle time of 45 minutes utilizing 6mL of 3% H2O2 solution.
Molecular characterization and biofilm-formation analysis of Listeria monocytogenes, Salmonella spp., and Escherichia coli isolated from Brazilian swine slaughterhouses
Authors: dos Santos Rebecca Lavarini , Davanzo Emilia Fernanda Agostinho , Palma Joana Marchesini , Castro Virgílio Hipólito de Lemos , da Costa Hayanna Maria Boaventura , Dallago Bruno Stéfano Lima , Perecmanis Simone , Santana Ângela Patrícia
Published: September 2022

This study aimed to verify the presence ofListeria monocytogenes,Salmonellaspp., andEscherichia coliin two Brazilian swine slaughterhouses, as well as to perform antibiograms, detect virulence and antimicrobial resistance genes, and evaluate thein vitrobiofilm-forming capability of bacterial isolates from these environments. OneSalmonellaTyphi isolate and 21E.coliisolates were detected, whileL.monocytogeneswas not detected.S. Typhi was isolated from the carcass cooling chamber’s floor, resistant to several antimicrobials, including nalidixic acid, cefazolin, chloramphenicol, doxycycline, streptomycin, gentamicin, tetracycline, and sulfonamide, and contained resistance genes, such astet(B),tet(C),tet(M), andampC. It also showed moderate biofilm-forming capacity at 37°C after incubating for 72 h. The prevalence of the 21E.coliisolates was also the highest on the carcass cooling chamber floor (three of the four samplings [75%]). TheE.coliisolates were resistant to 12 of the 13 tested antimicrobials, and none showed sensitivity to chloramphenicol, an antimicrobial prohibited in animal feed since 2003 in Brazil. The resistance genesMCR-1,MCR-3,sul1,ampC,clmA,cat1,tet(A),tet(B), andblaSHV, as well as the virulence genesstx-1,hlyA,eae,tir α,tir β,tir γ, andsaawere detected in theE.coliisolates. Moreover, 5 (23.8%) and 15 (71.4%)E.coliisolates presented strong and moderate biofilm-forming capacity, respectively. In general, the biofilm-forming capacity increased after incubating for 72 h at 10°C. The biofilm-forming capacity was the lowest after incubating for 24 h at 37°C. Due to the presence of resistance and virulence genes, multi-antimicrobial resistance, and biofilm-forming capacity, the results of this study suggest a risk to the public health as these pathogens are associated with foodborne diseases, which emphasizes the hazard of resistance gene propagation in the environment.
Novel AAV-mediated genome editing therapy improves health and survival in a mouse model of methylmalonic acidemia
Authors: Zhang Shengwen , Bastille Amy , Gordo Susana , Ramesh Nikhil , Vora Jenisha , McCarthy Elizabeth , Zhang Xiaohan , Frank Dylan , Ko Chih-Wei , Wu Carmen , Walsh Noel , Amarwani Shreya , Liao Jing , Xiong Qiang , Drouin Lauren , Hebben Matthias , Chiang Kyle , Chau B. Nelson
Published: September 2022

Methylmalonic acidemia (MMA) is an inborn error of metabolism mostly caused by mutations in the mitochondrial methylmalonyl-CoA mutase gene (MMUT). MMA patients suffer from frequent episodes of metabolic decompensation, which can be life threatening. To mimic both the dietary restrictions and metabolic decompensation seen in MMA patients, we developed a novel protein-controlled diet regimen in a Mmut deficient mouse model of MMA and demonstrated the therapeutic benefit of mLB-001, a nuclease-free, promoterless recombinant AAV GeneRideTM vector designed to insert the mouse Mmut into the endogenous albumin locus via homologous recombination. A single intravenous administration of mLB-001 to neonatal or adult MMA mice prevented body weight loss and mortality when challenged with a high protein diet. The edited hepatocytes expressed functional MMUT protein and expanded over time in the Mmut deficient mice, suggesting a selective growth advantage over the diseased cells. In mice with a humanized liver, treatment with a human homolog of mLB-001 resulted in site-specific genome editing and transgene expression in the transplanted human hepatocytes. Taken together, these findings support the development of hLB-001 that is currently in clinical trials in pediatric patients with severe forms of MMA.
Beta distribution misspecification tests with application to Covid-19 mortality rates in the United States
Authors: Santana-e-Silva José Jairo , Cribari-Neto Francisco , Vasconcellos Klaus L. P.
Published: September 2022

The beta distribution is routinely used to model variables that assume values in the standard unit interval, (0, 1). Several alternative laws have, nonetheless, been proposed in the literature, such as the Kumaraswamy and simplex distributions. A natural and empirically motivated question is: does the beta law provide an adequate representation for a given dataset? We test the null hypothesis that the beta model is correctly specified against the alternative hypothesis that it does not provide an adequate data fit. Our tests are based on the information matrix equality, which only holds when the model is correctly specified. They are thus sensitive to model misspecification. Simulation evidence shows that the tests perform well, especially when coupled with bootstrap resampling. We model state and county Covid-19 mortality rates in the United States. The misspecification tests indicate that the beta law successfully represents Covid-19 death rates when they are computed using either data from prior to the start of the vaccination campaign or data collected when such a campaign was under way. In the latter case, the beta law is only accepted when the negative impact of vaccination reach on death rates is moderate. The beta model is rejected under data heterogeneity, i.e., when mortality rates are computed using information gathered during both time periods.
Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib
Authors: Salichs Marta , Badiella Llorenç , Sarasola Patxi , Homedes Josep
Published: September 2022

Background

This prospective, multisite, blinded, randomized, non-inferiority clinical study aimed to confirm the efficacy and safety of enflicoxib in the treatment of pain and inflammation associated with canine osteoarthritis. A total of 180 dogs were randomized to receive enflicoxib (n = 78), mavacoxib (n = 80) or placebo (n = 22). Dogs underwent veterinary assessments from day 0 to day 42 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). The primary efficacy endpoint was the overall CSS from day 0 to day 42.

Results

The overall CSS expressed as area under the curve demonstrated non-inferiority of enflicoxib compared to mavacoxib, and both showed superiority over placebo. At the end of the study, average CSS, and the percentage of CSS responders for enflicoxib (3.64 and 74%) and mavacoxib (4.49 and 68%), was superior to placebo (7.15 and 29%). A faster onset of action was observed for enflicoxib as superiority over placebo was evidenced from the first efficacy assessment (day 7) onwards for both parameters, whereas mavacoxib was only significantly different from day 14 onwards. According to the owner assessment, the percentage of CBPI responders was 90%, 79%, and 43% for dogs treated with enflicoxib, mavacoxib and placebo, respectively, and superiority over placebo was demonstrated for both active treatments. In all secondary parameters, non-inferiority of enflicoxib versus mavacoxib was confirmed. The dog’s quality of life improved in all groups, but only enflicoxib showed superiority versus placebo. When assessing severely affected dogs only, results were similar, thus confirming the efficacy of enflicoxib in all stages of canine OA. There were no differences between groups in the frequency of adverse events, which were most frequently mild affecting the gastrointestinal tract and recovered without treatment.

Conclusions

Enflicoxib is efficacious and safe for the treatment of pain and inflammation in any stage of canine osteoarthritis with a faster onset of action compared to mavacoxib.