bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin 6 and Interferon gamma haplotypes are related to cytokine serum levels in dogs in an endemic Leishmania infantum region
Authors: Álvarez Luis , Marín-García Pablo-Jesús , Rentero-Garrido Pilar , Llobat Lola
Published: November 2022

Background: The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniasis is an endemic zoonosis. Several studies indicate a low prevalence of this disease in Ibizan hound dogs, whereas other canine breeds present a high prevalence. However, the molecular underlaying mechanisms yet remains unknown.
Methods: In this study, we analyze the haplotypes of genes encode cytokines related to immune response of Leishmania infantum infection in twenty-four Boxer and twentyfour Ibizan hound apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions.
Results: The results show that haplotypes of genes encoding Interleukin 6 (IL6) and Interferon gamma (IFNG) are related to Interferon gamma (IFN-γ), and Interleukins (IL) 2 and 18 serum levels. Our results indicate that the regulation of immune response is different in the two canine breeds analyzed and are related to the haplotype compositions of the genes encoding these cytokines.
Conclusions: Haplotypes in the IFNG and IL6 genes have been correlated to serum levels of IFN-γ, IL-2 and IL-18, and moderate effect on IL8 haplotype correlated to IL-8 and IL-18 serum levels has been found. The results indicate that the resistance to L. infantum infection could be a consequence of certain haplotypes with a high frequency in the Ibizan Hound dog breed, while susceptibility to the disease would be related to other specific haplotypes, with high frequency in Boxer. Future studies are needed to elucidate whether these differences and haplotypes are related to different phenotypes in immune response and expression gene regulation to L. infantum infections in dogs and its possible application of new treatments and vaccines.
Unusual findings in 68 cases of appendiceal diverticulum: Accompanying neoplastic lesion should be kept in mind
Authors: Ekinci Nese , Gun Eylul
Published: November 2022

Purpose:Congenital and acquired diverticula of the appendix are very rare and may be associated with a variety of lesions. In this study, we aimed to evaluate the cases of the appendiceal diverticulum (AD) in terms of histopathological features and accompanying neoplastic and non-neoplastic lesions.Methods:A retrospective analysis of the appendectomy specimens between January 2007 and June 2022 was performed. All of the cases with AD were reviewed and slides of all cases were re-examined by two pathologists, one of whom was highly experienced in gastrointestinal pathology. The cases were evaluated in terms of age, gender, histopathological features, accompanying neoplastic and non-neoplastic lesions, presence of periappendicular mucin, and misdiagnosis.Results:There were a total of 68 AD cases with 32 (47%) males and 36 (53%) females. The mean age was 54,1 years (24-93). Diverticulitis was seen in 44 cases (64,7%). In 28 (41,1%) cases ADs were accompanied by other lesions such as low-grade appendiceal mucinous neoplasm (LAMN, n=13), endometriosis (n=4), well-differentiated neuroendocrine tumor (n=3), sessile serrated adenoma (SSA, n=3), adenocarcinoma (n=2), LAMN and WD-NET (n=1), granular cell tumor (n=1), and hyperplastic polyp with inflammatory fibroid polyp (n=1). Periappendiceal acellular mucin deposition was seen in 23 (33,8%) cases with associated diverticulitis in 12 of them. In 7 of the 13 cases of LAMN there was mucin accumulation. AD was incidentally found in 15 appendectomies performed during other surgeries. Although defined macroscopically in 8 cases, the diagnosis of AD was missed during the microscopical examination.Conclusion:The probability of detecting a neoplastic lesion in cases with AD is quite high as proven in our study. Therefore, the entire appendix can be sampled in these cases. It is important to pay attention to macroscopic definitions in order not to miss a possible diverticulum in all cases with microscopic perforation and dense inflammation. The close association between LAMN and AD should be kept in mind.
Rapacaspase-9-based Suicide Gene Applied to the Safety of Il-1rap Car-t Cells
Authors: BOUQUET Lucie , WARDA Walid , ROCHA Mathieu NETO DA , TRAD Rim , NICOD Clémentine , HADERBACHE Rafik , GENIN Delphine , FERRAND Christophe , Deschamps Marina
Published: November 2022

Even if adoptive cell transfer (ACT) has already shown great clinical efficiency in different types of disease, such as cancer, some adverse events consistently occur, and suicide genes are an interesting system to manage these events. Our team developed a new medical drug candidate, a chimeric antigen receptor (CAR) targeting interleukin-1 receptor accessory protein (IL-1RAP), which needs to be evaluated in clinical trials with a clinically applicable suicide gene system. To prevent side effects and ensure the safety of our candidate, we devised two constructs carrying an inducible suicide gene, RapaCasp9-G or RapaCasp9-A, containing a single-nucleotide polymorphism (rs1052576) affecting the efficiency of endogenous caspase 9. These suicide genes are activated by rapamycin and based on the fusion of human caspase 9 with a modified human FK-binding protein, allowing conditional dimerization. RapaCasp9-G- and RapaCasp9-A-expressing gene-modified T cells (GMTCs) were produced from HDs (HDs) and acute myeloid leukemia (AML) donors. The RapaCasp9-G suicide gene demonstrated better efficiency, and we showed its in vitro functionality in different clinically relevant culture conditions. Moreover, as rapamycin is not pharmacologically inert, we also demonstrated its safe use as part of our therapy.
Morphometric study of the ossification centers of the presphenoid and basisphenoid parts of the sphenoid body in the human fetus
Authors: Grzonkowska Magdalena , Szpinda Michał , Badura Mateusz , Wiśniewski Marcin , Biernacki Maciej , Baumgart Mariusz
Published: November 2022

Purposes Understanding the growth and development of the sphenoid bone is crucial in assessing the normal and pathological development of the cranium. The aim of the present study was to examine the growth dynamics of the primary ossification centers of the sphenoid body in the human fetus, based on their linear, planar and volumetric parameters.
Material and Methods The examinations were carried out on 37 human fetuses of both sexes (16 males and 21 females) aged 18–30 weeks of gestation, which were preserved in 10% neutral formalin solution. Using CT, digital image analysis software, 3D reconstruction and statistical methods, we evaluated the size of the primary ossification centers of the sphenoid bone.
Results The morphometric characteristics of the primary ossification centers of the presphenoid and basisphenoid of the sphenoid body display no sex differences. These ossification centers grow linearly with respect to their sagittal diameter, projection surface area and volume for the presphenoid part and with respect to volume for the basisphenoid part, and logarithmically regarding the transverse diameter for the presphenoid part, as well as the sagittal and transverse diameters and projection surface area for the basisphenoid part.
Conclusions The numerical findings associated with the primary ossification centers of the sphenoid body may be considered as age-related normative data of clinical relevance in the estimation of gestational ages and the diagnostics of congenital defects.
Seismic Damage Classification for Axially-Loaded Reinforced Concrete Frame Members based on Compressive Strain
Authors: Shiradhonkar Saurabh R. , Sinha Ravi
Published: November 2022

Quantification of seismic damage to reinforced concrete (RC) members in terms of damages states is important for condition assessment and performance-based seismic design. This paper presents a classification for axially-loaded flexural-dominant RC members into clearly-differentiated damage states based on change in failure mode, principles of mechanics, and loss in lateral load capacity. The paper considers extreme fiber compressive strain as the Engineering Response Parameter (ERP) for classification of the damage states. The identification of member damage states based on compressive strain can be very useful for seismic assessment of the existing buildings and performance-based design of new buildings. Published experimentally-observed cyclic force-displacement relationships of RC columns have been numerically simulated and are used to develop statistics of compressive strain. These are further used to develop semi-empirical expressions for extreme fiber compressive strain in terms of RC member properties, viz. axial load ratio, longitudinal reinforcement ratio, and confinement reinforcement ratio. It is shown that the proposed expressions accurately predict experimentally observed compressive strain at different damage states. The fragility functions of damage states, that provide the probability of occurrence of the strain limits, are also presented. It is seen that the proposed expressions for strain and their limits accurately identify the damage states on the monotonic stress-strain relationship of confined concrete and validate the use of strain as an ERP. The present study also provides strain limits for different damage states with consistent level of conservatism.
Crustal structure and geothermal mechanism of Gonghe-Guide Basin based on EIGEN-6C4 satellite gravity and aeromagnetic data
Authors: Zhou Wenna , Li Qiang , Zhang Dailei , Tang Hai
Published: November 2022

Gonghe-Guide Basin is situated in the northeastern edge of the Tibetan Plateau. one of China's main targets for geothermal research and exploitation. It is also a crucial region for studying the Tibetan Plateau's uplift mechanisms. Therefore, the elaborate crustal structure of the entire basin is essential for recognizing the geothermal mechanisms, geothermal source targets and even the uplift mechanisms of the Tibetan Plateau. However, these issues remain enigmatic, partly because it is difficult to depict the crustal structure of entire base by using the profile results of magnetotelluric and seismic data. To overcome the limitations of profile results, we present a new crustal structure of the entire Gonghe-Guide Basin by using EIGEN-6C4 satellite gravity and aeromagnetic data. The gravity and magnetic data were processed using the wavelet multi-scale decomposition method and the iterative compact depth from extreme points imaging method. Satisfactory residual anomalies and inversion results were obtained. The gravity inversion results reveal pronounced low-density regions at the depths of 15–35 km in the middle-upper crustal, most likely caused by partial melting from heating the overlying hot dry rocks. The results correspond well with the magnetotelluric and seismic results and are an effective supplement. The magnetic inversion results show negative or no magnetism within a similar depth range. But at shallow depths of the same horizontal positions, there is high positive magnetism, which can be interpreted as granite. To confirm and validate this conclusion, a 2D geologic model of a profile from a typical area is created to show the detailed tectonic. Based on the new crustal structure results, the suggested geothermal target is the low/negative density corresponding to low/negative magnetism located at deep depths and high/ positive magnetism located at shallow depths. These density and magnetism anomalies are primarily located near the town of Guide, Gonghe, Xinjie, Chaka, Wayuxiangka, Tanggemu, Xinhai, which can be considered geothermal source targets. The geothermal source is thought to be due to mantle material upwelling or faults activity causing partial melting in the crust, and heat flows from deep to shallow along the faults in the region. Then we established a geological conceptual model to illustrate this process. This indicates that tectonic movement is taking place in the deep part of the earth in Gonghe-Guide Basin. The research on the geological structure and geothermal heat source mechanism in the Gonghe-Guide Basin can provide a primary reference for research on geothermal resources in other areas with similar geological structures.
Prescribing errors in children: What is the impact of a computerized physician order entry?
Authors: Satir Aylin N. , Pfiffner Miriam , Meier Christoph R. , Good Angela Caduff
Published: November 2022

Purpose: Prescribing errors represent a safety risk for hospitalized patients, especially in pediatrics. Computerized physician order entry (CPOE) might reduce prescribing errors, although its effect has not yet been thoroughly studied on pediatric general wards. This study investigated the impact of a CPOE on prescribing errors in children on general wards at the University Children’s Hospital Zurich.
Methods: We performed medication review on a total of 1000 patients before and after the implementation of a CPOE. The CPOE included limited clinical decision support (CDS) such as drug-drug interaction check and checks for duplicates. Prescribing errors, their type according to the PCNE classification, their severity (adapted NCC MERP index) as well as the interrater reliability (Cohen’s Kappa) were analyzed.
Results: CPOE significantly reduced the rate of errors from 25 errors / 100 prescriptions (95% CI: 23 – 27) to 16 errors / 100 prescriptions (95% CI 14 – 18). Particularly the prescribing quality was improved by reducing PCNE error 5.2 “lacking information” (e.g. lacking drug form or maximum possible number of doses for reserve medication). Medication reconciliation problems (PCNE error 8), such as drugs prescribed on paper as well as electronically, significantly increased after introduction of the CPOE. The most common pediatric prescribing errors, the dosing errors (PCNE errors 3), were not statistically significantly altered after introduction of the CPOE. Overall severity of errors was reduced. Interrater reliability showed moderate agreement (Κ = 0.48).
Conclusions: The CPOE increases patient safety by reducing the rate and severity of prescribing errors. The reason for the observed increase in medication reconciliation problems might be the hybrid-system with remaining paper-prescriptions for special medication. The lacking effect on dosing errors might be explained by the fact that a web application CDS covering dosing recommendations (PEDeDose) was already in use before implementation of the CPOE. Further investigations should focus on eliminating hybrid systems, interventions on how to increase the usability of the CPOE, and full integration of CDS tools such as automated dose check into the CPOE.
Sexual violence and associated factors among women of reproductive age in Rwanda: a nationwide cross-sectional survey
Authors: Nuwabaine Lilian , Kawuki Joseph , Amwiine Earnest , Asiimwe John Baptist , Sserwanja Quraish , Gatasi Ghislaine , Donkor Elorm , Atwijukiire Humphrey
Published: November 2022

Background
Sexual violence against women is a global public health issue with both short and long-term effects on the physical and mental health of women. This study aimed to determine the prevalence of sexual violence and its associated factors among women of reproductive age in Rwanda.
Methods
We used secondary data from the 2020 Rwanda Demographic and Health Survey of 1,700 participants, who were selected using multistage stratified sampling. Multivariable logistic regression was conducted to explore factors associated with sexual violence, using SPSS (version 25).
Results
Of the 1,700 women of reproductive age, 12.4% (95%CI: 11.0-14.1) had experienced sexual violence. Justified beating (AOR = 1.34, 95%CI: 1.16–1.65), not having health insurance (AOR = 1.46, 95%CI: 1.26–2.40), not being involved in healthcare decision-making (AOR = 1.64, 95%CI: 1.99–2.70), having a husband/partner with primary (AOR = 1.70, 95%CI: 5.47–6.21) or no education (AOR = 1.84, 95%CI: 1.21–3.37), as well as having a husband/partner who sometimes (AOR = 3.37, 95%CI: 1.56–7.30) or often (AOR = 12.87, 95%CI: 5.64–29.38) gets drunk were positively associated with sexual violence. However, women from male-headed households (AOR = 0.52, 95%CI: 0.29–0.92) were less likely to experience sexual violence.
Conclusions
There is a need to demystify negative culturally-rooted beliefs favouring sexual violence such as justified beating as well as increasing efforts to promote women's empowerment and healthcare access. Moreover, engaging men in anti-sexual violence strategies is paramount in addressing male-related issues that expose women to sexual violence.
Effect of antimicrobial therapy on progression free survival of immunotherapy and chemo-/immunotherapy in patients with non-small cell lung cancer
Authors: Uhlenbruch Mark , Krüger Stefan
Published: November 2022

Background: The choice between immunotherapy with a checkpoint inhibitor (CPI) and chemo-/immunotherapy (CIT) in patients with NSCLC stage IV is often discussed. There is some data that the effect of CPI-therapy is impaired by antimicrobial therapy (AMT). Little is known about the influence of AMT on CIT.
Patients and methods: We retrospectively analysed 114 patients (age 68 ± 8.5 y) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab, cemiplimab) or CIT (Carboplatin/Pemetrexed/Pembrolizumab, Carboplatin/Paclitaxel/Pembrolizumab). We registered patients’ characteristics including presence and timing of AMT. Group 1 consisted of 42 patients with AMT in the month before CPI or CIT, group 2 were 49 patients with AMT during CPI or CIT, and group 3 were 64 patients without AMT and CPI or CIT.
Results: Group 1-3 showed comparable patients characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.02 vs. 4 ± 1.02 months, p = 0.002, 95% CI: 1.88-9). In patients, who were treated with CIT, there was no difference in PFS in those with or without AMT in the month before therapy (10 ± 2.5 vs. 6 ± 1.2 months, p = 0.7). Interestingly, AMT during CIT or CPI therapy showed no effect on PFS.
Conclusions: In a real-life setting, we found that AMT reduces PFS when given in the month before CIT therapy. AMT before or during CIT does not seem to influence PFS. As a consequence, AMT before start of therapy might be a factor that could lead to a preference of CIT instead of CPI in NSCLC stage IV patients
Evaluation of Sewage Molecular Markers in A Highly Industrialized Zone in Peninsular Malaysia
Authors: AL-KHADHER Sadeq , Suratman Suhaimi , Zakaria Mohamad Pauzi
Published: November 2022

The anthropogenic inputs that have serious effects on riverine and coastline ecosystems could be identified using organic chemical tracers like linear alkylbenzenes (LABs). In order to identify the LABs, sediment samples taken from the Kim Kim river and the Port Dickson coast were collected. The origins of the LABs were discovered and identified with the aid of gas chromatography-mass spectrometry (GC-MS). The Pearson correlation coefficient, Post Hoc Tests, LSD Techniques, and Analysis of Variance (ANOVA) were used to establish the significance of differences in the LABs distribution and concentrations among sampling sites at p <0.05. Internal over exterior (I/E) congeners, homologs of C13 and C12, and long over short chain (L/S) were employed to determine the LABs degradation levels and sewage treatment. According to the statistical analysis of the study findings, LABs concentration in the tested areas ranged between 88.3; 112.0 and 119.0; 256.0 ng∙g−1 dw, respectively. With a high number of C13-LAB homologs in the majority of sampling locations, LAB homologs were substantially different at p < 0.05. The fact that the computed LAB ratios (I/E) fell between 1.7; 2.0 and 2.0; 4.1, showed that the investigated locations received effluents from sources related to primary and secondary treatment. In the locations that were investigated, LAB degradation ranged between 34, 38%, 40, and 64%. In conclusion, the need for ongoing wastewater treatment system upgrades and the strong markers of LABs in tracking sewage pollution.
Growth ZIF-8 on carbon cloth for electric field enhanced thin film microextraction of tetracyclines in milk and honey
Authors: Gu Xian-Chun , Sun Ji-Cheng , Yang Cheng , Shen Xiao-Fang , Pang Yue-Hong
Published: November 2022

Tetracyclines (TCs) are a prevalent type of broad-spectrum antibiotic, which could pose a great threat to human health. Herein, ZIF-8 modified carbon cloth (ZIF-8/CC) for electric field-enhanced thin-film microextraction (EE-TFME) of TCs (oxytetracycline, tetracycline and doxycycline) was developed. ZIF-8/CC was prepared by growing ZIF-8 in situ on the surface of CC as the positive electrode of EE-TFME. Compared to the bare carbon cloth electrode, the ZIF-8/CC electrode can enhance the TCs extraction capacity up to nearly twice. Furthermore, EE-TFME could reduce the extraction equilibrium time from 30 min to 20 min. The detection limit of combined high performance liquid chromatography (HPLC) was 2.0-2.5 ng/mL, and the RSDs of intra-day and inter-day were all below 7.1%. The EE-TFME-HPLC method developed based on ZIF-8/CC can be successfully applied to detection of TCs in honey and milk. The spiked recovery experiments of 50 ng/g and 100 ng/g were carried out on milk and honey samples, and the recovery rate of all TCs was between 82.4% and 102.9%, RSDs were less than 8.2%.
Metallothionein gene deficiency facilitates the differentiation of C2C12 myoblasts into slow-twitch myotubes
Authors: Kadota Yoshito , Yamanokuchi Ryo , Ohnishi Nodoka , Matsuoka Mami , Kawakami Takashige , Sato Masao , Suzuki Shinya
Published: November 2022

Metallothionein (MT) 1 and 2 are ubiquitously expressed cysteine-rich, low molecular weight proteins. MT expression is upregulated in skeletal muscle during aging. MTs also play role in multiple types of skeletal muscle atrophy. Meanwhile, it has been reported that MT1 and MT2 gene deficiency increases myogenesis in MT knockout (MTKO) mice. However, little is known about the effect of MTs on muscle formation and atrophy. In this study, we investigated the effect of MT1 and MT2 gene knock-out using the CRISPR-Cas9 system in an in vitro skeletal muscle differentiation model (C2C12 cell line). Although the number of myotubes in C2C12 MTKO cells was comparable to that of mock-transfected cells, MT deficiency promoted myocyte fusion. Muscle-specific transcription factors myoD and myogenin were found to be upregulated at the late stage of myotube differentiation. Furthermore, the fast-twitch myosin heavy chain (MyHC) protein expression was similar in MTKO and mock-transfected myotubes, but slow-MyHC expression was higher in MTKO cells than in mock cells. The MT gene deletion did not affect the number of fast MyHC-positive myotubes but increased the number of slow MyHC-positive myotubes. Treatment with the antioxidant N-acetylcysteine (NAC) inhibited the increase in the number of slow MyHC-positive myotubes as well as slow-MyHC expression in MTKO cells. In contrast, NAC treatment did not alter the number of fast MyHC-positive myotubes or the expression of fast-MyHC in MTKO cells. These results suggest that the antioxidant effects of MTs may be involved in slow-twitch myofiber formation in skeletal muscle.
Fungal communities on alpine cheese rinds in Southern Switzerland
Authors: De Respinis Sophie , Caminada AnnaPaola , Pianta Elisa , Buetti-Dinh Antoine , Scettrini Patrizia Riva , Petrini Liliane , Tonolla Mauro , Petrini Orlando
Published: November 2022

Background: The fungal biodiversity on cheese rinds has been extensively studied for some soft cheeses such as Brie, Camembert, and Roquefort, but scant information is available on the microbiota colonizing the rinds of cheese produced in the Southern Switzerland Alps. This study aimed at exploring the fungal communities present on rinds of cheese produced and matured in Southern Switzerland. We used classical techniques such as dilution series, culturing and macro- and microscopical morphology, matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) mass spectrometry, and sequencing, as well as metabarcoding targeting the ITS and β-tubulin gene regions, to characterize the fungal communities present of cheese rinds collected in five ripening cellars.
Results: Isolation by serial dilution yielded 201 isolates, of which 39 were yeasts and 162 filamentous fungi. Mucor and Penicillium were the dominant genera. Mucor racemosus, M. lanceolatus, P. camemberti, and P. chrysogenum/rubens were the most frequent species. All but two yeast isolates were identified as Debaryomyces hansenii. Overall, metabarcoding detected 80 fungal species, with Mucor spp. and Penicilliumspp. being the dominant taxa, as opposed to only 9 species recovered by serial dilutions. Culture-dependent and independent methods produced similar results in terms of dominant taxa and similarity of the fungal communities in the five cellars, metabarcoding, however, providing more detailed information.
Conclusions: Our study has shown that the mycobiota on the rinds of alpine cheese is a complex community defined by different parameters, including temperature, relative humidity, and type of cheese, as well as microenvironmental and possibly geographic factors.
Five-mer peptides, GSGFK and GSGNR suppress the aggregation of Aβ25-35 and resolve its aggregate form
Authors: Nakamura Rina , Konishi Motomi , Higashi Youichirou , Saito Motoaki , Akizawa Toshifumi
Published: November 2022

Background
The development of drugs for Alzheimer’s disease (AD), which is related to the misfolding and aggregation of Amyloid-β (Aβ), is high in demand due to the growing number of AD patients. In this study, we screened 22 kinds of 5-mer synthetic peptides derived from the Box A region of Tob1 protein to find a peptide effective against Aβ aggregation.
Methods
A Thioflavin T (ThT) assay was performed to evaluate aggregation and screening aggregation inhibitor. Six weeks male ICR mice were administered of saline, 9 nmol Aβ25–35, or a mixture of 9 nmol Aβ25–35 and 9 nmol GSGFK in the right lateral ventricle. The short-term spatial memory assessed using Y-maze. The BV-2 cells were harvested into 24-well plates (4 × 104 cells/well) and incubated for 48 h and then, the cells were treated with 0.01, 0.05, 0.1, 0.2, or 0.5 mM of GSGFK. After incubation for 24 h, bead uptake was evaluated using a laser confocal microscope and Cytation 5.
Results
We found two kinds of peptides, GSGNR and GSGFK, were not only suppressed aggregation of Aβ25–35 but also resolved the aggregated Aβ25–35. Results obtained from the Y-maze test on an Aβ25-35-induced AD mouse model indicated that GSGFK prevents the deficits in short-term memory induced by Aβ25–35. The effect of GSGFK on phagocytosis in microglia cells (BV-2 cells) proved that GSGFK activates the phagocytic ability of microglia.
Conclusions
In conclusion, 5-mer peptides prevent short-term memory deficit in Aβ25–35 induced AD mouse model by reducing the aggregated Aβ25–35. They may also upregulate the phagocytic ability of microglia, which makes 5-mer peptides suitable candidates as therapeutic drugs against AD.
ePRO Symptom Follow-Up of Colorectal Cancer Patients Receiving Oxaliplatin-Based Adjuvant Chemotherapy is Feasible and Enhances the Quality of Patient Care: a prospective multicenter study
Authors: Iivanainen Sanna , Ravichandra Ravi , Jekunen Antti , Arokoski Reetta , Mentu Santeri , Lang Laura , Ekström Jussi , Virtanen Henri , Kataja Vesa , Koivunen Jussi Pekka
Published: November 2022

Purpose: Electronic (e) patient reported outcomes (PROs) have been shown to improve the quality of life and survival in chemotherapy treated advanced cancer patients. We hypothesized that multidimensional ePRO centered approach could improve symptom management, streamline patient flow, and optimize the use of healthcare resources.
Methods: In this multicenter trial (NCT04081558), colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy as adjuvant or in the first or second line setting in advanced disease were included in the prospective ePRO cohort while a comparative retrospective cohort was collected from the same institutes. The investigated tool consisted of a weekly e-symptom questionnaire integrated to an urgency algorithm and laboratory value interface, which generated semi-automated decision support for chemotherapy cycle prescription, and individualized symptom management.
Results: Recruitment to the ePRO cohort occurred 1/2019-1/2021 (n=43). The comparator group (n=194) consisted of patients treated in the same institutes 1-7/2017. The analysis was limited to adjuvant treated (n=36 and n=35). The feasibility of the ePRO follow-up was good with 98% reporting easy usage and 86% improved care, while health care personnel valued the easy use and logical workflow. In the ePRO cohort, 42% needed a phone call before planned chemotherapy cycles while this was 100% in the retrospective cohort (p=1.4e-8). Peripheral sensory neuropathy was detected significantly earlier with ePRO followed (p=1e-5) but did not translate to earlier dose reduction, delays, or unplanned therapy termination compared to the retrospective cohort.
Conclusion: The results suggest that the investigated approach is feasible and streamlines workflow. Earlier symptom detection may improve the quality in cancer care.
Anxious brains: A combined data fusion machine learning approach to predict trait anxiety from gray and white matter features
Authors: Baggio Teresa , Grecucci Alessandro , Meconi Federica , Messina Irene
Published: November 2022

Trait anxiety relates to the steady propensity to experience and report negative emotions and thoughts such as fear and worries across different situations, along with a stable perception of the environment as characterized by threatening stimuli. Previous studies have tried to investigate neuroanatomical features related to anxiety mostly using univariate analyses and, thus, giving rise to contrasting results. The aim of this study is to find a predictive model of individual differences in trait anxiety from brain structural features, with a combined data fusion machine learning approach to allow generalization to new cases. Additionally, we aimed to perform a Network analysis to test the hypothesis that anxiety-related networks have a central role in modulating other networks not strictly associated with anxiety. Finally, we wanted to test the hypotheses that trait anxiety is associated with specific cognitive emotion regulation strategies, and that it decreases with ageing. Structural brain images of 158 participants were first decomposed into independent covarying gray and white matter networks with a data fusion unsupervised machine learning approach (Parallel ICA). Then, trait anxiety was predicted from these networks via supervised machine learning (Decision Trees) and backward regression. Two covarying gray and white matter independent networks successfully predicted trait anxiety. The first network included mainly parietal and temporal regions, such as the postcentral gyrus, the precuneus, and the middle and superior temporal gyrus, while the second included frontal and parietal regions such as the superior and middle temporal gyrus, the anterior cingulate and the precuneus. We also found that trait anxiety was positively associated with catastrophizing, rumination, other- and self-blame, and negatively associated with positive refocusing and reappraisal, and that it decreased with age. This paper provides new insights regarding the prediction of individual differences in trait anxiety from brain and psychological features and can pave the way for future diagnostic predictive models of anxiety.
Highly efficient D-type photonic crystal fiber surface plasmon resonance sensor for same space-time temperature and refractive index detection
Authors: Zhang Shan , Zhang Ping , Dong Zhaoyong , Xu Dongfu , Wang Dong , Li Jing
Published: November 2022

In order to realize temperature and refractive index (RI) detection of the analyte in the same space-time, a dual parameter detection photonic crystal fiber (PCF) optical sensor is proposed in this paper. Meanwhile, it can effectively avoid the interference of analyte temperature with RI detection. Further, a dual polished D-type structure is designed to provide mutually independent detection channels for temperature and RI, respectively. In addition, silver is used as the metal layer material, and polydimethylsiloxane (PDMS) and titanium dioxide (TiO2) are used as the temperature sensitive materials and RI sensitive materials, respectively. This structure design enables the two detection results to be output in parallel without interfering with each other. The proposed optical fiber sensor has a wide detection range and good detection performance. The temperature detection range can be as wide as -60°C to 100°C, and the RI detection range is 1.30-1.40. The best temperature resolution can be 1.42×10-2 RIU, and the temperature wavelength sensitivity is 0.7 nm/°C. While the RI wavelength sensitivity is up to 1.25×104 nm/RIU, and the wavelength resolution is 8×10-6 RIU. The detailed fabrication process of the sensor is given in this paper, as well as the practical application scenarios. Therefore, the optical fiber sensor proposed in this paper has research significance for the development of dual parameter detection optical fiber sensors.
Presence of retinopathy and incident kidney and cardiovascular events in type 2 diabetes with normoalbuminuria – a post-hoc analysis of the PRIORITY randomized clinical trial
Authors: Curovic Viktor , Tofte Nete , Lindhardt Morten , Adamova Katarina , Bakker Stephan J.L. , Beige Joachim , Beulens Joline W.J. , Birkenfeld Andreas L. , Currie Gemma , Delles Christian , Dimos Ingo , Francová Lidmila , Frimodt-Møller Marie , Girman Peter , Göke Rüdiger , Hansen Tine W. , Havrdova Tereza , Kooy Adriaan , Laverman Gozewijnw D. , Mischak Harald , Navis Gerjan , Nijpels Giel , Noutsou Marina , Ortiz Alberto , Parvanova Aneliya , Persson Frederik , Petrie John R. , Ruggenenti Piero L. , Rutters Femke , Rychlík Ivan , Siwy Justyna , Spasovski Goce , Speeckaert Marijn , Trillini Matias , Zürbig Petra , Leyen Heiko von der , Rossing Peter
Published: November 2022

Background
Diabetic retinopathy (DR) is a microvascular complication of diabetes highly associated to cardiovascular disease and diabetic kidney disease. However, these associations are not thoroughly investigated at an early type 2 diabetes disease stage. This study therefore evaluated the association between baseline DR status and development of cardiovascular events (CVEs), microalbuminuria, and kidney function decline and in persons with type 2 diabetes and normal urinary albumin excretion.
Methods
Post-hoc analysis of the PRIORITY study including 1758 persons with type 2 diabetes and normoalbuminuria followed for a median of 2.5 (IQR: 2.0–3.0) years. The study was originally designed to investigate a urinary proteomic risk classifier predictor of microalbuminuria development. DR at baseline was defined as non-proliferative and proliferative abnormalities, macular oedema, or history of laser treatment. Cox models were fitted to investigate the association of DR status with development of 1) a CVE composite defined as non-fatal myocardial infarction, stroke, coronary artery bypass graft, percutaneous coronary intervention, hospitalization for heart failure, or all-cause mortality; 2) persistent microalbuminuria (urinary albumin-creatinine ratio > 30mg/g); and 3) chronic kidney disease (CKD) G3 (eGFR < 60 mL/min/1.73m2). Models were adjusted for relevant risk factors.
Results
At baseline, 304 (17.3%) had DR. Compared to persons without DR, they were older (mean ± SD: 62.7 ± 7.7 vs 61.4 ± 8.3 years, p = 0.019), had longer diabetes duration (17.9 ± 8.4 vs. 10.6 ± 7.0 years, p < 0.001), and higher HbA1c (62 ± 13 vs. 56 ± 12 mmol/mol, p < 0.001). The adjusted hazard ratios of DR at baseline for development of CVE (n = 64), microalbuminuria (n = 197), and CKD (n = 166) were: 2.61 (95%CI: 1.44, 4.72), 1.50 (95%CI: 1.07, 2.11), and 0.87 (95%CI: 0.56, 1.34), and, compared to without DR. Baseline levels of the urinary proteomics classifier did not influence the results.
Conclusions
Presence of DR in normoalbuminuric type 2 diabetes was associated with an increased risk of developing CVE and microalbuminuria, but not with kidney function decline.
Metagenome Next-Generation Sequencing Technique in Diagnosis of Orthopedic Chronic Infectious Diseases (A Report of 12 Cases)
Authors: Li Wei , Zhang De-Bao , Xu Sheng-Ming , Bi Huang-Yi , Gu Gui-Shan
Published: November 2022

Objective: To analyze the role of the metagenome next-generation sequencing (mNGS) technique in identifying and treating the pathogen of orthopedic chronic infectious diseases.
Methods: The data of patients diagnosed with orthopedic chronic infectious diseases by a surgical team of the Department of Joint Surgery of the First Hospital of Jilin University from June to December 2021 were retrospectively analyzed. mNGS and pathogenic bacterial culture were performed on these patients, based on which, in combination with clinical manifestations and treatment effects, the role of mNGS in the diagnosis of pathogenic bacteria was determined. Results: All of the 12 patients had pain and swelling of the affected limb before hospitalization. Pathogenic bacteria were detected in eight patients by mNGS and in three patients by routine bacterial culture. 10 kinds of pathogenic bacteria (Staphylococcus aureus, Streptococcus dysgalactiae, Pseudomonas stutzeri, Chaetomium globosum, Acinetobacter baumannii, Prevotella copri, Staphylococcus epidermidis, Sporothrix schenckii, Pseudomonas aeruginosaand Torque teno virus) were detected by mNGS. The same bacterium was detected in two cases by both mNGS and bacterial culture. Conclusion: The mNGS technique provides an important diagnostic basis for pathogen detection in orthopedic chronic infectious diseases.
Investigation of the Usage Potential of Enzyme-linked Polymers in Different Morphological Structures for the Removal of Micropollutant From Leather Waste Water
Authors: ALTUNBAŞ Canan , ASLAN Ahmet , AÇIKEL Safiye Meriç , AKGÖL Sinan
Published: November 2022

Increasing numbers of chemical elements that are presenting very important problems, are threaten for the environmental health today. The big part of the pollution load in aquatic systems occurred from industrial wastes. The leather industry which emerges as one of the important industries, is considered in terms of its potential for pollution. Unlike the physical, chemical and advanced treatment methods used for the removal of micro- contaminants that are released during the transformation of from the raw skin to the finished leather, the use of immobilization polymers with enzymes known as catalysts is suitable for waste water removal in the leather industry, or in other sectors in order to reduce the environment pollution effect. In this case, the covalent immobilization method between Trametes versicolor laccase enzyme and epoxy group-containing p(HEMA-AGE) were optimized and the degradation conditions of Acid Black 210 dye were investigated. The results were compared with waste dye water which was released after dyeing in leather industry.
Delayed Neuregulin-1 Treatment Initiates a Late Neuroprotective Early Regenerative and Autophagic Spatial Profiles in Mice following Ischemic Stroke
Authors: Noll Jessica , Augello Catherine , Kurum Esra , Pan Liuliu , Pavenko Anna , Nam Andy , Ford Byron
Published: November 2022

Neuregulin-1 (NRG-1) has been shown to be neuroprotective and anti-inflammatory in rodent models following focal brain ischemia. However, the spatial transcriptional mechanisms involved in the effects of NRG-1 have not been investigated. In this study, we examined the spatial cellular and neuroinflammatory mechanisms employed by NRG-1 following stroke utilizing Nanostring Digital Spatial Profiling (DSP) technology. C57bl/6 mice were subjected to photothrombotic middle cerebral artery occlusion (MCAO). Animals were treated with NRG-1 (5ug/kg/day NRG-1 β) or vehicle beginning 24 hours after surgery, and then sacrificed at 3 days post-ischemia (dpi). Using GeoMX DSP technology, we examined the relative expression of 73 proteins in selected regions of interest (ROI) within the ischemic core, peri-infarct tissues, and peri-infarct normal tissue (PiNT) in controls and NRG-1 treated mice. FJB staining showed that delayed NRG-1 treatment did not significantly alter overall neuronal death, but it had profound effects on the neuroregenerative outgrowth environment. The ipsilateral core ROI demonstrated the most altered proteomic profile with 37 differentially regulated proteins related to autophagy and mitophagy, immune cell phagocytosis, and synaptic activity. NRG-1 upregulated synaptophysin by 2.10-fold while marginally rescuing neuronal proteins NeuN and MAP2. NRG-1 treatment induced the upregulation of ULK1, LC3B, ATG5, PINK1, and Park7 within the core region, suggesting successful autophagic flux restoration. NRG-1 treatment also increased Mertk, CD9, CSF1R/CD115, MHCII and Myelin Basic Protein (MBP). Phospho-Tau (S199) was increased 57-fold following stroke and further increased to 90-fold after NRG-1 treatment. The peri-infarct region showed increased astrocyte proteins along with BAG3, CD204/MSR1, phospho-Tau (S199) and Ki67, a marker of cell proliferation. Together, our findings showed that mechanisms of neuroprotection by NRG-1 following stroke occur in distinct spatial domains of the injured brain following ischemia. The data suggest that NRG-1 provides protection against further neuronal apoptosis and priming of an anti-inflammatory, neuroregenerative niche in a spatial manner, which could lead to novel treatment strategies for stroke.
Quorum sensing activities and genomic insights of plant growth-promoting rhizobacteria isolated from Assam tea
Authors: Chopra Ankita , Mongad Dattatray , Satpute Surekha , Mazumder Pranab Behari , Rahi Praveen
Published: November 2022

Secretion of quorum sensing (QS) molecules is important for the effective colonization of host plants by plant growth-promoting rhizobacteria. The current study aims at the isolation and characterization of tea rhizosphere bacteria, which produce the QS molecules, acyl homoserine lactone (AHLs), along with multiple plant growth-promoting (PGP) activities. Thirty-one strains were isolated from the tea rhizosphere, and screening for PGP activities resulted in the selection of strains RTE1 and RTE4 with multiple PGP traits, inhibiting the growth of tea fungal pathogens. Both strains also showed production of AHL molecules while screened using two biosensor strains, Chromobacterium violaceum CV026 and Escherichia coli MT 102(jb132). The strains identified as Burkholderia cepacia RTE1 and Pseudomonas aeruginosa RTE4 based on genome-based analysis like phylogeny, dDDH, and fastANI calculation. Detailed characterization of AHLs produced by the strains using reverse-phase TLC, fluorometry, and LC-MS indicated that the strain RTE1 produced a short chain, C8, and a long chain C12 AHL, while RTE4 produced short-chain AHLS C4 and C6. Confocal microscopy revealed the formation of thick biofilm by RTE1 and RTE4 (18 µm and 23 µm, respectively). Additionally, we found several genes involved in QS, and PGP, inducing systemic resistance (ISR) activities such as lasI/R, qscR, pqq, pvd, aldH, acdS, phz, Sod, rml, and Pch, and biosynthetic gene clusters like N-acyl homoserine lactone synthase, terpenes, pyochelin, and pyocyanin. Based on the functional traits like PGP, biofilm formation and production of AHL molecules, and genetic potential of the strains B. cepacia RTE1 and P. aeruginosa RTE4 appear promising candidates to improve the health and growth of tea plantations.
Objective assessment of intraoperative skills for robot-assisted partial nephrectomy (RAPN)
Authors: Farinha Rui , Breda Alberto , Porter James , Mottrie Alexandre , Cleynenbreugel Ben , Sloten Jozef Vander , Mottaran Angelo , Gallagher Anthony
Published: November 2022

Background
RAPN training usually takes place in-vivo and methods vary across countries/ institutions. No common system exists to objectively assess trainee capacity to perform RAPN at predetermined performance levels prior to in-vivo practice. The identification of objective performance metrics for RAPN training is a crucial starting point to improve training and surgical outcomes.
Objective
The authors sought to examine the reliability, construct and discriminative validity of objective intraoperative performance metrics which best characterize optimal and suboptimal performance of a reference approach for training novice RAPN surgeons.
Design, setting, and participants:
Seven Novice and 9 Experienced RAPN surgeons videorecorded one or two independently performed RAPN procedures in the human. The videos were anonymized and two experienced urology surgeons were trained to reliably score RAPN performance, using previously developed metrics. The assessors were blinded to the performing surgeon, hospital and surgeon group. They independently scored surgeon RAPN performance. Novice and Experienced group performance scores were compared for procedure steps completed and errors made. Each group was divided at the median for Total Errors score, and subgroup scores (i.e., Novice HiErrs and LoErrs, Experienced HiErrs and LoErrs) were compared.
Results
The mean inter-rater reliability (IRR) for scoring was 0.95 (range 0.84–1). Compared with Novices, Experienced RAPN surgeons made 69% fewer procedural Total Errors. This difference was accentuated when LoErr Expert RAPN surgeon’s performance was compared with the HiErrs Novice RAPN surgeon’s performance with an observed 170% fewer Total Errors. GEARS showed poor reliability (Mean IRR = 0.44; range 0.0–0.8), for scoring RAPN surgical performance.
Conclusions
The RAPN procedure metrics reliably distinguish Novice and Experienced surgeon performances. They further differentiated performance levels within a group with similar experience. Reliable and valid metrics will underpin quality-assured novice RAPN surgical training.
Analysis of the efficacy of a single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy
Authors: fu zhenyu , Tian Zhen , Chen Yongchang , Jia Zongming , Wang Chengyu , Zhang Xuefeng , Zhang Weijie , Li Gang , Wei Xuedong , Huang Yuhua
Published: November 2022

Purpose: The efficacy and complications of bilateral cutaneous ureterostomy with a single subumbilical stoma were compared with those of cutaneous ureterostomy with two stomas and an ileal conduit.
Methods: The clinical data for 108 patients who received bilateral cutaneous ureterostomy with a single subumbilical stoma (ureterostomy with a single stoma group), cutaneous ureterostomy with two stomas (ureterostomy with two stomas group), or an ileal conduit (ileal conduit group) after radical cystectomywere retrospectively analysed. The operative time, pathological stage, survival status, perioperative complication rate, rate of successful first extubation, rehospitalization rate at 6 months after surgery,ostomy-related medical costs ,and postoperative quality of life were compared between the three groups of patients.
Results: A significant difference in the operative time was found between the three groups (P = 0.001). No significant differences in pathological stage, survival status, perioperative complication rate, rehospitalization rate at 6 months after surgery, or BCI score were identified among the three groups. The difference in the successful first extubation rate between the three groups of patients was significant (P = 0.001). Significant differences in ostomy-related medical costs were observed among the three groups of patients (P = 0.006).
Conclusion: The survival and complication rates of patients undergoing three different urinary diversion strategies after radical cystectomy were similar, but the operative time of the single-stoma group was shorter than that of the ileal conduit group. Compared with the two-stoma group, the single-stoma group had a significantly higher rate of successful first extubation and lower ostomy-related medical costs.