bluuebunny/crossref_metadata_2025 huggingface dataset:
MACHINE LEARNING IN MANAGING THE PRODUCTION OF ENTOMOPHAGES
Authors: Chernova I. , Lysenko V.
Published: July 2023

The article is devoted to the issue of creating a multilayer neural network of direct signal propagation for intelligent decision support on the quality of entomological products in the production of entomophages. The relevance of the chosen direction of research is determined.

The purpose of the study was to develop a neural network to solve the problem of classifying the quality of entomological products in the production of entomophages.

The object of the study was the process of classifying the quality indicators of the Ephestia kuehniella in the production of the entomophages Habrobracon hebetor.

Research methods – neural network and heuristic approaches, computer modeling.

A three-layer forward signal propagation neural network was developed, which classifies the quality of Ephestia kuehniella in the production of the entomophage Habrobracon hebetor. The parameters of the input layer are the indicators of the quality of the Ephestia kuehniella - the mass of caterpillars of an older age, the parameters of the output layer - the quality class. The number of hidden layer neurons is calculated heuristically. To avoid retraining the network, training, control and test samples were formed. The network was trained using the Artificial Neural Network Scilab software package using the Levernberg-Marquardt algorithm. The average error of approximation of the learning results was (0.07-0.08) %, which indicates high classification accuracy.

Research results make it possible to reduce the influence of the human factor in decision-making processes in the production of entomophages, to structure data on product quality.
Reducing of Corrosion Rate in Boiler Tubes by Using Oxygen Scavengers
Authors: Jafar Saad A , Fathi Mohammed I
Published: July 2023

The corrosion behavior of carbon steel at different temperatures 100,120,140 and 160 Cͦ under different pressures 7,10 and 13 bar in pure distilled water and after adding three types of oxygen scavengers Hydroquinone, Ascorbic acid and Monoethanolamine in different concentrations 40,60 and 80 ppm has been investigated using weight loss method. The carbon steel specimens were immersed in water containing 8.2 ppm dissolved oxygen (DO) by using autoclave. It was found that corrosion behavior of carbon steel was greatly influenced by temperature with high pressure. The corrosion rate decreases, when adding any one of oxygen scavengers. The best results were obtained at a concentration of 80 ppm of each scavenger. It was observed that  hydroquinone  is the best among the other scavengers in reducing the corrosion rate at the temperatures and pressures of this investigation and most efficient in the consumption of oxygen especially 80 ppm, it reduces the concentration of oxygen in water from 8.2 to 0.8 ppm, while the ascorbic acid reduces the oxygen concentration to 1.4 and monoethanolamine reduces the concentration of oxygen to 1.9 . It has been observed that hydroquinone reacts with oxygen quickly and at low temperatures while the other scavengers react slowly with oxygen.
Rheological Evaluation of Polymer (Sav 10) For Polymer Flooding Applications
Authors: Salih Talib A. , Sahi Safaa Hussain , Hameed Omar  K.
Published: July 2023

Half of the oil production of the worldwide is a result  of the water flooding  project. But the main concern of this process is mobility control of the injected fluid, because the unfavorable mobility ratio leads to fingering effect. Adding polymer to the injection water increase the water viscosity, therefore, the displacement will be more stable and have a greater sweep efficiency.

   Using of polymer flooding has received more attention these days. Polymer has great potential in the Middle East region, especially in reservoir with high temperature and salinity.

   The main objective of this work is to show the effect of shear rate, salinity, temperature, polymer concentration on polymer viscosity and determine the target viscosity to further displacement experiments. Polymer solution was prepared with two types of water (fresh water, brine). The reason of using two types of water is the ability of polymer to prepare by fresh water or brine.

   Results from this study show that as the shear rate increases, polymer viscosity decreases. Also, the results show that in spite of polymer viscosity decreased with increase in temperature and salinity, polymer (SAV 10) shows that high temperatures have less effect on its viscosity at the same shear rate and has a salinity resistant up 200000 ppm. As polymer concentration increase, polymer viscosity increase until reach the target concentration which can be used for displacement experiments. It was found that the target concentration with viscosity 6.99 cp is 2000 ppm, which is closest to reservoir viscosity.
Experimental Study and Mathematical Modelling of Zinc Removal by Reverse Osmosis Membranes
Authors: Al-Alawy Ahmed Faiq , Salih Miqat Hasan
Published: July 2023

In this study, aromatic polyamide reverse osmosis membranes were used to remove zinc ions from electroplating wastewater. Influence of different operating conditions such as time, zinc concentration and pressure on reverse osmosis process efficiency was studied.  The experimental results showed, concentration of zinc in permeate increase with increases of time from 0 to 70 min, and flux of water through membrane decline with time. While, the concentrations of zinc in permeate increase with the increase in feed zinc concentration (10–300 mg/l), flux decrease with the increment of feed concentration. The raise of pressure from 1 to 4 bar, the zinc concentration decreases and the flux increase. The highest recovery percentage was found is 54.56% for reverse osmosis element, and the highest rejection of zinc was found is 99.49%. Experimental results showed that the concentrations of zinc ion in permeate was lower than the permissible limits (i.e. ˂ 10 ppm). A mathematical model describing the process was investigated and solved by using MATLAB PROGRAM. Theoretical results were consistent with the experimental results approximately 90%.
Synthesis Of Nano Ni-Mo/γ-Al2O3 CatalystSynthesis Of Nano Ni-Mo/γ-Al2O3 Catalyst
Authors: Mohamed Abdul-Halim A. K. , Atta Hawraa H.
Published: July 2023

Nano γ-Al2O3 support was prepared by co-precipitation method by using different calcination temperatures (550, 600, and 750) oC. Then nano NiMo/γ-Al2O3 catalyst was prepared by impregnation method were nickel carbonate (source of Ni) and ammonium paramolybdate (source of Mo) on the best prepared nano γ-Al2O3 support at calcination temperature 550 oC. Make the characterizations for prepared nano γ-Al2O3 support at different temperatures and for nano NiMo/γ-Al2O3 catalyst like X-ray diffraction, X-ray fluorescent, AFM, SEM, BET surface area, and pore volume.

The Ni and Mo percentages in the prepared nano NiMo/γ-Al2O3 catalyst determined by X-ray fluorescence were 2.924 wt % and 12.9 wt %, respectively. SEM of prepared nano γ-Al2O3 support at calcination temperature 550 oC. The average particles diameter of prepared γ-Al2O3 support determined by AFM at calcination temperatures 550, 600, and 750 oC and for prepared nano NiMo/γ-Al2O3 catalyst at calcination temperature 550 oC.
Removal of Ni(II), Pb(II), and Cu(II) from Industrial Wastewater by Using NF Membrane
Authors: Algureiri Ahmed H. , Abdulmajeed Yossor R.
Published: July 2023

This article reviews the technical applicability of nanofiltration membrane process for the removal of nickel, lead, and copper ions from industrial wastewater.

Synthetic industrial wastewater samples containing Ni(II), Pb(II), and Cu(II) ions at various concentrations (50, 100, 150 and 200 ppm), under different pressures (1, 2, 3 and 4 bar), temperatures (10, 20, 30 and 40 oC), pH (2, 3, 4, 5 and 5.5), and flow rates (1, 2, 3 and 4 L/hr), were prepared and subjected treated by NF systems in the laboratory. Suitable NF membrane was chosen after testing a number of NF membranes (University of Technology-Baghdad), in terms of production and removal. NF system was capable of removing more than (85%, 78%, and 66% for Ni(II), Pb(II), and Cu(II) ions respectively).   The permeate flux for all H.M ions for were ranges between (14 to 62 L/m2.hr). The results showed that the NF membrane was capable of treating industrial wastewater with any concentration of heavy metals ions and reducing the ion concentration to about (15, 22, and 34 ppm) for Ni(II), Pb(II), and Cu(II) ions respectively. The low level of the heavy metals concentration in the permeate implies that water with good quality could be reclaimed for further reuse. The NF membrane is characterized by efficiently H.M. ions removal medium with high productivity and very low pressure up to 1 bar, which means very little cost for NF system.
Study the Effect of Using Microwave Radiation and H-Donors on Improving Heavy Oil
Authors: Hussein Hussein Qasim , Khedheer Zeina Abbas
Published: July 2023

The present research has investigated the effect of microwave energy on improving the flow properties of heavy crude oil. The fragmentation of crude oil molecules was carried out with and without using 1 and 10 wt. % concentration of various types of H-donors like tetralin, cyclohexane, and naphtha.  Microwave power of 320, 385, and 540 W and radiation time 1-9 min, and temperature were studied. The kinematic viscosity and asphaltene content were measured for evaluation the improving of heavy crude oil.

   Results show that viscosity of crude oil decreased with increase H-donor concentration, a maximum percentage of viscosity reduction was10.63 % for tetralin at 6 min radiation time, while 8.67%, and 7.34% for cyclohexane and naphtha at 4 min respectively. The high H-donor polarity is the high viscosity reduction.

   The asphaltenes content of crude oil was decreased during microwave treatment process, a maximum percentage of reduction was 39.73% for tetralin at 6 min radiation time, while 34.40% and 46.29 % for cyclohexane and naphtha at 4 min respectively. The viscosity of crude oil was decreased with asphaltenes content decrease.

   The temperature of a crude oil was varied during the microwave treatment and it was depended on radiation time and radiation power and H-donor type.

   The best reduction of crude oil viscosity and asphaltenes content was achieved at a moderate radiation power385 W.
Diffuse Neurocysticercosis in a Survivor of Tuberculosis
Authors: Ahlawat Prashant , Upadhyay Prateek , Garg Tulika
Published: July 2023

Neurocysticercosis (NCC) is a prevalent parasitic infection of the central nervous system (CNS) caused by Taenia solium larvae. It is commonly found in developing countries with a high incidence of both NCC and CNS tuberculosis. In cases where patients have a history of pulmonary tuberculosis, the lesions arising from NCC can be misdiagnosed as tuberculomas. Furthermore, when papilledema (a sign of raised intracranial pressure) is present, CNS tuberculosis is often considered a more probable diagnosis compared to NCC. While NCC is common, disseminated cysticercosis is rare. In this article, we present a case of diffuse neurocysticercosis and discuss relevant management approaches.
FREQUENCY OF ORAL LESIONS AMONG DIABETIC PATIENTS, MUCOSAL ALTERATIONS AND RISK FACTORS
Authors: Gichki Abdul Samad , Ahmed Khalil , Asad Talha , Masood Bilal Ahmed
Published: July 2023

Objectives: To estimate the frequency of Oral lesions among diabetic patients in the Department of Oral Medicine.Methods and materials: Study design was cross sectional and was brought in the Department of Oral Medicine Dental Section Bolan Medical College Sandman Provincial Hospital Quetta, from June 2021 to May 2022. A total of 50, 35 male and 15 female with known history of diabetic were reported in the Department of Oral Medicine Dental Section Sandeman Provincial Hospital Quetta (SPH) for their routine Dental problems were included in this survey.Results: 72% reported patients were male and 28% were female. The mean age of the patients were 40.25 years. Majority of the diabetic patients age were between 52 to 62 ( n=23, (46%) years, and second majority cases were having age ranged between 41-51(n=17, 34%) years and third majority cases were having age ranged from 30-40(n=7, 14%) years. Dental caries was the most common fi ndings in this study 36%, followed by Xerostomia 28%, gingivitis 24%, abnormal taste 22%, Burning mouth 14%, Angular chelitis and Depapillated Tongue 12% each, Candidiasis 16%, oral ulcerations 10% and periodontitis 8% respectively. In this study Xerostomia and dental carries were statistically signifi cant between oral lesions and diabetic patients.Conclusion: IDiabetic patients had higher incidence of oral lesions and mucosal alterations than non-diabetic patients. Higher incidence of oral lesions brings out the requisite of the regular oral examination to make sure the initial diagnosis and handling Oral mucosal lesions in diabetic patients.
Optimalisasi Layanan Operasional Bus Trans Binjai Dalam Upaya Meningkatkan Pelayanan Publik Di Kota Binjai
Authors: Ali Khaidir
Published: July 2023

Transportation is a component of road traffic and transportation that contributes to the improvement of general welfare. The Minister of Transportation and the Mayor of Binjai inaugurated the operation of the Trans Binjai Bus in September 2017. This study aims to evaluate the quality of Trans Binjai Bus operational services in an effort to improve public services in Binjai City. To ensure customer satisfaction, the service quality included is used to improve community service. Qualitative method with descriptive analysis is used in this study to obtain a systematic, factual and accurate description of the problem under study. The results of the study show that the operational quality of Trans Binjai Bus services has been carried out quite well and as much as possible, using a lot of manual methods. The results show that a more modern and application-based concept should be applied to improve services
Type VII secretion system and its effect on group B Streptococcus virulence in isolates obtained from newborns with early onset disease and colonized pregnant women
Authors: Schindler Yulia , Rahav Galia , Nissan Israel , Valenci Gal , Ravins Miriam , Hanski Emanuel , Ment Dana , Tekes-Manova Dorit , Maor Yasmin
Published: July 2023

Introduction

GBS may cause a devastating disease in newborns. In early onset disease of the newborn the bacteria are acquired from the colonized mother during delivery. We characterized type VII secretion system (T7SS), exporting small proteins of the WXG100 superfamily, in group B Streptococci (GBS) isolates from pregnant colonized women and newborns with early onset disease (EOD) to better understand T7SS contribution to virulence in these different clinical scenarios.

Methods

GBS genomes [N=33, 17 EOD isolates (serotype III/ST17) and 16 colonizing isolates (12 serotype VI/ST1, one serotype VI/ST19, one serotype VI/ST6, and two serotype 3/ST19)] were analyzed for presence of T7SS genes and genes encoding WXG100 proteins. We also perform bioinformatic analysis. Galleria mellonella larvae were used to compare virulence between colonizing, EOD, and mutant EOD isolates. The EOD isolate number 118659 (III/ST17) was used for knocking out the essC gene encoding a membrane-bound ATPase, considered the driver of T7SS.

Results

Most GBS T7SS loci encoded core component genes: essC, membrane-embedded proteins (essA; essB), modulators of T7SS activity (esaA; esaB; esaC) and effectors: [esxA (SAG1039); esxB (SAG1030)].Bioinformatic analysis indicated that based on sequence type (ST) the clinicalGBS isolates encode at least three distinct subtypes of T7SS machinery. In all ST1isolates we identified two copies of esxA gene (encoding putative WXG100proteins), when only 23.5% of the ST17 isolates harbored the esxA gene. Five ST17isolates encoded two copies of the essC gene. Orphaned WXG100 molecule(SAG0230), distinct from T7SS locus, were found in all tested strains, except inST17 strains where the locus was found in only 23.5% of the isolates. In ST6 andST19 isolates most of the structure T7SS genes were missing. EOD isolates demonstrated enhanced virulence in G. mellonella modelcompared to colonizing isolates. The 118659DessC strain was attenuated in itskilling ability, and the larvae were more effective in eradicating 118659DessC.

Conclusions

We demonstrated that T7SS plays a role during infection. Knocking out the essC gene, considered the driver of T7SS, decreased the virulence of ST17 responsible for EOD, causing them to be less virulent comparable to the virulence observed in colonizing isolates.
A live fuel moisture climatology in California
Authors: Drucker Jack R. , Farguell Angel , Clements Craig B. , Kochanski Adam K.
Published: July 2023

In this study, observations of live fuel moisture content (LFMC) for predominantly sampled fuels in six distinct regions of California were examined from 2000 to 2021. To gather the necessary data, an open-access database called the Fuel Moisture Repository (FMR), was developed. By harnessing the extensive data aggregation and query capabilities of the FMR, which draws upon the National Fuel Moisture Database, valuable insights into the live fuel moisture seasonality were obtained. Specifically, our analysis revealed a distinct downtrend in LFMC across all regions, with the exception of the two Northernmost regions. The uptrends of LFMC seen in those regions are insignificant to the general downtrend seen across all of the regions. Although the regions do not share the same trends over the temporal span of the study, from 2017 to 2021, all the regions experienced a downtrend two times more severe than the general 22-year downtrend. Further analysis of the fuel types in each of the six regions, revealed significant variability in LFMC across different fuel types and regions. To understand potential drivers of this variability, the relationship between LFMC and drought conditions was investigated. This analysis found that LFMC fluctuations were closely linked to water deficits. However, the drought conditions varied across the examined regions, contributing to extreme LFMC variability. Notably, during prolonged drought periods of 2 or more years, fuels adapted to their environment by stabilizing or even increasing their maximum and minimum moisture values, contrary to the expected continual decrease. These LFMC trends have been found to correlate to wildfire activity and the specific LFMC threshold of 79% has been proposed as trigger of an increased likelihood of large fires. By analyzing the LFMC and fire activity data in each region, we found that more optimal local thresholds can be defined, highlighting the spatial variability of the fire response to the LFMC. This work expands on existing literature regarding the connections between drought and LFMC, as well as fire activity and LFMC. The study presents a 22-year dataset of LFMC spanning the entirety of California and analyses the LFMC trends in California that haven’t been rigorously studied before.
Safety and efficacy of transarterial chemoembolization combined with tyrosine kinase inhibitors and camrelizumab in the treatment of patients with advanced unresectable hepatocellular carcinoma
Authors: Li Jinpeng , Kong Mingxin , Yu Guangji , Wang Song , Shi Zhaozhang , Han Huihui , Lin Yanyan , Shi Jutian , Song Jinlong
Published: July 2023

Objective

This study was aimed to evaluate the efficacy and safety of transarterial chemoembolization combined with tyrosine kinase inhibitors and camrelizumab in the treatment of unresectable hepatocellular carcinoma and to explore a new therapeutic strategy for the treatment of advanced HCC.

Patients and methods

A total of 87 patients aged 18-75 years with at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1) were included in the study. TACE was administered as needed, and camrelizumab and TKI medication were initiated within two weeks and one week after TACE, respectively. The primary endpoints were progression-free survival and objective response rate.

Results

The 87 patients in this trial were last evaluated on September 28, 2022, and 35.8% were still receiving treatment at the data cutoff. A total of 34 patients (39.1%) died, and the median OS was not reached. The median PFS was 10.5 months (95% CI: 7.8-13.1). The ORR rate was 71.3% (62/87), and the DCR rate was 89.7% (78/87) per mRECIST. According to RECIST version 1.1, the ORR rate was 35.6% (31/87), and the DCR rate was 87.4% (76/87). Ten patients (11.5%) successfully underwent conversion therapy and all achieved R0 resection. Two patients achieved a complete pathological response, four achieved a major pathological response, and four had a partial response. All treatment-related adverse events were tolerated. No serious adverse events were observed, and no treatment-related deaths occurred.

Conclusions

TACE combined with TKI and camrelizumab was safe and effective in treating advanced HCC. Triple therapy may benefit patients with large tumor burden and portal vein cancer thrombus and is expected to provide a new treatment strategy for advanced HCC.

Clinical Trial Registration

ClinicalTrials.gov, identifier ChiCTR2000039508
EGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells
Authors: Melo Vinicio , Nelemans Levi Collin , Vlaming Martijn , Lourens Harm Jan , Wiersma Valerie R. , Bilemjian Vrouyr , Huls Gerwin , de Bruyn Marco , Bremer Edwin
Published: July 2023

A higher density of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment, particularly cytotoxic CD8+ T cells, is associated with improved clinical outcome in various cancers. However, local inhibitory factors can suppress T cell activity and hinder anti-tumor immunity. Notably, TILs from various cancer types express the co-stimulatory Tumor Necrosis Factor receptor CD27, making it a potential target for co-stimulation and re-activation of tumor-infiltrated and tumor-reactive T cells. Anti-cancer therapeutics based on exploiting CD27-mediated T cell co-stimulation have proven safe, but clinical responses remain limited. This is likely because current monoclonal antibodies fail to effectively activate CD27 signaling, as this receptor requires higher-order receptor cross-linking. Here, we report on a bispecific antibody, CD27xEGFR, that targets both CD27 and the tumor antigen, epidermal growth factor receptor (EGFR). By targeting EGFR, which is commonly expressed on carcinomas, CD27xEGFR induced cancer cell-localized crosslinking and activation of CD27. The design of CD27xEGFR includes an Fc-silent domain, which is designed to minimize potential toxicity by reducing Fc gamma receptor-mediated binding and activation of immune cells. CD27xEGFR bound to both of its targets simultaneously and triggered EGFR-restricted co-stimulation of T cells as measured by T cell proliferation, T cell activation markers, cytotoxicity and IFN-γ release. Further, CD27xEGFR augmented T cell cytotoxicity in a panel of artificial antigen-presenting carcinoma cell line models, leading to Effector-to-Target ratio-dependent elimination of cancer cells. Taken together, we present the in vitro characterization of a novel bispecific antibody that re-activates T cell immunity in EGFR-expressing cancers through targeted co-stimulation of CD27.
Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination
Authors: Harthaller Teresa , Falkensammer Barbara , Bante David , Huber Maria , Schmitt Melanie , Benainouna Habib , Rössler Annika , Fleischer Verena , von Laer Dorothee , Kimpel Janine , Würzner Reinhard , Borena Wegene
Published: July 2023

Introduction

The rapid evolution of SARS-CoV-2 has posed a challenge to long-lasting immunity against the novel virus. Apart from neutralizing function, binding antibodies induced by vaccination or infection play an important role in containing the infection.

Methods

To determine the proportion of wild-type (WT)–generated antibodies recognizant of more recent variants, plasma samples from either SARS-CoV-2 WT-infected (n = 336) or double-mRNA (Comirnaty)–vaccinated individuals (n = 354, age and sex matched to the convalescent group) were analyzed for binding antibody capacity against the S1 protein of the BA.1 omicron variant.

Results

Overall, 38.59% (95% CI, 37.01– 40.20) of WT-generated antibodies recognized Omicron BA.1 S1 protein [28.83% (95% CI, 26.73–30.91) after infection and 43.46% (95% CI, 41.61–45.31) after vaccination; p < 0.001]. Although the proportion of WT-generated binding and neutralizing antibodies also binding to BA.1 is substantially reduced, the avidity of the remaining antibodies against the Omicron variant was non-inferior to that of the ancestral virus: Omicron: 39.7% (95% CI: 38.1–41.3) as compared to the avidity to WT: 27.0% (95% CI, 25.5–28.4), respectively (p < 0.001). Furthermore, we noticed a modestly yet statistically significant higher avidity toward the Omicron epitopes among the vaccinated group (42.2%; 95% CI, 40.51–43.94) as compared to the convalescent counterparts (36.4%; 95% CI, 33.42–38.76) (p = 0.003), even after adjusting for antibody concentration.

Discussion

Our results suggest that an aspect of functional immunity against the novel strain was considerably retained after WT contact, speculatively counteracting the impact of immune evasion toward neutralization of the strain. Higher antibody levels and cross-binding capacity among vaccinated individuals suggest an advantage of repeated exposure in generating robust immunity.
Potential therapeutic targets of macrophages in inhibiting immune damage and fibrotic processes in musculoskeletal diseases
Authors: Zhu Jianshu , Fan Jiawei , Xia Yuanliang , Wang Hengyi , Li Yuehong , Feng Zijia , Fu Changfeng
Published: July 2023

Macrophages are a heterogeneous cell type with high plasticity, exhibiting unique activation characteristics that modulate the progression and resolution of diseases, serving as a key mediator in maintaining tissue homeostasis. Macrophages display a variety of activation states in response to stimuli in the local environment, with their subpopulations and biological functions being dependent on the local microenvironment. Resident tissue macrophages exhibit distinct transcriptional profiles and functions, all of which are essential for maintaining internal homeostasis. Dysfunctional macrophage subpopulations, or an imbalance in the M1/M2 subpopulation ratio, contribute to the pathogenesis of diseases. In skeletal muscle disorders, immune and inflammatory damage, as well as fibrosis induced by macrophages, are prominent pathological features. Therefore, targeting macrophages is of great significance for maintaining tissue homeostasis and treating skeletal muscle disorders. In this review, we discuss the receptor-ligand interactions regulating macrophages and identify potential targets for inhibiting collateral damage and fibrosis in skeletal muscle disorders. Furthermore, we explore strategies for modulating macrophages to maintain tissue homeostasis.
Prognostic nutritional index as a prognostic biomarker for gastrointestinal cancer patients treated with immune checkpoint inhibitors
Authors: Zhang Lilong , Ma Wangbin , Qiu Zhendong , Kuang Tianrui , Wang Kunpeng , Hu Baohong , Wang Weixing
Published: July 2023

Objective

Our study represents the first meta-analysis conducted to evaluate the prognostic utility of the baseline prognostic nutritional index (PNI) in patients with gastrointestinal cancer (GIC) who received immune checkpoint inhibitor (ICI) therapy.

Methods

We searched PubMed, the Cochrane Library, EMBASE, and Google Scholar until April 23, 2023, to obtain relevant articles for this study. Our analysis examined several clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).

Results

In this analysis, a total of 17 articles with 2883 patients were included. Our pooled results indicated that patients with high PNI levels had longer OS (HR: 0.530, 95% CI: 0.456-0.616, p < 0.001) and PFS (HR: 0.740, 95% CI: 0.649-0.844, p < 0.001), as well as higher ORR (OR: 1.622, 95% CI: 1.251-2.103, p < 0.004) and DCR (OR: 1.846, 95% CI: 1.428-2.388, p < 0.001). Subgroup analysis showed that PNI cutoff values of 40 to 45 showed greater predictive potential. Subgroup analysis also confirmed that the above findings still hold true in patients with esophageal cancer, gastric cancer, and hepatocellular carcinomas.

Conclusion

The PNI were reliable predictors of outcomes in GIC patients treated with ICIs.
Progress of PD-1/PD-L1 signaling in immune response to liver transplantation for hepatocellular carcinoma
Authors: Ju Feng , Wang Dawei , Huang Lan , Jiang Chun , Gao Ce , Xiong Cunquan , Zhai Guanghua
Published: July 2023

Primary liver cancer is one of the most common malignant tumors in China. The vast majority of primary liver cancer are hepatocellular carcinoma. Due to its high incidence and mortality from HCC, HCC has always been a feared type of cancer. Liver transplantation, as one of the important means to treat advanced liver cancer, has brought new hope to patients. However, as patients have been in a state of immunosuppression after liver transplantation, these patients face new problems of HCC recurrence and metastasis. A increasing number of studies have proved that blocking the PD-1/PD-L1 signaling pathway and restoring the immune killing inhibition of T cells can produce better therapeutic effects on tumors and chronic infectious diseases. As a promising treatment in the field of tumor immunotherapy, PD-1/PD-L1 inhibitors have achieved important results in liver cancer patients, but their application in liver transplantation patients is still highly controversial. This paper will introduce the mechanism of action of PD-1/PD-L1 signaling pathway and the current basic and clinical studies of PD-1/PD-L1 signaling pathway associated with immune response in HCC transplantation.
Genome-resolved metagenomics provides insights into the ecological roles of the keystone taxa in heavy-metal-contaminated soils
Authors: Li Liangzhi , Meng Delong , Yin Huaqun , Zhang Teng , Liu Yongjun
Published: July 2023

Microorganisms that exhibit resistance to environmental stressors, particularly heavy metals, have the potential to be used in bioremediation strategies. This study aimed to explore and identify microorganisms that are resistant to heavy metals in soil environments as potential candidates for bioremediation. Metagenomic analysis was conducted using microbiome metagenomes obtained from the rhizosphere of soil contaminated with heavy metals and mineral-affected soil. The analysis resulted in the recovery of a total of 175 metagenome-assembled genomes (MAGs), 73 of which were potentially representing novel taxonomic levels beyond the genus level. The constructed ecological network revealed the presence of keystone taxa, including Rhizobiaceae, Xanthobacteraceae, Burkholderiaceae, and Actinomycetia. Among the recovered MAGs, 50 were associated with these keystone taxa. Notably, these MAGs displayed an abundance of genes conferring resistance to heavy metals and other abiotic stresses, particularly those affiliated with the keystone taxa. These genes were found to combat excessive accumulation of zinc/manganese, arsenate/arsenite, chromate, nickel/cobalt, copper, and tellurite. Furthermore, the keystone taxa were found to utilize both organic and inorganic energy sources, such as sulfur, arsenic, and carbon dioxide. Additionally, these keystone taxa exhibited the ability to promote vegetation development in re-vegetated mining areas through phosphorus solubilization and metabolite secretion. In summary, our study highlights the metabolic adaptability and ecological significance of microbial keystone taxa in mineral-affected soils. The MAGs associated with keystone taxa exhibited a markedly higher number of genes related to abiotic stress resistance and plant growth promotion compared to non-keystone taxa MAGs.
Identifying pathogenicity-related genes in the pathogen Colletotrichum magnum causing watermelon anthracnose disease via T-DNA insertion mutagenesis
Authors: Guo Zhen , Wu Huijie , Peng Bin , Kang Baoshan , Liu Liming , Luo Chaoxi , Gu Qinsheng
Published: July 2023

Fruit rot caused by Colletotrichum magnum is a crucial watermelon disease threatening the production and quality. To understand the pathogenic mechanism of C. magnum, we optimized the Agrobacterium tumefaciens-mediated transformation system (ATMT) for genetic transformation of C. magnum. The transformation efficiency of ATMT was an average of around 245 transformants per 100 million conidia. Southern blot analysis indicated that approximately 75% of the mutants contained a single copy of T-DNA. Pathogenicity test revealed that three mutants completely lost pathogenicity. The T-DNA integration sites (TISs) of three mutants were Identified. In mutant Cm699, the TISs were found in the intron region of the gene, which encoded a protein containing AP-2 complex subunit σ, and simultaneous gene deletions were observed. Two deleted genes encoded the transcription initiation protein SPT3 and a hypothetical protein, respectively. In mutant Cm854, the TISs were found in the 5′-flanking regions of a gene that was similar to the MYO5 encoding Myosin I of Pyricularia oryzae (78%). In mutant Cm1078, the T-DNA was integrated into the exon regions of two adjacent genes. One was 5′-3′ exoribonuclease 1 encoding gene while the other encoded a WD-repeat protein retinoblastoma binding protein 4, the homolog of the MSl1 of Saccharomyces cerevisiae.
Subthalamic deep brain stimulation for primary dystonia: defining an optimal location using the medial subthalamic nucleus border as anatomical reference
Authors: Zhao Mingming , Chen Hui , Yan Xin , Li Jianguang , Lu Chao , Cui Bin , Huo Wenjun , Cao Shouming , Guo Hui , Liu Shuang , Yang Chunjuan , Liu Ying , Yin Feng
Published: July 2023

Introduction

Although the subthalamic nucleus (STN) has proven to be a safe and effective target for deep brain stimulation (DBS) in the treatment of primary dystonia, the rates of individual improvement vary considerably. On the premise of selecting appropriate patients, the location of the stimulation contacts in the dorsolateral sensorimotor area of the STN may be an important factor affecting therapeutic effects, but the optimal location remains unclear. This study aimed to define an optimal location using the medial subthalamic nucleus border as an anatomical reference and to explore the influence of the location of active contacts on outcomes and programming strategies in a series of patients with primary dystonia.

Methods

Data from 18 patients who underwent bilateral STN-DBS were retrospectively acquired and analyzed. Patients were assessed preoperatively and postoperatively (1 month, 3 months, 6 months, 1 year, 2 years, and last follow-up after neurostimulator initiation) using the Toronto Western Spasmodic Torticollis Rating Scale (for cervical dystonia) and the Burke–Fahn–Marsden Dystonia Rating Scale (for other types). Optimal parameters and active contact locations were determined during clinical follow-up. The position of the active contacts relative to the medial STN border was determined using postoperative stereotactic MRI.

Results

The clinical improvement showed a significant negative correlation with the y-axis position (anterior–posterior; A+, P−). The more posterior the electrode contacts were positioned in the dorsolateral sensorimotor area of the STN, the better the therapeutic effects. Cluster analysis of the improvement rates delineated optimal and sub-optimal groups. The optimal contact coordinates from the optimal group were 2.56 mm lateral, 0.15 mm anterior, and 1.34 mm superior relative to the medial STN border.

Conclusion

STN-DBS was effective for primary dystonia, but outcomes were dependent on the active contact location. Bilateral stimulation contacts located behind or adjacent to Bejjani’s line were most likely to produce ideal therapeutic effects. These findings may help guide STN-DBS preoperative planning, stimulation programming, and prognosis for optimal therapeutic efficacy in primary dystonia.
A longitudinal investigation of pragmatic language across contexts in autism and related neurodevelopmental conditions
Authors: Martin Gary E. , Lee Michelle , Bicknell Klinton , Goodkind Adam , Maltman Nell , Losh Molly
Published: July 2023

Background

Pragmatic language, or the use of language in social contexts, is a critical skill in daily life, supporting social interactions and the development of meaningful social relationships. Pragmatic language is universally impacted in autism spectrum disorder (ASD) and pragmatic deficits are also common in other neurodevelopmental conditions, particularly those related to ASD, such as fragile X syndrome (FXS). This study used a multi-method, longitudinal approach to characterize potentially unique pragmatic profiles across different neurodevelopmental disabilities, and across contexts that varied in degree of social demand. The utility of computational linguistic analyses, as an efficient tool for capturing pragmatic abilities, was also explored.

Methods

Pragmatic skills of boys with idiopathic ASD (ASD-O, n = 43), FXS with and without ASD (FXS-ASD, n = 57; FXS-O, n = 14), Down syndrome (DS, n = 22), and typical development (TD, n = 24) were compared using variables obtained from a standardized measure, narrative, and semi-naturalistic conversation at up to three time points.

Results

Pragmatic language was most significantly impacted among males with ASD-O and FXS-ASD across all three contexts, with more difficulties in the least structured context (conversation), and also some differences based on FXS comorbidity. Patterns of group differences were more nuanced for boys with FXS-O and DS, with context having less of an impact. Clinical groups demonstrated minimal changes in pragmatic skills with age, with some exceptions. Computational language measurement tools showed some utility for measuring pragmatic skills, but were not as successful as traditional methods at capturing differences between clinical groups.

Conclusion

Overlap and differences between ASD and other forms of neurodevelopmental disability in general, and between idiopathic and syndromic ASD in particular, have important implications for developing precisely tailored assessment and intervention approaches, consistent with a personalized medicine approach to clinical study and care in ASD.
Cigarette smoke stimulates clonal expansion of Jak2V617F and Tet2-/- cells
Authors: Ramanathan Gajalakshmi , Chen Jane H. , Mehrotra Nitya , Trieu Tiffany , Huang Aaron , Mas Eduard , Monterrosa Mena Jessica E. , Bliss Bishop , Herman David A. , Kleinman Michael T. , Fleischman Angela G.
Published: July 2023

Introduction

Somatic mutations in myeloid growth factor pathway genes, such as JAK2, and genes involved in epigenetic regulation, such as TET2, in hematopoietic stem cells (HSCs) leads to clonal hematopoiesis of indeterminate potential (CHIP) which presents a risk factor for hematologic malignancy and cardiovascular disease. Smoking behavior has been repeatedly associated with the occurrence of CHIP but whether smoking is an environmental inflammatory stressor in promoting clonal expansion has not been investigated.

Methods

We performed in vivo smoke exposures in both wildtype (WT) mice and transplanted mice carrying Jak2V617F mutant and Tet2 knockout (Tet-/-) cells to determine the impact of cigarette smoke (CS) in the HSC compartment as well as favoring mutant cell expansion.

Results

WT mice exposed to smoke displayed increased oxidative stress in long-term HSCs and suppression of the hematopoietic stem and progenitor compartment but smoke exposure did not translate to impaired hematopoietic reconstitution in primary bone marrow transplants. Gene expression analysis of hematopoietic cells in the bone marrow identified an imbalance between Th17 and Treg immune cells suggesting a local inflammatory environment. We also observed enhanced survival of Jak2V617F cells exposed to CS in vivo and cigarette smoke extract (CSE) in vitro. WT bone marrow hematopoietic cells from WT/Jak2V617F chimeric mice exposed to CS demonstrated an increase in neutrophil abundance and distinct overexpression of bone marrow stromal antigen 2 (Bst2) and retinoic acid early transcript 1 (Raet1) targets. Bst2 and Raet1 are indicative of increased interferon signaling and cellular stress including oxidative stress and DNA damage, respectively. In chimeric mice containing both WT and Tet2-/- cells, we observed an increased percentage of circulating mutant cells in peripheral blood post-cigarette smoke exposure when compared to pre-exposure levels while this difference was absent in air-exposed controls.

Conclusion

Altogether, these findings demonstrate that CS results in an inflamed bone marrow environment that provides a selection pressure for existing CHIP mutations such as Jak2V617F and Tet2 loss-of-function.
Revisited role of the placenta in bile acid homeostasis
Authors: Ontsouka Edgar , Schroeder Mariana , Albrecht Christiane
Published: July 2023

To date, the discussion concerning bile acids (BAs) during gestation is almost exclusively linked to pregnancy complications such as intrahepatic cholestasis of pregnancy (ICP) when maternal serum BA levels reach very high concentrations (>100 μM). Generally, the placenta is believed to serve as a protective barrier avoiding exposure of the growing fetus to excessive amounts of maternal BAs that might cause detrimental effects (e.g., intrauterine growth restriction and/or increased vulnerability to metabolic diseases). However, little is known about the precise role of the placenta in BA biosynthesis, transport, and metabolism in healthy pregnancies when serum BAs are at physiological levels (i.e., low maternal and high fetal BA concentrations). It is well known that primary BAs are synthesized from cholesterol in the liver and are later modified to secondary BA species by colonic bacteria. Besides the liver, BA synthesis in extrahepatic sites such as the brain elicits neuroprotective actions through inhibition of apoptosis as well as oxidative and endoplasmic reticulum stress. Even though historically BAs were thought to be only “detergent molecules” required for intestinal absorption of dietary fats, they are nowadays acknowledged as full signaling molecules. They modulate a myriad of signaling pathways with functional consequences on essential processes such as gluconeogenesis -one of the principal energy sources of the fetus- and cellular proliferation. The current manuscript discusses the potential multipotent roles of physiologically circulating BAs on developmental processes during gestation and provides a novel perspective in terms of the importance of the placenta as a previously unknown source of BAs. Since the principle “not too much, not too little” applicable to other signaling molecules may be also true for BAs, the risks associated with fetal exposure to excessive levels of BAs are discussed.
Blood flow restriction as a potential therapy to restore physical function following COVID-19 infection
Authors: Wedig Isaac J. , Durocher John J. , McDaniel John , Elmer Steven J.
Published: July 2023

Accumulating evidence indicates that some COVID-19 survivors display reduced muscle mass, muscle strength, and aerobic capacity, which contribute to impairments in physical function that can persist for months after the acute phase of illness. Accordingly, strategies to restore muscle mass, muscle strength, and aerobic capacity following infection are critical to mitigate the long-term consequences of COVID-19. Blood flow restriction (BFR), which involves the application of mechanical compression to the limbs, presents a promising therapy that could be utilized throughout different phases of COVID-19 illness. Specifically, we hypothesize that: 1) use of passive BFR modalities can mitigate losses of muscle mass and muscle strength that occur during acute infection and 2) exercise with BFR can serve as an effective alternative to high-intensity exercise without BFR for regaining muscle mass, muscle strength, and aerobic capacity during convalescence. The various applications of BFR may also serve as a targeted therapy to address the underlying pathophysiology of COVID-19 and provide benefits to the musculoskeletal system as well as other organ systems affected by the disease. Consequently, we present a theoretical framework with which BFR could be implemented throughout the progression from acute illness to outpatient rehabilitation with the goal of improving short- and long-term outcomes in COVID-19 survivors. We envision that this paper will encourage discussion and consideration among researchers and clinicians of the potential therapeutic benefits of BFR to treat not only COVID-19 but similar pathologies and cases of acute critical illness.
Are you threatening me? Development and validation of the Conflict Escalation Questionnaire
Authors: Scheppa-Lahyani Miriam Nicole , Zapf Dieter
Published: July 2023

This study aimed to develop and validate an instrument for measuring conflict escalation based on Glasl's conflict escalation model, which can also be used for measuring bullying conflicts. The instrument should be applicable both as a self-assessment and as an interviewer-assessment. In the first study, a first set of items measuring the stages of Glasl's model was developed and validated in an independent cross-sectional sample of 154 participants who completed the self-assessment. In 142 cases, interviews were conducted, and thus self and interviewer-assessments could be compared. In a second study, the final set of items was cross-validated on a second independent cross-sectional sample. In total, 105 participants completed the self-assessment only and 114 were part of the interview study. Because Glasl's model is complex, scale validation was based on a combination of classical statistical validation procedures. Both studies indicate good validity of the new instrument and provide evidence for Glasl's conflict escalation model. As expected, conflict escalation was positively related to negative affect, irritation, and depression. Relationship conflict was more prevalent in more highly escalated conflicts as compared to lower escalated conflicts. Victims of workplace bullying were classified in high escalation levels and showed higher inferiority in conflict situations compared to non-victims with highly escalated conflicts. The present instrument can be used to assess qualitative differences in conflict escalation and thus complements existing instruments to measure conflicts. It is especially useful for practitioners, as they can assess conflict escalation more accurately and thus better choose the appropriate form of intervention.