bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 pandemic impact on screening and diagnosis of prostate cancer: a systematic review
Authors: Mostafavi Zadeh Seyed Mostafa , Tajik Fatemeh , Gheytanchi Elmira , Kiani Jafar , Ghods Roya , Madjd Zahra
Published: September 2023

Introduction

The healthcare level has been greatly affected by the COVID-19 pandemic compared with before the outbreak. This study aimed to review the impact of COVID-19 on the screening and diagnosis of prostate cancer (PCa).

Method

The current study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The keywords used to perform the search strategy were COVID-19 and prostate neoplasms. The four primary electronic databases comprising PubMed/MEDLINE, Web of Science, Scopus and Embase were searched until 1 September 2022. After screening and selecting studies through the EndNote software, data were extracted from each included study by two independent authors. All studies were evaluated according to Newcastle–Ottawa Scale quality assessment tool.

Results

As a result, 40 studies were included, categorised into two subjects. The majority of studies indicated a significant decrease in screening prostate-specific antibody tests during the COVID-19 pandemic compared with the pre-pandemic period, leading to delays in cancer diagnosis. The decrease in the number of diagnosed cases with low/intermediate stages to some extent was more than those with advanced stages. The PCa screening and diagnosis reduction ranged from nearly 0% to 78% and from 4.1% to 71.7%, respectively.

Conclusion

Our findings showed that during the COVID-19 lockdown, delays in PCa screening tests and diagnoses led to the negative health effects on patients with PCa. Thus, it is highly recommended performing regular cancer screening to reduce the impact of the COVID-19 lockdown.

PROSPERO registration number

CRD42021291656.
Futility in acute care surgery: first do no harm
Authors: Hornor Melissa , Khan Uzer , Cripps Michael W , Cook Chapman Allyson , Knight-Davis Jennifer , Puzio Thaddeus J , Joseph Bellal
Published: September 2023

The consequences of the delivery of futile or potentially ineffective medical care and interventions are devastating on the healthcare system, our patients and their families, and healthcare providers. In emergency situations in particular, determining if escalating invasive interventions will benefit a frail and/or severely critically ill patient can be exceedingly difficult. In this review, our objective is to define the problem of potentially ineffective care within the specialty of acute care surgery and describe strategies for improving the care of our patients in these difficult situations.
The non-nutritive sweetener sucralose increases β-arrestin signaling at the constitutively active orphan G protein-coupled receptor GPR52
Authors: Power Madeline E. , Fernandez Nicholas R. , Oni Olaiya Peter , Kalia Aditaya , Rourke Jillian L.
Published: September 2023

Non-nutritive sweeteners are popular food additives owing to their low caloric density and powerful sweetness relative to natural sugars. Their lack of metabolism contributes to evidence proclaiming their safety, yet several studies contradict this, demonstrating that sweeteners activate sweet taste G protein-coupled receptors (GPCRs) and elicit deleterious metabolic functions through unknown mechanisms. We hypothesize that activation of GPCRs, particularly orphan receptors due to their abundance in metabolically active tissues, contributes to the biological activity of sweeteners. We quantified the response of 64 orphans to the sweeteners saccharin and sucralose using a high-throughput β-arrestin-2 recruitment assay (PRESTO-Tango). GPR52 was the sole receptor that significantly responded to a mixture of sucralose and saccharin. Subsequent experiments revealed sucralose as the activating sweetener. Activation of GPR52 was concentration-dependent, with an EC50 of 0.23 mmol/L and an Emax of 3.43 ± 0.24 fold change at 4 mmol/L. GPR52 constitutively activates CRE pathways; however, we show that sucralose-induced activation of GPR52 does not further activate this pathway. Identification of this novel sucralose–GPCR interaction supports the notion that sucralose elicits off-target signaling through the activation of GPR52, calling into question sucralose's assumed lack of bioactivity.
Frequency of cytosine methylation in the adjacent regions of soybean retrotransposon SORE-1 depends on chromosomal location
Authors: Nakashima Kenta , Yuhazu Mashiro , Mikuriya Shun , Kasai Megumi , Abe Jun , Taneda Akito , Kanazawa Akira
Published: September 2023

Mobilization of transposable elements (TEs) is suppressed by epigenetic mechanisms involving cytosine methylation. However, few studies have focused on clarifying relationships between epigenetic influences of TEs on the adjacent DNA regions and time after insertion of TEs into the genome and/or their chromosomal location. Here we addressed these issues using soybean retrotransposon SORE-1. We analyzed SORE-1, inserted in exon 1 of the GmphyA2 gene, one of the newest insertions in this family so far identified. Cytosine methylation was detected in this element but was barely present in the adjacent regions. These results were correlated, respectively, with the presence and absence of the production of short interfering RNAs. Cytosine methylation profiles of 74 SORE-1 elements in the Williams 82 reference genome indicated that methylation frequency in the adjacent regions of SORE-1 was profoundly higher in pericentromeric regions than in euchromatic chromosome arms and was only weakly correlated with the length of time after insertion into the genome. Notably, the higher level of methylation in the 5′ adjacent regions of SORE-1 coincided with the presence of repetitive elements in pericentromeric regions. Together, these results suggest that epigenetic influence of SORE-1 on the adjacent regions is influenced by its location on the chromosome.
Persistence of the N=50 shell closure over the isotopic chains of Sc, Ti, V and Cr nuclei using relativistic energy density functional
Authors: Yadav Praveen K. , Kumar Raj , Bhuyan M.
Published: September 2023

The analytical expression of the density-dependent binding energy per nucleon for the relativistic mean field (RMF), the so-called relativistic energy density functional (Relativistic-EDF), is used to obtain the isospin-dependent symmetry energy and its components for the isotopic chain of Sc-, Ti-, V- and Cr-nuclei. The procedure of the coherent density fluctuation model is employed to formulate the Relativistic-EDF and Brüeckner energy density functional (Brüeckner-EDF) at local density. A few signatures of shell and/or sub-shell closure are observed in the symmetry energy and its components, i.e. surface and volume symmetry energy, far from the [Formula: see text]-stable region for odd-[Formula: see text] Sc- and V-, and even–even Ti- and Cr- nuclei with nonlinear NL3 and G3 parameter sets. A comparison is made with the results obtained from Relativistic-EDF and Brüeckner-EDF with both NL3 and G3 for the considered isotopic chains. We find Relativistic-EDF outperforms the Brüeckner-EDF in predicting the shell and/or sub-shell closure of neutron-rich isotopes at [Formula: see text] for these atomic nuclei. Moreover, a relative comparison has been made for the results obtained with the nonlinear NL3 and G3 parameter sets.
Deep Ensemble of Classifiers for Alzheimer’s Disease Detection with Optimal Feature Set
Authors: Rajasree R. S. , Rajakumari S. Brintha
Published: September 2023

Machine learning (ML) and deep learning (DL) techniques can considerably enhance the process of making a precise diagnosis of Alzheimer’s disease (AD). Recently, DL techniques have had considerable success in processing medical data. They still have drawbacks, like large data requirements and a protracted training phase. With this concern, we have developed a novel strategy with the four stages. In the initial stage, the input data is subjected to data imbalance processing, which is crucial for enhancing the accuracy of disease detection. Subsequently, entropy-based, correlation-based, and improved mutual information-based features will be extracted from these pre-processed data. However, the curse of dimensionality will be a serious issue in this work, and hence we have sorted it out via optimization strategy. Particularly, the tunicate updated golden eagle optimization (TUGEO) algorithm is proposed to pick out the optimal features from the extracted features. Finally, the ensemble classifier, which integrates models like CNN, DBN, and improved RNN is modeled to diagnose the diseases by training the selected optimal features from the previous stage. The suggested model achieves the maximum F-measure as 97.67, which is better than the extant methods like [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text], respectively. The suggested TUGEO-based AD detection is then compared to the traditional models like various performance matrices including accuracy, sensitivity, specificity, and precision.
Boson–Boson Interactions at the LHC
Authors: Manjarrés Ramos J. , Gómez-Ceballos Guillelmo
Published: September 2023

Vector boson scattering is a key production process to probe the electroweak symmetry breaking of the Standard Model and is one of the most important topics of the physics program for the HL-LHC since it involves both self-couplings of vector bosons and their coupling with the Higgs boson. If the Higgs mechanism is not the sole source of electroweak symmetry breaking, the scattering amplitude deviates from the Standard Model prediction at high scattering energy. Moreover, deviations may be detectable even if a New Physics scale is higher than the reach of direct searches. In this review, the most recent experimental measurements of the production cross sections of vector boson pairs in association with two jets in proton–proton collisions at [Formula: see text] TeV at the LHC are reported, using data sets recorded by the ATLAS and CMS detectors. Applications to searches for New Physics, as well as prospects for measuring the electroweak vector boson scattering processes with larger data samples, are also summarized.
Effects of the order of endurance and high-intensity interval exercise in combined training on mouse skeletal muscle metabolism
Authors: Shirai Takanaga , Uemichi Kazuki , Takemasa Tohru
Published: September 2023

Endurance exercise (EE) mainly improves oxidative capacity, whereas high-intensity interval exercise (HIIE) also improves glycolytic capacity. There is growing evidence that suggests that combining EE with HIIE can lead to improved athletic performance and fitness outcomes compared with either form of exercise alone. This study aimed to elucidate whether the order in which EE and HIIE are performed in combined training affects oxidative metabolism and glycolysis in mouse skeletal muscle. Male ICR mice at 7 wk of age were divided into three groups: control (CON), EE-HIIE, and HIIE-EE. The total training period was 3 wk (3 times/week). Mice performed running on a treadmill as endurance exercise and swimming with a weight load of 10% of body weight as high-intensity interval exercise. EE before HIIE (EE-HIIE) improved running performance in the maximal EE capacity test (all-out test) and partly enhanced the expression levels of molecular signals involved in glycolysis compared with HIIE before EE (HIIE-EE). The order of exercise did not, however, impact the expression of proteins related to mitochondrial dynamics, including those involved in the morphological changes of mitochondria through repeated fusion and fission, as well as oxidative energy metabolism. The findings suggest that the order of exercise has no significant impact on the expression of proteins associated with glycolytic and oxidative energy metabolism. Nevertheless, our results indicate that the order of EE-HIIE may enhance running performance.
Ironing out the details: ferroptosis and its relevance to diabetic cardiomyopathy
Authors: Gawargi Flobater I. , Mishra Paras K.
Published: September 2023

Ferroptosis is a newly identified myocardial cell death mechanism driven by iron-dependent lipid peroxidation. The presence of elevated intramyocardial lipid levels and excessive iron in patients with diabetes suggest a predominant role of ferroptosis in diabetic cardiomyopathy. As myocardial cell death is a precursor of heart failure, and intensive glycemic control cannot abate the increased risk of heart failure in patients with diabetes, targeting myocardial cell death via ferroptosis is a promising therapeutic avenue to prevent and/or treat diabetic cardiomyopathy. This review provides updated and comprehensive molecular mechanisms underpinning ferroptosis, clarifies several misconceptions about ferroptosis, emphasizes the importance of ferroptosis in diabetes-induced myocardial cell death, and offers valuable approaches to evaluate and target ferroptosis in the diabetic heart. Furthermore, basic concepts and ideas presented in this review, including glutathione peroxidase-4-independent and mitochondrial mechanisms of ferroptosis, are also important for investigating ferroptosis in other diabetic organs, as well as nondiabetic and metabolically compromised hearts.
Malaria and Typhoid Fever Coinfection among Febrile Patients in Ngaoundéré (Adamawa, Cameroon): A Cross-Sectional Study
Authors: Sohanang Nodem Francky Steve , Ymele Didiane , Fadimatou Mouni , Fodouop Simeon-Pierre Chegaing
Published: September 2023

Background. Malaria and typhoid fever remain the major cause of morbidity and mortality in tropical and subtropical countries. It is common today to see patients being concurrently infected or treated for the two diseases. Objective. The aim of the present study was to determine the prevalence of malaria, typhoid fever, and their coinfection among febrile patients at Ngaoundéré Regional Hospital, Adamawa, Cameroon. Methodology. A cross-sectional and descriptive study was conducted on 208 febrile patients coming for medical consultation at Ngaoundéré Regional Hospital and suspected for malaria and/or typhoid fever from September to November 2019. After receiving the consent of each patient, clinical and sociodemographic information were collected using a pretested semistructured questionnaire. Thereafter, blood samples were collected and subjected to (i) blood film examination for malaria detection and (ii) qualitative and semiquantitative Widal assay for typhoid fever detection. Results. Plasmodium falciparum was the only species identified, and the prevalence of malaria was 50.0% (

n
=
104

). The seroprevalence of typhoid fever was 64.3% (

n
=
133

). The malaria and typhoid fever coinfection was 30.3% (

n
=
63

). The coinfection between S. paratyphi (A, B, and C) and malaria was also observed with the prevalence ranging from 32.2 to 63.9%. Female group and children from 2 to 10 years old were the most affected groups by the two infectious agents. Conclusion. Typhoid fever and malaria were more prevalent in Ngaoundéré City, particularly in children and women. Further studies should be done on the risk factors of malaria and typhoid fever coinfection in different study areas.
Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma
Authors: Kong Fanyong , Han Boxuan , Chen Jiaming , Shen Xixi , Hou Lizhen , Fang Jugao , Lian Meng
Published: September 2023

PPARG has been reported to promote chemosensitivity in hypopharyngeal squamous cell carcinoma (HSCC). However, few studies tested its significance in the texture of a complex molecular network regulating chemosensitivity in HSCC. Here, we first employed RNA expression data analysis and literature data mining to uncover candidate genes related to HSCC chemosensitivity. Then, we constructed the molecular network regulating chemosensitivity in HSCC. After that, we employed degree centrality (DC) and weighted centrality (WC) to test the significance of PPARG within the regulating network. Pathway enrichment was done to study the cofunctions of PPARG and the rest of the genes within the network. The findings of our study contribute to the construction of a comprehensive network that regulates HSCC chemosensitivity, consisting of 57 genes, including PPARG. Notably, within this network, PPARG demonstrates a ranking of #5 and #13 based on DC and WC, respectively. Moreover, PPARG is connected to 29 out of the 57 genes and plays roles in multiple functional groups. These top related genes include AKT1, TP53, PTEN, MAPK1, NOTCH1, BECN1, PTGS2, SPP1, and RAC1. PPARG gets enriched in several key functional groups that have been implicated in the regulation of chemosensitivity, including those associated with the response to nutrients, vitamins, and peptides, the cellular response to chemical stress, and the regulation of hormone secretion and growth. Our results emphasize the involvement of PPARG and its interconnectedness with other genes in the regulation of HSCC chemosensitivity.
Determination of Microbial Hygiene Indicators of Raw Cow Milk in Assosa District, Ethiopia
Authors: Fereja Abebe Bereda , Aboretugn Nigussu Fekade , Bulti Nigatu Qiltu
Published: September 2023

The study was conducted to evaluate raw cow milk microbial quality in the Assosa district from January to March 2021. Sixty farmers were chosen from 200 surveyed households for milk samples to determine microbial analysis using standard procedures. From each farmer, 450 mL of the fresh morning raw cow milk sample was collected aseptically using a sterile sampling bottle. The milk samples were analyzed in duplicates immediately after 12 hrs upon laboratory arrival. Milk microbial analysis, sampling, transportation, and handling followed standard procedures. The average aerobic mesophilic bacterial count, E. coli, Staphylococcus aureus, yeast and mold count, and coliform count were 9.0, 5.3, 7.8, 9.2, and 6.8 log10 CFU/mL, respectively. However, significant differences between urban and rural locations were observed except for the last parameter. The counts of all microbial parameters, including the pathogen Staphylococcus aureus found in this study, were higher than the acceptable limit set by the Ethiopian standard authority. This indicates that smallholder milk was highly contaminated and may have originated from a single source. Consequently, the hygienic quality of milk is not safe for consumption; instead, it can cause different types of foodborne pathogens. Therefore, identification of the contamination sources of milk and urgent remedial actions will be taken to protect consumers’ health.
Evaluation of Transplant Suitability in a Patient with Previous Colorectal Cancer and Subsequent Radiation Cystitis: Insights from a Complicated Case
Authors: Dogahe David , Cubilier Edouard , Taghavi Maxime , Kaysi Saleh , Nortier Joëlle , Mesquita Maria do Carmo Filomena
Published: September 2023

Assessing transplant suitability can be a meticulous process, involving multiple investigations and various specialties. This process is well described in the latest KDIGO guidelines. We recently asked ourselves if those guidelines are still relevant to current clinical practice given the rapid evolution of modern medicine, especially in the field of oncology. We present the complicated case of a 60-year-old woman with ESKD (end-stage kidney disease) and a prior history of cancer, with secondary urological complications, to illustrate different interesting considerations for KT (kidney transplant). Our patient was diagnosed with rectal cancer at the age of 46, for which she was treated with surgery and radiotherapy before developing chronic radiation cystitis. This was followed by repeated urinary tract infections and secondary nephrolithiasis, ultimately leading to severe bilateral hydronephrosis and obstructive ESKD. We know that the type of cancer and its characteristics should be evaluated in detail, and we should offer patient-tailored recommendations after a multidisciplinary evaluation. In our case, the prior rectal cancer is not to be feared because curative treatment has been achieved and the patient has been cancer-free for 14 years, knowing that this type of cancer is not at high risk of recurrence after transplantation. The frail urological anatomy, however, represents a bigger challenge. Not only does it complicate the technical feasibility of KT but it also increases the risk of complications and graft failure. It is difficult to clearly determine KT possibility when considering it in such patients. What is clear on the other hand is that such a decision should be taken considering the choice of the patient and the involved physicians. We should also consider the potential benefits and risks of KT in order to make an informed decision.
The Effect of Resin Matrix on the Properties of CF/PEI and CF/PAEK Thermoplastic Composites
Authors: Wang Wencai , Zhang Jindong , Gao Dongting , Yu Kun , Liu Gang , Wang Ming , Yao Jianan
Published: September 2023

As the adhesive for composites, the resin matrix directly impacts the molding process and product performance of thermoplastic composites (TPCs). Carbon fiber-reinforced polyetherimide (CF/PEI) and polyaryletherketone (CF/PAEK) composites were prepared by a compression molding process. The interface, interlaminar, and low-speed impact properties of TPCs were studied. The results show that the interfacial shear strength of the CF/PEI composite is ~116 MPa, while the CF/PAEK composite is ~78 MPa. However, the interlaminar and low-speed impact performance of CF/PAEK is better than CF/PEI. Type I fracture toughness (

G

IC

) and type II fracture toughness (

G

IIC

) of CF/PEI are ~1051 MPa and ~1060 MPa. But those of CF/PAEK are ~1786 MPa and ~2584 MPa, respectively. The compressive strength after the impact of CF/PAEK (~321 MPa) is 40% higher than CF/PEI (~230 MPa).
Diffuse Idiopathic Skeletal Hyperostosis Causing Progressive Dysphagia: A Case Report and Review
Authors: Davoodi Farzin , Bazgir Narges , Naseri Reza
Published: September 2023

Background. Diffuse idiopathic skeletal hyperostosis (DISH) is a rare noninflammatory disorder impacting spinal longitudinal ligament and enthesis. The majority of DISH cases are asymptomatic or have few manifestations. Manifestations include neck pain and stiffness, stridor, breathing disturbances, and dysphagia. Case Presentation. A mid-aged man with progressive dysphagia to solid food was admitted to Loghman Hakim Hospital. In cervical X-ray, a huge ossification in the anterior longitudinal ligament was evident. Eventually, he was diagnosed with DISH. Because of coronary artery disease, conservative treatment was considered for him. Conclusion. DISH is a rare disorder usually asymptomatic. In this case report, we present a DISH case with progressive dysphagia to solid foods.
Comprehensive Overview of Quality of Life Instruments Used in Studies of Children with Diabetes: A Systematic Mapping Review
Authors: Jespersen Louise Norman , Andersen Tue Helms , Grabowski Dan
Published: September 2023

Background. Quality of life (QoL) is extensively used as an outcome in the studies of children with diabetes. The interest in measuring QoL in relation to clinical treatment and interventions has led to an increase in the development and use of QoL measures. The vast number of available instruments can be a barrier for establishing evidence and can be overwhelming for clinicians and researchers who are interested in measuring QoL of children with diabetes. Aim. As a first step for reaching consensus, we aimed to provide a comprehensive overview of the application of QoL instruments used in children (2–18 years old) with diabetes. Method. A literature search for studies published from inception to January 2022 was conducted in the databases MEDLINE (Ovid), Embase (Ovid), PsycInfo (EBSCO), CINAHL (EBSCO), and ERIC (EBSCO). The search strategy combined the key concepts of “quality of life”, “diabetes”, and “children or adolescents”. Studies were found eligible if (1) the population was below 19 years of age; (2) had diabetes mellitus; and (3) a quantitative measure of QoL was used. Results. 3,775 unique articles were retrieved in the literature search and, across 503 articles included for synthesis, 67 QoL instruments were identified. The instruments were classified by i.a. population age, continent, use of pre–post measure, self-report or proxy, and type of diabetes. Conclusion. The extensive number of QoL instruments that are used for children with diabetes constitutes a substantial barrier for establishing evidence in relation to QoL in this research area.
Trust in Medical Professionals Moderates Depression in Hong Kong during COVID-19
Authors: Lai Daniel W. L. , Jin Jiahui , Yan Elsie , Lee Vincent W. P.
Published: September 2023

Objectives. Given the continuing COVID-19 pandemic and the associated prevention and control measures implemented, the psychological burden brought by the pandemic on citizens is expected to increase. This study is aimed at exploring the predictors of depressive symptoms among Hong Kong people during the epidemic, as well as factors that could potentially alleviate the negative effects of the epidemic. Methods. The third wave follow-up survey (December 2021 to January 2022) from a longitudinal prospective survey study conducted in Hong Kong was used for a cross-sectional analysis. The participants (

n
=
803

) are adults aged 18 and above in Hong Kong. Logistic and linear regression were performed to test the predictors and moderating effects, respectively, with depression as the outcome variable. Results. With minimized confounding effects of demographic variables, higher levels of concern about infection, experience with COVID-19 infection and previous epidemics, hassles, and trust in authority increased the odds of being depressed, while a higher level of trust in medical professionals reduced the odds of depression. Moreover, greater trust in medical professionals, as a moderator, lessened the positive associations between the levels of depression and hassles and concern about infection. Conclusions. Even though the threats of COVID-19 seem to have lowered, this study shows that a few factors associated with the pandemic continue to threaten people’s mental health. However, developing greater trust in medical experts may be an effective way to relieve psychological burden.
Seasonal Prevalence and Status of Anthelmintic Resistance of Goats’ Gastrointestinal Nematodes, Mirab Abaya, Southern Ethiopia
Authors: Negash Behailu , Seyoum Wasihun , Sheferaw Desie
Published: September 2023

Goats are an important source of livelihood especially for smallholder communities. But gastrointestinal nematodosis is the greatest threats of goat production. A repeated cross-sectional and field experimental study design was conducted from December 2020 to August 2021 in Mirab Abaya district, with the aim of seasonal prevalence gastrointestinal nematode infection and assessment of anthelmintic resistance. A systematic random sampling strategy was used to select the study goats. The overall prevalence of gastrointestinal nematode infections of goats in the study area was 57.9% (95% CI: 54.4-61.4), of which 48.7% (95% CI: 43.7-53.7) and 67.2% (95% CI: 62.3-71.7) accounted to dry and wet seasons, respectively. The multivariable logistic regression analysis showed that season, age, sex, and flock size were significantly (p<0.05) influenced the prevalence of gastrointestinal nematode infection of goats. The number of eggs per gram of faeces (EPG) was ranged from 100 to 2500. The overall mean egg per gram of faeces (EPG) was461.1±20.9. The mean EPG of wet season (532.7±28.6) was higher than the dry season (362.3±29.1). From faecal culture, 552 nematode larvae were recovered, and the most commonly identified nematode genera were Haemonchus (36.4%) that followed by Trichostrongylus (28.1%), Oesophagostomum (15.4%), Bunostomum (11.4), Teladorsagia (5.4%), and Strongyloides (3.0%) species. From the anthelmintic resistance test in the field, the percentage reduction and 95% confidence limit of albendazole were 96% (84.2-99.0) and 97.0% (84.6-99.4) in dry and wet seasons, respectively. Here, the lower limit of 95% CI was less than 90% both in dry and wet seasons; and hence, albendazole was suspected for resistance development by gastrointestinal nematode. From a pooled faecal culture that collected from albendazole-treated goats, Haemonchus species was recovered. Therefore, due attention shall be by animal health professionals in the area in the use of albendazole. Animal health extension work to create awareness of how anthelmintic is used is helpful in reducing the risk. Changing the type of anthelmintic drug after using for some period will minimize the risk of anthelmintic resistance development.
MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: September 2023

Despite the initial benefit from tyrosine kinase inhibitors (TKI) targeting oncogenic ALK and ROS1 gene fusions in non–small cell lung cancer, complete responses are rare and resistance ultimately emerges from residual tumor cells. Although several acquired resistance mechanisms have been reported at the time of disease progression, adaptative resistance mechanisms that contribute to residual diseases before the outgrowth of tumor cells with acquired resistance are less clear. For the patients who have progressed after TKI treatments, but do not demonstrate ALK/ROS1 kinase mutations, there is a lack of biomarkers to guide effective treatments. Herein, we found that phosphorylation of MIG6, encoded by the ERRFI1 gene, was downregulated by ALK/ROS1 inhibitors as were mRNA levels, thus potentiating EGFR activity to support cell survival as an adaptive resistance mechanism. MIG6 downregulation was sustained following chronic exposure to ALK/ROS1 inhibitors to support the establishment of acquired resistance. A higher ratio of EGFR to MIG6 expression was found in ALK TKI-treated and ALK TKI-resistant tumors and correlated with the poor responsiveness to ALK/ROS1 inhibition in patient-derived cell lines. Furthermore, we identified and validated a MIG6 EGFR-binding domain truncation mutation in mediating resistance to ROS1 inhibitors but sensitivity to EGFR inhibitors. A MIG6 deletion was also found in a patient after progressing to ROS1 inhibition. Collectively, this study identifies MIG6 as a novel regulator for EGFR-mediated adaptive and acquired resistance to ALK/ROS1 inhibitors and suggests EGFR to MIG6 ratios and MIG6-damaging alterations as biomarkers to predict responsiveness to ALK/ROS1 and EGFR inhibitors.
Figure S2 from HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer
Authors: Olson Devra , Taylor Janelle , Willis Kelsi , Hensley Kelly , Allred Sean , Zaval Margo , Farr Lauren , Thurman Robert , Jain Nishi , Hein Renee , Ulrich Michelle , Peterson Scott , Kulukian Anita
Published: September 2023

Tucatinib mediates an increase in HER2 through reduced ubiquitination of the receptor
FIGURE 5 from HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer
Authors: Olson Devra , Taylor Janelle , Willis Kelsi , Hensley Kelly , Allred Sean , Zaval Margo , Farr Lauren , Thurman Robert , Jain Nishi , Hein Renee , Ulrich Michelle , Peterson Scott , Kulukian Anita
Published: September 2023

Combining tucatinib and T-DM1 in HER2-positive breast cancer xenograft models increases antitumor activity. Mean tumor volume over time in T-DM1–resistant breast cancer PDX models (A) and BT-474 CDX model (B). Tucatinib was administered orally at 50 mg/kg twice daily for the duration of the study, while T-DM1 and the IgG1-DM1 nonbinding control ADC were dosed at 10 mg/kg (single dose). C, Summary table of tumor growth inhibition and response rates of subcutaneous-implant xenograft models. D, Mean tumor volume over time in intracranially implanted BT-474-RedLuc xenograft model. E, Kaplan–Meier survival plots of intracranial BT-474-RedLuc xenograft model. F, Summary table of tumor growth inhibition and median survival days of intracranial BT-474-RedLuc xenograft model. All P values were determined by comparing the tucatinib/T-DM1 combination with the closest single agent. Data shown as mean ± SEM.
FIGURE 1 from HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer
Authors: Olson Devra , Taylor Janelle , Willis Kelsi , Hensley Kelly , Allred Sean , Zaval Margo , Farr Lauren , Thurman Robert , Jain Nishi , Hein Renee , Ulrich Michelle , Peterson Scott , Kulukian Anita
Published: September 2023

Tucatinib sensitizes HER2-positive cancer cells to T-DM1. A, Summary table of IC50 and Emax values for T-DM1 alone and in combination with tucatinib in CTG Luminescent Cell Viability cytotoxicity assays. B, CTG assays in which T-DM1 and tucatinib were screened in a panel of HER2-positive breast cancer cell lines. Data shown as mean + SD. C, Heat maps of matrixed CTG drug combination experiments testing the synergistic activity of tucatinib and T-DM1.
Data from HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer
Authors: Olson Devra , Taylor Janelle , Willis Kelsi , Hensley Kelly , Allred Sean , Zaval Margo , Farr Lauren , Thurman Robert , Jain Nishi , Hein Renee , Ulrich Michelle , Peterson Scott , Kulukian Anita
Published: September 2023

The oncogenic receptor HER2 is overexpressed in many cancers, including up to 20% of breast cancers. Despite the availability of HER2-targeted treatments, patients’ disease often progresses during therapy, underscoring the need for novel treatment strategies. The addition of tucatinib, a reversible, highly selective HER2 tyrosine kinase inhibitor (TKI), to treatment with trastuzumab and capecitabine significantly improved survival outcomes of patients with HER2-positive metastatic breast cancer, including those with active brain metastases. We rationalized that combining tucatinib with other HER2-targeting agents with complementary mechanisms of action would further increase efficacy against tumors. We characterized the activity of tucatinib with the antibody–drug conjugate T-DM1 in preclinical models of breast cancer, including HER2-positive breast cancer cells and patient-derived xenograft (PDX) models. Mechanistic details on tucatinib activity were obtained in internalization and catabolism studies. In combination, tucatinib and T-DM1 showed an enhanced, often synergistic, cytotoxic response and demonstrated improved antitumor activity in vivo, including in PDX models refractory to T-DM1 single-agent activity. Mechanistically, tucatinib mediated an increase in inactive HER2 molecules at the cell surface through inhibition of HER2 ubiquitination, resulting in increased internalization and catabolism of T-DM1. The combination was correlated with enhanced HER2 pathway inhibition, decreased proliferation, and increased apoptosis. In a xenograft model of brain metastasis, tucatinib penetrated intracranial tumor tissues, inhibiting tumor growth and improving survival. These results suggest that tucatinib may be the optimal TKI partner for HER2-targeted therapies and support clinical studies of its combination with T-DM1, including in patients with brain metastases.
Significance:
The preclinical findings in breast cancer models presented here demonstrate that combining tucatinib with T-DM1 enhances the antitumor activity of either agent alone, supporting clinical studies of the combination in HER2-positive breast cancer, including in patients with brain metastases, which remains an important unmet medical need.
Early Metabolic Alteration Predicts Outcome With Middle Cerebral Artery Occlusion Treated by Mechanical Thrombectomy
Authors: Herpe Guillaume , Giraud Clément , Thomas Clément , Neau Jean‐Philippe , Velasco Stéphane , Dumas Victor , Pellerin Luc , Guillevin Carole , Guillevin Rémy
Published: September 2023

Background

Predicting clinical outcome based on either the postprocedural recanalization score (modified treatment in cerebral infarction) or the initial National Institute of Health Stroke Scale (NIHSS) clinical score performed immediately after the acute phase remains controversial. The
gold standard
to predict clinical outcome is the NIHSS score with diffusion weighted imaging. However, magnetic resonance spectroscopy could provide useful metabolic informations. Our study aimed to determine early metabolic factors predictive of long‐term clinical outcome after acute ischemic stroke in patients with middle cerebral artery occlusion successfully treated by mechanical thrombectomy.

Methods

Patients with proximal middle cerebral artery occlusion, an NIHSS score greater than 6 and successfully treated by mechanical thrombectomy with or without intravenous therapy were included. All patients underwent within 24 hours after mechanical thrombectomy, brain magnetic resonance imaging examination with multivoxel proton‐phosphorus‐magnetic resonance spectroscopy. Functional disability at 90 days with reference to pre‐stroke activities was categorized using the modified Rankin scale. Metabolite ratios were measured and confronted to modified Rankin scale.

Results

A total of 49 patients were included with initial mean NIHSS of 15.19±5.48. Time delay between: onset‐thrombectomy was 6.77 hours±3.22, thrombectomy‐magnetic resonance imaging was 29.83 hours±15.01. Results in the lesion compared with the contralateral area show an increase of Lac/Cr (0.88 versus 0.21;
P
<10
−10
) and a decrease of PhosphoMonoEster/PhosphoDiEster (0.80 versus 0.83;
P
=0.00165). Lac/Cr in the lesion was significantly higher in the poor outcome group than in the favorable outcome group (1.03±0.41 and 0.75±0.42;
P
=0.01). Our model built with NIHSS+proton‐magnetic resonance spectroscopy compared with the
gold standard model
(NIHSS+diffusion weighted imaging) is better (85.29% versus 77.55%) to predict clinical outcome.

Conclusion

Our study shows that early Lac/Cr alteration visible 24 hours after stroke is a strong predictor of 90 days clinical outcome for middle cerebral artery occlusion patients successfully treated by mechanical thrombectomy. Our NIHSS+proton‐magnetic resonance spectroscopy model is the first to predict patients’ long‐term functional outcome with an accuracy of 85.3%, superior to existing models including diffusion weighted imaging.
An annotated checklist of the Amphipoda (Crustacea) of Kuwait, north-western Arabian Gulf
Authors: AL-KANDARI MANAL , POLIKARPOV IGOR , NITHYANANDAN MANICKAM , AL-YAMANI FAIZA , GRINTSOV VLADIMIR
Published: September 2023

Kuwait’s intertidal and subtidal habitats were surveyed from 2013 to 2016 for amphipods, and earlier records from Kuwait and the rest of the Gulf were compared to provide the first annotated checklist of Amphipoda in Kuwait. A total of 82 sites in mainland and islands were surveyed including intertidal and subtidal zones. The resulting data identified 86 amphipod taxa belonging to 54 genera, 32 families and 3 suborders, including 20 new records to science that are currently being described. A total of 46 amphipod species, 34 genera and 19 families constituted new regional records either for Kuwait or the entire Gulf area. Information on local distribution, occurrence, and habitat are provided for each species. Within the tidal zonation, 50 species inhabited both the intertidal and subtidal areas, 19 were intertidal, 12 subtidal, and 3 species were found in the supratidal zone. Sandy and rocky shores supported the most diverse amphipod assemblages. A gradient of increasing amphipod species richness from north to south along Kuwait’s mainland coastline was revealed. The high level of regional endemism supported notable taxonomic distinction of the amphipod fauna of Kuwait from the other Gulf areas. Compositional dissimilarity among amphipod faunas increased with distance within a wide longitudinal gradient across the Gulf, Sea of Oman, and north-western Arabian Sea.
Coronamyia, a new genus of Neotropical Maruinini (Diptera, Psychodidae) with the description of four new species
Authors: BRAVO FREDDY , LOPES PRISCILA SILVA , ARAÚJO MAÍRA XAVIER
Published: September 2023

Coronamyia gen. nov., a new Neotropical genus of Psychodidae with records restricted to northeastern and southeastern Brazil is described, as well as four new species: C. paschoali sp. nov., C. santosi sp. nov., C. triangularis sp. nov., and C. trilobata sp. nov. The new genus is morphologically similar to Alepia Enderlein, 1937, but can be differentiated by the presence of a lightly sclerotized plate with long thin setae around the aedeagus, which is absent in Alepia. Coronamyia biapicalis comb. nov. is transferred from Alepia.
On the genus Tegestria Roewer, 1936, new senior synonym of Gintingius Roewer, 1938 with the description of a new species (Opiliones: Epedanidae: Sarasinicinae)
Authors: ZHANG CHAO , ZHAO JING JING , MARTENS JOCHEN
Published: September 2023

Tegestria altmannae sp. nov. is described and illustrated based on male and female specimens collected in Malaysia. It is characterized by the unarmed dorsal scutum, and basal segment of chelicerae dorsally with three seta-tipped tubercles. The type species of the monotypic genus Gintingius Roewer, 1938, G. robustus Roewer, 1938, is treated as a new synonym of Tegestria coniata Roewer, 1938 and the genus Gintingius as a new synonym of Tegestria Roewer, 1936, accordingly.
Historical Linguistics and the Biblical Languages
Authors: Ozoliņš Kaspars
Published: September 2023

This chapter discusses the various ways in which computational linguistics has been applied to biblical languages. It describes the development that started in the 1970s and 1980s with the first at-tempts in text representation and that continued with the creation of morphological and syntactic databases. Till the early twenty-first century most computational linguistic approaches concerned rule-based linguistic analysis, which allowed for a systematic and dis-tributional analysis of biblical corpora. Since the beginning of the twenty-first century statistical approaches and machine learning have entered the field of biblical studies, although most of their ap-plications to the Bible still have an experimental character. Because of the various computational approaches that have emerged in the last decades, computational linguistics is not one single theory, but rather an amalgam of approaches in a rapidly changing field. The relation with other linguistic theories is complex, because the data-bases that are used in the computational analysis of the Bible are each rooted in different linguistic theories. However, the various computational approaches have developed further in ways that are typical of computational corpus linguistics and that go beyond the linguistic theories underlying the annotations in the respective da-tabases. Because of the large amount of data it can handle, compu-tational linguistics provides valuable contributions to well-established fields in the study of the biblical languages, such as or-thography or syntax. In addition, more advanced computational techniques, such as author clustering and text-classification pro-vide new ways to approach long-standing problems such as source-critical questions and genre distinctions. The application of compu-tational linguistics to the biblical languages also touches upon fundamental questions about the interpretation of the Bible, be-cause it blurs the traditional distinction between the sciences, con-ceived of as a mode of scholarship involving calculation and pattern recognition, and the humanities, understood as a hermeneutic and critical mode of scholarship. Key words: Computational linguistics, databases, syntax, trans-parency and reproducibility
Computational Linguistic Analysis of the Biblical Text
Authors: van Peursen Willem Th.
Published: September 2023

Historical linguistics enjoys a venerable history among the many subfields of linguistic study. Many of the tools employed in histori-cal linguistics, as well as some of its theoretical concepts, are well-suited for biblical studies which engage in the ancient languages of the Bible. Knowledge about the kinds of language change common to many of the world’s languages can be useful as one type of evi-dence for the periodisation of biblical books. Additionally, knowledge about the external linguistic influences that shaped the biblical languages, as well as their prior histories (both Semitic and Indo-European) provide a helpful context for studying many syn-chronic aspects of the texts of Scripture. Furthermore, text-critical judgments about the biblical text can be strengthened when in-formed by knowledge of language change across the manuscript tradition. In short, historical linguistics offers a number of unique insights for biblical scholars engaging in the study of the biblical languages. Key words: Historical linguistics, diachronic, sound change, anal-ogy, Indo-European, Semitic
Persistent Ocean Anomalies as a Response to Northern Hemisphere Heating Induced by Biomass Burning Variability
Authors: Yamaguchi Ryohei , Kim Ji-Eun , Rodgers Keith B. , Stein Karl , Timmermann Axel , Lee Sun-Seon , Huang Lei , Stuecker Malte F. , Fasullo John T. , Danabasoglu Gokhan , Deser Clara , Lamarque Jean-Francois , Rosenbloom Nan A. , Edwards Jim
Published: September 2023

Biomass burning aerosol (BBA) emissions in the Coupled Model Intercomparison Project phase 6 (CMIP6) historical forcing fields have enhanced temporal variability during the years 1997–2014 compared to earlier periods. Recent studies document that the corresponding inhomogeneous shortwave forcing over this period can cause changes in clouds, permafrost, and soil moisture, which contribute to a net terrestrial Northern Hemisphere warming relative to earlier periods. Here, we investigate the ocean response to the hemispherically asymmetric warming, using a 100-member ensemble of the Community Earth System Model version 2 Large Ensemble forced by two different BBA emissions (CMIP6 default and temporally smoothed over 1990–2020). Differences between the two subensemble means show that ocean temperature anomalies occur during periods of high BBA variability and subsequently persist over multiple decades. In the North Atlantic, surface warming is efficiently compensated for by decreased northward oceanic heat transport due to a slowdown of the Atlantic meridional overturning circulation. In the North Pacific, surface warming is compensated for by an anomalous cross-equatorial cell (CEC) that reduces northward oceanic heat transport. The heat that converges in the South Pacific through the anomalous CEC is shunted into the subsurface and contributes to formation of long-lasting ocean temperature anomalies. The anomalous CEC is maintained through latitude-dependent contributions from narrow western boundary currents and basinwide near-surface Ekman transport. These results indicate that interannual variability in forcing fields may significantly change the background climate state over long time scales, presenting a potential uncertainty in CMIP6-class climate projections forced without interannual variability.