bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of age in dynamics of autoantibodies in pediatric Celiac disease
Authors: Trovato Chiara Maria , Montuori Monica , Leter Beatrice , Laudadio Ilaria , Russo Giusy , Oliva Salvatore
Published: March 2023

Background

Celiac disease (CD) is characterized by elevated serum titers of autoantibodies IgA anti-tissue transglutaminase 2 (TGA-IgA) and IgA anti-endomysial (EMA), with small bowel mucosa atrophy. We evaluated age differences between CD children exhibiting variable antibody titers at diagnosis.

Methods

CD children diagnosed between January 2014 and June 2019, according to 2012 ESPGHAN guidelines were studied. All had EMA and TGA-IgA measurements, while a proportion of them underwent esophagogastroduodenoscopy (EGD). Patients were grouped based on serum TGA-IgA titers normalized to the upper limit of normal (ULN) and differences in median age (years) assessed by analysis of variance (ANOVA) and creation of orthogonal contrasts.

Results

CD was diagnosed in 295 subjects (median age: 4.4 [IQR: 2.60–8.52]) with a biopsy sparing protocol (high titer: ≥ 10xULN) and in 204 by EGD biopsy. Of the latter, 142 (median age: 8.5 [IQR: 5.81–11.06]) and 62 (median age: 9.5 [IQR: 6.26–12.76]) had a low (< 5xULN) and a moderate (≥ 5 < 10xULN) TGA-IgA titer, respectively. Potential CD was diagnosed in 20 patients (median age: 3.6 [IQR: 2.47–6.91]). The median age was significantly lower in the no-biopsy group (ANOVA: F(3, 516) = 25.98, p < .001) than in low- and moderate titer groups (p < 0.0001), while there was no statistical difference between biopsy-sparing and potential CD groups.

Conclusion

CD patients with greatly elevated antibody titers (≥ 10xULN) were diagnosed at an earlier age than those with lower titers. This may indicate that an increase in TGA-IgA is independent of age and suggests a polarization of autoimmunity in younger individuals with higher serum antibody levels.
Vitamin E-induced coagulopathy in a young patient: a case report
Authors: Abrol Ritika , Kaushik Reshma , Goel Deepak , Sama Sonu , Kaushik Rajeev Mohan , Kala Mansi
Published: March 2023

Background

High-dose vitamin E intake is known to inhibit vitamin K-derived coagulation factor synthesis, which can cause serious bleeding events such as gastrointestinal bleeding and intracranial hemorrhage. We report a case of coagulopathy induced by marginally increased levels of vitamin E.

Case presentation

A 31-year-old Indian man presented with oral bleeding, black tarry stools, and bruising over his back. He had been taking non-steroidal anti-inflammatory drugs for low backache and vitamin E for hair loss. He had mild anemia with normal platelet count, thrombin time, and prolonged bleeding time, activated partial thromboplastin time, and prothrombin time. Serum fibrinogen was slightly raised. Mixing studies with pooled normal plasma, aged plasma, and adsorbed plasma were suggestive of deficiency of multiple coagulation factors due to acquired vitamin K deficiency. Serum phylloquinone was normal, while prothrombin induced by vitamin K absence-II level was increased. Serum alpha-tocopherol was slightly raised. Upper gastrointestinal endoscopy showed multiple gastroduodenal erosions. A final diagnosis of vitamin E toxicity-related coagulopathy was made. The patient responded well to pantoprazole, vitamin K supplementation, multiple fresh frozen plasma transfusions, and other supportive treatments besides the discontinuation of vitamin E supplementation. The coagulation parameters normalized, and the patient was discharged with complete resolution of symptoms and remained asymptomatic during the follow-up for 6 months.

Conclusions

Vitamin E-related inhibition of vitamin K-dependent factors with coagulopathy may occur even at marginally increased levels of serum vitamin E. This risk becomes significant in patients receiving other drugs that may increase the risk of bleeding.
Pharmacy students’ attitudes and intentions of pursuing postgraduate studies and training in pharmacogenomics and personalised medicine
Authors: Makrygianni Dimitra , Koufaki Margarita-Ioanna , Patrinos George P. , Vasileiou Konstantinos Z.
Published: March 2023

Background

Pharmacists’ contribution to pharmacogenomics (PGx) implementation in clinical practice is vital, but a great proportion of them are not aware of PGx and its applications. This highlights the university education’s crucial role to prepare pharmacists to face future challenges in such a constantly evolving and demanding environment.

Objectives

Our study aims to examine pharmacy students’ training satisfaction, knowledge, self-confidence and attitudes towards PGx on their intentions for postgraduate training in PGx and personalised medicine (PM).

Methods

An initial model on students’ intention to pursue postgraduate training in PGx and PM and its predicting factors, based on the Theory of Planned Behaviour (TPB), was proposed. Based on it, a questionnaire was developed and distributed to 346 pharmacy students of all study years, capturing the selected factors influencing students’ intentions to postgraduate training in PGx and PM, as well as their demographics. Structural equation modelling (SEM) analysis was employed to determine the effects of both the examined factors and demographics on students’ intentions.

Results

Students did not consider themselves adequately prepared for using PGx in clinical practice. Their attitudes towards PGx implementation were the most important factor influencing their intentions to pursue postgraduate training in PGx and PM. Other factors such as self-confidence and training satisfaction also affected students’ intentions, but to a lower extent. Students of the last two study years (40% of the whole sample) and male (36%) students stated to be less willing to pursue PGx-related studies in the future. Only 10% of the participants claimed to have undergone a recent PGx or genetic test, but this did not affect their intentions.

Conclusion

There is an important gap in pharmacy school curriculum regarding PGx and PM training which coupled with the slow rate of PGx and PM implementation into clinical practice seems to restrain students’ aspiration to further expand their knowledge and horizons in terms of PGx and PM.
Circular RNA circHMCU promotes breast tumorigenesis through miR-4458/PGK1 regulatory cascade
Authors: Qiu Shubian , Zou Lele , Qiu Ruimin , Wang Xin
Published: March 2023

Background

Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored.

Methods

The expression levels of circHMCU, miR-4458 and phosphoglycerate kinase 1 (PGK1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The glucose uptake, lactate production and ATP level were assayed by related commercial kits. Cell Counting Kit-8 (CCK8), 5’-ethynyl-2’-deoxyuridine (EdU) and flow cytometry assays were used to test cell proliferation and apoptosis, respectively. The migratory and invasive abilities were detected by transwell and wound-healing assays. The relationships among circHMCU, miR-4458 and PGK1 were verified by dual-luciferase reporter assay. The function of circHMCU in tumor growth was evaluated by animal studies.

Results

CircHMCU was upregulated in BC tissues and cell lines, whereas miR-4458 was downregulated. For biological experiments, circHMCU knockdown inhibited cell proliferation, migration, glycolysis, while promoted cell apoptosis. CircHMCU bound miR-4458, and miR-4458 targeted PGK1. MiR-4458 inhibition reversed circHMCM knockdown-mediated effects on BC cell malignant behaviors. MiR-4458 overexpression suppressed cell glycolysis, proliferation, and metastasis and promoted apoptosis in BC cells through PGK1 upregulation. Additionally, circHMCU suppressed tumor growth in vivo.

Conclusion

CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.
Zolbetuximab + CAPOX in 1L claudin-18.2+ (CLDN18.2+)/HER2− locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary phase 3 results from GLOW.
Authors: Xu Rui-hua , Shitara Kohei , Ajani Jaffer A. , Bang Yung-Jue , Enzinger Peter C. , Ilson David H. , Lordick Florian , Van Cutsem Eric , Gallego Plazas Javier , Huang Jing , Shen Lin , Oh Sang Cheul , Sunpaweravong Patrapim , Soo Hoo Hwoei Fen , Turk Haci M. , Park Jung Wook , Moran Diarmuid Martin , Bhattacharya Pranob P. , Arozullah Ahsan , Shah Manish A.
Published: March 2023

405736

Background: There is an unmet need for novel targeted therapies that improve outcomes for pts with HER2− LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 is expressed in normal gastric mucosa cells and retained in most G/GEJ adenocarcinomas. In the phase 3 SPOTLIGHT study, zolbetuximab, a CLDN18.2-targeted chimeric monoclonal antibody, significantly prolonged PFS and OS in pts with CLDN18.2+/HER2− LA unresectable or mG/GEJ adenocarcinoma when combined with mFOLFOX6. GLOW (NCT03653507) is a phase 3 global, double-blind study comparing zolbetuximab or PBO with capecitabine and oxaliplatin (CAPOX) as 1L treatment for this pt population. Methods: Pts with CLDN18.2+ (moderate-to-strong membranous CLDN18 staining in ≥75% tumor cells by IHC)/HER2− LA unresectable or mG/GEJ adenocarcinoma were randomized 1:1 to zolbetuximab IV 800 mg/m2 (cycle 1, day [D] 1) followed by 600 mg/m2 (D1 in subsequent cycles) + CAPOX (oral capecitabine 1000 mg/m2 BID on D1−14 of each cycle; oxaliplatin IV 130 mg/m2 on D1 of each cycle) for eight 21-day cycles vs PBO + CAPOX; pts continued for >8 cycles with zolbetuximab or PBO, plus capecitabine (investigator decision), until PD or a discontinuation criterium was met. The primary endpoint (EP) was PFS per RECIST v1.1 by IRC. OS was a key secondary EP; other secondary EPs included ORR and safety. Differences between treatment arms in PFS and OS were tested by stratified log-rank tests; OS was tested if PFS was significant. Results: 507 pts were randomized 1:1 to zolbetuximab + CAPOX (N = 254) or PBO + CAPOX (N = 253). Both PFS (median 8.21 vs 6.80 mo, HR 0.687, P=0.0007) and OS (median 14.39 vs 12.16 mo, HR 0.771, P=0.0118) were significantly prolonged with zolbetuximab + CAPOX (Table); in pts with measurable disease, ORR (95% CI) was 53.8% (46.58−60.99) vs 48.8% (41.76−55.84) in zolbetuximab vs PBO arm. The most common TEAEs with zolbetuximab + CAPOX were nausea (68.5% vs 50.2% in zolbetuximab vs PBO arm), vomiting (66.1% vs 30.9%), and decreased appetite (41.3% vs 33.7%); serious TEAEs (47.2% vs 49.8%), grade ≥3 TEAEs (72.8% vs 69.9%), and drug-related TEAEs leading to death (2.4% vs 2.8%) were similar in both arms. Conclusions: Targeting CLDN18.2 with zolbetuximab combined with CAPOX significantly prolonged PFS and OS in 1L pts with CLDN18.2+/HER2− LA unresectable or mG/GEJ adenocarcinoma. These results align with those observed in SPOTLIGHT and establish zolbetuximab + chemotherapy as a potential new standard-of-care option for these pts. Clinical trial information: NCT03653507 . [Table: see text]
Micronutrient Supplementation and Bone Health After Prophylactic Total Gastrectomy in Patients With CDH1 Variants
Authors: Gamble Lauren A , Lopez Rachael , Rajasimhan Suraj , Samaranayake Sarah G , Bowden Cassidy , Famiglietti Amber L , Blakely Andrew M , Jha Smita , Ahlman Mark A , Davis Jeremy L
Published: March 2023

Introduction

Patients with germline variants in CDH1 who undergo prophylactic total gastrectomy (TG) are at risk of altered nutrient and drug absorption due to modified gastrointestinal anatomy. Bone mineral density loss and micronutrient deficiencies have not been described previously in this patient population.

Methods

In this study we included 94 patients with germline CDH1 variants who underwent prophylactic TG between October 2017 and February 2022. We examined pre- and post-gastrectomy bone mineral density (BMD); serum biomarkers including calcium, phosphorus, alkaline phosphatase, and 25 (OH)-vitamin D; and postoperative adherence to calcium and multivitamin supplementation.

Results

Almost all patients (92/94, 98%) lost a substantial amount of weight post-TG, with an average weight loss of 26.5% at 12 months post-surgery. Serum biomarkers of mineral metabolism, namely calcium and phosphorus, did not change significantly after TG. However, average BMD was decreased in all patients at 12 months post-TG. Nonadherence to calcium supplementation was associated with a decrease in BMD. Nonadherence to multivitamin supplementation was associated with greater percent BMD loss in the femoral neck and total hip.

Conclusions

Appropriate micronutrient supplementation and nutritional counseling pre- and postoperatively in patients undergoing prophylactic TG are important to mitigate the long-term effects of gastrectomy on bone health.
COVID-19 as a Trigger for Type 1 Diabetes
Authors: Wang Yichen , Guo Hui , Wang Gongquan , Zhai Jiawei , Du Bing
Published: March 2023

Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet β cells, and genetic and environmental factors are thought to trigger autoimmunity. Convincing evidence indicates that viruses are associated with T1D development and progression. During the COVID-19 pandemic, cases of hyperglycemia, diabetic ketoacidosis, and new diabetes increased, suggesting that SARS-CoV-2 may be a trigger for or unmask T1D. Possible mechanisms of β-cell damage include virus-triggered cell death, immune-mediated loss of pancreatic β cells, and damage to β cells because of infection of surrounding cells. This article examines the potential pathways by which SARS-CoV-2 affects islet β cells in these 3 aspects. Specifically, we emphasize that T1D can be triggered by SARS-CoV-2 through several autoimmune mechanisms, including epitope spread, molecular mimicry, and bystander activation. Given that the development of T1D is often a chronic, long-term process, it is difficult to currently draw firm conclusions as to whether SARS-CoV-2 causes T1D. This area needs to be focused on in terms of the long-term outcomes. More in-depth and comprehensive studies with larger cohorts of patients and long-term clinical follow-ups are required.
Διερεύνηση της πιθανής συσχέτισης των επιπέδων της λεπτίνης, της αδιπονεκτίνης και της kisspeptin με τα ωοθηκικά αποθέματα των γυναικών αναπαραγωγικής ηλικίας
Authors: Νικολέττος Κωνσταντίνος
Published: March 2023

Σκοπός: Σκοπός της παρούσας διδακτορικής διατριβής είναι η διερεύνηση της πιθανής συσχέτισης των επιπέδων της λεπτίνης, της αδιπονεκτίνης και της kisspeptin με τα ωοθηκικά αποθέματα γυναικών αναπαραγωγικής ηλικίας.Υλικό και μέθοδος: Για τη μελέτη συμφώνησαν να συμμετάσχουν 80 γυναίκες ηλικίας 19-40 ετών. Από αυτές τελικά συμπεριλήφθηκαν οι 74 καθώς στις 6 κρίθηκε ακατάλληλο το δείγμα του αίματος λόγω αιμόλυσης. Οι γυναίκες κατηγοριοποιήθηκαν σε τρεις κύριες ομάδες σε σχέση με τα πρότυπα των ωοθηκικών τους αποθεματικών: γυναίκες με επαρκείς ωοθηκικές εφεδρείες (Ομάδα A - AOR) (n=30), γυναίκες με αυξημένες ωοθηκικές εφεδρείες (Ομάδα B - PCOS) (n=31) και γυναίκες με μειωμένες ωοθηκικές εφεδρείες (Ομάδα Γ - DOR) (n=13).Αποτελέσματα: Η ομάδα με μειωμένες ωοθηκικές εφεδρείες είχε στατιστικά σημαντικά υψηλότερη ηλικία και τιμές FSH σε σχέση με τις δύο άλλες ομάδες. Δεν βρέθηκε στατιστικά σημαντική διαφορά μεταξύ των ομάδων για τις τιμές της Ε2, TSH. Η τιμή του ΔΜΣ, της LH, της TT, της 17-OHP, της DHEA, της AMH και του AFC ήταν υψηλότερη στις γυναίκες με υψηλές ωοθηκικές εφεδρείες συγκριτικά με τις άλλες δύο ομάδες. Η AMH και το AFC ήταν χαμηλότερο στις γυναίκες με χαμηλές ωοθηκικές εφεδρείες σε σύγκριση με τις άλλες ομάδες όπως αναμενόταν. Τα επίπεδα της λεπτίνης ήταν αυξημένα στις γυναίκες με PCOS όμως δεν υπήρχε στατιστικά σημαντική διαφορά σε σχέση με τις δύο άλλες ομάδες. Όσον αφορά στην αδιπονεκτίνη, η σύγκριση των τιμών της μεταξύ των τριών ομάδων έδειξε ότι οι γυναίκες με PCOS είχαν χαμηλότερες τιμές σε σύγκριση με τις άλλες ομάδες χωρίς όμως να είναι στατιστικά σημαντική η διαφορά. Τέλος η σύγκριση των επιπέδων της kisspeptin μεταξύ των τριών ομάδων έδειξε ότι τα επίπεδα της kisspeptin ήταν αυξημένα στις γυναίκες με χαμηλές ωοθηκικές εφεδρείες, συγκριτικά με τις άλλες δύο ομάδες, χωρίς όμως να υπάρχει στατιστικά σημαντική διαφορά. Καθώς δεν βρέθηκε σημαντικά στατιστική διαφορά μεταξύ των ομάδων για τις τιμές της λεπτίνης, της αδιπονεκτίνης και της kisspeptin έγινε στη συνέχεια περαιτέρω σύγκριση αυτών των τριών παραμέτρων ανά δύο ομάδες μεταξύ τους. Όταν πραγματοποιήθηκε σύγκριση των τριών αυτών παραμέτρων μεταξύ ομάδας Α (AOR) και ομάδας Γ (DOR) τότε βρέθηκε στατιστικά σημαντική διαφορά για την kisspeptin. Συμπεράσματα: Η κατηγοριοποίηση των γυναικών που πραγματοποιήσαμε με βάση τις ωοθηκικές εφεδρείες συμφωνεί απόλυτα με τη διεθνή βιβλιογραφία. Όσον αφορά τη λεπτίνη, την αδιπονεκτίνη και την kisspeptin, η σύνδεσή τους με την αναπαραγωγή είναι αδιαμφισβήτητη. Παρόλα αυτά και τα τρία πεπτίδια επηρεάζονται από πολλούς παράγοντες ταυτόχρονα και στη δική μας μελέτη, ο αριθμός των δειγμάτων ήταν περιορισμένος. Ο συγκεκριμένος τομέας χρήζει περαιτέρω διερεύνησης με μεγαλύτερο αριθμό δειγμάτων για να οδηγηθούμε σε ασφαλέστερα συμπεράσματα.
Aufgetischt und abgeräumt
Authors: Ohnsorg Petra
Published: March 2023

Die interdisziplinäre Untersuchung der römischen Befunde und Funde der Ausgrabung an der Rittergasse 29A durch Petra Ohnsorg stellt einen weiteren wichtigen Referenzpunkt für das Verständnis des römischen Vicus von Basel dar. Bei der untersuchten Fläche handelt es sich um einen kleinen, peripheren Bereich der Siedlung. In der Fläche wurden mehrere Gruben erfasst, die zum Hinterhofbereich naher Gebäude gehört haben müssen. Durch die integrative Analyse von Keramik, Tierknochen, Botanik und Befund ist es Petra Ohnsorg gelungen, einen Ausschnitt des römischen Vicus in einer umfassenden Art und Weise zu beleuchten und die Resultate in einen grösseren Zusammenhang zu den bisherigen Erkenntnissen über das römische Basel zu stellen.
The identification of high-performing antibodies for Sequestosome-1 for use in Western blot, immunoprecipitation and immunofluorescence
Authors: Ayoubi Riham , Alshafie Walaa , Shlaifer Irina , Southern Kathleen , McPherson Peter S. , Laflamme Carl ,   NeuroSGC/YCharOS/EDDU collaborative group
Published: March 2023

Sequestosome-1, encoded by the gene SQSTM1, functions as a bridge between ubiquitinated proteins and the proteasome or autophagosome, thereby regulating protein degradation pathways. Loss of Sequestosome-1 is hypothesized to enhance neurodegeneration progression in several diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal disorders (FTD). Sequestosome-1 reproducible research would be facilitated with the availability of well-characterized anti-Sequestosome-1 antibodies. In this study, we characterized seventeen Sequestosome-1 commercial antibodies for Western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.
The Formation of Regulatory Universal Educational Actions in Primary Schoolchildren at Literary Reading Lessons
Authors: Pletnikova D. , Fugelova Tat'yana
Published: March 2023

The article provides a theoretical substantiation of the process of formation of regulative universal educational actions of younger schoolchildren on the basis of reflection. The concept of "regulative universal learning activities" is characterized, which are defined in the Federal State Educational Standard of Primary General Education as an essential component of meta-subject learning outcomes. The technique of using the techniques of reflection in the lessons of literary reading is described, which allows to increase the level of mastery of primary schoolchildren by the regulative universal educational actions of goal-setting, control and evaluation.
The Problem of Developing Scientific and Methodological Support of Subjects of Interdepartmental Cooperation in the Implementation of the Strategy for the Development of Education of the Russian Federation
Authors: Yakovlev Sergey
Published: March 2023

The paper discloses the structure of  scientific and methodological support for interagency cooperation in  the implementation of  the Strategy for the Development of Upbringing in the Russian Federation that includes the coordination of work of legislative authorities and public administration bodies of the education system, scientific institutions of the Russian Academy of Education system, institutions of secondary professional and higher education system and the system of advanced training of education workers, educational institutions and additional images. The content and structure of scientific and methodological support of interdepartmental cooperation in the implementation of the Strategy for the Development of Upbringing in the Russian Federation are proposed.
A importância das aulas de Educação Física na socialização e interação das crianças na escola em relação ao tempo em sala de aula e intervalo
Authors: Silva Thauany Cordeiro da , Vieira-Souza Lucio Marques , Getirana-Mota Márcio , Rosa Jean Lucas , Conti Letícia Ferreira , Moraes Filho João Alves de , Costa Lúcio Flávio Gomes Ribeiro da
Published: March 2023

O estudo teve como objetivo identificar a influência da Educação Física na socialização entre os escolares em relação ao tempo de aula e do recreio. Foi realizada pesquisa observacional quali-quantitativa, com análise descritiva dos dados, em uma escola particular de Petrolândia, Pernambuco, Brasil. Os resultados da pesquisa mostram que as aulas de Educação Física promovem maior interação entre os alunos. Em conclusão, observa-se que as aulas de Educação Física são de fundamental importância para a interação dos alunos dentro do ambiente escolar.
An Oblivious Ellipsoid Algorithm for Solving a System of (In)Feasible Linear Inequalities
Authors: Lamperski Jourdain , Freund Robert M. , Todd Michael J.
Published: March 2023

The ellipsoid algorithm is a fundamental algorithm for computing a solution to the system of m linear inequalities in n variables [Formula: see text] when its set of solutions has positive volume. However, when [Formula: see text] is infeasible, the ellipsoid algorithm has no mechanism for proving that (P) is infeasible. This is in contrast to the other two fundamental algorithms for tackling [Formula: see text], namely, the simplex and interior-point methods, each of which can be easily implemented in a way that either produces a solution of [Formula: see text] or proves that [Formula: see text] is infeasible by producing a solution to the alternative system [Formula: see text]. This paper develops an oblivious ellipsoid algorithm (OEA) that either produces a solution of [Formula: see text] or produces a solution of [Formula: see text]. Depending on the dimensions and other condition measures, the computational complexity of the basic OEA may be worse than, the same as, or better than that of the standard ellipsoid algorithm. We also present two modified versions of OEA, whose computational complexity is superior to that of OEA when [Formula: see text]. This is achieved in the first modified version by proving infeasibility without producing a solution of [Formula: see text], and in the second version by using more memory.

Funding: J. Lamperski and R. M. Freund were supported by the Air Force Office of Scientific Research [Grant FA9550-19-1-0240].
Single-shot Fresnel incoherent correlation holography via deep learning based phase-shifting technology
Authors: Huang Tao , Zhang Qinnan , Li Jiaosheng , Lu Xiaoxu , Di Jianglei , Zhong Liyun , Qin Yuwen
Published: March 2023

Fresnel incoherent correlation holography (FINCH) realizes non-scanning three-dimension (3D) images using spatial incoherent illumination, but it requires phase-shifting technology to remove the disturbance of the DC term and twin term that appears in the reconstruction field, thus increasing the complexity of the experiment and limits the real-time performance of FINCH. Here, we propose a single-shot Fresnel incoherent correlation holography via deep learning based phase-shifting (FINCH/DLPS) method to realize rapid and high-precision image reconstruction using only a collected interferogram. A phase-shifting network is designed to implement the phase-shifting operation of FINCH. The trained network can conveniently predict two interferograms with the phase shift of 2/3 π and 4/3 π from one input interferogram. Using the conventional three-step phase-shifting algorithm, we can conveniently remove the DC term and twin term of the FINCH reconstruction and obtain high-precision reconstruction through the back propagation algorithm. The Mixed National Institute of Standards and Technology (MNIST) dataset is used to verify the feasibility of the proposed method through experiments. In the test with the MNIST dataset, the reconstruction results demonstrate that in addition to high-precision reconstruction, the proposed FINCH/DLPS method also can effectively retain the 3D information by calibrating the back propagation distance in the case of reducing the complexity of the experiment, further indicating the feasibility and superiority of the proposed FINCH/DLPS method.
Cryogenically cooled Fe:ZnSe-based chirped pulse amplifier at 4.07 µm
Authors: Marra Z. Alphonse , Wu Yi , Zhou Fangjie , Chang Zenghu
Published: March 2023

A femtosecond chirped pulse amplifier based on cryogenically cooled Fe:ZnSe was demonstrated at 333 Hz—33 times higher than previous results achieved at near-room-temperature. The long upper-state lifetime allows free-running, diode-pumped Er:YAG lasers to be used as pump lasers. 250-fs, 4.59-mJ pulses are produced with a center wavelength of 4.07 µm, which avoids strong atmospheric CO2 absorption that cuts on around 4.2 µm. It is therefore possible to operate the laser in ambient air with good beam quality. By focusing the 18-GW beam in air, harmonics up to the ninth order were observed indicating its potential for use in strong-field experimentation.
Generation and characterization of frequency tunable sub-15-fs pulses in a gas-filled hollow-core fiber pumped by a Yb:KGW laser
Authors: Sabbah Mohammed , Belli Federico , Brahms Christian , Yu Fei , Knight Jonathan , Travers John C.
Published: March 2023

We investigate soliton self-compression and photoionization effects in an argon-filled antiresonant hollow-core photonic crystal fiber pumped with a commercial Yb:KGW laser. Before the onset of photoionization, we demonstrate self-compression of our 220 fs pump laser to 13 fs in a single and compact stage. By using the plasma driven soliton self-frequency blueshift, we also demonstrate a tunable source from 1030 to ∼700 nm. We fully characterize the compressed pulses using sum-frequency generation time-domain ptychography, experimentally revealing the full time-frequency plasma–soliton dynamics in hollow-core fiber for the first time.
Ultrafast lithium disilicate veneer debonding time assisted by a CO2 laser with temperature control
Authors: salam Ayat , Faris Rawaa A. , Al-janabi Abdulhadi
Published: March 2023

We report on using a CO2 (10.6 µm) laser to debond the lithium disilicate veneers. Sixty-four sound human premolar teeth and 64 veneer specimens were used in the study. The zigzag movement via CO2 laser handpiece along with an air-cooled jet to prevent temperature elevation above the necrosis temperature limit (5.5 C°) was applied. The optimal deboning irradiation time was super-fast, at about 5 seconds at 3 Watt CO2 laser power. It is 20 times less than any previously published work for veneers debonding. The enamel beneath the debonded veneers has been assessed by atomic force microscopy (AFM) and shear stress technique as criteria for the easiness of debonding. The fast deboning process with nonsignificant changes in enamel integrity and tooth vitality reflects the high potential of CO2 laser in veneers debonding.
Primate protein-ligand interfaces exhibit significant conservation and unveil human-specific evolutionary drivers
Authors: King Sean B. , Singh Mona
Published: March 2023

Despite the vast phenotypic differences observed across primates, their protein products are largely similar to each other at the sequence level. We hypothesized that, since proteins accomplish all their functions via interactions with other molecules, alterations in the sites that participate in these interactions may be of critical importance. To uncover the extent to which these sites evolve across primates, we built a structurally-derived dataset of ~4,200 one-to-one orthologous sequence groups across 18 primate species, consisting of ~68,000 ligand-binding sites that interact with DNA, RNA, small molecules, ions, or peptides. Using this dataset, we identify functionally important patterns of conservation and variation within the amino acid residues that facilitate protein-ligand interactions across the primate phylogeny. We uncover that interaction sites are significantly more conserved than other sites, and that sites binding DNA and RNA further exhibit the lowest levels of variation. We also show that the subset of ligand-binding sites that do vary are enriched in components of gene regulatory pathways and uncover several instances of human-specific ligand-binding site changes within transcription factors. Altogether, our results suggest that ligand-binding sites have experienced selective pressure in primates and propose that variation in these sites may have an outsized effect on phenotypic variation in primates through pleiotropic effects on gene regulation.
Interpreting the pervasive observation of U-shaped Site Frequency Spectra
Authors: Freund Fabian , Kerdoncuff Elise , Matuszewski Sebastian , Lapierre Marguerite , Hildebrandt Marcel , Jensen Jeffrey D. , Ferretti Luca , Lambert Amaury , Sackton Timothy B. , Achaz Guillaume
Published: March 2023

The standard neutral model of molecular evolution has traditionally been used as the null model for population genomics. We gathered a collection of 45 genome-wide site frequency spectra from a diverse set of species, most of which display an excess of low and high frequency variants compared to the expectation of the standard neutral model, resulting in U-shaped spectra. We show that multiple merger coalescent models often provide a better fit to these observations than the standard Kingman coalescent. Hence, in many circumstances these under-utilized models may serve as the more appropriate reference for genomic analyses. We further discuss the underlying evolutionary processes that may result in the widespread U-shape of frequency spectra.
A network-based analysis detects cocaine-induced changes in social interactions in Drosophila melanogaster
Authors: Petrović Milan , Meštrović Ana , Andretić Waldowski Rozi , Filošević Vujnović Ana
Published: March 2023

Addiction is a multifactorial biological and behavioral disorder that is studied using animal models, based on simple behavioral responses in isolated individuals. A couple of decades ago it was shown thatDrosophila melanogastercan serve as a model organism for behaviors related to alcohol, nicotine and cocaine (COC) addiction. Scoring of COC-induced behaviors in a large group of flies has been technologically challenging, so we have applied a local, middle and global level of network-based analyses to study social interaction networks (SINs) among a group of 30 untreated males compared to those that have been orally administered with 0.50 mg/mL of COC for 24 hours. In this study, we have confirmed the previously described increase in locomotion upon COC feeding. We have isolated new network-based measures associated with COC, and influenced by group on the individual behavior. COC fed flies showed a longer duration of interactions on the local level, and formed larger, more densely populated and compact, communities at the middle level. Untreated flies have a higher number of interactions with other flies in a group at the local level, and at the middle level, these interactions led to the formation of separated communities. Although the network density at the global level is higher in COC fed flies, at the middle level the modularity is higher in untreated flies. One COC specific behavior that we have isolated was an increase in the proportion of individuals that do not interact with the rest of the group, considered as the individual difference in COC induced behavior and/or consequence of group influence on individual behavior. Our approach can be expanded on different classes of drugs with the same acute response as COC to determine drug specific network-based measures and could serve as a tool to determinate genetic and environmental factors that influence both drug addiction and social interaction.
Protocol for a randomized controlled trial to assess the effect of Self-Management for Amputee Rehabilitation using Technology (SMART): An online self-management program for individuals with lower limb loss
Authors: Esfandiari Elham , Miller WC , King Sheena , Payne Michael , Mortenson W. Ben , Underwood Heather , MacKay Crystal , Ashe Maureen C.
Published: March 2023

Background

Lower limb loss (LLL) is a distressing experience with psychological, physical, and social challenges. Education is needed to enhance the coping skills and confidence of patients to improve LLL outcomes. However, access to rehabilitation services and education is limited outside of urban centers. To address this service gap, we co-created an eHealth platform, called Self-Management for Amputee Rehabilitation using Technology (SMART).

Objectives

First, we will test the effect of SMART and usual care compared with usual care only on walking capacity and confidence among individuals with LLL. Second, we will describe key implementation factors for program delivery and adoption at the person- and provider-level.

Methods

This is a Type 1 Effectiveness-Implementation Hybrid Design, mixed-methods, multi-site (British Columbia and Ontario, Canada), parallel, assessor-blinded randomized controlled trial. Participants will include adults with unilateral LLL, during early prosthetic fitting (<2 years after casting for initial prosthesis). Participants in both groups will receive usual care. The experimental group will receive SMART with weekly support sessions from a trained peer mentor for goal setting and action planning for six weeks. Participants will be encouraged to continue using SMART for an additional four weeks. The control group will receive usual care, and weekly social contacts for six weeks. The primary outcome measure is walking capacity operationalized as the performance based Timed Up and Go test. The secondary outcome is walking confidence using the Ambulatory Self-Confidence Questionnaire. Outcome measures will be assessed at baseline, immediately post-intervention, and four weeks follow-up. We will describe key implementation factors (such as, participant experience, intervention adoption, fidelity) throughout the study using questionnaires, semi-structured interviews, and direct observation.

Results

No participants have been enrolled.

Conclusions

SMART has the potential to provide knowledge and skill development to augment rehabilitation outcomes for adults with LLL.

Trial registration

NCT04953364 in Clinical Trial Registry (https://clinicaltrials.gov/).
Te Ara Waiora–Implementing human papillomavirus (HPV) primary testing to prevent cervical cancer in Aotearoa New Zealand: A protocol for a non-inferiority trial
Authors: Gibson-Helm Melanie , Slater Tania , MacDonald Evelyn J. , Stevenson Kendall , Adcock Anna , Geller Stacie , Parag Varsha , Lambert Charles , Bennett Matthew , Hibma Merilyn , Sykes Peter , Saville Marion , Hawkes David , Stanton Jo-Ann , Clueard Mary-Ann , Jelley Grahame , Lawton Bev
Published: March 2023

Background

Cervical cancer is caused by high-risk types of human papillomavirus (HPV). Testing for high-risk HPV is a more sensitive screening method than cervical cytology for detecting cervical changes that may lead to cancer. Consistent with recent evidence of efficacy and acceptability, Aotearoa New Zealand plans to introduce HPV testing as the primary approach to screening, replacing cervical cytology, from mid-2023. Any equitable cervical screening programme must be effective across a diverse population, including women that the current programme fails to reach, particularly Māori and those in rural areas. Currently, we do not know the best model for implementing an equitable HPV self-testing screening programme.

Methods

This implementation trial aims to assess whether a universal offer of HPV self-testing (offered to all people eligible for cervical screening) achieves non-inferior screening coverage (equal) to a universal offer of cervical cytology alone (the present programme). The study population is all people aged from 24.5 to 70 years due for cervical screening in a 12-month period (including those whose screening is overdue or who have never had screening). A range of quantitative and qualitative secondary outcomes will be explored, including barriers and facilitators across screening and diagnostic pathways. This study takes place in Te Tai Tokerau/Northland which covers a diverse range of urban and rural areas and has a large Indigenous Māori population. A total of fourteen practices will be involved. Seven practices will offer HPV self-testing universally to approximately 2800 women and will be compared to seven practices providing routine clinical care (offer of cervical cytology) to an approximately equal number of women.

Discussion

This trial will answer important questions about how to implement an equitable, high-quality, effective national programme offering HPV self-testing as the primary screening method for cervical cancer prevention.

Trial registration

Prospectively registered with the Australian New Zealand Clinical Trials Registry 07/12/2021: ACTRN12621001675819.
Combining MEK and SRC inhibitors for treatment of colorectal cancer demonstrate increased efficacy in vitro but not in vivo
Authors: Fan Fan , Ghosh Susmita , Powell Reid , Roszik Jason , Park Yongsun , Sobieski Mary , Sorokin Alexey , Stephan Clifford , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: March 2023

Metastatic colorectal cancer (mCRC) is the second leading cause of cancer deaths in the United States. More than 50% of patients with mCRC harbor mutations of the oncogenic driver RAS (KRAS or NRAS). Because directly targeting most mutations of RAS is technically challenging, researchers have concentrated on targeting MEK, a downstream mediator of RAS. However, targeting MEK as single-agent therapy is ineffective in patients with mCRC. We hypothesize that combining a MEK inhibitor with other agents can enhance the efficacy of MEK targeting in mCRC. Unbiased high-throughput screening (HTS) was performed to identify drugs that enhance the efficacy of MEK inhibitors. HTS was performed with KRAS-mutated CRC cells using the MEK inhibitor trametinib as a “backbone” and two “clinically ready” compound libraries approved by the U.S. Food and Drug Administration or in clinical trials. HTS demonstrated that the combination of the SRC inhibitor dasatinib and trametinib was synergistic in CRC cells in vitro (MTT and colony formation assays). Analysis of markers for cell proliferation and apoptosis using fluorescence-activated cell sorting, reverse-phase protein array, or Western blotting demonstrated decreased cell proliferation and increased cell death when targeting both SRC and MEK as compared to single agents in multiple CRC cell lines. However, combining dasatinib and trametinib in vivo at doses in mice equivalent to doses used in humans failed to significantly enhance the antitumor activity of trametinib when compared to that of trametinib alone. These results underscore the importance of performing careful preclinical in vivo validation studies using clinically relevant doses as a prerequisite for translating in vitro findings to the clinic.
Research on the evaluation method of agricultural intelligent robot design solutions
Authors: Tang Qian , Luo Ying-Wen , Wu Xiao-Di
Published: March 2023

Background

At present, agricultural robots are produced in large quantities and used in agricultural planting, and the traditional agricultural model is gradually shifting to rely on the Internet of Things and sensors to accurately detect crop growth information. The scientific and rational design of agricultural robots plays a huge role in planting and production efficiency, however, the factors affecting their design are complex and ambiguous, so it is necessary to use a rational evaluation system to make a preferential decision among multiple design options.

Purposes

In order to reduce the subjectivity and blindness of program selection in the process of agricultural robot design, make the decision more objective and reasonable, and thus enhance the practicality and scientificity of the program, a new comprehensive evaluation method based on user requirements is proposed.

Methods

First, after researching and interviewing users and farming operations, obtaining raw information on requirements, using the Kano model to classify the requirements and establishing an evaluation index system. Secondly, the combination of hierarchical analysis(AHP) and entropy weighting method is used to assign weights to the evaluation index system, calculate the weight value and importance ranking of each index, and carry out various program designs based on the ranking. Finally, the VIKOR method was applied to evaluate and rank the design solutions.

Results

The new evaluation method can better complete the preferential decision of the agricultural robot design scheme and get a more perfect design scheme, which reduces the influence of human subjective thinking in the decision-making process.

Conclusions

The method not only corrects the traditional evaluation method, but also effectively improves the accuracy and comprehensiveness of the design evaluation process. It also provides a reference for designers to preferably select design solutions and promotes the development of small mobile machines in the context of smart agriculture.
Reading fluency and statistical learning across modalities and domains: Online and offline measures
Authors: Lukács Ágnes , Dobó Dorottya , Szőllősi Ágnes , Németh Kornél , Lukics Krisztina Sára
Published: March 2023

The vulnerability of statistical learning has been demonstrated in reading difficulties in both the visual and acoustic modalities. We examined segmentation abilities of Hungarian speaking adolescents with different levels of reading fluency in the acoustic verbal and visual nonverbal domains. We applied online target detection tasks, where the extent of learning is reflected in differences between reaction times to predictable versus unpredictable targets. Explicit judgments of well-formedness were also elicited in an offline two-alternative forced choice (2AFC) task. Learning was evident in both the acoustic verbal and visual nonverbal tasks, both in online and offline measures, but learning effects were larger both in online and offline tasks in the verbal acoustic condition. We haven’t found evidence for a significant relationship between statistical learning and reading fluency in adolescents in either modality. Together with earlier findings, these results suggest that the relationship between reading and statistical learning is dependent on the domain, modality and nature of the statistical learning task, on the reading task, on the age of participants, and on the specific language. The online target detection task is a promising tool which can be adapted to a wider set of tasks to further explore the contribution of statistical learning to reading acquisition in participants from different populations.
Predicting spinal column profile from surface topography via 3D non-contact surface scanning
Authors: Rayward Lionel , Pearcy Mark , Izatt Maree , Green Daniel , Labrom Robert , Askin Geoffrey , Little J. Paige
Published: March 2023

Introduction

3D Non-Contact surface scanning (3DSS) is used in both biomechanical and clinical studies to capture accurate 3D images of the human torso, and to better understand the shape and posture of the spine–both healthy and pathological. This study sought to determine the efficacy and accuracy of using 3DSS of the posterior torso, to determine the curvature of the spinal column in the lateral lying position.

Methods

A cohort of 50 healthy adults underwent 3DSS and Magnetic Resonance Imaging (MRI) to correlate the contours of the external spine surface with the internal spinal column. The correlation analysis was composed of two phases: (1) MRI vertebral points vs MRI external spine surface markers; and (2) MRI external spine surface markers vs 3DSS external spine surface markers. The first phase compared the profiles of fiducial markers (vitamin capsules) adhered to the skin surface over the spinous processes against the coordinates of the spinous processes–assessing the linear distance between the profiles, and similarity of curvature, in the sagittal and coronal planes. The second phase compared 3DSS external spine surface markers with the MRI external spine surface markers in both planes, with further qualitative assessment for postural changes.

Results

The distance between the MRI vertebral points and MRI external spine surface markers showed strong statistically significant correlation with BMI in both sagittal and coronal planes. Kolmogorov-Smirnov (KS) tests showed similar no significant difference in curvature, k, in almost all participants on both planes. In the second phase, the coronal 3DSS external spine surface profiles were statistically different to the MRI external spine surface markers in 44% of participants. Qualitative assessment showed postural changes between MRI and 3DSS measurements in these participants.

Conclusion

These study findings demonstrate the utility and accuracy of using anatomical landmarks overlaid on the spinous processes, to identify the position of the spinal bones using 3DSS. Using this method, it will be possible to predict the internal spinal curvature from surface topography, provided that the thickness of the overlaying subcutaneous adipose layer is considered, thus enabling postural analysis of spinal shape and curvature to be carried out in biomechanical and clinical studies without the need for radiographic imaging.
Amino acid substitutions in human growth hormone affect secondary structure and receptor binding
Authors: Rajkovic Andrei , Kanchugal Sandesh , Abdurakhmanov Eldar , Howard Rebecca , Wärmländer Sebastian , Erwin Joseph , Barrera Saldaña Hugo A. , Gräslund Astrid , Danielson Helena , Flores Samuel Coulbourn
Published: March 2023

The interaction between human Growth Hormone (hGH) and hGH Receptor (hGHR) has basic relevance to cancer and growth disorders, and hGH is the scaffold for Pegvisomant, an anti-acromegaly therapeutic. For the latter reason, hGH has been extensively engineered by early workers to improve binding and other properties. We are particularly interested in E174 which belongs to the hGH zinc-binding triad; the substitution E174A is known to significantly increase binding, but to now no explanation has been offered. We generated this and several computationally-selected single-residue substitutions at the hGHR-binding site of hGH. We find that, while many successfully slow down dissociation of the hGH-hGHR complex once bound, they also slow down the association of hGH to hGHR. The E174A substitution induces a change in the Circular Dichroism spectrum that suggests the appearance of coiled-coiling. Here we show that E174A increases affinity of hGH against hGHR because the off-rate is slowed down more than the on-rate. For E174Y (and certain mutations at other sites) the slowdown in on-rate was greater than that of the off-rate, leading to decreased affinity. The results point to a link between structure, zinc binding, and hGHR-binding affinity in hGH.