bluuebunny/crossref_metadata_2025 huggingface dataset:
Military against Salazar: Abrilada of 1961
Authors:   Institute of the World History of the Russian Academy of Science., Filatov George
Published: April 2023

Created by António Salazar, the New State relied heavily on the sup-port of the armed forces. Nevertheless, in April 1961, a group of gener-als led by the Minister of Defense tried to remove him from power. Their dissatisfaction was caused not by the system, but by the war in Angola, the first stage of which was not successful for Portugal. Salazar was blamed for not listening to warnings from the military and intelli-gence agencies. No reforms were conducted in the overseas possessions to prevent the revolt, no additional forces were sent to the colony. At first, the military planned to remove Salazar in a constitutional way, according to the rules and institutions of the New State. First, the mili-tary had to obtain the support of the President Américo Thomaz. It re-sulted in many days of negotiations with the head of the country, in the hope that he would take the side of the military. It was only when it became clear that Tomás remained loyal to Salazar the generals decided to put troops on the streets. However, this decision came too late. Sala-zar and Tomás gave orders to remove the rebels from their posts, an-nouncing that on the radio. As a result, the chain of command was bro-ken, and the conspirators no longer had confidence that the troops would obey them. As a result, this attempted military coup did not go beyond the cabinet negotiations.
Techniques for creating and printing historical architectural artifacts in 3D
Authors: Hevko Igor , Potapchuk Olha , Lutsyk Iryna , Yavorska Viktoria , Tkachuk Viktoriia
Published: April 2023

The authors outline techniques for creating and printing three-dimensional models that can be used to graphically rebuild old architectural pieces. The construction of a model of the 1950s Parochial Cathedral of St. Mary of the Perpetual Assistance serves as an illustration of the methodologies' order of operation. The most widely used specialized software tools have been examined and evaluated, and the 3DS Max environment has been selected to create a three-dimensional model. The suggested software solutions provide effective methods for handling large amounts of data and are pertinent to current IT developments. They also boost the accuracy, speed, and granularity of fixing complex systems and extended databases. The order and nature of the operations for the cycles of analysis and modeling are supported. The cathedral model was constructed from old photos and sketches. To reconstruct the architectural object, the authors discuss techniques, an algorithm of steps, and the fundamentals of architectural and spacious modeling. The stereogram miniature of the demolished Cathedral is used to create the three-dimensional model. The measurement of picture parallax serves as the foundation for the reconstruction of spacious object configuration. The phases of the project's execution are chosen. Methods for implementing modeling using 3DS Max tools and getting the model ready for 3D printing in Cura are presented.
Performance of Organizational Staff and Guest Satisfaction in the Tourism Industry in Indonesia
Authors: Witarsa Witarsa , Darsana I Made , Sudjana I Made , Abdu Wamaungo Juma
Published: April 2023

The waiter’s role is of great importance in the smooth operation of a restaurant business within the tourism industry. Thus, it is necessary to critically examine the waiter’s performance concerning guest satisfaction in a tourism organization. In the case of this study, a waiter not only performs the role of a waitress but is also tasked to become an ambassador within the sector. Taking Warung Mesari in the context of this study, waiters must display good hospitality in welcoming visitors and introducing and preserving the restaurant’s image. Based on this view, the present study looks at the performance of waiters as a way to contribute to the increament in the number of guests satisfied with the services provided by warung Mesari. The research method used is descriptive-qualitative, with data collection techniques in the form of interviews, documentation studies, and observations. This study revealed that: the waiters were able to provide good service and establish good relationships with guests who visited the restaurant; the waiters have done their job successfully; the restaurant has received many positive guest comments from guests; the restaurant also gets repeater guests; and guests who have visited again invite their friends to visit the Warung Mesari restaurant.
Zastosowania dorobku metodologicznego Marii Wojtak w badaniach genologicznych i kontrastywnych w obszarze germanistycznym
Authors: Mac Agnieszka , Bilut-Homplewicz Zofia , Hanus Anna
Published: April 2023

Cel: Opracowanie ma na celu skonfrontowanie i ukazanie wykorzystania wybranych dokonań Marii Wojtak w zakresie opisu kategorii wzorca gatunkowego i analiz genologicznych w pracach germanistycznych i kontrastywnych. Metodologia: Wypracowany przez Autorkę katalog pojęć i instrumentarium badawcze zostaną zestawione z podobnymi ujęciami i propozycjami metodologicznymi charakterystycznymi dla podejść germanistycznych oraz przedyskutowane pod kątem ich rozbieżności, własności wspólnych oraz możliwości twórczego posłużenia się nimi, poprzez połączenie poszczególnych koncepcji w propozycjach metodologicznych. Wyniki i wnioski: Kontrastywne spojrzenie na koncepcje wyrosłe z dwóch odmiennych tradycji lingwistycznych pozwala z różnych perspektyw naświetlać opisywane w artykule zjawiska, co z jednej strony jawi się jako wyzwanie dotyczące postępowania badawczego, ale z drugiej może wskazać nowe kierunki eksploracji, wyzwolić inspiracje czy też impulsy badawcze prowadzące do twórczej refleksji metodologicznej. Wartość poznawcza: Artykuł jest przyczynkiem do dyskusji dotyczącej znaczenia badań kontrastywnych w zakresie dwóch obszarów badawczych, polonistycznego i germanistycznego, wskazuje na podobieństwa i różnice w metodologii koncepcji genologicznych oraz ich zastosowania, zapoznaje czytelników z badaniami wyżej wymienionych kultur piśmienniczych, inspirując do prowadzenia dalszych badań w tym zakresie.
Effect of two additional doses of intrathecal methotrexate during induction therapy on serious infectious toxicity in pediatric patients with acute lymphoblastic leukemia
Authors: Heilmann Janina , Vieth Simon , Möricke Anja , Attarbaschi Andishe , Barbaric Draga , Bodmer Nicole , Colombini Antonella , Dalla-Pozza Luciano , Elitzur Sarah , Izraeli Shai , Mann Georg , Niggli Felix , Silvestri Daniela , Stary Jan , Rizzari Carmelo , Valsecchi Maria Grazia , Zapotocka Ester , Zimmermann Martin , Cario Gunnar , Schrappe Martin , Conter Valentino
Published: April 2023

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses. The impact of additional intrathecal (IT) MTX on systemic toxicity in induction therapy is unknown. Between June 1st 2010 and February 28th 2017, a total of 6,136 ALL patients aged 1-17 years were enrolled onto the AIEOP-BFM ALL 2009 trial. The effect of three versus five doses of IT MTX during induction therapy on the incidence of severe infectious complications was analyzed. Among 4,706 patients treated with three IT MTX doses, 77 (1.6%) had a life-threatening infection during induction as compared to 59 of 1,350 (4.4%) patients treated with five doses (P<0.001; Odds Ratio 2.86 [95% Confidence Interval 1.99-4.13]). In a multivariate regression model, treatment with additional IT MTX proved to be the strongest risk factor for life-threatening infections (Odds Ratio 2.85 [1.96-4.14]). Fatal infections occurred in 16 (0.3%) and 38 (1.6%) patients treated with three or five IT MTX doses, respectively (P<0.001). As the relevance of additional intrathecal MTX in induction for relapse prevention in CNS2 patients is unclear, doses of intrathecal therapy have been reduced for these patients. (Clinicaltrials.gov identifiers: NCT01117441 and NCT00613457).
Information-theoretical approach to the analysis of students' plans for their future careers
Authors: Vinokurova Natalia
Published: April 2023

The article provides a statistical analysis of students' intentions regarding the choice of work after graduation. The data of a survey of students on the assessment of the importance of various motives for choosing targets are used. The main goal was to find the structure of the set of intentions, which is expressed in the form of a graph of direct connections. The interrelationships between assessments of intentions define the typology of students according to their target orientation. Due to the integrity of the intent measurement scale, two ways of evaluating relationships could be used: standard correlation and information-theoretic. As calculations have shown, both methods give similar results. For the analysis, those direct connections that were identified by both methods were used. This confirms to a certain extent the possibility of using Shannon information to find direct connections by the method of partial correlations in the case of nominal scales. The found graph of direct connections revealed the typology of students' intentions and thus allows us to talk about the students themselves.
Evaluasi Implementasi Program Penguatan Budaya Kerja SMK di Jawa Barat
Authors: Nasyaliyah Laila , Situmorang Robinson , Nurani Yuliani
Published: April 2023

This study aims to evaluate the implementation of government assistance programs to strengthen the work culture of vocational schools in West Java in 2020. This research was evaluation research using a goal-oriented evaluation model by Raplh W. Tyler, which used a quantitative approach. Data collection techniques used questionnaires and documentation. Respondents used as data sources were school principals or teachers in charge of the assistance program, with a sample of 10 SMK in West Java. This research data analysis technique used descriptive statistics. The results of the evaluation of this evaluation research were (1) Schools could apply work culture in the learning process and practice according to competency skills and aligned with the needs of the world of work (2) Students gained understanding and ability to apply work culture from the world of work. The conclusion from this research is that the beneficiaries of the assistance program have carried out all the program components properly.
Vocational High School Strategic Efforts in Dealing with ASEAN Economic Communities
Authors: Suranto Suranto , Rahmawati Lutfi , Rohmah Wafrotur , Gano-an Jonathan Camana , Amanda Bunga
Published: April 2023

This study aims to reveal the readiness and efforts of vocational high schools in dealing with the ASEAN economic community. This research was qualitative research with an ethnographic design. Informants in this study were the principal, deputy head of the curriculum, the head of the accounting department, and the accounting teachers at SMK Negeri 1 Karanganyar and SMK Muhammadiyah 2 Surakarta. The data collection techniques used in this study were interviews and observation. Data analysis was carried out through data collection, data reduction, and data presentation to draw conclusions. The results of this study showed that SMKN 1 Karanganyar and SMK Muhammadiyah 2 Surakarta made preparatory efforts to deal with the ASEAN economic community. Those preparatory efforts included increasing the students’ skills through learning, both theoretically and practically, inside and outside the school environment, such as collaborating with the industrial and the business field, implementing the 2013 curriculum, increasing teacher knowledge through MGMP (Deliberation Subject Teachers), inviting teachers from institutions or universities, and completing school infrastructure. The research conducted in both schools revealed differences in efforts to prepare their students. These differences include SMK Negeri 1 Karanganyar innovating to invite other teachers to update the knowledge of teachers and students, build their accounting laboratories, and support teachers to be assessors. Meanwhile, SMK Muhammadiyah 2 Surakarta lacks school innovation and teachers as assessors. Furthermore, the laboratory of accounting majors is also used as other majors.
Molecular Diagnosis Compared to Conventional Diagnosis for Rapid Detection of Resistant Strains of Candida Spp.
Authors: Bastos Rafael Carneiro , Alves Erivan Ferreira , Neves Andréa Maria , Vasconcelos Carlos Franciney Moreira , Brito Erika Helena Salles de , Fontenelle Raquel Oliveira dos Santos
Published: April 2023

Yeast Candida spp. can cause serious infections, especially in patients of the hospital environment. Variation in the virulence profile of Candida clinical isolates and high mortality rates indicate the importance of rapid and accurate identification, as well as susceptibility testing for successful candidiasis treatment. A total of 20 strains were isolated from patients from Tertiary Hospital of the Northern Zone of Ceará. PCR amplification followed by agarose gel electrophoresis (PCR-AGE) and the manual method (culturing on CHROMagar-Candida) and VITEK automated method were used to test a total of 20 fungal strains from clinics sources. Five strains of C. albicans, 2 of C. tropicalis and 4 strains of C. parapsilosis which were cultured for the determination of MIC (Minimum Inhibitory Concentration). The best sensitivity rate was demonstrated by automatic identification and PCR-AGE, where all 20 strains isolated with a sensitivity profile of 100% (20/20) were completely identified. According to the data obtained, resistance to amphotericin B (CIM ≥ 1 µg/ml) was observed in some isolates of C. tropicalis and C. parapsilosis. However, for the other antifungals, these same species presented 100% sensitivity (MIC ≤ 0.125 μg / ml; MIC ≤ 8 μg / ml). Isolates of C. albicans were sensitive to all antifungal agents with 100% sensitivity, although 75% of the isolates showed a tendency for less susceptibility to amphotericin B. In this study, we confirmed the efficacy and applicability of PCR-AGE in the identification and differentiation of yeast Candida spp. from clinical samples.
Epidemiological profile of pesticide poisoning cases in the State of Sergipe, Brazil: a retrospective analysis from 2007 to 2021
Authors: Luz Rafael Andersen Alves da Cruz , Oliveira Ana Beatriz Seixas , Garcia Vitor de Carvalho , Rafael Larissa Monteiro , Santos José Ronaldo dos , Lins Lívia Cristina Rodrigues Ferreira
Published: April 2023

We aimed to characterize the epidemiological profile of reported cases of pesticide poisoning in the state of Sergipe between 2007 and 2021. Secondary data were obtained from the National Database of Notifiable Diseases Information System (SINAN) and National Toxicological Information System (SINITOX), through the Department of Informatics  of the Unified Health System (DATASUS) and analysis performed using the free tool Google Sheets. During the studied  period, 960 cases of exogenous pesticide poisoning were registered in the state. The municipality of Aracaju had the highest percentage of the number of cases. The incidence prevailed in females, in the 20-39 age group, in the brown  race and among those with incomplete primary education. The most used toxic agent was rodenticide, suicide attempt  predominated as a circumstance of use. Most cases resulted from a single acute exposure, confirmed by the clinical-epidemiological method, and evolved to a cure without sequelae. This study traced the epidemiological profile of the  State of Sergipe with regard to the intoxication of the population and, in addition, brought little explored data and  information that directly impacts policies aimed at reducing morbidity and mortality resulting from the use of pesticides.
Renal Stones: A Clinical Review
Authors: Aggarwal Ramesh , Srivastava Anshuman , Jain Sachin Kumar , Sud Ritika , Singh Rati
Published: April 2023

Renal stones are a common condition causing significant morbidity and economic burden. The prevalence of urinary tract stones in the developed nations ranges from 4–20%. Renal stones are of different types, the most common being the calcium oxalate stones. Various dietary, non-dietary, and urinary risk factors contribute to their formation. Their frequent association with systemic diseases (like hypertension, diabetes, and obesity) highlights the role of dietary and lifestyle changes in their occurrence, recurrence, and possible prevention. Non-contrast computed tomography (CT) identifies almost every stone and is the preferred investigation for identification. Ultrasound has its advantages, as it is low cost and requires no radiation, but is observer dependent. Metabolic profiles (including blood calcium, phosphate, magnesium, creatinine, uric acid, sodium, and potassium) should be measured and a detailed urinalysis should be done. This review further discusses the formation in depth, and covers risk factors and management of renal stones, and lays down the importance of preventive measures to avoid their recurrence.
Orthogonal analysis of variants in APOE gene using in-silico approaches reveals novel disrupting variants
Authors: Li Chang , Hou Ian , Ma Mingjia , Wang Grace , Bai Yongsheng , Liu Xiaoming
Published: April 2023

Introduction: Alzheimer’s disease (AD) is one of the most prominent medical conditions in the world. Understanding the genetic component of the disease can greatly advance our knowledge regarding its progression, treatment and prognosis. Single amino-acid variants (SAVs) in the APOE gene have been widely investigated as a risk factor for AD Studies, including genome-wide association studies, meta-analysis based studies, and in-vivo animal studies, were carried out to investigate the functional importance and pathogenesis potential of APOE SAVs. However, given the high cost of such large-scale or experimental studies, there are only a handful of variants being reported that have definite explanations. The recent development of in-silico analytical approaches, especially large-scale deep learning models, has opened new opportunities for us to probe the structural and functional importance of APOE variants extensively.

Method: In this study, we are taking an ensemble approach that simultaneously uses large-scale protein sequence-based models, including Evolutionary Scale Model and AlphaFold, together with a few in-silico functional prediction web services to investigate the known and possibly disease-causing SAVs in APOE and evaluate their likelihood of being functional and structurally disruptive.

Results: As a result, using an ensemble approach with little to no prior field-specific knowledge, we reported 5 SAVs in APOE gene to be potentially disruptive, one of which (C112R) was classificed by previous studies as a key risk factor for AD.

Discussion: Our study provided a novel framework to analyze and prioritize the functional and structural importance of SAVs for future experimental and functional validation.
Corneal optical density: Structural basis, measurements, influencing factors, and roles in refractive surgery
Authors: He Ye , Ma Bo-Sheng , Zeng Jun-Hao , Ma Dai-Jin
Published: April 2023

The cornea is the main refractive medium of the human eye, and its clarity is critical to visual acuity. Corneal optical density (COD) is an important index to describe corneal transparency. Intact corneal epithelial and endothelial cells, regular arrangement of collagen fibers in the stroma, and normal substance metabolism are all integral for the cornea to maintain its transparency. In the last two decades, the Pentacam Scheimpflug imaging system has emerged as a breakthrough for the measurement of COD (also called corneal densitometry). It has been found that a wide variety of factors such as age, refractive status, and corneal diseases can affect COD. Different corneal refractive surgery methods also change COD in different corneal regions and layers and affect visual acuity following the surgery. Thus, COD has gradually become a significant indicator to evaluate corneal health, one on which the attention of clinicians has been increasingly focused.
Granulosa cell-derived extracellular vesicles mitigate the detrimental impact of thermal stress on bovine oocytes and embryos
Authors: Menjivar Nico G. , Gad Ahmed , Gebremedhn Samuel , Ghosh Soham , Tesfaye Dawit
Published: April 2023

Climate change-induced global warming results in rises in body temperatures above normal physiological levels (hyperthermia) with negative impacts on reproductive function in dairy and beef animals. Extracellular vesicles (EVs), commonly described as nano-sized, lipid-enclosed complexes, harnessed with a plethora of bioactive cargoes (RNAs, proteins, and lipids), are crucial to regulating processes like folliculogenesis and the initiation of different signaling pathways. The beneficial role of follicular fluid-derived EVs in inducing thermotolerance to oocytes during in vitro maturation (IVM) has been evidenced. Here we aimed to determine the capacity of in vitro cultured granulosa cell-derived EVs (GC-EVs) to modulate bovine oocytes’ thermotolerance to heat stress (HS) during IVM. Moreover, this study tested the hypothesis that EVs released from thermally stressed GCs (S-EVs) shuttle protective messages to provide protection against subsequent HS in bovine oocytes. For this, sub-populations of GC-EVs were generated from GCs subjected to 38.5°C (N-EVs) or 42°C (S-EVs) and supplemented to cumulus-oocyte complexes (COCs) matured in vitro at the normal physiological body temperature of the cow (38.5°C) or HS (41°C) conditions. Results indicate that S-EVs improve the survival of oocytes by reducing ROS accumulation, improving mitochondrial function, and suppressing the expression of stress-associated genes thereby reducing the severity of HS on oocytes. Moreover, our findings indicate a carryover impact from the addition of GC-EVs during oocyte maturation in the development to the blastocyst stage with enhanced viability.
Investigating the effect of synthesis selection on O3-sodium layered oxide structural changes and electrochemical properties
Authors: Acebo L. , Drewett N. E. , Saurel D. , Bonilla F. , Rojo T. , Galceran M.
Published: April 2023

Transition metal (TM) layered oxides constitute a promising family of materials for use in Na-ion battery cathodes. Here O3-Na (Ni1/3Mn1/3Fe1/3) O2 was synthesised using optimised sol-gel and solid-state routes, and the physico- and electrochemical natures of the resulting materials were thoroughly studied. Significant differences in electrochemical behaviour were observed, and the use of in operando XRD determined this stemmed from the suppression of the P3 phase in the sol-gel material during cycling. This was attributable to differences in the degree of transition metal migration in the materials ensuing from the selection of synthetic route. This demonstrates that not only the choice of material, but also that of synthesis route, can have dramatic impact on the resulting structural and electrochemical nature, making such considerations critical in the future development of advanced Na-ion cathode materials.
Clinical values of metagenomic next-generation sequencing in patients with severe pneumonia: a systematic review and meta-analysis
Authors: Lv Minjie , Zhu Changjun , Zhu Chenghua , Yao Jing , Xie Lixu , Zhang Changwen , Huang Jianling , Du Xingran , Feng Ganzhu
Published: April 2023

Background

Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to evaluate the diagnostic performance of mNGS for pathogen detection and its role in the prognosis of severe pneumonia.

Methods

We systematically searched the literature published in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, CNKI, Wanfang Data, and CBM from the inception to the 28th September 2022. Relevant trials comparing mNGS with conventional methods applied to patients with severe pneumonia were included. The primary outcomes of this study were the pathogen-positive rate, the 28-day mortality, and the 90-day mortality; secondary outcomes included the duration of mechanical ventilation, the length of hospital stay, and the length of stay in the ICU.

Results

Totally, 24 publications with 3220 patients met the inclusion criteria and were enrolled in this study. Compared with conventional methods (45.78%, 705/1540), mNGS (80.48%, 1233/1532) significantly increased the positive rate of pathogen detection [OR = 6.81, 95% CI (4.59, 10.11, P < 0.001]. The pooled 28-day and 90-day mortality in mNGS group were 15.08% (38/252) and 22.36% (36/161), respectively, which were significantly lower than those in conventional methods group 33.05% (117/354) [OR = 0.35, 95% CI (0.23, 0.55), P < 0.001, I2 = 0%] and 43.43%(109/251) [OR = 0.34, 95% CI (0.21, 0.54), P < 0.001]. Meanwhile, adjusted treatment based on the results of mNGS shortened the length of hospital stay [MD = -2.76, 95% CI (− 3.56, − 1.96), P < 0.001] and the length of stay in ICU [MD = -4.11, 95% CI (− 5.35, − 2.87), P < 0.001].

Conclusion

The pathogen detection positive rate of mNGS was much higher than that of conventional methods. Adjusted treatment based on mNGS results can reduce the 28-day and 90-day mortality of patients with severe pneumonia, and shorten the length of hospital and ICU stay. Therefore, mNGS advised to be applied to severe pneumonia patients as early as possible in addition to conventional methods to improve the prognosis and reduce the length of hospital stay.
A new approach to overcoming antibiotic-resistant bacteria: Traditional Chinese medicine therapy based on the gut microbiota
Authors: Xue Peng , Sang Rui , Li Nan , Du Siyuan , Kong Xiuwen , Tai Mingliang , Jiang Zhihao , Chen Ying
Published: April 2023

With the irrational use of antibiotics and the increasing abuse of oral antibiotics, the drug resistance of gastrointestinal pathogens has become a prominent problem in clinical practice. Gut microbiota plays an important role in maintaining human health, and the change of microbiota also affects the activity of pathogenic bacteria. Interfering with antibiotic resistant bacteria by affecting gut microbiota has also become an important regulatory signal. In clinical application, due to the unique advantages of traditional Chinese medicine in sterilization and drug resistance, it is possible for traditional Chinese medicine to improve the gut microbial microenvironment. This review discusses the strategies of traditional Chinese medicine for the treatment of drug-resistant bacterial infections by changing the gut microenvironment, unlocking the interaction between microbiota and drug resistance of pathogenic bacteria.
Comparative transcriptomes reveal pro-survival and cytotoxic programs of mucosal-associated invariant T cells upon Bacillus Calmette–Guérin stimulation
Authors: Sharma Manju , Niu Liang , Zhang Xiang , Huang Shouxiong
Published: April 2023

Mucosal-associated invariant T (MAIT) cells are protective against tuberculous and non-tuberculous mycobacterial infections with poorly understood mechanisms. Despite an innate-like nature, MAIT cell responses remain heterogeneous in bacterial infections. To comprehensively characterize MAIT activation programs responding to different bacteria, we stimulated MAIT cells with E. coli to compare with Bacillus Calmette-Guérin (BCG), which remains the only licensed vaccine and a feasible tool for investigating anti-mycobacterial immunity in humans. Upon sequencing mRNA from the activated and inactivated CD8+ MAIT cells, results demonstrated the altered MAIT cell gene profiles by each bacterium with upregulated expression of activation markers, transcription factors, cytokines, and cytolytic mediators crucial in anti-mycobacterial responses. Compared with E. coli, BCG altered more MAIT cell genes to enhance cell survival and cytolysis. Flow cytometry analyses similarly displayed a more upregulated protein expression of B-cell lymphoma 2 and T-box transcription factor Eomesodermin in BCG compared to E.coli stimulations. Thus, the transcriptomic program and protein expression of MAIT cells together displayed enhanced pro-survival and cytotoxic programs in response to BCG stimulation, supporting BCG induces cell-mediated effector responses of MAIT cells to fight mycobacterial infections.
Understanding bacterial biofilms: From definition to treatment strategies
Authors: Zhao Ailing , Sun Jiazheng , Liu Yipin
Published: April 2023

Bacterial biofilms are complex microbial communities encased in extracellular polymeric substances. Their formation is a multi-step process. Biofilms are a significant problem in treating bacterial infections and are one of the main reasons for the persistence of infections. They can exhibit increased resistance to classical antibiotics and cause disease through device-related and non-device (tissue) -associated infections, posing a severe threat to global health issues. Therefore, early detection and search for new and alternative treatments are essential for treating and suppressing biofilm-associated infections. In this paper, we systematically reviewed the formation of bacterial biofilms, associated infections, detection methods, and potential treatment strategies, aiming to provide researchers with the latest progress in the detection and treatment of bacterial biofilms.
Perioperative management of aortic stenosis in patients undergoing non-cardiac surgery
Authors: Herrera Roberto A. , Smith Mark M. , Mauermann William J. , Nkomo Vuyisile T. , Luis Sushil Allen
Published: April 2023

Aortic stenosis is one of the most common cardiac valve pathologies in the world and its prevalence increases with age. Although previously associated with increased perioperative mortality, more recent studies suggest that mortality rates may be decreasing. Recent guidelines suggest that major non-cardiac surgery can be performed safely in asymptomatic severe aortic stenosis patients with close hemodynamic monitoring. Among symptomatic patients, the guidelines recommend aortic valve intervention prior to major non-cardiac surgery because of a reduction in the incidence of postoperative heart failure and improved rates of long-term overall survival. This review provides a comprehensive and contemporary review of the perioperative management of patients with severe aortic valve stenosis.
Evaluating the TUITEK® patient support program in supporting caregivers of children diagnosed with growth hormone deficiency in Argentina
Authors: Assefi Aria Reza , Graham Selina , Crespo María Lourdes , Debicki Matías , Reston Jonathan , Gonzalez Judit , Jheeta Amrit , Koledova Ekaterina
Published: April 2023

Introduction

The appropriate use of recombinant human growth hormone (r-hGH) treatment provides an opportunity to improve growth outcomes among pediatric patients with growth hormone deficiency (GHD). However, a major challenge in clinical practice is to adequately recognize and address factors that negatively affect treatment adherence. TUITEK® patient support program (PSP) was designed to help caregivers of children diagnosed with GHD to personalize the care pathway, improve adherence, and achieve better outcomes. Effectiveness of TUITEK® PSP has been demonstrated previously in a smaller sample (n = 31) in Taiwanese population. Here, we present the results from Argentina.

Methods

TUITEK® PSP was piloted among 76 caregivers of children with GHD administering r-hGH using easypod™ (Merck KGaA, Darmstadt, Germany) auto-injector device in Argentina. Based on TUITEK® personalization questionnaire, caregivers were assigned to high- and low-risk groups across four categories that may influence adherence, including disease and treatment coherence (DTC), self-administration (SA), treatment-related anxiety (TRA), and emotional burden (EB). The caregivers who were included in atleast one high-risk group had the provision of telephone calls with a nurse practitioner every 2 weeks for 3 months. The Wilcoxon signed-rank test was employed to assess changes in questionnaire-based scoring patterns between baseline and follow-up evaluations.

Results

Statistically significant changes (p < 0.05) in questionnaire scores between baseline and follow-up evaluations were observed across the four categories. The mean/median DTC (n = 11) and SA (n = 23) scores changed from 2.45/3 and 2.17/2, respectively, to 4/4, with all the caregivers moving to low-risk group following program completion (100%) for both categories. The mean/median TRA score (n = 40) changed from 3.58/3 to 2.5/2 and 67.5% of patients (27/40) moved to low-risk group. The mean/median EB score (n = 32) changed from 3.69/3 to 3.13/3 however, none of the caregivers moved to low-risk group (0%).

Conclusion

TUITEK® PSP is a simple, practical, and time-efficient interventional tool that can be used to address key adherence-related issues among caregivers of children with GHD and provide personalized adherence support. Our findings demonstrate that TUITEK® PSP has the potential to improve treatment adherence and self-management, thereby improving growth outcomes in Argentina.
Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
Authors: Cao Shengji , Xiao Sitong , Zhang Jingyang , Li Shijun
Published: April 2023

Background

The genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.

Methods

This study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.

Results

First, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.

Conclusion

This study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.
The roles of hepatokine and osteokine in liver-bone crosstalk: Advance in basic and clinical aspects
Authors: Li Zhanghao , Wen Xiaoxin , Li Nanxi , Zhong Chuanxin , Chen Li , Zhang Feng , Zhang Ge , Lyu Aiping , Liu Jin
Published: April 2023

Both the liver and bone are important secretory organs in the endocrine system. By secreting organ factors (hepatokines), the liver regulates the activity of other organs. Similarly, bone-derived factors, osteokines, are created during bone metabolism and act in an endocrine manner. Generally, the dysregulation of hepatokines is frequently accompanied by changes in bone mass, and osteokines can also disrupt liver metabolism. The crosstalk between the liver and bone, particularly the function and mechanism of hepatokines and osteokines, has increasingly gained notoriety as a topic of interest in recent years. Here, based on preclinical and clinical evidence, we summarize the potential roles of hepatokines and osteokines in liver-bone interaction, discuss the current shortcomings and contradictions, and make recommendations for future research.
Mixed-flow pump performance improvement based on circulation method
Authors: Chen Jiaqi , Wang Mengcheng , Bao Yonghao , Chen Xiao , Xia Hepeng
Published: April 2023

Mixed-flow pumps have been extensively employed in daily life, improving their energy characteristics contribute to the reduction of energy consumption worldwide. In this study, to overcome the decrease of optimization upper limit caused by using a single type of parameter as the design parameter, a typical mixed-flow pump was chosen for study, and its impeller was parameterized by five geometric and eight hydrodynamic parameters. With head and efficiency as the constraint and optimization objective respectively, 27 schemes were constructed by the Taguchi method. The influence of design factors to the objective and constraint was analyzed based on range and regression analysis. The optimization mechanism was elucidated using the entropy production method. The result reveals that the geometric and hydrodynamic parameters have a significantly impact on the mixed-flow pump’s energy characteristics. The optimized model head is 12.43m, which meets the constraints, while the efficiency increases by 3.2%–88.51%. Therefore, considering both geometric and hydrodynamic parameters in the mixed-flow pump optimization is workable and necessary. This paper can provide practical instructions on the optimal design of different turbomachines.
Polymorphism in genes encoding two fatty acid binding proteins increases risk of ischemic stroke in a Chinese Han population
Authors: Cao Maolin , Zhang Yifei , Chen Dan , Zhong Jiaju , Zhang Xiaoli , Yang Ling , Li Xue , Fang Liang , Liu Beizhong , Gong Fang , Zhou Chanjuan
Published: April 2023

Background: Dyslipidemia is an independent predictor of ischemic stroke (IS). Genetic variations in lipid-metabolism related genes may increase the risk of IS. Fatty acid-binding protein 1 (FABP1) and fatty acid-binding protein 2 (FABP2) are lipid chaperones responsible for lipid transport and metabolism. The present study aimed to determine the association between FABP1 or FABP2 and ischemic stroke.

Methods: A total of 251 participants were recruited composed of 138 patients with ischemic stroke and 113 healthy subjects. DNA was extracted from peripheral blood samples. The rs2241883 polymorphism in FABP1 and rs1799883 polymorphism in FABP2 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Generalized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between two SNPs and environmental factors.

Results: The GA genotype of FABP2 rs1799883 increased susceptibility to ischemic stroke under overdominant inheritance model (p = 0.042). After adjusting for the risk factors of IS, it was associated with a significantly higher risk of IS in the codominant inheritance model (adjust OR = 3.431, 95%CI = 1.060–11.103, p = 0.04). The interactions of FABP1 rs2241883 and FABP2 rs1799883 were not associated with IS risk (p = 0.172). Moreover, interaction analysis of two genes (rs1799883 and rs2241883) and two environmental factors (smoking and alcohol consumption) was associated with an increased risk of IS (p = 0.011).

Conclusion: The GA genotype of FABP2 rs1799883, interactions between rs1799883, rs2241883 and smoking and alcohol consumption were associated with IS risk in Chinese Han populations.
Springer: An R package for bi-level variable selection of high-dimensional longitudinal data
Authors: Zhou Fei , Liu Yuwen , Ren Jie , Wang Weiqun , Wu Cen
Published: April 2023

In high-dimensional data analysis, the bi-level (or the sparse group) variable selection can simultaneously conduct penalization on the group level and within groups, which has been developed for continuous, binary, and survival responses in the literature. Zhou et al. (2022) (PMID: 35766061) has further extended it under the longitudinal response by proposing a quadratic inference function-based penalization method in gene–environment interaction studies. This study introduces “springer,” an R package implementing the bi-level variable selection within the QIF framework developed in Zhou et al. (2022). In addition, R package “springer” has also implemented the generalized estimating equation-based sparse group penalization method. Alternative methods focusing only on the group level or individual level have also been provided by the package. In this study, we have systematically introduced the longitudinal penalization methods implemented in the “springer” package. We demonstrate the usage of the core and supporting functions, which is followed by the numerical examples and discussions. R package “springer” is available at https://cran.r-project.org/package=springer.
Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns
Authors: Mhatre Anisha , Koroth Jinsha , Manjunath Meghana , Kumar S Sandeep , Gawari Ramesh , Choudhary Bibha
Published: April 2023

Introduction: In India, OVCa is women’s third most common and lethal cancer type, accounting for 6.7% of observed cancer incidences. The contribution of somatic mutations, aberrant expression of gene and splice forms in determining the cell fate, gene networks, tumour-specific variants, and the role of immune fraction infiltration have been proven essential in understanding tumorigenesis. However, their interplay in OVCa in a histotype-specific manner remains unclear in the Indian context. In the present study, we aimed to unravel the Indian population histotype-specific exome variants, differentially expressed gene modules, splice events and immune profiles of OVCa samples.

Methods: We analysed 10 tumour samples across 4 ovarian cancer histotypes along with 2 normal patient samples. This included BCFtool utilities and CNVkit for exome, WGCNA and DESeq2 for obtaining differential module hub genes and dysregulated miRNA targets, CIBERSORTx for individual immune profiles and rMATS for tumour specific splice variants.

Result: We identified population-specific novel mutations in Cancer Gene Census Tier1 and Tier2 genes. MUC16, MUC4, CIITA, and NCOR2 were among the most mutated genes, along with TP53. Transcriptome analysis showed significant overexpression of mutated genes MUC16, MUC4, and CIITA, whereas NCOR2 was downregulated. WGCNA revealed histotype-specific gene hubs and networks. Among the significant pathways, alteration in the immune system was one of the pathways, and immune profiling using CIBERSORTx revealed histotype-specific immune cell fraction. miRNA analysis revealed miR-200 family, miR-200a and miR-429 were upregulated in HGSOCs.Splice factor abrasion caused splicing perturbations, with the most abundant alternative splice event being exon skipping and the most spliced gene, SNHG17. Pathway analysis of spliced genes revealed translational elongation and Base excision repair as the pathways altered in OVCa.

Conclusion: Integrated exome, transcriptome, and splicing patterns revealed different population-specific molecular signatures of ovarian cancer histotypes in the Indian Cohort.
Uncoupled pyroptosis and IL-1β secretion downstream of inflammasome signaling
Authors: Li Yang , Jiang Qianzhou
Published: April 2023

Inflammasomes are supramolecular platforms that organize in response to various damage-associated molecular patterns and pathogen-associated molecular patterns. Upon activation, inflammasome sensors (with or without the help of ASC) activate caspase-1 and other inflammatory caspases that cleave gasdermin D and pro-IL-1β/pro-IL-18, leading to pyroptosis and mature cytokine secretion. Pyroptosis enables intracellular pathogen niche disruption and intracellular content release at the cost of cell death, inducing pro-inflammatory responses in the neighboring cells. IL-1β is a potent pro-inflammatory regulator for neutrophil recruitment, macrophage activation, and T-cell expansion. Thus, pyroptosis and cytokine secretion are the two main mechanisms that occur downstream of inflammasome signaling; they maintain homeostasis, drive the innate immune response, and shape adaptive immunity. This review aims to discuss the possible mechanisms, timing, consequences, and significance of the two uncoupling preferences downstream of inflammasome signaling. While pyroptosis and cytokine secretion may be usually coupled, pyroptosis-predominant and cytokine-predominant uncoupling are also observed in a stimulus-, cell type-, or context-dependent manner, contributing to the pathogenesis and development of numerous pathological conditions such as cryopyrin-associated periodic syndromes, LPS-induced sepsis, and Salmonella enterica serovar Typhimurium infection. Hyperactive cells consistently release IL-1β without LDH leakage and pyroptotic death, thereby leading to prolonged inflammation, expanding the lifespans of pyroptosis-resistant neutrophils, and hyperactivating stimuli-challenged macrophages, dendritic cells, monocytes, and specific nonimmune cells. Death inflammasome activation also induces GSDMD-mediated pyroptosis with no IL-1β secretion, which may increase lethality in vivo. The sublytic GSDMD pore formation associated with lower expressions of pyroptotic components, GSDMD-mediated extracellular vesicles, or other GSDMD-independent pathways that involve unconventional secretion could contribute to the cytokine-predominant uncoupling; the regulation of caspase-1 dynamics, which may generate various active species with different activities in terms of GSDMD or pro-IL-1β, could lead to pyroptosis-predominant uncoupling. These uncoupling preferences enable precise reactions to different stimuli of different intensities under specific conditions at the single-cell level, promoting cooperative cell and host fate decisions and participating in the pathogen “game”. Appropriate decisions in terms of coupling and uncoupling are required to heal tissues and eliminate threats, and further studies exploring the inflammasome tilt toward pyroptosis or cytokine secretion may be helpful.