bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Incidence Rate of Diabetes, Pre-diabetes, Uncontrolled Diabetes, and Their Predictors in the Adult Population in Southeastern Iran: Findings From KERCADR Study
Authors: Najafipour Hamid , Farjami Maryam , Sanjari Mojgan , Amirzadeh Raheleh , Shadkam Farokhi Mitra , Mirzazadeh Ali
Published: November 2021

Background: Diabetes mellitus is among the most serious health challenges worldwide. We assessed the prevalence of pre-diabetes (pre-DM) and diabetes (DM), the effectiveness of diabetes management, the 5-year incidence rate, and associated variables in the adult population in southeastern Iran.

Methods: In a random cluster household survey (2014–2018), 9,959 adult individuals aged 15–80 years were assessed for coronary artery disease risk factors, including diabetes mellitus in Kerman (KERCADRS, phase 2). Among these people, 2,820 persons had also participated in phase 1 of the study 5 years earlier (2009–2011). Univariable and multivariable survey logistic regression models were used to identify the potential predictors of diabetes and pre-diabetes.

Results: The prevalence of pre-DM was 12% (males 13.2% vs. females 11.1%), steadily increasing from 7.1% in the 15–24 years group to 18.4% in the 55–64 years group. The prevalence of DM was 10.2% (male and female, 7.9 and 10.8%, respectively), of which 1.9% were undiagnosed. DM was diagnosed in 10.6% of educated and 15.1% of illiterate people. The prevalence of diagnosed DM was lower in smokers (5.2 vs. 8.7%) and dependent opium users (5.4 vs. 8.8%). The prevalence of uncontrolled DM (HbA1c > 7%) was 48.8%, increasing with age. The frequency of uncontrolled DM among people without and with treatment was 32 and 55.9%, respectively. Illiterate people had worse uncontrolled DM (55.6 vs. 39.6%). The 5-year incidence rate (persons/100 person-years) was 1.5 for pre-DM and 1.2 for DM, respectively. The lowest and the highest incidence rate of DM belonged to the 15–34 years old group (0.5) and dependent opium users (2.4). The incidence rate was found to have a direct relationship with BMI and a reverse relationship with physical activity.

Conclusion: Pre-DM and DM affected 22.2% of the population. One-third of patients with diabetes had undiagnosed DM, and in 55.9% of people with diagnosed DM, treatment had been ineffective. Appropriate health interventions are needed to reduce the prevalence and health consequences of diabetes in the region.
Risk Culture and COVID-19 Protective Behaviors: A Cross-Sectional Survey of Residents in China
Authors: Bi Xuejing , Zhang Qiao , Fan Kaisheng , Tang SiYu , Guan HanWen , Gao XueQin , Cui Yu , Ma Yi , Wu QunHong , Hao YanHua , Ning Ning , Liu Chaojie
Published: November 2021

The COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) has spread across the world. However, our understanding of the public responses, in particular in adopting protective behaviors, has been limited. The current study aimed to determine the level of protective behaviors adopted by the residents in China and its association with their cultural attributes. A national cross-sectional online survey was conducted in mainland China from 4th to 13th August 2020. Protective behaviors were assessed as a summed score (ranging from 0 to 40) measured by ten items. The self-report tendency of study participants toward the four cultural attributes (individualism, egalitarianism, fatalism, hierarchy) was rated on a seven-point Likert scale. A total of 17651 respondents returned a valid questionnaire, representing 47.9% of those who accessed the online survey. Most (89.8%) respondents aged between 18 and 45 years in the age range of and 47.7% were male. High levels of protective behaviors (34.04 ± 5.78) were reported. The respondents had high scores in the cultural attributes of hierarchy (Median = 5) and egalitarianism (Median = 5), compared with low scores in individualism (Median = 1) and fatalism (Median = 1). High levels of protective behaviors were associated a higher tendency toward egalitarianism (AOR = 2.90, 95% CI 2.67–3.15) and hierarchy (AOR = 1.66, 95% CI 1.53–1.81) and a low tendency toward fatalism (AOR = 1.79, 95% CI 1.63–1.97) and individualism (AOR = 2.62, 95% CI 2.41–2.85). The cultural attributes explained 17.3% of the variations in the protective behavioral scores. In conclusion, the adoption of protective behaviors is associated a risk culture characterized by high levels of hierarchy and egalitarianism and low levels of individualism and fatalism. Government actions and communication strategies need to adapt to the cultural characteristics of their target audience.
The Impact of the COVID-19 Pandemic on Physician Visits in Japan
Authors: Kumagai Narimasa
Published: November 2021

Background: Emerging from the coronavirus disease 2019 (COVID-19) scenario, fears of social distancing and contagion have led to a decline in the number of physician visits in Japan, placing severe financial strain on most hospitals and clinics. In this context, this study examined the impact of the spread of COVID-19 on the utilization of outpatient services.

Methods: This study used monthly data drawn from the monthly statistics report of the social insurance medical fee payment fund in Japan and estimated fixed-effects models.

Results: The results showed that the decline in the number of physician visits because of the first state of emergency declaration in Japan was greater than that caused by COVID-19's spread during the same period. However, there was a decline in the impact of the declaration over time. After the second state of emergency declaration, the decline in the number of physician visits caused by the spread reduced by almost half. The nationwide preschool closure under the declaration of the first state of emergency also adversely impacted the number of physician visits. The reduced healthcare per capita costs of preschool children were greater among prefectures taking specific precautions. The results showed non-negligible regional differences in physician visits of preschool children during the sample period.

Conclusions: The findings imply that we should not overestimate the negative impacts of the state of emergency declaration without lockdown on physician visits. To restore the number of physician visits to its pre-pandemic level, it is crucial to facilitate a smooth transition of COVID-19 patients between hospitals and an effective compensation program for hospitals with COVID-19 patients.
La complejidad del trauma complejo del desarrollo
Authors: Lecannelier Felipe , Guajardo Humberto , Kushner Diana , Barrientos Carlos , Monje Germán
Published: November 2021

Las conceptualizaciones actuales sobre el trauma infantil buscan explicar el proceso que organiza la experiencia y estilo de funcionamiento de los niños que sufren vulneraciones múltiples, crónicas e interpersonales, especialmente durante los primeros años de vida. Esta conceptualización actual se la conoce como Trauma Complejo del Desarrollo (TCD), y constituye un avance en la comprensión del trauma, desde una perspectiva multinivel e interdisciplinaria. Sin embargo, consideramos que este fenómeno puede ser mejor comprendidos adoptando una visión de los sistemas complejos, la teoría del caos, combinado con los aportes de la teoría del apego, y un sinnúmero de enfoques actuales del desarrollo, de la psicobiología, y las nociones sobre la evolución de la mente, y la mente y acción corporalizada. El presente artículo presenta esta visión paradigmática bajo un modelo que se titula Modelo de Apego & Complejidad (MAC), al entregar una explicación alternativa al trauma complejo.
Diálogo Terapéutico, Insight y Reducción de Síntomas Ansioso-Depresivos en la Psicoterapia Psicoanalítica
Authors: Jibaja Zárate Carlos Alberto
Published: November 2021

El objetivo del estudio fue examinar las características del dialogo terapéutico generador de cambios en la capacidad del consultante para obtener insights, y su relación con los síntomas ansioso-depresivos, en las primeras 16 sesiones de psicoterapia psicoanalítica de duración abierta, una sesión por semana. Se codificaron las transcripciones de las sesiones grabadas de tres consultantes utilizando listas de chequeo, y se examinaron las ocurrencias de insights cognitivos y emocionales, cambios en la sintomatología ansioso-depresiva y “eventos significativos” (Greenberg, 1986) donde se produjeron insights emocionales. Se registró reducción de síntomas, correlaciones entre incremento de insights cognitivos y disminución de síntomas, y una secuencia de procesos de cambios en la capacidad del consultante para generar insights emocionales. Como conclusión se destaca el entrelazamiento de procesos intrapsíquicos y relacionales, en una secuencia de fases (sincronía-elaboración-resolución) del diálogo terapéutico, que promueve la capacidad del consultante para acumular insights y profundizar su auto comprensión en temas de conflicto, lo que guarda relación con el alivio sintomático.
Cognitive Conflicts in Functional Gastrointestinal Disorders
Authors: Benasayag Ruth , Mearin Fermín , Aguilera Mari , Feixas Guillem
Published: November 2021

The importance of psychological factors in functional gastrointestinal disorders (FGID) is well-stablished in the literature; however, cognitive factors have hardly been researched and, in particular, cognitive conflicts have not been explored for these disorders. The aim of this study is to compare the cognitive and symptomatic characteristics of a group of 66 FGID patients (33 diagnosed with irritable bowel syndrome and 33 with functional dyspepsia) with a control group of participants without FGID or psychopathological symptoms. Both groups were matched by sex and age. The evaluation of the clinical sample was carried out following the criteria of the DSM-IV-TR. The SCL 90-R, and also the Repertory Grid for the identification of cognitive conflicts (implicative dilemmas) and self-ideal discrepancy, were administered to both the clinical sample and the control group. Results showed that 85% of FGID patients met the criteria for one axis I disorder of the DSM-IV-TR, mainly anxiety and somatization disorders. Regarding axis II, 23% presented at least one personality disorder, the most common ones being those of avoidance and dependence. Regarding axis IV, the patients reported a higher number of problems relative to the primary support group. FGID patients showed greater symptoms compared to the control group on various SCL 90-R scales. On the other hand, FGID patients presented more implicative dilemmas than healthy controls, as well as lower self-esteem. No significant differences were observed depending on the type of FGID (irritable bowel syndrome or functional dyspepsia).
Harvest Date Effect on Forage Yield, Botanical Composition, and Nutritive Value of Novel Legume-Grass Mixtures
Authors: Peprah Samuel , Darambazar Enkhjargal , Biligetu Bill , Iwaasa Alan D. , Larson Kathy , Damiran Daalkhaijav , Lardner Herbert A.
Published: November 2021

The potential for novel forage mixtures to address reduced herbage for late season grazing was investigated. Forage legumes, sainfoin (Onobrychis viciifolia Scop.) (SF) cvs. AC Mountainview, Shoshone, and Nova (MountainSF, ShoshoneSF, and NovaSF), cicer milkvetch (Astragalus cicer L.) cv. AC Veldt (CMV), Canadian milkvetch (Astragalus canadensis L.) cv. Great Plains (CaMV), and alfalfa (Medicago sativa L.) cv. AC Yellowhead (ALF) were evaluated in binary mixtures with meadow bromegrass (Bromus riparius Rehm.) cv. Admiral (MBG), hybrid bromegrass (B. riparius × B. inermis Leyss.) cv. AC Success (HBG) and Russian wildrye [Psathyrostachys junceus (Fisch.) Nevski.] cv. Tom (RWR) for yield, botanical composition, and nutritive value on July and September harvest dates at Saskatoon and Swift Current, Saskatchewan, Canada from 2016 to 2018. Hybrid bromegrass-legume mixture produced 16–38% greater forage compared to RWR-legume (7.5 vs. 5.6 Mg ha−1 in July and 6.1 vs. 5.1 Mg ha−1 in September at Saskatoon, and 3.2 vs. 2.0 Mg ha−1 in July at Swift Current). MountainSF and ALF had the greatest legume contribution to total yield at July harvest at Swift Current (67.7 ± 3.2%) and Saskatoon (62.1 ± 2.1%), respectively, while CaMV had lowest composition at Swift Current (20.2 ± 2.5%) and Saskatoon (12.6 ± 3.5%). The CMV and ALF-grass mixtures at Saskatoon and legume-RWR mixtures at both sites in July had greatest CP content. The July harvest had greatest yield, legume content and nutritive value compared to the September harvest at both sites. Study results suggest if yield is the objective, then either ALF or CMV with HBG may be considered. If nutritive value is the goal, any legume with RWR is an option. Finally, ALF or CMV in mixture with either HBG or RWR could be summer or fall stockpile forage in the Northern Great Plains of western Canada.
Growth, Yield, Quality, and Phytochemical Behavior of Three Cultivars of Quinoa in Response to Moringa and Azolla Extracts under Organic Farming Conditions
Authors: El-Serafy Rasha S. , El-Sheshtawy Abdel-Nasser A. , Abd El-Razek Usama A. , Abd El-Hakim Ahmed F. , Hasham Mostafa M. A. , Sami Rokayya , Khojah Ebtihal , Al-Mushhin Amina A. M.
Published: November 2021

Increased demand for quinoa as a functional food has resulted in more quinoa-growing areas and initiatives to increase grain production, particularly in organic agriculture. Quinoa seeds are a superfood with incredible nutritional benefits. They are abundant in secondary metabolites with significant medicinal activity. This report was consequently performed to investigate whether Azolla fliculoides (AE) or moringa leaf extract (MLE) foliar spray can be supplemented as organic extracts to enhance quinoa growth and productivity under organic farming. Three quinoa cultivars, KVL–SRA2 (C1), Chipaya (C2), and Q–37 (C3), were grown organically and subjected to foliar spraying with AE or MLE at a 20% ratio, as well as their combination (AE+MLE). Plant performance of the three cultivars was significantly enhanced by MLE or AE applications as compared with control plants. The highest outputs were obtained by AE+MLE treatment, which significantly increased the seed yield by about 29% as compared with untreated plants. Seed quality exhibited a marked increase in response to AE+MLE that was superior in this regard as it showed higher protein, carbohydrates, saponine, tannins, phenolics, and flavonoids content. The C3-cultivar demonstrated the highest productivity, saponine, and flavonoids levels as compared to the other cultivars. Overall, the current study indicated that foliar spray with AE+MLE could enhance growth and productivity as well as quality and pharmaceutical active ingredients of quinoa cultivars grown under farming conditions.
The Shape Diversity of Olive Stones Resulting from Domestication and Diversification Unveils Traits of the Oldest Known 6500-Years-Old Table Olives from Hishuley Carmel Site (Israel)
Authors: Terral Jean-Frédéric , Bonhomme Vincent , Pagnoux Clémence , Ivorra Sarah , Newton Claire , Paradis Laure , Ater Mohammed , Kassout Jalal , Limier Bertrand , Bouby Laurent , Cornet Fiona , Barazani Oz , Dag Arnon , Galili Ehud
Published: November 2021

The first exploited and domesticated olive forms are still unknown. The exceptionally well-preserved stones from the submerged Hishuley Carmel site (Israel), dating from the middle of the 7th millennium BP, offer us the opportunity to study the oldest table olives discovered so far. We apply a geometrical morphometric analysis in reference to a collection of modern stones from supposed wild populations and traditional varieties of various origins, genetic lineages and uses. Analyses carried out on modern material allow the characterization of the extent of stone morphological variation in the olive tree and the differentiation of distinct morphotypes. They also allow to discuss the status of supposed wild populations and the divergence between groups of varieties and their wild progenitors, interpreted from evolutionary and biogeographical perspectives. The shape of archaeological stones compared to the differentiation model unveils morphological traits of olives most likely belonging to both wild olive trees and domesticated forms, with some of them showing a notable domestication syndrome. These forms at the early stages of domestication, some of which are surprisingly morphologically close to modern varieties, were probably used for dual use (production of olive oil and table olives), and possibly contributed to the dispersion of the olive tree throughout the Mediterranean Basin and to its subsequent diversification.
A Review of the Most Common and Economically Important Diseases That Undermine the Cultivation of Tomato Crop in the Mediterranean Basin
Authors: Panno Stefano , Davino Salvatore , Caruso Andrea Giovanni , Bertacca Sofia , Crnogorac Ana , Mandić Ana , Noris Emanuela , Matić Slavica
Published: November 2021

Tomato (Solanum lycopersicum L.), family Solanaceae, has become in the past fifty years one of the most important and extensively grown horticultural crops in the Mediterranean region and throughout the world. In 2019, more than 180 million tonnes of tomato have been produced worldwide, out of which around 42 million tonnes in Mediterranean countries. Due to its genetic properties, tomato is afflicted by numerous plant diseases induced by fungal, bacterial, phytoplasma, virus, and viroid pathogens. Not only is its genetic inheritance of great importance to the management of the numerous tomato pathogens, but equally as important are also the present climate changes, the recently revised phytopathological control measures, and the globalization of the seed industry. Thus, the recognition of symptoms and the knowledge of the distribution and spread of the disease and of the methods for early detection of the pathogens are the major prerequisites for a successful management of the disease. In this review, we will describe the main tomato pathogens in the Mediterranean area that impact mostly the tomato yield and provide the current and perspective measures necessary for their successful management.
Monitoring Optical Tool to Determine the Chlorophyll Concentration in Ornamental Plants
Authors: Jiménez-Lao Rafael , Garcia-Caparros Pedro , Pérez-Saiz Mónica , Llanderal Alfonso , Lao María Teresa
Published: November 2021

The accurate estimation of leaf photosynthetic pigments concentration is crucial to check the plant´s health. Traditional methods of measuring photosynthetic pigments involve complex procedures of solvent extraction followed by spectrophotometric determinations. Portable plant instruments such as Soil Plant Analysis Development (SPAD) meters can facilitate this task for the speed and simplicity of the measures. The relationship between chlorophyll index obtained by SPAD-502 and pigment concentration in several ornamental species can help in the management of ornamental plant production. Two trials have been carried out in two different growing seasons (spring and summer) and facilities (greenhouse and open air), involving 30 ornamental species. There was a high linear relationship between concentrations of Chla and Chlb, as well as between Chlt and Ct in different species studied under greenhouse and open field conditions. The ratio between Chla and Chlb was higher at open field conditions and similar between Chlt and Ct. There was also a good relationship between Chlorophyll index and Chlt under both growing conditions, as well as between Chlorophyll index and Ct under greenhouse conditions. However, linear relationships with different slopes were observed for groups of species at open field conditions.
A Simple Application for Computing Reference Evapotranspiration with Various Levels of Data Availability—ETo Tool
Authors: Rodrigues Gonçalo C. , Braga Ricardo P.
Published: November 2021

Reference evapotranspiration (ETo) estimations may be used to improve the efficiency of irrigated agriculture. However, its computation can be complex and could require numerous weather data that are not always available for many locations. Different methods are available to estimate ETo when limited data are available, and the assessment of the most accurate one can be difficult and time consuming. There are some standalone softwares available for computing ETo but none of them allow for the comparison of different methods for the same or different datasets simultaneously. This paper aims to present an application for estimating ETo using several methods that require different levels of data availability, namely FAO-56 Penman–Monteith (PM), the Original and the three modified Hargreaves–Samani (HS and MHS1, MHS2 and MHS3), Trajkovic (TR) and the single temperature procedure (MaxTET). Also, it facilitates the comparison of the accuracy estimation of two selected methods. From an example case, for where the application was used to compute ETo for three different locations, results show that the application can easily and successfully estimate ETo using the proposed methods, allowing for statistical comparison of those estimations. HS proves to be the most accurate method for the studied locations; however, the accuracy of all methods tends to be lower for costal locations than for more continental sites. With this application, users can select the best ETo estimation methods for a specific location and use it for irrigation purposes.
Ecological Engineering for Rice Insect Pest Management: The Need to Communicate Widely, Improve Farmers’ Ecological Literacy and Policy Reforms to Sustain Adoption
Authors: Heong Kong-Luen , Lu Zhong-Xian , Chien Ho-Van , Escalada Monina , Settele Josef , Zhu Zeng-Rong , Cheng Jia-An
Published: November 2021

Ecological engineering (EE) involves the design and management of human systems based on ecological principles to maximize ecosystem services and minimize external inputs. Pest management strategies have been developed but farmer adoption is lacking and unsustainable. EE practices need to be socially acceptable and it requires shifts in social norms of rice farmers. In many countries where pesticides are being marketed as “fast moving consumer goods” (FMCG) it is a big challenge to shift farmers’ loss-averse attitudes. Reforms in pesticide marketing policies are required. An entertainment education TV series was able to reach wider audience to improve farmers’ ecological literacy, shifting beliefs and practices. To sustain adoption of ecologically based practices organizational structures, incentives systems and communication strategies to support the new norms and practices are needed.
Phosphorus and Biofertilizer Application Effects on Growth Parameters, Yield and Chemical Constituents of Broccoli
Authors: Mohamed Mustafa H. M. , Ali Maha , Eid Rania S. M. , El-Desouky Heba S. , Petropoulos Spyridon A. , Sami Rokayya , Al-Mushhin Amina A. M. , Ismail Khadiga Ahmed , Zewail Reda M. Y.
Published: November 2021

Broccoli is a popular vegetable throughout the world and contains important nutritional features. This study was conducted to evaluate the effect the fertilization with different phosphorus sources (i.e., soil application of rock phosphate (RP) at 428 kg ha−1, calcium superphosphate (CSP) at 670 kg ha−1, phosphoric acid (PA) at 126 L ha−1 and monoammonium phosphate (MAP) at 334 kg ha−1) combined with biofertilizers (i.e., inoculation with phosphorin or mycorrhiza) on plant growth aspects, antioxidants enzyme activity, chemical constituents, yield and quality of broccoli leaves and heads (Brassica oleracea var. italica Plenck). The experiment was performed according to the randomized complete block design with three replications (n = 3), for two growing seasons (2018–2019) at the experimental farm of Benha University, Egypt. The obtained results showed that the highest values of plant height, leaf area, fresh and dry weight of leaves/plant, head weight and diameter, and the highest yield of heads ha−1 were recorded in plants that received MAP fertilizer and were inoculated with mycorrhiza. On the other hand, the highest value of head length, total carbohydrate and total soluble solids (TSS) content were observed in plants fertilized with PA and inoculated with mycorrhiza. The highest leaf nitrogen % and head ascorbic acid content, as well as the lowest head total phenol content were recorded in plants supplemented with MAP fertilizer and inoculated with mycorrhiza. Moreover, broccoli plants fertilized with PA and inoculated with mycorrhiza showed promising results in terms of phosphorus, potassium and total carbohydrate content, antioxidant activity and dehydrogenase activity. In conclusion, phosphorus may affect plant growth, yield and chemical parameters in broccoli plants depending on the fertilizer source, while inoculation with mycorrhiza may also have a beneficial impact on these parameters.
Chitosan Enhances the Anti-Biofilm Activity of Biodentine against an Interkingdom Biofilm Model
Authors: Abusrewil Sumaya , Brown Jason L. , Delaney Christopher , Butcher Mark C. , Tiba Mohammed , Scott J. Alun , Ramage Gordon , McLean William
Published: November 2021

Endodontic infection is a biofilm disease that is difficult to irradicate with current treatment protocols, and as such, persistent micro-organisms may lead to ongoing or recurrent disease. The potential for the use of enhanced filling materials to modify biofilm regrowth is a promising strategy. This current study aimed to evaluate the anti-biofilm efficacy of calcium silicate cements modified with chitosan. The development of mono-species and multi-species biofilms on ProRoot MTA, Biodentine and bovine dentine discs were explored using quantitative microbiology analysis. The effect on regrowth of biofilms was assessed following the addition of chitosan to each cement. In comparison to a dentine substrate, both materials did not show the ability to inhibit biofilm regrowth. Biodentine incorporated with chitosan displayed a dose-dependent reduction in multi-species biofilm regrowth, unlike MTA. Notably, interkingdom biofilms were shown to enhance bacterial tolerance in the presence of chitosan. This study demonstrates the potential to enhance the antimicrobial properties of Biodentine. The findings highlight the need for appropriate model systems when exploring antimicrobial properties of materials in vitro so that interspecies and interkingdom interactions that modify tolerance are not overlooked while still supporting the development of innovative materials.
Clinically Relevant Interactions with Anti-Infectives on Intensive Care Units—A Multicenter Delphi Study
Authors: Koeck Joachim Andreas , Hilgarth Heike , von Ameln-Mayerhofer Andreas , Meyn Damaris , Warlich Ruediger , Münstedt Andreas , Horn Dagmar , König Christina
Published: November 2021

Patients in intensive care units (ICUs) are at high risk of drug–drug interactions (DDIs) due to polypharmacy. Little is known about type and frequency of DDIs within German ICUs. Clinical pharmacists’ interventions (PI) recorded in a national database (ADKA-DokuPIK) were filtered for ICU patients. Binary DDIs involving ≥1 anti-infective agent with >1 database entry were selected. A modified two-step Delphi process with a group of senior hospital pharmacists was employed to evaluate selected DDIs for clinical relevance by using a five-point scale and to develop guidance for clinical practice. In total, 16,173 PI were recorded, including 1836 (11%) DDIs in the ICU setting. Of the latter, 41% (756/1836) included ≥1 anti-infective agent, 32% (590/1836) were binary DDIs, and 25% (455/1836) were listed at least twice. This translates into 88 different DDIs, 74% (65/88) of which were rated as being clinically relevant by our expert panel. The majority of DDIs (76% [67/88]) included macrolides, antifungals, or fluoroquinolones. This percentage was even higher in DDIs being rated as clinically relevant by the experts (85% [55/65]). It is noted that an inter-professional discussion and approach is needed in the individual patient management of DDIs. The guidance developed might be a tool for decision support.
Innovative High-Pressure Fabrication Processes for Porous Biomaterials—A Review
Authors: Prakasam Mythili , Silvain Jean-François , Largeteau Alain
Published: November 2021

Biomaterials and their clinical application have become well known in recent years and progress in their manufacturing processes are essential steps in their technological advancement. Great advances have been made in the field of biomaterials, including ceramics, glasses, polymers, composites, glass-ceramics and metal alloys. Dense and porous ceramics have been widely used for various biomedical applications. Current applications of bioceramics include bone grafts, spinal fusion, bone repairs, bone fillers, maxillofacial reconstruction, etc. One of the common impediments in the bioceramics and metallic porous implants for biomedical applications are their lack of mechanical strength. High-pressure processing can be a viable solution in obtaining porous biomaterials. Many properties such as mechanical properties, non-toxicity, surface modification, degradation rate, biocompatibility, corrosion rate and scaffold design are taken into consideration. The current review focuses on different manufacturing processes used for bioceramics, polymers and metals and their alloys in porous forms. Recent advances in the manufacturing technologies of porous ceramics by freeze isostatic pressure and hydrothermal processing are discussed in detail. Pressure as a parameter can be helpful in obtaining porous forms for biomaterials with increased mechanical strength.
Candida albicans Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
Authors: Haider Mohammed , Al-Rashed Fatema , Albaqsumi Zahraa , Alobaid Khaled , Alqabandi Rawan , Al-Mulla Fahd , Ahmad Rasheed
Published: November 2021

Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by opportunistic pathogens. Candida albicans is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by C. albicans in macrophage foaming and the associated inflammation is poorly understood. We investigated whether C. albicans induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed C. albicans (HKCA). HKCA-induced lipid accumulation in macrophages along with increased expression of inflammatory markers, including CD11b and CD11c or expression and secretion of IL-1β. HKCA also increased the expression of PPARγ, CD36, and FABP4 in macrophages. Mechanistically, we found that the foamy and inflammatory macrophage phenotype induced by HKCA requires FABP4 because disruption of FABP4 in macrophages either by chemical inhibitor BMS309404 or small interfering RNA (siRNA) abrogated foam cell formation and expression of inflammatory markers CD11b, CD11c, and IL-1β. Furthermore, HKCA-treated macrophages displayed high expression and secretion of MMP-9. Inhibition of FABP4 resulted in suppression of HCKA-induced MMP-9 production. Overall, our results demonstrate that C. albicans induces foam cell formation, inflammation, and MMP-9 expression in macrophages via the upregulation of FABP4, which may constitute a novel therapeutic target for treating C. albicans-induced atherosclerosis.
Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases
Authors: Silaghi Ciprian N. , Farcaș Marius , Crăciun Alexandra M.
Published: November 2021

Age-associated cardiovascular and neurodegenerative diseases lead to high morbidity and mortality around the world. Sirtuins are vital enzymes for metabolic adaptation and provide protective effects against a wide spectrum of pathologies. Among sirtuins, mitochondrial sirtuin 3 (SIRT3) is an essential player in preserving the habitual metabolic profile. SIRT3 activity declines as a result of aging-induced changes in cellular metabolism, leading to increased susceptibility to endothelial dysfunction, hypertension, heart failure and neurodegenerative diseases. Stimulating SIRT3 activity via lifestyle, pharmacological or genetic interventions could protect against a plethora of pathologies and could improve health and lifespan. Thus, understanding how SIRT3 operates and how its protective effects could be amplified, will aid in treating age-associated diseases and ultimately, in enhancing the quality of life in elders.
Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium Pseudoalteromonas tunicata
Authors: Salikin Nor Hawani , Dubois Malak , Nappi Jadranka , Lebhar Helene , Marquis Christopher , Egan Suhelen
Published: November 2021

Drug resistance among parasitic nematodes has resulted in an urgent need for the development of new therapies. However, the high re-discovery rate of anti-nematode compounds from terrestrial environments necessitates a new repository for future drug research. Marine epiphytes are hypothesised to produce nematicidal compounds as a defence against bacterivorous predators, thus representing a promising yet underexplored source for anti-nematode drug discovery. The marine epiphytic bacterium Pseudoalteromonas tunicata is known to produce several bioactive compounds. Screening heterologously expressed genomic libraries of P. tunicata against the nematode Caenorhabditis elegans, identified as an E. coli clone (HG8), shows fast-killing activity. Here we show that clone HG8 produces a novel nematode-killing protein-1 (Nkp-1) harbouring a predicted carbohydrate-binding domain with weak homology to known bacterial pore-forming toxins. We found bacteria expressing Nkp-1 were able to colonise the C. elegans intestine, with exposure to both live bacteria and protein extracts resulting in physical damage and necrosis, leading to nematode death within 24 h of exposure. Furthermore, this study revealed C. elegans dar (deformed anal region) and internal hatching may act as a nematode defence strategy against Nkp-1 toxicity. The characterisation of this novel protein and putative mode of action not only contributes to the development of novel anti-nematode applications in the future but reaffirms the potential of marine epiphytic bacteria as a new source of novel biomolecules.
Orai1–STIM1 Regulates Increased Ca2+ Mobilization, Leading to Contractile Duchenne Muscular Dystrophy Phenotypes in Patient-Derived Induced Pluripotent Stem Cells
Authors: Uchimura Tomoya , Sakurai Hidetoshi
Published: November 2021

Ca2+ overload is one of the factors leading to Duchenne muscular dystrophy (DMD) pathogenesis. However, the molecular targets of dystrophin deficiency-dependent Ca2+ overload and the correlation between Ca2+ overload and contractile DMD phenotypes in in vitro human models remain largely elusive. In this study, we utilized DMD patient-derived induced pluripotent stem cells (iPSCs) to differentiate myotubes using doxycycline-inducible MyoD overexpression, and searched for a target molecule that mediates dystrophin deficiency-dependent Ca2+ overload using commercially available chemicals and siRNAs. We found that several store-operated Ca2+ channel (SOC) inhibitors effectively prevented Ca2+ overload and identified that STIM1–Orai1 is a molecular target of SOCs. These findings were further confirmed by demonstrating that STIM1–Orai1 inhibitors, CM4620, AnCoA4, and GSK797A, prevented Ca2+ overload in dystrophic myotubes. Finally, we evaluated CM4620, AnCoA4, and GSK7975A activities using a previously reported model recapitulating a muscle fatigue-like decline in contractile performance in DMD. All three chemicals ameliorated the decline in contractile performance, indicating that modulating STIM1–Orai1-mediated Ca2+ overload is effective in rescuing contractile phenotypes. In conclusion, SOCs are major contributors to dystrophin deficiency-dependent Ca2+ overload through STIM1–Orai1 as molecular mediators. Modulating STIM1–Orai1 activity was effective in ameliorating the decline in contractile performance in DMD.
The Dual Role of Circular RNAs as miRNA Sponges in Breast Cancer and Colon Cancer
Authors: Huang Jiashu , Yu Shenghao , Ding Lei , Ma Lingyuan , Chen Hongjian , Zhou Hui , Zou Yayan , Yu Min , Lin Jie , Cui Qinghua
Published: November 2021

Breast cancer (BC) and colon cancer (CRC) are the two most deadly cancers in the world. These cancers partly share the same genetic background and are partially regulated by the same genes. The outcomes of traditional chemoradiotherapy and surgery remain suboptimal, with high postoperative recurrence and a low survival rate. It is, therefore, urgent to innovate and improve the existing treatment measures. Many studies primarily reported that the microRNA (miRNA) sponge functions of circular RNA (circRNA) in BC and CRC have an indirect relationship between the circRNA–miRNA axis and malignant behaviors. With a covalent ring structure, circRNAs can regulate the expression of target genes in multiple ways, especially by acting as miRNA sponges. Therefore, this review mainly focuses on the roles of circRNAs as miRNA sponges in BC and CRC based on studies over the last three years, thus providing a theoretical reference for finding new therapeutic targets in the future.
Targeted Therapies in Cancer: To Be or Not to Be, Selective
Authors: Montoya Skye , Soong Deborah , Nguyen Nina , Affer Maurizio , Munamarty Sailasya P. , Taylor Justin
Published: November 2021

Development of targeted therapies in recent years revealed several nonchemotherapeutic options for patients. Chief among targeted therapies is small molecule kinase inhibitors targeting key oncogenic signaling proteins. Through competitive and noncompetitive inhibition of these kinases, and therefore the pathways they activate, cancers can be slowed or completely eradicated, leading to partial or complete remissions for many cancer types. Unfortunately, for many patients, resistance to targeted therapies, such as kinase inhibitors, ultimately develops and can necessitate multiple lines of treatment. Drug resistance can either be de novo or acquired after months or years of drug exposure. Since resistance can be due to several unique mechanisms, there is no one-size-fits-all solution to this problem. However, combinations that target complimentary pathways or potential escape mechanisms appear to be more effective than sequential therapy. Combinations of single kinase inhibitors or alternately multikinase inhibitor drugs could be used to achieve this goal. Understanding how to efficiently target cancer cells and overcome resistance to prior lines of therapy became imperative to the success of cancer treatment. Due to the complexity of cancer, effective treatment options in the future will likely require mixing and matching these approaches in different cancer types and different disease stages.
Impact of Immunoscore on the Management of Stage II Colon Cancer Patients: A Physician Survey
Authors: Kasi Anup , Dotan Efrat , Poage Graham M. , Catteau Aurelie , Vernerey Dewi , George Manju , Barzi Afsaneh
Published: November 2021

Background: Adjuvant chemotherapy use in stage II colon cancer is controversial. Current prognostic risk factors do not take the tumor immune microenvironment into account. Consideration of the Immunoscore, which measures the host immune response at the tumor site, may assist clinicians in reducing adjuvant chemotherapy use in patients who are unlikely to benefit from it. This study sought to determine the potential clinical utility of the Immunoscore, via its effect on medical oncologists’ recommendations for management of patients with stage II colon cancer. Methods: De-identified vignettes of 10 patients with stage II colon cancer were presented to 25 practicing medical oncologists. Each participant completed surveys indicating recommendations for adjuvant chemotherapy and surveillance strategies. An educational session was subsequently conducted, and the same patient profiles were re-presented but included immunoscore results. Participants were again asked to provide their recommendations. A participant was counted as influenced if their responses were altered after immunoscore test results were provided. Results: All but one participant (96%) altered a management recommendation for ≥1 case. For individual cases, a mean of 55% (range, 40–80%) of participants altered their recommendations for adjuvant chemotherapy and/or surveillance. For the immunoscore-high cases (low-risk of recurrence), recommendations for adjuvant chemotherapy use decreased from 60% to 31%. Conclusions: These results indicate a willingness by oncologists to integrate immunoscore information into clinical practice recommendations. Incorporation of immunoscore data resulted in the reduction of nonvalue care in the simulated population. Confirmation in prospective studies is planned.
Could the Long-Term Oncological Safety of Laparoscopic Surgery in Low-Risk Endometrial Cancer also Be Valid for the High–Intermediate- and High-Risk Patients? A Multi-Center Turkish Gynecologic Oncology Group Study Conducted with 2745 Endometrial Cancer Cases. (TRSGO-End-001)
Authors: Vardar Mehmet Ali , Guzel Ahmet Baris , Taskin Salih , Gungor Mete , Ozgul Nejat , Salman Coskun , Kucukgoz-Gulec Umran , Khatib Ghanim , Taskiran Cagatay , Dünder Ilkkan , Ortac Firat , Yuce Kunter , Terek Cosan , Simsek Tayup , Ozsaran Aydın , Onan Anil , Coban Gonca , Topuz Samet , Demirkiran Fuat , Takmaz Ozguc , Kose M. Faruk , Gocmen Ahmet , Seydaoglu Gulsah , Gumurdulu Derya , Ayhan Ali
Published: November 2021

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high–intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high–intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high–intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high–intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high–intermediate- and high-risk endometrial cancer cases.
Fractionated protein and vitamin meal from wheat bran in the diets of laying quails
Authors: Rogachyev B. A. , Merzlyakova O. G. , Chegodaev B. G. , Lukyanchikova N. L.
Published: November 2021

The results of the experiment on the use of fractionated protein and vitamin meal from wheat bran with a particle size of 140, 400 and 800 microns as a new feed from environmentally friendly raw materials in the diet of quails have been presented. The experiment with duration of 92 days has been carried out according to the generally accepted method on laying quails of Japanese breed formed at the age of 60 days in four similar groups (one control and three experimental) of 50 heads in each. All poultry received compound feed (the main diet) prepared taking into account the age and physiological characteristics of quails, but in the diet of laying quails of the 1st, 2nd and 3rd experimental groups part of wheat (7 %) was replaced with protein and vitamin meal from wheat bran with the particle size of 140, 400 and 800 microns, respectively. The poultry was housed in the physiological yard of the Siberian Research and Design Technological Institute of Animal Husbandry of the Siberian Federal Scientific Center of Agrobiotechnology of the Russian Academy of Sciences in a cage battery under the required microclimate conditions. It has been found that feeding the laying quails with fractionated protein and vitamin meal from wheat bran with the particle size of 140 microns increased the egg production of the poultry by 4,59 %, the eggs weight by 4,63 %. The use of meal with the particle size of 140 and 400 microns in the diet increased the yield of egg mass by 9,48 and 3,79 %, reduced the feed consumption for obtaining 10 eggs by 26,74 and 17,67 %, respectively. Feeding of the laying quails meal with the particle size of 140, 400 and 800 microns increased the amino acid index of protein by 57,84, 34,31 and 17,64 %, respectively, the dry matter content in the shell by 2,19, 1,88 and 3,49 %. The introduction of fractionated wheat bran meal into the poultry diet did not significantly affect the yield of hatching eggs. The use of experimental meal with the particle size of 400 microns reduced incubation waste by 22,22 %, increased the hatchability of chicks by 6,77 %. The live weight of the chick when feeding the laying quails with meal of various fractions increased by 5,81–9,94 % (P < 0,05), the economics effect was 11,69–27,03 %.
Application of MDO technology for internal combustion engines
Authors: Chavdarov A. V.
Published: November 2021

The prospects of using nano-crystalline ceramic coatings on internal combustion engine parts obtained by micro-arc oxidation (MDO) technology are considered. The tendency of development of engine building on replacement of cast-iron blocks and sleeves on aluminum with the special coverings received by galvanic methods is shown. It is noted that this direction does not involve the use of repair technologies, which significantly affects consumers. Analysis and practical tests have shown the possibility of using MDO technology both in the manufacture of engine parts and for the performance of restoration work. It is concluded that it is necessary to introduce this technology into the mass production of engines and pistons, as well as the need to develop a set of equipment for repair work.