bluuebunny/crossref_metadata_2025 huggingface dataset:
In-Country Method Validation of a Paper-Based, Smartphone-Assisted Iron Sensor for Corn Flour Fortification Programs
Authors: Waller Anna W. , Gaytán-Martínez Marcela , Andrade Laborde Juan E.
Published: January 2022

Food fortification in low-income settings is limited due to the lack of simple quality control sensing tools. In this study, we field validated a paper-based, smartphone-assisted colorimetric assay (Nu3Px) for the determination of iron in fortified flours against the gold standard method, atomic emission spectrometry (AES). Samples from commercial brands (n = 6) were collected from supermarkets, convenience stores, and directly from companies in Mexico and characterized using both Nu3Px and AES. Nu3Px’s final error parameters were quantified (n = 45) via method validation final experiments (replication and comparison of methods experiment). Qualitative pilot testing was conducted, assessing Nu3Px’s accept/reject batch decision making (accept ≥ 40 μg Fe/g flour; reject < 40 μg Fe/g flour) against Mexico’s fortification policy. A modified user-centered design process was followed to develop and evaluate an alternative sampling procedure using affordable tools. Variation of iron content in Mexican corn flours ranged from 23% to 39%. Nu3Px’s random error was 12%, and its bias was 1.79 ± 9.99 μg Fe/g flour. Nu3Px had a true mean difference from AES equal to 0 and similar variances. AES and Nu3Px made similar classifications based on Mexico’s policy. Using simple, affordable tools for sampling resulted in similar output to the traditional sampling preparation (r = 0.952, p = 0.01). The affordable sample preparation kit has similar precision to using analytical tools. The sample preparation kit coupled with the smartphone app and paper-based assay measure iron within the performance parameters required for the application to corn flour fortification programs, such as in the case of Mexico.
Multiplex PCR Assay for Simultaneous Identification of Five Types of Tuna (Katsuwonus pelamis, Thunnus alalonga, T. albacares, T. obesus and T. thynnus)
Authors: Lee Ga-Young , Suh Seung-Man , Lee Yu-Min , Kim Hae-Yeong
Published: January 2022

There is a need to identify the species of similar types of fish, especially those that are commercially sold. Particularly, the price of tuna varies depending on its type, which is difficult to determine as they are sold in cut or processed forms. This study developed a multiplex polymerase chain reaction (PCR) assay to identify the five most common tuna species: bigeye, skipjack, Atlantic bluefin, albacore, and yellowfin tunas. Newly designed species-specific primer sets for these five tuna species were created. Subsequently, the amplicon sizes obtained were 270, 238, 200, 178, and 127 base pairs for bigeye, skipjack, Atlantic bluefin, albacore, and yellowfin tunas, respectively. Each primer’s specificity was further tested using 15 other fish species, and no cross-reactivity was observed. To identify multiple targets in a single reaction, multiplex PCR was optimized to increase its resolution and accuracy. The detection levels of the multiplex PCR assay were confirmed to be 1 pg for all the five tunas. Additionally, it was successfully applied to 32 types of commercial tuna products. Therefore, this multiplex PCR assay could be an efficient identification method for various tuna species.
Use of Artificial Neural Networks and NIR Spectroscopy for Non-Destructive Grape Texture Prediction
Authors: Basile Teodora , Marsico Antonio Domenico , Perniola Rocco
Published: January 2022

In this article, a combination of non-destructive NIR spectroscopy and machine learning techniques was applied to predict the texture parameters and the total soluble solids content (TSS) in intact berries. The multivariate models obtained by building artificial neural networks (ANNs) and applying partial least squares (PLS) regressions showed a better prediction ability after the elimination of uninformative spectral ranges. A very good prediction was obtained for TSS and springiness (R2 0.82 and 0.72). Qualitative models were obtained for hardness and chewiness (R2 0.50 and 0.53). No satisfactory calibration model could be established between the NIR spectra and cohesiveness. Textural parameters of grape are strictly related to the berry size. Before any grape textural measurement, a time-consuming berry-sorting step is compulsory. This is the first time a complete textural analysis of intact grape berries has been performed by NIR spectroscopy without any a priori knowledge of the berry density class.
New Insights into Food Fermentation
Authors: Lindner Juliano De Dea , Bernini Valentina
Published: January 2022

Food fermentation has been used for thousands of years for food preservation [...]
Ultrasound Assisted Extraction of Polyphenols from Ripe Carob Pods (Ceratonia siliqua L.): Combined Designs for Screening and Optimizing the Processing Parameters
Authors: Clodoveo Maria Lisa , Crupi Pasquale , Muraglia Marilena , Corbo Filomena
Published: January 2022

Carob pulp has recently received great attention due to its considerable content of polyphenols having a wide range of health promoting effects. In this work, ultrasound assisted extraction was optimized sequentially using a screening Plackett–Burman design and non-standard central composite design coupled to response surface methodology and desirability function statistical tools, to find the best conditions for the extraction of nine polyphenols from carob pods. The gathered mathematical models showed that the highest significant factors influencing the extraction of all compounds were solid–solvent ratio, solvent concentration, and particle size, with the optimal results obtained at values of 0.2 g/mL, 40% ethanol, and 0.3 mm, respectively. Extraction temperature, time, sonication power, and frequency were set at 35 °C, 15 min, 100 W, and 37 kHz, respectively. These parameters help to reduce energy costs and to obtain the best possible extraction of polyphenols.
Chia (Salvia hispanica L.) Flour and Oil Ameliorate Metabolic Disorders in the Liver of Rats Fed a High-Fat and High Fructose Diet
Authors: de Paula Dias Moreira Luiza , Enes Bárbara Nery , de São José Vinícius Parzanini Brilhante , Toledo Renata Celi Lopes , Ladeira Luiz Carlos Maia , Cardoso Rodrigo Rezende , da Silva Duarte Vinícius , Hermsdorff Helen Hermana Miranda , de Barros Frederico Augusto Ribeiro , Martino Hércia Stampini Duarte
Published: January 2022

We hypothesized that the consumption of chia (Salvia hispanica L.) flour (CF) and chia oil (CO) improves metabolic disorders in the liver of Wistar rats (Rattus norvegicus domestica) fed a high-fat and high-fructose (HFHF) diet. The animals were fed a HFHF diet (n = 30) or AIN93-M standard diet (n = 10) for eight weeks. After this period, the animals fed HFHF were divided into three groups (n = 10): HFHF diet, HFHF plus 14.7% of CF, and HFHF plus 4% of CO. Histological and biochemical analyses, gene expression, protein levels related to inflammation, and oxidative stress were evaluated in the liver. The HFHF diet caused lipogenesis, liver steatosis, oxidative stress, and inflammation in the animals. The CF and CO intake increased the liver total antioxidant capacity and superoxide dismutase, decreased nitric oxide levels and liver steatosis. Furthermore, the CF and CO led to the upregulation of Cpt1a and Adipor2, respectively, whereas CF downregulated Srebf1. CO intake decreased blood glucose, triglycerides, and the animals’ body weight. Chia did not show effects on mitigating liver pro-inflammatory status, which it may indicate occurs later. The addition of chia into an unbalanced diet is a good and relevant strategy to reduce liver metabolic disorders caused by the high consumption of fructose and saturated fat.
SARS-CoV-2 Remains Infectious on Refrigerated Deli Food, Meats, and Fresh Produce for up to 21 Days
Authors: Jia Mo , Taylor Tina M. , Senger Sterling M. , Ovissipour Reza , Bertke Andrea S.
Published: January 2022

SARS-CoV-2, the virus that causes COVID-19, has been detected on foods and food packaging and the virus can infect oral cavity and intestinal cells, suggesting that infection could potentially occur following ingestion of virus-contaminated foods. To determine the relative risk of infection from different types of foods, we assessed survival of SARS-CoV-2 on refrigerated ready-to-eat deli items, fresh produce, and meats (including seafood). Deli items and meats with high protein, fat, and moisture maintained infectivity of SARS-CoV-2 for up to 21 days. However, processed meat, such as salami, and some fresh produce exhibited antiviral effects. SARS-CoV-2 also remained infectious in ground beef cooked rare or medium, but not well-done. Although infectious SARS-CoV-2 was inactivated on the foods over time, viral RNA was not degraded in similar trends, regardless of food type; thus, PCR-based assays for detection of pathogens on foods only indicate the presence of viral RNA, but do not correlate with presence or quantity of infectious virus. The survival and high recovery of SARS-CoV-2 on certain foods support the possibility that food contaminated with SARS-CoV-2 could potentially be a source of infection, highlighting the importance of proper food handling and cooking to inactivate any contaminating virus prior to consumption.
Knowledge, Practices, and Risk Perception Associated with Foodborne Illnesses among Females Living in Dubai, United Arab Emirates
Authors: Osaili Tareq M. , Saeed Balsam Qubais , Taha Sadi , Omar Adrees Ahmed , Hasan Fayeza
Published: January 2022

Foodborne illnesses are a widespread and growing public health concern worldwide. The aim of this study was to investigate the knowledge, practices, and risk perception pertaining to food safety among females living in Dubai, United Arab Emirates (UAE). A questionnaire-based cross-sectional study was undertaken consisting of 827 female participants between January to April 2020. The study showed that the overall food safety risk perception was below satisfactory (53.3%). The highest score was seen in the “recognition of foodborne illnesses” aspect (76.7%). The participants were aware of “personal hygiene and cleaning” (61.7%), “cross-contamination prevention” (62.5%), “food purchasing” (60.0%), and “storage of frozen foods” (55.6%). The participants had a low level of knowledge pertaining to “food cooking” (26.0%) and “risk of microbiological infection” (13.3%). There was a statistically significant (p ≤ 0.05) association between knowledge and practices of respondents with employment status, age, and educational levels. In conclusion, the female respondents might act as vehicles for the spread of foodborne illnesses. To reduce this risk, providing food safety awareness programs to this portion of the population is paramount.
A Tail of Two Clumps
Authors: Raga Alejandro Cristian , Cantó Jorge , Castellanos-Ramírez Antonio , Castorena Jorge Ivan , Hernández-Martínez Liliana , Rodríguez-González Ary , Rivera-Ortíz Pedro
Published: January 2022

We present two axisymmetric simulations of a high velocity clump in a photoionized region: one for the case of a uniform, low density environment and a second one for the case of a clump first traveling within a high density medium and then emerging into a low density environment. We show that the second scenario results in the production of an axial tail of dense material with a linear velocity vs. position ramp (with zero velocity at the high/low density environment transition). This material comes from a confined bow shock (produced by the clump when it was within the dense cloud) that emerges into the low environmental density region.
Influential Effects of Emotional Intelligence on the Relationship between Job Stress and Burnout among General Hospital Administrative Staff
Authors: Han Woosok , Kim Jinkyung , Park Junghee , Lee Mihyang
Published: January 2022

Emotional intelligence plays an important role at the time of determination of job stress or in controlling emotions arising from job stress. This study uses a cross-sectional descriptive design to assess the extent of job stress, emotional intelligence, and burnout of general hospital administrative staff, and to identify an influencing effect of emotional intelligence on the relationship between job stress and burnout. Data were collected by using a structuralized questionnaire survey conducted on 191 administrative staff at 4 general hospitals in a metropolitan city in Korea in September 2021. The effects of emotional intelligence on the relationship between job stress and burnout were analyzed by using hierarchical multiple regression analysis. The results of analysis showed: (a) job stress and burnout displayed positive correlation (r = 0.57, p < 0.001) while (b) emotional intelligence and burnout displayed negative correlation (r = −0.26, p < 0.001), and (c) factors with significant effects on burnout included age (≥40 years), job stress, and emotional intelligence. Emotional intelligence had direct (independent) effects on burnout. Thus, the improvement of emotional intelligence is necessary to decrease burnout levels in general hospital administrative staff.
Physical Activity Related to Body Muscle Mass Index and Stiffness Index in 7-to-10-Year-Old Girls
Authors: Gu Yingzhi , Ito Tadashi , Ito Yuji , Noritake Koji , Ochi Nobuhiko , Matsunaga Naomichi , Takahashi Daiki , Sugiura Hideshi
Published: January 2022

The relationship between moderate-to-vigorous physical activity (MVPA) performance time and body muscle mass and stiffness index in pre-puberty school-aged girls has not been fully elucidated. The effect of sexual maturity on bone mass is more pronounced in girls. This study aimed to clarify the relationship between MVPA performance time and the above-mentioned factors. This was a prospective, population-based cohort study of 111 girls aged 7–10 years. Data were collected via medical examination, clinical measurements, and questionnaires. Spearman’s ρ analysis was used to determine the association between skeletal muscle mass index (SMI) and stiffness index, muscle strength, and MVPA performance time. Participants who met the recommended MVPA level accounted for only 24.3% (n = 27) of all participating girls (n = 111). The following factors were significantly positively correlated with MVPA level at spearman’s ρ analysis: SMI (r = 0.303, p = 0.001), stiffness index (r = 0.229, p = 0.015), grip strength (r = 0.283, p = 0.003), back muscle strength (r = 0.197, p = 0.038), and standing long jump distance (r = 0.288, p = 0.002). Multiple regression analysis’s results revealed that SMI (β = 0.237; p = 0.024) was associated with MVPA performance time. These results can help school-aged girls to pay adequate attention to having healthy physical activity habits to prevent the decline of skeletal muscle mass, stiffness index, and body muscle strength.
Public Attention and Sentiment toward Intimate Partner Violence Based on Weibo in China: A Text Mining Approach
Authors: Xu Heng , Zeng Jun , Tai Zhaodan , Hao Huihui
Published: January 2022

The mobile internet has resulted in intimate partner violence (IPV) events not being viewed as interpersonal and private issues. Such events become public events in the social network environment. IPV has become a public health issue of widespread concern. It is a challenge to obtain systematic and detailed data using questionnaires and interviews in traditional Chinese culture, because of face-saving and the victim’s shame factors. However, online comments about specific IPV events on social media provide rich data in understanding the public’s attitudes and emotions towards IPV. By applying text mining and sentiment analysis to the field of IPV, this study involved construction of a Chinese IPV sentiment dictionary and a complete research framework. We analyzed the trends of the Chinese public’s emotional evolution concerning IPV events from the perspectives of a time series as well as geographic space and social media. The results show that the anonymity of social networks and the guiding role of opinion leaders result in traditional cultural factors such as face-saving and family shame for IPV events being no longer applicable, leading to the spiral of an anti-silence effect. Meanwhile, in the process of public emotional communication, anger often overwhelms reason, and the spiral of silence remains in effect in social media. In addition, there are offensive words used in the IPV event texts that indicate misogyny in emotional, sexual, economic and psychological abuse. Fortunately, mainstream media, as crucial opinion leaders in the social network, can have a positive role in guiding public opinion, improving people’s ability to judge the validity of network information, and formulating people’s rational behaviour.
Discharge Planning of Older Persons from Hospital: Comparison of Observed Practice to Recommended Best Practice
Authors: Gane Elise M. , Schoeb Veronika , Cornwell Petrea , Cooray Cassandra Ranatunga , Cowie Brooke , Comans Tracy A.
Published: January 2022

Older people are particularly vulnerable to hospital re-presentation following discharge. Ideal discharge planning processes facilitate the transition from hospital to home and prevent subsequent re-presentations to hospital. The objective of this study was to examine discharge planning processes in two Australian hospitals, compare them between sites and to best-practice recommendations. An ethnographic observational study of discharge planning processes was conducted at two general medical inpatient wards at a large tertiary hospital and a smaller regional hospital in Brisbane, Australia. Participants were patients and ward staff involved in discharge planning during a hospital admission. A literature review was conducted to elicit best-practice recommendations for discharge planning. Data for this study (duration: 112 h) were collected directly using field notes by a research assistant embedded in the ward. A directed qualitative content analysis approach was used for data analysis. Results were compared to best-practice recommendations. Findings indicate that both hospitals implemented various best-practice interventions to enhance communication, collaboration, coordination and patient/family engagement for optimal discharge planning. Strategies used were context specific and effective to varying degrees. Clear responsibilities and goals within the multidisciplinary team helped to create cohesive, well-functioning teams. More work is needed to engage patients and families in discharge planning, and to encourage health professionals to consider patients and family as active team members in the discharge planning process.
A SARS-CoV-2 Infection High-Uptake Program on Healthcare Workers and Cancer Patients of the National Cancer Institute of Naples, Italy
Authors: Crispo Anna , Di Gennaro Piergiacomo , Coluccia Sergio , Gandini Sara , Montagnese Concetta , Porciello Giuseppe , Nocerino Flavia , Grimaldi Maria , Tafuri Mariangela , Luongo Assunta , Rotondo Emanuela , Amore Alfonso , Labonia Francesco , Meola Serena , Marone Stefanie , Pierro Giovanni , Menegozzo Simona , Miscio Leonardo , Perri Francesco , Rainisio Maurizio , Bianchi Attilio A. M. , Cavalcanti Ernesta , Cascella Marco , Celentano Egidio
Published: January 2022

Background: From the beginning of 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) quickly spread worldwide, becoming the main problem for the healthcare systems. Healthcare workers (HCWs) are at higher risk of infection and can be a dangerous vehicle for the spread of the virus. Furthermore, cancer patients (CPs) are a vulnerable population, with an increased risk of developing severe and lethal forms of Coronavirus Disease 19 (COVID-19). Therefore, at the National Cancer Institute of Naples, where only cancer patients are treated, a surveillance program aimed to prevent the hospital access of SARS-CoV-2 positive subjects (HCWs and CPs) was implemented. The study aims to describe the results of the monitoring activity for the SARS-CoV-2 spread among HCWs and CPs, from March 2020 to March 2021. Methods: This surveillance program included a periodic sampling through nasopharyngeal molecular swabs for SARS-CoV-2 (Real-Time Polymerase Chain Reaction, RT-PCR). CPs were submitted to the molecular test at least 48 h before hospital admission. Survival analysis and multiple logistic regression models were performed among HCWs and CPs to assess the main SARS-CoV-2 risk factors. Results: The percentages of HCWs tested with RT-PCR for the detection of SARS-CoV-2, according to the first and the second wave, were 79.7% and 91.7%, respectively, while the percentages for the CPs were 24.6% and 39.6%. SARS-CoV-2 was detected in 20 (1.7%) HCWs of the 1204 subjects tested during the first wave, and in 127 (9.2%) of 1385 subjects tested in the second wave (p < 0.001); among CPs, the prevalence of patients tested varied from 100 (4.6%) during the first wave to 168 (4.9%) during the second wave (p = 0.8). The multivariate logistic analysis provided a significant OR for nurses (OR = 2.24, 95% CI 1.23–4.08, p < 0.001) compared to research, administrative staff, and other job titles. Conclusions: Our findings show that the positivity rate between the two waves in the HCWs increased over time but not in the CPs; therefore, the importance of adopting stringent measures to contain the shock wave of SARS-CoV-2 infection in the hospital setting was essential. Among HCWs, nurses are more exposed to contagion and patients who needed continuity in oncological care for diseases other than COVID-19, such as suspected cancer.
Timing to Intubation COVID-19 Patients: Can We Put It Off until Tomorrow?
Authors: de Alencar Júlio César Garcia , Sternlicht Juliana Martes , Veiga Alicia Dudy Muller , Marchini Julio Flávio Meirelles , Ferreira Juliana Carvalho , de Carvalho Carlos Roberto Ribeiro , Marcilio Izabel , da Silva Katia Regina , Cobello Junior Vilson , Felix Marcelo Consorti , Gomez Luz Marina Gomez , de Souza Heraldo Possolo , Mauá Denis Deratani , Emergency USP COVID Group  , HCFMUSP COVID-19 Study Group
Published: January 2022

Background: The decision to intubate COVID-19 patients receiving non-invasive respiratory support is challenging, requiring a fine balance between early intubation and risks of invasive mechanical ventilation versus the adverse effects of delaying intubation. This present study analyzes the association between intubation day and mortality in COVID-19 patients. Methods: We performed a unicentric retrospective cohort study considering all COVID-19 patients consecutively admitted between March 2020 and August 2020 requiring invasive mechanical ventilation. The primary outcome was all-cause mortality within 28 days after intubation, and a Cox model was used to evaluate the effect of time from onset of symptoms to intubation in mortality. Results: A total of 592 (20%) patients of 3020 admitted with COVID-19 were intubated during study period, and 310 patients who were intubated deceased 28 days after intubation. Each additional day between the onset of symptoms and intubation was significantly associated with higher in-hospital death (adjusted hazard ratio, 1.018; 95% CI, 1.005–1.03). Conclusion: Among patients infected with SARS-CoV-2 who were intubated and mechanically ventilated, delaying intubation in the course of symptoms may be associated with higher mortality. Trial registration: The study protocol was approved by the local Ethics Committee (opinion number 3.990.817; CAAE: 30417520.0.0000.0068).
Temporal Gene Expression Profiles Reflect the Dynamics of Lymphoid Differentiation
Authors: Chalabi Smahane , Legrand Agnes , Michaels Victoria , Palomares Marie-Ange , Olaso Robert , Boland Anne , Deleuze Jean-François , Ezine Sophie , Battail Christophe , Tronik-Le Roux Diana
Published: January 2022

Understanding the emergence of lymphoid committed cells from multipotent progenitors (MPP) is a great challenge in hematopoiesis. To gain deeper insight into the dynamic expression changes associated with these transitions, we report the quantitative transcriptome of two MPP subsets and the common lymphoid progenitor (CLP). While the transcriptome is rather stable between MPP2 and MPP3, expression changes increase with differentiation. Among those, we found that pioneer lymphoid genes such as Rag1, Mpeg1, and Dntt are expressed continuously from MPP2. Others, such as CD93, are CLP specific, suggesting their potential use as new markers to improve purification of lymphoid populations. Notably, a six-transcription factor network orchestrates the lymphoid differentiation program. Additionally, we pinpointed 24 long intergenic-non-coding RNA (lincRNA) differentially expressed through commitment and further identified seven novel forms. Collectively, our approach provides a comprehensive landscape of coding and non-coding transcriptomes expressed during lymphoid commitment.
Sesquiterpene Lactones Potentiate Olaparib-Induced DNA Damage in p53 Wildtype Cancer Cells
Authors: Osborne Hugh C. , Larrosa Igor , Schmidt Christine K.
Published: January 2022

Despite notable advances in utilising PARP inhibitor monotherapy, many cancers are not PARP inhibitor-sensitive or develop treatment resistance. In this work, we show that the two structurally-related sesquiterpene lactones, a 2-bromobenzyloxy derivative of dehydrosantonin (BdS) and alantolactone (ATL) sensitise p53 wildtype, homologous recombination-proficient cancer cells to low-dose treatment with the PARP inhibitor, olaparib. Exposure to combination treatments of olaparib with BdS or ATL induces cell-cycle changes, chromosomal instability, as well as considerable increases in nuclear area. Mechanistically, we uncover that mitotic errors likely depend on oxidative stress elicited by the electrophilic lactone warheads and olaparib-mediated PARP-trapping, culminating in replication stress. Combination treatments exhibit moderately synergistic effects on cell survival, probably attenuated by a p53-mediated, protective cell-cycle arrest in the G2 cell-cycle phase. Indeed, using a WEE1 inhibitor, AZD1775, to inhibit the G2/M cell-cycle checkpoint further decreased cell survival. Around half of all cancers diagnosed retain p53 functionality, and this proportion could be expected to increase with improved diagnostic approaches in the clinic. Utilising sublethal oxidative stress to sensitise p53 wildtype, homologous recombination-proficient cancer cells to low-dose PARP-trapping could therefore serve as the basis for future research into the treatment of cancers currently refractory to PARP inhibition.
Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors
Authors: Iacovino Maria Lucia , Miceli Chiara Carmen , De Felice Marco , Barone Biagio , Pompella Luca , Chiancone Francesco , Di Zazzo Erika , Tirino Giuseppe , Della Corte Carminia Maria , Imbimbo Ciro , De Vita Ferdinando , Crocetto Felice
Published: January 2022

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification.
Retinal Plasticity
Authors: Strettoi Enrica , Di Marco Beatrice , Orsini Noemi , Napoli Debora
Published: January 2022

Brain plasticity is a well-established concept designating the ability of central nervous system (CNS) neurons to rearrange as a result of learning, when adapting to changeable environmental conditions or else while reacting to injurious factors. As a part of the CNS, the retina has been repeatedly probed for its possible ability to respond plastically to a variably altered environment or to pathological insults. However, numerous studies support the conclusion that the retina, outside the developmental stage, is endowed with only limited plasticity, exhibiting, instead, a remarkable ability to maintain a stable architectural and functional organization. Reviewed here are representative examples of hippocampal and cortical paradigms of plasticity and of retinal structural rearrangements found in organization and circuitry following altered developmental conditions or occurrence of genetic diseases leading to neuronal degeneration. The variable rate of plastic changes found in mammalian retinal neurons in different circumstances is discussed, focusing on structural plasticity. The likely adaptive value of maintaining a low level of plasticity in an organ subserving a sensory modality that is dominant for the human species and that requires elevated fidelity is discussed.
The Optimized Delivery of Triterpenes by Liposomal Nanoformulations: Overcoming the Challenges
Authors: Milan Andreea , Mioc Alexandra , Prodea Alexandra , Mioc Marius , Buzatu Roxana , Ghiulai Roxana , Racoviceanu Roxana , Caruntu Florina , Şoica Codruţa
Published: January 2022

The last decade has witnessed a sustained increase in the research development of modern-day chemo-therapeutics, especially for those used for high mortality rate pathologies. However, the therapeutic landscape is continuously changing as a result of the currently existing toxic side effects induced by a substantial range of drug classes. One growing research direction driven to mitigate such inconveniences has converged towards the study of natural molecules for their promising therapeutic potential. Triterpenes are one such class of compounds, intensively investigated for their therapeutic versatility. Although the pharmacological effects reported for several representatives of this class has come as a well-deserved encouragement, the pharmacokinetic profile of these molecules has turned out to be an unwelcomed disappointment. Nevertheless, the light at the end of the tunnel arrived with the development of nanotechnology, more specifically, the use of liposomes as drug delivery systems. Liposomes are easily synthesizable phospholipid-based vesicles, with highly tunable surfaces, that have the ability to transport both hydrophilic and lipophilic structures ensuring superior drug bioavailability at the action site as well as an increased selectivity. This study aims to report the results related to the development of different types of liposomes, used as targeted vectors for the delivery of various triterpenes of high pharmacological interest.
NMR and MD Analysis of the Bonding Interaction of Vancomycin with Muramyl Pentapeptide
Authors: Ślusarz Rafał , Dmochowska Barbara , Samaszko-Fiertek Justyna , Brzozowski Krzysztof , Madaj Janusz
Published: January 2022

The article describes an NMR spectroscopy study of interactions between vancomycin and a muramyl pentapeptide in two complexes: vancomycin and a native muramyl pentapeptide ended with D-alanine (MPP-D-Ala), and vancomycin and a modified muramyl pentapeptide ended with D-serine (MPP-D-Ser). The measurements were made in a 9:1 mixture of H2O and D2O. The obtained results confirmed the presence of hydrogen bonds previously described in the literature. At the same time, thanks to the pentapeptide model used, we were able to prove the presence of two more hydrogen bonds formed by the side chain amino group of L-lysine and oxygen atoms from the vancomycin carboxyl and amide groups. This type of interaction has not been described before. The existence of these hydrogen bonds was confirmed by the 1H NMR and molecular modeling. The formation of these bonds incurs additional through-space interactions, visible in the NOESY spectrum, between the protons of the L-lysine amino group and a vancomycin-facing hydrogen atom in the benzylic position. The presence of such interactions was also confirmed by molecular dynamics trajectory analysis.
The Promoter of the Immune-Modulating Gene TIR-Containing Protein C of the Uropathogenic Escherichia coli Strain CFT073 Reacts to the Pathogen’s Environment
Authors: Hemberger Jacqueline , Ittensohn Julia , Griffiths Hannah , Keller Maren , Costina Victor , Albrecht Simone , Miethke Thomas
Published: January 2022

The TIR-containing protein C (TcpC) of the uropathogenic Escherichia coli strain CFT073 modulates innate immunity by interfering with the Toll-like receptor and NALP3 inflammasome signaling cascade. During a urinary tract infection the pathogen encounters epithelial and innate immune cells and replicates by several orders of magnitude. We therefore analyzed whether these cell types and also the density of the pathogen would induce the recently defined promoter of the CFT073 tcpC gene to, in time, dampen innate immune responses. Using reporter constructs we found that the uroepithelial cell line T24/83 and the monocytic cell line THP-1 induced the tcpC promoter. Differentiation of monocytic THP-1 cells to macrophages increased their potential to switch on the promoter. Cell-associated CFT073 displayed the highest promoter activity. Since potassium represents the most abundant intracellular ion and is secreted to induce the NLRP3 inflammasome, we tested its ability to activate the tcpC promoter. Potassium induced the promoter with high efficiency. Sodium, which is enriched in the renal cortex generating an antibacterial hypersalinity, also induced the tcpC promoter. Finally, the bacterial density modulated the tcpC promoter activity. In the search for promoter-regulating proteins, we found that the DNA-binding protein H-NS dampens the promoter activity. Taken together, different cell types and salts, present in the kidney, are able to induce the tcpC promoter and might explain the mechanism of TcpC induction during a kidney infection with uropathogenic E. coli strains.
Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells
Authors: Egorova Anna , Shtykalova Sofia , Maretina Marianna , Selutin Alexander , Shved Natalia , Deviatkin Dmitriy , Selkov Sergey , Baranov Vladislav , Kiselev Anton
Published: January 2022

Suicide gene therapy was suggested as a possible strategy for the treatment of uterine fibroids (UFs), which are the most common benign tumors inwomen of reproductive age. For successful suicide gene therapy, DNAtherapeutics should be specifically delivered to UF cells. Peptide carriers are promising non-viral gene delivery systems that can be easily modified with ligands and other biomolecules to overcome DNA transfer barriers. Here we designed polycondensed peptide carriers modified with a cyclic RGD moiety for targeted DNA delivery to UF cells. Molecular weights of the resultant polymers were determined, and inclusion of the ligand was confirmed by MALDI-TOF. The physicochemical properties of the polyplexes, as well as cellular DNA transport, toxicity, and transfection efficiency were studied, and the specificity of αvβ3 integrin-expressing cell transfection was proved. The modification with the ligand resulted in a three-fold increase of transfection efficiency. Modeling of the suicide gene therapy by transferring the HSV-TK suicide gene to primary cells obtained from myomatous nodes of uterine leiomyoma patients was carried out. We observed up to a 2.3-fold decrease in proliferative activity after ganciclovir treatment of the transfected cells. Pro- and anti-apoptotic gene expression analysis confirmed our findings that the developed polyplexes stimulate UF cell death in a suicide-specific manner.
Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products
Authors: Gatin Anouchka , Duchambon Patricia , Rest Guillaume van der , Billault Isabelle , Sicard-Roselli Cécile
Published: January 2022

Protein dimerization via tyrosine residues is a crucial process in response to an oxidative attack, which has been identified in many ageing-related pathologies. Recently, it has been found that for isolated tyrosine amino acid, dimerization occurs through three types of tyrosine–tyrosine crosslinks and leads to at least four final products. Herein, considering two protected tyrosine residues, tyrosine-containing peptides and finally proteins, we investigate the dimerization behavior of tyrosine when embedded in a peptidic sequence. After azide radical oxidation and by combining UPLC-MS and H/D exchange analyzes, we were able to evidence: (i) the slow kinetics of Michael Addition Dimers (MAD) formation, i.e., more than 48 h; (ii) the co-existence of intermediates and final cyclized dimer products; and (iii) the probable involvement of amide functions to achieve Michael additions even in proteins. This raises the question of the possible in vivo existence of both intermediates and final entities as well as their toxicity and the potential consequences on protein structure and/or function.
TRIM37 Promotes Pancreatic Cancer Progression through Modulation of Cell Growth, Migration, Invasion, and Tumor Immune Microenvironment
Authors: Do Tuyen Thi , Yeh Chun-Chieh , Wu Guo-Wei , Hsu Chia-Chen , Chang Hung-Chih , Chen Hui-Chen
Published: January 2022

TRIM37 dysregulation has been observed in several cancer types, implicating its possible role in tumorigenesis. However, the role of TRIM37 in pancreatic cancer progression remains unclear. In the present study, we observed that TRIM37 knockdown resulted in reduced proliferation, clonogenicity, migration, and invasion ability of pancreatic cancer cells. Furthermore, an in vivo study using an orthotopic syngeneic animal model further confirmed that reduced expression of TRIM37 in cancer cells suppressed tumor growth in vivo. Moreover, in mice bearing TRIM37 knockdown pancreatic cancer cells, the proportion of CD11b+F4/80+MHCIIlow immunosuppressive macrophages was significantly reduced in tumor milieu, which might be due to the regulatory role of TRIM37 in cytokine production by pancreatic cancer cells. Collectively, these findings suggest a key role of TRIM37 in promoting pancreatic cancer progression.
Sustainable Human Development at the Municipal Level: A Data Envelopment Analysis Index
Authors: Lima Pedro A. B. , Paião Júnior Gilberto D. , Santos Thalita L. , Furlan Marcelo , Battistelle Rosane A. G. , Silva Gustavo H. R. , Ferraz Diogo , Mariano Enzo B.
Published: January 2022

The development of indexes for human development and environmental sustainability issues are an emerging topic in the current literature. However, the literature has put less emphasis on municipal indexes, which is the focus of this research. In this paper, we considered municipal environmental management as the adoption of environmental activities and the development of infrastructural and technical capacities in municipalities. This article aims to create a sustainable human development index with municipal data from the state of São Paulo in Brazil. Using information from the Municipal Human Development Index (IDHm) and the GreenBlue Municipal Program (PMVA), we applied the data envelopment analysis (DEA) technique to connect human development and environmental sustainability in 645 Brazilian municipalities. Our findings show that regions with higher human development present better DEA scores on the Sustainable Human Development Index. In contrast, regions with a low or a middle level of human development do not present significant change considering both dimensions. Moreover, our findings reveal that PMVA certification has a different and statistically significant impact on the DEA score considering certified, qualified, or not qualified regions. We found similar results for urbanized and service-oriented municipalities. Our indicator is an essential and straightforward tool for regional policymakers, helping to allocate resources and to find human development and environmental sustainability benchmarks among developing regions.
Observed Seismic Behavior of a HDRB and SD Isolation System under Far Fault Earthquakes
Authors: Salvatori Antonello , Bongiovanni Giovanni , Clemente Paolo , Ormando Chiara , Saitta Fernando , Scafati Federico
Published: January 2022

The behavior of a reinforced concrete building, seismically isolated with high damping rubber bearing (HDRB) and sliding devices (SD), observed during the most important events of the seismic sequence that struck central Italy from August 2016 to January 2017, is analyzed. Due to the epicenter distances, all the events had light effects at the site, thus the isolation system was not always put into action. A previous very low energy earthquake and the ambient vibration analysis are used for comparison. The study of the isolation system response is first carried out and the variability of the resonance frequencies with the input energy at the site is pointed out. These frequencies are quite close to those of the superstructure considered as fixed base. Small cracks were observed after the sequence in some partition walls of the building. The analysis of the superstructure was performed by means of a finite element model, assuming a non-linear model for the isolators, based on previous experimental data. The importance of a suitable decoupling between the superstructure and the ground and the contribution of the sliding devices under low energy earthquake is pointed out.
Cardiac Arrest during Interventional Radiology Procedures: A 7-Year Single-Center Retrospective Study
Authors: Nam In Chul , Lee Esther Sangeun , Shin Ji Hoon , Li Vincent Xinrui , Chu Hee Ho , Park Sung Eun , Won Jung Ho
Published: January 2022

An intervention radiology (IR) unit collected cardiac arrest data between January 2014 and July 2020. Of 344,600 procedures, there were 23 cardiac arrest patients (0.0067%). The patient data was compared to a representative sample (N = 400) of the IR unit to evaluate the incidence and factors associated with cardiac arrest during IR procedures. Age, procedure urgency, American Society of Anesthesiologists (ASA) physical status, procedure type, and underlying medical conditions were identified as valuable predictors of a patient’s susceptibility to cardiac arrest during an IR procedure. The proportion of pediatrics was higher for cardiac arrest patients, and most required immediate procedures. The distribution of high ASA physical status (III or greater) was skewed compared to that of the non-cardiac arrest patients. Vascular procedures were associated with higher risk than non-vascular procedures. The patients who underwent non-transarterial chemoembolization arterial procedures demonstrated relative risks of 4.4 and 11.7 for cardiac arrest compared to biliary procedures and percutaneous catheter drainage, respectively. In addition, the six patients (26.1%) who died before discharge all underwent vascular procedures. Relative to patients with acute kidney injury, patients with malignancy, hypertension, and diabetes mellitus demonstrated relative risks of 3.3, 3.4, and 4.8 for cardiac arrest, respectively.
Microwave Therapy for Cellulite: An Effective Non-Invasive Treatment
Authors: Bennardo Luigi , Fusco Irene , Cuciti Cristina , Sicilia Claudia , Salsi Benedetta , Cannarozzo Giovanni , Hoffmann Klaus , Nisticò Steven Paul
Published: January 2022

Background: Cellulite represents a common cosmetic problem that affects nearly all women. This study aimed to evaluate microwave therapy’s effectiveness for cellulite treatment. Methods: In this study, 26 women showing severe or moderate cellulite underwent four sessions of microwave therapy on the buttocks and posterior thighs. The following assessments were performed at baseline and the three-month follow-up after the last treatment: the Cellulite Severity Scale (CSS), Nürnberger–Müller classification scale, photographic evaluation, and buttocks/posterior thighs circumference measurements. A Likert scale questionnaire was used to assess patient satisfaction at the 3-month follow-up. Results: The treatment positively affected the cellulite severity as confirmed by the Cellulite Severity Scale (CSS) and Nürnberger–Müller classification scale results. CSS showed a significant amelioration in cellulite severity between the initial assessment and the 3-month follow-up for the buttocks and posterior thighs, with total average scores that ranged from 10.7 ± 3.1 to 4.5 ± 1.8 (p < 0.01). The treatment also resulted in a remarkable improvement in comfort/satisfaction and a buttocks and posterior thighs circumference reduction. No serious adverse events were observed. Conclusions: Microwave therapy has proven to be a safe treatment for improving cellulite appearance and reducing body circumferences.
The Acute Effects of an Ultramarathon on Atrial Function and Supraventricular Arrhythmias in Master Athletes
Authors: Cavigli Luna , Zorzi Alessandro , Spadotto Veronica , Mandoli Giulia , Melani Andrea , Fusi Chiara , D’Andrea Antonello , Focardi Marta , Valente Serafina , Cameli Matteo , Bonifazi Marco , D’Ascenzi Flavio
Published: January 2022

Background. Endurance sports practice has significantly increased over the last decades, with a growing proportion of master athletes. However, concerns exist regarding the potential proarrhythmic effects induced by ultra-endurance sports. This study aimed to analyse the acute effects of an ultramarathon race on atrial remodelling and supraventricular arrhythmias in a population of master athletes. Methods. Master athletes participating in an ultramarathon (50 km, 600 m of elevation gain) with no history of heart disease were recruited. A single-lead ECG was recorded continuously from the day before to the end of the race. Echocardiography and 12-lead resting ECG were performed before and immediately at the end of the race. Results. The study sample consisted of 68 healthy non-professional master athletes. Compared with baseline, P wave voltage was higher after the race (p < 0.0001), and more athletes developed ECG criteria for right atrial enlargement (p < 0.0001). Most of the athletes (97%) had ≥1 premature atrial beats (PAB) during the 24-h monitoring, also organised in triplets (17%) and non-sustained supraventricular tachycardias (NSSVTs) (19%). In contrast, exercise-induced PABs, triplets, and NSSVTs were rare. One athlete developed acute atrial fibrillation during the race. After the race, no significant differences were found in biatrial dimensions. Biatrial function, estimated by peak atrial longitudinal and contraction strains, were normal both before and after the race. Conclusions. In master athletes running an ultramarathon, acute exercise-induced atrial dysfunction was not detected, and exercise-induced supraventricular arrhythmias were uncommon. These results did not confirm the hypothesis of an acute atrial dysfunction induced by ultra-endurance exercise.