bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast Cancer Mortality in Young Women in Brazil
Authors: Silva Juliana Dalcin Donini E. , de Oliveira Rosana Rosseto , da Silva Mariana Teixeira , Carvalho Maria Dalva de Barros , Pedroso Raissa Bocchi , Pelloso Sandra Marisa
Published: January 2021

Objective

Malignant breast cancer is the leading cause of death by cancer in young women. The study aimed to determine if breast cancer mortality among young women has increased between the period from 1996 to 2017 in Brazil.

Methods

A time-series analysis of breast cancer mortality rate in young women (20–39 years old) was carried out. Mortality data, from 1996 to 2017, were collected from the Mortality Information System of the Health Ministry, and demographic data, from the Brazilian Institute of Geography and Statistics. Trends in mortality were performed by Joinpoint Regression, the spatial distribution of the mortality rate was done with the QGIZ Software version 2.18, and Spearman’s correlation coefficient was used to correlate the mortality rates with the Human Development Index.

Results

There was an increase in breast cancer mortality rates in young women in the majority of Brazilian states, with an upward trend in all regions. The correlation with the Municipal Human Development Index, income, and education had a significant impact on the mortality rate for women from 30–39 years old in both time frames evaluated and for women from 20–29 years old, only from 1996 to 2000.

Conclusion

The data obtained in the study, showed that even though the breast cancer mortality rate of young women is lower than women over 40 years old, it has been increasing in all regions of Brazil, mostly for women from 30–39 years old, suggesting that this group should be included in screening programs.
Cesarean Section Due to Social Factors Affects Children's Psychology and Behavior: A Retrospective Cohort Study
Authors: Shi Xiu-Yu , Wang Jing , Zhang Wei-Na , Zhao Meng , Ju Jun , Li Xiao-Yan , Lu Qian , Wang Bin , Zou Li-Ping
Published: January 2021

Background: Cesarean section (CS) use has reached a frequency well-above what is expected on the basis of obstetric indications. The large increase in CS use, often for non-medical indications, is of concern given the risks for both women and children. Research about the influence of CS on children's behavior is not new, but most studies didn't differentiate CS due to social factors (such as fear of labor pain, auspicious dates, etc.) from CS with medical indications. Medical indications for CS include fetal distress and intrauterine hypoxia, which may also affect the mental and physical health of the children, thus be a confounding factor. In China, a significant proportion of women undergo CS because of social factors, which provides us a good model to study whether non-fetal triggered delivery will affect children's behavior. Thus, we assessed the impact of CS due to social factors on child psychology and behavior.

Methods: We conducted a retrospective cohort study. Children were divided into three groups according to delivery mode: vaginal delivery (VD), CS with medical indications, and CS due to social factors (also called as elective cesarean section, ECS). Parents or guardians were required to complete four rating scales of Chinese version [Conners' Parent Rating Scale (CPRS), Child Behavior Checklist-Parent Form (CBCL-PF), Swanson, Nolan, and Pelham rating scale-Parent Form (SNAP-IV-PF), and Behavior Rating Inventory of Executive Function-Parent Form (BRIEF-PF)] on psychological and behavioral problems regarding their children.

Results: Among the 38,780 children aged 7–15 years, 29,103 (75.05%) were delivered by VD and 9,677 (24.95%) were delivered by CS (7,844 with medical indications; 1,833 by ECS). Ten covariates were found to significantly affect ECS. Four rating scales were used in this study: CPRS, CBCL-PF, SNAP-IV-PF, and BRIEF-PF. ECS affected child psychology and behavior in several aspects including inattention, hyperactivity/impulsivity, social problems, and executive dysfunction. Regarding to inattention, the ECS group had a higher SNAP-IV-PF inattention score (P = 0.03), compared with the VD group. Logistic multivariate stepwise regression analysis showed that in the ECS group, the ORs were 1.20 in the partially adjusted analyses of SNAP-IV-PF and CPRS. Regarding to social problems, ECS group had a higher CBCL-PF score for the social problems category compared with the VD group (P = 0.0001). Kruskal–Wallis rank sum tests showed that the ECS group had higher BRIEF-PF scores regarding Working Memory (P = 0.04), and Organize (P = 0.01) compared with the VD group.

Conclusions: CS affected the offspring's psychology and behavior. After removing possible influence of medical indications, the effect of CS due to social factors on the offspring's psychology and behavior still exists.
Exploration of the Optimal Desmopressin Treatment in Children With Monosymptomatic Nocturnal Enuresis: Evidence From a Chinese Cohort
Authors: Liu Jiaojiao , Ni Jiajia , Miao Qianfan , Wang Chunyan , Lin Fang , Cao Qi , Guo Wei , Yang Xue , Ji Xiaolu , Zhai Yihui , Bi Yunli , Shen Qian , Xu Hong
Published: January 2021

Objectives:Nocturnal enuresis (NE) is a common pediatric condition, and desmopressin (dDAVP) is a first-line therapy for NE. The standard initial dosage of dDAVP is 0. 2 mg/day, and most guidelines recommend that the dose should be increased at 0.2 mg increments until dryness is achieved or to the maximal recommended dose. However, previous evidence has shown that this strategy seems insufficient to further improve efficacy and results in unnecessarily high doses for some patients. Our study aimed to assess the efficacy of our modified dDAVP treatment regimen in children with MNE in China and evaluate predictive factors associated with the dDAVP response.

Methods:All MNE patients at the Department of Nephrology at Children's Hospital of Fudan University from January to December 2019 were prospectively and consecutively enrolled. dDAVP treatment comprised a dose titration period and a 3-month maintenance period. The efficacy of dDAVP was assessed according to the latest International Children's Continence Society criteria at the end of the study. Predictive factors were evaluated by logistic regression analysis.

Results:Overall, 322 MNE patients were enrolled in our study, and 225 (69.9%) completed the study. The intention to treat analysis showed that the overall dDAVP response rate was 69.9%: among these patients 32.3% were complete responders, and 37.6% were partial responders. At the end of the study, 194/225 (86.2%) patients received a final dose of 0.2 mg, 24/225 (10.7%) patients received a final dose of 0.3 mg, and 7/225 (3.1%) patients received a final dose of 0.4 mg. Multivariate analysis showed that patients requiring lower doses to achieve responses were significantly more likely to experience complete response during the maintenance period [odds ratio (OR)=9.683; 95% confidence interval (CI), 2.770–33.846].

Conclusions:Our results indicate that the dDAVP treatment regimen provides a comparable efficacy to the international conventional treatment regimen with a lower overall dose. Low-dose responders were likely to achieve a complete response without increasing the dose; in these cases, the maximum dose might not be necessary.
Taking Sleeping Pills and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Retrospective Cohort Study
Authors: Liao Chen-Yi , Chung Chi-Hsiang , Lu Kuo-Cheng , Cheng Cheng-Yi , Yang Sung-Sen , Chien Wu-Chien , Wu Chia-Chao
Published: January 2021

Background: Sleeping disorder has been associated with chronic kidney disease (CKD); however, the correlation between sleeping pills use and CKD has not been investigated in-depth yet. This study elucidated the potential association of sleeping pill use with the risk of CKD and CKD progression to end-stage renal disease (ESRD) requiring dialysis.

Methods: This study was based on a population-based cohort that included 209,755 sleeping pill users among 989,753 individuals. After applying the exclusion criteria, 186,654 sleeping pill users and 373,308 nonusers were enrolled to monitor the occurrence of CKD. Using a cumulative daily dose, we analyzed the types of sleeping pills related to the risk of CKD and ESRD. Propensity score matching and analysis using Cox proportional hazards regression were performed with adjustments for sex, age, and comorbidities.

Results: Sleeping pill use was related to increased CKD risk after adjusting for underlying comorbidities (adjusted hazard ratio [aHR] = 1.806, 95% confidence interval [CI]: 1.617–2.105, p < 0.001). With the exception of hyperlipidemia, most comorbidities correlated with an increased risk of CKD. Persistent use of sleeping pills after CKD diagnosis increased the risk of concurrent ESRD (aHR = 7.542; 95% CI: 4.267–10.156; p < 0.001). After the subgroup analysis for sleeping pill use, brotizolam (p = 0.046), chlordiazepoxide (p < 0.001), clonazepam (p < 0.001), diazepam (p < 0.001), dormicum (p < 0.001), estazolam (p < 0.001), fludiazepam (p < 0.001), flunitrazepam (p < 0.001), nitrazepam (p < 0.001), trazodone (p < 0.001), zolpidem (p < 0.001), and zopiclone (p < 0.001) were found to have significant correlation with increased CKD risk.

Conclusion: Sleeping pill use was related to an increased risk of CKD and ESRD. Further studies are necessary to corroborate these findings.
Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines
Authors: Abdullah-Koolmees Heshu , van Keulen Antonius M. , Nijenhuis Marga , Deneer Vera H. M.
Published: January 2021

Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient’s genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename “extensive metabolizer (EM)” to “normal metabolizer (NM)”. It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.
STAT3 Suppresses Cardiomyocytes Apoptosis in CVB3-Induced Myocarditis Via Survivin
Authors: Wang Qiaoyu , Zhu Qiongjun , Ye Qiaofang , Wang Jiajun , Dong Qianqian , Chen Youran , Wang Minna , Fu Yu , Wu Rongzhou , Wu Tingting
Published: January 2021

Background: Viral myocarditis (VMC) is a common inflammatory cardiovascular disease with unclear mechanisms, which mainly affects children and adolescents. Apoptosis is the key to CVB3-induced myocarditis, and blocking this process may be beneficial to the therapy of VMC. Hence, this study aimed to explore the protective function of STAT3 on cardiomyocyte apoptosis of VMC and its underlying mechanisms.

Methods and Results: In this research, we confirmed that STAT3 was significantly activated in both animal and cell models of VMC. To further clarify what role did STAT3 play in VMC, AG490, an inhibitor of STAT3, was used to suppress p-STAT3. Our results demonstrated that decreased expression of p-STAT3 caused by AG490 significantly aggravated severity of VMC with elevated myocardial inflammation, deteriorative ventricular systolic function and increased mortality. It suggested that STAT3 plays a protective role in VMC. To further identify the anti-apoptosis impact that activated STAT3 made, we constructed lentivirus to regulate the expression of STAT3 in NMCs. We found that up-regulated activated STAT3 attenuated cardiomyocyte apoptosis, but down-regulated one aggravated that, which verified activated STAT3 played an anti-apoptosis role in VMC. Following that, we explored what elements are involved in the anti-apoptotic mechanism of activated STAT3 by using survivin inhibitor YM155. The result showed the anti-apoptotic effect of activated STAT3 does not work in the case of survivin inhibition.

Conclusion: Our findings demonstrated STAT3 by targeting survivin alleviated cardiomyocyte apoptosis in CVB3-induced myocarditis.
Predicting a Potential Link to Antidepressant Effect: Neuroprotection of Zhi-zi-chi Decoction on Glutamate-induced Cytotoxicity in PC12 Cells
Authors: Zhang Yin , Luo Yusha , Zhang Dongqi , Pang Bo , Wen Jun , Zhou Tingting
Published: January 2021

Zhi-zi-chi Decoction (ZZCD), composed of Fructus Gardeniae (Zhizi in Chinese, ZZ in brief) and Semen sojae praeparatum (Dandouchi in Chinese, DDC in brief), has been used as a drug therapy for depression for thousands of years in China. However, the antidepressant mechanism of ZZCD still remains unknown. This study was aimed at exploring antidepressant effects of ZZCD from the aspect of neuroprotection based on herb compatibility. Glutamate-treated PC12 cells and chronic unpredictable mild stress (CUMS)-induced rats were established as models of depression in vitro and in vivo respectively. Cell viability, lactate dehydrogenase (LDH), apoptosis rate, reactive oxygen species (ROS), glutathione reductase (GR) and superoxide dismutase (SOD), and the expressions of Bax, Bcl-2 and cyclic adenosine monophosphate-response element binding protein (CREB) were measured to compare neuroprotection among single herbs and the formula in vitro. Behavior tests were conducted to validate antidepressant effects of ZZCD in vivo. Results showed that the compatibility of ZZ and DDC increased cell viability and activities of GR and SOD, and decreased the levels of LDH, apoptosis cells and ROS. Besides, the expressions of Bcl-2 and CREB were up-regulated while that of Bax was down-regulated by ZZCD. Furthermore, the compatibility of ZZ and DDC reversed abnormal behaviors in CUMS-induced rats and displayed higher efficacy than any of the single herbs. This study revealed that the antidepressant effects of ZZCD were closely associated with neuroprotection and elucidated synergistic effects of the compatibility of ZZ and DDC based on it.
A Longitudinal Study of T2 Mapping Combined With Diffusion Tensor Imaging to Quantitatively Evaluate Tissue Repair of Rat Skeletal Muscle After Frostbite
Authors: Gao Yue , Lu Zhao , Lyu Xiaohong , Liu Qiang , Pan Shinong
Published: January 2021

Purpose: T2 mapping and diffusion tensor imaging (DTI) enable the detection of changes in the skeletal muscle microenvironment. We assessed T2 relaxation times, DTI metrics, performed histological characterization of frostbite-induced skeletal muscle injury and repair, and provided diagnostic imaging biomarkers.

Design and Methods: Thirty-six Sprague Dawley rats (200 ± 10 g) were obtained. Thirty rats were used for establishing a skeletal muscle frostbite model, and six were untreated controls. Functional MR sequences were performed on rats on days 0, 3, 5, 10, and 14 (n = 6 per time point). Rats were then sacrificed to obtain the quadriceps muscles. Tensor eigenvalues (λ1, λ2, and λ3), mean diffusivity (MD), fractional anisotropy (FA), and T2 values were compared between the frostbite model and control rats. ImageJ was used to measure the extracellular area fraction (EAF), muscle fiber cross-sectional area (fCSA), and skeletal muscle tumor necrosis factor α (TNF-α), and Myod1 expression. The correlation between the histological and imaging parameters of the frostbitten skeletal muscle was evaluated. Kolmogorov–Smirnoff test, Leven’s test, one-way ANOVA, and Spearman coefficient were used for analysis.

Results: T2 relaxation time of frostbitten skeletal muscle was higher at all time points (p < 0.01). T2 relaxation time correlated with EAF, and TNF-α and Myod1 expression (r = 0.42, p < 0.05; r = 0.86, p < 0.01; r = 0.84, p < 0.01). The average tensor metrics (MD, λ1, λ2, and λ3) of skeletal muscle at 3 and 5 days of frostbite increased (p < 0.05), and fCSA correlated with λ1, λ2, and λ3, and MD (r = 0.65, p < 0.01; r = 0.48, p < 0.01; r = 0.52, p < 0.01; r = 0.62, p < 0.01).

Conclusion: T2 mapping and DTI imaging detect frostbite-induced skeletal muscle injury early. This combined approach can quantitatively assess skeletal muscle repair and regeneration within 2 weeks of frostbite. Imaging biomarkers for the diagnosis of frostbite were suggested.
Practices of Claiming Control and Independence in Couple Therapy With Narcissism
Authors: Janusz Bernadetta , Bergmann Jörg R. , Matusiak Feliks , Peräkylä Anssi
Published: January 2021

Four couple therapy first consultations involving clients with diagnosed narcissistic problems were examined. A sociologically enriched and broadened concept of narcissistic disorder was worked out based on Goffman’s micro-sociology of the self. Conversation analytic methods were used to study in detail episodes in which clients resist to answer a therapist’s question, block or dominate the development of the conversation’s topic, or conspicuously display their interactional independence. These activities are interpreted as a pattern of controlling practices that were prompted by threats that the first couple therapy consultation imposes upon the clients’ self-image. The results were discussed in the light of contemporary psychiatric discussions of narcissism; the authors suggest that beyond its conceptualization as a personality disorder, narcissism should be understood as a pattern of interactional practices.
A Perspective on Age Restrictions and Other Harm Reduction Approaches Targeting Youth Online Gambling, Considering Convergences of Gambling and Videogaming
Authors: Shi Jing , Colder Carras Michelle , Potenza Marc N. , Turner Nigel E.
Published: January 2021

Internet gambling has become a popular activity among some youth. Vulnerable youth may be particularly at risk due to limited harm reduction and enforcement measures. This article explores age restrictions and other harm reduction measures relating to youth and young adult online gambling. A systematic rapid review was conducted by searching eight databases. Additional articles on online gambling (e.g., from references) were later included. To place this perspective into context, articles on adult gambling, land-based gambling, and substance use and other problematic behaviors were also considered. Several studies show promising findings for legally restricting youth from gambling in that such restrictions may reduce the amount of youth gambling and gambling-related harms. However, simply labeling an activity as “age-restricted” may not deter youth from gambling; in some instances, it may generate increased appeal for gambling. Therefore, advertising and warning labels should be examined in conjunction with age restrictions. Recommendations for age enforcement strategies, advertising, education, and warning labels are made to help multiple stakeholders including policymakers and public health officials internationally. Age restrictions in online gambling should consider multiple populations including youth and young adults. Prevention and harm reduction in gambling should examine how age-restriction strategies may affect problem gambling and how they may be best enforced across gambling platforms. More research is needed to protect youth with respect to online gambling.
Gambling in COVID-19 Lockdown in the UK: Depression, Stress, and Anxiety
Authors: Sharman Steve , Roberts Amanda , Bowden-Jones Henrietta , Strang John
Published: January 2021

To combat the spread of COVID-19, the UK Government implemented a range of “lockdown” measures. Lockdown has necessarily changed the gambling habits of gamblers in the UK, and the impact of these measures on the mental health of gamblers is unknown. To understand the impact of lockdown on gamblers, in April 2020, after ~6 weeks of lockdown, participants (N = 1,028, 72% female) completed an online questionnaire. Gambling engagement data was collected for pre-lockdown via the Brief Problem Gambling Screen (BPGS) allowing participants to be classified as Non-Gamblers (NG), Non-Problem Gamblers (NPG) or Potential Problem Gamblers (PPG). The Depression, Stress, and Anxiety Scale (DASS21) was used to measure depression, stress, and anxiety scores both pre- and during-lockdown. Results indicate that depression, stress and anxiety has increased across the whole sample. Participants classified in the PPG group reported higher scores on each sub scale at both baseline and during lockdown. Increases were observed on each DASS21 subscale, for each gambler group, however despite variable significance and effect sizes, the magnitude of increases did not differ between groups. Lockdown has had a significant impact on mental health of participants; whilst depression stress and anxiety remain highest in potential problem gamblers, pre-lockdown gambler status did not affect changes in DASS21 scores.
Acknowledgment to Reviewers of Algorithms in 2020
Authors:   Algorithms Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Algorithms maintains its standards for the high quality of its published papers [...]
Non-Steroidal Anti-Inflammatory Drugs: Pharmacokinetics and Mitigation of Procedural-Pain in Cattle
Authors: Wagner Brooklyn K. , Nixon Emma , Robles Ivelisse , Baynes Ronald E. , Coetzee Johann F. , Pairis-Garcia Monique D.
Published: January 2021

Common routine management practices in cattle, such as castration and disbudding, are recognized as being painful. In the United States (U.S.), these procedures are frequently performed without pain mitigation and there are currently no drugs federally approved for such use. Non-steroidal anti-inflammatory drugs, such as meloxicam, flunixin meglumine and aspirin, are the most commonly used analgesics in U.S. food-animal production systems. However, the body of research investigating the effectiveness of these pharmaceuticals to control pain in cattle at castration and disbudding has not been comprehensively evaluated. Therefore, this review examined existing literature to summarize meloxicam, flunixin and aspirin (1) pharmacokinetics (PK) and (2) administration outcome in regard to pain control during castration and disbudding procedures, in cattle. Following systematic searches and screening, 47 PK and 44 publications were extracted for data and are presented. The sample size contained notable variability and a general deficiency of validated and replicated methodologies for assessing pain in cattle remain substantial challenges within this research area. Future research should prioritize replication of pain assessment methodologies across different experimental conditions to close knowledge gaps identified by the present study and facilitate examination of analgesic efficacy.
Energy Supplementation during the Last Third of Gestation Improves Mother–Young Bonding in Goats
Authors: Vázquez-García Juan M. , Álvarez-Fuentes Gregorio , Orozco-Gregorio Héctor O. , García-López Juan C. , González-Hernández Milagros , Rosales-Nieto César A.
Published: January 2021

We tested whether maternal energy supplementation during the last third of gestation improves birth weight, neonatal wellbeing, and mother–young bonding. Thirty-six pregnant French Alpine goats were randomly allocated among three nutritional treatments for the last third of pregnancy: (i) Control, fed alfalfa (T-0; n = 12); (ii) alfalfa + 150 g/head daily energy concentrate (T-150; n = 12); (iii) alfalfa + 300 g/head daily energy concentrate (T-300; n = 12). At birth, we collected progeny data on birth weight, birth type, sex, rectal temperature, heart rate, respiratory rate, time to standing, time to udder connection, and time to first feeding. For the dams, we collected data on the duration of labor, time to clean the progeny, and time to allow first suckling. At birth, body weight, rectal temperature, heart rate, and the respiratory rate did not differ among treatments (p > 0.05). In the dams, labor duration was not affected by the treatments (p > 0.05). The T-150 dams were faster to clean the newborn and allow first suckling (p < 0.05). The T-150 progeny were faster to stand and the T-300 progeny were faster to connect to the udder (p < 0.05). We conclude that energy supplementation of the dam during the last third of gestation does not affect the birth weight of the progeny, but enhances the mother–young bonding.
Effect of Intense Exercise on the Level of Bacteroidetes and Firmicutes Phyla in the Digestive System of Thoroughbred Racehorses
Authors: Górniak Wanda , Cholewińska Paulina , Szeligowska Natalia , Wołoszyńska Magdalena , Soroko Maria , Czyż Katarzyna
Published: January 2021

Exercise significantly affects the body of both animals and humans, including the composition of the digestive microbiome. This study aimed to determine the changes in the composition of the most numerous bacterial phyla (Firmicutes and Bacteroidetes, as well as the level of the Lactobacillaceae family) in the digestive system of horses under the influence of physical effort. The study included a group of 17 Thoroughbred racehorses at the age of 3 years, fed the same forage, from whom feces samples were collected individually before and 48 h after physical effort. The obtained samples were subjected to DNA isolation and RT-PCR analysis. The results showed a significant increase in the level of both phyla after exercise compared to the state before physical effort; there were no such differences in the level of facultative aerobes, i.e., the Lactobacillaceae family (although a decreasing tendency was found after exercise). In addition, the analysis of the level of the studied phyla indicates individual differences in horses’ response to the effort.
Current Knowledge on the Multifactorial Regulation of Corpora Lutea Lifespan: The Rabbit Model
Authors: Zerani Massimo , Polisca Angela , Boiti Cristiano , Maranesi Margherita
Published: January 2021

Our research group studied the biological regulatory mechanisms of the corpora lutea (CL), paying particular attention to the pseudopregnant rabbit model, which has the advantage that the relative luteal age following ovulation is induced by the gonadotrophin-releasing hormone (GnRH). CL are temporary endocrine structures that secrete progesterone, which is essential for maintaining a healthy pregnancy. It is now clear that, besides the classical regulatory mechanism exerted by prostaglandin E2 (luteotropic) and prostaglandin F2 (luteolytic), a considerable number of other effectors assist in the regulation of CL. The aim of this paper is to summarize our current knowledge of the multifactorial mechanisms regulating CL lifespan in rabbits. Given the essential role of CL in reproductive success, a deeper understanding of the regulatory mechanisms will provide us with valuable insights on various reproductive issues that hinder fertility in this and other mammalian species, allowing to overcome the challenges for new and more efficient breeding strategies.
Precursory Signals (SST and Soil Moisture) of Summer Surface Temperature Anomalies over the Tibetan Plateau
Authors: Wang Huimei , Liu Ge , Wang Sai , He Kejun
Published: January 2021

Understanding the variability of surface air temperature (SAT) over the Tibetan Plateau (TP) and its precursory signals is of great benefit to climate change adaptation and socioeconomic development. This study explores the precursory signals of summer SATs over the TP in oceanic and land boundary conditions. The results show that the summer eastern TP SAT is significantly correlated with three precursors in April: the high-latitude North Atlantic sea surface temperature (SST), the northern Indian Ocean SST, and the Indian soil moisture (SM). The April SST anomalies (SSTAs) in the high-latitude North Atlantic can exert a cross-season impact on the summer SAT over the TP through two processes. The SSTAs in the high-latitude North Atlantic maintain from April to summer and modulate atmospheric circulation over the eastern TP through exciting a downstream wave train during summer, and finally modulate the summer SAT over the eastern TP. In addition to the above process, the April SSTAs in the high-latitude North Atlantic may remotely regulate simultaneous SM in the Indian subcontinent through stimulating a downstream wave train pattern. Through a persistent SM–precipitation interaction, the April Indian SM anomaly can affect the local precipitation and associated condensation heating anomalies during the ensuing summer, which forces an anomalous cyclone–anticyclone pattern around the TP and accordingly affects the summer SAT over the eastern TP. Additionally, the SSTAs in the northern Indian Ocean can persist from April to summer and adjust the intensity and location of the western North Pacific subtropical high through the Kelvin-wave-induced Ekman divergence during summer, eventually affecting the summer eastern TP SAT. The three precursory signals, which synergistically contribute to the variability of the summer eastern TP SAT, can be applied in predicting the summer SAT over the eastern TP.
Reconstruction of the Interannual to Millennial Scale Patterns of the Global Surface Temperature
Authors: Scafetta Nicola
Published: January 2021

Climate changes are due to anthropogenic factors, volcano eruptions and the natural variability of the Earth’s system. Herein the natural variability of the global surface temperature is modeled using a set of harmonics spanning from the inter-annual to the millennial scales. The model is supported by the following considerations: (1) power spectrum evaluations show 11 spectral peaks (from the sub-decadal to the multi-decadal scales) above the 99% confidence level of the known temperature uncertainty; (2) spectral coherence analysis between the independent global surface temperature periods 1861–1937 and 1937–2013 highlights at least eight common frequencies between 2- and 20-year periods; (3) paleoclimatic temperature reconstructions during the Holocene present secular to millennial oscillations. The millennial oscillation was responsible for the cooling observed from the Medieval Warm Period (900–1400) to the Little Ice Age (1400–1800) and, on average, could have caused about 50% of the warming observed since 1850. The finding implies an equilibrium climate sensitivity of 1.0–2.3 °C for CO2 doubling likely centered around 1.5 °C. This low sensitivity to radiative forcing agrees with the conclusions of recent studies. Semi-empirical models since 1000 A.D. are developed using 13 identified harmonics (representing the natural variability of the climate system) and a climatic function derived from the Coupled Model Intercomparison Project 5 (CMIP5) model ensemble mean simulation (representing the mean greenhouse gas—GHG, aerosol, and volcano temperature contributions) scaled under the assumption of an equilibrium climate sensitivity of 1.5 °C. The harmonic model is evaluated using temperature data from 1850 to 2013 to test its ability to predict the major temperature patterns observed in the record from 2014 to 2020. In the short, medium, and long time scales the semi-empirical models predict: (1) temperature maxima in 2015–2016 and 2020, which is confirmed by the 2014–2020 global temperature record; (2) a relatively steady global temperature from 2000 to 2030–2040; (3) a 2000–2100 mean projected global warming of about 1 °C. The semi-empirical model reconstructs accurately the historical surface temperature record since 1850 and hindcasts mean surface temperature proxy reconstructions since the medieval period better than the model simulation that is unable to simulate the Medieval Warm Period.
Acknowledgment to Reviewers of Atmosphere in 2020
Authors:   Atmosphere Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Atmosphere maintains its standards for the high quality of its published papers [...]
Acknowledgment to Reviewers of Beverages in 2020
Authors:   Beverages Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Beverages maintains its standards for the high quality of its published papers [...]
The Impact of Electrical Stimulation of the Brain and Spinal Cord on Iron and Calcium-Phosphate Metabolism
Authors: Sokal Paweł , Świtońska Milena , Kierońska Sara , Rudaś Marcin , Harat Marek
Published: January 2021

Background: Deep-brain stimulation (DBS) electrically modulates the subcortical brain regions. Under conditions of monopolar cerebral stimulation, electrical current flows between electrode’s contacts and an implantable pulse generator, placed in the subclavicular area. Spinal cord stimulation (SCS) delivers an electrical current to the spinal cord. Epidural electrical stimulation is associated with the leakage of current, which can cause a generalized reaction. The aim of our study was to investigate whether the electrical stimulation of the cerebrum and spinal cord could have generalized effects on biochemical parameters. Materials and methods: A total of 25 patients with Parkinson’s disease (PD, n = 21) and dystonia (n = 4), who underwent DBS implantation, and 12 patients with chronic pain, who had SCS, received electrical stimulation. The blood levels of selected biochemical parameters were measured before and after overnight stimulation. Results: After DBS, the mean ± interquartile range (IQR) values for iron (off 15.6 ± 13.53 µmol/L; on: 7.65 ± 10.8 µmol/L; p < 0.001), transferrin (off: 2.42 ± 0.88 g/L; on: 1.99 ± 0.59 g/L; p < 0.001), transferrin saturation (off: 23.20 ± 14.50%; on: 10.70 ± 11.35%; p = 0.001), phosphate (off: 1.04 ± 0.2 mmol/L; on: 0.83 ± 0.2 mmol/L; p = 0.007), and total calcium (off: 2.39 ± 0.29 mmol/L; on: 2.27 ± 0.19 mmol/L; p = 0.016) were significantly reduced, whereas ferritin (off: 112.00 ± 89.00 ng/mL; on: 150.00 ± 89.00 ng/mL; p = 0.003) and C-reactive protein (off: 0.90 ± 19.39 mg/L; on: 60.35 ± 35.91 mg/L; p = 0.002) were significantly increased. Among patients with SCS, significant differences were observed for ferritin (off: 35 ± 63 ng/mL; on: 56 ± 62 ng/mL; p = 0.013), transferrin (off: 2.70 ± 0.74 g/L; on: 2.49 ± 0.69 g/L; p = 0.048), and C-reactive protein (off: 31.00 ± 36.40 mg/L; on: 36.60 ± 62.030 mg/L; p = 0.018) before and after electrical stimulation. No significant changes in the examined parameters were observed among patients after thalamotomy and pallidotomy. Conclusions: Leaking electric current delivered to the subcortical nuclei of the brain and the dorsal column of the spinal cord exposes the rest of the body to a negative charge. The generalized reaction is associated with an inflammatory response and altered iron and calcium-phosphate metabolism. Alterations in iron metabolism due to electrical stimulation may impact the course of PD. Future research should investigate the influence of electric current and electromagnetic field induced by neurostimulators on human metabolism.
2020 Buildings Young Investigator Award: Announcement and Interview with the Winner
Authors:   Buildings Editorial Office
Published: January 2021

After an extensive voting period, we are proud to present the winner of the Buildings Young Investigator Award: [...]
Progress on Diamane and Diamanoid Thin Film Pressureless Synthesis
Authors: Piazza Fabrice , Monthioux Marc , Puech Pascal , Gerber Iann C. , Gough Kathleen
Published: January 2021

Nanometer-thick and crystalline sp3-bonded carbon sheets are promising new wide band-gap semiconducting materials for electronics, photonics, and medical devices. Diamane was prepared from the exposure of bi-layer graphene to hydrogen radicals produced by the hot-filament process at low pressure and temperature. A sharp sp3-bonded carbon stretching mode was observed in ultraviolet Raman spectra at around 1344–1367 cm−1 while no sp2-bonded carbon peak was simultaneously detected. By replacing bi-layer graphene with few-layer graphene, diamanoid/graphene hybrids were formed from the partial conversion of few-layer graphene, due to the prevalent Bernal stacking sequence. Raman spectroscopy, electron diffraction, and Density Functional Theory calculations show that partial conversion generates twisted bi-layer graphene located at the interface between the upper diamanoid domain and the non-converted graphenic domain underneath. Carbon-hydrogen bonding in the basal plane of hydrogenated few-layer graphene, where carbon is bonded to a single hydrogen over an area of 150 μm2, was directly evidenced by Fourier transform infrared microscopy and the actual full hydrogenation of diamane was supported by first-principle calculations. Those results open the door to large-scale production of diamane, diamanoids, and diamanoid/graphene hybrids.
Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?
Authors: Gomez-Brouchet Anne , Gilhodes Julia , Van Acker Nathalie , Brion Regis , Bouvier Corinne , Assemat Pauline , Gaspar Nathalie , Aubert Sebastien , Guinebretiere Jean-Marc , Marie Beatrice , Larousserie Frederique , Entz-Werlé Natacha , De Pinieux Gonzague , Mascard Eric , Gouin Francois , Brousset Pierre , Tabone Marie-Dominique , Jimenez Marta , Le Deley Marie-Cecile , Blay Jean-Yves , Brugieres Laurence , Piperno-Neumann Sophie , Rédini Francoise
Published: January 2021

Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical (“OSNew”) biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA− patients (padj = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy (p = 0.0091; p = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA− patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163−) mostly residing in osteolytic territories and osteoid-matrix-associated CD68−/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets.
Activated Lymphocytes and Increased Risk of Dermatologic Adverse Events during Sorafenib Therapy for Hepatocellular Carcinoma
Authors: Corominas Josep , Sapena Victor , Sanduzzi-Zamparelli Marco , Millán Cristina , Samper Esther , Llarch Neus , Iserte Gemma , Torres Ferràn , Da Fonseca Leonardo G. , Muñoz-Martínez Sergio , Forner Alejandro , Bruix Jordi , Boix Loreto , Reig María
Published: January 2021

Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between peripheral immunity and the probability of developing eDAEs. Peripheral blood mononuclear cells of 52 HCC patients treated with sorafenib were analyzed at baseline and throughout the first eight weeks of therapy. T, B, Natural Killer cells, and their immune checkpoints expression data were characterized by flow cytometry. Cytokine release and immune-suppression assays were carried out ex vivo. Cox baseline and time-dependent regression models were applied to evaluate the probability of increased risk of eDAEs. DNAM-1, PD-1, CD69, and LAG-3 in T cells, plus CD16 and LAG-3 in NK cells, are significantly associated with the probability of developing eDAEs. While NK DNAM-1+ cells express activation markers, T DNAM-1+ cells induce immune suppression and show immune exhaustion. This is the first study to report an association between immune checkpoints expression in circulating immune cells and the increased incidence of eDAEs. Our results support the hypothesis for an off-target role of sorafenib in immune modulation. We also describe a novel association between DNAM-1 and immune exhaustion in T cells.
Site-Specific Dual-Labeling of a VHH with a Chelator and a Photosensitizer for Nuclear Imaging and Targeted Photodynamic Therapy of EGFR-Positive Tumors
Authors: Renard Emma , Collado Camps Estel , Canovas Coline , Kip Annemarie , Gotthardt Martin , Rijpkema Mark , Denat Franck , Goncalves Victor , van Lith Sanne A. M.
Published: January 2021

Variable domains of heavy chain only antibodies (VHHs) are valuable agents for application in tumor theranostics upon conjugation to both a diagnostic probe and a therapeutic compound. Here, we optimized site-specific conjugation of the chelator DTPA and the photosensitizer IRDye700DX to anti-epidermal growth factor receptor (EGFR) VHH 7D12, for applications in nuclear imaging and photodynamic therapy. 7D12 was site-specifically equipped with bimodal probe DTPA-tetrazine-IRDye700DX using the dichlorotetrazine conjugation platform. Binding, internalization and light-induced toxicity of DTPA-IRDye700DX-7D12 were determined using EGFR-overexpressing A431 cells. Finally, ex vivo biodistribution of DTPA-IRDye700DX-7D12 in A431 tumor-bearing mice was performed, and tumor homing was visualized with SPECT and fluorescence imaging. DTPA-IRDye700DX-7D12 was retrieved with a protein recovery of 43%, and a degree of labeling of 0.56. Spectral properties of the IRDye700DX were retained upon conjugation. 111In-labeled DTPA-IRDye700DX-7D12 bound specifically to A431 cells, and they were effectively killed upon illumination. DTPA-IRDye700DX-7D12 homed to A431 xenografts in vivo, and this could be visualized with both SPECT and fluorescence imaging. In conclusion, the dichlorotetrazine platform offers a feasible method for site-specific dual-labeling of VHH 7D12, retaining binding affinity and therapeutic efficacy. The flexibility of the described approach makes it easy to vary the nature of the probes for other combinations of diagnostic and therapeutic compounds.
Pure Ductal Carcinoma In Situ of the Breast: Analysis of 270 Consecutive Patients Treated in a 9-Year Period
Authors: Chiappa Corrado , Bonetti Alice , Jaber Giulio Jad , De Berardinis Valentina , Bianchi Veronica , Rovera Francesca
Published: January 2021

Introduction: Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that are confined within the basement membrane of the breast ductal system. This retrospective observational analysis aims at reviewing the issues of this histological type of cancer. Materials and methods: Patients treated for DCIS between 1 January 2009 and 31 December 2018 were identified from a retrospective database. The patients were divided into two groups of 5 years each, the first group including patients treated from 2009 to 2013, and the second group including patients treated from 2014 to 2018. Once the database was completed, we performed a statistical analysis to see if there were significant differences among the 2 periods. Statistical analyses were performed using GraphPad Prism software for Windows, and the level of significance was set at p < 0.05. Results: 3586 female patients were treated for breast cancer over the 9-year study period (1469 patients from 2009 to 2013 and 2117 from 2014 to 2018), of which 270 (7.53%) had pure DCIS in the final pathology. The median age of diagnosis was 59-year-old (range 36–86). In the first period, 81 (5.5%) women out of 1469 had DCIS in the final pathology, in the second, 189 (8.9%) out of 2117 had DCIS in the final pathology with a statistically significant increase (p = 0.0001). From 2009 to 2013, only 38 (46.9%) were in stage 0 (correct DCIS diagnosis) while in the second period, 125 (66.1%) were included in this stage. The number of patients included in clinical stage 0 increased significantly (p = 0.004). In the first period, 48 (59.3%) specimen margins were at a greater or equal distance than 2 mm (negative margins), between 2014 and 2018; 137 (72.5%) had negative margins. Between 2014 and 2018 the number of DCIS patients with positive margins decreased significantly (p = 0.02) compared to the first period examined. The mastectomies number increased significantly (p = 0.008) between the 2 periods, while the sentinel lymph node biopsy (SLNB) numbers had no differences (p = 0.29). For both periods analysed all the 253 patients who underwent the follow up are currently living and free of disease. We have conventionally excluded the 17 patients whose data were lost. Conclusion: The choice of the newest imaging techniques and the most suitable biopsy method allows a better pre-operative diagnosis of the DCIS. Surgical treatment must be targeted to the patient and a multidisciplinary approach discussed in the Breast Unit centres.
Revisiting Mitochondria Scored Cancer Progression and Metastasis
Authors: Gundamaraju Rohit , Lu Wenying , Manikam Rishya
Published: January 2021

The Warburg effect has immensely succored the study of cancer biology, especially in highlighting the role of mitochondria in cancer stemness and their benefaction to the malignancy of oxidative and glycolytic cancer cells. Mitochondrial genetics have represented a focal point in cancer therapeutics due to the involvement of mitochondria in programmed cell death. The mitochondrion has been well established as a switch in cell death decisions. The mitochondrion’s instrumental role in central bioenergetics, calcium homeostasis, and translational regulation has earned it its fame in metastatic dissemination in cancer cells. Here, we revisit and review mechanisms through which mitochondria influence oncogenesis and metastasis by underscoring the oncogenic mitochondrion that is capable of transferring malignant capacities to recipient cells.