bluuebunny/crossref_metadata_2025 huggingface dataset:
Criminal actions during the holodomor of 1932–1933
as genocide of the ukrainian people
Authors: Filina Antonina , Skabodina Alla , Kochigina Natalia
Published: June 2022

The purpose of the article is to study a horrific event that completely changed the
course of history and today has a diverse impact on millions of people around the world.
The methodological basis of the study is the use of general scientific methods:
the method of theoretical generalization of the criteria of genocide – to destroy
in whole or in part any national, ethnic, racial or religious group. The analysis of
documents and materials that left eyewitnesses of those events was also applied.
The scientific novelty of the obtained results is that the main negative
tendencies of the cause of the mechanism of genocide as a way of organized
destruction of the Ukrainian people are revealed.
The article studies the development trends of the Ukrainian tragedy of 1932–
1933. The study is based on information from the Institute of Demography and
Social Research, the examination of which provided data on the loss of the
population of Ukraine within the then USSR. The study made it possible to
determine that the Holodomor is the greatest tragedy in the history of Ukraine,
the most serious crime ever committed against our people.
Conclusions. It was found that in the vast majority of cities and villages of
Ukraine died of hunger and cold, whole villages and towns died. Predatory grain
procurement was carried out quickly, churches were closed and destroyed. The then
authorities carried out a «cleansing» of the Ukrainian intelligentsia.
Humanity, Ukrainian society, young people have no right to forget the greatest
tragedy of the twentieth century.
Keywords: Holodomor, memory, collectivization, Ukrainian SSR, genocide.
Agent-Based Modeling of COVID-19 Transmission in Philippine Classrooms
Authors: Macalinao Rojhun O. , Malaguit Jcob C. , Lutero Destiny S.
Published: June 2022

Onsite classes in the Philippines have been prohibited since March 2020 due to the SARS-CoV-2 which causes the COVID-19. This forced millions of learners to adapt with new modes of instruction that may not be optimal for their learning. In this study, we implemented an agent-based model in Netlogo that followed common classroom layouts to assess the effects of human interactions to virus transmission. Results show that the highest value of cumulative proportion of infected individuals inside the classroom (CPI) is achieved when the total allowable seating capacity in the classroom is increased from 25 to 50%. Also, varying transmission rates between 5 and 20% does not pose any significant effect on CPI. Furthermore, in three of the four seating arrangements, allowing in-class mobility and class rotations can pose significant increases in CPI averaging from 40 to 70%. Results also showed that factors including maximum number of students and number of initially infected individuals, significantly affect the likelihood of infection apart from the seating arrangement itself. To minimize the risk of transmission inside the classroom setup considered, it is vital to control these factors by adhering to mitigation efforts such as increased testing and symptoms checking, limiting the maximum number of students, and redefining breaks and class rotations.
Health and Welfare of Atlantic Salmon in FishGLOBE V5 – a Novel Closed Containment System at Sea
Authors: Lazado Carlo C. , Stiller Kevin T. , Shahzad Khurram , Reiten Britt Kristin M. , Marchenko Yuriy , Gerwins Jascha , Radonjic Filip Strand , Eckel Bernhard , Berge Arne , Espmark Åsa Maria
Published: June 2022

Closed-containment (CCS) systems offer several advantages in controlling the production environment for Atlantic salmon (Salmo salar) aquaculture, especially at sea, where fish are more exposed to challenging environmental conditions. Here, we report the health and welfare of Atlantic salmon in FishGLOBE V5, a 3500 m3 semi-closed containment system. A group of 200,000 post-smolts was followed from a recirculating aquaculture system (RAS) facility, then for three and a half months in FishGLOBE V5, and three months after release in net pens. Fish samples were collected at four time points during the production period, while water quality was evaluated when the fish were in FishGLOBE V5. The water quality in FishGLOBE V5 was within the recommended range for salmon post-smolts. The mortality rate was 1.4% in FishGLOBE V5 and 4.9% in net pens. There was an increase in the prevalence of eye, snout and dorsal fin damages before the fish left the FishGLOBE V5 phase. The plasma level of magnesium was slightly elevated during this phase as well, indicating osmotic imbalance and stress. Histological evaluation of skin and gills showed sporadic cases of non-specific pathologies. In particular, the transitory stay in FishGLOBE V5 partially improved skin health, but not gill health. Gene expression profiling of some biomarkers showed that rearing fish in FishGLOBE V5 could influence the expression of genes involved in stress response, mucus production, and epithelial integrity. This study documented that rearing salmon for a certain period in FishGLOBE V5 during production affected different health and welfare indicators. These changes should be taken into consideration for the improvement of FishGLOBE V5 as a viable technology for post-smolt production at sea.
Stem Cell Fate and Immunomodulation Promote Bone Regeneration via Composite Bio-Oss®/AviteneTM Biomaterial
Authors: Iaquinta Maria Rosa , Martini Fernanda , D’Agostino Antonio , Trevisiol Lorenzo , Bersani Massimo , Torreggiani Elena , Tognon Mauro , Rotondo John Charles , Mazzoni Elisa
Published: June 2022

Bone defects in maxillofacial regions lead to noticeable deformity and dysfunctions. Therefore, the use of biomaterials/scaffolds for maxillofacial bone regrowth has been attracting great interest from many surgical specialties and experts. Many approaches have been devised in order to create an optimal bone scaffold capable of achieving desirable degrees of bone integration and osteogenesis. Osteogenesis represents a complex physiological process involving multiple cooperating systems. A tight relationship between the immune and skeletal systems has lately been established using the concept of “osteoimmunology,” since various molecules, particularly those regulating immunological and inflammatory processes, are shared. Inflammatory mediators are now being implicated in bone remodeling, according to new scientific data. In this study, a profiler PCR array was employed to evaluate the expression of cytokines and chemokines in human adipose derived-mesenchymal stem cells (hASCs) cultured on porous hydroxylapatite (HA)/Collagen derived Bio-Oss®/Avitene scaffolds, up to day 21. In hASCs grown on the Bio-Oss®/Avitene biomaterial, 12 differentially expressed genes (DEGs) were found to be up-regulated, together with 12 DEG down-regulated. Chemokine CCL2, which affects bone metabolism, tested down-regulated. Interestingly, the Bio-Oss®/Avitene induced the down-regulation of pro-inflammatory inter-leukin IL-6. In conclusion, our investigation carried out on the Bio-Oss®/Avitene scaffold indicates that it could be successfully employed in maxillofacial surgery. Indeed, this composite material has the advantage of being customized on the basis of the individual patients favoring a novel personalized medicine approach.
Outcomes of Vital Sign Monitoring of an Acute Surgical Cohort With Wearable Sensors and Digital Alerting Systems: A Pragmatically Designed Cohort Study and Propensity-Matched Analysis
Authors: Iqbal Fahad Mujtaba , Joshi Meera , Fox Rosanna , Koutsoukou Tonia , Sharma Arti , Wright Mike , Khan Sadia , Ashrafian Hutan , Darzi Ara
Published: June 2022

Background: The implementation and efficacy of wearable sensors and alerting systems in acute secondary care have been poorly described.

Objectives: to pragmatically test one such system and its influence on clinical outcomes in an acute surgical cohort.

Methods: In this pragmatically designed, pre-post implementation trial, participants admitted to the acute surgical unit at our institution were recruited. In the pre-implementation phase (September 2017 to May 2019), the SensiumVitals™ monitoring system, which continuously measures temperature, heart, and respiratory rates, was used for monitoring alongside usual care (intermittent monitoring in accordance with the National Early Warning Score 2 [NEWS 2] protocol) without alerts being generated. In the post-implementation phase (May 2019 to March 2020), alerts were generated when pre-established thresholds for vital parameters were breached, requiring acknowledgement from healthcare staff on provided mobile devices. Hospital length of stay, intensive care use, and 28-days mortality were measured. Balanced cohorts were created with 1:1 ‘optimal’ propensity score logistic regression models.

Results: The 1:1 matching method matched the post-implementation group (n = 141) with the same number of subjects from the pre-implementation group (n = 141). The median age of the entire cohort was 52 (range: 18–95) years and the median duration of wearing the sensor was 1.3 (interquartile range: 0.7–2.0) days. The median alert acknowledgement time was 111 (range: 1–2,146) minutes. There were no significant differences in critical care admission (planned or unplanned), hospital length of stay, or mortality.

Conclusion: This study offered insight into the implementation of digital health technologies within our institution. Further work is required for optimisation of digital workflows, particularly given their more favourable acceptability in the post pandemic era. Clinical trials registration information: ClinicalTrials.gov Identifier: NCT04638738.
Functional Brain Controllability Alterations in Stroke
Authors: Li Xuhong , Fang Feng , Li Rihui , Zhang Yingchun
Published: June 2022

Motor control deficits are very common in stroke survivors and often lead to disability. Current clinical measures for profiling motor control impairments are largely subjective and lack precise interpretation in a “control” perspective. This study aims to provide an accurate interpretation and assessment of the underlying “motor control” deficits caused by stroke, using a recently developed novel technique, i.e., the functional brain controllability analysis. The electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) were simultaneously recorded from 16 stroke patients and 11 healthy subjects during a hand-clenching task. A high spatiotemporal resolution fNIRS-informed EEG source imaging approach was then employed to estimate the cortical activity and construct the functional brain network. Subsequently, network control theory was applied to evaluate the modal controllability of some key motor regions, including primary motor cortex (M1), premotor cortex (PMC), and supplementary motor cortex (SMA), and also the executive control network (ECN). Results indicated that the modal controllability of ECN in stroke patients was significantly lower than healthy subjects (p = 0.03). Besides, the modal controllability of SMA in stroke patients was also significant smaller than healthy subjects (p = 0.02). Finally, the baseline modal controllability of M1 was found to be significantly correlated with the baseline FM-UL clinical scores (r = 0.58, p = 0.01). In conclusion, our results provide a new perspective to better understand the motor control deficits caused by stroke. We expect such an analytical methodology can be extended to investigate the other neurological or psychiatric diseases caused by cognitive control or motor control impairment.
Bioclimatic Design of Low-Cost Rural Dwellings
Authors: Bera Mahadev , Nag Pranab Kumar
Published: June 2022

Bioclimatic design is a crucial strategy to achieving the eco-friendliness, human-friendliness, and energy-friendliness of the built environment. The building patterns, materials, innovation, and use depend on the inhabitant’s choices, lifestyle, and economic viability. The study focused on examining bioclimatic components of low-cost dwellings in rural coastal environments in eastern India. A survey questionnaire administered to about 1,300 respondents from 15 villages (classified as remote rural, rural, and semi-urban) yielded their perception of different dwelling environment issues. The statistical analysis of bioclimatic dimensions indicated a significant difference among the dwellings. The low-cost mud houses of the remote rural and rural areas in coastal regions often follow local practices. Besides, different dimensions covered in the survey provided insights for the comparative evaluation of different categories of dwelling units. Principal component analysis (PCA) identified the clusters and component structures of the built environment characteristics provided from the response of the villagers as their perception of the dwellings. PCA yielded three components—1) interior design (PC1, building form, partitioning of rooms, type and materials of the wall, roof and window), 2) innovation of the built environment (PC2, building envelope, insulation, and sanitation facilities), and 3) natural ventilation priority (PC3, window design, window opening, and glaze material), which together explained 69% of the total variance. The psychrometric chart provided in identifies passive design strategies in constructing dwellings to improve residents’ yearly total thermal comfort hours in hot and humid regions. The relative contributions to thermal comfort hours are sun shading of windows (25.5%), a passive solar direct gain high mass (6.2%), a passive solar direct gain low mass (0.4%), and a high thermal mass, including night flush (4.3%), direct and two-stage evaporative cooling (4.3%), and natural ventilation and fan-forced ventilation cooling (2.2%).
Diverse Control Mechanisms of the Interleukin-1 Cytokine Family
Authors: Evavold Charles L. , Kagan Jonathan C.
Published: June 2022

The majority of interleukin-1 (IL-1) family cytokines lack amino terminal secretion signals or transmembrane domains for secretion along the conventional biosynthetic pathway. Yet, these factors must be translocated from the cytoplasm across the plasma membrane into the extracellular space in order to regulate inflammation. Recent work has identified an array of mechanisms by which IL-1 family cytokines can be released into the extracellular space, with supramolecular organizing centers known as inflammasomes serving as dominant drivers of this process. In this review, we discuss current knowledge of the mechanisms of IL-1 family cytokine synthesis, processing, and release from cells. Using this knowledge, we propose a model whereby host metabolic state dictates the route of IL-1β secretion, with implications for microbial infection and sterile inflammation.
Case Report: Oxaliplatin-Induced Third-Degree Atrioventricular Block: First Discovery of an Important Side-Effect
Authors: Chen Xi , Wang Hui , Zhang Zijin , Xu Yan , An Xuanqi , Ai Xin , Li Lin
Published: June 2022

Background

The adverse effects of anticancer therapy in patients with malignancies and cardiovascular diseases are complicated. Oxaliplatin is one of the most commonly used chemotherapy drugs for gastric and colorectal cancers, and oxaliplatin-induced cardiotoxicity has rarely been reported.

Case Summary

We report a 76-year-old man with adenocarcinoma of the esophagogastric junction and a 40-day history of non-ST-elevation myocardial infarction who exhibited a new third-degree atrioventricular block after oxaliplatin administration. We immediately withdrew oxaliplatin treatment and, to avoid future episodes, we implanted a permanent pacemaker for safety and added diltiazem hydrochloride. The third-degree atrioventricular block disappeared after oxaliplatin withdrawal. We detected no recurrence of the third-degree atrioventricular block in future chemotherapies.

Conclusions

This is the first reported oxaliplatin-induced third-degree atrioventricular block, likely mediated by coronary artery spasm. Cancer patients with acute coronary syndrome are a unique and vulnerable population, whom physicians should carefully evaluate and monitor during anticancer treatment. Remarkably, even the most common chemotherapy drugs can cause life-threatening cardiac adverse events.
COVID-19 and the Heart: Could Transient Takotsubo Cardiomyopathy Be Related to the Pandemic by Incidence and Mechanisms?
Authors: Angelini Paolo , Postalian Alexander , Hernandez-Vila Eduardo , Uribe Carlo , Costello Briana
Published: June 2022

Typical emergency hospital care during the COVID-19 pandemic has centered on pulmonary-focused services. Nonetheless, patients with COVID-19 frequently develop complications associated with the dysfunction of other organs, which may greatly affect prognosis. Preliminary evidence suggests that cardiovascular involvement is relatively frequent in COVID-19 and that it correlates with significant worsening of clinical status and mortality in infected patients. In this article, we summarize current knowledge on the cardiovascular effects of COVID-19. In particular, we focus on the association between COVID-19 and transient takotsubo cardiomyopathy (TTC)—two conditions that preliminarily seem epidemiologically associated—and we highlight cardiovascular changes that may help guide future investigations toward full discovery of this new, complex disease entity. We hypothesize that coronary endothelial dysfunction, along with septic state, inflammatory storm, hypercoagulability, endothelial necrosis, and small-vessel clotting, may represent a fundamental hidden link between COVID-19 and TTC. Furthermore, given the likelihood that new genetic mutations of coronaviruses or other organisms will cause similar pandemics and endemics in the future, we must be better prepared so that a substantial complication such as TTC can be more accurately recognized, its pathophysiology better understood, and its treatment made more justifiable, timely, and effective.
The Northernmost Volcanoes in South America (Colombia, 5–6°N): The Potentially Active Samaná Monogenetic Volcanic Field
Authors: Sánchez-Torres Laura , Murcia Hugo , Schonwalder-Ángel Dayana
Published: June 2022

The northernmost volcanism in South America (5–6°N) is defined by the presence of several monogenetic volcanic edifices in Colombia, which have been grouped within the Samaná monogenetic volcanic field. Few volcanoes have been studied so far, but they are recognized as a cluster of volcanoes of intermediate-to-acid composition, formed by both explosive and effusive eruptions. This study aims to 1) characterize four more monogenetic volcanic edifices as part of the Samaná field, 2) highlight the potentially active volcanism in an area previously defined as non-volcanogenic, and 3) give insights into the magmatic evolution of the scarcely studied evolved monogenetic volcanism linked to subduction zones worldwide. To achieve these aims, this study uses petrography, mineral chemistry, whole-rock geochemistry, geochronological analyses, and geothermobarometric calculations. The analyses indicate that the field is formed by at least seven volcanoes with similar composition and that it is long-lived and potentially active. Mineralogically, the erupted products host plagioclase (An26–74) and amphibole (magnesio-hastingsite, tschermakite, and occasionally mangesio-hornblende) as the most abundant phases, although orthopyroxene (enstatite; Wo2–3, En70–76, Fs21–28) and clinopyroxene (diopside and augite; Wo44–45, En41–42, Fs13–15, and Wo42–44, En46–47, Fs10–11) also appear. Less abundant phases such as olivine (Fo81–88), biotite (magnesiobiotite), quartz, and Fe–Ti oxides (Usp4–89 Mag96–11, and Ilm61–92 Hem39–8) were also recognized. Chemically, the volcanoes are of andesitic-to-dacitic composition with calc-alkaline affinity and show similar behavior of LILE, HFSE, and REE, which is typical for magmatism in subduction environments. Ages yield a range between 1.32 ± 0.06 Ma (K/Ar) and 16,919 ± 220 years (14C). The results also indicate that the volcanoes share a common magmatic source that fed the individual eruptions and that the magma differentiation is mainly controlled by processes of fractional crystallization, although evidence of magma recharge processes or magma mixing and assimilation as a minor process are also recognized. Geothermobarometric calculations suggest that the different mineral phases are crystallized between 1,194 and 687 °C and a pressure between 0.88 and 0.19 GPa. This indicates that the aforementioned processes occurred not only at the main magmatic reservoir (∼33–21 km depth) but also at different stagnation zones at shallower levels of the crust (∼7–5 km). Taking this into account, it is shown that the magma evolution of this monogenetic field is more complex than individual batches of magma reaching the surface uninterrupted, as is normally described for monogenetic volcanic fields of more mafic compositions in other tectonic settings.
Early Spontaneous Abortion in Fresh- and Frozen-Embryo Transfers: An Analysis of Over 35,000 Transfer Cycles
Authors: Shuai Jun , Chen Qiao-li , Chen Wen-hong , Liu Wei-wei , Huang Guo-ning , Ye Hong
Published: June 2022

Background

The aim of this study was to explore the risk factors for early spontaneous abortion (ESA) in fresh- and frozen-embryo transfers.

Methods

This retrospective cohort study comprised a total of 35,076 patients, including 15,557 women in the fresh-embryo transfer group and 19,519 women in the frozen-embryo transfer group from January 2016 to December 2020. The primary outcome of this study was ESA, which we defined as the termination of embryonic development before 12 weeks of pregnancy (i.e., an early abortion after artificial multi-fetal pregnancy reduction was excluded).

Results

In the 35,076 ART transfer cycles, the incidence of ESA was 5.77% (2023/35,076), and the incidence rates for ESA in fresh and frozen cycles were 4.93% (767 of 15,557) and 6.43% (1,256 of 19,519), respectively. Using a multivariate logistic regression analysis model, maternal age, body mass index (BMI), and number of embryos transferred were independent predictors for ESA. In addition, frozen-thawed transfer was a risk factor for ESA as compared with fresh transfer (OR = 1.207; 95% CI, 1.094–1.331; P = 0.000), blastocyst transfer was risk factor for ESA as compared with cleavage transfer (OR =1.373; 95% CI, 1.186–1.591; P = 0.000 in the total group; OR = 1.291; 95% CI, 1.111–1.499; P = 0.001 in the frozen-transfer group), and unexplained infertility was a protective factor for ESA only in the frozen group (OR = 0.746; 95% CI, 0.565–0.984; P = 0.038).

Conclusions

Maternal age, BMI, number of embryos transferred, and frozen-thawed transfer were independent risk factors for ESA in assisted reproductive technology treatment cycles.
Characterization of Post-Hypoglycemic Hyperglycemia in Children and Adolescents With Type 1 Diabetes: The EPHICA Study
Authors: Colinet Victoria , Lysy Philippe A.
Published: June 2022

Background

In patients with diabetes, the dynamics in which hypoglycemia recovers impacts cardiovascular disease risk. Our study investigated the extents of “post-hypoglycemic hyperglycemia (PHH)” (i.e. hypoglycemia that recover to hyperglycemia in any circumstance) and factors likely to influence PHH characteristics in a pediatric cohort of patients with type 1 diabetes (T1D).

Methods

We collected retrospective continuous glucose monitoring (CGM) data from 142 pediatric patients with T1D to characterize episodes of PHH during a two-month follow-up period. Factors influencing PHH were determined using univariate and multivariate analyses.

Results

In our EPHICA cohort, PHH rate was 0.6 ± 0.3 episode/day and correlated (r=0.33; p<0.0001) with hyperglycemia rate (2.6 ± 0.5 episodes/day). The global proportion of hyperglycemia corresponding to PHH was 0.22 ± 0.1, yet 14.8% of patients had more than 1/3 of hyperglycemia related to PHH. Episodes of PHH lasted 239.6 ± 124.8 minutes with a hyperglycemic peak of 258.8 ± 47.1 mg/dL. Only 12.2% of PHH occurred at night. While a younger age (<12 years) and lower body mass index (BMI) (SDS: -2 to 1.6) were associated with higher daily PHH rates, teenagers (≥12 years) and obese patients experienced longer PHH and higher hyperglycemic peaks. Parameters of glycemic variability (i.e. HbA1C, IDAA1C and GTAA1C) moderately correlated with PHH duration and related hyperglycemic peak. Multivariate analysis confirmed these results, as factors likely to influence PHH rate were phenotype (age and BMI) and glycemic variability parameters (time in range, mean glycemia, HbA1C and GTAA1C).

Conclusion

Our EPHICA study highlights the importance of PHH as a prominent component of hyperglycemia in some children and adolescents with T1D. Factors associated with PHH features are age, BMI and parameters of glycemic control. Young and lean children are more prone to experience hypoglycemia that recover with hyperglycemia, but adolescents and obese children tend to experience hyperglycemia of longer duration.
Low Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate Are Associated With Coronary Heart Disease in Men With Type 2 Diabetes Mellitus
Authors: Zhang Xinxin , Xiao Jinfeng , Liu Tong , He Qing , Cui Jingqiu , Tang Shaofang , Li Xin , Liu Ming
Published: June 2022

Aims

Sex hormones play an important role in the pathogenesis of cardiovascular disease (CVD). This cross-sectional study aimed to explore the associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with coronary heart disease (CHD) and stroke in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).

Materials and Methods

A total of 995 patients with T2DM were included in the study analysis. Serum levels of DHEA and DHEAS were quantified using liquid chromatography–tandem mass spectrometry. Binary logistic regression analyses were performed to assess the associations of DHEA and DHEAS with CHD and stroke. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal DHEA and DHEAS cutoff values for the detection of CHD in men with T2DM.

Results

In men with T2DM, after adjustment for potential confounders in model 3, the risk of CHD decreased with an increasing serum DHEA level [odds ratio (OR) = 0.38, quartile 4 vs. quartile 1; 95% confidence interval (CI) = 0.16–0.90; p = 0.037 for trend). Consistently, when considered as a continuous variable, this association remained significant in the fully adjusted model (OR = 0.59, 95% CI = 0.40–0.87, p < 0.05). When taken as a continuous variable in model 3, serum DHEAS level was also inversely related to the risk of CHD among men (OR = 0.56, 95% CI = 0.38–0.82, p < 0.05). Similarly, this relationship remained statistically significant when DHEAS was categorized into quartiles (OR = 0.27, quartile 4 vs. quartile 1; 95% CI = 0.11–0.67; p = 0.018 for trend). ROC curve analyses revealed that the optimal cutoff values to detect CHD in men with T2DM were 6.43 nmol/L for DHEA and 3.54 μmol/L for DHEAS. In contrast, no significant associations were found between DHEA and DHEAS on the one hand and stroke on the other in men and women with T2DM (all p > 0.05).

Conclusions

Serum DHEA and DHEAS were significantly and negatively associated with CHD in middle-aged and elderly men with T2DM. This study suggests potential roles of DHEA and DHEAS in CHD pathogenesis.
Primary Congenital Hypothyroidism in Children Below 3 Years Old - Etiology and Treatment With Overtreatment and Undertreatment Risks, a 5-Year Single Centre Experience
Authors: Lipska Elżbieta , Lecka-Ambroziak Agnieszka , Witkowski Daniel , Szamotulska Katarzyna , Mierzejewska Ewa , Ołtarzewski Mariusz
Published: June 2022

Worldwide neonatal screening for congenital hypothyroidism (CH) is a gold standard of active surveillance in newborns. Prompt diagnosis, subsequent timely treatment implementation, and proper dosage of levothyroxine (L-T4) are crucial for normal growth and development, especially of the central nervous system. However, overtreatment may have a potential negative impact on further neurodevelopment. We retrospectively analysed data of 99 newborns with CH diagnosis, referred to the Endocrinology Outpatient Clinic of the Institute of Mother and Child in Warsaw, Poland from the CH screening program from 2017 to 2021. We evaluated the diagnostic process and treatment up to the age of 3 years. We compared groups of children from the first and the second screening groups (FSG, SSG) in the neonatal screening with an evaluation of ultrasound examination (thyroid dysgenesis vs. gland in situ, GIS). The overtreatment and undertreatment risks were assessed and an analysis of the new TSH thresholds was performed. Treatment was implemented at a median of 9 days of life (3 – 27); 8 days (3 – 17) in FSG and 19 (6 – 27) in SSG. The dose of L-T4 differed between FSG and SSG at all three analysed time points (start of the therapy, 12 months, and 3 years) with significantly higher doses in FSG. The same was observed for the patients with thyroid dysgenesis vs. GIS. Screening TSH level was ≥ 28mIU/l in 91.7% of patients with thyroid dysgenesis in comparison to 74.0% of patients with GIS (p= 0.038). The optimally treated group (fT4 in the upper half of the reference range, according to the guidelines) was up to 58.0% of the children during the follow-up. The risk for overtreatment was present in 1/5 of the study group after 12 months and 1/4 after 3 years of L-T4 therapy. Analysis of new TSH thresholds showed an increased prevalence of mild hypothyroidism, GIS, and either euthyroid state or overtreatment while treating with lower L-T4 doses in comparison to the rest of the cohort. The study confirmed the general efficacy of the CH diagnostic pathway and the timely implemented L-T4 therapy. The suspected overtreatment after the first 12 months of L-T4 therapy requires consideration of the earlier diagnosis re-evaluation.
Killer Timing: The Temporal Uterine Natural Killer Cell Differentiation Pathway and Implications for Female Reproductive Health
Authors: Fraser Rupsha , Zenclussen Ana Claudia
Published: June 2022

Natural killer (NK) cells are the predominant maternal uterine immune cell component, and they densely populate uterine mucosa to promote key changes in the post-ovulatory endometrium and in early pregnancy. It is broadly accepted that (a) immature, inactive endometrial NK (eNK) cells in the pre-ovulatory endometrium become activated and transition into decidual NK (dNK) cells in the secretory stage, peri-implantation endometrium, and continue to mature into early pregnancy; and (b) that secretory-stage and early pregnancy dNK cells promote uterine vascular growth and mediate trophoblast invasion, but do not exert their killing function. However, this may be an overly simplistic view. Evidence of specific dNK functional killer roles, as well as opposing effects of dNK cells on the uterine vasculature before and after conception, indicates the presence of a transitory secretory-stage dNK cell (s-dNK) phenotype with a unique angiodevelopmental profile during the peri-implantation period, that is that is functionally distinct from the angiomodulatory dNK cells that promote vessel destabilisation and vascular cell apoptosis to facilitate uterine vascular changes in early pregnancy. It is possible that abnormal activation and differentiation into the proposed transitory s-dNK phenotype may have implications in uterine pathologies ranging from infertility to cancer, as well as downstream effects on dNK cell differentiation in early pregnancy. Further, dysregulated transition into the angiomodulatory dNK phenotype in early pregnancy will likely have potential repercussions for adverse pregnancy outcomes, since impaired dNK function is associated with several obstetric complications. A comprehensive understanding of the uterine NK cell temporal differentiation pathway may therefore have important translational potential due to likely NK phenotypic functional implications in a range of reproductive, obstetric, and gynaecological pathologies.
Improved Model Predictive Dynamic Voltage Cooperative Control Technology Based on PMU
Authors: Liu Shu , Zhang Lin , Wu Zhenbin , Zhao Jian , Li Liang
Published: June 2022

With the access to a large number of intermittent and fluctuating new energy sources in the low-voltage distribution network, the complex relationship between producers and consumers makes the node voltage stability and other problems in the power system increasingly prominent. Aiming at the voltage stability problem caused by the intermittent and fluctuation of the new power system, based on the high-precision measurement data of PMU, this article used the model predictive control algorithm to realize regional voltage optimization and improve the stability of node voltage. First, the voltage sensitivity matrix is calculated using PMU measurement data and grid structure state information. Second, active power, reactive power, and voltage were taken as the input of the MPC algorithm, and the optimal compensation voltage instruction was obtained by rolling optimization, and the node voltage was compensated by SVG and SVC. Finally, a simulation experiment was carried out on the MATLAB/Simulink simulation platform, and the experimental results verified the correctness and effectiveness of the proposed control method.
Coupled Dynamic Response of an Offshore Multi-Purpose Floating Structure Suitable for Wind and Wave Energy Exploitation
Authors: Konispoliatis Dimitrios N. , Manolas Dimitrios I. , Voutsinas Spyros G. , Mavrakos Spyros A.
Published: June 2022

This paper presents the coupled analysis performed in the frequency and time domain, considering a multi-purpose floating structure suitable for offshore wind and wave energy source exploitation. The floating structure encompasses an array of hydrodynamically interacting Oscillating Water Column (OWC) devices, moored through tensioned tethers as a Tension Leg Platform (TLP), and supports a 10 MW Wind Turbine (WT). The analysis is built to incorporate properly the solutions of the diffraction and the pressure- and motion-dependent radiation problems around the floating structure, the mooring lines characteristics, the OWCs characteristics, and the aerodynamics of the WT by accounting for the aerodynamic modelling of the rotor, the elastic modelling of the turbine components, namely the blades, the drive train, and the tower. Numerical results are obtained through the developed analysis methods, presenting the fundamental hydrodynamic properties of the platform, as well as the ultimate and fatigue loads at several locations on the structure expected to be imposed on it over its lifetime. The effect of the installation sites (i.e., environmental excitation) on the lifetime loads is investigated by comparing the estimated loads at various Mediterranean Sea and North Sea locations. Finally, the OWC effect, due to the air pressure oscillation inside the wave energy converters, is discussed, highlighting its significant influence on the hybrid system’s loading conditions.
Meteorological Influence of Mineral Dust Distribution Over South-Western Africa Deserts Using Reanalysis and Satellite Data
Authors: Shikwambana Lerato , Kganyago Mahlatse
Published: June 2022

This study investigated the meteorological influence of mineral dust in the south-western African region using satellite and reanalysis datasets by studying 1) the seasonal transport and distribution of mineral dust in the region; 2) the relationship between precipitation, wind and desert dust, and 3) the long-term trends of dust column density, precipitation rate and surface wind speed. The results show that the Namib desert is the main source of dust in the region, with the density and distribution varying by seasons. The study found that the greatest dust distribution occurs in the June-July-August (JJA) season, attributed to the southwesterly winds which transport the dust into the interior of the region. Moreover, small dust aerosols less that 20 µm are observed at highest altitudes between 7 and 10.28 km. Favourable meteorological such as strong and fast winds and low precipitation, and low vegetation played a vital role in the production and distribution of dust aerosols. Over a long time (i.e., from 1990 to 2020), dust column density trend increased, while precipitation and surface wind speed trends decreased. This study provides significant basis for assessing and monitoring of the desertification processes and their effect on regional climate variability and change in Southwest Africa, where data is ground-based data is scarce and related efforts are rare.
How Well Does the ERA5 Reanalysis Capture the Extreme Climate Events Over China? Part II: Extreme Temperature
Authors: Xu Wanling , Lei Xiangyong , Chen Shiting , Yu Tingting , Hu Zengyun , Zhang Meng , Jiang Lizhi , Bao Ruijuan , Guan Xiaojun , Ma Miaomiao , Wei Jianhui , Gao Lu , Feng Aixia
Published: June 2022

The fifth-generation atmospheric reanalysis of the European Center for Medium-Range Weather Forecasts (ERA5) is the latest reanalysis product. However, the reliability of ERA5 to capture extreme temperatures is still unclear over China. Hence, based on conventional meteorological station data, a new criterion (DISO) was used to validate the ERA5 capturing extreme temperature indices derived from the Expert Team on Climate Change Detection and Indices (ETCCDI) across the six subregions of China on different timescales. The conclusions are as follows: the original daily temperatures (mean temperature, maximum temperature, and minimum temperature) can be well reproduced by ERA5 reanalysis over China. ERA5 tends to exhibit more misdetection for the duration of extreme temperature events than extreme temperature intensity and frequency. In addition, ERA5 performed best in the summer and worst in the winter, respectively. The trend of absolute indices (e.g., TXx and TNx), percentile-based indices (e.g., TX90p, TX10p, TN90p, and TN10p), and duration indices (e.g., WSDI, CSDI, and GSL) can be captured by ERA5, but ERA5 failed to capture the tendency of the diurnal temperature range (DTR) over China. Spatially, ERA5 performs well in southeastern China. However, it remains challenging to accurately recreate the extreme temperature events in the Tibetan Plateau. The elevation difference between the station and ERA5 grid point contributes to the main bias of reanalysis temperatures. The accuracy of ERA5 decreases with the increase in elevation discrepancy.
Bringing the Mechanistic Approach Back to Life: A Systematic Review of the Experimental Evidence for Coexistence and Four of Its Classical Mechanisms
Authors: Hawlena Hadas , Garrido Mario , Cohen Carmit , Halle Snir , Cohen Shahar
Published: June 2022

Coexistence theories develop rapidly at the ecology forefront suffering from interdisciplinary gaps and a lack of universality. The modern coexistence theory (MCT) was developed to address these deficiencies by formulating the universal conditions for coexistence. However, despite this theory's mechanistic foundation, initially, it has only rarely been used to determine the exact mechanisms that govern the competitive outcome. Recent theoretical developments have made MCT more accessible to experimentalists, but they can be challenging in practice. We propose that a comprehensive understanding of species co-occurrence patterns in nature can be reached by complementing the phenomenological approach with both the mechanistic view of MCT and coexistence experiments of the type that prevailed from the 1970s to the 2010s, which focused on specific mechanisms (designated the “mechanistic approach”). As a first step in this direction, we conducted a systematic review of the literature from 1967 to 2020, covering mechanistic experiments for invasibility—the criterion for species coexistence—and the best-studied classical coexistence mechanisms, namely, resource-ratio, natural enemy partitioning, frequency-dependent exploitation by generalist enemies, and the storage effect. The goals of the review were to evaluate (i) the percentage of the abovementioned mechanistic experiments that satisfy the theoretical criteria (designated “eligible studies”), (ii) the scope of these eligible studies, and (iii) their level of support for the theoretical predictions, and to identify their (iv) overarching implications and (v) research gaps. Through examination of 2,510 publications, the review reveals that almost 50 years after the theoretical formulations of the above four coexistence mechanisms, we still lack sufficient evidence to reveal the prevalence of coexistence and of each of the coexistence mechanisms, and to assess the dependency of the mechanisms on the natural history of the competing organisms. By highlighting, on the one hand, the overarching implications of the mechanistic approach to coexistence, and on the other hand, current research gaps, and by offering ways to bridge these gaps in the future, we seek to bring the mechanistic approach back to life.
Functional Variants Associated With CMPK2 and in ASB16 Influence Bovine Digital Dermatitis
Authors: Oelschlaegel Diana , Wensch-Dorendorf Monika , Kopke Grit , Jungnickel Roswitha , Waurich Benno , Rosner Frank , Döpfer Dörte , Brenig Bertram , Swalve Hermann H.
Published: June 2022

Bovine digital dermatitis (BDD) is an infectious disease of the hoof in cattle with multifactorial etiology and a polygenic influence on susceptibility. With our study, we identified genomic regions with the impact on occurrence and development of BDD. We used 5,040 genotyped animals with phenotype information based on the M-stage system for genome-wide association. Significant associations for single-nucleotide polymorphisms were found near genesCMPK2(chromosome 11) andASB16(chromosome 19) both being implicated in immunological processes. A sequence analysis of the chromosomal regions revealed rs208894039 and rs109521151 polymorphisms as having significant influence on susceptibility to the disease. Specific genotypes were significantly more likely to be affected by BDD and developed chronic lesions. Our study provides an insight into the genomic background for a genetic predisposition related to the pathogenesis of BDD. Results might be implemented in cattle-breeding programs and could pave the way for the establishment of a BDD prescreening test.
Sensory Neuron Expressed FcγRI Mediates Postinflammatory Arthritis Pain in Female Mice
Authors: Liu Yan , Caterina Michael J. , Qu Lintao
Published: June 2022

Persistent arthritis pain after resolution of joint inflammation represents a huge health burden in patients with rheumatoid arthritis (RA). However, the underling mechanisms are poorly understood. We and other groups recently revealed that FcγRI, a key immune receptor, is functionally expressed in joint nociceptors. Thus, we investigated a potential role of sensory neuron expressed FcγRI in postinflammatory arthritis pain in a mouse model of collagen antibody-induced arthritis (CAIA). Here, we show that global deletion of Fcgr1 significantly attenuated mechanical hyperalgesia in the ankle and hind paw of female mice in both inflammatory and postinflammatory phases of CAIA. No obvious differences in cartilage destruction were observed after resolution of joint inflammation between genotypes. In situ hybridization (ISH) revealed that a larger proportion of dorsal root ganglion (DRG) neurons expressed Fcgr1 mRNA signal in the late phase of CAIA. Conditional deletion of Fcgr1 in primary sensory neurons produced similar analgesic effects without affecting joint swelling. Knockdown of Fcgr1 expression within DRG in the postinflammatory phase of CAIA alleviated persistent pain. Inflammation within DRG after resolution of joint inflammation in the CAIA model was evidenced by T cell and neutrophil infiltration and upregulated mRNA expression of numerous inflammatory mediators. Yet, such changes were not altered by genetic deletion of Fcgr1. We suggest that neuroinflammation within the DRG after resolution of joint inflammation might upregulate FcγRI signaling in DRG neurons. Sensory neuron expressed FcγRI thus merits exploration as a potential target for the treatment of arthritis pain that persists in RA patients in remission.
Current Advances in PD-1/PD-L1 Blockade in Recurrent Epithelial Ovarian Cancer
Authors: Zhang Yuedi , Cui Qiulin , Xu Manman , Liu Duo , Yao Shuzhong , Chen Ming
Published: June 2022

Immunotherapies have revolutionized the treatment of a variety of cancers. Epithelial ovarian cancer is the most lethal gynecologic malignancy, and the rate of advanced tumor progression or recurrence is as high as 80%. Current salvage strategies for patients with recurrent ovarian cancer are rarely curative. Recurrent ovarian cancer is a “cold tumor”, predominantly due to a lack of tumor antigens and an immunosuppressive tumor microenvironment. In trials testing programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) blockade as a monotherapy, the response rate was only 8.0-22.2%. In this review, we illustrate the status of cold tumors in ovarian cancer and summarize the existing clinical trials investigating PD-1/PD-L1 blockade in recurrent ovarian cancer. Increasing numbers of immunotherapy combination trials have been set up to improve the response rate of EOC. The current preclinical and clinical development of immunotherapy combination therapy to convert an immune cold tumor into a hot tumor and their underlying mechanisms are also reviewed. The combination of anti-PD-1/PD-L1 with other immunomodulatory drugs or therapies, such as chemotherapy, antiangiogenic therapies, poly (ADP-ribose) polymerase inhibitors, adoptive cell therapy, and oncolytic therapy, could be beneficial. Further efforts are merited to transfer these results to a broader clinical application.
ALOX12: A Novel Insight in Bevacizumab Response, Immunotherapy Effect, and Prognosis of Colorectal Cancer
Authors: Weng Siyuan , Liu Zaoqu , Xu Hui , Ge Xiaoyong , Ren Yuqing , Dang Qin , Liu Long , Zhang Jian , Luo Peng , Ren Jianzhuang , Han Xinwei
Published: June 2022

Colorectal cancer is a highly malignant cancer with poor prognosis and mortality rates. As the first biological agent approved for metastatic colorectal cancer (mCRC), bevacizumab was confirmed to exhibit good performance when combined with chemotherapy and immunotherapy. However, the efficacy of both bevacizumab and immunotherapy is highly heterogeneous across CRC patients with different stages. Thus, exploring a novel biomarker to comprehensively assess the prognosis and bevacizumab and immunotherapy response of CRC is of great significance. In our study, weighted gene co-expression network analysis (WGCNA) and the receiver operating characteristic (ROC) curves were employed to identify bevacizumab-related genes. After verification in four public cohorts and our internal cohort, ALOX12 was identified as a key gene related to bevacizumab response. Prognostic analysis and in vitro experiments further demonstrated that ALOX12 was closely associated with the prognosis, tumor proliferation, invasion, and metastasis. Multi-omics data analysis based on mutation and copy number variation (CNV) revealed that RYR3 drove the expression of ALOX12 and the deletion of 17p12 inhibited ALOX12 expression, respectively. Moreover, we interrogated the relationship between ALOX12 and immune cells and checkpoints. The results exhibited that high ALOX12 expression predicted a higher immune infiltration and better immunotherapy response, which was further validated in Tumor Immune Dysfunction and Exclusion (TIDE) and Subclass Mapping (SubMap) methods. Above all, our study provides a stable biomarker for clinical protocol optimization, prognostic assessment, precise treatment, and individualized treatment of CRC.