bluuebunny/crossref_metadata_2025 huggingface dataset:
Does positive MGMT methylation outbalance the limitation of subtotal resection in glioblastoma IDH-wildtype patients?
Authors: Mareike Müller , Franziska Staub-Bartelt , Julia Ehrmann , Daniel Hänggi , Michael Sabel , Jörg Felsberg , Marion Rapp
Published: June 2021

Background

The impact on survival of complete resection (CR) in patients with malignant glioma and MGMT promoter methylation on adjuvant therapy strategies has been proven in the past. However, it is not known whether a MGMT promoter methylation can compensate a subtotal resection. Therefore, we analyzed the progress of postoperative residual tumor tissue depending on the molecular tumor status.

Methods

We included all glioblastoma, IDH-wildtype (WHO grade IV) patients with postoperative residual tumor tissue, who were treated at our neurooncological department between 2010 and 2018. Correlation of molecular patterns with clinical data and survival times was performed. The results were compared to patients following CR.

Results

267 patients with glioblastoma, IDH-wildtype (WHO grade IV) received surgery of whom 81 patients with residual tumor were included in the analysis. MGMT promoter was methylated in 31 patients (38.27%). Median OS and PFS were significantly increased in patients with methylated MGMT promoter (mOS: 16 M vs. 13 M, p = 0.009; mPFS: 13 M vs. 5 M, p = 0.003). In comparison to survival of patients following CR, OS was decreased in patients with residual tumor regardless MGMT methylation.

Conclusion

Our data confirm impact of MGMT promoter methylation in patients with glioblastoma, IDH-wildtype on OS and PFS. However, in comparison to patients after CR, a methylated MGMT promoter cannot compensate the disadvantage due to residual tumor volume. In terms of personalized medicine and quality of life as major goal in oncology, neuro-oncologists have to thoroughly discuss advantages and disadvantages of residual tumor volume versus possible neurological deficits in CR.
Biofilms in the gravity sewer interfaces: making a friend from a foe
Authors: Augustyniak Adrian , Sikora Pawel , Grygorcewicz Bartłomiej , Despot Daneish , Braun Burga , Rakoczy Rafał , Szewzyk Ulrich , Barjenbruch Matthias , Stephan Dietmar
Published: June 2021

Sewer systems are an integral part of our modern civilization and are an imperative underground infrastructure asset that our society relies on. In Western Europe alone, 92% of the resident pollution is connected to sewer systems. This extensive coverage of sewerage systems presents an ideal habitation for microorganisms to strive. Sewers can be considered continuous flow bioreactors. They are always colonized by bacteria, either in a planktonic state traveling along the pipe with the water flow or dragged in sediment, or organized as biofilms. Many studies have been devoted to the detrimental effects of microorganisms on sewer systems made of concrete. However, their metabolic activity can also be beneficial, lead to more effective wastewater treatment, or be beneficial for concrete pipes. This aspect has not been thoroughly studied to date and requires further investigation. Therefore, in this Review, we highlighted the positive and negative activity of biofilms and their participation in five proposed mass exchange points in gravity sewers. Furthermore, we systematized and reviewed state of the art regarding methods that could be potentially used to remove or engineer these biological structures to increase the sustainability of sewers and achieve a better pre-treatment of wastewater. We have also indicated research gaps that could be followed in future studies.
Antioxidant and polyphenol content of different Vitis vinifera seed cultivars and two facilities of production of a functional bakery product
Authors: Kapcsándi Viktória , Hanczné Lakatos Erika , Sik Beatrix , Linka László Ádám , Székelyhidi Rita
Published: June 2021

This study aimed to examine the differences between the antioxidant capacity, and the total polyphenol content of the seed of eight different grape varieties. We also attempt to create a functional loaf enriched with grape seed meal. To achieve this goal, 3, 6, and 9% of the grape seed meal were added to the loaves made of bread flour and gluten-free flour mixture, and then the changes in their antioxidant and polyphenol content were examined. Based on the results, there were significant differences between the polyphenol and antioxidant content of grape seed varieties. The antioxidant content of the grape seeds varied between 228.50 mg AAE/g (94.80 mg TE/g) and 438.33 mg AAE/g (181.86 mg TE/g) in case of fatty samples, and between 176.29 mg AAE/g (41.24 mg TE/g) and 424.91 mg AAE/g (99.40 mg TE/g) in case of defatted samples. The total polyphenol content of the fatty samples changed between 91.16 and 221.81 mg GAE/g; in case of defatted samples, it ranged from 46.01 to 207.68 mg GAE/g. Rhine Riesling contained the greatest amount of these compounds. The functionality of loafs was confirmed by spectrophotometric analysis. Total polyphenol content ranged from 0.91 to 3.16 mg GAE/g in case of wheat loafs, and from 1.39 to 5.92 mg GAE/g in case of gluten-free loafs, while the total antioxidant content changed between 0.70 and 6.44 mg AAE/g in case of wheat loafs, and ranged from 2.55 to 9.75 in case of gluten-free loafs.

Graphic abstract
Diagnostic yield of small bowel capsule endoscopy in obscure gastrointestinal bleeding: a real-world prospective study
Authors: Romeo Samanta , Neri Benedetto , Mossa Michelangela , Riccioni Maria Elena , Scucchi Ludovica , Sena Giorgia , Potenza Saverio , Petruzziello Carmelina , Biancone Livia
Published: June 2021

Small bowel capsule endoscopy (SBCE) visualizes the small bowel (SB) mucosa. Gastrointestinal (GI) bleeding from SB accounts for the majority of SBCE indications. We aimed to assess, in a “real-world” prospective study, the diagnostic yield of SBCE in a cohort of consecutive patients with obscure gastrointestinal bleeding (OGIB). Secondary end point was to assess the frequency of adverse events and the role of SBCE in determining the diagnostic work-up and clinical outcome. From 2016 to 2018, all patients referred for SBCE examination were enrolled. Indication for SBCE was re-assessed by 2 dedicated gastroenterologists. Inclusion criteria: (1) age ≥ 18 and ≤ 85 years; (2) diagnosis of OGIB; 3) non-diagnostic standard bidirectional endoscopy; (4) informed consent. Exclusion criteria: (1) deglutition impairment; (2) SBCE contraindications; (3) pregnancy. The cohort included 50 patients [males 18 (36%), age 68 (27–83)]. SBCE indication: patients with ongoing overt OGIB (Group A) (n = 11; 22%), previous overt OGIB (Group B) (n = 14; 28%), occult bleeding (with Iron Deficiency Anaemia) (Group C) (n = 25; 50%). SBCE detected clinically relevant lesions in 46 (92%) cases. Clinically relevant lesions were more frequent in Group C (24/25; 96%), followed by Group A (10/11; 91%) and Group B (12/14; 85.5%). After SBCE, treatment was medical (60%); endoscopic (14%), surgical (36%) or conservative (18%). Clinical follow-up showed complete resolution in 63.2%, partial/absent resolution in 18.4% of cases. In a prospective study, the high diagnostic yield of SBCE supports its role as first-line investigation in patients with OGIB. However, this achievement requires an accurate and timely assessment by dedicated gastroenterologists.
Improved indocyanine green retention after short-term lenvatinib withdrawal in three patients with hepatocellular carcinoma
Authors: Sugimoto Rie , Inada Hiroki , Tanaka Yuki , Senju Takeshi , Aratake Yoshifusa , Nakanishi Akira , Miki Masami , Lee Lingaku , Hisano Terumasa , Matsumoto Yoshihiro , Mano Yohei , Iguchi Tomohiro , Sugimachi Keishi , Okumura Yukihiko , Taguchi Kenichi , Furukawa Masayuki
Published: June 2021

Use of lenvatinib, which has a high response rate in advanced hepatocellular carcinoma, sometimes results in tumor shrinkage and resectability of previously unresectable liver cancers. In Asia, including Japan, liver reserve, one of the determinants of resectability, is mainly determined by the indocyanine green (ICG) retention rate. Three patients with advanced liver cancer treated at our institution had very poor ICG retention rates during treatment with lenvatinib. Lenvatinib may reduce blood flow in both cancerous and non-cancerous regions by inhibiting vascular endothelial growth factor. Therefore, accurate determination of liver function likely requires withdrawal of this treatment several days before ICG retention testing.
Multidrug-resistant Acinetobacter baumannii infections in COVID-19 patients hospitalized in intensive care unit
Authors: Russo Alessandro , Gavaruzzi Francesca , Ceccarelli Giancarlo , Borrazzo Cristian , Oliva Alessandra , Alessandri Francesco , Magnanimi Eugenia , Pugliese Francesco , Venditti Mario
Published: June 2021

Objectives

Superinfections in patients hospitalized in intensive care unit (ICU) are an important and challenging complication, also in COVID-19. However, no definitive data are available about the role of multidrug-resistant Acinetobacter baumannii (MDR-AB) in COVID-19.

Methods

This was a single-center, cross-sectional study including patients with MDR-AB infections admitted to ICU with or without COVID-19, between January 2019 and January 2021. The primary objective of the study was to evaluate risk factor for MDR-AB infections in ICU patients hospitalized for COVID-19 or other etiology. The secondary endpoints were 30-days mortality in all study population and risk factors associated with development of bloodstream infection (BSI).

Results

During the study period 32 adults with COVID-19 were enrolled and compared with 115 patients admitted in the same ICU for other reasons. We observed a total of 114 deaths, with a survival rate of 29.3%: 18.8% in COVID-19 and 32.2% in control group. Relative risk for MDR-AB infection in COVID-19 showed that serum lactate levels mmol/l > 2, Acinetobacter baumannii colonization, BSI and steroid therapy were observed more frequently in COVID-19 patients. Cox regression analysis showed that serum lactate levels > 2 mmol/l, Acinetobacter baumannii colonization, BSI, and steroid therapy were associated with 30-days mortality. Finally, patients with COVID-19, white blood cells count > 11,000 mm3, serum lactate levels > 2 mmol/l, infections at time of ICU admission, Acinetobacter baumannii colonization, and steroid therapy were independently associated with development of BSI.

Conclusions

Our data highlight the impact of BSI on outcome, the role of Acinetobacter baumannii colonization and the use of steroids on the risk to develop MDR-AB infections also during COVID-19.
Consumption of Mineral Fertilizers in the Polish Agriculture – Trends and Directions of Changes
Authors: Piwowar Arkadiusz
Published: June 2021

Balanced, rational fertilization determines high and valuable yields of crops. Polish agriculture has been considered traditional, pro-ecological, with relatively low consumption of agrochemicals for many decades. Transformations in the economic and social area, in particular Poland’s accession to the European Union, have significantly changed this picture. This paper presents the results of the research on the trends in fertilizer consumption in the Polish agriculture. The main time range of the analyses covered the period of 2013–2017. The source materials used in the study were statistical data for the entire country and provinces, published by the Central Statistical Office (GUS), as well as results of empirical studies. According to analyses, the pressure associated with the increase in the use of mineral fertilizers in Poland is growing. In the economic year 2017/2018, the average consumption of mineral fertilizers in Poland was at a level of 141.6 kg NPK per hectare of agricultural lands and was higher by 39.2 kg than in the 2004/2005 season. The empirical studies were carried out in six randomly selected provinces in Poland. Total 1034 surveys completed by farmers were analysed. Comparative analyses were carried out using a multiple correspondence analysis (MPA). Based on the analysis performed, it can be stated that the direction of changes in the consumption of fertilizers depends on the area and economic size of the agricultural holding as well as on the district in which the agricultural holding is located. The article points out problems in the area of sustainable fertilizer consumption in Poland (high consumption of nitrogen fertilizers, low level of soil liming, etc.). Perspective directions of changes (precision agriculture, innovative fertilizers, increased farmers’ awareness of nutrient efficiency and reduction of negative impact on the environment) were also summarized.
A cooperative coevolution algorithm for complex hybrid seru-system scheduling optimization
Authors: Wu Yuting , Wang Ling , Chen Jing-fang
Published: June 2021

Under the current volatile business environment, the requirement of flexible production is becoming increasingly urgent. As an innovative production mode, seru-system with reconfigurability can overcome the lack of flexibility in traditional flow lines. Compared with pure seru-system, the hybrid seru-system composed of both serus and production lines is more practical for adapting to many production processes. This paper addresses a specific hybrid seru-system scheduling optimization problem (HSSOP), which includes three strongly coupled sub-problems, i.e., hybrid seru formation, seru scheduling and flow line scheduling. To minimize the makespan of the whole hybrid seru-system, we propose an efficient cooperative coevolution algorithm (CCA). To tackle three sub-problems, specific sub-algorithms are designed based on the characteristic of each sub-problem, i.e., a sub-space exploitation algorithm for hybrid seru formation, an estimation of distribution algorithm for seru scheduling, and a first-arrive-first-process heuristic for flow line scheduling. Since three sub-problems are coupled, a cooperation coevolution mechanism is proposed for the integrated algorithm by information sharing. Moreover, a batch reassign rule is designed to overcome the mismatch of partial solutions during cooperative coevolution. To enhance the exploitation ability, problem-specific local search methods are designed and embedded in the CCA. In addition to the investigation about the effect of parameter setting, extensive computational tests and comparisons are carried out which demonstrate the effectiveness and efficiency of the CCA in solving the HSSOP.
Exploring technology opportunities and evolution of IoT-related logistics services with text mining
Authors: Chen Mu-Chen , Ho Pui Hung
Published: June 2021

Many IoT technologies have been applied in the logistics industry in recent years, and they have had a substantial impact on many sectors such as shipping, air freight, warehousing, inventory, etc. Exploring technology opportunities and carrying out technological trend analysis are essential for IoT’s evolution, and there are many techniques or methods for doing so. In this paper, data analysis and text mining techniques, technology opportunity analysis (TOA) and technology-service evolution analysis (TSEA) have been applied to analyze and observe IoT technologies’ and services’ evolution. Academic journals, market reports, and patents have been collected and reviewed on the topic of IoT in the logistics field in this paper. Moreover, by using TOA, technology opportunities have been analyzed to explore IoT-related logistics services. The results of TOA, for example, show that cloud technology is essential to develop smart logistics services, and communication RFID technologies are key to developing information logistics services. Finally, TSEA enables the observation of IoT technology and logistics service evolution by combining unstructured and semi-structured data from text documents. Observing the results of TSEA, the evolution of IoT in logistics is identified, and the results of TSEA also confirm those of TOA using unstructured or semi-structured text data from documents only. The results of this paper are discussed and compared with those of some previous review studies. In summary, the results of this paper provide methodological guidelines on this topic for a comprehensive understanding of IoT-related logistics services.
Mechanical criterion for coal and gas outburst: a perspective from multiphysics coupling
Authors: Liu Ting , Lin Baiquan , Fu Xuehai , Liu Ang
Published: June 2021

Although a series of hypotheses have been proposed, the mechanism underlying coal and gas outburst remains unclear. Given the low-index outbursts encountered in mining practice, we attempt to explore this mechanism using a multiphysics coupling model considering the effects of coal strength and gas mass transfer on failure. Based on force analysis of coal ahead of the heading face, a risk identification index Cm and a critical criterion (Cm ≥ 1) of coal instability are proposed. According to this criterion, the driving force of an outburst consists of stress and gas pressure gradients along the heading direction of the roadway, whereas resistance depends on the shear and tensile strengths of the coal. The results show that outburst risk decreases slightly, followed by a rapid increase, with increasing vertical stress, whereas it decreases with increasing coal strength and increases with gas pressure monotonically. Using the response surface method, a coupled multi-factor model for the risk identification index is developed. The results indicate strong interactions among the controlling factors. Moreover, the critical values of the factors corresponding to outburst change depending on the environment of the coal seams, rather than being constants. As the buried depth of a coal seam increases, the critical values of gas pressure and coal strength decrease slightly, followed by a rapid increase. According to its controlling factors, outburst can be divided into stress-dominated, coal-strength-dominated, gas-pressure-dominated, and multi-factor compound types. Based on this classification, a classified control method is proposed to enable more targeted outburst prevention.
Phenological Changes of Soybean in Response to Climate Conditions in Frigid Region in China over the Past Decades
Authors: Gong Lijuan , Tian Baoxing , Li Yuguang , Wu Shuang
Published: June 2021

Plant phenology becoming a focus of current research worldwide is a sensitive indicator of global climate change. To understand observed soybean phenology and explore its climatic determinants in frigid region (Northeast China and northeast in Inner Mongolia), we studied the phenological changes of soybean [Glycine max (L.) Merr.] for the frigid region during 1981–2017, then analyzed the contribution of major causal climate factors to phenology based on multiple stepwise regression. Altogether, the average temperature from sowing to maturity (WGP) was significant increasing, accumulated precipitation and sunshine hours were decreasing. More than 50% of observations showed delays in sowing, emergence and maturity stage and short durations of sowing to flowering (VGP), flowering to maturity (RGP) and sowing to maturity (WGP). The late sowing was getting the following phenological timing backward, but the flowering and maturity delaying trends were much less than that of sowing timing due to the warming accelerated growth of soybean. Detailed analysis indicated mean temperature and accumulated precipitation of the 1–3 months immediately preceding the mean emergence, flowering and maturity dates influenced the phenological timing in higher latitude areas (HLJ and FL), while in JL and LN, accumulated precipitation and sunshine hours(replacing mean temperature) were the climatic determinants. These results brought light the importance of research and policy to support strategies for adaptation to local condition under the climate change.
Relationship Between Genitourinary Syndrome of Menopause and 3D High-Frequency Endovaginal Ultrasound Measurement of Vaginal Wall Thickness
Authors: Peker Hakan , Gursoy Ali
Published: June 2021

Background

To date, there is no certain method for diagnosis of genitourinary syndrome of menopause (GSM) and vaginal atrophy.

Aim

We aim to evaluate vaginal wall thickness (VWT) using 3D high frequency endovaginal ultrasound (3D EVUS) in GSM and also to investigate whether there is any association between VWT and postmenopausal sexual dysfunction.

Methods

Postmenopausal women applied for routine gynecologic examination were assessed at the Outpatient Clinic of Gynecology, Maltepe University Hospital. After pelvic examination, GSM symptoms were questioned for all women and vaginal health scoring tool was applied. Twenty women with GSM and 20 women without GSM were included in the study.

Outcomes

All patients filled in the Female Sexual Function Index (FSFI) and underwent 3D EVUS to evaluate VWT.

RESULTS

The women with GSM had significantly lower anterior and posterior VWT (P=.007 and P=.049, respectively). The total FSFI score, lubrication and pain sub-scores in patients with GSM was significantly lower than the patients without GSM. Anterior VWT was positively correlated with BMI and pain sub-score of FSFI (r=0.279, P=.047; r=0.344, P=.013, respectively). A significant negative correlation was detected between anterior vaginal VWT and age, time since menopause and satisfaction sub-score of FSFI (r=-0.332, P=.017; r=-0.354, P=.011; r=-0.301, P=.032, respectively). Posterior VWT was positively correlated with FSFI total score, arousal, lubrication and pain sub-scores (r=0.451, P=.001; r=0.437, P=.001; r=0.415, P=.002; r=0.335, P=.016; respectively).

Clinical Implications

Based on our results, measurement of VWT using 3D EVUS can be a useful non-invasive tool for the objective diagnosis of GSM.

Strengths and Limitations

Considering that only total vaginal thickness can be measured with traditional transabdominal and transvaginal techniques, the main strength of the study is the use of 3D EVUS for separate measurement of anterior and posterior VWT. The study has sufficient statistical power. The small sample size of study is the main limitation.

CONCLUSION

The 3D EVUS can be used for objective diagnosis of GSM and can also shed light on the causes of various sexual dysfunction symptoms in postmenopausal women, as it enables measuring the anterior and posterior walls of the vagina separately.
Anatomy and physiology of the palatine tonsils, adenoids, and lingual tonsils
Authors: Arambula Alexandra , Brown Jason R. , Neff Laura
Published: June 2021

Objective

This review aims to discuss the basic anatomy and physiology of the palatine and pharyngeal tonsils, with reference to how this foundational understanding may affect patient management and surgical procedures in these regions of the upper airway.

Methods

A literature search was performed using PubMed and Google Scholar using the MeSH terms tonsils, adenoids, anatomy, physiology, and adenotonsillectomy. Primary sources were excluded if they were abstracts only, non‐English language, or non‐human studies. Thirty‐five sources were included in this review.

Results and conclusions

The pharyngeal and palatine tonsils are compact yet physiologically complex mucosa‐associated lymphoid tissues that make up a portion of Waldeyer's ring. As part of the mucosal immune system, these structures function in exogenous antigen sampling and stimulation of immune responses. Aberrant immune activation and/or regulation can lead to a myriad of pathologies, with adenotonsillar hypertrophy, chronic tonsillitis/adenoiditis, and recurrent otitis media among the most commonly encountered conditions by otolaryngologists. While the pathophysiology of these conditions is still incompletely understood, current evidence and future investigations may reveal patterns amenable to targeted medical management. When medical management fails, tonsillectomy and/or adenoidectomy may be indicated for patient care. Though routine procedures, the execution of tonsil and/or adenoid removal requires a thorough understanding of the anatomy of these lymphoepithelial organs so as to minimize the risk for rare serious complications that can occur.
Role and relation in Confucian IR: Relating to strangers in the states of nature
Authors: Shih Chih-yu
Published: June 2021

The literature on International Relations theory has yet to align relational theory with role theory, despite the fact that these two theories share so much epistemological common ground. This article uses role theory to bridge the gap between the Confucian and Western conceptions of relationality, whose practitioners regard each other as strangers. With the support of role theory, the comparative analysis of relationality in this article has mainly focused on two different types of relations: prior rule-based relations and improvised relations. The differences in the cultural preparation for these two relations partially explain the plurality of the relational universe and the perception of stranger. Role theory is one way to reconnect the seemingly irreconcilable relational universes. To illustrate the value of a composite agenda of relational theory and role theory, the article will use Kim Jong-un of North Korea as its case. Confucian relations propose that, for all nations, the necessity of having a certain role relation is a more important agenda than insisting on exactly what role to take.
Introduction: Rethinking the Criminalization of Childbirth: Infanticide in Premodern Europe and the Modern Americas
Authors: McDougall Sara , Turner Felicity
Published: June 2021

On October 2, 2020, a newborn infant girl was discovered in the trash in an airport bathroom in Doha, Qatar. There was a rush to secure the infant's life, which was successful. There was a rush, also, to find the infant's mother, an effort that involved subjecting several women to intrusive physical examinations to determine if they had recently given birth, leading, eventually, to international outcry.
Pre-operative assessment of pediatric congenital heart disease patients in the COVID-19 era: lessons learned
Authors: Younis Nour K. , Zareef Rana O. , Diab Marwa A. , El Sedawi Omar , El-Rassi Issam M. , Bitar Fadi , Arabi Mariam
Published: June 2021

Background:

Equal to COVID-19 patients, non-COVID-19 patients are affected by the medical and social drawbacks of the COVID-19 pandemic. A significant reduction in elective life-changing surgeries has been witnessed in almost all affected countries. This study discusses an applicable and effective pre-operative assessment protocol that can be applied during the COVID-19 era.

Methods:

Our study is a descriptive retrospective observational study that involves children with CHD requiring open-heart surgeries at our tertiary care centre between March and November, 2020. We reviewed the charts of eligible patients aged 18 years and below. We identified the total numbers of scheduled, performed, and postponed surgeries, respectively. A thorough description of the clinical and physical presentation of the postponed cases, who tested positive for SARS-CoV-2, is provided.

Results:

Sixty-eight open-heart surgeries were scheduled at our centre between March and November, 2020. Three surgeries (4%) were postponed due to COVID-19. The three patients were asymptomatic COVID-19 cases detected on routine SARS-CoV-2 polymerase chain reaction testing. No symptoms of cough, chest pain, dyspnea, rhinorrhea, diarrhea, abdominal pain, anosmia, and ageusia were reported by our patients. All patients were afebrile and hemodynamically stable. Owing to the pre-operative assessment protocol that was implemented after the first case was detected, only three healthcare workers were at risk of COVID-19 transmission and were imposed to infectious evaluation and home quarantine.

Conclusions:

Adopting our discussed preoperative COVID-19 assessment protocol for CHD patients is an effective method to detect COVID-19 infections, optimise patient care, and ensure healthcare workers’ safety.
Strengthening approaches to respond to the social and emotional well-being needs of Aboriginal and Torres Strait Islander people: the Cultural Pathways Program
Authors: Brodie Tina , Pearson Odette , Cantley Luke , Cooper Peita , Westhead Seth , Brown Alex , Howard Natasha J
Published: June 2021

Aboriginal and Torres Strait Islander holistic health represents the interconnection of social, emotional, spiritual and cultural factors on health and well-being. Social factors (education, employment, housing, transport, food and financial security) are internationally described and recognised as the social determinants of health. The social determinants of health are estimated to contribute to 34% of the overall burden of disease experienced by Aboriginal and Torres Strait Islander people. Primary health care services currently ‘do what it takes’ to address social and emotional well-being needs, including the social determinants of health, and require culturally relevant tools and processes for implementing coordinated and holistic responses. Drawing upon a research-setting pilot program, this manuscript outlines key elements encapsulating a strengths-based approach aimed at addressing Aboriginal and Torres Strait Islander holistic social and emotional well-being.

The Cultural Pathways Program is a response to community identified needs, designed and led by Aboriginal and Torres Strait Islander people and informed by holistic views of health. The program aims to identify holistic needs of Aboriginal and Torres Strait Islander people as the starting point to act on the social determinants of health. Facilitators implement strengths-based practice to identify social and cultural needs (e.g. cultural and community connection, food and financial security, housing, mental health, transport), engage in a goal setting process and broker connections with social and health services. An integrated culturally appropriate clinical supervision model enhances delivery of the program through reflective practice and shared decision making. These embedded approaches enable continuous review and improvement from a program and participant perspective. A developmental evaluation underpins program implementation and the proposed culturally relevant elements could be further tailored for delivery within primary health care services as part of routine care to strengthen systematic identification and response to social and emotional well-being needs.
COVID-19 and the Paradox of Scientific Advice
Authors: Pamuk Zeynep
Published: June 2021

The scientific advisory committee is a neglected political institution whose importance became clear during the COVID-19 pandemic. What I call “the paradox of scientific advice” consists in that the two basic expectations from scientific advisory committees—neutrality and usefulness—are inherently in tension. To be useful, advisers must help governments set and attain their goals. Judgments about values and ends are necessary for useful advice, as are subjective judgments in the face of uncertainty and disagreement. This puts the committee in a double bind: if it tries to be more useful, it compromises the neutrality that is the source of its authority and legitimacy; if it tries to remain neutral, it sacrifices usefulness. I argue that this dilemma cannot be solved within the committee but that broader democratic scrutiny could mitigate its force. Advisory committees, in turn, should be structured to facilitate this scrutiny.
Paleoclimate Signals and Groundwater Age Distributions From 39 Public Water Works in the Netherlands; Insights From Noble Gases and Carbon, Hydrogen and Oxygen Isotope Tracers
Authors: Broers Hans Peter , Sültenfuß Jürgen , Aeschbach Werner , Kersting Arne , Menkovich Armin , de Weert Jasperien , Castelijns Jeroen
Published: June 2021

Knowing the age distribution of water abstracted from public water supply wells helps to ensure customer trust in drinking water sources and underpin predictions of water quality evolution. We sampled the mixed water of 39 large public supply well fields for major ion chemistry, 3H, 3He, 18O, 2H, 14CDIC, 13CDIC and noble gases and determined the Noble Gas Temperature (NGT). We used a discrete travel time distribution model to quantify the age distributions using 3H, 4He, 14C apparent age and NGT as the 4 distinctive tracers. Helium‐4 and NGT provided information on the older part of the age distributions and showed that the 14C apparent ages are often the result of mixing of waters ranging between 2,000 and 35,000 years old, instead of being discrete ages with a limited variance as previously assumed. The results reveal a large range of age distributions, comprising vulnerable well fields with >60% young water (<100 years) and well fields with >30% paleo groundwater (>25,000 years) and all forms of intermediate distributions. The age distributions match the hydrogeological setting; well fields with age distributions skewed towards older ages appear in the Roer Valley Graben structure, where fluvial and marine aquitards and sealed faults provide protection from recent recharge. Waters from this graben exhibit paleoclimate signals, with a clear relation between NGT (range 3.2–9.3 °C), 4He (up to 3.3 × 10−6 ccSTP/g) and δ18O (range −8.5‰ to −5.9‰VSMOW). Moreover, 3He/4He ratios of these graben waters suggest a certain influx of He from mantle origin.
Directional and Frequency Spread of Surface Ocean Waves From SWIM Measurements
Authors: Le Merle Eva , Hauser Danièle , Peureux Charles , Aouf Lotfi , Schippers Patricia , Dufour Christophe , Dalphinet Alice
Published: June 2021

The “China France Oceanography Satellite” (CFOSAT) launched in 2018 now routinely provides directional ocean wave spectra at the global scale. It consists of analyzing the normalized radar cross‐section measured by the near‐nadir pointing Ku‐Band real‐aperture scanning radar SWIM (Surface Waves Investigation and Monitoring). The significant wave height, dominant wavelength and direction are provided as the main parameters, but here, we analyze additional parameters, namely the frequency width of the omni‐directional spectra, the directional spread of the dominant waves, and the related Benjamin‐Feir index. This latter was proposed in the literature to estimate the probability of extreme waves. We discuss the geographical distributions of these parameters, their relation with sea‐state conditions, and their similarities and differences with respect to the same parameters obtained from the MFWAM numerical wave model and buoy data. We find that the SWIM omni‐directional spectra are narrower and more peaked than the model spectra and that these differences are more obvious in the high sea‐state conditions encountered in the Southern Ocean. We find that under the intense conditions of the Southern Ocean, the SWIM directional spread at the peak is the smallest for swell, the largest for young wind seas, and takes intermediate values for mature wind seas. The directional Benjamin‐Feir index is similar for SWIM and MFWAM, but this is mainly due to compensating effects in the parameters contributing to this index. The results indicate that these shape parameters may be used in the future to better describe the wave space‐time evolution.
Explore the Echo Characteristics of HF Radar in Artificial Disturbance Ionosphere Using Ray‐Tracing Technology
Authors: Hu Y. G. , Zhu X. L. , Jiang C. H. , Zhao Z. Y. , Zhang Y. N.
Published: June 2021

Artificial ionospheric hole created by the release of neutral gases (such as sulfur hexafluoride) has a significant impact on the propagation of radio waves. Based on the ray‐tracing method, the propagation patterns of HF radio waves in the ionospheric hole and the characteristics of its echoes are discussed in this paper. The results show that the HF waves will be deflected and bended while passing through the ionospheric hole, thus changing its original path. The sounding frequency, elevation angle, position of transmitter and receiver, and the dynamic variation of the hole all affect the reception of echoes. Generally, when the frequency is low, the echoes received on the ground mainly come from rays with low‐elevation angles, and the multi‐hop rays are more likely to occur. While with a high frequency, the received echoes are mainly contributed by high‐elevation rays. It is not conducive to the reception of the echoes if the transmitter and receiver is too far away from the hole. Single‐peak, double‐peak and multi‐peak echo signals can be found in the group path‐amplitude diagram, and the maximum group path difference can reflect the size of the ionospheric hole to some extent. Due to the dynamic evolution of the hole, the propagation of HF waves and received echoes also changes over time. The group path‐time diagrams show that the come‐back echoes mainly appear in the period of 20–100 s after release. The results of this paper have a guiding significance for the diagnosis and application of active experiments.
Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons
Authors: Runge Karen , Mathieu Rémi , Bugeon Stéphane , Lafi Sahra , Beurrier Corinne , Sahu Surajit , Schaller Fabienne , Loubat Arthur , Herault Leonard , Gaillard Stéphane , Pallesi-Pocachard Emilie , Montheil Aurélie , Bosio Andreas , Rosenfeld Jill A. , Hudson Eva , Lindstrom Kristin , Mercimek-Andrews Saadet , Jeffries Lauren , van Haeringen Arie , Vanakker Olivier , Van Hecke Audrey , Amrom Dina , Küry Sebastien , Ratner Chana , Jethva Reena , Gamble Candace , Jacq Bernard , Fasano Laurent , Santpere Gabriel , Lorente-Galdos Belen , Sestan Nenad , Gelot Antoinette , Giacuzz Sylvie , Goebbels Sandra , Represa Alfonso , Cardoso Carlos , Cremer Harold , de Chevigny Antoine
Published: June 2021

While the transcription factor NEUROD2 has recently been associated with epilepsy, its precise role during nervous system development remains unclear. Using a multi-scale approach, we set out to understand howNeurod2deletion affects the development of the cerebral cortex in mice. InNeurod2KO embryos, cortical projection neurons over-migrated, thereby altering the final size and position of layers. In juvenile and adults, spine density and turnover were dysregulated in apical but not basal compartments in layer 5 neurons. Patch-clamp recordings in layer 5 neurons of juvenile mice revealed increased intrinsic excitability. Bulk RNA sequencing showed dysregulated expression of many genes associated with neuronal excitability and synaptic function, whose human orthologs were strongly associated with autism spectrum disorders (ASD). At the behavior level,Neurod2KO mice displayed social interaction deficits, stereotypies, hyperactivity, and occasionally spontaneous seizures. Mice heterozygous forNeurod2had similar defects, indicating thatNeurod2is haploinsufficient. Finally, specific deletion ofNeurod2in forebrain excitatory neurons recapitulated cellular and behavioral phenotypes found in constitutive KO mice, ﻿revealing the region-specific contribution of dysfunctionalNeurod2in symptoms. Informed by these neurobehavioral features in mouse mutants, we identified eleven patients from eight families with a neurodevelopmental disorder including intellectual disability and ASD associated withNEUROD2pathogenic mutations. Our findings demonstrate crucial roles forNeurod2in neocortical development, whose alterations can cause neurodevelopmental disorders including intellectual disability and ASD.
Interactive relations between maternal prenatal stress, fetal brain connectivity, and gestational age at delivery
Authors: Thomason Moriah E. , Hect Jasmine L. , Waller Rebecca , Curtin Paul
Published: June 2021

Studies reporting significant associations between maternal prenatal stress and child outcomes are frequently confounded by correlates of prenatal stress that influence the postnatal rearing environment. The major objective of this study is to identify whether maternal prenatal stress is associated with variation in human brain functional connectivity prior to birth. We utilized fetal fMRI in 118 fetuses [48 female; mean age 32.9 weeks (SD = 3.87)] to evaluate this association and further addressed whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Community detection was used to empirically define networks and enrichment was used to isolate differential within- or between-network connectivity effects. Significance for χ2enrichment was determined by randomly permuting the subject pairing of fetal brain connectivity and maternal stress values 10,000 times. Mixtures modelling was used to test whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Increased maternal prenatal negative affect/stress was associated with alterations in fetal frontoparietal, striatal, and temporoparietal connectivity (β = 0.82,p < 0.001). Follow-up analysis demonstrated that these associations were stronger in women with better health behaviors, more positive interpersonal support, and lower overall stress (β = 0.16,p = 0.02). Additionally, magnitude of stress-related differences in neural connectivity was marginally correlated with younger gestational age at delivery (β = −0.18,p = 0.05). This is the first evidence that negative affect/stress during pregnancy is reflected in functional network differences in the human brain in utero, and also provides information about how positive interpersonal and health behaviors could mitigate prenatal brain programming.
Stresses affect inbreeding depression in complex ways: disentangling stress-specific genetic effects from effects of initial size in plants
Authors: Sandner Tobias M. , Matthies Diethart , Waller Donald M.
Published: June 2021

The magnitude of inbreeding depression (ID) varies unpredictably among environments. ID often increases in stressful environments suggesting that these expose more deleterious alleles to selection or increase their effects. More simply, ID could increase under conditions that amplify phenotypic variation (CV²), e.g., by accentuating size hierarchies among plants. These mechanisms are difficult to distinguish when stress increases both ID and phenotypic variation. We grew in- and outbred progeny of Mimulus guttatus under six abiotic stress treatments (control, waterlogging, drought, nutrient deficiency, copper addition, and clipping) with and without competition by the grass Poa palustris. ID differed greatly among stress treatments with δ varying from 7% (control) to 61% (waterlogging) but did not consistently increase with stress intensity. Poa competition increased ID under nutrient deficiency but not other stresses. Analyzing effects of initial size on performance of outbred plants suggests that under some conditions (low N, clipping) competition increased ID by amplifying initial size differences. In other cases (e.g., high ID under waterlogging), particular environments amplified the deleterious genetic effects of inbreeding suggesting differential gene expression. Interestingly, conditions that increased the phenotypic variability of inbred progeny regularly increased ID whereas variability among outbred progeny showed no relationship to ID. Our study reconciles the stress- and phenotypic variability hypotheses by demonstrating how specific conditions (rather than stress per se) act to increase ID. Analyzing CV² separately in inbred and outbred progeny while including effects of initial plant size improve our ability to predict how ID and gene expression vary across environments.
Osmotic pressure modulates single cell cycle dynamics inducing reversible growth arrest and reactivation of human metastatic cells
Authors: Taïeb Hubert M. , Garske Daniela S. , Contzen Jörg , Gossen Manfred , Bertinetti Luca , Robinson Tom , Cipitria Amaia
Published: June 2021

Biophysical cues such as osmotic pressure modulate proliferation and growth arrest of bacteria, yeast cells and seeds. In tissues, osmotic regulation takes place through blood and lymphatic capillaries and, at a single cell level, water and osmoregulation play a critical role. However, the effect of osmotic pressure on single cell cycle dynamics remains poorly understood. Here, we investigate the effect of osmotic pressure on single cell cycle dynamics, nuclear growth, proliferation, migration and protein expression, by quantitative time-lapse imaging of single cells genetically modified with fluorescent ubiquitination-based cell cycle indicator 2 (FUCCI2). Single cell data reveals that under hyperosmotic stress, distinct cell subpopulations emerge with impaired nuclear growth, delayed or growth arrested cell cycle and reduced migration. This state is reversible for mild hyperosmotic stress, where cells return to regular cell cycle dynamics, proliferation and migration. Thus, osmotic pressure can modulate the reversible growth arrest and reactivation of human metastatic cells.
The amniotic fluid cell-free transcriptome in spontaneous preterm labor
Authors: Bhatti Gaurav , Romero Roberto , Gomez-Lopez Nardhy , Pique-Regi Roger , Pacora Percy , Jung Eunjung , Yeo Lami , Hsu Chaur-Dong , Kavdia Mahendra , Tarca Adi L.
Published: June 2021

The amniotic fluid (AF) cell-free RNA was shown to reflect physiological and pathological processes in pregnancy, but its value in the prediction of spontaneous preterm delivery is unknown. Herein we profiled cell-free RNA in AF samples collected from women who underwent transabdominal amniocentesis after an episode of spontaneous preterm labor and subsequently delivered within 24 h (n = 10) or later (n = 28) in gestation. Expression of known placental single-cell RNA-Seq signatures was quantified in AF cell-free RNA and compared between the groups. Random forest models were applied to predict time-to-delivery after amniocentesis. There were 2385 genes differentially expressed in AF samples of women who delivered within 24 h of amniocentesis compared to gestational age-matched samples from women who delivered after 24 h of amniocentesis. Genes with cell-free RNA changes were associated with immune and inflammatory processes related to the onset of labor, and the expression of placental single-cell RNA-Seq signatures of immune cells was increased with imminent delivery. AF transcriptomic prediction models captured these effects and predicted delivery within 24 h of amniocentesis (AUROC = 0.81). These results may inform the development of biomarkers for spontaneous preterm birth.
Determining future aflatoxin contamination risk scenarios for corn in Southern Georgia, USA using spatio-temporal modelling and future climate simulations
Authors: Kerry Ruth , Ingram Ben , Garcia-Cela Esther , Magan Naresh , Ortiz Brenda V. , Scully Brian
Published: June 2021

Aflatoxins (AFs) are produced by fungi in crops and can cause liver cancer. Permitted levels are legislated and batches of grain are rejected based on average concentrations. Corn grown in Southern Georgia (GA), USA, which experiences drought during the mid-silk growth period in June, is particularly susceptible to infection by Aspergillus section Flavi species which produce AFs. Previous studies showed strong association between AFs and June weather. Risk factors were developed: June maximum temperatures > 33 °C and June rainfall < 50 mm, the 30-year normals for the region. Future climate data were estimated for each year (2000–2100) and county in southern GA using the RCP 4.5 and RCP 8.5 emissions scenarios. The number of counties with June maximum temperatures > 33 °C and rainfall < 50 mm increased and then plateaued for both emissions scenarios. The percentage of years thresholds were exceeded was greater for RCP 8.5 than RCP 4.5. The spatial distribution of high-risk counties changed over time. Results suggest corn growth distribution should be changed or adaptation strategies employed like planting resistant varieties, irrigating and planting earlier. There were significantly more counties exceeding thresholds in 2010–2040 compared to 2000–2030 suggesting that adaptation strategies should be employed as soon as possible.