bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige)
Authors: Manganotti Paolo , Naccarato Marcello , Scali Ilario , Cappellari Manuel , Bonetti Bruno , Burlina Alessandro , Turinese Emanuele , Bogo Sabrina , Teatini Francesco , Franchini Enrica , Caneve Giorgio , Ruzza Giampietro , Gaudenzi Anna , Bombardi Roberto , Bozzato Giulio , Padoan Roberta , Gentile Carolina , Rana Michele , Turazzini Michelangelo , Alessandra Danese , Brigo Francesco , Nardone Raffaele , Quatrale Rocco , Menegazzo Elisabetta , Masato Maela , Novello Stefano , Passadore Paolo , Baldi Antonio , Valentinis Luca , Baracchini Claudio , Pieroni Alessio , Basile Anna Maria , Semplicini Claudio , Piffer Silvio , Giometto Bruno , Tonello Simone , Bonifatti Domenico Marco , Lorenzut Simone , Merlino Giovanni , Valente Maria Rosaria , Paladin Francesco , Tonon Agnese , de Luca Cristina , Perini Francesco , Centonze Sandro , Bovi Paolo
Published: March 2021

Background

Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke.

Methods

We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies.

Results

In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers.

Conclusions

Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.
Impact of the COVID-19 pandemic lockdown on the utilization of acute surgical care in the State of Salzburg, Austria: retrospective, multicenter analysis
Authors: Presl Jaroslav , Varga Martin , Mittermair Christof , Mitterwallner Stefan , Weitzendorfer Michael , Gabersek Ana , Borhanian Kurosch , Heuberger Andreas , Weiss Helmut , Emmanuel Klaus , von Rahden Burkhard , Koch Oliver Owen
Published: March 2021

Background

Some medical disciplines have reported a strong decrease of emergencies during the coronavirus disease 2019 (COVID-19) pandemic; however, the effect of the lockdown on general surgery emergencies remains unclear.

Methods

This study is a retrospective, multicenter analysis of general surgery emergency operations performed during the period from 1 March to 15th 2020 lockdown and in the same time period of 2019 in three medical centers providing emergency surgical care to the area Salzburg-North, Austria.

Results

In total 165 emergency surgeries were performed in the study period of 2020 compared to 287 in 2019. This is a significant decrease of 122 (42.5%) emergency surgeries during the COVID-19 lockdown (p = 0.005). The length of hospital stay was reduced to 3 days in 2020 compared to 4 in 2019. Appendectomy remained the most performed emergency surgery for both periods; however the number of surgeries was reduced to less than a half, with 72 cases in 2019 and 33 cases in 2020 (p = 0.118). Emergency colon surgery observed the strongest decrease of 75% from 17 cases in 2019 to 4 in 2020. In addition, the emergency abdominal wall hernia, cholecystectomies for acute cholecystitis, small surgeries and proctological emergencies recorded drops of 70%, 39%, 33% and 47% respectively. The strongest reduction in frequencies of emergency surgeries was reported from the designated COVID center in the examined region.

Conclusions

Emergency general surgery is an essential service that continues to run under all circumstances. Our data show that COVID-19-related restrictions have resulted in a significant decrease in the utilization of acute surgical care.
Temperature-dependent development and survival of an invasive genotype of wheat curl mite, Aceria tosichella
Authors: Karpicka-Ignatowska Kamila , Laska Alicja , Rector Brian G. , Skoracka Anna , Kuczyński Lechosław
Published: March 2021

Quantifying basic biological data, such as the effects of variable temperatures on development and survival, is crucial to predicting and monitoring population growth rates of pest species, many of which are highly invasive. One of the most globally important pests of cereals is the eriophyoid wheat curl mite (WCM), Aceria tosichella, which is the primary vector of several plant viruses. The aim of this study was to evaluate temperature-dependent development and survival of WCM at a wide range of constant temperatures in the laboratory (17–33 °C). The development time of each stage depended significantly on temperature and it was negatively correlated with temperature increase. At high temperatures (27–33 °C), individuals had shorter developmental times, with the shortest (6 days) at 33 °C, whereas at the lowest tested temperatures (17–19 °C), developmental time was almost 3× longer. Moreover, temperature had a clear effect on survival: the higher the temperature, the lower the survival rate. These data provide information promoting more efficient and effective manipulation of WCM laboratory colonies, and further our understanding of the ramifications of temperature change on WCM physiology and implications for the growth and spread of this globally invasive pest.
Metabolomic and elemental profiling of human tissue in kidney cancer
Authors: Nizioł Joanna , Copié Valérie , Tripet Brian P. , Nogueira Leonardo B. , Nogueira Katiane O. P. C. , Ossoliński Krzysztof , Arendowski Adrian , Ruman Tomasz
Published: March 2021

Introduction

Kidney cancer is one of the most frequently diagnosed and the most lethal urinary cancer. Despite advances in treatment, no specific biomarker is currently in use to guide therapeutic interventions.

Objectives

Major aim of this work was to perform metabolomic and elemental profiling of human kidney cancer and normal tissue and to evaluate cancer biomarkers.

Methods

Metabolic and elemental profiling of tumor and adjacent normal human kidney tissue from 50 patients with kidney cancer was undertaken using three different analytical methods.

Results

Five potential tissue biomarkers of kidney cancer were identified and quantified using with high-resolution nuclear magnetic resonance spectroscopy. The contents of selected chemical elements in tissues was analyzed using inductively coupled plasma optical emission spectrometry. Eleven mass spectral features differentiating between kidney cancer and normal tissues were detected using silver-109 nanoparticle enhanced steel target laser desorption/ionization mass spectrometry.

Conclusions

Our results, derived from the combination of ICP-OES, LDI MS and 1H NMR methods, suggest that tissue biomarkers identified herein appeared to have great potential for use in clinical prognosis and/or diagnosis of kidney cancer.
Air pollution exposure—the (in)visible risk factor for respiratory diseases
Authors: Bălă Gabriel-Petrică , Râjnoveanu Ruxandra-Mioara , Tudorache Emanuela , Motișan Radu , Oancea Cristian
Published: March 2021

There is increasing interest in understanding the role of air pollution as one of the greatest threats to human health worldwide. Nine of 10 individuals breathe air with polluted compounds that have a great impact on lung tissue. The nature of the relationship is complex, and new or updated data are constantly being reported in the literature. The goal of our review was to summarize the most important air pollutants and their impact on the main respiratory diseases (chronic obstructive pulmonary disease, asthma, lung cancer, idiopathic pulmonary fibrosis, respiratory infections, bronchiectasis, tuberculosis) to reduce both short- and the long-term exposure consequences. We considered the most important air pollutants, including sulfur dioxide, nitrogen dioxide, carbon monoxide, volatile organic compounds, ozone, particulate matter and biomass smoke, and observed their impact on pulmonary pathologies. We focused on respiratory pathologies, because air pollution potentiates the increase in respiratory diseases, and the evidence that air pollutants have a detrimental effect is growing. It is imperative to constantly improve policy initiatives on air quality in both high- and low-income countries.
Dynamic response of rock slope with anti-dip weak interlayer and its influencing factors under seismic actions
Authors: Wang Tong , Gao Chengliang , Huang Fei , Peng Di , Tian Shuwen , Li Huilan
Published: March 2021

The load features of ground motion are mainly reflected by three factors: amplitude, frequency, and duration. The combination of these factors determines the response of rock-soil mass and the structure safety under seismic load. By finite element method, this paper analyzes the influence of the three factors of ground motion on the dynamic response of a slope. The analysis shows that the slope displacement increased with the elevation from the bottom. The anti-dip fault puts the slope in an unfavorable deformation state. Due to the large residual deformation in the fault zone, a large displacement occurred on the slope top. It was also learned that the adjustment of amplitude only leads to proportional growth in the absolute value of the acceleration of the slope. Under the same conditions, the dynamic responses in different parts of the target slope are not greatly affected by the changing amplitude, but depend more on the material and spectral features of the rock-soil mass. The research results provide a reference for the evaluation and prediction of slope seismic stability and the evolution of slope damage under earthquakes with different frequencies, amplitudes, and durations.
Development and validation of a quantitative qPCR assay for detecting Natterjack toad (Epidalea calamita) eDNA samples
Authors: Reyne Marina , Naaum Amanda M. , Marnell Ferdia , Reid Neil , Helyar Sarah J.
Published: March 2021

The Natterjack toad (Epidalea calamita) is the rarest amphibian species in Ireland, regionally Red-Listed as Endangered. We applied an eDNA approach to detect species presence in breeding pond water samples. We developed a species-specific qPCR assay targeting the cytochrome c oxidase subunit I (COI). The assay was tested in silico, in vitro (DNA extracted from tissue) and in vivo (DNA extracted from water samples). Water samples were collected from five ponds with known Natterjack toad presence or absence to validate the sensitivity and specificity of the assay. The assay was shown to be highly specific to the Natterjack toad and tested positive only against toad tissue samples and eDNA samples from ponds with known species presence. We believe this method can be used for rapid assessment of species occurrence.
Anomalous self-experience, body image disturbance, and eating disorder symptomatology in first-onset anorexia nervosa
Authors: Moccia Lorenzo , Conte Eliana , Ambrosecchia Marianna , Janiri Delfina , Di Pietro Salvatore , De Martin Valentina , Di Nicola Marco , Rinaldi Lucio , Sani Gabriele , Gallese Vittorio , Janiri Luigi
Published: March 2021

Purpose

Anorexia nervosa-restrictive subtype (AN-R) is a life-threatening disorder relying on behavioural abnormalities, such as excessive food restriction or exercise. Such abnormalities may be secondary to an “objectified” attitude toward body image and self. This is the first study exploring the impact of anomalous self-experience (ASEs) on abnormal body image attitude and eating disorder (ED) symptomatology in individuals with AN-R at onset.

Methods

We recruited Italian female participants, 40 with AN-R (mean age 18.3 ± 2.3) and 45 age and educational level-matched healthy controls (HCs) (mean age 18.2 ± 2.6). ASEs, body image attitude, and ED symptom severity were assessed through the examination of anomalous self-experience (EASE), the body uneasiness test (BUT), and the eating disorder examination questionnaire (EDE-Q), respectively. We conducted multivariate analysis of variance to investigate distribution patterns of variables of interest, and mediation analysis to test the effect of ASEs and body image on ED symptomatology.

Results

Individuals with AN-R scored higher than HCs on the EASE (p < .0001). A direct effect of ASEs on ED severity (p = 0.009; bootstrapped LLCI = 0.067, ULCI = 0.240) was found in AN-R. After modelling the effect of abnormal body image attitude, the relationship between EASE total score and ED symptomatology was significantly mediated by BUT (p = 0.002; bootstrapped LLCI = 0.001, ULCI = 0.172).

Conclusion

Although the exact pathways linking AN-R to self-disorder remain to be identified, a broader exploration of transdiagnostic features in AN, including explorations of different dimensions of self-experience and intersubjectivity, may shed further light on the clinical phenomenology of the disorder.

Level of evidence

Level III, case–control analytic study.
PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile
Authors: Faja F. , Finocchi F. , Carlini T. , Rizzo F. , Pallotti F. , Spaziani M. , Balercia G. , Lenzi A. , Paoli D. , Lombardo F.
Published: March 2021

Purpose

Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases.

Methods

Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples.

Results

Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number.

Conclusions

Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer.
Cultural aspects of ants, bees and wasps, and their products in sub-Saharan Africa
Authors: van Huis Arnold
Published: March 2021

This study’s purpose was to make an overview of how ants, bees, wasps, and their products, such as honey are utilized, perceived, and experienced in daily life across sub-Saharan Africa. Ethno-entomological information was collected by interviews with more than 300 people from 27 countries and by literature studies. Queens of the antCarebara viduaare deliberately eaten and unintentionally bee larvae with honey and sugar ants with sugar. Honey, apart from food, is widely used to treat numerous medical problems and as a stimulant (for the memory) or as a cosmetic. In the Qur’an, the medical value of honey is recognized. Seed stores of ants may be harvested by humans. In Sudan, bee stings are used to cure arthritis as bee venom has bioactive properties. Wasp nests are used to cure inflammations such as mumps. Certain insect properties are used in conveying these treatments to persons it is employed to, such as wasps feed do make dogs vicious. Some stories seem to make no sense like the snake-trapping ants in Madagascar, but a scientific explanation is provided. Certain insects’ looks may inspire people to construct stories or have proverbs such as the very narrow waist of wasps, suggesting sterility. Bee swarms and driver ants are feared all over and believed to be employed (by witchdoctors) to punish. Not all stories of events with bees or ants are similar across sub-Saharan Africa. Social insects are also used to stimulate cohesion between people.
Hem-o-Lok polymer clips for major vascular control in paediatric minimally invasive surgery
Authors: Haffenden Verity , Peters Robert T , Wilkinson David , Lansdale Nick
Published: March 2021

Purpose

The challenge of endoscopic large vessel control has brought sweat to the brow of many a surgeon, yet the optimal method for use in a small working space remains unknown. Reports of delayed, major haemorrhage with exclusive energy device use have raised significant concerns. We, therefore, report outcomes of an alternative sealing device (Weck Hem-o-Lok polymer clips) in laparoscopic and thoracoscopic surgery.

Methods

A retrospective review of all patients (< 18 years) who underwent laparoscopic splenectomy or thoracoscopic pulmonary resection between February 2018 and August 2020 (30 months) was undertaken. Data are presented as median (IQR).

Results

Thirty-three patients were identified (16 female); 16 underwent laparoscopic splenectomy and 17 thoracoscopic lobectomy/excision of congenital pulmonary airway malformation (CPAM) or resection of pulmonary sequestration. Age at surgery was 7 years 7 months (6 years 2 months–9 years 9 months) and weight 23.0 kg (20.2–37.4 kg) in the splenectomy group: it was 16 months (13–19 months) and 12.0 kg (10.4–13.2 kg) in the thoracic group. Hem-o-Lok clips (medium–large) were used to individually clip: (1) the main splenic artery and vein; or (2) pulmonary arterial branches and vein; or (3) systemic sequestration vessels, using a 5 mm endoscopic applicator. In most cases, two clips were placed proximally and one distally: the vessel then divided without energy. There were no incidences of clip failure during application or migration. There was no significant intra-operative or post-operative bleeding.

Conclusion

Hem-o-Lok polymer clips are a safe and reliable method for major vascular control during endoscopic surgery in small children.
Bionanotechnology
Authors: Fruk Ljiljana , Kerbs Antonina
Published: March 2021

Connecting theory with real-life applications, this is the first ever textbook to equip students with a comprehensive knowledge of all the key concepts in bionanotechnology. By bridging the interdisciplinary gap from which bionanotechnology emerged, it provides a systematic introduction to the subject, accessible to students from a wide variety of backgrounds. Topics range from nanomaterial preparation, properties and biofunctionalisation, and analytical methods used in bionanotechnology, to bioinspired and DNA nanotechnology, and applications in biosensing, medicine and tissue engineering. Throughout the book, features such as 'Back to basics' and 'Research report' boxes enable students to build a strong theoretical knowledge and to link this to practical applications and up-to-date research. With over 200 detailed, full-colour illustrations and more than 100 end-of-chapter problems, this is an essential guide to bionanotechnology for any student studying this exciting, fast-developing and interdisciplinary field.
Association between dietary flavonoid intakes and C-reactive protein levels: a cross-sectional study in Taiwan
Authors: Hsieh Cheng-Tzu , Wang Jui , Chien Kuo-Liong
Published: March 2021

Although the intake of specific flavonoid-rich foods may reduce C-reactive protein (CRP) levels, the association between dietary flavonoid intakes and CRP is inconsistent. We aim to describe dietary flavonoid intakes in a Taiwanese nationally representative sample and to investigate the association between flavonoid intakes and CRP. We conducted a cross-sectional study based on 2592 adults from the Nutrition and Health Survey in Taiwan 2005–8. Flavonoid intakes were estimated by linking the 24-h dietary recall with the U.S. Department of Agriculture flavonoid database and divided into quartiles. Adjusted estimates of the flavonoid intakes for the continuous and binary (elevated CRP: >0⋅3 mg/dl) variables were performed by using general linear and logistic regression. We found that tea, orange, tofu and sweet potato leaves/water spinach constituted the major food items of the total flavonoid intake. The total flavonoid intake was lower among women and elderly. Compared with the lowest total flavonoid intake quartile, participants in higher quartiles were associated with a lower CRP status (adjusted odds ratio (OR): 0⋅61, 95 % confidence interval (CI): 0⋅44–0⋅86 for the highest quartiles). The trends were similar for flavonol and flavan-3-ol intakes. Compared with non-consumers, tea consumers were likely to have a lower CRP status (adjusted OR: 0⋅74, 95 % CI: 0⋅57–0⋅97). In brief, a higher total flavonoid intake and tea consumption were inversely associated with CRP levels, indicating that a high-flavonoid diet may contribute to anti-inflammatory effects. A Taiwanese flavonoid content table is necessary for conducting further studies related to flavonoids in Taiwan.
Understanding the Welby-Russell Correspondence
Authors: Metzger Scott
Published: March 2021

A shallow reading of the 1905 correspondence between Victoria Welby and Bertrand Russell yields the impression that Welby has misunderstood Russell's “On Denoting.” I argue that a deeper reading reveals that Welby should be understood, not as misunderstanding Russell, but as bringing a pragmatic attitude to bear on Russell's theory of descriptions in order to expose the limits of his strictly logical analysis.
The Myth of a State of Intending
Authors: Russell Devlin
Published: March 2021

Recent work by Joseph Raz, Niko Kolodny, and Sergio Tenenbaum suggest that there are no normative constraints peculiar to intentions as such. Such constraints are a myth. We can understand the rationality of intention without positing that intention is a mental state. I argue that, further, we can understand the descriptive nature of intention (i.e., its role in intrapersonal coordination) without positing that intention is a mental state. Such a posit is itself a myth. Instead, intention is an action with certain characteristic sub-actions that play a coordinating role.
Ultra-processed foods, changes in blood pressure and incidence of hypertension: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Scaranni Patricia de Oliveira da Silva , Cardoso Leticia de Oliveira , Chor Dora , Melo Enirtes Caetano Prates , Matos Sheila Maria Alvim , Giatti Luana , Barreto Sandhi Maria , da Fonseca Maria de Jesus Mendes
Published: March 2021

Objective:

To estimate changes in blood pressure and the incidence of hypertension associated with consumption of ultra-processed foods (UPF) by Brazilian civil servants at a 4-year follow-up.

Design:

Longitudinal analysis of the ELSA-Brasil with non-hypertensive individuals at baseline. We applied the FFQ at the baseline and categorised energy intake by degree of processing, using the NOVA classification. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at baseline (2008–2010) and again at first follow-up (2012–2014). Incidence of arterial hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg or antihypertensive medication during the previous 2 weeks. A mixed-effect linear regression model and mixed-effect logistic regression model were used to estimate associations between UPF consumption and, respectively, changes in blood pressure and incidence of hypertension.

Setting:

Brazil.

Participants:

Civil servants of Brazilian public academic institutions in six cities (n8754), aged 35–74 years at baseline (2008–2010).

Results:

UPF consumption contributed 25·2 % (sd= 9·6) of total energies consumed. After adjustment, participants with high UPF consumption presented a 23 % greater risk of developing hypertension (OR = 1·23, 95 % CI 1·06, 1·44) than those with low UPF consumption. We did not find association between UPF consumption and changes in blood pressure over time.

Conclusions:

The higher the UPF consumption, the higher the risk of hypertension in adults. Reducing UPF consumption is thus important to promote health and prevent hypertension.
Defizite im verbalen Gedächtnis als transdiagnostisches Korrelat psychotischer Störungen
Authors: Gebhardt Nadja , Roesch Ely Daniela
Published: March 2021

Zusammenfassung. Defizite im verbalen Gedächtnis bei psychotischen Störungen könnten ein definierendes transdiagnostisches Merkmal sein, und in Vorstudien gefundene Unterschiede im Ausmaß dieser könnten auf methodische Effekte zurückgehen. Um dies zu untersuchen, wurden in der vorliegenden Studie Patient*innen mit verschiedenen psychotischen Störungen ( n=145) in einem Verfahren (California Verbal Learning Test, CVLT) verglichen und in einer Diskriminanzanalyse mit Defiziten im verbalen Gedächtnis als Kriterium von einer Vergleichsstichprobe von Patient*innen mit depressiver Störung ( n=89) unterschieden. Es ergibt sich Evidenz für die transdiagnostische Vergleichbarkeit der Defizite im verbalen Gedächtnis, jedoch werden anhand dieser in der Diskriminanzanalyse nur 63 % der Patient*innen korrekt klassifiziert. Dies liegt vor allem daran, dass die Patient*innen mit depressiver Störung ebenfalls unerwartet starke Einbußen zeigen.
Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential
Authors: Huang Shuai , Cao Bihui , Zhang Jinling , Feng Yunfei , Wang Lu , Chen Xiaopei , Su Hang , Liao Shengrong , Liu Jinggong , Yan Jun , Liang Baoxia
Published: March 2021

Cucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discovered the excellent cytotoxicity of CuB towards human nasopharyngeal carcinoma cells and elucidated its potential ferroptosis-inducing mechanisms. Morphology alterations of mitochondrial ultrastructure, as observed via transmission electron microscopy, showed that CuB-treated cells undergo ferroptosis. CuB caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. Furthermore, CuB exhibited anti-tumour effects in vitro by inhibiting cellular microtubule polymerization, arresting cell cycle and suppressing migration and invasion. Finally, CuB significantly inhibited tumour progression without causing obvious side effects in vivo. Altogether, our study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer, and it provided valuable insights for developing effective anti-tumour agents with novel molecular mechanisms derived from natural products.
The key cyclic electron flow protein PGR5 associates with cytochrome b6f, and its function is partially influenced by the LHCII state transition
Authors: Wu Xinyi , Wu Jianqiang , Wang Yu , He Meiwen , He Mingming , Liu Weikang , Shu Sheng , Sun Jin , Guo Shirong
Published: March 2021

In plants and algae, PGR5-dependent cyclic electron flow (CEF) is an important regulator of acclimation to fluctuating environments, but how PGR5 participates in CEF is unclear. In this work, we analyzed two PGR5s in cucumber (Cucumis sativus L.) under different conditions and found that CsPGR5a played the dominant role in PGR5-dependent CEF. The results of yeast two-hybrid, biomolecular fluorescence complementation (BiFC), blue native PAGE, and coimmunoprecipitation (CoIP) assays showed that PGR5a interacted with PetC, Lhcb3, and PsaH. Furthermore, the intensity of the interactions was dynamic during state transitions, and the abundance of PGR5 attached to cyt b6f decreased during the transition from state 1 to state 2, which revealed that the function of PGR5a is related to the state transition. We proposed that PGR5 is a small mobile protein that functions when attached to protein complexes.

Two PGR5s are present in some species of algae and higher plants, and CsPGR5a plays the dominant role in PGR5-dependent cyclic electron flow in cucumber. PGR5 is a small and mobile protein that functions when attached to protein complexes. In this study, the function of PGR5 was found to be partially related to the state transition.
Continental-scale analysis of shallow and deep groundwater contributions to streams
Authors: Hare Danielle K. , Helton Ashley M. , Johnson Zachary C. , Lane John W. , Briggs Martin A.
Published: March 2021

Groundwater discharge generates streamflow and influences stream thermal regimes. However, the water quality and thermal buffering capacity of groundwater depends on the aquifer source-depth. Here, we pair multi-year air and stream temperature signals to categorize 1729 sites across the continental United States as having major dam influence, shallow or deep groundwater signatures, or lack of pronounced groundwater (atmospheric) signatures. Approximately 40% of non-dam stream sites have substantial groundwater contributions as indicated by characteristic paired air and stream temperature signal metrics. Streams with shallow groundwater signatures account for half of all groundwater signature sites and show reduced baseflow and a higher proportion of warming trends compared to sites with deep groundwater signatures. These findings align with theory that shallow groundwater is more vulnerable to temperature increase and depletion. Streams with atmospheric signatures tend to drain watersheds with low slope and greater human disturbance, indicating reduced stream-groundwater connectivity in populated valley settings.
Germline inherited small RNAs facilitate the clearance of untranslated maternal mRNAs in C. elegans embryos
Authors: Quarato Piergiuseppe , Singh Meetali , Cornes Eric , Li Blaise , Bourdon Loan , Mueller Florian , Didier Celine , Cecere Germano
Published: March 2021

Inheritance and clearance of maternal mRNAs are two of the most critical events required for animal early embryonic development. However, the mechanisms regulating this process are still largely unknown. Here, we show that together with maternal mRNAs, C. elegans embryos inherit a complementary pool of small non-coding RNAs that facilitate the cleavage and removal of hundreds of maternal mRNAs. These antisense small RNAs are loaded into the maternal catalytically-active Argonaute CSR-1 and cleave complementary mRNAs no longer engaged in translation in somatic blastomeres. Induced depletion of CSR-1 specifically during embryonic development leads to embryonic lethality in a slicer-dependent manner and impairs the degradation of CSR-1 embryonic mRNA targets. Given the conservation of Argonaute catalytic activity, we propose that a similar mechanism operates to clear maternal mRNAs during the maternal-to-zygotic transition across species.
Neuropathy-causing TRPV4 mutations disrupt TRPV4-RhoA interactions and impair neurite extension
Authors: McCray Brett A. , Diehl Erika , Sullivan Jeremy M. , Aisenberg William H. , Zaccor Nicholas W. , Lau Alexander R. , Rich Dominick J. , Goretzki Benedikt , Hellmich Ute A. , Lloyd Thomas E. , Sumner Charlotte J.
Published: March 2021

TRPV4 is a cell surface-expressed calcium-permeable cation channel that mediates cell-specific effects on cellular morphology and function. Dominant missense mutations of TRPV4 cause distinct, tissue-specific diseases, but the pathogenic mechanisms are unknown. Mutations causing peripheral neuropathy localize to the intracellular N-terminal domain whereas skeletal dysplasia mutations are in multiple domains. Using an unbiased screen, we identified the cytoskeletal remodeling GTPase RhoA as a TRPV4 interactor. TRPV4-RhoA binding occurs via the TRPV4 N-terminal domain, resulting in suppression of TRPV4 channel activity, inhibition of RhoA activation, and extension of neurites in vitro. Neuropathy but not skeletal dysplasia mutations disrupt TRPV4-RhoA binding and cytoskeletal outgrowth. However, inhibition of RhoA restores neurite length in vitro and in a fly model of TRPV4 neuropathy. Together these results identify RhoA as a critical mediator of TRPV4-induced cell structure changes and suggest that disruption of TRPV4-RhoA binding may contribute to tissue-specific toxicity of TRPV4 neuropathy mutations.
A chromosome-level genome of Astyanax mexicanus surface fish for comparing population-specific genetic differences contributing to trait evolution
Authors: Warren Wesley C. , Boggs Tyler E. , Borowsky Richard , Carlson Brian M. , Ferrufino Estephany , Gross Joshua B. , Hillier LaDeana , Hu Zhilian , Keene Alex C. , Kenzior Alexander , Kowalko Johanna E. , Tomlinson Chad , Kremitzki Milinn , Lemieux Madeleine E. , Graves-Lindsay Tina , McGaugh Suzanne E. , Miller Jeffrey T. , Mommersteeg Mathilda T. M. , Moran Rachel L. , Peuß Robert , Rice Edward S. , Riddle Misty R. , Sifuentes-Romero Itzel , Stanhope Bethany A. , Tabin Clifford J. , Thakur Sunishka , Yamamoto Yoshiyuki , Rohner Nicolas
Published: March 2021

Identifying the genetic factors that underlie complex traits is central to understanding the mechanistic underpinnings of evolution. Cave-dwellingAstyanax mexicanuspopulations are well adapted to subterranean life and many populations appear to have evolved troglomorphic traits independently, while the surface-dwelling populations can be used as a proxy for the ancestral form. Here we present a high-resolution, chromosome-level surface fish genome, enabling the first genome-wide comparison between surface fish and cavefish populations. Using this resource, we performed quantitative trait locus (QTL) mapping analyses and found new candidate genes for eye loss such asdusp26. We used CRISPR gene editing inA. mexicanusto confirm the essential role of a gene within an eye size QTL,rx3, in eye formation. We also generated the first genome-wide evaluation of deletion variability across cavefish populations to gain insight into this potential source of cave adaptation. The surface fish genome reference now provides a more complete resource for comparative, functional and genetic studies of drastic trait differences within a species.
Emerging dominance of summer rainfall driving High Arctic terrestrial-aquatic connectivity
Authors: Beel C. R. , Heslop J. K. , Orwin J. F. , Pope M. A. , Schevers A. J. , Hung J. K. Y. , Lafrenière M. J. , Lamoureux S. F.
Published: March 2021

Hydrological transformations induced by climate warming are causing Arctic annual fluvial energy to shift from skewed (snowmelt-dominated) to multimodal (snowmelt- and rainfall-dominated) distributions. We integrated decade-long hydrometeorological and biogeochemical data from the High Arctic to show that shifts in the timing and magnitude of annual discharge patterns and stream power budgets are causing Arctic material transfer regimes to undergo fundamental changes. Increased late summer rainfall enhanced terrestrial-aquatic connectivity for dissolved and particulate material fluxes. Permafrost disturbances (<3% of the watersheds’ areal extent) reduced watershed-scale dissolved organic carbon export, offsetting concurrent increased export in undisturbed watersheds. To overcome the watersheds’ buffering capacity for transferring particulate material (30 ± 9 Watt), rainfall events had to increase by an order of magnitude, indicating the landscape is primed for accelerated geomorphological change when future rainfall magnitudes and consequent pluvial responses exceed the current buffering capacity of the terrestrial-aquatic continuum.
Worldwide continuous gap-filled MODIS land surface temperature dataset
Authors: Shiff Shilo , Helman David , Lensky Itamar M.
Published: March 2021

Satellite land surface temperature (LST) is vital for climatological and environmental studies. However, LST datasets are not continuous in time and space mainly due to cloud cover. Here we combine LST with Climate Forecast System Version 2 (CFSv2) modeled temperatures to derive a continuous gap filled global LST dataset at a spatial resolution of 1 km. Temporal Fourier analysis is used to derive the seasonality (climatology) on a pixel-by-pixel basis, for LST and CFSv2 temperatures. Gaps are filled by adding the CFSv2 temperature anomaly to climatological LST. The accuracy is evaluated in nine regions across the globe using cloud-free LST (mean values: R2 = 0.93, Root Mean Square Error (RMSE) = 2.7 °C, Mean Absolute Error (MAE) = 2.1 °C). The provided dataset contains day, night, and daily mean LST for the Eastern Mediterranean. We provide a Google Earth Engine code and a web app that generates gap filled LST in any part of the world, alongside a pixel-based evaluation of the data in terms of MAE, RMSE and Pearson’s r.
Integrated genomic analysis reveals regulatory pathways and dynamic landscapes of the tRNA transcriptome
Authors: Sun Zefang , Tan Jia , Zhao Minqiong , Peng Qiyao , Zhou Mingqing , Zuo Shanru , Wu Feilong , Li Xueguang , Dong Yangyang , Xie Ming , Yang Yide , Zhou Junhua , Liu Xianghua , He Quanze , He Zuping , Yu Xing , He Quanyuan
Published: March 2021

tRNAs and tRNA-derived RNA fragments (tRFs) play various roles in many cellular processes outside of protein synthesis. However, comprehensive investigations of tRNA/tRF regulation are rare. In this study, we used new algorithms to extensively analyze the publicly available data from 1332 ChIP-Seq and 42 small-RNA-Seq experiments in human cell lines and tissues to investigate the transcriptional and posttranscriptional regulatory mechanisms of tRNAs. We found that histone acetylation, cAMP, and pluripotency pathways play important roles in the regulation of the tRNA gene transcription in a cell-specific manner. Analysis of RNA-Seq data identified 950 high-confidence tRFs, and the results suggested that tRNA pools are dramatically distinct across the samples in terms of expression profiles and tRF composition. The mismatch analysis identified new potential modification sites and specific modification patterns in tRNA families. The results also show that RNA library preparation technologies have a considerable impact on tRNA profiling and need to be optimized in the future.
A refined proposal for the origin of dogs: the case study of Gnirshöhle, a Magdalenian cave site
Authors: Baumann Chris , Pfrengle Saskia , Münzel Susanne C. , Molak Martyna , Feuerborn Tatiana R. , Breidenstein Abagail , Reiter Ella , Albrecht Gerd , Kind Claus-Joachim , Verjux Christian , Leduc Charlotte , Conard Nicholas J. , Drucker Dorothée G. , Giemsch Liane , Thalmann Olaf , Bocherens Hervé , Schuenemann Verena J.
Published: March 2021

Dogs are known to be the oldest animals domesticated by humans. Although many studies have examined wolf domestication, the geographic and temporal origin of this process is still being debated. To address this issue, our study sheds new light on the early stages of wolf domestication during the Magdalenian period (16–14 ka cal BP) in the Hegau Jura region (Southwestern Germany and Switzerland). By combining morphology, genetics, and isotopes, our multidisciplinary approach helps to evaluate alternate processes driving the early phases of domestication. The isotope analysis uncovered a restricted, lowδ15N protein diet for all analyzed Gnirshöhle specimens, while morphological examinations and phylogenetic relationships did not unequivocally assign them to one or the other canid lineage. Intriguingly, the newly generated mitochondrial canid genomes span the entire genetic diversity of modern dogs and wolves. Such high mitochondrial diversity could imply that Magdalenian people tamed and reared animals originating from different wolf lineages. We discuss our results in light of three ecological hypotheses and conclude that both domestication and the existence of a specialized wolf ecomorph are highly probable. However, due to their proximity to humans and a restricted diet, we propose domestication as the most likely scenario explaining the patterns observed herein.
Transfer learning for ECG classification
Authors: Weimann Kuba , Conrad Tim O. F.
Published: March 2021

Remote monitoring devices, which can be worn or implanted, have enabled a more effective healthcare for patients with periodic heart arrhythmia due to their ability to constantly monitor heart activity. However, these devices record considerable amounts of electrocardiogram (ECG) data that needs to be interpreted by physicians. Therefore, there is a growing need to develop reliable methods for automatic ECG interpretation to assist the physicians. Here, we use deep convolutional neural networks (CNN) to classify raw ECG recordings. However, training CNNs for ECG classification often requires a large number of annotated samples, which are expensive to acquire. In this work, we tackle this problem by using transfer learning. First, we pretrain CNNs on the largest public data set of continuous raw ECG signals. Next, we finetune the networks on a small data set for classification of Atrial Fibrillation, which is the most common heart arrhythmia. We show that pretraining improves the performance of CNNs on the target task by up to $$6.57\%$$

6.57
%

, effectively reducing the number of annotations required to achieve the same performance as CNNs that are not pretrained. We investigate both supervised as well as unsupervised pretraining approaches, which we believe will increase in relevance, since they do not rely on the expensive ECG annotations. The code is available on GitHub at https://github.com/kweimann/ecg-transfer-learning.
A novel highly quantitative and reproducible assay for the detection of anti-SARS-CoV-2 IgG and IgM antibodies
Authors: Noda Kenta , Matsuda Kouki , Yagishita Shigehiro , Maeda Kenji , Akiyama Yutaro , Terada-Hirashima Junko , Matsushita Hiromichi , Iwata Satoshi , Yamashita Kazuto , Atarashi Yusuke , Watanabe Shunsuke , Ide Nobuyuki , Yoshida Tomokazu , Ohmagari Norio , Mitsuya Hiroaki , Hamada Akinobu
Published: March 2021

The quantitative range and reproducibility of current serological tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are not optimized. Herein, we developed a diagnostic test that detects SARS-CoV-2 IgG and IgM with high quantitativeness and reproducibility and low interference. The system was based on the high-sensitivity chemiluminescence enzyme immunoassay (HISCL) platform and detects IgG and IgM specific to SARS-CoV-2 spike and nucleocapsid proteins. Quantification accuracy and reproducibility were evaluated using serially diluted samples from 60 SARS-CoV-2-infected patients. Assay performance was evaluated using serum samples from the SARS-CoV-2-infected patients and 500 SARS-CoV-2-negative serum samples collected before the emergence of SARS-CoV-2. The system showed high quantification accuracy (range, 102), high reproducibility (within 5%), and no cross-reaction between SARS1- and MERS-S proteins. Detection accuracy was 98.3% and 93.3% for IgG and IgM against spike proteins and 100% and 71.7% for IgG and IgM against nucleocapsid proteins, respectively. Mean antibody levels were > 10 times that in negative samples upon admission and > 100 times that at convalescent periods. Clinical severity upon admission was not correlated with IgG or IgM levels. This highly quantitative, reproducible assay system with high clinical performance may help analyze temporal serological/immunological profiles of SARS-CoV-2 infection and SARS-CoV-2 vaccine effectiveness.
Alterations in skin microbiome mediated by radiotherapy and their potential roles in the prognosis of radiotherapy-induced dermatitis: a pilot study
Authors: Ramadan Mohammed , Hetta Helal F. , Saleh Moustafa M. , Ali Mohamed E. , Ahmed Ali Aya , Salah Mohammed
Published: March 2021

Radiotherapy-induced dermatitis (RID) is an inflammatory cutaneous disorder that is acquired as an adverse effect of undergoing radiotherapy. Skin microbiome dysbiosis has been linked to the outcomes of several dermatological diseases. To explore the skin microbiota of RID and deduce their underlying impact on the outcome of RID, cutaneous microbiomes of 78 RID patients and 20 healthy subjects were characterized by sequencing V1-V3 regions of 16S rRNA gene. In total, a significantly apparent reduction in bacterial diversity was detected in microbiomes of RID in comparison to controls. Overall, the raised Proteobacteria/ Firmicutes ratio was significantly linked to delayed recovery or tendency toward the permanence of RID (Kruskal Wallis: P = 2.66 × 10–4). Moreover, applying enterotyping on our samples stratified microbiomes into A, B, and C dermotypes. Dermotype C included overrepresentation of Pseudomonas, Staphylococcus and Stenotrophomonas and was markedly associated with delayed healing of RID. Strikingly, coexistence of diabetes mellitus and RID was remarkably correlated with a significant overrepresentation of Klebsiella or Pseudomonas and Staphylococcus. Metabolic abilities of skin microbiome could support their potential roles in the pathogenesis of RID. Cutaneous microbiome profiling at the early stages of RID could be indicative of prospective clinical outcomes and maybe a helpful guide for personalized therapy.
Class II phosphatidylinositol 3-kinase-C2α is essential for Notch signaling by regulating the endocytosis of γ-secretase in endothelial cells
Authors: Shimizu Shota , Yoshioka Kazuaki , Aki Sho , Takuwa Yoh
Published: March 2021

The class II α-isoform of phosphatidylinositol 3-kinase (PI3K-C2α) plays a crucial role in angiogenesis at least in part through participating in endocytosis and, thereby, endosomal signaling of several cell surface receptors including VEGF receptor-2 and TGFβ receptor in vascular endothelial cells (ECs). The Notch signaling cascade regulates many cellular processes including cell proliferation, cell fate specification and differentiation. In the present study, we explored a role of PI3K-C2α in Delta-like 4 (Dll4)-induced Notch signaling in ECs. We found that knockdown of PI3K-C2α inhibited Dll4-induced generation of the signaling molecule Notch intracellular domain 1 (NICD1) and the expression of Notch1 target genes including HEY1, HEY2 and NOTCH3 in ECs but not in vascular smooth muscle cells. PI3K-C2α knockdown did not inhibit Dll4-induced endocytosis of cell surface Notch1. In contrast, PI3K-C2α knockdown as well as clathrin heavy chain knockdown impaired endocytosis of Notch1-cleaving protease, γ-secretase complex, with the accumulation of Notch1 at the perinuclear endolysosomes. Pharmacological blockage of γ-secretase also induced the intracellular accumulation of Notch1. Taken together, we conclude that PI3K-C2α is required for the clathrin-mediated endocytosis of γ-secretase complex, which allows for the cleavage of endocytosed Notch1 by γ-secretase complex at the endolysosomes to generate NICD1 in ECs.