bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a Global Pact for the Environment
Authors: Aguila Yann
Published: March 2021

These Proceedings remarks aim to address interrogations on a Global Pact for the Environment. A Global Pact for the Environment is a project for an international treaty that seeks to recognize environmental rights and duties for citizens, states, and businesses.
Sustainable Development and International Law
Authors: McCorquodale Robert , McInerney-Lankford Siobhan
Published: March 2021

Public international law norms are relevant to a wide range of the sustainable development goals. Yet there is a frequent failure to connect the two spheres and there is very limited literature on the interaction between public international law, and the policy and political frameworks that underpin development.
Remarks by Rüdiger Wolfrum
Authors: Wolfrum Rüdiger
Published: March 2021

It has been argued that the expected sea-level rise will lead to the shifting of baselines. It is further held that, as a matter of consequence, this means that all maritime borders depending upon baselines will have to shift accordingly or have to be renegotiated. This would affect the boundaries vis-à-vis neighboring states, opposite or adjacent, as well as the delineation of the exclusive economic zone and the delineation of the continental shelf if no outer continental shelf (no shelf beyond 200 nm) exists. The Baselines Committee of the International Law Association (ILA) stated that in “extreme circumstances [landward changes of the baseline] could result in total territorial loss and the consequent total loss of baselines and of the maritime zones measured from those baselines. The existing law of the normal baselines does not offer an adequate solution to this potentially serious problem.” I see the logic of the arguments based upon Articles 3, 4, and 5 of the United Nations Convention on the Law of the Sea (UNCLOS). Nevertheless, I disagree with the interpretation of UNCLOS Articles 3 and 4. In consequence thereof, I disagree with the qualification that baselines are “ambulatory.” In my view, other considerations have to be taken into account—see below. I am pleased to note that the ILA Committee on sea-level rise in its report took a more balanced view than the Baselines Committee.
Opening Remarks by Saskia Bruines
Authors: Bruines Saskia
Published: March 2021

Ladies and Gentlemen, as Deputy Mayor of The Hague, I am glad that this esteemed panel will discuss the promise of cities in relation to international law. As a representative of the international city of peace and justice, this subject is of course close to my heart.
Opening Remarks by Janne E. Nijman
Authors: Nijman Janne E.
Published: March 2021

Ladies and Gentlemen, a warm welcome to the Closing Plenary of the 2020 Virtual Annual Meeting of the ASIL. A warm welcome also on behalf of the City of The Hague. We just listened to the deputy mayor, who kindly supports this Plenary. My name is Janne Nijman, I am the academic director of the Asser Institute in The Hague, and professor in Amsterdam and Geneva.
The Interlinking Crises of COVID and Police Violence on the June 2020 Global Anti-racism Debate
Authors: Achiume E. Tendayi
Published: March 2021

To complement the insights of my co-panelists, I will offer some reflections from the perspective of my UN mandate, on the ongoing global anti-racism debate as it has been structured by the COVID-19 pandemic, and the national and transnational uprisings against systemic racism in law enforcement.
Cervicofacial surgery and implantable hearing device extrusion: management of challenging cases
Authors: Carnevale C , Til-Pérez G , Arancibia-Tagle D , Tomás-Barberán M , Sarría-Echegaray P
Published: March 2021

Objective

To describe our management of implantable hearing device extrusion in cases of previous cervicofacial surgery.

Methods

A review was conducted of a retrospectively acquired database of surgical procedures for implantable hearing devices performed at our department between January 2011 and December 2019. Cases of device extrusion and previous cervicofacial surgery are included. Medical and surgical management is discussed.

Results

Four cases of implant extrusion following cervicofacial surgery were identified: one involving a Bonebridge system and three involving cochlear implants. In all cases, antibiotic treatment was administered and surgical debridement performed. The same Bonebridge system was implanted in the middle fossa. The three cochlear implants were removed, and new devices were implanted in a more posterior region.

Conclusion

Previous cervicofacial surgery is a risk factor for hearing implant extrusion. The middle fossa approach is the best option for the Bonebridge system. Regarding the cochlear implant, it is always suitable to place it in a more posterior area. An inferiorly based fascio-muscular flap may be a good option to reduce the risk of extrusion.
Fairness, equity, and justice in the Paris Agreement: Terms and operationalization of differentiation
Authors: Will Ulrike , Manger-Nestler Cornelia
Published: March 2021

The Paris Agreement (2015) and the Rulebook (2018) introduce the terms ‘fair’ and ‘climate justice’ for burden-sharing and differentiation. The article analyses to what extent these terms amend the existing term ‘equity’ and the principle of common but differentiated responsibilities (CBDR).

The principle of CBDR is an open balancing concept with one clear requirement: Contracting parties contribute to climate protection to a different extent. The terms which appear to have normative weight (‘equity’ and ‘climate justice’), in international climate agreements, are limited to their procedural relevance. They aim at an equal participation in sub-institutions of the Paris Agreement or at making arguments for differentiation transparent. The term ‘fair’ focuses on the discourse on individual concepts of differentiation and on narrowing down common criteria in the long-run.

Considering the operationalization of differentiation beyond the terms, it becomes clear that criteria are hardly specified, not weighted against each other and that self-differentiation dominates pre-defined criteria, in particular within the central rules on mitigation and financial transfers. However, the Paris Agreement still specifies criteria with different relevance: Capabilities are followed by vulnerability and the responsibility for emissions.

After all, the prevailing procedural terms and rules of differentiation might give orientation, inspire subsequent decisions and the nationally determined contributions (NDCs). The more transparent the various specifications of differentiation are, the more the rules of differentiation can be narrowed. If the reference of criteria to individual states is possible, the Paris Agreement might be implemented effectively which allows for better compliance with the Agreement.
Ibn Sīnā's Remarks on a Khwarizmian Sound
Authors: BENKATO ADAM
Published: March 2021

In his study of Arabic phonetics, Asbāb ḥudūṯ al-ḥurūf (The Causes of the Genesis of the Consonants), Ibn Sīnā briefly surveys some speech sounds found in languages other than Arabic, among them one particular to Khwarizmian, an Iranian language attested primarily in glosses to Arabic manuscripts of the 13th century. This study attempts to elucidate the sound Ibn Sīnā describes both through reference to his own system of phonetic terminology and through comparison with extant material in the Khwarizmian language.
Estimating genetic diversity, mating system and pollen dispersal to inform ex situ conservation of the tree Genipa americana L.
Authors: Melo Marília Freitas de Vasconcelos , Sebbenn Alexandre Magno , Rossini Bruno Cesar , Muniz Ana Veruska Cruz da Silva , Rodrigues Carlos Jose , Marino Celso Luis , Moraes Mario Luiz Teixeira de
Published: March 2021

Using microsatellite loci, we assessed the mating system and genetic diversity of the dioecious tropical tree Genipa americana in a natural population (NP) and a progeny test (PT). For NP, we also estimated the paternity correlation within and among fruits and mean pollen dispersal distance. As expected for dioecious species, all offspring originated from outcrossing (t = 1). Mating among relatives (1 − ts) and paternity correlation (rp) were variable among progenies (1 − ts = 0.03–0.19; rp = 0.04–0.40), but greater in NP than in PT. Fixation index (F) was generally significant and lower in adults than in offspring, indicating selection against inbred individuals. Paternity correlation was higher within (0.40) than among (0.26) fruits, indicating a lower effective number of pollen donors (Nep) within (2.5) than among (3.8) fruits. Due to the higher rp in NP, the effective size within progenies (Ne) was lower (2.69) than PT (3.27). The pollen dispersal pattern was strongly leptokurtic, suggesting long-distance pollen dispersal (mean of 179 m). The results show that both populations can be used for seed collection in environmental reforestation programmes; however, considering that PT is structured in maternal progenies, NP is more suitable for seed collection due to the lower probability of mating among related trees.
End-tidal capnography monitoring in infants ventilated on the neonatal intensive care unit
Authors: Williams Emma , Dassios Theodore , O’Reilly Niamh , Walsh Alison , Greenough Anne
Published: March 2021

Objective

To assess whether end-tidal capnography (EtCO2) monitoring reduced the magnitude of difference in carbon dioxide (CO2) levels and the number of blood gases in ventilated infants.

Study design

A case–control study of a prospective cohort (n = 36) with capnography monitoring and matched historical controls (n = 36).

Result

The infants had a median gestational age of 31.6 weeks. A reduction in the highest CO2 level on day 1 after birth was observed after the introduction of EtCO2 monitoring (p = 0.043). There was also a reduction in the magnitude of difference in CO2 levels on days 1 (p = 0.002) and 4 (p = 0.049) after birth. There was no significant difference in the number of blood gases.

Conclusion

Continuous end-tidal capnography monitoring in ventilated infants was associated with a reduction in the degree of the magnitude of difference in CO2 levels and highest level of CO2 on the first day after birth.
Evidence that polyploidy in esophageal adenocarcinoma originates from mitotic slippage caused by defective chromosome attachments
Authors: Scott Stacey J. , Li Xiaodun , Jammula Sriganesh , Devonshire Ginny , Lindon Catherine , Fitzgerald Rebecca C. , D’Avino Pier Paolo
Published: March 2021

Polyploidy is present in many cancer types and is increasingly recognized as an important factor in promoting chromosomal instability, genome evolution, and heterogeneity in cancer cells. However, the mechanisms that trigger polyploidy in cancer cells are largely unknown. In this study, we investigated the origin of polyploidy in esophageal adenocarcinoma (EAC), a highly heterogenous cancer, using a combination of genomics and cell biology approaches in EAC cell lines, organoids, and tumors. We found the EAC cells and organoids present specific mitotic defects consistent with problems in the attachment of chromosomes to the microtubules of the mitotic spindle. Time-lapse analyses confirmed that EAC cells have problems in congressing and aligning their chromosomes, which can ultimately culminate in mitotic slippage and polyploidy. Furthermore, whole-genome sequencing, RNA-seq, and quantitative immunofluorescence analyses revealed alterations in the copy number, expression, and cellular distribution of several proteins known to be involved in the mechanics and regulation of chromosome dynamics during mitosis. Together, these results provide evidence that an imbalance in the amount of proteins implicated in the attachment of chromosomes to spindle microtubules is the molecular mechanism underlying mitotic slippage in EAC. Our findings that the likely origin of polyploidy in EAC is mitotic failure caused by problems in chromosomal attachments not only improves our understanding of cancer evolution and diversification, but may also aid in the classification and treatment of EAC and possibly other highly heterogeneous cancers.
Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism
Authors: Corrado Mauro , Samardžić Dijana , Giacomello Marta , Rana Nisha , Pearce Erika L. , Scorrano Luca
Published: March 2021

Optic atrophy 1 (OPA1), a mitochondria-shaping protein controlling cristae biogenesis and respiration, is required for memory T cell function, but whether it affects intrathymic T cell development is unknown. Here we show that OPA1 is necessary for thymocyte maturation at the double negative (DN)3 stage when rearrangement of the T cell receptor β (Tcrβ) locus occurs. By profiling mitochondrial function at different stages of thymocyte maturation, we find that DN3 cells rely on oxidative phosphorylation. Consistently, Opa1 deletion during early T cell development impairs respiration of DN3 cells and reduces their number. Opa1-deficient DN3 cells indeed display stronger TCR signaling and are more prone to cell death. The surviving Opa1−/− thymocytes that reach the periphery as mature T cells display an effector memory phenotype even in the absence of antigenic stimulation but are unable to generate metabolically fit long-term memory T cells. Thus, mitochondrial defects early during T cell development affect mature T cell function.
Biomechanical properties of retina and choroid: a comprehensive review of techniques and translational relevance
Authors: Ferrara Mariantonia , Lugano Gaia , Sandinha Maria Teresa , Kearns Victoria R. , Geraghty Brendan , Steel David H. W.
Published: March 2021

Studying the biomechanical properties of biological tissue is crucial to improve our understanding of disease pathogenesis. The biomechanical characteristics of the cornea, sclera and the optic nerve head have been well addressed with an extensive literature and an in-depth understanding of their significance whilst, in comparison, knowledge of the retina and choroid is relatively limited. Knowledge of these tissues is important not only to clarify the underlying pathogenesis of a wide variety of retinal and vitreoretinal diseases, including age-related macular degeneration, hereditary retinal dystrophies and vitreoretinal interface diseases but also to optimise the surgical handling of retinal tissues and, potentially, the design and properties of implantable retinal prostheses and subretinal therapies. Our aim with this article is to comprehensively review existing knowledge of the biomechanical properties of retina, internal limiting membrane (ILM) and the Bruch’s membrane–choroidal complex (BMCC), highlighting the potential implications for clinical and surgical practice. Prior to this we review the testing methodologies that have been used both in vitro, and those starting to be used in vivo to aid understanding of their results and significance.
Training model for the intraluminal continuous suturing technique for microvascular anastomosis
Authors: Xiao Zongyu , Samii Madjid , Wang Ji , Pan Qi , Xu Zhimin , Ju Hu
Published: March 2021

Microvascular anastomosis is a critical procedure in cerebral bypass surgeries. In some rare cases, the extraluminal interrupted technique is not optimal because the vessels are immobile and cannot be rotated, and anastomosis can be performed effectively through the intraluminal continuous suturing technique. The authors reported the application of the intraluminal continuous suturing technique in microanastomosis training with silicone tube, rat’s common iliac arteries and abdominal aorta. A silicone tube with a diameter of 1.5 mm was used to practice microanastomosis in intraluminal continuous suturing technique. Then the technique was applied in side-to-side, end-to-side anastomoses of common iliac arteries and the end-to-end abdominal aorta anastomoses of rat. The suturing time and patency rates were compared with an alternative intraluminal continuous suturing technique and one-way-up interrupted suturing technique in silicone tube and rat vessel anastomoses. The intraluminal continuous suturing technique could be gained through practicing with silicone tube, and the technique has also been demonstrated effective in side-to-side, end-to-side anastomoses of common iliac arteries of rat and the abdominal aorta end-to-end anastomoses. In all the animal experimental groups with different suturing techniques, there was no difference between the patency rates, all the immediate patency rate was 100%. There was no significant suturing time difference between the two intraluminal continuous suturing techniques, but the two intraluminal continuous suturing techniques were faster than the interrupted technique. The intraluminal continuous suturing technique described in the study could be used as an efficient method for side-to-side, end-to-side and end-to-end anastomosis, especially under the situation the posterior wall of the anastomosis could not be rotated. Proficiency of the technique could be achieved through practicing in laboratory with silicone tube and live animals.
Energy-efficient butanol production by Clostridium acetobutylicum with histidine kinase knockouts to improve strain tolerance and process robustness
Authors: Du Guangqing , Zhu Chao , Xu Mengmeng , Wang Lan , Yang Shang-Tian , Xue Chuang
Published: March 2021

Engineering histidine kinases in C. acetobutylicum enhanced cell viability and solventogenesis in ABE fermentation and enabled robust and energy-efficient butanol production.
Understanding cation-disordered rocksalt oxyfluoride cathodes
Authors: Chen Dongchang , Ahn Juhyeon , Self Ethan , Nanda Jagjit , Chen Guoying
Published: March 2021

A “concerted-densification” based failure mechanism, involving atomic-level changes in both transition-metal cationic sublattice and oxygen/fluorine anionic sublattice, is proposed for the degradation of F-DRX cathode materials.
On the mechanism of photocatalytic reactions on CuxO@TiO2 core–shell photocatalysts
Authors: Wang Kunlei , Bielan Zuzanna , Endo-Kimura Maya , Janczarek Marcin , Zhang Dong , Kowalski Damian , Zielińska-Jurek Anna , Markowska-Szczupak Agata , Ohtani Bunsho , Kowalska Ewa
Published: March 2021

Stable and enhanced UV/vis photocatalytic activity via the Z-scheme mechanism of CuxO@TiO2 prepared by the microemulsion method.
Highly sensitive 2D organic field-effect transistors for the detection of lithium-ion battery electrolyte leakage
Authors: Yang Ben , Zhang Shiqi , Wang Yan , Dai Shilei , Wang Xin , Sun Quan , Huang Yunhui , Huang Jia
Published: March 2021

A broad range of conjugated 2D organic polymer semiconductor films were prepared, and we utilized the resulting OFET devices to monitor lithium-ion batterie leakage.
Perpendicularly oriented 2D perovskite thin films prepared using the bar-coating method and DMSO additive
Authors: Akiyoshi Misato , Yoshizawa-Fujita Masahiro , Takeoka Yuko , Rikukawa Masahiro
Published: March 2021

Additive-induced perpendicularly oriented 2D perovskite films prepared using the bar-coating method.
Construction and theoretical insights into the ESIPT fluorescent probe for imaging formaldehyde in vitro and in vivo
Authors: Bi Anyao , Liu Min , Huang Shuai , Zheng Fan , Ding Jipeng , Wu Junyong , Tang Gao , Zeng Wenbin
Published: March 2021

Schematic illustration of construction and theoretical insight studies with the ESIPT fluorescent probe for formaldehyde detection in cells and the AD brain model.
Reactivity of P4 butterfly complexes towards NHCs – generation of a metal-bridged P2 dumbbell complex
Authors: Reichl Stephan , Grünbauer Rebecca , Balázs Gábor , Scheer Manfred
Published: March 2021

P4 butterfly complexes can be relieved by nucleophiles like NHCs to give P1 and unprecedented allylic-P3 or P2-dumbbell complexes.
Screening of immunosuppressive cells from colorectal adenocarcinoma and identification of prognostic markers
Authors: Li Fazhan , Zhou Jun , Li Zedong , Zhang Leiyi
Published: March 2021

Background: Colorectal cancer (CRC) is the most common type of gastrointestinal malignant tumour. Colorectal adenocarcinoma (COAD) – the most common type of CRC – is particularly dangerous. The role of the immune system in the development of tumour-associated inflammation and cancer has received increasing attention recently.

Methods: In the present study, we compiled the expression profiles of 262 patients with complete follow-up data from The Cancer Genome Atlas (TCGA) database as an experimental group and selected 65 samples from the Gene Expression Omnibus (GEO) dataset (of which 46 samples were with M0) as a verification group. First, we screened the immune T helper 17 (Th17) cells related to the prognosis of COAD. Subsequently, we identified Th17 cells-related hub genes by utilising Weighted Gene Co-expression Network Analysis (WGCNA) and Least Absolute Shrinkage and Selector Operation (LASSO) regression analysis. Six genes associated with the prognosis in patients with COAD were identified, including: KRT23, ULBP2, ASRGL1, SERPINA1, SCIN, and SLC28A2. We constructed a clinical prediction model and analysed its predictive power.

Results: The identified hub genes are involved in developing many diseases and closely linked to digestive disorders. Our results suggested that the hub genes could influence the prognosis of COAD by regulating Th17 cells’ infiltration.

Conclusions: These newly discovered hub genes contribute to clarifying the mechanisms of COAD development and metastasis. Given that they promote COAD development, they may become new therapeutic targets and biomarkers of COAD.
Fallbericht: Best Supportive Care (BSC) in der Palliativmedizin – was bedeutet BSC eigentlich?
Authors: Kretschmer Eva-Maria , Krones Tanja , Blum David
Published: February 2021

Wir berichten über einen multimorbiden 56-jährigen Patienten, welcher mit unbehandelter Tumorerkrankung nach Multiorganversagen auf die Palliativstation verlegt wurde. Aufgrund einer Eisenmangelanämie wurde eine Magen-Darm-Diagnostik zum Ausschluss einer gastrointestinalen Blutung durchgeführt. Diese Untersuchung zeigte ein Adenokarzinom des proximalen Kolons. Im Rahmen der Narkoseeinleitung zur Resektion des Tumors aspirierte der Patient und entwickelte einen schweren septischen Schock mit Multiorganversagen.

Entsprechend der interdisziplinären Tumorboardempfehlung für Best Supportive Care (BSC) sowie dem vom Patienten gewünschten Abbruch der Therapie, erfolgte die Zuweisung auf die Palliativstation. Der voll urteilsfähige Patient hatte im Zuge der aus seiner Sicht dramatischen Ereignisse keine weiteren intensivmedizinischen Maßnahmen gewünscht.

Im weiteren Verlauf der insgesamt fünfwöchigen Behandlung auf der Palliativstation stabilisierte sich der Patient. Dank intensiver Gespräche mit unterschiedlichen Professionen der Palliativmedizin über Therapieziele und die eigenen Präferenzen beschäftigte sich der Patient mit dem Lebensende und bereitete sich auf den Tod vor. Es zeigte sich, dass die Ablehnung weiterer intensivmedizinischer Maßnahmen aus Patientensicht keinen generellen Verzicht auf die Behandlung der Tumorerkrankung beinhaltete.

Schließlich konnte bei vollständiger Rekonvaleszenz die geplante onkologische Therapie mit neoadjuvanter Chemotherapie und Tumorresektion erfolgreich durchgeführt werden.
Kolumne: Veränderungsprozess aufmerksam begleiten
Authors: Geiersberger Anna-Sophie
Published: March 2021

Die Pandemie hat unser aller Verständnis von Nachhaltigkeit verändert. Unternehmen müssen sich damit beschäftigen, wie sie mit möglichen Folgen der neuen Arbeitswirklichkeit umgehen, ohne traditionelle Nachhaltigkeitsziele aus den Augen zu verlieren.
Picosecond high-voltage pulse measurements
Authors: Ulmaskulov M. R. , Shunailov S. A. , Sharypov K. A. , Ulmaskulov E. M.
Published: March 2021

This paper presents capacitive sensors based on oxide dielectric substrates that provide a high attenuation factor of up to 30 · 103 with a transient time of ∼38 ps. The sensors made it possible to significantly reduce the number of attenuators and increase the bandwidth of the measuring path. The presented sensors have been used successfully for recording high voltage to MV pulses in the time range from a few nanoseconds to tens of picoseconds. The use of the sensors as the point receiving antennas for recording radio pulses in the GHz frequency range with high electric fields is also discussed, along with the trough directional coupler as a unit for additional attenuation of the voltage of the sensor response. The couplers have a high attenuation factor of 1–5 · 103 with a transient time of ∼38 ps. Using the couplers as attenuators for recording waveforms further improves the parameters (bandwidth, transient time) of the measuring circuit. A discussion of some features of the operational mode of this type of sensor and coupler with a focus on wave processes is also presented. This discussion can be used to analyze the general approaches to the improvement of the sensor and coupler as components of the measuring circuit. In this paper, the authors also propose methods for calibrating and calculating the attenuation factor of the sensors.
Measurement of L-shell emission from mid-Z targets under non-LTE conditions using Transmission Grating Spectrometer and DANTE power diagnostics
Authors: Fraenkel M. , Ehrlich Y. , Shpilman Z. , Henis Z. , Frank Y. , Marley E. V. , Pérez-Callejo G. , Emig J. , Heeter R. F. , Liedahl D. A. , Foord M. E. , Schneider M. B.
Published: March 2021

In this work, we present the measurement of L-band emission from buried Sc/V targets in experiments performed at the OMEGA laser facility. The goal of these experiments was to study non-local thermodynamic equilibrium plasmas and benchmark atomic physics codes. The L-band emission was measured simultaneously by the time resolved DANTE power diagnostic and the recently fielded time integrated Soreq-Transmission Grating Spectrometer (TGS) diagnostic. The TGS measurement was used to support the spectral reconstruction process needed for the unfolding of the DANTE data. The Soreq-TGS diagnostic allows for broadband spectral measurement in the 120 eV–2000 eV spectral band, covering L- and M-shell emission of mid- and high-Z elements, with spectral resolution λ/Δλ = 8–30 and accuracy better than 25%. The Soreq-TGS diagnostic is compatible with ten-inch-manipulator platforms and can be used for a wide variety of high energy density physics, laboratory astrophysics, and inertial confinement fusion experiments.
Local crystal symmetry and structure at CaTiO3 twin boundaries
Authors: Morikawa D. , Tsuda K.
Published: March 2021

The local crystal symmetry and crystal structure at CaTiO3 twin boundaries were examined using convergent-beam electron diffraction (CBED). CBED patterns obtained right at the twin boundaries exhibited one mirror symmetry not observed in the bulk form. Two types of crystal structures were identified at the boundaries on different boundary widths and symmetry breaking. Quantitative analysis using CBED patterns revealed atomic shifts of Ti and Ca. A distortion of oxygen octahedra was also produced, which was smaller than the corresponding distortion obtained in the bulk form. The refined crystal structure conforms to the polar structure expected only at CaTiO3 twin boundaries.
KUA–LAKO–MO‘O: a methodology for exploring Indigenous conceptualisations of nature and conservation in Hawai‘i
Authors: ‘Ohukani‘ōhi‘a Samuel M. , Winter Kāwika B. , Demotta Michael
Published: March 2021

Biocultural conservation is an approach to conservation that wields the relationships between a culture and the natural world to strengthen conservation efforts. Hawaiian biocultural frameworks are complex but can be initially explored by a methodological approach that we term KUA–LAKO–MO‘O, which links native species and ecosystems to (1) the pantheon of Oceanian deities, to which all elements of the environment are associated, (2) the rich biocultural applications (i.e. material culture) that emerged from centuries of life in the islands, and (3) the oral histories that weave knowledge of biodiversity and ecosystem function into everyday life, ethics, and sustainable existence. This methodology can be applied to primary kānaka ‘ōiwi (Native Hawaiian) sources held within the world’s largest printed archive of an oceanic Indigenous culture. The results of such an approach can reveal conceptualisations of, and relationships to, nature held within an Indigenous culture. The ongoing revitalisation of the intellectual, philosophical, ethical, and spiritual perspectives of kānaka ‘ōiwi in the course of the contemporary Hawaiian Renaissance can inform biocultural conservation efforts and transform conservation biology in Hawai‘i by embracing a biocultural approach and putting humanity and nature back on a path of coprosperity. This methodology could be applied anywhere people have forged deep, long-standing relationships with their environments for similar results.
Cell cycle–dependent active stress drives epithelia remodeling
Authors: Devany John , Sussman Daniel M. , Yamamoto Takaki , Manning M. Lisa , Gardel Margaret L.
Published: March 2021

Significance

The morphology of biological tissue is determined by the shape and density of constituent cells. Here, we measure the dynamics of cells in model epithelial tissues to study the evolution of their shape and density over time. Guided by a mathematical model, we find that cell shape is controlled by rigidity and active stresses within the tissue. We then show that cell cycle dynamics are the source of active stress that drives epithelial remodeling.
Three-step nucleation of metal–organic framework nanocrystals
Authors: Liu Xiangwen , Chee See Wee , Raj Sanoj , Sawczyk Michal , Král Petr , Mirsaidov Utkur
Published: March 2021

Significance

Nucleation is ubiquitous in many natural and industrial processes, yet our understanding of how a nucleus first emerges is limited. According to classical nucleation theory, a nucleus from which crystals grow forms in a single, spontaneous step. In this work, we combine ultralow-dose in situ liquid-phase and cryogenic transmission electron microscopy to show that metal–organic frameworks (MOFs) nucleate through a different, nonclassical pathway with three distinct steps. These steps are phase separation, condensation, and crystallization. Our observations of intermediate steps during the crystallization of MOFs provide important insight for controlling the nucleation and growth of both crystalline and amorphous materials.
TAp73 represses NF-κB–mediated recruitment of tumor-associated macrophages in breast cancer
Authors: Wolfsberger Johanna , Sakil Habib A. M. , Zhou Leilei , van Bree Niek , Baldisseri Elena , de Souza Ferreira Sabrina , Zubillaga Veronica , Stantic Marina , Fritz Nicolas , Hartman Johan , Rolny Charlotte , Wilhelm Margareta T.
Published: March 2021

Significance

Breast cancer is one of the most prevalent cancers worldwide. Understanding this complex disease is therefore of great importance. Here, we report that loss of TAp73, a known tumor suppressor and member of the p53 protein family, leads to increased activation of the NF-κB pathway, secretion of the chemokine CCL2, and an increase in protumoral macrophage infiltration in human breast cancer. Both high levels of CCL2 and high macrophage infiltration are known to correlate with poor prognosis in breast cancer patients. This study identifies TAp73 as a regulator of macrophage recruitment and highlights a role for TAp73 in immune cell regulation in cancer.
A metapopulation model of social group dynamics and disease applied to Yellowstone wolves
Authors: Brandell Ellen E. , Dobson Andrew P. , Hudson Peter J. , Cross Paul C. , Smith Douglas W.
Published: March 2021

Significance

How do social and infectious disease dynamics interact in group-living mammals? A significant cost to group living is increased transmission of pathogens. When a pathogen invades a group, members will be more vulnerable to mortality, Allee effects, and, ultimately, group extinction. The presence of a pathogen reduces the size of the population by reducing the number of social groups, allowing uninfected groups to grow larger from a reduction in intergroup aggression. Concomitantly, Allee effects are exacerbated in infected groups; this reduces the probability of pathogen persistence as infected groups die out more rapidly. Social structuring changes prevalence across scales and influences pathogen invasion and persistence. The models described here provide a framework for understanding the dynamics of these interactions.
Metabolic supervision by PPIP5K, an inositol pyrophosphate kinase/phosphatase, controls proliferation of the HCT116 tumor cell line
Authors: Gu Chunfang , Liu Juan , Liu Xiaojing , Zhang Haibo , Luo Ji , Wang Huanchen , Locasale Jason W. , Shears Stephen B.
Published: March 2021

Significance

Central carbon metabolism has the overlapping functions of converting substrate into biomass and the extraction and storage of chemical energy. These metabolic pathways are rewired by cancer cells to selectively support increased biomass demands. This reprogramming is a potential therapeutic target if a molecular-level understanding of the relevant control processes can be attained. Through genomic editing of an HCT116 colonic tumor cell line, we uncover metabolic supervision by a single pair of cell-signaling enzymes, the PPIP5Ks. Our global measurements of steady-state metabolite levels, plus isotope tracing analysis, show in detail how HCT116 cells recruit PPIP5Ks to select specific metabolic pathways to provide adequate precursor supply for biomass production. Crucially, in the absence of PPIP5K activity, HCT116 tumorigenesis is reduced.
RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion
Authors: Fic Weronika , Bastock Rebecca , Raimondi Francesco , Los Erinn , Inoue Yoshiko , Gallop Jennifer L. , Russell Robert B. , St Johnston Daniel
Published: March 2021

Cdc42-GTP is required for apical domain formation in epithelial cells, where it recruits and activates the Par-6–aPKC polarity complex, but how the activity of Cdc42 itself is restricted apically is unclear. We used sequence analysis and 3D structural modeling to determine which Drosophila GTPase-activating proteins (GAPs) are likely to interact with Cdc42 and identified RhoGAP19D as the only high-probability Cdc42GAP required for polarity in the follicular epithelium. RhoGAP19D is recruited by α-catenin to lateral E-cadherin adhesion complexes, resulting in exclusion of active Cdc42 from the lateral domain. rhogap19d mutants therefore lead to lateral Cdc42 activity, which expands the apical domain through increased Par-6/aPKC activity and stimulates lateral contractility through the myosin light chain kinase, Genghis khan (MRCK). This causes buckling of the epithelium and invasion into the adjacent tissue, a phenotype resembling that of precancerous breast lesions. Thus, RhoGAP19D couples lateral cadherin adhesion to the apical localization of active Cdc42, thereby suppressing epithelial invasion.
Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection
Authors: Le Bert Nina , Clapham Hannah E. , Tan Anthony T. , Chia Wan Ni , Tham Christine Y.L. , Lim Jane M. , Kunasegaran Kamini , Tan Linda Wei Lin , Dutertre Charles-Antoine , Shankar Nivedita , Lim Joey M.E. , Sun Louisa Jin , Zahari Marina , Tun Zaw Myo , Kumar Vishakha , Lim Beng Lee , Lim Siew Hoon , Chia Adeline , Tan Yee-Joo , Tambyah Paul Anantharajah , Kalimuddin Shirin , Lye David , Low Jenny G.H. , Wang Lin-Fa , Wan Wei Yee , Hsu Li Yang , Bertoletti Antonio , Tam Clarence C.
Published: March 2021

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.
Impact of Key Assumptions About the Population Biology of Soil-Transmitted Helminths on the Sustainable Control of Morbidity
Authors: Vegvari Carolin , Giardina Federica , Malizia Veronica , de Vlas Sake J , Coffeng Luc E , Anderson Roy M
Published: March 2021

The design and evaluation of control programs for soil-transmitted helminths (STHs) is based on surveillance data recording measurements of egg counts in the stool of infected individuals, which underpin estimates of the prevalence and average intensity of infection. There is considerable uncertainty around these measurements and their interpretation. The uncertainty is composed of several sources of measurement error and the limit of detection of fecal smear tests on the one hand, and key assumptions on STH biology on the other hand, including assumptions on the aggregation of worms within hosts and on the impact of density-dependent influences on worm reproduction. Using 2 independently developed models of STH transmission we show how different aspects of STH biology and human behavior impact on STH surveillance and control programs and how accounting for uncertainty can help to develop optimal and sustainable control strategies to meet the World Health Organization (WHO) morbidity target for STHs.
Profile of Chronic Comorbid Conditions and Obstetrical Complications Among Pregnant Women With Human Immunodeficiency Virus and Receiving Antiretroviral Therapy in the United States
Authors: Venkatesh Kartik K , Morrison Leavitt , Tuomala Ruth E , Stek Alice , Read Jennifer S , Shapiro David E , Livingston Elizabeth G
Published: March 2021

Background

To evaluate the frequency and associated characteristics of chronic comorbid conditions and obstetrical complications among pregnant women with human immunodeficiency virus (HIV) and receiving antiretroviral therapy (ART) in comparison to those without HIV.

Methods

We compared 2 independent concurrent US pregnancy cohorts: (1) with HIV (International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1025, 2002–2013) and (2) without HIV (Consortium for Safe Labor Study, 2002–2007). Outcomes were ≥2 chronic comorbid conditions and obstetrical complications. For women with HIV, we assessed whether late prenatal care (≥14 weeks), starting ART in an earlier era (2002–2008), and a detectable viral load at delivery (≥400 copies/mL) were associated with study outcomes.

Results

We assessed 2868 deliveries (n = 2574 women) with HIV and receiving ART and 211 910 deliveries (n = 193 170 women) without HIV. Women with HIV were more likely to have ≥2 chronic comorbid conditions versus those without HIV (10 vs 3%; adjusted OR [AOR]: 2.96; 95% CI: 2.58–3.41). Women with HIV were slightly less likely to have obstetrical complications versus those without HIV (both 17%; AOR: .84; 95% CI: .75–.94), but secondarily, higher odds of preterm birth <37 weeks. Late entry to prenatal care and starting ART in an earlier era were associated with a lower likelihood of ≥2 chronic comorbidities and obstetrical complications; detectable viral load at delivery was associated with a higher likelihood of obstetric complications.

Conclusions

Pregnant women with HIV receiving ART have more chronic comorbid conditions, but not necessarily obstetrical complications, than their peers without HIV.
Completion Rate and Safety of Programmatic Screening and Treatment for Latent Tuberculosis Infection in Elderly Patients With Poorly Controlled Diabetic Mellitus: A Prospective Multicenter Study
Authors: Huang Hung-Ling , Huang Wei-Chang , Lin Kun-Der , Liu Shin-Shin , Lee Meng-Rui , Cheng Meng-Hsuan , Chin Chun-Shih , Lu Po-Liang , Sheu Chau-Chyun , Wang Jann-Yuan , Lee I-Te , Chong Inn-Wen
Published: March 2021

Background

Poor control of diabetes mellitus (DM) increases active tuberculosis (TB) risk. Understanding risk factors for latent TB infection (LTBI) in this population and intervention completion rates is crucial for policy making.

Methods

Under a collaborative multidisciplinary team consisting of public health professionals, endocrinologists, and pulmonologists, patients aged >45 years with poorly controlled DM (pDM), defined as having a glycated hemoglobin level of ≥9% within the preceding year, were enrolled by endocrinologists from 2 hospitals; these patients underwent LTBI screening by using QuantiFERON (QFT). Once-weekly isoniazid and rifapentine for 12 weeks (3HP) or daily isoniazid for 9 months (9H) was administered by pulmonologists. QFT-positivity predictors were evaluated using logistic regression. Completion rates and safety were also investigated.

Results

Among 980 patients with pDM (age: 64.2 ± 9.7 years), 261 (26.6%) were QFT-positive. Age, DM duration, chronic kidney disease stage ≥3, and dipeptidyl peptidase-4 inhibitor use, not using metformin, were associated with QFT-positivity. Preventive therapy (3HP: 138; 9H: 62) was administered in 200 (76.6%) QFT-positive patients. The completion rates of 3HP and 9H were 84.1% and 79.0%, respectively (P = .494). Nine (6.5%) and zero patients in the 3HP and 9H groups, respectively, developed systemic drug reactions (P = .059); 78.3% and 45.2% had ≥1 adverse drug reactions (P < .001); and post-treatment QFT conversion rates were 32% and 20%, respectively (P = .228).

Conclusions

LTBI prevalence exceeds 25% in elderly patients with pDM. Under care from a collaborative multidisciplinary team, the completion rate of preventive therapy, regardless of regimen could approach, or even exceed 80% in this population.
Outcomes of single ventricle palliation in infants with heterotaxy syndrome
Authors: Vodiskar Janez , Kido Takashi , Strbad Martina , Cleuziou Julie , Hager Alfred , Ewert Peter , Hörer Jürgen , Ono Masamichi
Published: March 2021

OBJECTIVES

Heterotaxy is a known risk factor for morbidity and mortality in single ventricle palliation. In this study, we examined our experience with this challenging group of patients.

METHODS

Records of patients born between 2001 and 2019 with heterotaxy, who needed staged single ventricle palliation were retrospectively analysed.

RESULTS

A total of 53 patients were included in this study. Thirty-five (66%) patients had a right ventricular dominance, common atrioventricular septal defect was present in 37 (70%) patients. Anomalous pulmonary venous drainage was present in 29 (55%) patients. Forty-six (86%) patients underwent first-stage palliation. Forty-one (77.3%) patients received a bidirectional cavopulmonary connection. Thirty-one (58%) patients received total cavopulmonary connection (TCPC). Overall survival rate was 92% at 1 month, 74% at 1 year and 68% at 10 years. Twelve (22.6%) patients died before second palliation stage. Four (10%) patients died before TCPC. No patient died after TCPC. Independent risk factors for mortality in the multivariate COX regression were a presence of restrictive pulmonary blood flow (HR 3.23; 95% CI 1.02–10.2; P = 0.05) and greater than mild atrioventricular valve regurgitation (HR 3.57; 95% CI 1.27–10.0; P = 0.02).

CONCLUSIONS

Mortality and morbidity in patients with single ventricle and heterotaxy are high. Restrictive pulmonary blood flow needing early modulation and greater than mild atrioventricular valve regurgitation at presentation are independent risk factors for mortality. Total anomalous pulmonary venous connection was not identified as a risk factor in the current era.
Coprime Ehrhart Theory and Counting Free Segments
Authors: Manecke Sebastian , Sanyal Raman
Published: February 2021

A lattice polytope is free (or empty) if its vertices are the only lattice points it contains. In the context of valuation theory, Klain [16] proposed to study the functions $\alpha _i(P;n)$ that count the number of free polytopes in $nP$ with $i$ vertices. For $i=1$, this is the famous Ehrhart polynomial; for $i> 3$, the computation is likely impossible; and for $i=2,3$ it is computationally challenging.

In this paper, we develop a theory of coprime Ehrhart functions that count lattice points with relatively prime coordinates and use it to compute $\alpha _2(P;n)$ for unimodular simplices. We show that the coprime Ehrhart function can be explicitly determined from the Ehrhart polynomial and we give some applications to combinatorial counting.
AGN and star formation across cosmic time
Authors: Symeonidis M , Page M J
Published: March 2021

We investigate the balance of power between stars and AGN across cosmic history, based on the comparison between the infrared (IR) galaxy luminosity function (LF) and the IR AGN LF. The former corresponds to emission from dust heated by stars and AGN, whereas the latter includes emission from AGN-heated dust only. We find that at all redshifts (at least up to z ∼ 2.5), the high-luminosity tails of the two LFs converge, indicating that the most IR-luminous galaxies are AGN-powered. Our results shed light to the decades-old conundrum regarding the flatter high-luminosity slope seen in the IR galaxy LF compared to that in the UV and optical. We attribute this difference to the increasing fraction of AGN-dominated galaxies with increasing total IR luminosity (LIR). We partition the LIR−z parameter space into a star formation-dominated and an AGN-dominated region, finding that the most luminous galaxies at all epochs lie in the AGN-dominated region. This sets a potential ‘limit’ to attainable star formation rates, casting doubt on the abundance of ‘extreme starbursts’: if AGN did not exist, LIR > 1013 L⊙ galaxies would be significantly rarer than they currently are in our observable Universe. We also find that AGN affect the average dust temperatures (Tdust) of galaxies and hence the shape of the well-known LIR−Tdust relation. We propose that the reason why local ULIRGs are hotter than their high-redshift counterparts is because of a higher fraction of AGN-dominated galaxies amongst the former group.
Systematicin vitrospecificity profiling reveals nicking defects in natural and engineered CRISPR–Cas9 variants
Authors: Murugan Karthik , Suresh Shravanti K , Seetharam Arun S , Severin Andrew J , Sashital Dipali G
Published: March 2021

Cas9 is an RNA-guided endonuclease in the bacterial CRISPR–Cas immune system and a popular tool for genome editing. The commonly used Streptococcus pyogenes Cas9 (SpCas9) is relatively non-specific and prone to off-target genome editing. Other Cas9 orthologs and engineered variants of SpCas9 have been reported to be more specific. However, previous studies have focused on specificity of double-strand break (DSB) or indel formation, potentially overlooking alternative cleavage activities of these Cas9 variants. In this study, we employed in vitro cleavage assays of target libraries coupled with high-throughput sequencing to systematically compare cleavage activities and specificities of two natural Cas9 variants (SpCas9 and Staphylococcus aureus Cas9) and three engineered SpCas9 variants (SpCas9 HF1, HypaCas9 and HiFi Cas9). We observed that all Cas9s tested could cleave target sequences with up to five mismatches. However, the rate of cleavage of both on-target and off-target sequences varied based on target sequence and Cas9 variant. In addition, SaCas9 and engineered SpCas9 variants nick targets with multiple mismatches but have a defect in generating a DSB, while SpCas9 creates DSBs at these targets. Overall, these differences in cleavage rates and DSB formation may contribute to varied specificities observed in genome editing studies.