bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Evaluation of a Novel TALEN Targeting CCR5 Confirms Efficacy and Safety in Conferring Resistance to HIV‐1 Infection
Authors: Romito Marianna , Juillerat Alexandre , Kok Yik Lim , Hildenbeutel Markus , Rhiel Manuel , Andrieux Geoffroy , Geiger Johannes , Rudolph Carsten , Mussolino Claudio , Duclert Aymeric , Metzner Karin J. , Duchateau Philippe , Cathomen Toni , Cornu Tatjana I.
Published: October 2020

Therapies to treat patients infected with human immunodeficiency virus (HIV) aim at preventing viral replication but fail to eliminate the virus. Although transplantation of allogeneic CCR5Δ32 homozygous stem cell grafts provided a cure for a few patients, this approach is not considered a general therapeutic strategy because of potential side effects. Conversely, gene editing to disrupt the C‐C chemokine receptor type 5 (CCR5) locus, which encodes the major HIV coreceptor, has shown to confer resistance to CCR5‐tropic HIV strains. Here, an engineered transcription activator‐like effector nuclease (TALEN) that enables efficient CCR5 editing in hematopoietic cells is presented. After transferring TALEN‐encoding mRNA into primary CD4+ T cells, up to 89% of CCR5 alleles are disrupted. Genotyping confirms the genetic stability of the CCR5‐edited cells, and genome‐wide off‐target analyses established the absence of relevant mutagenic events. When challenging the edited T cells with CCR5‐tropic HIV, protection in a dose‐dependent manner is observed. Functional assessments reveal no significant differences between edited and control cells in terms of proliferation and their ability to secrete cytokines upon exogenous stimuli. In conclusion, a highly active and specific TALEN to disrupt CCR5 is successfully engineered, paving the way for its clinical application in hematopoietic stem cell grafts.
Low serum 25‐hydroxyvitamin D3 levels and late delayed radiation‐induced brain injury in patients with nasopharyngeal carcinoma: A case–control study
Authors: Deng Zhezhi , Li Minping , Guo Junjie , Zhou Dongxiao , Huang Xurui , Huang Yongxin , Huang Haiwei
Published: October 2020

Background and Purpose

Inflammatory reaction plays a critical role in the pathogenesis of late delayed radiation‐induced brain injury (RBI). Low vitamin D levels are closely associated with various immuno‐inflammatory diseases, but the relationship with late delayed RBI remains unknown. Here, we aimed to determine the association of serum vitamin D levels with clinical parameters in late delayed RBI patients with nasopharyngeal carcinoma.

Methods

25‐Hydroxyvitamin D3 levels and clinical and cerebrospinal fluid parameters were evaluated in 21 patients with RBI and compared with 90 age‐, sex‐, and season‐matched healthy controls.

Results

25‐(OH)D3 levels were lower in patients with RBI compared to controls (40.39 ± 22.11 vs. 64.54 ± 19.89 nmol/L, p < .001), especially for aged ≥60 years (vs. <60 years, p = .038), females (vs. males, p = .012), short latency (<5 years) (vs. ≥5 years, p = .015), and severe impairment (LENT/SOMA score ≥3) (vs. LENT/SOMA score <3, p = .010). Serum 25‐(OH)D3 levels were associated with age (r = −.464, p = .015), Latency of RBI (r = .416, p = .031) and LENT/SOMA Scale (r = −.488, p = .010).

Conclusions

Our data showed that serum 25‐(OH)D3 levels were reduced in late delayed RBI patients with nasopharyngeal carcinoma.
Charting a New Path Towards Degrading Every Protein
Authors: Nabet Behnam
Published: October 2020

Strategies to directly alter protein abundance such as small‐molecule‐induced targeted protein degradation (TPD) are innovative pharmacological modalities with promising clinical potential. Herein, I describe my experience with the development of the degradation tag (dTAG) system, which is a chemical biology strategy to induce rapid and precise degradation of any target protein. Open‐source collaborative discovery has been critical for advancing the versatility and accessibility of the dTAG system and will be necessary to understand the benefits and limits of TPD‐based strategies in the clinic.
A FRET‐Based Fluorescent Probe to Screen Anticancer Drugs, Inhibiting p73 Binding to MDM2
Authors: Han A. Ro , Durgannavar Trishaladevi , Ahn Dohee , Chung Sang J.
Published: October 2020

The protein p73 acts as a transcription factor, resulting in tumour suppression. MDM2, an oncogenic protein, can negatively influence p73‐mediated apoptosis by binding to p73 transactivation domains (TAD). Inhibition of the protein‐protein interaction between p73 and oncogenic proteins is an attractive strategy for promoting p73‐mediated apoptosis. Herein, we describe the use of a modified p73‐TAD peptide for the FRET‐based assay of the binding of p73‐TAD to MDM2. The FRET probe, equipped with 1‐naphthylamine (λex=330 nm, λem=445 nm), serves as a FRET acceptor, and the tryptophan of the protein acts as FRET donor (λex=280 nm, λem=340 nm). Sensitized emission from the FRET probe was observed upon excitation of the protein‐FRET‐probe complex at the excitation wavelength of Trp. Furthermore, addition of the MDM2 inhibitor Nutiln‐3 drastically reduced the FRET signal, thus indicating that the FRET probe competes with Nutiln‐3 for MDM2 binding. The developed FRET binding assay might be applicable in high‐throughput screening of novel drugs that inhibit interactions between p73 and MDM2.
A case of laparoscopic resection of leiomyosarcoma arising in the mesentery of descending colon: a case report and review of the literature
Authors: Koyama Ryota , Maeda Yoshiaki , Minagawa Nozomi , Shinohara Toshiki
Published: October 2020

Leiomyosarcoma of mesenteric origin is rare and may be managed by laparoscopic surgery as a less invasive procedure, on the condition that the tumor can be resected with a safe margin.
Spontaneous disruption of the dividing membrane in monochorionic diamniotic twin pregnancy
Authors: Yokoyama Nobuko , Sagawa Kei , Miyazaki Miwa , Suzuki Shunji
Published: October 2020

Spontaneous disruption of the dividing membrane in MD twins is rare and be associated with a higher incidence of prematurity and neonatal morbidity. In the present case, a spontaneous disrupted dividing membrane could be noted by ultrasonography.
Cocaine‐related vasculitis
Authors: Liaqat Hassan , Shirvanian Narine , Ammad Ud Din Mohammad , Amin Ali
Published: October 2020

Patients presenting with pancytopenia and a painful purpuric rash should be evaluated for levamisole‐induced vasculitis and counseled about cocaine cessation as continued exposure can lead to permanent deformity of the involved areas.
Photoswitchable Catalysis Mediated by Nanoparticles
Authors: Sobczak Grzegorz , Sashuk Volodymyr
Published: October 2020

Photoswitchable catalysis utilizes spatiotemporal light delivery to provide control over reaction rate and selectivity. The inception and further development of this field was related to bulk solutions. This minireview describes the recent evolution of nanoparticle‐based colloidal systems and explains the principles ruling therein. Subsequently, examples of such systems are reported with thorough analysis and comparison. Finally, we provide an outlook on possible new directions in this field.
Cellulose‐Based Reduced Nanographene Oxide on Gold Nanoparticle Supports for CO2 Electrocatalysis
Authors: Koyejo Adefunke O. , Kesavan Lokesh , Damlin Pia , Salomäki Mikko , Yao Jenevieve G. , Hakkarainen Minna , Kvarnström Carita
Published: October 2020

Cellulose‐based reduced graphene oxide materials (r‐nGO) were fabricated and anchored onto polyvinyl alcohol stabilized gold nanoparticles. Their potential in applications in the electrocatalytic reduction of CO2 (ER‐CO2) is demonstrated. The nGO was synthesized by microwave‐assisted cellulose carbonization followed by two different reduction methods, that is, with super‐heated water (i) or caffeic acid (ii). These materials, denoted as r‐nGO (i) r‐nGO‐CA (ii), were utilized to immobilize colloidal gold nanoparticles (Au NPs) in an aqueous environment. The two r‐nGO‐supported Au NP materials were deposited on glassy carbon electrode surfaces and studied as catalysts for ER‐CO2. ER‐CO2 was investigated at room temperature and pressure (RTP) using ionic liquids (RTILs) or an aprotic solvent acetonitrile (ACN). Tetrabutylammonium hexafluoroborate (TBAPF6) was used as an electrolyte salt in the case of ACN. The current response resulting from ER‐CO2 was measured under cyclic voltammetric conditions using a one‐compartment three‐electrode cell. Results showed that, r‐nGO‐supported gold nanoparticles catalyze ER‐CO2 and they significantly reduce the overpotential of CO2 reduction from −1.9 V to −1.6 V vs. Ag/AgCl. Moreover, of all the materials studied, Au/r‐nGO was superior in reducing CO2 in both RTILs and TBAPF6/ACN. These outcomes serve as grounds for the further development of electrocatalysts from bio‐based reduced graphene oxides.
7‐Hydroxycoumarin as a Novel Film‐Forming Additive for LiNi0.5Mn1.5O4 Cathode at Elevated Temperature
Authors: Shang Huimin , Jiang Jinjin , Zhang Huan , Niu Wenchao , Qiao Yingjun , Zhou Hanxiao , Li Tianhui , Qu Meizhen , Peng Gongchang , Xie Zhengwei
Published: October 2020

A novel additive, 7‐hydroxycoumarin (7‐HC), is employed to construct a stable interface film on the LiNi0.5Mn1.5O4 cathode to improve the cyclic stability of Li/LiNi0.5Mn1.5O4 cells at elevated temperature (ca. 55 °C). In the 0.01 wt% 7‐hydroxycoumarin‐containing electrolyte, the capacity retention of Li/LiNi0.5Mn1.5O4 cell increases from 78.15 % to 95.64 % at elevated temperature after 100 cycles at 1 C rate. Through theoretical calculations and ex‐situ analysis, it suggests that 7‐HC is susceptible to oxidation than other components of the electrolyte to form a thin and stable film on the surface of LiNi0.5Mn1.5O4 cathode. The thin and stable film can effectively reduce the interface oxidation reaction and the “cross‐talk” between the positive electrode and negative electrode and effectively inhibit the structural changes of LiNi0.5Mn1.5O4 caused by dissolved transition metals in subsequent cycles, thereby improving the cyclic stability of the cell at elevated temperature.
Sodium Cyclopentadienide as a New Type of Electrolyte for Sodium Batteries
Authors: Binder Markus , Mandl Magdalena , Zaubitzer Steve , Wohlfahrt‐Mehrens Margret , Passerini Stefano , Böse Olaf , Danzer Michael A. , Marinaro Mario
Published: October 2020

Owing to the low cost and high abundance of sodium, sodium‐based batteries, especially those employing metallic sodium anodes, are considered for post‐lithium energy storage. In order to develop high‐performance and long‐lasting sodium‐metal batteries, however, the reversible Na‐metal stripping and plating challenge must be addressed. Most organic electrolytes suffer from non‐uniform and continuous formation of the solid electrolyte interphase as well as unfavorable dendritic growth. The use of sodium cyclopentadienide dissolved in tetrahydrofuran as the electrolyte reveals an improved reversibility of sodium dissolution and electrodeposition combined with an electrochemical stability window of around 2.2 V vs. Na/Na+ and an ionic conductivity of 1.36 mS cm−1 at 25 °C. Furthermore, the plated electrodes showed a remarkable morphology of the Na deposits, that is, no dendrite formation, whereby the above‐mentioned electrolyte could overcome the aforementioned cycling issues, thus suggesting suitability for further studies.
Assessing The Key Photophysical Properties of Triangulenium Dyes for DNA Binding by Alteration of the Fluorescent Core
Authors: Lewis Benjamin W. , Bisballe Niels , Santella Marco , Summers Peter A. , Vannier Jean‐Baptiste , Kuimova Marina K. , Laursen Bo W. , Vilar Ramon
Published: October 2020

Four‐stranded G‐quadruplex (G4) DNA is a non‐canonical DNA topology that has been proposed to form in cells and play key roles in how the genome is read and used by the cellular machinery. Previously, a fluorescent triangulenium probe (DAOTA‐M2) was used to visualise G4s in cellulo, thanks to its distinct fluorescence lifetimes when bound to different DNA topologies. Herein, the library of available triangulenium probes is expanded to explore how modifications to the fluorescent core of the molecule affect its photophysical characteristics, interaction with DNA and cellular localisation. The benzo‐bridged and isopropyl‐bridged diazatriangulenium dyes, BDATA‐M2 and CDATA‐M2 respectively, featuring ethyl‐morpholino substituents, were synthesised and characterised. The interactions of these molecules with different DNA topologies were studied to determine their binding affinity, fluorescence enhancement and fluorescence lifetime response. Finally, the cellular uptake and localisation of these optical probes were investigated. Whilst structural modifications to the triangulenium core only slightly alter the binding affinity to DNA, BDATA‐M2 and CDATA‐M2 cannot distinguish between DNA topologies through their fluorescence lifetime. It is argued theoretically and experimentally that this is due to reduced effectiveness of photoinduced electron transfer (PET) quenching. This work presents valuable new evidence into the critical role of PET quenching when using the fluorescence lifetime of triangulenium dyes to discriminate G4 DNA from duplex DNA, highlighting the importance of fine tuning redox and spectral properties when developing new triangulenium‐based G4 probes.
Generation and Identification of the Linear OCBNO and OBNCO Molecules with 24 Valence Electrons
Authors: Deng Guohai , Pan Sudip , Jin Jiaye , Wang Guanjun , Zhao Lili , Zhou Mingfei , Frenking Gernot
Published: October 2020

Two structural isomers containing five second‐row element atoms with 24 valence electrons were generated and identified by matrix‐isolation IR spectroscopy and quantum chemical calculations. The OCBNO complex, which is produced by the reaction of boron atoms with mixtures of carbon monoxide and nitric oxide in solid neon, rearranges to the more stable OBNCO isomer on UV excitation. Bonding analysis indicates that the OCBNO complex is best described by the bonding interactions between a triplet‐state boron cation with an electron configuration of (2s)0(2pσ)0(2pπ)2 and the CO/NO− ligands in the triplet state forming two degenerate electron‐sharing π bonds and two ligand‐to‐boron dative σ bonds.
Planar Tetracoordinate Silicon in Organic Molecules As Carbenoid‐Type Amphoteric Centers: A Computational Study
Authors: Zhang Yuwei , Zhang Caiyun , Mo Yirong , Cao Zexing
Published: October 2020

Designing and synthesizing a stable compound with a planar tetracoordinate silicon (ptSi) center is a challenging goal for chemists. Here, a series of potential aromatic ptSi compounds composed of four conjugated rings shared by a centrally embedded Si atom are theoretically designed and computationally verified. Both Born–Oppenheimer molecular dynamics (BOMD) simulations and potential energy surface scannings verify the high stability and likely existence of these compounds, particularly Si‐16‐5555 (SiN4C8H8) with 16 π electrons, under standard ambient temperature and pressure. Notably, the Hückel aromaticity rule, which works well for single rings, is inconsistent with the high stability of Si‐16‐5555 where the 16 p electrons are spread over four five‐membered rings fused together. Bonding analyses show that the strong electron donation from the peripheral 12‐membered conjugated ring with 16 π electrons to the vacant central atomic orbital Si 3pz leads to the stabilization for both the ptSi coordination and planar aromaticity. The partial occupation of Si 3pz results in the peculiar carbenoid‐type behaviors for the amphoteric center. By modulating the electron density on the ring with substituent groups, we can regulate the nucleophilic and electrophilic properties of the central Si.
Synthesis and Coordination Ability of a Donor‐Stabilised Bis‐Phosphinidene
Authors: Hadlington Terrance J. , Kostenko Arseni , Driess Matthias
Published: October 2020

Chelating phosphines have long been a mainstay as efficient directing ligands in transition‐metal catalysis. Low‐valent derivatives, namely chelating phosphinidenes, are to date unknown, and could lead to chelating complexes containing more than one metal centre due to the intrisic capacity of phosphinidenes to bind two metal fragments at one P‐centre. Here we describe the synthesis of the first such chelating bis‐phosphinidene ligand, XantP2 (2), generated by the reduction of a diphosphino xanthene derivative, Xant(PH2)2 (1) with iPrNHC (iPrNHC=[:C{N(iPr)C(H)}2]). Initial studies have shown that this novel chelating ligand can act as a bidentate ligand towards element dihalides (i.e. FeCl2, ZnI2, GeCl2, SnBr2), forming cationic complexes with the tetryl elements. In contrast, XantP2 demonstrates an ability to bind multiple metal centres in the reaction with CuCl, leading to a cationic Cu3P3 ring complex, with Cu centres bridged by phosphinidene arms. Density Functional Theory calculations show that 2 indeed holds 4 lone pairs of electrons, shedding further light on the coordination capacity for this novel ligand class through observation of directionality and hybridisation of these electron pairs.
Ion Exchange Membrane “ABC” – A Key Material for Upgrading Process Industries
Authors: Wang Yaoming , Yang Zhengjin , Wu Liang , Ge Liang , Xu Tongwen
Published: October 2020

Ion exchange membrane plays a crucial role in transforming and upgrading traditional chemical manufacturing procedures and boosting a multitude of new applications. Due to the strict regulations on wastewater discharge and increasing demands of renewable energy, anion exchange membrane (“A” membrane), bipolar membrane (“B” membrane) and cation exchange membrane (“C” membrane) have become a key material for upgrading various process industries. Herein, we summarized several novel synthetic routes for “ABC” membranes fabrication from the viewpoints of designing novel membrane synthetic routes, regulating the ionic transport channels, imparting dynamic transfer regions, introducing intrinsic micro‐porosity into the membrane and among others. The account includes a brief introduction to membrane structure designs and fabrications, emerging and industrial applications, and perspectives on ion exchange membranes.

Who is the most influenced person in your academic career?

My supervisor academician Binglin He.

How do you get into the field of ion exchange membrane?

I got in contact with ion exchange membranes during my postdoc research in Nankai University under the guidance of Prof. Binglin He. My supervisor is known as “father of China's ion exchange resin”. But in the synthesis of ion exchange resin, the resin pellets larger than 6 mm or smaller than 4 mm cannot be used and are directly discarded. Therefore, Prof. He asked me to explore how to convert them into membrane shape so as to reuse the wasted resin. Since then I entered the field of ion exchange membrane.

In your opinion, what is the most promising ion exchange membrane in the next couple years?

Alkaline stable anion‐exchange membranes that can be used for hydrogen production from electrolytic water splitting, fuel cells, and electrochemical ammonia synthesis, etc.

Besides the fundamental research, why do you spend a lot time and

energy to industrialize the ion exchange membrane?

Ion exchange membrane is relatively a narrow product in the field of separation membrane materials. Nowadays, there are tremendous demands of these kind of membranes due to the stricter regulations on wastewater disposal. However, the development of ion exchange membranes in China lags far behind that in other developed countries. As a scientist in this filed, I believe that I have the responsibility to promote the development and advancement of our domestic ion exchange membrane. For this reason, four licensed patents of us have been transferred for industrialization and more than 400000 m2 of membranes were used per year in various industries.

What is the greatest honor for your academic achievement?

My students are my greatest honor. I am proud of more and more students being graduated from my lab, who have played/will play important roles in making our country stronger.

What's your hobbies?

Walking, playing basketball and cards.
Cilium axoneme internalization and degradation in chytrid fungi
Authors: Venard Claire M , Vasudevan Krishna Kumar , Stearns Tim
Published: October 2020

Loss of the cilium is important for cell cycle progression and certain developmental transitions. Chytrid fungi are a group of basal fungi that have retained centrioles and cilia, and they can disassemble their cilia via axoneme internalization as part of the transition from free‐swimming spores to sessile sporangia. While this type of cilium disassembly has been observed in many single‐celled eukaryotes, it has not been well characterized because it is not observed in common model organisms. To better characterize cilium disassembly via axoneme internalization, we focused on chytrids Rhizoclosmatium globosum and Spizellomyces punctatus to represent two lineages of chytrids with different motility characteristics. Our results show that each chytrid species can reel in its axoneme into the cell body along its cortex on the order of minutes, while S. punctatus has additional faster ciliary compartment loss and lash‐around mechanisms. S. punctatus retraction can also occur away from the cell cortex and is partially actin dependent. Post‐internalization, the tubulin of the axoneme is degraded in both chytrids over the course of about 2 hr. Axoneme disassembly and axonemal tubulin degradation are both partially proteasome dependent. Overall, chytrid cilium disassembly is a fast process that separates axoneme internalization and degradation.
Camellia Pollen‐Derived Carbon with Controllable N Content for High‐Performance Supercapacitors by Ammonium Chloride Activation and Dual N‐Doping
Authors: Cao Lihua , Li Huiling , Xu Zhaoxiu , Gao Ruirui , Wang Suqing , Zhang Guoying , Jiang Shaohua , Xu Wenhui , Hou Haoqing
Published: October 2020

Biomass‐derived carbon materials are an amazing electrode material for supercapacitor, owing to their abundant, porous structure and composition. Herein, a controllable N content carbon material with hierarchical porous structure was fabricated via an integrated carbonization, activation and nitrogen‐doping process. N‐rich camellia pollen is used as carbon precursor, while NH4Cl is employed as both activation agent and dopant. The optimal N‐doped carbon with higher N content (3.82 at%), suitable pore size distribution and larger specific surface area (810 m2 g−1), provides abundant ion transport channels and exposes more accessible active sites. Thus, a high specific capacitance of 280 F g−1 (1 A g−1) in 6 M KOH (three‐electrode system) can be obtained with making full use of N−HPC‐1. Moreover, the assembled symmetrical supercapacitor delivers high energy densities both in 6 M KOH (13.3 Wh kg−1) and 1 M Na2SO4 (20 Wh kg−1) that can be used for LED lighting. More than that, it is also demonstrates excellent cycle stability in 6 M KOH (85.4% after 20000 cycles at 20 A g−1). In view of the above‐mentioned merits, this N‐doped hierarchical porous carbon is anticipated to be a promising material for application in supercapacitors and other fields.
Use tools, have fun to successfully manage remote employees
Authors: Pavlik Amelia
Published: October 2020

Thanks to COVID‐19, in a matter of days, admissions and enrollment management office teams around the country were forced to adopt remote work arrangements that had often never been tried before.
Pandemic opportunities lead to largest, most diverse enrollment yet
Authors: Sutton Halley
Published: October 2020

When COVID‐19 hit the nation and courses were forced into online learning, the J. Mack Robinson College of Business at Georgia State University had a secret weapon to offer students. “Sometimes it's better to be lucky than it is to be smart,” Richard D. Phillips, Ph.D., Dean of the J. Mack Robinson College of Business, said. Months before the COVID‐19 pandemic, GSU had started work on a new classroom facility located in downtown Atlanta, which included a suite of high‐end digitally enabled classrooms with high‐end simulcast capabilities to stream lectures. “The goal 18 months ago was just to make it easy for students at their desk at five o'clock to decide where and how they want to participate that day,” Phillips said.
Spatial Distribution and Location of Natural Organic Matter on Sediment Particles by Scanning Electron Microscopic Analysis and the Development of a New Persistent Organic Pollutant–Sediment Kinetic Desorption Model
Authors: Clay Marra M. , Morgan Jack A. , Dunnivant Frank M.
Published: October 2020

Natural organic matter (NOM) has long been shown to be the dominant factor in determining equilibrium and kinetic processes during sorption and desorption phenomena in sediment and soil experiments. Although several models have been suggested for predicting these processes, few offer mechanistic interpretations because the spatial location of organic matter on sediment particles is unknown. This investigation manually examined sediment particles from multiple locations, containing varying concentrations of NOM, using scanning electron microscopy with energy dispersive X-ray spectroscopy to determine the types of particles present by categorizing them as individual particles, aggregates, and “other” (detritus, algae, etc.). These types of particles were subsequently analyzed for their elemental composition, specifically the spatial location of carbon. By creating a carbon map of each particle, this investigation has determined that organic matter tends to occur in 2 forms: large aggregates or dispersed across individual sediment particles. These findings were then used to propose a more mechanistically sound mathematical model for pollutant desorption phenomena, assigning the traditional labile kinetic release component to the dispersed NOM spread randomly across sediment particles and the nonlabile kinetic release component to diffusion from densely packed NOM aggregates. Environ Toxicol Chem 2021;40:323–332. © 2020 SETAC
Reconstructing prehistoric demography: What role for extant hunter‐gatherers?
Authors: Page Abigail E. , French Jennifer C.
Published: October 2020

Demography is central to biological, behavioral, and cultural evolution. Knowledge of the demography of prehistoric populations of both Homo sapiens and earlier members of the genus Homo is, therefore, key to the study of human evolution. Unfortunately, demographic processes (fertility, mortality, migration) leave little mark on the archeological and paleoanthropological records. One common solution to this issue is the application of demographic data from extant hunter‐gatherers to prehistory. With the aim of strengthening this line of enquiry, here we outline some pitfalls and their interpretative implications. In doing so, we provide recommendations about the application of hunter‐gatherer data to the study of demographic trends throughout human evolution. We use published demographic data from extant hunter‐gatherers to show that it is the diversity seen among extant hunter‐gatherers—both intra‐ and inter‐population variability—that is most relevant and useful for understanding past hunter‐gatherer demography.
Aflatoxin exposure among lactating women in southern Ethiopia
Authors: Boshe Bergene , Gebremedhin Samson , Alemayehu Fikadu , Eshete Mesfin , Taye Mestawet , Stoecker Barbara J.
Published: October 2020

In Ethiopia and many other low‐income countries, little is known about the exposure of lactating women to aflatoxin, which is a major health concern to the mother and her nursing infant. We determined the aflatoxin B1 contamination of family foods (AFB1) and urinary aflatoxin M1 (AFM1) of lactating women in Sidama, southern Ethiopia, and compared the levels across agroecological settings (lowland, midland, highland) and two seasons. We conducted two surveys (n = 360) that represented the dry and wet seasons of the locality. AFM1 and AFB1 were determined using enzyme‐linked immunosorbent assay (ELISA). Statistical analysis was made using Mann–Whitney U test and Kruskal–Wallis test. The median (interquartile range) AFB1 was 0.94 (0.63–1.58) ppb. AFB1 was detected in 95.6% of the food samples, and 13.6% exceeded the 2.0 ppb threshold. We observed an increasing trend for aflatoxin exposure from highland to lowland (p < .001), but there was no difference between seasons (p = .743). The median (interquartile range) urinary AFM1 was 214 (undetectable to 2,582) ppt, and AFM1 was detectable in 53.3% of the samples. Urinary AFM1 showed significant difference among agroecological zones (p < .001) but not between seasons (p = .275). A significant but weak correlation was observed between AFB1 and urinary AFM1 (rs = 0.177, p = .001). We concluded that lactating women in Sidama, especially those in the lowland area, have unsafe exposure to aflatoxin.
Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model
Authors: Steinbach Robert , Gaur Nayana , Roediger Annekathrin , Mayer Thomas E. , Witte Otto W. , Prell Tino , Grosskreutz Julian
Published: October 2020

Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract‐based‐spatial‐statistics of fractional anisotropy (FA), mean‐ (MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model‐derived parameters. Case–control comparisons revealed widespread ALS‐related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel‐wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS.
Reply to the Letter to the Editor regarding “Early oral hydration protects against pharyngocutaneous fistula after total laryngectomy or total pharyngolaryngectomy”
Authors: Le Flem Matthieu , Santini Laure , Boulze Carole , Alshukry Abdallah , Giovanni Antoine , Dessi Patrick , Fakhry Nicolas
Published: October 2020

see page 716–717.
Real‐world, population‐based cohort study of toxicity and resource utilization of second‐line ipilimumab for metastatic melanoma in Ontario, Canada
Authors: Dai Wei Fang , Beca Jaclyn , Croxford Ruth , Isaranuwatchai Wanrudee , Menjak Ines B. , Petrella Teresa M. , Mittmann Nicole , Earle Craig C. , Gavura Scott , Mercer Rebecca E. , Hanna Timothy P. , Chan Kelvin K. W.
Published: October 2020

Second‐line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real‐world toxicity of second‐line ipilimumab compared to standard second‐line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second‐line ipilimumab after September 2012 were considered as cases, and those who received second‐line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment‐related mortality, any‐cause hospital visits, ipilimumab‐related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second‐line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second‐line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any‐cause (60.1% vs 45.7%; OR = 1.81; P value = .019) and ipilimumab‐related (47.2% vs 31.9%; OR = 1.91; P value = .011) hospital visits. Adjusting for different follow‐up days, ipilimumab was associated with higher rates of all‐cause (RR = 1.56 [95%CI: 1.12‐2.16]), and ipilimumab‐related (RR = 2.18 [95% CI: 1.45‐3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value = .04). Compared to historical second‐line treatments, second‐line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world.
Assessment of local coupled cluster methods for excited states of BODIPY/Aza‐BODIPY families
Authors: Feldt Milica , Brown Alex
Published: October 2020

It was previously reported that Laplace transformed local CC2 (LCC2*) provided the best agreement (MAE = 0.145 eV) when comparing vertical excitation energies to experimental λmax for a benchmark set of 17 BODIPY/Aza‐BODIPY molecules. However, these energies did not agree with values obtained from canonical CC2. Here we report LCC2* computations of vertical excitation energies on the same benchmark set of molecules using a newly implemented treatment of the ground state. Comparison with resolution‐of‐identity approximate coupled cluster to second‐order (RI‐CC2) results demonstrate that the new LCC2* results agree quantitatively. Furthermore, these values can easily be corrected empirically to also provide excellent agreement with the experiment. We show that the local algebraic diagrammatic construction to second‐order (LADC(2)) method exhibits the same differences between implementations as seen for LCC2. The source of the difference is traced to an improved treatment of the ground state in the local methods, which decreases agreement with the experiment (as attributed to a fortuitous cancellation of errors) but significantly improves agreement with RI‐CC2. While the absolute vertical excitation energies now show larger deviations, there remains a strong linear correlation between the LCC2* results and the experiment. For the 17 BODIPY/Aza‐BODIPY molecules vertical excitation energies are determined using DLPNO‐STEOM‐CCSD and shown to have excellent agreement with experimental λmax (MAE = 0.145 eV), which is the best of all the single‐reference methods. The vertical excitation energies are determined using LCC2*, empirically corrected LCC2*, and RI‐CC2 for a series of eight large BODIPYs and Aza‐BODIPYs.
Nonparametric Methods in Population Pharmacokinetics
Authors: Goutelle Sylvain , Woillard Jean‐Baptiste , Neely Michael , Yamada Walter , Bourguignon Laurent
Published: October 2020

Population pharmacokinetic (PK) modeling is a widely used approach to analyze PK data obtained from groups of individuals, in both industry and academic research. The approach can also be used to analyze pharmacodynamic (PD) data and pooled PK/PD data. There are 2 main families of population PK methods: parametric and nonparametric. The objectives of this article are to present an overview of nonparametric methods used in population pharmacokinetic modeling and to explain their specific characteristics to inform scientists and clinicians about their potential value for data analysis, simulation, dosage design, and therapeutic drug monitoring (TDM). Nonparametric methods have several interesting characteristics for population PK analysis, including computation of exact likelihoods, the ability to accommodate parameter probability distributions of any shape (eg, non‐Gaussian), and to detect subpopulations and outliers. Nonparametric population methods are also highly relevant for model‐based TDM and design of individualized drug dosage regimens. Several algorithms have been developed to estimate model parameter values within an individual and compute that individual's dosage to achieve target drug exposure with maximum precision and accuracy. Nonparametric modeling methods for both population and individual PK analysis are available under user‐friendly packages.
Water extract of onion catalyst: An economical green route for the synthesis of 2‐substituted and 1,2‐disubstituted benzimidazole derivatives with high selectivity
Authors: Kaliyan Prabakaran , Selvaraj Loganathan , Muthu Seenivasa Perumal
Published: October 2020

An efficient, environmental friendly and substrate controlled method of synthesis of 2‐substituted benzimidazole derivatives 3 and 1,2‐disubstituted benzimidazole derivatives 4 with high selectivity has been achieved from the reaction of o‐phenylenediamine 1 and aldehydes 2 in the presence of water extract of onion and selecting suitable reaction medium. This method is widely applicable for variety of aldehydes such as aromatic/aliphatic/heterocyclic aldehydes and 1,2‐diamines to afford 2‐substituted benzimidazole derivatives 3 and 1,2‐disubstituted benzimidazole derivatives 4 in good to excellent yields (up to 96%). The developed method of water extract of onion catalysis produced 2‐substituted benzimidazoles 3 from aromatic aldehydes having electron‐withdrawing groups, whereas aromatic aldehydes bearing electron donating groups selectively furnished 1,2‐disubstituted benzimidazole 4 derivatives. The process described here has several advantages of cheap, low energy consumption, commercially available starting materials, operational simplicity and nontoxic catalyst. The use of water extract of onion makes this present methodology green and giving a useful contribution to the existing methods available for the preparation of benzimidazole derivatives. In addition, Hammett correlation of substituent constant (σ) vs percentage (%) yield has been established.
Leaching kinetics of electronic waste for the recovery of copper: Rate‐controlling step and rate process in a multisize particle system
Authors: Dávila‐Pulido Gloria I. , Salinas‐Rodríguez Armando , Carrillo‐Pedroza Francisco R. , González‐Ibarra Adrián A. , Méndez‐Nonell Juan , Garza‐García Mitzué
Published: October 2020

Electronic waste (e‐waste) contains metallic values that can be recovered by hydrometallurgical methods. This investigation addresses the leaching kinetics of e‐waste for the recovery of copper in H2SO4‐H2O2 media with the objective of determining the rate‐controlling step in monosize particle systems. The results are then used to develop a kinetic model for copper dissolution in multisize particle systems. It is shown that in a monosize particle system, Cu dissolves completely in 150 min at 2 M H2SO4 and 0.2 M H2O2. The rate‐controlling step for this process is chemical reaction with an activation energy of 47.8 kJ/mol. The kinetic model for Cu dissolution in multisize particle systems is developed by applying an optimization method that considers the size distribution and the copper content of each of the size fractions. The results show that the model predicts satisfactorily the Cu dissolution kinetics and reveals that Cu particles with mean sizes of 79, 141, 237, 398.5, and 605 μm react completely in times varying from 15 to 120 min. Coarser Cu particles do not react completely in a time interval of up to 120 min. E‐waste losses 57.6% of its initial weight when subjected to the leaching process and solid residue has gold and silver grades of 2 402.35 and 9 035.29 g/ton, respectively.
Speech Outcomes After Sphincter Pharyngoplasty for Velopharyngeal Insufficiency
Authors: Lam Austin S. , Kirkham Erin M. , Dahl John P. , Kinter Sara L. , Perkins Jonathan A. , Sie Kathleen C.Y.
Published: October 2020

Objectives/Hypothesis

To investigate perceptual speech outcomes following sphincter pharyngoplasty (SP) and to identify patient characteristics associated with velopharyngeal insufficiency (VPI) resolution or improvement.

Methods

Retrospective review of prospectively collected data was performed of consecutive patients that underwent SP for management of VPI between 1994 and 2016 at a single tertiary care pediatric hospital. Demographic data, nasendoscopic findings, and speech characteristics were recorded using a standardized protocol. Pre‐ and post‐operative VPI was graded on a five‐point Likert scale. Frequency of post‐operative VPI resolution and improvement was assessed and associations with patient characteristics were analyzed. The association between odds of VPI resolution or improvement and five patient characteristics identified a priori was performed controlling for confounding factors.

Results

Two‐hundred ninety‐six subjects were included. All patients had at least minimal VPI pre‐operatively; 72% were graded moderate or severe. Sixty‐four percent experienced resolution and 83% improved at least one point on the VPI‐severity scale. Of the five patient characteristics, only history of cleft palate repair was significantly associated with decreased odds of VPI improvement but not resolution when controlling for other variables.

Conclusions

Sphincter pharyngoplasty resulted in resolution of VPI in 64% and improvement in 83% of subjects. Children with a history of cleft palate had significantly decreased odds of VPI improvement compared to those without a history of cleft palate. Neither syndrome diagnosis nor 22q11 deletion had a significant association with speech outcomes after sphincter pharyngoplasty.

Level of Evidence

4 Laryngoscope, 131:E2046–E2052, 2021
Tracking Spontaneous Vestibular Schwannoma Regression with Volumetric Measurements
Authors: Patel Evan J. , Deep Nicholas L. , Schecht Michael , Hagiwara Mari , Roland John T.
Published: October 2020

Objective

To characterize a series of patients with MRI evidence of spontaneous vestibular schwannoma (VS) regression.

Study Design

Retrospective case series.

Methods

Retrospective review between 2012 and 2020 from a single, tertiary‐care center of all patients with an untreated, sporadic VS and spontaneous regression in volumetric tumor size over the course of observation. The main outcome measures included VS size and location, presenting symptoms, medication use, changes in pure‐tone averages and word recognition scores.

Results

The 13 treatment‐naïve patients (62% female, mean age 67.1 years) with spontaneous VS regression represented 3.9% of all patients undergoing observation with serial imaging during the study period. Median tumor size from initial MRI was 529.0 mm3 (range: 108 mm3–13,180 mm3). The mean interval between MRI measurements was 5.5 years (SD 4.4 years). The average percent decrease in tumor size was 36.1% (SD 21.9%) and the average rate of volume decrease was 15.8 mm3/yr (SD 25.4 mm3/yr). Five patients were classified as having major regression, defined by a relative decrease in volume of >40%, while eight patients had minor regression (<40% relative volume reduction). No significant differences in initial tumor size, rate of regression, or audiometric changes were observed between the major and minor regression cohorts.

Conclusions

Patients with evidence of a spontaneously shrinking VS have a heterogeneous presentation. Due to the scarcity of this phenomenon, predicting which tumors will eventually undergo regression remains unclear. Employing volumetric measurements to compare serial MRI scans may improve the accuracy of detecting shrinking tumors.

Level of Evidence

4 Laryngoscope, 131:E1647–E1652, 2021
High‐frequency time‐series autonomous observations of sea surface pCO2 and pH
Authors: Wu Yingxu , Dai Minhan , Guo Xianghui , Chen Jinshun , Xu Yi , Dong Xu , Dai Junwei , Zhang Zhirong
Published: October 2020

Carbon dioxide partial pressure (pCO2) in surface water was continuously measured every 3 h from July 2012 to June 2013 using an autonomous pCO2 system (MAPCO2) deployed on a moored buoy on the East China Sea shelf (31°N, 124.5°E). Sea surface pCO2 and pH had the largest variations in summer, ranging from 215 to 470 μatm, and 7.941 to 8.263 (averagely 8.084 ± 0.080), respectively. They varied little in winter, ranging from 328 to 395 μatm, and 8.003 to 8.074 (averagely 8.052 ± 0.010), respectively. The seasonal average sea surface pCO2 was respectively 335 ± 70 μatm, 422 ± 43 μatm, 362 ± 11 μatm, and 311 ± 59 μatm in summer, autumn, winter, and spring, and was overall undersaturated with respect to atmosphere on a yearly basis. Although the average sea surface pCO2 in summer was below the atmospheric level, the net CO2 flux has suggested a CO2 source status due to the influence of typhoon. Our observation thus demonstrated the significant, even dominant impact of episodic typhoon events on surface ocean CO2 chemistry and air–sea CO2 gas exchange, which would be impossible to capture by shipboard observation. The high wind stress and curl associated with the northward movement of typhoon induced complex sea surface water movement, vertical mixing, and subsequent biological drawdown, which differed in pre‐, onset, and post‐typhoon stages. Based on our estimates, the degassing fluxes during typhoon reached as high as 82 mmol m−2 CO2 and 242 mmol m−2 CO2 in summer and autumn, respectively, accounting for twice as large as the summer CO2 sink during non‐typhoon period, and 28% of the total CO2 source in autumn.
Larval cross‐shore transport estimated from internal waves with a background flow: The effects of larval vertical position and depth regulation
Authors: Garwood Jessica C. , Lucas Andrew J. , Naughton Perry , Roberts Paul L. D. , Jaffe Jules S. , deGelleke Laura , Franks Peter J. S.
Published: October 2020

Cross‐shore velocities in the coastal ocean typically vary with depth. The direction and magnitude of transport experienced by meroplanktonic larvae will therefore be influenced by their vertical position. To quantify how swimming behavior and vertical position in internal waves influence larval cross‐shore transport in the shallow (~ 20 m), stratified coastal waters off Southern California, we deployed swarms of novel, subsurface larval mimics, the Mini‐Autonomous Underwater Explorers (M‐AUEs). The M‐AUEs were programmed to maintain a specified depth, and were deployed near a mooring. Transport of the M‐AUEs was predominantly onshore, with average velocities up to 14 cm s−1. To put the M‐AUE deployments into a broader context, we simulated > 500 individual high‐frequency internal waves observed at the mooring over a 14‐d deployment; in each internal wave, we released both depth‐keeping and passive virtual larvae every meter in the vertical. After the waves' passage, depth‐keeping virtual larvae were usually found closer to shore than passive larvae released at the same depth. Near the top of the water column (3–5‐m depth), ~ 20% of internal waves enhanced onshore transport of depth‐keeping virtual larvae by ≥ 50 m, whereas only 1% of waves gave similar enhancements to passive larvae. Our observations and simulations showed that depth‐keeping behavior in high‐frequency internal waves resulted in enhanced onshore transport at the top of the water column, and reduced offshore dispersal at the bottom, compared to being passive. Thus, even weak depth‐keeping may allow larvae to reach nearshore adult habitats more reliably than drifting passively.