bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Virtual Care Expansion With Environmental Sustainability and Reduced Patient Costs During the COVID-19 Pandemic in Ontario, Canada
Authors: Welk Blayne , McArthur Eric , Zorzi Alexandra P.
Published: October 2022

Importance

There is a growing focus on environmental sustainability in health care.

Objective

To estimate the environmental and patient-level financial benefits associated with the widespread adoption of virtual care during the COVID-19 pandemic.

Design, Setting, and Participants

This population-based cross-sectional study obtained data from linked administrative databases in the universal health care system of Ontario, Canada, from March 2020 to December 2021. Participants included all people with a physician claim for at least 1 episode of virtual care.

Exposures

Patients were stratified by age, socioeconomic status quintiles, Charlson Comorbidity Index, and area of residence (rural or urban).

Main Outcomes and Measures

The primary outcomes were total travel distance and estimated travel-related carbon dioxide emissions avoided owing to virtual care visits. Different model assumptions were used to account for electric and hybrid vehicles and public transit use. The secondary outcomes were estimated patient costs (gasoline, parking, or public transit expenses) avoided.

Results

During the 22-month study period, 10 146 843 patients (mean [SD] age, 44.1 [23.1] years; 5 536 611 women [54.6%]) had 63 758 914 physician virtual care visits. These visits were associated with avoidance of 3.2 billion km of travel distance and between 545 and 658 million kg of carbon dioxide emissions. Patients avoided an estimated total of $569 to $733 million (Canadian [US $465-$599 million]) in parking, public transit, and gasoline costs. Carbon dioxide emission avoidance and patient cost savings were more apparent in patients living in rural areas, those with higher comorbidity, and those who were older than 65 years.

Conclusions and Relevance

Results of this study suggest that virtual care was associated with a large amount of carbon dioxide emissions avoided owing to reduced patient travel and with millions of dollars saved in parking, gasoline, or public transit costs. These benefits are likely to continue as virtual care is maintained as part of the health care system.
Combined Ophthalmic Artery and Central Retinal Vein Occlusion Secondary to Advanced Mantle Cell Lymphoma
Authors: Salman Ali R. , Olsen Timothy W.
Published: October 2022

This case report describes a diagnosis of ophthalmic artery and central retinal vein occlusion in a female patient with a history of end-stage mantle cell lymphoma.
Combined Retinoschisis and Rhegmatogenous Retinal Detachment With a Very Large Outer Retinal Hole
Authors: Gasparian Suzie A. , Almeida David R. P. , Chin Eric. K.
Published: October 2022

This case report describes a diagnosis of retinoschisis and retinal detachment in a patient in their 40s who presented with acute onset of flashes and floaters.
Elevated Intraocular Pressure Associated With Anterior Chamber Migration of Fluocinolone Acetonide Implant 1 Year After Administration
Authors: Jomaa Emilie , Schweitzer Cédric , Delyfer Marie-Noëlle
Published: October 2022

This case report describes the migration of a fluocinolone acetonide implant to the anterior chamber 1 year after it was placed.
A Geographic Analysis of Google Characterizations of Who Is an "Eye Doctor" Across the US
Authors: Soares Rebecca R. , Nahar Ankur , Mahmoudzadeh Raziyeh , Kazan Adina S. , Williamson John E. , Wong Michael K. , Hsu Jason , Chiang Allen , Yonekawa Yoshihiro
Published: October 2022

Importance

In order to continue to clarify and maintain their role as eye physicians and surgeons, ophthalmologists may want to understand how they are viewed in the public eye and online.

Objective

To determine the representation of ophthalmologists (OMD) and optometrists (ODs) when a Google search for “eye doctor near me” is made from each county in the US.

Design, Setting, and Participants

This population-based cross-sectional study used publicly available data on OMDs and ODs and a Google search application programming interface (API) to search the phrase “eye doctor near me” from the geographic coordinates of each county centroid in the US (searched June 30, 2021). The top 10 sites and 3 Google map links, excluding physician ratings sites, were recorded. Data from the US Centers for Medicare and Medicaid Services were used to estimate the real number of OMDs and ODs per county.

Main Outcome and Measures

The primary outcome was the mean proportion of OMDs listed by Google search as compared with the real proportion of OMDs for the US overall and for each state and county.

Results

A total of 2955 counties from 52 states and territories were included. The overall mean proportion of OMDs (OMDs with ODs) from the Google search of all counties was 4726.97 of 16 345.93 (28.91%), which was also less than the real proportion of ODs (15 778 of 41 975 [37.58%], a difference of 8.67%; 95% CI, 37.13-38.05%; P < .001). OMDs were underrepresented by Google in 35 of 52 states and territories (67.3%).

Conclusions and Relevance

In most counties in the US, Google search of the phrase “eye doctor near me” may underrepresent ophthalmologists. Ophthalmologists may want to pursue search engine optimization to try to achieve balanced representation online.
Quantifying Total and Out-of-Pocket Costs Associated With Head and Neck Cancer Survivorship
Authors: Massa Sean T. , Chidambaram Smrithi , Luong Peter , Graboyes Evan M. , Mazul Angela L.
Published: October 2022

Importance

Oncologic treatment is costly to the health care system and to individuals, but patients with head and neck cancer (HNC) also have long-term care needs after treatment. Survivors of HNC require specific consideration given their rapidly growing numbers. This subpopulation of cancer survivors often experiences long-term treatment-associated morbidity.

Objective

To describe the total and out-of-pocket (OOP) costs associated with HNC survivorship and the risk factors for financial toxicity among this population.

Design, Setting, and Participants

This was a retrospective review and economic evaluation of a cohort of US adults with a diagnosis of HNC from 2006 to 2018. The study used data the from IBM MarketScan Commercial Claims Database. Data were analyzed from November 2020 to June 2022.

Exposures

Treatment for HNC.

Main Outcomes and Measures

Total and OOP medical costs were assessed monthly and reported relative to the date of HNC diagnosis. The primary outcome was the difference between a patient’s mean monthly survivorship costs (13-60 months after diagnosis) and mean monthly baseline costs (7-12 months before diagnosis). Univariate and multivariable linear regression models were created for total and OOP costs to generate coefficient estimates with 95% CIs.

Results

The study cohort of this economic evaluation included 19 098 patients with HNC (median [range] age, 56 [18-64] years; 14 144 [74.1%] men and 4954 [25.9%] women; race and ethnicity were not considered). Throughout the survivorship period, median total and OOP costs were $372 per month and $31 per month higher than baseline costs, respectively, with variation in expenses by demographic information, health plan type, and oncologic variables. In the multivariable model, greater total and OOP excess survivorship costs were associated with female sex ($343/mo; 95% CI, $126 to $560 and $9/mo; 95% CI, $4 to $14). Highest and lowest total excess survivorship costs associated with cancer site were seen for hypopharyngeal ($1908/mo; 95% CI, $1102 to $2714) and oropharyngeal cancers (−$703/mo; 95% CI, −$967 to −$439) vs oral cavity cancers. Compared with surgery or radiation therapy alone, multimodal treatment was generally associated with excess OOP survivorship costs.

Conclusions and Relevance

The findings of this retrospective economic evaluation review suggest that the costs of HNC survivorship remain persistently elevated above baseline costs for at least 5 years after diagnosis. High survivorship costs were associated with female sex, hypopharyngeal tumors, and treatment with multimodal therapy. Practitioners should seek to minimize costs for these patients at higher-risk of financial toxicity after treatment and work to provide directed supportive services.
Passivating {100} Facets of PbS Colloidal Quantum Dots via Perovskite Bridges for Sensitive and Stable Infrared Photodiodes
Authors: Chen Duo , Liu Yuxuan , Xia Bing , Chen Long , Yang Yang , Yang Gaoyuan , Liu Jing , Lu Shuaicheng , Ge Ciyu , Liu Peilin , Yang Junrui , Liang Guijie , Lan Xinzheng , Zeng Xiangbin , Li Luying , Zhang Jianbing , Xiao Zewen , Gao Liang , Tang Jiang
Published: October 2022

Solution‐processed PbS colloidal quantum dots (CQDs) are promising optoelectronic materials for next‐generation infrared imagers due to their monolithic integratability with silicon readout circuit and tunable bandgap controlled by CQDs size. However, large‐size PbS CQDs (diameter >4 nm) for longer shortwave‐infrared photodetection consist mainly of {100} facets with incomplete surface passivation and unsatisfied stability. Here, it is reported that perovskite‐bridged PbS CQDs, in which the {100} facets of the CQDs are epitaxially bridged with CsPbI3–xBrx perovskite, can achieve improved passivation and enhanced stability in comparison with the traditional strategies. The resultant infrared CQDs photodiodes exhibit significantly reduced dark current, nearly 50% enhanced photoresponse, and improved work stability. These superior properties synergistically produce the most balanced performance (with a high −3 dB bandwidth of 42 kHz and an impressive specific detectivity of 6.2 × 1012 Jones) among the reported CQDs photodetectors.
Cyclodextrin Nano‐Assemblies Enabled Robust, Highly Stretchable, and Healable Elastomers with Dynamic Physical Network
Authors: Li Sijia , Liu Jize , Wei Zehui , Cui Qinke , Yang Xin , Yang Yong , Zhang Xinxing
Published: October 2022

Artificial materials with biomimic self‐healing ability are fascinating, however, the balance between mechanical properties and self‐healing performance is always a challenge. Here, a robust, highly stretchable self‐healing elastomer with dynamic reversible multi‐networks based on polyurethane matrix and cyclodextrin‐assembled nanosheets is proposed. The introduction of cyclodextrin nano‐assemblies with abundant surface hydroxyl groups not only forms multiple interfacial hydrogen bonding but also enables a strain‐induced reversible crystalline physical network owing to the special nanoconfined effect. The formation and dissociation of a dynamic crystalline physical network under stretching–releasing cycles skillfully balance the contradiction between mechanical robustness and self‐healing ability. The resulting nanocomposites exhibit ultra‐robust tensile strength (40.5 MPa), super toughness (274.7 MJ m−3), high stretchability (1696%), and desired healing efficiency (95.5%), which can lift a weight ≈ 100 000 times their own weight. This study provides a new approach to the development of mechanically robust self‐healing materials for engineering applications such as artificial muscles and healable robots.
Recent Advances in Catalytic Asymmetric Syntheses of Functionalized Heterocycles via Halogenation/Chalcogenation of Carbon‐Carbon Unsaturated Bonds
Authors: Liu Shengshu , Zhang Bing‐Qian , Xiao Wen‐Ying , Li Yin‐Long , Deng Jun
Published: October 2022

Halogen (fluorine, chlorine, bromine, iodine) or chalcogen (sulfur, selenium)‐containing heterocycles are widely recognized as key building blocks in many natural products and bioactive targets. Catalytic asymmetric halogenation/chalcogenation of carbon‐carbon unsaturated bonds via onium ion transformations are efficient methods to obtain diverse chiral heterocyclic backbones. In the past few years, catalytic enantioselective versions of halo/thio/seleno‐functionalizations with various halogen and chalcogen electrophiles have experienced constant development. This review highlights those advances in preparing functionalized heterocycles promoted by chiral organocatalysts or metal‐based catalysts.

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Photobiocatalytic Cascades for Acylating N‐Heterocycles with Natural Amino Acids via the 2‐Keto Acids
Authors: Cui Xuexian , Geng Wen‐Chao , Jiang Huifeng , Wu Bian
Published: October 2022

Photobiocatalysis fully utilizing the unique reactivity of photocatalysis and efficient transforming biobased feedstocks of biocatalysis represents a promising approach for future green synthesis. However, photobiocatalytic cascade with biobased starting substrates has been rarely reported. Here, we present photobiocatalytic cascades that modify the N‐heterocycle with keto acids biocatalytically synthesized from natural amino acids. The types of aliphatic, aromatic, and polar natural amino acids are compatible with the photobiocatalytic cascades system. In addition, the cascade is compatible with a range of N‐heterocycles with moderate to good yield (up to 82%). Furthermore, the cascade system can reach gram scale (0.91 g) with a good separation yield, demonstrating the potential for scaling up production to practical application. This photobiocatalytic cascade can synthesize a range of important N‐heterocyclic derivatives from natural amino acids in a green fashion and paves the way for greener synthesis by combining biocatalysis and photocatalysis.

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BF3 ⋅ Et2O Promoted Inverse‐Electron‐Demand Oxa‐Diels‐Alder Reaction of Alkylidene Isoxazol‐5‐ones with Unactivated Alkenes
Authors: Zheng Yu , Qian Shencheng , Xu Pengcheng , Ma Tianting , Huang Shenlin
Published: October 2022

The synthesis of fused dihydropyran isoxazole derivatives has been developed by employing an intermolecular inverse‐electron‐demand Diels‐Alder reaction of readily available alkylidene isoxazol‐5‐ones with unactivated alkenes. The reaction was promoted by inexpensive and commercially available BF3 ⋅ Et2O without the use of metal Lewis acids. This cycloaddition transformation could proceed under mild conditions with broad substrate scope, providing a variety of bicyclic 5,6‐dihydro‐4H‐pyrano[3,2‐d]isoxazoles.

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Metal‐Free Cascade 1,4‐Conjugate Addition/Selective Annulation Strategy for Divergent Synthesis of Polysubstituted Imidazoles and 4‐Alkenylquinazolines
Authors: Tang Qiang , Xu Keke , He Xinwei , Shang Yongjia
Published: October 2022

A metal‐free cascade annulation of propagylamines with amidines for divergent synthesis of polysubstituted imidazoles and 4‐alkenylquinazolines has been developed. The reaction is believed to proceed by sequential 1,4‐conjugate addition of amidines to propargylamines, 5‐exo‐dig annulation/aromatization to form the polysubstituted imidazoles, and nucleophilic addition/elimination/aromatization to quinazoline skeleton. In this reaction, a broad range of electron‐rich, electron‐neutral, and electron‐deficient propagylamines react well with amidines to give polysubstituted imidazoles and 4‐alkenylquinazolines in 53–93% yields. Moreover, the utility of this method was showcased by gram‐scale experiments and synthetic transformations of the product.

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Responses of invasive and native plants to different forms and availability of phosphorus
Authors: Zhang Zhen , Pan Mingxin , Zhang Xue , Liu Yanjie
Published: October 2022

Premise

Many studies have assessed the various responses of alien plants to changes in overall nutrient or different nitrogen (N) availabilities. However, in natural soils, nutrients are present as different elements (e.g., N and phosphorus [P]) and forms (e.g., inorganic and organic). Few studies have explored whether invasive and native species differ in their responses to varying P availability and forms.

Methods

We grew five taxonomically related pairs of common herbaceous, invasive and native species alone or in competition under six different conditions of P availability or forms and assessed their growth performance.

Results

Invasive species overall did not produce more biomass than native species did in the various P conditions. However, the biomass response to organic forms of P was, relative to the response to inorganic forms of P, stronger for the invasive species than that for the native species and agreed with invasive species mainly allocating biomass to the root system under organic P conditions.

Conclusions

While invasive species were not more promiscuous than the native species, they took great advantage of the organic P forms. Therefore, the invasion risk of alien species may increase in habitats with more organic P sources.
Mosaic Williams syndrome: A case report
Authors: Kalantari Silvia , Biagio Marta Di , Valente Enza Maria , Rossi Elena , Sirchia Fabio
Published: October 2022

Williams syndrome (WS) is a well‐known genetic disorder caused by heterozygous microdeletions of the 7q11.23 chromosome region. The main clinical features of the syndrome are characteristic facial dysmorphisms, cardiovascular and endocrine anomalies, short stature, mild‐to‐moderate intellectual disability, and a recognizable cognitive and behavioral profile. Differently from large chromosomal imbalances and aneuploidies, mosaicism has only rarely been found in microdeletion syndromes, and mosaic cases with WS phenotype have never been reported. We here describe a 51‐year‐old female patient with the typical clinical features of WS, whose chromosomal microarray analysis and fluorescence in situ hybridization disclosed a 54%–68% germline mosaicism for 7q11.23 deletion.
Simian homologues of human herpesviruses and implications for novel viral introduction to free‐living mountain gorillas
Authors: Smiley Evans Tierra , Lowenstine Linda J. , Ssebide Benard , Barry Peter A. , Kinani Jean Felix , Nizeyimana Fred , Noheli Jean Bosco , Okello Ricky , Mudakikwa Antoine , Cranfield Michael R. , Mazet Jonna A. K. , Johnson Christine K. , Gilardi Kirsten V.
Published: October 2022

The endangered mountain gorilla (Gorilla beringei beringei) in Rwanda, Uganda, and the Democratic Republic of Congo is frequently in contact with humans through tourism, research activities, and illegal entry of people into protected gorilla habitat. Herpesviruses, which are ubiquitous in primates, have the potential to be shared in any setting where humans and gorillas share habitat. Based on serological findings and clinical observations of orofacial ulcerated lesions resembling herpetic lesions, an alpha‐herpesvirus resembling human herpes simplex virus type 1 (HSV‐1) has long been suspected to be present in human‐habituated mountain gorillas in the wild. While the etiology of orofacial lesions in the wild has not been confirmed, HSV‐1 has been suspected in captively‐housed mountain gorillas and confirmed in a co‐housed confiscated Grauer's gorilla (Gorilla beringei graueri). To better characterize herpesviruses infecting mountain gorillas and to determine the presence/absence of HSV‐1 in the free‐living population, we conducted a population‐wide survey to test for the presence of orally shed herpesviruses. DNA was extracted from discarded chewed plants collected from 294 individuals from 26 groups, and samples were screened by polymerase chain reaction using pan‐herpesvirus and HSV‐1‐specific assays. We found no evidence that human herpesviruses had infected free‐ranging mountain gorillas. However, we found gorilla‐specific homologs to human herpesviruses, including cytomegaloviruses (GbbCMV‐1 and 2), a lymphocryptovirus (GbbLCV‐1), and a new rhadinovirus (GbbRHV‐1) with similar characteristics (i.e., timing of primary infection, shedding in multiple age groups, and potential modes of transmission) to their human counterparts, human cytomegalovirus, Epstein‐Barr virus and Kaposi's sarcoma‐associated herpesvirus, respectively.
Cu Single Atom Nanozyme Based High‐Efficiency Mild Photothermal Therapy through Cellular Metabolic Regulation
Authors: Chang Mengyu , Hou Zhiyao , Wang Man , Wen Ding , Li Chunxia , Liu Yuhui , Zhao Yanli , Lin Jun
Published: October 2022

Upregulation of heat shock proteins (HSPs) drastically compromises the treatment effect of mild photothermal therapy (PTT). Herein, we designed a polyporous Cu single atom nanozyme (Cu SAzyme) loaded with licogliflozin (LIK066) for HSP‐silencing induced mild PTT. On one hand, LIK066 inhibits glucose uptake by shutting sodium‐dependent glucose transporter (SGLT) “valve”, effectively blocking the energy source for adenosine triphosphate (ATP) generation. Without sufficient energy, cancer cells cannot synthesize HSPs. On the other hand, Cu SAzyme presents extraordinary multienzyme activities to induce reactive oxygen species (ROS) storm formation, which can damage the existing HSPs in cancer cells. Through a two‐pronged strategy of SGLT inhibitor and ROS storm, LIK066‐loaded Cu SAzyme shows high efficiency for comprehensive removal of HSPs to realize mild PTT.
Nanoporous Single‐Crystalline Oxide Catalysts for Preferential Oxidation of CO in H2 with an Ultra‐wide Temperature Window
Authors: Li Wenting , Xie Kui
Published: October 2022

Preferential oxidation of CO in H2 (PROX) reaction is a promising solution to the on‐board purification of CO‐contaminated H2 fuel for use in next‐generation proton‐exchange membrane fuel cells (PEMFC). However, achieving high CO selectivity, activity and structural stability across the wide temperature window remains a great challenge. Herein, we fabricate centimeter scale interfacial PROX catalysts grown from nanoporous single‐crystalline Pr2O3 and Nd2O3 monoliths with lattice surface‐deposited Pt clusters at nanoscale. We demonstrate complete and selective removal of CO in H2 over an unprecedented wide temperature window (253–403 K). The monoliths are integrated with an operational PEMFC to purify the H2 fuel contaminated with CO (30 ppm) and enable stable power output for >400 h; over two thousand times longer than without. This work demonstrates that the nanoporous single‐crystalline oxide monoliths can simultaneously achieve the stability and overall performance required to realize practically useful PEMFCs.
Ultra‐Tough and Recyclable Ionogels Constructed by Coordinated Supramolecular Solvents
Authors: Li Lingling , Li Weizheng , Wang Xiaoliang , Zou Xiuyang , Zheng Sijie , Liu Ziyang , Li Qingning , Xia Qunmeng , Yan Feng
Published: October 2022

The mechanical properties of most hydrogels (ionogels) are considerably affected by covalently cross‐linked networks. However, the interactions between solvent/solvent molecules and solvent/polymer chains are usually ignored. Herein, a series of ultra‐tough ionogels were prepared via a supramolecular solvent, halometallate ionic liquid, in which cations and coordinating anions form a 3D supramolecular network. The linear polymer chains are physically cross‐linked with supramolecular solvents synergistically enhancing the strength (14.3 MPa), toughness (78 MJ m−3), and Young's modulus (55 MPa) of ionogels, effectively dispersing the stress concentration under load, and obtaining better fatigue resistance and higher fracture energy (198 kJ m−2). Furthermore, the reversible cross‐linking enables green recovery and recycling of ionogels, simply by water. This strategy shows broad applicability based on a variety of supramolecular solvents and coordinatable polymers.
Preparation of graded materials for miscible polycarbonate/poly(methyl methacrylate) blends by segregation under shear flow
Authors: Moonprasith Nantina , Tatsumichi Mizuki , Nakamura Kodai , Kida Takumitsu , Tsubouchi Kyoko , Hiraoka Tatsuhiro , Yamaguchi Masayuki
Published: October 2022

Exposure to shear flow produced by a pressure‐driven capillary rheometer provides a concentration gradient without phase separation in miscible polymer blends of bisphenol‐A polycarbonate containing low‐molecular‐weight poly(methyl methacrylate) (PMMA). The strand surface extruded from the rheometer contains a large amount of PMMA. However, the strand is transparent because there is no light scattering due to phase separation. The segregation behavior, that is, enrichment of the PMMA content at the strand surface, is enhanced when the molecular weight of PMMA is low. Furthermore, the segregation is also enhanced at high temperatures and at high shear rates. By contrast, the die length barely affects the degree of segregation. The segregation phenomenon should be noted because it may facilitate the modification of the surface properties of various products.
Ökologische Betrachtung neuentwickelter Carbonbetonbauteile
Authors: Wappler Stefan
Published: October 2022

Als Ergebnis des C3‐Projekts zeichnet sich der CUBE durch eine Vielzahl von neuen Bauteilen, Materialien und Konstruktionen aus. Der Beitrag untersucht ausgewählte Bauteile auf ihre ökologische Nachhaltigkeit, auch wenn bei Entwurf und Ausführung des Gebäudes konstruktive und statische, teilweise auch finanzielle Anforderungen stärker im Vordergrund standen. Für einzelne Wand‐ und Deckenbauteile wurde eine Ökobilanzierung nach EN 15804 erstellt. Die Ergebnisse wurden mit denen von Stahlbetonbauteilen verglichen. Für die gekrümmte TWIST‐Fläche stehen keine Stahlbetonvergleichsbauteile zur Verfügung. Hier wurde ein repräsentativer Ausschnitt im Regelquerschnitt untersucht. Insgesamt sind die Umweltwirkungen der Carbonbetonbauteile vergleichbar mit denen von Stahlbetonbauteilen. Im Gegensatz zu Letzteren zeigen sich jedoch erhebliche Potenziale zur kurzfristigen Verbesserung der Umweltwirkungen.
Anti‐Proliferative Acyl Phenols and Arylnonanoids from the Fruit Rind of Myristica malabarica Lam.
Authors: Bauri Ajoy Kumar , Du Yongle , Brodie Peggy Jane , Foro Sabine , Kingston David G. I.
Published: October 2022

Phytochemical investigation of the methanol extract of the fruit rind of Myristica malabarica led to the isolation of eight known compounds that were identified as malabaricones A−D, promalabaricones B and C, 1‐(2,6‐dihydroxyphenyl)tetradecan‐1‐one, and ericanone by comparison with literature spectroscopic data. The structures of malabaricones A−D, promalabaricone B, and 1‐(2,6‐dihydroxyphenyl)tetradecan‐1‐one were confirmed by X‐ray crystallography. In vitro assay of the isolated phenols indicated that they exhibited moderate anti‐proliferative activity against the A2780 human ovarian cancer cell. Compounds (1, 3, 5, 6 and 7) had the most potent activities, whereas the anti‐proliferative activities of compounds 2 and 4 were less potent.
Phytochemical Diversity in Relation to Cytogenetic Variability inInula racemosaHook.f., an Endangered Medicinal Plant of Himalayas
Authors: Mudassir Jeelani Syed , Shahnawaz Mohd. , Prakash Gupta Ajai , Lattoo Surrinder K.
Published: October 2022

Inula racemosa, a resourceful critically endangered medicinal herb in the Himalayas is traditionally utilized to cure various human disorders. The species is a wealthy source of sesquiterpene lactones has many pharmacological properties. To quantify and identify the best genetic stocks for a maximum build‐up of desired metabolites (isoalantolactone and alantolactone) among existent cytotypes in the species, LC‐MS/MS analysis was made. The other comprehensive experiments carried out at present included detailed meiotic examinations of different populations collected from different areas of Kashmir Himalayas. The results presented the occurrence of variable chromosome numbers asn=10 andn=20 in different populations, but the tetraploid cytotype (n=20) is new for the species. The LC‐MS/MS investigation revealed significant variability in the content of sesquiterpene lactones in different plant tissues (stem, leaf, and root). An upsurge in the quantity of isoalantolactone and alantolactone was noticed with increasing ploidy levels along the increasing altitudes. Therefore, a habit to accumulate abundant quantities of secondary metabolites and increased adaptability by species/cytotypes thriving at higher altitudes is seen among tetraploid cytotypes during the present investigation. Also, the chromosomal variations seem to enhance the flexibility of polyploid species primarily at upper elevations. Thus, the present study strongly provides quantification of elite cytotypes/chemotypes with optimum concentration of secondary metabolites.
Antiviral Disaccharide Lead Compounds against SARS‐CoV‐2 through Computer‐Aided High‐Throughput Screen
Authors: Li Binjie , Zhang Tianji , Li Jin‐ping , Yu Ming‐jia
Published: October 2022

SARS‐CoV‐2 infects human epithelial cells through specific interaction with angiotensin‐converting enzyme 2 (ACE2). In addition, heparan sulfate proteoglycans act as the attachment factor to promote the binding of viral spike protein receptor binding domain (RBD) to ACE2 on host cells. Though the rapid development of vaccines has contributed significantly to preventing severe disease, mutated SARS‐CoV‐2 strains, especially the SARS‐CoV‐2 Omicron variant, show increased affinity of RBD binding to ACE2, leading to immune escape. Thus, there is still an unmet need for new antiviral drugs. In this study, we constructed pharmacophore models based on the spike RBD of SARS‐CoV‐2 and SARS‐CoV‐2 Omicron variant and performed virtual screen for best‐hit compounds from our disaccharide library. Screening of 96 disaccharide structures identified two disaccharides that displayed higher binding affinity to RBD in comparison to reported small molecule antiviral drugs. Further, screening PharmMapper demonstrated interactions of the disaccharides with a number of inflammatory cytokines, suggesting a potential for disaccharides with multiple‐protein targets.
Isolated laryngeal Mucormycosis requiring laryngectomy
Authors: Lackey Taylor G. , Duffy James R. , Marshall Carrie , Fink Daniel S.
Published: October 2022

We report a case of isolated laryngeal mucormycosis in a patient who presented in diabetic ketoacidosis (DKA). The patient was managed with antifungal therapy and eventual total laryngectomy. To our knowledge, this is the first case presented of mucormycosis with isolated laryngeal involvement.
A Plausible Prebiotic Path to Nucleosides: Ribosides and Related Aldosides Generated from Ribulose, Fructose, and Similar Abiotic Precursors
Authors: Roche Tyler P. , Fialho David M. , Menor‐Salván Cesar , Krishnamurthy Ramanarayanan , Schuster Gary B. , Hud Nicholas V.
Published: October 2022

The prebiotic origins of ribose, nucleosides, and eventually RNA are enduring questions whose answers are central to the RNA world hypothesis. The abiotic synthesis of sugars was first demonstrated over a century ago, but no known prebiotic reaction produces ribose (an aldose sugar) selectively and in good yield. In contrast, ribulose, and fructose (ketose sugars) and other monosaccharides are formed in high yield by several robust abiotic reactions. It is reported here that ketose sugars ‐ both ketopentoses and ketohexoes ‐ serve as precursors for the formation of ribosides and other aldosides, as demonstrated by glycoside‐forming reactions involving barbituric acid, a plausibly prebiotic nucleobase. Moreover, a one‐pot reaction of glyceraldehyde and barbituric acid was discovered which under mild conditions, and without special minerals or other catalysts, results in the formation of glycosides. These results reveal that an exclusive or high‐yielding generation of free ribose was not required for its incorporation into processes that provided the foundations for life.
Palladium‐Catalyzed Directed Atroposelective C−H Iodination to Synthesize Axial Chiral Biaryl N‐Oxides via Enantioselective Desymmetrization Strategy
Authors: Yao Linxi , Gashaw Woldegiorgis Alemayehu , Huang Shaoying , Wang Yongtao , Lin Xufeng
Published: October 2022

The discovery of enantioselective desymmetrization reactions to provide practical synthesis of enantio‐enriched atropisomeric biaryls is a challenging topic in the field of asymmetric catalysis. Herein, we report a highly enantioselective desymmetrization reaction for the synthesis of axially chiral biarylN‐oxides by atroposelective C−H iodination by using Pd(II) coordinated byN‐benzoyl‐l‐phenylalanine as a chiral catalyst at room temperature. A broad range of products were obtained in high yields (up to 99 %) with excellent enantioselectivities (up to 98 %ee). The products could be synthesized in gram scale, one of which was proved to be a powerful organocatalyst in asymmetric allylation reaction. Mechanistic evidence as well as DFT calculations point towards the factors that lead to high reactivity and excellent enantiocontrol in this reaction.
Metastatic prostate cancer diagnosed by fine‐needle aspiration: Contemporary cytopathologic and biomarker assessment with clinical correlates
Authors: Cantley Richard L. , Wang Xiaoming , Reichert Zachery R. , Chinnaiyan Arul M. , Mannan Rahul , Cao Xuhong , Spratt Daniel E. , Vaishampayan Ulka N. , Alumkal Joshi J. , Morgan Todd M. , Palapattu Ganesh , Davenport Matthew S. , Pantanowitz Liron , Mehra Rohit
Published: October 2022

Introduction

The diagnosis of metastatic prostatic cancer (MPC) by fine needle aspiration (FNA) can usually be rendered by typical cytomorphologic and immunohistochemical (IHC) features. However, MPC diagnosis may be complicated by transformation to atypical phenotypes such as small cell carcinoma, typically under pressure from androgen deprivation therapy (ADT). Predictive and prognostic biomarkers can also be assessed by IHC. This study illustrates how careful assessment of cytologic and biomarker features may provide therapeutic and prognostic information in MPC.

Design

We reviewed our anatomic pathology archives for MPC diagnosed by FNA from January 2014 to June 2021. Clinical histories, cytology slides, and cell blocks were reviewed. Extensive IHC biomarker workup was performed, including markers of prostate lineage, cell‐cycle dysfunction, Ki‐67, neuroendocrine markers, PDL1, and androgen receptor splice variant 7. Cases were reclassified into three categories: conventional type, intermediary type, and high‐grade neuroendocrine carcinoma (HGNC).

Results

Eighteen patients were identified. Twelve had conventional MPC, including six of six ADT‐naive patients. Six of twelve (50%) with prior ADT were reclassified as intermediary or HGNC. Four intermediary cases included two with squamous differentiation and two with pro‐proliferative features. Two HGNC cases had typical small cell carcinoma cytomorphology. Expression of PDL1 was identified in two cases and ARv7 in three cases. Five of five intermediary and HGNC patients died of disease versus six of eleven with with conventional type.

Conclusions

Aggressive cytomorphologic variants were commonly identified in patients with prior ADT. Identification of nonconventional cytomorphology and increased proliferation can provide important prognostic information. Recognition of these changes is important for an accurate diagnosis, and the identification of high‐grade variants can affect therapeutic decision‐making. Clinically actionable biomarkers such as PDL1 and ARv7 can be assessed by IHC.
Evaluation of a scientific data search infrastructure
Authors: Orhean Alexandru Iulian , Giannakou Anna , Antypas Katie , Raicu Ioan , Ramakrishnan Lavanya
Published: October 2022

The ability to search over large scientific datasets has become crucial to next‐generation scientific discoveries as data generated from scientific facilities grow dramatically. In previous work, we developed and deployed ScienceSearch, a search infrastructure for scientific data which uses machine learning to automate metadata creation. Our current deployment is deployed atop a container based platform at a HPC center. In this article, we present an evaluation and discuss our experiences with the ScienceSearch infrastructure. Specifically, we present a performance evaluation of ScienceSearch's infrastructure focusing on scalability trends. The obtained results show that ScienceSearch is able to serve up to 130 queries/min with latency under 3 s. We discuss our infrastructure setup and evaluation results to provide our experiences and a perspective on opportunities and challenges of our search infrastructure.
BH4Ng+ (Ar−Rn): Viable Compounds with a B−Ng Covalent Bond
Authors: Pino‐Rios Ricardo , Vásquez‐Espinal Alejandro , Pan Sudip , Cerpa Erick , Tiznado William , Merino Gabriel
Published: October 2022

In this work, we explore, using high‐level calculations, the ability of BH4+ to interact with noble gases. The He system is energetically unstable, while the Ne system could only be observed at cryogenic temperatures. In the case of the Ar, Kr and Xe systems, all are energetically stable, even at room temperature. The different chemical bond descriptors reveal a covalent character between B and the noble gas from Ar to Rn. However, this interaction gradually weakens the multicentric bond between the boron atom and the H2 fragment. Thus, although BH4Rn+ exhibits a strong covalent bond, it tends to dissociate at room temperature into BH2Rn++H2.
Photoinduced Intervalence Charge Transfers: Spectroscopic Tools to Study Fundamental Phenomena and Applications
Authors: Ramírez‐Wierzbicki Ivana , Cotic Agustina , Cadranel Alejandro
Published: October 2022

The front cover artwork is provided by Dr. Alejandro Cadranel's group at the University of Buenos Aires and the Friedrich‐Alexander Universität Erlangen‐Nürnberg. The image shows a ground state that forms, upon photon absorption, an excited state mixed valence system, which is characterized by a double‐well potential energy surface. Inspection of the excited state with light reveals photoinduced intervalence charge transfers (cover design by Gonzalo Peñaloza). Read the full text of the Concept at 10.1002/cphc.202200384.
Activity‐Based Models to Predict Kinetics of Levulinic Acid Esterification
Authors: Klinksiek Marcel , Baco Sindi , Leveneur Sébastien , Legros Julien , Held Christoph
Published: October 2022

The solvent is of prime importance in biomass conversion as it influences dissolution, reaction kinetics, catalyst activity and thermodynamic equilibrium of the reaction system. So far, activity‐based models were developed to predict kinetics and equilibria, but the influence of the catalyst on kinetics has not been succesfully predicted by thermodynamic models. In this work, the thermodynamic model ePC‐SAFT advanced was used to predict the activities of the reactants and of the catalyst at various conditions (temperature, reactant concentrations, γ‐valerolactone GVL cosolvent addition, catalyst concentration) for the homogeneously acid‐catalyzed esterification of levulinic acid (LA) with ethanol. Different kinetic models were applied, and it was found that the catalyst influence on kinetics could be predicted correctly by simultaneously solving the dissociation equilibrium of H2SO4 catalyst along the reaction coordinate and by relating reaction kinetics to proton activity. ePC‐SAFT advanced model parameters were only fitted to reaction‐independent phase equilibrium data. The key reaction properties were determined by applying ePC‐SAFT advanced to one experimental kinetic curve for a set of temperatures, yielding the reaction enthalpy at standard state
, activation energy
and the intrinsic reaction rate constant k=0.011 s−1 at 323 K, which is independent of catalyst concentration. The new procedure allowed an a‐priori identification of the effects of catalyst, solvent and reactant concentration on LA esterification.
Nucleic Acid Aptamers for Pesticides, Toxins, and Biomarkers in Agriculture
Authors: Hu Rongping , Shi Jun , Tian Cheng , Chen Xiaojuan , Zuo Hua
Published: October 2022

Nucleic acid aptamers are short single‐stranded DNA/RNA (ssDNA/RNA) oligonucleotides that can selectively bind to the targets. They are widely used in medicine, biosensing, and diagnostic assay. They have also been identified and extensively used for various targets in agriculture. In this review we summarize the progress of nucleic acid aptamers on pesticides (herbicides, insecticides, and fungicides), toxins, specific biomarkers of crops, and plant growth regulators in agricultural field in recent years. The basic process of aptamer selection, the already identified DNA/RNA aptamers and the aptasensors are discussed. We also discuss the future perspectives and the challenges for aptamer development in agriculture.
Dynamic 3D Combinatorial Generation of hPSC‐Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities
Authors: Whye Dosh , Wood Delaney , Kim Kristina H. , Chen Cidi , Makhortova Nina , Sahin Mustafa , Buttermore Elizabeth D.
Published: October 2022

Neuromesodermal progenitors represent a unique, bipotent population of progenitors residing in the tail bud of the developing embryo, which give rise to the caudal spinal cord cell types of neuroectodermal lineage as well as the adjacent paraxial somite cell types of mesodermal origin. With the advent of stem cell technologies, including induced pluripotent stem cells (iPSCs), the modeling of rare genetic disorders can be accomplished in vitro to interrogate cell‐type specific pathological mechanisms in human patient conditions. Stem cell‐derived models of neuromesodermal progenitors have been accomplished by several developmental biology groups; however, most employ a 2D monolayer format that does not fully reflect the complexity of cellular differentiation in the developing embryo. This article presents a dynamic 3D combinatorial method to generate robust populations of human pluripotent stem cell‐derived neuromesodermal organoids with multi‐cellular fates and regional identities. By utilizing a dynamic 3D suspension format for the differentiation process, the organoids differentiated by following this protocol display a hallmark of embryonic development that involves a morphological elongation known as axial extension. Furthermore, by employing a combinatorial screening assay, we dissect essential pathways for optimally directing the patterning of pluripotent stem cells into neuromesodermal organoids. This protocol highlights the influence of timing, duration, and concentration of WNT and fibroblast growth factor (FGF) signaling pathways on enhancing early neuromesodermal identity, and later, downstream cell fate specification through combined synergies of retinoid signaling and sonic hedgehog activation. Finally, through robust inhibition of the Notch signaling pathway, this protocol accelerates the acquisition of terminal cell identities. This enhanced organoid model can serve as a powerful tool for studying normal developmental processes as well as investigating complex neurodevelopmental disorders, such as neural tube defects. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Robust generation of 3D hPSC‐derived spheroid populations in dynamic motion settings

Support Protocol 1: Pluronic F‐127 reagent preparation and coating to generate low‐attachment suspension culture dishes

Basic Protocol 2: Enhanced specification of hPSCs into NMP organoids

Support Protocol 2: Combinatorial pathway assay for NMP organoid protocol optimization

Basic Protocol 3: Differentiation of NMP organoids along diverse cellular trajectories and accelerated terminal fate specification into neurons, neural crest, and sclerotome derivatives
Clinical status and assessment of caries on first permanent molars in a group of 6‐ to 13‐year‐old Tunisian school children
Authors: Chouchene Farah , Masmoudi Fatma , Baaziz Ahlem , Maatouk Fethi , Ghedira Hichem
Published: October 2022

Aim

The present survey aimed to highlight the clinical status of first permanent molars (FPMs) among a group of children aged between 6 and 13 years in public primary schools in Tunisia and to determine the association between FPMs' dental caries, gingival bleeding, malocclusion, dental fluorosis, and enamel defects.

Materials and Methods

The survey involved a cross‐sectional study based on a dental examination conducted in public primary schools in Monastir Tunisia. A dental caries assessment was performed on FPMs using the International Caries Detection and Assessment System classification; the number of carious lesions in permanent and temporary dentition was established using the decayed/missing/filled teeth (DMFT) index. The Gingival Index and the Dental Aesthetic Index were used to determine the occurrence of gingival bleeding and malocclusions. Dean's index and the modified Development Defects of Enamel index were used to define the enamel defects. The χ2 test was used to assess the difference between more than two groups, and the level of statistical significance was set at .05%.

Results

A total of 545 children and 2080 FPMs were examined. The prevalence of dental caries in FPMs was recorded to be 35.8%. The overall mean DMFT index of the study population was 1.62 and the mean DMFT index was 1.41. The proportion of carious FPMs increased significantly with the age of the children (p < .05). The mandibular first permanent molar presented higher caries prevalence than its maxillary counterpart (p < .05). The presence of surfaces affected by molar incisor hypomineralization was recorded in 4.3% and the presence of surfaces affected by fluorosis was recorded in 4.6% of FPMs. No association was reported between FPMs' dental caries, gingival bleeding, malocclusion, and enamel defects (p > .05).

Conclusion

Although the prevalence of caries in FPMs was considered moderate, health promotion programs should be implemented on a large scale to decrease the prevalence of dental caries among school children.
Predictors of outcomes after surgery for medically intractable insular epilepsy: A systematic review and individual participant data meta‐analysis
Authors: Obaid Sami , Chen Jia‐Shu , Ibrahim George M. , Bouthillier Alain , Dimentberg Evan , Surbeck Werner , Guadagno Elena , Brunette‐Clément Tristan , Shlobin Nathan A. , Shulkin Aidan , Hale Andrew T. , Tomycz Luke D. , Von Lehe Marec , Perry Michael Scott , Chassoux Francine , Bouilleret Viviane , Taussig Delphine , Fohlen Martine , Dorfmuller Georg , Hagiwara Koichi , Isnard Jean , Oluigbo Chima O. , Ikegaya Naoki , Nguyen Dang K. , Fallah Aria , Weil Alexander G.
Published: October 2022

Insular epilepsy (IE) is an increasingly recognized cause of drug‐resistant epilepsy amenable to surgery. However, concerns of suboptimal seizure control and permanent neurological morbidity hamper widespread adoption of surgery for IE. We performed a systematic review and individual participant data meta‐analysis to determine the efficacy and safety profile of surgery for IE and identify predictors of outcomes. Of 2483 unique citations, 24 retrospective studies reporting on 312 participants were eligible for inclusion. The median follow‐up duration was 2.58 years (range, 0‐17 years), and 206 (66.7%) patients were seizure‐free at last follow‐up. Younger age at surgery (≤18 years; HR = 1.70, 95% CI = 1.09‐2.66, P = .022) and invasive EEG monitoring (HR = 1.97, 95% CI = 1.04‐3.74, P = .039) were significantly associated with shorter time to seizure recurrence. Performing MR‐guided laser ablation or radiofrequency ablation instead of open resection (OR = 2.05, 95% CI = 1.08‐3.89, P = .028) was independently associated with suboptimal or poor seizure outcome (Engel II‐IV) at last follow‐up. Postoperative neurological complications occurred in 42.5% of patients, most commonly motor deficits (29.9%). Permanent neurological complications occurred in 7.8% of surgeries, including 5% and 1.4% rate of permanent motor deficits and dysphasia, respectively. Resection of the frontal operculum was independently associated with greater odds of motor deficits (OR = 2.75, 95% CI = 1.46‐5.15, P = .002). Dominant‐hemisphere resections were independently associated with dysphasia (OR = 13.09, 95% CI = 2.22‐77.14, P = .005) albeit none of the observed language deficits were permanent. Surgery for IE is associated with a good efficacy/safety profile. Most patients experience seizure freedom, and neurological deficits are predominantly transient. Pediatric patients and those requiring invasive monitoring or undergoing stereotactic ablation procedures experience lower rates of seizure freedom. Transgression of the frontal operculum should be avoided if it is not deemed part of the epileptogenic zone. Well‐selected candidates undergoing dominant‐hemisphere resection are more likely to exhibit transient language deficits; however, the risk of permanent deficit is very low.