bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring risk factors for persistent neurocognitive sequelae after hospitalization for COVID‐19
Authors: Ch'en Peter Y. , Gold Laura S. , Lu Qiongshi , Ye Ting , Andrews James S. , Patel Payal
Published: June 2023

Objective

In this study of patients hospitalized during acute SARS‐CoV2 infection with 6‐months of follow‐up data, we identified risk factors associated with the development of neuro‐PASC.

Methods

We conducted an exploratory, observational single‐center cohort study of patients hospitalized for COVID‐19 from November 2020 to March 2022. Our primary outcome was persistent neurocognitive symptoms, defined as fatigue, headache, loss of taste/smell, brain fog, confusion, concentration/memory/word finding difficulty, and/or change in speech present at 1‐month and persisting for 6‐months following acute SARS‐CoV2 infection. Secondary outcomes included persistent impairment scores on PROMIS cognitive function and abilities scales. Multivariate logistic regression analyses identified potential risk factors for neuro‐PASC.

Results

Of 89 participants, 60% reported persistent neurocognitive symptoms at 6‐months; fatigue was the most prevalent, occurring in 53% of participants, followed by brain fog in 34% of participants.

Lower self‐reported socioeconomic status and increased pre‐COVID‐19 anxiety scores on the Hospital Anxiety and Depression Scale were associated with increased odds of developing persistent neurocognitive symptoms. Being female and of Hispanic descent were associated with increased odds of persistent cognitive function and ability impairment.

Interpretation

Sociodemographic factors and pre‐COVID‐19 anxiety symptoms may be important risk factors for neuro‐PASC. These findings underscore the need to assess various sociodemographic factors in research on PASC. Our study also highlights premorbid mental health symptoms as a potential predictor of persistent neurocognitive symptoms following hospitalization with SARS‐CoV2 infection.
New ASAM criteria will force change for residential programs
Authors: Enos Gary
Published: June 2023

When final publication of the fourth edition of The ASAM Criteria occurs in the fall, substance use treatment providers will see a document more relevant to the continuum‐of‐care approach that is taking hold in the industry. The co‐CEO of one of the nation's most prominent treatment facilities believes the field's traditional residential programs will have to adjust the most to the latest edition of the industry's main guide to level‐of‐care placement and treatment planning.
NASADAD explainer: Role of the SOTA 2023
Authors: Knopf Alison
Published: June 2023

Many people may not be aware that the State Opioid Treatment Authority (SOTA) is the single authority that can oversee opioid treatment programs (OTPs). The SOTA, in most states, is overseen by the director of the state alcohol and drug agency, also known as the Single State Agency (SSA) for alcohol and other drugs. The director of the SSA is a member of the National Association of State Alcohol and Drug Abuse Directors (NASADAD), which last month issued a fact sheet describing the role of the SOTA.
FDA approves Brixadi, new buprenorphine treatment option
Authors: Knopf Alison
Published: June 2023

Last month the U.S. Food and Drug Administration approved Brixadi (buprenorphine) extended‐release injection for subcutaneous use to treat moderate to severe opioid use disorder (OUD). Brixadi is available in two formulations: A weekly injection that can be used in patients who have started treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine, and a monthly version for patients already being treated with buprenorphine. It is not for induction or new treatment. The weekly doses are 8 milligrams (mg), 16 mg, 24 mg, 32 mg; and the monthly doses are 64 mg, 96 mg, and 128 mg. The approved weekly formulation in various lower strengths offers a new option for people in recovery who may benefit from a weekly injection to maintain treatment adherence. Brixadi will be available through a risk evaluation and mitigation strategy program and administered only by health care providers in a health care setting. The FDA granted approval of Brixadi to Braeburn Inc.
Design and Development of In‐Process‐Resolution‐Tunable Stereolithography System Utilizing Two‐Photon Polymerization
Authors: Shinohara Makoto , Ushida Takashi , Furukawa Katsuko S.
Published: June 2023

Two‐photon lithography is considered a promising technology because it can achieve high resolution up to scale of 100 nm among additional processing technologies; further, it can be used to fabricate nano‐/microstructures. However, it requires an unrealistic long time to obtain a practical model that is close to the human organ diameter in the order of millimeters. In this study, an in‐process‐resolution‐tunable (iPRT) stereolithography system is reported, that realizes an optimal laser processing pathway using a new algorithm that automatically generates the processing pathway obtained by dividing the fabrication area by the effect of microstructure disappearance during the surface offset. It is demonstrated that the aforementioned algorithm can produce structures up to 50 times faster than the conventional methods and can be applied to cell culture scaffold for regenerative medicine.
Enhanced Transdermal Peptide‐Modified Flexible Liposomes for Efficient Percutaneous Delivery of Chrysomycin A to Treat Subcutaneous Melanoma and Intradermal MRSA Infection
Authors: Cai Yue , Chu Yuteng , Gong Yubei , Hong Yulu , Song Fuhang , Wang Hong , Zhang Huawei , Sun Xuanrong
Published: June 2023

Superficial skin diseases, including skin infections and tumors, are common healthcare burdens. In this study, the in vivo activity of chrysomycin A (CA) is explored, and a transdermal liposomal CA formulation is further constructed for the simultaneous treatment of cutaneous melanoma and cutaneous methicillin‐resistant Staphylococcus aureus (MRSA) infection. The prepared liposomes (TD‐LP‐CA) display a strong antitumor effect with an IC50 value of less than 0.1 µm in B16‐F10 cells, suppress the proliferation of MRSA with a minimum inhibitory concentration (MIC) of 1 µm, and eradicate established MRSA biofilms at 10× MIC in vitro. More importantly, TD‐LP‐CA shows enhanced stratum corneum (SC) penetration, reaching more than 500 µm beneath the skin's surface due to modification with the TD peptide, and demonstrates excellent subcutaneous tumor penetration after skin application in vivo. TD‐LP‐CA displays an excellent therapeutic effect against intradermal MRSA infection in mice after topical dermal administration, as well as a moderate inhibitory effect on subcutaneous melanoma with a 75% tumor inhibition rate. The liposomes prepared herein can be a promising carrier for transcutaneous CA transfer for the treatment of superficial diseases such as skin tumors and infections due to their ability to overcome the skin barrier.
Interfacial Passivation Enormously Enhances Electroluminescence of Triphenylphosphine Cu4I4 Cube
Authors: Li Ying , Zhang Xianfa , Man Yi , Xu Shiwei , Zhang Jing , Zhang Guangming , Chen Shuo , Duan Chunbo , Han Chunmiao , Xu Hui
Published: June 2023

Defect is one of the key factors limiting optoelectronic performances of organic–inorganic hybrid systems. Although high‐efficiency bidentate ligands based electroluminescent (EL) clusters reported, until present, only few EL clusters based on monodentate ligands are realized since their structural instability induces more surface/interface defects. Herein, this bottleneck is first overcome in virtue of interfacial passivation by electron transporting layers (ETL). Through using TmPyPB with meta‐linked pyridines as ETL, photoluminescent (PL) and EL quantum efficiencies of the simplest monophosphine Cu4I4 cube [TPP]4Cu4I4 are greatly improved by ≈2 and 23 folds, respectively, as well as ≈200 folds increased luminance, corresponding to a huge leap from nearly unlighted (<20 nits) to highly bright (>3000 nits). The passivation effect of TmPyPB on surface defects of cluster layer is embodied as preventing interfacial charge trapping and suppressing exciton nonradiation.
Large‐Area Flexible Thin Film Encapsulation with High Barrier and Super‐Hydrophobic Property
Authors: Li Chao , Yue Shizhong , Tian Wang , Ye Yumin , Liu Jun , Huang Yanbin , Huang Zhitao , Wu Yulin , Sun Jiaqian , Zhao Zeren , Dong Keqian , Liu Kong , Wang Zhijie , Qu Shengchun
Published: June 2023

With the development of optoelectronic devices toward miniaturization, flexibility, and large‐scale integration, conventional submillimeter rigid encapsulation techniques rarely achieve conformational functionality while blocking water and oxygen. At the same time, the sensitivity of electronic devices with organic/metal/semiconductor components to humidity and oxygen severely impairs their operational stability and lifetime. Here, a nanometer to micrometer scale organic/inorganic hybrid thin film encapsulation (TFE) with the self‐cleaning ability for flexible encapsulation is developed. The water vapor transmittance rate of polyethylene terephthalate substrate coated with the TFE is as low as 1.65 × 10−4 g m−2 day−1, and the barrier improvement factor reaches 104 at 38 °C and 90% relative humidity. This value is equivalent to 9.81 × 10−6 g m−2 day−1 at ambient conditions, sufficient to improve the lifetime of water‐sensitive electronic devices. Meanwhile, this TFE shows a super‐hydrophobic performance, with a water contact angle of 168.4°. In addition, the resulting barrier films exhibit outstanding optical properties, with an average optical transmittance of 86.88% in the visible region. This versatile TFE can promote the development of optoelectronic devices toward miniaturization and large‐scale integration in the future.
X‐Ray Visualized Synovial Fluid Carbon Dioxide Sensor for Early Detection of Prosthetic Hip Infections
Authors: Kiridena Sachindra Dulashini , Wijayaratna Uthpala Nawamali , Wang Rong , Anker Jeffrey Nathan
Published: June 2023

A radiographically visualized implantable dissolved carbon dioxide (CO2) sensor is developed to non‐invasively detect and monitor hip infections. The sensor is based on a pH‐responsive hydrogel as the sensing material, immersed in a carbonate buffer contained in a capsule with a CO2‐permeable membrane. Dissolved CO2 decreases the buffer pH causing the polyacrylic acid‐based hydrogel to shrink. The hydrogel length is determined using plain radiography by measuring the movement of a radiodense tantalum bead embedded in the hydrogel with respect to a metal wire in the casing. The sensor shows a clear response in the range of 15–115 mm Hg CO2, with a 4.3 mm Hg precision at 15 mm Hg CO2 level and a 6.4‐hour response time. The hydrophobic CO2‐permeable membrane is impermeable to aqueous molecules rendering the CO2 measurement independent of the external solution pH, which can be measured with a separate X‐ray visualized sensor. Separating the sensor from the aqueous environment is also expected to reduce the potential for biofouling and increase longevity. In summary, the first dissolved gas sensor that can be visualized radiographically is described; it has potential applications in detecting and studying implant infection and local carbon tissue CO2 levels.
Micro‐Scaling Metal‐Organic Framework Films through Direct Laser Writing for Chemical Sensing
Authors: Olorunyomi Joseph F. , Singh Ruhani , Nasa Zeyad , Caruso Rachel A. , Doherty Cara M.
Published: June 2023

A zeolitic imidazolate framework (ZIF‐8) containing two enzymes that form a cascade biocatalyst has been integrated with 3D structures that are fabricated through a two‐photon polymerization using direct laser writing lithography. Glucose oxidase (GOx) and horseradish peroxidase (HRP) are encapsulated by the biomimetic self‐assembly process of ZIF‐8 to form the GOx/HRP/ZIF‐8 composite which grows in situ on the surface of microprinted carbon‐coated hexagonal substrates (cHS). The GOx/HRP/ZIF‐8/cHS film is applied to glucose detection through enzymatic oxidation of glucose to gluconic acid, forming H2O2, in the presence of GOx and the subsequent reduction of H2O2 to water in the presence of HRP and Amplex Red. This reaction is monitored using fluorimetry as the oxidation of Amplex Red with H2O2 catalyzed by HRP forms red‐emitting resorufin. The GOx/HRP/ZIF‐8/cHS film responds to glucose concentrations with a linear range of 10–200 µm, which correlates to the salivary glucose level in healthy humans. The GOx/HRP/ZIF‐8/cHS film shows more than eight times and 13 times enhanced activity than GOx/HRP/cHS (without ZIF‐8) and GOx/HRP/ZIF‐8 on a non‐3D patterned substrate, respectively. The GOx/HRP/ZIF‐8/cHS film retains more than 80% or 100% of its initial activity after being stored for over 2 months at ≤24 or 4 °C, respectively.
A Spectrofluorometric Method for Real‐Time Graft Assessment and Patient Monitoring
Authors: Huwyler Florian , Eden Janina , Binz Jonas , Cunningham Leslie , Sousa Da Silva Richard X. , Clavien Pierre‐Alain , Dutkowski Philipp , Tibbitt Mark W. , Hefti Max
Published: June 2023

Biomarkers are powerful clinical diagnostics and predictors of patient outcome. However, robust measurements often require time and expensive laboratory equipment, which is insufficient to track rapid changes and limits direct use in the operating room. Here, this study presents a portable spectrophotometric device for continuous real‐time measurements of fluorescent and non‐fluorescent biomarkers at the point of care. This study measures the mitochondrial damage biomarker flavin mononucleotide (FMN) in 26 extended criteria human liver grafts undergoing hypothermic oxygenated perfusion to guide clinical graft assessment. Real‐time data identified seven organs unsuitable for transplant that are discarded. The remaining grafts are transplanted and FMN values correlated with post‐transplant indicators of liver function and patient recovery. Further, this study shows how this device can be used to monitor dialysis patients by measuring creatinine in real‐time. Our approach provides a simple method to monitor biomarkers directly within biological fluids to improve organ assessment, patient care, and biomarker discovery.
Recurrence patterns among patients with sinonasal mucosal melanoma: A multi‐institutional study
Authors: Pandrangi Vivek C. , Mace Jess C. , Abiri Arash , Adappa Nithin D. , Beswick Daniel M. , Chang Eugene H. , Eide Jacob G. , Fung Nicholas , Hong Michelle , Johnson Brian J. , Kohanski Michael A. , Kshirsagar Rijul S. , Kuan Edward C. , Le Christopher H. , Lee Jivianne T. , Nabavizadeh Seyed A. , Obermeyer Isaac P. , Palmer James N. , Pinheiro‐Neto Carlos D. , Smith Timothy L. , Snyderman Carl H. , Suh Jeffrey D. , Wang Eric W. , Wang Marilene B. , Choby Garret , Geltzeiler Mathew
Published: June 2023

Objective

To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM).

Methods

This was a multi‐institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan‐Meier tests were used to evaluate disease‐free survival (DFS), overall survival (OS), and post‐recurrence survival (PRS) reported with standard errors (SE) and log‐rank testing used for comparison. Cox‐regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported.

Results

Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60‐month DFS (SE) was 15.5% (2.9%), 60‐month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60‐month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60‐month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12‐month PRS (HR = 0.32, 95% CI = 0.11–0.92, p = 0.034), and no treatment group was associated with improved 24‐ or 60‐month PRS (p > 0.05).

Conclusion

SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12‐month PRS.
The Metabolostasis Network and the Cellular Depository of Aggregation‐Prone Metabolites
Authors: Levkovich Shon A. , Gazit Ehud , Laor Bar‐Yosef Dana
Published: June 2023

The vital role of metabolites across all branches of life and their involvement in various disorders have been investigated for decades. Many metabolites are poorly soluble in water or in physiological buffers and tend to form supramolecular aggregates. On the other hand, in the cell, they should be preserved in a pool and be readily available for the execution of biochemical functions. We thus propose that a quality‐control network, termed “metabolostasis”, has evolved to regulate the storage and retrieval of aggregation‐prone metabolites. Such a system should control metabolite concentration, subcellular localization, supramolecular arrangement, and interaction in dynamic environments, thus enabling normal cellular physiology, healthy development, and preventing disease onset. The paradigm‐shifting concept of metabolostasis calls for a reevaluation of the traditional view of metabolite storage and dynamics in physiology and pathology and proposes unprecedented directions for therapeutic targets under conditions where metabolostasis is imbalanced.
Cobalt‐Catalyzed Asymmetric Remote Borylation of Alkyl Halides
Authors: Zhang Minghao , Ye Zhiyang , Zhao Wanxiang
Published: June 2023

Enantioselective functionalization of racemic alkyl halides is an efficient strategy to assemble complex chiral molecules, but remains one of the biggest challenges in organic chemistry. The distant and selective activation of unreactive C−H bonds in alkyl halides has received growing interest as it enables rapid generation of molecular complexity from simple building blocks. Here, we reported a cobalt‐catalyzed remote borylation of alkyl (pseudo)halides (alkyl−X, X=I, Br, Cl, OTs) with pinacolborane (HBpin) and presented a robust approach for the generation of valuable chiral secondary organoboronates from racemic alkyl halides. This migration borylation reaction is compatible with primary, secondary, and tertiary bromides, offering direct access to a broad range of alkylboronates. The extension of this catalytic system to the borylation of aryl halides was also demonstrated. Preliminary mechanistic studies revealed that this remote borylation involved a radical reaction pathway.
Beyond Solvothermal: Alternative Synthetic Methods for Covalent Organic Frameworks
Authors: Hu Jiyun , Huang Zhiyuan , Liu Yi
Published: June 2023

Covalent organic frameworks (COFs) are crystalline porous organic materials that hold a wealth of potential applications across various fields. The development of COFs, however, is significantly impeded by the dearth of efficient synthetic methods. The traditional solvothermal approach, while prevalent, is fraught with challenges such as complicated processes, excessive energy consumption, long reaction times, and limited scalability, rendering it unsuitable for practical applications. The quest for simpler, quicker, more energy‐efficient, and environmentally benign synthetic strategies is thus paramount for bridging the gap between academic COF chemistry and industrial application. This Review provides an overview of the recent advances in alternative COF synthetic methods, with a particular emphasis on energy input. We discuss representative examples of COF synthesis facilitated by microwave, ultrasound, mechanic force, light, plasma, electric field, and electron beam. Perspectives on the advantages and limitations of these methods against the traditional solvothermal approach are highlighted.
Green deep‐UV photoresist based on chitosan for microelectronics
Authors: Sysova Olha , Durin Paule , Gablin Corinne , Léonard Didier , Téolis Alexandre , Trombotto Stéphane , Delair Thierry , Berling Dominique , Servin Isabelle , Tiron Raluca , Bazin Arnaud , Leclercq Jean‐Louis , Chevolot Yann , Soppera Olivier
Published: June 2023

Photolithography is a core part in microelectronic processes. This technological step implies the use of numerous hazardous carcinogenic compounds in the  formulations, the use of solvents for processing synthetic polymers to obtain micro and nanostructures. We proposed the use of chitosan‐based biosourced water‐soluble resins to significantly reduce the environmental impact of the photolithography step, for 193 nm photolithography. We show in this report that chitosan‐based photoresist is suitable for microelectronic application, and in particular, we could significantly improve photosensitivity by adding a water‐soluble photoacid generator (PAG). UV–visible and Fourier transform infrared‐attenuated total reflectance characterizations reveal an increase of the macromolecular chain scission kinetics in the presence of PAG. Moreover, the local decrease of the pH favors the solubility of chitosan in irradiated areas. Finally, the photolithography tests demonstrate that the dose to clear and the optimal dose for photopatterning are divided by a factor of two. Moreover, the physical etching transfer tests show that the presence of PAG does not decrease the transfer performance, making these aqueous‐based formulated resins still more adapted for the fabrication of microelectronic devices.
Treatment outcomes of advanced/metastatic extramammary Paget's disease in Korean patients: KCSG‐RC20‐06
Authors: Sohn Byeong Seok , Kim Jeongeun , Kim Miso , Hong Jung Yong , Lee Jieun , Park Song Ee , Kim Hyojeong , Lee Hyo Jin , Kang Eun Joo , Lee Soon Il , Lee In Hee , Huh Seok Jae , Jo Jeongmin , Kim Ho Young
Published: June 2023

Background

Extramammary Paget's disease (EMPD) is rare. There are no standard treatments due to its rarity and few clinical trials.

Methods

The objective of this multicenter study was to investigate treatment outcomes of Korean patients with advanced/metastatic EMPD. Data were collected retrospectively from 14 institutions participating in Korean Cancer Study Group (KCSG) Rare Cancer Committee.

Results

A total of 37 patients were identified. Of these 37 patients, 6 received locoregional therapy as a first‐line treatment. In 31 patients who received systemic chemotherapy as a first‐line treatment, platinum‐based chemotherapy (n = 22) achieved an objective response rate (ORR) of 45.5% and a median progression‐free survival (PFS) of 7.89 months. Taxane‐based chemotherapy (n = 8) achieved an objective response rate of 62.5% and median PFS of 9.73 months. In second‐line chemotherapy, platinum‐based chemotherapy (n = 4) had a disease control rate (DCR) of 75.0% and median PFS of 3.45 months. Taxane‐based chemotherapy (n = 8) had a DCR of 75.0% and a median PFS of 8.67 months. Six patients received anti‐human epidermal growth factor receptor 2 (HER2) antibody during first‐ and second‐line chemotherapy. Overall, systemic chemotherapy combined with anti‐HER2 antibody had an ORR of 100% and a median PFS of 13.31 months. The ORR and PFS with systemic chemotherapy combined with trastuzumab was better than platinum‐ and taxane‐based chemotherapy only.

Conclusions

Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that the combination of trastuzumab with taxane has longer survival than trastuzumab monotherapy or conventional platinum‐ or taxane‐based chemotherapy.
Phenolic Characterization and Antioxidant Activity of Chrysanthemum indicum and Opisthopappus Shih during Different Growth Stages
Authors: Wei Dongwei , Sun Wuyong , Huang Mingren , Zeng Xiaoning , Chen Yun , Yuan Zhiliang
Published: June 2023

Recently, much attention has been devoted to natural phenolics because of their ideal structure and chemistry for free radical scavenging activities, which may play important roles in long‐term health and a reduction in the risk of developing chronic degenerative diseases. Chrysanthemum indicum (C. indicum) has been widely used as a health food and as a popular herb in China for many centuries. Opisthopappus Shih (O. shih) often takes the place of its related genera, C. indicum, in functional tea or medicine prescriptions in place of origin. In this article, a comparative study on the phenolics and antioxidant activity of C. indicum and O. shih during different growth stages was investigated. The antioxidant properties of plant extracts were tested using DPPH and ABTS assays. The characterization of potential phytochemicals was carried out using Fourier transform infrared (FT‐IR) spectroscopy. Total phenolics (TPC) and total flavonoid content (TFC) were measured using Folin‐Ciocalteu and aluminum chloride colorimetric methods, respectively. An HPLC method was used to simultaneously quantify five phenolic compounds, including chlorogenic acid, luteolin, rutin, quercetin, and apigenin. Results indicated that the Trolox equivalent antioxidant activity (TEAC) values of C. indicum and O. shih had extremely large variations at different growth stages. The most abundant phenolics and potent antioxidant activity of two related plants appear at the early vegetative and then flowering stages. Antioxidant activities and phenolic content of O. shih were higher than those of corresponding organs of C. indicum at the same collection time. The whole plant of O. shih, especially its leaves and flowers, are good candidates for obtaining nutraceuticals and functional food ingredients.
Antiproliferative Activity and Ultrastructural Changes in Promastigote and Amastigote forms of Leishmania amazonensis Caused by Limonene‐Acylthiosemicarbazide Hybrids
Authors: Graça Contato Alex , Kaplum Vanessa , Botura Scariot Débora , Pelegrin Garcia Francielle , Falzirolli Hugo , Vandresen Fábio , Ueda‐Nakamura Tânia , de Oliveira Silva Sueli , Conceição da Silva Cleuza , Vataru Nakamura Celso
Published: June 2023

Leishmaniasis is a tropical zoonotic disease. It is found in 98 countries, with an estimated 1.3 million people being affected annually. During the life cycle, the Leishmania parasite alternates between promastigote and amastigote forms. The first line treatment for leishmaniasis are the pentavalent antimonials, such as N‐methylglucamine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®). These drugs are commonly related to be associated with dangerous side effects such as cardiotoxicity, nephrotoxicity, hepatotoxicity, and pancreatitis. Considering these aspects, this work aimed to obtain a new series of limonene‐acylthiosemicarbazides hybrids as an alternative for the treatment of leishmaniasis. For this, promastigotes, axenic amastigotes, and intracellular amastigotes of Leishmania amazonensis were used in the antiproliferative assay; J774‐A1 macrophages for the cytotoxicity assay; and electron microscopy techniques were performed to analyze the morphology and ultrastructure of parasites. ATZ−S‐04 compound showed the best result in both tests. Its IC50, in promastigotes, axenic amastigotes and intracellular amastigotes was 0.35±0.08 μM, 0.49±0.06 μM, and 15.90±2.88 μM, respectively. Cytotoxicity assay determined a CC50 of 16.10±1.76 μM for the same compound. By electron microscopy, it was observed that ATZ−S‐04 affected mainly the Golgi complex, in addition to morphological changes in promastigote forms of L. amazonensis.
Impact of vascular complications after transcatheter aortic valve implantation. VASC‐OBSERVANT II sub‐study
Authors: Aurigemma Cristina , Trani Carlo , D'Errigo Paola , Barbanti Marco , Biancari Fausto , Tarantini Giuseppe , Santoro Gennaro , Baiocchi Massimo , Baglio Giovanni , Seccareccia Fulvia , Rosato Stefano ,   the OBSERVANT II Research Group
Published: June 2023

Background

Trans‐femoral (TF) access is the commonest approach for transcatheter aortic valve implantation (TAVI). However this vascular approach is associated with vascular complications (VC) which in turn have prognostic implications. The aim of this study is to evaluate the clinical impact of access site VC in patients undergoing TAVI with newer generation transcatheter prostheses enrolled in the national observational prospective multicenter study OBSERVANT II.

Methods

Vascular events were defined according to the Valve Academic Research Consortium (VARC)‐2 criteria. The population enrolled in OBSERVANT II was divided into 3 groups: patients without VC (No‐VC), patients with minor VC or percutaneous closure device failure (Minor‐VC) and patients with major VC (Major‐VC). The primary endpoint was 1‐year major adverse cardiac and cerebrovascular event (MACCE), a composite endpoint of all‐cause mortality, stroke, myocardial infarction and coronary revascularization. A multivariate Cox regression model was used for risk estimation of MACCE between the three analyzed groups.

Results

2.504 patients were included in this analysis: 2.167 patients in No‐VC group; 249 patients in the Minor‐VC and 88 patients in the Major‐VC. At 1‐year Minor‐VC group had a freedom from MACCE comparable to the No‐VC group, while Major‐VC patients had significantly worse outcome (Log‐rank test: p = 0.003). These results were driven by higher 1‐year mortality in the Major‐VC (p < 0.0001). Major‐VC was an independent predictor of MACCE in adjusted analysis (hazard ratio 1.89, 95% confidence interval 1.18‐3.03, p = 0.008).

Conclusions

Despite a low incidence of major VC with current TF‐TAVI devices, our data confirm that major VC is still associated with a significantly worse clinical outcome.
“Sandwich” Diimine‐Copper Catalyzed Trifluoroethylation and Pentafluoropropylation of Unactivated C(sp3)−H Bonds by Carbene Insertion
Authors: Le Thanh V. , Romero Irvin , Daugulis Olafs
Published: June 2023

We report here “sandwich”‐diimine copper complex‐catalyzed trifluoroethylation and pentafluoropropylation of unactivated C(sp3)−H bonds in alkyl esters, halides, and protected amines by employing CF3CHN2 and CF3CF2CHN2 reagents. Reactions proceed in dichloromethane solvent at room temperature. Identical C−H functionalization conditions and stoichiometries are employed for generality and convenience. Selectivities for C−H insertions are higher for compounds possessing stronger electron‐withdrawing substituents. Preliminary mechanistic studies point to a mechanism involving a pre‐equilibrium forming a “sandwich”‐diimine copper‐CF3CHN2 complex followed by rate‐determining loss of nitrogen affording the reactive copper carbene. It reacts with trifluoromethyldiazomethane about 6.5 times faster than with 1‐fluoroadamantane explaining the need for slow addition of the diazo compound.
2,2’‐Biquinoline‐Based Recyclable Electroauxiliaries for the Generation of Alkyl Radicals via C−C Bond Cleavage
Authors: Ratnam Shahilan , Unone Shreya , Janssen‐Müller Daniel
Published: June 2023

Alkyl radical precursors are essential for a wide variety of photocatalytic and 3d‐metal‐catalyzed C−C bond forming reactions. Neutral organic heterocycles as electroauxiliaries such as 4‐alkyl Hantzsch esters have become reliable tools for alkyl radical formation. Here we show that 2,2’‐biquinoline‐derived alkyl‐substituted dihydroquinolines act as competent radical precursors with the ability to form primary, secondary and tertiary alkyl radicals. Hydroalkylation of benzalmalononitriles and N‐Boc protected diazenes has been achieved through copper catalysis under mild conditions of 50 °C with good to very good yields of up to 85 %. Furthermore, the dihydroquinolines’ reactivity towards a denitrative alkylation of nitroolefins such as β‐nitrostyrene was discovered. Most importantly, the released biquinoline can be recycled, which greatly improves the overall atom‐economy of these alkyl radical precursors in comparison to previous N‐heterocyclic electroauxiliaries.
Revisiting the TCNQF40/1−/2− Catalysis Mechanism for the [Fe(CN)6]3−/4−‐S2O32−/S4O62− Redox Reaction
Authors: Alzubidi Anbrah E. , Bond Alan M. , Martin Lisandra L.
Published: June 2023

The front cover artwork was done by Michelle Farrelly, a member of the Martin group at Monash University. The image represents a perspective of a cuvette in which the catalysis of the thiosulfate‐ferricyanide reaction was achieved by a TCNQF4‐based redox reaction in aqueous solution. The primary method used to monitor these reactions was spectrophotometry. Read the full text of the Research Article at 10.1002/cphc.202200942.
Endoscopic clearance of non‐complex biliary stones using fluoroscopy‐free direct solitary cholangioscopy: Initial multicenter experience
Authors: Ridtitid Wiriyaporn , Rerknimitr Rungsun , Ramchandani Mohan , Lakhtakia Sundeep , Shah Raj J , Shah Janak N , Thosani Nirav , Goenka Mahesh K , Costamagna Guido , Wagh Mihir S , Perri Vincenzo , Peetermans Joyce , Goswamy Pooja G , Liu Zoe , Yin Srey , Banerjee Subhas
Published: June 2023

Background and Aims

Fluoroscopy‐free endoscopic retrograde cholangiopancreatography for common bile duct stone (CBDS) clearance is usually offered only to pregnant patients. We initiated a multicenter, randomized controlled trial comparing clearance of non‐complex CBDSs using fluoroscopy‐free direct solitary cholangioscopy (DSC) to standard endoscopic retrograde cholangiography (ERC) to evaluate the wider applicability of the DSC‐based approach. Here we report the initial results of stone clearance and safety in roll‐in cases for the randomized controlled trial.

Methods

Twelve expert endoscopists at tertiary care centers in four countries prospectively enrolled 47 patients with non‐complex CBDSs for DSC‐assisted CBDS removal in an index procedure including fluoroscopy‐free cannulation. Successful CBDS clearance was first determined by DSC and subsequently validated by final occlusion cholangiogram as the ERC gold standard.

Results

Fully fluoroscopy‐free cannulation was successful in 42/47 (89.4%) patients. Brief fluoroscopy with minimal contrast injection was used in 4/47 (8.5%) patients during cannulation. Cannulation failed in 1/47 (2.1%) patients. Fluoroscopy‐free complete stone clearance was reached in 38/46 (82.6%) cases. Residual stones were detected in the validation ERC occlusion cholangiogram in three cases. Overall serious adverse event rate was 2.1% (95% confidence interval 0.1–11.3): postprocedural pancreatitis in one patient.

Conclusions

In patients with non‐complex CBDS, the fluoroscopy‐free technique is easily transferred to endoscopic retrograde cholangiopancreatography experts with acceptable rates of cannulation and stone clearance and few serious adverse events. (ClinicalTrials.gov number, NCT03421340)
Impact of the COVID‐19 pandemic on the performance of endoscopy in the Tohoku region of Japan
Authors: Iijima Katsunori , Matsuhashi Tamotsu , Shimodaira Yosuke , Mikami Tatsuya , Yoshimura Tetsuro , Yanai Shunichi , Kudara Norihiko , Tsuji Tsuyotoshi , Matsushita Hiro‐o , Watanabe Hiroyuki , Koike Tomoyuki , Kato Katsuaki , Abe Yasuhiko , Shirahata Nakao , Hikichi Takuto , Katakura Kyoko , Kono Koji , Sakuraba Hirotake , Ueno Yoshiyuki , Ohira Hiromasa , Masamune Atsushi , Matsumoto Takayuki , Fukuda Shinsaku ,   Japan Gastroenterological Endoscopy Society‐Tohoku
Published: June 2023

Objectives

The whole picture of the disturbance in endoscopy performance caused by the coronavirus disease 2019 (COVID‐19) pandemic in Japan remains to be clarified. Therefore, the Japan Gastroenterological Endoscopy Society‐Tohoku conducted this questionnaire survey in Tohoku region of Japan.

Methods

A questionnaire on the number of diagnostic endoscopy procedures and resulting diagnosed cancers in 2019 and 2020 was sent to all guidance/guidance cooperation hospitals in the Japan Gastroenterological Endoscopy Society who worked in the Tohoku region. The percentage change was calculated by comparing the numbers in 2020 with those in 2019 (the pre‐COVID‐19 period).

Results

Among the applicable 89 guidance/guidance cooperation hospitals, 83 (94%) returned the questionnaire. The number of endoscopy procedures promptly decreased to the nadir in April and May 2020 (during the first state of emergency in Japan); however, it recovered relatively quickly, within a few months after the state of emergency was lifted. Consequently, the annual reduction in the number of endoscopy procedures in 2020 (in comparison to 2019) was 10.1% for esophagogastroduodenoscopy and 7.9% for colonoscopy. The reduction in the number of diagnostic endoscopy procedures led to a 5.5% reduction in esophagogastric cancer and 2.7% in colorectal cancer.

Conclusions

This is the most comprehensive survey on the impact of the COVID‐19 pandemic on the performance of endoscopy and the resulting diagnosis of cancer in Japan. Understanding the magnitude of the decline in endoscopic examinations and cancer detection due to the pandemic is critical to understanding how many people will ultimately be affected and establishing a strategy for providing endoscopy during national emergencies.
Detection of boldenone in the urine of female horses—ex vivo formation versus administration
Authors: Viljanto Marjaana , Kaabia Zied , Taylor Polly , Hincks Pamela , Muir Tessa , Habershon‐Butcher Jocelyn , Bailly‐Chouriberry Ludovic , Scarth James
Published: June 2023

Boldenone is an anabolic–androgenic steroid (AAS) that is prohibited in equine sports. However, in certain situations, it is endogenous, potentially formed by the microbes in urine. An approach to the differentiation based on the detection of the biomarkers Δ1‐progesterone, 20(S)‐hydroxy‐Δ1‐progesterone and 20(S)‐hydroxyprogesterone was assessed, and their concentrations were monitored in the urine of untreated female horses (n = 291) alongside boldenone, boldienone, testosterone and androstenedione. Using an ultra‐sensitive analytical method, boldenone (256 ± 236 pg/mL, n = 290) and the biomarkers (Δ1‐progesterone up to 57.6 pg/mL, n = 8; 20(S)‐hydroxy‐Δ1‐progesterone 85.3 ± 181 pg/mL, n = 130; 20(S)‐hydroxyprogesterone 43.5 ± 92.1 pg/mL, n = 158) were detected at low concentrations. The ex vivo production of Δ1‐steroids was artificially induced following the storage of urine samples at room temperature for 7 days in order to assess the concentrations and ratios of the monitored steroids. The administration of inappropriately stored feed source also resulted in an increase in 20(S)‐hydroxy‐Δ1‐progesterone concentrations and the biomarker ratios. Using the results from different datasets, an approach to differentiation was developed. In situations where the presence of boldenone exceeds a proposed action limit of 5 ng/mL, the presence of the biomarkers would be investigated. If Δ1‐progesterone is above 50 pg/mL or if 20(S)‐hydroxy‐Δ1‐progesterone is above 100 pg/mL with the ratio of 20(S)‐hydroxy‐Δ1‐progesterone:20(S)‐hydroxyprogesterone greater than 5:1, then this would indicate ex vivo transformation or consumption of altered feed rather than steroid administration. There remains a (small) possibility of a false negative result, but the model increases confidence that adverse analytical findings reported in female horses are caused by AAS administrations.
Retention of essential fatty acids in fish differs by species, habitat use and nutritional quality of prey
Authors: Bandara Tharindu , Brugel Sonia , Andersson Agneta , Lau Danny Chun Pong
Published: June 2023

Algae‐produced long‐chain polyunsaturated fatty acids (LC‐PUFA; with ≥20 carbon atoms) are key biomolecules for consumer production and animal health. They are transferred to higher trophic levels and accumulated in food chains. However, LC‐PUFA accumulation in consumers and their trophic transfer vary with the diet quality and the physiological demand for LC‐PUFA of consumers. The goal of this study was to investigate spatial and taxonomic differences in LC‐PUFA retention of coastal fish predators that potentially differ in their habitat use (benthic versus pelagic) and prey quality. We analyzed the fatty acid (FA) composition of common fish species, namely roach and European perch, as well as their potential prey from benthic and pelagic habitats in three bays of the northern Baltic Sea. We then assessed whether the fish LC‐PUFA retention differed between species and among the study bays with different diet quality, that is, LC‐PUFA availability. Our data indicated taxon‐specific differences in the retention of LC‐PUFA and their precursor FA in fish (i.e., short‐chain PUFA with <20 carbon atoms). Perch did not show any spatial variation in the retention of all these FA, while roach showed spatial differences in the retention of docosahexaenoic acid (DHA) and their precursor FA, but not eicosapentaenoic acid (EPA). Data suggest that diet quality and trophic reliance on benthic prey underlay the DHA retention differences in roach. Although the PUFA supply might differ among sites, the low spatial variation in LC‐PUFA content of perch and roach indicates that both fishes were able to selectively retain dietary LC‐PUFA. Climate change together with other existing human‐caused environmental stressors are expected to alter the algal assemblages and lower their LC‐PUFA supply for aquatic food webs. Our findings imply that these stressors will pose heterogeneous impacts on different fish predators. We advocate further investigations on how environmental changes would affect the nutritional quality of the basal trophic level, and their subsequent impacts on LC‐PUFA retention, trophic ecology, and performance of individual fish species.
Understanding the state‐dependent impact of species correlated responses on community sensitivity to perturbations
Authors: Medeiros Lucas P. , Saavedra Serguei
Published: June 2023

Understanding how communities respond to perturbations requires us to consider not only changes in the abundance of individual species but also correlated changes that can emerge through interspecific effects. However, our knowledge of this phenomenon is mostly constrained to situations where interspecific effects are fixed. Here, we introduce a framework to disentangle the impact of species correlated responses on community sensitivity to perturbations when interspecific effects change over time due to cyclic or chaotic population dynamics. We partition the volume expansion rate of perturbed abundances (community sensitivity) into contributions of individual species and of species correlated responses by converting the time‐varying Jacobian matrix containing interspecific effects into a time‐varying covariance matrix. Using population dynamics models, we demonstrate that species correlated responses change considerably across time and continuously alternate between reducing and having no impact on community sensitivity. Importantly, these alternating impacts depend on the abundance of particular species and can be detected even from noisy time series. We showcase our framework using two experimental predator–prey time series and find that the impact of species correlated responses is modulated by prey abundance—as theoretically expected. Our results provide new insights into how and when species interactions can dampen community sensitivity when abundances fluctuate over time.
Long‐term drivers of shoreline change over two centuries on a headland‐embayment beach
Authors: Grottoli Edoardo , Biausque Mélanie , Jackson Derek W. T. , Cooper J. Andrew G.
Published: June 2023

Shoreline evolution over the last two centuries was analysed for Dundrum Bay, Co. Down, Northern Ireland, using historical and recent shoreline datasets from 1833 to 2020. The area of interest comprises two sandy beaches and vegetated coastal dune fields, Newcastle–Murlough and Ballykinler, separated by an inlet channel which connects the inner with the outer bay. Twenty‐four temporal shorelines were extracted, and a quantitative assessment of their positional uncertainty was performed. This was combined with analysis of foredune volume variations by applying the Structure‐from‐Motion‐Multi‐View‐Stereo technique to 1963 aerial photography and comparing it with a 2014 Light Detection And Ranging (LiDAR) dataset to better inform on links between the sediment dynamics and the observed shoreline changes. Storm events were identified using recorded extreme water levels (EWLs) (1901–2020) and hindcasted wave data (1948–2020). In the first 87 years, the shoreline was largely stable, and change was focused at the inlet area. In the 20th century, localised retreat characterised the western (Newcastle–Murlough) sector, whereas the eastern sector (Ballykinler) experienced general shoreline advance. The rate and extent of shoreline retreat in the western sector increased post‐1997 in concert with accelerated accretion at Ballykinler. The strongest erosional episodes were recorded in 1920–1951, 1997–2005, and 2012–2014. Although no direct link was established between single storms and shoreline retreat rates, the three major retreat periods coincided with several consecutive EWLs or EWLs with a return period greater than 100 years. These were generated by storm directions ranging from south to southwest. The long‐term pattern of shoreline change points to a complex coastal system that is still evolving.
Building a better Mungbean: Breeding for reproductive resilience in a changing climate
Authors: Van Haeften Shanice , Dudley Caitlin , Kang Yichen , Smith Daniel , Nair Ramakrishnan M. , Douglas Colin A. , Potgieter Andries , Robinson Hannah , Hickey Lee T. , Smith Millicent R.
Published: June 2023

Mungbean (Vigna radiata (L.) R. Wilczek var. radiata) is a significant food and cash crop grown in tropical and subtropical regions. Mungbean production and consumer demand have increased substantially over the last two decades, owing to its agronomic, nutritional and economic benefits. Despite increased breeding efforts and the expansion of mungbean production in various agro‐climatic regions, further production is hindered by low yield and variability, which is partly attributed to the impacts of abiotic stress. Abiotic stress impacts on the physiology, morphology and reproductive ability of mungbean which influences yield. Exposure to abiotic stresses at the reproductive stage is considered the most critical for yield production. In this review, we evaluate how abiotic stress impacts mungbean growth and productivity when occurring during the reproductive stage and traits that may confer adaptation. We present the limitations of current research including limited number of genotypes, lack of field experiments and detailed experimental information. We highlight the opportunities to exploit new tools and technologies, such as high‐throughput phenotyping platforms, gene editing, and genomic selection, to accelerate breeding efforts to develop more resilient mungbean cultivars for today and tomorrow.