bluuebunny/crossref_metadata_2025 huggingface dataset:
Addiction Medicine Physicians and Medicinal Cannabinoids
Authors: Potenza Marc N. , Bunt Gregory , Khalsa Jag H.
Published: May 2023

This Viewpoint communicates the importance of clinicians, particularly addiction clinicians, to be educated about both harmful and beneficial effects of cannabis and related products before making therapeutic recommendations.
Association of the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet With the Risk of Dementia
Authors: Chen Hui , Dhana Klodian , Huang Yuhui , Huang Liyan , Tao Yang , Liu Xiaoran , Melo van Lent Debora , Zheng Yan , Ascherio Alberto , Willett Walter , Yuan Changzheng
Published: May 2023

Importance

Dementia threatens the well-being of older adults, making efforts toward prevention of great importance.

Objective

To evaluate the association of the Mediterranean–Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet with the risk of dementia in 3 prospective studies and a meta-analysis.

Design, Setting, and Participants

Cohort analyses included the Whitehall II study (WII), the Health and Retirement Study (HRS), and the Framingham Heart Study Offspring cohort (FOS), and the meta-analysis included 11 cohort studies. Participants were middle-aged and older women and men from WII in 2002 to 2004, HRS in 2013, and FOS in 1998 to 2001 without dementia at the study baseline. Data were analyzed from May 25 to September 1, 2022.

Exposures

MIND diet score was measured using food frequency questionnaires, and scores ranged from 0 to 15, with a higher score indicating higher adherence to the MIND diet.

Main Outcome and Measures

Incident all-cause dementia, with cohort-specific definitions.

Results

Included in this study were 8358 participants (mean [SD] age, 62.2 [6.0] years; 5777 male [69.1%]) from WII, 6758 participants (mean [SD] age, 66.5 [10.4] years; 3965 female [58.7%]) from HRS, and 3020 participants (mean [SD] age, 64.2 [9.1] years; 1648 female [54.6%]) from FOS. The mean (SD) baseline MIND diet score was 8.3 (1.4) in WII, 7.1 (1.9) in HRS, and 8.1 (1.6) in FOS. Over 166 516 person-years, a total of 775 participants (220 in WII, 338 in HRS, and 217 in FOS) developed incident dementia. In the multivariable-adjusted Cox proportional hazard model, higher MIND diet score was associated with lower risk of dementia (pooled hazard ratio [HR] for every 3-point increment, 0.83; 95% CI, 0.72-0.95; P for trend = .01; I2 = 0%). The associations were consistently observed in subgroups defined by sex, age, smoking status, and body mass index. In the meta-analysis of 11 cohort studies with 224 049 participants (5279 incident dementia cases), the highest tertile of MIND diet score was associated with lower risk of dementia compared with the lowest tertile (pooled HR, 0.83; 95% CI, 0.76-0.90; I2 = 35%).

Conclusions and Relevance

Results suggest that adherence to the MIND diet was associated with lower risk of incident dementia in middle-aged and older adults. Further studies are warranted to develop and refine the specific MIND diet for different populations.
Outcomes of Postoperative Overnight High-Acuity Care in Medium-Risk Patients Undergoing Elective and Unplanned Noncardiac Surgery
Authors: Ludbrook Guy , Grocott Michael P. W. , Heyman Kathy , Clarke-Errey Sandy , Royse Colin , Sleigh Jamie , Solomon L. Bogdan
Published: May 2023

Importance

Postoperative complications are increasing, risking patients’ health and health care sustainability. High-acuity postoperative units may benefit outcomes, but existing data are very limited.

Objective

To evaluate whether a new high-acuity postoperative unit, advanced recovery room care (ARRC), reduces complications and health care utilization compared with usual ward care (UC).

Design, Setting, and Participants

In this observational cohort study, adults who were undergoing noncardiac surgery at a single-center tertiary adult hospital, anticipated to stay in hospital for 2 or more nights, were scheduled for postoperative ward care, and at medium risk (defined as predicted 30-day mortality of 0.7% to 5% by the National Safety Quality Improvement Program risk calculator) were included. Allocation to ARRC was based on bed availability. From 2405 patients assessed for eligibility with National Safety Quality Improvement Program risk scoring, 452 went to ARRC and 419 to UC, with 8 lost to 30-day follow-up. Propensity scoring identified 696 patients with matched pairs. Patients were treated between March and November 2021, and data were analyzed from January to September 2022.

Interventions

ARRC is an extended postanesthesia care unit (PACU), staffed by anesthesiologists and nurses (1 nurse to 2 patients) collaboratively with surgeons, with capacity for invasive monitoring and vasoactive infusions. ARRC patients were treated until the morning after surgery, then transferred to surgical wards. UC patients were transferred to surgical wards after usual PACU care.

Main Outcome and Measures

The primary end point was days at home at 30 days. Secondary end points were health facility utilization, medical emergency response (MER)–level complications, and mortality. Analyses compared groups before and after propensity scoring matching.

Results

Of 854 included patients, 457 (53.5%) were male, and the mean (SD) age was 70.0 (14.4) years. Days at home at 30 days was greater with ARRC compared with UC (mean [SD] time, 17 [11] vs 15 [11] days; P = .04). During the first 24 hours, more patients were identified with MER-level complications in ARRC (43 [12.4%] vs 13 [3.7%]; P < .001), but after return to the ward, these were less frequent from days 2 to 9 (9 [2.6%] vs 22 [6.3%]; P = .03). Length of hospital stay, hospital readmissions, emergency department visits, and mortality were similar.

Conclusions and Relevance

For medium-risk patients, brief high-acuity care with ARRC allowed enhanced detection and management of early MER-level complications, which was followed by a decreased incidence of subsequent MER-level complications after discharge to the ward and by increased days at home at 30 days.
The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: A study on Japanese male welders
Authors: Tsuji Mayumi , Hori Hajime , Koriyama Chihaya , Tanaka Rie , Isse Toyohi , Ishihara Yasuhiro , Ishizuka Tsunetoshi , Hasegawa Wataru , Goto Motohide , Yatera Kazuhiro , Kunugita Naoki , Kuwamura Mami , Sakuragi Toshihide , Yasumura Yoshiko , Yamamoto Megumi , Ueno Susumu
Published: May 2023

Objectives

The mask fit test confirms whether the wearing condition of the wearer’s face and the facepiece of the respirators are used appropriately. This study aimed to examine whether the results of the mask fit test affect the association between the concentration of metals related to welding fumes in biological samples and the results of time-weighted average (TWA) personal exposures.

Methods

A total of 94 male welders were recruited. Blood and urine samples were obtained from all participants to measure the metal exposure levels. Using personal exposure measurements, the 8-h TWA (8 h-TWA) of respirable dust, TWA of respirable Mn, and 8-h TWA of respirable Mn were calculated. The mask fit test was performed using the quantitative method specified in the Japanese Industrial Standard T8150:2021.

Results

Fifty-four participants (57%) passed the mask fit test. Only in the Fail group of the mask fit test, it was observed that blood Mn concentrations be positively associated with the results of TWA personal exposure after adjusting for multivariate factors (8-h TWA of respirable dust; coefficient, 0.066; standard error (SE), 0.028; P = 0.018, TWA of respirable Mn: coefficient, 0.048; SE, 0.020; P = 0.019, 8 h-TWA of respirable Mn: coefficient, 0.041; SE, 0.020; P = 0.041).

Conclusions

The results clarify that welders with high concentrations of welding fumes in their breathing air zone are exposed to dust and Mn if there is leaking air owing to the lack of fitness between respirators and the wearer’s face when using human samples in Japan.
Proposal of a classification method for public space usage based on pedestrian trajectory data
Authors: Masumura Akinobu , Sadohara Satoru
Published: May 2023

Herein, we propose a machine learning method based on pedestrian trajectory data to classify public space usage states and discriminate unknown usage states. Assuming that there are several frequent patterns in the usage state of public spaces, each element of the data set representing the usage state of public spaces can be classified into several clusters. Each cluster is defined as a “type” of usage state. They were classified into usage state “types” via principal component analysis and x‐means clustering. We employed data from the detection and recording of pedestrian trajectories by six 3D laser (LiDAR) sensors, conducted by the authors during the summer of 2019 in a public space in Yokohama, Japan. In the training phase, we defined “types” of usage states based on the data obtained for 3 weeks. In the test phase, the “type” of usage state was determined for the data of other periods. Consequently, 16 types that appeared at specific times and days were identified, and 1.1% of the test data were determined to be “new usage states,” which were not found in the training data. This method helps understand long‐term and complex variations in public space utilization patterns.
The Tricarboxylic Acid Cycle as a Central Regulator of the Rate of Aging: Implications for Metabolic Interventions
Authors: Borkum Jonathan M.
Published: May 2023

Certain metabolic interventions such as caloric restriction, fasting, exercise, and a ketogenic diet extend lifespan and/or health span. However, their benefits are limited and their connections to the underlying mechanisms of aging are not fully clear. Here, these connections are explored in terms of the tricarboxylic acid (TCA) cycle (Krebs cycle, citric acid cycle) to suggest reasons for the loss of effectiveness and ways of overcoming it. Specifically, the metabolic interventions deplete acetate and likely reduce the conversion of oxaloacetate to aspartate, thereby inhibiting the mammalian target of rapamycin (mTOR) and upregulating autophagy. Synthesis of glutathione may provide a high‐capacity sink for amine groups, facilitating autophagy, and prevent buildup of alpha‐ketoglutarate, supporting stem cell maintenance. Metabolic interventions also prevent the accumulation of succinate, thereby slowing DNA hypermethylation, facilitating the repair of DNA double‐strand breaks, reducing inflammatory and hypoxic signaling, and lowering reliance on glycolysis. In part through these mechanisms, metabolic interventions may decelerate aging, extending lifespan. Conversely, with overnutrition or oxidative stress, these processes function in reverse, accelerating aging and impairing longevity. Progressive damage to aconitase, inhibition of succinate dehydrogenase, and downregulation of hypoxia‐inducible factor‐1α, and phosphoenolpyruvate carboxykinase (PEPCK) emerge as potentially modifiable reasons for the loss of effectiveness of metabolic interventions.
Electrochemical Hydrosilylation of Electron‐Withdrawing Alkenes
Authors: Zhou He‐Yang , Fei Lu‐Qi , Zhang Jia‐Lan , Pan Ying‐Ming , Tang Hai‐Tao
Published: May 2023

In the presence of the Suginome reagent (PhMe2Si−Bpin), a large panel of electron‐withdrawing alkenes was successfully converted into the hydrosilylated product in good to excellent yields. This direct electrochemical hydrosilylation does not require exogenous oxidants and catalysts. Preliminary mechanistic study supported the involvement of a silyl radical, which reacted on the alkene.

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Flexible Memristive Organic Solar Cell Using Multilayer 2D Titanium Carbide MXene Electrodes
Authors: Nirmal Kiran A. , Ren Wanqi , Khot Atul C. , Kang Dae Yun , Dongale Tukaram D. , Kim Tae Geun
Published: May 2023

Hybrid systems have attracted significant attention within the scientific community due to their multifunctionality, which has resulted in increasing demands for wearable electronics, green energy, and miniaturization. Furthermore, MXenes are promising two‐dimensional materials that have been applied in various areas due to their unique properties. Herein, a flexible, transparent, and conductive electrode (FTCE) based on a multilayer hybrid MXene/Ag/MXene structure that can be applied to realize an inverted organic solar cell (OSC) with memory and learning functionalities is reported. This optimized FTCE exhibits high transmittance (84%), low sheet resistance (9.7 Ω sq−1), and reliable operation (even after 2000 bending cycles). Moreover, the OSC using this FTCE achieves a power conversion efficiency of 13.86% and sustained photovoltaic performance, even after hundreds of switching cycles. The fabricated memristive OSC (MemOSC) device also exhibits reliable resistive switching behavior at low operating voltages of 0.60 and −0.33 V (similar to biological synapses), an excellent ON/OFF ratio (103), stable endurance performance (4 × 103), and memory retention properties (104 s). Moreover, the MemOSC device can mimic synaptic functionalities on a biological time scale. Thus, MXene can potentially be used as an electrode for highly efficient OSCs with memristive functions for future intelligent solar cell modules.
Optical Verification of Physically Unclonable Function Devices Based on Spin‐Orbit Torque Switching
Authors: Lee Jeong Kyu , Lee Jiyoung , Yoon Seok In , Lee Min Hyeok , Lee Jin Seo , Jang Yunho , Kim Dae‐Yun , Choe Sug‐Bong , Park Jongsun , Kim Young Keun
Published: May 2023

Physically unclonable functions (PUFs) are used for various applications such as anticounterfeiting, authentication, and secret key generation. They are generally evaluated through electrical measurements, requiring much time and effort due to the many electrical connections required. This study proposes an optical verification of spin‐orbit torque (SOT) devices for PUF design. SOT devices have gained much attention because they resist degradation and thermal changes and can generate secret keys with high reproducibility. A simple optical method based on the magneto‐optical Kerr effect is introduced to verify the authenticity of the proposed SOT PUF device. Furthermore, this study assesses the feasibility of using a W/CoFeB/MgO/Ta structure as a PUF. The 24‐bit device shows a reliability of 97.8 ± 1.03%, making it a promising candidate for use as a spintronics‐based PUFs.
Improved multimodal prediction of progression from MCI to Alzheimer's disease combining genetics with quantitative brain MRI and cognitive measures
Authors: Reas Emilie T. , Shadrin Alexey , Frei Oleksandr , Motazedi Ehsan , McEvoy Linda , Bahrami Shahram , van der Meer Dennis , Makowski Carolina , Loughnan Robert , Wang Xin , Broce Iris , Banks Sarah J. , Fominykh Vera , Cheng Weiqiu , Holland Dominic , Smeland Olav B. , Seibert Tyler , Selbæk Geir , Brewer James B. , Fan Chun C. , Andreassen Ole A. , Dale Anders M. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: May 2023

Introduction

There is a pressing need for non‐invasive, cost‐effective tools for early detection of Alzheimer's disease (AD).

Methods

Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), Cox proportional models were conducted to develop a multimodal hazard score (MHS) combining age, a polygenic hazard score (PHS), brain atrophy, and memory to predict conversion from mild cognitive impairment (MCI) to dementia. Power calculations estimated required clinical trial sample sizes after hypothetical enrichment using the MHS. Cox regression determined predicted age of onset for AD pathology from the PHS.

Results

The MHS predicted conversion from MCI to dementia (hazard ratio for 80th versus 20th percentile: 27.03). Models suggest that application of the MHS could reduce clinical trial sample sizes by 67%. The PHS alone predicted age of onset of amyloid and tau.

Discussion

The MHS may improve early detection of AD for use in memory clinics or for clinical trial enrichment.

HIGHLIGHTS

A multimodal hazard score (MHS) combined age, genetics, brain atrophy, and memory.

The MHS predicted time to conversion from mild cognitive impairment to dementia.

MHS reduced hypothetical Alzheimer's disease (AD) clinical trial sample sizes by 67%.

A polygenic hazard score predicted age of onset of AD neuropathology.
Regulated High‐Spin State and Constrained Charge Behavior of Active Cobalt Sites in Covalent Organic Frameworks for Promoting Electrocatalytic Oxygen Reduction
Authors: Mei Zhi‐yuan , Zhao Genfu , Xia Chenfeng , Cai Sheng , Jing Qi , Sheng Xuelin , Wang Han , Zou Xiaoxiao , Wang Lilian , Guo Hong , Xia Bao Yu
Published: May 2023

A novel type of covalent organic frameworks has been developed by assembling definite cobalt‐nitrogen‐carbon configurations onto carbon nanotubes using linkers that have varying electronic effects. This innovative approach has resulted in an efficient electrocatalyst for oxygen reduction, which is understood by a combination of in situ spectroelectrochemistry and the bond order theorem. The strong interaction between the electron‐donating carbon nanotubes and the electron‐accepting linker mitigates the trend of charge loss at cobalt sites, while inducing the generation of high spin state. This enhances the adsorption strength and electron transfer between the cobalt center and reactants/intermediates, leading to an improved oxygen reduction capability. This work not only presents an effective strategy for developing efficient non‐noble metal electrocatalysts through reticular chemistry, but also provides valuable insights into regulating the electronic configuration and charge behavior of active sites in designing high‐performance electrocatalysts.
1,3‐Imidazol‐basierte mesoionische Carbene und anionische Dicarbene: Erweiterung der Grenzen klassischer N‐heterocyclischer Carbene
Authors: Ghadwal Rajendra S.
Published: May 2023

Klassische N‐heterocyclische Carbene (NHCs) mit dem Carbenzentrum an der C2‐Position des 1,3‐Imidazolgerüsts (d.h. C2‐Carbene) sind als vielseitige neutrale Liganden sowohl in der Molekularforschung als auch in den Materialwissenschaften bekannt. Die Effizienz und der Erfolg der NHCs in verschiedenen Bereichen ist im Wesentlichen auf ihre überzeugenden stereoelektronischen Eigenschaften zurückzuführen, insbesondere auf die starke σ‐Donoreigenschaft. Die NHCs mit dem Carbenzentrum an der ungewöhnlichen C4‐ (oder C5‐) Position, die sogenannten abnormalen NHCs (aNHCs) oder mesoionischen Carbene (iMICs), sind jedoch deutlich stärkere σ‐Donatoren als C2‐Carbene. Deshalb haben iMICs ein erhebliches Potenzial als Liganden in der nachhaltigen Synthese und Katalyse. Das Haupthindernis auf diesem Weg ist die anspruchsvolle synthetische Zugänglichkeit zu iMICs. Das Ziel dieses Übersichtsartikels ist es, die aktuellen Fortschritte, insbesondere der Forschungsgruppe des Autors, im Hinblick auf den Zugang zu stabilen iMICs, die Quantifizierung ihrer Eigenschaften sowie die Erforschung ihrer Anwendungen in Synthese und Katalyse aufzuzeigen. Darüber hinaus werden die synthetische Eignung und die Verwendung vicinaler C4,C5‐anionische Dicarbene (ADCs), die ebenfalls auf einem 1,3‐Imidazolgerüst basieren, vorgestellt. Wie auf den folgenden Seiten deutlich wird, haben iMICs und ADCs das Potenzial, die Grenzen der klassischen NHCs zu erweitern, indem sie den Zugang zu konzeptionell neuartigen Hauptgruppenelement‐Heterocyclen, Radikalen, molekularen Katalysatoren, Ligandensätzen und mehr ermöglichen.
Flexural, impact, and dynamic mechanical analysis of glass fiber/ABS and glass fiber/carbon fiber/ABS composites
Authors: Aravind D. , Senthilkumar K. , Rajini N. , Siengchin Suchart , Yorseng Krittirash , Kumar T. Senthil Muthu , Chandrasekar M. , Mohammad Faruq , Al‐Lohedan Hamad A.
Published: May 2023

In this study, a hybrid manufacturing technique was proposed to fabricate composites of acrylonitrile butadiene styrene (ABS) with Bidirectional woven glass fiber mat (GF)/ABS and GF/Bidirectional woven carbon fiber mat (CF)/ABS. The composites were fabricated using fused deposition modeling 3D printing, followed by hot compression molding, and their flexural, impact, and dynamic mechanical behaviors were examined. Results indicated that composites with GF and ABS combinations had shown the highest maximum flexural strength (64.46 MPa) and impact strength (0.089 J/mm2). The hybrid composites showed intermediate performance between ABS and GF/ABS composites, with higher flexural strain before failure than ABS and GF/ABS. A comprehensive analysis utilizing scanning electron microscopy was carried out to evaluate the adhesion characteristics of the fiber‐matrix interface in impact‐tested samples. Dynamic mechanical analysis showed that GF/ABS composites had offered superior E′, E″, and tanδ than the hybrid configuration. The peak tan delta values obtained from ABS, GF/ABS, and GF/CF/ABS composites were utilized to determine their respective glass transition temperatures. The observed values for ABS, GF/ABS, and GF/CF/ABS composites were 109.65, 69.95, and 71.5°C, respectively. Some potential applications for the composites fabricated in this study could include the development of lightweight and strong components for aerospace or automotive industries.
Design of crosslinked networks with hydroxyurethane linkages via bio‐based alkyl methacrylates and diamines
Authors: Farkhondehnia Mohammad , Maric Milan
Published: May 2023

A hybrid methodology is used to combine the favorable properties of non‐isocyanate polyurethanes (NIPUs) in the side chains with poly(methacrylates) as the backbone into thermoset hybrid resins with hydroxyurethane linkages (HNIPU)s. Using NIPUs linkages avoids the use of toxic isocyanates in the poly(urethane) segments. The backbone is synthesized from cyclic carbonated copolymer templates derived from atom transfer radical polymerization (ATRP) of an alkyl methacrylate (C13MA with average side‐chain length of 13)/glycidyl methacrylate (GMA) mixtures (initial GMA mol fraction = 0.1–0.4). The resulting flexible resins with pendent epoxy functional groups were subsequently carbonated and then reacted with 1,10‐diaminodecane (90°C, 24 h) to form rigid side chains via hydroxyurethane linkages. Manipulating template functionality (2–11 urethane linkages out of 35 backbone units) yielded crosslinked networks with Young's moduli from 0.1 to 71.9 MPa while decreasing tensile elongation at break from 105% to 10%. Swelling ratios (SR) of the networks in tetrahydrofuran (THF) decrease as urethane linkage concentration increases, indicating tighter networks, consistent with the rheologically obtained molecular weight between crosslinks. Gel content indicated less than 15% of the networks are soluble in THF. The HNIPU networks derived show their ready tunability by simply changing the precursor functionality.
Association Between Plasma Rituximab Concentration and the Risk of Major Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides During Rituximab Maintenance Therapy
Authors: Khoudour Nihel , Delestre Florence , Jabot‐Hanin Fabienne , Jouinot Anne , Nectoux Juliette , Letouneur Franck , Izac Brigitte , Vidal Michel , Guillevin Loïc , Puéchal Xavier , Charles Pierre , Terrier Benjamin , Blanchet Benoit
Published: May 2023

Objective

Interindividual variability in response to rituximab remains unexplored in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides. Rituximab pharmacokinetics (PK) and pharmacodynamics (PD) as well as genetic polymorphisms could contribute to variability. This ancillary study of the MAINRITSAN 2 trial aimed to explore the relationship between rituximab plasma concentration, genetic polymorphisms in PK/PD candidate genes, and clinical outcomes.

Methods

Patients included in the MAINRITSAN2 trial (ClinicalTrials.gov identifier: NCT01731561) were randomized to receive a 500‐mg fixed‐schedule rituximab infusion or an individually tailored regimen. Rituximab plasma concentrations at month 3 (CM3) were assessed. DNA samples (n = 53) were genotyped for single‐nucleotide polymorphisms within 88 putative PK/PD candidate genes. The relationship between PK/PD outcomes and genetic variants was investigated using logistic linear regression in additive and recessive genetic models.

Results

One hundred and thirty‐five patients were included. The frequency of underexposed patients (<4 μg/ml) in the fixed‐schedule group was statistically lower compared to that in the tailored‐infusion group (2.0% versus 18.0%; P = 0.02, respectively). Low rituximab plasma concentration at 3 months (CM3 <4 μg/ml) was an independent risk factor for major relapse (odds ratio 6.56 [95% confidence interval (95% CI) 1.26–34.09]; P = 0.025) at month 28 (M28). A sensitivity survival analysis also identified CM3 <4 μg/ml as an independent risk factor for major relapse (hazard ratio [HR] 4.81 [95% CI 1.56–14.82]; P = 0.006) and relapse (HR 2.70 [95% CI 1.02–7.15]; P = 0.046). STAT4 rs2278940 and PRKCA rs8076312 were significantly associated with CM3 but not with major relapse onset at M28.

Conclusion

These results suggest that drug monitoring could be useful to individualize the schedule of rituximab administration within the maintenance phase.
Establishment and validation of a prognostic nomogram for postoperative patients with gastric cardia adenocarcinoma: A study based on the Surveillance, Epidemiology, and End Results database and a Chinese cohort
Authors: Wang Lei , Ge Jingjing , Feng Liwen , Wang Zehua , Wang Wenjia , Han Huiqiong , Qin Yanru
Published: May 2023

Background

Gastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram.

Methods

In this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training (n = 1013) and internal validation (n = 435) cohorts at a 7:3 ratio. The study also included an external validation cohort (n = 218) from a Chinese hospital. The study used the Cox and LASSO models to pinpoint the independent risk factors linked to GCA. The prognostic model was constructed according to the results of the multivariate regression analysis. To assess the predictive accuracy of the nomogram, four methods were used: C‐index, calibration curve, time‐dependent ROC curve, and DCA curve. Kaplan–Meier survival curves were also generated to illustrate the differences in cancer‐specific survival (CSS) between the groups.

Results

The results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer‐specific survival in the training cohort. Both the C‐index and AUC values depicted in the nomogram were greater than 0.71. The calibration curve revealed that the nomogram's CSS prediction was consistent with the actual outcomes. The decision curve analysis suggested moderately positive net benefits. Based on the nomogram risk score, significant differences in survival between the high‐ and low‐risk groups were observed.

Conclusions

Race, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability.
LAG‐3 transcriptomic expression patterns across malignancies: Implications for precision immunotherapeutics
Authors: Adashek Jacob J. , Kato Shumei , Nishizaki Daisuke , Miyashita Hirotaka , De Pradip , Lee Suzanna , Pabla Sarabjot , Nesline Mary , Conroy Jeffrey M. , DePietro Paul , Lippman Scott , Kurzrock Razelle
Published: May 2023

Background

Lymphocyte activation gene 3 (LAG‐3) or CD223 is a transmembrane protein that serves as an immune checkpoint which attenuates T‐cell activation. Many clinical trials of LAG‐3 inhibitors have had modest effects, but recent data indicate that the LAG‐3 antibody relatlimab, together with nivolumab (anti‐PD‐1), provided greater benefit than nivolumab alone in patients with melanoma.

Methods

In this study, the RNA expression levels of 397 genes were assessed in 514 diverse cancers at a clinical‐grade laboratory (OmniSeq: https://www.omniseq.com/). Transcript abundance was normalized to internal housekeeping gene profiles and ranked (0–100 percentile) using a reference population (735 tumors; 35 histologies).

Results

A total of 116 of 514 tumors (22.6%) had high LAG‐3 transcript expression (≥75 percentile rank). Cancers with the greatest proportion of high LAG‐3 transcripts were neuroendocrine (47% of patients) and uterine (42%); colorectal had among the lowest proportion of high LAG‐3 expression (15% of patients) (all p < 0.05 multivariate); 50% of melanomas were high LAG‐3 expressors. There was significant independent association between high LAG‐3 expression and high expression of other checkpoints, including programmed death‐ligand 1 (PD‐L1), PD‐1, and CTLA‐4, as well as high tumor mutational burden (TMB) ≥10 mutations/megabase, a marker for immunotherapy response (all p < 0.05 multivariate). However, within all tumor types, there was inter‐patient variability in LAG‐3 expression level.

Conclusions

Prospective studies are therefore needed to determine if high levels of the LAG‐3 checkpoint are responsible for resistance to anti‐PD‐1/PD‐L1 or anti‐CTLA‐4 antibodies. Furthermore, a precision/personalized immunotherapy approach may require interrogating individual tumor immunograms to match patients to the right combination of immunotherapeutic agents for their malignancy.
Clinical characteristics and prognosis analysis of patients with de novo ASXL1‐mutated AML treated with the C‐HUNAN‐AML‐15 protocol: A multicenter study by the South China Pediatric AML Collaborative Group
Authors: Zeng Minhui , Chen Keke , Tian Xin , Zou Runying , Feng Xiaoqin , Li Chunfu , Li Jian , Zheng Mincui , Mai Huirong , Yang Lihua , He Yingyi , Xu Honggui , Wen Hong , He Xiangling
Published: May 2023

Background

ASXL1 mutation is an independent prognostic factor in adult acute myeloid leukemia (AML), but its effect on the prognosis of pediatric AML is poorly understood.

Aims

This study aimed to investigate the clinical characteristics and prognostic factors of ASXL1‐mutant pediatric AML from a large Chinese multicenter cohort.

Methods

A total of 584 pediatric patients with newly diagnosed AML from 10 centers in South China were enrolled. The exon 13 of ASXL1 was amplified by polymerase chain reaction (PCR), and then analyzed the mutation status of the locus. (n = 59 for ASXL1‐mut group, n = 487 for ASXL1‐wt group).

Results

ASXL1 mutations were found in 10.81% of all patients with AML. A complex karyotype was significantly less common in the ASXL1‐mut AML group than in the ASXL1‐wt group (1.7% vs. 11.9%, p = 0.013). Furthermore, TET2 or TP53 mutations were predominantly found in the ASXL1+ group (p = 0.003 and 0.023, respectively). The 5‐year overall survival (OS) and event‐free survival (EFS) of the total cohort were 76.9% and 69.9%. In ASXL1‐mut AML patients, a white blood cell (WBC) count ≥50 × 109/L had significantly poorer 5‐year OS and EFS than a WBC count <50 × 109/L (78.0% vs. 44.6%, p = 0.001; 74.8% vs. 44.6%, p = 0.003, respectively), while receiving hematopoietic stem cell transplantation (HSCT) had a higher 5‐year OS and EFS (84.5% vs. 48.5%, p = 0.024; 79.5% vs. 49.3%, p = 0.047, respectively). In the multivariate Cox regression analysis, patients with high‐risk AML undergoing HSCT tended to have a better 5‐year OS and EFS than those receiving chemotherapy as a consolidation (HR = 0.168 and 0.260, both p < 0.001), and WBC count ≥50 × 109/L or failure to achieve complete response after the first course were independent adverse predictors of OS and EFS (HR = 1.784 and 1.870, p = 0.042 and 0.018; HR = 3.242 and 3.235, both p < 0.001).

Conclusion

The C‐HUANA‐AML‐15 protocol is a well‐tolerated and effective in the treatment of pediatric AML. ASXL1 mutation is not an independent adverse prognosis predictor for survival in AML, whereas ASXL1‐mut patients tend to have a poor prognosis if WBC count ≥50 × 109/L, but they can benefit from HSCT.
TFAM knockdown undermines SQSTM1 mRNA stability but retards autophagy flux and inhibits tumor cells proliferation under starvation conditions
Authors: Jiang Xu , Xu Ying , Yang Jingrui , Wang Jing , Gao Liu , Yu Li
Published: May 2023

Although starvation stress can alter the homeostasis of mitochondria and promote autophagy, there is still a lack of research focusing on the connection between them. In this study, we found that, accompanied by the upregulation of autophagy flux, the membrane mitochondrial potential (MMP), the content of reactive oxygen species (ROS), the production of ATP, and the copy number of mitochondrial DNA (mt‐DNA) were changed when limiting amino acids supply. We screened and analyzed altered genes related to mitochondrial homeostasis under starvation stress and verified that the expression of mitochondrial transcription factor A (TFAM) was prominently upregulated. Inhibition of TFAM led to the change of mitochondrial function and homeostasis, caused the decrease of SQSTM1 mRNA stability and ATG101 protein level and restricted the autophagy process of cells under amino acid deficient conditions. In addition, the TFAM knockdown and starvation treatment aggravated the DNA damage and reduced proliferation rate of tumor cells. Therefore, our data shows the correlation between mitochondria homeostasis and autophagy, reveals the effect of TFAM on autophagy flux under starvation stress and provides experimental basis for the combined starvation therapy targeting mitochondria to inhibit tumor growth.
Asymmetric Catalytic Transformations of Aza‐ortho‐ and Aza‐para‐Quinone Methides
Authors: Zurro Mercedes , Maestro Aitor
Published: May 2023

The catalytic methodologies for the derivatization of aza‐QM have recently appeared in the literature and involve organocatalytic and organometallic approaches. This review aims at analyzing the diverse catalytic systems involving chiral NHC carbenes, phosphoric acids, phosphoramidites, phosphine and copper and palladium catalysis showing its applicability for the synthesis of a diverse away of N‐containing compounds which in many cases have biological activity.
Thin Layer Chromatography‐Freeze Surface‐Enhanced Raman Spectroscopy: A Powerful Tool for Monitoring Synthetic Reactions
Authors: Fukunaga Yu , Ogawa Rintaro , Homma Amane , Okada Tetsuo
Published: May 2023

Thin layer chromatography (TLC) is widely used to confirm the formation of the target compound in chemical synthesis. The key issue in TLC is spot identification as it primarily relies on retention factors. Coupling of TLC with surface‐enhanced Raman spectroscopy (SERS), which gives direct molecular information, is an appropriate choice, to overcome this challenge. However, interference from the stationary phase and impurities on the nanoparticles added for SERS measurements significantly degrades TLC‐SERS efficiency. It was found that freezing effectively eliminates such interferences and dramatically improves the performance of TLC‐SERS. In this study, TLC‐freeze SERS is applied to the monitoring of four chemically important reactions. The proposed method can identify the product and side‐products of similar structures, detect compounds with high sensitivity, and provide information of quantities that allows the reliable determination of the reaction time based on kinetic analysis.
Pushing the Boundary of Covalency in Lanthanoid‐Tellurium Bonds: Insights from the Synthesis, Molecular and Electronic Structures of Low‐Coordinate, Monomeric Europium(II) and Ytterbium(II) Tellurolates
Authors: Deka Rajesh , Dey Sourav , Guo Zhifang , Butcher Ray J. , Junk Peter C. , Turner David R. , Singh Harkesh B. , Deacon Glen B.
Published: May 2023

Owing to the strict hard/soft dichotomy between the lanthanoids and tellurium atoms, and the strong affinity of lanthanoid ions for high coordination numbers, low‐coordinate, monomeric lanthanoid tellurolate complexes have remained elusive as compared to the lanthanoid complexes with lighter group 16 elements (O, S, and Se). This makes the development of suitable ligand systems for low‐coordinate, monomeric lanthanoid tellurolate complexes an appealing endeavor. In a first report, a series of low‐coordinate, monomeric lanthanoid (Yb, Eu) tellurolate complexes were synthesized by utilizing hybrid organotellurolate ligands containing N‐donor pendant arms. The reaction of bis[2‐((dimethylamino)methyl)phenyl] ditelluride,1and 8,8′diquinolinyl ditelluride,2withLn0metals (Ln=Eu, Yb) resulted in the formation of monomeric complexes [LnII(TeR)2(Solv)2] [R=C6H4‐2‐CH2NMe2] [3:Ln=Eu, Solv=tetrahydrofuran;4:Ln=Eu, Solv=acetonitrile;5:Ln=Yb, Solv=tetrahydrofuran;6:Ln=Yb, Solv=pyridine] and [EuII(TeNC9H6)2(Solv)n] (7: Solv=tetrahydrofuran, n=3;8: Solv=1,2‐dimethoxyethane, n=2), respectively. Complexes3–4and7–8represent the first sets of examples of monomeric europium tellurolate complexes. The molecular structures of complexes3–8are validated by single–crystal X‐ray diffraction studies. The electronic structures of these complexes were investigated using Density Functional Theory (DFT) calculations, which revealed appreciable covalency between the tellurolate ligands and lanthanoids.
Recent Advances in Activatable Probes for Molecular Imaging by Stimuli‐Controlled Disassembly
Authors: Huang Weijing , Yang Yanling , Ye Deju
Published: May 2023

Comprehensive Summary

Stimuli‐controlled disassembly process has shown promise to direct delivery of probes and/or spatial‐temporally control imaging signals for molecular imaging in vivo. Via the disassembly process, well defined nanoprobes with a stimulus‐responsive moiety can be controllably converted into small‐molecular imaging agents in response to a stimulus, leading to a switch in imaging signals. Moreover, the on‐site released small‐molecule probes could enhance penetration into the deep tissue for improved imaging of deep‐seated molecular targets. Therefore, such a stimuli‐controllable disassembly approach has been widely utilized to build activatable molecular imaging probes for the noninvasive detection of various molecular targets in living subjects. In this review article, we first briefly introduce the general principle of stimuli‐controlled disassembly. We then summarize the activatable probes based on different internal or external stimulus that has been utilized to control disassembly process. Activatable probes by using multiple stimuli to control cascaded in situ self‐assembly and disassembly processes are also discussed. Finally, we close with a conclusion of current challenges and perspective in this field. We wish this review paper will give readers useful information on molecular imaging via the intelligent stimuli‐controlled disassembly process.
Bipolar cells containing protein kinase Cα mediate attentional facilitation of the avian retinal ganglion cells by the retinopetal signal
Authors: Uchiyama Hiroyuki , Matsutani Shinji , Ohno Hiroshi , Yamaoka Seiya , Mizokami Takuya , Sugimoto Shiho , Hirashima Yasuhiro
Published: May 2023

Birds have a well‐developed retinopetal system projecting from the midbrain to the contralateral retina. The signal sent to the retina through the retinopetal system facilitates visual responses of the retinal ganglion cells (RGCs), and the retinopetal signals function as attentional signals during visual search. Thus, the retinopetal signal somehow reaches and facilitates visual responses of the RGCs. However, the tertiary neuron of the retinopetal system, the isthmo‐optic target cell (IOTC), is unlikely to contact most RGCs directly, because the IOTCs form axon terminals localized in the outermost sublayer (lamina 1) of the inner plexiform layer (IPL) where few RGC dendrites terminate. Therefore, some other intrinsic retinal neurons must be involved in the centrifugal attentional enhancement of visual responses of the RGCs. We investigated connections of the target cells of the IOTCs in chicken and quail, using light and electron microscopic immunohistochemistry. We show that axon terminals of the IOTC make synaptic contacts with protein kinase Cα (PKCα)‐immunoreactive (ir) bipolar cells (PKCα‐BCs) in lamina 1 of the IPL. Furthermore, with prolonged electrical stimulation of the isthmo‐optic nucleus (ION) on one side, whose neurons send their axons to the contralateral retina and make synaptic contacts there with IOTCs, phosphorylation of cAMP response element‐binding protein was observed in the PKCα‐BCs in the contralateral retina, but not in the ipsilateral retina. This suggests that electrical stimulation of ION activated PKCα‐BCs through synapses from IOTCs to PKCα‐BCs, thus stimulating transcription in PKCα‐BCs. Thus, centrifugal attentional signals may facilitate visual responses of RGCs via the PKCα‐BCs.
Impact of infections on the incidence of acute inflammatory demyelinating polyneuropathy in children
Authors: Gilbert Hannah , Abend Nicholas S. , Hutchinson Melissa , Messer Ricka , Moharir Mahendranath , Nash Kendall , Palaganas Jamie , Piantino Juan , Shah Samir S. , Hall Matt , Wells Elizabeth , Press Craig A. ,   Pediatric Neurohospitalist Work Group
Published: May 2023

Objectives

Acute inflammatory demyelinating polyneuropathy (AIDP) is the leading cause of acute flaccid paralysis in children and hypothesized to be triggered by antecedent infection. We sought to determine the association between AIDP and commonly acquired community infections in children. We utilized the reduction in these infections due to measures during coronavirus disease 2019 (COVID‐19) to serve as a natural experiment and determine their contribution to AIDP.

Methods

This cross‐sectional study used administrative and billing data from children's hospitals contributing to the Pediatric Health Information System. We included hospitalizations of children with a diagnosis of AIDP from (January 2017 through February 2021). Encounters for infection‐ (including respiratory, gastrointestinal, and COVID‐19) related diagnoses were measured as a marker of community incidence.

Results

A total of 1111 index encounters for AIDP were included. Pre‐COVID‐19, AIDP was not associated with respiratory or gastrointestinal infections, specifically, influenza or campylobacter. During the COVID‐19 period from March 2020 to February 2021, respiratory, gastrointestinal, and influenza infections decreased compared to expected (for the same time of year pre‐COVID‐19) by 59.6%–90.1%, 51.5%–68.9%, and 54.5%–97.9%, respectively. In contrast, AIDP hospitalizations and all hospitalizations only decreased by 11.5%–39.3% and 14.2%–25%, respectively. COVID‐19 was not positively associated with AIDP overall or at individual hospitals.

Interpretation

Common community‐acquired infections including COVID‐19 were not strongly associated with hospitalizations for AIDP in children. AIDP persisted despite the dramatic reduction in infection‐related encounters during the pandemic. These results suggest that recent antecedent community‐acquired infections were not the primary driver of AIDP and that alternative triggers should be explored.
Cysteine‐Based Perfluorinated Derivatives: A Theoretical and Experimental Study**
Authors: Chalán‐Gualán Sisa , Ramos‐Tomillero Iván , Terencio Thibault , De Lima Lola , Navas‐León Daniela G. , Suárez Margarita , Santiago Vispo Nelson , Albericio Fernando , Rodríguez Hortensia
Published: May 2023

Cysteine‐based perfluoroaromatic (hexafluorobenzene (HFB) and decafluorobiphenyl (DFBP)) were synthesized and established as a chemoselective and available core to construct molecular systems ranging from small molecules to biomolecules with interesting properties. The DFBP was found more effective than HFB for the monoalkylation of decorated thiol molecules. As proof of concept of the potential application of perfluorinated derivatives as non‐cleavable linkers, some antibody‐perfluorinated conjugates were prepared via thiol through two different strategies, i) using thiol from reduced cystamine coupling to carboxylic acids from mAb by amide bond, and ii) using thiols from reduction of mAb disulfide bond. Conjugates cell binding analysis demonstrated that the bioconjugation does not affect the macromolecular entity. Besides, some molecular properties of synthesized compounds are evaluated through spectroscopic characterization (FTIR and 19F NMR chemical shifts) and theoretical calculations. The comparison of calculated and experimental 19F NMR shifts and IR wavenumbers give excellent correlations, asserting as powerful tools in structurally identifying HFB and DFBP derivatives. Moreover, molecular docking was also developed to predict cysteine‐based perfluorated derivatives’ affinity against topoisomerase Il and cyclooxygenase 2 (COX‐2). The results suggested that mainly cysteine‐based DFBP derivatives could be potential topoisomerase II α and COX‐2 binders, becoming potential anticancer agents and candidates for anti‐inflammatory treatment.
Study on the Preparation and Morphology Mechanism of Micron‐Sized Hexagonal Flake Basic Zinc Chloride (Zn5(OH)8Cl2·H2O) by Ammonia Precipitation Method
Authors: Fan Tianbo , Zhao Yibo , Wang Xin an , Liu Sen , Li Xue , Guo Hongfan , Li Li
Published: May 2023

The chemical formula of basic zinc chloride is Zn5(OH)8Cl2 · H2O (denoted as ZHC). It is a new type of zinc source additive, widely used in the feed industry. In this article, micron‐sized hexagonal flake ZHC with a diameter of 10–60 µm is directly prepared by ammonia precipitation method using ZnCl2 as raw material. The products are characterized and analyzed by X‐ray diffraction, scanning electron microscopy, and laser particle size analyzer. The effects of reaction temperature, ammonia flow rate, aging time, and reactant concentration on the product morphology are studied. Under the optimum reaction conditions, the ZnCl2 concentration is 2.0 mol L−1, NH3 flow rate is 300 mL min−1, the reaction time is 1 h, the reaction temperature is 80 °C, and the aging time is 5 h. Lastly, the yield reaches 49.06%. The growth habit of ZHC is theoretically analyzed by the Morphology program. The calculation results are in good agreement with the experimental results. The change of (003) crystal plane exposure caused by temperature is an important reason for the non‐ideality of macroscopic morphology.
Sculptra®—History and how it is best used today
Authors: Eason Chelsea , Snyder Alan , Favre Clint , Schlesinger Todd
Published: May 2023

Introduction

Sculptra® is an injectable biostimulatory soft tissue filler containing microparticles of poly‐L‐lactic acid (PLLA) that is FDA‐approved for the correction of HIV‐associated facial lipoatrophy and nasolabial fold contour deficiencies and other facial wrinkles in immunocompetent patients. Injectable PLLA has been shown to provide gradual improvement in cutaneous thickness by inciting a subclinical inflammatory response that stimulates increased collagen deposition in the dermis, with results lasting up to 2 years.

Discussion

The utilization of Sculptra® in aesthetics has expanded to many off‐label indications including panfacial revolumization, improvement in skin quality, and use in various non‐facial sites such as the neck/décolleté, abdomen, arms, hands, thighs, and gluteal area. Clinical experience and scientific investigation have driven changes in the way PLLA is used. Simpler methods of product preparation, improved injection techniques, and attention to appropriate patient selection have led to improved outcomes and ease of use.

Conclusion

PLLA's long safety history and ability to produce subtle yet significant results through a biostimulatory mechanism make it an attractive and versatile option for cutaneous volume augmentation.