bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune‐independent acquired resistance to PD‐L1 antibody initiated by PD‐L1 upregulation via PI3K/AKT signaling can be reversed by anlotinib
Authors: Gao Yuan , Feng Yingfang , Liu Shaochuan , Zhang Yan , Wang Jing , Qin Tingting , Chen Peng , Li Kai
Published: June 2023

Despite the benefit with cancer immunotherapies in clinical implication, immunotherapeutic resistance occurred in many patients and the mechanism remains unknown. Increasing evidence has revealed that cell‐intrinsic programmed cell death ligand 1 (PD‐L1) may play a non‐negotiable part in immunotherapeutic resistance. Our present study aimed to elucidate the immune‐independent acquired resistance mechanism to PD‐L1 antibody. We found elevated PD‐L1 expression induced by PD‐L1 antibodies in cancer cell and vascular endothelial cells (VECs) with substantially acquired resistance to PD‐L1 antibodies. Moreover, proliferation of resistant cells was accelerated and the apoptosis was reduced in the absence of immune compared with parental cells. Subsequently, we confirmed that the activation of the PI3K/AKT pathway is involved in the upregulation of PD‐L1 expression. Finally, we found that low dose of anlotinib downregulated PD‐L1 expression only in VECs via inhibiting the PI3K/AKT pathway; however, the same effect was not observed in cancer cells. To sum up, our findings revealed that upregulation of PD‐L1 via activation of the PI3K/AKT signal pathway may promote acquired resistance to PD‐L1 antibodies in an immune‐independent manner.

Significance

These findings provide new mechanisms of immunotherapeutic resistance and effective evidence of anlotinib combined with immunotherapy.
Estimates of bladder cancer burden attributable to high fasting plasma glucose: Findings of the Global Burden of Disease Study 2019
Authors: Wu Ying , Deng Yujiao , Dai Zhijun , Ma Yubo , Lyu Lijuan , Lei Chen , Zheng Yi , Li Yizhen , Wang Ziming , Gao Jie
Published: June 2023

Background

High fasting plasma glucose (FPG) has been listed as one of the risk factors for bladder cancer. We here estimated the global, regional, and national levels of bladder cancer burden attributable to high FPG from 1990 to 2019.

Methods

Bladder cancer data attributable to high FPG were extracted from the Global Burden of Disease Study 2019, and analyzed by age, sex, year, and location. Age‐standardized rates were utilized to evaluate the burden between different populations. The temporal trend of the burden was estimated through the Joinpoint analysis.

Results

In 2019, high FPG contributed to 22,823.33 (95% uncertainty interval [UI], 4694.88–48,962.26) deaths and 399,654.91 (95% UI, 81,609.35–865,890.95) disability‐adjusted life years (DALYs) of bladder cancer globally. Since 1990, the global age‐standardized death and DALY rates of bladder cancer attributable to high FPG increased apparently by 39.18% and 41.48%, respectively. During the last 30 years, high FPG‐related age‐standardized death and DALY rates of bladder cancer have increased in all countries. In 2019, Central Europe showed the greatest high FPG‐related age‐standardized death and DALY rates of bladder cancer, but Andean Latin America had the lowest rates. Nationally, Lebanon showed the greatest high FPG‐related age‐standardized death and DALY rates of bladder cancer in 2019. High FPG‐attributable deaths and DALYs of bladder cancer were more considerable among males and older people. Countries with high SDI showed higher levels of age‐standardized death and DALY rates of bladder cancer due to high FPG and presented remarkable upward trends in rates in the last 30 years.

Conclusions

Globally, the high FPG‐associated bladder cancer burden has remarkably increased in all countries, and showed a higher level among countries with higher SDI. Monitoring FPG levels among patients with bladder cancer is critical to lower the corresponding burden.
Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer
Authors: Hatta Takahiro , Hase Tetsunari , Hara Toru , Kimura Tomoki , Kojima Eiji , Abe Takashi , Horio Yoshitsugu , Goto Yasuhiro , Ozawa Naoya , Yogo Naoyuki , Shibata Hirofumi , Shimokata Tomoya , Oguri Tetsuya , Yamamoto Masashi , Yanagisawa Kiyoshi , Ando Masahiko , Ando Yuichi , Kondo Masashi , Ishii Makoto , Hasegawa Yoshinori
Published: June 2023

Background

The Cockcroft–Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non‐small‐cell lung cancer remain unknown.

Methods

We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin–pemetrexed. Glomerular filtration rate values in Calvert's formula were back‐calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups.

Results

Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression‐free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76–1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65–1.17; p = 0.363), with higher grade 3–4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20–0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23–0.82; p = 0.010).

Conclusions

Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.
Child‐Centred Play Therapy and Rhythmic Relating improves emotion regulation in autism: A single‐N pilot intervention study
Authors: Daniel Stuart , Berkovits Lauren , Eisenhower Abbey , Blacher Jan
Published: June 2023

Emotion Regulation is a key factor in the psychological well‐being of children on the autism spectrum. Therapeutic co‐regulation is posited here as fundamental to addressing Emotion Regulation needs. A therapeutic combination of Child‐Centred Play Therapy and Rhythmic Relating is assessed in its potential to improve Emotion Regulation outcomes (over 10 months; 25 weekly sessions), via co‐regulatory experience, in a case study of a 5‐year‐old autistic boy. The parent‐rated Emotion Regulation Checklist (Shields & Cicchetti, Developmental Psychology, 33, 1997, 906) was completed every week. Mean Start and Finish scores were taken for checklist total and all subscales. Emotion Regulation percentage‐change‐over‐time values are calculated for the participant and, using percentiles, are compared and statistically ranked in relation to our comparison group: Autistic boys without concurrent cognitive impairment, not receiving psychological or behavioural therapies (over 10 months; N = 66). A graphical representation of Emotion Regulation demonstrates weekly change. As compared to our comparison group, our participant's overall Emotion Regulation improvements (over 10 months) are statistically likely to be due to his participation in therapy (p < 0.04). Graphical representation of Emotion Regulation over time demonstrates a compelling blind correlation between the period of significant positive change in our participant's Emotion Regulation and the therapist's clinical notes on positive change observed in the clinic.
New Olimycins from a Cold‐Seep‐Derived Streptomyces olivaceus
Authors: Dong Yun , Jin Enjing , Wang Runyi , Bao Yilei , Li Huayue
Published: June 2023

Cold‐seeps are areas of the ocean floor in which hydrogen sulfide and methane are released into the open water. The cold‐seep microbes are an emerging source of novel bioactive natural products. Four new ansa‐ring opened linear ansamycin analogues, named olimycins E−H (1–4) were isolated from the cold‐seep‐derived Streptomyces olivaceus OUCLQ19‐3. The planar and stereochemical structures of the isolated compounds were elucidated based on extensive MS and NMR spectroscopic analyses together with ECD calculations.
High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations
Authors: Shieh Meg , Amkraut Keren , Spiridigliozzi Gail A. , Adayev Tatyana , Nicholson Kaylea , McConkie‐Rosell Allyn , McDonald Marie , Pennington Malinda , Sebastian Siby , Lachiewicz Ave M.
Published: June 2023

Key Clinical Message

A high performing male with an unmethylated full mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene surpassed our expectations into young adulthood. Although initial genetic findings helped make a correct fragile X syndrome (FXS) determination, the report was insufficient. Ten years later, we repeated and conducted additional genetic and clinical studies to determine whether more information could assist with treatment and counseling. The genetic findings were very consistent with his high functioning and would have enabled us to be more confident about a good developmental outcome had they been available previously. As FXS enters the mainstream of well‐understood genetic disorders and technological advancements improve genetic tests, it should be clearer to clinical providers what a full FXS assessment could include to provide high quality information for care. For individuals with FXS who are high functioning, their families and clinical professionals would benefit from knowing more genetic findings, including, most importantly, methylation status, but also the FMR1 protein (FMRP) level and mRNA level. While we now know that obtaining only the CGG repeat number is not always adequate to inform accurate clinical care, future studies are likely to show the benefit of studying other biomarkers, such as mRNA levels.
Histopathologic diagnosis of ultra‐early autoimmune gastritis: A case report
Authors: Terao Shuichi , Suzuki Shiho , Kushima Ryoji
Published: June 2023

Key Clinical Message

We describe an ultra‐early stage of autoimmune gastritis (AIG) that occurs prior to the well‐known early‐stage AIG. The key pathology is the shortening of the second layer with degenerated parietal cells. In the management of patients with autoimmune diseases, AIG should be considered even if the endoscopy findings are normal.
Solitary median maxillary central incisor in association with taurodontism and oligodontia: A case report
Authors: Sheikhhassani Yasmin , Sarrafzadeh Arash , Jadidi Soheila
Published: June 2023

Key Clinical Message

In this case report, we have highlighted the probability of coinciding multiple dental anomalies, such as SMMCI, taurodontism, and oligodontia. Thus, further research is necessary to establish a correlation between oligodontia, taurodontism, and SMMCI.
Smegma pearl: A benign penile lesion in infants
Authors: Baral Kushal , Poudel Susmita
Published: June 2023

Key clinical message

Provide comprehensive knowledge to healthcare practitioners regarding the benign characteristics of smegma pearls, aiming to alleviate anxiety and minimize unwarranted medical interventions.

Penile nodules in infant are distressing to the mother and also cause diagnostic dilemmas to primary care physician. Most of the penile nodules are benign and the only treatment is reassurance to the mother. Smegma pearl occurs due to accumulation of the desquamated epithelial cells under the penile foreskin and are visualized as yellowish white lumps. We present a similar case who presented to the primary health centre at rural Nepal.
Complete hematologic response after belinostat treatment and allogeneic stem cell transplantation for multiple relapsed/refractory angioimmunoblastic T‐cell lymphoma: A case report
Authors: Camus Vincent , Etancelin Pascaline , Drieux Fanny , Veresezan Elena‐Liana , Picquenot Jean‐Michel , Penther Dominique , Viennot Mathieu , Ruminy Philippe , Contentin Nathalie , Lemasle Emilie , Leprêtre Stéphane , Dubois Sydney , Penichoux Juliette , Stamatoullas Aspasia , Zduniak Alexandra , Lanic Hélène , Jardin Fabrice
Published: June 2023

Key Clinical Message

This case report highlights the potential of belinostat for the treatment of relapsed/refractory peripheral T‐cell lymphomas, for which effective therapies are still scarce.

Peripheral T‐cell lymphomas have an aggressive disease course associated with poor outcomes. We report a young patient with highly pretreated relapsed/refractory nodal follicular helper T‐cell lymphoma (angioimmunoblastic‐type [nTFHL‐AI]), who successfully received an allogeneic stem cell transplantation following belinostat therapy. The complete hematologic response achieved has lasted more than 2 years.
Pulmonary miliary sarcoidosis masquerading the reactivation of tuberculosis 30 years later
Authors: Okuma Takashi , Mizushima Reimi , Takeda Yukihisa , Toriyama Kazutoshi , Watanabe Yusuke , Nakamura Hiroyuki , Aoshiba Kazutetsu
Published: June 2023

Key Clinical Message

Sarcoidosis may occur after treatment with pulmonary tuberculosis and requires differential diagnosis from tuberculosis reactivation. Miliary sarcoidosis should be promptly differentiated from miliary tuberculosis associated with high mortality.

Clinical, histological, and radiological similarities between sarcoidosis and tuberculosis render differential diagnosis challenging. The association between these two diseases has long been discussed, although the coexistence or subsequent occurrence of tuberculosis and sarcoidosis is rare. We report a case of miliary sarcoidosis that developed 30 years after tuberculous pleurisy treatment. Sarcoidosis may occur after treatment with pulmonary tuberculosis and requires differential diagnosis from tuberculosis reactivation. Although miliary sarcoidosis is uncommon, it should be promptly differentiated from miliary tuberculosis associated with high mortality. This study reignites the debate on the causal association between tuberculosis and sarcoidosis.
Accelerated Polymerization of Lactide Driven by a DBU‐based Salt and a 15‐Crown‐5 Ether Sacrificial Kinetic Booster
Authors: Moins Sébastien , Coulembier Olivier
Published: June 2023

The recent advances in polymerization of lactide (LA) from organic salts enriched the toolbox to prepare well‐defined materials. Herein we report the use of crown ether (CE) as an additive to polymerize the L‐LA when initiated by 12‐hydroxydodecanoic acid (HDA) activated by one equivalent of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). While both size and structure of the ether additive play an important role on the overall rate of reaction, the CE decomplexation is crucial to outpace transfer reactions and also permit the process to be moderately conducted under air atmosphere by an efficient water trapping process.
Shining Light on Carbon Dots: New Opportunities in Photocatalysis
Authors: Sbacchi Maria , Mamone Martina , Morbiato Laura , Gobbo Pierangelo , Filippini Giacomo , Prato Maurizio
Published: June 2023

Photocatalysis is an emerging field that exploits light‐absorbing catalysts to yield transformations not even achievable in the dark. Considering the drawbacks of metal‐based photocatalysts, Carbon Dots (CDs) recently emerged as suitable green alternatives for different photocatalytic reactions. These carbon nanoparticles are easy to prepare, non‐toxic and potentially recyclable. Moreover, CDs usually display core‐shell structures which are highly tunable via synthetic and post‐synthetic strategies. This Concept Article focuses on the recent advancements in the CD‐based photocatalysis, highlighting the link between their superficial and core composition and their resulting photo‐redox abilities, and giving future perspectives on their application in cutting‐edge areas.
γ‐Hydroxybuttersäure
Authors: Theofel Nadine , Tsokos Michael , Scholtis Stefan
Published: June 2023

Die Analyse und Interpretation von GHB‐Konzentrationen ist alles andere als trivial. Dies ist insbesondere im forensisch‐toxikologischen Umfeld der Fall. So muss zum einen die endogene Konzentration berücksichtigt werden und zum anderen der Umstand, dass GHB nach Eintritt des Todes noch gebildet werden kann. Hinzu kommt, dass Untersuchungen hinsichtlich GHB zusätzlich angefordert werden müssen, da GHB im Rahmen der Systematischen Toxikologischen Analyse nicht untersucht wird. Weiterhin ist das Nachweisfenster von GHB in Blut oder Urin sehr kurz. Die Analyse erfolgt in der Regel mit chromatographischen Systemen, die an ein Massenspektrometer gekoppelt sind. Dieser Aufsatz fasst die GHB‐positiven Fälle der letzten fünf Jahre zusammen und stellt zwei Fälle detaillierter vor.
One‐Pot Synthesis of Axially and Centrally Chiral A‐type Nanogrids
Authors: Wei Ying , Du Xue , Huang Wan‐Xin , Fu Ming‐Yang , Zhang Zheng , Zhong Chun‐Xiao , Wang Yi‐Ru , Ling Hai‐Feng , Xie Ling‐Hai , Huang Wei
Published: June 2023

Comprehensive Summary

A novel type of A‐type nanogrids (AGs) with axial and central chirality was synthesized via Friedel‐Crafts gridization of thiophenes and difluorenyl biaromatic derivatives, yielding 9%—30%. Additionally, the effect of stereoisomers of 1,1’‐binaphthyl difluorenols (BINDFOH) was investigated to demonstrate that R/S‐BINDFOH is more advantageous for the synthesis of AGs than Mix‐BINDFOH. Furthermore, tests on OFET memory devices showed that AGs have a larger storage window, indicating potential for data storage applications.
Queuine Analogues Incorporating the 7‐Aminomethyl‐7‐deazaguanine Core: Structure–Activity Relationships in the Treatment of Experimental Autoimmune Encephalomyelitis
Authors: Cotter Michelle , Varghese Sreeja , Chevot Franciane , Fergus Claire , Kelly Vincent P. , Connon Stephen J. , Southern J. Mike
Published: June 2023

A library of queuine analogues targeting the modification of tRNA isoacceptors for Asp, Asn, His and Tyr catalysed by queuine tRNA ribosyltransferase (QTRT, also known as TGT) was evaluated in the treatment of a chronic multiple sclerosis model: murine experimental autoimmune encephalomyelitis. Several active 7‐deazaguanines emerged, together with a structure–activity relationship involving the necessity for a flexible alkyl chain of fixed length.
Cannabis use among adults undergoing cancer treatment
Authors: Azizoddin Desiree R. , Cohn Amy M. , Ulahannan Susanna V. , Henson Christina E. , Alexander Adam C. , Moore Kathleen N. , Holman Laura L. , Boozary Laili Kharazi , Sifat Munjireen S. , Kendzor Darla E.
Published: June 2023

Background

Little is known about the risks and benefits of cannabis use in the context of cancer care. This study characterized the prevalence, reasons for use, and perceived benefits of cannabis and compared symptoms and perceived risks between those who reported past 30‐day cannabis use and those who did not.

Methods

Adults undergoing cancer treatment at a National Cancer Institute–designated cancer center completed measures of sociodemographic characteristics, cannabis use, use modalities, reasons for use, perceived harms/benefits of use, physical and psychological symptoms, and other substance/medication use. Analyses compared patients who used or did not use cannabis in the past 30 days.

Results

Participants (N = 267) were 58 years old on average, primarily female (70%), and predominantly White (88%). Over a quarter of respondents (26%) reported past 30‐day cannabis use, and among those, 4.5% screened positive for cannabis use disorder. Participants who used cannabis most often used edibles (65%) or smoked cannabis (51%), and they were younger and more likely to be male, Black, and disabled, and to have lower income and Medicaid insurance than participants who did not use cannabis. Those who used cannabis reported more severe symptoms and perceived cannabis as less harmful than those who did not use cannabis. The most common medical reasons for cannabis use were pain, cancer, sleep problems, anxiety, nausea/vomiting, and poor appetite. Participants reported the greatest cannabis‐related symptom relief from sleep problems, nausea/vomiting, headaches, pain, muscle spasms, and anxiety.

Conclusions

Patients with cancer who used cannabis perceived benefits for many symptoms, although they showed worse overall symptomatology.

Plain language summary

Among adults undergoing cancer treatment, 26% reported cannabis use in the past 30 days. Those who used cannabis were more likely to be male and disabled and to have lower income and Medicaid insurance than those who did not use cannabis.

Participants most commonly reported using cannabis for pain, cancer, sleep, anxiety, and nausea/vomiting and reported the greatest perceived benefits for sleep, nausea/vomiting, headaches, pain, muscle spasms, and anxiety, yet participants who used cannabis also reported feeling worse physically and psychologically compared to those who did not use cannabis.

Participants who used cannabis were more likely to report that cannabis was less risky to their health than alcohol, smoking, and opioids than those who did not use cannabis.
Longitudinal strain analysis for assessment of early cardiotoxicity during anthracycline treatment in childhood sarcoma: A single center experience
Authors: Alpman Maria Sjöborg , Jarting Annica , Magnusson Kerstin , Manouras Aristomenis , Henter Jan‐Inge , Broberg Agneta Månsson , Herold Nikolas
Published: June 2023

Background

The growing population of long‐term childhood cancer survivors encounter a substantial burden of cardiovascular complications. The highest risk of cardiovascular complications is associated with exposure to anthracyclines and chest radiation. Longitudinal cardiovascular surveillance is recommended for childhood cancer patients; however, the optimal methods and timing are yet to be elucidated.

Aims

We aimed to investigate the feasibility of different echocardiographic methods to evaluate left ventricular systolic function in retrospective datasets, including left ventricular ejection fraction (LVEF), fractional shortening (FS), global longitudinal strain (GLS) and longitudinal strain (LS) as well as the incidence and timing of subclinical left ventricular dysfunction detected by these methods.

Methods and Results

A retrospective longitudinal study was performed with re‐analysis of longitudinal echocardiographic data, acquired during treatment and early follow‐up, including 41 pediatric sarcoma patients, aged 2.1–17.8 years at diagnosis, treated at Astrid Lindgren Children's Hospital, Stockholm, Sweden, during the period 2010–2021. All patients had received treatment according to protocols including high cumulative doxorubicin equivalent doses (≥250 mg/m2). In 68% of all 366 echocardiograms, LS analysis was feasible. Impaired LS values (<17%) was demonstrated in >40%, with concomitant impairment of either LVEF or FS in 20% and combined impairment of both LVEF and FS in <10%. Importantly, there were no cases of abnormal LVEF and FS without concomitant LS impairment.

Conclusion

Our findings demonstrate feasibility of LS in a majority of echocardiograms and a high incidence of impaired LS during anthracycline treatment for childhood sarcoma. We propose inclusion of LS in pediatric echocardiographic surveillance protocols.
Context‐aware application scheduling in fog computing environment
Authors: Islam Mir Salim Ul , Kumar Ashok
Published: June 2023

Fog computing emerges as the new computing environment that stays in the proximity of end‐users and harnesses resources at the edge of the network to extend cloud‐facilities. It provides attractive solutions to the diverse range of Internet of Things (IoT) applications by executing them in the vicinity of end‐users. It is challenging to schedule these latency‐sensitive, computation‐intensive, and resource‐hungry applications on distributed, heterogeneous, and resource‐constrained Fog computing environment while ensuring time‐bound service delivery and satisfying Quality of Service (QoS) requirements of end‐users. In this paper, a context‐aware application scheduling technique is proposed for Fog computing environments that employs various parameters of device‐ and application‐level context to minimize service delivery time and satisfy QoS requirements of various IoT applications such as surveillance and game‐based applications. The performance of the proposed technique is evaluated in a simulated Fog environment and compared with baseline application scheduling techniques. The simulation results demonstrate that the proposed context‐aware scheduling techniques result in significant improvement in service delivery time and QoS compared to baseline scheduling techniques.
Adsorption and Aggregation Behavior in Aqueous Solution of Tetrasiloxane‐based Carboxylate Surfactants via “Thiol‐ene” Photochemical Reaction
Authors: Meng Lina , Wang Wenyu , Li Lei , Feng Shengyu
Published: June 2023

Anionic silicone surfactants have long been a neglected field. In this paper three anionic silicone surfactants were synthesized first time from dichloromethylvinylsilane through hydrolysis‐condensation, “thiol‐ene” photo‐ chemical and then salting reaction. The critical aggregate concentration (CAC), surface tension, minimum surface area per surfactant molecule and surface pressure at CAC were studied by both surface tension and electrical conductivity. The results showed that they had significant surface activity at the gas/liquid interface and were capable to reduce the surface tension of water to approximately 20 mN m−1. The results of transmission electron microscopy showed that the three silicone surfactants self‐assembled into spherical aggregates of uniform size in aqueous solution above the CAC. The dynamic light scattering results demonstrated that the size of the aggregates was determined to be in the range from 60 to 300 nm at 0.05 mol L−1 and the order of the size of the aggregates is (Me3SiO)3SiCO2Li<(Me3SiO)3SiCO2Na<(Me3SiO)3SiCO2K.
Response to the FDA Decision Regarding DPYD Testing Prior to Fluoropyrimidine Chemotherapy
Authors: Hertz Daniel L. , Smith D. Max , Scott Stuart A. , Patel Jai N. , Hicks J. Kevin
Published: June 2023

Fluoropyrimidine (FP) chemotherapy is associated with severe, life‐threatening toxicities, particularly among patients who carry deleterious germline variants in the DPYD gene. Pretreatment DPYD testing is standard of care throughout most of Europe; however, it has not been recommended in clinical practice guidelines in the United States. Due to increased risk of severe toxicity, a Citizen's Petition asked the US Food and Drug Administration (FDA) to update language in FP drug labels to recommend DPYD testing as part of a boxed warning and recommend FP dose reduction in patients carrying deleterious germline variants. In response, the FDA updated the capecitabine package insert to inform patients about the toxicity risk and test availability and consider DPYD testing. However, the FDA did not include a testing recommendation or requirement, or a boxed warning. Additionally, the FDA did not recommend FP dose adjustment in DPYD variant carriers. This review provides a critical assessment of the DPYD‐FP pharmacogenetic association using the FDA's previously published Pharmacogenetic Pyramid, demonstrating that the evidence is compelling for recommending DPYD testing prior to FP treatment. Additionally, the FDA's stated concerns about recommending DPYD testing and DPYD‐guided FP dose adjustment are addressed and discussed in the context of the FDA's other genetic testing and dose adjustment recommendations. We call on the FDA to follow our European counterparts in recommending DPYD testing and genotype‐based dose adjustment to ensure patients with cancer receive safe and effective FP chemotherapy.
Genotypic variation in germination rate, seedling vigor, and seed phenotype of Kentucky bluegrass cultivars
Authors: Folck Amanda J. , Bigelow Cale A. , Jiang Yiwei , Patton Aaron J.
Published: June 2023

Kentucky bluegrass (Poa pratensis L.) is the most widely used cool‐season turfgrass for athletic fields, but its seeds germinate slowly. The objective was to determine the germination rate, seedling vigor, and seed phenotype of Kentucky bluegrass cultivars. Germination and seedling vigor tests were conducted using a seed incubator set at alternating 25/15°C (day/night) temperatures and an 8 h day−1 photoperiod. Twenty‐one cultivars were tested using two seed lots for each. Germination was most rapid among the experimental genotype PST‐T15‐44 and the commercial cultivar "After Midnight, as they took the minimum days to reach 50% germination in only 7.9–8.0 or 8.8 days, respectively. Cultivars Tirem and Volt required >12 days in both lots to reach 50% germination (12.0–13.7 days). There was a difference of 5–6 days in 50% germination between cultivars. Seedling vigor was also measured but few differences between cultivars were noted. Data on seed phenotype including seed length, width, area, circularity, and thousand seed weights (TSW) all varied by cultivar. ‘‘After Midnight’’ had the longest seeds (3.065 mm). ‘‘Moonlight SLT’’ seeds were the shortest in length (2.366 mm), narrowest in width (0.717 mm), and smallest in area (1.328 cm2). Across all cultivars, seed length and circularity were correlated with germination rate (r = 0.62, p = 0.0025; r = −0.53, p = 0.0141). Seed phenotyping could be an important tool in breeding for improved germination rate. By identifying and using rapidly germinating Kentucky bluegrass cultivars, it may be possible to establish turf more rapidly.
Going green: Environmental risk management, market value and performance
Authors: Dal Maso Lorenzo , Gianfagna Laura , Maglione Federico , Lattanzi Nicola
Published: June 2023

This study investigates the relationship between environmental performance and market values of firms exposed to environmental risk that manage effectively to reduce it. Using a sample of 8112 US firm‐year observations during 2012–2020, we document a positive relationship between firms' environmental performance and market‐to‐book value. Moreover, we show that this relationship holds primarily when firms are more vulnerable to environmental risk and proactively manage to reduce it. Our paper not only agrees with the previous literature showing that it pays to be good but, most importantly, shows that such an approach is reflected in higher valuation mostly when companies use sound environmental risk‐control strategies. Contributions and implications are discussed.
Foreign ownership, passive‐learning knowledge spillovers, and corporate social responsibility reporting in China
Authors: Li Xuan , Zhang Chi , Gao Wenliang , Geng Yanli , Sun Weizhang
Published: June 2023

As there are many studies on the predictors of corporate social responsibility (CSR) reporting, the influences of foreign direct investments (FDIs) knowledge spillovers (KSs) on CSR reporting in developing countries remain unclear. This paper introduces the passive‐learning KSs concept to explain whether, why, and how domestic firms learn CSR knowledge from their foreign counterparts. First, we investigate the relationship between foreign ownership and the quality of CSR reporting (CSRQ). Second, we test the moderating effect of three types of direct institutional pressures: the green development policy, the mandatory CSR reporting requirement, and CSR regulations issued by the State‐owned Assets Supervision and Administration Commission. Third, we examine the moderating effect of board interlocks to explore the indirect impacts of institutional pressures. We run regressions on a sample of Chinese A‐share listed companies and the hypotheses are generally supported. This paper contributes to the literature on CSR reporting and FDIs KSs by adopting the passive‐learning KSs theory to explain CSR KSs in developing countries.
Reproducible reformation of a bilayer lipid membrane using microair bubbles
Authors: Hashimoto Izumi , Osaki Toshihisa , Sugiura Hirotaka , Mimura Hisatoshi , Takamori Sho , Miki Norihisa , Takeuchi Shoji
Published: June 2023

Planar bilayer lipid membranes (BLMs) are widely used as models for cell membranes in various applications, including drug discovery and biosensors. However, the nanometer‐thick bilayer structure, assembled through hydrophobic interactions of amphiphilic lipid molecules, makes such BLM systems mechanically and electrically unstable. In this study, we developed a device to reform BLMs using a microair bubble. The device consists of a double well divided by a separator with a microaperture, where a BLM was formed by infusing a lipid‐dispersed solvent and an aqueous droplet into each well in series. When the BLM ruptured, a microair bubble was injected from the bottom of the well to split the merged aqueous droplet at the microaperture, which resulted in the reformation of two lipid monolayers on the split droplets. By bringing the two droplets into contact, a new BLM was formed. An angled step design was introduced in the BLM device to guide the bubble and ensure the splitting of the merged droplet. We also elucidated the optimal bubble inflow rate for the reproducible BLM reformation. Using a 4‐channel parallel device, we demonstrated the individual and repeatable reformation of BLMs. Our approach will aid the development of automated and arrayed BLM systems.
A novel qPCR‐based technique for identifying avian sex: An illustration within embryonic craniofacial bone
Authors: Houchen Claire J. , Bergman‐Gonzalez Maria , Bumann Erin E.
Published: June 2023

Sex is a biological variable important to consider in all biomedical experiments. However, doing so in avian embryos can be challenging as sex can be morphologically indistinguishable. Unlike humans, female birds are the heterogametic sex with Z and W sex chromosomes. The female‐specific W chromosome has previously been identified in chick using a species‐specific polymerase chain reaction (PCR) technique. We developed a novel reverse transcription quantitative PCR (RT‐qPCR) technique that amplifies the W chromosome gene histidine triad nucleotide‐binding protein W (HINTW) in chick, quail, and duck. Accuracy of the HINTW RT‐qPCR primer set was confirmed in all three species using species‐specific PCR, including a novel quail‐specific HINTW PCR primer set. Bone development‐related gene expression was then analyzed by sex in embryonic lower jaws of duck and quail, as adult duck beak size is known to be sexually dimorphic while quail beak size is not. Trends toward sex differences were found in duck gene expression but not in quail, as expected. With these novel RT‐qPCR and PCR embryo sexing methods, sex of chick, quail, and duck embryos can now be assessed by either/both RNA and DNA, which facilitates analysis of sex as a biological variable in studies using these model organisms.
Application of Optical Hydrogels in Environmental Sensing
Authors: Yang Shuo , Sarkar Shruti , Xie Xing , Li Dan , Chen Jianmin
Published: June 2023

The ever‐increasing complexity of environmental pollutants urgently warrants the development of new detection technologies. Sensors based on the optical properties of hydrogels enabling fast and easy in situ detection are attracting increasing attention. In this paper, the data from 138 papers about different optical hydrogels (OHs) are extracted for statistical analysis. The detection performance and potential of various types of OHs in different environmental pollutant detection scenarios were evaluated and compared to those obtained using the standard detection method. Based on this analysis, the target recognition and sensing mechanisms of two main types of OHs are reviewed and discussed: photonic crystal hydrogels (PCHs) and fluorescent hydrogels (FHs). For PCHs, the environmental stimulus response, target receptors, inverse opal structures, and molecular imprinting techniques related to PCHs are reviewed and summarized. Furthermore, the different types of fluorophores (i.e., compound probes, biomacromolecules, quantum dots, and luminescent microbes) of FHs are discussed. Finally, the potential academic research directions to address the challenges of applying and developing OHs in environmental sensing are proposed, including the fusion of various OHs, introduction of the latest technologies in various fields to the construction of OHs, and development of multifunctional sensor arrays.
Universal Encapsulation Adhesive for Lead Sedimentation and Attachable Perovskite Solar Cells with Enhanced Performance
Authors: Zhu Xuehao , Cai Haoyu , Bai Cong , Wu Zhengzhe , Shen Wenjian , Xiong Yiming , Zhao Juan , Huang Fuzhi , Cheng Yibing , Zhong Jie
Published: June 2023

In this work, a modified polyurethane adhesive (PUA) was prepared to realize a convenient encapsulation strategy for lead sedimentation and attachable perovskite solar cells (A‐PSCs). The modified PUA can completely self‐heal within 45 min at room temperature with an efficient lead ion‐blocking rate of 99.3%. The PUA film can be coated on a metal electrode with slight efficiency improvement from 23.96% to 24.15%. The thermal stability at 65 °C and the humidity stability at 55% relative humidity (RH) are superior to the devices encapsulated with polyisobutylene. The PUA film has strong adhesion to the flexible substrate and the initial efficiency of the flexible perovskite module (17.2%) encapsulated by PUA remains 92.6% within 1825 h. These results suggest that PUA encapsulation is universal for rigid and flexible PSCs with enhanced stability and low lead hazards. Moreover, it was found that flexible PSCs can be well attached to various substrates with PUA, providing a facile route for the A‐PSCs in various scenarios without additional encapsulation and installation.
Design of a flexible but robust setup for temperature‐dependent electrochemistry down to cryogenic temperatures
Authors: Fink Michael F. , Schönfeld Sophie , Schreck Constantin , Hörner Gerald , Weber Birgit
Published: June 2023

Electrochemistry and its analytics are essential in a variety of scientific and technological fields where properties related to reduction‐oxidation reactions, so‐called redox properties, are to be explored. While methodological standards for experiments are well established at room temperature, this is still untrue at sub‐zero/cryogenic temperatures, the conditions required for the survey of (ultra−)rapid processes and their intermediates. Problems due to “hand‐waving” temperature regulation/conditioning and common usage of pseudo‐reference electrodes renders cryo‐electrochemistry a great challenge. Herein, we describe a robust setup for performing reliable cryo‐electrochemical experiments down to −80 °C. It combines highly stable but flexible temperature conditioning with gas‐tight sealing of the electrochemical cell setup. Modification of a commercial palladium hydride reference electrode (PdH RE) allows for rapid temperature cycling under cryogenic conditions in aprotic organic solvents. Validation of the setup with the well‐known Ferrocene|Ferrocenium (Fc|Fc+) redox couple gave good compliance with literature data at room temperature in a range of organic solvent‐based electrolytes. Evaluation of temperature‐dependent diffusion kinetic parameters, such as diffusion coefficients (D) and diffusional activation energies (Ea,D) from CVs at multiple potential scan‐rates and temperature levels emphasize the reliability of the presented cryo‐electrochemical setup.
Evaluating scaling of capillary photo‐biofilm reactors for high cell density cultivation of mixed trophies artificial microbial consortia
Authors: Kenkel Amelie , Karande Rohan , Bühler Katja
Published: June 2023

Capillary biofilm reactors (CBRs) are attractive for growing photoautotrophic bacteria as they allow high cell‐density cultivation. Here, we evaluated the CBR system's suitability to grow an artificial consortium composed of Synechocystis sp. PCC 6803 and Pseudomonas sp. VBL120. The impact of reactor material, flow rate, pH, O2, and medium composition on biomass development and long‐term biofilm stability at different reactor scales was studied. Silicone was superior over other materials like glass or PVC due to its excellent O2 permeability. High flow rates of 520 μL min−1 prevented biofilm sloughing in 1 m capillary reactors, leading to a 54% higher biomass dry weight combined with the lowest O2 concentration inside the reactor compared to standard operating conditions. Further increase in reactor length to 5 m revealed a limitation in trace elements. Increasing trace elements by a factor of five allowed for complete surface coverage with a biomass dry weight of 36.8 g m−2 and, thus, a successful CBR scale‐up by a factor of 25.

Practical application: Cyanobacteria use light energy to upgrade CO2, thereby holding the potential for carbon‐neutral production processes. One of the persisting challenges is low cell density due to light limitations and O2 accumulation often occurring in established flat panel or tubular photobioreactors. Compared to planktonic cultures, much higher cell densities (factor 10 to 100) can be obtained in cyanobacterial biofilms. The capillary biofilm reactor (CBR) offers good growth conditions for cyanobacterial biofilms, but its applicability has been shown only on the laboratory scale. Here, a first scale‐up study based on sizing up was performed, testing the feasibility of this system for large‐scale applications. We demonstrate that by optimizing nutrient supply and flow conditions, the system could be enlarged by factor 25 by enhancing the length of the reactor. This reactor concept, combined with cyanobacterial biofilms and numbering up, holds the potential to be applied as a flexible, carbon‐neutral production platform for value‐added compounds.
Review and comparison of different strategies to define earthquake design accelerations
Authors: Ordaz Mario , Salgado‐Gálvez Mario A. , Cardona Omar D.
Published: June 2023

In the task of defining earthquake design accelerations, different approaches have been used worldwide and recent advances have led to changes in the rationale behind the choice of these coefficients. Considering that the two main objectives of earthquake engineering are to guarantee a certain level of earthquake safety while allowing designs to be feasible from an economic perspective, given the scarcity of resources, this paper reviews and compares different approaches that have been used to define the earthquake design coefficient, starting from the classic one, based on the selection of a fixed return period, and covering other more complex proposals that include, in one way or another, the physical vulnerability of the buildings. For each case, we assess how these two earthquake engineering objectives are addressed and review, from the coding perspective, their advantages and limitations. Our findings indicate that only one of these approaches, denoted as optimal design and proposed in 1976 by Rosenblueth, explicitly accounts for both earthquake safety and construction costs. We conclude that instead of aiming to have a uniform criterion to define the design accelerations (e.g., uniform return period or uniform collapse probabilities), an optimization criterion must be used, despite the challenges it presents from the perspective of building codes.
Unsupervised machine learning for detecting soil layer boundaries from cone penetration test data
Authors: Hudson Kenneth S. , Ulmer Kristin J. , Zimmaro Paolo , Kramer Steven L. , Stewart Jonathan P. , Brandenberg Scott J.
Published: June 2023

Cone penetration test (CPT) data contains detailed stratigraphic information that is useful in a wide variety of applications. Separating a CPT profile into discrete layers is an important part of many analyses such as critical layer selection in liquefaction triggering analysis, effective stress seismic ground response analysis, analysis of pile shaft and tip resistance, and soil‐pile interaction analysis. The discretization of the profile into layers is often done manually, relying on the judgment of the analyst. This manual approach is cumbersome for datasets that include large numbers of CPT profiles (such as the Next Generation Liquefaction [NGL] database and the New Zealand Geotechnical Database) and it may not be consistent or repeatable because different analysts may discretize a given CPT log in different ways. To overcome these difficulties, we present an approach to automatically divide a CPT profile into discrete layers. Automated layer detection is performed using an unsupervised machine learning technique called agglomerative clustering in combination with two cost functions to identify an optimal number of layers. The algorithm is illustrated using CPT profiles from the NGL database, where the approach is being used in the development of liquefaction triggering and manifestation models. Although the algorithm shows promise for replicating our judgment regarding layering, we recommend visual review of the layering produced by the algorithm to check for reasonableness given the site geology and intended use of the CPT data.
Classifying excessive exercise: Examining the relationship between compulsive exercise with obsessive‐compulsive disorder symptoms and disordered eating symptoms
Authors: Cosh Suzanne M. , Eshkevari Ertimiss , McNeil Dominic G. , Tully Phillip J.
Published: June 2023

Objective

There remains a lack of consensus around nosology for compulsive exercise (CE). Although widely observed in eating disorders (ED), CE shares theoretical overlap with obsessive‐compulsive disorder (OCD), where exercise compulsions occur in response to obsessions. Yet, there is limited and mixed evidence of a relationship between CE with OCD. This study aims to explore the appropriate diagnostic classification of CE through examination of CE in relation to OCD, obsessional thinking, and ED symptoms.

Method

Two hundred and eighty one adults with mental health symptoms, dieting, and exercise behaviour completed measures of OCD, CE, and disordered eating symptoms. Regression and Receiver Operating Characteristic analyses examined relationships between dimensions of CE with OCD and ED symptoms, and the predictive ability of CE assessment for detecting threshold OCD and ED symptoms.

Results

CE assessment was poor at predicting threshold OCD symptoms, probable Anorexia Nervosa, and Binge Eating Disorder and moderate at detecting probable disordered eating and Bulimia Nervosa. Associations between CE and OCD symptoms were not significant after adjustment for ED symptoms. Obsessional thinking was associated only with lack of exercise enjoyment.

Conclusions

Results indicate that excessive exercise might represent a distinct disorder, with some shared traits across CE, OCD and ED symptoms. Findings question the utility of adaptation of OCD diagnostic criteria for CE. Assessment and treatment implications are considered.
A physical topology for optimizing partition tolerance in consortium blockchains to reach CAP guarantee bound
Authors: Wang Han , Li Hui , Ye Qiongwei , Lu Ping , Yang Yong , Chong Peter Han Joo , Chu Xiaoli , Lv Qi , Smahi Abla
Published: June 2023

Decentralized cryptocurrency systems, known as blockchains, have shown promise as an infrastructure for mutually distrustful parties to securely agree on transactions. Nevertheless, blockchain systems are constrained by the CAP Trilemma. Due to performance degradation, it is impossible to address this issue by improving simply the consensus layer or the network layer. To alleviate the CAP constraint in consortium blockchains, we propose a topological construction method to optimize the physical layer based on multi‐dimensional hypercubes with excellent partition tolerance in probability. The basic topology has the advantage of solving the mismatch problem between the overlay network and the underlying network. It is further extended to hierarchical recursive topologies with more intermediate links or short links to balance the reliability requirement with the cost of building the physical network. We prove that the proposed hypercube topology has better partition tolerance than the regular rooted tree and ring lattice topologies, and effectively fits the upper‐layer protocols at the consensus and network layers. As a result, combined with suitable transmission and consensus protocols that satisfy strong consistency and availability, the proposed topology‐constructed blockchain can reach the CAP guarantee bound.