bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Insights into the Very Low Activity of the Homocoenzyme B12 Adenosylmethylcobalamin in Coenzyme B12‐Dependent Diol Dehydratase and Ethanolamine Ammonia‐Lyase
Authors: Shibata Naoki , Higuchi Yoshiki , Kräutler Bernhard , Toraya Tetsuo
Published: August 2022

The X‐ray structures of coenzyme B12 (AdoCbl)‐dependent eliminating isomerases complexed with adenosylmethylcobalamin (AdoMeCbl) have been determined. As judged from geometries, the Co−C bond in diol dehydratase (DD) is not activated even in the presence of substrate. In ethanolamine ammonia‐lyase (EAL), the bond is elongated in the absence of substrate; in the presence of substrate, the complex likely exists in both pre‐ and post‐homolysis states. The impacts of incorporating an extra CH2 group are different in the two enzymes: the DD active site is flexible, and AdoMeCbl binding causes large conformational changes that make DD unable to adopt the catalytic state, whereas the EAL active site is rigid, and AdoMeCbl binding does not induce significant conformational changes. Such flexibility and rigidity of the active sites might reflect the tightness of adenine binding. The structures provide good insights into the basis of the very low activity of AdoMeCbl in these enzymes.
Qualitative Vignettes Drawing on Real Cases as Method in Organizational Research
Authors: Marques Nascimento Macêdo Nívea Marcela , Bispo Marcelo de Souza
Published: August 2022

This paper aims to present the importance of qualitative vignettes based on real cases in organizational research and b) to show how to create such vignettes from our experience researching collective decision‐making at a university senate. We defend that qualitative vignette based on real cases are a promising methodological resource in organizational research because they open space for people to reflect on what they do, evoking their actions and the dynamic of social practices of groups they are involved. We concluded that vignettes based on real cases increase the trustworthiness of data generated by the research and are also a good option to be combined with other qualitative methods.
Development of Urease Inhibitors by Fragment‐Based Dynamic Combinatorial Chemistry
Authors: Wu Yao , Zhao Shuang , Liu Changming , Hu Lei
Published: August 2022

In this study, fragment‐based dynamic combinatorial chemistry (DCC) was explored for the development of novel urease inhibitors. Based on a rationally designed fragment, two iteratively evolved dynamic combinatorial libraries (DCLs) were generated and screened in the presence of urease template. The best ligand identified revealed not only strong urease inhibition but also low cytotoxicity. Additionally, a possible inhibitory mechanism was elucidated in the binding kinetics study and docking simulation.
Risk of prostate cancer and death after benign transurethral resection of the prostate—A 20‐year population‐based analysis
Authors: Hilscher Maria , Røder Andreas , Helgstrand J. Thomas , Klemann Nina , Brasso Klaus , Vickers Andrew Julian , Stroomberg Hein Vincent
Published: August 2022

Background

The oncological risks after benign histology on a transurethral resection of the prostate (TURP) remain largely unknown. Here, the risk of prostate cancer incidence and mortality following a benign histological assessment of TURP is investigated in a population‐based setting.

Methods

Between 1995 and 2016, 64,059 men in Denmark underwent TURP without prior biopsy of the prostate; 42,558 of these men had benign histology. The risks of prostate cancer, prostate cancer with a Gleason score ≥ 3 + 4, and prostate cancer–specific death were assessed with competing risks. Specific risks for pre‐TURP prostate‐specific antigen (PSA) levels at 10 and 15 years were visualized by locally estimated scatterplot smoothing.

Results

The median age at TURP was 72 years (interquartile range [IQR], 65–78 years), and the median follow‐up was 15 years (IQR, 10–19 years). The 10‐year risks of any prostate cancer and prostate cancer with a Gleason score ≥ 3 + 4 and the 15‐year risk of prostate cancer death showed clear visual relations with increasing PSA. The 15‐year cumulative incidence of prostate cancer–specific death after benign TURP was 1.4% (95% confidence interval [CI], 1.3%–1.6%) for all men and 0.8% (95% CI, 0.6%–1.1%) for men with PSA levels <10 ng/ml. The primary limitation was exclusion due to missing PSA data.

Conclusions

Men with low PSA levels and a benign TURP can be reassured about their cancer risk and do not need to be monitored differently than any other men. Patients with high PSA levels can be considered for further follow‐up with prostate magnetic resonance imaging. These findings add to the literature suggesting that normal histology from the prostate entails a low risk of death from the disease.

Lay summary

There is little knowledge about the oncological risks after the surgical treatment of benign prostatic hyperplasia.

This study shows a very low risk of adverse oncological outcomes in men with prostate‐specific antigen (PSA) levels below 10 ng/ml at the time of transurethral resection of the prostate.

Patients with higher PSA levels may need more extensive follow‐up.
Surface Chemistry of the Molecular Solar Thermal Energy Storage System 2,3‐Dicyano‐Norbornadiene/Quadricyclane on Ni(111)
Authors: Hemauer Felix , Bauer Udo , Fromm Lukas , Weiß Cornelius , Leng Andreas , Bachmann Philipp , Düll Fabian , Steinhauer Johann , Schwaab Valentin , Grzonka Robert , Hirsch Andreas , Görling Andreas , Steinrück Hans‐Peter , Papp Christian
Published: August 2022

The front cover artwork is provided by the group of Prof. Dr. Christian Papp at Physical Chemistry II of FAU Erlangen‐Nürnberg and FU Berlin. The image shows the isomerization reaction of the molecule pair 2,3‐dicyano‐norbornadiene/quadricyclane as potential molecular solar thermal (MOST) energy storage system. Read the full text of the Research Article at 10.1002/cphc.202200199.
Visible‐Light‐Driven Metal‐Free C−H Functionalization: Access to New Bioactive Tetrahydroisoquinoline‐Butenolide Hybrids via Domino Amine Oxidation/Vinylogous Mannich Reaction
Authors: Kersting Lena , Kuhn Leah , Anokhin Maksim , Schuster Florian , Häberli Cécile , Sambyal Shainy , Kumar Halmuthur M. Sampath , Keiser Jennifer , Alabugin Igor , Tsogoeva Svetlana B.
Published: August 2022

The front cover artwork is provided by Svetlana B. Tsogoeva (Friedrich‐Alexander‐Universität Erlangen‐Nürnberg, Germany). The image shows a new efficient metal‐free, visible‐light‐mediated, aerobic amine oxidation/vinylogous Mannich domino reaction, using fluorescein as a photosensitizer and thiourea as a simple additive. Read the full text of the Research Article at 10.1002/cptc.202200109.
Tetrahydropalmatine induces the polarization of M1 macrophages to M2 to relieve limb ischemia‐reperfusion‐induced lung injury via inhibiting the TLR4/NF‐κB/NLRP3 signaling pathway
Authors: Wen Heng , Lu Dongshi , Chen Hanjian , Zhu Yeke , Xie Qing , Zhang Zhao , Wu Zhouyang
Published: August 2022

Tetrahydropalmatine (THP) is the main component of the Chinese medicine Corydalis yanhusuo, which has been reported to alleviate limb ischemia‐reperfusion‐induced acute lung injury (LIR‐ALI). This study aimed to investigate the mechanism underlying the effect of THP on relieving LIR‐ALI. LIR‐ALI model was established in rats with the presence or absence of THP pretreatment. Then, BEAS‐2B cells and THP‐1 macrophages were cocultured with rat serum from the Sham group and the Model group in the presence or absence of THP pretreatment. Subsequently, lung/body weight and lung wet/dry ratio of rats were calculated. Histological changes of lung tissues were observed by hematoxylin‐eosin staining. Expression of CD86 and CD163 in lung tissues of rats was assessed by quantitative reverse transcription polymerase chain reaction, immunohistochemistry staining, and flow cytometry analysis. Levels of inflammatory cytokines were measured by enzyme linked immunosorbent assay. The expression of proteins related to toll‐like receptor 4 (TLR4)/nuclear factor‐κB (NF‐κB)/NLRP3 signaling was detected by western blot analysis. Results revealed that THP significantly relieved LIR‐ALI in rats. Moreover, THP also reduced CD86 expression but elevated CD163 expression in lung tissues of rats with LIR‐ALI. Furthermore, THP inhibited inflammation in serum and bronchoalveolar lavage fluid of rats with LIR‐ALI and inactivated the TLR4/NF‐κB/NLRP3 signaling in vivo. Additionally, coculture of serum from rats in the Model group also reduced viability, promoted inflammation, inactivated TLR4/NF‐κB/NLRP3 expression in BEAS‐2B cells and inhibited macrophage polarization, while these effects were all reversed by THP treatment. Collectively, THP could induce the polarization of M1 macrophage to M2 to suppress inflammation via inhibiting TLR4/NF‐κB/NLRP3 signaling, thereby attenuating LIR‐ALI.
Inference of population structure and admixture proportion from Y chromosomal data of Chinese population
Authors: Song Mengyuan , Wang Xindi , Zhao Chenxi , Qian Xiaoqin , Lang Min , Hou Yiping , Song Feng
Published: August 2022

In the past two decades, Y chromosome data has been generated for human population genetic studies. These Y chromosome datasets were produced with various testing methods and markers, thus difficult to combine them for a comprehensive analysis. In this study, we combine four human Y chromosomal datasets of Han, Tibetan, Hui, and Li ethnic groups. The dataset contains 27 microsatellites and 137 single nucleotide polymorphisms these populations share in common. We assembled a single dataset containing 2439 individuals from 25 nationwide populations in China. A systematic analysis of genetic distance and clustering was performed. To determine the gene flow of the studied population with worldwide populations, we modeled the ancestry informative markers. The reference panel was regarded as a mixture of South Asian (SAS), East Asian (EAS), European (EUR), African (AFR), and American (AMR) populations from 1000 Genomes data of Y chromosome using nonlinear data‐fitting. We then calculated the admixture proportion of these four studied populations with 26 worldwide populations. The results showed that the Han and Hui have great genetic affinity, and Hui is the most admixed ethnic group, with 61.53% EAS, 34.65% SAS, 1.91% AFR, 1.56% AMR, and 0.04% EUR ancestry component (the AMR is highly admixed and thus should be ignored). All the other three ethnic groups contained more than 97% EAS ancestry component. The Li is the least admixed population in this study. The combined dataset in this study is the largest of this kind reported to date and proposes reference population data for use in future paternal genetic studies and forensic genealogical identification.
Concepts and recent advances in microchip electrophoresis coupled to mass spectrometry: Technologies and applications
Authors: Naghdi Elahe , Moran Griffin E. , Reinau Marika Ejby , De Malsche Wim , Neusüß Christian
Published: August 2022

The online coupling of microchip electrophoresis (ME) as a fast, highly efficient, and low‐cost miniaturized separation technique to mass spectrometry (MS) as an information‐rich and sensitive characterization technique results in ME–MS an attractive tool for various applications. In this paper, we review the basic concepts and latest advances in technology for ME coupled to MS during the period of 2016–2021, covering microchip materials, structures, fabrication techniques, and interfacing to electrospray ionization (ESI)–MS and matrix‐assisted laser desorption/ionization–MS. Two critical issues in coupling ME and ESI–MS include the electrical connection used to define the electrophoretic field strength along the separation channel and the generation of the electrospray for MS detection, as well as, a miniaturized ESI‐tip. The recent commercialization of ME–MS in zone electrophoresis and isoelectric focusing modes has led to the widespread application of these techniques in academia and industry. Here we summarize recent applications of ME–MS for the separation and detection of antibodies, proteins, peptides, carbohydrates, metabolites, and so on. Throughout the paper these applications are discussed in the context of benefits and limitations of ME–MS in comparison to alternative techniques.
Mulberry leaves juice attenuates arsenic‐induced neurobehavioral and hepatic disorders in mice
Authors: Islam Zohurul , Islam Jahidul , Tony Selim Reza , Anjum Adiba , Ferdous Rafia , Roy Apurba Kumar , Hossain Shakhawoat , Salam Kazi Abdus , Nikkon Farjana , Hossain Khaled , Saud Zahangir Alam
Published: August 2022

Arsenic (As) poisoning has caused an environmental catastrophe in Bangladesh as millions of people are exposed to As‐contaminated drinking water. Chronic As‐exposure causes depression, memory impairment, and liver injury in experimental animals. This study was carried out to assess the protective effect of mulberry leaves juice (Mul) against As‐induced neurobehavioral and hepatic dysfunctions in Swiss albino mice. As‐exposed mice spent significantly reduced time in open arms and increased time spent in closed arms in the elevated plus maze (EPM) test, whereas they took significantly longer time to find the hidden platform in the Morris water maze (MWM) test and spent significantly less time in the desired quadrant when compared to the control mice. A significant reduction in serum BChE activity, an indicator of As‐induced neurotoxicity‐associated behavioral changes, was noted in As‐exposed mice compared to control mice. Supplementation of Mul to As‐exposed mice significantly increased serum BChE activity, increased the time spent in open arms and reduced time latency to find the hidden platform, and stayed more time in the target quadrant in EPM and MWM tests, respectively, compared to As‐exposed‐only mice. Also, a significantly reduced activity of BChE, AChE, SOD, and GSH in brain, and elevated ALP, AST, and ALT activities in serum were noted in As‐exposed mice when compared to control mice. Mul supplementation significantly restored the activity of these enzymes and also recovered As‐induced alterations in hepatic tissue in As‐exposed mice. In conclusion, this study suggested that mulberry leaves juice attenuates As‐induced neurobehavioral and hepatic dysfunction in mice.
The effect of soda taxes beyond beverages in Philadelphia
Authors: Lozano‐Rojas Felipe , Carlin Patrick
Published: August 2022

Soda taxes are implemented in several cities across the United States (US) with the aim of reducing sugar intake from sugar sweetened beverages (SSBs). Sugar is linked to obesity and to higher risk of diabetes and cardiovascular conditions. Sodas are targeted with these taxes since they are the main source of sugar for consumers in the US. In presence of potential substitutes, the policy can be undermined by consumers changing their sources of sugar. We examine the heterogeneous effects of the 2017 Philadelphia soda tax on purchases of other items containing sugar. We present an empirical evaluation focusing on the potential substitution toward additional sugary foods in Philadelphia and counties bordering Philadelphia. We find an increase in sugar from purchases of sweetened foods of about 4.3% following the introduction of the tax in Philadelphia and of 3.7% in the neighboring localities. The substitution to sugary foods in Philadelphia offsets 19% of the decrease of sugar from SSBs. Additionally, we find that the substitution offsets 37% of the decrease of sugar from SSBs when including counties bordering Philadelphia. These results suggest that while SSB taxes might be effective at lowering consumption of SSBs, substitution patterns may limit the effectiveness of the tax to reduce overall sugar intake.
Patterns and correlates of hepatitis C virus phylogenetic clustering among people living with HIV in Australia in the direct‐acting antiviral era: A molecular epidemiology study among participants in the CEASE cohort
Authors: Bartlett Sofia R. , Verich Andrey , Carson Joanne , Hosseini‐Hooshyar Samira , Read Phillip , Baker David , Post Jeffrey J. , Finlayson Robert , Bloch Mark , Doyle Joseph S. , Shaw David , Hellard Margaret , Martinez Maria , Marks Philippa , Dore Gregory J. , Matthews Gail V. , Applegate Tanya , Martinello Marianne
Published: August 2022

Background and Aims

In moving towards the elimination of hepatitis C virus (HCV) infection among people living with HIV, understanding HCV transmission patterns may provide insights to guide and evaluate interventions. In this study, we evaluated patterns of, and factors associated with HCV phylogenetic clustering among people living with HIV/HCV co‐infection in Australia in the direct‐acting antiviral era.

Methods

HCV RNA was extracted from dried blood spot (DBS) samples collected between 2014 and 2018 in the CEASE cohort study. The HCV Core‐E2 region was amplified by a polymerase chain reaction and Sanger sequenced. Maximum likelihood phylogenetic trees (1000 bootstrap replicates) were used to identify patterns of clustering (3% genetic distance threshold). Mixed‐effects logistic regression was used to determine correlates of phylogenetic clustering. Factors assessed were sexual risk behavior, education, injecting drug use, housing, employment, HIV viral load, age, sex, and sexuality.

Results

Phylogenetic trees were reconstructed for HCV subtype 1a (n = 139) and 3a (n = 63) sequences, with 29% (58/202) in a pair or cluster. Overall (n = 202), phylogenetic clustering was positively associated with younger age (under 40; adjusted odds ratio [aOR] 2.52, 95% confidence interval [CI] 1.20–5.29), and among gay and bisexual men (n = 168), was positively associated with younger age (aOR 2.61, 95% CI 1.10–6.19), higher education (aOR 2.58, 95% CI 1.09–6.13), and reporting high‐risk sexual behavior (aOR 3.94, 95% CI 1.31–11.84). During follow‐up, five reinfections were observed, but none were in phylogenetic clusters.

Conclusion

This study found a high proportion of phylogenetic relatedness, predominantly among younger people and gay and bisexual men reporting high‐risk sexual behavior. Despite this, few reinfections were observed, and reinfections demonstrated little relationship with known clusters. These findings highlight the importance of rapid HCV treatment initiation, together with monitoring of the phylogeny.
National trends in obesity in pregnant women from Uruguay, 2012–2019: A population‐based cross‐sectional study
Authors: Cormick Gabriela , Tomasso Giselle , Aleman Alicia , Gibbons Luz , Belizán José M.
Published: August 2022

Synopsis

There is a sustained annual increase of overweight and obesity in pregnant women in Uruguay with almost 45% incidence of overweight or obesity in 2019.
Efficacy of 12 weeks oral beta‐alanine supplementation in patients with chronic obstructive pulmonary disease: a double‐blind, randomized, placebo‐controlled trial
Authors: De Brandt Jana , Derave Wim , Vandenabeele Frank , Pomiès Pascal , Blancquaert Laura , Keytsman Charly , Barusso‐Grüninger Marina S. , de Lima Fabiano F. , Hayot Maurice , Spruit Martijn A. , Burtin Chris
Published: August 2022

Background

Beta‐alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise‐induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD.

Methods

In this double‐blind, randomized, placebo (PL)‐controlled trial (clinicaltrials.gov identifier: NCT02770417), 40 patients (75% male) with COPD (mean ± standard deviation: age 65 ± 6 years; FEV1% predicted 55 ± 14%) were assigned to 12 weeks oral BA or PL supplementation (3.2 g/day). The primary outcome, i.e. muscle carnosine, was quantified from m. vastus lateralis biopsies obtained before and after intervention. Co‐primary outcomes, i.e. incremental and constant work rate cycle capacity, were also assessed. Linear mixed model analyses were performed. Compliance with and side effects of supplement intake and secondary outcomes (quadriceps strength and endurance, and muscle oxidative/carbonyl stress) were also assessed.

Results

Beta‐alanine supplementation increased muscle carnosine in comparison with PL in patients with COPD (mean difference [95% confidence interval]; +2.82 [1.49–4.14] mmol/kg wet weight; P < 0.001). Maximal incremental cycling capacity (VO2peak: +0.5 [−0.7 to 1.7] mL/kg/min; P = 0.384, Wpeak: +5 [−1 to 11] W; P = 0.103) and time to exhaustion on the constant work rate cycle test (+28 [−179 to 236] s; P = 0.782) did not change significantly. Compliance with supplement intake was similar in BA (median (quartile 1–quartile 3); 100 (98–100)%) and PL (98 (96–100)%) (P = 0.294) groups, and patients did not report side effects possibly related to supplement intake. No change was observed in secondary outcomes.

Conclusions

Beta‐alanine supplementation is efficacious in augmenting muscle carnosine (+54% from mean baseline value) without side effects in patients with COPD in comparison with PL. However, accompanied beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress were not observed.
Reducing the occurrence of mouthing and jumping in a dog through conditional discrimination training
Authors: Davidson Matthew A. , Rosales‐Ruiz Jesús
Published: August 2022

Many approaches for reducing unwanted behavior use punishment, extinction, or noncontingent reinforcement. Other methods focus on teaching and reinforcing alternative behaviors that can replace the unwanted behavior. Another strategy can be to change the stimulus control of the unwanted behavior. The present study investigated if conditional discrimination training using positive reinforcement could reduce undesirable behaviors in a pet dog. After conditional discrimination training, two unwanted behaviors (jumping and mouthing) occurred reliably in the presence of new discriminative stimuli, while other behaviors occurred in the presence of the discriminative stimuli that had previously produced these unwanted behaviors. This experiment demonstrates that conditional discrimination training can be an effective way to control the frequency of an unwanted behavior by controlling the frequency of the presentation of a discriminative stimulus.
Amaranth calcium oxalate crystals are associated with chloroplast structures and proteins
Authors: Cerritos‐Castro Ivan Takeshi , Patrón‐Soberano Araceli , Bojórquez‐Velázquez Esaú , González‐Escobar Jorge Luis , Vargas‐Ortiz Erandi , Muñoz‐Sandoval Emilio , Barba de la Rosa Ana Paulina
Published: August 2022

Calcium oxalate (CaOx) crystals in plants are formed in crystal idioblasts cells and have specific geometric shapes. Their proposed functions include calcium homeostasis and carbon source, among others. Amaranth is a plant that presents high tolerance to abiotic stresses and accumulates considerable amounts of CaOx crystals; however, few studies have focused on characterizing the crystals ultrastructure and none is related to identifying proteins bound to them. This information is of great interest to understand the mechanisms related to CaOx crystal formation and to support their proposed functions. Thus, this work aimed to characterize CaOx crystals in amaranth leaves. Crystals were purified and the proteins bound to them were isolated and identified by nLC–MS/MS. Leaf sections were analyzed by light and electron microscopy. The identified proteins were related to the chloroplast such as ATPb synthase, RuBisCO large subunit, and cell wall‐related proteins, which were validated by immunohistochemistry and immunogold labeling. In addition, it was observed that CaOx crystal idioblasts were formed from parenchyma cells associated with mesophyll and veins, in which the thylakoid membranes of degraded chloroplasts turned into crystal chambers. These results significantly advance our understanding of the mechanisms of CaOx crystal formation and the potential function as an alternative carbon source in leaves.
Estimating the costs of physician turnover in hospital medicine
Authors: Pappas Matthew A. , Stoller James K. , Shaker Victoria , Houser James , Misra‐Hebert Anita D. , Rothberg Michael B.
Published: August 2022

Background and Objective

Costs of physician turnover are lacking for specialties organized around a site of care. We sought to estimate the cost of physician turnover in adult hospital medicine (HM).

Design, Setting, Participants

A retrospective cohort study within a large integrated health system between July 2017 and June 2020. To understand likely variation across the country, we also simulated costs using national wage data and a range of assumptions.

Main Outcome and Measures

Direct costs of turnover borne by our department and institution and indirect costs from reduced hospital billing. In our simulation, we measured costs per hired hospitalist.

Results

Between July 2017 and June 2020, 34 hospitalists left the practice, 97 hospitalists were hired, and a total of 234 hospitalists provided adult care at six hospitals. Direct costs of turnover totaled $6166 per incoming physician. Additional clinical coverage required at times of transition was the largest expense, followed by physician time recruiting and interviewing prospective candidates. The salary difference between outgoing and incoming hospitalists was cost‐saving, while reduced billing would add to indirect costs per hire. In our simulation using national wage data, programs hiring one hospitalist would spend a mean of $56,943 (95% CI: $27,228–$86,659), programs hiring five hospitalists would spend a mean of $33,333 per hospitalist (95% CI: $9375–$57,292), and programs hiring 10 hospitalists would spend a mean of $30,382 per hospitalist (95% CI: $6877–$53,887).

Conclusions

The financial cost of turnover in HM appears to be substantially lower than earlier estimates of the cost of turnover from non‐hospitalist specialties.
Pencil‐beam scanning proton therapy for the treatment of glomus jugulare tumours
Authors: Kubeš Jiří , Vondráček Vladimír , Andrlik Michal , Navrátil Matěj , Sláviková Silvia , Klika Daniel , Haas Alexandra , Dědečková Kateřina , Kopečková Kateřina , Ondrová Barbora , Rotnáglová Eliška , Vinakurau Štěpán , Grebenyuk Alexander , Rosina Jozef
Published: August 2022

Introduction

Glomus jugulare tumours (GJT) are benign tumours that arise locally and destructively in the base of the skull and can be successfully treated with radiotherapy. Patients have a long‐life expectancy and the late effects of radiotherapy can be serious. Proton radiotherapy reduces doses to critical organs and can reduce late side effects of radiotherapy. The aim of this study was to report feasibility and early clinical results of 12 patients treated using proton therapy.

Methods

Between December 2013 and June 2019, 12 patients (pts) with GJT (median volume 20.4 cm3; range 8.5–41 cm3) were treated with intensity modulated proton therapy (IMPT). Median dose was 54 GyE (Gray Equivalents) (50–60 GyE) with daily fractions of 2 GyE. Twelve patients were analysed with a median follow‐up time of 42.2 months (11.3–86.7). Feasibility, dosimetric parameters, acute and late toxicity and local effect on tumour were evaluated in this retrospective study.

Results

All patients finished treatment without interruption, with excellent dosimetric parameters and mild acute toxicity. Stabilisation of tumour size was detected on MRI in all patients. No changes in symptoms were observed in comparison with pre‐treatment conditions. No late effects of radiotherapy were observed.

Conclusion

Pencil‐beam scanning proton radiotherapy is highly feasible in the treatment of large GJT with mild acute toxicity and promising short‐term results. Longer follow‐up and larger patient cohorts are required to further identify the role of pencil‐beam scanning (PBS) for this indication.
Novel mutations in antiviral multiresistant HSV‐2 genital lesion: A case report
Authors: Khellaf Lucas , Bouscarat Fabrice , Burrel Sonia , Fidouh Nadhira , Hachon Lorry , Bucau Margot , Lariven Sylvie , Boutolleau David , Joly Véronique , Ghosn Jade , Le Pluart Diane , Thy Michaël
Published: August 2022

HSV‐2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV‐positive individuals receiving long‐term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV‐2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV‐related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV‐1 TK, known to be associated with ACV resistance for HSV‐1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV‐2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.
Interpersonal emotion regulation strategies: Enabling flexibility in high‐stress work environments
Authors: Gagnon Stéphanie , Monties Vanessa
Published: August 2022

While scholars have demonstrated that emotions play a central role in cognition, behavior, and decision making, most of the studies on emotions in work contexts show that emotions, or their expression, are often suppressed. We thus investigated how workers in high‐stress work environments deal with emotions and remain functional by focusing on the range of extrinsic regulation strategies used by workers in these environments. Drawing from participant observations and in‐depth, semistructured interviews, we show how police officers are flexible in their choices of emotion‐regulation strategies and how contextual factors emerge as the crux of this process. We contribute to the understanding of regulatory flexibility—defined as the process of matching emotion regulation strategies to environmental circumstances as they unfold in real work situations—by identifying two main enabling factors: coregulation and third party interference.
Generalized Volterra‐type operators on generalized Fock spaces
Authors: Yang Zi‐cong , Zhou Ze‐hua
Published: August 2022

Let φ and g be entire functions on the complex plane . The generalized Volterra‐type operators and induced by φ and g are defined by
and
where f is an entire function and .

In this paper, we characterize the boundedness and compactness of the generalized Volterra‐type operators and acting between the generalized Fock spaces , induced by smooth radial weights ϕ that decay faster than the classical Gaussian ones. In addition, we obtain a upper pointwise estimate for the Bergman kernel for .
Regioisomeric Giant Triblock Molecules: Role of the Linker
Authors: Liu Zhongguo , Wang Shuai , Yang Ze , Dong Xue‐Hui
Published: August 2022

In this study, polyhedral oligomeric silsesquioxane (POSS) based giant triblock molecules with precisely defined regio‐configuration are modularly prepared through highly efficient coupling reactions. The length of the linker connecting neighboring nanoparticles is elaborately designed to regulate the geometric constraints. The triblock molecules adopt a folded packing during phase separation, and the regio‐configuration imparts direct influence on the self‐assembly behaviors. The ortho‐isomers form periodic structures with a larger domain size, larger interfacial curvature, and enhanced phase stability. The regio‐effect is closely related to the length and symmetry of the linker. As the linker extends, the neighboring particles gradually decouple, and the regio‐effect diminishes. The symmetry of the linker shows an even more profound impact. This work quantitatively scrutinized the role of the linker, opening an avenue for engineering the assembled structures with molecular precision.
Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands
Authors: Plaza‐Cayón Alejandro , González‐Muñiz Rosario , Martín‐Martínez Mercedes
Published: August 2022

The cation nonselective channel TRPM8 is activated by multiple stimuli, including moderate cold and various chemical compounds (i.e., menthol and icilin [Fig. 1], among others). While research continues growing on the understanding of the physiological involvement of TRPM8 channels and their role in various pathological states, the information available on its activation mechanisms has also increased, supported by mutagenesis and structural studies. This review compiles known information on specific mutations of channel residues and their consequences on channel viability and function. Besides, the comparison of sequence of animals living in different environments, together with chimera and mutagenesis studies are helping to unravel the mechanism of adaptation to different temperatures. The results of mutagenesis studies, grouped by different channel regions, are compared with the current knowledge of TRPM8 structures obtained by cryo‐electron microscopy. Trying to make this review self‐explicative and highly informative, important residues for TRPM8 function are summarized in a figure, and mutants, deletions and chimeras are compiled in a table, including also the observed effects by different methods of activation and the corresponding references. The information provided by this review may also help in the design of new ligands for TRPM8, an interesting biological target for therapeutic intervention.
Tropical tropopause in Tibet: Insights from ground‐based global navigation satellite system and space‐based radio occultation observations
Authors: Jiang Guangwei , Shan Yingying , Guo Chunxi , Zhao Hong , Wang Bin , Zhao Dajiang
Published: August 2022

Changes in the tropopause can explain regional and global weather and climate. In Tibet, there are few radiosonde stations, and the detection height is not high enough. Radio occultation (RO) data are insufficient because of the small regional scale, which is not conducive to the analysis of tropopause change. Moreover, in some middle and high latitudes, it was more difficult to identify the tropopause height from the temperature profile. In this study, an improved method has been developed for the inversion of the tropical tropopause based on a ground‐based global navigation satellite system (GNSS) network combined with reanalysis data. Using zenith tropospheric delay data from 49 GNSS reference stations in Tibet from January 2017 to December 2019, combined with ERA5 reanalysis, the tropical tropopause (TPH) was successfully inversed, its temporal and spatial distribution is analysed, and compared with ERA5‐derived TPH obtained by the temperature profile of the interpolated co‐site points. In more than 90% of cases, the difference between the two is <2 km. The root mean square of the tropopause difference detected by GNSS‐derived TPH and RO‐derived TPH was ±1.25 km; the accuracies were at the same level. By combining the tropopause obtained from ground‐based GNSS and that from space‐based RO, temporal and spatial changes in the tropopause were analysed. The tropopause in Tibet has a latitude‐zoning distribution with obvious unimodal seasonal changes. Monthly changes excluding seasonal variation indicate a slight downward trend from 2017 to 2019. At the same time, changes in the tropopause are closely related to those in weather and climate. The results of this study confirm that the combination of ground‐based GNSS and space‐based RO can realize long‐term, continuous, and full coverage monitoring of the regional tropopause. This expands the application possibilities of ground‐based GNSS.
Using a daily diary for monitoring intrusive memories of trauma: A translational data synthesis study exploring convergent validity
Authors: Singh Laura , Ahmed Pihlgren Sara , Holmes Emily A. , Moulds Michelle L.
Published: August 2022

Objective

Intrusive memories are a core feature of posttraumatic stress disorder and have transdiagnostic relevance across mental disorders. Establishing flexible methods to monitor intrusions, including patterns and characteristics, is a key challenge. A daily diary has been developed in experimental settings to provide symptom count data, without the need for retrospective self‐report over extended time periods (e.g., 1 week, 1 month). We conducted an exploratory, pre‐registered data synthesis investigating convergence between the diary and questionnaire measures of intrusive symptoms long used in clinical practice (Impact of Event Scale, IES, and revised version, IES‐R, Intrusion subscale).

Results

Utilising datasets using the daily diary from 11 studies (4 real‐world trauma studies, seven analogue trauma studies; total N = 578), we found significant positive associations between the diary and IES/IES‐R Intrusion subscale. Exploratory analyses indicated that the magnitude of this association was stronger for the IES (vs. the IES‐R), and in individuals with real‐world (vs. analogue) trauma.

Conclusion

This study provides first evidence of convergent validity of a daily diary for monitoring intrusions with a widely used questionnaire. A diary may be a more flexible methodology to obtain information about intrusions (frequency, characteristics, triggers, content), relative to questionnaires which rely on retrospective reporting of symptoms over extended timeframes. We discuss potential benefits of daily monitoring of intrusions in clinical and research contexts.
Mental health service areas in Switzerland
Authors: Stulz Niklaus , Jörg Reto , Reim‐Gautier Constanze , Bonsack Charles , Conus Philippe , Evans‐Lacko Sara , Gabriel‐Felleiter Kerstin , Heim Eva , Jäger Matthias , Knapp Martin , Richter Dirk , Schneeberger Andres , Thornicroft Graham , Traber Rafael , Wieser Simon , Tuch Alexandre , Hepp Urs
Published: August 2022

Objectives

Small area analysis is a health services research technique that facilitates geographical comparison of services supply and utilization rates between health service areas (HSAs). HSAs are functionally relevant regions around medical facilities within which most residents undergo treatment. We aimed to identify HSAs for psychiatric outpatient care (HSA‐PSY) in Switzerland.

Methods

We used HSAr, a new and automated methodological approach, and comprehensive psychiatric service use data from insurances to identify HSA‐PSY based on travel patterns between patients' residences and service sites. Resulting HSA‐PSY were compared geographically, demographically and regarding the use of inpatient and outpatient psychiatric services.

Results

We identified 68 HSA‐PSY, which were reviewed and validated by local mental health services experts. The population‐based rate of inpatient and outpatient service utilization varied considerably between HSA‐PSY. Utilization of inpatient and outpatient services tended to be positively associated across HSA‐PSY.

Conclusions

Wide variation of service use between HSA‐PSY can hardly be fully explained by underlying differences in the prevalence or incidence of disorders. Whether other factors such as the amount of services supply did add to the high variation should be addressed in further studies, for which our functional mapping on a small‐scale regional level provides a good analytical framework.
Minimizing recovery cost of network optimization problems
Authors: Ales Zacharie , Elloumi Sourour
Published: August 2022

We propose a two‐stage recoverable robustness approach that minimizes the recovery cost. In many applications, once the uncertainty is revealed, it can be more important to recover a solution which is as similar as possible to the nominal solution than to minimize the nominal objective value of . This for example occurs when the nominal solution is implemented on a regular basis or when the uncertainty is revealed late. We define the proactive problem which minimizes the weighted recovery costs over a discrete set of scenarios while ensuring optimality of the nominal objective value of . We model the recovery cost of a scenario by a distance between the first‐stage nominal solution and the second‐stage solution recovered for this scenario. We show for two different solution distances and that the proactive problem is ‐hard for both the integer min‐cost flow problem with uncertain arc demands and for the integer max‐flow problem with uncertain arc capacities. For these two problems, we prove that once uncertainty is revealed, even identifying a reactive solution with a minimal distance to a given solution is ‐hard for , and is polynomial for . We highlight the benefits of the proactive approach in a case study on a railroad planning problem. First, we compare it to the anchored and the ‐distance approaches. Then, we show the efficiency of the proactive solution over reactive solutions. Finally, we illustrate the recovery cost reduction when relaxing the optimality constraint on the nominal objective of the proactive solution . We also consider the min–max version of the proactive problem where we minimize the maximal recovery cost over all scenarios. We show that the same complexity results hold for this version. We also exhibit a class of problems for which the set of extreme points of the convex hull of a discrete uncertainty set always contain a worst‐case scenario. We show that this result does not hold for three distinct classes deduced from the first one.
What lies between a plan and its execution?
Authors: Vasbinder Jan W.
Published: August 2022

We plan to make dreams come true. But it is an exception when such plans lead to the desired result. Why is that? Why is it so difficult to make a dream come true? Or better: Why is it so difficult to realize plans? Why, in pursuing plans, do we spend inordinate amounts of energy, time and resources addressing the wrong questions and fighting the wrong battles? Yet, we have the illusion that we are in control. Why? One reason is that we do not recognize the complexity of the system that we want to change. Those living in the Western world or in the Westernized world have been educated in linear cause and effect relationships, of being in control, in fighting ourselves out of a conflict.
Meta‐analysis with sample‐standardization in multi‐site studies
Authors: Shu Di , Webster‐Clark Michael , Platt Robert W. , Toh Sengwee
Published: August 2022

Purpose

To conceptualize a particular target population and estimand for multi‐site pharmacoepidemiologic studies within data networks and to analytically examine sample‐standardization as a meta‐analytic method compared with inverse‐variance weighted meta‐analyses.

Methods

The target population of interest is all and only all individuals from the data‐contributing sites. Standardization, a general conditioning technique frequently employed for confounding control, was adopted to estimate the network‐wide causal treatment effect. Specifically, the proposed sample‐standardization yields a meta‐analysis estimator, that is, a weighted summation of site‐specific results, where the weight for a site is the proportion of its size in the entire network. This sample‐standardization estimator was evaluated analytically in comparison to estimators from inverse‐variance weighted fixed‐effect and random‐effects meta‐analyses in terms of statistical consistency.

Results

A proof is reported to justify the consistency of the sample‐standardization estimator with and without treatment effect heterogeneity by site. Both inverse‐variance weighted fixed‐effect and random‐effects meta‐analyses were found to generally result in inconsistent estimators in the presence of treatment effect heterogeneity by site for this particular target population and estimand.

Conclusions

Sample‐standardization is a valid approach to generate causal inference in multi‐site studies when the target population comprises all and only all individuals within the network, even in the presence of heterogeneity of treatment effect by site. Multi‐site studies should clearly specify the target population and estimand to help select the most appropriate meta‐analytic methods.
Laser‐enhanced contact optimization oniTOPCon solar cells
Authors: Fellmeth Tobias , Höffler Hannes , Mack Sebastian , Krassowski Eve , Krieg Katrin , Kafle Bishal , Greulich Johannes
Published: August 2022

The authors present their work on laser‐enhanced contact optimization (LECO) oniTOPCon solar cells. LECO improves the metal‐semi‐conductor contact resistivityρcon the boron emitter and the n‐TOPCon side from an underfired (thermal budget too low) state of 2.9 and 14.1 mΩcm2to an enhanced state of 1.8 and 2.9 mΩcm2. Therefore, it enables the reduction of the optimal peak firing temperature, which leads to a decrease of metal induced recombination mainly on the boron emitter side and to minor degree on the n‐TOPCon side, as shown in this work. Ultimately, LECO improvesiTOPCon solar cells conversion efficiency by 0.6%abscompared with the optimal fired, untreated reference. Submitting those cells to 140°C and 2 suns equivalent irradiation for more than 4 h shows no impact on the conversion efficiency or any sign of light and elevated temperature‐induced degradation (LeTID). Confirmed by ISE CalLab, LECO improvediTOPCon solar cells reach 23.8% and 24.1% conversion efficiency on industrial typical wafer formats and processes.