bluuebunny/crossref_metadata_2025 huggingface dataset:
The Bacillus phage SPβ and its relatives: a temperate phage model system reveals new strains, species, prophage integration loci, conserved proteins and lysogeny management components
Authors: Kohm Katharina , Floccari Valentina A. , Lutz Veronika T. , Nordmann Birthe , Mittelstädt Carolin , Poehlein Anja , Dragoš Anna , Commichau Fabian M. , Hertel Robert
Published: March 2022

The Bacillus phage SPβ has been known for about 50 years, but only a few strains are available. We isolated four new wild‐type strains of the SPbeta species. Phage vB_BsuS‐Goe14 introduces its prophage into the spoVK locus, previously not observed to be used by SPβ‐like phages. Sequence data revealed the genome replication strategy and the genome packaging mode of SPβ‐like phages. We extracted 55 SPβ‐like prophages from public Bacillus genomes, thereby discovering three more integration loci and one additional type of integrase. The identified prophages resemble four new species clusters and three species orphans in the genus Spbetavirus. The determined core proteome of all SPβ‐like prophages consists of 38 proteins. The integration cassette proved to be not conserved, even though, present in all strains. It consists of distinct integrases. Analysis of SPβ transcriptomes revealed three conserved genes, yopQ, yopR, and yokI, to be transcribed from a dormant prophage. While yopQ and yokI could be deleted from the prophage without activating the prophage, damaging of yopR led to a clear‐plaque phenotype. Under the applied laboratory conditions, the yokI mutant showed an elevated virion release implying the YokI protein being a component of the arbitrium system.
Bridging ‘Home’ Political and Economic Rationalities with ‘Host’ Demands and Constraints: The Case of Regional Chinese State‐owned Multinational Corporations
Authors: Li Xinxiang , Bo Le , Shen Dan , Soobaroyen Teerooven
Published: March 2022

Regional state‐owned multinational corporations (SOMNCs) are a major constituent of the ‘going out’ strategy of the Chinese state. Although SOMNCs are nominally infused with political rationalities, they also have explicit contractual economic targets. We therefore explore the underlying rationalities of regional SOMNCs and the roles of expatriate managers in relation to their international expansion strategies. We mobilize Foucault's conception of ‘governmentality’ in providing a holistic understanding of the case of a regional SOMNC (and its subsidiary in Ghana), notably how its managers rationalize their decisions in terms of reconciling political vision with local contexts, tackling domestic competition via foreign market exploration, mobilizing local engagement, improving expatriate managers’ morale, and reinterpreting an interdependent government–business relationship. Our study suggests that coexisting economic and political considerations between the regional government and SOMNCs are instrumentalized with a view to ‘governmentalizing’ overseas operations via business strategies and localization management practices in the Ghanaian subsidiary. In such an interdependent relationship, political appeals and market imperatives are mutually beneficial and complementary, with expatriate managers skilfully using their affiliation with their government. Our theoretical contribution lies in adapting a governmentality driven framework to forge an alliance between liberal forms of management and non‐liberal forms of governing and control.
The Birth of a Field: Joshua Marshman and the Beginning of Systematic Transcriptional/Reconstructive Studies on Chinese Historical Phonology
Authors: Orlandi Georg
Published: March 2022

This article evaluates the pioneering works on Chinese historical phonology by Joshua Marshman (1768–1837), who is routinely credited as the first scholar to have produced a romanisation of the Chinese language for English speakers. This article seeks to demonstrate that Marshman's transcriptional/reconstructive approach has led to an advancement in the field of Chinese historical phonology mainly on two aspects: (i) it led to the establishment of a general theory of phonetic description; (ii) it paved the way to the formulation of a mechanic and systematic model for the individuation of sound changes. For these reasons, Marshman must be regarded as the first real forerunner of modern historical Chinese phonology.
Extraction and detection of morin from Sanghuangporus lonicericola by magnetic molecularly imprinted polymers coupled with HPLC analysis
Authors: Zhang Wei , Luo Yunjing , Xie Ziqi , Kong Chenchen , Na Zhen
Published: March 2022

In this study, morin magnetic molecularly imprinted polymers (Morin‐MMIPs) were synthesized based on magnetic nanoparticles and surface molecularly imprinted technology with superparamagnetism and extraction selectivity. The polymers allowed the separating of morin from complex matrices in the presence of an external magnetic field with no need for centrifugation or filtration. The microstructure of the polymers was characterized by scanning electron microscopy and transmission electron microscopy. Meanwhile, the functional group and magnetic properties of the polymers were characterized using Fourier transform infrared spectroscopy (FT‐IR) and magnetic vibration meter (VSM). The maximum adsorption capacity of MMIPs was 3.24 mg/g, which was 2.55 times higher than that of MNIPs (1.27 mg/g). Morin was quantified by HPLC‐DAD, which showed good linearity in the concentration range of 0.05–60 µg/ml with the correlation coefficient R2 = 0.9993. The limit of detection (LOD) was 0.08 µg/ml, and the spiked recoveries were 87.5–106.8%. The calculation of the adsorption isotherm and kinetic model revealed the adsorption mechanisms, and the adsorption process was consistent with the Langmuir adsorption isotherm and pseudo‐secondary kinetic models. Likewise, the material has been successfully used to extract and separate morin from food samples. The method reported in this paper has the advantages of fast adsorption speed, high selectivity, and environmental friendliness. It provided a reliable method for the separation and detection of morin or other natural products.
Effects of a brief blanching process on quality, safety, and shelf life of refrigerated cucumber pickles
Authors: LaFountain Lisa J. , Johanningsmeier Suzanne D. , Breidt Frederick , Stoforos George N. , Price Robert E.
Published: March 2022

Refrigerated pickles are characterized by crisp, crunchy texture, opaque flesh, and fresh flavor. Typically produced without a thermal process, microbial safety relies on preventive controls, brine composition, and sufficient hold time prior to consumption. We hypothesized that brief blanching of whole cucumbers prior to pickling could provide an additional hurdle for pathogenic microbes without negatively impacting finished product quality. Blanch treatments (15, 90, or 180 s) in 80°C water were conducted in duplicate on two lots of cucumbers prior to cutting into spears, acidifying, and storing at 4°C. Enumeration of total aerobes, lactic acid bacteria, and glucose‐fermenting coliforms was conducted for fresh and blanched cucumber. Texture, color, cured appearance development, and volatile compound profiles were analyzed for fresh and blanched cucumber and corresponding pickle products during refrigerated storage. The 90 s blanch consistently achieved a minimum 2‐log reduction in cucumber microbiota and a predicted 5‐log reduction of Escherichia coli O157:H7 up to 1.1 mm into the cucumber fruit. Blanching had no impact on tissue firmness during refrigerated storage for 1 year (p > 0.098). There were no differences in flavor‐active lipid oxidation products (E,Z)‐2,6‐nonadienal and (E)‐2‐nonenal, and consumers (n = 110) were unable to differentiate between control and 90 s blanched cucumber pickles stored for 62 days. Exocarp color and mesocarp opacity were preserved by the blanching treatment, potentially extending product shelf life. This method offers processors an option for reducing the risk of microbial contamination while maintaining the quality attributes associated with refrigerated cucumber pickles.

Practical Application

Refrigerated pickles do not undergo thermal processing, which can leave them vulnerable to microbial contamination. This study illustrates that adding a brief blanching step in refrigerated pickle processing can reduce indigenous microbiota without negatively impacting quality attributes. This blanching process could assist pickled vegetable manufacturers in providing additional safeguards for consumers while maintaining a high‐quality product.
Antimicrobial Resistance as a Global Health Threat: The Need to Learn Lessons from the COVID‐19 Pandemic
Authors: Cameron Anishka , Esiovwa Regina , Connolly John , Hursthouse Andrew , Henriquez Fiona
Published: March 2022

The global COVID‐19 pandemic has exacerbated existing health, social, and economic challenges and threatened progress towards achieving the UN sustainable development goals. We discuss lessons learned from the COVID‐19 pandemic for global policymaking for health security governance, with a particular focus on antimicrobial resistance. We identify One Health as the primary foundation of public health risk management owing to the collaborative, multidisciplinary, and multisectoral efforts that underpin the One Health approach and that enhance understanding of the complex interactions at the human–animal–environment interface. We discuss the narrow human‐centric focus of the One Health approach, highlight the underrepresentation of the environmental sector in One Health networks, and encourage greater representation from the environmental sector. Furthermore, we highlight the importance of the social sciences for health security research and the need for effective communication and trust. Finally, we underscore the importance of strengthened and collaborative health, social care, and disaster management systems. The application of these lessons will facilitate holistic, multisectoral, collaborative, and ethical actions on antimicrobial resistance.
Identification of a DNA damage repair gene‐related signature for lung squamous cell carcinoma prognosis
Authors: Jia Bin , Gong Ting , Sun Bingsheng , Zhang Zhenfa , Zhong Diansheng , Wang Changli
Published: March 2022

Background

DNA damage repair (DDR) plays a role in the tumorigenesis and progression of lung squamous cell carcinoma (LUSC), but the predictive value of DDR in LUSC has not been fully elucidated.

Methods

The LUSC datasets were retrieved from the Cancer Genome Atlas databases. Univariate Cox regression and least absolute shrinkage and selection operator regression were integrated to identify critical genes and construct a DDR gene signature. We performed Kaplan–Meier (KM) curve to compare the overall survival (OS) between the two groups based on DDR signature and used the CIBERSORT tool to compare the immune cell composition. Further gene set enrichment analysis (GSEA) was performed on the differential expressed genes.

Result

We established the DDR‐related gene signature on LUSC. KM curve showed the low‐risk group had a better prognosis than the high‐risk group in the training set (p = 0.022673) and the complete set (p = 0.003201). The area under receiver operating characteristic curve for OS was 0.98, 0.96, and 0.97 in the training dataset, testing dataset, and the complete dataset, respectively. The composition of immune cells was different between the high‐ and low‐risk group. The GSEA result suggests that genes of the patients in low‐risk group were mainly enriched in the DNA adducts; drug metabolism‐cytochrome P450, metabolism of xenobiotics by cytochrome P450.

Conclusion

This study identified DDR‐associated potential biomarkers related to overall survival of LUSC and establishes the DDR‐associated gene signature.
PhycoCanopy: An R Shiny tool for exploring primary production in macroalgal canopies
Authors: Johnson Mark P.
Published: March 2022

Macroalgal canopies are considered important for coastal food webs and may have a role in carbon sequestration. Until recently, measures of canopy photosynthesis have been relatively rare, and simulations have sometimes omitted key aspects (e.g. self‐shading, photosynthesis in air). PhycoCanopy offers a way of exploring how different algal parameters and environmental settings can affect net canopy photosynthesis.

The model uses the approach of dividing the canopy into vertical layers, calculating the available light for photosynthesis in each layer with respect to attenuation by the water column and the canopy. A total of 23 parameters can be varied to investigate the consequences of changes in key processes such as the tidal cycle, position of algae relative to the low tide mark and photosynthesis in air.

Predicted net photosynthesis can vary within a day as the timing of tides interacts with the light level at different times. The model offers a means of exploring the sensitivity of different parameters and building a fuller understanding of canopy photosynthesis.

PhycoCanopy allows users to visualize net canopy photosynthesis and to make predictions in situations where parameters are well characterized. The results give an integrated insight into net photosynthesis, particularly as intertidal observations cannot be maintained continuously over the tidal cycle. The model also demonstrates important covariates, such as the area of algal thallus m−2 (thallus area index, TAI), that should be measured to interpret observed variation in canopy photosynthesis.
How substance use prevention research gets used in United States federal policy
Authors: Long Elizabeth C. , Scott Jennifer Taylor , Craig Logan E. , Prendergast Sarah , Pugel Jessica , Crowley Daniel Max
Published: March 2022

Background and Aims

The growing body of research evidence on substance use and substance use disorder (SU/SUD) prevention could be leveraged to strengthen the intended impact of policies that address SU/SUD. The aim of the present study was to explore how research was used in United States federal legislation that emphasized SU/SUD prevention.

Design

Using a mixed‐methods approach, we assessed whether the use of research predicted a bill's legislative progress. We randomly sampled 10 bills that represented different types of research keywords to examine how research was used in these bills, applying content analysis.

Setting

United States Congress.

Participants/Cases

Federal legislation introduced between the 101st and the 114th Congresses (1989–2017; n = 1866).

Measurements

The quantitative outcome measures were bills' likelihood of passing out of committee and being enacted. Qualitative outcomes included the ways research was used in legislation.

Findings

Bills that used any research language were 2.2 times more likely to pass out of committee (OR = 2.18; 95% CI, 1.75, 2.72) and 82% more likely to be enacted (OR = 1.82; 95% CI, 1.23, 2.69) than bills not using research language. Bills using dissemination words were 57% more likely to pass out of committee (OR = 1.57; CI, 1.08, 2.28) and analysis words were 93% more likely (OR = 1.93; 95% CI, 1.51, 2.47) than bills not using dissemination or analysis words. Research was used to (i) define the problem to justify legislative action, (ii) address the problem by providing funding, and (iii) address the problem through industry regulations. However, there was a lack of research use that targets underlying risk and protective factors.

Conclusions

In the US Congress, substance use and substance use disorder prevention bills that use research language appear to be more likely to progress in the legislative cycle than bills that do not, suggesting that legislation using research may be viewed as more credible.
Functional characterization of cAMP signaling of variant porcine MC1R alleles in PK15 cells
Authors: Lan Jin , Wang Min , Qin Ke , Liu Xiaofeng , Shi Xuan , Sun Guanjie , Liu Xiaohong , Chen Yaosheng , He Zuyong
Published: March 2022

The melanocortin 1 receptor (MC1R), encoded by the classical extension (E) coat color locus, is expressed on the surface of melanocytes and plays a critical role in switching melanin synthesis from pheomelanin (red/yellow) to eumelanin (black/brown). Different MC1R alleles associated with various coat color patterns in pigs have been identified over the past decades. However, functional analysis of variant porcine MC1R alleles has not yet been performed. Therefore, in this study, we examined the subcellular localization and cyclic adenosine monophosphate (cAMP) signaling capability of MC1R variants in porcine kidney epithelial cells (PK15) overexpressing different MC1R alleles. Transcriptional slippage may partially restore the reading frame of the EP allele, possibly accounting for the observed spot phenotype. The A243T substitution in the e allele severely disrupted the membrane localization of the MC1R receptor, resulting in a severely impaired cAMP signaling capability. Both the V95M and L102P substitutions in the ED1 allele may contribute to the constitutively active function of MC1R, thus accounting for the dominant black phenotype. The D124N substitution in the ED2 allele severely attenuated the cAMP signaling capability of MC1R; however, whether this mutation contributes to the distinct phenotype of Hampshire pigs requires further investigation. Thus, our results provide new insights into the functional characteristics of MC1R variants and their roles in porcine coat color formation.
Fatty acid desaturase 2 affects the milk‐production traits in Chinese Holsteins
Authors: Fu Yihan , Jia Ruike , Xu Lingna , Su Dingran , Li Yanhua , Liu Lin , Ma Zhu , Sun Dongxiao , Han Bo
Published: March 2022

As a member of the fatty acid desaturase family, fatty acid desaturase 2 (FADS2) gene is a rate‐limiting enzyme in the synthesis of unsaturated fatty acids and within/near to the reported QTL regions for milk‐production traits. We previously found that FADS2 is differentially expressed during different lactations of Chinese Holstein cows, and participates in lipid metabolic processes by influencing the insulin, PI3K‐Akt, MAPK, AMPK, mTOR and PPAR signaling pathways. Therefore, we considered this gene as a candidate gene for milk‐production traits. In this study, we identified 12 SNPs in FADS2 by re‐sequencing, including two SNPs in the 5′ flanking region, one in the seventh exon, five in introns, two in the 3′ untranslated region and two in the 3′ flanking region. The 29:g.40378819C>T is a missense mutation that causes alanine (GCG) to be replaced with valine (GTG). Through single marker association analysis, we found that all of the 12 SNPs were significantly associated with 305 day milk yield, fat yield, fat percentage, protein yield or protein percentage (p < 0.0493). The results of the subsequent haplotype association analysis also confirmed the associations between the gene and milk‐production traits. In summary, this study suggests that there is a significant genetic association between FADS2 and milk‐production traits, and that the SNPs with significant genetic effects can provide important molecular information for the development of a genomic selection chip in dairy cattle.
A step towards better audit: The Robson Ten Group classification system for outcomes other than cesarean section
Authors: Savchenko Julia , Ladfors Lars , Hjertberg Linda , Hildebrand Eric , Brismar Wendel Sophia
Published: March 2022

Introduction

The Robson Ten Group Classification System is widely used for the audit of cesarean section (CS) rates. However, CS rate alone is a poor quality indicator and should be balanced with other obstetric endpoints. The aim of this study was to evaluate whether Swedish national data on obstetric outcomes other than CS, stratified by the Robson classification, could be analyzed in a useful way.

Material and methods

All births in Sweden from 2017 through 2020 recorded in the nationwide Swedish Pregnancy Register were categorized using the Robson classification with subdivision of some groups. Five outcomes were explored: CS, operative vaginal delivery, postpartum hemorrhage, obstetric anal sphincter injury (OASIS) and Apgar score <7 at 5 minuteutes. Rates of each outcome and contribution of each group to the total outcome rate were calculated.

Results

The largest Robson groups were nulliparous and multiparous women with single‐term cephalic pregnancies, unscarred uterus and spontaneous labor. Intrapartum CS rates were highest for multiple pregnancies, women with induced labor after previous CS, and nulliparous women with induced labor. Nulliparous women and multiparous women with a previous CS with attempted vaginal birth had the highest operative vaginal delivery and OASIS rates. The postpartum hemorrhage rate was highest for multiple pregnancies and transverse lie, followed by prelabor CS in nulliparous and multiparous women with single‐term cephalic pregnancies and unscarred uterus. The highest rates of Apgar score <7 at 5 minute were observed in preterm deliveries, multiple pregnancies, transverse lie and breech presentation. The largest contribution to the total CS rate was made by women with previous CS delivered by prelabor CS, and nulliparous women with induced or spontaneous labor. The largest contribution to all other outcomes was made by nulliparous women with spontaneous or induced labor and, notably, multiparous women with spontaneous labor and unscarred uterus.

Conclusions

The Robson classification provides a useful framework for analyzing CS rates along with rates of operative vaginal delivery, OASIS, postpartum hemorrhage and low Apgar score. Parallel interpretation of several outcomes allows a systematic and multidimensional audit, helpful for families and healthcare professionals, and can be used for comparisons, assessment of trends and subpopulations.
Combined laparoscopic and thoracoscopic approaches for Bochdalek hernia with hernia sac in an 8‐years‐old boy: Case report
Authors: Tanaka Keiichiro , Mikami Takafumi , Kato Haruki , Okazaki Tadaharu
Published: March 2022

Bochdalek hernia (BH) is characterized by a defect of the posterolateral diaphragm and intrathoracic herniation of abdominal organs. The laparoscopic or thoracoscopic approach has recently become the surgical standard. However, studies on combined approaches are limited. An 8‐year‐old boy diagnosed with left BH was treated using a combined laparoscopic and thoracoscopic approach. On laparoscopy, BH with hernia sac was identified. Spleen, pancreas tail, kidney, and transverse colon had herniated into the left thoracic cavity. After the adhesion between transverse colon and hernia sac was dissected, all abdominal organs were restored to the abdominal cavity. On thoracoscopy, an 8 × 8 cm hernia orifice defect was identified and closed by suture. The postoperative course was uneventful, with no recurrence. A combined laparoscopic and thoracoscopic approach is safe and effective with a good field of view for left BH with hernia sac in children. To the best of our knowledge, this is the first case with left BH reporting the use of both approaches in a child without conversion.
Business and society in the age of COVID‐19: Introduction to the special issue
Authors: Kurland Nancy B. , Baucus Melissa , Steckler Erica
Published: March 2022

This article introduces the eight articles and three invited essays that comprise the special issue: Business and Society in the Age of COVID‐19. In doing so, it also surveys COVID‐19‐related research in the Business & Society field, revealing five themes.
Are patients living far from hospital at higher risk of late adjuvant chemotherapy for colon cancer?
Authors: Vermeulin Thomas , Lahbib Hana , Lucas Mélodie , Czernichow Pierre , Jusot Florence , Di Fiore Frédéric , Merle Véronique
Published: March 2022

Aims

Late adjuvant chemotherapy (aCT) administration after colectomy (>56 d) is known to be associated with impaired prognosis. We aim to identify risk factors associated with late aCT, especially the travel time between patients' home and hospital.

Methods

We performed a retrospective monocentre cohort study. Patients included had a colectomy for a stage III or high risk stage II colon cancer between 2009 and 2015 performed at a French university hospital. Risk factors for late aCT were identified using a fractional polynomial logistic regression.

Results

Ninety‐four patients were included. The risk of late aCT was associated with travel time length, emergent colectomy, the need for scheduled care before aCT, and length of time between colectomy and postoperative multidisciplinary meeting advising aCT.

Conclusion

Our study suggests that, in patients with colon cancer, factors unrelated to disease severity and complexity could be associated with a higher risk of late aCT.
Therapeutic drug monitoring of thiopurines: Effect of reduced 6‐thioguanine nucleotide target levels in inflammatory bowel disease patients
Authors: Boekema Monique , Horjus – Talabur Horje Carmen S. , Roosenboom Britt , Roovers Lian , van Luin Matthijs
Published: March 2022

Aims

The effect of the Dutch nationwide adjustment of reducing 6‐thioguanine nucleotide (6‐TGN) target values (from 600–1200 to 320–630 pmol/8 × 108 red blood cells [RBC]) on toxicity and clinical outcome of thiopurine treatment in patients with inflammatory bowel disease has not yet been established. Therefore, the authors determined the incidence of toxicity‐induced discontinuations and efficacy at both target concentrations.

Methods

This retrospective study was performed in inflammatory bowel disease patients treated with azathioprine or mercaptopurine. Two groups were defined: the former target (FT) group with target concentrations of 600–1200 pmol/8 × 108 RBC and the adjusted target (AT) group with target concentrations of 320–630 pmol/8 × 108 RBC. Patients were followed for maximum 52 weeks or until discontinuation of thiopurine therapy. Data were collected from the local hospital electronic health software of Rijnstate Hospital.

Results

In total, 151 patients were included, 76 in the FT group and 75 in the AT group. At week 52, 100 out of 151 patients (66%) of the total population discontinued thiopurine therapy. Forty‐eight of the discontinuations were due toxicity (48%). The incidence of toxicity induced discontinuations was 35% in the AT group vs. 47% in the FT group (P = .25). No loss of efficacy was seen in the AT group.

Conclusion

After reduction of the target range, there was a trend towards fewer toxicity‐induced discontinuations, albeit not statistically significant. In addition, this study did not find any indication that the reduction of the target range diminished efficacy.
Outbound knowledge transfer in high‐tech small firms: The role of process innovation and development cost
Authors: de Jong Jeroen P.J. , Turro Andreu
Published: March 2022

Innovation‐related knowledge can be voluntarily transferred to other organizations for direct or indirect benefits, but firms can also suffer from involuntary transfer when their knowledge leaks and gets stolen. Despite its relevance to managers, outbound knowledge transfer has been understudied. Previous theoretical perspectives suggest that the primary reason why firms innovate—to conquer markets with product innovation or to improve internal processes with process innovation—matters for how outbound knowledge transfer takes shape. Also, higher stakes represented by innovation development cost can be expected to moderate the relationship between innovation type and outbound transfer. We analyse survey data of 176 high‐tech small firms to find that, indeed, process innovations are much more likely shared voluntarily, although product innovations leak away without the firm's consent. Development cost moderates voluntary transfer: Low‐cost process innovations are barely shared, reflecting a lack of adopter interest, whereas high‐cost process innovations are more likely to leak away to similar levels as product innovations. Overall, high‐tech small firms are more inclined to voluntary transfer their process innovations.
Debate: Stigma implications for diagnosing personality disorders in adolescents
Authors: Sheehan Lindsay , Gaurean Beatrice , Corrigan Patrick W.
Published: March 2022

Diagnosing personality disorders (PDs) in adolescence is a complex and often controversial decision. While early diagnosis provides a pathway to treatment, stigmatizing labels might unintentionally increase prejudice and discrimination for youth and their families, resulting in harm and treatment avoidance. In this paper, we outline stigma‐related considerations for diagnosing PDs in adolescence, including types of stigma (public stigma, self‐stigma, associative stigma) and moderators of stigma (continuum beliefs, biogenetic attributions, PD sub‐diagnosis). Research indicates that PDs are among the most stigmatizing diagnoses in adults, particularly among healthcare providers. Experiences with stigma may differentially impact adolescents, who are undergoing rapid changes in identity development and profound influences from educational systems, peers, and social media. Youth who receive mental health services (especially those embedded in schools) worry about whether and how to talk about a diagnosis. However, adolescents with significant behavioral symptoms are often seen as different from their peers even prior to a formal diagnosis. Systematic efforts are needed to anticipate and mitigate stigma‐related impacts on adolescents who might be diagnosed with PDs.
GNAQ T96S mutation abrogates the ability of wild‐type GNAQ to induce apoptosis by phosphorylating annexin A2 in natural killer/T cell lymphoma
Authors: Zhao Wugan , Zhang Min , Wang Guannan , Liu Enjie , Jiang Guozhong , Zhang Yanping , Zhang Dandan , Jian Xiangyu , Zhao Haiyu , Zhang Chongli , Li Wencai
Published: March 2022

Our previous study identified annexin A2 (ANXA2) as a Gaq‐interacting partner in natural killer/T cell lymphoma (NKTCL) cells transfected with the GNAQ T96S mutation vector by immunoprecipitation and mass spectrometry; however, the detailed molecular mechanisms by which GNAQ T96S might regulate ANXA2 remain to be defined in NKTCL. Herein, we found that the GNAQ T96S mutation significantly promotes the phosphorylation of ANXA2 at the Y24 site, whereas phosphorylation of ANXA2 abolishes the ability of WT GNAQ to trigger cell apoptosis. Further investigation revealed that a GNAQ T96S peptide inhibitor induced apoptosis by competing with ANXA2 binding to GNAQ T96S in NKTCL cells. In vivo animal experiments showed that a GNAQ T96S peptide inhibitor suppresses the growth of NKTCL cells carrying the GNAQ T96S mutation. Our current data suggest a role for GNAQ T96S/Src/ANXA2 in mediating the apoptosis of NKTCL cells, and the GNAQ T96S peptide could be a promising agent for therapy in NKTCL patients.
Perioperative circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma
Authors: Nakano Kosuke , Koh Yoko , Yamamichi Gaku , Yumiba Satoru , Tomiyama Eisuke , Matsushita Makoto , Hayashi Yujiro , Wang Cong , Ishizuya Yu , Yamamoto Yoshiyuki , Kato Taigo , Hatano Koji , Kawashima Atsunari , Ujike Takeshi , Fujita Kazutoshi , Kiyotani Kazuma , Katayama Kotoe , Yamaguchi Rui , Imoto Seiya , Imamura Ryoichi , Nonomura Norio , Uemura Motohide
Published: March 2022

Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study was to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan‐cancer gene panel and next‐generation sequencing could identify patients with poor prognosis who require perioperative chemotherapy. Second, we investigated whether ctDNA is useful for minimal residual disease (MRD) detection and treatment monitoring in UTUC. This study included 50 patients with untreated UTUC, including 43 cases of localized UTUC. We performed targeted ultradeep sequencing of plasma cell‐free DNA (cfDNA) and buffy coat DNA and whole‐exome sequencing of cancer tissues, allowing exclusion of possible false positives. We attempted to stratify the prognosis according to the perioperative ctDNA levels in patients with localized UTUC. In patients with metastatic UTUC, ctDNA was evaluated before, during, and after systemic treatment. In total, 23 (46%) of 50 patients with untreated UTUC were ctDNA positive, and 17 (40%) of 43 patients with localized UTUC were ctDNA positive. Of the detected TP53 mutations, 19% were false positives due to clonal hematopoiesis of indeterminate potential. Among preoperative risk factors, only the preoperative ctDNA fraction>2% was a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the existence of ctDNA early points after the operation was significantly associated with worse RFS, suggesting the presence of MRD. ctDNA also showed a potential as a real‐time marker for systemic therapy in patients with metastatic UTUC. Detection of ctDNA may indicate potential metastasis and guide decisions on perioperative chemotherapy.
Characterization of patients with occupational allergy to two new epoxy hardener compounds
Authors: Suomela Sari , Pesonen Maria , Ylinen Katriina , Aalto‐Korte Kristiina , Suuronen Katri
Published: March 2022

Background

The practical importance of two recently described epoxy hardener allergens—1,3‐benzenedimethanamine, N‐(2‐phenylethyl) derivatives (1,3‐BDMA‐D) and hydrogenated formaldehyde benzenamine polymer (FBAP)—as occupational allergens remains to be defined.

Objectives

To describe patients diagnosed at the Finnish Institute of Occupational Health (FIOH) with positive reactions to 1,3‐BDMA‐D or FBAP.

Methods

We searched FIOH's patch‐test files from January 2017 to December 2020 for patients examined due to suspected occupational contact allergy to epoxy compounds. We analyzed the patch‐test results and sources of exposure to various epoxy hardeners and focused on occupations, symptoms, and the sources of exposure to 1,3‐BDMA‐D and FBAP.

Results

During the study period, 102 patients were examined at FIOH for suspected occupational contact allergy to epoxy compounds. Of these, 19 (19%) were diagnosed with contact allergy to 1,3‐BDMA‐D (n = 10) or FBAP (n = 12). The largest occupational group was sewage pipe reliners (n = 8). Seven different hardener products contained FBAP, whereas 1,3‐BDMA‐D was present in only one hardener used by spray painters.

Conclusions

A substantial number of patients with suspected occupational epoxy resin system allergy tested positive to in‐house test substances of 1,3‐BDMA‐D and/or FBAP.
Stakeholder mapping as a transdisciplinary exercise for jaguar conservation in the Brazilian Atlantic Forest
Authors: Sandroni Laila Thomaz , de Barros Ferraz Katia Maria Paschoaletto Micchi , Marchini Silvio , Percequillo Alexandre , Coates Robert , Paolino Roberta Montanheiro , Barros Yara , Landis Mariana , Ribeiro Yuri Geraldo Gomes , Munhoes Leticia Prado
Published: March 2022

Transdisciplinary projects are fundamental to a more effective and just conservation, but their application and coherent framing present challenges, since their nature is to bring together different epistemological backgrounds and world views. This paper identifies the possibilities offered by stakeholder mapping as a tool for generating common understandings in transdisciplinary conservation research projects. Lessons are drawn from experiential learning through the case of jaguar conservation in the Brazilian Atlantic Forest (BAF). Stakeholder mapping proved to be an essential diagnostic tool that generated an overview of the material context of human–jaguar interactions in the BAF to stakeholders engaged in the project. The process and overview drew attention to gaps in stakeholder knowledge that need to be addressed to enhance conviviality between humans and jaguars in fragmented landscapes. Recognizing these knowledge gaps assists in the production of methodologies that can effectively encompass different social groups, and increase all parties' perceptions of the legitimacy of conservation activities. We argue that, due to its collective nature, stakeholder mapping can foster mutual learning and deeper communication in the context of divergent framings of complex nature conservation problems, such as in jaguar conservation.
Which preoperative assessment modalities best identify patients who are suitable for enhanced recovery after liver transplantation? A systematic review of the literature and expert panel recommendations
Authors: Crespo Gonzalo , Hessheimer Amelia J. , Armstrong Matthew J , Berzigotti Annalisa , Monbaliu Diethard , Spiro Michael , Raptis Dimitri Aristotle , Lai Jennifer C. ,   the ERAS4OLT.org Working Group
Published: March 2022

Background

To implement Enhanced Recovery After Surgery (ERAS) protocols for liver transplant (LT) candidates, it is essential to identify tools that can help risk stratify patients by their risk of early adverse post‐LT outcomes.

Objective

We aimed to identify pre‐LT tools that assess functional capacity, frailty, and muscle mass that can best risk stratify patients by their risk of adverse post‐LT outcomes.

Methods

We first conducted a systematic review following PRISMA guidelines, expert panel review and recommendations using the GRADE approach (PROSPERO ID CRD42021237434). After confirming there are no studies evaluating assessment modalities for ERAS protocols for LT recipients specifically, the approach of the review focused on pre‐LT modalities that identify LT recipients at higher risk of worse early post‐LT outcomes (≤90 days), considering that this is particularly pertinent when evaluating candidates for ERAS.

Results

Twenty‐two studies were included in the review, encompassing three different types of pre‐LT modalities: evaluation of physical function (including frailty and general physical scores like the Karnofsky Performance Status (KPS), assessment of cardiopulmonary capacity, and estimation of muscle mass and composition. The majority of studies evaluated frailty assessment and muscle mass. Most studies, except for liver frailty index (LFI), were retrospective and single‐center. All assessment modalities could identify, in different grade, LT recipients with higher risk of early post‐LT mortality, length of stay or postoperative complications.

Conclusions

We identified four pre‐LT assessment tools that could be used to identify patients who are suitable for ERAS protocols: (1) KPS (quality of evidence moderate, grade of recommendation strong); (2) LFI (quality of evidence moderate, grade of recommendation strong); (3) abdominal muscle mass by CT (quality of evidence moderate, grade of recommendation strong); and (4) cardiopulmonary exercise testing (CPET) (quality of evidence moderate, grade of recommendation weak). We recommend that selection of the appropriate tool depends on the specific clinical setting and available resources to administer the tool, and that use of a tool be incorporated into the routine preoperative assessment when considering implementation of ERAS protocols for LT.
Increased intrarenal post‐glomerular blood flow is a key condition for the development of calcineurin inhibitor‐induced renal tubular acidosis in kidney transplant recipients
Authors: Kaneko Shuzo , Usui Joichi , Takahashi Kazuhiro , Oda Tatsuya , Yamagata Kunihiro
Published: March 2022

Background: Hyperchloremic metabolic acidosis (HCMA) from renal tubular acidosis (RTA) is common in kidney transplant (KT) recipients. Calcineurin inhibitors (CNIs) are a potential cause of RTA, and whether HCMA is a determinant of poor graft prognosis is controversial.

Methods: The subjects were living‐donor KT recipients (LDKTRs,n = 47) and matched donors (n = 43). All cases of rejection, extrarenal causes, and respiratory disorders were excluded. HCMA was defined as having a [Na+]–[Cl−] value of ≤34 or starting alkalization. We determined the potential causes of HCMA in LDKTRs at 3 months (m) and 1 year (y) post‐KT. We examined renal hemodynamic parameters in 26 LDKTRs at 1 y post‐KT: namely, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF; GFR/RPF) and pre‐/post‐glomerular vascular resistance (pre‐/postVR).

Results: The HCMA incidence in the 3‐m post‐KT LDKTR group was higher than that of the donors (51.0% vs. 6.9%,p < 0.001, adjusted odds ratio: 6.7–15.7). Among adjusted factors, the most dominant HCMA contributor was low hemoglobin concentration (Hb ≤ 12 g/dl). Compared to non‐HCMA cases, HCMA patients had low FF and low post‐VR (p = 0.008, 0.003, respectively) suggesting increased intrarenal post‐glomerular blood flow. The high pathological score of alternative arteriolar hyalinosis (aah) ≥2 was a significant HCMA risk. The tacrolimus trough level was not high in HCMA but was significantly high in HCMA in the low post‐VR setting (p = 0.002).

Conclusion: Among LDKTRs, low hemoglobin level is an important contributor to the manifestation of HCMA in the induction period, and increased intrarenal post‐glomerular blood flow is a key condition for the development of CNI‐induced RTA.
Pharmacokinetic drug interactions of asciminib with the sensitive cytochrome P450 probe substrates midazolam, warfarin, and repaglinide in healthy participants
Authors: Hoch Matthias , Sengupta Tirtha , Hourcade‐Potelleret Florence
Published: March 2022

Asciminib, a first‐in‐class BCR‐ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP), is a new treatment option for patients with chronic myeloid leukemia who no longer benefit from currently approved tyrosine kinase inhibitors. In vitro, asciminib reversibly inhibits cytochrome P450 (CYP) 3A4/5, CYP2C9, and CYP2C8. This phase I, open‐label, two‐stage study in healthy participants evaluated the effect of asciminib (40 mg b.i.d. at steady‐state) as a potential perpetrator on single‐dose pharmacokinetics of a two‐drug cocktail containing midazolam (CYP3A substrate) and warfarin (CYP2C9 substrate) in stage 1 (n = 22), and of repaglinide (CYP2C8 substrate) in stage 2 (n = 25). For midazolam plus asciminib versus midazolam, geometric mean (Gmean) ratios (90% confidence interval) for midazolam area under the curve from zero to infinity (AUCinf) and maximum plasma concentration (Cmax) were 1.28 (1.15, 1.43) and 1.11 (0.96, 1.28), respectively. For warfarin plus asciminib versus warfarin, Gmean ratios for S‐warfarin AUCinf and Cmax were 1.41 (1.37, 1.45) and 1.08 (1.04, 1.13), respectively. Results for R‐warfarin were in line with those for S‐warfarin. For repaglinide plus asciminib versus repaglinide, Gmean ratios for AUCinf and Cmax were 1.08 (1.02, 1.14) and 1.14 (1.01, 1.28), respectively. The treatments were generally well tolerated, and the asciminib safety profile was consistent with previous studies of asciminib in the absence of probe substrates. Overall, the results indicate that asciminib (40 mg b.i.d.) is a weak inhibitor of CYP3A and CYP2C9 and has no meaningful effect on CYP2C8.
Oral sulfate solution benefits polyp and adenoma detection during colonoscopy: Meta‐analysis of randomized controlled trials
Authors: Chen Cheng , Shi Mengyang , Liao Zhongli , Chen Weiqing , Wu Yongzhong , Tian Xu
Published: March 2022

Objectives

Although oral sulfate solution (OSS) has been revealed to be not only safe and efficacious but also noninferior to polyethylene glycol with ascorbic acid (PEG + ASC), it is unclear whether OSS can ultimately increase the polyp detection rate (PDR) and adenoma detection rate (ADR). We performed this meta‐analysis to estimate the effect of OSS on PDR and ADR during colonoscopy.

Methods

We searched PubMed, EMBASE, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) investigating the comparative effect of OSS versus PEG + ASC on the PDR and ADR during colonoscopy. Cecal intubation time (CIT), cecal intubation rate (CIR), and bowel preparation score were also evaluated. Review Manager (RevMan) version 5.3.0 was used to perform statistical analysis.

Results

Eight RCTs involving 2059 patients fulfilled the selection criteria. Meta‐analysis suggested that OSS significantly increased the PDR (47.34% vs. 40.14%, risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03−1.24, P = 0.01) and ADR (44.60% vs. 38.14%, RR 1.17, 95% CI 1.03−1.33, P = 0.01) during colonoscopy. Subgroup analysis showed that the beneficial effects of OSS on PDR and ADR were consistent among patients with mean age >55 years and with body mass index <25 kg/m2 receiving outpatient colonoscopy, morning colonoscopy, and the 2‐L bowel preparation protocol. Meanwhile, patients receiving OSS had a beneficial bowel preparation score.

Conclusion

Compared with polyethylene glycol‐based regimens, the OSS bowel preparation regimen significantly increased the PDR and ADR in patients undergoing colonoscopy.
Utility of dobutamine stress echocardiography in aortic valve regurgitation and reduced left ventricular function
Authors: Saito Chihiro , Arai Kotaro , Ashihara Kyomi , Niinami Hiroshi , Hagiwara Nobuhisa
Published: March 2022

Objective

Predictors for post‐operative reverse remodeling in patients with severe aortic regurgitation (AR) and reduced left ventricular ejection fraction (LVEF) are unknown. We performed low‐dose dobutamine stress echocardiography (DSE) in patients with severe AR and reduced LVEF to evaluate the relationship between contractile reserve (CR) and reverse remodeling after surgery.

Methods

In 31 patients with chronic severe AR and reduced LVEF (LVEF < 50%), we performed pre‐operative DSE, assessed CR, and examined whether changes in preoperative DSE were associated with improvement of post‐operative LVEF after aortic valve surgery.

Results

The pre‐operative echocardiographic findings were as follows: left ventricular (LV) end‐diastolic dimension: 67 ± 10 mm, LV end‐systolic dimension: 52 ± 13 mm, and LVEF: 42 ± 8%. All patients underwent aortic valve surgery. Patients with pre‐operative LVEF of ≥45% exhibited a significant increase in LVEF; however, patients with pre‐operative LVEF of <45% showed no significant change. When we examined the results of DSE performed in patients with pre‐operative LVEF of <45%, ΔLVEF of ≥6% (with CR) during DSE was related to an improvement in post‐operative LVEF; ΔLVEF of ≥6% during DSE predicted an improvement in post‐operative LVEF, with sensitivity 100%; specificity 78%; and area under curve (AUC) .92.

Conclusions

DSE might be a helpful tool for predicting post‐operative reverse remodeling in patients with severe AR and moderately reduced LVEF.