bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating CRISPR‐Cas9‐Mediated Null Mutations and Screening Targeting Efficiency in Human Pluripotent Stem Cells
Authors: Bower Oliver J. , McCarthy Afshan , Lea Rebecca A. , Alanis‐Lobato Gregorio , Zohren Jasmin , Gerri Claudia , Turner James M.A. , Niakan Kathy K.
Published: August 2021

CRISPR‐Cas9 mutagenesis facilitates the investigation of gene function in a number of developmental and cellular contexts. Human pluripotent stem cells (hPSCs), either embryonic or induced, are a tractable cellular model to investigate molecular mechanisms involved in early human development and cell fate decisions. hPSCs also have broad potential in regenerative medicine to model, investigate, and ameliorate diseases. Here, we provide an optimized protocol for efficient CRISPR‐Cas9 genome editing of hPSCs to investigate the functional role of genes by engineering null mutations. We emphasize the importance of screening single guide RNAs (sgRNAs) to identify those with high targeting efficiency for generation of clonally derived null mutant hPSC lines. We provide important considerations for targeting genes that may have a role in hPSC maintenance. We also present methods to evaluate the on‐target mutation spectrum and unintended karyotypic changes. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Selecting and ligating sgRNAs into expression plasmids

Basic Protocol 2: Validation of sgRNA via in vitro transcription and cleavage assay

Basic Protocol 3: Nucleofection of primed human embryonic stem cells

Basic Protocol 4: MiSeq analysis of indel mutations

Basic Protocol 5: Single cell cloning of targeted hPSCs

Basic Protocol 6: Karyotyping of targeted hPSCs
EGFR analysis on scrapings from cytology smears in lung carcinoma, an effective alternative to testing on trucut biopsies
Authors: Mohan Anish A. , Vallonthaiel Archana George , Nambiar Ajit , Ariyannur Prasanth , Joy Reenu Anne , Thelakkattusserry Sukrishna Kamalasanan , Vikkath Narendranath , Joseph Tinku , Mehta Asmita , Perathur Arvind
Published: August 2021

Background

Lung carcinomas are a leading cause of cancer morbidity and mortality. Many cases present at an advanced stage of disease where definitive treatment by surgical resection is not feasible. Molecular testing using materials derived from minimally invasive procedures aid in targeted therapy with least iatrogenic burden to the patient.

Methods

Cases diagnosed as non‐small cell lung carcinoma (NSCLC) on cytology were included in the study. Scrapings from the smears with adequate tumor cell load were submitted for molecular testing. The DNA was extracted and quantified. Mutations in exons 18, 19, 20, and 21 of the EGFR gene were detected using Sanger sequencing. DNA quantity and EGFR mutation status on equal number of consecutive trucut biopsy specimens were also analyzed.

Results

Seventy cases of NSCLC tested for EGFR mutation had a median DNA concentration of 40.2 ng/μl and 31% cases showed mutation. Majority of mutations (14/21, 66.66%) were identified in exon 19. Among 70 trucut biopsy samples, DNA concentration was 41.42 ng/μl and 30% cases showed mutation. No significant difference was seen in DNA quantity and EGFR mutation between cytology smears and trucut biopsies.

Conclusion

EGFR testing on cytology smears provides adequate DNA yield with minimal invasiveness and is equally effective as biopsies. Testing on samples like pleural effusion allows for concomitant diagnosis, staging, and molecular testing in one procedure. Tests done on the smears rather than on cell block or trucut biopsies ensures superior quality DNA from the tumor cells as they are unexposed to cross linking formalin fixative.
COVID‐19 post‐vaccination lymphadenopathy: Report of cytological findings from fine needle aspiration biopsy
Authors: Tan Nicholas Jin Hong , Tay Kai Xun Joshua , Wong Soon Boon Justin , Nga Min En
Published: August 2021

The coronavirus COVID‐19 pandemic has spurred the rapid development of vaccines, with vaccination programmes already underway in many countries. Regional lymphadenopathy is one of the documented side effects of vaccination. We document the fine needle aspiration cytological findings of an enlarged supraclavicular lymph node in a 34‐year‐old Asian female following the first dose of the Pfizer‐BioNTech COVID‐19 mRNA vaccine, which appears to be the first such report in a premorbidly well patient with no known history of malignancy. The cytological findings featured a reactive pattern in keeping with follicular hyperplasia, with prominent germinal centre elements including lymphohistiocytic aggregates and tingible‐body macrophages. Despite an increased proportion of larger lymphocytes, the overall pattern was in keeping with a reactive pattern, bearing in mind the temporal and geographic relation to the vaccination injection. In instances of localised lymphadenopathy, particularly in supraclavicular or axillary locations, pathologists should be cognizant of the possibility of post‐vaccination reactive lymphadenopathy, and seek clinical and radiological hints favouring a benign process, whilst recognising potential morphological overlaps with lymphoproliferative disorders. Awareness of this diagnostic pitfall is especially important as COVID‐19 vaccination coverage is ramped up worldwide, leading to an expected increase in incidence of post‐vaccination reactive lymphadenopathy.
The future of personalized medicine in psoriasis
Authors: Hong Julie , Mosca Megan , Hadeler Edward , Hakimi Marwa , Bhutani Tina , Liao Wilson
Published: August 2021

Psoriasis is a complex, heterogeneous condition arising from a combination of genetic, environmental, and immunological factors. Although many treatments exist for psoriasis, the heterogenous nature of the patients' response to treatment makes it difficult to predict whether a treatment will be effective for every individual patient or aspect of psoriasis. Precision medicine, otherwise known as personalized medicine, is a novel approach to improve clinical outcome in psoriasis, curb the risk of developing adverse events, and predict which treatment options will be effective for each patient. Here, we discuss several aspects of precision medicine related to psoriasis, including application of ‐omics technologies and clinical parameters to identify disease biomarkers and predict therapy outcomes; identification of predictors of psoriatic arthritis and other comorbidities; implementation of a personalized care model using mobile apps and telemedicine; and the development of machine learning algorithms that provide automated recommendations for providers and patients. These topics form the basis of the future of personalized medicine in psoriatic disease.
The species range‐size patterns for vascular plants of Seorak Mountain (Korea): Relationship between group of life forms and phytogeography affinity along the elevational gradient
Authors: Lee Mi‐Hyun , Song Ju Hyeon , Byeon Seong Yeob , Lee Jeong Eun , Kim Ho Jin , Chae Seung‐Beom , Yun Chung Weon , Kim Ji‐Dong
Published: August 2021

Research on species richness patterns and the advanced elevational Rapoport rule (ERR) has been widespread in recent years; however, there is a lack of such research for the temperate mountainous regions in northeast Asia. Here, we collected plant species from the Seorak Mountain in northeast Asia through field surveys. The species were divided into 11 groups according to the life‐form types and phytogeography affinities of each species. The ERR was evaluated using Steven's method and by examining the species richness patterns of each group. The species richness patterns revealed a positive multimodal pattern along the elevation gradient, but phytogeography affinities (increasing trend) and life‐form analysis (unimodal) exhibited different patterns. The elevation gradients (1,350 m for the mean elevation–range relationships), which are affected by the boundary effect and different life forms, did not consistently support the ERR. However, herbs as well as rare, endemic, and red list species showed consistent support for the ERR, which could be attributed to the influence by phytogeography affinities. Therefore, the results from Seorak Mountain showed that the ERR was not consistent for different plant life forms in the same area; however, phytogeography affinities could support and explain ERR.
Drivers of the circumferential variation of stemflow inputs on the boles of Pinus sylvestris L. (Scots pine)
Authors: Pinos Juan , Latron Jérôme , Levia Delphis F. , Llorens Pilar
Published: August 2021

The spatial variability of stemflow on the bole of trees has rarely been the focal point of stemflow studies, despite its potential importance for stemflow‐induced changes to soils. This study helps close this data gap by supplying quantitative data on possible drivers of circumferential variation of stemflow on the boles of two Pinus sylvestris L. (Scots pine). Hence, the objectives of the present study were to quantify the circumferential spatial variability of stemflow on tree stems and to assess how some biotic and abiotic factors affect this variability. Continuous stemflow data observed for two trees within a mature stand of Scots pine during a 20‐month period (May 2018 to December 2019) showed the existence of preferential flowpaths around the stem, with patterns of stemflow distribution differing between the two trees. Data suggest that biotic factors (trunk lean, bark morphology and tree neighbourhood) have a greater influence on stemflow distribution on tree stems than abiotic factors (rainfall intensity peaks). Our comprehensive spatio‐temporal fine‐scale measurements strongly support prior observations of non‐uniform stemflow. Further studies of stemflow distribution across tree species and aboveground vegetative surfaces are needed to improve our mechanistic understanding of stemflow dynamics vis‐à‐vis rainfall interception processes and to gain further insight as to how the circumferential variation of stemflow on tree boles alters stemflow–soil interactions.
Microwave‐Assisted Condensation of Benzylic Alcohols and Alkynes Promoted by Zinc Halides: Concise Access to Alkenyl Halides
Authors: Nandi Poulomi , Goel Komal , Sreenivasulu Chinnabattigalla , Satyanarayana Gedu
Published: August 2021

A simple Lewis acid‐mediated route for the synthesis of alkenyl halides are described under microwave‐assisted conditions. The reaction proceeds through the condensation between secondary alcohols and terminal acetylenes and regioselective hydrohalogenation across the triple bond in the presence of simple and commercially available zinc halides. Unlike earlier reports, this methodology is successfully exemplified with three halide sources. As a result, a diverse range of alkenyl halide products has been accomplished. Further, indenes were obtained as the end products when tertiary alcohols and arylacetylenes were used, wherein the Thorpe–Ingold and electronic effects, would be dominant. Furthermore, when an electron‐rich arylacetylene was employed, the reaction directed to yield carbonyl products.
Influence of seasonal soil temperature variation and global warming on the seismic response of frozen soils in permafrost regions
Authors: Park Jamin , Kwon Oh‐Sung , Di Sarno Luigi
Published: August 2021

There has been growing interest in seismic hazards in permafrost regions as development in those regions has increased. Because major infrastructure, such as natural gas pipelines, has been constructed in permafrost regions, it is necessary to evaluate the seismic safety of such a network system. As frozen soil's dynamic properties differ from those of its unfrozen state, the characteristics of seismic waves propagated through frozen soil layers in permafrost differ from those propagated through unfrozen soil. Thus, the dynamic properties and composition of frozen soil layers located between bedrock and the ground surface need to be realistically considered in evaluating the seismic hazards of permafrost regions. The frozen soil layer's composition greatly depends on soil temperatures which vary seasonally and are gradually increasing due to global warming, therefore it is necessary to consider soil temperature variation. In this study, comprehensive parametric site response analysis was carried out based on measured data regarding seasonal and annual temperature variation to investigate seismic hazards. The soil temperature variation between summer and winter and temperature increases due to global warming were the main considerations. The analysis results clearly show that the soil temperature variation significantly impacts seismic hazards in the permafrost region, leading to different site response characteristics than those in the non‐permafrost region.
Heat transfer characteristics and entropy generation analysis in a plate heat exchanger using ethylene glycol and water mixture‐based Al2O3nanofluid
Authors: Yashawantha Kyathanahalli Marigowda , Vinod A. Venu
Published: August 2021

The present study aims to study the heat transfer and entropy generation analysis in a plate heat exchanger by dispersing Al2O3nanoparticles into a water and ethylene glycol mixture (base fluid) of a 65:35 volume ratio. The study was carried out by varying the nanofluid concentration from 0.2 to 2 wt%. The effects of Peclet number and weight concentration of water:ethylene glycol–Al2O3nanofluid on heat transfer characteristics and entropy generation were investigated. The nanofluid and distilled water were considered as a cold medium and hot medium on the plate heat exchanger, respectively, for the experimental study. The study showed considerable improvement in convective heat transfer coefficient and Nusselt number with the increase in nanofluid concentration. The study showed a 19.32% enhancement in overall heat transfer coefficient compared with base fluid at identical Peclet number. Pressure drop and pumping power were increased due to the addition of nanoparticles. Improved effectiveness was observed with the increase in concentration at higher Peclet numbers. Thermal entropy generation and friction entropy generation showed descending and ascending trends, respectively, for the considered weight concentration of nanofluid for the increased Peclet number. The Bejan number and entropy generation number demonstrated the roles of heat and friction in the entropy generation. A correlation was developed to predict the Nusselt number considering the experimental data. The prediction of the Nusselt number obtained from the present study showed good agreement with the experimental results.
Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma
Authors: Qiu Yuqin , Wang Xiaogang , Fan Zhenjia , Zhan Shanhui , Jiang Xin , Huang Jinchang
Published: August 2021

Background

Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. N6‐methyladenosine‐related lncRNAs (m6A‐related long noncoding RNAs [lncRNAs]) have been confirmed to be associated with the development of multiple tumors, but its role in ccRCC is not clear.

Methods

Gene expression data and clinical information of ccRCC patients were extracted from The Cancer Genome Atlas Database. The prognostic m6A‐related lncRNAs were obtained by Pearson's correlation analysis and univariate Cox regression analysis. Afterward, the cluster classification and its correlation with prognosis, clinical characteristics, and immunity were analyzed. LASSO regression was used to establish the prognostic risk model. The predictive performance of the prognostic model was evaluated and validated by survival analysis and receiver operating characteristic curve analysis, et al. The expression of immune checkpoints and immune cell infiltration in patients with different risks were systematically analyzed.

Results

A total of 27 prognostic m6A‐related lncRNAs were identified. These m6A‐related lncRNAs were differentially expressed between tumor and normal tissues. Among them, 24 high‐risk m6A‐related lncRNAs were overexpressed in Cluster 2 and correlated with poor prognosis, low stromal score, high expression of immune checkpoints, and immunosuppressive cells infiltration. Based upon, a prognostic risk model composed of seven m6A‐related lncRNAs was constructed. After a series of analyses, it was proved that this model had good sensitivity and specificity, and could predict the prognosis of patients with different clinical stratification. The expression of PD‐1, PD‐L1, CTLA‐4, LAG‐3, TIM‐3, and TIGIT were significantly increased in the high‐risk patients, and there was a correlation between the risk score and immune cell infiltration.

Conclusions

The seven m6A‐related lncRNAs prognostic risk signature showed reliable prognostic predictive power for ccRCC and was associated with the expression of immune checkpoints and immune cell infiltration. This seven m6A‐related lncRNAs signature will be helpful in managing ccRCC and guiding individualized immunotherapy.
A case of clear cell renal cell carcinoma with vena cava thrombus responding to presurgical avelumab, and axitinib
Authors: Suzuki Issei , Kijima Toshiki , Takada‐Owada Atsuko , Nakamura Gaku , Uematsu Toshitaka , Sakamoto Kazumasa , Nishihara Daisaku , Ishida Kazuyuki , Kamai Takao
Published: August 2021

Introduction

We report a case of renal cell carcinoma with vena cava thrombus showing a marked reduction with presurgical avelumab plus axitinib, facilitating nephrectomy with thrombectomy.

Case presentation

A 50‐year‐old man was taken to emergent care unit due to spontaneous renal rupture and was diagnosed to have left‐sided renal cell carcinoma with level IV tumor thrombus. After hemostasis was obtained via transcatheter arterial embolization, avelumab plus axitinib was introduced because upfront surgery was deemed unfeasible due to poor performance status and possible retroperitoneal tumor dissemination. After four treatment cycles, thrombus was reduced to level II, and nephrectomy with thrombectomy was performed. Histological analyses revealed massive CD8+ T cell infiltration in the thrombus, suggesting immunotherapy efficacy. He has remained recurrence‐free without any additional treatment for eight months.

Conclusion

For locally advanced renal cell carcinoma with vena cava thrombus, presurgical combination therapy with avelumab plus axitinib could be an option to facilitate curative surgery.
Viability of five fairway turfgrasses with and without chemical inputs
Authors: Pease Benjamin W. , Stier John C.
Published: August 2021

Interest in low‐input alternative fairway turfs has increased because of restrictions. This study compared the volumetric soil water content (VSWC) and turf quality of five fairway turfs under reduced irrigation and low nitrogen. The main plots were ‘Epic’ strong creeping red fescue (Festuca rubra ssp. rubra L., SCRF), ‘Vesper’ velvet bentgrass (Agrostis canina L., VBG), ‘Shark’ creeping bentgrass (Agrostis stolonifera L., CBG), ‘Diva’ Kentucky bluegrass (Poa pratensis L., KBG), and a 5:95 Vesper–Epic mixture (VBG–SCRF). Urea at annual N rates (0 and 98 kg ha–1) and three fungicide programs (none, integrated pest management, and full preventative) were applied. Turf quality and VSWC were assessed from June to September. Rating date interacted with all main factors in both years. On most 2010 dates, SCRF had lower quality (<3.1) than VBG–SCRF (<4.8) and VBG had higher quality than both (>5.1). In 2011, VBG and CBG were usually similar (>5.8), with acceptable quality all year. The KBG had acceptable quality (>5.0), declining in late 2011 through weed infestation of nonfertilized plots. In 2010, fertilized experimental units had lower VSWC (39.9%) than nonfertilized units (41.1%); VBG and KBG had higher VSWC than VBG–SCRF and CBG. Drought never occurred, as VSWC was above 20%. In 2011, the turf type × rating date interaction was significant. Creeping bentgrass had lower VSWC than at least one other turf type on 15 of 16 dates. Velvet bentgrass and VBG–SCRF provided the best turf quality of the grasses tested in this setting.
Integrating membrane separation with gold‐catalyzed carboxylative cyclization of propargylamine and catalyst recovery via organic solvent nanofiltration
Authors: ACA Bayrakdar Tahani , Nahra Fady , Ormerod Dominic , Nolan Steven P
Published: August 2021

BACKGROUND

Transition metal catalysis has, over recent decades, developed into one of the most important methods of constructing molecules. However, although efficient in the construction of complex molecules, these catalysts can be expensive as they are often based upon second‐ and third‐row transition metals which have, for the most part, low terrestrial abundance. Present removal and recovery techniques for homogeneous catalysts tend, at best, to focus on recovering the metal center and to consider ligands as single‐use components. Recovery of the whole catalyst would be more beneficial from economic and environmental points of view.

RESULTS

The integration of a membrane separation protocol with gold‐catalyzed carboxylative cyclization of propargylamine was investigated. Filtration conditions were identified in membrane screening experiments with the dinuclear catalyst [Au2Cl2(L)] (Au‐1) and the mononuclear catalyst [Au(IPr)Cl] (Au‐2). Recovery of the whole catalyst was then investigated. Catalyst Au‐1 proved unstable and led to metal recovery for reprocessing upon completion of the process. However, the membrane methodology does allow recovery of the catalyst within the reaction mixture which increases its efficiency. On the other hand, catalyst Au‐2 proved more stable and can be recovered along with its ancillary ligands.

CONCLUSIONS

For both catalysts a membrane‐based recovery protocol was successfully demonstrated. This protocol was either internal or external in that the Au complex along with its ligands can be recovered after reaction. This initial work shows the possibility that ligands do not always need to be considered as single‐use components. © 2021 Society of Chemical Industry (SCI).
Comparative Effectiveness of Recurrent Laryngeal Nerve Monitoring Techniques in Pediatric Surgery
Authors: Lawlor Claire M. , Meisner Jay , Jennings Russell W. , Zendejas Benjamin , Choi Sukgi S.
Published: August 2021

Objectives/Hypothesis

The recurrent laryngeal nerve (RLN) is at risk during pediatric cervical, thoracic, and cardiac surgery. We aim to determine the feasibility and effectiveness of RLN monitoring techniques in all pediatric patients.

Study Design

Retrospective case series.

Methods

Retrospective review of patients/procedures with RLN(s) at risk and RLN monitoring at Boston Children's Hospital July 2019–October 2020. Primary outcomes: pre/postoperative vocal fold mobility by awake flexible fiberoptic laryngoscopy (FFL).

Results

One hundred one patients (median [interquartile range, IQR] age 14.6 months [4.6–49.7 months], weight 10 kg [5.2–16.2 kg]) underwent 122 procedures with RLN(s) at risk. RLN monitoring attempted 111 cases, successful 96 (84%). Surgical indications: esophageal atresia/tracheoesophageal fistula, and tracheobronchomalacia. Sixty‐two (56%) procedures in reoperative field. Median follow‐up 112 days (IQR 41–230). Pre/postoperative FFL performed 84 procedures (69%), 19 new postoperative RLN injuries (16%), median age 12 months, reoperative fields 11 (18%). Prass probes: 34 cases (28 successful, 82%), 6 injuries (18%), age 12.2 (5.8–23.6) months. Dragonfly electrodes: 45 cases (37 successful, 82%), 8 injuries (18%), age 7.5 (3.8–19) months. Nerve integrity monitoring (NIM) integrated electrode endotracheal tube: 33 cases (33 successful, 100%), 5 injuries (15%), age 90 (58.8–136.7) months. Automatic periodic stimulation (APS): 16 cases, 13 successful (81%), four injuries (25%), age 7.2 (5.3–20.6) months. NIM RLN monitoring is significantly more successful than Prass, Dragonfly (95%CI −0.3 to 0.02, P = .02; and 95%CI 0.05–0.31, P = .008). Rates of injury are not different between types of RLN monitoring (P = .94), with APS use (P = .47), or with monitoring success (95%CI −0.36 to 0.09, P = .28).

Conclusions

RLN monitoring is feasible in pediatric patients of all ages. Although NIM type RLN monitoring success is superior, all forms offer similar rates of nerve protection.

Level of Evidence

3 Laryngoscope, 132:889–894, 2022
The clinico‐radiological findings of MSUD in a group of Egyptian children: Contribution to early diagnosis and outcome
Authors: Mohamed Montaser M. , Bakheet Mohamed A. , Magdy Rofaida M. , El‐Abd Heba S. , Alam‐Eldeen Mohamad Hasan , Abo‐Haded Hany M.
Published: August 2021

Background

Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of amino acid metabolism, with unique clinico‐radiological findings. This study aims to show the benefit of using the clinico‐radiological findings for early diagnosis of children with MSUD, and confirming this diagnosis using the tandem mass spectrometry (MS/MS), in order to avoid deleterious outcome.

Methods

A prospective cohort study conducted in the period from August 2016 to December 2020. Twenty‐one children were included either by selective screening or by high‐risk screening. All children had clinical and neurodevelopmental evaluation, brain magnetic resonance imaging (MRI) assessment, and blood amino acids analysis at diagnosis. Patients were followed clinically.

Results

Most children had acute onsets neuro‐developmental symptoms, with wide range of brain parenchyma involvement on MRI (hyperintensity). Diagnosis of MSUD was confirmed by detecting high serum levels of leucine/isoleucine (mean value 2085.5 μmol/L) in all patients, and elevated levels of serum valine in (81%) of children. In addition, all children showed elevated leucine: alanine ratio, and leucine: phenylalanine ratio.

Conclusions

The characteristic clinico‐radiological features can help in the early diagnosis of MSUD children, thus preventing the delay in laboratory diagnosis and improving their outcomes.
Special transformation properties for certain equations with applications in Plasma Physics
Authors: Charalambous Kyriacos , Sophocleous Christodoulos
Published: August 2021

Nonlocal transformation properties are derived for a nonlinear system which appears in certain problems in Plasma Physics. Such properties exist since the system admits conservation laws. These conservation laws lead to auxiliary systems which are studied in the point of view of equivalence transformations and Lie point symmetry analysis. The existence of infinite dimensional symmetries, in some cases, leads to the construction of linearizing mappings.
Weight and body composition changes affect resting energy expenditure predictive equations during a 12‐month weight‐loss intervention
Authors: Dahle Jared H. , Ostendorf Danielle M. , Pan Zhaoxing , MacLean Paul S. , Bessesen Daniel H. , Heymsfield Steven B. , Melanson Edward L. , Catenacci Victoria A.
Published: August 2021

Objective

Mathematical equations that predict resting energy expenditure (REE) are widely used to derive calorie prescriptions during weight‐loss interventions. Although such equations are known to introduce group‐ and individual‐level error into REE prediction, their validity has largely been assessed in weight‐stable populations. Therefore, this study sought to characterize how weight change affects the validity of commonly used REE predictive models throughout a 12‐month weight‐loss intervention.

Methods

Changes in predictive error of four models (Mifflin‐St‐Jeor, Harris‐Benedict, Owen, and World Health Organization/Food and Agriculture) were assessed at 1‐, 6‐, and 12‐month time points in adults (n = 66, 76% female, aged 18‐55 years, BMI = 27‐45 kg/m2) enrolled in a randomized clinical weight‐loss trial.

Results

All equations experienced significant negative shifts in bias (measured − predicted REE) toward overprediction from baseline to 1 month (p < 0.05). Three equations showed reversal of bias in the positive direction (toward underprediction) from baseline to 12 months (p < 0.05). Early changes in bias were correlated with decreased fat‐free mass (p ≤ 0.01).

Conclusions

Changes in body composition and mass during a 12‐month weight‐loss intervention significantly affected REE predictive error in adults with overweight and obesity. Weight history should be considered when using mathematical models to predict REE during periods of weight fluctuation.
Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer
Authors: Asrani Kaushal , Torres Alba FC , Woo Juhyung , Vidotto Thiago , Tsai Harrison K , Luo Jun , Corey Eva , Hanratty Brian , Coleman Ilsa , Yegnasubramanian Srinivasan , De Marzo Angelo M , Nelson Peter S , Haffner Michael C , Lotan Tamara L
Published: August 2021

Neuroendocrine prostate cancer (NEPC) is a rare but aggressive histologic variant of prostate cancer that responds poorly to androgen deprivation therapy. Hybrid NEPC‐adenocarcinoma (AdCa) tumors are common, often eluding accurate pathologic diagnosis and requiring ancillary markers for classification. We recently performed an outlier‐based meta‐analysis across a number of independent gene expression microarray datasets to identify novel markers that differentiate NEPC from AdCa, including up‐regulation of insulinoma‐associated protein 1 (INSM1) and loss of Yes‐associated protein 1 (YAP1). Here, using diverse cancer gene expression datasets, we show that Hippo pathway‐related genes, including YAP1, are among the top down‐regulated gene sets with expression of the neuroendocrine transcription factors, including INSM1. In prostate cancer cell lines, transgenic mouse models, and human prostate tumor cohorts, we confirm that YAP1 RNA and YAP1 protein expression are silenced in NEPC and demonstrate that the inverse correlation of INSM1 and YAP1 expression helps to distinguish AdCa from NEPC. Mechanistically, we find that YAP1 loss in NEPC may help to maintain INSM1 expression in prostate cancer cell lines and we further demonstrate that YAP1 silencing likely occurs epigenetically, via CpG hypermethylation near its transcriptional start site. Taken together, these data nominate two additional markers to distinguish NEPC from AdCa and add to data from other tumor types suggesting that Hippo signaling is tightly reciprocally regulated with neuroendocrine transcription factor expression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
CLN6 deficiency causes selective changes in the lysosomal protein composition
Authors: Tuermer Andreas , Mausbach Simone , Kaade Edgar , Damme Markus , Sylvester Marc , Gieselmann Volkmar , Thelen Melanie
Published: August 2021

Neuronal ceroid lipofuscinoses (NCLs) collectively account for the highest prevalence of inherited neurodegenerative diseases in childhood. This disease group is classified by the deposition of similar autofluorescence storage material in lysosomes that is accompanied by seizures, blindness and premature mortality in later disease stages. Defects in several genes affecting various proteins lead to NCL, one of them being CLN6, a transmembrane protein resident in the endoplasmic reticulum. Dysfunctionality of CLN6 causes variant late infantile NCL (vLINCL). The function of CLN6 and how its deficiency affects lysosomal integrity remains unknown. In this work, we performed a comparative proteomic analysis of isolated lysosomal fractions from liver tissue of nclf mice, a natural mouse model displaying a similar disease course than its human counterpart. We could identify a drastic reduction in the protein amounts of selected lysosomal proteins, amongst them several members of the NCL protein family. Most of these proteins were N‐glycosylated, soluble hydrolases and their reduction in protein levels was verified by western blotting and enzymatic assays. Hereby we could directly link Cln6 dysfunction to changes in the lysosomal compartment and to other NCL forms.
The equatorial wave skeleton of the Madden–Julian Oscillation
Authors: Castanheira José M. , Marques Carlos A. F.
Published: August 2021

An analysis of the energy equation of the three‐dimensional normal modes of the atmospheric circulation provides evidence on the behaviour of the most important equatorial waves which compose the Madden–Julian Oscillation. They are the equatorial Rossby waves of zonal wavenumber 1 and 3 and the Kelvin waves of zonal wavenumber 1. In the mean, the equatorial Rossby waves gain energy by convective heating and atmospheric column stretching and transfer it to the circulation field, whereas the Kelvin waves draw energy from the circulation field and dissipate it by surface friction. The convergence associated with the Kelvin waves contributes to the moisture fuelling of the convection centre. Therefore, the coupling between equatorial Rossby and Kelvin waves is mediated by convective heating/column stretching excitation of Rossby waves and moisture convergence by Kelvin waves.
Effect of the Hydrophilic/Hydrophobic Pendants on Physicochemical Properties: Applications Based on Cyclotriphosphazene Core
Authors: Özcan Elif , Uslu Aylin
Published: August 2021

This study focused on investigating the effect of hydrophilic and hydrophobic substituents on the physicochemical properties for medical applications. In this study, to understand the effect of hydrophilic and hydrophobic substituents on physicochemical parameters such as lipophilicity and thermosensitivity, a series of cis‐tris nongeminal [N3P3(R1‐4)3(Ra‐f)3] cyclotriphosphazenes [R1‐4=diethylene glycol monomethyl ether (DEGME), triethylene glycol monomethyl ether (TEGME), methoxypolyethylene glycol (mPEG350), methoxypolyethylene glycol‐550 (mPEG550); (2–5) respectively; Ra‐f=pyrazole, 3,5‐dimethylpyrazole, imidazole, 2‐methyl imidazole, benzimidazole, 5,6‐dimethyl benzimidazole, [2(a–f), 3(a–f), 4(a–f), 5(a–f)] respectively] were synthesized and fully characterized by mass, 31P and 1H NMR spectroscopies. Solubility and thermosensitivity based on substituent dependent LCST (lower critical solution temperature) behaviour of all synthesized molecules are investigated. Each compound analysed by HPLC to determine the lipophilicity values (logPo/w) between n‐octanol and water. A good correlation (r=0.9975 and R2=0.9948) was observed between the experimentally determined logPo/w and estimated milogP values. The results showed that LCST values of the reported compounds were linearly correlated with their lipophilicity values.
Effects of the Center Units of Small‐Molecule Donors on the Morphology, Photovoltaic Performance, and Device Stability of All‐Small‐Molecule Organic Solar Cells
Authors: Li Shaman , Ma Qing , Qiu Beibei , Meng Lei , Zhang Jinyuan , Wu Yilei , Zhang Zhanjun , Zhang Zhi-Guo , Li Yongfang
Published: August 2021

Rational design and synthesis of new small‐molecule donors are critically important to achieve highly efficient small‐molecule organic solar cells (SM‐OSCs) with desirable device stability. Herein, two new acceptor–donor–acceptor (A–D–A) structured small‐molecule donor materials SM‐DTBDT and SM‐BDT with dithieno[2,3‐d:2′,3′‐d′]benzo[1,2‐b:4,5‐b′]dithiophene (DTBDT) and benzodithiophene (BDT) as the core D‐units are designed and synthesized, respectively. After thermal annealing treatment, the power conversion efficiencies (PCEs) of the SM‐DTBDT‐ and SM‐BDT‐based devices with Y8 as acceptor material reach 12.45% and 10.68%, respectively. The main reason for the different device performance can be ascribed to the different crystallinity and morphology features of the small‐molecule donor:Y8 blend films. Compared with the SM‐BDT:Y8 blend films, the SM‐DTBDT:Y8 blend films show a smoother surface, more uniform phase separation, mixed edge‐on and face‐on orientations, and enhanced crystallinity, resulting in the more efficient exciton dissociation and charge transport. In addition, it is observed that the SM‐DTBDT‐based devices also exhibit better stability. This work shows that fine‐tuning the center units of small‐molecule donors can not only increase the photovoltaic performance but can also be an effective method to improve the device stability.
High‐Efficiency Monolithic Photosupercapacitors: Smart Integration of a Perovskite Solar Cell with a Mesoporous Carbon Double‐Layer Capacitor
Authors: Berestok Taisiia , Diestel Christian , Ortlieb Niklas , Buettner Jan , Matthews Joel , Schulze Patricia S. C. , Goldschmidt Jan Christoph , Glunz Stefan W. , Fischer Anna
Published: August 2021

The integration of solar cells with supercapacitors into hybrid monolithic power packs can provide energy autonomy to smart electronic devices of the Internet of Things (IoT) by mediating between intermittent load and supply. Herein, such a photorechargeable supercapacitor (also called a photosupercapacitor) is developed via a three‐electrode integration of a p–i–n halide perovskite solar cell with a gel electrolyte‐type supercapacitor that uses mesoporous N‐doped carbon nanospheres (MPNC) as the active electrode material. Benefiting from the large surface area, well‐defined mesoporous structure, and homogeneous particle size of the MPNC material, the supercapacitor demonstrates high capacitance, resulting in large energy and power densities with a high charge/discharge efficiency. Its integration with a large‐area (1 cm2) FA0.75Cs0.25Pb(I0.8Br0.2)3 perovskite solar cell, with an optimized layer sequence to minimize degradation, results in a photosupercapacitor exhibiting fast (< 5 s) photocharging up to 1 V. The outstanding peak overall photoelectrochemical energy conversion efficiency of 11.5% is a result of a high solar cell power conversion efficiency of 12.5%, a high supercapacitor storage efficiency of 92%, and low internal energy losses due to monolithic integration. These results underline the high potential of this type of device toward application in the IoT.
Empirical analysis of practitioners' perceptions of test flakiness factors
Authors: Ahmad Azeem , Leifler Ola , Sandahl Kristian
Published: August 2021

Identifying the root causes of test flakiness is one of the challenges faced by practitioners during software testing. In other words, the testing of the software is hampered by test flakiness. Since the research about test flakiness in large‐scale software engineering is scarce, the need for an empirical case‐study where we can build a common and grounded understanding of the problem as well as relevant remedies that can later be evaluated in a large‐scale context is a necessity. This study reports the findings from a multiple‐case study. The authors conducted an online survey to investigate and catalogue the root causes of test flakiness and mitigation strategies. We attempted to understand how practitioners perceive test flakiness in closed‐source development, such as how they define test flakiness and what practitioners perceive can affect test flakiness. The perceptions of practitioners were compared with the available literature. We investigated whether practitioners' perceptions are reflected in the test artefacts such as what is the relationship between the perceived factors and properties of test artefacts. This study reported 19 factors that are perceived by professionals to affect test flakiness. These perceived factors are categorized astest code,system under test,CI/test infrastructure, andorganization‐related. The authors concluded that some of the perceived factors in test flakiness in closed‐source development are directly related to non‐determinism, whereas other perceived factors concern different aspects, for example, lack of good properties of a test case, deviations from the established processes, and ad hoc decisions. Given a data set from investigated cases, the authors concluded that two of the perceived factors (i.e., test case size and test case simplicity) have a strong effect on test flakiness.
The impact of colectomy on the course of extraintestinal manifestations in Swiss inflammatory bowel disease cohort study patients
Authors: Roth René , Vavricka Stephan , Scharl Michael , Schreiner Philipp , Safroneeva Ekaterina , Greuter Thomas , Zeitz Jonas , Misselwitz Benjamin , Schoepfer Alain , Barry Mamadou Pathé , Rogler Gerhard , Biedermann Luc ,   Swiss IBD cohort study
Published: August 2021

Background and Aims

Extraintestinal manifestations are reported to occur in up to 45% of inflammatory bowel disease (IBD) patients during the course of disease. It is unknown whether colectomy reduces the rate of de novo extraintestinal manifestations (EIMs) or impacts on severity of EIMs following a parallel versus independent disease course from underlying IBD.

Methods

Using data from the Swiss Inflammatory Bowel Disease Cohort Study we aimed to analyse the course of EIMs in ulcerative colitis (UC) and Crohn’s disease (CD) patients undergoing colectomy during the cohort’s prospective follow‐up.

Results

One hundred and twenty‐one IBD patients (33 CD, 81 UC and seven unclassified) underwent colectomy during prospective follow‐up in the Swiss Inflammatory Bowel Disease Cohort Study. Within the 114 patients with UC or CD any EIM was reported in 40 (nine CD and 31 UC) patients. Activity of EIMs ceased entirely after colectomy in 21 patients (52.5%). Complete cessation of EIM after colectomy was higher in patients with UC versus CD with 58.1% versus 33.3%. After colectomy, 29 out of the 114 patients (25.4%) experienced any EIM. Two thirds of these (19 patients) represented persisting EIMs, while in one third (10 patients) EIM represented a de‐novo event after colectomy. Overall, 13.5% of IBD patients developed a de‐novo EIM after colectomy.

Conclusions

In IBD patients undergoing colectomy, EIMs present prior to surgery will persist in about half of patients. Complete cessation of EIM after colectomy may be less common in CD than in UC. In patients who never experienced EIMs prior to colectomy de‐novo manifestations thereafter should be expected in up to one in seven patients.
$$ \mathcal{N} $$ = 2 supersymmetric partially massless fields and other exotic non-unitary superconformal representations
Authors: Bittermann Noah , Garcia-Saenz Sebastian , Hinterbichler Kurt , Rosen Rachel A.
Published: August 2021

Abstract

We find and classify the simplest $$ \mathcal{N} $$
N
= 2 SUSY multiplets on AdS4 which contain partially massless fields. We do this by studying representations of the $$ \mathcal{N} $$
N
= 2, d = 3 superconformal algebra of the boundary, including new shortening conditions that arise in the non-unitary regime. Unlike the $$ \mathcal{N} $$
N
= 1 case, the simplest $$ \mathcal{N} $$
N
= 2 multiplet containing a partially massless spin-2 is short, containing several exotic fields. More generally, we argue that $$ \mathcal{N} $$
N
= 2 supersymmetry allows for short multiplets that contain partially massless spin-s particles of depth t = s − 2.
Gynecologic tumor board: a radiologist’s guide to vulvar and vaginal malignancies
Authors: Chow Lucy , Tsui Brian Q. , Bahrami Simin , Masamed Rinat , Memarzadeh Sanaz , Raman Steven S. , Patel Maitraya K.
Published: August 2021

Primary vulvar and vaginal cancers are rare female genital tract malignancies which are staged using the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging. These cancers account for approximately 2,700 deaths annually in the USA. The most common histologic subtype of both vulvar and vaginal cancers is squamous cell carcinoma, with an increasing role of the human papillomavirus (HPV) in a significant number of these tumors. Lymph node involvement is the hallmark of FIGO stage 3 vulvar cancer while pelvic sidewall involvement is the hallmark of FIGO stage 3 vaginal cancer. Imaging techniques include computed tomography (CT), positron emission tomography (PET)-CT, magnetic resonance imaging (MRI), and PET-MRI. MRI is the imaging modality of choice for preoperative clinical staging of nodal and metastatic involvement while PET-CT is helpful with assessing response to neoadjuvant treatment and for guiding patient management. Determining the pretreatment extent of disease has become more important due to modern tailored operative approaches and use of neoadjuvant chemoradiation therapy to reduce surgical morbidity. Moreover, imaging is used to determine the full extent of disease for radiation planning and for evaluating treatment response. Understanding the relevant anatomy of the vulva and vaginal regions and the associated lymphatic pathways is helpful to recognize the potential routes of spread and to correctly identify the appropriate FIGO stage. The purpose of this article is to review the clinical features, pathology, and current treatment strategies for vulvar and vaginal malignancies and to identify multimodality diagnostic imaging features of these gynecologic cancers, in conjunction with its respective 2009 FIGO staging system guidelines.
„In Videobehandlungen trotz Distanz Nähe schaffen“
Authors: Gumz Antje , Kanal Sulenur , Ünser Aydan , Kästner Denise , Beck-Hiestermann Franziska Marie Lea
Published: August 2021

Hintergrund

Durch die im Zuge des Ausbruchs der „coronavirus disease 2019“ (COVID-19) im März 2020 erlassenen Kontaktverbote haben Psychotherapeuten deutlich mehr und die meisten von ihnen erstmalig Videobehandlungen (VB) angeboten. Bisher gibt es nur wenig Forschung dazu, wie Therapeuten die VB während der Pandemie erlebt haben, und es liegen keine Studien vor, die mögliche verfahrensspezifische Besonderheiten betrachten.

Ziel

Es soll analysiert werden, welche subjektiven Erfahrungen Therapeuten unterschiedlicher Richtlinienverfahren mit der Durchführung von VB in Zeiten der COVID-19-Pandemie gemacht haben und welche Vor- und Nachteile sie erlebten.

Methoden

Es handelt sich um eine „Mixed-methods“-Studie mit einer querschnittlichen Onlineerhebung. Neben quantitativen Daten wurden anhand von 7 offenen Fragen die subjektiven Erfahrungen der Therapeuten mit der Durchführung von VB erhoben und mithilfe der qualitativen Inhaltsanalyse ausgewertet. Die identifizierten Kategorien wurden einer Häufigkeitsanalyse unterzogen. Angaben von 174 ärztlichen oder psychologischen Psychotherapeuten gingen in die Auswertung ein.

Ergebnisse

Besonders häufig genannte Vorteile waren die örtliche und zeitliche Flexibilität, die Kontinuität des Kontaktes in Pandemiezeiten und die Vermeidung des Infektionsrisikos. Der meistbenannte Nachteil war, dass Sinneseindrücke, Mimik, Gestik, Blickkontakt und nonverbale Kommunikation fehlen. Die meisten, aber nicht alle Patienten nahmen VB gut an. Technische Probleme erschwerten die Umsetzung.

Schlussfolgerungen

Für viele Therapeuten blieb VB eine „Notlösung“, die nicht auf Dauer angelegt sei. Allerdings könnte VB über die Pandemiezeit hinaus helfen, Versorgungsprobleme (z. B. Unterversorgung auf dem Land) zu lösen. Die Ergebnisse der Studie leisten einen wichtigen Beitrag dazu, Chancen und Risiken der VB für die psychotherapeutische Versorgung abzuwägen sowie mögliche Gefahren und Schwierigkeiten im Auge zu behalten.