bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulforaphane inhibits CD44v6/YAP1/TEAD signaling to suppress the cancer phenotype
Authors: Chen Xi , Adhikary Gautam , Ma Emily , Newland John J. , Naselsky Warren , Xu Wen , Eckert Richard L. 
Published: October 2022

AbstractSulforaphane (SFN) is a promising cancer prevention and treatment agent that strongly suppresses the cutaneous squamous cell carcinoma (CSCC) cell cancer phenotype. We previously showed that yes‐associated protein 1 (YAP1)/TEAD signaling is a key procancer stimulator of the aggressive CSCC cell cancer phenotype. However, SFN‐responsive upstream regulators of YAP1/TEAD signaling are not well characterized and so there is a pressing need to identify these factors. We show that CD44v6 knockdown reduces YAP1/TEAD‐dependent transcription and target gene expression, and that this is associated with reduced spheroid formation, invasion and migration. CD44v6 knockout cell lines also display reduced YAP1/TEAD activity and target gene expression and attenuated spheroid formation, invasion, migration and tumor formation. An important finding is that SFN treatment suppresses CD44v6 level leading to a reduction in YAP1/TEAD signaling and marker gene expression. Sox2 level and epithelial‐mesenchymal transition (EMT) are also reduced. Forced expression of constitutive active YAP1 in CD44v6 knockdown cells partially restores the aggressive cancer phenotype. These important findings suggest that CD44v6 drives YAP1/TEAD signaling to enhance the CSCC cell cancer phenotype and that SFN treatment reduces CD44v6 level/function which, in turn, reduces YAP1/TEAD signaling leading to reduced stemness, EMT and tumor growth.
Outcomes of single digit replantation for amputation proximal to the flexor digitorum superficialis insertion: A systematic review with meta‐analysis
Authors: Wong Shifa , Banhidy Norbert , Kanapathy Muholan , Nikkhah Dariush 
Published: October 2022

AbstractBackgroundA single digit amputated proximal to the flexor digitorum superficialis (FDS) insertion is a relative contraindication to replantation. The aim of this study is to conduct a systematic review on replantation of these injuries to synthesize best available evidence on outcomes.MethodsThis review was registered in PROSPERO under registration number CRD42021277305. A MEDLINE, CENTRAL, and EMBASE databases search yielded 1536 studies. Primary clinical studies on single digit replantation and functional outcome with at least 10 cases were included. Data on revision amputation and replantation distal to the FDS were collected as comparators. Data extracted included demographics, type of digit, level of injury, secondary surgeries, duration of sick leave, survival, function, and patient‐reported outcomes. All studies were assessed using the Risk of Bias In Non‐randomized Studies of Intervention (ROBINS‐I) tool and data synthesis was completed using RevMan and Microsoft Excel.ResultsSix studies representing 182 replanted single digits that were amputated proximal to the FDS insertion were included. The average PIPJ motion of replanted single digits was 50° in those amputated proximal to the FDS insertion compared to 82.5 in those amputated distal to the FDS. The average Michigan Hand Questionnaire (MHQ) score was 84.78 in replantation group versus 76.81 in the amputation group which was statistically significant (p < .00001). Mean Disability of Arm, Shoulder, and Hand Questionnaire (DASH) score was 12 in replantation group compared to 18.5 in amputation group, however this was not statistically significant (p = .17).ConclusionFew studies exist on outcomes of single digit replantations proximal to FDS insertion. Although range of motion is inferior in the replant group, this has increased since initial studies were performed, and patient satisfaction and patient reported outcomes are high. This is promising evidence for achieving reasonable outcomes in replantation of single digits amputated proximal to the FDS.Level of evidenceLevel III.
Protocatechuic Acid Ameliorates High Fat Diet‐Induced Obesity and Insulin Resistance in Mice
Authors: Xiang Yuyao , Huang Ruolan , Wang Yongliang , Han Shanshan , Qin Xiaochen , Li Zhenzhen , Wang Xu , Han Yuqing , Wang Tao , Xia Bo , Wu Jiangwei , Yang Gongshe 
Published: October 2022

ScopeInsulin resistance is a common feature of obesity and type 2 diabetes and partly results from an imbalance between food intake and energy expenditure. Therefore, efficient and safe insulin resistance treatment therapies are warranted. This work is aim to access the impact of protocatechuic acid (PCA), a catechol‐type O‐diphenol phenolic acid, in high fat diet (HFD)‐induced glucose, and lipid dysregulation.Methods and resultsFive‐week‐old male C57BL/6 mice are fed with HFD for 4 weeks and then are randomly divided into two cohorts: one cohort feed with HFD is free access to sterile water for 4 weeks, another cohort is free access to PCA‐containing water (2.7 mM) for 4 weeks with HFD. In this study, using a hyperinsulinemic–euglycemic mouse clamp, it is showed that PCA‐treated mice display improved systemic insulin resistance via enhanced fatty acid mobilization and utilization, thereby reducing ectopic lipid accumulation and promoting hepatic and peripheral insulin action.ConclusionsThis study provides insights on the potent pharmacological effects of PCA from food sources on improving high fat diet (HFD)‐induced whole‐body insulin resistance and type 2 diabetes.
Mean kurtosis‐Curve (MK‐Curve) correction improves the test–retest reproducibility of diffusion kurtosis imaging at 3 T
Authors: Christiaanse Ernst , Wyss Patrik O. , Scheel‐Sailer Anke , Frotzler Angela , Lehnick Dirk , Verma Rajeev K. , Berger Markus F. , Leemans Alexander , De Luca Alberto 
Published: October 2022

AbstractDiffusion kurtosis imaging (DKI) is applied to gain insights into the microstructural organization of brain tissues. However, the reproducibility of DKI outside brain white matter, particularly in combination with advanced estimation to remedy its noise sensitivity, remains poorly characterized. Therefore, in this study, we investigated the variability and reliability of DKI metrics while correcting implausible values with a fit method called mean kurtosis (MK)‐Curve. A total of 10 volunteers (four women; age: 41.4 ± 9.6 years) were included and underwent two MRI examinations of the brain. The images were acquired on a clinical 3‐T scanner and included a T1‐weighted image and a diffusion sequence with multiple diffusion weightings suitable for DKI. Region of interest analysis of common kurtosis and tensor metrics derived with the MK‐Curve DKI fit was performed, including intraclass correlation (ICC) and Bland–Altman (BA) plot statistics. A p value of less than 0.05 was considered statistically significant. The analyses showed good to excellent agreement of both kurtosis tensor‐ and diffusion tensor‐derived MK‐Curve–corrected metrics (ICC values: 0.77–0.98 and 0.87–0.98, respectively), with the exception of two DKI‐derived metrics (axial kurtosis in the cortex: ICC = 0.68, and radial kurtosis in deep gray matter: ICC = 0.544). Non‐MK‐Curve–corrected kurtosis tensor‐derived metrics ranged from 0.01 to 0.52 and diffusion tensor‐derived metrics from 0.06 to 0.66, indicating poor to moderate reliability. No structural bias was observed in the BA plots for any of the diffusion metrics. In conclusion, MK‐Curve–corrected DKI metrics of the human brain can be reliably acquired in white and gray matter at 3 T and DKI metrics have good to excellent agreement in a test–retest setting.
Recommending ultra‐processed oral nutrition supplements for unintentional weight loss: Are there risks?
Authors: Rivero‐Mendoza Daniela , Caldwell Cecelia L. , Cooper Hannah , Goldberg Jessica , Lamothe Meagan , Logan Sarah , Smith Elena B. , Torna Elena , Zeldman Jamie A. , Dahl Wendy J. 
Published: October 2022

AbstractOral nutrition supplements (ONS) are widely recommended for the management of unintentional weight loss in patient populations, long‐term care residents, and community‐dwelling older adults. Most marketed ONS are ultra‐processed, with precision nutrition and aseptic composition, as well as convenience and availability, driving their selection. However, therapeutic effectiveness is mixed and the potential health risks of consuming ultra‐processed ONS long‐term in lieu of less‐processed foods have received little attention. A diverse and balanced microbiota supporting immunity and wellness is maintained by a diet rich in plant‐sourced foods. The implications of ultra‐processed ONS displacing plant‐sourced foods, and specifically the potential for undesirable impacts on the gut microbiota, require consideration. Most ONS are either devoid of fiber or are supplemented with isolated or purified fibers that may contribute to adverse gastrointestinal symptoms and appetite suppression. In contrast, the diversity of microbial‐available, nondigestible carbohydrates, together with the array of phytochemicals found in plant‐sourced foods, support microbial diversity and its resiliency. This review outlines the clinical dilemma of recommending commercial ultra‐processed ONS vs nutritionally adequate (eg, high‐energy/high‐protein) foods and beverages that contribute to diet quality, maintenance of a diverse and stable gut microbiota composition, and support nutrition status and health. Ultra‐processed ONS may fall short of expected health benefits, and overreliance may potentially contribute to the risk for patient and older adult populations because of the displacement of a variety of healthful foods.
Host‐guest tuning of the CO2 reduction activity of an iron porphyrin cage
Authors: Surendran Adarsh Koovakattil , Tripodi Guilherme L. , Pluhařová Eva , Pereverzev Aleksandr Y. , Bruekers Jeroen P. J. , Elemans Johannes A. A. W. , Meijer Evert Jan , Roithová Jana 
Published: October 2022

AbstractEfficient electrocatalytic CO2 reduction requires developing catalysts with high selectivities and high activities, which is simultaneously difficult to achieve. Here, we present a new approach to tune the CO2 reduction activity based on host‐guest chemistry enabled by an iron porphyrin cage catalyst. The cage design allows the hosting of alkali metals in the side walls causing a change in the electrostatic potential inside the cage cavity. Density functional theory calculations show that the guest potassium ions assist the reduction of CO2 by inverting the two‐electron transfer from iron(0) to CO2 from endothermic to exothermic. Accordingly, electrochemical experiments with the cage catalyst show that in the presence of the potassium ions, the overpotential for the CO2 reduction decreases, and the catalytic activity increases while the high selectivity of the cage is retained. A novel coupling between the electrochemical cell and a mass spectrometer allowed the trapping of the key intermediates. Cryogenic ion spectroscopy characterization of the intermediates showed the details of the potassium ions hosting in the reduced cage and of the stabilization of the Fe‐COOH intermediates by the interaction with the potassium ions at the single‐molecule level.Key points
Host‐guest chemistry of iron porphyrin‐cage catalysts in electrocatalytic CO2 reduction results in an increase in the activity and the selectivity of the catalysis.

Electrochemistry—mass spectrometry coupling allowed studying of the reaction intermediates in CO2 reduction by mass spectrometry and by helium tagging infrared photodissociation spectroscopy.

DFT calculations showed the details of the CO2 reduction pathway inside of the cage cavity and the working principles of the reactivity enhancement by the host‐guest chemistry.
Children and pain: Assessment and management according to parents' perspective
Authors: Ndengeyingoma Assumpta , Lebel Valérie , Alvarez Sandra Bonilla 
Published: October 2022

AbstractPain in children is frequent. Parents evaluate their children's pain to decide how to manage it or to share information with caregivers. This qualitative descriptive study aims to identify elements influencing the evaluation and management of pain in children from a parent's perspective. Participants were recruited through a pediatric center and university family medicine clinic. Participants had to have used medication for their child that was prescribed “as needed” to manage their child's pain in the month preceding the interview, whether it was a prescription‐strength medication or an over‐the‐counter strength prescription. Semi‐directed interviews 30–45 min in duration were conducted with 16 parents in the Outaouais region of Quebec (Canada), either at the participant's home or by phone (after the declaration of the COVID‐19 pandemic). A thematic analysis was completed to identify themes in the data from these individual interviews. The evaluation of children's pain by their parents is influenced by the parents' experience with pain and the expression of the pain by the children, whereas the actions to relieve the pain are based on the beliefs surrounding pain management in children. Evaluation of pain is complex since many parents' beliefs influence this evaluation and the subsequent pain management. The study results raise healthcare professionals' awareness regarding several elements which influence the evaluation of children's pain and its management by their parents.
Practical Synthesis of Polyamine Succinamides and Branched Polyamines
Authors: Alkhzem Abdulaziz H. , Laabei Maisem , Woodman Timothy J. , Blagbrough Ian S. 
Published: October 2022

AbstractAntibiotic resistance is now a growing threat to human health, further exacerbated by the lack of new antibiotics. We describe the practical synthesis of a series of substituted polyamine succinamides and branched polyamines that are potential new antibiotics against both Gram‐positive and Gram‐negative bacteria, including MRSA and Pseudomonas aeruginosa. They are prepared via 1,4‐Michael addition of acrylonitrile and then hydrogenation of the nitrile functional groups to primary amines. They are built upon the framework of the naturally occurring polyamines thermine (3.3.3, norspermine) and spermine (3.4.3), homo‐ and heterodimeric polyamine succinic amides. Linking two of the same or different polyamines together via amide bonds can be achieved by introducing a carboxylic acid group on the first polyamine, then coupling that released carboxylic acid to a free primary amine in the second polyamine. If the addition of positive charges on the amino groups along the polyamine chains are a key factor in their antimicrobial activity against Gram‐negative bacteria, then increasing them will increase the antimicrobial activity. Synthesising polyamine amide dimers will increase the total net positive charge compared to their monomers. The design and practical synthesis of such homo‐ and hetero‐dimers of linear polyamines, spermine and norspermine, are reported. Several of these compounds do not display significant antibacterial activity against Gram‐positive or Gram‐negative bacteria, including MRSA and Pseudomonas aeruginosa. However, the most charged analogue, a branched polyamine carrying eight positive charges at physiological pH, displays antibiofilm activity with a 50 % reduction in PAO1 at 16–32 μg mL−1.
Synthesis and Anti‐Inflammatory Activity of 2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐Derived NRF2 Activators
Authors: Mak Kit‐Kay , Shiming Zhang , Epemolu Ola , Dinkova‐Kostova Albena T. , Wells Geoffrey , Gazaryan Irina G. , Sakirolla Raghavendra , Mohd Zulkefeli , Pichika Mallikarjuna Rao 
Published: October 2022

AbstractThis is the first study investigating the nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) activity of compounds containing a new scaffold, tetrahydrobenzo[b]thiophene. Eighteen compounds were synthesised and confirmed their NRF2 activation through NQO1 enzymatic activity and mRNA expression of NQO1 and HO‐1 in Hepa‐1c1c7 cells. The compounds disrupted the interaction between Kelch‐like ECH‐associated protein 1 (KEAP1) and NRF2 via interfering with the KEAP1’s Kelch domain. The compounds exhibited anti‐inflammatory activity in Escherichia coli Lipopolysaccharide (LPSEc)‐stimulated RAW 264.7 cells. The anti‐inflammatory activity of the compounds was associated with their ability to activate NRF2. The compounds reversed the elevated levels of pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and IFN‐γ) and inflammatory mediators (PGE2, COX‐2, and NF‐κB). The compounds were metabolically stable in human, rat, and mouse liver microsomes and showed optimum half‐life (T1/2) and intrinsic clearance (Clint). The binding mode of the compounds and physicochemical properties were predicted via in silico studies.
A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary
Authors: Posner Atara , Prall Owen WJ , Sivakumaran Tharani , Etemadamoghadam Dariush , Thio Niko , Pattison Andrew , Balachander Shiva , Fisher Krista , Webb Samantha , Wood Colin , DeFazio Anna , Wilcken Nicholas , Gao Bo , Karapetis Christos S , Singh Madhu , Collins Ian M , Richardson Gary , Steer Christopher , Warren Mark , Karanth Narayan , Wright Gavin , Williams Scott , George Joshy , Hicks Rodney J , Boussioutas Alex , Gill Anthony J , Solomon Benjamin J , Xu Huiling , Fellowes Andrew , Fox Stephen B , Schofield Penelope , Bowtell David , Mileshkin Linda , Tothill Richard W 
Published: October 2022

AbstractCancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18‐class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high–medium confidence predictions. Classification performance was similar in clinicopathology‐resolved CUPs – 80% had high–medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology‐unresolved CUPs had high–medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology‐unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one‐third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Synthesis of titanium phosphate/polypyrrole nanocomposites for removal of methyl orange from water
Authors: Gupta Sakshi , Ben Sachin Kumar , Chandra Vimlesh 
Published: October 2022

AbstractIn this paper, titanium (IV) phosphate (TiP), polypyrrole (PPy), and titanium (IV) phosphate‐polypyrrole (TiP/PPy) nanocomposites were synthesized for adsorption of methyl orange (MO) dye from water. X‐ray diffraction data showed the formation of pure samples with crystallite size 14.1 and 14.2 nm of TiP and TiP/PPy nanocomposite respectively. The specific surface area of TiP (77.127 m2 g−1) was higher than PPy (17.004 m2 g−1) and TiP/PPy nanocomposite (25.247 m2 g−1). The equilibrium adsorption capacity (qe) was found to be 9.801 and 30.69 mg g−1 for PPy and TiP/PPy nanocomposite respectively. The Langmuir model was successfully fitted, and the TiP/PPy nanocomposite (69.4 mg g−1) had a greater maximum adsorption capacity (qm) than PPy (51.9 mg g−1). The MO adsorption removal efficiency was dependent on the pH of the solution and was found to be 86.7% and 30.7% for TiP/PPy nanocomposite and PPy respectively at pH 4. Thermodynamics studied confirmed the spontaneous and exothermic nature of the adsorption process. The presence of common ions decreased MO adsorption capacity and the maximum decrease was found for sodium carbonate. Electrostatic interaction, π–π stacking, and hydrogen bonding were responsible for adsorption of MO dye on the TiP/PPy nanocomposite and PPy.
The plastomes of Hyalomonas oviformis and Hyalogonium fusiforme evolved dissimilar architectures after the loss of photosynthesis
Authors: DeShaw Alexandra E. , Figueroa‐Martinez Francisco , Pröschold Thomas , Lorenz Maike , Nedelcu Aurora M. , Smith David R. , Reyes‐Prieto Adrián 
Published: October 2022

AbstractThe loss of photosynthesis in land plants and algae is typically associated with parasitism but can also occur in free‐living species, including chlamydomonadalean green algae. The plastid genomes (ptDNAs) of colorless chlamydomonadaleans are surprisingly diverse in architecture, including highly expanded forms (Polytoma uvella and Leontynka pallida) as well as outright genome loss (Polytomella species). Here, we explore the ptDNAs of Hyalomonas (Hm.) oviformis (SAG 62‐27; formerly known as Polytoma oviforme) and Hyalogonium (Hg.) fusiforme (SAG 62‐1c), each representing independent losses of photosynthesis within the Chlamydophyceae. The Hm. oviformis ptDNA is moderately sized (132 kb) with a reduced gene complement (but still encoding the ATPase subunits) and is in fact smaller than that of its photosynthetic relative Hyalomonas chlamydogama SAG 11‐48b (198.3 kb). The Hg. fusiforme plastome, however, is the largest yet observed in nonphotosynthetic plants or algae (~463 kb) and has a coding repertoire that is almost identical to that of its photosynthetic relatives in the genus Chlorogonium. Furthermore, the ptDNA of Hg. fusiforme shows no clear evidence of pseudogenization, which is consistent with our analyses showing that Hg. fusiforme is the nonphotosynthetic lineage of most recent origin among known colorless Chlamydophyceae. Together, these new ptDNAs clearly show that, in contrast to parasitic algae, plastid genome compaction is not an obligatory route following the loss of photosynthesis in free‐living algae, and that certain chlamydomonadalean algae have a remarkable propensity for genomic expansion, which can persist regardless of the trophic strategy.