bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective, real‐world experience of perampanel monotherapy in patient with first new onset focal seizure: A Thailand experience
Authors: Chinvarun Yotin
Published: November 2021

Objective

Real‐world data on efficacy and tolerability of perampanel (PER) monotherapy in treatment‐naïve patients with focal onset seizures (FOS) and/or focal‐to‐bilateral tonic‐clonic seizures (FBTCS) to assess efficacy effectiveness and tolerability.

Methods

This is a retrospective review of study patients with new FOS with or without FBTCS, aged ≥15 years, who had been prescribed PER as monotherapy. Treatment outcome included retention rate, responder, and seizure‐free rate at observational point 3, 6, and 12 months (OP3, OP6, and OP12). Treatment‐emergent adverse events (TEAEs) and adverse drug reactions were recorded.

Results

A total of 41 patients enrolled in the study (male:female; 17:22, mean age =46.1 ± 21.8 years), with new FOS and/or FBTCS. The proportions of individuals remaining on PER monotherapy at 3, 6, and 12 months were evaluated. The median PER dosage was 4 mg (range 2‐8 mg). The retention rates at OP3, OP6, and OP12 were 88%, 73%, and 61%, respectively. The seizure freedom rates at OP3, OP6, and OP12 were 78%, 80%, and 76%, respectively. About 14% had discontinued the PER monotherapy because of lack of efficacy. Sixteen individuals (41%) had TEAEs; common AEs were dizziness, somnolence, and ataxia; and only one case had depression. The AEs with somnolence and ataxia were found higher in elderly (15% and 30%) than adult patients (7% and 3%), respectively. Only 14% had intolerant adverse events, and it was found higher in elderly (23%).

Significance

Real‐world data of PER monotherapy in treatment‐naïve patients with focal onset seizures demonstrated good effectiveness and a good safety profile at relatively low doses. By starting with low dosage and slow titration of PER help to minimize the impact of adverse effects, maximize adherence, and increase patient retention. PER has a once‐daily dosing schedule that supports patient adherence contributes to achieving seizure freedom.
Typification of nine names of Asian species and varieties of Dioscorea (Dioscoreaceae)
Authors: Hoque Akramul , Lakshminarasimhan Pakshirajan , Bandyopadhyay Subir , Maity Debabrata
Published: November 2021

The yam genus Dioscorea includes some of the world's most important food and medicinal plants The names of most Asian species and infraspecific taxa are in need of typification because their publication predated the 1935 Cambridge Rules of Botanical Nomenclature in which the concept of nomenclatural types was first introduced. Here, the Dioscorea collections cited in the protologues and uncited material associated with the names at their first publications are evaluated in the light of the latest Shenzhen Code (2018) and lectotypes of eight names designated, viz. D. lepcharum, D. nummularia var. glauca, D. pentaphylla var. communis, D. pentaphylla var. linnaei, D. pentaphylla var. malaica, D. pentaphylla var. rheedei, D. pentaphylla var. thwaitesii and D. rogersii. Most of the original materials concerned were collected from India, and the rest from other parts of South Asia and South East Asia (Bangladesh, Sri Lanka, Philippines and Malaysia). The single specimen cited in the protologue of D. wightii Hook.f. is affirmed here as the holotype.
Study of jelly drying cashew apples (Anacardium occidentale L.) processing
Authors: Dao Tan Phat , Vu Duc Ngoc , Nguyen Duong Vu , Pham Van Thinh , Tran Thi Yen Nhi
Published: November 2021

Cashew apples, a by‐product accrued during the manufacture of cashew nuts, have abundant nutritional values but are not widely utilized due to the presence of substances that cause acrid taste. In this study, we attempted the production of a dried jelly cashew apple product and optimized three main processing stages including blanching, osmotic, and drying. The results showed suitable conditions at 6 mm thickness in the blanching process. The osmotic process recorded a temperature of 35°C, within 1.5 h, the ratio of sugar syrup/ingredient 2:1 with sugar syrup 60 Bx, and the addition of 0.6% citric acid on the total weight of ingredients and 0.02% CaCl2. The drying process at 55°C within 267 min had the highest ascorbic acid content (TAA), total phenolic content (TPC), and content of tannin compounds (TTC) retention. These parameters refer to a product that has good organoleptic acceptability in terms of taste, acrid content, and a high ability to retain major nutrients. Furthermore, the product recovery efficiency is 21.45%. Jelly drying cashew apples (JDC) are formed to help take advantage of by‐products, contributing to adding value for the cashew industry.
Effect of Ni/Cu ratio on activity and selectivity of CO2 methanation over Ni‐Cu/SiO2 catalysts
Authors: Dias Yan Resing , Perez‐Lopez Oscar William
Published: November 2021

In the present work two series of Ni‐Cu/SiO2 catalysts were evaluated in CO2 methanation. Samples with fixed Ni/Cu ratio and variable total metal loadings, and samples with fixed Ni loadings and variable Ni/Cu ratio were prepared by wet impregnation and characterized by N2 physisorption, X‐ray diffractometry, H2 temperature programmed reduction , scanning electron microscopy with energy dispersive spectroscopy , and temperature programmed oxidation. The catalytic tests were carried out from 250 to 450 °C, H2/CO2 = 4 and 1 atm in a fixed bed tubular reactor with online analysis by gas chromatography. Higher Ni loadings lead to higher Ni° crystallite sizes for samples with fixed Ni/Cu ratio, whereas no difference was observed for samples with variable Ni/Cu ratio. In addition, higher Ni/Cu ratios shifted the reduction temperature to higher values, revealing an increase in metal‐support interaction. Catalysts with Ni/Cu = 10 ratio presented almost equal CO2 conversion regardless of the Ni content, which is attributed to the increase in the Ni° crystallite size as the Ni content increases, whereas the selectivity for CH4 increased with the Ni content due to Ni migration to the surface. For catalysts with fixed Ni content, the higher the Ni/Cu ratio, the greater the CO2 conversion and the CH4 selectivity, demonstrating that the proper adjustment of the Ni/Cu ratio is essential for a high CH4 yield. The catalyst with the highest Ni/Cu ratio achieved a CO2 conversion of 63.3% and CH4 selectivity of 95.7% at 400 °C, showing the greatest resistance to sintering during 5 hr and low carbon formation, which can be attributed to the small crystallite size (∼15 nm) and high metal‐support interaction, resulting from an appropriate Ni/Cu ratio. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd.
Gold mineralization in the Ajibarang and Majenang blocks, Central Java, Indonesia: Evidence of mineral fertility of the Banyumas basin
Authors: Prihatmoko Sukmandaru , Idrus Arifudin
Published: November 2021

Banyumas basin is not only of interest as a hydrocarbon exploration target but also because of its potential to host epithermal gold and porphyry‐type deposits. To date, very few studies have been done on the significance of basin tectonics related to mineralization, but such studies are critically needed. This paper is aimed at reviewing and describing characteristics of gold and base‐metal mineralization that were recently discovered in the Banyumas basin, focusing on the Ajibarang and Majenang blocks, followed by a discussion of the mineral fertility of the basin. Various primary data collected by the authors during fieldwork with several mineral exploration companies together with data from current research results are reviewed, interpreted, and discussed. Two different styles of gold mineralization are recognized, that is, carbonate‐base metal‐gold/intermediate‐sulphidation epithermal mineralization in the Ajibarang Block and porphyry‐style mineralization in the Majenang Block, which occur in close proximity to each other (40–50 km distance) in different geological settings. The Ajibarang mineralization is hosted by a turbidite sedimentary sequence forming part of the Halang Formation, which is phreatically brecciated (diatreme), whereas the Majenang mineralization was formed in the Kumbang Formation in a volcanic and intrusive (diorite) environment. Diatreme breccias associated with gold‐base metal mineralization in the Ajibarang Block may be related to remnant hydrothermal activity, recognized in Landsat TM imagery as circular structures. However, it remains unclear whether any volcanic/intrusive activity was directly involved in the formation of the mineralization. In contrast, the Majenang porphyry mineralization is clearly related to magmatism as it is hosted by volcanics of the Kumbang Formation and a diorite as the causative intrusion. The recent discovery of mineralization in both locations suggests the mineralization fertility of the Banyumas basin may be significant, making the region a valuable target for future exploration.
Social isolation, social support, and loneliness and their relationship with cognitive health and dementia
Authors: Joyce Johanna , Ryan Joanne , Owen Alice , Hu Jessie , McHugh Power Joanna , Shah Raj , Woods Robyn , Storey Elsdon , Britt Carlene , Freak‐Poli Rosanne ,   ASPREE Investigator Group
Published: November 2021

Background

Poor social health is prevalent in older adults and may be associated with worse cognition, and increased dementia risk. The aim of this study was to determine whether social isolation, social support and loneliness are independently associated with cognitive function and incident dementia over 5 years in older adults, and to investigate potential gender differences.

Methods

Participants were 11,498 community‐dwelling relatively healthy Australians aged 70–94, in the ASPREE Longitudinal Study of Older Persons (ALSOP). Social isolation, social support, loneliness and cognitive function were assessed through self‐report. Outcomes examined were cognitive decline (>1.5 SD decline in cognitive performance since baseline) and incident dementia (adjudicated according to DSM‐IV criteria).

Results

Most participants self‐reported good social health (92%) with very few socially isolated (2%), with low social support (2%) or lonely (5%). Among women, social isolation and low social support were consistently associated with lower cognitive function (e.g., social support and cognition β = −1.17, p < 0.001). No consistent longitudinal associations were observed between baseline social health and cognitive decline (over median 3.1 years) or incident dementia (over median 4.4 years; social isolation: HR = 1.00, p = 0.99; low social support: HR = 1.79, p = 0.11; loneliness: HR = 0.72, p = 0.34 among women and men).

Conclusion

Our study provides evidence that social isolation and a low social support are associated with worse cognitive function in women, but not men. Social health did not predict incident cognitive decline or dementia, but we lacked power to stratify dementia analyses by gender.
Multi‐objective fitting of concentration‐discharge relationships
Authors: Tunqui Neira José Manuel , Andréassian Vazken , Tallec Gaëlle , Mouchel Jean‐Marie
Published: November 2021

Concentration–discharge () relationships are widely used to assess the link between hydrological and biogeochemical processes at the catchment scale. relationships are mainly calibrated using mono‐objective methods to represent, either concentrations or discharge‐weighted concentrations (i.e., load). Based on its wide use in hydrological modelling, we test a multi‐objective calibration for the relationship parameters, using both concentration and load, and compare it to a mono‐objective calibration applied on either concentrations or load. This work is carried out on a high‐frequency dataset (ORACLE‐Orgeval Observatory, France). Our findings show that the multi‐objective calibration yield a better representation of relationships parameters during the high and low‐flow events. The multi‐objective calibration can be used for all forms of relationships and avoids issues of under‐representation of dilution processes characterized by high‐discharge, low‐concentration periods.
Changes in snowmelt runoff timing in the contiguous United States
Authors: Uzun Sukru , Tanir Tugkan , Coelho Gustavo de A. , Souza de Lima Andre de , Cassalho Felicio , Ferreira Celso M.
Published: November 2021

Changes in timing of snowmelt‐fed streamflow have great importance for water supply, flood management, and ecological processes, as well as being a common indicator of climate change. In this study, snowmelt runoff timing change in the contiguous United States between 1957 and 2016 was investigated by analysing data from 97 streamflow gages. The annual snowmelt runoff timing shift was identified using ‘Center Time (CT)’ and ‘Spring Pulse Onset (SPO)’ methods, jointly with the monthly fractional streamflow (MFS) analysis, conducted between January and June. Since snowmelt‐derived streamflow timing change is mainly induced by regional meteorological factors, such as air temperature and precipitation, their trends and relationship with CT were also examined. Shifts toward earlier snowmelt runoff timing were found by both methods, CT (8.3 days on average) and SPO (8.5 days on average). Although the results of the CT change are stronger than the SPO change, both outcomes are mostly correlated, particularly in the central and northwestern parts of the country. MFS trends support the outcomes of CT and SPO. In January, February, and especially March, a higher number of the stations indicated increasing trends in MFS. In April, May, and June, their number decreased and the number of gages with diminishing trends rose sharply. The timing difference is highly related to temperature change. Annual average temperature and temperature in the melting period increase considerably. The annual average temperature is significantly negatively correlated with CT in the vast majority of the regions. Although precipitation is not as effective as the temperature, its trends have impacts on snowmelt runoff timing change depending on the region and elevation. These results demonstrate the importance of the impacts of snowmelt runoff timing changes due to global warming on the regional and large‐scale hydrology in the contiguous United States.
Potential effectiveness of a therapeutic HPV intervention campaign in Uganda
Authors: Spencer Jennifer C. , Campos Nicole G. , Burger Emily A. , Sy Stephen , Kim Jane J.
Published: November 2021

Cervical cancer is a major source of morbidity and mortality in Uganda. In addition to prophylactic HPV vaccination, secondary prevention strategies are needed to reduce cancer burden. We evaluated the potential cancer reductions associated with a hypothetical single‐contact therapeutic HPV intervention—with 70% coverage and variable efficacy [30%‐100%]—using a three‐stage HPV modeling framework reflecting HPV and cervical cancer burden in Uganda. In the reference case, we assumed prophylactic preadolescent HPV vaccination starting in 2020 with 70% coverage. A one‐time therapeutic intervention targeting 35‐year‐old women in 2025 (not age‐eligible for prophylactic vaccination) averted 1801 cervical cancers per 100 000 women over their lifetime (100% efficacy) or 533 cancers per 100 000 (30% efficacy). Benefits were considerably smaller in birth cohorts eligible for prophylactic HPV vaccination (768 cases averted per 100 000 at 100% efficacy). Evaluating the population‐level impact over 40 years, we found introduction of a therapeutic intervention in 2025 with 100% efficacy targeted annually to 30‐year‐old women averted 139 000 incident cervical cancers in Uganda. This benefit was greatly reduced if efficacy was lower (30% efficacy; 41 000 cases averted), introduction was delayed (2040 introduction; 72 000 cases averted) or both (22 000 cases averted). We demonstrate the potential benefits of a single‐contact HPV therapeutic intervention in a low‐income setting, but show the importance of high therapeutic efficacy and early introduction timing relative to existing prophylactic programs. Reduced benefits from a less efficacious intervention may be somewhat offset if available within a shorter time frame.
A guide for physiotherapeutic care during pregnancy, labor, and the postpartum period during the COVID‐19 pandemic
Authors: Pitangui Ana Carolina Rodarti , Driusso Patrícia , Mascarenhas Lilian Rose , Silva Marcela Ponzio Pinto , de Oliveira Sunemi Mariana Maia , de Oliveira Claudia , Gallo Rubneide Barreto Silva , de Menezes Franco Maira , Ferreira Cristine Homsi Jorge
Published: November 2021

Synopsis

Telephysiotherapy is a viable alternative for maintaining care during the pregnancy‐puerperal cycle; however, face‐to‐face consultations should be taken into account and considered, according to the local epidemiological situation.
Evaluation of a pharmacist‐led intervention on naloxone co‐prescribing in patients receiving chronic opioid therapy
Authors: Dhakal Dimple , Sojka Luanne , Griesbach Sara , Panich Jennifer
Published: November 2021

Introduction

Although both the 2016 Centers for Disease Control and Prevention (CDC) guidelines and the 2020 Food and Drug Administration (FDA) safety announcement recommend naloxone co‐prescribing to patients receiving long‐term opioid therapy (LTOT) for non‐cancer pain, the rate of naloxone co‐prescription in this population remains low.

Objectives

The primary objective of this project was to determine whether a pharmacist intervention would lead to increased rates of naloxone co‐prescribing among providers.

Methods

This was a before‐and‐after interventional study to evaluate changes in naloxone co‐prescribing rates in response to clinical pharmacist recommendation of naloxone for LTOT patients to providers. The primary end point was rate of naloxone co‐prescription after pharmacist intervention. Providers of LTOT patients were emailed patient‐specific recommendations. Additional end points included calculation of the naloxone possession rate among patients and identification of patient‐specific predictors for not having naloxone co‐prescribed at baseline.

Results

A total of 152 patients met inclusion criteria throughout the intervention period. Out of the 152 patients who were eligible for naloxone, 90 (59.2%) were prescribed naloxone before the intervention and 131 (86.2%) were prescribed naloxone after the pharmacist provided interventions. This increase in naloxone prescription (27%) was statistically significant (P < .001). Our results also showed that LTOT patients who were prescribed opioids by adult primary care providers were at risk for lack of naloxone co‐prescribing at baseline (adjusted odds ratio [aOR] 3.66, P = .013) as compared with patients taking opioids prescribed by a pain management provider. The overall possession rate among patients with naloxone co‐prescribed by the end of the intervention period was 56.4% (74/131 patients).

Conclusion

A pharmacist‐led intervention was found to increase the naloxone co‐prescribing rate for LTOT patients. However, co‐prescribing naloxone does not guarantee patient possession; only 56.4% of patients with a naloxone prescription appeared to have naloxone at home. Future studies should explore ways to increase naloxone possession rates.
Measurement of synergy in merger & acquisitions: A panel data approach using composite variable (principal component analysis)
Authors: Kalsie Anjala , Singh Neha
Published: November 2021

The primary purpose of this research is to look into the Impact of cash payment on Operating and Financial synergies generated post the merger. The two‐stage least squares method Instrumental‐variables regression technique is employed to test the hypothesis of impact of cash payment on the synergies gained by the acquirer post the merger. The uniqueness of this paper is that it develops an effective technique for evaluating the phenomena of M&As using a composite synergy variable that accurately reflects the dynamic phenomenon. The paper uses “Principal Component Analysis” (PCA) estimation to generate dependent variable which is a conglomerate of several factors. For all models, the findings of the study reveal that payment in cash has a favorable and significant relationship with Operational and Financial Synergy, demonstrating the increased viability of acquiring entities in post‐M&A stage. Synergistic advantages of M&A appear to be perceived by enhanced Operating Income, improvement in R&D expenditure (statistically significant) and a positive Return on Asset (non‐significant). The paper looks at a wide variety of domestic M&A transactions in India. So far, no systematic research has been done to determine the possible realization of synergistic gains for Indian firms undergoing M&As.
Understanding the binding mechanism for potential inhibition of SARS‐CoV‐2 Mpro and exploring the modes of ACE2 inhibition by hydroxychloroquine
Authors: Choudhury Manisha , Dhanabalan Anantha K. , Goswami Nabajyoti
Published: November 2021

As per the World Health Organization report, around 226 844 344 confirmed positive cases and 4 666 334 deaths are reported till September 17, 2021 due to the recent viral outbreak. A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) is responsible for the associated coronavirus disease (COVID‐19), which causes serious or even fatal respiratory tract infection and yet no approved therapeutics or effective treatment is currently available to combat the outbreak. Due to the emergency, the drug repurposing approach is being explored for COVID‐19. In this study, we attempt to understand the potential mechanism and also the effect of the approved antiviral drugs against the SARS‐CoV‐2 main protease (Mpro). To understand the mechanism of inhibition of the malaria drug hydroxychloroquine (HCQ) against SARS‐CoV‐2, we performed molecular interaction studies. The studies revealed that HCQ docked at the active site of the Human ACE2 receptor as a possible way of inhibition. Our in silico analysis revealed that the three drugs Lopinavir, Ritonavir, and Remdesivir showed interaction with the active site residues of Mpro. During molecular dynamics simulation, based on the binding free energy contributions, Lopinavir showed better results than Ritonavir and Remdesivir.
Clinical and biochemical indexes of 11 COVID‐19 patients and the genome sequence analysis of the tested SARS‐CoV‐2
Authors: Yu Zhikang , Wu Heming , Huang Qingyan , Zhong Zhixiong
Published: November 2021

Background

At present, SARS‐CoV‐2 epidemic in the world rapidly spread. It is a serious global public health emergency.

Methods

In this study, we described the clinical characteristics of 11 COVID‐19 patients hospitalized in the Meizhou People's Hospital, and viral genome sequences of SARS‐CoV‐2 from these patients were analyzed.

Results

Of the 11 patients, six cases developed fever, 9 cases developed a cough, and two cases developed headache and chills. Four patients (36.4%) had underlying diseases. Pneumonia is the most common complication. The laboratory test results showed that there were no adult patients with increased lymphocyte/lymphocyte percentage (LYM/LYM%). Most patients had normal total protein (TP) and albumin (ALB), but only two patients had decreased. Most patients had increased or normal levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), activated partial thromboplastin time (APTT), fibrinogen (FIB), creatine kinase isoenzymes (CK‐MB), and lactate dehydrogenase (LDH). Neutrophil (NEU) (r = 0.664, p = 0.026), CK‐MB (r = 0.655, p = 0.029) and blood urea nitrogen (BUN) (r = 0.682, p = 0.021) were significantly associated with SARS‐CoV‐2 virus cycle threshold (Ct) value. Multiple sequence alignment (MSA) shows that two different SNPs were identified at positions 8781 and 28144, and have a complete linkage genetic form of 8781C‐28144T and 8781T‐28144C.

Conclusions

The reports of the 11 COVID‐19 patients in our hospital will provide useful information for the diagnosis, treatment, and drug development of SARS‐CoV‐2.
An SNP reducing SNORD105 and PPAN expression decreases the risk of hepatocellular carcinoma in a Chinese population
Authors: Chen Xuekun , Zhang Qing , Yang Zhenzhen , Yu Huan , Qu Yiling , Tan Rui , Gao Yuzhen , He Yan , Li Lijuan
Published: November 2021

Background

With hepatocellular carcinoma (HCC) becoming a heavy disease burden in China, it is particular to reveal its pathological mechanism. Recent researches have indicated that small nucleolar RNAs (snoRNAs) may be involved in various cancers including HCC. Polymorphisms within snoRNAs may affect its function or expression level, and even its host gene, then produce series of effects related to itself or its host gene.

Methods

The association of the single nucleotide polymorphism (SNP) rs2305789 in SNORD105 with HCC susceptibility was evaluated in two independent case‐control sets (712 HCC and 801 controls). The contribution of rs2305789 to HCC risk was investigated using case‐control, genotype‐phenotype correlation analysis, and functional assays.

Results

The SNP rs2305789 was significantly associated with a decreased risk of HCC in both case‐control sets (OR = 0.80, 95% CI: 0.69–0.93, p = 0.003). Compared with the AA genotype, the GG genotype was significantly correlated with lower expression of both SNORD105 and PPAN (p < 0.01). Furthermore, the overexpressed SNORD105 up‐regulated PPAN expression level (p < 0.05). Finally, the in vivo experiment showed that the overexpressed SNORD105 increased cell viability and motility in both HepG2 and Huh7 cell lines (p < 0.05).

Conclusions

To sum up, our results suggested that rs2305789 decreased the risk of HCC by reducing the expression of both SNORD105 and PPAN, which reduced HCC cell viability and motility.
Lnc‐CPLC promotes the progression of colorectal cancer via regulating ZBTB34 by competitively binding miR‐4319
Authors: Liao Jingnan , Liu Jinglan , Wang Jinjin , Wang Mingyuan
Published: November 2021

Long noncoding RNAs (lncRNAs) have been considered as regulatory molecules that play crucial roles in diverse biological processes, including the regulation of tumor progression. However, in colorectal cancer (CRC), due to the complex regulatory relationships involved in lncRNAs, the details of the specific mechanism still need to be elucidated. To discover the key regulatory role of lncRNA in CRC, we used bioinformatics analysis methods for preliminary screening. Through the combination of in vitro and in vivo verification, we further comprehensively analyzed the specific regulation of the key gene and the related key lncRNA in CRC. We found that ZBTB34 and lnc‐CPLC (CRC progression‐associated lncRNA) had a strong correlation, which plays a key role in the regulation of CRC. Furthermore, by exerting the “sponge” function, lnc‐CPLC could bind to miR4319 and release its binding to the 3'UTR of ZBTB34 mRNA. Our results reveal the mechanism of the lnc‐CPLC/miR‐4319/ZBTB34 signal axis in CRC and provide evidence for elucidating the complex molecular mechanisms in tumors.
Casein kinase II activates Bik to induce death of hyperplastic mucous cells in a cell cycle‐dependent manner
Authors: Mebratu Yohannes A. , Imani Jewel , Jones Jane T. , Tesfaigzi Yohannes
Published: November 2021

Extensive inflammation causes epithelial cell hyperplasia in the airways and Bcl‐2‐interacting killer (Bik) reduces epithelial cell and mucous cell hyperplasia without affecting resting cells to restore homeostasis. These observations suggest that Bik induces apoptosis in a cell cycle‐specific manner, but the mechanisms are not understood. Mice were exposed to an allergen for 3, 14, or 30 days and Bik expression was induced in airway epithelia of transgenic mice. Bik reduced epithelial and mucous cell hyperplasia when mice were exposed to an allergen for 3 or 14 days, but not when exposure lasted for 30 days, and Ki67‐positivity was reduced. In culture, Bik expression killed proliferating cells but not quiescent cells. To capture the stage of the cell cycle when Bik induces cell death, airway cells that express fluorescent ubiquitin cell cycle indicators were generated that fluoresce red or green during the G0/G1 and S/G2/M phases of the cells cycle, respectively. Regardless of the cell cycle stage, Bik expression eliminated green‐fluorescent cells. Also, Bik, when tagged with a blue‐fluorescent protein, was only detected in green cells. Bik phosphorylation mutants at threonine 33 or serine 35 demonstrated that phosphorylation activated Bik to induce death even in quiescent cells. Immunoprecipitation and proteomic approaches identified casein kinase IIα to be responsible for phosphorylating and activating Bik to kill cells in S/G2/M. As casein kinase 2 alpha (CKIIα) is expressed only during the G2/M phase, we conclude that Bik activation in airway epithelial cells selectively targets hyperplastic epithelial cells, while leaving resting airway cells unaffected.
Activation of Akt–mTORC1 signalling reverts cancer‐dependent muscle wasting
Authors: Geremia Alessia , Sartori Roberta , Baraldo Martina , Nogara Leonardo , Balmaceda Valeria , Dumitras Georgia Ana , Ciciliot Stefano , Scalabrin Marco , Nolte Hendrik , Blaauw Bert
Published: November 2021

Background

Cancer‐related muscle wasting occurs in most cancer patients. An important regulator of adult muscle mass and function is the Akt–mTORC1 pathway. While Akt–mTORC1 signalling is important for adult muscle homeostasis, it is also a major target of numerous cancer treatments. Which role Akt–mTORC1 signalling plays during cancer cachexia in muscle is currently not known. Here, we aimed to determine how activation or inactivation of the pathway affects skeletal muscle during cancer cachexia.

Methods

We used inducible, muscle‐specific Raptor ko (mTORC1) mice to determine the effect of reduced mTOR signalling during cancer cachexia. On the contrary, in order to understand if skeletal muscles maintain their anabolic capacity and if activation of Akt–mTORC1 signalling can reverse cancer cachexia, we generated mice in which we can inducibly activate Akt specifically in skeletal muscles.

Results

We found that mTORC1 signalling is impaired during cancer cachexia, using the Lewis lung carcinoma and C26 colon cancer model, and is accompanied by a reduction in protein synthesis rates of 57% (P < 0.01). Further reduction of mTOR signalling, as seen in Raptor ko animals, leads to a 1.5‐fold increase in autophagic flux (P > 0.001), but does not further increase muscle wasting. On the other hand, activation of Akt–mTORC1 signalling in already cachectic animals completely reverses the 15–20% loss in muscle mass and force (P < 0.001). Interestingly, Akt activation only in skeletal muscle completely normalizes the transcriptional deregulation observed in cachectic muscle, despite having no effect on tumour size or spleen mass. In addition to stimulating muscle growth, it is also sufficient to prevent the increase in protein degradation normally observed in muscles from tumour‐bearing animals.

Conclusions

Here, we show that activation of Akt–mTORC1 signalling is sufficient to completely revert cancer‐dependent muscle wasting. Intriguingly, these results show that skeletal muscle maintains its anabolic capacities also during cancer cachexia, possibly giving a rationale behind some of the beneficial effects observed in exercise in cancer patients.
Biomineralization induced by chitosan and collagen‐based materials with fluoride for dentin coverage: Chemical and morphological analysis
Authors: Nahórny Sidnei , de Oliveira Ivone Regina , Soares Luís Eduardo Silva
Published: November 2021

The prevention and treatment of erosive tooth wear are becoming increasingly important due to its increasing prevalence. The use of natural solutions to modify dental surfaces has become an area of research. Organic materials such as chitosan and hydrolyzed collagen may be a promising option to treat dentin. This in vitro study aimed to evaluate the influence of chitosan or hydrolyzed collagen, alone or combined with acidulated phosphate fluoride (APF) gel, on the composition and morphology of dentin after erosion. Bovine dentin samples were prepared (n = 84) and treated with artificial saliva (AS, negative control); APF gel (F, positive control); chitosan solution (Chi); hydrolyzed collagen solution (Col); fluoride/chitosan composition (F_Chi); and fluoride/hydrolyzed collagen composition (F_Col). Erosive cycles (six cycles of immersion in orange juice for 1 min, followed by immersion in AS for 1 hr) were performed. The materials were characterized by their morphology, composition, and particle size distribution. Micro‐energy dispersive X‐ray fluorescence spectroscopy and scanning electron were used to evaluate the dentin's inorganic chemical composition and morphology. The F_Col and F groups had a reduction in calcium loss by 17 and 26%, respectively (p < .001). Both of these groups still had a covering layer of agglomerates at the dentin surface after the erosive cycles. The fluoridated chitosan or collagen solutions improved the dentin resistance to erosion as a novel hybrid‐fluoride‐based material approach to provide surface protection from erosion.
A defect in molybdenum cofactor binding causes an attenuated form of sulfite oxidase deficiency
Authors: Kaczmarek Alexander Tobias , Bender Daniel , Gehling Titus , Kohl Joshua Benedict , Daimagüler Hülya‐Sevcan , Santamaria‐Araujo José Angel , Liebau Max Christoph , Koy Anne , Cirak Sebahattin , Schwarz Guenter
Published: November 2021

Isolated sulfite oxidase deficiency (ISOD) is a rare recessive and infantile lethal metabolic disorder, which is caused by functional loss of sulfite oxidase (SO) due to mutations of the SUOX gene. SO is a mitochondrially localized molybdenum cofactor (Moco)‐ and heme‐dependent enzyme, which catalyzes the vital oxidation of toxic sulfite to sulfate. Accumulation of sulfite and sulfite‐related metabolites such as S‐sulfocysteine (SSC) are drivers of severe neurodegeneration leading to early childhood death in the majority of ISOD patients. Full functionality of SO is dependent on correct insertion of the heme cofactor and Moco, which is controlled by a highly orchestrated maturation process. This maturation involves the translation in the cytosol, import into the intermembrane space (IMS) of mitochondria, cleavage of the mitochondrial targeting sequence, and insertion of both cofactors. Moco insertion has proven as the crucial step in this maturation process, which enables the correct folding of the homodimer and traps SO in the IMS. Here, we report on a novel ISOD patient presented at 17 months of age carrying the homozygous mutation NM_001032386.2 (SUOX):c.1097G > A, which results in the expression of SO variant R366H. Our studies show that histidine substitution of Arg366, which is involved in coordination of the Moco‐phosphate, causes a severe reduction in Moco insertion efficacy in vitro and in vivo. Expression of R366H in HEK SUOX−/− cells mimics the phenotype of patient's fibroblasts, representing a loss of SO expression and specific activity. Our studies disclose a general paradigm for a kinetic defect in Moco insertion into SO caused by residues involved in Moco coordination resulting in the case of R366H in an attenuated form of ISOD.
The influence of IL1RN VNTR polymorphism on HPV infection among some tribal communities
Authors: Goswami Anindita , Bhuniya Utpal , Chatterjee Soumendranath , Mandal Paramita
Published: November 2021

Persistent infection of human Papillomavirus is the main etiological factor for cervical cancer. Austro‐Asiatic tribes are early settlers in India and they have unique genetic variations compared to other people. The immunological response is crucial for the prevention of viral associated diseases. Interleukin‐1 receptor antagonist (IL‐1RN) is considered being an important regulator of host immune surveillance. A total of 45 Santali tribal women and 10 Kora tribal women were enrolled in the present study and demographic variables were recorded during collection. Genomic DNA was extracted from cervical/vaginal swab samples. IL1RN variable number of tandem repeats (VNTR) polymorphisms and HPV types were determined by PCR‐based assay. Association between IL1RN VNTR polymorphisms with the HPV infections among the tribal communities was determined by logistic regression analysis. HPV18 prevalence was significantly higher among tribal women. We observed that the polymorphism A2*A2 (p = 0.022; odds ratio [OR] (95% confidence interval [CI]) = 0.16 (0.03–0.86)] were more resistant to oncogenic HPV infection. Use of oral contraceptives was associated with higher relative risk (p = 0.008; OR [95% CI] = 5.39 [1.47–19.8]) for oncogenic HPV18 positivity among the tribal women. The A2 allele homozygosity of IL1RN VNTR was identified to be associated with the protection from oncogenic HPV infection among various tribal communities of West Bengal and therefore may be a useful marker of host immune response among them.
Rhamnogalacturonan I‐rich polysaccharide isolated from fermented persimmon fruit increases macrophage‐stimulatory activity by activating MAPK and NF‐κB signaling
Authors: Shin Hyun Young , Hwang Ki Cheol , Mi Xiao‐Jie , Moon Sung‐Kwon , Kim Yeon‐Ju , Kim Hoon
Published: November 2021

BACKGROUND

Persimmon (Diospyros kaki) is a familiar and widespread fruit, cultivated worldwide. To date, physiological and chemical changes in fermented persimmon fruit and its active compounds have been rarely investigated. Moreover, comparative studies on the pharmacological activities of fermented persimmon fruit‐derived compounds have not been reported.

RESULTS

To investigate the effect of traditional fermented foods on immunostimulatory activity, non‐fermented persimmon fruit (D. kaki, DK) and fermented persimmon fruit (fermented D. kaki, FDK) were prepared and further fractionated into low‐ and high‐molecular weight fractions. FDK exhibited significantly higher activity toward the production of macrophage‐stimulatory mediators compared with that of DK, and the high‐molecular weight fraction (FDK‐H) isolated from FDK was shown to have more potent activity than FDK. FDK‐H not only increased the expression of immunostimulatory genes (TNF‐α, IL‐6, IL‐12, and iNOS), but also stimulated the phosphorylation of both MAPK (ERK, JNK, and p38) and NF‐κB (p65 and IκB) signaling molecules underlying macrophage activation. The putative chemical characteristic of FDK‐H was identified as a pectic rhamnogalacturonan (RG) I‐rich polysaccharide with a high molecular weight of 304 kDa containing galacturonic acid, arabinose, rhamnose, and galactose as the major monosaccharide units.

CONCLUSION

The present study reveals that traditional fermentation is a useful method for increasing the macrophage‐immunostimulatory activity of persimmon fruit, and the increased activity may be associated with structural modification of persimmon polysaccharides. This study may serve to identify a functional ingredient as an immunostimulatory agent, and our results may be applied to develop a new immunostimulatory product using FDK‐H. © 2021 Society of Chemical Industry.
Effects of exogenous sucrose and selenium on plant growth, quality, and sugar metabolism of pea sprouts
Authors: Tan Chuntao , Zhang Liang , Duan Xuewu , Chai Xirong , Huang Riming , Kang Yunyan , Yang Xian
Published: November 2021

BACKGROUND

Pea sprouts are considered a healthy food. Sucrose is a key nutritional factor affecting taste and flavor. Meanwhile, selenium (Se) is an essential micronutrient that plays multiple roles in wide variety of physiological processes and improves crop quality and nutritional value. Nonetheless, the effects of the combination of sucrose and Se treatment on growth, quality, and sugar metabolism of pea sprouts have not been explored.

RESULTS

The results revealed that sucrose at 10 mg L−1 obviously increased fresh weight, vitamin C, soluble protein, soluble sugar, fructose, glucose, and sucrose contents. Se treatments also improved nutritional quality, but higher Se (2.5 mg L−1) significantly inhibited the growth of seedlings. Interestingly, the combined application of sucrose (10 mg L−1) and Se (1.25 mg L−1) could effectively promote vitamin C, sucrose, and fructose contents, especially the Se content, compared with Se application alone. Additionally, there were significant differences in the regulation of sugar metabolism between Se alone and combined application of sucrose and Se. Acid invertase and neutral invertase play a pivotal role in the accumulation of soluble sugar under Se treatments alone, and acid invertase might be the key enzyme to limit sugar accumulation under combined application of sucrose and Se.

CONCLUSION

The moderate combined application of sucrose (10 mg L−1) and Se (1.25 mg L−1) more effectively regulated sugar metabolism and improved nutritional quality than Se application alone did. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Urinary volatomic profile of traditional tobacco smokers and electronic cigarettes users as a strategy to unveil potential health issues
Authors: Berenguer Cristina , Pereira Jorge A. M. , Câmara José S.
Published: November 2021

Many harmful and potentially harmful constituents are present in tobacco products. Cigarette smoke is known to cause different forms of cancer and trigger the development of chronic diseases. In the last decade, electronic cigarettes have emerged as a healthier alternative associated to less harmful effects in comparison to traditional tobacco. However, the lack of standardization of electronic cigarettes products makes it difficult to establish and compare the real effects on health of products from different manufacturers. To better understand the impact of smoking and vaping, the volatomic composition of urine samples from traditional tobacco smokers and electronic cigarette users was established and compared with nonsmokers (control group), using headspace solid‐phase microextraction combined with gas chromatography–mass spectrometry. A total of 45 urinary volatile organic metabolites belonging to different chemical families were identified in the urine of the studied groups. Benzene derivatives, terpenes, and aromatics were the chemical families that contributed the most to the urinary profile of smokers. The vapers urinary volatomic pattern was also dominated by terpenes and aromatics, in addition to alcohols. The orthogonal partial least squares‐discriminant analysis of the data obtained indicated that the urinary profile of vapers is more closely related to the control group, reinforcing the hypothesis of the lowest harmfulness of electronic cigarettes. Further studies recruiting a higher number of subjects are therefore necessary to consolidate the data obtained.
MiR‐32‐5p promoted epithelial‐to‐mesenchymal transition of oral squamous cell carcinoma cells via regulating the KLF2/CXCR4 pathway
Authors: Qin Shi‐Yu , Li Bo , Chen Mei , Qin Ming‐Qun , Liu Ji‐Mu , Lv Qiu‐Li
Published: November 2021

Oral squamous cell carcinoma (OSCC) is one of the most common carcinomas of the oral cavity. However, the regulatory mechanisms on miR‐32‐5p remain poorly understood in OSCC. The expression of miR‐32‐5p, Krüppel‐like factor 2 (KLF2), C‐X‐C motif chemokine receptor 4 (CXCR4), and epithelial‐to‐mesenchymal transition (EMT)‐related proteins (E‐cadherin, Vimentin, N‐cadherin, and Snail) were evaluated were assessed using RT‐qPCR and Western blot. 3‐(4, 5‐Dimethylthiazolyl2)‐2, 5‐diphenyltetrazolium bromide assay, wound healing assay, and transwell assay were employed to detect cell proliferation, migration, and invasion of OSCC cells. Finally, dual‐luciferase reporter assay was performed to verify the binding relationship between KLF2 and miR‐32‐5p. MiR‐32‐5p was highly expressed while KLF2 was lowly expressed in OSCC cells, and miR‐32‐5p knockdown or KLF2 overexpression could markedly reduce cell proliferation, migration, invasion, and EMT of OSCC cells. What is more, KLF2 was the target of miR‐32‐5p, and knockdown of KLF2 abolished the inhibitory effect of miR‐32‐5p inhibitor on progression of OSCC. Finally, CXCR4 expression was negatively regulated by KLF2, and inhibition of CXCR4 obviously alleviated the biological effects of si‐KLF2 on the progression of OSCC. MiR‐32‐5p could enhance cell proliferation, migration, invasion, and EMT of OSCC cells, and the discovery of miR‐32‐5p/KLF2/CXCR4 axis might provide potential therapeutic targets for OSCC.
ASPM facilitates colorectal cancer cells migration and invasion by enhancing β‐catenin expression and nuclear translocation
Authors: Wang Lu , Hu Xiao‐Dan , Li Shou‐Ying , Liang Xu‐Yang , Ren Lin , Lv Sheng‐Xiang
Published: November 2021

Increased abnormal spindle‐like microcephaly (ASPM) expression has been linked to clinical stage and poor prognosis in cancers, but the molecular mechanisms by which ASPM promotes cell metastasis in colorectal cancer (CRC) has not been identified. This study showed that the abilities of cell migration, invasion, and epithelial–mesenchymal transition (EMT) were attenuated in ASPM‐deficient CRC cell lines. Furthermore, we reported that attenuation of ASPM expression inhibited CRC cell metastasis in vivo. Additionally, the expression of ASPM was positively correlated with β‐catenin level in CRC tissues. Mechanistically, ASPM can upregulate β‐catenin transcription by stimulating the β‐catenin promoter and enhancing the nuclear translocation of β‐catenin in CRC cells, which leads to the activation of the Wnt/β‐catenin pathway. Finally, we showed that ASPM effectively induced CRC cell migration and invasion in a β‐catenin‐dependent manner.
Haller's Ansa: An Unrecognized Route of Facial Movement After Skull Base Surgery
Authors: Thielhelm Torin P. , Dinh Christine T. , Sargi Zoukaa , Ivan Michael E. , Ein Liliana
Published: November 2021

A direct communication between the glossopharyngeal and facial nerves known as Haller's ansa exists in a minority of patients. Clinical manifestations of this anastomosis are not commonly observed. We describe post‐operative facial movement with swallowing after facial nerve sacrifice in two patients who underwent surgery for skull base tumors. Patient 1, a 49‐year‐old male, received a transcochlear approach for resection of endolymphatic sac tumor and intratemporal facial nerve sacrifice without nerve reconstruction. Patient 2, a 23‐year‐old female, underwent surgery for left jugular paraganglioma, requiring facial nerve sacrifice and cable graft. Both patients had preoperative facial weakness and intraoperative preservation of the glossopharyngeal nerve. A literature review related to Haller's ansa was performed using PubMed, EMBASE, and Scopus from 1920‐2021. Post‐operatively, both patients demonstrated oral commissure movement with swallowing, suggesting a communication between the glossopharyngeal nerve and the facial nerve (Haller's ansa). Although anatomical references to Haller's ansa exist, there are no reported clinical manifestations of this neural anastomosis. Glossopharyngeal‐facial nerve communications may contribute to facial tone and movement. Pre‐ and post‐operative assessment of facial nerve movement with swallowing may help assess for the presence of Haller's ansa. Better understanding of this neural anastomosis may have implications for facial reanimation surgery. Laryngoscope, 132:1750–1752, 2022