bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractCervical 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

SynopsisTelephysiotherapy 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

AbstractIntroductionAlthough 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.ObjectivesThe primary objective of this project was to determine whether a pharmacist intervention would lead to increased rates of naloxone co‐prescribing among providers.MethodsThis 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.ResultsA 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).ConclusionA 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

AbstractThe 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

AbstractAs 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

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

AbstractBackgroundWith 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.MethodsThe 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.ResultsThe 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).ConclusionsTo 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

AbstractLong 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

AbstractExtensive 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

AbstractBackgroundCancer‐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.MethodsWe 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.ResultsWe 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.ConclusionsHere, 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

AbstractThe 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

AbstractIsolated 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

AbstractPersistent 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.