bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspective on this Article from Early Changes in Gene Expression Induced by Tobacco Smoke: Evidence for the Importance of Estrogen within Lung Tissue
Authors: Meireles Sibele I. , Esteves Gustavo H. , Hirata Roberto , Peri Suraj , Devarajan Karthik , Slifker Michael , Mosier Stacy L. , Peng Jing , Vadhanam Manicka V. , Hurst Harrell E. , Neves E. Jordao , Reis Luiz F. , Gairola C. Gary , Gupta Ramesh C. , Clapper Margie L.
Published: April 2023

Perspective on this Article from Early Changes in Gene Expression Induced by Tobacco Smoke: Evidence for the Importance of Estrogen within Lung Tissue
Perspectives on This Article from Association between Folate Levels and CpG Island Hypermethylation in Normal Colorectal Mucosa
Authors: Wallace Kristin , Grau Maria V. , Levine A. Joan , Shen Lanlan , Hamdan Randala , Chen Xinli , Gui Jiang , Haile Robert W. , Barry Elizabeth L. , Ahnen Dennis , McKeown-Eyssen Gail , Baron John A. , Issa Jean Pierre J.
Published: April 2023

Perspectives on This Article from Association between Folate Levels and CpG Island Hypermethylation in Normal Colorectal Mucosa
Data from Long-term Epigenetic Therapy with Oral Zebularine Has Minimal Side Effects and Prevents Intestinal Tumors in Mice
Authors: Yoo Christine B. , Chuang Jody C. , Byun Hyang-Min , Egger Gerda , Yang Allen S. , Dubeau Louis , Long Tiffany , Laird Peter W. , Marquez Victor E. , Jones Peter A.
Published: April 2023

Abstract
Recent successes in the application of epigenetic drugs for the treatment of myelodysplastic syndrome have raised questions on the safety of long-term administration of DNA methylation inhibitors. We treated preweaned cancer prone ApcMin/+ (Min) mice continuously with the DNA methylation inhibitor zebularine in their drinking water to determine the effects of the drug on normal mouse development as well as cancer prevention. Zebularine caused a tissue-specific reduction in DNA methylation at B1 short interspersed nucleotide elements in the small and large intestines of female Min mice but not in other organs examined after chronic oral treatment. No significant difference in the average weights of mice was observed during the treatment. In addition, analysis of global gene expression of colonic epithelial cells from the females indicated that only 3% to 6% of the genes were affected in their expression. We did not detect toxicity and abnormalities from the histopathologic analysis of liver and intestinal tissues. Lastly, we tested whether prevention of tumorigenesis can be achieved with chronic oral administration of zebularine in Min mice. The average number of polyps in Min females decreased from 58 to 1, whereas the average polyp number remained unaffected in Min males possibly due to differential activity of aldehyde oxidase. Taken together, our results show for the first time that long-term oral administration of zebularine causes a gender-specific abrogation of intestinal tumors while causing a tissue-specific DNA demethylation. Importantly, prolonged treatment of mice with epigenetic drugs resulted in only minor developmental and histologic changes.
Data from Finasteride Does Not Increase the Risk of High-Grade Prostate Cancer: A Bias-Adjusted Modeling Approach
Authors: Redman Mary W. , Tangen Catherine M. , Goodman Phyllis J. , Lucia M. Scott , Coltman Charles A. , Thompson Ian M.
Published: April 2023

Abstract
Finasteride taken for 7 years in the Prostate Cancer Prevention Trial (PCPT) reduced the risk of prostate cancer by 25%, but with an apparent increased risk of high-grade disease. Subsequent analyses found that finasteride biases toward improved prostate cancer detection and accuracy in prostate cancer grading at biopsy. In our first analysis of the present study, we accounted for these biases in estimating the effect of finasteride on the risk of overall and high-grade prostate cancer. This analysis used PCPT data that included 3-month longer collection of endpoints than in the original report with observed prostate cancer rates of 22.9% (4.8% with high grade; placebo) versus 16.6% (5.8% with high grade; finasteride). Based on these updated results, the bias-adjusted prostate cancer rates are estimated to be 21.1% (4.2% high grade; placebo) and 14.7% (4.8% high grade; finasteride), a 30% risk reduction in prostate cancer [relative risk (RR), 0.70; 95% confidence interval (95% CI), 0.64-0.76; P < 0.0001] and a nonsignificant 14% increase in high-grade cancer (RR, 1.14; 95% CI, 0.96-1.35; P = 0.12) with finasteride. We then estimated rates of high-grade prostate cancer based on an analysis that incorporated grading information from radical prostatectomies in 500 subjects diagnosed with cancer. The resulting estimates were high-grade cancer rates of 8.2% (placebo) versus 6.0% (finasteride), a 27% risk reduction (RR, 0.73; 95% CI, 0.56-0.96; P = 0.02) with finasteride. Our third analysis examined the impact of biopsy sensitivity on the relative risk of high-grade prostate cancer and found that differential sensitivity of biopsy between the treatment arms can have a significant impact on risk ratio estimates. These collective results suggest that the observed, unadjusted higher risk of high-grade disease with finasteride seems to have been due to facilitated diagnosis resulting primarily from increased biopsy sensitivity with finasteride. Therefore, men undergoing regular prostate cancer screening or who express an interest in cancer prevention should be informed of the opportunity to take finasteride for preventing prostate cancer.
Data from Oral Epithelium as a Surrogate Tissue for Assessing Smoking-Induced Molecular Alterations in the Lungs
Authors: Bhutani Manisha , Pathak Ashutosh Kumar , Fan You-Hong , Liu Diane D. , Lee J. Jack , Tang Hongli , Kurie Jonathan M. , Morice Rodolfo C. , Kim Edward S. , Hong Waun Ki , Mao Li
Published: April 2023

Abstract
The lungs and oral cavity of smokers are exposed to tobacco carcinogens. We hypothesized that tobacco-induced molecular alterations in the oral epithelium are similar to those in the lungs, and thus the oral epithelium may be used as a surrogate tissue for assessing alterations in the lungs. We used methylation-specific PCR to analyze promoter methylation of the p16 and FHIT genes at baseline and 3 months after intervention in 1,774 oral and bronchial brush specimens from 127 smokers enrolled in a randomized placebo-controlled chemoprevention trial. The association between methylation patterns in oral tissues and bronchial methylation indices (methylated sites / total sites per subject) was analyzed in a blinded fashion. At baseline, promoter methylation in bronchial tissue was present in 23% of samples for p16, 17% for FHIT, and 35% for p16 and FHIT; these percentages were comparable to methylation in oral tissue: 19% (p16), 15% (FHIT), and 31% (p16 and FHIT). Data from both oral and bronchial tissues were available for 125 individuals, in whom the two sites correlated strongly with respect to alterations (P < 0.0001 for both p16 and FHIT). At baseline, the mean bronchial methylation index was far higher in patients with oral tissue methylation (in either of the two genes; 39 patients) than in patients without oral tissue methylation (86 patients): 0.53 ± 0.29 versus 0.27 + 0.26 methylation index (P < 0.0001). Similar correlations occurred at 3 months after intervention. Our results support the potential of oral epithelium as a surrogate tissue for assessing tobacco-induced molecular damage in the lungs and thus have important implications for designing future lung cancer prevention trials and for research into the risk and early detection of lung cancer.
Data from Intravesical Delivery of Rapamycin Suppresses Tumorigenesis in a Mouse Model of Progressive Bladder Cancer
Authors: Seager Catherine M. , Puzio-Kuter Anna M. , Patel Trushar , Jain Shalini , Cordon-Cardo Carlos , Mc Kiernan James , Abate-Shen Cory
Published: April 2023

Abstract
Early-stage bladder cancer occurs as two distinct forms: namely, low-grade superficial disease and high-grade carcinoma in situ (CIS), which is the major precursor of muscle-invasive bladder cancer. Although the low-grade form is readily treatable, few, if any, effective treatments are currently available for preventing progression of nonmuscle-invasive CIS to invasive bladder cancer. Based on our previous findings that the mammalian target of Rapamycin (mTOR) signaling pathway is activated in muscle-invasive bladder cancer, but not superficial disease, we reasoned that suppression of this pathway might block cancer progression. To test this idea, we performed in vivo preclinical studies using a genetically engineered mouse model that we now show recapitulates progression from nonmuscle-invasive CIS to muscle-invasive bladder tumors. We find that delivery of Rapamycin, an mTOR inhibitor, subsequent to the occurrence of CIS effectively prevents progression to invasive bladder cancer. Furthermore, we show that intravesical delivery of Rapamycin directly into the bladder lumen is highly effective for suppressing bladder tumorigenesis. Thus, our findings show the potential therapeutic benefit of inhibiting mTOR signaling for treatment of patients at high risk of developing invasive bladder cancer. More broadly, our findings support a more widespread use of intravesical delivery of therapeutic agents for treatment of high-risk bladder cancer patients, and provide a mouse model for effective preclinical testing of potential novel agents.
Data from The Great Escape: Microbiotal LPS Takes a Toll on the Liver
Authors: Weiss David S.
Published: April 2023

Abstract
The interaction between the intestinal microbiota and host is much more complex than previously appreciated, and we are now learning that it can have an impact on extraintestinal human diseases. In this issue of the journal (beginning on page 1090), Lin and colleagues present important data linking the microbiota, lipopolysaccharide (LPS), and toll-like receptor (TLR)4 with hepatitis in a mouse model. These provocative results and those from other recent studies highlight the microbiota as a potential target for therapeutic intervention in several liver diseases. Cancer Prev Res; 5(9); 1078–80. ©2012 AACR.
Data from Association between Folate Levels and CpG Island Hypermethylation in Normal Colorectal Mucosa
Authors: Wallace Kristin , Grau Maria V. , Levine A. Joan , Shen Lanlan , Hamdan Randala , Chen Xinli , Gui Jiang , Haile Robert W. , Barry Elizabeth L. , Ahnen Dennis , McKeown-Eyssen Gail , Baron John A. , Issa Jean Pierre J.
Published: April 2023

Abstract
Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association of blood folate levels and dietary and lifestyle factors with CpG island (CGI) methylation in normal colorectal mucosa. Subjects were enrolled in a multicenter chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas. We collected 1,000 biopsy specimens from 389 patients, 501 samples from the right colon and 499 from the rectum at the follow-up colonoscopy. We measured DNA methylation of estrogen receptor alpha (ERα) and secreted frizzled related protein-1 (SFRP1), using bisulfite pyrosequencing. We used generalized estimating equations regression analysis to examine the association between methylation and selected variables. For both ERα and SFRP1, percentage methylation was significantly higher in the rectum than in the right colon (P = 0.001). For each 10 years of age, we observed a 1.7% increase in methylation level for ERα and a 2.9% increase for SFRP1 (P < 0.0001). African Americans had a significantly lower level of ERα and SFRP1 methylation than Caucasians and Hispanics. Higher RBC folate levels were associated with higher levels of both ERα (P = 0.03) and SFRP1 methylation (P = 0.01). Our results suggest that CGI methylation in normal colorectal mucosa is related to advancing age, race, rectal location, and RBC folate levels. These data have important implications regarding the safety of supplementary folate administration in healthy adults, given the hypothesis that methylation in normal mucosa may predispose to colorectal neoplasia. Cancer Prev Res; 3(12); 1552–64. ©2010 AACR.
Development of image super-resolution framework
Authors: Shekar Sanvi , Deepthi Kakarla , Rahul D. , K. S. Dhawan , Hegde Vinay V.
Published: April 2023

There are some scenarios where the images taken are of low resolution and it is hard to judge the features from them, resulting in the need for enhancement. Super-resolution is a technique to produce a high-resolution image from a lower-resolution image. The intention here is to develop a system that enhances images of faces and satellite images by integrating these models and providing an interface to access this model. There have been various ways of achieving super-resolution using different techniques. Throughout the years, techniques involving deep learning methods, interpolation techniques, and recursive networks have been explored. We find it promising to use generative adversarial networks (GANs). The system has been deployed through Google Collaborate, Python libraries, and the TensorFlow framework. To assess the developed system, which consists of images, three metrics have been calculated. namely, peak signal-to-noise ratio, mean squared error, and structural similarity index. The model successfully demonstrated the capability of GANs by efficiently generating a high-resolution image from a low-resolution image for the given cases. The model would then be run on a standalone server for free Internet access for users to use super-resolution facial images and satellite images.
Desenvolvimento do sistema nociceptivo e supressor da dor
Authors: Okada Massako , Teixeira Manoel Jacobsen , Tengan Sérgio K. , Moraes Lygia Oliveira de
Published: April 2023

Há várias evidências de que nas fases precoces em desenvolvimento fetal ocorra a deflagração de mecanismos deacarretam a estruturação anatômica e funcional do sistema nervoso sensitivo. Após o nascimento muitas modificações ocorrem durante os primeiros meses de vida extra-uterina. O conhecimento destas condições é necessário para melhorar a compreensão da dor e as atitudes analgésicas.
Foreword
Authors: Zinchenko Yu. P.
Published: April 2023

Foreword. Natsional’nyy psikhologocheskiy zhurnal
Contribution of E.O. Smirnova to the practice of education
Authors: Galiguzova Lyudmila N. , Meshcheryakova Sofia Yu.
Published: April 2023

Background. The relevance of the article is determined by the importance of summarizing and highlighting the many-sided contribution to the practice of education by E.O. Smirnova on the eve of her 75th birthday. Objective. \e aim of the article is to describe the main directions and results of E.O. Smirnova’s e]ort to implement her scientiAc and practical developments achieved by sciences and colleagues in the Laboratory for the Mental Development of Preschoolers at PI RAE and in the Center for Games and Toys of Moscow State University of Psychology and Education in practice. Results. \e theoretical foundations, structure, content and scope of a number of works important for the Aeld of education, addressed to students of pedagogical universities, teachers, psychologists of preschool educational institutions, and parents, are described. \e main works include the textbook “Child Psychology”, the programme for upbringing and development of young children “First Steps”, methodological manuals “Diagnosis of the mental development of a child from birth to 3 years”, “Interpersonal relations of preschoolers: diagnosis, problems, correction”, etc. Popular science publications for parents are presented, including “\e Art of Communication with a Child. From one to six years old”, “Preschooler in the modern world”. \e activity of E.O. Smirnova on training personnel for the education system is described. Conclusion. \e results of E.O Smirnova’s activity on the introduction of scientiAc developments into practice contribute to the provision of high-quality education at the preschool level, which founds a successful educational strategy for the further education of children.
Living with love as the meaning of being in the existential paradigm of relationships
Authors: Utrobina Valeria G.
Published: April 2023

Background. \e article focuses on the notion of love from the standpoint of Christian psychology and anthropology as well as on its impact on the change in existential meaning of life and interpersonal relationships. Such an attributive principle of life as “living with love” is considered in the context of the existential meaning of being, professional activity and interpersonal relationships in line with the concept developed by Professor Elena Olegovna Smirnova. An understanding of the concept of “life with love” is presented and the main properties of Christian love in the existential paradigm of relationships are indicated. Objective. \e main aim of the study was to analyse life and professional work of the famous scientist, Professor Elena Olegovna Smirnova, from the standpoint of Christian love as the meaning of being in the existential paradigm of relationships. Results. It has been shown that love, considered from a Christian position, changes a person as a personality. \is process includes change in the attitude towards other people as well as towards oneself, and also gives a special meaning to life. It is asserted that life with love is life with God in soul, with the joy of life and with the desire to make this World a better place for close people and humanity as a whole. Life with love is an understanding of the meaning of your life and gaining strength of mind for the responsible implementation of your mission, as well as a state of calm happiness, silence in the heart and peace of mind. Conclusion. \e results obtained made it possible to show the psychological representation of the lifestyle and professional creativity of the outstanding scientist E.O. Smirnova in accordance with the attributive principle of Christian love “life with love”. \e study also demonstrates the possibility to ]nd new meanings of life and relationships through Christian Love.
Profile of intellectual abilities and personality traits in adults with high-functioning autism
Authors: Kozunova Galina L. , Novikov Artem Yu. , Chernyshev Boris V.
Published: April 2023

Background. Autism is a pervasive neurodevelopmental disorder caused by disruption of the prenatal brain development. In mild forms of autism, children may camouflage their symptoms, which may cause their mental disorder to stay undiagnosed into adulthood. Studies of personality and intelligence characteristics in adult patients with autism will reduce the difficulties of diagnosing mild forms of this disorder in a population of high-functioning socially adapted individuals. Objective. The study aims to describe the profile of intellectual abilities in adults with high-functioning autism and its relationship with the severity of clinical symptoms and personal traits. Sample. 30 participants with high-functioning autism (9 males and 21 females) aged between 20 and 44 years and 30 neurotypical controls took part in the research. Methods. The subjects underwent a short version of the Wechsler test (WAIS-III) and completed the Carver and White questionnaire “Behavioral Activation and Inhibition Systems”. Patients with autism also completed the Autism Quotient questionnaire designed by Baron and Cohen to assess severity of their symptoms, and their diagnosis was verified by an experienced psychiatrist. We analyzed intergroup differences using analysis of variance, as well as nonparametric correlational analysis between IQ, clinical symptoms, and personal traits. Results. Patients with autism did not differ from the control group in general intelligence, but they showed significantly lower verbal abilities (F(1, 42) = 8.4; p = 0.006). Reduction of verbal abilities in patients with autism directly correlated with severity of their clinical symptoms (R = –0.59; p = 0.001). We also found a decrease in the sensitivity of the behavior approach system in the clinical group (F(1.52) = 4.9; p = 0.03), manifested mostly in a low level of spontaneous fun seeking. In contrast to the neurotypical controls, where a higher sensitivity of the behavior activation system positively correlated with verbal abilities (R = 0.52; p = 0.02), in patients with autism, motivational traits were not associated with any intellectual abilities. Conclusion. The results demonstrate that adult persons with autism spectrum disorders have a relative reduction in verbal fluency. It can be assumed that this profile of intellectual abilities may be a long-term result of a delay in speech development at an early age.
miR-34a-5p as molecular hub of pathomechanisms in Huntington’s disease
Authors: Hart Martin , Diener Caroline , Lunkes Laetitia , Rheinheimer Stefanie , Krammes Lena , Keller Andreas , Meese Eckart
Published: April 2023

Background

Although a pivotal role of microRNA (miRNA, miR) in the pathogenesis of Huntington’s disease (HD) is increasingly recognized, the molecular functions of miRNAs in the pathomechanisms of HD await further elucidation. One of the miRNAs that have been associated with HD is miR-34a-5p, which was deregulated in the mouse R6/2 model and in human HD brain tissues.

Methods

The aim of our study was to demonstrate interactions between miR-34a-5p and HD associated genes. By computational means we predicted 12 801 potential target genes of miR-34a-5p. An in-silico pathway analysis revealed 22 potential miR-34a-5p target genes in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway “Huntington’s disease”.

Results

Using our high-throughput miRNA interaction reporter assay (HiTmIR) we identified NDUFA9, TAF4B, NRF1, POLR2J2, DNALI1, HIP1, TGM2 and POLR2G as direct miR-34a-5p target genes. Direct binding of miR-34a-5p to target sites in the 3’UTRs of TAF4B, NDUFA9, HIP1 and NRF1 was verified by a mutagenesis HiTmIR assay and by determining endogenous protein levels for HIP1 and NDUFA9. STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) analysis identified protein–protein interaction networks associated with HD like “Glutamine Receptor Signaling Pathway” and “Calcium Ion Transmembrane Import Into Cytosol”.

Conclusion

Our study demonstrates multiple interactions between miR-34a-5p and HD associated target genes and thereby lays the ground for future therapeutic interventions using this miRNA.
An optimized workflow for MS-based quantitative proteomics of challenging clinical bronchoalveolar lavage fluid (BALF) samples
Authors: Weise Danielle O. , Kruk Monica E. , Higgins LeeAnn , Markowski Todd W. , Jagtap Pratik D. , Mehta Subina , Mickelson Alan , Parker Laurie L. , Wendt Christine H. , Griffin Timothy J.
Published: April 2023

Background

Clinical bronchoalveolar lavage fluid (BALF) samples are rich in biomolecules, including proteins, and useful for molecular studies of lung health and disease. However, mass spectrometry (MS)-based proteomic analysis of BALF is challenged by the dynamic range of protein abundance, and potential for interfering contaminants. A robust, MS-based proteomics compatible sample preparation workflow for BALF samples, including those of small and large volume, would be useful for many researchers.

Results

We have developed a workflow that combines high abundance protein depletion, protein trapping, clean-up, and in-situ tryptic digestion, that is compatible with either qualitative or quantitative MS-based proteomic analysis. The workflow includes a value-added collection of endogenous peptides for peptidomic analysis of BALF samples, if desired, as well as amenability to offline semi-preparative or microscale fractionation of complex peptide mixtures prior to LC–MS/MS analysis, for increased depth of analysis. We demonstrate the effectiveness of this workflow on BALF samples collected from COPD patients, including for smaller sample volumes of 1–5 mL that are commonly available from the clinic. We also demonstrate the repeatability of the workflow as an indicator of its utility for quantitative proteomic studies.

Conclusions

Overall, our described workflow consistently provided high quality proteins and tryptic peptides for MS analysis. It should enable researchers to apply MS-based proteomics to a wide-variety of studies focused on BALF clinical specimens.
High SARS-CoV-2 seroprevalence among street adolescents in Lomé, Togo, 2021
Authors: Sadio Arnold Junior , Ferré Valentine Marie , Konu Rodion Yao , Dagnra Anoumou Claver , Descamps Diane , Ekouevi Didier Koumavi , Charpentier Charlotte
Published: April 2023

Background

There is almost no data on the circulation of SARS-CoV-2 among street adolescents. We conducted a study to document the immunization status of street adolescents in Togo against different variants of SARS-CoV-2.

Methods

A cross-sectional study was carried out in 2021 in Lomé, the city with the highest number of COVID 19 cases in Togo (60%). Adolescents aged 13- and 19 years old living on the street were eligible for inclusion. A standardized questionnaire was administered face-to-face to adolescents. A sample of blood was taken and aliquots of plasma were transported to the virology laboratory of the Hôpital Bichat-Claude Bernard (Paris, France). SARS-CoV-2 anti-S and anti-N IgG were measured using chemiluminescent microparticle immunoassay. A quantitative miniaturized and parallel-arranged ELISA assay was used to detect IgG antibodies specifically directed against the different SARS-CoV-2 Variants of Concern (VOC).

Results

A total of 299 street adolescents (5.2% female), median age 15 years, interquartile range (14-17 years), were included in this study. The prevalence of SARS-CoV-2 infection was 63.5% (95%CI: 57.8–69.0). Specific-IgG against the ancestral Wuhan strain was developed by 92.0% of subjects. The proportion of patients being immunized against each VOC was 86.8%, 51.1%, 56.3%, 60.0, and 30.5% for the Alpha, Beta, Gamma, Delta, and Omicron VOCs, respectively.

Conclusion

This study showed a very high prevalence with approximately 2/3 of Togolese street adolescents having antibodies to SARS-CoV-2 due to a previous infection. These results confirm an under-reporting of COVID-19 cases in Togo, questioning the hypothesis of low virus circulation in Togo and even in Africa.
Clinical significance of nonerythrocytic spectrin Beta 1 (SPTBN1) in human kidney renal clear cell carcinoma and uveal melanoma: a study based on Pan-Cancer Analysis
Authors: Tang Wenting , Shao Qiong , He Zhanwen , Zhang Xu , Li Xiaojuan , Wu Ruohao
Published: April 2023

Background

Nonerythrocytic spectrin beta 1 (SPTBN1) is an important cytoskeletal protein that involves in normal cell growth and development via regulating TGFβ/Smad signaling pathway, and is aberrantly expressed in various cancer types. But, the exact role of SPTBN1 in pan-cancer is still unclear. This report aimed to display expression patterns and prognostic landscapes of SPTBN1 in human cancers, and further assess its prognostic/therapeutic value and immunological role in kidney renal carcinoma (KIRC) and uveal melanoma (UVM).

Methods

We firstly analyzed expression patterns and prognostic landscapes of SPTBN1 in human cancers using various databases and web-based tools. The relationships between SPTBN1 expression and survival/tumor immunity in KIRC and UVM were further investigated via R packages and TIMER 2.0 platform. The therapeutic roles of SPTBN1 in KIRC and UVM were also explored via R software. Following this, the prognostic value and cancer immunological role of SPTBN1 in KIRC and UVM were validated in our cancer patients and GEO database.

Results

Overall, cancer tissue had a lower expression level of SPTBN1 frequently in pan-cancer, compared with those in adjacent nontumor one. SPTBN1 expression often showed a different effect on survival in pan-cancer; upregulation of SPTBN1 was protective to the survival of KIRC individuals, which was contrary from what was found in UVM patients. In KIRC, there were significant negative associations between SPTBN1 expression and pro-tumor immune cell infiltration, including Treg cell, Th2 cell, monocyte and M2-macrophage, and expression of immune modulator genes, such as tumor necrosis factor superfamily member 9 (TNFSF9); while, in UVM, these correlations exhibited opposite patterns. The following survival and expression correlation analysis in our cancer cohorts and GEO database confirmed these previous findings. Moreover, we also found that SPTBN1 was potentially involved in the resistance of immunotherapy in KIRC, and the enhance of anti-cancer targeted treatment in UVM.

Conclusions

The current study presented compelling evidence that SPTBN1 might be a novel prognostic and therapy-related biomarker in KIRC and UVM, shedding new light on anti-cancer strategy.
A meta-analysis of internet-based cognitive behavioral therapy for military and veteran populations
Authors: Liu Jenny JW , Ein Natalie , Forchuk Callista , Wanklyn Sonya G. , Ragu Suriya , Saroya Samdarsh , Nazarov Anthony , Richardson J. Don
Published: April 2023

Background

Military and veteran populations are unique in their trauma exposures, rates of mental illness and comorbidities, and response to treatments. While reviews have suggested that internet-based Cognitive Behavioral Therapy (iCBT) can be useful for treating mental health conditions, the extent to which they may be appropriate for military and veteran populations remain unclear. The goals of the current meta-analysis are to: (1) substantiate the effects of iCBT for military and veteran populations, (2) evaluate its effectiveness compared to control conditions, and (3) examine potential factors that may influence their effectiveness.

Methods

This review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting and Cochrane review guidelines. The literature search was conducted using PsycInfo, Medline, Embase, and Proquest Dissertation & Theses on June 4, 2021 with no date restriction. Inclusion criteria included studies that: (1) were restricted to adult military or veteran populations, (2) incorporated iCBT as the primary treatment, and (3) evaluated mental health outcomes. Exclusion criteria included: (1) literature reviews, (2) qualitative studies, (3) study protocols, (4) studies that did not include a clinical/analogue population, and (5) studies with no measure of change on outcome variables. Two independent screeners reviewed studies for eligibility. Data was pooled and analyzed using random-effects and mixed-effects models. Study data information were extracted as the main outcomes, including study condition, sample size, and pre- and post-treatment means, standard deviations for all assessed outcomes, and target outcome. Predictor information were also extracted, and included demographics information, the types of outcomes measured, concurrent treatment, dropout rate, format, length, and delivery of intervention.

Results

A total of 20 studies and 91 samples of data were included in the meta-analysis. The pooled effect size showed a small but meaningful effect for iCBT, g = 0.54, SE = 0.04, 95% CI (0.45, 0.62), Z = 12.32, p < .001. These effects were heterogenous across samples, (I2 = 87.96), Q(90) = 747.62, p < .001. Predictor analyses found length of intervention and concurrent treatment to influence study variance within sampled studies, p < .05. Evaluation of iCBT on primary outcomes indicated a small but meaningful effect for PTSD and depression, while effects of iCBT on secondary outcomes found similar results with depression, p < .001.

Conclusions

Findings from the meta-analysis lend support for the use of iCBT with military and veteran populations. Conditions under which iCBT may be optimized are discussed.
Speech disorders in patients with Tongue squamous cell carcinoma: A longitudinal observational study based on a questionnaire and acoustic analysis
Authors: Guo Kaixin , Xiao Yudong , Deng Wei , Zhao Guiyi , Zhang Jie , Liang Yujie , Yang Le , Liao Guiqing
Published: April 2023

Background

Speech disorders are common dysfunctions in patients with tongue squamous cell carcinoma (TSCC) that can diminish their quality of life. There are few studies with multidimensional and longitudinal assessments of speech function in TSCC patients.

Methods

This longitudinal observational study was conducted at the Hospital of Stomatology, Sun Yat-sen University, China, from January 2018 to March 2021. A cohort of 92 patients (53 males, age range: 24–77 years) diagnosed with TSCC participated in this study. Speech function was assessed from preoperatively to one year postoperatively using the Speech Handicap Index questionnaire and acoustic parameters. The risk factors for postoperative speech disorder were analyzed by a linear mixed-effects model. A t test or Mann‒Whitney U test was applied to analyze the differences in acoustic parameters under the influence of risk factors to determine the pathophysiological mechanisms of speech disorders in patients with TSCC.

Results

The incidence of preoperative speech disorders was 58.7%, which increased up to 91.4% after surgery. Higher T stage (P＜0.001) and larger range of tongue resection (P = 0.002) were risk factors for postoperative speech disorders. Among the acoustic parameters, F2/i/decreased remarkably with higher T stage (P = 0.021) and larger range of tongue resection (P = 0.009), indicating restricted tongue movement in the anterior-posterior direction. The acoustic parameters analysis during the follow-up period showed that F1 and F2 were not significantly different of the patients with subtotal or total glossectomy over time.

Conclusions

Speech disorders in TSCC patients is common and persistent. Less residual tongue volume led to worse speech-related QoL, indicating that surgically restoring the length of the tongue and strengthening tongue extension postoperatively may be important.
The results of clinician-focused implementation strategies on uptake and outcomes of Measurement-Based Care (MBC) in general mental health care
Authors: van Sonsbeek Maartje A. M. S. , Hutschemaekers Giel J. M. , Veerman Jan W. , Vermulst Ad , Tiemens Bea G.
Published: April 2023

Background

Measurement-Based Care (MBC) is the routine administration of measures, clinicians’ review of the feedback and discussion of the feedback with their clients, and collaborative evaluation of the treatment plan. Although MBC is a promising way to improve outcomes in clinical practice, the implementation of MBC faces many barriers, and its uptake by clinicians is low. The purpose of this study was to investigate whether implementation strategies that were developed with clinicians and aimed at clinicians had an effect on (a) clinicians’ uptake of MBC and (b) clients’ outcomes of MBC.

Methods

We used an effectiveness-implementation hybrid design based on Grol and Wensing’s implementation framework to assess the impact of clinician-focused implementation strategies on both clinicians’ uptake of MBC and outcomes obtained with MBC for clients in general mental health care. We hereby focused on the first and second parts of MBC, i.e., the administration of measures and use of feedback. Primary outcome measures were questionnaire completion rate and discussion of the feedback with clients. Secondary outcomes were treatment outcome, treatment length, and satisfaction with treatment.

Results

There was a significant effect of the MBC implementation strategies on questionnaire completion rate (one part of clinicians’ uptake), but no significant effect on the amount of discussion of the feedback (the other part of clinicians’ uptake). Neither was there a significant effect on clients’ outcomes (treatment outcome, treatment length, and satisfaction with treatment). Due to various study limitations, the results should be viewed as exploratory.

Conclusions

Establishing and sustaining MBC in real-world general mental health care is complex. This study helps to disentangle the effects of MBC implementation strategies on differential clinician uptake, but the effects of MBC implementation strategies on client outcomes need further examination.
Safety, pharmacokinetics, and pharmacodynamics of SHR7280, an oral gonadotropin-releasing hormone receptor antagonist, in healthy men: a randomized, double-blind, placebo-controlled phase 1 study
Authors: Li Xin , Sun Feifei , Zhang Xiaolei , Lin Pingping , Shen Kai , Shen Yu , Ma Lingyu , Cao Yu , Wang Chenjing
Published: April 2023

Background

Gonadotropin-releasing hormone (GnRH) antagonists are a promising therapeutic approach for treating hormone-dependent prostate cancer. Currently, the mainstream GnRH antagonists are polypeptide agents administered through subcutaneous injection. In this study, we evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of SHR7280, an oral small molecule GnRH antagonist, in healthy men.

Methods

This phase 1 trial was a randomized, double-blind, placebo-controlled, and dose-ascending study. Eligible healthy men were randomized in a 4:1 ratio to receive either oral SHR7280 tablets or placebo twice daily (BID) for 14 consecutive days. The SHR7280 dose was initiated at 100 mg BID and then sequentially increased to 200, 350, 500, 600, 800, and 1000 mg BID. Safety, PK, and PD parameters were assessed.

Results

A total of 70 subjects were enrolled and received the assigned drug, including 56 with SHR7280 and 14 with placebo. SHR7280 was well-tolerated. The incidence of adverse events (AEs, 76.8% vs 85.7%) and treatment-related AEs (75.0% vs 85.7%), as well as the severity of AEs (moderate AEs, 1.8% vs 7.1%) were similar between the SHR7280 group and placebo group. SHR7280 was rapidly absorbed in a dose-dependent manner, with a median Tmax of each dose group ranging from 0.8 to 1.0 h on day 14 and a mean t1/2 ranging from 2.8 to 3.4 h. The PD results demonstrated that SHR7280 exhibited a rapid and dose-proportional suppression of hormones, including LH, FSH, and testosterone, with maximum suppression achieved at doses of 800 and 1000 mg BID.

Conclusions

SHR7280 showed an acceptable safety profile, as well as favorable PK and PD profiles within a dose range of 100 to 1000 mg BID. This study proposes a rationale for further investigation of SHR7280 as a potential androgen deprivation therapy.

Trial registration

Clinical trials.gov NCT04554043; registered September 18, 2020.
Exploring the feasibility of establishing a core set of sexual, reproductive, maternal, newborn, child, and adolescent health indicators in humanitarian settings: results from a multi-methods assessment in Jordan
Authors: Hammad Majd , Foster Angel M. , Aissaoui Anya , Clark Emily , Elamurugan Kaeshan , Rajendra Kanya Lakshmi , El Mowafi Ieman Mona , Kobeissi Loulou
Published: April 2023

Background

Reliable and rigorously collected sexual, reproductive, maternal, newborn, child, and adolescent health (SRMNCAH) data in humanitarian settings is often sparse and variable in quality across different humanitarian settings. To address this gap in data quality, the World Health Organization (WHO) developed a core set of indicators for monitoring and evaluating SRMNCAH services and outcomes in humanitarian settings, and assessed their feasibility in the field in Jordan, in addition to three other countries; with the goal of aggregating information from global consultations and field-level assessments to reach consensus on a set of core SRMNCAH indicators for services and outcome evaluation in humanitarian settings among WHO global partners.

Methods

The feasibility assessment in Jordan focused on the following constructs: relevance/usefulness, feasibility of measurement, systems and resources, and ethical issues. The multi-methods assessment included five components; a desk review, key informant interviews, focus group discussions, facility assessments, and observational sessions.

Results

Findings suggest that there is widespread support among regional, national, as well as global stakeholders for developing a core list of SRMNCAH indicators for monitoring and evaluation of services and outcomes in humanitarian settings in Jordan. There are numerous resources and data collection systems that could be leveraged, built upon, and improved to ensure the feasibility of collecting this proposed set of indicators. However, the data collection load requested from donors, the national government, international and UN agencies, coordination/cluster systems must be better harmonized, standardized, and less burdensome.

Conclusions

Despite stakeholder support in developing a core set of indicators, this would only be useful if it has the buy-in from the international community. Greater harmonization and coordination, alongside increased resource allocation, would improve data collection efforts and allow stakeholders to meet indicators’ reporting requirements.
Identifying and mapping individual medicinal plant Lamiophlomis rotata at high elevations by using unmanned aerial vehicles and deep learning
Authors: Ding Rong , Luo Jiawei , Wang Chenghui , Yu Lianhui , Yang Jiangkai , Wang Meng , Zhong Shihong , Gu Rui
Published: April 2023

Background

The identification and enumeration of medicinal plants at high elevations is an important part of accurate yield calculations. However, the current assessment of medicinal plant reserves continues to rely on field sampling surveys, which are cumbersome and time-consuming. Recently, unmanned aerial vehicle (UAV) remote sensing and deep learning (DL) have provided ultrahigh-resolution imagery and high-accuracy object recognition techniques, respectively, providing an excellent opportunity to improve the current manual surveying of plants. However, accurate segmentation of individual plants from drone images remains a significant challenge due to the large variation in size, geometry, and distribution of medicinal plants.

Results

In this study, we proposed a new pipeline for wild medicinal plant detection and yield assessment based on UAV and DL that was specifically designed for detecting wild medicinal plants in an orthomosaic. We used a drone to collect panoramic images of Lamioplomis rotata Kudo (LR) in high-altitude areas. Then, we annotated and cropped these images into equally sized sub-images and used a DL model Mask R-CNN for object detection and segmentation of LR. Finally, on the basis of the segmentation results, we accurately counted the number and yield of LRs. The results showed that the Mask R-CNN model based on the ResNet-101 backbone network was superior to ResNet-50 in all evaluation indicators. The average identification precision of LR by Mask R-CNN based on the ResNet-101 backbone network was 89.34%, while that of ResNet-50 was 88.32%. The cross-validation results showed that the average accuracy of ResNet-101 was 78.73%, while that of ResNet-50 was 71.25%. According to the orthomosaic, the average number and yield of LR in the two sample sites were 19,376 plants and 57.93 kg and 19,129 plants and 73.5 kg respectively.

Conclusions

The combination of DL and UAV remote sensing reveals significant promise in medicinal plant detection, counting, and yield prediction, which will benefit the monitoring of their populations for conservation assessment and management, among other applications.
Health service engagement, side effects and concerns among men with anabolic-androgenic steroid use: a cross-sectional Norwegian study
Authors: Henriksen Hans Christian Bordado , Havnes Ingrid Amalia , Jørstad Marie Lindvik , Bjørnebekk Astrid
Published: April 2023

Background

Recreational use of anabolic-androgenic steroids (AAS) is a public health concern world-wide associated with a range of physical and psychological side effects. Still, people who use AAS tend to be reluctant to seek treatment. This study aims to explore use characteristics, treatment-seeking behaviour, side effects and associated health concerns among men with AAS use.

Methods

The study includes cross-sectional self-report data from 90 men with a current or previous use of AAS exceeding 12 months, where 41 (45.6%) had sought treatment at least once during their lifetime, and 49 (54.4%) had not. Health service engagement was examined with descriptive statistics on reasons for contacting health services, transparency about AAS use, satisfaction with health services and reasons for not seeking treatment. Furthermore, experienced side effects and health concerns were compared between the treatment seeking and the non-treatment seeking group, using two-sample t-tests and Chi2 or Fisher exact tests for numerical and categorical variables, respectively.

Results

All 90 AAS-using men reported side effects from AAS use. Treatment seekers were significantly younger, experienced more side effects including gynecomastia, excessive sweating, fatigue, depression and anxiety, and expressed more concern for testosterone deficiency. Preventive health check-up was the most common reason for seeking treatment (n = 22, 53.7%), and 38 men (93%) were transparent about AAS use during consultations with health professionals. The main reported reasons for not seeking healthcare services were that the experienced side effects were not considered to be of treatment demanding nature (n = 39, 79.6%) and the belief that healthcare providers had scarce knowledge about AAS use and its health impacts (n = 12, 24.5%).

Conclusions

Reluctance to seek treatment among people who use AAS, despite having associated side effects and health concerns, may contribute to continued health risks. It is important to fill the knowledge gap on how to reach and treat this new patient group, and policy makers and treatment providers need to be educated on how to meet their treatment needs.
Significantly reducing the presurgical preparation time for anterior pelvic fracture surgery by faster creating patient-specific curved plates
Authors: Xu Sendren Sheng-Dong , Yeh Tsu-Te , Chen Jia-En , Li Yuan-Ta
Published: April 2023

Background

To shorten the preoperative preparation time, reconstruction plates were designed using the computed tomography (CT)-based three-dimensional (3D) medical imaging surgical planning software OOOPDS. In addition, 3D printing was used to generate curved plates for anterior pelvic fracture surgeries.

Methods

This study analyzed two groups with the same 21 patients who underwent surgery for traumatic anterior pelvic ring fractures. In Group 1, the direct reconstruction plates were preoperatively contoured according to the anatomical 3D-printed pelvic model. In Group 2, the fixation plates were contoured according to the 3D printed plate templates, which were created based on the simulated plate templates by the OOOPDS software. The processing time, including the 3D printing time for the pelvic models in Group 1, the 3D printing time for the fixation plate templates in Group 2, and the pre-contouring time for the plates in both groups, was recorded.

Results

The mean time of pre-contouring for the curved reconstruction plates in Group 2 was significantly less than in Group 1 (−55 min; P < 0.01). The mean time of 3D printing for the 3D plate template model in Group 2 was significantly less than that for the 3D pelvic model in Group 1 (−869 min; P < 0.01). Experimental results showed that the printing time for the plate pre-contouring and the 3D plate templates could be effectively reduced by approximately 93% and 90%, respectively.

Conclusion

This method can shorten the preoperative preparation time significantly.