bluuebunny/crossref_metadata_2025 huggingface dataset:
What does the public know about technological solutions for achieving carbon neutrality? Citizens' knowledge of energy transition and the role of media
Authors: Arlt Dorothee , Schumann Christina , Wolling Jens
Published: August 2023

The present study explores the relation between media use and knowledge in the context of the energy transition. To identify relevant knowledge categories, we relied on the expertise of an interdisciplinary research team. Based on this expertise, we identified awareness-knowledge of changes in the energy system and principles-knowledge of hydrogen as important knowledge categories. With data obtained from a nationwide online survey of the German-speaking population (n = 2,025) conducted in August 2021, we examined the level of knowledge concerning both categories in the German population. Furthermore, we studied its associations with exposure to journalistic media and direct communication from non-media actors (e.g., scientists). Our results revealed a considerable lack of knowledge for both categories. Considering the media variables, we found only weak, and in some cases even negative, relations with the use of journalistic media or other actors that spread information online. However, we found comparably strong associations between both knowledge categories and the control variables of sex, education, and personal interest. We use these results to open up a general discussion of the role of the media in knowledge acquisition processes.
Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome
Authors: Shah Mohd Zahoor ul haq , Shrivastva Vinoy kumar , Mir Manzoor Ahmad , Sheikh Wajid Mohammad , Ganie Mohd Ashraf , Rather Gulzar Ahmed , Shafi Majid , Bashir Showkeen Muzamil , Ansari Mohammad Azam , Al-Jafary Meneerah A. , Al-Qahtani Mohammad H. , Homeida Abdalelgadir Musa , Al-Suhaimi Ebtesam A.
Published: August 2023

Introduction

Polycystic Ovary syndrome (PCOS) affects the health of many women around the world. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis.

Methods

Eighteen mature parkes strain mice (4-5 weeks old) weighing 18–21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kg bw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days.

Results

In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice.

Discussion

Quercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn’t act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.
New therapeutic directions in type II diabetes and its complications: mitochondrial dynamics
Authors: Wang Shengnan , Zhao Haiyang , Lin Suxian , Lv Yang , Lin Yue , Liu Yinai , Peng Renyi , Jin Huanzhi
Published: August 2023

As important organelles of energetic and metabolism, changes in the dynamic state of mitochondria affect the homeostasis of cellular metabolism. Mitochondrial dynamics include mitochondrial fusion and mitochondrial fission. The former is coordinated by mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy 1 (Opa1), and the latter is mediated by dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1) and mitochondrial fission factor (MFF). Mitochondrial fusion and fission are generally in dynamic balance and this balance is important to preserve the proper mitochondrial morphology, function and distribution. Diabetic conditions lead to disturbances in mitochondrial dynamics, which in return causes a series of abnormalities in metabolism, including decreased bioenergy production, excessive production of reactive oxygen species (ROS), defective mitophagy and apoptosis, which are ultimately closely linked to multiple chronic complications of diabetes. Multiple researches have shown that the incidence of diabetic complications is connected with increased mitochondrial fission, for example, there is an excessive mitochondrial fission and impaired mitochondrial fusion in diabetic cardiomyocytes, and that the development of cardiac dysfunction induced by diabetes can be attenuated by inhibiting mitochondrial fission. Therefore, targeting the restoration of mitochondrial dynamics would be a promising therapeutic target within type II diabetes (T2D) and its complications. The molecular approaches to mitochondrial dynamics, their impairment in the context of T2D and its complications, and pharmacological approaches targeting mitochondrial dynamics are discussed in this review and promise benefits for the therapy of T2D and its comorbidities.
Gene-environment interactions and the effect on obesity risk in low and middle-income countries: a scoping review
Authors: Pledger Sophia L. , Ahmadizar Fariba
Published: August 2023

Background

Obesity represents a major and preventable global health challenge as a complex disease and a modifiable risk factor for developing other non-communicable diseases. In recent years, obesity prevalence has risen more rapidly in low- and middle-income countries (LMICs) compared to high-income countries (HICs). Obesity traits are shown to be modulated by an interplay of genetic and environmental factors such as unhealthy diet and physical inactivity in studies from HICs focused on populations of European descent; however, genetic heterogeneity and environmental differences prevent the generalisation of study results to LMICs. Primary research investigating gene-environment interactions (GxE) on obesity in LMICs is limited but expanding. Synthesis of current research would provide an overview of the interactions between genetic variants and environmental factors that underlie the obesity epidemic and identify knowledge gaps for future studies.

Methods

Three databases were searched systematically using a combination of keywords such as “genes”, “obesity”, “LMIC”, “diet”, and “physical activity” to find all relevant observational studies published before November 2022.

Results

Eighteen of the 1,373 articles met the inclusion criteria, of which one was a genome-wide association study (GWAS), thirteen used a candidate gene approach, and five were assigned as genetic risk score studies. Statistically significant findings were reported for 12 individual SNPs; however, most studies were small-scale and without replication.

Conclusion

Although the results suggest significant GxE interactions on obesity in LMICs, updated robust statistical techniques with more precise and standardised exposure and outcome measurements are necessary for translatable results. Future research should focus on improved quality replication efforts, emphasising large-scale and long-term longitudinal study designs using multi-ethnic GWAS.
The clinical value of progestin-primed ovarian stimulation protocol for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis
Authors: Lin Guangyao , Zhong Xiufang , Li Shengnan , Liu Xiyu , Xu Lianwei
Published: August 2023

Background

To determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished ovarian reserve (DOR) than clomiphene citrate (CC)/letrozole (LE) plus gonadotropin in IVF or ICSI treatment.

Methods

Nine databases were searched until May 24, 2023, to identify relevant studies. Forest plots were used to present the results of this meta-analysis. Begg’s and Egger’s tests were applied to estimate publication bias. Subgroup and sensitivity analysis were performed to check the potential sources of heterogeneity and verify the robustness of the pooled results, respectively.

Results

A total of 14 studies with 4182 participants were included for meta-analysis. There was evidence of a statistically notable increase in clinical pregnancy rate (OR = 1.39, 95%CI [1.01, 1.91], p = 0.05), optimal embryos rate (OR = 1.50, 95%CI [1.20, 1.88], p = 0.0004), and cumulative pregnancy rate (OR = 1.73, 95%CI [1.14, 2.60], p = 0.009), the duration and the amount of gonadotropin required (MD = 1.56, 95%CI [0.47, 2.66], p = 0.005; SMD = 1.51, 95%CI [0.90, 2.12], p < 0.00001), along with decrease cycle cancellation rate (OR = 0.78, 95%CI [0.64, 0.95], p = 0.02), luteinizing hormone (LH) level on the day of hCG (SMD = -0.81, 95%CI [-1.10, -0.53], p < 0.00001), and premature LH surge rate (OR = 0.10, 95%CI [0.07, 0.15], p < 0.00001) when PPOS was used. No evidence for publication bias within results was revealed.

Conclusions

Based on evidence-based results, PPOS protocol seems to improve IVF/ICSI outcomes for women with DOR. More research with larger sample sizes and rigorous designs are required to further explore the value of PPOS among women diagnosed with DOR.

Systematic review registration

www.crd.york.ac.uk, identifier CRD42023430202.
Effect of insulin resistance on gonadotropin and bone mineral density in nondiabetic postmenopausal women
Authors: Ye Shujin , Shi Lan , Zhang Zhifen
Published: August 2023

Objective

The effects of insulin resistance (IR) on bone mineral density (BMD) are unclear. This investigation aimed to assess the impact of IR and hyperinsulinemia on bone health. Determine whether IR mediates the link between follicle-stimulating hormone (FSH) and bone mass in nondiabetic postmenopausal women.

Design

Retrospective cross-sectional study.

Setting

Health checkup center of Hangzhou Women’s Hospital.

Methods

This study comprised 437 nondiabetic postmenopausal women. BMD was evaluated using dual-energy X-rays. Fasting sera were analyzed for insulin and glucose levels, and indicators related to IR were determined. By pathway analysis, we examined the indirect effects of FSH on BMD via the mediators Homeostatic Model Assessment for insulin resistance (HOMA-IR) and fasting insulin (FINS) after correction for confounding factors.

Result

After adjusting for age and body mass index (BMI) in linear regression, HOMA-IR and FINS were linked with FSH (P<0.05). IR was stronger among women in the normal BMD group than those in the osteoporosis or osteopenia group. In unadjusted models, BMD was greater in those with higher HOMA-IR and FINS (β=0.027, P=0.006 and β=0.033, P=0.003, respectively). After correcting for BMI and other possible variables, these associations remained. In addition, path models for FSH demonstrated a negative association with BMD by HOMA-IR (95% confidence interval [CI]: -0.0174 to -0.0014) and FINS (95% CI: -0.0188 to -0.002).

Conclusion

Greater IR was associated with increased BMD in nondiabetic postmenopausal women, regardless of BMI and other variables. HOMA-IR or FINS could play a novel mediating role in FSH-induced BMD suppression.
Population genomic analyses of protected incense trees Aquilaria sinensis reveal the existence of genetically distinct subpopulations
Authors: Law Sean Tsz Sum , Nong Wenyan , Yip Ho Yin , Liu Eric Ka Yip , Ng Terence Pun Tung , Tsang Ryan Ho Leung , Xia Nianhe , Shaw Pang-Chui , Lam Hon Ming , Lau David Tai Wai , Hui Jerome Ho Lam
Published: August 2023

The incense tree Aquilaria sinensis (Thymelaeaceae) can produce agarwood with commercial values and is now under threat from illegal exploitation in Hong Kong, impairing the local population and biodiversity. Together with other species of Aquilaria, it is listed in the CITES Appendix II, which strictly regulates its international trade. To understand the population structure of A. sinensis and to make relevant conservation measures, we have sequenced 346 individuals collected in Hong Kong and southern mainland China. Population genomic analyses including principal component analysis, neighbor-joining tree construction, ADMIXTURE, and hierarchical pairwise-FST analyses suggested that genetically distinct populations are contained in certain areas. Genomic scan analyses further detected single-nucleotide polymorphism (SNP) outliers related to plant defense, including the CYP71BE gene cluster. In addition to the population analyses, we have developed a modified hexadecyltrimethyl-ammonium bromide (CTAB) DNA extraction protocol for obtaining DNA from agarwood samples in this study, and resequencing of DNA extracted from two agarwood samples using this method allows us to successfully map to the sample corresponding localities in the phylogenetic tree. To sum up, this study suggested that there is a genetically distinct subpopulation of incense tree in Hong Kong that would require special conservation measures and established a foundation for future conservation measures.
Invertebrate communities of Bay of Fundy salt marsh pools: comparison of a natural and recovering marsh
Authors: Noel Paula E. , Sharma Bidhya , Chmura Gail L.
Published: August 2023

Disturbed salt marshes may recover with little additional management once tidal inundation is restored. We assessed the success of such recovery by comparing the invertebrate biota of Bay of Fundy salt marsh pools in a reference site at Dipper Harbour to that of Saints Rest marsh that had been drained for over a century and to which tidal flooding had been returned ~50 years prior to our study. The sediments and vegetation of salt marsh pools were sampled seasonally throughout one year. Average biomass of pool invertebrates ranged from 1.8 to 4.0 g dry wt m−2, depending on the amount of vegetation cover in the pools. The most abundant organisms of the pools were the gastropod Ecrobia truncata (=Hydrobia tottentei), Tubificidae (=Naididae) oligochaetes, and Chironomidae (=Chironomini). We compared overall abundance and biomass of the invertebrates in the pool communities, assessing the month of sampling, pool elevation, and source marsh as explanatory variables. Our analyses revealed that marsh origin of pools seldom explained a significant amount of variance, and when it did, the proportion of variance explained was usually lower than elevation of pools and month of sampling. Diversity of invertebrates found in all pools was higher at the recovering site with species richness >40% higher than in the reference site. We conclude that after an estimated 50 years since dyke failure and return of tidal flooding to Saints Rest marsh, that the ecosystem function represented by pools and their fauna has recovered.
Identification of SNPs in MITF associated with beak color of duck
Authors: Pan Rui , Hua Tian , Guo Qixin , Bai Hao , Jiang Yong , Wang Zhixiu , Bi Yulin , Chen Guohong , Wu Xinsheng , Chang Guobin
Published: August 2023

Introduction: Beak color—a pigment-related trait—is an important feature of duck breeds. Recently, little research has addressed genetic mechanism of the beak colors in poultry, whereas the process and the regulation factors of melanin deposition have been well described.

Methods: To investigate the genetic mechanism of beak colors, we conducted an integrated analysis of genomic selection signatures to identify a candidate site associated with beak color. For this, we used black-billed (Yiyang I meat duck synthetic line H1, H2, H3&HF) and yellow-billed ducks (Cherry Valley ducks and white feather Putian black duck). Quantitative real-time PCR and genotyping approaches were used to verify the function of the candidate site.

Results: We identified 3,895 windows containing 509 genes. After GO and KEGG enrichment analysis, nine genes were selected. Ultimately, MITF was selected by comparing the genomic differentiation (FST). After loci information selection, 41 extreme significantly different loci were selected, which are all located in intron regions of MITF and are in almost complete linkage disequilibrium. Subsequently, the site ASM874695v1:10:g.17814522T > A in MITF was selected as the marker site. Furthermore, we found that MITF expression is significantly higher in black-beaked ducks than in yellow-beaked ducks of the F2 generation (p < 0.01). After genotyping, most yellow-billed individuals are found with homozygous variant; at the same time, there are no birds with homozygous variant in black-billed populations, while the birds with homozygous and heterozygous variant share the same proportion.

Conclusion:MITF plays a very critical role in the melanogenesis and melanin deposition of duck beaks, which can effectively affect the beak color. The MITF site, ASM874695v1:10:g.17814522T > A could be selected as a marker site for the duck beak color phenotype.
Case report: PIK3CA somatic mutation leading to Klippel Trenaunay Syndrome and multiple tumors
Authors: Serio Viola Bianca , Palmieri Maria , Innamorato Simona , Loberti Lorenzo , Fallerini Chiara , Ariani Francesca , Antolini Enrica , Covarelli Jasmine , Vaghi Massimo , Frullanti Elisa , Renieri Alessandra , Pinto Anna Maria
Published: August 2023

We report a case of Klippel Trenaunay Syndrome that was monitored both clinically and molecularly over a period of 9 years. A somatic mosaic mutation of PIK3CA (p(E545G)) was identified using both cfDNA NGS liquid biopsy and tissue biopsy. At the age of 56, due to intervening clonal mutations in PIK3CA background, she developed a squamous cell carcinoma in the right affected leg which was treated surgically. Nine years later, lung bilateral adenocarcinoma arose on PIK3CA mutated tissues supported by different clonal mutations. One year later, the patient died from metastases led by a new FGFR3 clone unresponsive to standard-of-care, immunotherapy-based. Our results highlight the presence of a molecular hallmark underlying neoplastic transformation that occurs upon an angiodysplastic process and support the view that PIK3CA mutated tissues must be treated as precancerous lesions. Importantly, they remark the effectiveness of combining cfDNA NGS liquid and tissue biopsies to monitor disease evolution as well as to identify aggressive clones targetable by tailored therapy, which is more efficient than conventional protocols.
Cryoablation and immunity in non-small cell lung cancer: a new era of cryo-immunotherapy
Authors: Velez Antonio , DeMaio Andrew , Sterman Daniel
Published: August 2023

Despite remarkable advances in tumor response and patient survival in the past decade, systemic immunotherapies for lung cancer result in an objective response in only around half of patients treated. On the basis of this limitation, combination strategies are being investigated to improve response rates. Cryoablation has been proposed as one such technique to induce immunogenic cell death and synergize with systemic immunotherapies, including immune checkpoint inhibitors. Cryoablation has been traditionally delivered percutaneously with imaging guidance although recent technological advances allow for bronchoscopic delivery. Herein, we review the pre-clinical and clinical evidence for the use of cryoablation in non-small cell lung cancer and potential induction of anti-tumor immunity. We highlight ongoing studies involving this approach and propose areas of future investigation.
Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement
Authors: Geng Hongzhi , Jia Sixun , Zhang Ying , Li Jiaqi , Yang Qin , Zeng Liangyu , Zong Xiangping , Lu Yutong , Lu Shuangzhu , Zhou Jin , Li Caixia , Wu Depei
Published: August 2023

Introduction

Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) shows poor response rates in non–germinal center B cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL) patients with multiple extranodal involvement. This study aims to evaluate anti-tumor activity and safety of zanubrutinib with R-CHOP (ZR-CHOP) in treatment naïve non-GCB DLBCL with extranodal involvement.

Methods

In this single-arm, phase 2, prospective, single-center study, patients with newly diagnosed non-GCB DLBCL with extranodal involvement enrolled between October 2020 to March 2022 received ZR-CHOP for 6 cycles followed by 2 cycles of maintenance treatment with rituximab and zanubrutinib. The primary endpoint included progression-free survival (PFS) in the intent-to-treat (ITT) population whereas the secondary endpoints included overall response rate (ORR), complete response (CR), and duration of response. Further, next-generation sequencing (NGS) was used for detection of different oncogenic mutations closely related to DLBCL pathogenesis.

Results

From October 2020 to March 2022, 26 patients were enrolled, and 23 of them were evaluated for efficacy after receiving 3 cycles of ZR-CHOP treatment. 1-year PFS and OS were 80.8% and 88.5% respectively while expected PFS and OS for 2-years are 74.0% and 88.5% respectively with median follow-up of 16.7 months and ORR was 91.3% (CR: 82.61%; PR: 8.70%). Oncogenic mutations closely related to DLBCL pathogenesis were assessed in 20 patients using NGS. B-cell receptor and NF-κB pathway gene mutations were detected in 10 patients, which occurred in MYD88 (7/19), CD79B (4/19), CARD11 (5/19), and TNFAIP3 (2/19). Hematological adverse events (AEs) ≥ grade 3 included neutropenia (50%), thrombocytopenia (23.1%), and anemia (7.7%) whereas non-hematological AEs ≥ grade 3 included pulmonary infection (19.2%).

Conclusion

ZR-CHOP is safe and effective for treating treatment naïve non-GCB DLBCL patients with extranodal involvement.

Clinical Trial Registration

Clinicaltrials.gov, NCT04835870
Genomic diversity and evolution analysis of severe fever with thrombocytopenia syndrome in East Asia from 2010 to 2022
Authors: Wang Yao , Pang Bo , Wang Zequn , Tian Xueying , Xu Xiaoying , Chong Xiaowen , Liang Hao , Ma Wei , Kou Zengqiang , Wen Hongling
Published: August 2023

Background

Conducting an up-to-date analysis on the genomic diversity and evolution patterns of severe fever with thrombocytopenia syndrome virus (SFTSV) is crucial for elucidating the underlying mechanisms of its emergency and pathogenicity, as well as assessing the extent of its threat to public health.

Methods

Complete genome sequences of SFTSV were obtained from GenBank until December 19, 2022. A thorough phylogenetic analysis was conducted using comprehensive bioinformatics methods to estimate the genomic diversity and evolution.

Results

The phylogenetic classification of SFTSV strains yielded seven lineages (A-G) for each genome segment. SFTSV displayed notable variations in evolutionary patterns among different regions and segments, without a linear accumulation of nucleotide substitutions within segments and regions. The comprehensive analysis revealed 54 recombination events and 17 reassortment strains, including the first discovery of recombination events involving sea-crossing and species-crossing. Selection analysis identified three positive sites (2, 671, 1353) in RNA-dependent RNA polymerase, three positive sites (22, 298, 404) in glycoprotein, and two positive sites (9, 289) in nonstructural protein. No positive selection sites were found in nucleoprotein.

Conclusion

Our study unveiled the existence of multiple evolutionary forces influencing SFTSV, contributing to its increasing genetic diversity, which had the potential to modify its antigenicity and pathogenicity. Furthermore, our study highlights the importance of tracking the spread of SFTSV across regions and species.
Characterization of host substrates of SARS-CoV-2 main protease
Authors: Melano Ivonne , Lo Yan-Chung , Su Wen-Chi
Published: August 2023

The main protease (Mpro) plays a crucial role in coronavirus, as it cleaves viral polyproteins and host cellular proteins to ensure successful replication. In this review, we discuss the preference in the recognition sequence of Mpro based on sequence-based studies and structural information and highlight the recent advances in computational and experimental approaches that have aided in discovering novel Mpro substrates. In addition, we provide an overview of the current understanding of Mpro host substrates and their implications for viral replication and pathogenesis. As Mpro has emerged as a promising target for the development of antiviral drugs, further insight into its substrate specificity may contribute to the design of specific inhibitors.
Risk factors for infection in patients with a failed kidney allograft on immunosuppressive medications
Authors: Ogawa Lauren , Beaird Omer E. , Schaenman Joanna M.
Published: August 2023

Patients with a failing kidney allograft are often continued on immunosuppression (IS) to preserve residual kidney function and prevent allosensitization. It has been previously accepted that maintaining patients on immunosuppressive therapy results in an increased risk of infection, hospitalization, and mortality. However, as the management of IS in patients with a failed kidney allograft continues to evolve, it is important to review the data regarding associations between infection and specific immunosuppression regimens. We present a review of the literature of failed kidney allograft management and infection risk, and discuss practices for infection prevention. Fifteen studies, published from 1995 to 2022, which investigated the experience of patients with failed allograft and infection, were identified. Infection was most commonly documented as a general event, but when specified, included infections caused by Candida, Mycobacterium tuberculosis, and Aspergillus. In addition, the definition of reduced “IS” varied from decreased doses of a triple drug regimen to monotherapy, whereas others did not specify which medications patients were receiving. Despite attempts at lowering net immunosuppression, patients with failed allografts remain at risk of acquiring opportunistic and non-opportunistic infections. Although opportunistic infections secondary to IS are expected, somewhat surprisingly, it appears that the greatest risk of infection may be related to complications of dialysis. Therefore, mitigating strategies, such as planning for an arteriovenous (AV) fistula over a hemodialysis catheter placement, may reduce infection risk. Additional studies are needed to provide more information regarding the types and timing of infection in the setting of a failed kidney allograft. In addition, more data are needed regarding specific medications, doses, and timing of taper of IS to guide future patient management and inform strategies for infection surveillance and prophylaxis.
Development and results of the epilepsy surgery in Armenia: hope for a better future
Authors: Sukhudyan Biayna , Minkin Krasimir , Badalyan Sevak , Gabrovski Kaloyan , Gevorgyan Ani , Tovmasyan Irina , Babloyan Ara , Dimova Petia
Published: August 2023

Purpose

We present our experience with the national epilepsy surgery program in Armenia by tracing the development of epilepsy surgery in the largest pediatric neurology department at “Arabkir” Medical Center. This development was possible on the basis of a strong collaboration with the Epilepsy Surgery center at the University Hospital “Sofia St. Ivan Rilski,” Sofia, Bulgaria.

Materials and methods

Our material included 28 consecutive patients with lesional drug-resistant epilepsy evaluated. All patients underwent 3 T MRI and Video-EEG monitoring. Brain 18FDG-PET was done in 13 patients in St. Petersburg. Fifteen patients (53%) had preoperative neuropsychological examination before surgery. All operations were done by the same neurosurgical team on site in Arabkir Hospital.

Results

The majority of the patients in our cohort benefited from the epilepsy surgery as 25 (89%) are free of disabling seizures (Engel class I) and three patients (11%) did not improve substantially (Engel class IV). Eleven patients (39%) are already ASM-free after surgery, 4 (14%) are on monotherapy, 11(39%) get two drugs, and 2(7%) are on polytherapy, one of them still continues having seizures. In 12 patients (43%), we were able either to withdraw therapy or to decrease one of the ASM.

Conclusion

We believe that, although small, yet encompassing patients along the usual age spectrum and with the most frequent pathologies of drug-resistant epilepsies, our experience can serve as a model to develop epilepsy surgery in countries with limited resources.
Design issues in crossover trials involving patients with Parkinson’s disease
Authors: Sparrow David , DeMolles Deborah , Dubaz Ornella , Durso Raymon , Rosner Bernard
Published: August 2023

Background and objectives

Crossover designs are frequently used to assess treatments for patients with Parkinson’s disease. Typically, two-period two-treatment trials include a washout period between the 2 periods and assume that the washout period is sufficiently long to eliminate carryover effects. A complementary strategy might be to jointly model carryover and treatment effects, though this has rarely been done in Parkinson’s disease crossover studies. The primary objective of this research is to demonstrate a modeling approach that assesses treatment and carryover effects in one unified mixed model analysis and to examine how it performs in a simulation study and a real data analysis example, as compared to other data analytic approaches used in Parkinson’s disease crossover studies.

Methods

We examined how three different methods of analysis (standard crossover t-test, mixed model with a carryover term included in model statement, and mixed model with no carryover term) performed in a simulation study and illustrated the methods in a real data example in Parkinson’s disease.

Results

The simulation study based on the presence of a carryover effect indicated that mixed models with a carryover term and an unstructured correlation matrix provided unbiased estimates of treatment effect and appropriate type I error. The methods are illustrated in a real data example involving Parkinson’s disease. Our literature review revealed that a majority of crossover studies included a washout period but did not assess whether the washout was sufficiently long to eliminate the possibility of carryover.

Discussion

We recommend using a mixed model with a carryover term and an unstructured correlation matrix to obtain unbiased estimates of treatment effect.
The Parkinson’s disease waiting room of the future: measurements, not magazines
Authors: Alberts Jay L. , Shuaib Umar , Fernandez Hubert , Walter Benjamin L. , Schindler David , Miller Koop Mandy , Rosenfeldt Anson B.
Published: August 2023

Utilizing technology to precisely quantify Parkinson’s disease motor symptoms has evolved over the past 50 years from single point in time assessments using traditional biomechanical approaches to continuous monitoring of performance with wearables. Despite advances in the precision, usability, availability and affordability of technology, the “gold standard” for assessing Parkinson’s motor symptoms continues to be a subjective clinical assessment as none of these technologies have been fully integrated into routine clinical care of Parkinson’s disease patients. To facilitate the integration of technology into routine clinical care, the Develop with Clinical Intent (DCI) model was created. The DCI model takes a unique approach to the development and integration of technology into clinical practice by focusing on the clinical problem to be solved by technology rather than focusing on the technology and then contemplating how it could be integrated into clinical care. The DCI model was successfully used to develop the Parkinson’s disease Waiting Room of the Future (WROTF) within the Center for Neurological Restoration at the Cleveland Clinic. Within the WROTF, Parkinson’s disease patients complete the self-directed PD-Optimize application on an iPad. The PD-Optimize platform contains cognitive and motor assessments to quantify PD symptoms that are difficult and time-consuming to evaluate clinically. PD-Optimize is completed by the patient prior to their medical appointment and the results are immediately integrated into the electronic health record for discussion with the movement disorder neurologist. Insights from the clinical use of PD-Optimize has spurred the development of a virtual reality technology to evaluate instrumental activities of daily living in PD patients. This new technology will undergo rigorous assessment and validation as dictated by the DCI model. The DCI model is intended to serve as a health enablement roadmap to formalize and accelerate the process of bringing the advantages of cutting-edge technology to those who could benefit the most: the patient.
The utility of ChatGPT in the assessment of literature on the prevention of migraine: an observational, qualitative study
Authors: Moskatel Leon S. , Zhang Niushen
Published: August 2023

Background

It is not known how large language models, such as ChatGPT, can be applied toward the assessment of the efficacy of medications, including in the prevention of migraine, and how it might support those claims with existing medical evidence.

Methods

We queried ChatGPT-3.5 on the efficacy of 47 medications for the prevention of migraine and then asked it to give citations in support of its assessment. ChatGPT’s evaluations were then compared to their FDA approval status for this indication as well as the American Academy of Neurology 2012 evidence-based guidelines for the prevention of migraine. The citations ChatGPT generated for these evaluations were then assessed to see if they were real papers and if they were relevant to the query.

Results

ChatGPT affirmed that the 14 medications that have either received FDA approval for prevention of migraine or AAN Grade A/B evidence were effective for migraine. Its assessments of the other 33 medications were unreliable including suggesting possible efficacy for four medications that have never been used for the prevention of migraine. Critically, only 33/115 (29%) of the papers ChatGPT cited were real, while 76/115 (66%) were “hallucinated” not real papers and 6/115 (5%) shared the names of real papers but had not real citations.

Conclusion

While ChatGPT produced tailored answers on the efficacy of the queried medications, the results were unreliable and inaccurate because of the overwhelming volume of “hallucinated” articles it generated and cited.
Comparison of adverse effects of anti-tumor therapy for breast cancer shortly after COVID-19 diagnosis vs. the control period
Authors: Ding Mao , Xiang Hongyu , Ye Jingming , Cheng Yuanjia , Liu Qian , Xu Ling
Published: August 2023

Background

COVID-19 is an acute infectious disease caused by SARS-CoV-2. The best time to restart antitumor therapy in breast cancer patients after SARS-CoV-2 infection is unknown. This study aimed to evaluate treatment-related adverse events in breast cancer patients who received antitumor therapies within a short time after SARS-CoV-2 infection (observation) as well as before (control) and to provide safety data.

Methods

We conducted a self-controlled cohort study using the data from the Breast Disease Center of Peking University First Hospital. We identified patients who received antitumor therapy within 28 days after COVID-19 infection between December 20, 2022, and January 20, 2023. The primary outcome was treatment-related adverse events. McNemar’s test was used to compare the incidence rate of adverse reactions between periods.

Results

We identified 183 patients with breast cancer, of whom 109 were infected with SARS-CoV-2 within 28 days before antitumor treatment and were included. In total, 28 patients (25.7%) received neoadjuvant therapy, 60 (55.0%) received adjuvant therapy, and 21 (19.3%) received advanced rescue therapy. None of patients required hospitalization for severe or critical COVID-19, but 15 patients (13.8%) still had sequelae of COVID-19 while receiving antitumor treatment. The most common adverse events were peripheral neuropathy (n = 32 [29.4%]), pain (n = 29 [26.6%]), fatigue (n = 28 [25.7%]), nausea (n = 23 [21.1%]), and neutropenia (n = 19 [17.4%]). There was no increased risk of overall treatment-related adverse events (n = 87 [79.8%] vs. n = 91 [83.5%]; p = 0.42) or serious adverse events (n = 13 [11.9%] vs. n = 12 [11.0%]; p = 1.00) from receiving antitumor therapy shortly after the diagnosis of COVID-19. We also found no increased risk in subgroup analyses, and no patients discontinued antitumor therapy due to adverse events.

Conclusion

Restarting antitumor therapy 2-4 weeks after having mild or moderate COVID-19 is a relatively safe strategy for breast cancer patients that does not increase the risk of treatment-related adverse events.
Case Report: ALK rearranged locally advanced lung adenocarcinoma showing inconsistent radiographic findings and pathological responses during neoadjuvant alectinib therapy
Authors: Cao Peijun , Zhao Qingchun , Li Yongwen , Shi Ruifeng , Zhu Guangsheng , Zhang Zihe , Zhang Hongbing , Liu Minghui , Wei Sen , Liu Hongyu , Chen Jun
Published: August 2023

Alectinib has been approved as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung carcinoma. Oncologists are also exploring the possibility of applying alectinib in the perioperative period. Here, we present a patient with locally advanced lung adenocarcinoma associated with EML4-ALK fusion mutation, who received neoadjuvant chemotherapy and alectinib treatment, and then underwent thoracoscopic left lower lung lobectomy. The patient initially received eight chemotherapy cycles and achieved partial remission. After eight cycles of chemotherapy, the lymph nodes in the hilar region again enlarged. The patient was then switched to 4 months of alectinib therapy, but no significant lesion changes were detected on imaging during this period. This raised the question of whether the patient developed alectinib resistance. The pathological findings of the postoperative lung lobe specimens indicated extensive necrosis in the tumor area with no residual tumor cells and massive chronic inflammatory cell infiltration around the tumor area, confirming inconsistency between the imaging findings and pathological results. Multi-point tumor specimen sampling was postoperatively performed. Tumor immune-related gene expression was detected in the sample with the help of the PanCancer IO360™ panel based on the nCounter platform. This is a rare case of a patient who was treated with neoadjuvant alectinib and had paradoxical radiographic findings and pathological responses. The possibility that intratumoral immune heterogeneity was responsible for this phenomenon has been discussed. Based on the findings, it is argued that the pathological response should be an important basis for assessing the effectiveness of neoadjuvant alectinib therapy.
Glucosyl hesperidin exhibits more potent anxiolytic activity than hesperidin accompanied by the attenuation of noradrenaline induction in a zebrafish model
Authors: Nishida Takumi , Horita Chihoko , Imagawa Mikiya , Hibarino Momoka , Tateno Sayaka , Kubo Yurina , Kawabe Momoko , Morishita Naoki , Endo Shin , Shiozaki Kazuhiro
Published: August 2023

Anxiety is a symptom of various mental disorders, including depression. Severe anxiety can significantly affect the quality of life. Hesperidin (Hes), a flavonoid found in the peel of citrus fruits, reportedly has various functional properties, one of which is its ability to relieve acute and chronic stress. However, Hes is insoluble in water, resulting in a low absorption rate in the body and low bioavailability. Glucosyl hesperidin (GHes) is produced by adding one glucose molecule to hesperidin. Its water solubility is significantly higher than that of Hes, which is expected to improve its absorption into the body and enhance its effects. However, its efficacy in alleviating anxiety has not yet been investigated. Therefore, in this study, the anxiolytic effects of GHes were examined in a zebrafish model of anxiety. Long-term administration of diets supplemented with GHes did not cause any toxicity in the zebrafish. In the novel tank test, zebrafish in the control condition exhibited an anxious behavior called freezing, which was significantly suppressed in GHes-fed zebrafish. In the black-white preference test, which also induces visual stress, GHes-fed zebrafish showed significantly increased swimming time in the white side area. Furthermore, in tactile (low water-level stress) and olfactory-mediated stress (alarm substance administration test) tests, GHes suppressed anxious behavior, and these effects were stronger than those of Hes. Increased noradrenaline levels in the brain generally cause freezing; however, in zebrafish treated with GHes, the amount of noradrenaline after stress was lower than that in the control group. Activation of c-fos/ERK/Th, which is upstream of the noradrenaline synthesis pathway, was also suppressed, while activation of the CREB/BDNF system, which is vital for neuroprotective effects, was significantly increased. These results indicate that GHes has a more potent anxiolytic effect than Hes in vivo, which may have potential applications in drug discovery and functional food development.
Protein tyrosine phosphatase non-receptor type 2 as the therapeutic target of atherosclerotic diseases: past, present and future
Authors: Tang Xiao-Er , Cheng Ya-Qiong , Tang Chao-Ke
Published: August 2023

Tyrosine-protein phosphatase non-receptor type 2(PTPN2), an important member of the protein tyrosine phosphatase family, can regulate various signaling pathways and biological processes by dephosphorylating receptor protein tyrosine kinases. Accumulating evidence has demonstrated that PTPN2 is involved in the occurrence and development of atherosclerotic cardiovascular disease. Recently, it has been reported that PTPN2 exerts an anti-atherosclerotic effect by regulating vascular endothelial injury, monocyte proliferation and migration, macrophage polarization, T cell polarization, autophagy, pyroptosis, and insulin resistance. In this review, we summarize the latest findings on the role of PTPN2 in the pathogenesis of atherosclerosis to provide a rationale for better future research and therapeutic interventions.
The landscape of lncRNAs in gastric cancer: from molecular mechanisms to potential clinical applications
Authors: Silva Jéssica Manoelli Costa , Teixeira Eliel Barbosa , Mourão Ronald Matheus da Silva , Ferraz Rafaella Sousa , Moreira Fabiano Cordeiro , Assumpção Paulo Pimentel de , Calcagno Danielle Queiroz
Published: August 2023

Gastric cancer (GC) is a highly prevalent and deadly malignant neoplasm worldwide. Currently, long non-coding RNAs (lncRNAs) have recently been identified as crucial regulators implicated in GC development and progression. Dysregulated expression of lncRNAs is commonly associated with enhanced tumor migration, invasiveness, and therapy resistance, highlighting their potential as promising targets for clinical applications. This review offers a comprehensive historical overview of lncRNAs in GC, describes the molecular mechanisms, and discusses the prospects and challenges of establishing lncRNAs as precision biomarkers.
The effects of high-velocity hamstring muscle training on injury prevention in football players
Authors: Kamandulis Sigitas , Cadefau Joan Aureli , Snieckus Audrius , Mickevicius Mantas , Lukonaitiene Inga , Muanjai Pornpimol , Satkunskiene Danguole , Molina Victor , Blas Foix Xavier de , Conte Daniele
Published: August 2023

Background: Explosive and fast body movements, sprints, jumps and quick changes of direction, which are characteristic of the football training, place considerable strain on the hamstring muscles. Due to the high occurrence of hamstring injuries, new preventive strategies are required that focus on high-velocity training. The purpose was to assess the effectiveness of high-velocity elastic-band training in reducing the occurrence of hamstring injuries in football players.

Methods: Male football players from 15 teams (n = 319) playing in national competitions participated in this study. The players were involved in a 5-week exercise period in either the intervention group (INT) or the control group (CON), with a follow-up period of ∼4 months where hamstring injuries and exposure time were recorded. The INT group had two to three sessions per week of elastic-band training with low-load, high-velocity leg curls while lying prone; the CON group performed self-paced football-specific drills.

Results: The incidence rate of hamstring injuries was 6.5% in the INT group (8 out of 123 players) and 9.2% in the CON group (18 out of 196 players). Although the INT group showed almost 1/3 reduction in hamstring injury incidence compared to the CON group, the difference was not statistically significant (p > 0.05). Moreover, no differences (p > 0.05, odds ratio [OR] = trivial-to-small) in distribution between the groups were found in hamstring injury characteristics (leg dominance and mechanism) except for the distribution of injuries that occurred during matches or training (p = 0.036; OR = 6.14, moderate).

Conclusion: The program of high-velocity elastic-band training did not prove to be effective in preventing hamstring muscle injuries in football players despite displaying some positive indications that could be considering when creating injury prevention programs.
QTL mapping and transcriptomic analysis of fruit length in cucumber
Authors: Xing Yanan , Cao Yilin , Ma Yanan , Wang Fu , Xin Shijie , Zhu Wenying
Published: August 2023

A total of 151 recombinant inbred lines (RILs) were derived from the cross between ‘Cucumis sativus L. hardwickii’ (HW) and a cultivated Northern Chinese inbred line ‘XinTaiMiCi’ (XTMC). We used resequencing to construct the genetic map and analyze the genetic background of RIL population, and combined with the phenotypes of RIL population and the analysis of RNA-seq data, we located the major loci controlling the fruit length of cucumber and related analysis. A genetic map containing 600 bin markers was constructed via re-sequencing. Based on the phenotype data collected in two different seasons (spring 2021 and autumn 2022), the major quantitative trait loci (QTLs) controlling cucumber fruit length were located and their transcriptomic analysis carried out. The results revealed three QTLs (Fl2.1, Fl4.1, and Fl6.1) detected repeatedly in the two seasons, of which Fl4.1 was the dominant QTL. From the functional annotation of corresponding genes there, we discovered the gene Csa4G337340 encoding an auxin efflux carrier family protein. The expression of that gene was significantly lower in XTMC and the long-fruit RIL lines than in HW and the short-fruit RIL lines; hence, we speculated the gene could be negatively correlated with the fruit length of cucumber. Transcriptomic analysis showed that 259 differentially expressed genes (DEGs) were enriched in the plant hormone signal transduction pathway. In addition, among those DEGs, 509 transcription factors were detected, these distributed in several transcription factor gene families, such as bHLH, AP2/ErF -ERF, C2H2, and NAC. Therefore, we concluded that the major gene controlling the fruit length of cucumber is located in the interval of Fl4.1, whose gene Csa4G337340 may be involved in the negative regulation of fruit length. Further, genes related to plant hormone signal transduction and several transcription factors were also found involved in the regulation of cucumber fruit length. Our results provide a reference for the fine mapping of major genes and analyzing the mechanism of cucumber fruit length.