bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiome insights into pediatric familial adenomatous polyposis
Authors: Attard Thomas M. , Septer Seth , Lawson Caitlin E. , Attard Mark I. , Lee Sonny T. M. , Umar Shahid
Published: November 2022

Background

Individuals with familial adenomatous polyposis (FAP) harbor numerous polyps with inevitable early progression to colon cancer. Complex microbiotic-tumor microenvironment perturbations suggest a dysbiotic relationship between polyp and microbiome. In this study, we performed comprehensive analyses of stool and tissue microbiome of pediatric FAP subjects and compared with unaffected cohabiting relatives through 16S V4 region amplicon sequencing and machine learning platforms.

Results

Within our FAP and control patient population, Firmicutes and Bacteroidetes were the predominant phyla in the tissue and stool samples, while Proteobacteria dominated the polyp/non-polyp mucosa. A decline in Faecalibacterium in polyps contrasted with a decline in Bacteroides in the FAP stool. The alpha- and beta-diversity indices differed significantly within the polyp/non-polyp groups, with a concurrent shift towards lower diversity in polyps. In a limited 3-year longitudinal study, the relative abundance of Proteobacteria and Fusobacteria was higher in polyps compared to non-polyp and stool specimens over time. Through machine learning, we discovered that Archaeon_enrichment_culture_clone_A13, Micrococcus_luteus, and Eubacterium_hallii in stool and PL-11B10, S1-80, and Blastocatellaceae in tissues were significantly different between patients with and without polyps.

Conclusions

Detection of certain bacterial concentrations within stool or biopsied polyps could serve as adjuncts to current screening modalities to help identify higher-risk patients.
metaMIC: reference-free misassembly identification and correction of de novo metagenomic assemblies
Authors: Lai Senying , Pan Shaojun , Sun Chuqing , Coelho Luis Pedro , Chen Wei-Hua , Zhao Xing-Ming
Published: November 2022

Evaluating the quality of metagenomic assemblies is important for constructing reliable metagenome-assembled genomes and downstream analyses. Here, we present metaMIC (https://github.com/ZhaoXM-Lab/metaMIC), a machine learning-based tool for identifying and correcting misassemblies in metagenomic assemblies. Benchmarking results on both simulated and real datasets demonstrate that metaMIC outperforms existing tools when identifying misassembled contigs. Furthermore, metaMIC is able to localize the misassembly breakpoints, and the correction of misassemblies by splitting at misassembly breakpoints can improve downstream scaffolding and binning results.
Bioactive isopimarane and 3,4-seco isopimarane diterpenoids from Isodon amethystoides
Authors: Zhao Chenliang , Zhou Lang , Xie Wenjian , Zhao Lihan , Zhang Chiyuan , He Kang , Ye Jianghai , Zhang Jingjie , Pan Lutai , Zou Juan , Zhang Hongjie
Published: November 2022

Isodon amethystoides (Lamiaceae) is a popular plant in folk medicine in the southern provinces of China. Our phytochemical investigation of the twigs and leaves of this plant led to the discovery of five new diterpenoids with isopimarane and 3,4-seco isopimarane scaffolds [isoamethinols A–E (1–5)], along with the known compound 3,4-seco isopimara-4(18),7,15-triene-3-oic acid methylester (6). The chemical structures of these compounds, including the absolute configurations of the new diterpenoids, were determined by comprehensive spectroscopic analyses and single crystal X-ray diffraction measurements. These compounds were evaluated for their biological activities against a panel of human cancer cell lines, gram-positive bacterial strains and HIV. Notably, the 3,4-seco-isopimarane isoamethinol D (4) showed toxicity to the cervical Hela cancer (Hela) cells with an IC50 value of 27.21 μM and the lung (A549) cancer cells with an IC50 value of 21.47 μM. Compound 4 also exhibited mild antimicrobial activity against the oral bacterial strain Streptococcus mutans. These findings suggested that the diterpenoids with a 3,4-seco-isopimarane diterpenoids isolated from I. amethystoides could provide a novel structure scaffold for the discovery of anticancer and antimicrobial compounds.

Graphical Abstract
Insecticide resistance in malaria and arbovirus vectors in Papua New Guinea, 2017–2022
Authors: Katusele Michelle , Lagur Solomon , Endersby-Harshman Nancy , Demok Samuel , Goi Joelyn , Vincent Naomi , Sakur Muker , Dau Absalom , Kilepak Lemen , Gideon Stephen , Pombreaw Christine , Makita Leo , Hoffmann Ary , Robinson Leanne J. , Laman Moses , Karl Stephan
Published: November 2022

Background

Insecticide resistance (IR) monitoring is essential for evidence-based control of mosquito-borne diseases. While widespread pyrethroid resistance in Anopheles and Aedes species has been described in many countries, data for Papua New Guinea (PNG) are limited. Available data indicate that the local Anopheles populations in PNG remain pyrethroid-susceptible, making regular IR monitoring even more important. In addition, Aedes aegypti pyrethroid resistance has been described in PNG. Here, Anopheles and Aedes IR monitoring data generated from across PNG between 2017 and 2022 are presented.

Methods

Mosquito larvae were collected in larval habitat surveys and through ovitraps. Mosquitoes were reared to adults and tested using standard WHO susceptibility bioassays. DNA from a subset of Aedes mosquitoes was sequenced to analyse the voltage-sensitive sodium channel (Vssc) region for any resistance-related mutations.

Results

Approximately 20,000 adult female mosquitoes from nine PNG provinces were tested. Anopheles punctulatus sensu lato mosquitoes were susceptible to pyrethroids but there were signs of reduced mortality in some areas. Some Anopheles populations were also resistant to DDT. Tests also showed that Aedes. aegypti in PNG are resistant to pyrethroids and DDT and that there was also likelihood of bendiocarb resistance. A range of Vssc resistance mutations were identified. Aedesalbopictus were DDT resistant and were likely developing pyrethroid resistance, given a low frequency of Vssc mutations was observed.

Conclusions

Aedes aegypti is highly pyrethroid resistant and also shows signs of resistance against carbamates in PNG. Anopheles punctulatus s.l. and Ae. albopictus populations exhibit low levels of resistance against pyrethroids and DDT in some areas. Pyrethroid-only bed nets are currently the only programmatic vector control tool used in PNG. It is important to continue to monitor IR in PNG and develop proactive insecticide resistance management strategies in primary disease vectors to retain pyrethroid susceptibility especially in the malaria vectors for as long as possible.

Graphic abstract
Roles of physical exercise-induced MiR-126 in cardiovascular health of type 2 diabetes
Authors: Ma Yixiao , Liu Hua , Wang Yong , Xuan Junjie , Gao Xing , Ding Huixian , Ma Chunlian , Chen Yanfang , Yang Yi
Published: November 2022

Although physical activity is widely recommended for preventing and treating cardiovascular complications of type 2 diabetes mellitus (T2DM), the underlying mechanisms remain unknown. MicroRNA-126 (miR-126) is an angiogenetic regulator abundant in endothelial cells (ECs) and endothelial progenitor cells (EPCs). It is primarily involved in angiogenesis, inflammation and apoptosis for cardiovascular protection. According to recent studies, the levels of miR-126 in the myocardium and circulation are affected by exercise protocol. High-intensity interval training (HIIT) or moderate-and high-intensity aerobic exercise, whether acute or chronic, can increase circulating miR-126 in healthy adults. Chronic aerobic exercise can effectively rescue the reduction of myocardial and circulating miR-126 and vascular endothelial growth factor (VEGF) in diabetic mice against diabetic vascular injury. Resistance exercise can raise circulating VEGF levels, but it may have a little influence on circulating miR-126. The Several targets of miR-126 have been suggested for cardiovascular fitness, such as sprouty-related EVH1 domain-containing protein 1 (SPRED1), phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), vascular cell adhesion molecule 1 (VCAM1), high-mobility group box 1 (HMGB1), and tumor necrosis factor receptor-associated factor 7 (TRAF7). Here, we present a comprehensive review of the roles of miR-126 and its downstream proteins as exercise mechanisms, and propose that miR-126 can be applied as an exercise indicator for cardiovascular prescriptions and as a preventive or therapeutic target for cardiovascular complications in T2DM.
Towards real-time probabilistic ash deposition forecasting for New Zealand
Authors: Trancoso Rosa , Behr Yannik , Hurst Tony , Deligne Natalia I
Published: November 2022

Volcanic ashfall forecasts are highly dependent on eruption source parameters (ESPs) and synoptic weather conditions at the time and location of the eruption. In New Zealand, MetService and GNS Science have been jointly developing an ashfall forecast system that incorporates four-dimensional high-resolution numerical weather prediction (NWP) and ESPs into the HYSPLIT model, a state-of-the art hybrid Eulerian and Lagrangian dispersion model widely used for volcanic ash. However, these forecasts are based on discrete ESPs combined with a deterministic weather forecast and thus provide no information on output uncertainty. This shortcoming hinders stakeholder decision making, particularly near the geographical margin of forecasted ashfall and in areas with large gradients in forecasted ash deposition. Our study presents a new approach that incorporates uncertainty from both eruptive and meteorological inputs to deliver uncertainty in the model output. To this end, we developed probability density functions (PDFs) for three key ESPs (plume height, mass eruption rate, eruption duration) tailored to New Zealand’s volcanoes and combine them with NWP ensemble datasets to generate probabilistic ashfall forecasts using the HYSPLIT model. We show that the Latin Hypercube Sampling (LHS) technique can be used to representatively span this four-dimensional parameter space and allow us to add uncertainty quantification to rapid response forecast systems. For a case study of a hypothetical eruption at Tongariro, New Zealand we suggest that large parts of New Zealand’s North Island would not receive adequate warning for potential ashfall if uncertainties were not included in the forecasts. We also propose new probabilistic summary products to support public information and emergency responders decision making.
Early prediction model for prognosis of patients with hepatitis-B-virus-related acute-on-chronic liver failure received glucocorticoid therapy
Authors: Gao Shuai , Han Li-Yan , Fan Yu-Chen , Wang Kai
Published: November 2022

Background

Early prediction for short-term prognosis is essential for the management of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). In this study, we aim to establish a noninvasive model for predicting the 90-day mortality in patients with HBV–ACLF received glucocorticoid therapy.

Methods

Two hundred and eighty patients with HBV–ACLF were enrolled from July 2010 to June 2022. All patients received routine medicine treatment and 204 of them received additional glucocorticoid treatment. Then, the patients who received glucocorticoid treatment were randomly divided into a training cohort and a validation cohort. An early prediction model for 90-day mortality of HBV–ACLF was established in the training cohort and then validated in the validation cohort.

Results

HBV–ACLF patients received glucocorticoid treatment showed significantly better survival that those not (P < 0.01). In the training cohort, a noninvasive model was generated with hepatic encephalopathy grade, INR, total bilirubin, age and SIRS status, which was named HITAS score. It showed significantly better predictive value for 90-day mortality of HBV–ACLF than MELD score and Child–Turcotte–Pugh score in both the training cohort and validation cohort. Using the Kaplan–Meier analysis with cutoff points of 2.5 and 3.47, the HITAS score can classify HBV–ACLF patients into different groups with low, intermediate and high risk of death after glucocorticoid therapy.

Conclusions

We proposed a HITAS score, which was an early prediction model for the prognosis of HBV–ACLF. It might be used to identify HBV–ACLF patients with favorable responses to glucocorticoid treatment.
A multilevel examination of the association between COVID-19 restrictions and residence-to-crime distance
Authors: Lentz Theodore S. , Headley Konkel Rebecca , Gallagher Hailey , Ratkowski Dominick
Published: November 2022

Restrictions resulting from the COVID-19 pandemic interrupted people’s daily routine activities. Rooted in crime pattern and routine activity theories, this study tests whether the enactment of a Safer-at-Home mandate was associated with changes in the distance between individuals’ home addresses and the locations of where they committed crimes (i.e., residence-to-crime distance). Analyses are based on violent (N = 282), property (N = 1552), and disorder crimes (N = 1092) reported to one police department located in a United States’ Midwest suburb. Multilevel models show that residence-to-crime distances were significantly shorter during the Safer-at-Home order, compared to the pre- and post-Safer-at-Home timeframes, while controlling for individual and neighborhood characteristics. Additionally, these relationships varied by crime type. Consistent with the literature, the findings support the argument that individuals tend to offend relatively near their home address. The current findings extend the state of the literature by highlighting how disruptions to daily routine activities stemming from the COVID-19 pandemic led to alterations in crime patterns, in which analyses indicated shorter distances between home address and offense locations.
Exploring the link between eating disorders and persistent genital arousal disorder/genito-pelvic dysesthesia: first description and a systematic review of the literature
Authors: Imgart Hartmut , Zanko Annika , Lorek Sandra , Schlichterle Patti-Sue , Zeiler Michael
Published: November 2022

Background

Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD) characterized by recurrent physiological genital without corresponding psychological arousal is a poorly understood and researched condition. Based on the first two case descriptions of eating disorders directly linked to PGAD/GPD the aim of this paper was to systematically review the literature on possible associations between eating disorders and PGAD/GPD.

Method

A systematic literature search on eating disorders and PGAD/GPD was conducted in PubMed, PsycINFO, and Scopus, complemented by Google Scholar. We included case reports, case series, cross-sectional studies and review articles published in peer-reviewed journals written in English or German-language.

Results

The included original papers described a total of 2078 cases with PGAD/GPD symptomatology. Of these, 892 participants fulfilled all five PGAD/GPD core criteria. The aetiology of PGAD/GPD is unknown. Multifactorial genesis of PGAD/GPD is presumed including neurological, pharmacological, hormonal, vascular and psychological causes. A high degree of psychological comorbidity is reported. No study was found that drew a direct link between eating disorders and PGAD/GPD. Although PGAD/GPD symptoms also occur in adolescents, there are no findings in this regard. However, we found a gap in data collection: eating disorders as potential psychiatric comorbidities were systematically recorded in only a few studies.

Conclusion

The existing literature have not yet considered a possible link between eating disorders and PGAD/GPD so far. According to the authors’ knowledge, this work is the first review to systematically explore the associations. We suspect underreporting of PGAD/GPD cases in eating disorders and particularly during adolescence. We argue that there are several common factors that appear to be important in the etiology, course, and treatment of both disorders (e.g. hormonal dysregulation or sensory sensitivity and avoidance), warranting future research on the possible comorbidity of these disorders.
Mechanisms by which adverse childhood experiences, other traumas and PTSD influence the health and well-being of individuals with eating disorders throughout the life span
Authors: Brewerton Timothy D.
Published: November 2022

Background

Multiple published sources from around the world have confirmed an association between an array of adverse childhood experiences (ACEs) and other traumatic events with eating disorders (EDs) and related adverse outcomes, including higher morbidity and mortality.

Methods

In keeping with this Special Issue’s goals, this narrative review focuses on the ACEs pyramid and its purported mechanisms through which child maltreatment and other forms of violence toward human beings influence the health and well-being of individuals who develop EDs throughout the life span. Relevant literature on posttraumatic stress disorder (PTSD) is highlighted when applicable.

Results

At every level of the pyramid, it is shown that EDs interact with each of these proclaimed escalating mechanisms in a bidirectional manner that contributes to the predisposition, precipitation and perpetuation of EDs and related medical and psychiatric comorbidities, which then predispose to early death. The levels and their interactions that are discussed include the contribution of generational embodiment (genetics) and historical trauma (epigenetics), social conditions and local context, the ACEs and other traumas themselves, the resultant disrupted neurodevelopment, subsequent social, emotional and cognitive impairment, the adoption of health risk behaviors, and the development of disease, disability and social problems, all resulting in premature mortality by means of fatal complications and/or suicide.

Conclusions

The implications of these cascading, evolving, and intertwined perspectives have important implications for the assessment and treatment of EDs using trauma-informed care and trauma-focused integrated treatment approaches. This overview offers multiple opportunities at every level for the palliation and prevention of EDs and other associated trauma-related conditions, including PTSD.
Analytical studies on medieval lead ingots from Wrocław and Kraków (Poland): a step towards understanding bulk trade of lead from Kraków and Silesia Upland Pb–Zn deposits
Authors: Miazga Beata , Duma Paweł , Cembrzyński Paweł , Matyszczak Milena , Piekalski Jerzy
Published: November 2022

Origins of medieval lead artefacts are hard to establish due to re-smelting and mixing. One can obtain conclusive evidence from ingots that served for bulk trade and originated directly from the mines. This paper aims to analyse the thirteenth century lead ingot from Wrocław (Poland). To establish its origins we analysed its structure and chemical composition. We used archaeometric methods: light and electron microscopic observations, X-ray fluorescence spectrometry, X-ray diffraction, infrared spectroscopy, inductively coupled plasma-optical emission spectrometry and Pb isotopic analysis. We compared our measurements with measurements of analogical ingot found on Kraków Market Square and a database of lead ores from Europe and the Middle East. The research indicated that both ingots originated from -Kraków and Silesia Upland Pb–Zn ore deposits (Poland), intensively mined from the twelfth century. The results complement the view of trade routes established based on written records and add valuable data for future comparative studies.
A comparative evaluation of the effects of seed invigoration treatments with precursor zinc salt and nano-sized zinc oxide (ZnO) particles on vegetative growth, grain yield, and quality characteristics of Zea mays
Authors: Tondey Manisha , Kalia Anu , Singh Alla , Abd-Elsalam Kamel , Hassan Montaser M. , Dheri Gurmeet Singh
Published: November 2022

Introduction

The zinc micronutrient fertilizers have a critical impact on the grain productivity and quality attributes of maize. However, the low use-efficiency issues of the applied Zn-fertilizers are required to be addressed through the development of novel formulations and alternative application techniques.

Objectives

This field study investigates the comparative impact of seed invigoration (including seed priming and coating) treatments with bulk zinc and ZnO nanoparticles (ZnONPs).

Methods

The two seed treatments with two different zinc sources at three different concentrations of 0, 20, and 40 mg L−1 each, for a total of ten treatments, were evaluated for vegetative growth, photosynthetic pigments, grain yield, and quality traits in Zea mays.

Results

The total chlorophyll content was improved by ZnONPs seed priming at the V8 stage. However, there were plants that grew tall, bearing longer ears with bulk ZnSO4 and the untreated control. Yield-contributing factors like number of seeds per cob, and 1000-grain weight were marginally improved by ZnONPs treatment. Overall, only cob weight, starch, total soluble protein, and soil nutrient (N, P, K, and Zn) content were significantly enhanced by ZnONPs treatment. Furthermore, no negative effect was recorded on the soil microbiological and enzymatic activities seed treatment with both the zinc sources.

Conclusion

The seed treatment, i.e. coating and priming with ZnONPs, did not significantly alter the grain yield, but the seed starch and total soluble protein content were improved.
Thermal decarboxylation of acidic cannabinoids in Cannabis species: identification of transformed cannabinoids by UHPLC-Q/TOF–MS
Authors: Seo Chaeyoung , Jeong Minsun , Lee Sangin , Kim Eun Jae , Rho Soohyang , Cho Mansoo , Lee Yong Sup , Hong Jongki
Published: November 2022

Decarboxylation of cannabidiolic acid (CBDA) is an important step for efficient production of the active pharmaceutical component cannabidiol (CBD) in Cannabis species. Acidic cannabinoids (ACBs) can be easily transformed into neutral cannabinoids via loss of carbon dioxide when exposed to heat. During the thermal process, several transformed products including psychotropic △9-tetrahydrocannabinol (△9-THC) and its isomers were produced through decarboxylation, hydration, isomerization, and oxidation, as identified by ultra-high-performance liquid chromatography quadrupole/time-of-flight mass spectrometry (UHPLC-Q/TOF MS). Their identification was carried out using authenticated standards and interpreting the MS/MS fragmentations. To investigate thermal decarboxylation, CBDA was extracted and isolated from inflorescence of Cannabis by ultrasonication extraction and two-step column chromatography. To investigate the decarboxylation yield of isolated CBDA and ACBs in Cannabis extract, samples were examined over a range of reaction temperatures (110–130 °C) and times (5–60 min). Time profiles of CBDA degradation and CBD formation were obtained as functions of the reaction temperature. In particular, most of the CBDA was converted into CBD at 130 °C for 20 min; this CBD was partially transformed to psychotropic THC isomers via cyclization. In addition to THC isomers, cannabielsoin acid (CBEA) and cannabielsoin (CBE) were also observed as minor oxidative transformed products. Based on structural identification and profiling data, thermal transformation pathways of CBDA are plausibly suggested. The results of decarboxylation of ACBs will provide important information on production of neutral cannabinoids, especially CBD, in Cannabis plants and quality control of Cannabis-based products in pharmaceutical and cosmetic industries.
Ovicidal and insecticidal effects of microbial pathogens against invasive Coconut Rugose spiralling whitefly (RSW), Aleurodicus rugioperculatus Martin and impact on their chrysopid predator Mallada boninensis (Okamoto)
Authors: Elango K. , Arun kumar N. , Dhanasekar V.
Published: November 2022

Background

The Rugose spiraling whitefly (RSW),Aleurodicus rugioperculatusMartin (Hemiptera: Aleyrodidae), has been reported as an invasive pest of coconut in different parts of peninsular India during 2016. It mainly caused damage to coconut palms, bananas, custard apples and other broad-leaved plants as hosts. Presently it is spread all over India and the coconut growing farmers are facing hard ships due to this infestation of RSW in coconut ecosystem. Still now the management of this invasive pest is fully based on the biological control, particularly with predators and parasitoids and the study on the microbial control of RSW was minimum. Hence, an attempt was made to study the ovicidal and insecticidal effects of microbial pathogens, viz.Isaria fumosoroseaWize,Beauveria bassiana(Balsamo) Vuillemi,Metarhizium anisopliae(Metschnikoff),Lecanicillium lecanii(Zimmerm.) with a spore load of 1 × 108 cfu against different life stages of RSW and their chrysopid predator,Mallada boninensis(Okamoto)(Neuroptera: Chrysopidae) under laboratory as well as field conditions.

Results

The results revealed that under laboratory conditions,I. fumosoroseacaused 34.54% egg mortality, 37.39% nymphal mortality and 48.30% adult mortality, followed byL. lecanii(24.54, 30.76 and 28.01%) andM. anisopliae(20.56, 32.51 and 42.92%) for egg, nymphal and adult mortality, respectively. Under field conditions,I. fumosoroseacaused (29.60%), followed byM. anisopliae(24.30%) andB. bassiana(21.00%) nymphal mortality, respectively, at 15 days after spray, also, it was found effective in reducing the RSW population on coconut. The impact of fungal entomopathogens against the predator revealed thatI. fumosoroseatreated eggs ofM. boninensisrecorded maximum 90.33% grub emergence than other treatments.

Conclusion

The present study concludes that the RSW can be controlled effectively byI. fumosoroseaalong with the chrysopid predator,M. boninensisunder field conditions as they showed maximum ovicidal and insecticidal actions against different life stages of RSW and safer to the major predator of RSW and fall under harmless category as per the classification of IOBC.
Treatment with biological therapy is associated with faster recovery and lower frequency of treatment switch among rheumatic patients with Chikungunya fever
Authors: Ranzolin Aline , Marques Claudia Diniz Lopes , da Rocha Junior Laurindo Ferreira , Duarte Angela Luzia Branco Pinto , de Lima Hugo Deleon , de Almeida Martins Lays Miranda , de Almeida Anderson Rodrigues , de Oliveira Priscilla Stela Santana , de Melo Rêgo Moacyr Jesus Barreto , da Rocha Pitta Maira Galdino , Bredemeier Markus , Laurindo Ieda Maria Magalhães
Published: November 2022

Background/Objective

The effects of Chikungunya virus (CHIKV) infection on patients with rheumatic diseases have not been extensively studied. Our aim was to compare the clinical course of patients with rheumatoid arthritis and spondyloarthritis, categorized according to the use or not of biologic disease modifying anti-rheumatic drugs (bDMARDs), during and after infection by CHIKV.

Methods

Patients from a northeastern Brazilian city that suffered an epidemic outbreak of Chikungunya fever (CHIK) between Oct 2015 and Jul 2016, on regular follow-up in a longitudinal registry of rheumatic patients (BiobadaBrasil), were invited to participate. Participants underwent a standardized clinical interview and collection of blood sample for serological tests (IgM/IgG) for CHIKV. A positive IgG was considered evidence of previous CHIKV infection.

Results

105 patients (84 with rheumatoid arthritis, 17 with ankylosing spondylitis, and 4 with psoriatic arthritis) were evaluated. Most patients (58, 55.2%) were on therapy with bDMARDs. The overall prevalence of seropositivity for CHIKV was 47.6% (39.7% in patients on bDMARDs and 57.4% in those exclusively on conventional synthetic (cs-) DMARDs (p = 0.070). Among seropositive patients, asymptomatic disease had similar frequency in those treated and not treated with bDMARDs (39.1% versus 33.3%, respectively; p = 0.670). However, patients exclusively on csDMARDs presented significantly higher prevalence of articular symptoms beyond 3 months and switched treatment more often than patients on bDMARDs (p < 0.05 for both comparisons).

Conclusions

Among rheumatic patients with CHIK, those on bDMARDs had shorter persistence of articular symptoms and switched treatment scheme less often than patients exclusively treated with csDMARDs.
Psychiatric morbidity and quality of life in infertile females: a cross-sectional, case-controlled hospital-based study
Authors: Dar Mansoor Ahmad , Shah Seema Batool , Ahmad Syed Nawaz , Shora Tajali Nazir , Kumari Pinki , Tailie Junaid Ahmad
Published: November 2022

Background

Infertility is a huge global problem with a significant mental health burden. Infertility could become a source of continuous stress leading to psychosocial issues including stress, anxiety, depression, and low self-esteem in these women. A cross-sectional, case-controlled study was conducted between January 2021 and November 2021 to study the effect of infertility on mental health and quality of life. A semi-structured questionnaire was used for sociodemographic and clinical variables. The Oslo Social Support Scale-3 and FertiQol were used to study social support and quality of life respectively. Psychiatric morbidity was assessed using ICD-10 symptom checklist. A total of 56 cases and 102 controls were studied.

Results

The mean age of cases and controls was 30.4 ± 3.5 years and 31.9 ± 2.9 years, respectively. Young infertile females, primary infertility, and female factor for infertility were associated with higher psychiatric morbidity. Psychiatric morbidity was seen in 46.4% of infertile women. FertiQoL score for the infertile group was 64.61 ± 5 with the lowest score in the emotional domain (45.10) and mind-body domain (54.86) (p < 0.0001). The scores in the relational domain and social domain were higher (85.2 and 73.3, respectively). The scores in the mind-body domain and emotional domain were poor among the infertile women regardless of the presence of psychiatric morbidity (48.27 vs 59.80 and 43.57 vs 46.57) (p < 0.0001–0.04).

Conclusions

Our study emphasizes the role of more qualitative instruments like FertiQoL in studying the well-being of infertile women. Even in the absence of psychiatric morbidity, the QoL score could still predict mental well-being in fertility-related issues.
Evaluation of molecular signatures in the urinary bladder and upper tract urothelial carcinomas: a prospective controlled clinical study
Authors: Dawood Eman E. , Awadalla Amira , Hashem Abdelwahab , Shokeir Ahmed A. , Abdel-Aziz A. F.
Published: November 2022

Background

Urothelial carcinomas (UC) can be either in the upper or in the lower urinary tract or both. Urothelial bladder cancer (UBC) is more common than upper tract urothelial carcinoma (UTUC). This research was designed to study the difference between UBC and UTUC using the molecular pathways including (MAPK/ERK) pathway, cell cycle regulating genes, and oncogenic genes.

Methods

To study the discrepancy between UBC and UTUC, a prospective trial was carried out for 31 radical cystectomy and 19 nephrouretrectomy fresh-frozen specimens of UBC and UTUC patients, respectively. The expression level of mRNA of eight genes namely EGFR, ELK1, c-fos, survivin, TP53, RB1, FGFR3, and hTERT was assessed in normal adjacent tissues, UTUC, and UBC by RT-PCR.

Results

Comparison between UTUC and UBC regarding the expression level of mRNA of the EGFR, ELK1, c-fos, survivin, TP53, and FGFR3 had significant difference (p-value < 0.001), while the expression level of RB1 and hTERT level had no significance. Sensitivity/specificity of EGFR, Elk1, c-fos, survivin, TP53, and FGFR3 was 0.78/0.90, 0.84/0.90, 0.84/0.80, 0.84/0.96, 0.94/0.93, and 0.89/0.93, respectively, to differentiate between UTUC and UBC.

Conclusions

Despite the fact that UTUC and UBC share the same origin, there is a clear evidence that there is a molecular difference between them. This molecular difference could be the reason that UTUC is more aggressive than UBC.
Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600–Mutant Low-Grade Glioma
Authors: Bouffet Eric , Geoerger Birgit , Moertel Christopher , Whitlock James A. , Aerts Isabelle , Hargrave Darren , Osterloh Lisa , Tan Eugene , Choi Jeea , Russo Mark , Fox Elizabeth
Published: November 2022

PURPOSE

BRAF V600 mutations occur in many childhood cancers, including approximately 20% of low-grade gliomas (LGGs). Here, we describe a phase I/II study establishing pediatric dosing and pharmacokinetics of trametinib with or without dabrafenib, as well as efficacy and safety in a disease-specific cohort with BRAF V600–mutant LGG; other cohorts will be reported elsewhere.

METHODS

This is a four-part, phase I/II study (ClinicalTrials.gov identifier: NCT02124772 ) in patients age < 18 years with relapsed/refractory malignancies: trametinib monotherapy dose finding (part A) and disease-specific expansion (part B), and dabrafenib + trametinib dose finding (part C) and disease-specific expansion (part D). The primary objective assessed in all patients in parts A and C was to determine pediatric dosing on the basis of steady-state pharmacokinetics. Disease-specific efficacy and safety (across parts A-D) were secondary objectives.

RESULTS

Overall, 139 patients received trametinib (n = 91) or dabrafenib + trametinib (n = 48). Trametinib dose-limiting toxicities in > 1 patient (part A) included mucosal inflammation (n = 3) and hyponatremia (n = 2). There were no dose-limiting toxicities with combination therapy (part C). The recommended phase II dose of trametinib, with or without dabrafenib, was 0.032 mg/kg once daily for patients age < 6 years and 0.025 mg/kg once daily for patients age ≥ 6 years; dabrafenib dosing in the combination was as previously identified for monotherapy. In 49 patients with BRAF V600–mutant glioma (LGG, n = 47) across all four study parts, independently assessed objective response rates were 15% (95% CI, 1.9 to 45.4) for monotherapy (n = 13) and 25% (95% CI, 12.1 to 42.2) for combination (n = 36). Adverse event–related treatment discontinuations were more common with monotherapy (54% v 22%).

CONCLUSION

The trial design provided efficient evaluation of pediatric dosing, safety, and efficacy of single-agent and combination targeted therapy. Age-based and weight-based dosing of trametinib with or without dabrafenib achieved target concentrations with manageable safety and demonstrated clinical efficacy and tolerability in BRAF V600–mutant LGG.
Clinical Impact of ASCO Choosing Wisely Guidelines on Staging Imaging for Early-Stage Breast Cancers: A Time Series Analysis Using SEER-Medicare Data
Authors: Baltz Alan P. , Siegel Eric R. , Kamal Arif H. , Siegel Robert , Kozlik Mary May , Crist Stéphanie T. S. , Makhoul Issam ,   on behalf of the ASCO Quality Publications Task Force
Published: November 2022

PURPOSE:

American Society for Clinical Oncology released the Choosing Wisely list in 2012, highlighting low-value procedures that lack evidence, advising against the use of positron emission tomography, computerized tomography, and radionuclide bone scans for the staging of early-stage breast cancer at low risk for metastasis. The objective of the study was to assess the impact of the American Society of Clinical Oncology Choosing Wisely guidelines on inappropriate staging imaging among early-stage breast cancers.

METHODS:

The Surveillance, Epidemiology, and End Results Program-Medicare data set was used to identify 50,004 women age 66 years and older with new incident diagnosis of early-stage breast cancer (stage 0 through stage 2a; T < 4, N = 0, and M = 0). The primary outcome was the incidence of patients with inappropriate imaging following an early-stage breast cancer diagnosis. The primary outcome was identified within 6 months of the first diagnosis. An interrupted time series analysis using negative binomial regression was performed for outpatient claims for these diagnostic studies versus the two interruptions of guidelines release and guidelines reinforcement. Mean images per patient, percent change for the study period, and rate of change per year were calculated.

RESULTS:

Imaging rates fell by a modest 2.32% following guidelines release in April 2012 (point estimate = −2.32%; 95% CI, −6.34% to 1.88%). By contrast, imaging rates fell by a four-fold larger amount (point estimate = −9.36%; 95% CI, −13.20% to −5.35%) following guidelines published reminders in journals (or reinforcement) in October 2013. Mean imaging studies per patient (95% CI) declined from 1.80 (1.76 to 1.84) in January 2012 to 1.50 (1.48 to 1.53) by January 2015, representing a 16% decline in imaging overuse in 2015 compared with 3 years earlier. The rate of change (95% CI) in images per patient was initially small at −0.47% (−4.27% to 3.33%) per year between April 2012 and October 2013, but almost eight times faster at −3.70% (−5.81% to −1.60%) per year after October 2013.

CONCLUSION:

This analysis demonstrates a substantial decrease in the prevalence of imaging overuse in early-stage breast cancers correlating with the 2013 reinforcement of American Society of Clinical Oncology's 2012 Choosing Wisely guidelines. The creation and dissemination of such resources serves as a powerful tool to improve clinical practice, cost-effectiveness, and patient safety from secondary malignancies, anxiety, and overdiagnosis.
Statistics of phase fluctuations of an acoustic wave propagating through a turbulent flow
Authors: Prabhudesai G. , Perrard S. , Pétrélis F. , Fauve S.
Published: November 2022

We investigate the statistics of phase fluctuations of an acoustic wave propagating through a turbulent flow in line of sight (LOS) configuration. Experiments are performed on a closed von Kármán swirling flow whose boundaries are maintained at a constant temperature. In particular, we analyze the root mean square (RMS) and the power spectrum density (PSD) of phase fluctuations. A model is developed and analytical predictions obtained for these quantities using geometrical acoustics are shown to be in agreement with experimental observations.
Sinicizing European Languages: Lexicographical and Literary Practices of Pidgin English in Nineteenth-Century China
Authors: Liu Yuqing
Published: November 2022

This article reconsiders the social, economic, and literary significance of Chinese Pidgin English (CPE) in Chinese society by exploring lexicographical and literary practices of pidgin in nineteenth-century China. Resituating the history of CPE in Chinese language history, this article problematizes the concept of pidgin and pursues three arguments. First, the author maintains that CPE arose from the marginalized status of the Euro-American traders who were restricted from learning the Chinese language in Canton. Second, by exploring foreign-language glossaries, this article foregrounds the key role of sinographs and Chinese topolects in mediating and remolding foreign languages. Last, by examining the appropriation of foreign sounds in Cantonese folk songs and Pan Youdu's poetry, this article demonstrates the complex flow of these sounds among different languages and the power of pidgin in transgressing linguistic boundaries.
Localism of Daoxue in North China during the Yuan Dynasty: A Case Study of An Xi (1270–1311)
Authors: Koh Khee Heong
Published: November 2022

The transmission of Daoxue, or Neo-Confucianism, during the Yuan Dynasty cannot be understood as a sharp dichotomy between reliance on state-sponsored institutions in North China and private ones in the south. Through the study of An Xi, who was a student and teacher of Daoxue, and his family from modern day Hebei, this article shows that private intellectual activities of Yuan Daoxue masters were influential locally in the north. Although An Xi has traditionally been recognized as a member of the Daoxue scholar Liu Yin's tradition, this article further argues that An Xi developed his own independent thinking and was not simply a follower of Liu Yin. An Xi was a self-taught Daoxue master who idolized Zhu Xi and took his teaching as the only standard. This self-taught model would later become more common in North China during the Ming Dynasty.
Ts66Yah, a mouse model of Down syndrome with improved construct and face validity
Authors: Duchon Arnaud , del Mar Muñiz Moreno Maria , Chevalier Claire , Nalesso Valérie , Andre Philippe , Fructuoso-Castellar Marta , Mondino Mary , Po Chrystelle , Noblet Vincent , Birling Marie-Christine , Potier Marie-Claude , Herault Yann
Published: November 2022

Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21). The understanding of genotype–phenotype relationships, the identification of driver genes and various proofs of concept for therapeutics have benefited from mouse models. The premier model, named Ts(1716)65Dn/J (Ts65Dn), displayed phenotypes related to human DS features. It carries an additional minichromosome with the Mir155 to Zbtb21 region of mouse chromosome 16, homologous to Hsa21, encompassing around 90 genes, fused to the centromeric part of mouse chromosome 17 from Pisd-ps2/Scaf8 to Pde10a, containing 46 genes not related to Hsa21. Here, we report the investigation of a new model, Ts66Yah, generated by CRISPR/Cas9 without the genomic region unrelated to Hsa21 on the minichromosome. As expected, Ts66Yah replicated DS cognitive features. However, certain phenotypes related to increased activity, spatial learning and molecular signatures were changed, suggesting genetic interactions between the Mir155-Zbtb21 and Scaf8-Pde10a intervals. Thus, Ts66Yah mice have stronger construct and face validity than Ts65Dn mice for mimicking consequences of DS genetic overdosage. Furthermore, this study is the first to demonstrate genetic interactions between triplicated regions homologous to Hsa21 and others unrelated to Hsa21.

This article has an associated First Person interview with the first author of the paper.
17q12 deletion syndrome mouse model shows defects in craniofacial, brain and kidney development, and glucose homeostasis
Authors: Warren Emily B. , Briano Juan A. , Ellegood Jacob , DeYoung Taylor , Lerch Jason P. , Morrow Eric M.
Published: November 2022

17q12 deletion (17q12Del) syndrome is a copy number variant (CNV) disorder associated with neurodevelopmental disorders and renal cysts and diabetes syndrome (RCAD). Using CRISPR/Cas9 genome editing, we generated a mouse model of 17q12Del syndrome on both inbred (C57BL/6N) and outbred (CD-1) genetic backgrounds. On C57BL/6N, the 17q12Del mice had severe head development defects, potentially mediated by haploinsufficiency of Lhx1, a gene within the interval that controls head development. Phenotypes included brain malformations, particularly disruption of the telencephalon and craniofacial defects. On the CD-1 background, the 17q12Del mice survived to adulthood and showed milder craniofacial and brain abnormalities. We report postnatal brain defects using automated magnetic resonance imaging-based morphometry. In addition, we demonstrate renal and blood glucose abnormalities relevant to RCAD. On both genetic backgrounds, we found sex-specific presentations, with male 17q12Del mice exhibiting higher penetrance and more severe phenotypes. Results from these experiments pinpoint specific developmental defects and pathways that guide clinical studies and a mechanistic understanding of the human 17q12Del syndrome. This mouse mutant represents the first and only experimental model to date for the 17q12 CNV disorder.

This article has an associated First Person interview with the first author of the paper.
Reporting Attendance and Resistance Exercise Compliance in Men with Localized Prostate Cancer
Authors: LOPEZ PEDRO , TAAFFE DENNIS R. , NEWTON ROBERT U. , SPRY NIGEL , JOSEPH DAVID , TANG COLIN , BUFFART LAURIEN M. , GALVÃO DANIEL A.
Published: November 2022

Purpose

Resistance exercise is a well-established intervention to counteract musculoskeletal and metabolic toxicities from prostate cancer treatment. In this study, we reported resistance exercise attendance and compliance, and examined if these variables can influence changes in outcomes of interest in men with localized or locally advanced prostate cancer.

Methods

A total of 83 prostate cancer patients (age, 68.2 ± 7.0 yr; body mass index, 27.7 ± 3.8 kg·m−2) who had undergone 6 months of resistance-based exercise and had data available on exercise training from logbook records were examined. Attendance outcomes such as missed sessions, interruptions and permanent discontinuation, and metrics such as dosage completed (sessions × number of exercises × sets × repetitions × external load), compliance, tolerance, reductions, and escalations were assessed. Outcomes assessed were body composition, physical function, and muscle strength.

Results

Median resistance exercise attendance was 80.6%, with a median resistance exercise compliance of 88.5% (interquartile range [IQR], 61.1%–107.1%) per participant. A median of 11 (IQR, 1–26) and 0 (IQR, 0–2) sessions were escalated or reduced, respectively. Significant improvements were observed in whole-body lean mass, 400-m walk, repeated chair rise, leg press, and chest press strength after 6 months of intervention (P < 0.05) regardless of resistance exercise compliance (P
trend = 0.199–0.950). Participants with higher levels of resistance exercise compliance presented greater improvements in trunk fat mass (P
trend = 0.026) and appendicular lean mass (P
trend = 0.047).

Conclusions

A higher resistance exercise compliance led to greater improvements in regional fat and lean mass, whereas physical function and muscle strength improvements were achieved with lower compliance. In addition, patients experienced a high number of dose escalations during the intervention. These findings are important to improve the reproducibility/precision of exercise medicine prescription.
Drivers of site productivity for oak in Poland
Authors: Xo Viet Hoang Duong , Tymińska-Czabańska Luiza , Socha Jarosław
Published: November 2022

The site index (SI) is the most commonly used and representative measure of the phytocentric approach; it evaluates the site productivity based on the stand height and age. In the case of mixed stands with complex structures, phytocentric methods are very limited, while in non-forest areas, they are not ap­plicable. In situations where the applicability of phytocentric methods is limited, the site productivity is de­termined by geocentric methods. Geocentric methods allow direct modelling of site productivity, expressed by SI predicted from various environmental variables. The aim of this study was to develop a geocentric model for oak. Site productivity expressed by SI was described by the environmental variables and stand characteristics. To develop the SI model, we used the data from 2490 NFI plots with dominant oak species (Quercus sessilis and Quercus robur). A generalized additive model was used in modelling site productivity. We documented a significant relationship between SI and the environmental variables, age of stands and stand density. Furthermore, the site productivity for oak is shaped by climate factors, soil type, geology, and altitude. The model developed based on the geocentric method, explained 55.1% of the variation of SI