bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise combined with vitamin D supplementation has additive health effects on short physical performance battery and stair climbing in older adults: a scope review of randomised controlled trials
Authors: Zhang Jinghua , Zhu Zheng , Niu YanJun , Cao Zhen-Bo
Published: November 2024

This scoping review aimed to evaluate the effect of exercise combined with vitamin D supplementation on skeletal muscle health in older individuals. We implemented a systematic search of electronic databases, including PubMed, the Cochrane Library, Web of Science and Embase, which was conducted from the time of library construction to January 2024. Eligible studies were randomised controlled trials including men and women aged ≥ 65 years or mean age ≥ 65 years; exercise training and vitamin D supplementation; outcomes of muscular strength, function, muscular power, body composition and quality of life; and results compared with those of exercise intervention alone. The results showed thirteen studies including 1483 participants were identified. The proportions of male and female sex were 22·05 and 77·95 %, respectively. Exercise intervention methods included resistance exercises and multimodal exercise training. All vitamin D interventions involved supplementation with vitamin D3. A significant increase was identified in short physical performance battery and stair climbing but not in skeletal muscle mass, skeletal strength, the timed up and go test and gait speed in older adults after exercise combined with vitamin D supplementation. In conclusion, exercise combined with vitamin D supplementation has additive health effects on short physical performance battery and stair climbing. Furthermore, when vitamin D was deficient at baseline, the combined effect of exercise and vitamin D intervention significantly increased the timed up and go test and gait speed in older adults. In future randomised controlled trials on this topic, baseline vitamin D nutritional status, health condition and sex should be considered.
Concentration, motivation, activity, and subjective fatigue in patients with single-sided deafness
Authors: Gürses Emre , Kılıç Samet , Çıldır Bünyamin
Published: November 2024

Objective

To evaluate four dimensions of fatigue, including subjective fatigue severity, concentration problems, reduced motivation, and activity in patients with single-sided deafness.

Methods

Following audiological assessment, the Checklist Individual Strength scale and Montreal Cognitive Assessment were performed on 41 adults with single-sided deafness and 41 sex-matched adults with normal bilateral hearing in the study group and control group, respectively. Subjective fatigue severity, concentration, motivation, activity level and cognitive performance were analysed between and within groups.

Results

Individuals with single-sided deafness exhibited reduced concentration and motivation; however, their activity level was average. Subjective fatigue symptoms were more prevalent in individuals with single-sided deafness than in control participants. The concentration problem was related to decreased cognitive performance.

Conclusion

This study revealed negative somatic consequences of single-sided deafness. Self-perceived fatigue is likely underestimated in this population due to the limited studies reported in the literature. Further studies should focus on counselling, follow up and hearing rehabilitation concerning ameliorating fatigue.
Effects of time-restricted eating on body composition, biomarkers of metabolism, inflammation, circadian system and oxidative stress in overweight and obesity: an exploratory review
Authors: Lages Marlene , Carmo-Silva Sara , Barros Renata , Guarino Maria Pedro
Published: November 2024

Obesity is a chronic, complex and multi-factorial condition with an increasing prevalence worldwide. Irregular eating schedules might be a contributing factor to these numbers through the dysregulation of the circadian system. Time-restricted eating (TRE), an approach that limits eating windows, has been studied as a strategy to treat obesity, aligning eating occasions with metabolic circadian rhythms. This review aims to provide an overview of the impact of TRE protocols on metabolic, inflammatory, oxidative stress and circadian rhythm biomarkers in people with overweight or obesity. Most studies report significant weight loss following TRE protocols. While glucose levels decreased in nearly all TRE interventions, only a few studies demonstrated statistically significant differences when compared to the control groups. The findings for c-reactive protein and TNF-α were inconsistent, with limited significant differences. Changes in lipid profile changes were variable and generally did not reach statistical significance. Both 4-hour and 6-hour TRE interventions significantly reduced 8-isoprostane levels. Additionally, TRE significantly altered clock gene expression, as well as that of genes associated with metabolic regulation in subcutaneous adipose tissue. While the evidence is still inconsistent, limiting eating to a consistent daily window of 8 to 12 h can improve insulin sensitivity, reduce blood glucose, cholesterol and triglyceride levels and promote weight loss. These effects are likely attributable to both direct metabolic impacts and indirect benefits from weight loss and improved dietary habits. However, data on circadian, inflammatory and specific metabolic biomarkers remain scarce and occasionally contradictory, highlighting the need for further research on these interventions.
Haemoparasite infection risk in multi-host avian system: an integrated analysis
Authors: Podmokła Edyta , Dubiec Anna , Pluciński Bartosz , Zając Bartłomiej , Gustafsson Lars
Published: November 2024

Avian blood parasites play a crucial role in wildlife health and ecosystem dynamics, exhibiting heterogeneous spatial distribution influenced by various factors. Although factors underlying heterogeneity in infection with blood parasites have been explored in many avian hosts, their importance in the context of host species and the parasite taxon remains poorly understood, particularly in cohabiting host species. Using next-generation sequencing for parasite screening, we investigate the association between Haemoproteus, Plasmodium and Trypanosoma infections in relation to individual parameters, host densities and landscape features in 3 cavity-nesting passerines: great tit (Parus major), blue tit (Cyanistes caeruleus) and collared flycatcher (Ficedula albicollis) in a highly fragmented forest habitat. Overall, Haemoproteus infections predominated, followed by Plasmodium and Trypanosoma, with great tits most and collared flycatchers least parasitized. There were no common patterns across host species in the probability of infection with locally transmitted parasites from each genus. Specifically, in all cases, the effect of particular parameters, if present, was observed only in 1 host species. Body condition influenced Haemoproteus and Plasmodium infections differently in tits. Host density, whether own species or all pooled, explained Haemoproteus infections in great tits and collared flycatchers, and Plasmodium in great tits. Landscape metrics, such as moisture index and distance to coast edge and pastures, affected infection probability in specific host–parasite combinations. Relative risk maps revealed infection risk gradients, but spatial variation repeatability over time was low. Our study highlights the complex dynamics of avian blood parasites in multi-host systems, shedding light on host–parasite interactions in natural ecosystems.
Taxonomy and systematics of Emprostiotrema Cianferoni and Ceccolini, 2021 (Digenea: Emprostiotrematidae), parasites of rabbitfish (Siganidae) from the Indo-West Pacific marine region
Authors: Huston Daniel C. , Cutmore Scott C. , Cribb Thomas H. , Sasal Pierre , Yong Russell Q.-Y.
Published: November 2024

Emprostiotrema contains just 3 species: E. fusum, E. kuntzi and E. sigani. As adults, all 3 species infect rabbitfishes (Siganidae: Siganus). New collections from 11 species of Siganus from northern Australia, Indonesia, New Caledonia, French Polynesia, Palau and Japan enabled an exploration of species composition within this genus. Phylogenetic analyses demonstrate a deep distinction between 2 major clades; clade 1 comprises most of the sequences of specimens from Australia as well as all of those from Japan, Palau and New Caledonia and clade 2 comprises all sequences of specimens from French Polynesia, 2 sequences from Australia and the single sequence from Bali. In all analyses, both major clades have genetic structuring leading to distinct geographic lineages. Morphologically, specimens relating to clades 1 and 2 differ but overlap in body shape, oral sucker and egg size. Principle component analysis shows a general (but not complete) separation between specimens relating to the 2 clades. We interpret the 2 clades as representing 2 species: clade 1 is identified as E. fusum and is reported in this study from 10 species of siganids from Australia, Japan, Palau and New Caledonia; clade 2 is described as E. gotozakiorum n. sp., for all specimens from French Polynesia and rare specimens from Australia and Indonesia. We recognize E. sigani as a junior synonym of E. fusum. Although species of Emprostiotrema occur widely in the tropical Indo-Pacific, they have not been detected from Ningaloo Reef (Western Australia), the southern Great Barrier Reef or Moreton Bay (southern Queensland).
Examining the mental health trajectories of children and adolescents: a cross-cohort analysis
Authors: McNicholas Fiona , Gavin Blanaid , Sellers Ruth , Ji Iris , Zhang Xiaoning , Browne Wendy V , Harold Gordon
Published: November 2024

Background

Epidemiological samples provide opportunity to understand the development of mental health trajectories to better understand whether such epidemiological data can help to plan and modify service delivery for youth mental health. Variation between countries is not well understood and thus applying evidence from other countries to national strategies limits support service policy and planning. We therefore examine developmental patterns of youth mental health across different countries using the Growing Up in Ireland (GUI) Cohorts, with comparison to existing UK longitudinal cohort data (Millennium Cohort Study, MCS; Growing up in Scotland, GUS).

Methods

Youth mental health problems within each cohort across development (5–17/18 years) were assessed using parent reported Strengths and Difficulties Questionnaire (SDQ) scores. Using latent growth curve analyses, we examined trajectories of emotional, conduct, and hyperactivity problems for boys and girls, separately for each cohort.

Results

Across cohorts, we observed similar developmental patterns for emotional, conduct, and hyperactivity problems. However, the GUI emotional problems in Ireland emerged earlier than in the UK. By adolescence, GUI emotional scores were similar to the UK, suggesting that the differences in emotional problems between the ROI and UK had narrowed by adolescence. Covariates also had different associations with youth mental health trajectories across cohorts.

Conclusions

Utilizing multiple nationally representative cohort longitudinal datasets can help inform clinically meaningful conclusions and potential recommendations on population level multi-tiered service needs and development in the area of child and adolescent mental health support and future provision.
Recruiting Places: Pearl Primus's Plans for Global Activism through Community-Engaged Dance Theatre
Authors: Friedman Jessica
Published: November 2024

In the summer of 1944, Black modern dancer Pearl Primus searched for authenticity. Over the past year, she had achieved critical success for her modern dance choreography that protested racial injustice in the South, informed by a leftist political mission. However, she thought something was missing. She explained to Dance Magazine, “I had done dances about sharecroppers and lynchings without ever having been close to such things.” In search of that missing component, Primus traveled from New York City, her home since she was a toddler, to the US South. A budding anthropologist, she went to live among Southern communities as a way to retool her protest choreography and make it more authentic. Unbeknownst to them, Southern community members would be recruited by her to provide inspiration for her performances and the leftist political stance that fueled those works. In identifying authentic expressive practices of the South through her anthropological practice, transferring what she found to her choreography, and then performing that repertoire on New York stages, she would further develop her ability to instill in Northern audiences the necessity of leftist activism.
Ketamine for the Treatment of Psychiatric Disorders: A Systematic Review and Meta-Analysis
Authors: Kwan Angela T.H. , Lakhani Moiz , Singh Gurkaran , Le Gia Han , Wong Sabrina , Teopiz Kayla M. , Dev Donovan A. , Manku Arshpreet Singh , Sidhu Gurnoor , McIntyre Roger S.
Published: November 2024

Background

Inadequate response to first- and second-line pharmacological treatments for psychiatric disorders is commonly observed. Ketamine has demonstrated efficacy in treating adults with treatment-resistant depression (TRD), with additional off-label benefits reported for various psychiatric disorders. Herein, we performed a systematic review and meta-analysis to examine the therapeutic applications of ketamine across multiple mental disorders, excluding mood disorders.

Methods

We conducted a multidatabase literature search of randomized controlled trials and open-label trials investigating the therapeutic use of ketamine in treating mental disorders. Studies utilizing the same psychological assessments for a given disorder were pooled using the generic inverse variance method to generate a pooled estimated mean difference.

Results

The search in OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), EBSCO CINAHL Plus, Scopus, and Web of Science yielded 44 studies. Ketamine had a statistically significant effect on PTSD Checklist for DSM-5 (PCL-5) scores (pooled estimate = ‒28.07, 95% CI = [‒40.05, ‒16.11], p < 0.001), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores (pooled estimate = ‒14.07, 95% CI = [‒26.24, ‒1.90], p = 0.023), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (pooled estimate = ‒8.08, 95% CI = [‒13.64, ‒2.52], p = 0.004) in individuals with PTSD, treatment-resistant PTSD (TR-PTSD), and obsessive compulsive disorder (OCD), respectively. For alcohol use disorders and at-risk drinking, there was disproportionate reporting of decreased urge to drink, increased rate of abstinence, and longer time to relapse following ketamine treatment.

Conclusions

Extant literature supports the potential use of ketamine for the treatment of PTSD, OCD, and alcohol use disorders with significant improvement of patient symptoms. However, the limited number of randomized controlled trials underscores the need to further investigate the short- and long-term benefits and risks of ketamine for the treatment of psychiatric disorders.
Ayahuasca: pharmacology, safety, and therapeutic effects
Authors: dos Santos Rafael Guimarães , Hallak Jaime Eduardo Cecilio
Published: November 2024

Ayahuasca is a botanical hallucinogen traditionally used for therapeutic and ritual purposes by indigenous groups from Northwestern Amazonian countries such as Brazil, Peru, Colombia, and Ecuador. Ayahuasca is made by the decoction of two plants, which are rich in the 5-HT1A/2A partial agonist dimethyltryptamine or DMT (from the leaves of the Psychotria viridis bush) and β-carbolines such as harmine, from the stalks of the Banisteriopsis caapi vine. There is an increasing interest in the possible therapeutic effects of ayahuasca, especially for psychiatric disorders (major depression, posttraumatic stress disorder, and substance use disorder). This review summarizes information on the pharmacology, safety, and therapeutic potentials of ayahuasca. Although human experimental and naturalist studies published until now suggest a good safety and tolerability profile, often associated with improvements in depressive and anxious symptoms, there are few controlled studies, with small sample sizes, using only single doses, and with short follow-ups. Potential benefits of ayahuasca should be evaluated in larger samples in both experimental and observational studies and using different doses in controlled trials.
The impact of COVID-19 on referrals among general practitioners and specialists in Shanghai, China
Authors: Xu Zhongqing , Fan Jingchun , Shi Dandan , Ding Jingjing , Zhou Jun , Feng Xianzhen , Hambly Brett D. , Tao Kun , Bao Shisan
Published: November 2024

Background:

The COVID-19 pandemic has impacted patient’s visits to general practitioners (GPs). However, it is unclear what the impact of COVID-19 has been on the interaction among the local primary care clinics, the GP Department within the hospital and specialists.

Methods:

The interaction among GPs referring to hospital-based specialists and specialists to local doctors was determined, comparing pre-pandemic 2019 and 2020 during the pandemic.

Results:

Reduced referrals from GPs to specialists were consistent with the reduction in specialist referrals back to the local doctors, which dropped by approximately 50% in 2020, particularly in the two most common chronic conditions (hypertension and diabetes mellitus).

Discussion:

Reduced referral of patients from local clinics to Tongren Hospital is probably due to the extensive online training provided to the local GPs to become more competent in handling local patients via telehealth. Our data provide some insight to assist in combatting the pandemic of COVID-19, offering objective evidence of the impact of COVID-19 on patient management by GPs.
Stigma in Mexican patients with Lung Cancer: Psychometric Properties of the Cataldo Lung Cancer Stigma Scale (CLCSS) - Brief version
Authors: Flores-Juárez Joel , Galindo-Vázquez Oscar , Ortega-Andeane Patricia , Fresán-Orellana Ana , Montero-Pardo Xolyanetzin , Estapé Tania , Arroyo-Hernández Marisol , Cabrera-Miranda Luis Antonio , Arrieta Oscar
Published: November 2024

Introduction

Stigma in lung cancer patients may be associated with various negative outcomes such as increased psychosocial symptoms, severity of physical symptoms, and may act as a barrier to medical help-seeking behavior. The Cataldo Lung Cancer Stigma Scale (CLCSS) is one of the most widely used instruments for assessing health-related stigma in lung cancer patients.

Objectives

To determine the psychometric properties of the CLCSS in a Mexican sample of lung cancer patients.

Methods

A non-experimental, instrumental design was employed, using non-probabilistic sampling based on availability. The sample included 265 lung cancer patients. Confirmatory Factor Analysis (CFA) was conducted to assess construct validity, and Cronbach’s alpha and McDonald’s Omega were used for internal consistency and test-retest reliability, respectively, through Pearson correlation coefficient.

Results

The 17-item version yielded a model with 4 factors (stigma and shame, social isolation, discrimination, and smoking) explaining 50.74% of the variance, with adequate values of internal consistency and test-retest reliability.

Significance of results

The Mexican version of the CLCSS is culturally appropriate, brief, psychometrically valid, and reliable for assessing health-related stigma in Mexican lung cancer patients.
Unexpected Warming From Land Radiative Management
Authors: Cheng Yu , McColl Kaighin A.
Published: November 2024

“Land radiative management” (LRM)—deliberately increasing surface albedo to decrease temperatures—has been proposed as a form of geoengineering to mitigate the effects of regional warming. Here, we show that, contrary to expectations, LRM causes temperatures to increase in surrounding regions. The basic reason for the increase is unintended impacts on precipitation. Precipitation is suppressed over the LRM region, but this effect also extends to nearby areas unprotected by LRM. The reduction in precipitation and soil moisture in these regions leads to higher temperatures than would be expected in the absence of LRM. The resulting warming outside the LRM region is comparable to the cooling achieved inside it. This implies that, if wealthy regions unilaterally adopt LRM to cool, their neighbors may experience warming, worsening heat inequality.
Direction Finding Studies of Simultaneous Auroral 2fce and 3fce Roar Cyclotron Harmonic Radio Emissions
Authors: Godfrey T. M. , LaBelle J.
Published: November 2024

Auroral roar originates in Earth's ionosphere at altitudes of several hundred kilometers where the upper hybrid frequency matches a harmonic of the electron gyrofrequency. These radio emissions are important for remote sensing of ionospheric plasma conditions and processes, and their physics is similar to that of astrophysical radio emissions. In this study, direction finding was used to establish the distribution of direction of arrival (DOA) angles for the third harmonic emissions and to compare the direction angles of second harmonic and events when they occur simultaneously. Data were collected for 42 events from 9 May 2022 to 20 May 2023 by a three antenna array in Toolik Lake, AK (68.6°N, 149.6°W, 68.5° magnetic latitude) with a DOA distribution centered overhead. 30% of the events coming from the south, for which azimuth deviations due to refraction are less significant, were on the same azimuth within 10°, the uncertainty of the measurement. This is a lower bound on the fraction of simultaneous harmonic and emissions that come from the same auroral arc. All events coming from the south that had a and azimuth angle of arrival within 10° had a higher elevation than elevation within experimental uncertainty, supporting the mechanism by which these emissions are excited at the “double resonance” points on the bottomside of the ionosphere.
iFLOW: A Framework and GUI to Quantify Effective Thermal Diffusivity and Advection in Permeable Materials From Temperature Time Series
Authors: Bertagnoli A. , Luce C. , van Kampen R. , Schneidewind U. , van Berkel M. , Tranmer A. W. , Vandersteen G. , Krause S. , Tonina D.
Published: November 2024

iFLOW is a free, open‐source, and python‐based framework and graphical user interface to visualize and analyze temperature time series, and extract one dimensional thermal velocity, vT, and bulk effective thermal diffusivity, ke. Information of thermal properties of the sediment‐water mixture (bulk) and water allows quantifying the one‐dimensional Darcian flux, q, and seepage velocity, v, from vT. Available software packages were developed to quantify q and ke only based on a specific mathematical model or focused on specific data processing or parameter estimation techniques, and all these steps were lumped together preventing users to identify potential source of errors. iFLOW proposes a novel organizational philosophy with a modular framework that parses the analysis process into three fundamental steps: (a) the mathematical model, (b) signal processing, and (c) parameter estimation. iFLOW houses a suite of models and analysis techniques. This suite can be readily added to and expanded through its modular framework. iFLOW contains a wizard to guide users through the selection process with respect to the three fundamental steps. Users can analyze and visualize intermediate results to identify problematic issues in the time series data and improve data interpretation. Here, we present iFLOW and summarize its performance using a set of one‐dimensional synthetic heat transport simulations.
Genetic contributions to body mass index over adolescence and its associations with adult weight gain: a 25-year follow-up study of Finnish twins
Authors: Obeso Alvaro , Drouard Gabin , Jelenkovic Aline , Aaltonen Sari , Palviainen Teemu , Salvatore Jessica E. , Dick Danielle M. , Kaprio Jaakko , Silventoinen Karri
Published: November 2024

Introduction

High body mass index (BMI) in adolescence is a strong predictor of adult obesity. However, the nature of this association is unclear. We investigated how adolescent BMI is associated with adult weight change using longitudinal data from ages 11.5 to 37 years and examined the genetic factors behind these associations.

Data and Methods

The study cohort consisted of 1400 Finnish twin individuals (40% males) with 494 complete twin pairs who reported their body mass index (BMI) at five ages: 11.5, 14, 17.5, 24, and 37 years. BMI trajectories (defined as BMI changes (i.e., slope) and BMI at baseline age (i.e., intercept)) were calculated in adulthood (from 17.5 to 37 years of age) using linear mixed-effects models. Polygenic Risk Scores of BMI (PRSBMI) and genetic twin models were utilised to analyse the role of genetic factors underlying BMI trajectories and their associations with BMI at 11.5 and 14 years of age.

Results

Mean BMI increased in adulthood (4.06 kg/m2 in men and 3.39 kg/m2 in women). The BMI changes correlated with BMI at the baseline age of 17.5 years (i.e. intercept) (r = 0.24 in men and r = 0.35 in women) as well as with BMI in adolescence (11.5 and 14 years of age). Genetic factors contributed to the BMI changes during adulthood (correlation with PRSBMI
r = 0.25 in men and r = 0.27 in women; heritability estimates 0.63 and 0.64 respectively) as well as to their correlations with BMI at the baseline age (r
A = 0.5 in men and 0.54 in women) and BMI during adolescence (at 11.5 and 14 years of age) (r
A = 0.63–0.64).

Conclusion

We found that genetic factors play a role in BMI change in adulthood, and part of this genetic component overlaps with the genetics of BMI in adolescence. Genetic predisposition to high BMI in adolescence is also related to adult weight gain.
Breathing new insights into the role of mutant p53 in lung cancer
Authors: Chen Tianwei , Ashwood Lauren M. , Kondrashova Olga , Strasser Andreas , Kelly Gemma , Sutherland Kate D.
Published: November 2024

The tumour suppressor gene p53 is one of the most frequently mutated genes in lung cancer and these defects are associated with poor prognosis, albeit some debate exists in the lung cancer field. Despite extensive research, the exact mechanisms by which mutant p53 proteins promote the development and sustained expansion of cancer remain unclear. This review will discuss the cellular responses controlled by p53 that contribute to tumour suppression, p53 mutant lung cancer mouse models and characterisation of p53 mutant lung cancer. Furthermore, we discuss potential approaches of targeting mutant p53 for the treatment of lung cancer.
Polyol pathway-generated fructose is indispensable for growth and survival of non-small cell lung cancer
Authors: Schwab Annemarie , Siddiqui Mohammad Aarif , Ramesh Vignesh , Gollavilli Paradesi Naidu , Turtos Adriana Martinez , Møller Sarah Søgaard , Pinna Luisa , Havelund Jesper F. , Rømer Anne Mette A. , Ersan Pelin Gülizar , Parma Beatrice , Marschall Sabine , Dettmer Katja , Alhusayan Mohammed , Bertoglio Pietro , Querzoli Giulia , Mielenz Dirk , Sahin Ozgur , Færgeman Nils J. , Asangani Irfan A. , Ceppi Paolo
Published: November 2024

Despite recent treatment advances, non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide, and therefore it necessitates the exploration of new therapy options. One commonly shared feature of malignant cells is their ability to hijack metabolic pathways to confer survival or proliferation. In this study, we highlight the importance of the polyol pathway (PP) in NSCLC metabolism. This pathway is solely responsible for metabolizing glucose to fructose based on the enzymatic activity of aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD). Via genetic and pharmacological manipulations, we reveal that PP activity is indispensable for NSCLC growth and survival in vitro and in murine xenograft models. Mechanistically, PP deficiency provokes multifactorial deficits, ranging from energetic breakdown and DNA damage, that ultimately trigger the induction of apoptosis. At the molecular level, this process is driven by pro-apoptotic JNK signaling and concomitant upregulation of the transcription factors c-Jun and ATF3. Moreover, we show that fructose, the PP end-product, as well as other non-glycolytic hexoses confer survival to cancer cells and resistance against chemotherapy via sustained NF-κB activity as well as an oxidative switch in metabolism. Given the detrimental consequence of PP gene targeting on growth and survival, we propose PP pathway interference as a viable therapeutic approach against NSCLC.
DDR1 promotes metastasis of cervical cancer and downstream phosphorylation signal via binding GRB2
Authors: Zhang Jin , Maimaiti Aynuer , Chang Xihan , Sun Pengcheng , Chang Xiaohan
Published: November 2024

Cervical cancer is a leading cause of cancer-related death among women and its recurrence and metastasis poses challenges to treatment. Discoidin domain receptor 1 (DDR1) was associated with cellular migration and invasion in several types of cancers. However, its function in cervical cancer is still unclear. In this study, we found that DDR1 was significantly more expressed in cervical cancer samples than in normal tissues. SRY-Box transcription factor 2 (SOX2), a known oncogene in cervical cancer, showed a positive correlation with DDR1 and regulated DDR1 transcription, contributing to the elevated expression of DDR1 in cervical cancer. Regarding the function of DDR1 in cervical cancer, the overexpression of DDR1 caused an increase in the migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. In contrast, cervical cancer cells with reduced DDR1 expression exhibited a lower migration rate, fewer invasive cells, and decreased levels of EMT markers. In vivo, mice injected with cervical cancer cells with overexpressed DDR1 showed more pulmonary metastasis and nodule number. Opposite results were found in mice injected with DDR1 silenced cervical cancer cells. Since DDR1 can cause phosphorylation of downstream targets, a phosphorylation omics was employed to reveal the downstream targets of DDR1, including eukaryotic translation initiation factor 4E binding protein 1 and EPH receptor A2. Furthermore, DDR1 bound directly with Src homology 2 domain of growth factor receptor bound protein 2 (GRB2) which mediated the function of DDR1 in the malignant behaviors of cervical cancer and the phosphorylation of downstream targets. In conclusion, DDR1 binds directly to GRB2 and then affects downstream phosphorylation signals, ultimately exacerbating the metastasis of cervical cancer cells. This work sheds light on the mechanism by which DDR1 functions in cervical cancer cells, providing therapeutic strategy for the treatment of cervical cancer.
The outcomes of SGLT-2 inhibitor utilization in diabetic kidney transplant recipients
Authors: Sheu Jia-Yuh , Chang Li-Yang , Chen Jui-Yi , Pan Heng-Chih , Tseng Chi-Shin , Chueh Jeff S. , Wu Vin-Cent
Published: November 2024

Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated efficacy in reducing cardiovascular events and potentially improving kidney function in diabetic patients. This investigation analyzes the TriNetX database to assess the efficacy of SGLT-2i in diabetic kidney transplant recipients (KTR) concerning all-cause mortality, major adverse cardiac events (MACE), and major adverse kidney events (MAKE). The study includes type 2 diabetic patients over 18 who underwent kidney transplants between June 1, 2015, and June 1, 2023, with a focus on SGLT-2i use within the first three months post-transplant. After propensity score matching, the study compares 1970 SGLT-2i users with matched non-users. With a median follow-up of 3.4 years, SGLT-2i users showed significantly lower rates of all-cause mortality (adjusted hazard ratio [aHR]: 0.32), MACE (aHR: 0.48), and MAKE (aHR: 0.52). These findings indicate that SGLT-2i significantly reduces mortality and adverse events in diabetic KTR, underscoring its potential to improve post-transplant outcomes.
Telomere-to-telomere genome assembly of a male goat reveals variants associated with cashmere traits
Authors: Wu Hui , Luo Ling-Yun , Zhang Ya-Hui , Zhang Chong-Yan , Huang Jia-Hui , Mo Dong-Xin , Zhao Li-Ming , Wang Zhi-Xin , Wang Yi-Chuan , He-Hua EEr , Bai Wen-Lin , Han Di , Dou Xing-Tang , Ren Yan-Ling , Dingkao Renqing , Chen Hai-Liang , Ye Yong , Du Hai-Dong , Zhao Zhan-Qiang , Wang Xi-Jun , Jia Shan-Gang , Liu Zhi-Hong , Li Meng-Hua
Published: November 2024

A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).
The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway
Authors: Ghosh Dhiman , Torres Felix , Schneider Matthias M. , Ashkinadze Dzmitry , Kadavath Harindranath , Fleischmann Yanick , Mergenthal Simon , Güntert Peter , Krainer Georg , Andrzejewska Ewa A. , Lin Lily , Wei Jiapeng , Klotzsch Enrico , Knowles Tuomas , Riek Roland
Published: November 2024

The complex kinetics of disease-related amyloid aggregation of proteins such as α-Synuclein (α-Syn) in Parkinson’s disease and Aβ42 in Alzheimer’s disease include primary nucleation, amyloid fibril elongation and secondary nucleation. The latter can be a key accelerator of the aggregation process. It has been demonstrated that the chaperone domain BRICHOS can interfere with the secondary nucleation process of Aβ42. Here, we explore the mechanism of secondary nucleation inhibition of the BRICHOS domain of the lung surfactant protein (proSP-C) against α-Syn aggregation and amyloid formation. We determine the 3D NMR structure of an inactive trimer of proSP-C BRICHOS and its active monomer using a designed mutant. Furthermore, the interaction between the proSP-C BRICHOS chaperone and a substrate peptide has been studied. NMR-based interaction studies of proSP-C BRICHOS with α-Syn fibrils show that proSP-C BRICHOS binds to the C-terminal flexible fuzzy coat of the fibrils, which is the secondary nucleation site on the fibrils. Super-resolution fluorescence microscopy demonstrates that proSP-C BRICHOS runs along the fibrillar axis diffusion-dependently sweeping off monomeric α-Syn from the fibrils. The observed mechanism explains how a weakly binding chaperone can inhibit the α-Syn secondary nucleation pathway via avidity where a single proSP-C BRICHOS molecule is sufficient against up to ~7-40 α-Syn molecules embedded within the fibrils.
Analyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline
Authors: Wiegrebe Simon , Gorski Mathias , Herold Janina M. , Stark Klaus J. , Thorand Barbara , Gieger Christian , Böger Carsten A. , Schödel Johannes , Hartig Florian , Chen Han , Winkler Thomas W. , Küchenhoff Helmut , Heid Iris M.
Published: November 2024

Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable for longGWAS. The linear mixed model identifies 13 independent genetic variants associated with eGFR-decline, including 6 novel variants, and links them to age-dependent eGFR-genetics. We demonstrate that age-dependent and age-independent eGFR-genetics exhibit a differential pattern regarding clinical progression traits and kidney-specific gene expression regulation. Overall, our results provide insights into kidney aging and linear mixed model-based longGWAS generally.
Staphylococcus epidermidis alters macrophage polarization and phagocytic uptake by extracellular DNA release in vitro
Authors: Weißelberg Samira , Both Anna , Failla Antonio Virgilio , Huang Jiabin , Linder Stefan , Ohnezeit Denise , Bartsch Patricia , Aepfelbacher Martin , Rohde Holger
Published: November 2024

Biofilm formation shields Staphylococcus epidermidis from host defense mechanisms, contributing to chronic implant infections. Using wild-type S. epidermidis 1457, a PIA-negative mutant (1457-M10), and an eDNA-negative mutant (1457ΔatlE), this study examined the influence of biofilm matrix components on human monocyte-derived macrophage (hMDM) interactions. The wild-type strain was resistant to phagocytosis and induced an anti-inflammatory response in hMDMs, while both mutants were more susceptible to phagocytosis and triggered a pro-inflammatory response. Removing eDNA from the 1457 biofilm matrix increased hMDM uptake and a pro-inflammatory reaction, whereas adding eDNA to the 1457ΔatlE mutant reduced phagocytosis and promoted an anti-inflammatory response. Inhibiting TLR9 enhanced bacterial uptake and induced a pro-inflammatory response in hMDMs exposed to wild-type S. epidermidis. This study highlights the critical role of eDNA in immune evasion and the central role of TLR9 in modulating macrophage responses, advancing the understanding of implant infections.
Learning high-accuracy error decoding for quantum processors
Authors: Bausch Johannes , Senior Andrew W. , Heras Francisco J. H. , Edlich Thomas , Davies Alex , Newman Michael , Jones Cody , Satzinger Kevin , Niu Murphy Yuezhen , Blackwell Sam , Holland George , Kafri Dvir , Atalaya Juan , Gidney Craig , Hassabis Demis , Boixo Sergio , Neven Hartmut , Kohli Pushmeet
Published: November 2024

Building a large-scale quantum computer requires effective strategies to correct errors that inevitably arise in physical quantum systems1. Quantum error-correction codes2 present a way to reach this goal by encoding logical information redundantly into many physical qubits. A key challenge in implementing such codes is accurately decoding noisy syndrome information extracted from redundancy checks to obtain the correct encoded logical information. Here we develop a recurrent, transformer-based neural network that learns to decode the surface code, the leading quantum error-correction code3. Our decoder outperforms other state-of-the-art decoders on real-world data from Google’s Sycamore quantum processor for distance-3 and distance-5 surface codes4. On distances up to 11, the decoder maintains its advantage on simulated data with realistic noise including cross-talk and leakage, utilizing soft readouts and leakage information. After training on approximate synthetic data, the decoder adapts to the more complex, but unknown, underlying error distribution by training on a limited budget of experimental samples. Our work illustrates the ability of machine learning to go beyond human-designed algorithms by learning from data directly, highlighting machine learning as a strong contender for decoding in quantum computers.
Coupling of unactivated alkyl electrophiles using frustrated ion pairs
Authors: Roediger Sven , Le Saux Emilien , Boehm Philip , Morandi Bill
Published: November 2024

Cross-electrophile coupling reactions have evolved into a major strategy for rapidly assembling important organic molecules1. Two readily accessible electrophiles are coupled to form new C–C bonds, providing a key advantage over traditional cross-coupling strategies that require the preformation of reactive organometallic species. Yet, the formation of C(sp3)–C(sp3) bonds that form the core of nearly all organic compounds remains highly challenging with current approaches, calling for the design of innovative new strategies. Here we report a distinct, transition-metal-free platform to form such bonds without the need for activating or stabilizing groups on the coupling partners. The reaction is enabled by an unusual single-electron transfer in a frustrated ion pair, and it can couple fragments containing functional groups that would be challenging in related transition-metal-catalysed processes. Moreover, we could further leverage this new mechanistic manifold in the design of other reactions, showing the broad potential of this type of reactivity. We anticipate that our results will provide a framework for further exploration of this reactivity pattern to tackle challenging problems in organic synthesis.
Nonlinear receptive fields evoke redundant retinal coding of natural scenes
Authors: Karamanlis Dimokratis , Khani Mohammad H. , Schreyer Helene M. , Zapp Sören J. , Mietsch Matthias , Gollisch Tim
Published: November 2024

The role of the vertebrate retina in early vision is generally described by the efficient coding hypothesis1,2, which predicts that the retina reduces the redundancy inherent in natural scenes3 by discarding spatiotemporal correlations while preserving stimulus information4. It is unclear, however, whether the predicted decorrelation and redundancy reduction in the activity of ganglion cells, the retina’s output neurons, hold under gaze shifts, which dominate the dynamics of the natural visual input5. We show here that species-specific gaze patterns in natural stimuli can drive correlated spiking responses both in and across distinct types of ganglion cells in marmoset as well as mouse retina. These concerted responses disrupt redundancy reduction to signal fixation periods with locally high spatial contrast. Model-based analyses of ganglion cell responses to natural stimuli show that the observed response correlations follow from nonlinear pooling of ganglion cell inputs. Our results indicate cell-type-specific deviations from efficient coding in retinal processing of natural gaze shifts.
Examining the role of common variants in rare neurodevelopmental conditions
Authors: Huang Qin Qin , Wigdor Emilie M. , Malawsky Daniel S. , Campbell Patrick , Samocha Kaitlin E. , Chundru V. Kartik , Danecek Petr , Lindsay Sarah , Marchant Thomas , Koko Mahmoud , Amanat Sana , Bonfanti Davide , Sheridan Eamonn , Radford Elizabeth J. , Barrett Jeffrey C. , Wright Caroline F. , Firth Helen V. , Warrier Varun , Strudwick Young Alexander , Hurles Matthew E. , Martin Hilary C.
Published: November 2024

Although rare neurodevelopmental conditions have a large Mendelian component1, common genetic variants also contribute to risk2,3. However, little is known about how this polygenic risk is distributed among patients with these conditions and their parents nor its interplay with rare variants. It is also unclear whether polygenic background affects risk directly through alleles transmitted from parents to children, or whether indirect genetic effects mediated through the family environment4 also play a role. Here we addressed these questions using genetic data from 11,573 patients with rare neurodevelopmental conditions, 9,128 of their parents and 26,869 controls. Common variants explained around 10% of variance in risk. Patients with a monogenic diagnosis had significantly less polygenic risk than those without, supporting a liability threshold model5. A polygenic score for neurodevelopmental conditions showed only a direct genetic effect. By contrast, polygenic scores for educational attainment and cognitive performance showed no direct genetic effect, but the non-transmitted alleles in the parents were correlated with the child’s risk, potentially due to indirect genetic effects and/or parental assortment for these traits4. Indeed, as expected under parental assortment, we show that common variant predisposition for neurodevelopmental conditions is correlated with the rare variant component of risk. These findings indicate that future studies should investigate the possible role and nature of indirect genetic effects on rare neurodevelopmental conditions, and consider the contribution of common and rare variants simultaneously when studying cognition-related phenotypes.
Early-twentieth-century cold bias in ocean surface temperature observations
Authors: Sippel Sebastian , Kent Elizabeth C. , Meinshausen Nicolai , Chan Duo , Kadow Christopher , Neukom Raphael , Fischer Erich M. , Humphrey Vincent , Rohde Robert , de Vries Iris , Knutti Reto
Published: November 2024

The observed temperature record, which combines sea surface temperatures with near-surface air temperatures over land, is crucial for understanding climate variability and change1–4. However, early records of global mean surface temperature are uncertain owing to changes in measurement technology and practice, partial documentation5–8, and incomplete spatial coverage9. Here we show that existing estimates of ocean temperatures in the early twentieth century (1900–1930) are too cold, based on independent statistical reconstructions of the global mean surface temperature from either ocean or land data. The ocean-based reconstruction is on average about 0.26 °C colder than the land-based one, despite very high agreement in all other periods. The ocean cold anomaly is unforced, and internal variability in climate models cannot explain the observed land–ocean discrepancy. Several lines of evidence based on attribution, timescale analysis, coastal grid cells and palaeoclimate data support the argument of a substantial cold bias in the observed global sea-surface-temperature record in the early twentieth century. Although estimates of global warming since the mid-nineteenth century are not affected, correcting the ocean cold bias would result in a more modest early-twentieth-century warming trend10, a lower estimate of decadal-scale variability inferred from the instrumental record3, and better agreement between simulated and observed warming than existing datasets suggest2.