bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective study on the toxicity induced by stereotactic body radiotherapy: overview of the reunion experience on prostate cancer in elderly patients
Authors: Slama Youssef , Baumont Gilles , Arcambal Angelique , Begue Mickael , Maillot Olivier , Sayah Rima , Castanet Romain , Caboche Raoul , Liberati Pedro , Slaoui Hakim , Bouaziz Medi , Borson Olivier , Nguyen Nam P. , Dutheil Fabien 
Published: February 2024

IntroductionProstate cancer is the fourth most commonly diagnosed cancer among men worldwide. Various tools are used to manage disease such as conventional radiotherapy. However, it has been demonstrated that large prostate volumes were often associated with higher rates of genitourinary and gastrointestinal toxicities. Currently, the improvements in radiotherapy technology have led to the development of stereotactic body radiotherapy, which delivers higher and much more accurate radiation doses. In order to complete literature data about short-term outcome and short-term toxic effects of stereotactic body radiotherapy, we aimed to share our experience about gastrointestinal and genitourinary toxicities associated with stereotactic body radiotherapy in prostate cancer in patients over 70 years old.MethodsWe retrospectively reviewed the medical records of elderly patients with prostate cancer treated between 2021 and 2022. The elderly patients were treated with a non-coplanar robotic stereotactic body radiotherapy platform using real-time tracking of implanted fiducials. The prostate, with or without part of the seminal vesicles, was treated with a total dose of 36.25 Gy delivered in five fractions, each fraction being administered every other day.ResultsWe analyzed a total of 80 elderly patients, comprising 38 low-, 37 intermediate- and 5 high-risk patients. The median follow-up duration was 12 months. We did not observe biochemical/clinical recurrence, distant metastasis, or death. Grade 2 acute genitourinary toxicity was observed in 9 patients (11.25%) and Grade 2 acute gastrointestinal toxicity in 4 patients (5.0%). We did not observe any grade 3 or more acute or late toxicities.ConclusionOver the follow-up period, we noted a low frequency of gastrointestinal and genitourinary toxicities induced by stereotactic body radiotherapy in the context of prostate cancer in elderly patients. Therefore, stereotactic body radiotherapy seems to represent a promising treatment option for elderly patients, with acceptable acute toxicity.
Reporting of social determinants of health in randomized controlled trials conducted in the pediatric intensive care unit
Authors: Huang Emma , Albrecht Lisa , O’Hearn Katie , Nicolas Naisha , Armstrong Jennifer , Weinberg Maya , Menon Kusum 
Published: February 2024

IntroductionThe influence of social determinants of health (SDOH) on access to care and outcomes for critically ill children remains an understudied area with a paucity of high-quality data. Recent publications have highlighted the importance of incorporating SDOH considerations into research but the frequency with which this occurs in pediatric intensive care unit (PICU) research is unclear. Our objective was to determine the frequency and categories of SDOH variables reported and how these variables were defined in published PICU randomized controlled trials (RCTs).MethodsWe searched Medline, Embase, Lilacs, and Central from inception to Dec 2022. Inclusion criteria were randomized controlled trials of any intervention on children or their families in a PICU. Data related to study demographics and nine WHO SDOH categories were extracted, and descriptive statistics and qualitative data generated.Results586 unique RCTs were included. Studies had a median sample size of 60 patients (IQR 40-106) with 73.0% of studies including ≤100 patients and 41.1% including ≤50 patients. A total of 181 (181/586, 30.9%) studies reported ≥1 SDOH variable of which 163 (163/586, 27.8%) reported them by randomization group. The most frequently reported categories were food insecurity (100/586, 17.1%) and social inclusion and non-discrimination (73/586, 12.5%). Twenty-five of 57 studies (43.9%) investigating feeding or nutrition and 11 of 82 (13.4%) assessing mechanical ventilation reported baseline nutritional assessments. Forty-one studies investigated interventions in children with asthma or bronchiolitis of which six reported on smoking in the home (6/41, 14.6%).DiscussionReporting of relevant SDOH variables occurs infrequently in PICU RCTs. In addition, when available, categorizations and definitions of SDOH vary considerably between studies. Standardization of SDOH variable collection along with consistent minimal reporting requirements for PICU RCT publications is needed.
Alpha-hederin reprograms multi-miRNAs activity and overcome small extracellular vesicles-mediated paclitaxel resistance in NSCLC
Authors: Chang Yuzhen , Gao Xinyu , Jiang Yuchen , Wang Jingyi , Liu Liu , Yan Jun , Huang Gang , Yang Hao 
Published: February 2024

Background: Small extracellular vesicles (sEVs) mediate intercellular communication in the tumor microenvironment (TME) and contribute to the malignant transformation of tumors, including unrestricted growth, metastasis, or therapeutic resistance. However, there is a lack of agents targeting sEVs to overcome or reverse tumor chemotherapy resistance through sEVs-mediated TME reprogramming.Methods: The paclitaxel (PTX)-resistant A549T cell line was used to explore the inhibitory effect of alpha-hederin on impeding the transmission of chemoresistance in non-small cell lung cancer (NSCLC) through the small extracellular vesicles (sEVs) pathway. This investigation utilized the CCK-8 assay and flow cytometry. Transcriptomics, Western blot, oil red O staining, and targeted metabolomics were utilized to evaluate the impact of alpha-hederin on the expression of signaling pathways associated with chemoresistance transmission in NSCLC cells before and after treatment. In vivo molecular imaging and immunohistochemistry were conducted to assess how alpha-hederin influences the transmission of chemoresistance through the sEVs pathway. RT-PCR was employed to examine the expression of miRNA and lncRNA in response to alpha-hederin treatment.Results: The resistance to PTX chemotherapy in A549T cells was overcome by alpha-hederin through its dependence on sEV secretion. However, the effectiveness of alpha-hederin was compromised when vesicle secretion was blocked by the GW4869 inhibitor. Transcriptomic analysis for 463 upregulated genes in recipient cells exposed to A549T-derived sEVs revealed that these sEVs enhanced TGFβ signaling and unsaturated fatty acid synthesis pathways. Alpha-hederin inhibited 15 types of unsaturated fatty acid synthesis by reducing the signaling activity of the sEVs-mediated TGFβ/SMAD2 pathway. Further, we observed that alpha-hederin promoted the production of three microRNAs (miRNAs, including miR-21-5p, miR-23a-3p, and miR-125b-5p) and the sorting to sEVs in A549T cells. These miRNAs targeted the TGFβ/SMADs signaling activity in sEVs-recipient cells and sensitized them to the PTX therapy.Conclusion: Our finding demonstrated that alpha-hederin could sensitize PTX-resistant NSCLC cells by sEV-mediated multiple miRNAs accumulation, and inhibiting TGFβ/SMAD2 pathways in recipient cells.
Exploring the impact of seasonal variations on the chemical composition, antinociceptive, and anti-inflammatory properties of Pogostemon heyneanus Benth. essential oil
Authors: Santos Paulo Vinicius Lima , Jerônimo Lucas Botelho , Ribeiro Weyda Suyane Campos , Lopes Gustavo Moraes , Leão Neto João Henrique de Castro , da Silva Hugo Borges Oliveira , da Silva Pedro Iuri C. , Silva Renata Cunha , da Silva Joyce Kelly , Freitas Jofre Jacob S. , Mourão Rosa Helena V. , Setzer William N. , Maia José Guilherme S. , Figueiredo Pablo Luis B. 
Published: February 2024

Background:Pogostemon heyneanus leaves infusions are relevant in ethnopharmacology for treating colds, coughs, headaches, and asthma.Purpose: The essential oil chemical composition of a Pogostemon heyneanus specimen was monthly monitored from October 2021 to July 2022 to evaluate the climatic influences on its yield and chemical composition and antinociceptive, andanti-inflammatory properties.Methods: The leaves, collected monthly over a 10-month period, were submitted to hydrodistillation. The oils obtained were analyzed by gas chromatography coupled to a mass spectrometer and gas chromatography coupled to flame ionization detector. The P. heyneanus essential oil (PhEO) was tested in vivo to evaluate its peripheral analgesic actions through the abdominal writhing test induced by acetic acid, and peripheral analgesia by tail immersion. Neurogenic and inflammatory pain were evaluated by formalin test, and acute oral toxicity of the oil was also verified.Results: PhEO presented 27 chemical constituents with the highest predominance of patchoulol (43.6%–76.9%), α-bulnesene (0.2%–12.7%), α-guaiene (0.4%–8.9%), seychellene (3.8%–5.1%) and pogostol (0.0%–8.2%). The climatic parameters insolation, humidity, rainfall, and temperature did not influence the essential oil yield or the main chemical constituents, except for pogostol, which presented a strong (r = 0.73) and statistically significant (p &lt; 0.05) correlation with temperature. PhEO did not display toxicity at the maximum 300 mg/kg dosage. The oil showed low peripheral and central analgesic action at 100 mg/kg, while in the neurogenic and inflammatory pain inhibition tests, no actions related to PhEO were observed. In the carrageenan-induced peritonitis test, PhEO did not reduce the migration of leukocytes to the peritoneal cavity compared to the control group.Conclusion:Pogostemon heyneanus is a resistant plant to seasonal influences and a source of patchoulol. Despite ethnopharmacological indications, no in-vivo biological activities such as neurogenic or inflammatory pain were identified in the present work. So, the low influence of the climatic parameters on chemical composition can infer that the low pharmacological activity is also not subject to climatic variations, that is, it does not change due to the climate.
Will wealth inequality decrease happiness?—Empirical evidence from China
Authors: Wang Jingtao 
Published: February 2024

IntroductionThis article delves into the broad social and economic impacts of wealth inequality, specifically focusing on its effects on happiness, as analyzed using micro survey data from the China Family Panel Studies (CFPS).MethodsThis article employs the panel OLS regression method with time and province fixed effects for the main result and heterogeneity analysis, then uses the mediating effect and moderating effect test for the mechanisms.Results and discussionThe article presents several key findings: 1. Impact of Wealth Inequality on Happiness. The study confirms that wealth inequality significantly reduces happiness, a conclusion reinforced by a range of consistency tests and endogeneity checks. 2. Heterogeneity Analysis. Three areas of heterogeneity are examined: Hukou status, education level, and family members’ average income. The results indicate that the happiness of families with a family head holding an urban Hukou, higher education, or a higher per-member income level is less affected by wealth inequality. 3. Mechanisms Affecting Happiness. At the micro-level, the article identifies two mediating pathways—health and marital status—through which wealth inequality negatively influences happiness. At the macro-level, it is found that social security expenditure and economic development can moderate these effects and enhance subjective happiness under the same conditions of wealth inequality. The contributions of this study are specific as: 1. This study addresses some of the existing gaps in the research regarding the relationship between wealth inequality and happiness. 2. The article utilizes relative deprivation as a measure of wealth inequality, considered a more apt metric for studying happiness compared to absolute inequality. 3. This research offers insights into the mechanisms behind the observed effects, considering both micro-level (individual and family) and macro-level (societal and economic) factors.
Gut microbial diversity moderates polygenic risk of schizophrenia
Authors: Zhang Liyuan , Yuan Xiuxia , Li Xue , Zhang Xiaoyun , Mao Yiqiao , Hu Shaohua , Andreassen Ole A. , Wang Yunpeng , Song Xueqin 
Published: February 2024

BackgroundSchizophrenia (SCZ) is a heritable disorder with a polygenic architecture, and the gut microbiota seems to be involved in its development and outcome. In this study, we investigate the interplay between genetic risk and gut microbial markers.MethodsWe included 159 first-episode, drug-naïve SCZ patients and 86 healthy controls. The microbial composition of feces was characterized using the 16S rRNA sequencing platform, and five microbial α-diversity indices were estimated [Shannon, Simpson, Chao1, the Abundance-based Eoverage Estimator (ACE), and a phylogenetic diversity-based estimate (PD)]. Polygenic risk scores (PRS) for SCZ were constructed using data from large-scale genome-wide association studies. Effects of microbial α-diversity, microbial abundance, and PRS on SCZ were evaluated via generalized linear models.ResultsWe confirmed that PRS was associated with SCZ (OR = 2.08, p = 1.22×10−5) and that scores on the Shannon (OR = 0.29, p = 1.15×10−8) and Simpson (OR = 0.29, p = 1.25×10−8) indices were inversely associated with SCZ risk. We found significant interactions (p &lt; 0.05) between PRS and α-diversity indices (Shannon, Simpson, and PD), with the effects of PRS being larger in those exhibiting higher diversity compared to those with lower diversity. Moreover, the PRS effects were larger in individuals with a high abundance of the genera Romboutsia, Streptococcus, and Anaerostipes than in those with low abundance (p &lt; 0.05). All three of these genera showed protective effects against SCZ.ConclusionThe current findings suggest an interplay between the gut microbiota and polygenic risk of SCZ that warrants replication in independent samples. Experimental studies are needed to determine the underpinning mechanisms.
In constant search of the good: a qualitative study into insiders’ perspectives on living well with dementia
Authors: Yaron Gili , Bakker Franka , de Bruin Simone 
Published: February 2024

IntroductionThe new concept of ‘living well with dementia’ is currently gaining traction in practice, policy, and research. However, people with dementia and their carers’ own understanding of this concept has not received much scholarly attention. This is because empirical studies into living well with dementia are predominantly quantitative; there are only a few qualitative studies on this topic. This study therefore sets out to investigate what living well means for ‘insiders’ in an everyday context.MethodsTo explore insiders’ own perspectives on living well with dementia, we conducted interviews and focus group discussions with 21 dementia stakeholders. The study included ten individuals with mild-to-moderate dementia living at home, five family carers who are or have been involved in the care for a person with dementia, and six health and social care professionals.ResultsLiving well with dementia, for our study participants, revolves around shaping their daily lives according to their values. In this sense, living well with dementia is no different than without. As it involves the values of the person with dementia and those of their social network, living well is both an individual and a collective concern. Having dementia undermines people with dementia's ability to substantiate their values, but it is still possible to live well. As they attempt to shape living well with dementia, respondents encounter tensions within the social network and within the person with dementia. To handle these tensions, they work for mutual attunement by using sensitivity and switching between leading and following in social interactions.DiscussionLiving well with dementia in a daily context is a dynamic process in which people with dementia, family carers, and professionals constantly seek the good together. This insight contributes to a better understanding of stakeholders’ ongoing, invisible efforts to mutually attune. It may also help bypass dichotomizing approaches to dementia. Finally, it opens up new venues for research into reciprocity in the care collective. The article closes with recommendations to improve dementia care and support in light of these findings.
Evolutionary conservation of putative suicidality-related risk genes that produce diminished motivation corrected by clozapine, lithium and antidepressants
Authors: Ajayi Titilade , Thomas Alicia , Nikolic Marko , Henderson Lauryn , Zaheri Alexa , Dwyer Donard S. 
Published: February 2024

BackgroundGenome wide association studies (GWAS) and candidate gene analyses have identified genetic variants and genes that may increase the risk for suicidal thoughts and behaviors (STBs). Important unresolved issues surround these tentative risk variants such as the characteristics of the associated genes and how they might elicit STBs.MethodsPutative suicidality-related risk genes (PSRGs) were identified by comprehensive literature search and were characterized with respect to evolutionary conservation, participation in gene interaction networks and associated phenotypes. Evolutionary conservation was established with database searches and BLASTP queries, whereas gene-gene interactions were ascertained with GeneMANIA. We then examined whether mutations in risk-gene counterparts in C. elegans produced a diminished motivation phenotype previously connected to suicide risk factors.Results and conclusionsFrom the analysis, 105 risk-gene candidates were identified and found to be: 1) highly conserved during evolution, 2) enriched for essential genes, 3) involved in significant gene-gene interactions, and 4) associated with psychiatric disorders, metabolic disturbances and asthma/allergy. Evaluation of 17 mutant strains with loss-of-function/deletion mutations in PSRG orthologs revealed that 11 mutants showed significant evidence of diminished motivation that manifested as immobility in a foraging assay. Immobility was corrected in some or all of the mutants with clozapine, lithium and tricyclic antidepressant drugs. In addition, 5-HT2 receptor and muscarinic receptor antagonists restored goal-directed behavior in most or all of the mutants. These studies increase confidence in the validity of the PSRGs and provide initial clues about possible mechanisms that mediate STBs.
Locked down-locked in: experiences of families of young children with autism spectrum disorders in Delhi, India
Authors: Kaur Abhipreet , Lall Gitanjali , Abhilashi Minal , Naithani Lavangi , Verma Mamta , Roy Reetabrata , Juneja Monica , Gulati Sheffali , Taylor Carol , Leadbitter Kathy , Patel Vikram , Green Jonathan , Divan Gauri 
Published: February 2024

IntroductionThe onset of the COVID-19 pandemic and subsequent lockdowns in March 2020 disrupted the lives of families across India. The lockdown related restrictions brought forth a multitude of challenges including loss of employment, social isolation, school closures and financial burdens. Specifically, it also resulted in the restriction of health-care services for children with neurodevelopmental disabilities.MethodsThis qualitative study was conducted as a part of a larger trial in India to understand the experiences of families of young children with autism during the pandemic. In-depth interviews were carried out with 14 caregivers residing in New Delhi, India.ResultsOur findings identified pandemic and lockdown’s universal impacts on family life and financial stability stemming from job loss, business closure, and salary deductions, affecting quality of life of families. Furthermore, COVID-19 pandemic’s impact on autistic children was evident through limited access to essential services and financial challenges related service interruptions even after resumption of services. The lockdown’s novelty also affected children’s behavior, with both challenging behavioral changes and positive impacts. Primary caregivers, predominantly mothers, assumed additional responsibilities in household tasks, schooling, and therapy administration. While some these experiences were universally experienced, a few of these improved outcomes for autistic children. Despite challenges, parents expressed gratitude for their family’s safety and well-being during the difficult time.DiscussionsThese findings inform service provision for vulnerable families and offer implications for designing interventions such as credit schemes for families, guidance and resources for establishing and maintaining routines of children with autism, adopting flexible and adaptable approaches to service delivery, and special provisions for children with autism to be able to maintain their routines outside of home. Furthermore, the study highlights the need for comprehensive support, including educational resources and stress management counselling to empower parents in supporting essential care and routines for their children during such unprecedented times.
Bone union and mobility outcomes for reconstructed open tibial fractures: a plastic surgical experience from a major trauma center
Authors: Sreedharan Sadhishaan , Bruscino-Raiola Frank , Lew Philip , Ling Yuan , Ferris Scott 
Published: February 2024

IntroductionThe goal in open tibial fracture management is to achieve a united tibia in an extremity that allows pain free mobilization. The objective of this study was to assess factors that lead to this functional outcome in lower limb reconstruction, from a plastic surgical perspective.Materials and methodsThe Plastic and Reconstructive Surgery lower limb database at a tertiary trauma hospital was searched for open tibial injuries from February 2015 to March 2020. The nature and severity of injury, timing and details of all operations including reconstructions were collected prospectively. Mobility including gait aids, pain, and complications were retrospectively collected. Union was assessed in two ways, depending on fracture location. Metaphyseal and diaphyseal tibial fractures were provided mRUST scores (union defined as RUST &gt; 13) and epiphyseal tibial fractures were categorically classified as “united” or “non-union” by two independent radiologists.ResultsDuring the five-year study period there were 148 open leg injuries in the database. Twenty-one patients underwent a primary amputation due to severity of their initial injury. One hundred patients underwent primary limb salvage. Sixty-one patients in the limb salvage group achieved primary tibial union with a mean follow-up time of 19.4 months post injury. Twenty-three additional patients were confirmed to subsequently unite. Patient who achieved union were more likely to mobilise without gait aids.DiscussionIn this study definitive external fixation and soft tissue infection were both associated with higher rates of non-union. Longer times to soft tissue reconstruction was not associated with an increase in acute soft tissue complications. More importantly bone union, pain and mobility did not decline. After undertaking a primary limb salvage pathway for 100 patients, the ultimate tibial fracture union rate was 84% and the confirmed ambulation rate was 96%.