bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanded gene and taxon sampling of diplomonads shows multiple switches to parasitic and free-living lifestyle
Authors: Wiśniewska Monika M. , Salomaki Eric D. , Silberman Jeffrey D. , Terpis Kristina X. , Mazancová Eva , Táborský Petr , Jinatham Vasana , Gentekaki Eleni , Čepička Ivan , Kolisko Martin 
Published: September 2024

AbstractBackgroundDiplomonads are anaerobic flagellates classified within Metamonada. They contain both host-associated commensals and parasites that reside in the intestinal tracts of animals, including humans (e.g.,Giardia intestinalis), as well as free-living representatives that inhabit freshwater and marine anoxic sediments (e.g.,Hexamita inflata). The evolutionary trajectories within this group are particularly unusual as the free-living taxa appear to be nested within a clade of host-associated species, suggesting a reversal from host-dependence to a secondarily free-living lifestyle. This is thought to be an exceedingly rare event as parasites often lose genes for metabolic pathways that are essential to a free-living life strategy, as they become increasingly reliant on their host for nutrients and metabolites. To revert to a free-living lifestyle would require the reconstruction of numerous metabolic pathways. All previous studies of diplomonad evolution suffered from either low taxon sampling, low gene sampling, or both, especially among free-living diplomonads, which has weakened the phylogenetic resolution and hindered evolutionary insights into this fascinating transition.ResultsWe sequenced transcriptomes from 1 host-associated and 13 free-living diplomonad isolates; expanding the genome scale data sampling for diplomonads by roughly threefold. Phylogenomic analyses clearly show that free-living diplomonads form several branches nested within endobiotic species. Moreover, the phylogenetic distribution of genes related to an endobiotic lifestyle suggest their acquisition at the root of diplomonads, while traces of these genes have been identified in free-living diplomonads as well. Based on these results, we propose an evolutionary scenario of ancestral and derived lifestyle transitions across diplomonads.ConclusionsFree-living taxa form several clades nested within endobiotic taxa in our phylogenomic analyses, implying multiple transitions between free-living and endobiotic lifestyles. The evolutionary history of numerous virulence factors corroborates the inference of an endobiotic ancestry of diplomonads, suggesting that there have been several reversals to a free-living lifestyle. Regaining host independence may have been facilitated by a subset of laterally transferred genes. We conclude that the extant diversity of diplomonads has evolved from a non-specialized endobiont, with some taxa becoming highly specialized parasites, others becoming free-living, and some becoming capable of both free-living and endobiotic lifestyles.
Strategies to improve the implementation of preventive care in primary care: a systematic review and meta-analysis
Authors: Heath Laura , Stevens Richard , Nicholson Brian D. , Wherton Joseph , Gao Min , Callan Caitriona , Haasova Simona , Aveyard Paul 
Published: September 2024

Abstract

Background

Action on smoking, obesity, excess alcohol, and physical inactivity in primary care is effective and cost-effective, but implementation is low. The aim was to examine the effectiveness of strategies to increase the implementation of preventive healthcare in primary care.

Methods
CINAHL, CENTRAL, The Cochrane Database of Systematic Reviews, Dissertations & Theses – Global, Embase, Europe PMC, MEDLINE and PsycINFO were searched from inception through 5 October 2023 with no date of publication or language limits. Randomised trials, non-randomised trials, controlled before-after studies and interrupted time series studies comparing implementation strategies (team changes; changes to the electronic patient registry; facilitated relay of information; continuous quality improvement; clinician education; clinical reminders; financial incentives or multicomponent interventions) to usual care were included. Two reviewers screened studies, extracted data, and assessed bias with an adapted Cochrane risk of bias tool for Effective Practice and Organisation of Care reviews. Meta-analysis was conducted with random-effects models. Narrative synthesis was conducted where meta-analysis was not possible. Outcome measures included process and behavioural outcomes at the closest point to 12 months for each implementation strategy.

Results
Eighty-five studies were included comprising of 4,210,946 participants from 3713 clusters in 71 cluster trials, 6748 participants in 5 randomised trials, 5,966,552 participants in 8 interrupted time series, and 176,061 participants in 1 controlled before after study. There was evidence that clinical reminders (OR 3.46; 95% CI 1.72–6.96; I2 = 89.4%), clinician education (OR 1.89; 95% CI 1.46–2.46; I2 = 80.6%), facilitated relay of information (OR 1.95, 95% CI 1.10–3.46, I2 = 88.2%), and multicomponent interventions (OR 3.10; 95% CI 1.60–5.99, I2 = 96.1%) increased processes of care. Multicomponent intervention results were robust to sensitivity analysis. There was no evidence that other implementation strategies affected processes of care or that any of the implementation strategies improved behavioural outcomes. No studies reported on interventions specifically designed for remote consultations. Limitations included high statistical heterogeneity and many studies did not account for clustering.

Conclusions
Multicomponent interventions may be the most effective implementation strategy. There was no evidence that implementation interventions improved behavioural outcomes.

Trial registration
PROSPERO CRD42022350912.
Metformin use and preeclampsia risk in women with diabetes: a two-country cohort analysis
Authors: Gordon Hannah , Salim Noor , Tong Stephen , Walker Susan , De Silva Manarangi , Cluver Catherine , Mehdipour Parinaz , Hiscock Richard , Sutherland Lauren , Doust Ann , Bergman Lina , Wikström Anna-Karin , Lindquist Anthea , Hesselman Susanne , Hastie Roxanne 
Published: September 2024

Abstract
Background
Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy.

Methods
We utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model.

Results
The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89–1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60–1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41–1.48]).

Conclusions
In this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes.
Enhancing organoid culture: harnessing the potential of decellularized extracellular matrix hydrogels for mimicking microenvironments
Authors: Li Chen , An Ni , Song Qingru , Hu Yuelei , Yin Wenzhen , Wang Qi , Le Yinpeng , Pan Wenting , Yan Xinlong , Wang Yunfang , Liu Juan 
Published: September 2024

AbstractOver the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM–cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.
“Balancing work and movement”: barriers and enablers for being physically active at Indian workplaces – findings from SMART STEP trial
Authors: Chandrasekaran Baskaran , Arumugam Ashokan , Pesola Arto J , Rao Chythra R 
Published: September 2024

Abstract
Background
Non-communicable diseases are rising rapidly in low- and middle-income countries, leading to increased morbidity and mortality. Reducing sedentary behavior (SB) and increasing physical activity (PA) offer numerous health benefits. Workplaces provide an ideal setting for promoting SB/PA interventions; however, understanding the barriers and enablers is crucial for optimizing these interventions in workplace environments.

Methods
Nested within a cluster randomised controlled trial (the SMART-STEP trial), the present study employed in-depth interviews with 16 office workers who have completed 24 weeks of two distinct (technology assisted and traditional) workplace SB/PA interventions. Using a deductive analysis, semi-structured interviews were administered to explore the barriers and enablers to the SB/PA interventions at individual, interpersonal and organisational level using the socio-ecological model.

Results
Several individual (poor goal setting, perceived health benefits & workload, attitude, intervention engagement), interpersonal (lack of peer support) and organisational (task prioritisation, lack of organisational norm and material or social reward) barriers were identified. Indian women engaged in desk-based office jobs often find themselves burdened with intense home and childcare responsibilities, often without sufficient support from their spouses. A primary concern among Indian office workers is the poor awareness and absence of cultural norms regarding the health risks associated with SB.

Conclusions
Raising awareness among workplace stakeholders—including office workers, peers, and the organization—is crucial before designing and implementing SB/PA interventions in Indian workspaces. Personalized interventions for Indian female office workers engaged in desk-bound work are warranted.
LINC01089 in cancer: multifunctional roles and therapeutic implications
Authors: Yi Qiang , Zhu Gangfeng , Ouyang Xinting , Zhu Weijian , Zhong Kui , Chen Zheng , Zhong Jinghua 
Published: September 2024

AbstractLINC01089 is a prime example of a long non-coding RNA that plays a pivotal role in the progression of human cancers. The gene encoding this lncRNA is located on 12q24.31. LINC01089 has been demonstrated to exert tumor-suppressive effects in various cancers, including colorectal cancer, gastric cancer, lung cancer, ovarian cancer, cervical cancer, papillary thyroid carcinoma, breast cancer, and osteosarcoma. However, its role in hepatocellular carcinoma shows significant discrepancies across different studies. In this review, we systematically explore the functions of LINC01089 in human cancers through bioinformatics analysis, clinical studies, animal models, and fundamental experimental research. Furthermore, we delve into the biological mechanisms and functions of LINC01089, and discuss its potential as a future biomarker and therapeutic target in detail.
Evaluating ECM stiffness and liver cancer radiation response via shear-wave elasticity in 3D culture models
Authors: Lu Shao-Lun , Pei Yu , Liu Wei-Wen , Han Kun , Cheng Jason Chia-Hsien , Li Pai-Chi 
Published: September 2024

AbstractBackgroundThe stiffness of the tumor microenvironment (TME) directly influences cellular behaviors. Radiotherapy (RT) is a common treatment for solid tumors, but the TME can impact its efficacy. In the case of liver cancer, clinical observations have shown that tumors within a cirrhotic, stiffer background respond less to RT, suggesting that the extracellular matrix (ECM) stiffness plays a critical role in the development of radioresistance.MethodsThis study explored the effects of ECM stiffness and the inhibition of lysyl oxidase (LOX) isoenzymes on the radiation response of liver cancer in a millimeter-sized three-dimensional (3D) culture. We constructed a cube-shaped ECM-based millimeter-sized hydrogel containing Huh7 human liver cancer cells. By modulating the collagen concentration, we produced two groups of samples with different ECM stiffnesses to mimic the clinical scenarios of normal and cirrhotic livers. We used a single-transducer system for shear-wave-based elasticity measurement, to derive Young’s modulus of the 3D cell culture to investigate how the ECM stiffness affects radiosensitivity. This is the first demonstration of a workflow for assessing radiation-induced response in a millimeter-sized 3D culture.ResultsIncreased ECM stiffness was associated with a decreased radiation response. Moreover, sonoporation-assisted LOX inhibition with BAPN (β-aminopropionitrile monofumarate) significantly decreased the initial ECM stiffness and increased RT-induced cell death. Inhibition of LOX was particularly effective in reducing ECM stiffness in stiffer matrices. Combining LOX inhibition with RT markedly increased radiation-induced DNA damage in cirrhotic liver cancer cells, enhancing their response to radiation. Furthermore, LOX inhibition can be combined with sonoporation to overcome stiffness-related radioresistance, potentially leading to better treatment outcomes for patients with liver cancer.ConclusionsThe findings underscore the significant influence of ECM stiffness on liver cancer’s response to radiation. Sonoporation-aided LOX inhibition emerges as a promising strategy to mitigate stiffness-related resistance, offering potential improvements in liver cancer treatment outcomes.
Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients
Authors: Keller Nancy , Midgley Julian , Khalid Ehtesham , Lesmana Harry , Mathew Georgie , Mincham Christine , Teig Norbert , Khan Zubair , Khosla Indu , Mehr Sam , Guran Tulay , Buder Kathrin , Xu Hong , Alhasan Khalid , Buyukyilmaz Gonul , Weaver Nicole , Saba Julie D. 
Published: September 2024

Abstract
Background
Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5’phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects.

Results
Overall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes.

Conclusion
Our results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving.
One immune cell to bind them all: platelet contribution to neurodegenerative disease
Authors: Rodriguez Moore Gabriela , Melo-Escobar Isabel , Stegner David , Bracko Oliver 
Published: September 2024

AbstractAlzheimer’s disease (AD) and related dementias (ADRD) collectively affect a significant portion of the aging population worldwide. The pathological progression of AD involves not only the classical hallmarks of amyloid beta (Aβ) plaque buildup and neurofibrillary tangle development but also the effects of vasculature and chronic inflammatory processes. Recently, platelets have emerged as central players in systemic and neuroinflammation. Studies have shown that patients with altered platelet receptor expression exhibit accelerated cognitive decline independent of traditional risk factors. Additionally, platelets from AD patients exhibit heightened unstimulated activation compared to control groups. Platelet granules contain crucial AD-related proteins like tau and amyloid precursor protein (APP). Dysregulation of platelet exocytosis contributes to disease phenotypes characterized by increased bleeding, stroke, and cognitive decline risk. Recent studies have indicated that these effects are not associated with the quantity of platelets present in circulation. This underscores the hypothesis that disruptions in platelet-mediated inflammation and healing processes may play a crucial role in the development of ADRD. A thorough look at platelets, encompassing their receptors, secreted molecules, and diverse roles in inflammatory interactions with other cells in the circulatory system in AD and ADRD, holds promising prospects for disease management and intervention. This review discusses the pivotal roles of platelets in ADRD.
Joint effect of docosahexaenoic acid intake and tobacco smoke exposure on learning disability in children and adolescents: a cross-sectional study from the NHANES database
Authors: Liu Ling , Shu Xiuli , Xu Zijun , Jiang Haibo 
Published: September 2024

Abstract
Background
Docosahexaenoic acid (DHA) has been reported to be associated with the children’s neurodevelopment, who may be exposed to tobacco smoke simultaneously. The evidence about joint effect of DHA intake and tobacco smoke exposure on children and adolescents’ learning disabilities (LD) was limited. The objective of this study was to assess the joint effect of DHA intake and tobacco smoke exposure on children and adolescents’ LD.

Methods
A cross-sectional analysis of the NHANES 1999–2004 was performed. Children and adolescents aged 6–15 years old were included. The outcome was diagnosed by parental report of ever health professionals or school representative-identified LD. Dietary DHA intake data were obtained by food frequency questionnaire and tobacco smoke exposure levels were evaluated by serum cotinine levels. Weighted univariable and multivariate logistic regression analyses were conducted to determine the joint effect of DHA intake and tobacco smoke exposure on LD in children and adolescents, with odds ratios (ORs) and 95% confidence intervals (CIs). This joint association was further assessed after stratification by age, gender, body mass index, the history of attention deficit disorder and seen mental health professional.

Results
We identified 5,247 children and adolescents in present study, of whom 593 (11.30%) had LD. After adjusting covariates, we observed children and adolescents with DHA intake (OR = 0.76, 95%CI: 0.61–0.96) was related to lower incidence of LD; children who exposure to tobacco smoke was related to higher incidence of LD (OR = 1.54, 95%CI: 1.07–2.23); children and adolescents who exposure to tobacco smoke and without DHA intake were related to highest odds of LD (OR = 2.08, 95%CI: 1.37–3.17, P for trend = 0.042), that was, DHA and tobacco smoke exposure may have a joint effect on the odds of LD in children and adolescents. Subgroup analyses suggested this joint effect was robust especially among children and adolescents with normal & underweight BMI and without the history of attention deficit disorder and seen mental health professional.

Conclusion
Increasing the DHA intake and reducing tobacco smoke exposure may have a potential role in the prevention of LD in children and adolescents. This joint effect warrants further investigation by large-scale prospective study.