bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of LINC-PINT polymorphisms with lumbar disc herniation risk among Chinese Han population: a case control study
Authors: Wu Yimin , Bai Ming , Yu Yingnan , Wang Yupeng , Zhang Yuan 
Published: August 2023

Abstract
Background
Lumbar disc herniation (LDH) is a complex spinal disease, with multiple genetic polymorphisms being related to its risk. Nevertheless, the role of LINC-PINT polymorphisms in LDH risk has remained unknown. Therefore, this study aimed to investigate the association between LINC-PINT polymorphisms and LDH risk.

Methods
DNA was extracted from 504 LDH patients and 500 healthy controls. Three single nucleotide polymorphisms (SNPs) in LINC-PINT were selected and genotyped using Agena MassARRAY. We used logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) under multiple genetic models to evaluate the association between LINC-PINT polymorphisms and LDH risk. Haploview 4.2 and SNPStats software were used to evaluate the linkage strength of SNPs and the correlation between haplotypes and LDH risk. The impact of SNP-SNP interactions on LDH risk was analyzed using multi-factor dimensionality reduction (MDR).

Results
Results showed that rs157916 (G vs. A: OR = 1.23, FDR-p = 0.029) and rs7801029 (G vs. C: OR = 1.39, FDR-p = 0.006; GG vs. CC: OR = 2.34, FDR-p = 0.038; recessive: OR = 2.13, FDR-p = 0.045; additive: OR = 1.39, FDR-p = 0.030) were associated with an increased risk of LDH. Furthermore, LINC-PINT rs157916 and rs780129 were found to be significantly associated with LDH risk in males. The “GGG” haplotype was associated with increased LDH risk (OR = 1.41, FDR-p = 0.006). MDR analysis indicated that the interaction between rs7801029 and rs16873842 was associated with an increased risk of LDH (OR = 1.47, p = 0.004). Additionally, there were significant differences in C-reactive protein levels among different genotypes of rs157916 and rs780129 (p < 0.05).

Conclusion
This study suggests that LINC-PINT gene polymorphisms (rs157916 and rs7801029) are considered risk factors for LDH in the Chinese Han population and provide a scientific basis for early screening, prevention, and diagnosis of LDH.
New immunotherapy strategies for patients with sarcomas: highlights from the 2023 ASCO annual meeting
Authors: Roulleaux-Dugage Matthieu , Italiano Antoine 
Published: August 2023

AbstractImmunotherapy has revolutionized cancer treatment, but currently, immuno-oncology agents have not been approved for patients with soft tissue sarcomas. However, there is growing evidence suggesting that immunotherapy could be an effective therapeutic strategy for this group of diseases. Here, we reviewed the latest advances of immunotherapy trials from the 2023 American Society of Clinical Oncology Annual Meeting, including some novel and encouraging combination regimens. Further research is still needed to fully understand the optimal use of these agents in sarcoma treatment.
Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels
Authors: Liepinsh Edgars , Svalbe Baiba , Stelfa Gundega , Grinberga Solveiga , Zvejniece Liga , Schiöth Helgi B. , Dambrova Maija 
Published: August 2023

AbstractDeletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice.
Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury
Authors: Grimm Sandra L. , Reddick Samuel , Dong Xiaoyu , Leek Connor , Wang Amy Xiao , Gutierrez Manuel Cantu , Hartig Sean M. , Moorthy Bhagavatula , Coarfa Cristian , Lingappan Krithika 
Published: August 2023

Abstract
Background
Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions.

Methods
Wild-type and miR-30a−/− neonatal mice were exposed to hyperoxia [95% FiO2, postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a−/− mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a−/− male and female lung transcriptome data.

Results
Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a−/− mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a−/− female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand–receptor interaction. Gene expression signature in the miR-30a−/− female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium.

Conclusions
miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.
KITENIN promotes aerobic glycolysis through PKM2 induction by upregulating the c-Myc/hnRNPs axis in colorectal cancer
Authors: Varlı Mücahit , Kim Sung Jin , Noh Myung-Giun , Kim Yoon Gyoon , Ha Hyung-Ho , Kim Kyung Keun , Kim Hangun 
Published: August 2023

AbstractPurposeThe oncoprotein KAI1 C-terminal interacting tetraspanin (KITENIN; vang-like 1) promotes cell metastasis, invasion, and angiogenesis, resulting in shorter survival times in cancer patients. Here, we aimed to determine the effects of KITENIN on the energy metabolism of human colorectal cancer cells.Experimental designThe effects of KITENIN on energy metabolism were evaluated using in vitro assays. The GEPIA web tool was used to extrapolate the clinical relevance of KITENIN in cancer cell metabolism. The bioavailability and effect of the disintegrator of KITENIN complex compounds were evaluated by LC–MS, in vivo animal assay.ResultsKITENIN markedly upregulated the glycolytic proton efflux rate and aerobic glycolysis by increasing the expression of GLUT1, HK2, PKM2, and LDHA. β-catenin, CD44, CyclinD1 and HIF-1A, including c-Myc, were upregulated by KITENIN expression. In addition, KITENIN promoted nuclear PKM2 and PKM2-induced transactivation, which in turn, increased the expression of downstream mediators. This was found to be mediated through an effect of c-Myc on the transcription of hnRNP isoforms and a switch to the M2 isoform of pyruvate kinase, which increased aerobic glycolysis. The disintegration of KITENIN complex by silencing the KITENIN or MYO1D downregulated aerobic glycolysis. The disintegrator of KITENIN complex compound DKC1125 and its optimized form, DKC-C14S, exhibited the inhibition activity of KITENIN-mediated aerobic glycolysis in vitro and in vivo.ConclusionsThe oncoprotein KITENIN induces PKM2-mediated aerobic glycolysis by upregulating the c-Myc/hnRNPs axis.
Rhox6 regulates the expression of distinct target genes to mediate mouse PGCLC formation and ESC self-renewal
Authors: Li Xiaofeng , Chen Peng , Ji Junxiang , Duan Quanchao , Cao Jianjian , Huang Ru , Ye Shou-Dong 
Published: August 2023

Abstract
Background
Mouse embryonic stem cells (mESCs) not only retain the property of self-renewal but also have the ability to develop into primordial germ cell-like cells (PGCLCs). However, knowledge about the mechanisms of transcriptional regulation is still limited. Rhox6, a member of the homeobox family that is located on the X chromosome, is highly expressed within PGCLCs in vivo and in vitro. However, the detailed effects of Rhox6 on PGCLC specification and mESC maintenance remain unclear.

Results
In this study, we found that overexpression of Rhox6 favors the formation of PGCLCs, while depletion of Rhox6 inhibits the generation of PGCLCs. Mechanistically, Rhox6 directly induces the expression of Nanos3 during the specification of PGCLCs. Subsequently, downregulation of Nanos3 expression is sufficient to decrease the ability of Rhox6 to induce PGCLC formation. Moreover, we found that depletion of Rhox6 expression facilitates the self-renewal of mESCs. High-throughput sequencing revealed that suppression of Rhox6 transcription significantly increases the expression of pluripotency genes. Functional studies further demonstrated that Rhox6 directly represses the transcription of Tbx3. Therefore, knockdown of the expression of the latter impairs the self-renewal of mESCs promoted by Rhox6 downregulation.

Conclusions
Our study reveals that overexpression of Rhox6 is beneficial for PGCLC generation through induction of Nanos3, while downregulation of Rhox6 contributes to mESC self-renewal by increasing Tbx3. These findings help elucidate the early development of mouse embryos.
Overview of the current use of levosimendan in France: a prospective observational cohort study
Authors: Cholley Bernard , Bojan Mirela , Guillon Benoit , Besnier Emmanuel , Mattei Mathieu , Levy Bruno , Ouattara Alexandre , Tafer Nadir , Delmas Clément , Tonon David , Rozec Bertrand , Fellahi Jean-Luc , Lim Pascal , Labaste François , Roubille François , Caruba Thibaut , Mauriat Philippe ,   for the ARCOTHOVA study group, Barbot Olivier , Laurent Berthomieu , Besselat Anne-Marie , Katrien Blanchart , Bougle Adrien , Bourgoin Pierre , Arnaud Causeret , Charbonneau Hélène , Cristinar Mircea , Desebbe Olivier , Eljezi Veldat , Genet Thibaud , Grenier Maxime , Guinot Pierre Grégoire , Lebel Stéphane , Levy Yael , Lion François , Mansourati Jacques , Marlière Stéphanie , Martin Anne-Céline , Mebazaa Alexandre , Mohammad Usman , Monsegu Jacques , Nessler Nicolas , Orsel Isabelle , Puymirat Etienne , Recher Morgan , Soussi Sabri , Troussard Vincent , Uhry Sabrina , Zirphile Xavier 
Published: August 2023

Abstract
Background
Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale.

Method
The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year.

Results
The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up.

Conclusions
We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.
Outpatient compared to inpatient thyroidectomy on 30-day postoperative outcomes: a national propensity matched analysis
Authors: Traill Lauren , Kendall Mark C. , Caramez Maria Paula , Apruzzese Patricia , De Oliveira Gildasio 
Published: August 2023

Abstract
Background
To address the postoperative outcomes between outpatient and inpatient neck surgery involving thyroidectomy procedures.

Methods
A cohort analysis of surgical patients undergoing primary, elective, total thyroidectomy from multiple United States medical institutions who were registered with the American College of Surgeons National Surgical Quality Improvement Program from 2015 to 2018. The primary outcome was a composite score that included any 30-day postoperative adverse event.

Results
A total of 55,381 patients who underwent a total thyroidectomy were identified comprising of 14,055 inpatient and 41,326 outpatient procedures. A cohort of 13,496 patients who underwent outpatient surgery were propensity matched for covariates with corresponding number of patients who underwent inpatient thyroidectomies. In the propensity matched cohort, the occurrence of any 30-day after surgery complications were greater in the inpatient group, 424 out of 13,496 (3.1%) compared to the outpatient group, 150 out of 13,496 (1.1%), P < 0.001. Moreover, death rates were greater in the inpatient group, 22 out 13,496 (0.16%) compared to the outpatient group, 2 out of 13,496 (0.01%), P < 0.001. Similarly, hospital readmissions occurred with greater frequency in the inpatient group, 438 out of 13,496 (3.2%) compared to the outpatient group, 310 out of 13,496 (2.3%), P < 0.001.

Conclusion
Thyroidectomy procedures performed in the outpatient setting had less rates of adverse events, including serious postoperative complications (e.g., surgical site infection, pneumonia, progressive renal insufficiency). In addition, patients who had thyroidectomy in the outpatient setting had less 30-day readmissions and mortality. Surgeons should recognize the benefits of outpatient thyroidectomy when selecting disposition of patients undergoing neck surgery.
Identification of robust and generalizable biomarkers for microbiome-based stratification in lifestyle interventions
Authors: Chen Jiarui , Siliceo Sara Leal , Ni Yueqiong , Nielsen Henrik B. , Xu Aimin , Panagiotou Gianni 
Published: August 2023

Abstract
Background
A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure.

Results
Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota’s resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting “responders” and “non-responders” independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities.

Conclusions
We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached.
Study protocol for a multi-level cross-sectional study on the equitable reach and implementation of coordinated specialty care for early psychosis
Authors: Oluwoye Oladunni , Lissau Ari , Stokes Sheldon , Selloni Alexandria T. , James Najé , Amiri Solmaz , McDonell Michael G. , Anglin Deidre M. 
Published: August 2023

Abstract
Background
Approximately 115,000 young adults will experience their first episode of psychosis (FEP) each year in the USA. Coordinated specialty care (CSC) for early psychosis is an evidence-based early intervention model that has demonstrated effectiveness by improving quality of life and reducing psychiatric symptoms for many individuals. Over the last decade, there has significant increase in the implementation of CSC programs throughout the USA. However, prior research has revealed difficulties among individuals and their family members accessing CSC. Research has also shown that CSC programs often report the limited reach of their program to underserved populations and communities (e.g., ethnoracial minorities, rural and low socioeconomic neighborhoods). Dissemination and implementation research focused on the equitable reach and implementation of CSC is needed to address disparities at the individual level.

Methods
The proposed study will create a novel integrative multi-level geospatial database of CSC programs implemented throughout the USA that will include program-level data (e.g., geocoded location, capacity, setting, role availability), provider-level data (race, ethnicity, professional credentials), and neighborhood-level census data (e.g., residential segregation, ethnic density, area deprivation, rural-urban continua, public transit time). This database will be used to characterize variations in CSC programs by geographical location and examine the overall reach CSC programs to specific communities. The quantitative data will be combined with qualitative data from state administrators, providers, and service users that will inform the development of dissemination tools, such as an interactive dashboard, that can aid decision making.

Discussion
Findings from this study will highlight the impact of outer contextual determinants on implementation and reach of mental health services, and will serve to inform the future implementation of CSC programs with a primary focus on equity.
The cognitive behavioural approach to the treatment of hallucinations. Is every experience of hallucination a part of the symptoms associated to psychosis - or even schizophrenia ?
Authors: Goujon M. J. , Gallois E. 
Published: August 2023

IntroductionWe report here our experience of treating hallucinations (auditory, visual, sensorial) using Cognitive Behavioural Therapy (CBT), along with medications. Our experience goes towards the conclusion that diagnosis is usually made prior to medical treatment of symptoms with high doses of neuroleptic drugs.ObjectivesOur aim was to make a clear difference between hallucinations which need high doses of neuroleptics for cure and hallucinations that could respond to lesser drug treatment associated with CBT.MethodsOur method was based on individual sessions of CBT.ResultsOur behavioural-cognitive method yielded high success rates as evidenced by thorough investigation into patients’ medical record including past medical history, prior drug use and life-threatening events.This work is preliminary to a follow-up with the rigorous method for evaluation.ConclusionsFurther, we aim to promote out-patient follow-ups in our unit after a very short inpatient assessment and treatment.Our therapeutic approach is now approved by our team and new patients are currently being included.Disclosure of InterestNone Declared
Efficacious Web-Based Psychotherapy to Address Depression and Anxiety Among Patients Receiving Oncological and Palliative Care: an Open-Label Randomised Controlled Trial
Authors: Alavi N. , Omrani M. , Shirazi A. , Layzell G. , Eadie J. , Jagayat J. , Stephenson C. , Kain D. , Soares C. , Yang M. 
Published: August 2023

IntroductionOncological and palliative care patients face unique stressors which increase their risk of developing depression and anxiety. Cognitive behavioural therapy (CBT) and mindfulness has established success in improving this population’s mental health. Traditional face-to-face psychotherapy is costly, has long wait lists, often lacks accessibility, and has strict scheduling, each of which can make attending psychotherapy physically, mentally, and financially out of reach for oncological and palliative patients. Web-based CBT (e-CBT) is a promising alternative that has shown efficacy in this and other patient populations.ObjectivesTo quantify the efficacy of online CBT and mindfulness therapy in oncological and palliative patients experiencing depression and anxiety symptoms.MethodsParticipants with depression or anxiety related to their diagnosis were recruited from care settings in Kingston, Ontario, and randomly assigned to 8 weekly e-CBT/mindfulness modules (N= 25) or treatment as usual (TAU; N=24). Modules consisted of CBT concepts, problem-solving, mindfulness, homework, and personalised feedback from their therapist through a secure platform (Online Psychotherapy Tool- OPTT) Participants completed PHQ-9 and GAD-7 in weeks 1, 4, and 8. (NCT04664270: REB# 6031471).ResultsSignificant decreases in PHQ-9 and GAD-7 scores within individuals support the hypothesis of efficacy. At this time, 10 e-CBT/mindfulness and 12 TAU have completed the study. Decreases in PHQ-9 and GAD-7 scores within e-CBT group support the hypothesis of efficacy. Specifically, PHQ-9 scores decreased over the 3 repeated measures (ANOVA, 2 groups, 3 repeated measures and the decrease in GAD-7 scores was similarly large)ConclusionsAs hypothesized, the results suggest that e-CBT/mindfulness therapy is an affordable, accessible, and efficacious mental health treatment for this population. The virtual, asynchronous delivery format is particularly appropriate given the unique barriers.Disclosure of InterestN. Alavi Shareolder of: OPTT inc, Grant / Research support from: department psychiatry Queen’s University, M. Omrani Shareolder of: OPTT inc, A. Shirazi: None Declared, G. Layzell: None Declared, J. Eadie: None Declared, J. Jagayat: None Declared, C. Stephenson: None Declared, D. Kain: None Declared, C. Soares: None Declared, M. Yang: None Declared