bluuebunny/crossref_metadata_2025_split huggingface dataset:
H3.3 contributes to chromatin accessibility and transcription factor binding at promoter-proximal regulatory elements in embryonic stem cells
Authors: Tafessu Amanuel , O’Hara Ryan , Martire Sara , Dube Altair L. , Saha Purbita , Gant Vincent U. , Banaszynski Laura A. 
Published: February 2023

Abstract
Background
The histone variant H3.3 is enriched at active regulatory elements such as promoters and enhancers in mammalian genomes. These regions are highly accessible, creating an environment that is permissive to transcription factor binding and the recruitment of transcriptional coactivators that establish a unique chromatin post-translational landscape. How H3.3 contributes to the establishment and function of chromatin states at these regions is poorly understood.

Results
We perform genomic analyses of features associated with active promoter chromatin in mouse embryonic stem cells (ESCs) and find evidence of subtle yet widespread promoter dysregulation in the absence of H3.3. Loss of H3.3 results in reduced chromatin accessibility and transcription factor (TF) binding at promoters of expressed genes in ESCs. Likewise, enrichment of the transcriptional coactivator p300 and downstream histone H3 acetylation at lysine 27 (H3K27ac) is reduced at promoters in the absence of H3.3, along with reduced enrichment of the acetyl lysine reader BRD4. Despite the observed chromatin dysregulation, H3.3 KO ESCs maintain transcription from ESC-specific genes. However, upon undirected differentiation, H3.3 KO cells retain footprinting of ESC-specific TF motifs and fail to generate footprints of lineage-specific TF motifs, in line with their diminished capacity to differentiate.

Conclusions
H3.3 facilitates DNA accessibility, transcription factor binding, and histone post-translational modification at active promoters. While H3.3 is not required for maintaining transcription in ESCs, it does promote de novo transcription factor binding which may contribute to the dysregulation of cellular differentiation in the absence of H3.3.
Adjustment for baseline characteristics in randomized trials using logistic regression: sample-based model versus true model
Authors: Perneger Thomas , Combescure Christophe , Poncet Antoine 
Published: February 2023

Abstract
Background
Adjustment for baseline prognostic factors in randomized clinical trials is usually performed by means of sample-based regression models. Sample-based models may be incorrect due to overfitting. To assess whether overfitting is a problem in practice, we used simulated data to examine the performance of the sample-based model in comparison to a “true” adjustment model, in terms of estimation of the treatment effect.

Methods
We conducted a simulation study using samples drawn from a “population” in which both the treatment effect and the effect of the potential confounder were specified. The outcome variable was binary. Using logistic regression, we compared three estimates of the treatment effect in each situation: unadjusted, adjusted for the confounder using the sample, adjusted for the confounder using the true effect. Experimental factors were sample size (from 2 × 50 to 2 × 1000), treatment effect (logit of 0, 0.5, or 1.0), confounder type (continuous or binary), and confounder effect (logit of 0, − 0.5, or − 1.0). The assessment criteria for the estimated treatment effect were bias, variance, precision (proportion of estimates within 0.1 logit units), type 1 error, and power.

Results
Sample-based adjustment models yielded more biased estimates of the treatment effect than adjustment models that used the true confounder effect but had similar variance, accuracy, power, and type 1 error rates. The simulation also confirmed the conservative bias of unadjusted analyses due to the non-collapsibility of the odds ratio, the smaller variance of unadjusted estimates, and the bias of the odds ratio away from the null hypothesis in small datasets.

Conclusions
Sample-based adjustment yields similar results to exact adjustment in estimating the treatment effect. Sample-based adjustment is preferable to no adjustment.
Comparing the effects of breastfeeding in the laid-back and cradle position upon the experiences of primiparous women: a parallel randomized clinical trial
Authors: Bashiri Asefe , Amiri-Farahani Leila , Salehiniya Hamid , Pezaro Sally 
Published: February 2023

Abstract
Background and aim
Appropriate positioning is crucial to successful breastfeeding and its continuation. Positioning can create, prevent, or correct breastfeeding problems. This study aimed to determine and compare the effects of both the laid-back and cradle positions upon the breastfeeding experiences of primiparous (cisgender) women.

Methods
A parallel randomized clinical trial was conducted with a sample of primiparous women (n = 168) with a gestational age of between 31 and 34 weeks, referring to the perinatal clinic of Shahid Gharazi Hospital in Malayer (Hamadan Province, Iran). Participants were recruited via convenience sampling and allocated to one of two groups: intervention (laid-back position) (n = 85) and control (cradle position) (n = 83) using the random block method. Breastfeeding education was given to both groups during two sessions (weeks 31–34 and 35-–37 of pregnancy) by “baby-friendly” accredited hospitals in Iran. The intervention group was instructed on how to breastfeed using the laid-back position. The control group was instructed on how to breastfeed using the cradle position. In the immediate postnatal period, breastfeeding positions were assessed in both groups. Breastfeeding experiences were measured once at the time of participants returning home and again at both 1 week and 2 weeks following birth, using the breastfeeding experience scale. Data analysis was undertaken using the SPSS software version 21. A value of P < 0.05 was considered significant.

Results
No statistically significant difference was observed between the two groups in terms of concerns relating to participants nor their breasts, milk insufficiency, neonate, process, or breastfeeding experience at any time point measured. The means (SDs) of breastfeeding experience at the time of discharge, 1 week, and 2 weeks after childbirth in intervention group were 26.07 (4.533), 26.85 (3.812), and 26.65 (4.632) respectively. The means (SDs) of breastfeeding experience at the time of discharge, 1 week, and 2 weeks after childbirth in control group were 25.42 (3.315), 26.68 (3.872), and 25.41 (4.05) respectively.

Conclusion
There is no difference in breastfeeding experiences whether the laid-back or cradle position is used. Thus, broader education on breastfeeding and the provision of comprehensive support may be more effective in optimizing one’s experience of breastfeeding.

Trial registration
Registration date: 2021 July 21, Code: IRCT20180427039436N10, https://irct.ir/user/trial/57054/view
Vulvar leiomyoma in an adolescent girl: a case report and review of the literature
Authors: Goyal Lajya Devi , Garg Priyanka , Kaur Manmeet 
Published: February 2023

Abstract
Background
Vulvar leiomyoma is a rare soft tissue tumor, with only around 300 cases described in the literature. Owing to its low incidence of just 0.03% of all gynecological tumors, it often poses a great diagnostic challenge, especially in teenagers. We report this rare occurrence of vulvar leiomyoma in a teenage girl who was primarily left untreated due to cultural taboos and fear of loss of virginity. The main aim in presenting such rare case studies is to raise awareness and expand the diagnostic horizon of the surgeon for appropriate management.

Case presentation
We describe a case of a 15-year-old North Indian, sexually inactive unmarried girl, who presented with a history of painless swelling in the left labia majora for the last 1 year, which gradually increased in size. There was no associated pain or any other difficulty. Local examination revealed a 14 × 10 cm solid, unilateral nonpedunculated mass on the left labia majora with superficial vascularity. Differential diagnoses of sarcoma, lipoma, Bartholin cyst, and fibroid were kept in mind. Ultrasonography revealed a solid mass with superficial vascularity with normal internal genitalia. The mass was enucleated with an intact capsule under anesthesia. Histopathology confirmed it to be benign vulvar leiomyoma. The patient was discharged after 3 days in a satisfactory condition.

Conclusion
Leiomyoma of the vulva is an exceptionally rare tumor and is seldom seen in teenagers. It is often misinterpreted as a Bartholin cyst and should be kept as one of the differential diagnosis in teenage girls presenting with unilateral vulvar swelling. Vulvar leiomyoma can be completely cured by surgical removal if diagnosed timely without compromising virginity, so should never be missed in adolescents.
Paraphilia without symptoms of primary psychiatric disorder: a case report
Authors: Pang Nicholas Tze Ping , Masiran Ruziana , Alimuddin Aishah Siddiqah 
Published: February 2023

Abstract
Background
Paraphilias are recurrent and arousing fantasies, thoughts, and behaviors that cause distress to sufferers and surrounding people. This case report details the challenge of managing multiple paraphilias with compulsive sexual behavior.

Case presentation
A 48-year-old Malay man presented with compulsive sexual behavior, encompassing voyeuristic, frotteurism, and exhibitionistic behavior, increasing progressively over the years, with accompanying overvalued ideas of erotomania. Despite the high level of dysfunction occupationally and socially, there were no apparent psychotic, manic, or depressive symptoms. An organic workup was unremarkable, and he was diagnosed with multiple paraphilias. Treatment with selective serotonin reuptake inhibitors was commenced, and psychologically he was managed with techniques specific to compulsive sexual behavior.

Conclusion
Though rare in the literature, both paraphilic disorders and compulsive sexual behaviors are very distressing to sufferers and their families alike, and thorough biopsychological investigations are essential to ensure reversible causes are not overlooked.
Sex differences in subjective cognitive impairment and clinical correlates in Chinese patients with subthreshold depression
Authors: lv Qinyu , Li Xin , Zhang Yao , Lu Daofeng , Lu Jiajing , Xie Qingfang , Li Hong , Wu Yiming , Wang Chongze , Yi Zhenghui 
Published: February 2023

Abstract
Objective
Subthreshold depression (SD) is a global mental health problem given its high prevalence, comorbidity, functional impairment, and its association with increased service utilization. However, currently little is known about sex differences of SD in cognitive impairment with clinical correlates. This study aims to explore sex differences in subjective cognitive impairment and clinically associated risk factors in Chinese patients with subthreshold depression (SD).

Methods
A total of 126 patients with SD, 40 males and 86 females, aged 18–45 years, were included in this cross-sectional observational study. Their general information, psychological assessments, and psychiatric symptom assessments were collected online. The Patient Health Questionnaire depression-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Perceived Deficits Questionnaire-Depression (PDQ-D), and Toronto Alexithymia Scale (TAS-20) with 3 subdomains were used. The obtained scores were analyzed with partial correlation and multiple linear regression analysis models.

Results
Our results showed that females had significantly higher PDQ-D-20 total score than males. However, the differences in TAS-20 and subdomain score according to sex were not significant. Notably, TAS-20 and DDF (difficulty describing feelings) subdomain contributed to cognitive impairment in males, whereas both PHQ-9 total score and TAS-20 or DDF subdomain contributed to cognitive impairment in females.

Conclusion
These findings revealed significant sex differences in cognitive impairment and clinical correlates in SD, which should be further followed-up in the future.
Prognostic value of 18F-FDG PET/CT-based radiomics combining dosiomics and dose volume histogram for head and neck cancer
Authors: Wang Bingzhen , Liu Jinghua , Zhang Xiaolei , Wang Zhongxiao , Cao Zhendong , Lu Lijun , Lv Wenbing , Wang Aihui , Li Shuyan , Wu Xiaotian , Dong Xianling 
Published: February 2023

Abstract
Objectives
By comparing the prognostic performance of 18F-FDG PET/CT-based radiomics combining dose features [Includes Dosiomics feature and the dose volume histogram (DVH) features] with that of conventional radiomics in head and neck cancer (HNC), multidimensional prognostic models were constructed to investigate the overall survival (OS) in HNC.

Materials and methods
A total of 220 cases from four centres based on the Cancer Imaging Archive public dataset were used in this study, 2260 radiomics features and 1116 dosiomics features and 8 DVH features were extracted for each case, and classified into seven different models of PET, CT, Dose, PET+CT, PET+Dose, CT+Dose and PET+CT+Dose. Features were selected by univariate Cox and Spearman correlation coefficients, and the selected features were brought into the least absolute shrinkage and selection operator (LASSO)-Cox model. A nomogram was constructed to visually analyse the prognostic impact of the incorporated dose features. C-index and Kaplan–Meier curves (log-rank analysis) were used to evaluate and compare these models.

Results
The cases from the four centres were divided into three different training and validation sets according to the hospitals. The PET+CT+Dose model had C-indexes of 0.873 (95% CI 0.812–0.934), 0.759 (95% CI 0.663–0.855) and 0.835 (95% CI 0.745–0.925) in the validation set respectively, outperforming the rest models overall. The PET+CT+Dose model did well in classifying patients into high- and low-risk groups under all three different sets of experiments (p < 0.05).

Conclusion
Multidimensional model of radiomics features combining dosiomics features and DVH features showed high prognostic performance for predicting OS in patients with HNC.
Relevance of 18F-DOPA visual and semi-quantitative PET metrics for the diagnostic of Parkinson disease in clinical practice: a machine learning-based inference study
Authors: Iep Alex , Chawki Mohammad B. , Goldfarb Lucas , Nguyen Loc , Brulon Vincent , Comtat Claude , Lebon Vincent , Besson Florent L. 
Published: February 2023

Abstract
Purpose
To decipher the relevance of visual and semi-quantitative 6-fluoro-(18F)-L-DOPA (18F-DOPA) interpretation methods for the diagnostic of idiopathic Parkinson disease (IPD) in hybrid positron emission tomography (PET) and magnetic resonance imaging.

Material and methods
A total of 110 consecutive patients (48 IPD and 62 controls) with 11 months of median clinical follow-up (reference standard) were included. A composite visual assessment from five independent nuclear imaging readers, together with striatal standard uptake value (SUV) to occipital SUV ratio, striatal gradients and putamen asymmetry-based semi-quantitative PET metrics automatically extracted used to train machine learning models to classify IPD versus controls. Using a ratio of 70/30 for training and testing sets, respectively, five classification models—k-NN, LogRegression, support vector machine, random forest and gradient boosting—were trained by using 100 times repeated nested cross-validation procedures. From the best model on average, the contribution of PET parameters was deciphered using the Shapley additive explanations method (SHAP). Cross-validated receiver operating characteristic curves (cv-ROC) of the most contributive PET parameters were finally estimated and compared.

Results
The best machine learning model (k-NN) provided final cv-ROC of 0.81. According to SHAP analyses, visual PET metric was the most important contributor to the model overall performance, followed by the minimum between left and right striatal to occipital SUV ratio. The 10-time cv-ROC curves of visual, min SUVr or both showed quite similar performance (mean area under the ROC of 0.81, 0.81 and 0.79, respectively, for visual, min SUVr or both).

Conclusion
Visual expert analysis remains the most relevant parameter to predict IPD diagnosis at 11 months of median clinical follow-up in 18F-FDOPA. The min SUV ratio appears interesting in the perspective of simple semi-automated diagnostic workflows.
Neurocircuitry underlying the antidepressant effect of retrograde facial botulinum toxin in mice
Authors: Ni Linhui , Chen Hanze , Xu Xinxin , Sun Di , Cai Huaying , Wang Li , Tang Qiwen , Hao Yonggang , Cao Shuxia , Hu Xingyue 
Published: February 2023

Abstract
Backgrounds
Botulinum toxin type A (BoNT/A) is extensively applied in spasticity and dystonia as it cleaves synaptosome-associated protein 25 (SNAP25) in the presynaptic terminals, thereby inhibiting neurotransmission. An increasing number of randomized clinical trials have suggested that glabellar BoNT/A injection improves depressive symptoms in patients with major depressive disorder (MDD). However, the underlying neuronal circuitry of BoNT/A-regulated depression remains largely uncharacterized.

Results
Here, we modeled MDD using mice subjected to chronic restraint stress (CRS). By pre-injecting BoNT/A into the unilateral whisker intrinsic musculature (WIM), and performing behavioral testing, we showed that pre-injection of BoNT/A attenuated despair- and anhedonia-like phenotypes in CRS mice. By applying immunostaining of BoNT/A-cleaved SNAP25 (cl.SNAP25197), subcellular spatial localization of SNAP25 with markers of cholinergic neurons (ChAT) and post-synaptic membrane (PSD95), and injection of monosynaptic retrograde tracer CTB-488-mixed BoNT/A to label the primary nucleus of the WIM, we demonstrated that BoNT/A axonal retrograde transported to the soma of whisker-innervating facial motoneurons (wFMNs) and subsequent transcytosis to synaptic terminals of second-order neurons induced central effects. Furthermore, using transsynaptic retrograde and monosynaptic antegrade viral neural circuit tracing with c-Fos brain mapping and co-staining of neural markers, we observed that the CRS-induced expression of c-Fos and CaMKII double-positive neurons in the ventrolateral periaqueductal grey (vlPAG), which sent afferents to wFMNs, was down-regulated 3 weeks after BoNT/A facial pre-administration. Strikingly, the repeated and targeted silencing of the wFMNs-projecting CaMKII-positive neurons in vlPAG with a chemogenetic approach via stereotactic injection of recombinant adeno-associated virus into specific brain regions of CRS mice mimicked the antidepressant-like action of BoNT/A pre-treatment. Conversely, repeated chemogenetic activation of this potential subpopulation counteracted the BoNT/A-improved significant antidepressant behavior.

Conclusion
We reported for the first time that BoNT/A inhibited the wFMNs-projecting vlPAG excitatory neurons through axonal retrograde transport and cell-to-cell transcytosis from the injected location of the WIM to regulate depressive-like phenotypes of CRS mice. For the limited and the reversibility of side effects, BoNT/A has substantial advantages and potential application in MDD.
Two new methods applied to crown width additive models: a case study for three tree species in Northeastern China
Authors: Wang Junjie , Jiang Lichun , Xin Shidong , Wang Youzhu , He Pei , Yan Yunfei 
Published: February 2023

Abstract
Key message
The non-linear seemingly unrelated regression mixed-effects model (NSURMEM) and generalized additive model (GAM) were applied for the first time in crown width (CW) additive models of larch (Larix gmelinii Rupr.), birch (Betula platyphylla Suk.), and poplar (Populus davidiana Dode). The crown radii in four directions (CR) exhibited different growth trends and responded differently to tree size and competition variables. In the absence of calibration, GAM was more accurate than NSURMEM for CR and CW predictions.

Context
Crown radii in four directions (CR) and crown width (CW) are fundamental indicators used to describe tree crowns. The complexity of the CR growth in four directions of different tree species in natural forests is often ignored. There is logical additivity among CR and CW that is also often overlooked. Furthermore, the existing methods applied to CW additive models have some drawbacks.

Aims
We aim to: (i) evaluate the utility of two new methods in developing CW additive models for larch (Larix gmelinii Rupr.), birch (Betula platyphylla Suk.), and poplar (Populus davidiana Dode) in natural secondary forests of Northeastern China; and (ii) explore the growth patterns of CR in four directions to gain important ecological insights.

Methods
The non-linear seemingly unrelated regression mixed-effects model (NSURMEM) and generalized additive model (GAM) were used to develop CW additive models and to explore crown growth patterns. The predictive ability of the additive models was evaluated using leave-one-plot-out cross-validation (LOOCV).

Results
At a fair level without calibration, GAM provided slightly better results than NSURMEM. The response of the four CR to tree size and competition variables is different and may be non-uniform due to complex stand conditions and tree growth strategies.

Conclusion
The newly provided methods applied to additive models are available for external datasets. GAM is recommended in the absence of calibration. This study has important implications for the understanding of natural forest dynamics and decision-making for critical stand management.