bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reprogramming of adult human dermal fibroblasts to induced dorsal forebrain precursor cells maintains aging signatures
Authors: McCaughey-Chapman Amy , Tarczyluk-Wells Marta , Combrinck Catharina , Edwards Nicole , Jones Kathryn , Connor Bronwen 
Published: January 2023

Introduction: With the increase in aging populations around the world, the development of in vitro human cell models to study neurodegenerative disease is crucial. A major limitation in using induced pluripotent stem cell (hiPSC) technology to model diseases of aging is that reprogramming fibroblasts to a pluripotent stem cell state erases age-associated features. The resulting cells show behaviors of an embryonic stage exhibiting longer telomeres, reduced oxidative stress, and mitochondrial rejuvenation, as well as epigenetic modifications, loss of abnormal nuclear morphologies, and age-associated features.Methods: We have developed a protocol utilizing stable, non-immunogenic chemically modified mRNA (cmRNA) to convert adult human dermal fibroblasts (HDFs) to human induced dorsal forebrain precursor (hiDFP) cells, which can subsequently be differentiated into cortical neurons. Analyzing an array of aging biomarkers, we demonstrate for the first time the effect of direct-to-hiDFP reprogramming on cellular age.Results: We confirm direct-to-hiDFP reprogramming does not affect telomere length or the expression of key aging markers. However, while direct-to-hiDFP reprogramming does not affect senescence-associated β-galactosidase activity, it enhances the level of mitochondrial reactive oxygen species and the amount of DNA methylation compared to HDFs. Interestingly, following neuronal differentiation of hiDFPs we observed an increase in cell soma size as well as neurite number, length, and branching with increasing donor age suggesting that neuronal morphology is altered with age.Discussion: We propose direct-to-hiDFP reprogramming provides a strategy for modeling age-associated neurodegenerative diseases allowing the persistence of age-associated signatures not seen in hiPSC-derived cultures, thereby facilitating our understanding of neurodegenerative disease and identification of therapeutic targets.
Altered brain activities in mesocorticolimbic pathway in primary dysmenorrhea patients of long-term menstrual pain
Authors: Liu Ni , Li Yingqiu , Hong Yueying , Huo Jianwei , Chang Tai , Wang Haoyuan , Huang Yiran , Li Wenxun , Zhang Yanan 
Published: January 2023

BackgroundPatients with primary dysmenorrhea (PDM) often present with abnormalities other than dysmenorrhea including co-occurrence with other chronic pain conditions and central sensitization. Changes in brain activity in PDM have been demonstrated; however, the results are not consistent. Herein, this study probed into altered intraregional and interregional brain activity in patients with PDM and expounded more findings.MethodsA total of 33 patients with PDM and 36 healthy controls (HCs) were recruited and underwent a resting-state functional magnetic resonance imaging scan. Regional homogeneity (ReHo) and mean amplitude of low-frequency fluctuation (mALFF) analysis were applied to compare the difference in intraregional brain activity between the two groups, and the regions with ReHo and mALFF group differences were used as seeds for functional connectivity (FC) analysis to explore the difference of interregional activity. Pearson's correlation analysis was conducted between rs-fMRI data and clinical symptoms in patients with PDM.ResultsCompared with HCs, patients with PDM showed altered intraregional activity in a series of brain regions, including the hippocampus, the temporal pole superior temporal gyrus, the nucleus accumbens, the pregenual anterior cingulate cortex, the cerebellum_8, the middle temporal gyrus, the inferior temporal gyrus, the rolandic operculum, the postcentral gyrus and the middle frontal gyrus (MFG), and altered interregional FC mainly between regions of the mesocorticolimbic pathway and regions associated with sensation and movement. The anxiety symptoms are correlated with the intraregional activity of the right temporal pole superior temporal gyrus and FC between MFG and superior frontal gyrus.ConclusionOur study showed a more comprehensive method to explore changes in brain activity in PDM. We found that the mesocorticolimbic pathway might play a key role in the chronic transformation of pain in PDM. We, therefore, speculate that the modulation of the mesocorticolimbic pathway may be a potential novel therapeutic mechanism for PDM.
Identify potential driver genes for PAX-FOXO1 fusion-negative rhabdomyosarcoma through frequent gene co-expression network mining
Authors: Zhan Xiaohui , Liu Yusong , Jannu Asha Jacob , Huang Shaoyang , Ye Bo , Wei Wei , Pandya Pankita H. , Ye Xiufen , Pollok Karen E. , Renbarger Jamie L. , Huang Kun , Zhang Jie 
Published: January 2023

BackgroundRhabdomyosarcoma (RMS) is a soft tissue sarcoma usually originated from skeletal muscle. Currently, RMS classification based on PAX–FOXO1 fusion is widely adopted. However, compared to relatively clear understanding of the tumorigenesis in the fusion-positive RMS, little is known for that in fusion-negative RMS (FN-RMS).MethodsWe explored the molecular mechanisms and the driver genes of FN-RMS through frequent gene co-expression network mining (fGCN), differential copy number (CN) and differential expression analyses on multiple RMS transcriptomic datasets.ResultsWe obtained 50 fGCN modules, among which five are differentially expressed between different fusion status. A closer look showed 23% of Module 2 genes are concentrated on several cytobands of chromosome 8. Upstream regulators such as MYC, YAP1, TWIST1 were identified for the fGCN modules. Using in a separate dataset we confirmed that, comparing to FP-RMS, 59 Module 2 genes show consistent CN amplification and mRNA overexpression, among which 28 are on the identified chr8 cytobands. Such CN amplification and nearby MYC (also resides on one of the above cytobands) and other upstream regulators (YAP1, TWIST1) may work together to drive FN-RMS tumorigenesis and progression. Up to 43.1% downstream targets of Yap1 and 45.8% of the targets of Myc are differentially expressed in FN-RMS vs. normal comparisons, which also confirmed the driving force of these regulators.DiscussionWe discovered that copy number amplification of specific cytobands on chr8 and the upstream regulators MYC, YAP1 and TWIST1 work together to affect the downstream gene co-expression and promote FN-RMS tumorigenesis and progression. Our findings provide new insights for FN-RMS tumorigenesis and offer promising targets for precision therapy. Experimental investigation about the functions of identified potential drivers in FN-RMS are in progress.
What Helping Babies Breathe knowledge and skills are formidable for healthcare workers?
Authors: Patel Archana B. , Bang Akash , Kurhe Kunal , Bhargav Savita , Hibberd Patricia L. 
Published: January 2023

IntroductionMost neonatal deaths occur in the first week of life, due to birth asphyxia. Helping Babies Breathe (HBB), is a simulation-based neonatal resuscitation training program to improve knowledge and skills. There is little information on which knowledge items or skill steps are challenging for the learners.MethodsWe used training data from NICHD's Global Network study to understand the items most challenging for Birth Attendants (BA) to guide future curriculum modifications. HBB training was provided in 15 primary, secondary and tertiary level care facilities in Nagpur, India. Refresher training was provided 6 months later. Each knowledge item and skill step was ranked from difficulty level 1 to 6 based on whether 91%–100%, 81%–90%, 71%–80%, 61%–70%, 51%–60% or &lt;50% of learners answered/performed the step correctly.ResultsThe initial HBB training was conducted in 272 physicians and 516 midwives of which 78 (28%) physicians and 161 (31%) midwives received refresher training. Questions related to timing of cord clamping, management of a meconium-stained baby, and steps to improve ventilation were most difficult for both physicians and midwives. The initial steps of Objective Structured Clinical Examination (OSCE)-A i.e. equipment checking, removing wet linen and immediate skin-to-skin contact were most difficult for both groups. Midwives missed stimulating newborns while physicians missed cord clamping and communicating with mother. In OSCE-B, starting ventilation in the first minute of life was the most missed step after both initial and 6 months refresher training for physicians and midwives. At the retraining, the retention was worst for cutting the cord (physicians level 3), optimal rate of ventilation, improving ventilation &amp; counting heart rate (midwives level 3), calling for help (both groups level 3) and scenario ending step of monitoring the baby and communicating with mother (physicians level 4, midwives 3).ConclusionAll BAs found skill testing more difficult than knowledge testing. The difficulty level was more for midwives than for physicians. So, the HBB training duration and frequency of retraining can be tailored accordingly. This study will also inform subsequent refinement in the curriculum so that both trainers and trainees will be able to achieve the required proficiency.
Long COVID in children and adolescents: COVID-19 follow-up results in third-level pediatric hospital
Authors: Jamaica Balderas Lourdes María del Carmen , Navarro Fernández Amairani , Dragustinovis Garza Susana Azeneth , Orellana Jerves María Isabel , Solís Figueroa Walter Ernesto , Koretzky Solange Gabriela , Márquez González Horacio , Klünder Klünder Miguel , Espinosa Juan Garduño , Nieto Zermeño Jaime , Villa Guillén Mónica , Rosales Uribe Rómulo Erick , Olivar López Victor 
Published: January 2023

IntroductionIn children, the manifestations of coronavirus disease 2019 (COVID-19) in the acute phase are considered mild compared with those in adults; however, some children experience a severe disease that requires hospitalization. This study was designed to present the operation and follow-up results of the Post-COVID-19 Detection and Monitoring Sequels Clinic of Hospital Infantil de Mexico Federico Gómez in managing children with a history of SARS-CoV-2 infection.MethodsThis was a prospective study conducted from July 2020 to December 2021, which included 215 children aged 0–18 years who tested positive for SARS-CoV-2 on polymerase chain reaction and/or immunoglobulin G test. The follow-up was conducted in the pulmonology medical consultation; ambulatory and hospitalized patients were assessed at 2, 4, 6, and 12 months.ResultsThe median age of the patients was 9.02 years, and neurological, endocrinological, pulmonary, oncological, and cardiological comorbidities were the most commonly observed among the patients. Moreover, 32.6% of the children had persistent symptoms at 2 months, 9.3% at 4 months, and 2.3% at 6 months, including dyspnea, dry cough, fatigue, and runny nose; the main acute complications were severe pneumonia, coagulopathy, nosocomial infections, acute renal injury, cardiac dysfunction, and pulmonary fibrosis. The more representative sequelae were alopecia, radiculopathy, perniosis, psoriasis, anxiety, and depression.ConclusionsThis study showed that children experience persistent symptoms, such as dyspnea, dry cough, fatigue, and runny nose, although to a lesser extent than adults, with significant clinical improvement 6 months after the acute infection. These results indicate the importance of monitoring children with COVID-19 through face-to-face consultations or telemedicine, with the objective of offering multidisciplinary and individualized care to preserve the health and quality of life of these children.
Alteration of the gut microbiota after surgery in preterm infants with necrotizing enterocolitis
Authors: Lin Huijia , Xu Cuifang , Chen Junjin , Ma Xiaolu , Shi Liping , Shi Wei , Du Lizhong , Ni Yan 
Published: January 2023

PurposeTo investigate the dynamic changes in the intestinal microbiota in preterm infants with necrotizing enterocolitis (NEC) before and after treatment via a prospective case-control study.MethodsPreterm infants with NEC and preterm infants with similar age and weight (control group) were enrolled in this study. They were divided into NEC_Onset (diagnosis time), NEC_Refeed (refeed time), NEC_FullEn (full enteral nutrition time), Control_Onset, and Control_FullEn groups according to the time of the fecal material collected. Except for basic clinical information, fecal specimens of the infants were obtained as well at indicated times for 16S rRNA gene sequencing. All infants were followed up after discharge from the NICU, and the growth data of the corrected age of 12 months were acquired from the electronic outpatient system and telephonic interviews.ResultsA total of 13 infants with NEC and 15 control infants were enrolled. A gut microbiota analysis showed that the Shannon and Simpson indices were lower in the NEC_FullEn group than in the Control_FullEn group (p &lt; .05). Methylobacterium, Clostridium_butyricum, and Acidobacteria were more abundant in infants with NEC during diagnosis. Methylobacterium and Acidobacteria were remained plentiful in the NEC group until the end of treatment. These bacteria species were significantly positively correlated with CRP and negatively correlated with platelet count. The rate of delayed growth was higher in the NEC group than in the control group (25% vs. 7.1%) at 12 months of corrected age, but there was no significant difference. In addition, the pathways of synthesis and degradation of ketone bodies were more active in the NEC subgroups, including both the NEC_Onset group and the NEC_FullEn group. The pathway of sphingolipid metabolism was more active in the Control_FullEn group.ConclusionEven after reaching the full enteral nutrition period, alpha diversity in infants with NEC who underwent surgery was lower than that in the control group infants. It may take more time to reestablish the normal gut flora of NEC infants after surgery. The pathways of the synthesis and degradation of ketone bodies and sphingolipid metabolism might be related to the pathogenesis of NEC and physical development after the occurrence of NEC.
University students’ experience of online space while engaging in synchronous learning via videoconferencing amidst the pandemic
Authors: Lee Ahram , Lee Jee Young , Jung Eunju 
Published: January 2023

BackgroundThe high infectivity and fatality of COVID-19 has changed the mode of higher education from onsite to online. Although many studies investigated the effectiveness and satisfaction of online education, little is known regarding university students’ lived experience of online space during synchronous learning via videoconferencing.ObjectiveThe present study explored how university students experienced online space when engaging in synchronous learning via videoconferencing platforms during the outbreak of the pandemic.MethodThe phenomenological approach was chosen to primarily explore students’ experience of online space as well as their experience of embodiment and relations to self and others. Interviews were conducted with nine university students who voluntarily participated to share their experience of online space.ResultsThree core themes were generated from the descriptions of experiences provided by the participants. For each core theme, two sub-themes were emerged and described. The analysis of the themes demonstrated that online space was experienced as being separate from home but also inseparable because it was an extension of the comforts of home. This inseparableness is also reflected in the virtual classroom where the rectangular screen presented on the monitor is always shared with everyone in the class. Moreover, online space was perceived as having no transitional space in which spontaneity and new encounters occur. Finally, the presence of self and others was experienced differently in online space due to the participants’ choices of being seen or heard using their microphones and cameras. This led to a different sense of togetherness in online space. The insights gained from the study were discussed in relation to considerations for online learning in the post-pandemic era.ConclusionBased on the emerged themes from the results, the current study concluded that the online space created by technologies cannot be a complete substitute for traditional face-to-face classrooms and suggested possible implications for designing and using online space in university education.
Implementation of a community health worker-focused team-based model of care: What modifications do clinics make?
Authors: Sotelo Guerra Laura J. , Ortiz Janette , Liljenquist Kendra , Szilagyi Peter G. , Fiscella Kevin , Porras-Javier Lorena , Johnson Gina , Friesema Lisa , Coker Tumaini R. 
Published: January 2023

BackgroundTeam-based care offers potential for integrating non-clinicians, such as community health workers (CHWs), into the primary care team to ensure that patients and families receive culturally relevant care to address their physical, social, and behavioral health and wellness needs. We describe how two federally qualified health center (FQHC) organizations adapted an evidence-based, team-based model of well-child care (WCC) designed to ensure that the parents of young children, aged 0–3, have their comprehensive preventive care needs met at WCC visits.MethodsEach FQHC formed a Project Working Group composed of clinicians, staff, and parents to determine what adaptations to make in the process of implementation of PARENT (Parent-Focused Redesign for Encounters, Newborns to Toddlers), a team-based care intervention that uses a CHW in the role of a preventive care coach. We use the Framework for Reporting Adaptations and Modifications to Evidence-based interventions (FRAME) to chronicle the various intervention modifications and the adaptation process, focusing on when and how modifications occurred, whether it was planned or unplanned, and the reasons and goals for the modification.ResultsThe Project Working Groups adapted several elements of the intervention in response to clinic priorities, workflow, staffing, space, and population need. Modifications were planned and proactive, and were made at the organization, clinic, and individual provider level. Modification decisions were made by the Project Working Group and operationalized by the Project Leadership Team. Examples of modifications include the following: (1) changing the parent coach educational requirement from a Master's degree to a bachelor's degree or equivalent experience to reflect the needs of the coach role; (2) the use of FQHC-specific templates for the coach's documentation of the pre-visit screening in the electronic health record; and (3) the use of electronic social needs referral tools to help the coach track and follow up on social need referrals. The modifications did not change the core elements (i.e., parent coach provision of preventive care services) or intervention goals.ConclusionsFor clinics implementing team-based care interventions, the engagement of key clinical stakeholders early and often in the intervention adaptation and implementation process, and planning for intervention modifications at both at an organizational level and at a clinical level are critical for local implementation.
Robot-assisted laparoscopic orchiopexy: A comparative analysis with laparoscopic orchiopexy
Authors: Rensing Adam J. , Qadar Abdul , Higganbotham Clark , Frimberger Dominic , Meenakshi-Sundaram Bhalaajee 
Published: January 2023

BackgroundWhile undescended testes are relatively common, the nonpalpable testis remains a challenging problem. The gold standard treatment remains the laparoscopic orchiopexy. However, today robot-assisted surgery has challenged traditional laparoscopy in many areas of urology. Yet the value of this new approach remains controversial, given concerns with operative time and cost. We reviewed our contemporary results of both robot-assisted orchiopexy (RALO) and traditional laparoscopic orchiopexy (TLO). Our primary aims were to retrospectively compare success rates, and operative time. Our secondary aims were to compare costs and complications related to each method.MethodsIn this study, all patients treated with laparoscopic and robot-assisted laparoscopic orchiopexy from April 2017 to January 2022 were reviewed using CPT code 54692. Exclusion criteria included bilateral concomitant orchiopexy or concomitant “major surgery,” or follow up less than 6 months. Also excluded were 1st stage orchiopexies. For the purposes of comparison, 1-stage and 2nd stage orchiopexies were included in the analysis. Patient demographics, surgical operative notes and documentation were all reviewed.ResultsAfter exclusion criteria was applied, 16 and 17 remained in the laparoscopic and robot-assisted cohorts, respectively. Upon follow up, all patients in both the laparoscopic and robot-assisted cohorts were noted to have a healthy testicle palpable in the dependent portion of the scrotum. The median operative time in the TLO group was 71 minutes, compared to 101 minutes in the RALO group (p&gt;0.0001). When comparing median hospital charges, the TLO group was lower at $38,813, compared to $46,455 in the RALO group (p = 0.0069). There was one postoperative complication in the TLO group (localized wound infection), compared to zero in the RALO group.ConclusionsThe robot-assisted orchiopexy is safe and effective. However, at this time it remains more costly in terms of time and resources.
Clinical features and prognostic factors analysis of intravenous leiomyomatosis
Authors: Chen Jingying , Bu Hualei , Zhang Zhaoyang , Chu Ran , Qi Gonghua , Zhao Chen , Wang Qiuman , Ma Xinyue , Wu Huan , Dou Zhiyuan , Wang Xia , Kong Beihua 
Published: January 2023

BackgroundThe treatment and prognostic factors of intravenous leiomyomatosis (IVL) remain lacking systematic evidence.MethodsA retrospective study was conducted on IVL patients from the Qilu Hospital of Shandong University, and IVL cases were published in PubMed, MEDLINE, Embase and Cochrane Library databases. Descriptive statistics were used for the basic characteristics of patients. The Cox proportional hazards regression analysis was used to assess the high-risk factors related to the progression-free survival (PFS). The comparison of survival curves was performed by Kaplan–Meier analysis.ResultsA total of 361 IVL patients were included in this study, 38 patients from Qilu Hospital of Shandong University, and 323 patients from the published literature. Age ≤45 years was observed in 173 (47.9%) patients. According to the clinical staging criteria, stage I/II was observed in 125 (34.6%) patients, and stage III/IV was observed in 221 (61.2%) patients. Dyspnea, orthopnea, and cough were observed in 108 (29.9%) patients. Completed tumor resection was observed in 216 (59.8%) patients, and uncompleted tumor resection was observed in 58 (16.1%) patients. Median follow-up period was 12 months (range 0–194 months), and 68 (18.8%) recurrences or deaths were identified. The adjusted multivariable Cox proportional hazard analysis showed age ≤45 years (vs. &gt;45) (hazard ratio [HR] = 2.09, 95% confidence interval [CI] 1.15–3.80, p = 0.016), and uncompleted tumor resection (vs. completed tumor resection) (HR = 22.03, 95% CI 8.31–58.36, p &lt; 0.001) were high-risk factors related to the PFS.ConclusionPatients with IVL have a high probability of recurrence after surgery and a poor prognosis. Patients younger than 45 years and with uncompleted tumor resection are at higher risk of postoperative recurrence or death.