bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic pregnenolone analog promotes microtubule dynamics and neural development
Authors: Kolas Viktoryia , Bandonil Jose Sandino A. , Wali Niaz , Hsia Kuo-Chiang , Shie Jiun-Jie , Chung Bon-chu 
Published: December 2022

Abstract
Background
Pregnenolone (P5) is a neurosteroid that promotes microtubule polymerization. It also reduces stress and negative symptoms of schizophrenia, promotes memory, as well as recovery from spinal cord injury. P5 is the first substance in the steroid-synthetic pathway; it can be further metabolized into other steroids. Therefore, it is difficult to differentiate the roles of P5 versus its metabolites in the brain. To alleviate this problem, we synthesized and screened a series of non-metabolizable P5 derivatives for their ability to polymerize microtubules similar to P5.

Results
We identified compound #43 (3-beta-pregnenolone acetate), which increased microtubule polymerization. We showed that compound #43 modified microtubule dynamics in live cells, increased neurite outgrowth and changed growth cone morphology in mouse cerebellar granule neuronal culture. Furthermore, compound #43 promoted the formation of stable microtubule tracks in zebrafish developing cerebellar axons.

Conclusions
We have developed compound #43, a nonmetabolized P5 analog, that recapitulates P5 functions in vivo and can be a new therapeutic candidate for the treatment of neurodevelopmental diseases.
Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone
Authors: Zeng Yan , Riquelme Manuel A. , Hua Rui , Zhang Jingruo , Acosta Francisca M. , Gu Sumin , Jiang Jean X. 
Published: December 2022

Abstract
Background
Mechanical loading promotes bone formation and osteocytes are a major mechanosensory cell in the bone. Both Piezo1 channels and connexin 43 hemichannels (Cx43 HCs) in osteocytes are important players in mechanotransduction and anabolic function by mechanical loading. However, the mechanism underlying mechanotransduction involving Piezo1 channels and Cx43 HCs in osteocytes and bone remains unknown.

Results
We showed that, like mechanical loading, Piezo1 specific agonist Yoda1 was able to increase intracellular Ca2+ signaling and activate Cx43 HCs, while Yoda1 antagonist Dooku1 inhibited Ca2+ and Cx43 HC activation induced by both mechanical loading and Yoda1. Moreover, the intracellular Ca2+ signal activated by Yoda1 was reduced by the inhibition of Cx43 HCs and pannexin1 (Panx1) channels, as well as ATP-P2X receptor signaling. Piezo1 and Cx43 HCs were co-localized on the osteocyte cell surface, and Yoda1-activated PI3K-Akt signaling regulated the opening of Cx43 HCs. Furthermore, Cx43 HCs opening by mechanical loading on tibias was ablated by inhibition of Piezo1 activation in vivo.

Conclusion
We demonstrated that upon mechanical stress, increased intracellular Ca2+ activated by Piezo1 regulates the opening of HCs through PI3K-Akt and opened Cx43 HCs, along with Panx1 channels, and ATP-P2X signaling sustain the intracellular Ca2+ signal, leading to bone anabolic function.
MicroRNA-378a-3p prevents initiation and growth of colorectal cancer by fine tuning polyamine synthesis
Authors: Liu Ningning , Zhang Tianpeng , Steer Clifford J. , Song Guisheng 
Published: December 2022

Abstract
Background
Inhibitors of ornithine decarboxylase (ODC) are effective at preventing colorectal cancer (CRC). However, their high toxicity limits their clinical application. This study was aimed to explore the potential of microRNAs (miRNAs) as an inhibitor of ODC.

Methods
miRNA array was used to identify dysregulated miRNAs in CRC tumors of mice and patients. Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) were used to induce CRC in mice. miRNA function in carcinogenesis was determined by soft-agar colony formation, flow cytometry, and wound healing of CRC cells. Mini-circle was used to deliver miRNA into colons.

Results
MiRNA profiling identified miR-378a-3p (miR-378a) as the most reduced miRNA in CRC tumors of patients and mice treated with AOM/DSS. Pathway array analysis revealed that miR-378a impaired c-MYC and ODC1 pathways. Further studies identified FOXQ1 (forkhead box Q1) and ODC1 as two direct targets of miR-378a. FOXQ1 activated transcription of c-MYC, a transcription activator of ODC1. In addition to directly targeting ODC1, miR-378a also inhibited expression of ODC1 via the FOXQ1-cMYC axis, thereby inhibiting polyamine synthesis in human CRC cells. Phenotypically, by reducing polyamine synthesis, miR-378a induced apoptosis and inhibited proliferation and migration of CRC cells, while disrupting the association of miR-378a with FOXQ1 and ODC1 offset the effects of miR-378a, suggesting that FOXQ1 and ODC1 were required for miR-378a to inhibit CRC cell growth. MiR-378a treatment robustly prevented growth of HCC by inhibiting polyamine synthesis in AOM/DSS mice.

Conclusion
MiR-378a prevents CRC by inhibiting polyamine synthesis, suggesting its use as a novel ODC inhibitor against CRC.
In vivo genome-wide CRISPR screening identifies ZNF24 as a negative NF-κB modulator in lung cancer
Authors: Liu Lu , Lei Yuxi , Chen Wensheng , Zhou Qian , Zheng Zongyao , Zeng Guandi , Liu Wanting , Feng Pengju , Zhang Zhiyi , Yu Lei , Chen Liang 
Published: December 2022

AbstractSystemic identification of tumor suppressor genes (TSGs) and elucidation of their signaling provide a new angle for understanding of tumorigenesis, which is important for developing successful treatment for lung cancer patients. In our current work, we conducted an in vivo screen for lung cancer TSGs through CRISPR/Cas9 mediated knockout of genes at genome-wide scale. We found that ZNF24 was a potent and clinically relevant TSG of lung cancer. Ectopic expression of ZNF24 arrested lung cancer cells in S phase. Mechanistically, ZNF24 bound to promoter region of P65 to negatively regulate its transcription and thereby the signaling activity of NF-κB pathway. This signaling cascade is clinically relevant. Importantly, we found that combinational inhibition of KRAS, NF-κB, and PD-1 effectively shrank autochthonous KrasG12D/ZNF24−/− lung cancers in transgenic mouse model. Our current work thus revealed an important role played by loss of function of ZNF24 in lung tumorigenesis and shed new light in precision medicine for a portion of lung cancer patients.
Experiences with teachers in childhood and their association with wellbeing in adulthood
Authors: Dittmann Christian , Forstmeier Simon 
Published: December 2022

AbstractBackgroundPrior research mainly focussed on the impact of the teacher-student relationship on teachers emotions and wellbeing. Current data shows a relationship between the quality of the teacher-student relationship and children's mental health. Unfortunately, it has not yet been investigated whether meaningful experiences with teachers also have an impact on students' well-being and whether an effect can still be found in adulthood. This work examines the impact of meaningful experiences with teachers during childhood and adolescence on the well-being of adults.MethodsThe data in this study was collected by using a questionnaire. The current well-being of the participants was assessed with measures of life satisfaction, resilience, anxiety, stress, depressiveness, and self-esteem. Also, participants were asked to briefly write about their most meaningful experiences with teachers and rate them regarding their valence. These experiences were categorized into seven categories using a summarizing content analysis. We then conducted a statistical analysis with the data obtained.ResultsThe results showed a highly significant correlation between the participants’ self-esteem and the valence ratings of their experiences. Furthermore, the experience category had a substantial effect on individual self-esteem. Overall, this study demonstrated that a relationship exists between the well-being of adults and their experiences with teachers during childhood and adolescence.ConclusionThe results of this study call for a reflective, fair, authentic, and empathetic approach to students. Accordingly, teachers should be intensively trained to establish a relationship with their students that is characterized by appreciation and empathy.
The impact of an additional implant under the saddle of removable partial dentures in Kennedy Class II edentulism on oral health-related quality of life and oral function: a case series report
Authors: Nogawa Toshifumi , Takayama Yoshiyuki , Ishikawa Makoto , Yokoyama Atsuro 
Published: December 2022

Abstract
Background
Implant-supported removable partial dentures (ISRPDs) provide effective prosthodontic treatment for partially edentulous patients. ISRPDs offer greater patient satisfaction and better oral function compared with removable partial dentures (RPDs) by enhancing denture stability and support. However, few clinical studies have focused on RPD design in patients with mandibular Kennedy Class II edentulism. The aim of this case reports was to investigate the oral function, oral health-related quality of life, and satisfaction of four patients with unilateral distal-extension mandibular RPDs with the same design which were replaced with ISRPDs. In addition, we investigated how each patient’s evaluation varied with the change from RPD to ISRPD.

Case presentation
Four patients had unilateral distal-extension mandibular edentulism and were missing the first and second molars and the first and second premolars. They received one implant (4.0 mm in diameter, 8.0 mm in length; IAT EXA PLUS Bone level; Nippon Piston Ring Co. Ltd, Saitama, Japan) at the position equivalent to the first molar in the edentulous residual ridge perpendicular to the occlusal plane. Implant position was determined by surgical guide plate. RPDs were fabricated after the residual mucosal membrane had healed. The basic design of the RPD was as follows: a cobalt–chromium alloy cast metal framework denture with a lingual bar as the major connector, a double Akers clasp on the molars and an auxiliary retainer on the premolar as indirect retainers, and a wrought wire clasp and a cast cingulum rest (combination clasp) as direct retainers. Masticatory performance, occlusal force, oral health-related quality of life, and satisfaction were estimated at baseline, and at time points after insertion of the RPD and after insertion of the adapted ISRPD. Each evaluation item showed a tendency for improvement on insertion of the new RPD. Masticatory performance and satisfaction tended to be better after insertion of the ISRPD than after insertion of the RPD.

Conclusion
Our findings suggest that ISRPDs provided better patient satisfaction and masticatory performance than RPDs in patients with mandibular Kennedy Class II edentulism.
Trial registration UMIN Clinical Trials Registry and Japan Registry of Clinical Trials, UMIN000025283 and jRCTs012180003. Registered 19 February 2016 and 17 December 2018, https://www.umin.ac.jp/ and https://jrct.niph.go.jp/
Factors associated with utilization of modern postpartum family planing methods during the extended postpartum period among mothers who gave birth in the last 12 months at Injibara town, Northwest, Ethiopia: a cross-sectional study
Authors: Andualem Getachew , Aklilu Almaz , Belay Getahun , Feyisa Wondu , Alemnew Fentahun 
Published: December 2022

Abstract
Background
The extended postpartum period is the first twelve months following childbirth and is an important entry point for family planning service providers to reduce unintended and too closely spaced pregnancies. A modern postpartum family planning service is one of the recommended public health interventions for reducing maternal and child morbidity and mortalities in sitting where maternal mortality is high, like in Ethiopia.

Objective
This study was aimed to assess factors associated with the utilization of modern family planning methods during the extended postpartum period among mothers who gave birth in the last 12 months at Injibara town, Northwest, Ethiopia.

Methods
A community-based cross-sectional study design was employed from March 1–15/2019 at Injibara town among 402 mothers. The data was collected by a simple random sampling technique and analyzed using the SPSS 23.0 version. Logistic regression analyses were employed to estimate the crude and adjusted odds ratio with a confidence interval of 95% and a P-value of < 0.05 in multivariable analysis considered statistically significant. Frequency tables and descriptive summaries were used to describe the study variables.

Results
The total sample size of this study was 402 and among them, 400 postpartum mothers participated in the study with a response rate of 99.5%. The utilization of modern family planning methods during the extended postpartum period among postpartum mothers was 58.5% [95% CI: 53.5- 63%]. Of these, 38.9% and 32.9% of the mothers were using injectables and implants respectively. Secondary and above educational level, having ≥ 3 antenatal care visits, resumption of menstruation, discussing with the partner on utilization of family planning method, being counseled on family planning method utilization during antenatal care visits and immediately after delivery, linkage of the mothers to a family planning unit during child immunization, and having good knowledge of family planning methods were associated with utilization of modern family planning methods during the extended postpartum period.

Conclusion
The utilization of modern family planning methods during the extended postpartum period among postpartum women was low compared to the world health organization recommendation. Socio-demographic, health care service uptakes, and reproductive characteristics were associated with the utilization of modern family planning methods during the extended postpartum period. We suggest emphasizing the education and counseling of women on the utilization of family planning during maternal and child health care service utilization. Mothers should be encouraged to start using modern family planning methods before the resumption of menses.
Diagnostic performance of quantitative Ga-SPECT/CT for patients with lower-limb osteomyelitis
Authors: Nishikawa Yoshito , Fukushima Yoshimitsu , Kirinoki Sonoko , Takagi Gen , Suda Masaya , Maki Toshio , Kumita Shinichiro 
Published: December 2022

AbstractBackgroundPatients with lower-limb osteomyelitis (LLOM) may experience major adverse events, such as lower-leg amputations or death; therefore, early diagnosis and risk stratification are essential to improve outcomes. Ga-scintigraphy is commonly used for diagnosing inflammatory diseases. Although the diagnostic performance of planar and SPECT imaging for localized lesions is limited, SPECT/CT, which simultaneously acquires functional and anatomical definition, has resulted in significant improvements to diagnostic confidence. While quantitative Ga-SPECT/CT is an emerging approach to improve diagnoses, its diagnostic performance has not been sufficiently evaluated to date. Therefore, this study aimed to evaluate the diagnostic performance of Ga-SPECT/CT with quantitative analyses for patients with LLOM.MethodsA total of 103 consecutive patients suspected of LLOM between April 2012 and October 2016 were analyzed. All patients underwent Ga-scintigraphy with SPECT/CT imaging. Findings were assessed visually, with higher than background accumulation considered positive, and quantitatively, using Ga-SPECT/CT images to calculate the lesion-to-background ratio (LBR), the maximum standardized uptake value (SUVmax), and total lesion uptake (TLU). Diagnoses were confirmed using pathological examinations and patient outcomes, and diagnostic performances of planar, SPECT, and SPECT/CT images were compared. To evaluate prognostic performance, all patients were observed for 5 years for occurrences of major adverse events (MAE), defined as recurrence of osteomyelitis, major leg amputation, or fatal event. Multivariate Cox regression was performed to evaluate outcome factors.ResultsThe overall diagnoses indicated that 54 out of 103 patients had LLOM. LBR, SUVmax, and TLU were significantly higher in patients with LLOM (12.23 vs. 1.00, 4.85 vs. 1.34, and 68.77 vs. 8.63, respectively;p < 0.001). Sensitivity and specificity were 91% and 96% for SPECT/CT with LBR, 89% and 94% for SPECT/CT with SUVmax, and 91% and 92% for SPECT/CT with TLU, respectively. MAE occurred in 23 of 54 LLOM patients (43%). TLU was found to be an independent prognostic factor (p = 0.047).ConclusionsGa-SPECT/CT using quantitative parameters, namely LBR and TLU, had better diagnostic and prognostic performances for patients with LLOM compared to conventional imaging. The results suggest that Ga-SPECT/CT is a good alternative for diagnosing LLOM in countries where FDG-PET/CT is not commonly available.
Two cases of childhood absence epilepsy who showed seizure disappearance after ethosuximide drug eruption
Authors: Nakamura Takuji , Uda Keiko , Matsuo Muneaki , Zaitsu Masafumi 
Published: December 2022

Abstract
Background
Recent studies suggest potential roles of immune response in the pathophysiology of epilepsy. Anti-seizure medications (ASMs) are known to have side effects of drug eruption caused by immune responses. A few reports in adults have demonstrated disappearance of seizures after an ASM drug eruption episode. In this paper, we described 2 cases of childhood absence epilepsy (CAE) who showed seizure disappearance after ethosuximide (ESM) drug eruption, suggesting the possibility that the epilepsy disappears due to immune responses to ASM.

Case presentation
Case 1 was an 8-year-old girl diagnosed with CAE. She was treated with valproate acid (VPA) initially, and then ESM was administered as an additional treatment. Her epileptic seizure disappeared 4 days after initiation of ESM. However, drug eruption appeared 1 week after the administration of ESM. Even after discontinuation of ESM administration, she maintains no seizure after the drug eruption. Case 2 was a 5-year-old boy diagnosed as CAE. He was treated with VPA initially, and ESM was administered additionally. Drug eruption appeared 1 month after the administration of ESM. Even after ESM was terminated, he maintained seizure freedom after the appearance of eruption.

Conclusions
Epileptic seizures may have been suppressed due to the immune responses caused by ASM eruption. Further studies are needed to elucidate the pathophysiologic effects of drug eruption on epilepsy through immune responses.
Not doomed: sociology and psychiatry, and ignorance and expertise
Authors: Ikkos George 
Published: December 2022

SummaryThis paper presents and responds to On the Heels of Ignorance, a sociological study which identifies five fundamental epistemological paradigm changes in American psychiatry in the service of its survival and details several tactics that have been employed to facilitate these professional reinventions. Issues raised in this presentation include the relationship between psychiatry, society and the state, and the nature and significance of psychiatric expertise. The dynamic of these relationships and the complexities of the required expertise create their own challenges for the advancement and professional accountability of the specialty. The conclusion suggests some future imperatives.
Social psychiatry lives!
Authors: Huxley Peter , Poole Rob 
Published: December 2022

SummaryIn this journal Ikkos examines the work of the American sociologist Owen Whooley, who argues that US psychiatry has gone through five paradigm shifts without defining the object of its own expertise. We look at the substance of Whooley's methods and assumptions and offer our observations on Ikkos's argument and conclusions.
Dissociation and its biological and clinical associations in functional neurological disorder: systematic review and meta-analysis
Authors: Campbell Malcolm C. , Smakowski Abigail , Rojas-Aguiluz Maya , Goldstein Laura H. , Cardeña Etzel , Nicholson Timothy R. , Reinders Antje A. T. S. , Pick Susannah 
Published: December 2022

BackgroundStudies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive review is lacking.AimsTo systematically review the severity of dissociative symptoms and prevalence of comorbid dissociative disorders in FND and summarise their biological and clinical associations.MethodWe searched Embase, PsycInfo and MEDLINE up to June 2021, combining terms for FND and dissociation. Studies were eligible if reporting dissociative symptom scores or rates of comorbid dissociative disorder in FND samples. Risk of bias was appraised using modified Newcastle–Ottawa criteria. The findings were synthesised qualitatively and dissociative symptom scores were included in a meta-analysis (PROSPERO CRD42020173263).ResultsSeventy-five studies were eligible (FNDn= 3940; controln= 3073), most commonly prospective case–control studies (k= 54). Dissociative disorders were frequently comorbid in FND. Psychoform dissociation was elevated in FND compared with healthy (g= 0.90, 95% CI 0.66–1.14,I2= 70%) and neurological controls (g= 0.56, 95% CI 0.19–0.92,I2= 67%). Greater psychoform dissociation was observed in FND samples with seizure symptoms versus healthy controls (g= 0.94, 95% CI 0.65–1.22,I2= 42%) and FND samples with motor symptoms (g= 0.40, 95% CI −0.18 to 1.00,I2= 54%). Somatoform dissociation was elevated in FND versus healthy controls (g= 1.80, 95% CI 1.25–2.34,I2= 75%). Dissociation in FND was associated with more severe functional symptoms, worse quality of life and brain alterations.ConclusionsOur findings highlight the potential clinical utility of assessing patients with FND for dissociative symptomatology. However, fewer studies investigated FND samples with motor symptoms and heterogeneity between studies and risk of bias were high. Rigorous investigation of the prevalence, features and mechanistic relevance of dissociation in FND is needed.
Use of Anticancer Therapies and Economic Burden Near the End of Life in Japan: Results From Claims Database
Authors: Kajimoto Yusuke , Honda Kazunori , Nozawa Kazuki , Mukai Mineko , Teng Lida , Igarashi Ataru 
Published: December 2022

PURPOSE In patients with cancer, aggressive treatment near the end of life (EOL) may decrease quality of life and increase medical costs. In this study, we examined the use of anticancer therapies near the EOL in Japan. METHODS We used a commercial database of health insurance claims in Japan, to examine patient data on cancer and death until August 2020. We assessed the proportion of patients using anticancer therapies within 14 days of death, associated factors, and medical costs from the payer's perspective. RESULTS The database documented 5,759 patients with cancer who died between December 2013 and August 2020. Among them, 4.8% of patients and 3.9% of age-adjusted patients received anticancer therapy within 14 days of death. Patients age < 60 years were associated with a high probability of receiving anticancer therapy near the EOL. The estimated annual anticancer therapy and related costs were Japanese yen 1,296 million (US dollars 12.6 million). CONCLUSION We found the percentage of patients receiving anticancer therapies within 14 days of death in Japan, its associated factors, and economic burden. Our findings can serve as a benchmark for optimizing EOL care.