bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory monocytes and microglia play independent roles in inflammatory ictogenesis
Authors: Howe Charles L. , LaFrance-Corey Reghann G. , Overlee Brittany L. , Johnson Renee K. , Clarkson Benjamin D. S. , Goddery Emma N. 
Published: January 2022

Abstract
Background
The pathogenic contribution of neuroinflammation to ictogenesis and epilepsy may provide a therapeutic target for reduction of seizure burden in patients that are currently underserved by traditional anti-seizure medications. The Theiler's murine encephalomyelitis virus (TMEV) model has provided important insights into the role of inflammation in ictogenesis, but questions remain regarding the relative contribution of microglia and inflammatory monocytes in this model.

Methods
Female C57BL/6 mice were inoculated by intracranial injection of 2 × 105, 5 × 104, 1.25 × 104, or 3.125 × 103 plaque-forming units (PFU) of the Daniel’s strain of TMEV at 4–6 weeks of age. Infiltration of inflammatory monocytes, microglial activation, and cytokine production were measured at 24 h post-infection (hpi). Viral load, hippocampal injury, cognitive performance, and seizure burden were assessed at several timepoints.

Results
The intensity of inflammatory infiltration and the extent of hippocampal injury induced during TMEV encephalitis scaled with the amount of infectious virus in the initial inoculum. Cognitive performance was preserved in mice inoculated with 1.25 × 104 PFU TMEV relative to 2 × 105 PFU TMEV, but peak viral load at 72 hpi was equivalent between the inocula. CCL2 production in the brain was attenuated by 90% and TNFα and IL6 production was absent in mice inoculated with 1.25 × 104 PFU TMEV. Acute infiltration of inflammatory monocytes was attenuated by more than 80% in mice inoculated with 1.25 × 104 PFU TMEV relative to 2 × 105 PFU TMEV but microglial activation was equivalent between groups. Seizure burden was attenuated and the threshold to kainic acid-induced seizures was higher in mice inoculated with 1.25 × 104 PFU TMEV but low-level behavioral seizures persisted and the EEG exhibited reduced but detectable abnormalities.

Conclusions
The size of the inflammatory monocyte response induced by TMEV scales with the amount of infectious virus in the initial inoculum, despite the development of equivalent peak infectious viral load. In contrast, the microglial response does not scale with the inoculum, as microglial hyper-ramification and increased Iba-1 expression were evident in mice inoculated with either 1.25 × 104 or 2 × 105 PFU TMEV. Inoculation conditions that drive inflammatory monocyte infiltration resulted in robust behavioral seizures and EEG abnormalities, but the low inoculum condition, associated with only microglial activation, drove a more subtle seizure and EEG phenotype.
Designing and validation of a reproductive health need assessment tool for women experienced domestic violence
Authors: Dolatian Mahrokh , Ebadi Abbas , Hasanpoor-Azghady Seyedeh Batool , NayebiNia Anvar Sadat 
Published: January 2022

Abstract
Background
Violence as a serious health problem and one of the main manifestations of gender inequality brings about adverse health effects for women. Therefore, it is of utmost importance to recognize the reproductive health status of women subjected to violence in order to provide the health services they need. Considering that one of the ways to determine reproductive health status is the use of valid questionnaires in this field, this study aimed to determine the components of reproductive health in domestic violated women and design a valid and reliable assessment tool.

Methods
The present study was conducted based on a mixed-method design. The first part of the study (qualitative section) was conducted based on conventional content analysis. In this part, unstructured in-depth interviews were conducted with 18 violated women and 9 experts. In the next stage, the item pool was formed and the Reproductive Health Needs of Violated Women Scale was designed based on the review of the literature and the results of the qualitative section with 39 items using the Waltz approach. For psychometric assessment of the above instrument, face and content validity, item analysis, and construct validity were examined using exploratory factor analysis.

Results
Based on the results of factor analysis, the four following factors were extracted with a total variance of 47.62: "men's participation", "self-care", "support and health services", as well as "sexual and marital relationships. The internal consistency of the instrument was calculated at α = 0.70–0.89 and α = 0.94 for different constructs and the whole instrument, respectively. Moreover, intra-cluster correlation coefficients were obtained at ICC = 0.96–0.99 and ICC = 0.98 for constructs and the whole instruments, respectively.

Conclusions
Based on the results of the current study, the present scale is a tool that specifically assesses the reproductive health needs of violated women and has appropriate validity and reliability. The results of the assessment using the aforementioned instruments can be of great help in promoting the reproductive health of women subjected to violence.
Associated factors of first-birth interval among women in reproductive age, addressing maternal and child health
Authors: Dehesh Tania , Malekmohammadi Neda , Dehesh Paria 
Published: January 2022

AbstractBackgroundThe first-birth interval directly influences family size and maternal and child mortality. The objective of this study is to investigate factors associated with the time of the first-birth after the first marriage among women in Iran.MethodsIn this cross-sectional study, the first birth history of 1350 women aged 15–49 years was collected in Kerman (southern Iran) in 2018. To assess the predictor variables of the first-birth interval and calculate the adjusted hazard ratios, multivariate Cox regression was used. The P-value < 0.05 was considered as significant. The statistical analysis of data was performed using SPSS version 22.ResultsThe average of the first-birth interval was 2.5 ∓ 0.8 years. Woman’s age at marriage (HR 1.48, 95% CI 1.32–2.48), husband’s age at marriage (HR 1.88, 95% CI 1.62–2.03), age at the first menstruation (HR 1.53, 95% CI 1.24–2.53), being rural residents (HR 2.041, 95% CI 1.26–2.95), and having engagement period (HR 1.85, 95% CI 1.52–3.05) were associated with short first-birth interval, and woman’s BMI (HR 1.72, 95% CI 1.54–2.77), woman’s university educational level (HR 1.47, 95% CI 1.35–2.57), husband’ s university educational level (HR 1.39, 95% CI 1.32–2.51), contraception use (HR 2.28, 95% CI 1.12–2.86) and income sufficiency (HR 2.25, 95% CI 1.12–2.96) were associated with long first-birth interval.ConclusionsBeing a rural resident is the most influential predictor of short first-birth interval and income sufficiency is the most influential predictor of long first-birth interval.
Assessing effects of exoskeleton misalignment on knee joint load during swing using an instrumented leg simulator
Authors: Bessler-Etten Jule , Schaake Leendert , Prange-Lasonder Gerdienke B. , Buurke Jaap H. 
Published: January 2022

Abstract
Background
Exoskeletons are working in parallel to the human body and can support human movement by exerting forces through cuffs or straps. They are prone to misalignments caused by simplified joint mechanics and incorrect fit or positioning. Those misalignments are a common safety concern as they can cause undesired interaction forces. However, the exact mechanisms and effects of misalignments on the joint load are not yet known. The aim of this study was therefore to investigate the influence of different directions and magnitudes of exoskeleton misalignment on the internal knee joint forces and torques of an artificial leg.

Methods
An instrumented leg simulator was used to quantify the changes in knee joint load during the swing phase caused by misalignments of a passive knee brace being manually flexed. This was achieved by an experimenter pulling on a rope attached to the distal end of the knee brace to create a flexion torque. The extension was not actuated but achieved through the weight of the instrumented leg simulator. The investigated types of misalignments are a rotation of the brace around the vertical axis and a translation in anteroposterior as well as proximal/distal direction.

Results
The amount of misalignment had a significant effect on several directions of knee joint load in the instrumented leg simulator. In general, load on the knee joint increased with increasing misalignment. Specifically, stronger rotational misalignment led to higher forces in mediolateral direction in the knee joint as well as higher ab-/adduction, flexion and internal/external rotation torques. Stronger anteroposterior translational misalignment led to higher mediolateral knee forces as well as higher abduction and flexion/extension torques. Stronger proximal/distal translational misalignment led to higher posterior and tension/compression forces.

Conclusions
Misalignments of a lower leg exoskeleton can increase internal knee forces and torques during swing to a multiple of those experienced in a well-aligned situation. Despite only taking swing into account, this is supporting the need for carefully considering hazards associated with not only translational but also rotational misalignments during wearable robot development and use. Also, this warrants investigation of misalignment effects in stance, as a target of many exoskeleton applications.
The phosphatase and tensin homolog gene inserted between NP and P gene of recombinant Newcastle disease virus oncolytic effect test to glioblastoma cell and xenograft mouse model
Authors: Jang Sung Hoon , Jung Bo-Kyoung , An Yong Hee , Jang Hyun 
Published: January 2022

Abstract
Background
Glioblastoma is one of the most serious brain cancer. Previous studies have demonstrated that PTEN function disorder affects the causing and exacerbation of glioblastoma. Newcastle disease virus (NDV) has been studied as a cancer virotherapeutics. In this study, PTEN gene was delivered to glioblastoma by recombinant NDV (rNDV) and translated into protein at the cytoplasm of the glioblastoma.

Methods
We did comparison tests PTEN protein expression efficiency and oncolytic effect depend on the PTEN gene insertion site at the between NP and P genes and the between P and M gene. PTEN protein mRNA transcription, translation in glioblastoma cell, and functional PTEN protein effect of the rNDV in vitro and in vivo test performed using western blotting, RT-qPCR, MTT assay, and Glioblastoma xenograft animal model test.

Results
The result of this study demonstrates that rNDV-PTEN kills glioblastoma cells and reduces cancer tissue better than rNDV without the PTEN gene. In molecular immunological and cytological assays, PTEN expression level was high at located in the between NP and P gene, and PTEN gene was successfully delivered to the glioblastoma cell using rNDV and PTEN gene translated to functional protein and inhibits hTERT and AKT gene.

Conclusions
PTEN gene enhances the oncolytic effect of the rNDV. And our study demonstrated that NP and P gene site is better than P and M gene site which is commonly and conventionally used. PTEN gene containing rNDV is a good candidate virotherapeutics for glioblastoma.
Association between intraoperative computed tomography navigation system and incidence of surgical site infection in patients with spinal surgeries: a retrospective analysis
Authors: Kumagai Gentaro , Wada Kanichiro , Tanaka Sunao , Asari Toru , Nitobe Yohshiro , Ishibashi Yasuyuki 
Published: January 2022

Abstract
Purpose
Although the use of intraoperative computed tomography (CT)-based navigation systems is unlikely to cause intraoperative contamination more than the use of intraoperative fluoroscopy, the association between intraoperative CT/navigation and surgical site infections (SSIs) remains unclear. We investigated the incidence of SSIs and the association between intraoperative CT/navigation and SSIs for spinal surgeries.

Methods
Of the 512 patients who underwent spinal surgery between April 2016 and December 2020, 304 underwent C-arm intraoperative fluoroscopy and/or Medtronic O-arm intraoperative CT/navigation system. We investigated the incidence of SSIs in patients with four techniques; no intraoperative imaging C-arm only, O-arm only, and both O- and C-arm used. Multivariate logistic analyses were conducted using the prevalence of SSIs as the dependent variable. The independent variables were age, sex, and potential confounders including preoperative Japanese Orthopaedic Association (JOA) score, use of instrumentation, C-arm, and/or O-arm.

Results
The incidence of the SSIs in patients with no imaging, C-arm only, O-arm only, and both modalities used was 1.9%, 7.3%, 4.7%, and 8.3%, respectively. There was no significant difference in the incidence of SSIs between the four techniques. Multivariate logistic analyses showed a significant correlation between the prevalence of SSI and JOA scores (odds ratio, 0.878; 95% CI 0.759–0.990) and use of instrumentation (odds ratio, 6.241; 95% CI 1.113–34.985), but not use of O-arm.

Conclusions
The incidence of the SSIs in patients with only O-arm used was 4.7%. Preoperative clinical status and use of instrumentation, but not use of the O-arm, were associated with SSIs after spinal surgeries.
Impact of valvuloarterial impedance on left ventricular reverse remodeling after aortic valve neocuspidization
Authors: Yamamoto Naoki , Ito Hisato , Inoue Kentaro , Futsuki Ayano , Hirano Koji , Shomura Yu , Ozu Yasuhisa , Katayama Yoshihiko , Komada Takuya , Takao Motoshi 
Published: January 2022

Abstract
Background
Aortic valve neocuspidization (AVNeo) has emerged as a promising aortic valve procedure, and is expected to have a larger effective orifice area (EOA) than commercially available bioprostheses. It is, however, unclear which indices could facilitate left ventricular (LV) reverse remodeling after AVNeo. The aim of this study is to verify the impact of global left ventricular afterload on the LV reverse remodeling following AVNeo.

Methods
Data-available consecutive 38 patients (median age, 77; interquartile range, 72.8–82.0) undergoing AVNeo for severe aortic stenosis were enrolled in this study. Preoperative and the last follow-up echocardiographic data were retrospectively analyzed including the valvuloarterial impedance (Zva), a marker of global LV afterload. Reduction in LV geometry index (LVGI) and relative wall thickness (RWT) were used as an indicator for LV reverse remodeling.

Results
The Zva reduced in 24 patients (63.2%) during the follow-up period (median, 12 months). Reduction in Zva significantly correlated to improvement of LV geometry (LVGI (r = 0.400, p = 0.013) and RWT (r = 0.627, p < 0.001)), whereas increase in EOA index did not significantly correlate to LVGI (r = 0.009, p = 0.957), or RWT (r = 0.105, p = 0.529)). The reduction in Zva was the multivariate predictor of LV reverse remodeling.

Conclusions
Low global LV afterload led to significant LV reverse remodeling even after AVNeo, which could achieve better valve performance than the conventional bioprostheses.
Phelan-McDermid syndrome: a classification system after 30 years of experience
Authors: Phelan Katy , Boccuto Luigi , Powell Craig M. , Boeckers Tobias M. , van Ravenswaaij-Arts Conny , Rogers R. Curtis , Sala Carlo , Verpelli Chiara , Thurm Audrey , Bennett William E. , Winrow Christopher J. , Garrison Sheldon R. , Toro Roberto , Bourgeron Thomas 
Published: January 2022

AbstractPhelan-McDermid syndrome (PMS) was initially called the 22q13 deletion syndrome based on its etiology as a deletion of the distal long arm of chromosome 22. These included terminal and interstitial deletions, as well as other structural rearrangements. Later, pathogenetic variants and deletions of the SHANK3 gene were found to result in a phenotype consistent with PMS. The association between SHANK3 and PMS led investigators to consider disruption/deletion of SHANK3 to be a prerequisite for diagnosing PMS. This narrow definition of PMS based on the involvement of SHANK3 has the adverse effect of causing patients with interstitial deletions of chromosome 22 to “lose” their diagnosis. It also results in underreporting of individuals with interstitial deletions of 22q13 that preserve SHANK3. To reduce the confusion for families, clinicians, researchers, and pharma, a simple classification for PMS has been devised. PMS and will be further classified as PMS-SHANK3 related or PMS-SHANK3 unrelated. PMS can still be used as a general term, but this classification system is inclusive. It allows researchers, regulatory agencies, and other stakeholders to define SHANK3 alterations or interstitial deletions not affecting the SHANK3 coding region.
Key patient-reported outcomes in children and adolescents with intoxication-type inborn errors of metabolism: an international Delphi-based consensus
Authors: Bösch Florin , Zeltner Nina A. , Baumgartner Matthias R. , Huemer Martina , Landolt Markus A. 
Published: January 2022

Abstract
Background
Acute intoxication-type inborn errors of metabolism (IT-IEM) such as urea cycle disorders and non-acute IT-IEM such as phenylketonuria (PKU) and their treatment have a major impact on the life of affected children and families. Yet patients’ and parents’ perspectives on the burdens of IT-IEM and its effects on everyday functioning and well-being have rarely been addressed. Patient- and observer-reported outcomes (PROs/ObsROs) are critically important to evaluate and target health care and treatment efficacy. Therefore, it is mandatory to define PROs/ObsROs relevant to patients with IT-IEM, their families, and health care professionals and to provide valid, standardised and reliable measuring instruments. To achieve consensus we performed a two-round, electronic-based modification of a Delphi survey including 27 parents of affected children, nine teenage patients and 35 health professionals (physicians, nutritionists, psychologists). The final set of PROs/ObsROs was discussed and defined in an online consensus meeting with a subsample of three health professionals, three parents and two patients. For this final set, appropriate measures (PROMs/ObsROMs) were assembled.

Results
Seventeen PROs/ObsROs constitute the final core set for paediatric IT-IEM. They cover social (e.g. social participation), emotional (e.g. positive affect), and disease-related aspects (e.g. attitude towards treatment) of patients’ lives as well as the experience of parents (e.g. parental stress).

Conclusion
To promote a holistic treatment approach, this consensus-driven set of relevant PROs/ObsROs should be incorporated into daily IT-IEM care and considered as the key psychological outcomes in clinical trials. We have identified existing—psychometrically and contextual—appropriate PROMs/ObsROMs with open access to facilitate this process.
The increased in vivo firing of pyramidal cells but not interneurons in the anterior cingulate cortex after neuropathic pain
Authors: Zhu Da-Yu , Cao Ting-Ting , Fan Hong-Wei , Zhang Ming-Zhe , Duan Hao-Kai , Li Jing , Zhang Xia-Jing , Li Yun-Qing , Wang Pan , Chen Tao 
Published: January 2022

AbstractChronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which was further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.
Impact of frontline treatment approach on outcomes in patients with secondary AML with prior hypomethylating agent exposure
Authors: Short Nicholas J. , Venugopal Sangeetha , Qiao Wei , Kadia Tapan M. , Ravandi Farhad , Macaron Walid , Dinardo Courtney D. , Daver Naval , Konopleva Marina , Borthakur Gautam , Shpall Elizabeth J. , Popat Uday , Champlin Richard E. , Mehta Rohtesh , Al-Atrash Gheath , Oran Betul , Jabbour Elias , Garcia-Manero Guillermo , Issa Ghayas C. , Montalban-Bravo Guillermo , Yilmaz Musa , Maiti Abhishek , Kantarjian Hagop 
Published: January 2022

Abstract
Background
Treated secondary acute myeloid leukemia (ts-AML)—i.e., AML arising from a previously treated antecedent hematologic disorder—is associated with very poor outcomes. The optimal frontline treatment regimen for these patients is uncertain.

Methods
We retrospectively analyzed 562 patients who developed AML from preceding myelodysplastic syndrome or chronic myelomonocytic leukemia for which they had received a hypomethylating agent (HMA). Patients with ts-AML were stratified by frontline AML treatment with intensive chemotherapy (IC, n = 271), low-intensity therapy (LIT) without venetoclax (n = 237), or HMA plus venetoclax (n = 54).

Results
Compared with IC or LIT without venetoclax, HMA plus venetoclax resulted in higher CR/CRi rates (39% and 25%, respectively; P = 0.02) and superior OS (1-year OS 34% and 17%, respectively; P = 0.05). The benefit of HMA plus venetoclax was restricted to patients with non-adverse risk karyotype, where HMA plus venetoclax resulted in a median OS of 13.7 months and 1-year OS rate of 54%; in contrast, for patients with adverse risk karyotype, OS was similarly dismal regardless of treatment approach (median OS 3–5 months). A propensity score analysis accounting for relevant clinical variables confirmed the significant OS benefit of HMA plus venetoclax, as compared with other frontline treatment approaches. In a landmark analysis, patients with ts-AML who underwent subsequent hematopoietic stem cell transplantation (HSCT) had superior 3-year OS compared to non-transplanted patients (33% vs. 8%, respectively; P = 0.003).

Conclusions
The outcomes of ts-AML are poor but may be improved with use of an HMA plus venetoclax-based regimen, followed by HSCT, particularly in those with a non-adverse risk karyotype.