bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinitis pigmentosa and molar tooth sign caused by novel AHI1 compound heterozygote pathogenic variants
Authors: Chen Chunyan , Gao Jiong , Lv Qing , Xu Chen , Xia Yu , Du Ailian 
Published: October 2021

Abstract
Background
Joubert syndrome (JS) is a group of rare congenital disorders characterized by cerebellar vermis dysplasia, developmental delay, and retina dysfunctions. Herein, we reported a Chinese patient carrying a new variant in the AHI1 gene with mild JS, and the 3D structure of the affected Jouberin protein was also predicted.

Case presentation
The patient was a 31-year-old male, who presented difficulty at finding toys at the age of 2 years, night blindness from age of 5 years, intention tremor and walking imbalance from 29 years of age. Tubular visual field and retina pigmentation were observed on ophthalmology examinations, as well as molar tooth sign on brain magnetic resonance imaging (MRI). Whole exome sequence revealed two compound heterozygous variants at c.2105C>T (p.T702M) and c.1330A>T (p.I444F) in AHI1 gene. The latter one was a novel mutation. The 3D protein structure was predicted using I-TASSER and PyMOL, showing structural changes from functional β-sheet and α-helix to non-functional D-loop, respectively.

Conclusions
Mild JS due to novel variants at T702M and I444F in the AHI1 gene was reported. The 3D-structural changes in Jouberin protein might underlie the pathogenesis of JS.
Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing
Authors: Chen Chao , Chen Min , Zhu Yaping , Jiang Lu , Li Jia , Wang Yaoshen , Lu Zhe , Guo Fengyu , Wang Hairong , Peng Zhiyu , Yang Yun , Sun Jun 
Published: October 2021

Abstract
Background
Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly determining paternal haplotypes for noninvasive prenatal diagnosis of monogenic disorders without requiring proband’s samples.

Methods
The study recruited 40 families at high risk for autosomal recessive diseases. The targeted linked-read sequencing was performed on high molecular weight (HMW) DNA of parents using customized probes designed to capture targeted genes and single-nucleotide polymorphisms (SNPs) distributed within 1Mb flanking region of targeted genes. Plasma DNA from pregnant mothers also underwent targeted sequencing using the same probes to determine fetal haplotypes according to parental haplotypes. The results were further confirmed by invasive prenatal diagnosis.

Results
Seventy-eight parental haplotypes of targeted gene were successfully determined by targeted linked-read sequencing. The predicted fetal inheritance of variant was correctly deduced in 38 families in which the variants had been confirmed by invasive prenatal diagnosis. Two families were determined to be no-call.

Conclusions
Targeted linked-read sequencing method demonstrated to be an effective means to phase personal haplotype for noninvasive prenatal diagnosis of monogenic disorders.
A first case of ductal adenocarcinoma of the prostate having characteristics of neuroendocrine phenotype with PTEN, RB1 and TP53 alterations
Authors: Kobayashi Hiroaki , Kosaka Takeo , Nakamura Kohei , Shojo Kazunori , Hongo Hiroshi , Mikami Shuji , Nishihara Hiroshi , Oya Mototsugu 
Published: October 2021

Abstract
Background
Ductal adenocarcinoma and neuroendocrine cancer are rare subtypes of prostate cancer with poor prognosis and limited therapeutic options. We present the first case of ductal adenocarcinoma having a neuroendocrine phenotype.

Case presentation
A 63-year-old man presented with gross hematuria and urinary retention, and his serum prostate-specific antigen level was 4.58 ng/mL. We performed transurethral resection of the prostate, and the diagnosis was ductal adenocarcinoma with a Gleason score of 5 + 4 for acinar adenocarcinoma. Magnetic resonance imaging showed local invasion of left lobe of the prostate and bone metastasis of the left trochanteric section of the femur. Multidisciplinary treatments such as androgen deprivation therapy, chemoradiation therapy, and surgery for metastatic lesions have led to long-term survival. Since next-generation sequencing revealed PTEN and RB1 co-loss and TP53 mutations, we re-evaluated the immunohistochemistry and he was found to be positive for synaptophysin.

Conclusions
This is the first Japanese case of ductal adenocarcinoma with a neuroendocrine phenotype. Genetic analysis may help not only guide the therapeutic strategies, but also sometimes with the diagnosis.
Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide
Authors: Zeng Yuying , Zhang Yun , Huang Xinyan , Song Lizhen , Polsky Katherine , Wu Yifan , Kheradmand Farrah , Guo Yubiao , Green Linda K. , Corry David B. , Knight John M. 
Published: October 2021

AbstractBackgroundInhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic moldAspergillus niger(A. niger).MethodsC57BL/6J mice were intranasally challenged with the viable spores ofA. nigerwith and without 1 μg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined.ResultsIn comparison to mice challenged only withA. niger, addition of LPS (1 μg) toA. nigerabrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies.ConclusionsIn contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.
Biodegradable mesoporous manganese carbonate nanocomposites for LED light-driven cancer therapy via enhancing photodynamic therapy and attenuating survivin expression
Authors: Li Lihua , Chen Lingling , Huang Ling , Ye Xiangling , Lin Zefeng , Wei Xiaoming , Yang Xianfeng , Yang Zhongmin 
Published: October 2021

AbstractTriple-negative breast cancer (TNBC) is one of the most daunting diseases, low toxicity and efficient approaches are in urgent demand. Herein, we developed degradable mesoporous manganese carbonate nanocubes (MnCO3NCs), incorporated with survivin shRNA-expressing plasmid DNA (iSur-pDNA) and riboflavin (Rf), namely MRp NCs, for synergistic TNBC therapy. The MnCO3, itself, could generate O2and CO2under H2O2and thus relieve the hypoxia and acidic tumor microenvironment (TME). Furthermore, the MnCO3NCs exhibited high Rf loading capacity and iSur-pDNA delivery ability after polyethyleneimine modification. Specifically, MRp NCs decompose in TME, meanwhile they deprived the endogenous expression of survivin gene and significantly amplified the generation of reactive oxygen species after exposure to LED light, resulting in serious tumor destruction. The multifunctional MRp NCs with LED light-driven characters are able to provide a high efficiency, low toxicity and promising strategy for TNBC therapy.
Interaction and conflict between outreach workers and research officers in implementing collaborative action research in the field of harm reduction: a qualitative study
Authors: Khatmi Nicolas , Michels David , Rojas Castro Daniela , Roux Perrine 
Published: October 2021

AbstractBackgroundThe effectiveness of collaborative approaches in health interventions is underlined in the literature. Given the serious challenges to adequately managing the HCV epidemic in people who inject drugs (PWID), and the need to improve existing harm reduction (HR) interventions in this population, it seems important to investigate how collaboration between stakeholders is ensured in action research interventions. The present study aimed to explore interactions between outreach workers and research officers collaborating in the implementation of an action research project for PWID entitled OUTSIDER.MethodsUsing three focus groups, we studied the views of 24 outreach workers involved in the implementation and evaluation of a harm reduction educational intervention to help PWID inject more safely in off-site settings.ResultsThe analysis of participants’ discourses highlighted the mixed perceptions they had about OUTSIDER. Several limitations to collaboration emerged. Epistemological (theoretical vs. practical knowledge), methodological (science vs. intervention), axiological (standardised vs. adapted approach), and material (mobilised vs. available resources) issues all placed a burden on the outreach worker–research officer relationship. Outreach workers’ acceptance of the project’s intervention dimension but rejection of its scientific dimension highlights a lack of contractualisation between the stakeholders involved, and a more general problematisation of the role of outreach workers in implementing action research in HR. How collaboration was perceived and practised by outreach workers participating in OUTSIDER can be considered a reflection of the current challenges to implementing action research in HR.ConclusionThis study of the interaction between the research and implementation dimensions of an action research project explored the tensions between different intervention stakeholders that must work together. Equitable participation and integration of the expertise, practices, and knowledge of all stakeholders involved is essential for successful action research. Given current HCV epidemiological challenges, new forms of cooperation are needed when developing healthcare services and when strengthening collaborative approaches.
Effect of endometrial thickness changes on clinical pregnancy rates after progesterone administration in a single frozen-thawed euploid blastocyst transfer cycle using natural cycles with luteal support for PGT-SR- and PGT-M-assisted reproduction: a retrospective cohort study
Authors: Jin Ziqi , Li Jingdi , Yang EnTong , Shi Hao , Bu Zhiqin , Niu Wenbin , Wang Fang , Huo Mingzhu , Song Hui , Zhang YiLe 
Published: October 2021

Abstract
Background
To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle.

Methods
All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group.

Results
Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01–1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates.

Conclusions
In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.
Use of laboratory testing for prediction of postoperative bleeding volume in cardiovascular surgery
Authors: Kawahara Yoshie , Ohtsuka Kohei , Tanaka Kimine , Yamanaka Mayumi , Kamiya Hiroyuki , Kunisawa Takayuki , Fujii Satoshi 
Published: October 2021

Abstract
Background
Coagulopathy and following massive bleeding are complications of cardiovascular surgery, particularly occurring after procedures requiring prolonged cardiopulmonary bypass (CPB). Reliable and rapid tests for coagulopathy are desirable for guiding transfusion. Measuring multiple coagulation parameters may prove useful. The purpose of this study is to determine the laboratory parameters predicting massive bleeding.

Methods
In a prospectively collected cohort of 48 patients undergoing cardiovascular surgery, markers of coagulation and fibrinolysis were measured using automated analyzer and their correlations with bleeding volume were determined.

Results
Operation time was 318 (107–654) min. CPB time was 181 (58–501) min. Bleeding volume during surgery was 2269 (174–10,607) ml. Number of transfusion units during surgery were packed red blood cells 12 (0–30) units, fresh frozen plasma 12 (0–44) units, platelets 20 (0–60) units and intraoperative autologous blood collection 669 (0–4439) ml. Post-surgery activities of coagulation factors II (FII), FV, FVII, FVIII, FIX, FX, FXI and FXII were decreased. Values of fibrinogen, antithrombin, α2 plasmin inhibitor (α2PI) and FXIII were also decreased. Values of thrombin-antithrombin complex (TAT) were increased. Values of FII, FIX, FXI and α2PI before surgery were negatively correlated with bleeding volume (FII, r = − 0.506: FIX, r = − 0.504: FXI, r = − 0.580; α2PI, r = − 0.418). Level of FIX after surgery was negatively correlated with bleeding volume (r = − 0.445) and level of TAT after surgery was positively correlated with bleeding volume (r = 0.443).

Conclusions
These results suggest that several clinical and routine laboratory parameters of coagulation were individually associated with bleeding volume during cardiovascular surgery. Determining the patterns of coagulopathy may potentially help guide transfusion during cardiovascular surgery.
The influence of medical insurance and social security cards on the floating population's settlement intention
Authors: Li Yulin , Huang Lingling , Xiang Li , Dou Dongmei 
Published: October 2021

Abstract
Background
Medical insurance and social security cards are an important incentive for the floating population to live a stable life in their current residence, but there has been little studies on their effect on settlement intentions. Therefore, the purpose of this paper was to study the impact of basic medical insurance for urban employees and application for personal social security cards on the settlement intentions of the floating population. With the increase of the desire to settle, the health management and the development of public health will be improved.

Methods
Based on the 2017 survey data from the dynamic monitoring of China's floating population, we explored the influence of basic medical insurance for urban employees and social security cards on the floating population's settlement intentions. Additionally, this study also examined the comprehensive causal relationship, with social integration as the mediator variable. We used SPSS 21.0 software. The input method was used to analyze the influence of the above variables by binary logistic regression. Then we used AMOS22.0 software to establish the structural equation model of the relationship between the above three independent variables. Finally, we used bootstrapping method to analyze the direct effect, indirect effect and total effect of independent variables on settlement intention.

Results
The settlement intention of members of the floating population after participating in basic medical insurance for urban employees was 23.2% higher than that of those who did not participate. The decision as to whether to apply for a personal social security card is related to their settlement intention. The standardized regression coefficients among social insurance and security, social integration, and settlement intention were positive values, and the Z values of the overall effect, indirect effect, and direct effect were all greater than 1.96; the confidence interval of the indirect effect did not include 0. We found that this model is a partial intermediary model, with an intermediary ratio of 10.66%.

Conclusions
This article highlights the important impact of basic medical insurance for urban employees and individual social security cards on the floating population. The conclusions of this study provide suggestions for the government to use when designing policies to enhance the settlement intentions of the floating population and to improve the development of public health undertakings.
Economic impact of Juvenile Idiopathic Arthritis: a systematic review
Authors: García-Rodríguez Fernando , Gamboa-Alonso Augusto , Jiménez-Hernández Sol , Ochoa-Alderete Lucero , Barrientos-Martínez Valeria Alejandra , Alvarez-Villalobos Neri Alejandro , Luna-Ruíz Gabriela Andrea , Peláez-Ballestas Ingris , Villarreal-Treviño Ana Victoria , de la O-Cavazos Manuel Enrique , Rubio-Pérez Nadina 
Published: October 2021

AbstractBackgroundJuvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this systematic review was to collect and cluster the information currently available on healthcare costs associated with JIA after the introduction of biological therapies.MethodsWe comprehensively searched in MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Databases for studies from January 2000 to March 2021. Reviewers working independently and in duplicate appraised the quality and included primary studies that report total, direct and/or indirect costs related to JIA for at least one year. The costs were converted to United States dollars and an inflationary adjustment was made.ResultsWe found 18 eligible studies including data from 6,540 patients. Total costs were reported in 10 articles, ranging from $310 USD to $44,832 USD annually. Direct costs were reported in 16 articles ($193 USD to $32,446 USD), showing a proportion of 55 to 98 % of total costs. Those costs were mostly related to medications and medical appointments. Six studies reported indirect costs ($117 USD to $12,385 USD). Four studies reported costs according to JIA category observing the highest in polyarticular JIA. Total and direct costs increased up to three times after biological therapy initiation. A high risk of reporting bias and inconsistency of the methodology used were found.ConclusionThe costs of JIA are substantial, and the highest are derived from medication and medical appointments. Indirect costs of JIA are underrepresented in costs analysis.
Efficacy of an exoskeleton-based physical therapy program for non-ambulatory patients during subacute stroke rehabilitation: a randomized controlled trial
Authors: Louie Dennis R. , Mortenson W. Ben , Durocher Melanie , Schneeberg Amy , Teasell Robert , Yao Jennifer , Eng Janice J. 
Published: October 2021

Abstract
Background
Individuals requiring greater physical assistance to practice walking complete fewer steps in physical therapy during subacute stroke rehabilitation. Powered exoskeletons have been developed to allow repetitious overground gait training for individuals with lower limb weakness. The objective of this study was to determine the efficacy of exoskeleton-based physical therapy training during subacute rehabilitation for walking recovery in non-ambulatory patients with stroke.

Methods
An assessor-blinded randomized controlled trial was conducted at 3 inpatient rehabilitation hospitals. Patients with subacute stroke (< 3 months) who were unable to walk without substantial assistance (Functional Ambulation Category rating of 0 or 1) were randomly assigned to receive exoskeleton-based or standard physical therapy during rehabilitation, until discharge or a maximum of 8 weeks. The experimental protocol replaced 75% of standard physical therapy sessions with individualized exoskeleton-based sessions to increase standing and stepping repetition, with the possibility of weaning off the device. The primary outcome was walking ability, measured using the Functional Ambulation Category. Secondary outcomes were gait speed, distance walked on the 6-Minute Walk Test, days to achieve unassisted gait, lower extremity motor function (Fugl-Meyer Assessment), Berg Balance Scale, Patient Health Questionnaire, Montreal Cognitive Assessment, and 36-Item Short Form Survey, measured post-intervention and after 6 months.

Results
Thirty-six patients with stroke (mean 39 days post-stroke) were randomized (Exoskeleton = 19, Usual Care = 17). On intention-to-treat analysis, no significant between-group differences were found in the primary or secondary outcomes at post-intervention or after 6 months. Five participants randomized to the Exoskeleton group did not receive the protocol as planned and thus exploratory as-treated and per-protocol analyses were undertaken. The as-treated analysis found that those adhering to exoskeleton-based physical therapy regained independent walking earlier (p = 0.03) and had greater gait speed (p = 0.04) and 6MWT (p = 0.03) at 6 months; however, these differences were not significant in the per-protocol analysis. No serious adverse events were reported.

Conclusions
This study found that exoskeleton-based physical therapy does not result in greater improvements in walking independence than standard care but can be safely administered at no detriment to patient outcomes.
Clinical Trial Registration The Exoskeleton for post-Stroke Recovery of Ambulation (ExStRA) trial was registered at ClinicalTrials.gov (NCT02995265, first registered: December 16, 2016)