bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a HOXD13 variant in a Mongolian family with incomplete penetrance syndactyly by exon sequencing
Authors: Husile Husile , Wu Zhifeng , Yang Liqing , Cao Yaning , Wu Qizhu 
Published: October 2022

AbstractBackgroundSyndactyly (SD) refers to a deformity caused by the fusion and limb differentiation disorder of soft tissues and/or skeletons to varying extents between adjacent fingers (toes). The main features of this disease are phenotypic heterogeneity and genetic heterogeneity. In this study, we examined four generations of a Chinese Mongolian with different phenotypes of syndactylia and analysed and identified the pathogenic genetic variants of SD by exon sequencing.MethodsThe clinical phenotypes of patients were analysed, and the hands and feet were examined by X-ray. The pedigree was drawn, and the family data were analysed. Peripheral blood was collected from the family members, and genomic DNA was extracted. The candidate genes of SD were identified by exon sequencing, and the mutation sites of the captured candidate genes were amplified by PCR and verified by Sanger sequencing.ResultsThe family has congenital syndactyly, which is an autosomal dominant disease. At present, this condition has been passed down for 4 generations and was identified in 9 patients, including 4 males and 5 females. Five patients, I2, II4, III5, III,7and III10, had unilateral syndactyly, and four patients, III16, IV3, IV6and IV7, had bilateral finger syndactyly. All of their toes were unaffected. The proband and the other patients in this family had a c.917G > A (p.R306Q) mutation, which is located at position 917 of the second exon of theHOXD13gene. This mutation results in a change in the amino acid at position 306, in which arginine is changed to glutamine. This mutation cosegregates in unaffected individuals and affected patients in this family. Moreover, 201 Mongolian genome databases and a thousand human genome databases were referenced to further confirm that the pathogenic genetic variant that causes syndactyly in this family is found inHOXD13.ConclusionThis study found that the mutation site of the pathogenic gene in this family wasHOXD13, c.917G > A (p.R306Q). The phenotype of the family member III12was normal, but this member was also a carrier of the pathogenic genetic variant. This indicates that the disease of this family has incomplete penetrance characteristics. Our results further enrich the expression profile of theHOXD13gene.
Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy
Authors: Mao Liang , Li Yun-Da , Chen Ruo-Lan , Li Gang , Zhou Xiao-Xia , Song Fei , Wu Chan , Hu Yu , Hong Yi-Xiang , Dang Xitong , Li Gui-Rong , Wang Yan 
Published: October 2022

AbstractExosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of β-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.
Platelet membrane-camouflaged nanoparticles carry microRNA inhibitor against myocardial ischaemia‒reperfusion injury
Authors: Wang Tianyi , Zhou Tingting , Xu Mingming , Wang Shuo , Wu Anqi , Zhang Mingyang , Zhou You Lang , Shi Jiahai 
Published: October 2022

AbstractThe incidence of myocardial ischaemia‒reperfusion injury (MIRI) is increasing every year, and there is an urgent need to develop new therapeutic approaches. Nrf2 is thought to play a protective role during MIRI and it is regulated by microRNAs (miRNAs). This study focused on PLGA nanoparticles camouflaged by platelet membrane vesicles (PMVs) (i.e., PMVs@PLGA complexes) carrying microRNA inhibitors, which regulate Nrf2 and can play a therapeutic role in the MIRI process. In vitro and in vivo characterization showed that PMVs@PLGA has excellent transfection efficiency, low toxicity and good targeting. MicroRNAs that effectively regulate Nrf2 were identified, and then PMVs@PLGA-miRNA complexes were prepared and used for in vitro and in vivo treatment. PMVs@PLGA-miRNA complexes can effectively target the delivery of inhibitors to cardiomyocytes. Our results suggest that PMVs@PLGA complexes are a novel delivery system and a novel biological approach to the treatment of MIRI.
Comparative clinical outcome following individualized follitropin delta dosing in Chinese women undergoing ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection
Authors: Yang Rui , Zhang Yunshan , Liang Xiaoyan , Song Xueru , Wei Zhaolian , Liu Jianqiao , Yang Yezhou , Tan Jichun , Zhang Qingxue , Sun Yingpu , Wang Wei , Qian Weiping , Jin Lei , Wang Shuyu , Xu Yang , Yang Jing , Goethberg Marie , Mannaerts Bernadette , Wu Wen , Zheng Zugeng , Qiao Jie 
Published: October 2022

Abstract
Background
To compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women.

Methods
This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20–40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10–11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%).

Results
378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3—11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa.

Conclusion
Follitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women.

Clinical trial registration number
NCT03296527.
Sociodemographic differences in 24-hour time-use behaviours in New Zealand children
Authors: Hedayatrad Leila , Stewart Tom , Paine Sarah-Jane , Marks Emma , Walker Caroline , Duncan Scott 
Published: October 2022

Abstract
Background
The time that children spend in physical activity, sedentary behaviour, and sleep each day (i.e., 24-h time-use behaviours), is related to physical and mental health outcomes. Currently, there is no comprehensive evidence on New Zealand school-aged children’s 24-h time-use behaviours, adherence to the New Zealand 24-h Movement Guidelines, and how these vary among different sociodemographic groups.

Methods
This study utilises data from the 8-year wave of the Growing Up in New Zealand longitudinal study. Using two Axivity AX3 accelerometers, children’s 24-h time-use behaviours were described from two perspectives: activity intensity and activity type. Compositional data analysis techniques were used to explore the differences in 24-h time-use compositions across various sociodemographic groups.

Results
Children spent on average, 31.1%, 22.3%, 6.8%, and 39.8% of their time in sedentary, light physical activity, moderate-to-vigorous physical activity, and sleep, respectively. However, the daily distribution of time in different activity types was 33.2% sitting, 10.8% standing, 7.3% walking, 0.4% running, and 48.2% lying. Both the activity intensity and activity type compositions varied across groups of child ethnicity, gender, and household income or deprivation.
The proportion of children meeting each of the guidelines was 90% for physical activity, 62.5% for sleep, 16% for screen time, and 10.6% for the combined guidelines. Both gender and residence location (i.e., urban vs. rural) were associated with meeting the physical activity guideline, whereas child ethnicity, mother’s education and residence location were associated with meeting the screen time guideline. Child ethnicity and mother’s education were also significantly associated with the adherence to the combined 24-h Movement Guidelines.

Conclusions
This study provided comprehensive evidence on how New Zealand children engage in 24-h time-use behaviours, adherence to the New Zealand 24-h Movement Guidelines, and how these behaviours differ across key sociodemographic groups. These findings should be considered in designing future interventions for promoting healthy time-use patterns in New Zealand children.
Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis
Authors: Hu Xinli , Zhang Haojie , Zhang Qianxin , Yao Xue , Ni Wenfei , Zhou Kailiang 
Published: October 2022

AbstractStimulator of interferons genes (STING), which is crucial for the secretion of type I interferons and proinflammatory cytokines in response to cytosolic nucleic acids, plays a key role in the innate immune system. Studies have revealed the participation of the STING pathway in unregulated inflammatory processes, traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid haemorrhage (SAH) and hypoxic–ischaemic encephalopathy (HIE). STING signalling is markedly increased in CNS injury, and STING agonists might facilitate the pathogenesis of CNS injury. However, the effects of STING-regulated signalling activation in CNS injury are not well understood. Aberrant activation of STING increases inflammatory events, type I interferon responses, and cell death. cGAS is the primary pathway that induces STING activation. Herein, we provide a comprehensive review of the latest findings related to STING signalling and the cGAS–STING pathway and highlight the control mechanisms and their functions in CNS injury. Furthermore, we summarize and explore the most recent advances toward obtaining an understanding of the involvement of STING signalling in programmed cell death (autophagy, necroptosis, ferroptosis and pyroptosis) during CNS injury. We also review potential therapeutic agents that are capable of regulating the cGAS–STING signalling pathway, which facilitates our understanding of cGAS–STING signalling functions in CNS injury and the potential value of this signalling pathway as a treatment target.
Accuracy and comparison of sensor-based gait speed estimations under standardized and daily life conditions in children undergoing rehabilitation
Authors: Rast Fabian Marcel , Aschwanden Seraina , Werner Charlotte , Demkó László , Labruyère Rob 
Published: October 2022

Abstract
Background
Gait speed is a widely used outcome measure to assess the walking abilities of children undergoing rehabilitation. It is routinely determined during a walking test under standardized conditions, but it remains unclear whether these outcomes reflect the children's performance in daily life. An ankle-worn inertial sensor provides a usable opportunity to measure gait speed in the children's habitual environment. However, sensor-based gait speed estimations need to be accurate to allow for comparison of the children's gait speed between a test situation and daily life. Hence, the first aim of this study was to determine the measurement error of a novel algorithm that estimates gait speed based on data of a single ankle-worn inertial sensor in children undergoing rehabilitation. The second aim of this study was to compare the children’s gait speed between standardized and daily life conditions.

Methods
Twenty-four children with walking impairments completed four walking tests at different speeds (standardized condition) and were monitored for one hour during leisure or school time (daily life condition). We determined accuracy by comparing sensor-based gait speed estimations with a reference method in both conditions. Eventually, we compared individual gait speeds between the two conditions.

Results
The measurement error was 0.01 ± 0.07 m/s under the standardized and 0.04 ± 0.06 m/s under the daily life condition. Besides, the majority of children did not use the same speed during the test situation as in daily life.

Conclusion
This study demonstrates an accurate method to measure children's gait speed during standardized walking tests and in the children's habitual environment after rehabilitation. It only requires a single ankle sensor, which potentially increases wearing time and data quality of measurements in daily life. We recommend placing the sensor on the less affected side, unless the child wears one orthosis. In this latter case, the sensor should be placed on the side with the orthosis. Moreover, this study showed that most children did not use the same speed in the two conditions, which encourages the use of wearable inertial sensors to assess the children's walking performance in their habitual environment following rehabilitation.
One-stop computerized virtual planning system for the surgical management of posterior wall acetabular fractures
Authors: Chen Jianan , Zheng Yifan , Fang Zhixun , Zhou Wei , Xu Dan , Wang Guodong , Cai Xianhua , Liu Ximing 
Published: October 2022

Abstract
Background
Posterior wall acetabular fractures remain one of the most difficult fracture injuries to treat. Accurate assessment of fracture characteristics and appropriate preoperative surgical strategies are essential for excellent reduction. This paper evaluates the feasibility and effectiveness of a one-stop computerized virtual planning system for the surgical management of posterior wall acetabular fractures.

Methods
52 cases of posterior wall acetabular fractures treated surgically were selected in our department between January 2015 and December 2020 for retrospective analysis. 52 cases were classified into group A (25 patients) and group B (27 patients) according to whether computerized virtual planning procedures were performed preoperatively. In group A, virtual surgical simulation was conducted using a one-stop computerized planning system preoperatively. In group B, traditional surgery was employed. Reduction quality, surgical time, blood loss, hip function, complications, and instrumentation time were compared between the two groups.

Results
The actual surgery for all patients in group A was essentially the same as the virtual surgery before the operation. Compared to group B, patients in group A had markedly shorter surgical time (−43 min), shorter instrumentation time (−20 min), and less intraoperative blood loss (−130 ml). However, no significant statistical difference was observed in reduction quality and hip function. The complication rate was slightly lower in group A (4/25) than in group B (7/27), without a significant difference.

Conclusion
The one-stop computerized virtual planning system is a highly effective, user-friendly and educational tool for allowing the cost-efficient surgical simulation of posterior wall acetabular fractures and providing a more individualized therapeutic schedule. The one-stop computerized planning system is feasible to treat posterior wall acetabular fractures, which is an effective method than the conventional treatment of posterior wall acetabular fractures.
Trial registration: retrospective registration.
Metabolic profiling and pharmacokinetic studies of Baihu-Guizhi decoction in rats by UFLC-Q-TOF–MS/MS and UHPLC-Q-TRAP-MS/MS
Authors: He Yan , Zhou Zhenkun , Li Weijie , Zhang Yanqiong , Shi Ruoyao , Li Tao , Jin Linlin , Yao Hongliang , Lin Na , Wu Hao 
Published: October 2022

Abstract
Background
Baihu-Guizhi decoction (BHGZD) is a well-documented traditional Chinese Medicine (TCM) prescription that has been extensively applied to treating rheumatoid arthritis. Despite of its beneficial outcomes, the chemical constituents of BHGZD have not been fully portrayed and the in vivo absorption, distribution, metabolism, and excretion (ADME) patterns of absorbed components have never been described.

Methods
Characterization of absorbed components and in vivo biotransformation profiling of these feature compounds were based on the ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Furthermore, the ultra-high-performance liquid chromatography tandem ion trap quadrupole mass spectrometry (UHPLC-Q-TRAP-MS/MS) system were performed to investigate the pharmacokinetics of active ingredients from BHGZD.

Results
In this study, we have identified and tentatively characterized 18 feature absorbed prototype and 15 metabolites of BHGZD in rat serum and the in vivo transformation pathways of these absorbed constituents were proposed. Besides, we have established novel quantitative methodology of five crucial components of BHGZD and have monitored the pharmacokinetic behaviors of these constituents spontaneously in rat serum after BHGZD gavage. After rats received two ways of BHGZD gavage, the pharmacokinetic behaviors of each compound exhibited relatively similar behaviors, as evidenced by similar curve track as well as relatively close time to reach maximum concentration (Tmax) and half washout time (T1/2). Whereas the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) values of five analytes with multiple dosage were a bit higher than single dosage.

Conclusion
This study added knowledge into the material basis and bio-transformation patterns of BHGZD in vivo, which would be of great value for exploring pharmacological effects and mechanism of BHGZD.
Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy
Authors: Eichler F. , Sevin Caroline , Barth M. , Pang F. , Howie K. , Walz M. , Wilds A. , Calcagni C. , Chanson C. , Campbell L. 
Published: October 2022

Abstract
Background
Metachromatic leukodystrophy (MLD), a relentlessly progressive and ultimately fatal condition, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ARSA). Historically management has been palliative or supportive care. Hematopoietic stem cell transplantation is poorly effective in early-onset MLD and benefit in late-onset MLD remains controversial. Hematopoietic stem cell gene therapy, Libmeldy (atidarsagene autotemcel), was recently approved by the European Medicines Agency for early-onset MLD. Treatment benefit is mainly observed at an early disease stage, indicating the need for early diagnosis and intervention. This study contributes insights into the caregiver language used to describe initial MLD symptomatology, and thereby aims to improve communication between clinicians and families impacted by this condition and promote a faster path to diagnosis.

Results
Data was collected through a moderator-assisted online 60-min survey and 30-min semi-structured follow-up telephone interview with 31 MLD caregivers in the United States (n = 10), France (n = 10), the United Kingdom (n = 5), and Germany (n = 6). All respondents were primary caregivers of a person with late infantile (n = 20), juvenile (n = 11) or borderline late infantile/juvenile (n = 1) MLD (one caregiver reported for 2 children leading to a sample of 32 individuals with MLD). Caregivers were asked questions related to their child’s initial signs and symptoms, time to diagnosis and interactions with healthcare providers. These results highlight the caregiver language used to describe the most common initial symptoms of MLD and provide added context to help elevate the index of suspicion of disease. Distinctions between caregiver descriptions of late infantile and juvenile MLD in symptom onset and disease course were also identified.

Conclusions
This study captures the caregiver description of the physical, behavioral, and cognitive signs of MLD prior to diagnosis. The understanding of the caregiver language at symptom onset sheds light on a critical window of often missed opportunity for earlier diagnosis and therapeutic intervention in MLD.