bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of an ultra-sensitive human IL-33 biomarker assay for age-related macular degeneration and asthma drug development
Authors: Mai Elaine , Chan Joyce , Goon Levina , Ego Braeden K. , Bevers Jack , Wong Tiffany , Wong Manda , Corpuz Racquel , Xi Hongkang , Wu Jia , Schneider Kellen , Seshasayee Dhaya , Grimbaldeston Michele , Nakamura Gerald , Indjeian Vahan B. , van Lookeren Campagne Menno , Loyet Kelly M. , Comps-Agrar Laetitia 
Published: December 2021

Abstract
Background
Over the past decade, human Interleukin 33 (hIL-33) has emerged as a key contributor to the pathogenesis of numerous inflammatory diseases. Despite the existence of several commercial hIL-33 assays spanning multiple platform technologies, their ability to provide accurate hIL-33 concentration measurements and to differentiate between active (reduced) and inactive (oxidized) hIL-33 in various matrices remains uncertain. This is especially true for lower sample volumes, matrices with low hIL-33 concentrations, and matrices with elevated levels of soluble Interleukin 1 Receptor-Like 1 (sST2), an inactive form of ST2 that competes with membrane bound ST2 for hIL-33 binding.

Results
We tested the performance of several commercially available hIL-33 detection assays in various human matrices and found that most of these assays lacked the sensitivity to accurately detect reduced hIL-33 at biologically relevant levels (sub-to-low pg/mL), especially in the presence of human sST2 (hsST2), and/or lacked sufficient target specificity. To address this, we developed and validated a sensitive and specific enzyme-linked immunosorbent assay (ELISA) capable of detecting reduced and total hIL-33 levels even in the presence of high concentrations of sST2. By incorporating the immuno-polymerase chain reaction (iPCR) platform, we further increased the sensitivity of this assay for the reduced form of hIL-33 by ~ 52-fold. Using this hIL-33 iPCR assay, we detected hIL-33 in postmortem human vitreous humor (VH) samples from donors with age-related macular degeneration (AMD) and found significantly increased hIL-33 levels when compared to control individuals. No statistically significant difference was observed in aqueous humor (AH) from AMD donors nor in plasma and nasosorption fluid (NF) from asthma patients compared to control individuals.

Conclusions
Unlike existing commercial hIL-33 assays, our hIL-33 bioassays are highly sensitive and specific and can accurately quantify hIL-33 in various human clinical matrices, including those with high levels of hsST2. Our results provide a proof of concept of the utility of these assays in clinical trials targeting the hIL-33/hST2 pathway.
TRPC3, but not TRPC1, as a good therapeutic target for standalone or complementary treatment of DMD
Authors: Creisméas Anna , Gazaille Claire , Bourdon Audrey , Lallemand Marc-Antoine , François Virginie , Allais Marine , Ledevin Mireille , Larcher Thibaut , Toumaniantz Gilles , Lafoux Aude , Huchet Corinne , Anegon Ignacio , Adjali Oumeya , Le Guiner Caroline , Fraysse Bodvaël 
Published: December 2021

Abstract
Background
Duchenne muscular dystrophy (DMD) is an X-linked inherited disease caused by mutations in the gene encoding dystrophin that leads to a severe and ultimately life limiting muscle-wasting condition. Recombinant adeno-associated vector (rAAV)-based gene therapy is promising, but the size of the full-length dystrophin cDNA exceeds the packaging capacity of a rAAV. Alternative or complementary strategies that could treat DMD patients are thus needed. Intracellular calcium overload due to a sarcolemma permeability to calcium (SPCa) increase is an early and critical step of the DMD pathogenesis. We assessed herein whether TRPC1 and TRPC3 calcium channels may be involved in skeletal muscle SPCa alterations and could represent therapeutic targets to treat DMD.

Methods
All experiments were conducted in the DMDmdx rat, an animal model that closely reproduces the human DMD disease. We measured the cytosolic calcium concentration ([Ca2+]c) and SPCa in EDL (Extensor Digitorum Longus) muscle fibers from age-matched WT and DMDmdx rats of 1.5 to 7 months old. TRPC1 and TRPC3 expressions were measured in the EDL muscles at both the mRNA and protein levels, by RT-qPCR, western blot and immunocytofluorescence analysis.

Results
As expected from the malignant hyperthermia like episodes observed in several DMDmdx rats, calcium homeostasis alterations were confirmed by measurements of early increases in [Ca2+]c and SPCa in muscle fibers. TRPC3 and TRPC1 protein levels were increased in DMDmdx rats. This was observed as soon as 1.5 months of age for TRPC3 but only at 7 months of age for TRPC1. A slight but reliable shift of the TRPC3 apparent molecular weight was observed in DMDmdx rat muscles. Intracellular localization of both channels was not altered. We thus focused our attention on TRPC3. Application of Pyr10, a specific inhibitor of TRPC3, abolished the differences between SPCa values measured in WT and DMDmdx. Finally, we showed that a rAAV-microdystrophin based treatment induced a high microdystrophin expression but only partial prevention of calcium homeostasis alterations, skeletal muscle force and TRPC3 protein increase.

Conclusions
All together our results show that correcting TRPC3 channel expression and/or activity appear to be a promising approach as a single or as a rAAV-based complementary therapy to treat DMD.
Prevalence and associated factors of infertility among 20–49 year old women in Henan Province, China
Authors: Liang Shoujing , Chen Yuanhui , Wang Qian , Chen Huanhuan , Cui Chenchen , Xu Xiaohang , Zhang Qingwen , Zhang Cuilian 
Published: December 2021

Abstract
Background
Infertility is a reproductive health problem which affects not only individuals, families and social populations. Recently, the infertility rate in China has a trend of increase year by year, and few studies have reported the infertility rate in Henan Province, China. The aim of this study was to investigate the current prevalence and associated factors of infertility among women of childbearing age in Henan Province, China.

Methods
This cross-sectional study was conducted from March 2019 to October 2019. We sampled 765 women who were 20–49 years old in eight hospitals of four cities in Henan Province, China. This survey included a questionnaire, physical examination, vaginal ultrasound examinations, and serum anti-Mullerian hormone (AMH) assessment, all of which were conducted under uniform standards by trained personnel. According to the data collected from questionnaire, participants were divided into infertile and fertile groups and analyzed associated factors.

Results
Among all the 765 participants in this study, the prevalence of infertility was 24.58%. The prevalence of primary infertility was 6.54%, and the prevalence of secondary infertility was 18.04%. In logistic multivariate regression analyses, infertility was associated with age (p < 0.001), history of gynecological surgery (p < 0.001), sweet food (p = 0.003) and decreased ovarian reserve (DOR) (p < 0.001). After further analyses, factors associated with primary infertility were age of marriage (p = 0.006), age of first sexual intercourse (p = 0.003), long-term air-conditioning environment (p < 0.001), decreased ovarian reserve (p = 0.005) and age (p = 0.002). And factors associated with secondary infertility were history of gynecological surgery (p < 0.001), decreased ovarian reserve (p = 0.002), waist-to-hip ratio (WHR) above 0.85 (p = 0.043), delivery times (p = 0.001) and ages (p < 0.001).

Conclusion
The prevalence of infertility among women aged 20–49 was 24.58% and only 61.17% infertile women sought medical help in Henan Province, China. Age, history of gynecological surgeries and DOR may increase the risk of infertility. Local public health departments and medical professionals need to discharge their duty of reducing the high incidence of infertility and protecting women’s reproductive health.
The mediational role of social support in the relationship between stress and antenatal anxiety and depressive symptoms among Australian women: a mediational analysis
Authors: Bedaso Asres , Adams Jon , Peng Wenbo , Sibbritt David 
Published: December 2021

Abstract
Background
Pregnancy can be a stressful period for most women and their family members, and the mental wellbeing of pregnant women can face serious challenges. Social support can play a role in improving the psychological well-being of pregnant women by enhancing the stress coping ability and alleviating stressful conditions. The current study aimed to assess the mediating effects of social support in the relationship between perceived stress and depressive symptoms as well as anxiety symptoms during pregnancy among Australian women.

Methods
Of the 8,010 women who completed Survey 6 of the 1973–78 Australian Longitudinal Study on Women’s Health (ALSWH) cohort in 2012, those who reported being pregnant (n = 493) were included in the current analyses. Antenatal depressive and anxiety symptoms were assessed using the 10 item Center for Epidemiological Studies Depression (CES-D-10) scale, and the 9-item Goldberg Anxiety and Depression scale (GADS) respectively. The 19 item-Medical Outcomes Study Social Support index (MOSS) was used to examine social support. A parallel mediation model was used to explore the mediational role of each domain of social support between perceived stress and antenatal depressive and anxiety symptoms.

Result
The study found that emotional/informational support has a partial mediating effect on the relationship between perceived stress and antenatal depressive symptoms (β = 0.371, 95% CI: 0.067, 0.799) and on the relationship between perceived stress and antenatal anxiety symptoms (β = 0.217, 95% CI: 0.029, 0.462). Affectionate support/positive social interaction and tangible support was found to play no significant mediation role between stress and antenatal depressive and anxiety symptoms.

Conclusions
Emotional/informational support appears to play a mediating role in the relationship between stress and antenatal depressive as well as between stress and antenatal anxiety symptoms. In order to further protect pregnant women from the effects of stress, policy makers and maternal health professionals are advised to develop community-based social support programs to enhance prenatal psychosocial support and ensure pregnant women have adequate emotional/information support.
Contraception for married adolescents (15–19 years) in India: insights from the National Family Health Survey-4 (NFHS-4)
Authors: Singh Ijyaa , Shukla Ankita , Thulaseedharan Jissa Vinoda , Singh Gurpreet 
Published: December 2021

AbstractPurposeDespite the fact that marriage below the age of 18 years is illegal in India, a considerable number of females get married and start childbearing during their adolescent years. There is low prevalence of contraceptive methods and high unmet need for family planning (FP). Realizing this, new government programs have been launched to increase the uptake of sexual and reproductive health services among adolescents. However, evidence specific to this age group remains scarce.Aim and objectivesThe present study was conducted to assess the prevalence of modern contraceptives among married adolescents, and to determine its association with sociodemographic variables, health worker outreach, and media exposure to FP messages in India.MethodsData for this analysis was drawn from the fourth round of the National Family Health Survey (NFHS-4) conducted in India during 2015–16. The sample size is restricted to 13,232 currently married adolescent girls aged 15–19 years, who were not pregnant at the time of the survey. Bivariate and multivariate analysis were conducted to assess the levels of contraceptive use and its predictors among married adolescents.ResultsThe use of modern contraceptives among married adolescents increased from 4 to 10% between 1992–93 and 2015–16. The uptake of modern contraceptives was found to be low among the uneducated, those residing in rural areas, among backward classes, those practising Hindu religion, women in the poorest wealth quintile, women without children, and those with no exposure to FP messages via media or health care workers. Among those who met health care workers and discussed FP issues with them, 34.11% were using modern contraceptives as compared to 11.53% of those who did not have discussions with health care workers.ConclusionsThe evidence suggests that contact with health care workers significantly influences the use of modern contraceptives. Further focus on increasing contact between married adolescents’ and health care workers, and improving the quality of counselling will protect adolescents from early marriage and pregnancy.
Proximal and distal movement patterns during a graphomotor task in typically developing children and children with handwriting problems
Authors: Steinhart Shoshana , Weiss Patrice L. , Friedman Jason 
Published: December 2021

Abstract
Background
Therapists specializing in handwriting difficulties in children often address motor problems including both proximal and distal movements in the upper extremity. Kinematic measures can be used to investigate various aspects of handwriting. This study examined differences in movement patterns in proximal and distal joints of the upper extremity during graphomotor tasks between typically developing children with and without handwriting problems. Additionally, it explored relationships between movement patterns, speed, and legibility of writing.

Methods
Forty-one children, aged 7–11 years, were assessed with the Aleph Aleph Ktav Yad Hebrew Handwriting assessment and the Beery Test of Visual Motor Integration and, based on their scores, were divided into a research group (with handwriting difficulties) and a control group (without handwriting difficulties). Upper extremity joint movement patterns were analyzed with a motion capture system. Differences in the quality of shapes traced and copied on a graphics tablet positioned horizontally and vertically were compared. Between-group differences and relationships with speed and legibility were analyzed.

Results
In both groups, there was greater movement in the distal compared to the proximal joints, greater movement when performing the task in a horizontal compared to a vertical plane, and greater movement when tracing than copying. Joint movements in the arm executed scaled-down versions of the shapes being drawn. While the amount of joint displacement was similar between groups, children in the research group showed greater dissimilarity between the drawn shape and the shape produced by the proximal joints. Finally, the drawing measure on the tablet was a significant predictor of legibility, speed of writing, visual motor integration and motor coordination, whereas the dissimilarity measure of joint movement was a significant predictor of speed of writing and motor coordination.

Conclusions
This study provides support for the role of the distal upper extremity joints in the writing process and some guidance to assist clinicians in devising treatment strategies for movement-related handwriting problems. While we observed differences in proximal joint movements between the children with and without handwriting difficulties, the extent to which they are responsible for the differences in drawing quality remains to be determined. Further studies should use a similar methodology to examine additional tasks such as drawing shapes of varying sizes.
3C protease of enterovirus 71 cleaves promyelocytic leukemia protein and impairs PML-NBs production
Authors: Li Zhuoran , Wu Ya’ni , Li Hui , Li Wenqian , Tan Juan , Qiao Wentao 
Published: December 2021

Abstract
Background
Enterovirus 71 (EV71) usually infects infants causing hand-foot-mouth disease (HFMD), even fatal neurological disease like aseptic meningitis. Effective drug for preventing and treating EV71 infection is unavailable currently. EV71 3C mediated the cleavage of many proteins and played an important role in viral inhibiting host innate immunity. Promyelocytic leukemia (PML) protein, the primary organizer of PML nuclear bodies (PML-NBs), can be induced by interferon and is involved in antiviral activity. PML inhibits EV71 replication, and EV71 infection reduces PML expression, but the molecular mechanism is unclear.

Methods
The cleavage of PMLIII and IV was confirmed by co-transfection of EV71 3C protease and PML. The detailed cleavage sites were evaluated further by constructing the Q to A mutant of PML. PML knockout cells were infected with EV71 to identify the effect of cleavage on EV71 replication. Immunofluorescence analysis to examine the interference of EV71 3C on the formation of PML-NBs.

Results
EV71 3C directly cleaved PMLIII and IV. Furthermore, 3C cleaved PMLIV at the sites of Q430–A431 and Q444–S445 through its protease activity. Overexpression of PMLIV Q430A/Q444A variant exhibited stronger antiviral potential than the wild type. PMLIV Q430A/Q444A formed normal nuclear bodies that were not affected by 3C, suggesting that 3C may impair PML-NBs production via PMLIV cleavage and counter its antiviral activities. PML, especially PMLIV, which sequesters viral proteins in PML-NBs and inhibits viral production, is a novel target of EV71 3C cleavage.

Conclusions
EV71 3C cleaves PMLIV at Q430–A431 and Q444–S445. Cleavage reduces the antiviral function of PML and decomposes the formation of PML-NBs, which is conducive to virus replication.
A case of Pseudomyxoma Peritonei of an unexpected origin
Authors: Csanyi-Bastien Marie , Blanchard France , Lamy Aude , Sabourin Jean-Christophe 
Published: December 2021

Abstract
Background
Pseudomyxoma peritonei (PMP) is a complex and partially understood disease defined by mucin deposits in the peritoneal cavity, mostly of appendiceal origin caused by the rupture of a mucocele often containing Low or High grade Appendiceal Mucinous Neoplasm (LAMN/HAMN). Other origins include primitive ovarian mucinous cystadenoma or cystadenocarcinoma almost always with an associated teratoma, but to our knowledge no case of ovarian teratomatous appendiceal-like mucocele with LAMN has been reported as a cause of PMP.

Case presentation
A 25-year old female with infertility was diagnosed with an isolated left ovarian tumor in a context of PMP. Histological examination revealed an ovarian teratoma containing an appendiceal-like structure with mucocele and LAMN, without any associated lesion of the appendix on full histological analysis. Molecular characterization of the ovarian lesion showed co-KRAS and GNAS mutations, as described in PMP of appendiceal origin, while only KRAS mutations are reported in primitive ovarian mucinous tumor.

Conclusions
Detection of co-KRAS and GNAS mutations in our case of ovarian teratomatous appendiceal-like mucocele with LAMN shows that when PMP derives from a mucinous ovarian lesion (with histological proof of none-appendiceal involvement), it is probably of a digestive teratomatous origin, emphasizing the need to actively search for tetatomatous signs in a context of ovarian PMP.
Lateral pillar is the key in supporting pre-collapse osteonecrosis of the femoral head: a finite element model analysis of propensity-score matched cohorts
Authors: Bahk Ji Hoon , Jo Woo-Lam , Kim Seung-Chan , Kwon Soon-Yong , Lim Young Wook 
Published: December 2021

Abstract
Background
This study was designed as a cohort study using propensity-score matching to age, gender, and body mass index (BMI) for finite element model (FEM) analysis from pre-collapse CT images of collapsed and non-collapsed hips. Through FEM analysis, a global graphical output around the hip joint can provide simple impression of stress distribution: concentration or dispersion.

Methods
A total of 32 hips with ARCO stage 2 or 3 ONFH who were on follow up for over a one-year period were retrospectively reviewed. 16 hips with no interval progression of collapse were set as the study group, then 16 hips with progression of collapse which required arthroplasty were set as the control group using propensity-score matching. FEM was generated through Mechanical Finder for each patient, then 4500 N of load was applied to 1000 mm2 area at the top of iliac crest to analyze the models in terms of equivalents for yield stress.

Results
Age, sex, and BMI had no significant differences between the two groups, while location (p = 0.015) was lateral, and size (p = 0.015) was significantly greater in the collapsed group. Non-collapsed hips mostly exhibited stress dispersion allocated to medial and lateral pillars, while collapsed hips exhibited stress concentration focused on the lateral pillar and the primary compression trabecula. (p = 0.001).

Conclusion
Through FEM analysis, stress concentration to the lateral pillar and the primary compression trabeculae can be used to predict future collapse in ONFH with high probability. Results provide a simple and intuitive, yet valuable information to aid surgeons. Therefore, especially for young patients, holding out the lateral pillar through joint preserving procedures might be the key in preventing further collapse.
The morphology of the proximal femur in cementless short-stem total hip arthroplasty: No negative effect on offset reconstruction, leg length difference and implant positioning
Authors: Luger Matthias , Feldler Sandra , Klasan Antonio , Gotterbarm Tobias , Schopper Clemens 
Published: December 2021

Abstract
Background
Correct reconstruction of hip offset (HO) and leg length are important for clinical–functional outcome and patient satisfaction in total hip arthroplasty (THA). The morphology of the proximal femur can pose a risk for increased leg length difference (LLD) in cementless straight-stem THA. We therefore wanted to evaluate, if this is also applicable in THA with a cementless meta-diaphyseal short stem.

Methods
In a retrospective study, 106 patients (index surgery 2014–2019) with unilateral THA and a morphologically healthy hip as a reference (Kellgren–Lawrence ≤ 1) were included. The same cementless short stem with meta-diaphyseal fixation and cementless press-fit cup was implanted. The proximal femur was rated by Dorr’s classification, and subgroups were formed afterward. Measurements were carried out on preoperative and 3 months postoperative anterior–posterior radiographs of the pelvis. Kruskal–Wallis test, Fisher’s exact test and binary logistic regression were performed to evaluate the influence of the anatomical shape on postoperative leg length difference and offset reconstruction.

Results
The Dorr type did not show any significance influence on LLD (p = 0.532), or postoperative difference in femoral offset (p = 0.243), acetabular offset (p = 0.106) and hip offset (p = 0.698). Stem alignment (p = 0.705) and canal fill indices (CFI I: p = 0.321; CFI II: p = 0.411; CFI III: p = 0.478) were also without significant differences. Logistic regression did not show any significant increased risk for a LLD ≥ 5 mm or ≥ 10 mm as well as HO ≥ 5 mm or ≥ 10 mm.

Conclusion
Reconstruction of hip offset and postoperative leg length difference is not negatively influenced by Dorr type, canal flare index, cortical index and canal-to-calcar ratio in cementless short-stem THA. Implant positioning and canal fill are also not negatively affected by the anatomical shape of the proximal femur.
Level of evidence: Level IV.