bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical features and relapse risks of IgG4-related ophthalmic disease: a single-center experience in China
Authors: Zhao Zhen , Mou Dapeng , Wang Ziqiao , Zeng Qiaozhu , Wang Zhenfan , Xue Jimeng , Ren Limin , Liu Yanying , Su Yin 
Published: March 2021

Abstract
Background
IgG4-related ophthalmic disease (IgG4-ROD) is one of the phenotypes of IgG4-related disease (IgG4-RD), and its lesions are mainly located in the ocular. Currently, there are few studies on IgG4-ROD and no study has compared the phenotypic differences between IgG4-ROD and non IgG4-ROD (nIgG4-ROD). Thus, it is difficult to establish the optimal treatment strategy for IgG4-ROD. The aim of this study was to identify the disparities between the two groups and to clarify the risk factors for IgG4-ROD relapse.

Methods
434 IgG4-RD patients met comprehensive diagnostic criteria and diagnosed at Peking University People’s Hospital between January 2009 and January 2020 were recruited in this study. Patients were divided into IgG4-ROD and nIgG4-ROD group according to the ophthalmic involvement. Demographic, clinical, and laboratory data of two groups were collected and compared. Cox regression analysis was used to identify the independent risk factors for IgG4-ROD relapse.

Results
255 IgG4-ROD patients were identified in this study. IgG4-ROD group had almost equal sex ratio, younger age of disease onset and diagnosis comparing with nIgG4-ROD patients. As compared to nIgG4-ROD group, higher percentage of IgG4-ROD patients met the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) for IgG4-RD; moreover, IgG4-ROD patients had higher AECC scores and IgG4-RD responder index (RI). Allergic diseases and multiorgan involvement were more common in IgG4-ROD group. IgG4-ROD was frequently associated with salivary gland, paranasal sinus, lung, and lymph node involvement, while retroperitoneal fibrosis and biliary system lesions were more common in nIgG4-ROD. IgG4-ROD patients had higher serum IgG4 levels, IgG4/IgG ratio, IgE levels, and lower CRP levels. The initial glucocorticoid plus immunosuppressant was a protective factor for IgG4-ROD relapse. IgG4-ROD patients treated with initial glucocorticoid plus immunosuppressant had longer relapse-free survival time than patients treated with initial glucocorticoid monotherapy.

Conclusions
IgG4-ROD patients had distinctive clinical features compared with nIgG4-ROD patients. The initial glucocorticoid plus immunosuppressant was a protective factor for IgG4-ROD relapse, which could prolong the relapse-free survival time of IgG4-ROD patients. These findings may have important implications for understanding and management of IgG4-ROD.
Associations between childhood family emotional health, fronto-limbic grey matter volume, and saliva 5mC in young adulthood
Authors: Pfeiffer J. R. , Bustamante Angela C. , Kim Grace S. , Armstrong Don , Knodt Annchen R. , Koenen Karestan C. , Hariri Ahmad R. , Uddin Monica 
Published: March 2021

AbstractBackgroundPoor family emotional health (FEH) during childhood is prevalent and impactful, and likely confers similar neurodevelopmental risks as other adverse social environments. Pointed FEH study efforts are underdeveloped, and the mechanisms by which poor FEH are biologically embedded are unclear. The current exploratory study examined whether variability in 5-methyl-cytosine (5mC) and fronto-limbic grey matter volume may represent pathways through which FEH may become biologically embedded.ResultsIn 98 university students aged 18–22 years, retrospective self-reported childhood FEH was associated with right hemisphere hippocampus (b = 10.4,p = 0.005), left hemisphere amygdala (b = 5.3,p = 0.009), and right hemisphere amygdala (b = 5.8,p = 0.016) volumes. After pre-processing and filtering to 5mC probes correlated between saliva and brain, analyses showed that childhood FEH was associated with 49 5mC principal components (module eigengenes; MEs) (prange = 3 × 10–6to 0.047). Saliva-derived 5mC MEs partially mediated the association between FEH and right hippocampal volume (Burlywood ME indirect effectb = − 111,p = 0.014), and fully mediated the FEH and right amygdala volume relationship (Pink4 ME indirect effectb = − 48,p = 0.026). Modules were enriched with probes falling in genes with immune, central nervous system (CNS), cellular development/differentiation, and metabolic functions.ConclusionsFindings extend work highlighting neurodevelopmental variability associated with adverse social environment exposure during childhood by specifically implicating poor FEH, while informing a mechanism of biological embedding. FEH-associated epigenetic signatures could function as proxies of altered fronto-limbic grey matter volume associated with poor childhood FEH and inform further investigation into primarily affected tissues such as endocrine, immune, and CNS cell types.
Autoantibodies to speckled protein family in primary biliary cholangitis
Authors: Granito Alessandro , Muratori Luigi , Tovoli Francesco , Muratori Paolo 
Published: March 2021

AbstractThe autoantibody profile of primary biliary cholangitis (PBC) includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in more than 50% of PBC patients. One of the two immunofluorescence patterns which are historically considered “PBC-specific” is the so-called “multiple nuclear dots” (MND) targeting nuclear body proteins such as Sp100, Sp140, Sp140L proteins, promyelocytic leukemia protein (PML) and small ubiquitin-related modifier proteins (SUMO). It has been hypothesized a role of nuclear body protein alterations in immune disorders such as PBC, thus suggesting novel and more refined therapeutic approaches.
Microbleeds show a characteristic distribution in cerebral fat embolism
Authors: Giyab Omar , Balogh Bendegúz , Bogner Péter , Gergely Orsi , Tóth Arnold 
Published: March 2021

AbstractThis systematic review aims to test the hypothesis that microbleeds detected by MRI are common and show a characteristic pattern in cerebral fat embolism (CFE). Eighty-four papers involving 140 CFE patients were eligible for this review based on a systematic literature search up to 31 January 2020. An additional case was added from hospital records. Patient data were individually scrutinised to extract epidemiological, clinical and imaging variables. Characteristic CFE microbleed pattern resembling a “walnut kernel” was defined as punctuate hypointensities of monotonous size, diffusely located in the subcortical white matter, the internal capsule and the corpus callosum, with mostly spared corona radiata and non-subcortical centrum semiovale, detected by susceptibility- or T2* weighted imaging. The presence rate of this pattern and other, previously described MRI markers of CFE such as the starfield pattern and further diffusion abnormalities were recorded and statistically compared. The presence rate of microbleeds of any pattern, the “walnut kernel microbleed pattern”, diffusion abnormality of any pattern, the starfield pattern, and cytotoxic edema in the corpus callosum was found to be 98.11%, 89.74%, 97.64%, 68.5%, and 77.27% respectively. The presence rate between the walnut kernel and the starfield pattern was significantly (p < 0.05) different. Microbleeds are common and mostly occur in a characteristic pattern resembling a “walnut kernel” in the CFE MRI literature. Microbleeds of this pattern in SWI or T2* MRI, along with the starfield pattern in diffusion imaging appear to be the most important imaging markers of CFE and may aid the diagnosis in clinically equivocal cases.
Clinical presentation of congenital syphilis in a rotavirus vaccine cohort study in Lusaka: a case series
Authors: Sukwa Nsofwa , Simuyandi Michelo , Chirwa Masuzyo , Kumwimba Yvonne Mutombo , Chilyabanyama Obvious N. , Laban Natasha , Koyuncu Aybüke , Chilengi Roma 
Published: March 2021

Abstract
Background
Despite an otherwise robust national antenatal clinic program, maternal and congenital syphilis remains an important public health issue in Zambia. This case series reports the clinical presentation of seven infants diagnosed with congenital syphilis in Lusaka, Zambia.

Case presentations
The cases in this series were incidental findings from a cohort of infants enrolled in a rotavirus vaccine immunogenicity study recruiting infants at 6 weeks of age. As part of clinical care for enrolled participants, we screened mothers of children who presented with adverse events of (i) repeated upper respiratory tract infections/coryza, (ii) skin lesions, and (iii) poor weight gain, for syphilis using rapid plasma reagin test. From a cohort of 214 mother–infant pairs enrolled between September and December 2018, a total of 115 (44.4%) of the mothers reported to have not been screened during antenatal care. Of these, four (3.5%) reported to have tested positive; and only two received treatment. Seven out of 57 (26.6%) children meeting the screening criteria had a positive rapid plasma reagin test result. The mean age at diagnosis was 4.5 months (1.3 months standard deviation), and the common presenting features included coryza (6/7), skin lesions (4/7), conjunctivitis (3/7), pallor/anemia (5/7), wasting (2/7), and underweight (5/7). Three of the seven infants were exposed to human immunodeficiency virus. Following diagnosis, all seven cases received standard treatment according to national treatment guidelines. That is, 6/7 cases received inpatient care with benzylpenicillin for 10 days, while 1/7 was treated as an outpatient and received daily procaine penicillin for 10 days.

Conclusion
These findings suggest that, though screening for syphilis is part of the standard antenatal care in Zambia, it is not offered optimally. There is urgent need to address programmatic shortcomings in syphilis screening and treatment to avoid long-term sequelae. Additionally, clinicians need to raise their index of suspicion and rule out syphilis when confronted with these clinical symptoms, regardless of the mother’s human immunodeficiency virus status.
Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis
Authors: Li Yan , Zhang Jian , Shi Jihong , Liu Kaituo , Wang Xujie , Jia Yanhui , He Ting , Shen Kuo , Wang Yunchuan , Liu Jiaqi , Zhang Wei , Wang Hongtao , Zheng Zhao , Hu Dahai 
Published: March 2021

Abstract
Background
Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties.

Methods
ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson’s trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice.

Results
The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs.

Conclusions
This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.
Setting the mountain ablaze? The Royal Highland Festival in Bhutan from the semi-nomads’ perspective
Authors: Wangdi Jigme , Dorji Tashi , Wangchuk Kesang 
Published: March 2021

AbstractA study was conducted to assess the effects of the Royal Highland Festival (RHF) from the perspective of yak herders in Laya, Bhutan. Sixty-six respondents were randomly selected from amongst the domicile herders who were regular visitors to the festival. A survey was carried out through a questionnaire with mixed questions. Herders’ opinions suggest good progress of RHF as reflected by improved community vitality and networking with stakeholders. Tourists, both international and domestic, were the major contributors to the income of yak herders during the festival. Livestock products were the biggest income earner, followed by homestays. Herders were encouraged to produce more quantities of livestock products and desired to diversify yak products. Animal shows were adequate and encouraged breed improvement. The grazing resources and the environment were unharmed by the presence of animals in the festival. However, yak herders expressed concerns over the lack of skills and knowledge for yak product diversification and management of festival waste. Herders felt the need to shift the festival venue to benefit highlanders in other areas of Bhutan. The study recommends authorities to consider imparting skills to Laya communities on developing diverse and value-added yak products. Homestay owners require more capacity to manage and maintain farmhouses with proper sanitation. Effective management of festival wastes calls for a farsighted plan. Finally, to inculcate a sense of pride and ownership, the communities of Laya must be empowered to self-organize the festival, while government authorities should consider shifting the festival venue to other highland areas.
Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET
Authors: François Bruno , Fiancette Maud , Helms Julie , Mercier Emmanuelle , Lascarrou Jean-Baptiste , Kayanoki Toshihiko , Tanaka Kosuke , Fineberg David , Vincent Jean-Louis , Wittebole Xavier 
Published: March 2021

Abstract
Background
The phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin (ART-123) for treatment of sepsis-associated coagulopathy (SAC), which correlates with increased mortality risk in patients with sepsis. Although no significant reduction in mortality was observed with ART-123 compared with placebo in the full analysis set (FAS), an efficacy signal of ART-123 was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin. Post hoc analysis was performed of patients treated in France, the country with the largest enrollment (19% of the FAS) and consistent patient enrollment throughout the study duration.

Methods
Adult patients with SAC (international normalized ratio > 1.4; platelets > 30 × 109/L to < 150 × 109/L or platelet decrease > 30% within 24 h) and evidence of bacterial infection were included. The primary efficacy outcome was 28-day all-cause mortality. Safety outcomes included adverse, serious adverse, and major bleeding events. This analysis assessed patient characteristics and efficacy and safety outcomes in France compared with the rest of the world (ROW; excluding France). Mortality rates were assessed in patients in France or the ROW with characteristics previously associated with ART-123 efficacy.

Results
Baseline characteristics were similar between France and the ROW, but some measurements of disease severity were higher in patients in France. The 28-day all-cause mortality absolute risk reductions (ARRs) with ART-123 were 8.3% in France and 1.1% in the ROW. The greater ARR in France may be related to a higher rate of sustained coagulopathy and lower rate of heparin use. In France and the ROW, 84.6% and 78.0% of patients sustained coagulopathy from the time of initial SAC diagnosis to first treatment with the study drug, and 65.8% and 43.9% did not receive heparin, respectively. The ARRs for these subgroups of patients in France were 13.4% and 16.6%, respectively. Safety of ART-123 was comparable between France and the ROW.

Conclusions
Results from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART-123, a fact that should be confirmed in future studies with more restrictive inclusion criteria.
Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture
Authors: Iskandar Katia , Molinier Laurent , Hallit Souheil , Sartelli Massimo , Hardcastle Timothy Craig , Haque Mainul , Lugova Halyna , Dhingra Sameer , Sharma Paras , Islam Salequl , Mohammed Irfan , Naina Mohamed Isa , Hanna Pierre Abi , Hajj Said El , Jamaluddin Nurul Adilla Hayat , Salameh Pascale , Roques Christine 
Published: March 2021

AbstractData on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.
Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy
Authors: Ouyang Wei , Zhang Yucong , Long Gongwei , Sun Guoliang , Liu Man , Li Fan , Yang Chunguang , Zeng Xing , Yang Jun , Yu Xiao , Wang Zhihua , Liu Zheng , Guan Wei , Hu Zhiquan , Wang Shaogang , Liu Xiaming , Li Heng , Xu Hua , Ye Zhangqun 
Published: March 2021

Abstract
Background
To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods
We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results
In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion
The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
Perception of quality of life by children and adolescents with cleft lip/palate after orthodontic and surgical treatment: gender and age analysis
Authors: Ruiz-Guillén Ana , Suso-Ribera Carlos , Romero-Maroto Martín , Gallardo Carmen , Peñacoba Cecilia 
Published: March 2021

Abstract
Background
The quality of life (QoL) of children and adolescents with cleft lip/palate (CL/P) has been shown to be a predictor of good psychosocial functioning in this population group. This study aimed to measure QoL, from the patient´s perception of change produced by the different surgical and orthodontic treatments carried out since early childhood, and if gender and age are modulating the outcome variables results.

Materials and methods
A cross-sectional research study was carried out. The study included 60 patients with cleft lip, cleft palate, or cleft lip/palate, aged between 8 and 18, who were in orthodontic treatment and had undergone at least one surgery. They were asked to complete the Quality-of-Life Adolescent Cleft Questionnaire (QoLAdoCleft), which allows the assessment of the QoL through self-perception of improvement after surgical and orthodontic interventions. In particular, this questionnaire (administered only once), allows the evaluation of self-perception of QoL at the present time and before orthodontic and surgical treatment. This double assessment was carried out for the domains of physical, psychological, and social health. The results were analysed by looking at the interaction of gender and age.

Results
Statistically significant differences were found in the perception of the current QoL in comparison to the retrospective perception in all the dimensions considered. The perception of QoL improved in all cases. The results also showed a moderation of gender in the relation between perception of previous behaviour and social function and actual behaviour and social function.

Conclusion
The results indicated that patients perceived their quality of life had improved as a result of the treatments received, with the highest effect sizes found in the physical health domain. Specifically, the improvement in QoL in behaviour and social function tended to be influenced to a greater extent by perception of previous QoL. In this sense, personalized preventative measures from holistic and biopsychosocial approaches are necessary.