bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal implications in COVID-19
Authors: Zoghi Ghazal , Moosavy Seyed Hamid , Yavarian Sadegh , HasaniAzad Mehdi , Khorrami Farid , Sharegi Brojeni Masoud , Kheirandish Masoumeh
Published: November 2021

Background

Coronavirus disease 2019 (COVID-19 patients mostly present with respiratory symptoms; however, gastrointestinal (GI) manifestations can also be seen either alone or along with respiratory symptoms. We aimed to evaluate the GI symptoms related to COVID-19.

Methods

This cross-sectional study retrospectively evaluated the medical files of 507 patients with confirmed or highly probable COVID-19. Based on their symptoms, patients were categorized into four groups: with GI symptoms alone (GIA), with respiratory symptoms alone (RA), with both GI and respiratory symptoms (GIR), and without GI or respiratory symptoms (WGIR).

Results

Of the 507 COVID-19 patients, 47.9% had at least one GI symptom; the most common was nausea and/or vomiting (31.6%). Patients in the GIA group were significantly older than those in the RA (P = 0.041) and GRI (P = 0.004) groups (54.70 ± 18.14 vs. 48.68 ± 14.67 and 46.80 ± 17.17 years, respectively). Groups were homogeneous with respect to gender. Leukopenia and lymphopenia were both less frequent in patients with GI symptoms compared to those without GI symptoms. Positive RT-PCR was significantly less frequent among patients with GI symptoms (44% vs. 100%, P < 0.001). Although mortality was lower in patients with GI symptoms (9.1%) in comparison with those without GI symptoms (13.3%), the difference was not statistically significant (P = 0.134).

Conclusion

The typical respiratory symptoms of COVID-19 are quite commonly accompanied by GI symptoms, with nausea and/or vomiting being the most prevalent. A subgroup of COVID-19 patients may exclusively present with GI symptoms. Special attention should be paid to these patients in order to avoid misdiagnosis or delayed treatment.
Clinical efficacy and safety of full-dose versus half-dose corticosteroids plus leflunomide for IgA nephropathy
Authors: Li Yebei , Xiong Yi , Huang Tianlun , Liu Xin , Xu Gaosi
Published: November 2021

Background

The results of leflunomide (LEF) in patients with IgA nephropathy (IgAN) were inconsistent.

Methods

A total of 149 kidney biopsy-confirmed IgAN patients with an estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m2 and protein excretion levels ≥0.75 g/d were enrolled, with 65 subjects receiving half-dose CS plus LEF (LEF group), and the 84 counterpart patients accepting full-dose corticosteroid (Full CS group). The primary outcomes included the complete remission (CR) rates and incidence of adverse events (AEs). The secondary outcomes were the overall remission (OR) rates and a combined event (eGFR reduced ≥30%, end-stage renal disease [ESRD], hemodialysis, peritoneal dialysis or kidney transplantation).

Results

During the 18 months of follow-up, the CR rates were 72 and 64% in the LEF and Full CS groups (P = 0.299), respectively. The proportion of patients with OR rates in the LEF group and Full CS group was 89% versus 75%, respectively (P = 0.027). Serious AEs were observed only in the Full CS group (P = 0.017). The incidences of total AEs (P = 0.036) and infections (P = 0.024) were lower in the LEF group than in the Full CS group.

Conclusions

LEF combined with half-dose CS is superior to full-dose CS in the treatment of IgAN.
Clinical features, treatment and prognosis of MuSK antibody-associated myasthenia gravis in Northwest China: a single-centre retrospective cohort study
Authors: Zhao Sijia , Zhang Kai , Ren Kaixi , Lu Jiarui , Ma Chao , Zhao Cong , Li Zhuyi , Guo Jun
Published: November 2021

Background and purpose

To summarize the clinical characteristics of patients with muscle-specific kinase antibody-associated myasthenia gravis (MuSK-MG) and to evaluate the therapeutic responses to different treatment regimes.

Methods

Eighteen MuSK-MG patients admitted in our department between October 2017 and September 2020 were included. Clinical parameters were collected and the responses to different immunosuppressive drugs were assessed by MGFA Postintervention Status (MGFA-PIS). Meanwhile, the correlation between QMG scores and MuSK antibody titers were analyzed and MuSK antibody (MuSK-ab) titers were compared before and after therapy based on different immunosuppressive treatment regimes.

Results

Female predominance (ratio of females to males, 15:3) was evident in the study population, with the average onset age of (40.28 ± 18.57) years and the median disease course of 30.50 months (interquartile range [IQR], 17.50–44.75 months). Ocular manifestation was the most common onset symptom (11/18; 61.11%), and mild symmetrical ptosis was most frequent. Bulbar symptoms had the highest incidence of 88.89% over the entire disease course. Abnormal responses to RNS test were recorded most frequently on the musculus deltoideus (83.33%). All patients were treated with prednisone (Pred) alone or plus azathioprine (AZA), tacrolimus (TAC) or low-dose rituximab (RTX), and 17 (94.44%) of them achieved a favorable outcome defined as minimal manifestation (MM) or better. In general, an obvious positive correlation between QMG score and MuSK-ab titer (r = 0.710, P < 0.001) were found in all patients. A more significant reduction of MuSK-ab titers was observed in patients receiving TAC or RTX plus Pred than those receiving AZA plus Pred.

Conclusions

The prominent clinical manifestations of ocular and bulbar muscles involvements, together with abnormal RNS response mostly recorded on the musculus deltoideus and better efficacy associated with TAC or low-dose RTX plus Pred, provide a more exhaustive picture of MuSK-MG, particularly in Northwest China.
How effective is fine motor training in children with ADHD? A scoping review
Authors: Lelong Miriam , Zysset Annina , Nievergelt Mirjam , Luder Reto , Götz Ulrich , Schulze Christina , Wieber Frank
Published: November 2021

Background

Motor deficiencies are observed in a large number of children with ADHD. Especially fine motor impairments can lead to academic underachievement, low self-esteem and frustration in affected children. Despite these far-reaching consequences, fine motor deficiencies have remained widely undertreated in the ADHD population. The aim of this review was to systematically map the evidence on existing training programs for remediating fine motor impairments in children with ADHD and to assess their effectiveness.

Methods

The scoping review followed the PRISMA-ScR guidelines. In March 2020, PsycINFO, MEDLINE (PubMed), Web of Science, Google Scholar and The Cochrane Database of Systematic Reviews were searched for evidence. The eligibility criteria and the data charting process followed the PICO framework, complemented by study design. The investigated population included children with a formal ADHD diagnosis (either subtype) or elevated ADHD symptoms aged between 4 and 12 years, both on and off medication. All training interventions aiming at improving fine motor skills, having a fine motor component or fine motor improvements as a secondary outcome were assessed for eligibility; no comparators were specified.

Results

Twelve articles were included in the final report, comprising observational and experimental studies as well as a review. Both offline and online or virtual training interventions were reported, often accompanied by physical activity and supplemented by training sessions at home. The training programs varied in length and intensity, but generally comprised several weeks and single or multiple training sessions per week. All interventions including more than one session were effective in the treatment of fine motor deficiencies in children with ADHD and had a wide range of additional positive outcomes. The effects could be maintained at follow-up.

Conclusions

Fine motor training in children with ADHD can be very effective and multiple approaches including specific fine motor and cognitive training components, some kind of physical activity, feedback mechanisms, or multimodal treatments can be successful. Training programs need to be tailored to the specific characteristics of the ADHD population. A mHealth approach using serious games could be promising in this context due to its strong motivational components.
Elucidating the context for implementing nonpharmacologic care for neonatal opioid withdrawal syndrome: a qualitative study of perinatal nurses
Authors: Shuman Clayton J. , Wilson Roxanne , VanAntwerp Katherine , Morgan Mikayla , Weber Ashley
Published: November 2021

Background

Up to 95% of neonates exposed to opioids in utero experience neonatal opioid withdrawal syndrome at birth. Nonpharmacologic approaches (e.g., breastfeeding; rooming-in; skin-to-skin care) are evidence-based and should be implemented. These approaches, especially breastfeeding, rely on engagement of the neonates’ mothers to help deliver them. However, little is known about the structural and social dynamic context barriers and facilitators to implementing maternal-delivered nonpharmacologic care.

Methods

Using a qualitative descriptive design, perinatal nurses from a Midwest United States hospital family birthing center, neonatal intensive care unit, and inpatient pediatric unit were interviewed. These units were involved in caring for mothers and neonates affected by opioid use. Telephone interviews followed a semi-structured interview guide developed for this study, were audio-recorded, and lasted about 30–60 min. Interviews were transcribed verbatim and independently analyzed by five investigators using the constant comparative method. Themes were discussed until reaching consensus and subsequently mapped to a conceptual model adapted for this study.

Results

Twenty-one nurses participated in this study (family birth center, n = 9; neonatal intensive care, n = 6; pediatrics, n = 6). Analysis resulted in four major themes: 1) Lack of education and resources provided to staff and mothers; 2) Importance of interdisciplinary and intradisciplinary care coordination; 3) Flexibility in nurse staffing models for neonatal opioid withdrawal syndrome; and 4) Unit architecture and layout affects maternal involvement. Minor themes supported each of the four major themes. All themes mapped to the conceptual model.

Conclusions

This study provides a more comprehensive understanding of the barriers and facilitators affecting implementation of maternal involvement in nonpharmacologic care of newborns with neonatal opioid withdrawal syndrome. Future efforts implementing nonpharmacologic approaches must consider the context factors affecting implementation, including structural and social factors within the units, hospital, and broader community.
Spatial patterns and determinants of undernutrition among late-adolescent girls in Ethiopia by using Ethiopian demographic and health surveys, 2000, 2005, 2011 and 2016: a spatial and multilevel analysis
Authors: Derseh Nebiyu Mekonnen , Gelaye Kassahun Alemu , Muluneh Atalay Goshu
Published: November 2021

Background

Undernutrition among late-adolescent girls (15–19 years) in Ethiopia is the highest among Southern and Eastern African countries. However, the spatial variation of undernutrition as a national context is not well understood in Ethiopia. This study aimed at the spatial patterns and determinants of undernutrition among late-adolescent girls in Ethiopia.

Methods

Secondary data analysis was conducted from women’s data of four consecutive Ethiopian Demographic and Health Surveys (EDHS) from 2000 to 2016. A total of 12,056 late-adolescent girls were included in this study. The global spatial autocorrelation was assessed using the Global Moran’s I autocorrelation to evaluate the presence of geographical clustering and variability of undernutrition. SaTScan cluster analysis by using the Bernoulli model to detect most likely SaTScan cluster areas of significant high-rate and low-rate of undernutrition was explored. A Multilevel binary logistic regression model with cluster-level random effects was fitted to determine factors associated with undernutrition among late-adolescent girls in Ethiopia.

Results

Undernutrition was clustered nationally during each survey (Global Moran’s I = 0.009–0.045, Z-score = 5.55–27.24, p-value < 0.001). In the final model, individual and community level factors accounted for about 31.02% of the regional variations for undernutrition. The odds of undernutrition among 18–19 years of adolescent girls, was 57% (AOR = 0.43; 95% CI: (0.35–0.53) lower than those 15–17 years old. Late-adolescent girls with higher educational status were 4.40 times (AOR = 4.40; 95% CI: (1.64–11.76) more likely to be undernourished than those with no educational status. The odds of undernutrition among late-adolescent girls, with the occupation of sales, was 40% (AOR = 0.60; 95% CI: 0.43–0.84) lower than those with not working adolescents. The odds of undernutrition, among late-adolescent girls, having an unimproved latrine type, was 1.79 times (AOR = 1.79; 95% CI: 1.15–2.79) higher than those participants with improved latrine type. The odds of undernutrition among late-adolescent girls with rural residents was 2.33 times higher (AOR = 2.33; 95% CI: 1.29–4.22) than those with urban residents.

Conclusion

Undernutrition among late-adolescent girls was spatially clustered in Ethiopia. The local significant clusters with high prevalence of undernutrition was observed in Northern and Eastern Ethiopia. Those regions with a high prevalence of undernutrition should design interventions to combat undernutrition.
Bone metastasis from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP); a case report
Authors: Fakhar Yasaman , Khooei Alireza , Aghaee Atena , Mohammadzadeh Kosari Hadis , Wartofsky Leonard , Zakavi Seyed Rasoul
Published: November 2021

Background

The term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently proposed as a non-malignant thyroid lesion with indolent behavior that does not require post-operative radio-iodine treatment. We are reporting a case of NIFTP with bone metastasis that is the second case reported so far.

Case presentation

We describe a 38-year-old woman who presented with an indeterminate thyroid nodule and underwent total thyroidectomy with the finding of NIFTP on careful pathologic examination. However, her initial follow-up evaluation revealed a serum thyroglobulin level of > 300 ng/ml and a diagnostic whole body 131I scan demonstrated a focus of increased uptake in the left hemipelvis, confirmed on CT scan to be a lytic lesion in the left iliac bone. She was treated with 7.4GBq (200 mCi) of 131I and her follow-up 1 year later revealed an undetectable serum thyroglobulin and a negative whole body 131I scan with no visible uptake in the iliac bone indicating an excellent response.

Conclusion

This case presentation reminds us to be alert to the rare occurrence of distant metastasis in NIFTP and the need for a case by case analysis and continuing post-operative follow-up for detection of residual or recurrent disease.
Learning from low-rank multimodal representations for predicting disease-drug associations
Authors: Hu Pengwei , Huang Yu-an , Mei Jing , Leung Henry , Chen Zhan-heng , Kuang Ze-min , You Zhu-hong , Hu Lun
Published: November 2021

Background

Disease-drug associations provide essential information for drug discovery and disease treatment. Many disease-drug associations remain unobserved or unknown, and trials to confirm these associations are time-consuming and expensive. To better understand and explore these valuable associations, it would be useful to develop computational methods for predicting unobserved disease-drug associations. With the advent of various datasets describing diseases and drugs, it has become more feasible to build a model describing the potential correlation between disease and drugs.

Results

In this work, we propose a new prediction method, called LMFDA, which works in several stages. First, it studies the drug chemical structure, disease MeSH descriptors, disease-related phenotypic terms, and drug-drug interactions. On this basis, similarity networks of different sources are constructed to enrich the representation of drugs and diseases. Based on the fused disease similarity network and drug similarity network, LMFDA calculated the association score of each pair of diseases and drugs in the database. This method achieves good performance on Fdataset and Cdataset, AUROCs were 91.6% and 92.1% respectively, higher than many of the existing computational models.

Conclusions

The novelty of LMFDA lies in the introduction of multimodal fusion using low-rank tensors to fuse multiple similar networks and combine matrix complement technology to predict potential association. We have demonstrated that LMFDA can display excellent network integration ability for accurate disease-drug association inferring and achieve substantial improvement over the advanced approach. Overall, experimental results on two real-world networks dataset demonstrate that LMFDA able to delivers an excellent detecting performance. Results also suggest that perfecting similar networks with as much domain knowledge as possible is a promising direction for drug repositioning.
Navigating medical assistance in dying from Bill C-14 to Bill C-7: a qualitative study
Authors: Pesut Barbara , Thorne Sally , Wright David Kenneth , Schiller Catharine , Huggins Madison , Puurveen Gloria , Chambaere Kenneth
Published: November 2021

Background

Even as healthcare providers and systems were settling into the processes required for Medical Assistance in Dying (MAID) under Bill C-14, new legislation was introduced (Bill C-7) that extended assisted death to persons whose natural death is not reasonably foreseeable. The purpose of this paper is to describe the experiences of nurses and nurse practitioners with the implementation and ongoing development of this transition.

Methods

This qualitative longitudinal descriptive study gathered data through semi-structured telephone interviews with nurses from across Canada; cross sectional data from 2020 to 2021 is reported here. The study received ethical approval and all participants provided written consent.

Findings

Participants included nurses (n = 34) and nurse practitioners (n = 16) with significant experience with MAID. Participants described how MAID had transitioned from a new, secretive, and anxiety-producing procedure to one that was increasingly visible and normalized, although this normalization did not necessarily mitigate the emotional impact. MAID was becoming more accessible, and participants were learning to trust the process. However, the work was becoming increasingly complex, labour intensive, and often poorly remunerated. Although many participants described a degree of integration between MAID and palliative care services, there remained ongoing tensions around equitable access to both. Participants described an evolving gestalt of determining persons’ eligibility for MAID that required a high degree of clinical judgement. Deeming someone ineligible was intensely stressful for all involved and so participants had learned to be resourceful in avoiding this possibility. The required 10-day waiting period was difficult emotionally, particularly if persons worried about losing capacity to give final consent. The implementation of C-7 was perceived to be particularly challenging due to the nature of the population that would seek MAID and the resultant complexity of trying to address the origins of their suffering within a resource-strapped system.

Conclusions

Significant social and system calibration must occur to accommodate assisted death as an end-of-life option. The transition to offering MAID for those whose natural death is not reasonably foreseeable will require intensive navigation of a sometimes siloed and inaccessible system. High quality MAID care should be both relational and dialogical and those who provide such care require expert communication skills and knowledge of the healthcare system.
Pathogens with potential impact on reproduction in captive and free-ranging European bison (Bison bonasus) in Poland - a serological survey
Authors: Didkowska Anna , Klich Daniel , Hapanowicz Anna , Orłowska Blanka , Gałązka Marta , Rzewuska Magdalena , Olech Wanda , Anusz Krzysztof
Published: November 2021

Background

The European bison is an endangered species, and as such it is extremely important to monitor herds for pathogens which can lead to reproductive failure. The aim of the present study was to determine the current prevalence of antibodies to pathogens known to potentially influence reproduction in European bison. Serum samples from 183 bison, originating from different parts of Poland, were tested using commercial ELISA tests for antibodies to Chlamydia spp., Coxiella burnetti, Leptospira interrogans, Neospora caninum and Toxoplasma gondii; the findings were compared between captive and main free-ranging herds, and with regard to the influence of demographic factors such as age and sex. The prevalence of seropositivity was also checked with regard to location and the animal species sharing it.

Results

Chlamydia spp. antibodies were present in 48 out of 130 (36.9%) tested samples. Coxiella burnetii was found in one sample out of 178 (0.58%). N. caninum in 36 out of 172 (20.9%) and T. gondii in 23 out of 172 (13.4%). No sample was positive for leptospirosis. Neither sex nor age appeared to have a significant effect on the occurrence of antibodies to the identified species. The prevalence of Chlamydia spp. in the samples varied significantly according to location; however, similar frequency ranges were observed between free ranging and captive herds. In contrast, antibodies to N. caninum were more common in free-ranging herds than captive herds, with the highest frequency observed in the Bieszczady Mountains.

Conclusions

Chlamydia spp., N. caninum and T. gondii might have a similar impact on the reproductive potential of European bison as they have on cattle. The high occurrence of antibodies to N. caninum in bison from the Bieszczady Mountains may be associated with the relatively high density of the wolf population in the area.
RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression
Authors: Wang Lei , Liu Xiu-Xiu , Yang Yu-Meng , Wang Yan , Song Yuan-Yuan , Gao Shan , Li Lu-Yuan , Zhang Zhi-Song
Published: November 2021

Background

The rhomboids are a family of multi-transmembrane proteins, many of which have been implicated in facilitating tumor progression. Little is yet known, however, about rhomboid-associated biomarkers in cancers. An analysis of such biomarkers could yield important insights into the role of the rhomboids in cancer pathology.

Methods

In this study, we carried out the univariate Cox regression analysis and compared gene expression patterns of several rhomboid genes in 30 types of cancers by using The Cancer Genome Atlas (TCGA) database and the methods delineated in Gene Expression Profiling Interactive Analysis (GEPIA). We then used datasets GSE47032, GSE126964, GSE68417 and 75 paired pathological specimens to verify the influences of the rhomboid genes in cancer progression. Moreover, we carried out Weighted Gene Correlation Network Analysis (WGCNA) to investigate gene-related functions and we exploited potential correlations between rhomboid genes expression and immune cell infiltration in cancer tissues. Furthermore, we constructed gene-knockdown cancer cell lines to investigate rhomboid gene functions.

Results

We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels. Silencing of the RHBDF2 gene in KIRC cell lines leads to significantly diminished cell proliferation and migration; this is in good agreement with the identification of an enhanced presence of a number of cell growth and migration promoting signaling molecules in KIRC tumors. We found that, although high level of RHBDF2 correlated with increased infiltration of lymphocytes in cancer tissues, artificially overexpressed RHBDF2 led to an inhibition of the activity of the infiltrated immune cells through sustaining PD-L1 protein level. Furthermore, we show that RHBDF2 related cell migration and PD-L1 regulation were potentially mediated by EGFR signaling pathway.

Conclusions

RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression and may serve as a critical prognostic biomarker for the disease.
Development and validation of ferroptosis-related lncRNAs prognosis signatures in kidney renal clear cell carcinoma
Authors: Xing Xiao-Liang , Yao Zhi-Yong , Ou Jialan , Xing Chaoqun , Li Feng
Published: November 2021

Background

Ferroptosis is a recently recognised new type of cell death which may be a potential target for cancer therapy. In the present study, we aimed to screen ferroptosis-related differentially expressed long non-coding RNAs as biomarkers to predict the outcome of kidney renal clear cell carcinoma.

Methods

RNAseq count data and corresponding clinical information were obtained from the Cancer Genome Atlas database. Lists of ferroptosis-related genes and long non-coding RNAs were obtained from the FerrDb and GENCODE databases, respectively. The candidate prognostic signatures were screened by Cox regression analyses and least absolute shrinkage and selection operator analyses.

Results

Three ferroptosis-related long non-coding RNAs (DUXAP8, LINC02609, and LUCAT1) were significantly correlated with the overall survival of kidney renal clear cell carcinoma independently. Kidney renal clear cell carcinoma patients with high-risk values displayed worse OS. Meanwhile, the expression of these three ferroptosis-related long non-coding RNAs and their risk scores were significantly correlated with clinicopathological features. Principal component analyses showed that patients with kidney renal clear cell carcinoma have differential risk values were well distinguished by the three ferroptosis-related long non-coding RNAs.

Conclusions

The present study suggests that the risk assessment model constructed by these three ferroptosis-related long non-coding RNAs could accurately predict the outcome of kidney renal clear cell carcinoma. We also provide a novel perspective for cancer prognosis screening.
Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
Authors: Zhang Han , Wu Yijun , Li Hao , Sun Liping , Meng Xiangkai
Published: November 2021

Background

The prognosis of high grade serous ovarian cancer (HGSOC) patients is closely related to the immune microenvironment and immune response. Based on this, the purpose of this study was to construct a model to predict chemosensitivity and prognosis, and provide novel biomarkers for immunotherapy and prognosis evaluation of HGSOC.

Methods

GSE40595 (38 samples), GSE18520 (63 samples), GSE26712 (195 samples), TCGA (321 samples) and GTEx (88 samples) were integrated to screen differential expressed genes (DEGs) of HGSOC. The prognosis related DEGs (DEPGs) were screened through overall survival analysis. The DEGs-encoded protein–protein interaction network was constructed and hub genes of DEPGs (DEPHGs) were generated by STRING. Immune characteristics of the samples were judged by ssGSEA, ESTIMATE and CYBERSORT. TIMER was used to analyze the relationship between DEPHGs and tumor-infiltrating immunocytes, as well as the immune checkpoint genes, finally immune-related DEPHGs (IDEPHGs) were determined, and whose expression in 12 pairs of HGSOC tissues and tumor-adjacent tissues were analyzed by histological verification. Furthermore, the chemosensitivity genes in IDEPHGs were screened according to GSE15622 (n = 65). Finally, two prediction models of paclitaxel sensitivity score (PTX score) and carboplatin sensitivity score (CBP score) were constructed by lasso algorithm. The area under curve was calculated to estimate the accuracy of candidate gene models in evaluating chemotherapy sensitivity.

Results

491 DEGs were screened and 37 DEGs were identified as DEPGs, and 11 DEPHGs were further identified. Among them, CXCL13, IDO1, PI3, SPP1 and TRIM22 were screened as IDEPHGs and verified in the human tissues. Further analysis showed that IDO1, PI3 and TRIM22 could independently affect the chemotherapy sensitivity of HGSOC patients. The PTX score was significantly better than TRIM22, PI3, SPP1, IDO1 and CXCL13 in predicting paclitaxel sensitivity, so was CBP score in predicting carboplatin sensitivity. What’s more, both of the HGSOC patients with high PTX score or high CBP score had longer survival time.

Conclusions

Five IDEPHGs identified through comprehensive bioinformatics analysis were closely related with the prognosis, immune microenvironment and chemotherapy sensitivity of HGSOC. Two prediction models based on IDEPHGs might have potential application of chemotherapy sensitivity and prognosis for patients with HGSOC.
Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance
Authors: Xuan Xiuyun , Tian Chunxia , Zhao Mengjie , Sun Yanhong , Huang Changzheng
Published: November 2021

Increasing evidence indicates that the tumor microenvironment appears to play an increasingly important role in cancer progression and therapeutic resistance. Several types of cells within the tumor stroma had distinct impacts on cancer progression, either promoting or inhibiting cancer cell growth. Mesenchymal stem cells (MSCs) are a distinct type of cells that is linked to tumor development. MSCs are recognized for homing to tumor locations and promoting or inhibiting cancer cell proliferation, angiogenesis and metastasis. Moreover, emerging studies suggests that MSCs are also involved in therapeutic resistance. In this review, we analyzed the existing researches and elaborate on the functions of MSCs in cancer progression and anticancer therapeutic resistance, demonstrating that MSCs may be a viable cancer therapeutic target.
DNA methylation and gene expression changes in mouse pre- and post-implantation embryos generated by intracytoplasmic sperm injection with artificial oocyte activation
Authors: Yin Mingru , Yu Weina , Li Wenzhi , Zhu Qianqian , Long Hui , Kong Pengcheng , Lyu Qifeng
Published: November 2021

Background

The application of artificial oocyte activation (AOA) after intracytoplasmic sperm injection (ICSI) is successful in mitigating fertilization failure problems in assisted reproductive technology (ART). Nevertheless, there is no relevant study to investigate whether AOA procedures increase developmental risk by disturbing subsequent gene expression at different embryonic development stages.

Methods

We used a mouse model to explore the influence of AOA treatment on pre- and post-implantation events. Firstly, the developmental potential of embryos with or without AOA treatment were assessed by the rates of fertilization and blastocyst formation. Secondly, transcriptome high-throughput sequencing was performed among the three groups (ICSI, ICSI-AOA and dICSI-AOA groups). The hierarchical clustering and Principal Component Analysis (PCA) analysis were used. Subsequently, Igf2r/Airn methylation analysis were detected using methylation-specific PCR sequencing following bisulfite treatment. Finally, birth rate and birth weight were examined following mouse embryo transfer.

Results

The rates of fertilization and blastocyst formation were significantly lower in oocyte activation-deficient sperm injection group (dICSI group) when compared with the ICSI group (30.8 % vs. 84.4 %, 10.0 % vs. 41.5 %). There were 133 differentially expressed genes (DEGs) between the ICSI-AOA group and ICSI group, and 266 DEGs between the dICSI-AOA group and ICSI group. In addition, the imprinted gene, Igf2r is up regulated in AOA treatment group compared to control group. The Igf2r/Airn imprinted expression model demonstrates that AOA treatment stimulates maternal allele-specific mehtylation spreads at differentially methylated region 2, followed by the initiation of paternal imprinted Airn long non-coding (lnc) RNA, resulting in the up regulated expression of Igf2r. Furthermore, the birth weight of newborn mice originating from AOA group was significantly lower compared to that of ICSI group. The pups born following AOA treatment did not show any other abnormalities during early development. All offspring mated successfully with fertile controls.

Conclusions

AOA treatment affects imprinted gene Igf2r expression and mehtylation states in mouse pre- and post-implantation embryo, which is regulated by the imprinted Airn. Nevertheless, no significant differences were found in post-natal growth of the pups in the present study. It is hoped that this study could provide valuable insights of AOA technology in assisted reproduction biology.
Potential value of the calibrated automated thrombogram in patients after a cerebral venous sinus thrombosis; an exploratory study
Authors: van der Bruggen Myrthe M. , Kremers Bram , van Oerle Rene , van Oostenbrugge Robert J. , ten Cate Hugo
Published: November 2021

Background

Cerebral venous sinus thrombosis (CVST) is a relatively rare, but potentially lethal condition. In approximately 15% of the patients, the cause of CVST remains unclear. Conventional clotting tests such as prothrombin time and activated partial thromboplastin time are not sensitive enough to detect prothrombotic conditions nor mild haemostatic abnormalities. The calibrated automated thrombogram (CAT) is a physiological function test that might be able to detect minor aberrations in haemostasis. Therefore, we aimed to detect the presence of a prothrombotic state in patients who endured idiopathic CVST with the CAT assay.

Methods

Five adult patientswith an idiopathic, radiologically proven CVST that had been admitted during the past 3 years were included in this study. The control group consisted offiveage/gender matched healthy volunteers. Exclusion criteria were known haematological disorders, malignancy (current/past) or hormonal and anticoagulant therapy recipients. We obtained venous blood samples from all participants following cessation of anticoagulation. Using the CAT assay, we determined lag time, normalized endogenous thrombin potential (ETP), ETP reduction and normalized peak height. In addition, prothrombin concentrations were determined.

Results

We found no significant differences in lag time (4.7 min [4.5–4.9] vs 5.3 min [3.7–5.7],p = 0.691), normalized ETP (142% [124–148] vs 124% [88–138],p = 0.222), ETP reduction (29% [26–35] vs 28% [24–58],p > 0.999), and normalized peak height (155% [153–175] vs 137 [94–154],p = 0.056) between patients and their age/gender matched controls. In addition, prothrombin concentrations did not significantly differ between patients and controls (120% [105–132] vs 127% [87–139],p > 0.999).

Conclusion

Reasons for absent overt hypercoagulability within this study population may be the small patient sample, long time since the event (e.g. 3 years) and avoidance of acquired risk factors like oral contraception. Given the fact that CVST is a serious condition with a more than negligible risk of venous thrombosis event recurrence, exclusion of clinically relevant hypercoagulability remains a challenging topic to further study at the acute and later time points, particularly in patients with idiopathic CVST.
Addressing missing values in routine health information system data: an evaluation of imputation methods using data from the Democratic Republic of the Congo during the COVID-19 pandemic
Authors: Feng Shuo , Hategeka Celestin , Grépin Karen Ann
Published: November 2021

Background

Poor data quality is limiting the use of data sourced from routine health information systems (RHIS), especially in low- and middle-income countries. An important component of this data quality issue comes from missing values, where health facilities, for a variety of reasons, fail to report to the central system.

Methods

Using data from the health management information system in the Democratic Republic of the Congo and the advent of COVID-19 pandemic as an illustrative case study, we implemented seven commonly used imputation methods and evaluated their performance in terms of minimizing bias in imputed values and parameter estimates generated through subsequent analytical techniques, namely segmented regression, which is widely used in interrupted time series studies, and pre–post-comparisons through paired Wilcoxon rank-sum tests. We also examined the performance of these imputation methods under different missing mechanisms and tested their stability to changes in the data.

Results

For regression analyses, there were no substantial differences found in the coefficient estimates generated from all methods except mean imputation and exclusion and interpolation when the data contained less than 20% missing values. However, as the missing proportion grew, k-NN started to produce biased estimates. Machine learning algorithms, i.e. missForest and k-NN, were also found to lack robustness to small changes in the data or consecutive missingness. On the other hand, multiple imputation methods generated the overall most unbiased estimates and were the most robust to all changes in data. They also produced smaller standard errors than single imputations. For pre–post-comparisons, all methods produced p values less than 0.01, regardless of the amount of missingness introduced, suggesting low sensitivity of Wilcoxon rank-sum tests to the imputation method used.

Conclusions

We recommend the use of multiple imputation in addressing missing values in RHIS datasets and appropriate handling of data structure to minimize imputation standard errors. In cases where necessary computing resources are unavailable for multiple imputation, one may consider seasonal decomposition as the next best method. Mean imputation and exclusion and interpolation, however, always produced biased and misleading results in the subsequent analyses, and thus, their use in the handling of missing values should be discouraged.
Age at diagnosis in patients with chronic congenital endocrine conditions: a regional cohort study from a reference center for rare diseases
Authors: Kallali Wafa , Messiaen Claude , Saïdi Roumaisah , Lessim Soucounda , Viaud Magali , Dulon Jerome , Nedelcu Mariana , Samara Dinane , Houang Muriel , Donadille Bruno , Courtillot Carine , de Filippo GianPaolo , Carel Jean-Claude , Christin-Maitre Sophie , Touraine Philippe , Netchine Irene , Polak Michel , Léger Juliane
Published: November 2021

Background

For chronic congenital endocrine conditions, age at diagnosis is a key issue with implications for optimal management and psychological concerns. These conditions are associated with an increase in the risk of comorbid conditions, particularly as  it concerns growth, pubertal development and fertility potential. Clinical presentation and severity depend on the disorder and the patient’s age, but diagnosis is often late.

Objective

To evaluate age at diagnosis for the most frequent congenital endocrine diseases affecting growth and/or development.

Patients and Methods

This observational cohort study included all patients (n = 4379) with well-defined chronic congenital endocrine diseases—non-acquired isolated growth hormone deficiency (IGHD), isolated congenital hypogonadotropic hypogonadism (ICHH), ectopic neurohypophysis (NH), Turner syndrome (TS), McCune-Albright syndrome (MAS), complete androgen insensitivity syndrome (CAIS) and gonadal dysgenesis (GD)—included in the database of a single multisite reference center for rare endocrine growth and developmental disorders, over a period of 14 years. Patients with congenital hypothyroidism and adrenal hyperplasia were excluded as they are generally identified during neonatal screening.

Results

Median age at diagnosis depended on the disease: first year of life for GD, before the age of five years for ectopic NH and MAS, 8–10 years for IGHD, TS (11% diagnosed antenatally) and CAIS and 17.4 years for ICHH. One third of the patients were diagnosed before the age of five years. Diagnosis occurred in adulthood in 22% of cases for CAIS, 11.6% for TS, 8.8% for GD, 0.8% for ectopic NH, and 0.4% for IGHD. A male predominance (2/3) was observed for IGHD, ectopic NH, ICHH and GD.

Conclusion

The early recognition of growth/developmental failure during childhood is essential, to reduce time-to-diagnosis and improve outcomes.
Burden of anemia and its underlying causes in 204 countries and territories, 1990–2019: results from the Global Burden of Disease Study 2019
Authors: Safiri Saeid , Kolahi Ali-Asghar , Noori Maryam , Nejadghaderi Seyed Aria , Karamzad Nahid , Bragazzi Nicola Luigi , Sullman Mark J. M. , Abdollahi Morteza , Collins Gary S. , Kaufman Jay S. , Grieger Jessica A.
Published: November 2021

Background

Anemia is a common disease which affects around 40% of children and 30% of reproductive age women and can have major health consequences. The present study reports the global, regional and national burden of anemia and its underlying causes between 1990 and 2019, by age, sex and socio-demographic index (SDI).

Methods

Publicly available data on the point prevalence and years lived with disability (YLDs) were retrieved from the global burden of disease (GBD) 2019 study for 204 countries and territories between 1990 and 2019. The point prevalence, YLD counts and rates per 100,000 population were presented, along with their corresponding 95% uncertainty intervals.

Results

In 2019, the global age-standardized point prevalence and YLD rates for anemia were 23,176.2 (22,943.5–23,418.6) and 672.4 (447.2–981.5) per 100,000 population, respectively. Moreover, the global age-standardized point prevalence and YLD rate decreased by 13.4% (12.1–14.5%) and 18.8% (16.9–20.8%), respectively, over the period 1990–2019. The highest national point prevalences of anemia were found in Zambia [49327.1 (95% UI: 46,838.5–51,700.1)], Mali [46890.1 (95% UI: 44,301.1–49,389.8)], and Burkina Faso [46117.2 (95% UI: 43,640.7–48,319.2)]. In 2019, the global point prevalence of anemia was highest in the 15–19 and 95+ age groups in females and males, respectively. Also, the burden of anemia was lower in regions with higher socio-economic development. Globally, most of the prevalent cases were attributable to dietary iron deficiency, as well as hemoglobinopathies and hemolytic anemias.

Conclusions

Anemia remains a major health problem, especially among females in less developed countries. The implementation of preventive programs with a focus on improving access to iron supplements, early diagnosis and the treatment of hemoglobinopathies should be taken into consideration.
The emerging role of ISWI chromatin remodeling complexes in cancer
Authors: Li Yanan , Gong Han , Wang Pan , Zhu Yu , Peng Hongling , Cui Yajuan , Li Heng , Liu Jing , Wang Zi
Published: November 2021

Disordered chromatin remodeling regulation has emerged as an essential driving factor for cancers. Imitation switch (ISWI) family are evolutionarily conserved ATP-dependent chromatin remodeling complexes, which are essential for cellular survival and function through multiple genetic and epigenetic mechanisms. Omics sequencing and a growing number of basic and clinical studies found that ISWI family members displayed widespread gene expression and genetic status abnormalities in human cancer. Their aberrant expression is closely linked to patient outcome and drug response. Functional or componential alteration in ISWI-containing complexes is critical for tumor initiation and development. Furthermore, ISWI-non-coding RNA regulatory networks and some non-coding RNAs derived from exons of ISWI member genes play important roles in tumor progression. Therefore, unveiling the transcriptional regulation mechanism underlying ISWI family sparked a booming interest in finding ISWI-based therapies in cancer. This review aims at describing the current state-of-the-art in the role of ISWI subunits and complexes in tumorigenesis, tumor progression, immunity and drug response, and presenting deep insight into the physiological and pathological implications of the ISWI transcription machinery in cancers.
Pediatric eye emergency department activity during the first wave of Covid-19 pandemic
Authors: Franzolin Elia , Longo Rosa , Gusson Elena , Ficial Benjamim , Marchini Giorgio
Published: November 2021

Background

We investigated the volume and the characteristics of pediatric eye emergency department (PEED) consultations performed at our tertiary eye center during the early months of the COVID-19 pandemic and we compared them to those carried out in the same time interval of the previous three years.

Methods

Ophthalmic emergency examinations of patients aged ≤18 years old and done during the national COVID-19 lockdown (March 9th, 2020 – May 3rd, 2020) and in the corresponding date range of the previous three years (2017, 2018, and 2019) have been considered and reviewed. The following features were retrieved and analyzed: age, gender, duration and type of accused symptoms, traumatic etiology, and the discharge diagnosis.

Results

136, 133, and 154 PEED visits have been performed respectively in 2017, 2018, and 2019, while 29 patients presented in 2020. Therefore, the volume of PEED activity decreased by 79.4% (p < 0.0001). Demographical and clinical characteristics were comparable to those of the pre-COVID period. Despite the absolute reduction in the number of traumas, urgent conditions increased significantly from 30.7 to 50.7% (p = 0.024).

Conclusions

PEED activity decreased consistently after the onset of the pandemic and it was mainly attended by those children whose conditions required prompt assistance, reducing the number of patients diagnosed with milder pathologies. At the end of the emergency, better use of PEED could avoid overcrowding and minimize waste, allowing resource optimization for the management of urgent cases.