bluuebunny/crossref_metadata_2025 huggingface dataset:
ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia
Authors: Karnes Jason H. , Rollin Jerome , Giles Jason B. , Martinez Kiana L. , Steiner Heidi E. , Shaffer Christian M. , Momozawa Yukihide , Inai Chihiro , Bombin Andrei , Shi Mingjian , Mosley Jonathan D. , Stanaway Ian , Selleng Kathleen , Thiele Thomas , Mushiroda Taisei , Pouplard Claire , Heddle Nancy M. , Kubo Michiaki , Phillips Elizabeth J. , Warkentin Theodore E. , Gruel Yves , Greinacher Andreas , Roden Dan M.
Published: April 2022

Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. We performed a genome-wide association study (GWAS) with positive functional assay as the outcome in a large discovery cohort of patients divided into 3 groups: (1) functional assay-positive cases (n = 1269), (2) antibody-positive (functional assay-negative) controls (n = 1131), and (3) antibody-negative controls (n = 1766). Significant associations (α = 5 × 10−8) were investigated in a replication cohort (α = 0.05) of functional assay-confirmed HIT cases (n = 177), antibody-positive (function assay-negative) controls (n = 258), and antibody-negative controls (n = 351). We observed a strong association for positive functional assay with increasing PF4/heparin immunoglobulin-G (IgG) level (odds ratio [OR], 16.53; 95% confidence interval [CI], 13.83-19.74; P = 1.51 × 10−209) and female sex (OR, 1.15; 95% CI, 1.01-1.32; P = .034). The rs8176719 C insertion variant in ABO was significantly associated with positive functional assay status in the discovery cohort (frequency = 0.41; OR, 0.751; 95% CI, 0.682-0.828; P = 7.80 × 10−9) and in the replication cohort (OR, 0.467; 95% CI, 0.228-0.954; P = .0367). The rs8176719 C insertion, which encodes all non-O blood group alleles, had a protective effect, indicating that the rs8176719 C deletion and the O blood group were risk factors for HIT (O blood group OR, 1.42; 95% CI, 1.26-1.61; P = 3.09 × 10−8). Meta-analyses indicated that the ABO association was independent of PF4/heparin IgG levels and was stronger when functional assay-positive cases were compared with antibody-positive (functional assay-negative) controls than with antibody-negative controls. Sequencing and fine-mapping of ABO demonstrated that rs8176719 was the causal single nucleotide polymorphism (SNP). Our results clarify the biology underlying HIT pathogenesis with ramifications for prediction and may have important implications for related conditions, such as vaccine-induced thrombotic thrombocytopenia.
Investigation of improving the pre-training and fine-tuning of BERT model for biomedical relation extraction
Authors: Su Peng , Vijay-Shanker K.
Published: April 2022

Background

Recently, automatically extracting biomedical relations has been a significant subject in biomedical research due to the rapid growth of biomedical literature. Since the adaptation to the biomedical domain, the transformer-based BERT models have produced leading results on many biomedical natural language processing tasks. In this work, we will explore the approaches to improve the BERT model for relation extraction tasks in both the pre-training and fine-tuning stages of its applications. In the pre-training stage, we add another level of BERT adaptation on sub-domain data to bridge the gap between domain knowledge and task-specific knowledge. Also, we propose methods to incorporate the ignored knowledge in the last layer of BERT to improve its fine-tuning.

Results

The experiment results demonstrate that our approaches for pre-training and fine-tuning can improve the BERT model performance. After combining the two proposed techniques, our approach outperforms the original BERT models with averaged F1 score improvement of 2.1% on relation extraction tasks. Moreover, our approach achieves state-of-the-art performance on three relation extraction benchmark datasets.

Conclusions

The extra pre-training step on sub-domain data can help the BERT model generalization on specific tasks, and our proposed fine-tuning mechanism could utilize the knowledge in the last layer of BERT to boost the model performance. Furthermore, the combination of these two approaches further improves the performance of BERT model on the relation extraction tasks.
Novel drug-target interactions via link prediction and network embedding
Authors: Amiri Souri E. , Laddach R. , Karagiannis S. N. , Papageorgiou L. G. , Tsoka S.
Published: April 2022

Background

As many interactions between the chemical and genomic space remain undiscovered, computational methods able to identify potential drug-target interactions (DTIs) are employed to accelerate drug discovery and reduce the required cost. Predicting new DTIs can leverage drug repurposing by identifying new targets for approved drugs. However, developing an accurate computational framework that can efficiently incorporate chemical and genomic spaces remains extremely demanding. A key issue is that most DTI predictions suffer from the lack of experimentally validated negative interactions or limited availability of target 3D structures.

Results

We report DT2Vec, a pipeline for DTI prediction based on graph embedding and gradient boosted tree classification. It maps drug-drug and protein–protein similarity networks to low-dimensional features and the DTI prediction is formulated as binary classification based on a strategy of concatenating the drug and target embedding vectors as input features. DT2Vec was compared with three top-performing graph similarity-based algorithms on a standard benchmark dataset and achieved competitive results. In order to explore credible novel DTIs, the model was applied to data from the ChEMBL repository that contain experimentally validated positive and negative interactions which yield a strong predictive model. Then, the developed model was applied to all possible unknown DTIs to predict new interactions. The applicability of DT2Vec as an effective method for drug repurposing is discussed through case studies and evaluation of some novel DTI predictions is undertaken using molecular docking.

Conclusions

The proposed method was able to integrate and map chemical and genomic space into low-dimensional dense vectors and showed promising results in predicting novel DTIs.
Transcriptome analysis of blastoderms exposed to prolonged egg storage and short periods of incubation during egg storage
Authors: Brady K. , Talbot C. C. , Long J. A. , Welch G. , French N. , Nicholson D. , Bakst M. R.
Published: April 2022

Background

Cool temperature egg storage prior to incubation is a common practice in the broiler industry; however, prolonged egg storage causes increased embryonic mortality and decreased hatchability and growth in surviving chicks. Exposing eggs to short periods of incubation during egg storage (SPIDES) reduces the adverse consequences of prolonged storage. SPIDES increases blastodermal cell viability by reducing apoptosis, though the counteracting mechanisms are unclear. To define the impact of prolonged storage and SPIDES, transcriptome analysis compared gene expression from blastoderms isolated from eggs exposed to the following treatments: control (CR, stored at 17 °C for 4 days), prolonged storage (NSR, stored at 17 °C for 21 days), SPIDES (SR, stored at 17 °C for 21 days with SPIDES), and incubated control (C2, stored at 17 °C for 4 days followed by incubation to HH (Hamburger–Hamilton) stage 2, used as the ideal standard development) (n = 3/group). Data analysis was performed using the CLC Genomics Workbench platform. Functional annotation was performed using DAVID and QIAGEN Ingenuity Pathway Analysis.

Results

In total, 4726 DEGs (differentially expressed genes) were identified across all experimental group comparisons (q < 0.05, FPKM> 20, |fold change| > 1.5). DEGs common across experimental comparisons were involved in cellular homeostasis and cytoskeletal protein binding. The NSR group exhibited activation of ubiquitination, apoptotic, and cell senescence processes. The SR group showed activation of cell viability, division, and metabolic processes. Through comparison analysis, cellular respiration, tRNA charging, cell cycle control, and HMBG1 signaling pathways were significantly impacted by treatment and potential regulatory roles for ribosomal protein L23a (RPL23A) and MYC proto-oncogene, BHLH transcription factor (MYC) were identified.

Conclusions

Prolonged egg storage (NSR) resulted in enriched cell stress and death pathways; while SPIDES (SR) resulted in enriched basic cell and anti-apoptotic pathways. New insights into DNA repair mechanisms, RNA processing, shifts in metabolism, and chromatin dynamics in relation to egg storage treatment were obtained through this study. Although egg storage protocols have been examined through targeted gene expression approaches, this study provided a global view of the extensive molecular networks affected by prolonged storage and SPIDES and helped to identify potential upstream regulators for future experiments to optimize egg storage parameters.
Abundant small RNAs in the reproductive tissues and eggs of the honey bee, Apis mellifera
Authors: Watson Owen T. , Buchmann Gabriele , Young Paul , Lo Kitty , Remnant Emily J. , Yagound Boris , Shambrook Mitch , Hill Andrew F. , Oldroyd Benjamin P. , Ashe Alyson
Published: April 2022

Background

Polyandrous social insects such as the honey bee are prime candidates for parental manipulation of gene expression in offspring. Although there is good evidence for parent-of-origin effects in honey bees the epigenetic mechanisms that underlie these effects remain a mystery. Small RNA molecules such as miRNAs, piRNAs and siRNAs play important roles in transgenerational epigenetic inheritance and in the regulation of gene expression during development.

Results

Here we present the first characterisation of small RNAs present in honey bee reproductive tissues: ovaries, spermatheca, semen, fertilised and unfertilised eggs, and testes. We show that semen contains fewer piRNAs relative to eggs and ovaries, and that piRNAs and miRNAs which map antisense to genes involved in DNA regulation and developmental processes are differentially expressed between tissues. tRNA fragments are highly abundant in semen and have a similar profile to those seen in the semen of other animals. Intriguingly we also find abundant piRNAs that target the sex determination locus, suggesting that piRNAs may play a role in honey bee sex determination.

Conclusions

We conclude that small RNAs may play a fundamental role in honey bee gametogenesis and reproduction and provide a plausible mechanism for parent-of-origin effects on gene expression and reproductive physiology.
Identification and functional validation of HLA-C as a potential gene involved in colorectal cancer in the Korean population
Authors: Lim Eun Bi , Oh Ho-Suk , Kim Kang Chang , Kim Moon-Ho , Kim Young Jin , Kim Bong Jo , Nho Chu Won , Cho Yoon Shin
Published: April 2022

Background

Colorectal cancer (CRC) is the third most common cancer worldwide and is influenced by environmental and genetic factors. Although numerous genetic loci for CRC have been identified, the overall understanding of the genetic factors is yet to be elucidated. We sought to discover new genes involved in CRC applying genetic association analysis and functional study.

Results

We conducted exome array analysis on 194 CRC and 600 control subjects for discovering new candidate CRC genes. Fisher’s exact test detected one exome-wide significant functional locus for CRC on SMCO1 (P < 10–6) and two suggestive functional loci on HLA-C and NUTM1 (10–6 ≤ P < 10–4). To evaluate the biological role of three candidate CRC genes, the differential expression of these genes between CRC and non-cancer colorectal cells was analyzed using qRT-PCR and publicly available gene expression data. Of three genes, HLA-C consistently revealed the significant down-regulation in CRC cells. In addition, we detected a reduction in cell viability in the HLA-C overexpression CRC cell line, implying the functional relevance of HLA-C in CRC. To understand the underlying mechanism exerted by HLA-C in CRC development, we conducted RNA sequencing analyses of HLA-C overexpression CRC cells and non-cancer colorectal cells. Pathway analysis detected that significantly down-regulated genes in HLA-C overexpression CRC cells were highly enriched in cancer-related signaling pathways such as JAK/STAT, ErbB, and Hedgehog signaling pathways.

Conclusions

Exome array CRC case–control analysis followed by functional validation demonstrated that HLA-C likely exerts its influence on CRC development via cancer-related signaling pathways.
The effects of moderate neuromuscular blockade combined with transverse abdominal plane block on surgical space conditions during laparoscopic colorectal surgery: a randomized clinical study
Authors: Ke Fang , Shen Zijin , Wu Cheng , Zhang Lin , Dong Rong
Published: April 2022

Background

Deep neuromuscular blockade may be beneficial on surgical space conditions during laparoscopic surgery. The effects of moderate neuromuscular blockade combined with transverse abdominal plane block (TAPB) on surgical space conditions during laparoscopic surgery have not been described. This work investigated whether the above combination is associated with similar surgical space conditions to those of deep neuromuscular blockade.

Methods

Eighty patients undergoing elective laparoscopic surgery for colorectal cancer were randomly divided into two groups. The intervention group was treated with moderate neuromuscular blockade (train-of-four (TOF) count between 1 and 3) combined with TAPB (M group), while the control group was treated with deep neuromuscular blockade (D group), with a TOF count of 0 and a post-tetanic count (PTC) ≥1. Both groups received the same anesthesia management. The distance between the sacral promontory and the umbilical skin during the operation was compared between the two groups. The surgeon scored the surgical space conditions according to a five-point ordinal scale. Patients’ pain scores were evaluated 8 h after the operation.

Results

The distance from the sacral promontory to the umbilical skin after pneumoperitoneum was similar between the D group and M group (16.03 ± 2.17 cm versus 16.37 ± 2.78 cm; P = 0.544). The 95% confidence intervals of the difference in the distance from the sacral promontory to the umbilical skin between the two groups were − 1.45–0.77 cm. According to the preset non-inferior standard of 1.5 cm, (− 1.45, ∞) completely fell within (− 1.50, ∞), and the non-inferior effect test was qualified. No significant difference was found in the surgical rating score between the two groups. The dosage of rocuronium in the group D was significantly higher than that in the group M (P < 0.01). The M group had significantly lower pain scores than the D group 8 h after the operation (P < 0.05).

Conclusions

Moderate neuromuscular blockade combined with TAPB applied to laparoscopic colorectal cancer surgery can provide surgical space conditions similar to those of deep neuromuscular blockade. In addition, it reduces the use of muscle relaxants, relieves postoperative pain within 4 h after operation, and shorten the extubation time and stay in PACU when neostigmine was used as muscle relaxant antagonist.

Trial registration

chictr.org.cn (ChiCTR2000034621), registered on July 12, 2020.
Cognitive impairment and edentulism among older adults: an observational study using claims data
Authors: Choi Sung Eun , Mo Emily , Palmer Nathan , Fox Kathe , Da Silva John D. , Nagai Shigemi , Barrow Jane R.
Published: April 2022

Background

The scientific link between mastication strength and cognitive function has not yet been strongly corroborated in population studies. Utilizing large-scale claims, we aim to investigate the association between edentulism and cognitive impairment in older American adults.

Methods

Using de-identified claims from a commercial insurer from 2015–2019, we conducted a retrospective cohort study using multilevel regression models to evaluate the association between denture status and clinically diagnosed cognitive impairment. Secondary analysis included symptomatic cognitive impairment in the outcome.

Results

Adjusting for individual-level risk factors, denture status was significantly associated with clinical cognitive impairment with odds ratios of 1.13 (95%CI: 1.02–1.25) and 1.26, (95%CI: 1.09–1.45) for complete dentures on one or both jaws, respectively. Including symptomatic cognitive impairment in the analysis did not substantially change our fundamental findings.

Conclusion

Prevention and treatment of oral diseases should be considered a key component in preserving the overall wellness of older adults.
Analysis of national surveillance of respiratory pathogens for community-acquired pneumonia in children and adolescents
Authors: Roh Eui Jeong , Lee Mi-Hee , Lee Ji Young , Kim Hyo-Bin , Ahn Young Min , Kim Ja Kyoung , Kim Hyoung Young , Jung Sung-Su , Kim Minji , Kang Eun Kyeong , Yang Eun-Ae , Lee Soo Jin , Park Yang , Seo Ju-Hee , Lee Eun , Yang Eun Seok , Park Kang Seo , Shin Meeyong , Chung Hai Lee , Jang Yoon Young , Choi Bong Seok , Jung Jin-A. , Yu Seung Taek , Sung Myongsoon , Kim Jin Tack , Kim Bong-Seong , Hwang Yoon Ha , Sol In-Suk , Yang Hyeon-Jong , Han Man Yong , Yew Hae Young , Cho Hyoung Min , Kim Hye-young , Ahn Yeon-Hwa , Lee Eun Sil , Kim Dong Hyeok , Hwang Kyujam , Jung Sang Oun , Shim Jung Yeon , Chung Eun Hee
Published: April 2022

Background

Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP.

Methods

The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020.

Results

A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports.

Conclusions

This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.
Correlation between intestinal flora disruption and protein–energy wasting in patients with end-stage renal disease
Authors: Hu Jianguang , Zhong Xiaoshi , Liu Yan , Yan Jing , Zhou Daoyuan , Qin Danping , Xiao Xiao , Zheng Yuanyuan , Wen Luona , Tan Rongshao , Liang Pan , Liu Yun
Published: April 2022

Background

Different dialysis treatments may affect the composition and structure of the intestinal flora of dialysis-treated chronic kidney disease (CKD) patients. This study aimed to analyze the correlations between the different flora and the nutritional indexes and further explore the potential metabolic pathways in patients with CKD in end-stage renal disease (ESRD).

Methods

Altogether, 102 patients with ESRD were recruited and categorized into the hemodialysis (HD) group (N = 49) and the peritoneal dialysis (PD) group (N = 53). Their biochemical indexes, anthropometric indicators, and inflammatory markers were determined. The total genomic DNA was extracted for 16S ribosomal DNA sequencing. Furthermore, bioinformatics analysis was employed for functional analysis.

Results

Anthropometric indicators, including handgrip strength, mid-upper arm circumference, mid-upper arm muscle circumference, and body mass index, in the HD and PD groups showed a positive correlation with butyric acid-producing bacteria (RosellaandPhascolarctobacterium) and a negative correlation with conditional pathogens (Escherichiaspp.). Meanwhile, the inflammatory markers, including high-sensitivity C-reactive protein and interleukin-6, were significantly higher in the PD-protein–energy wasting (PEW) group than in the PD-non-protein–energy wasting (NPEW) group; although they showed an increasing trend in the HD-PEW group, no significant difference was noted.Rosellawas considerably scarce in the HD-PEW group than in the HD-NPEW group, whereasEscherichiawas substantially more abundant in the PD-PEW group than in the PD-NPEW group. Compared with the HD group, the essential amino acid synthesis pathway, amino acid metabolism-related enzyme pathways, and aminoacyl-transfer RNA biosynthesis pathways were weakened in the PD group. Most carbohydrate metabolic pathways were weakened, although the tricarboxylic acid cycle was slightly enhanced. Concurrently, the fatty acid metabolism was enhanced, whereas fatty acid synthesis was weakened; the metabolic pathways of B vitamins were also weakened. These potential metabolic pathways of the various compounds released by intestinal flora showed a significant correlation with blood biochemical indexes, anthropometric indicators, and inflammatory markers.

Conclusion

In patients with ESRD, different dialysis treatments affected the abundance of butyric acid-producing bacteria (RosellaandPhascolarctobacterium) and conditional pathogens (Escherichiaspp.). Butyric acid-producing bacteria showed a positive correlation with PEW and showed a negative correlation withEscherichia. Improving the intestinal diversity and increasing the amount of butyric acid-producing bacteria, such asBlautella, Faecococcus, andPhascolarctobacterium, are potential therapeutic approaches to enhance protein–energy consumption in patients with ESRD.
Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice
Authors: Yamamoto Takaya , Tsukita Yoko , Katagiri Yu , Matsushita Haruo , Umezawa Rei , Ishikawa Yojiro , Takahashi Noriyoshi , Suzuki Yu , Takeda Kazuya , Miyauchi Eisaku , Saito Ryota , Katsuta Yoshiyuki , Kadoya Noriyuki , Jingu Keiichi
Published: April 2022

Background

In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC).

Methods

All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan–Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates.

Results

A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01).

Conclusions

In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.
Efficacy and safety of vedolizumab for pediatrics with inflammatory bowel disease: a systematic review
Authors: Fang Shengbo , Song Yanqing , Zhang Chunyan , Wang Libo
Published: April 2022

Background

Vedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD).

Methods

PubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to December 3rd 2021.

Results

Ten studies, comprising 455 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (25/85) at 14 weeks, 32% (17/53) at 22 weeks, and 46% (43/92) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 48% (52/101) at 14 weeks, 53% (24/45) at 22 weeks, and 45% (50/112) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events.

Conclusions

According to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks, and about half of patients achieved remission at 1 year with reasonable safety profile. Long-term benefit profile data and high quality evidence are still needed.
Factors affecting family planning literacy among women of childbearing age in the rural Lake zone, Tanzania
Authors: Kassim Mohamed , Ndumbaro Faraja
Published: April 2022

Background

Low uptake of various recommended modern family planning methods is associated with inadequate family planning literacy among potential beneficiaries of the methods. As such, understanding factors affecting family planning literacy is key to addressing this problem. This study, therefore, explored factors affecting family planning literacy among women of childbearing age in the rural Lake Zone of Tanzania.

Methods

The study utilized an exploratory descriptive qualitative research approach using focus group discussions to collect data. A total of eight focus group discussion sessions were held to solicit information from childbearing age women involved in the study. Thematic analysis was used to analyze the data collected from the study participants.

Results

Several factors were found to negatively affect the family planning literacy of women of childbearing age in the communities under review. These factors were low levels of education, religious affiliation, and low family income. Other factors that were also found to negatively affect women’s family planning literacy include fertility preference, negative perceptions of family planning, preference of unproven family planning methods, limited access to reliable sources of family planning information, household responsibilities, and poor male partner support on family planning matters.

Conclusion

This study has identified a multitude of factors affecting the family planning literacy of women of childbearing age. These factors can limit the women’s capacity to make informed decisions on the utilization of modern family planning methods. Thus, addressing these factors is pivotal in increasing the women’s overall uptake of various recommended family planning methods and enhancing their reproductive health outcomes.
Predictors of mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis
Authors: Owusuaa Catherine , Dijkland Simone A. , Nieboer Daan , van der Rijt Carin C. D. , van der Heide Agnes
Published: April 2022

Background

Better insight in patients’ prognosis can help physicians to timely initiate advance care planning (ACP) discussions with patients with chronic obstructive pulmonary disease (COPD). We aimed to identify predictors of mortality.

Methods

We systematically searched databases Embase, PubMed, MEDLINE, Web of Science, and Cochrane Central in April 2020. Papers reporting on predictors or prognostic models for mortality at 3 months and up to 24 months were assessed on risk-of-bias. We performed a meta-analysis with a fixed or random-effects model, and evaluated the discriminative ability of multivariable prognostic models.

Results

We included 42 studies (49–418,251 patients); 18 studies were included in the meta-analysis. Significant predictors of mortality within 3–24 months in the random-effects model were: previous hospitalization for acute exacerbation (hazard ratio [HR] 1.97; 95% confidence interval [CI] 1.32–2.95), hospital readmission within 30 days (HR 5.01; 95% CI 2.16–11.63), cardiovascular comorbidity (HR 1.89; 95% CI 1.25–2.87), age (HR 1.48; 95% CI 1.38–1.59), male sex (HR 1.68; 95% CI 1.38–1.59), and long-term oxygen therapy (HR 1.74; 95% CI 1.10–2.73). Nineteen previously developed multicomponent prognostic models, as examined in 11 studies, mostly had moderate discriminate ability.

Conclusion

Identified predictors of mortality may aid physicians in selecting COPD patients who may benefit from ACP. However, better discriminative ability of prognostic models or development of a new prognostic model is needed for further large-scale implementation.

Registration: PROSPERO (CRD42016038494), https://www.crd.york.ac.uk/prospero/.
Effectiveness of a group intervention using pain neuroscience education and exercise in women with fibromyalgia: a pragmatic controlled study in primary care
Authors: Areso-Bóveda Paula B. , Mambrillas-Varela Julia , García-Gómez Bárbara , Moscosio-Cuevas José Ignacio , González-Lama Jesús , Arnaiz-Rodríguez Eva , del Barco María Begoña Arroyo , Teodoro-Blanco Pilar San
Published: April 2022

Background

Very positive effects have been described in the application of pain neuroscience education (PNE) to chronic pain and migraine. However, there are few data on the applicability of this therapeutic approach in actual clinical practice in a primary care (PC) setting. The aim of this study was to explore the efficacy in fibromyalgia (FM) of an intervention based on PNE and exercise compared to treatment as usual (TAU).

Methods

Pragmatic nonrandomised controlled trial set in 5 healthcare centres and one physiotherapy centre in PC. Fifty-three women with FM (2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia) were studied, 35 in the intervention group (IG) and 18 in the control group (CG). The women in the IG were interviewed individually and then received 6 weekly sessions plus one review session (1 month later): those in the CG received their TAU. The subject assignation to the CG or the IG was determined according to their availability to attend the sessions. They all filled in several questionnaires (prior to and 1 year after the intervention) to evaluate the impact of FM in their daily lives, catastrophism, anxiety and depression, severity and impact of pain in daily personal performance and functional capacity.

Results

The reductions (improvements) in the scores of all tests (baseline-final) were greater in the IG (p < 0.05) when adjusted for age and baseline values, with moderate or high effect size. After 1 year, 20% (CI − 1 to 42%) more women in the IG, compared to the CG, had a FIQ score < 39 (mild functional impairment). 17/38 (49%) women in the IG no longer met FM criteria at the end of follow-up.

Conclusions

An intervention based on PNE and exercise in patients with FM is feasible and seems effective in PC.

Trial registration

The study was retrospectively registered at ClinicalTrials.gov (Trial Registration NCT04539171), on 04/09/2020.
Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients
Authors: Baek Han-sang , Jeong Chaiho , Shin Kabsoo , Lee Jaejun , Suh Heysun , Lim Dong-Jun , Kang Moo Il , Ha Jeonghoon
Published: April 2022

Background

Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival.

Methods

Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary’s Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction.

Results

Among the 191 patients, 64 (33.5%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (25 months vs. 18 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.480 (p = 0.006). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for mortality of 0.324 (p = 0.002). Patients with thyrotoxicosis showed a worse hazard ratio for mortality than those without thyroid irAE, although the difference was not statistically significant.

Conclusions

It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.
Expression profile of circRNA in peripheral blood mononuclear cells of patients with rheumatoid arthritis
Authors: Lu Huangxin , Yang Yifan , Kuang Dong , Liu Ping , Yang Junping
Published: April 2022

Background

Circular RNAs (circRNAs) is a newly discovered non-coding RNA that can be used as biomarkers in clinical blood samples. This study aims to screen differentially expressed circular RNAs in PBMCs of patients with rheumatoid arthritis (RA) to determine new biomarkers for the diagnosis of RA.

Methods

The differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) of 4 RA patients and 4 healthy participants were screened and analyzed by gene microarray technology. We then validated some of the differentially expressed circRNAs in PBMCs of 20 RA patients, 10 systemic lupus erythematosus (SLE) patients and 20 healthy participants using reverse transcription-quantitative polymerase chain reaction amplification (RT-qPCR). Spearman correlation test was performed to analyze the correlation between differentially expressed circRNAs and clinical variables in RA patients. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic value of circRNAs.

Results

Differential analysis obtained 149 circRNAs with significant up-regulated expression and 250 circRNAs with significant down-regulated expression, which predicted the miRNA targets and binding sites. Compared with SLE and health control group, hsa_circ_101328 was found to be a common gene with differential expression of RA. Besides, correlation analysis revealed significant correlation between hsa_circ_101328 and positive CRP. ROC curve analysis showed that hsa_circ_101328 has the potential of RA diagnosis.

Conclusion

We identified some dysregulated circRNAs in PBMCs from RA patients, and hsa_circ_101328 may be a novel and effective biomarker for early diagnosis of RA.
Efficacy, dose–response, and aerosol delivery of dry powder synthetic lung surfactant treatment in surfactant-deficient rabbits and premature lambs
Authors: Walther Frans J. , Waring Alan J. , Otieno Monicah , DiBlasi Robert M.
Published: April 2022

Background

Dry powder (DP) synthetic lung surfactant may be an effective means of noninvasive delivery of surfactant therapy to premature infants supported with nasal continuous positive airway pressure (nCPAP) in low-resource settings.

Methods

Four experimental DP surfactant formulations consisting of 70% of phospholipids (DPPC:POPG 7:3), 3% Super Mini-B (SMB) or its sulfur-free derivate B-YL as SP-B peptide mimic, 25% of lactose or trehalose as excipient, and 2% of NaCl were formulated using spray drying. In vitro surface activity was confirmed with captive bubble surfactometry. Surfactant particle size was determined with a cascade impactor and inhaled dose was quantified using a spontaneously breathing premature lamb lung model supported with CPAP. In vivo surfactant efficacy was demonstrated in three studies. First, oxygenation and lung compliance were monitored after intratracheal instillation of resuspended DP surfactant in intubated, ventilated, lavaged, surfactant-deficient juvenile rabbits. In dose–response studies, ventilated, lavaged, surfactant-deficient rabbits received 30, 60, 120 or 240 mg/kg of DP B-YL:Lactose or B-YL:Trehalose surfactant by aerosol delivery with a low flow aerosol chamber via their endotracheal tube. Noninvasive aerosolization of DP B-YL:Trehalose surfactant via nasal prongs was tested in spontaneous breathing premature lambs supported with nCPAP. Intratracheal administration of 200 mg/kg of Curosurf®, a liquid porcine surfactant, was used as a positive control.

Results

Mass median aerosol diameter was 3.6 μm with a geometric standard deviation of 1.8. All four experimental surfactants demonstrated high surface efficacy of intratracheal instillation of a bolus of ~ 100 mg/kg of surfactant with improvement of oxygenation and lung compliance. In the dose–response studies, rabbits received incremental doses of DP B-YL:Lactose or B-YL:Trehalose surfactant intratracheally and showed an optimal response in oxygenation and lung function at a dose of 120–240 mg/kg. Aerosol delivery via nasal prongs of 1 or 2 doses of ~ 100 mg/kg of B-YL:Trehalose surfactant to premature lambs supported with nCPAP resulted in stabilization of spontaneous breathing and oxygenation and lung volumes comparable to the positive control.

Conclusion

These studies confirm the clinical potential of DP synthetic lung surfactant with B-YL peptide as a SP-B mimic to alleviate surfactant deficiency when delivered as a liquid bolus or as an aerosol.
Metformin and high-sensitivity cardiac troponin I and T trajectories in type 2 diabetes patients: a post-hoc analysis of a randomized controlled trial
Authors: Stultiens Johanna M. G. , Top Wiebe M. C. , Kimenai Dorien M. , Lehert Philippe , Bekers Otto , Stehouwer Coen D. A. , Kooy Adriaan , Meex Steven J. R.
Published: April 2022

Background

Metformin has favorable effects on cardiovascular outcomes in both newly onset and advanced type 2 diabetes, as previously reported findings from the UK Prospective Diabetes Study and the HOME trial have demonstrated. Patients with type 2 diabetes present with chronically elevated circulating cardiac troponin levels, an established predictor of cardiovascular endpoints and prognostic marker of subclinical myocardial injury. It is unknown whether metformin affects cardiac troponin levels. The study aimed to evaluate cardiac troponin I and T trajectories in patients with diabetes treated either with metformin or placebo.

Methods

This study is a post-hoc analysis of a randomized controlled trial (HOME trial) that included 390 patients with advanced type 2 diabetes randomized to 850 mg metformin or placebo up to three times daily concomitant to continued insulin treatment. Cardiac troponin I and T concentrations were measured at baseline and after 4, 17, 30, 43 and 52 months. We evaluated cardiac troponin trajectories by linear mixed-effects modeling, correcting for age, sex, smoking status and history of cardiovascular disease.

Results

This study enrolled 390 subjects, of which 196 received metformin and 194 received placebo. In the treatment and placebo groups, mean age was 64 and 59 years; with 50% and 58% of subjects of the female sex, respectively. Despite the previously reported reduction of macrovascular disease risk in this cohort by metformin, linear mixed-effects regression modelling did not reveal evidence for an effect on cardiac troponin I and cardiac troponin T levels [− 8.4% (− 18.6, 3.2), p = 0.150, and − 4.6% (− 12, 3.2), p = 0.242, respectively]. A statistically significant time-treatment interaction was found for troponin T [− 1.6% (− 2.9, − 0.2), p = 0.021] but not troponin I concentrations [− 1.5% (− 4.2, 1.2), p = 0.263].

Conclusions

In this post-hoc analysis of a 4.3-year randomized controlled trial, metformin did not exert a clinically relevant effect on cardiac troponin I and cardiac troponin T levels when compared to placebo. Cardioprotective effects of the drug observed in clinical studies are not reflected by a reduction in these biomarkers of subclinical myocardial injury.

Trial registration ClinicalTrials.gov identifier NCT00375388.
Patients with low back pain presenting for chiropractic care who want diagnostic imaging are more likely to receive referral for imaging: a cross-sectional study
Authors: Jenkins Hazel J. , Kongsted Alice , French Simon D. , Jensen Tue Secher , Doktor Klaus , Hartvigsen Jan , Hancock Mark
Published: April 2022

Background

It is unclear if the use of imaging for low back pain (LBP) is impacted by patient beliefs. This study aimed to: (1) describe beliefs about the importance of imaging and whether patients wanted imaging when presenting for chiropractic care for LBP; (2) describe associations between baseline patient characteristics and imaging beliefs and whether patients wanted imaging; and (3) determine whether patients who believed imaging to be important in the management of LBP, or who wanted to receive imaging, were more likely to receive an imaging referral.

Methods

Cross-sectional observational data was collected between November 2016 to December 2019 from 10 primary care chiropractic clinics in Denmark. Consecutive patients aged 18 or older and presenting with a new episode of LBP were included (N = 2818). Beliefs about the importance of imaging (two questions) and whether imaging was wanted (one question) were collected at the initial visit, together with baseline participant characteristics and whether an imaging referral was provided. Associations between imaging beliefs/desire to receive imaging and participant characteristics were explored using multivariable logistic regression analysis. The relationships between imaging beliefs and desire to receive imaging with subsequent imaging referral were assessed using multivariable logistic regression analysis adjusted for pre-selected confounder variables.

Results

Approximately one third of participants believed imaging to be important for the management of LBP (29.5% (95%CI 27.8, 31.3) or 41.5% (95%CI 39.6, 43.3) depending on the two imaging beliefs questions). Approximately one quarter (26.1%, 95%CI 24.5, 27.7) of participants wanted to receive an imaging referral. Participants were more likely to believe in the importance of imaging or want an imaging referral if they had a longer duration of LBP, history of previous imaging for LBP, or a lower completed education level. Participants who wanted imaging at the initial consult were more likely to receive an imaging referral (Odds ratio; 95%CI 1.6; 1.2, 2.1).

Conclusions

Approximately one third of patients presenting for chiropractic care in Denmark believed imaging to be important in the management of LBP. One quarter wanted imaging at the initial consult. Patients’ desire for imaging appeared to impact the use of diagnostic imaging.
Kinematic alignment versus mechanical alignment in primary total knee arthroplasty: an updated meta-analysis of randomized controlled trials
Authors: Liu Binfeng , Feng Chengyao , Tu Chao
Published: April 2022

Background

The purpose of this study was to perform an updated meta-analysis to compare the outcomes of kinematic alignment (KA) and mechanical alignment (MA) in patients undergoing total knee arthroplasty.

Methods

PubMed, EMBASE, Web of Science, Google Scholar, and the Cochrane Library were systematically searched. Eligible randomized controlled trials regarding the clinical outcomes of patients undergoing total knee arthroplasty with KA and MA were included for the analysis.

Results

A total of 1112 participants were included in this study, including 559 participants with KA and 553 patients with MA. This study revealed that the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Society Score (knee and combined), and knee flexion range were better in the patients with kinematic alignment than in the mechanical alignment. In terms of radiological results, the femoral knee angle, mechanical medial proximal tibial angle, and joint line orientation angle were significantly different between the two techniques. Perioperatively, the walk distance before discharge was longer in the KA group than in the MA group. In contrast, other functional outcomes, radiological results, perioperative outcomes, and postoperative complication rates were similar in both the kinematic and mechanical alignment groups.

Conclusions

The KA technique achieved better functional outcomes than the mechanical technique in terms of KSS (knee and combined), WOMAC scores, and knee flexion range.

PROSPERO trial registration number CRD42021264519. Date registration: July 28, 2021.