bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological and prognostic study of IgA-dominant postinfectious glomerulonephritis
Authors: Huang Ziyuan , Chen Bo , Zhou Ying , Liang Yan , Qiu Wenxian , Lv Yinqiu , Ding Xiaokai , Zhang Ji , Chen Chaosheng
Published: July 2021

Background

The clinicopathological and prognostic features of IgA-dominant postinfectious glomerulonephritis and its difference from the primary IgA nephropathy remains to be investigated.

Methods

The clinical and pathological data of 6542 patients who underwent renal biopsy from 2009 to 2020 in our hospital were reviewed and 50 patients who met the selection criteria of IgA-dominant postinfectious glomerulonephritis were enrolled to conduct a retrospective and observational single-center study. The selection criteria were: meet the characteristics of IgA dominance or codominance in immunofluorescence, and conform to 3 of the following 5 criteria: 1.Clinical or laboratory evidence show that there is infection before or at the onset of glomerulonephritis; 2.The level of serum complement decreased; 3.Renal pathology is consistent with endocapillary proliferative glomerulonephritis; 4. Glomerular immunofluorescence staining showed complement C3 dominance or codominance; 5. Hump-like subepithelial immune complex deposition was observed under electron microscopy. According to age, sex, renal function (estimated glomerular filtration rate, eGFR) and follow-up time, the control group was constructed with 1:3 matched cases of primary IgA nephropathy. The clinicopathological and prognostic differences between the two groups were analyzed.

Results

The most common histological pattern of IgA-dominant postinfectious glomerulonephritis was acute endocapillary proliferative glomerulonephritis and exudative glomerulonephritis. Immunofluorescence showed mainly IgA deposition or IgA deposition only, mainly deposited in the mesangial area (deposition rate 100 %), with typical C3 high-intensity staining (intensity++~+++), mainly deposited in the mesangial area (deposition rate 92.0 %). The fluorescence intensity of kappa is usually not weaker than lambda. The probability of the appearance of typical hump-like electron deposition under electron microscopy is low. Compared to primary IgA nephropathy, patients with IgA-dominant postinfectious glomerulonephritis had higher proportion of crescents (p = 0. 005) and endocapillary hypercellularity (p < 0.001) in pathological manifestations. Using serum creatinine level doubled of the baseline or reached end-stage renal disease as the endpoint, the prognosis of IgA-dominant postinfectious glomerulonephritis patients was worse than that of primary IgA nephropathy patients (p = 0.013).

Conclusions

The clinicopathological features of patients with IgA-dominant postinfectious glomerulonephritis was different from that of primary IgA nephropathy, and the prognosis was worse.
The association between protease inhibitors and anal cancer outcomes in veterans living with HIV treated with definitive chemoradiation: a retrospective study
Authors: Yoder Alison K. , Lakomy David S. , Dong Yongquan , Raychaudhury Suchismita , Royse Kathryn , Hartman Christine , Richardson Peter , White Donna L. , Kramer Jennifer R. , Lin Lilie L. , Chiao Elizabeth
Published: July 2021

Background

The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer.

Methods

Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression.

Results

A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratiop-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p < 0.01).

Conclusion

The use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.
Bronchopulmonary dysplasia in extremely premature infant with congenital lobar emphysema: a case report
Authors: Lin Bingchun , Li Huitao , Yang Chuanzhong
Published: July 2021

Background

Congenital lobar emphysema (CLE) is a congenital pulmonary cystic disease, characterized by overinflation of the pulmonary lobe and compression of the surrounding areas. Most patients with symptoms need an urgent surgical intervention. Caution and alertness for CLE is required in cases of local emphysema on chest X-ray images of extremely premature infants with bronchopulmonary dysplasia (BPD).

Case presentation

Here, we report a case of premature infant with 27 + 4 weeks of gestational age who suddenly presented with severe respiratory distress at 60 days after birth. Chest X-ray and computed tomography (CT) indicated emphysema in the middle lobe of the right lung. The diagnosis of CLE was confirmed by histopathological examinations.

Conclusions

Although extremely premature infants have high-risk factors of bronchopulmonary dysplasia due to their small gestational age, alertness for CLE is necessary if local emphysema is present. Timely pulmonary CT scan and surgical interventions should be performed to avoid the delay of the diagnosis and treatment.
Descriptive epidemiology of measles cases in Bauchi State, 2013–2018
Authors: Ori Polycarp Uchechukwu , Adebowale Ayo , Umeokonkwo Chukwuma David , Osigwe Ugochukwu , Balogun Muhammad Shakir
Published: July 2021

Background

Measles accounts for high morbidity and mortality in children, especially in developing countries. In 2017, about 11,190 measles cases were recorded in Nigeria, including Bauchi State. The aim of this study was to describe the trend and burden of measles in Bauchi State, Nigeria.

Method

We analyzed secondary data of measles cases extracted from the Measles Surveillance data system in Bauchi State from January 2013 to June 2018. The variables extracted included age, sex, doses of vaccination, case location and outcome. Data were analyzed using descriptive statistics, logistic regression, and multiplicative time series model (α = 0.05).

Results

A total of 4935 suspected measles cases with an average annual incidence rate of 15.3 per 100,000 population and 57 deaths (Case Fatality Rate, CFR: 1.15%) were reported. Among the reported cases, 294 (6%;) were laboratory-confirmed, while clinically compatible and epi-linked cases were 402 (8%) and 3879 (70%), respectively. Of the 4935 measles cases, 2576 (52%) were males, 440 (9%) were under 1 year of age, and 3289 (67%) were between 1 and 4 years. The average annual incidence rate among the 1–4 year age-group was 70.3 per 100,000 population. The incidence rate was lowest in 2018 with 2.1 per 100,000 and highest in 2015 with 26.2 per 100,000 population. The measles cases variation index per quarter was highest in quarter 1 (198.86), followed by quarter 2 (62.21) and least in quarter 4 (10.37) of every year. Only 889 (18%) of the measles cases received at least one dose of measles vaccine, 2701 (54.7%) had no history of measles vaccination while 1346 (27.3%) had unknown vaccination status. The fatality of measles in Bauchi State were significantly associated with being under 5 years (AOR = 5.58; 95%CI: 2.19–14.22) and not having at least a dose of MCV (OR = 7.14; 95%CI: 3.70–14.29).

Conclusion

Measles burden remains high in Bauchi State despite a decrease in its incidence over the study years. Most of the cases occurred in the first quarter of every year. Improved routine measles surveillance for prompt case management could reduce the burden of the disease in Bauchi State.
Income in relation to obesity measures in an East German adult population: findings from the LIFE-Adult-Study
Authors: Enzenbach Cornelia , Kowall Bernd
Published: July 2021

Background

Obesity has been postulated to be a consequence of economic disadvantage. However, epidemiological studies failed to demonstrate a consistent link between income and body fat indicators. We examined income as a possible cause of obesity in an East German general population, focusing on appropriate representation of study variables, as well as on confounding and modification of the income-obesity association.

Methods

We used data of 9599 participants in the baseline examination of the LIFE-Adult-Study, conducted in the city of Leipzig from 2011 to 2014. Body mass index (BMI) and waist circumference (WC) as obesity measures were based on standardised measurements, net equivalised income (NEI) on self-reports. We estimated adjusted means of BMI and WC within NEI categories representing the range from risk of poverty to affluence. We stratified the analyses by gender, age, and education.

Results

A substantial part of the age-adjusted associations of income with obesity measures was attributable to other SES indicators. Adjusted for these variables, NEI was comparably associated with BMI and WC. Among women, BMI and WC decreased across NEI categories. The inverse associations tended to be stronger at non-working age (≥ 65 years) than at working age (< 65 years). Conversely, among working-age men, BMI and WC increased with increasing NEI. Among older men, risk of poverty was related to higher values of the obesity measures. The aforementioned associations were predominantly stronger in highly educated participants compared to those with medium/low education. The differences in mean BMI and WC between persons at risk of poverty and higher income groups were rather small, ranging from 1 to 2 kg/m2 for BMI and 2 to 4 cm for WC.

Conclusions

Our investigation indicates an association between income and body fatness in an East German adult population that depends on the sociodemographic context of the people. However, it does not suggest that income disparities are a major driver of body fat accumulation in this population. Differential selection of study participants, error in the measurement of long-term income, and possibly reverse causality may have affected our conclusions.
Patterns of use and perceived value of social media for population health among population health stakeholders: a cross-sectional web-based survey
Authors: Yoon Sungwon , Wee Sharon , Lee Vivian S. Y. , Lin Jing , Thumboo Julian
Published: July 2021

Background

Although existing studies have described patterns of social media use in healthcare, most are focused on health professionals in one discipline. Population health requires a multi-disciplinary approach to ensure diversity and to include diverse stakeholders. To date, what is known about using social media in population health is focused on its potential as a communication tool. This study aims to investigate patterns of use and perceived value of social media usage among stakeholders in population health practice, policy, or research.

Methods

We conducted a web-based survey of delegates attending the Singapore Population Health Conversations and Workshop. We designed a 24-item questionnaire to assess 1) social media use in terms of type of platform and frequency of use; 2) perceptions of social media relevance and impact on population health; and 3) top three areas in population health that would benefit from social media. We used descriptive and logistic regression analyses to assess the relationships between variables.

Results

Of the 308 survey respondents, 97.7% reported that they use social media in some form. Messaging (96.8%) was the most dominant activity when using social media. Challenges in implementing social media for population health were time investment by health care professionals (56.2%) and patient adoption (52.9%). The top three population health areas that would benefit most from using social media were the promotion of healthy behaviors (60.7%), community engagement (47.7%), and preventive care (40.6%). Older respondents (> = 40 years) were less likely to view social media as useful for the promotion of healthy behaviors (OR = 0.34; 95% CI: 0.19–0.60). Non-social/healthcare professionals were more likely to consider social media to be useful for community engagement (OR = 1.74; 95% CI: 1.10–2.76). For preventive care, older respondents (OR = 0.51; 95% CI: 0.32–0.82) and non-social/healthcare professionals were less likely to view social media as useful (OR = 0.61; 95% CI: 0.38–0.97).

Conclusions

Our findings suggest that it may be important to select the specific care areas that would benefit most from using social media. The time investment needed by population health professionals should be fully addressed in planning to maximize the application and potential value of social media.
Frequency of repositioning for preventing pressure ulcers in patients hospitalized in ICU: protocol of a cluster randomized controlled trial
Authors: Cortés Olga L. , Herrera-Galindo Mauricio , Villar Juan Carlos , Rojas Yudi A. , del Pilar Paipa María , Salazar Luzdary
Published: July 2021

Background

Despite being considered preventable, ulcers due to pressure affect between 30 and 50% of patients at high and very high risk and susceptibility, especially those hospitalized under critical care. Despite a lack of evidence over the efficacy in prevention against ulcers due to pressure, hourly repositioning in critical care as an intervention is used with more or less frequency to alleviate pressure on patients’ tissues. This brings up the objective of our study, which is to evaluate the efficacy in prevention of ulcers due to pressure acquired during hospitalization, specifically regarding two frequency levels of repositioning or manual posture switching in adults hospitalized in different intensive care units in different Colombian hospitals.

Methods

A nurse-applied cluster randomized controlled trial of parallel groups (two branches), in which 22 eligible ICUs (each consisting of 150 patients), will be randomized to a high-frequency level repositioning intervention or to a conventional care (control group). Patients will be followed until their exit from each cluster. The primary result of this study is originated by regarding pressure ulcers using clusters (number of first ulcers per patient, at the early stage of progression, first one acquired after admission for 1000 days). The secondary results include evaluating the risk index on the patients’ level (Hazard ratio, 95% IC) and a description of repositioning complications. Two interim analyses will be performed through the course of this study. A statistical difference between the groups < 0.05 in the main outcome, the progression of ulcers due to pressure (best or worst outcome in the experimental group), will determine whether the study should be put to a halt/determine the termination of the study.

Conclusion

This study is innovative in its use of clusters to advance knowledge of the impact of repositioning as a prevention strategy against the appearance of ulcers caused by pressure in critical care patients. The resulting recommendations of this study can be used for future clinical practice guidelines in prevention and safety for patients at risk.

Trial registration

PENFUP phase-2 was Registered in Clinicaltrials.gov (NCT04604665) in October 2020.
Evaluating the relationships among stress, resilience and psychological well-being among young adults: a structural equation modelling approach
Authors: Klainin-Yobas Piyanee , Vongsirimas Nopporn , Ramirez Debbie Q. , Sarmiento Jenneth , Fernandez Zenaida
Published: July 2021

Background

Resilience reflects individuals’ ability to bounce back quickly in the face of stressful situations. Resilience is positively correlated with psychological well-being (PWB) and negatively related to poor mental health. However, there is limited longitudinal research to confirm the causal relationships between resilience and PWB. This study aimed to examine the relationships among stress, resilience, and PWB among youths in the Philippines across two samples. A descriptive comparative study was conducted and two repeated cross-sectional samples were recruited. Eligible participants were undergraduate students from a university in the Philippines regardless of sociological backgrounds. Data were collected via anonymous online questionnaires; and analyzed by using descriptive statistics and structural equation modelling (SEM).

Results

A total of 630 were recruited (Sample 1 = 221 and Sample 2 = 409). Most of whom were female, Filipino, Christian and students from Nursing School. Results from SEM indicated that the hypothesized two-group models had an adequate fit with sample data. Furthermore, perceived control and resilience were significant predictors of the autonomy & growth factor of PWB. Perceived stress and resilience significantly predicted the negative triad factor of PWB. These findings were comparable across the two samples providing strong evidence to support causal relationships among the study variables.

Conclusion

There is a need to offer stress management interventions and resilience-based programs to enhance PWB. Additional research should be conducted to test the efficacy of the interventions.
Comparison of coenzyme Q10 or fish oil for prevention of intermittent hypoxia-induced oxidative injury in neonatal rat lungs
Authors: D’Agrosa Christina , Cai Charles L. , Siddiqui Faisal , Deslouches Karen , Wadowski Stephen , Aranda Jacob V. , Beharry Kay D.
Published: July 2021

Background

Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats.

Methods

Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O2 with brief hypoxia (12% O2); or (2) room air (RA) with brief hypoxia (12% O2), until P14 during which they were supplemented with daily oral CoQ10, fish oil, or olive oil from P0 to P14. Pups were studied at P14 or placed in RA until P21 with no further treatment. Lungs were assessed for histopathology and morphometry; biomarkers of oxidative stress and lipid peroxidation; and antioxidants.

Results

Of the two neonatal IH paradigms 21%/12% O2 IH resulted in the most severe outcomes, evidenced by histopathology and morphometry. CoQ10 was effective for preserving lung architecture and reduction of IH-induced oxidative stress biomarkers. In contrast, fish oil resulted in significant adverse outcomes including oversimplified alveoli, hemorrhage, reduced secondary crest formation and thickened septae. This was associated with elevated oxidants and antioxidants activities.

Conclusions

Data suggest that higher FiO2 may be needed between IH episodes to curtail the damaging effects of IH, and to provide the lungs with necessary respite. The negative outcomes with fish oil supplementation suggest oxidative stress-induced lipid peroxidation.
Downregulation of Tim-1 inhibits the proliferation, migration and invasion of glioblastoma cells via the miR-133a/TGFBR1 axis and the restriction of Wnt/β-catenin pathway
Authors: Wei Li , Peng Ya , Shao Naiyuan , Zhou Peng
Published: July 2021

Background

Glioblastoma remains one of the most lethal brain cancers. T-cell immunoglobulin and mucin domain 1 (Tim-1) is associated with various immune diseases. The molecular mechanism of Tim-1 in regulating glioblastoma cell proliferation, invasion, and migration is still unknown. Moreover, it has shown that miR-133a plays an important role in glioblastoma. However, little is known about the interaction between Tim-1 and miR-133a in glioblastoma.

Methods

Tim-1 expression in glioblastoma and normal brain tissues was detected by qPCR, Western Blot and IHC. After Tim-1 knockdown in U251 and U87 cells, genes showing significantly differential expression, along with the significant differential miRNAs were analyzed using RNA-seq analysis. The binding sites were verified using dual-luciferase reporter gene assay. U251 and U87 cells were allocated into the small harpin-negative control (sh-NC), sh-Tim-1, sh-Tim-1 + inhibitor NC, and sh-Tim-1 + miR-133a inhibitor group. Cell proliferation, migration, and invasion were determined by CCK-8, flow cytometry, wound-healing and Transwell assays, respectively. Next, U251 and U87 cells were allocated into the mimic NC, miR-133a mimic, miR-133a mimic + pcDNA3.1, and miR-133a mimic + pcDNA3.1-TGFBR1 groups, followed by the detection of cell proliferation, migration, and invasion. Western blot was used to identify the expression of vital kinases in the Wnt/β-catenin pathway.

Results

Tim-1 was highly expressed in glioblastoma tissues compared with that in normal brain tissues. RNA-seq analysis showed that Tim-1 knockdown could lead to the downregulation of TGFBR1 and the upregulation of miR-133a. The binding sites between TGFBR1 and miR-133a were confirmed. Tim-1 knockdown impaired the invasion, migration, proliferation of U251 and U87 cells, which could be reversed by miR-133a downregulation. miR-133a upregulation inhibited the proliferation, invasion, and migration of U251 and U87 cells, which could be reversed by TGFBR1 upregulation. Tim-1 knockdown and miR-133a upregulation could inhibit the activation of the Wnt/β-catenin pathway, while the elevation of TGFBR1 showed opposite effects.

Conclusion

Tim-1 knockdown inhibited glioblastoma cell proliferation, invasion, and migration through the miR-133a/TGFBR1 axis and restrained the activation of the Wnt/β-catenin pathway.
Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma
Authors: Mao Yinling , Lv Jiachen , Jiang Li , Wang Yihui
Published: July 2021

Background

Long non-coding RNAs (lncRNAs), acting as competing endogenous RNA (ceRNA) have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD).

Methods

However, their potential implications for recurrence free survival prognosis and functional roles remains largely unclear in COAD. In this study, we downloaded the TCGA dataset (training dataset) and GSE39582 (validation dataset) of COAD patients with prognostic information.

Results

A total of 411 differentially expressed genes (DElncRNAs: 12 downregulated and 43 upregulated), 18 DE miRNAs (9 downregulated and 9 upregulated) and 338 DEmRNAs (113 downregulated and 225 upregulated) were identified in recurrence samples compared with non-recurrence samples with the thresholds of FDR < 0.05 and |log2FC|> 0.263. Based on six signature lncRNAs (LINC00899, LINC01503, PRKAG2-AS1, RAD21-AS1, SRRM2-AS1 and USP30-AS1), the risk score (RS) system was constructed. Two prognostic clinical features, including pathologic stage and RS model status were screened for building the nomogram survival model. Moreover, a recurrent-specific ceRNA network was successfully constructed with 2 signature lncRNAs, 4 miRNAs and 113 mRNAs. Furthermore, we further manifested that SRRM2-AS1 predicted a poor prognosis in COAD patients. Furthermore, knockdown of SRRM2-AS1 significantly suppressed cell proliferation, migration, invasion and EMT markers in HT-29 and SW1116 cells.

Conclusion

These identified novel lncRNA signature and ceRNA network associated with recurrence prognosis might provide promising therapeutic targets for COAD patients.
The vaccine coverage and vaccine immunity status and risk factors of non-protective levels of antibodies against vaccines in children with juvenile idiopathic arthritis: cross-sectional Russian tertiary Centre study
Authors: Kostik Mikhail M. , Lubimova Natalia A. , Fridman Irina V. , Goleva Olga V. , Kharit Susanna M.
Published: July 2021

Background

Immunosuppressive drugs, incomplete vaccine coverage, immune system dysregulation might be factors of a low level of anti-vaccine antibodies in JIA patients. The study aimed to evaluate vaccine coverage, post-vaccine immunity, and risk factors of non-protective levels of antibodies against measles, mumps, rubella, hepatitis B, and diphtheria in JIA patients.

Methods

A cross-sectional study included 170 children diagnosed with JIA aged 2 to 17 years who received routine vaccinations against measles, rubella, mumps (MMR), diphtheria, and hepatitis B national vaccine schedule. In all patients, the levels of post-vaccination antibodies (IgG) for measles, rubella, mumps, hepatitis B, and diphtheria were measured with ELISA.

Results

Protective level of antibodies were 50% against hepatitis B, 52% - diphtheria, 58% - measles, 80% - mumps, 98% rubella. MMR’s best coverage had patients with enthesitis-related arthritis-85%, compared to oligoarthritis-70%, polyarthritis-69%, systemic arthritis-63%. Diphtheria coverage was 50, 51, 46, 63%, respectively. Incomplete MMR vaccination had 39% patients, treated with biologics, 22% with methotrexate and 14% with NSAID (p = 0.025), and 61, 46, 36% for diphtheria (p = 0.021). Incomplete vaccination was a risk factor of non-protective level of antibodies against measles (HR = 2.03 [95%CI: 1.02; 4.0], p = 0.042), mumps (HR = 6.25 [95%CI: 2.13; 17.9], p = 0.0008) and diphtheria (HR = 2.39 [95%CI: 1.18; 4.85], p = 0.016) vaccines, as well as JIA category, biologics, corticosteroids and long-term methotrexate treatment for distinct vaccines. One-third part of JIA patients continued vaccination against MMR and diphtheria without serious adverse events and JIA flare. There were no differences between patients who continued MMR vaccination or denied in the means of JIA category and treatment options. Patients, continued diphtheria vaccination rare received methotrexate (p = 0.02), biologics (p = 0.004), but had higher levels of anti-diphtheria antibodies (p = 0.024) compare who omitted vaccination. Methotrexate (OR = 9.5 [95%CI: 1.004; 90.3]) and biologics (OR = 4.4 [95%CI: 1.6; 12.1]) were predictors of omitted diphtheria revaccination.

Conclusion

Children with JIA may have lower anti-vaccine antibody levels and required routine checks, especially in children with incomplete vaccination, biologics, systemic arthritis, and long-term methotrexate treatment. Revaccination of JIA patients was safe and effective.
The potential roles of m6A modification in regulating the inflammatory response in microglia
Authors: Li Qi , Wen Shaohong , Ye Weizhen , Zhao Shunying , Liu Xiangrong
Published: July 2021

Background

Microglia are key regulators of the inflammatory response in the brain. Adenosine in RNAs can be converted to m6A (N6-methyladenosine), which regulates RNA metabolism and functions as a key epitranscriptomic modification. The m6A modification pattern and m6A-related signatures under pro-inflammatory and anti-inflammatory conditions of microglia remain unclear.

Methods

Primary rat microglia were differentiated into pro-inflammatory M1-like (M1-L), anti-inflammatory M2-like (M2-L), and resting, unstimulated (M0-L) phenotypes. m6A mRNA and lncRNA epitranscriptomic microarray analyses were performed, and pathway analysis was conducted to understand the functional implications of m6A methylation in mRNAs and lncRNAs. The m6A methylation level and gene expression of mRNAs and lncRNAs were subsequently verified by m6A Me-RIP and qRT-PCR.

Results

A total of 1588 mRNAs and 340 lncRNAs, 315 mRNAs and 38 lncRNAs, and 521 mRNAs and 244 lncRNAs were differentially m6A methylated between M1-L and M0-L (M1-L/M0-L), M2-L and M0-L (M2-L/M0-L), M2-L and M1-L (M2-L/M1-L), respectively. Furthermore, 4902 mRNAs, 4676 mRNAs, and 5095 mRNAs were identified distinctively expressed in M1-L/M0-L, M2-L/M0-L, and M2-L/M1-L, respectively. Pathway analysis of differentially m6A methylated mRNAs and lncRNAs in M1-L/M0-L identified immune system, signal transduction, and protein degradation processes. In contrast, the distinct m6A methylated mRNAs in M2-L/M0-L were involved in genetic information processing, metabolism, cellular processes, and neurodegenerative disease-related pathways. We validated m6A methylation and the expression levels of five mRNAs and five lncRNAs, which were involved in upregulated pathways in M1-L/M0-L, and five mRNAs involved in upregulated pathways in M2-L/M0-L.

Conclusions

These findings identify a distinct m6A epitranscriptome in microglia, and which may serve as novel and useful regulator during pro-inflammatory and anti-inflammatory response of microglia.
Impact of cesarean section on timely initiation of breastfeeding in Ethiopia: a systematic review and meta-analysis
Authors: Getaneh Temesgen , Negesse Ayenew , Dessie Getenet , Desta Melaku , Temesgen Habtamu , Getu Tadesse , Gelaye Kihinetu
Published: July 2021

Background

Timely initiation of breastfeeding is feeding of breast milk within one hour of birth, however, three in five babies were not breastfed in the first hour of birth globally. There is evidence that cesarean section is the major constraint for this low prevalence, but the impact of cesarean section on timely initiation of breastfeeding in Ethiopia is limited. Therefore, this meta-analysis aimed to provide evidence for policy makers, health professionals and program implementers.

Methods

This systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Electronic bibliographic databases such as PubMed/Medline, EMBASE, PsycINFO, CINHAL, Scopus, Google Scholar, Science Direct and Cochrane Library were used to search relevant studies and was conducted up to February 2021. Random effects model meta-analysis was applied to estimate the pooled impact of cesarean section on timely initiation of breastfeeding with 95% confidence intervals (CI). I2 statistical test and, funnel plot and Egger’s test were used to check heterogeneity and publication bias across included studies respectively.

Results

According to meta-analysis of 17 studies, the pooled estimate of timely initiation of breastfeeding among women who had cesarean section in Ethiopia was 40.1% (95% CI 33.29, 46.92). The meta-analysis of 29,919 study participants showed that cesarean section was associated with a 79% lower odds of timely initiation of breastfeeding compared with vaginal birth (OR 0.21; 95% CI 0.16, 0.28).

Conclusions

In Ethiopia, almost only one-third of mothers who gave birth by cesarean section initiate breastfeeding within one hour of birth, much lower than the pooled prevalence among general population. Special health promotion, intervention and healthcare provider support during immediate or early skin to skin contact, and having focused breastfeeding guidelines for post-operative patient and trained health professionals should be considered for mothers who give birth through cesarean section.
Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects
Authors: Jiang Anlong , Su Ping , Li Shupeng , Wong Albert H. C. , Liu Fang
Published: July 2021

Major depressive disorder (MDD) is associated with significant morbidity and mortality. Most antidepressant medications target the serotonin and norepinephrine transporters, but a significant minority of patients do not respond to treatment and novel therapeutic targets are needed. We previously identified a protein complex composed of the α7 nicotinic acetylcholine receptor (nAChR) and NMDA glutamate receptors (NMDARs), through which α7nAChR upregulates NMDAR function. Disruption of the α7nAChR–NMDAR complex with an interfering peptide blocked α7nAChR-mediated upregulation of NMDAR function and cue-induced reinstatement of nicotine seeking in rat models of relapse. Here we report that disrupting the α7nAChR–NMDAR complex with the interfering peptide also has antidepressant-like effects in the forced swim test (FST), a common rat behaviour screening test for antidepressant effects. Furthermore, the interfering peptide significantly increases extracellular signal-regulated kinase (ERK) activity in the animals subjected to the FST. Our results provide a novel potential therapeutic target for the development of new antidepressant medications.
Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy
Authors: Wang Chunmeng , Shi Fengxia , Liu Yang , Zhang Yajing , Dong Liang , Li Xiang , Tong Chuan , Wang Yao , Su Liping , Nie Jing , Han Weidong
Published: July 2021

CD19-directed chimeric antigen receptor T cell (CART19) therapy is efficient and approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). To increase durable antitumor response, we previously designed tandem CART19/20 cells and shown longer progression-free survival. However, a proportion of CART19/20-treated patients will finally progress and require salvage therapies. In this study, we analyzed data from five patients with relapsed/refractory DLBCL who had disease progression or relapse following CART19/20 therapy and then treated with PD-1-blocking antibodies as salvage therapy. Two of five patients acquired complete remissions after anti-PD-1 therapy, including one patient remained ongoing remission for more than 21 months. One patient achieved a partial remission, and the other two had progressive diseases. No ≥ grade 3 treatment-related adverse events or cytokine release syndrome was observed. Immunohistochemistry of tumor specimens revealed higher PD-1/PD-L1 expression in responsive patients with anti-PD-1 therapy as compared to that in non-responders. After anti-PD-1 treatment, circulating T cells were activated in responders, and no significant expansion of CART19/20 cells was detected. Our data suggest that PD-1 blockade therapy can be active in patients with relapsed/refractory DLBCL after failure of CAR T cell therapy who had PD-L1 expression in tumor cells and high PD-1 level in tumor-infiltrated T cells.
Using routinely recorded data in a UK RCT: a comparison to standard prospective data collection methods
Authors: Powell G. A. , Bonnett L. J. , Smith C. T. , Hughes D. A. , Williamson P. R. , Marson A. G.
Published: July 2021

Background

Routinely recorded data held in electronic health records can be used to inform the conduct of randomised controlled trials (RCTs). However, limitations with access and accuracy have been identified. Objective: Using epilepsy as an exemplar condition, we assessed the attributes and agreement of routinely recorded data compared to data collected using case report forms in a UK RCT assessing antiepileptic drug treatments for individuals newly diagnosed with epilepsy.

Methods

The case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK multicentre RCT assessing the clinical and cost-effectiveness of antiepileptic drugs as treatments for epilepsy. Ninety-eight of 470 eligible participants provided consent for access to routinely recorded secondary care data that were retrieved from NHS Digital Hospital Episode Statistics (N=71) and primary and secondary care data from The Secure Anonymised Information Linkage Databank (N=27). We assessed data items relevant to the identification of individuals eligible for inclusion in SANAD II, baseline and follow-up visits. The attributes of routinely recorded data were assessed including the degree of missing data. The agreement between routinely recorded data and data collected on case report forms in SANAD II was assessed using calculation of Cohen’s kappa for categorical data and construction of Bland-Altman plots for continuous data.

Results

There was a significant degree of missing data in the routine record for 15 of the 20 variables assessed, including all clinical variables. Agreement was poor for the majority of comparisons, including the assessments of seizure occurrence and adverse events. For example, only 23/62 (37%) participants had a date of first-ever seizure identified in routine datasets. Agreement was satisfactory for the date of prescription of antiepileptic drugs and episodes of healthcare resource use.

Conclusions

There are currently significant limitations preventing the use of routinely recorded data for participant identification and assessment of clinical outcomes in epilepsy, and potentially other chronic conditions. Further research is urgently required to assess the attributes, agreement, additional benefits, cost-effectiveness and ‘optimal mix’ of routinely recorded data compared to data collected using standard methods such as case report forms at clinic visits for people with epilepsy.

Trial registration

Standard and New Antiepileptic Drugs II (SANAD II (EudraCT No: 2012-001884-64, registered 05/09/2012; ISRCTN Number: ISRCTN30294119, registered 03/07/2012))
SENSory re-learning of the UPPer limb (SENSUPP) after stroke: development and description of a novel intervention using the TIDieR checklist
Authors: Carlsson Håkan , Rosén Birgitta , Björkman Anders , Pessah-Rasmussen Hélène , Brogårdh Christina
Published: July 2021

Background

Sensorimotor impairments of upper limb (UL) are common after stroke, leading to difficulty to use the UL in daily life. Even though many have sensory impairments in the UL, specific sensory training is often lacking in stroke rehabilitation. Thus, the aim of this paper is to provide a detailed description of the novel intervention “SENSory re-learning of the UPPer limb after stroke (SENSUPP)” that we have developed to improve functioning in the UL in persons with mild to moderate impairments after stroke.

Methods

The SENSUPP protocol was designed using information from literature reviews, clinical experience and through consultation of experts in the field. The protocol integrates learning principles based on current neurobiological knowledge and includes repetitive intensive practice, difficulty graded exercises, attentive exploration of a stimulus with focus on the sensory component, and task-specific training in meaningful activities that includes feedback. For reporting the SENSUPP protocol, the Template for Intervention Description and Replication (TIDieR) checklist was used.

Results

The essential features of the SENSUPP intervention comprise four components: applying learning principles based on current neurobiological knowledge, sensory re-learning (exercises for touch discrimination, proprioception and tactile object recognition), task-specific training in meaningful activities, and home-training. The training is performed twice a week, in 2.5-h sessions for 5 weeks.

Conclusion

Since there is close interaction between the sensory and motor systems, the SENSUPP intervention may be a promising method to improve UL functioning after stroke. The TIDieR checklist has been very useful for reporting the procedure and development of the training.

Trial registration

ClinicalTrials.govNCT03336749. Registered on 8 November 2017.
The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches
Authors: Steinbrink Julie M. , Myers Rachel A. , Hua Kaiyuan , Johnson Melissa D. , Seidelman Jessica L. , Tsalik Ephraim L. , Henao Ricardo , Ginsburg Geoffrey S. , Woods Christopher W. , Alexander Barbara D. , McClain Micah T.
Published: July 2021

Background

Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response toCandidainfections in human patients remains poorly defined.

Methods

In order to better define the host response toCandidainfection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive forCandidaspecies and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers.

Results

Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection).

Conclusions

Transcriptional analysis of circulating leukocytes in patients with acuteCandidainfections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.
Clinical characteristics and outcomes of patients with pediatric acute lymphoblastic leukemia after induction of chemotherapy: a pilot descriptive correlational study from Palestine
Authors: Shawahna Ramzi , Mosleh Sultan , Odeh Yahya , Halawa Rami , Al-Ghoul Majd
Published: July 2021

Objective

Pediatric acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer among children. This study was conducted to describe and correlate the clinical characteristics and outcomes of treatment of patients with pediatric ALL in the main referral hospital in Palestine.

Results

Complete data of 69 patients were included in this analysis. The majority (79.7%) of the patients had B-ALL phenotype. After induction chemotherapy, remission was experienced by the vast majority of the patients and 5 (7.2%) experienced relapses. Cytogenetics for patients with B-ALL phenotype indicated that 10 (18.2%) patients had t(12, 21) translocation, 5 (9.1%) had hyperdiploidy, 4 (7.3%) had t(1, 19) translocation, and 2 (3.6%) had t(9, 22) translocation. The initial white blood cells (p value < 0.001), absolute neutrophils (p value = 0.011), and hemoglobin (p value < 0.001) were significantly lower in patients with B-cell ALL. Platelet counts were significantly lower (p value = 0.012) in patients with splenomegaly and those with bleeding symptoms (p value = 0.008). Presence of palmar pollar was positively associated (p value = 0.035) with T-cell ALL. Presence of hepatomegaly was positively associated (p value < 0.001) with splenomegaly.
Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease
Authors: Xiao Zhenxu , Wu Xue , Wu Wanqing , Yi Jingwei , Liang Xiaoniu , Ding Saineng , Zheng Li , Luo Jianfeng , Gu Hongchen , Zhao Qianhua , Xu Hong , Ding Ding
Published: July 2021

Background

Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported.

Methods

We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform.

Results

All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = −0.536, P < 0.0001), memory (r = −0.481, P < 0.0001), attention (r = −0.437, P < 0.0001), visuospatial function (r = −0.385, P < 0.0001), and language (r = −0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = −0.301, P < 0.001).

Conclusions

Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.
Fulminant myocarditis induced by immune checkpoint inhibitor nivolumab: a case report and review of the literature
Authors: Wang Feifei , Liu Yang , Xu Wei , Zhang Changjing , Lv Jianhong , Ma Shaolin
Published: July 2021

Background

Nivolumab, an anti-programmed cell death protein 1 antibody, is commonly used as an immune checkpoint inhibitor in various cancers. Various adverse events are associated with these therapies, including hepatitis, dermatitis, and myocarditis. Myocarditis is a relatively rare but potentially fatal immune-mediated adverse reaction.

Case presentation

We report a case of colon cancer in a 56-year-old Chinese patient with lung and liver metastasis who developed fulminant myocarditis by nivolumab and survived with the support of extracorporeal membrane oxygenation. After six cycles (within 3 months) of nivolumab treatment, the patient developed chest tightness and was hospitalized. A diagnosis of fulminant myocarditis associated with immunotherapy was confirmed based on the clinical manifestations and laboratory examinations. He recovered well and was discharged on day 45 after management with extracorporeal membrane oxygenation, intravenous methylprednisolone, and immunoglobulin.

Conclusions

This case illustrates a severe cardiovascular complication of immunotherapy, strongly suggesting the necessity of close monitoring for outpatient usage of nivolumab. Additionally, our experience provided an efficient management strategy of extracorporeal membrane oxygenation in terms of life-threatening conditions.