bluuebunny/crossref_metadata_2025 huggingface dataset:
Migraine, interferon β1a and siponimod immunomodulator therapies
Authors: Dahaba Ashraf A. , Bornemann-Cimenti Helmar
Published: April 2022

Background

Autoimmunity seems to play a great role in the pathogenesis of migraine headache pain. There is far more evidence that interferon can exacerbate migraines. We report a case where remission of severe comorbid migraine attacks happened with the start of interferon β1a (Merck, Netherlands) immunomodulation therapy. Therapy for multiple sclerosis was decided according to the severity of the debilitating comorbid migraine headache pain rather than the evolution of multiple sclerosis the far more serious disease.

Case presentation

A 63-years old patient suffered for 30-years from migraine headache of severe disability assessment scale (MIDAS) Grade-IV = 27. He also suffered for 25-years from optic-sensory relapsing remitting multiple sclerosis (RRMS). Subcutaneous interferon β1a 44-µg immunomodulation therapy for 4-years resulted in multiple sclerosis complete remission. The start of interferon β1a therapy for multiple sclerosis seemed to help resolving the comorbid migraine attacks. The visual aura premonitory symptom preceding migraine headache would end up with a feeling of post visual aura clearer field of vision and a feeling of wellbeing. As the patient developed secondary progressive multiple sclerosis (SPMS), oral siponimod 2 mg (Novartis, Ireland), currently the only available therapy for SPMS, replaced his interferon therapy. This was associated with a relapse of migraine severe attacks. Reverting back to interferon therapy was again associated with migraine headache remission.

Conclusions

Interferon β1a might be an efficic therapy for “autoimmune migraine”. With numerous immunomodulators currently available for other systemic autoimmune diseases associated with comorbid migraine; examining the effect of these immunomodulatory therapies on comorbid migraine headache could be beneficial in finding a specific immunomodulator therapy for “autoimmune migraine”.
Analysis of 61 SNPs from the CAD specific genomic loci reveals unique set of SNPs as significant markers in the Southern Indian population of Hyderabad
Authors: Gorre Manjula , Rayabarapu Pranavchand , Battini Sriteja Reddy , Irgam Kumuda , Battini Mohan Reddy
Published: April 2022

Background

The present study is a part of the major project on coronary artery disease (CAD) carried out at Indian Statistical Institute, Hyderabad to investigate the pattern of association of SNPs selected from the CAD specific genomic loci. The study is expected to portray the genetic susceptibility profile of CAD specifically in the Southern Indian population of Hyderabad.

Methods

The study was conducted in a cohort of 830 subjects comprising 350 CAD cases and 480 controls from Hyderabad. A prioritized set of 61 SNPs selected from the NHGRI GWAS catalogue were genotyped using FluidigmNanofluidic SNP Genotyping System and appropriate statistical analyses were used in interpreting the results.

Results

After data pruning, out of 45 SNPs qualified for the association analysis, four SNPs were found to be highly significantly associated with increased risk for CAD even after Bonferroni correction for multiple testing (p < 0.001). These results were also replicated in the random subsets of the pooled cohort (70, 50 and 30%) suggesting internal consistency. The ROC analysis of the risk scores of the significant SNPs suggested highly significant area under curve (AUC = 0.749;p < 0.0001) implying predictive utility of these risk variants.

Conclusions

Thers10455872ofLP(A)gene in particular showed profound risk for CAD (OR 35.9; CI 16.7–77.2) in this regional Indian population. The other significant SNP associations observed with respect to the pooled CAD cohort and in different anatomical and phenotypic severity categories reflected on the role of genetic heterogeneity in the clinical heterogeneity of CAD. The SNPrs7582720ofWDR12gene, albeit not individually associated with CAD, was found to be conferring significant risk through epistatic interaction with two SNPs (rs6589566, rs1263163inZPR1,APOA5-APOA4genes) of the 11q23.3 region.
Can transrectal ultrasonography distinguish anorectal malignant melanoma from low rectal adenocarcinoma? A retrospective paired study for ten years
Authors: Yan Jingwen , Jing Jigang , Wu Shuang , Geiru Lacong , Zhuang Hua
Published: April 2022

Background

Anorectal malignant melanoma (ARMM) and low rectal adenocarcinoma (LRAC) have some similarities in clinical behaviors, histopathological characteristics and ultrasonographic findings, diagnostic errors are common. By comparing the transrectally ultrasonographic features between the two tumors, we propose to provide more possibilities in differentiating them.

Methods

The data of 9 ARMMs and 27 age- and gender-matched LRACs (the lower margin below the peritoneal reflection) in West China Hospital Sichuan University between April 2008 and July 2019 were retrospectively reviewed. The ultrasonic features between the two groups were compared.

Results

Transrectal ultrasonography (TRUS) showed that the length of ARMM was shorter than that of LRAC (28.22 ± 12.29 mm vs. 40.22 ± 15.16 mm), and ARMM had a lower position than that of LRAC (the distance to anal verge was 50.78 ± 11.70 vs. 63.81 ± 18.73 mm). Unlike LRAC, the majority of ARMM in our study was confined to the intestinal mucosa/submucosa (66.67/25.93%) (P < 0.05).

Conclusions

Based on the data of our study, several ultrasonographic findings (length, invasion depth, and position) of ARMM were significantly different from LRAC. Accordingly, more attention should be paid to masses at anorectal junction with lower position, shorter length, and shallower infiltration depth. Instead of the most common tumor, LRAC, ARMM should be taken into account to avoid a misdiagnosis, which will result in a poorer prognosis.
Case report: post-salmonellosis abscess positive for Salmonella Oranienburg
Authors: Castlemain Brenda M. , Castlemain Brian D.
Published: April 2022

Background

Salmonella gastroenteritis is a self-limited infection in immunocompetent adults. Salmonella Oranienburg is a serovar that has recently caused outbreaks of gastroenteritis traced to contact with a pet turtle. Extraintestinal focal infections (EFIs) with invasive Salmonella have been reported uncommonly, examples of which include mycotic aneurysm and spinal osteomyelitis.

Case presentation

The patient is an otherwise healthy 39-year-old male with sleep apnea presenting with pain and swelling in the left anterior chest wall several months after an episode of Salmonella gastroenteritis and bacteremia which was treated successfully with intravenous (IV) antibiotics. He was found to have a costochondral joint abscess with operative cultures positive for S. Oranienburg, a serovar reported to have been associated with pet turtles and onions in recent CDC and FDA news releases. Of note, the joint abscess began development 2–3 months after his episode of Salmonella bacteremia. At the time of surgical treatment, nearly 6 months had passed since the initial episode of gastroenteritis and bacteremia.

Conclusions

Delayed development of a sternocostal joint abscess after Salmonella bacteremia in an otherwise healthy adult male is an unusual presentation. The patient had two different exposures: a fast food chicken lunch and a pet turtle at home. Extraintestinal focal infections with invasive Salmonella are very uncommonly reported in healthy adult patients treated in developed countries. To our knowledge, we report this sequala for the first time.
Association of blood eicosapentaenoic acid levels with intracerebral hemorrhage during the COVID-19 pandemic: preliminary experience from a single-center in Japan
Authors: Hira Kenichiro , Ueno Yuji , Miyamoto Nobukazu , Nakajima Sho , Kijima Chikage , Hattori Nobutaka
Published: April 2022

Background

The COVID-19 pandemic has forced lockdowns and declarations of states of emergency, resulting in marked changes to daily life such as dietary habits in many countries. Though serum omega-3 polyunsaturated fatty acids levels have been shown to be useful markers for recurrent vascular events or worse prognosis in cardiovascular diseases and ischemic stroke, the relationship between serum omega-3 PUFA levels and the occurrence of intracerebral hemorrhage has essentially been unknown. We explored the association of serum omega-3 polyunsaturated fatty acids with intracerebral hemorrhage during the COVID-19 pandemic.

Methods

Participants comprised patients admitted to Juntendo University Hospital (Tokyo, Japan) with intracerebral hemorrhage between January 1, 2016 and April 30, 2020. Clinical characteristics including serum omega-3 polyunsaturated fatty acid levels were compared between patients developing intracerebral hemorrhage during the period from January 1, 2016 to February 29, 2020, and the subsequent COVID-19 pandemic period (March 1 to April 30, 2020). Clinical characteristics independently related to intracerebral hemorrhage during the COVID-19 pandemic were analyzed by comparing these two cohorts of intracerebral hemorrhage patients in different periods.

Results

A total of 103 patients (age, 67.0 ± 13.9 years; 67 males) with intracerebral hemorrhage were enrolled. Intracerebral hemorrhage developed in 91 patients before and 12 patients during the COVID-19 pandemic. Monthly averages of intracerebral hemorrhage patients admitted to our hospital during and before the COVID-19 pandemic were 6 and 1.82, respectively. Serum eicosapentaenoic acid levels were significantly lower in intracerebral hemorrhage patients during the COVID-19 pandemic than before (31.87 ± 12.93 μg/ml vs. 63.74 ± 43.29 μg/ml,p = 0.007). Multiple logistic regression analysis showed that, compared to before the COVID-19 pandemic, dyslipidemia (odds ratio 0.163, 95% confidence interval 0.031–0.852;p = 0.032) and eicosapentaenoic acid levels (odds ratio 0.947, 95% confidence interval 0.901–0.994;p = 0.029) were associated with intracerebral hemorrhage during the COVID-19 pandemic.

Conclusions

From our preliminary results, low eicosapentaenoic acid levels were linked with intracerebral hemorrhage during the COVID-19 pandemic. Low levels of eicosapentaenoic acid might be an endogenous surrogate marker for intracerebral hemorrhage during the COVID-19 pandemic.
Effects of needs-based education for prenatal anxiety in advanced multiparas: a randomized controlled trial
Authors: Shen Quan , Huang Can-Ran , Rong Liu , Ju Shan , Redding Sharon R. , Ouyang Yan-Qiong , Wang Rong
Published: April 2022

Background

Prenatal anxiety is a common concern which may have adverse effects on maternal and infant health outcomes. Studies addressing needs-based education interventions for prenatal anxiety are limited.

Aim

To explore the effects of needs-based education on alleviating prenatal anxiety among advanced multiparas when compared with routine prenatal health education.

Methods

A total of 86 advanced multiparas were randomized into the intervention group (n = 43) or the control group (n = 43) in this study. The control group received routine prenatal care. The intervention group received five needs-based education programs presented by trained researchers. The Pregnancy-related Anxiety Questionnaire was used to evaluate changes in anxiety level of participants. Concurrent physiological parameters, including blood pressure, heart rate and non-stress test were also measured.

Results

Scores on the Pregnancy-related Anxiety Questionnaire of the intervention group were significantly lower than those of the control group (t = 4.21, P < 0.05). Systolic blood pressure (t = 3.64, P < 0.05) and heart rate (t = 2.39, P < 0.05) of the intervention group were also significantly lower than the control group whereas no differences were noted in diastolic blood pressure and non-stress test.

Conclusion

A needs-based education program is an effective intervention strategy to allay prenatal anxiety in advanced multiparas.

Trial registration

The trial was retrospectively registered in the Chinese Clinical Trial Registry as number ChiCTR2100047552.
Angle closure secondary to lens remnants in a patient with presumed aphakia: case report
Authors: Wu Kristi Y. , Lyons Lance J. , Roddy Gavin W.
Published: April 2022

Background

Eyes with a short axial length or anterior chamber depth often develop narrowed anterior chamber angles in association with an enlarging crystalline lens. We report a case of a patient who presented in angle closure, with a distant history of prior intervention for congenital cataracts and was presumed to be aphakic.

Case presentation

A 78-year-old male presented with acute onset unilateral eye pain and blurred vision. He was found to have increased intraocular pressure, anteriorly bowed iris, and angle closure. Despite prior documentation of aphakia after treatment for congenital cataracts, detailed workup revealed residual crystalline lens material pushing the peripheral iris anteriorly. Further history confirmed that the patient underwent a procedure in the 1940’s to remove lens material centrally but was not truly aphakic. The patient was treated with anterior chamber paracentesis and intraocular pressure lowering drops. His intraocular pressure remains controlled with medical therapy alone.

Conclusions

Patients that appear to be aphakic centrally may still present with angle closure secondary to residual peripheral lens material. This case highlights the importance of keeping this etiology on the differential in a patient with presumed aphakia.
Long term outcome study of a salutogenic psychoeducational recovery oriented intervention (Inte.G.R.O.) in severe mental illness patients
Authors: Veltro Franco , Latte Gianmarco , Pontarelli Irene , Pontarelli Cristina , Nicchiniello Ilenia , Zappone Lilia
Published: April 2022

Aim

Inte.G.R.O. is a standardized Salutogenic-Psychoeducational intervention designed to help people with severe mental illness manage their life-stress and achieve personal recovery goals through the improvement of social functioning. The aim of this study is to evaluate the long-term outcome of this approach, characterized by health promotion rather than correction of dysfunctional strategies.

Methods

41 people underwent an observational study with a three time-point evaluation (t0, pre- treatment; t1, 12 months; t2, 36 months). At each time point, social functioning was assessed as primary outcome by the Personal and Social Functioning scale (PSP); furthermore, psychopathological status was assessed by Brief Psychiatric Rating Scale (BPRS), stress management was measured by means of Stress-Scale and cognitive flexibility variables were assessed by Modified Five-Point Test (M-FPT).

Results

Personal and Social Functioning increased at t1 and t2 vs t0; psychopathological status improved at t2 vs t0; stress management improved at t2 vs t1; cognitive flexibility improved at t2 vs t0.

Conclusions

these results substantially confirm after a three-year follow-up the improvements in functioning, psychopathology, stress management and cognitive flexibility seen in previous studies. Furthermore, they show a complex time-dependent fashion. Overall, they confirm a remarkable and long-term impact of Inte.G.R.O. on key Recovery variables. Further studies are needed to address extent and duration of these improvements.
A novel joint index based on peripheral blood CD4+/CD8+ T cell ratio, albumin level, and monocyte count to determine the severity of major depressive disorder
Authors: Zhou Dechun , Yu Hongfeng , Yao Hongfeng , Yuan Shijin , Xia Yan , Huang Lei , Shen Yuedi , Zhang Jun , Chen Wei
Published: April 2022

Background

Inflammation and immune status are correlated with the severity of major depressive disorder (MDD).The purpose of this study was to establish an optimization model of peripheral blood parameters to predict the severity of MDD.

Methods

MDD severity in the training and validation cohorts (n = 99 and 97) was classified using the Hamilton Depression Scale, Thirty-eight healthy individuals as controls. Significant severity-associated factors were identified using a multivariate logistic model and combined to develop a joint index through binary logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to identify the optimal model and evaluate the discriminative performance of the index.

Results

In the training cohort, lower CD4+/CD8+ T cell ratio, albumin level, and a higher monocyte percentage (M%) were significant as operating sociated with severe disease (P < 0.05 for all). The index was developed using these factors and calculated as CD4+/CD8+ T cell ratio, albumin level, and M%, with a sensitivity and specificity of 90 and 70%, respectively. The AUC values for the index in the training and validation cohorts were 0.85 and 0.75, respectively, indicating good discriminative performance.

Conclusion

We identified disease severity-associated joint index that could be easily evaluated: CD4+/CD8+ T cell ratio, albumin level, and M%.
Factors associated with motorcycle-related road traffic crashes in Africa, a Scoping review from 2016 to 2022
Authors: Konlan Kennedy Diema , Hayford Linda
Published: April 2022

Background

The toll associated with road traffic crashes (RTC) is high, and the burden of injury is disproportionately borne by pedestrians and motor riders, particularly in developing countries. This study synthesized the factors associated with motorcycle-related RTC in Africa.

Methods

The PICO framework and the PRISMA guidelines for conducting reviews were incorporated in searching, screening, and reporting the findings. Advanced search in five electronic databases (Google Scholar, PubMed Central, Scopus, CINAHL, and Embase) yielded 2552 titles and 22 from manual search, filtered for 2016 to 2022 (to generate 1699) and then further for primary studies (854). Through the title, abstract and full-text screening, 22 were appropriate for this review. Data extraction was done by the two researchers independently, and the results were compared. Convergent synthesis was adopted to integrate results, transformed into a narrative, and analyzed using thematic synthesis.

Results

The four main themes identified were the rider-related, non-rider-related factors, prevalence and severity of injuries from RTC, and the measures to reduce RTC. The behavioral factors associated with RTC were alcohol use, smoking, use of illicit drugs, tiredness of rider, poor knowledge on traffic regulations, more than one pillow rider, lack of rider license, non-observance of traffic regulations, and non-use of personal protective equipment. Road traffic crashes were common among younger age and male gender. Other factors identified included poor road network, unplanned stoppage by police, unlawful vehicular packing, increased urbanization, and slippery floors.

Conclusion

There is the need to institute multi-sectoral measures that target riders’ behavior change. Coordinated efforts should target governments, enforcement authorities, and regulatory bodies to enforce enactment that ensures safe use of roads.
Modifiable risk factors in adults with and without prior cardiovascular disease: findings from the Indonesian National Basic Health Research
Authors: Arsyad Dian Sidik , Westerink Jan , Cramer Maarten J. , Ansar Jumriani , Wahiduddin  , Visseren Frank L. J. , Doevendans Pieter A. , Ansariadi
Published: April 2022

Backgrounds

The majority of risk factors for cardiovascular diseases (CVDs) are modifiable. Continuous monitoring and control of these factors could significantly reduce the risk of CVDs-related morbidity and mortality. This study estimated the prevalence of modifiable risk factors in Indonesia and its co-occurence of multiple risk factors stratified by prior CVDs diagnosis status and sex.

Methods

Adult participants (> 15 years, N = 36,329, 57% women) with median age of 40 years were selected from a nationwide Indonesian cross-sectional study called Basic Health Research or Riset Kesehatan Dasar (Riskesdas) conducted in 2018. Thirteen risk factors were identified from the study, including smoking, a high-risk diet, inadequate fruit and vegetable consumption, a low physical activity level, the presence of mental-emotional disorders, obesity, a high waist circumference (WC), a high waist-to-height ratio (WtHR), hypertension, diabetes, a high total cholesterol level, a high low-density lipoprotein (LDL) cholesterol level, and a low high-density lipoprotein (HDL) cholesterol level. Age-adjusted prevalence ratios stratified by CVDs status and sex were calculated using Poisson regression with the robust covariance estimator.

Results

CVDs were found in 3% of the study population. Risk factor prevalence in the overall population ranged from 5.7 to 96.5% for diabetes and inadequate fruit and vegetable consumption respectively. Smoking, a high-risk food diet, and a low HDL cholesterol level were more prevalent in men, whereas a low physical activity level, the presence of mental-emotional disorders, obesity, a high WC, a high WtHR, hypertension, diabetes, a high total cholesterol level, and a high LDL cholesterol level were more prevalent in women. Approximately 22% of men and 18% of women had at least 4 risk factors, and these proportions were higher in participants with prior CVDs diagnosis.

Conclusions

There is a high prevalence of modifiable risk factors in the Indonesian adult population. Sex, age, and the presence of CVD are major determinants of the variations in risk factors. The presence of multiple risk factors, which are often inter-related, requires a comprehensive approach through health promotion, lifestyle modification and patient education.
Application of structural allogenous bone graft in two-stage exchange arthroplasty for knee periprosthetic joint infection: a case control study
Authors: Chuang Chieh An , Lee Sheng-Hsun , Chang Chih-Hsiang , Hu Chih-Chien , Shih Hsin-Nung , Ueng Steve W. N. , Chang Yuhan
Published: April 2022

Background

Knee prosthetic joint infection (PJI) is a common but devastating complication after knee arthroplasty. The revision surgeries for knee PJI may become more challenging when it is associated with large bone defects. The application of structural bone allograft in knee revision surgeries with large bone defects is not a new technique. However, there is a lack of literature reporting its efficacy in PJI cases. This study aimed to investigate the outcome of structural fresh frozen allogenous bone grafts in treating patients in knee PJI with large bone defects.

Methods

We performed a retrospective cohort analysis of knee PJI cases treated with two-stage exchange arthroplasty at our institution from 2010 to 2016. 12 patients with structural allogenous bone graft reconstructions were identified as the study group. 24 patients without structural allograft reconstructions matched with the study group by age, gender, and Charlson comorbidity index were enrolled as the control group. The functional outcome of the study group was evaluated with the Knee Society Score (KSS). Treatment success was assessed according to the Delphi-based consensus definition. The infection relapse rate and implant survivorship were compared between groups.

Results

Revision knees with structural allograft presented excellent improvement in the KSS (33.1 to 75.4). There was no significant difference between infection relapse-free survival rate and prosthesis survival rate in the two groups. The 8-year prosthesis survival rate was 90.9% in the study group and 91% in the control group (p = 0.913). The 8-year infection relapse-free survival rate was 80 and 83.3% in the study group and control group, respectively (p = 0.377).

Conclusion

The structural fresh frozen allogenous bone graft provided an effective way for bone defect reconstruction in knee PJI with an accountable survival rate. Meanwhile, using structural allografts did not increase the relapse rate of infection.
The relationship between sex hormones and glycated hemoglobin in a non-diabetic middle-aged and elderly population
Authors: Xu Yiting , Cao Weijie , Shen Yun , Tang Junling , Wang Yufei , Ma Xiaojing , Bao Yuqian
Published: April 2022

Background

Sex hormones are strongly linked to the occurrence and development of diabetes, and influence glycated hemoglobin (HbA1c) levels in diabetic population; but, the relationship between sex hormones and HbA1c in non-diabetic population remains unknown. This study aimed to explore the extent of influence of sex hormones on HbA1c levels in non-diabetic population.

Methods

A total of 1409 non–diabetic subjects, including 601 men and 808 postmenopausal women were recruited from Shanghai community. HbA1c was detected using high performance liquid chromatography, and hemoglobin level was determined by sodium lauryl sulfate colorimetry. Serum estradiol (E2), total testosterone (TT), and sex hormone binding globulin (SHBG) were measured by chemiluminescent microparticle immunoassays.

Results

The level of HbA1c was 5.6 (5.4–5.9) % in all subjects, with 5.6 (5.4–5.8) % in men and 5.7 (5.5–5.9) % in postmenopausal women. After adjusting for age, body mass index (BMI), and hemoglobin, E2 was positively correlated with HbA1c in men (r = 0.122, P = .003), and SHBG was inversely correlated with HbA1c (r = − 0.125, P < .001) in women. Other hormones were not correlated with HbA1c (all P > .05). Multivariate linear regression analysis showed that, except for traditional factors, such as age, hemoglobin, and BMI, E2 was another determinant of HbA1c (standardized β = 0.137, P = .003) in men; besides, in women, SHBG was another determinant of HbA1c (standardized β = − 0.178, P < .001), except for age and systolic blood pressure.

Conclusion

After controlling for confounding factors, two sex hormones, as E2 and SHBG could influence HbA1c levels in non-diabetic population.
Barriers, facilitators, and proposals for improvement in the implementation of a collaborative care program for depression: a qualitative study of primary care physicians and nurses
Authors: Aragonès Enric , López-Cortacans Germán , Cardoner Narcís , Tomé-Pires Catarina , Porta-Casteràs Daniel , Palao Diego ,   the INDI·I Research Team, Bellerino Eva , Cavero Myriam , Aguilar Eva , Subirà Marta , Caballero Antonia , Casaus Pilar , Monreal José Antonio , Pérez-Sola Víctor , Cirera Miquel , Loren Maite , Palacios Laura
Published: April 2022

Background

Primary care plays a central role in the treatment of depression. Nonetheless, shortcomings in its management and suboptimal outcomes have been identified. Collaborative care models improve processes for the management of depressive disorders and associated outcomes. We developed a strategy to implement the INDI collaborative care program for the management of depression in primary health care centers across Catalonia. The aim of this qualitative study was to evaluate a trial implementation of the program to identify barriers, facilitators, and proposals for improvement.

Methods

One year after the implementation of the INDI program in 18 public primary health care centers we performed a qualitative study in which the opinions and experiences of 23 primary care doctors and nurses from the participating centers were explored in focus groups. We performed thematic content analysis of the focus group transcripts.

Results

The results were organized into three categories: facilitators, barriers, and proposals for improvement as perceived by the health care professionals involved. The most important facilitator identified was the perception that the INDI collaborative care program could be a useful tool for reorganizing processes and improving the management of depression in primary care, currently viewed as deficient. The main barriers identified were of an organizational nature: heavy workloads, lack of time, high staff turnover and shortages, and competing demands. Additional obstacles were inertia and resistance to change among health care professionals. Proposals for improvement included institutional buy-in to guarantee enduring support and the organizational changes needed for successful implementation.

Conclusions

The INDI program is perceived as a useful, viable program for improving the management of depression in primary care. Uptake by primary care centers and health care professionals, however, was poor. The identification and analysis of barriers and facilitators will help refine the strategy to achieve successful, widespread implementation.

Trial registration

ClinicalTrials.gov identifier: NCT03285659; Registered 18th September, 2017.
Circ_0036412 affects the proliferation and cell cycle of hepatocellular carcinoma via hedgehog signaling pathway
Authors: Wang Liyan , Li Bin , Yi Xiaoyuan , Xiao Xuhua , Zheng Qinghua , Ma Lei
Published: April 2022

Background

Hepatocellular carcinoma (HCC), as the most common type of liver cancer, is characterized by high recurrence and metastasis. Circular RNA (circRNA) circ_0036412 was selected for studying the underlying mechanisms of HCC.

Methods

Quantitative real time-polymerase chain reaction (qRT-PCR) and western blot analyzed gene and protein expression. Functional experiments evaluated HCC cell proliferation, apoptosis and cell cycle in vitro. In vivo experiments detected HCC carcinogenesis in vivo. Fluorescence in situ hybridization (FISH) assays evaluated the subcellular distribution. Luciferase reporter, Chromatin immunoprecipitation (ChIP), DNA pulldown, RNA-binding protein immunoprecipitation (RIP), and RNA pulldown assays detected the underlying mechanisms.

Results

Circ_0036412 is overexpressed in HCC cells and features circular structure. PRDM1 activates circ_0036412 transcription to regulate the proliferation and cell cycle of HCC cells in vitro. Circ_0036412 modulates Hedgehog pathway. GLI2 propels HCC growth in vivo. Circ_0036412 up-regulates GLI2 expression by competitively binding to miR-579-3p, thus promoting the proliferation and inhibiting cell cycle arrest of HCC cells. Circ_0036412 stabilizes GLI2 expression by recruiting ELAVL1. Circ_0036412 propels the proliferation and inhibits cell cycle arrest of HCC cells in vitro through Hedgehog pathway.

Conclusions

Circ_0036412 affects the proliferation and cell cycle of HCC via Hedgehog signaling pathway. It offers an insight into the targeted therapies of HCC.

Graphical Abstract
A randomized controlled trial of the influence of yoga for women with symptoms of post-traumatic stress disorder
Authors: Yi Lei , Lian Yunling , Ma Ning , Duan Ni
Published: April 2022

Background

Survivors in motor vehicle accident (MVA) may have posttraumatic stress disorder (PTSD). Yoga is a complementary approach for PTSD therapy.

Methods

This randomized controlled trial explored whether yoga intervention has effects on reducing the symptoms of PTSD in women survived in MVA. Participants (n = 94) were recruited and randomized into control group or yoga group. Participants attended 6 45-minuite yoga sessions in 12 weeks. Depression Anxiety Stress Scales (DASS) and Impact of Events Scale-Revised (IES-R) were used to assess psychological distress.

Results

Post-intervention IES-R total score of yoga group was significantly lower than that of control group (p = 0.01). At both post-intervention and 3-months post intervention, the DASS-21 total scores of yoga group were both significantly lower than those of control group (p = 0.043, p = 0.024). Yoga group showed lower anxiety and depression level compared to control group at both post-intervention (p = 0.033, p < 0.001) and post-follow-up (p = 0.004, p = 0.035). Yoga group had lower levels of intrusion and avoidance compared to control group after intervention (p = 0.002, p < 0.001).

Conclusion

Results illustrate that yoga intervention may alleviate anxiety and depression and improve the symptoms of PTSD in women with PTSD following MVA.
Basal and one-month differed neutrophil, lymphocyte and platelet values and their ratios strongly predict the efficacy of checkpoint inhibitors immunotherapy in patients with advanced BRAF wild-type melanoma
Authors: Guida Michele , Bartolomeo Nicola , Quaresmini Davide , Quaglino Pietro , Madonna Gabriele , Pigozzo Jacopo , Di Giacomo Anna Maria , Minisini Alessandro Marco , Tucci Marco , Spagnolo Francesco , Occelli Marcella , Ridolfi Laura , Queirolo Paola , De Risi Ivana , Valente Monica , Sciacovelli Angela Monica , Chiarion Sileni Vanna , Ascierto Paolo Antonio , Stigliano Lucia , Strippoli Sabino
Published: April 2022

Background

To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response toimmune checkpoint inhibitors (ICI) in metastatic melanoma (MM).

Methods

We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve.

Results

At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Δplatelets (p = 0.039), ΔWBC (p < 0.001), and Δneutrophils (p = 0.020), and with lower Δlymphocytes (p < 0.001). Moreover, higher ΔNLR and ΔPLR identified patients with worse PFS, OS and DCR. In the multivariable model, only ΔNLR influenced PFS (p = 0.004), while OS resulted affected by higher ΔWBC (p < 0.001) and lower Δlymphocytes (p = 0.038). Higher ΔWBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and ΔNLR, normal LDH/lower ΔNLR showed a higher PFS than high LDH/higher ΔNLR (20 vs 5 months). Moreover, normal LDH/higher Δlymphocytes had a higher OS than high LDH/lower Δlymphocytes (50 vs. 10 months).

Conclusions

Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data.
Ruxolitinib suppresses liver fibrosis progression and accelerates fibrosis reversal via selectively targeting Janus kinase 1/2
Authors: Song Zhenghui , Liu Xinhui , Zhang Wan , Luo Yue , Xiao Hua , Liu Yun , Dai Guanqi , Hong Jian , Li Aimin
Published: April 2022

Background

JAK1 and JAK2 have been implicated in fibrosis and cancer as a fibroblast-related marker; however, their role in liver fibrosis has not been elucidated. Here, we aim to determine the effect and underlying mechanism of JAK1/2 inhibition on liver fibrosis and hepatic stellate cells (HSCs) and further explore the therapeutic efficacy of Ruxolitinib, a JAK1/2 selective inhibitor, on preventing and reversing liver fibrosis in mice.

Methods

Immunohistochemistry staining of JAK1 and JAK2 were performed on liver tissue in mice with hepatic fibrosis and human liver tissue microarray of liver cirrhosis and liver cancer. LX-2 cells treated with specific siRNA of JAK1 and JAK2 were used to analysis activation, proliferation and migration of HSCs regulated by JAK1/2. The effects of Ruxolitinib (JAK1/2 inhibitor) on liver fibrosis were studied in LX-2 cells and two progressive and reversible fibrosis animal models (carbon tetrachloride (CCl4), Thioacetamide (TAA)).

Results

We found that JAK1/2 expression was positively correlated with the progression of HCC in humans and the levels of liver fibrosis in mice. Silencing of JAK1/2 down-regulated their downstream signaling and inhibited proliferation, migration, and activation of HSCs in vitro, while Ruxolitinib had similar effects on HSCs. Importantly, Ruxolitinib significantly attenuated fibrosis progression, improved cell damage, and accelerated fibrosis reversal in the liver of mice treated with CCl4 or TAA.

Conclusions

JAK1/2 regulates the function of HSCs and plays an essential role in liver fibrosis and HCC development. Its inhibitor, Ruxolitinib, may be an effective drug for preventing and treating liver fibrosis.
Associated predictors of functional impairment among adolescents with ADHD—a cross-sectional study
Authors: Meyer Jenny , Alaie Iman , Ramklint Mia , Isaksson Johan
Published: April 2022

Background

Attention-deficit/hyperactivity disorder (ADHD) in adolescence is associated with functional impairment in several domains of life. To enable development of interventions that more effectively target functional impairment in this age group, the associations between clinical characteristics and impairment need to be clarified. The aim of this study was to investigate the associations between ADHD and functional impairment, if they varied by sex, and the potential impact of comorbid psychiatric symptoms on the associations.

Methods

This was a cross-sectional study including adolescents with ADHD (n = 164) and a reference group of adolescents without ADHD (n = 106). Self-ratings and parental ratings of functional impairment in different life domains were used as outcomes in all analyses. Differences between groups were investigated with comparative analyses. General linear models (GLMs) were used to explore associations between ADHD symptoms and functional impairment in adolescents with ADHD, while adjusting for of comorbid symptoms, sex, and medication.

Results

Adolescents with ADHD displayed higher levels of functional impairment than peers without ADHD, and girls with ADHD rated higher impairment than their male counterparts. The combined ADHD presentation was associated with the highest levels of self-reported impairment, while parental ratings indicated comparable levels of overall impairment across presentations. In the adjusted GLMs, symptoms of inattention were strongly associated with self- and parent-rated impairment in school, but symptoms of hyperactivity/impulsivity were not, whereas symptoms of both inattention and hyperactivity/impulsivity were modestly associated with self-rated impairment with friends. Further, both emotional and conduct problems were associated with impairment in daily life.

Conclusions

Our results suggest that attention difficulties, in particular, seem to impair academic functioning in adolescents with ADHD, and interventions targeting such difficulties are warranted. In addition, comorbid symptoms need to be assessed and treated, and self-reports of functioning should be included in research and clinical practice involving adolescents.
Frequency of BRCA1 and BRCA2 mutations in ovarian cancer patients in South-East Poland
Authors: Jasiewicz Andrzej , Rudnicka Helena , Kluźniak Wojciech , Gronwald Wojciech , Kluz Tomasz , Cybulski Cezary , Jakubowska Anna , Lubiński Jan , Gronwald Jacek
Published: April 2022

Background

Mutations in BRCA1 and BRCA2 genes are well-established risk factors of breast and ovarian cancer. In our former study, we observed that approximately 6% of unselected ovarian cancer patients in the region of Podkarpacie (South-East Poland) carry BRCA1 causative founder variants, which is significantly lower than in other regions of Poland. Therefore, it is deeply justified to do research based on the sequencing of whole BRCA1 and BRCA2 genes.

Methods

We examined 158 consecutive unselected cases of ovarian cancer patients from the region of Podkarpacie. We performed BRCA1 and BRCA2 genes Next-Generation Sequencing study in all cases.

Results

Altogether, in 18 of 158 (11.4%) ovarian cancer patients with BRCA1 or BRCA2 pathogenic mutations were found. BRCA1 pathogenic variants were detected in 11 of the 158 (7.0%) ovarian cancer cases. 10 of 11 (91%) detected BRCA1 mutations were founder mutations, detectable with the standard test used in Poland. BRCA2 pathogenic variants were found in 7 of the 158 (4.4%) cases. No BRCA2 pathogenic variants were founder mutations. The median age of patients at the diagnosis of the 18 hereditary ovarian cancers was 57.5 years.

Conclusions

The frequency of BRCA1 or BRCA2 gene mutation carriers among patients with ovarian cancer from the Podkarpacie region is comparable to other regions of Poland. However, a significantly higher percentage of BRCA2 gene mutations was observed, that were not detectable with a standard test for detection of founder mutations. Diagnostics based only on testing the BRCA1/2 Polish founder mutations is characterized by relatively low sensitivity in the case of ovarian cancer patients from South-East Poland and should be supplemented by NGS study, in particular of the BRCA2 gene.
Breast cancer metastasis to brain results in recruitment and activation of microglia through annexin-A1/formyl peptide receptor signaling
Authors: Foo Sok Lin , Sachaphibulkij Karishma , Lee Corinne L. Y. , Yap Gracemary L. R. , Cui Jianzhou , Arumugam Thiruma , Lim Lina H. K.
Published: April 2022

Background

Despite advancements in therapies, brain metastasis in patients with triple negative subtype of breast cancer remains a therapeutic challenge. Activated microglia are often observed in close proximity to, or within, malignant tumor masses, suggesting a critical role that microglia play in brain tumor progression. Annexin-A1 (ANXA1), a glucocorticoid-regulated protein with immune-regulatory properties, has been implicated in the growth and metastasis of many cancers. Its role in breast cancer-microglia signaling crosstalk is not known.

Methods

The importance of microglia proliferation and activation in breast cancer to brain metastasis was evaluated in MMTV-Wnt1 spontaneous mammary tumor mice and BALBc mice injected with 4T1 murine breast cancer cells into the carotid artery using flow cytometry. 4T1 induced-proliferation and migration of primary microglia and BV2 microglia cells were evaluated using 2D and coculture transwell assays. The requirement of ANXA1 in these functions was examined using a Crispr/Cas9 deletion mutant of ANXA1 in 4T1 breast cancer cells as well as BV2 microglia. Small molecule inhibition of the ANXA1 receptor FPR1 and FPR2 were also examined. The signaling pathways involved in these interactions were assessed using western blotting. The association between lymph node positive recurrence-free patient survival and distant metastasis-free patient survival and ANXA1 and FPR1 and FPR2 expression was examined using TCGA datasets.

Results

Microglia activation is observed prior to brain metastasis in MMTV-Wnt1 mice with primary and secondary metastasis in the periphery. Metastatic 4T1 mammary cancer cells secrete ANXA1 to promote microglial migration, which in turn, enhances tumor cell migration. Silencing of ANXA1 in 4T1 cells by Crispr/Cas9 deletion, or using inhibitors of FPR1 or FPR2 inhibits microglia migration and leads to reduced activation of STAT3. Finally, elevated ANXA1, FPR1 and FPR2 is significantly associated with poor outcome in lymph node positive patients, particularly, for distant metastasis free patient survival.

Conclusions

The present study uncovered a network encompassing autocrine/paracrine ANXA1 signaling between metastatic mammary cancer cells and microglia that drives microglial recruitment and activation. Inhibition of ANXA1 and/or its receptor may be therapeutically rewarding in the treatment of breast cancer and secondary metastasis to the brain.
TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation
Authors: Tolić Anja , Ravichandran Mirunalini , Rajić Jovana , Đorđević Marija , Đorđević Miloš , Dinić Svetlana , Grdović Nevena , Jovanović Jelena Arambašić , Mihailović Mirjana , Nestorović Nataša , Jurkowski Tomasz P. , Uskoković Aleksandra S. , Vidaković Melita S.
Published: April 2022

Background

Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA—the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP–TET interplay.

Results

Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo.

Conclusions

According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine.
Serum IGF-1 in patients with rheumatoid arthritis: correlation with disease activity
Authors: Lee Hanna , Suh Young Sun , Lee Sang-Il , Cheon Yun-Hong , Kim Mingyo , Noh Hae Sook , Kim Hyun-Ok
Published: April 2022

Objective

Insulin-like growth factor (IGF)-1 participates in modulating immunity and inflammation. Its bioactivity is controlled by six IGF-binding proteins (IGFBP-1 to IGFBP-6). In particular, the IGFBP-3 level is reportedly linked to the disease activity of rheumatoid arthritis (RA), consistent with our previous study. Therefore, the present study aimed to reproduce the previous results.

Results

The serum IGFBP-3 level was not significantly different among the three groups according to disease activity based on the DAS28-ESR/CRP (p > 0.05) but was significantly different between the low- and high-disease-activity groups based on the DAS28-CRP (p = 0.036). Meanwhile, the interleukin-6 (IL-6) level moderately correlated with DAS28-CRP (Spearman’s rho = 0.583,p < 0.001).
Reimagining peer review as an expert elicitation process
Authors: Marcoci Alexandru , Vercammen Ans , Bush Martin , Hamilton Daniel G. , Hanea Anca , Hemming Victoria , Wintle Bonnie C. , Burgman Mark , Fidler Fiona
Published: April 2022

Journal peer review regulates the flow of ideas through an academic discipline and thus has the power to shape what a research community knows, actively investigates, and recommends to policymakers and the wider public. We might assume that editors can identify the ‘best’ experts and rely on them for peer review. But decades of research on both expert decision-making and peer review suggests they cannot. In the absence of a clear criterion for demarcating reliable, insightful, and accurate expert assessors of research quality, the best safeguard against unwanted biases and uneven power distributions is to introduce greater transparency and structure into the process. This paper argues that peer review would therefore benefit from applying a series of evidence-based recommendations from the empirical literature on structured expert elicitation. We highlight individual and group characteristics that contribute to higher quality judgements, and elements of elicitation protocols that reduce bias, promote constructive discussion, and enable opinions to be objectively and transparently aggregated.