bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of morphine use in acute cardiogenic pulmonary oedema on mortality outcomes: a systematic review and meta-analysis
Authors: Witharana Thivanka N. , Baral Ranu , Vassiliou Vassilios S.
Published: March 2022

Background:

Morphine is commonly used in the management of acute cardiogenic pulmonary oedema. The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) do not recommend the routine use of opioids in acute heart failure (AHF) due to dose-dependent side effects. However, the effect of morphine remains unclear. Our study aims to investigate the link between morphine use in acute cardiogenic pulmonary oedema and mortality.

Methods:

PubMed and Embase databases were searched from inception to October 2021. All studies were included (randomized, non-randomized, observational, prospective and retrospective). The references for all the articles were reviewed for potential articles of interest with no language restrictions. Studies looking at in-hospital mortality along with other outcomes were chosen. The Newcastle–Ottawa scale was used to appraise the studies. Heterogeneity was assessed using I2. Meta-analysis was conducted using the Review Manager Software version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), by computing odds ratios (ORs) for pooled in-hospital mortality and clinical outcomes.

Results:

Six observational studies out of the 73 publications identified were eligible for the meta-analysis giving a total sample size of 152,859 (mean age 75, males 48%). Of these, four were retrospective analyses. The use of morphine in acute cardiogenic pulmonary oedema was associated with an increased rate of in-hospital mortality [OR = 2.39, confidence interval (CI) = 1.13 to 5.08, p = 0.02], increased need for invasive ventilation (OR = 6.14, CI = 5.84 to 6.46, p < 0.00001), increased need for non-invasive ventilation (OR = 1.85, CI = 1.45 to 2.36, p < 0.00001) and increased need for vasopressors/inotropes (OR = 2.93, CI = 2.20 to 3.89, p < 0.00001).

Conclusion:

Based on the observational studies, morphine use in acute cardiogenic pulmonary oedema is associated with worse outcomes. Further randomized controlled trials are needed to confirm any causative effect of morphine on mortality rates in acute cardiogenic pulmonary oedema.
Graft Choice for Anterior Cruciate Ligament Reconstruction in Women Aged 25 Years and Younger: A Systematic Review
Authors: Etzel Christine M. , Nadeem Maheen , Gao Burke , Boduch Abigail N. , Owens Brett D.
Published: March 2022

Context:

Although anterior cruciate ligament (ACL) tears are relatively common in athletic populations, few studies have systematically reviewed graft choice in young women.

Objective:

To quantitatively and qualitatively examine reported outcomes for graft choice in women aged 25 years and younger undergoing primary ACL reconstruction.

Data Source:

A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. An electronic search in the PubMed (includes MEDLINE) and EMBASE databases was completed using a combination of key terms.

Study Selection:

Studies were included if they reported graft choice outcomes in women aged 25 years and younger.

Study Design:

Systematic review.

Level of Evidence:

Level 4.

Data Extraction:

The following information was extracted: title, author, year of publication, number of female patients and age, graft type, follow-up, and patient-reported outcome measures. The following outcome scores were identified as being reported or not reported by each study: graft failure, contralateral ACL (CACL) rupture, IKDC (International Knee Documentation Committee), graft survival (Kaplan-Meier), Lysholm, Tegner, KT-1000, kneeling pain, return to sport, and Lachman.

Results:

Of 1170 identified articles, 16 met inclusion criteria, reporting on 1385 female patients aged 25 years and younger. Comparison of 655 bone–patellar tendon–bone (BPTB) versus 525 hamstring tendon (HT) autografts showed significant differences in mean failure rate between BPTB autografts (6.13% ± 2.58%) and HT autografts (17.35% ± 8.19%), P = 0.001. No statistically significant differences in CACL failure rates were found between BPTB autografts and HT autografts ( P = 0.25). Pooled results for IKDC were possible in 3 of the HT autograft studies, showing a mean score of 88.31 (95% CI 83.53-93.08). Pooled Lysholm score results were possible in 2 of the HT autograft studies, showing a mean score of 93.46 (95% CI 91.90-95.01).

Conclusion:

In female patients aged 25 years and younger, BPTB autografts showed significantly less graft failure compared with HT autografts. However, BPTB autografts had comparable patient-reported outcomes compared with HT autografts with the available data. The overall state of evidence for graft choice in female patients aged 25 years and younger is low. Future studies should report statistics by age and sex to allow for further analysis of graft choice for this specific population that is known to be more vulnerable to ACL injury.
Contrast With Compression Therapy Enhances Muscle Function Recovery and Attenuates Glycogen Disruption After Exercise
Authors: Colantuono Vincent M. , Oakley Ryan , Hatfield Disa L. , Penailillo Luis , Lateef Shabnam , Earp Jacob E.
Published: March 2022

Background:

Exercise-associated muscle damage (EAMD) temporally impairs muscle function and intramuscular glycogen storage. Contrast with compression (CwC) therapy provides localized EAMD treatment with minimal changes in core/tissue temperature that can impair glycogen resynthesis.

Hypothesis:

CwC will enhance the recovery of strength, power, and joint mobility, reduce markers of EAMD, and attenuate the disruption of glycogen storage observed after damaging exercise.

Study Design:

Randomized controlled trial with crossover design.

Level of Evidence:

Level 2.

Methods:

Ten men completed 2 bouts of eccentric elbow flexor exercise, separated by 1 week, using contralateral arms. After each bout, participants received either CwC therapy (at 0, 24, and 48 h postexercise) or no therapy with intervention order and limb randomly assigned. Prior to (pre-exercise) and 1, 24, 48, and 72 h after each exercise bout, muscular strength, muscular power, intramuscular glycogen, creatine kinase, muscle thickness, muscle soreness, pressure pain threshold, active elbow flexion, passive elbow extension, and dietary intake were assessed. Comparisons were made between conditions over time (interaction effects) using separate repeated-measures analyses of variance/multivariate analyses of variance and effect sizes (Cohen d) to describe treatment effect at each time point.

Results:

Significant interaction effects were observed for muscular strength ( d = 0.67-1.12), muscular power ( d = 0.20-0.65), intramuscular glycogen ( d = 0.29-0.81), creatine kinase ( d = 0.01-0.96), muscle thickness ( d = 0.35-0.70), muscle soreness ( d = 0.18-0.85), and active elbow flexion ( d = 0.65-1.17) indicating a beneficial effect of CwC over time ( P ≤ 0.05). In contrast, no significant interaction effect was observed for pressure pain threshold or passive elbow extension ( P > 0.05).

Conclusion:

These results support the use of CwC for the recovery of muscle function after damaging exercise in male patients and indicate that CwC attenuates, but does not remove, the disruption of intramuscular glycogen stores observed after intense eccentric exercise.

Clinical Relevance:

Glycolysis-dependent athletes may benefit from CwC therapy after training/competition that causes EAMD.
Polymorphous low-grade neuroepithelial tumor of the young: Rare tumor and review of the literature
Authors: Palejwala Ali H , O’Neal Christen M , Quinton Michael R , Battiste James D , Peterson Jo Elle G , Dunn Ian F
Published: March 2022

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described low-grade neuroepithelial tumor with an infiltrative growth pattern and oligodendrocyte-like cells that are CD34 immunopositive. Correlating histology and results from molecular testing is critical to correctly diagnosing PLNTY, as its histologic appearance is similar to oligodendrogliomas and shares genetic abnormalities common to other low-grade epilepsy associated tumors (LEATs). In this case report, we describe a 31-year-old female with intractable epilepsy found to have a temporal mass and diagnosed with PLNTY after histopathologic and molecular testing. We describe the radiographic, histologic, and genetic features in relation to the epileptic and oncologic outcomes for this patient. Then, we compare these features and outcomes to other cases of PLNTY described in the literature.
Conspiratorial thinking in the Latino community on the 2020 election
Authors: Cortina Jeronimo , Rottinghaus Brandon
Published: March 2022

Political knowledge is the cornerstone of a functional representative democracy, but belief in conspiracy theories disrupts that connection and may be dangerous with consequences for democracy. Pundits and politicians have speculated about the cause and effect of misinformation and conspiracy theories, but no work has examined what causes beliefs in conspiracy theories or misinformation among Latinos specifically. In a unique survey of Texas Latinos prior to the 2020 election, we find belief in conspiracy theories is most related to support for Donald Trump and greater reliance on Spanish-language media and social media. The results highlight how conspiratorial thinking manifests in specific ethnic groups and the need to counter those beliefs in Spanish-language media.
Leveraging online shopping behaviors as a proxy for personal lifestyle choices: New insights into chronic disease prevention literacy
Authors: Wang Yongzhen , Liu Xiaozhong , Börner Katy , Lin Jun , Ju Yingnan , Sun Changlong , Si Luo
Published: March 2022

Objective

Ubiquitous internet access is reshaping the way we live, but it is accompanied by unprecedented challenges in preventing chronic diseases that are usually planted by long exposure to unhealthy lifestyles. This paper proposes leveraging online shopping behaviors as a proxy for personal lifestyle choices to improve chronic disease prevention literacy, targeted for times when e-commerce user experience has been assimilated into most people's everyday lives.

Methods

Longitudinal query logs and purchase records from 15 million online shoppers were accessed, constructing a broad spectrum of lifestyle features covering various product categories and buyer personas. Using the lifestyle-related information preceding online shoppers’ first purchases of specific prescription drugs, we could determine associations between their past lifestyle choices and whether they suffered from a particular chronic disease.

Results

Novel lifestyle risk factors were discovered in two exemplars—depression and type 2 diabetes, most of which showed reasonable consistency with existing healthcare knowledge. Further, such empirical findings could be adopted to locate online shoppers at higher risk of these chronic diseases with decent accuracy [i.e. (area under the receiver operating characteristic curve) AUC=0.68 for depression and AUC=0.70 for type 2 diabetes], closely matching the performance of screening surveys benchmarked against medical diagnosis.

Conclusions

Mining online shopping behaviors can point medical experts to a series of lifestyle issues associated with chronic diseases that are less explored to date. Hopefully, unobtrusive chronic disease surveillance via e-commerce sites can grant consenting individuals a privilege to be connected more readily with the medical profession and sophistication.
COVID-19-Associated Ischemic Colitis: A Rare Manifestation of COVID-19 Infection—Case Report and Review
Authors: Uhlenhopp Dustin J. , Ramachandran Rajarajeshwari , Then Eric , Parvataneni Swetha , Grantham Tyler , Gaduputi Vinaya
Published: March 2022

Following the first report of COVID-19 infection in December 2019 as a respiratory illness, it has proven to be a multisystem disease. There are few reported cases of ischemic colitis with COVID-19 infection in the medical literature to date and we have limited understanding of its pathophysiology. We report 2 cases of ischemic colitis as the only manifestation of COVID-19. In addition, we review the current limited literature regarding COVID-19-associated ischemic colitis.
Building Families Through Healthcare: Experiences of Lesbians Using Reproductive Services
Authors: Gregory Kelly B , Mielke John G , Neiterman Elena
Published: March 2022

The use of assisted human reproduction (AHR) represents a meaningful and important life event for lesbians wishing to create biologically related families. Despite increasing numbers of lesbians utilizing AHR services, barriers to access persist. This qualitative study investigated the experiences of lesbians and their interactions with reproductive services in Ontario, Canada, where limited public funding is available for all AHR patients and where the lesbian, gay, bisexual, transgender, and queer (LGBTQ) community makes up to 30% of clientele. Eleven semi-structured interviews were conducted, and findings revealed a wide range of experiences. Lesbian patients expressed a desire for more support from their care providers in navigating a complex and costly medical journey through a system largely designed for the needs of heterosexual patients. Additionally, private fertility clinics, as the environment for accessing publicly funded services, were felt to contribute pressure to pay out-of-pocket for add-on medical procedures. To improve the quality of care, participants recommended providing more high-level information on the medical journey and taking an individual approach with lesbian patients, in particular, assuming a patient has sufficient fertility until proven otherwise.
Social and Religious Inculturation of Health Care in the Roman Catholic Mission in Georgia
Authors: Chkuaseli Ana
Published: March 2022

This article examines the social and religious aspects of medical activities conducted by Roman Catholic missionaries in Georgia from the seventeenth century. The writings of Cristoforo di Castelli, Giudice di Milano, and Arcangelo Lamberti and a Georgian-Italian bilingual manuscript “Glossary of Medicinal Plants” have been analyzed to determine the theoretical and practical issues related to missionary activities. This article shows to what extent the missionaries acquired and applied Georgian traditional medical knowledge and which processes of inculturation they triggered. Research has shown that the development of Georgian medicine was influenced by a synthesis of indigenous and Western medical practices.
Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study
Authors: Albert Michael H. , Sirait Tiarlan , Eikema Dirk-Jan , Bakunina Katerina , Wehr Claudia , Suarez Felipe , Fox Maria Laura , Mahlaoui Nizar , Gennery Andrew R. , Lankester Arjan C. , Beier Rita , Bernardo Maria Ester , Bigley Venetia , Lindemans Caroline A. , Burns Siobhan O. , Carpenter Ben , Dybko Jaroslaw , Güngör Tayfun , Hauck Fabian , Lum Su Han , Balashov Dmitry , Meisel Roland , Moshous Despina , Schulz Ansgar , Speckmann Carsten , Slatter Mary A. , Strahm Brigitte , Uckan-Cetinkaya Duygu , Meyts Isabelle , Vallée Tanja C. , Wynn Robert , Neven Bénédicte , Morris Emma C. , Aiuti Alessandro , Maschan Alexei , Aljurf Mahmoud , Gedde-Dahl Tobias , Gurman Gunhan , Bordon Victoria , Kriván Gergely , Locatelli Franco , Porta Fulvio , Valcárcel David , Beguin Yves , Faraci Maura , Kröger Nicolaus , Kulagin Aleksandr , Shaw Peter J. , Veelken Joan Hendrik , Diaz de Heredia Cristina , Fagioli Franca , Felber Matthias , Gruhn Bernd , Holter Wolfgang , Rössig Claudia , Sedlacek Petr , Apperley Jane , Ayas Mouhab , Bodova Ivana , Choi Goda , Cornelissen J.J. , Sirvent Anne , Khan Anjum , Kupesiz Alphan , Lenhoff Stig , Ozdogu Hakan , von der Weid Nicolas , Rovira Montserrat , Schots Rik , Vinh Donald C.
Published: March 2022

Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT.
miR390 family of Cymbidium goeringii is involved in the development of reproductive organs in transgenic Arabidopsis
Authors: Xu Zihan , Liu Qian , Chen Yue , He Yuanhao , Hu Fengrong
Published: March 2022

Background

miR390s is an ancient family with a high level of conservation among plant miRNAs. Through the auxin signal transduction pathway, miR390 participates in diverse biological processes of plant growth and development. As an important Chinese traditional orchid, Cymbidium goeringii has unique flower shape and elegant fragrance. But its development has been greatly restricted because of the low flower bud differentiation and the difficult reproduction. This study aims to provide guidance for the role of cgo-miR390 in reproductive organ development to enhance the ornamental and economic value of Cymbidium.

Results

MIR390a, MIR390b and MIR390c of C. goeringii were cloned, and their length ranged from 130 to 150 nt. Each precursor sequence of cgo-miR390 contains 2 to 3 mature miRNAs. Three kinds of cgo-miR390s displayed distinct temporal and spatial expression patterns during floral development in C. goeringii. The overexpression of MIR390s alters morphology and function of stamens and pistils in Arabidopsis, such as enlargement of anther aspect ratio and separation of stylar and stigmas, which affects the development of fruits and seeds. In particular, the pollen amount decreased and the seed abortion rate increased in cgo-MIR390c-overexpressed plants.

Conclusions

cgo-miR390 family affected the development of reproductive organs in transgenic Arabidopsis. The study provides references for the genetic improvement for orchid with potentially great economic benefit.
Information exchange networks for chronic diseases in primary care practices in Germany: a cross-sectional study
Authors: Arnold Christine , Hennrich Patrick , Wensing Michel
Published: March 2022

Background

Coordination of care requires information exchange between health workers. The structure of their information exchange networks may influence the quality and efficiency of healthcare delivery. The aim of this study was to explore and classify information exchange networks in primary care for patients with chronic diseases in Germany.

Methods

A cross-sectional study was carried out between 2019 and 2021. As part of a larger project on coordination of care, this study focused on information exchange in practice teams regarding patients with type 2 diabetes (DM), coronary heart disease (CHD) and chronic heart failure (CHF). Social network analysis was applied to determine the number of connections, density and centralization for each of the health conditions for each of the practices. On the basis of the descriptive findings, we developed typologies of information exchange networks in primary care practices.

Results

We included 153 health workers from 40 practices, of which 25 practices were included in the social network analysis. Four types of information exchange structures were identified for the three chronic diseases: highly connected networks with low hierarchy, medium connected networks with medium hierarchy, medium connected networks with low hierarchy and lowly connected networks. Highly connected networks with low hierarchy were identified most frequently (18 networks for DM, 17 for CHD and 14 for CHF). Of the three chronic conditions, information sharing about patients with DM involved the most team members. Information exchange outside the family practice took place mainly with nurses and pharmacists.

Conclusions

This study identified four types of information exchange structures, which provides a practical tool for management and improvement in primary care. Some practices had few information transfer connections and could hardly be considered a network.

Trial registration

We registered the study prospectively on 7 November 2019 at the German Clinical Trials Register (DRKS, www.drks.de) under ID no. DRKS00019219.
A prenatal standard for fetal weight improves the prenatal diagnosis of small for gestational age fetuses in pregnancies at increased risk
Authors: Visentin Silvia , Londero Ambrogio P. , Cataneo Ilaria , Bellussi Federica , Salsi Ginevra , Pilu Gianluigi , Cosmi Erich
Published: March 2022

Objective

Our aim was to assess diagnostic accuracy in the prediction of small for gestational age (SGA <10th centile) and fetal growth restricted (FGR) (SGA <3rd centile) fetuses using three different sonographic methods in pregnancies at increased risk of fetal growth restriction: 1) fetal abdominal circumference (AC) z-scores, 2) estimated fetal weight (EFW) z-scores according to postnatal reference standard; 3) EFW z-scores according to a prenatal reference standard.

Methods

Singleton pregnancies at increased risk of fetal growth restriction seen in two university hospitals between 2014 and 2015 were studied retrospectively. EFW was calculated using formulas proposed by the INTERGROWTH-21st project and Hadlock; data derived from publications by the INTEGROWTH-twenty-first century project and Hadlock were used to calculate z-scores (AC and EFW). The accuracy of different methods was calculated and compared.

Results

The study group included 406 patients. Prenatal standard EFW z-scores derived from INTERGROWTH-21st project and Hadlock and co-workers performed similarly and were more accurate in identifying SGA infants than using AC z-scores or a postnatal reference standard. The subgroups analysis demonstrated that EFW prenatal standard was more or similarly accurate compared to other methods across all subgroups, defined by gestational age and birth weight.

Conclusions

Prenatal standard EFW z-scores derived from either INTERGROWTH-21 st project or Hadlock and co-workers publications demonstrated a statistically significant advantage over other biometric methods in the diagnosis of SGA fetuses.
Mixed effect analysis of factors influencing the use of insecticides treated bed nets among pregnant women in Ghana: evidence from the 2019 Malaria Indicator Survey
Authors: Klu Desmond , Aberese-Ako Matilda , Manyeh Alfred Kwesi , Immurana Mustapha , Doegah Phidelia , Dalaba Maxwell , Acquah Evelyn , Alhassan Robert Kaba , Ansah Evelyn Korkor
Published: March 2022

Background

Malaria during pregnancy is a major cause of maternal morbidity globally and leads to poor birth outcomes. The World Health Organization has recommended the use of insecticide treated bed nets (ITN) as one of the effective malaria preventive strategies among pregnant women in malaria endemic areas. This study, therefore, seeks to examine the individual and household factors associated with the use of ITNs among pregnant women in Ghana.

Methods

Data for this study was obtained from the 2019 Ghana Malaria Indicator Survey (GMIS) conducted between September 25 and November 24, 2019. The weighted sample comprised 353 pregnant women aged 15–49 years. Data was analyzed with SPSS version 22 using both descriptive and multilevel logistics regression modelling. Statistically significant level was set at p < 0.05.

Results

The study found that 49.2% of pregnant women in Ghana use ITN to prevent malaria. Pregnant women aged 35–49 years (AOR = 3.403, CI: 1.191–9.725), those with no formal education (AOR = 5.585, CI = 1.315–23.716), and those who had secondary education (AOR = 3.509, CI = 1.076–11.440) had higher odds of using ITN. Similarly, higher odds of ITN usage was found among who belonged to the Akan ethnic group (AOR = 7.234, CI = 1.497–34.955), dwell in male-headed households (AOR = 2.232, CI = 1.105–4.508) and those whose household heads are aged 60–69 years (AOR = 4.303, CI = 1.160–15.966). However, pregnant women who resided in urban areas (AOR = 0.355, CI = 0.216–0.582), those whose household heads aged 40–49 years (AOR = 0.175, CI = 0.066–0.467) and those who belonged to richer (AOR =0.184, CI = 0.050–0.679) and richest (AOR = 0.107, CI = 0.021–0.552) households had lower odds of using ITN for malaria prevention.

Conclusions

Individual socio-demographic and household factors such as pregnant women’s age, educational level, place of residence, ethnicity, sex and age of household head, and household wealth quintile are associated with the use of ITN for malaria prevention among pregnant women. These factors ought to be considered in strengthening malaria prevention campaigns and develop new interventions to help increase ITN utilization among vulnerable population living in malaria- endemic areas.
Hsa-miR-181a-5p, hsa-miR-182-5p, and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors at the molecular response
Authors: Mohd Yacob Aliza , Muhamad Nor Asiah , Chang Kian Meng , Akmal Hisham Hamidah , Mat Yusoff Yuslina , Ibrahim Latifah
Published: March 2022

Background

Tyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukemia (CML) show a high success rate. However, a low number of patients with long-term treatment-free remission (TFR) were observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months, with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranting new biomarkers for CML.

Methods

Next Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at the molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real-time RT-qPCR in triplicate.

Results

Hsa-miR-181a-5p was expressed significantly (p-value< 0.05) with 2.14 and 2.33-fold down-regulation in both patient groups, respectively meanwhile hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation. The down-regulation was consistent with decreased amounts of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with the substantial presence of BCR-ABL1 in CML patients treated with TKIs at the molecular response.

Conclusions

Therefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.
The impact of neurological performance and volumetrics on overall survival in brain metastasis in colorectal cancer: a retrospective single-center case series
Authors: Sander Caroline , Frydrychowicz Clara , Prasse Gordian , Taubenheim Sabine , Arlt Felix , Meixensberger Jürgen , Fehrenbach Michael Karl
Published: March 2022

Background

Brain metastasis (BM) of colorectal cancer is a disease with a poor prognosis of only a few months survival. However, it is difficult to estimate the individual prognosis of each patient due to the lack of definitive prognosis parameters. The number of metastases and the Karnofsky performance score are known predictors for survival. We investigated whether or not the neurological performance score and the tumor volumetrics are equally suitable predictors for survival.

Design

All patients with histologically diagnosed BM linked to colorectal cancer between 2012 and March 2020 were reviewed. The Medical Research Council Neurological Performance Score was used to quantify neurological performance. Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression.

Results

Twenty-five patients were included in our analysis with an overall survival of 4.9 months after surgery of the BM. Survival decreased in the univariate analysis with increasing postoperative neurological performance score, low Karnofsky performance score, absence of radiation therapy and radiation therapy modality. The neurological performance score is a reliable scoring parameter for estimating the prognostic course analogous to the Karnofsky performance score. Neither preoperative nor post resection residual tumor volume had any impact on overall survival in our small cohort.

Conclusion

Our data suggest that the postoperative neurological performance is a valuable prognostic factor for colorectal cancer patients with BM. Tumor volumetrics show no correlation to survival. Further investigations with a larger number of cases are mandatory.
Novel biallelic USH2A variants in a patient with usher syndrome type IIA- a case report
Authors: Young Su Ling , Stanton Chloe M. , Livesey Benjamin J. , Marsh Joseph A. , Cackett Peter D.
Published: March 2022

Background

Usher Syndrome is the commonest cause of inherited blindness and deafness. The condition is clinically and genetically heterogeneous, with no current treatment. We report a case carrying novel biallelic variants in USH2A causing progressive early adolescent onset visual and hearing impairment consistent with Usher Syndrome Type IIA.

Case presentation

Our patient presented at age 13 with progressive visual field loss and hearing loss, associated with early onset of cataract in her 40s requiring lens extraction. Now 52 years old, latest best corrected visual acuity (BCVA) stands at Logmar Right Eye (RE) 0.8 and Left Eye (LE) 0.2, with significantly constricted visual fields bilaterally. She was registered partially sighted age 46. Clinical and molecular genetic assessment of the proband was consistent with a diagnosis of Usher Syndrome Type IIA. Genetic testing identified two novel USH2A variants, resulting in the premature termination codon p.Leu30Ter and a missense mutation p.Cys3251Tyr. Segregation analysis confirmed that these variants were biallelic in the affected case. Comprehensive in silico analysis confirmed that these mutations are the probable cause of Usher Syndrome Type IIA in this individual.

Conclusions

The identification of novel mutations in USH2A increases the spectrum of genetic variations that lead to Usher Syndrome, aiding genetic diagnosis, assessment of patient prognosis, and emphasising the importance of genetic testing to identify new mutations in patients with undiagnosed progressive visual loss.
Diagnosis of lung squamous cell carcinoma based on metagenomic Next-Generation Sequencing
Authors: Wei Ping , Gao Yang , Zhang Jing , Lin Jianlong , Liu Huibin , Chen Keqiang , Lin Weikai , Wang Xiaojia , Wang Chune , Liu Chao
Published: March 2022

Background

The clinical treatment of patients suspected of pulmonary infections often rely on empirical antibiotics. However, preliminary diagnoses were based on clinical manifestations and conventional microbiological tests, which could later be proved wrong. In this case, we presented a patient whose initial diagnosis was lung abscess, but antibiotic treatments had no effect, and metagenomic Next-Generation Sequencing (mNGS) indicated presence of neoplasm.

Case presentation

A 62-year-old female was diagnosed with lung abscess at three different health facilities. However, mNGS of bronchoalveolar lavage fluid did not support pulmonary infections. Rather, the copy number variation analysis using host DNA sequences suggested neoplasm. Using H&E staining and immunohistochemistry of lung biopsy, the patient was eventually diagnosed with lung squamous cell carcinoma.

Conclusions

mNGS not only detects pathogens and helps diagnose infectious diseases, but also has potential in detecting neoplasm via host chromosomal copy number analysis. This might be beneficial for febrile patients with unknown or complex etiology, especially when infectious diseases were initially suspected but empirical antibiotic regimen failed.
Serum D-lactate, a novel serological biomarker, is promising for the diagnosis of periprosthetic joint infection
Authors: Chen Yanyang , Wang Huhu , Chen Xiyao , Ma Hairong , Zheng Jingjie , Cao Li
Published: March 2022

Background

Although many markers are used for diagnosis of periprosthetic joint infection (PJI), serological screening and diagnosis for PJI are still challenging. We evaluated the performance of serum D-lactate and compared it with ESR, coagulation-related biomarkers and synovial D-lactate for the diagnosis of PJI.

Methods

Consecutive patients with preoperative blood and intraoperative joint aspiration of a prosthetic hip or knee joint before revision arthroplasty were prospectively included. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society, and the diagnostic values of markers were estimated based on receiver operating characteristic (ROC) curves by maximizing sensitivity and specificity using optimal cutoff values.

Results

Of 52 patients, 26 (50%) were diagnosed with PJI, and 26 (50%) were diagnosed with aseptic failure. ROC curves showed that serum D-lactate, fibrinogen (FIB) and ESR had equal areas under the curve (AUCs) of 0.80, followed by D-dimer and fibrin degradation product, which had AUCs of 0.67 and 0.69, respectively. Serum D-lactate had the highest sensitivity of 88.46% at the optimal threshold of 1.14 mmol/L, followed by FIB and ESR, with sensitivities of 80.77% and 73.08%, respectively, while there were no significant differences in specificity (73.08%, 73.08% and 76.92%, respectively).

Conclusion

Serum D-lactate showed similar performance to FIB and ESR for diagnosis of PJI. The advantages of serum D-lactate are pathogen-specific, highly sensitive, minimally invasive and rapidly available making serum D-lactate useful as a point-of-care screening test for PJI.
Does ultrasound education improve anatomy learning? Effects of the Parallel Ultrasound Hands-on (PUSH) undergraduate medicine course
Authors: Chen Wei-Ting , Kang Yi-No , Wang Ting-Cheng , Lin Che-Wei , Cheng Chung-Yi , Suk Fat-Moon , Hsu Chin-Wang , Huang Sha-Ku , Huang Wen-Cheng
Published: March 2022

Background

As ultrasound has become increasingly prominent in medicine, portable ultrasound is perceived as the visual stethoscope of the twenty-first century. Many studies have shown that exposing preclinical students to ultrasound training can increase their motivation and ultrasound competency. However, few studies have discussed the effect of ultrasound training on anatomy learning.

Method

The Parallel Ultrasound Hands-on (PUSH) course was designed to investigate whether or not ultrasonography training affects anatomy knowledge acquisition. The PUSH course included anatomical structures located in the chest and abdomen (target anatomy) and was conducted in parallel to the compulsory gross anatomy course.

Learners (n = 140) voluntarily participated in this elective course (learners in the course before the midterm examination (Group 1, n = 69), or after the midterm examination (Group 2, n = 71)). Anatomy examination scores (written and laboratory tests) were utilized to compare the effects of the PUSH course.

Result

Group 1 obtained significantly higher written test scores on the midterm examination (mean difference [MD] = 1.5(7.6%), P = 0.014, Cohen’s d = 0.43). There was no significant difference in the final examination scores between the two groups (Written Test: MD = 0.3(1.6%), P = 0.472). In Laboratory test, both mid-term (MD:0.7(2.8%), P = 0.308) and final examination (MD:0.3(1.5%), P = 0.592) showed no significant difference between two groups. Students provided positive feedback in overall learning self-efficacy after the PUSH course (Mean = 3.68, SD = ±0.56 on a 5-point Likert scale). Learning self-efficacy in the cognitive domain was significantly higher than that in the affective domain (MD = 0.58; P < 0.001) and psychomotor domain (MD = 0.12; P = 0.011).

Conclusion

The PUSH course featured a hands-on learning design that empowered medical students to improve their anatomy learning.
BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1
Authors: Wang Qiang , Wu Yinghui , Lin Meng , Wang Gaigai , Liu Jinyan , Xie Min , Zheng Bo , Shen Cong , Shen Jun
Published: March 2022

Background

Osteosarcoma (OS) is the most common malignant tumor of bone, and the clinical efficacy of current treatments and associated survival rates need to be further improved by employing novel therapeutic strategies. Although various studies have shown that BMI1 protein is universally upregulated in OS cells and tissues, its specific role and underlying mechanism have not yet been fully explored.

Methods

Expression of BMI1 protein in OS cells was detected by western blot. The effect of BMI1 on proliferation and migration of OS cells (143B and U-2OS cell lines) was investigated in vitro using CCK-8, colony formation and transwell assays, and in vivo using subcutaneous tumorigenesis and lung metastasis assays in xenograft nude mice. Expression of epithelial–mesenchymal transition (EMT)-associated proteins was detected by immunofluorescence imaging. Bioinformatic analysis was performed using ENCODE databases to predict downstream targets of BMI1. SIK1 mRNA expression in osteosarcoma cells was detected by quantitative real-time reverse transcription PCR (qPCR). Chromatin immunoprecipitation-qPCR (ChIP-qPCR) was used to investigate expression of BMI1-associated, RING1B-associated, H2AK119ub-associated and H3K4me3-associated DNA at the putative binding region of BMI1 on the SIK1 promoter in OS cells.

Results

Using both in vitro and in vivo experimental approaches, we found that BMI1 promotes OS cell proliferation and metastasis. The tumor suppressor SIK1 was identified as the direct target gene of BMI1 in OS cells. In vitro experiments demonstrated that SIK1 could inhibit proliferation and migration of OS cells. Inhibition of SIK1 largely rescued the altered phenotypes of BMI1-deficient OS cells. Mechanistically, we demonstrated that BMI1 directly binds to the promoter region of SIK1 in a complex with RING1B to promote monoubiquitination of histone H2A at lysine 119 (H2AK119ub) and inhibit H3K4 trimethylation (H3K4me3), resulting in inhibition of SIK1 transcription. We therefore suggest that BMI1 promotes OS cell proliferation and metastasis by inhibiting SIK1.

Conclusions

Our results reveal a novel molecular mechanism of OS development promoted by BMI1 and provides a new potential target for OS treatment.
How to make healthy early childhood development more likely in marginalized Roma communities: a concept mapping approach
Authors: Chovan Shoshana , Filakovska Bobakova Daniela , Bosakova Lucia , Madarasova Geckova Andrea , Reijneveld Sijmen A. , de Kroon Marlou L. A.
Published: March 2022

Background

This study aims to assess which measures could improve the healthy early childhood development of children from marginalized Roma communities and to identify priority measures.

Methods

Concept mapping approach was used, using mixed methods. In total 54 professionals, including social workers, educators, health care providers, municipality representatives, and project managers participated in our study.

Results

Four distinct clusters of measures targeting living conditions, public resources, healthcare and community interventions, and 27 individual priority measures of highest urgency and feasibility were identified. The cluster ‘Targeting living conditions’, was rated as the most urgent but least feasible, whereas the cluster ‘Targeting health care’, was considered least urgent but most feasible. Among the 27 priority measures, ‘Planning parenthood’ and ‘Scaling up existing projects’ had the highest priority.

Conclusion

Our results reflect the public and political discourse and indicate significant barriers to implementation. Reducing inequalities in early childhood needs to be addressed through coordinated efforts.
Chicago sky blue 6B inhibits α-synuclein aggregation and propagation
Authors: Min Joo-Ok , Strohäker Timo , Jeong Byung-Chul , Zweckstetter Markus , Lee Seung-Jae
Published: March 2022

Abnormal deposition of α-synuclein aggregates in Lewy bodies and Lewy neurites is the hallmark lesion in Parkinson’s disease (PD). These aggregates, thought to be the culprit of disease pathogenesis, spread throughout the brain as the disease progresses. Agents that inhibit α-synuclein aggregation and/or spread of aggregates would thus be candidate disease-modifying drugs. Here, we found that Chicago sky blue 6B (CSB) may be such a drug, showing that it inhibits α-synuclein aggregation and cell-to-cell propagation in both in vitro and in vivo models of synucleinopathy. CSB inhibited the fibrillation of α-synuclein in a concentration-dependent manner through direct binding to the N-terminus of α-synuclein. Furthermore, both seeded polymerization and cell-to-cell propagation of α-synuclein were inhibited by CSB treatment. Notably, CSB alleviated behavioral deficits and neuropathological features, such as phospho-α-synuclein and astrogliosis, in A53T α-synuclein transgenic mice. These results indicate that CSB directly binds α-synuclein and inhibits its aggregation, thereby blocking α-synuclein cell-to-cell propagation.
Anti-tumor activity of cetuximab plus avelumab in non-small cell lung cancer patients involves innate immunity activation: findings from the CAVE-Lung trial
Authors: Della Corte Carminia Maria , Fasano Morena , Ciaramella Vincenza , Cimmino Flora , Cardnell Robert , Gay Carl M. , Ramkumar Kavya , Diao Lixia , Di Liello Raimondo , Viscardi Giuseppe , Famiglietti Vincenzo , Ciardiello Davide , Martini Giulia , Napolitano Stefania , Tuccillo Concetta , Troiani Teresa , Martinelli Erika , Wang Jing , Byers Lauren , Morgillo Floriana , Ciardiello Fortunato
Published: March 2022

Background

We recently conducted Cetuximab-AVElumab-Lung (CAVE-Lung), a proof-of-concept, translational and clinical trial, to evaluate the combination of two IgG1 monoclonal antibodies (mAb): avelumab, an anti-PD-L1 drug, and cetuximab, an anti-epidermal growth factor receptor (EGFR) drug, as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients. We have reported clinically relevant anti-tumor activity in 6/16 patients. Clinical benefit was accompanied by Natural Killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC). Among the 6 responding patients, 3 had progressed after initial response to a previous treatment with single agent anti-PD-1, nivolumab or pembrolizumab.

Methods

We report long-term clinical follow-up and additional findings on the anti-tumor activity and on the immune effects of cetuximab plus avelumab treatment for these 3 patients.

Results

As of November 30, 2021, 2/3 patients were alive. One patient was still on treatment from 34 months, while the other two patients had progression free survival (PFS) of 15 and 19 months, respectively. Analysis of serially collected peripheral blood mononuclear cells (PBMC) revealed long-term activation of NK cell-mediated ADCC. Comprehensive genomic profile analysis found somatic mutations and germline rare variants in DNA damage response (DDR) genes. Furthermore, by transcriptomic analysis of The Cancer Genome Atlas (TCGA) dataset we found that DDR mutant NSCLC displayed high STING pathway gene expression. In NSCLC patient-derived three-dimensional in vitro spheroid cultures, cetuximab plus avelumab treatment induced additive cancer cell growth inhibition as compared to single agent treatment. This effect was partially blocked by treatment with an anti-CD16 mAb, suggesting a direct involvement of NK cell activation. Furthermore, cetuximab plus avelumab treatment induced 10-, 20-, and 20-fold increase, respectively, in the gene expression of CCL5 and CXCL10, two STING downstream effector cytokines, and of interferon β, as compared to untreated control samples.

Conclusions

DDR mutations may contribute to DDR-induced STING pathway with sustained innate immunity activation following cetuximab plus avelumab combination in previously treated, PD-1 inhibitor responsive NSCLC patients.
PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p
Authors: Zhang Ying , Chen Chuangzhen , Liu Zhaoyong , Guo Huancheng , Lu Weiqing , Hu Wang , Lin Zhixiong
Published: March 2022

Background

Emerging evidence has demonstrated that RNA-binding protein dysregulation is involved in esophageal squamous cell carcinoma (ESCC) progression. However, the role of poly (A) binding protein cytoplasmic 1 (PABPC1) in ESCC is unclear. We therefore aimed to explore the functions and potential mechanisms of PABPC1 in ESCC progression.

Methods

PABPC1 expression was characterized using immunohistochemistry and qRT-PCR in ESCC tissues and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to detect histone acetylation in the promoter region of PABPC1. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of PABPC1 in ESCC angiogenesis and malignant procession.

Results

PABPC1 expression was upregulated in ESCC tissues compared with in normal esophageal epithelial tissues. Elevated PABPC1 expression was correlated with tumor cell differentiation and poor prognosis in patients. Sp1 and p300 cooperated to increase the level of H2K37ac in the PABPC1 promoter. Functionally, PABPC1 overexpression enhanced esophageal squamous cell proliferation and invasion by activating the IFN/IFI27 signaling pathway. PABPC1 interacted with eIF4G to increase the stability of IFI27 mRNA by competing with RNA exosomes in ESCC. Furthermore, PABPC1/IFI27 could increase miR-21-5p expression to enable exosomal delivery of miR-21-5p to human umbilical vein endothelial cells to increase angiogenesis via inhibiting CXCL10.

Conclusion

PABPC1 plays a critical role in ESCC malignant progression by interacting with eIF4G to regulate IFI27 mRNA stability and promote angiogenesis via exosomal miR-21-5p/CXCL10. Taken together, our results suggest that PABPC1 is a promising therapeutic target for ESCC.