bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation strategies for the patient safety reporting system using Consolidated Framework for Implementation Research: a retrospective mixed-method analysis
Authors: Koike Daisuke , Ito Masahiro , Horiguchi Akihiko , Yatsuya Hiroshi , Ota Atsuhiko
Published: March 2022

Background

Healthcare-related adverse events occur because of complex healthcare systems. The patient safety reporting system is a core component of patient safety initiatives in hospitals. However, hospital management often encounters a cultural barrier with its implementation and struggles to overcome the same. Implementation science would be useful for analysing implementation strategies. This study determines the effects of the implemented strategy on an increase in the number of patient safety reports and the determinants of successful implementation, using the implementation framework.

Methods

Mixed method analysis was performed in Fujita Health University Hospital (FHUH), a large volume hospital in Japan. We identified strategies to implement the patient safety reporting system by scrutinising internal documents using the Consolidated Framework for Implementation Research (CFIR). The electronic reporting systems developed in 2004 in the FHUH and the number of reports were analysed using the staff data and hospital volumes.

Results

Reports (n = 110,058) issued between April 2004 and March 2020 were analysed. The number of reports increased from 2004 to 2008 and from 2013 to 2019, reaching 14,037 reports per year. Between 2009 and 2012, the FHUH experienced a stagnation period where the number of reports were not increasing. From the qualitative materials, we identified 74 strategies which contributed to the implementation of the patient safety reporting system. Among these, the domain of ‘intervention characteristics’ in the CFIR contained 12 strategies, ‘outer settings’ contained 20, ‘inner settings’ contained 21, ‘characteristics of individuals’ contained 8, and ‘process’ contained 13. There were two concentrated periods of the implemented strategies, the number was 17 in 2007 and 10 in 2016. These concentrated periods preceded a remarkable increase in the number of patient safety reports.

Conclusions

A safety culture had been fostered in FHUH in the study period. A relationship between number of strategies and development of a reporting culture was observed. The intensity of adequate strategies was needed for implementation of patient safety reporting system. Therefore, the implementation framework is useful for analysing patient safety initiatives for safety culture.
Multimodal ocular imaging of known and novel corneal stromal disorders in dogs
Authors: Park Sangwan , Sebbag Lionel , Moore Bret A. , Casanova M. Isabel , Leonard Brian C. , Daley Nicole L. , Steele Kirsten A. , Li Jennifer Y. , Murphy Christopher J. , Thomasy Sara M.
Published: March 2022

Background

Imaging features obtained with Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM) for corneal stromal disorders have been sparsely reported in dogs. This case report is a compilation of imaging features for three cases of different stromal disorders of the canine cornea which have not yet been reported elsewhere.

Case presentation

Lipid deposition in case 1 appeared as needle-shaped hyperreflective lines along the collagen lamellae, which correlated histologically with lipid clefts. In case 2, glycosaminoglycan accumulation by mucopolysaccharidosis type 1 caused diffuse stromal hyperreflectivity and depletion of keratocytes on IVCM and was associated with secondary corneal degeneration presumed to be calcium deposition. In case 3, posterior corneal stromal opacities in the absence of ocular inflammation were identified. Hyperreflective particles were scattered in the middle and posterior corneal stroma on FD-OCT. With IVCM, hyperreflective deposits were identified within keratocytes and the number of enlarged keratocytes containing hyperreflective deposits increased towards the posterior stroma. The bilateral, non-inflammatory nature and unique appearance with IVCM is most consistent with a posterior stromal dystrophy reminiscent of pre-Descemet corneal dystrophy described in humans.

Conclusions

In vivo multimodal corneal imaging facilitated instantaneous microstructural analysis and may be valuable in the differential diagnosis of corneal stromal disorders in veterinary clinical practice. The non-specific nature of imaging findings occurs in some conditions such as mucopolysaccharidosis, thus in vivo corneal imaging should be complemented with other gold standard methods of definitive diagnosis.
Susceptibility to malaria during the prevention of re-establishment phase in Sri Lanka
Authors: Jeevatharan Hamsananthy , Wickremasinghe Rajitha
Published: March 2022

Background

Sri Lanka eliminated malaria in November 2012 and was certified malaria-free by the World Health Organization (WHO) in September 2016 but is facing a challenge to prevent re-establishment of malaria. Influx of travellers from malarious countries and the presence of malaria vectors in formerly endemic areas make the country both receptive and vulnerable. Susceptibility to malaria, the predisposition of populations to be infected by malaria parasites, is influenced by biologic and generic factors such as the age-sex composition, socio economic status, and the migration history of the population. The aim of this study was to assess susceptibility to malaria during the prevention of re-establishment phase in Sri Lanka.

Methods

A national survey was conducted among 3454 households. A multistage cluster sampling technique was used to select the households. Susceptibility was assessed based on pre-defined variables by interviewing heads of households using an interviewer-administered questionnaire. Basic socio-demographic information, travel history, history of fever and past malaria infections in the preceding three years were collected. Data were analysed using SPSS version 20 package.

Results

The percentage of the population who had been overseas within the last 3 years in the urban sector (4.5%, n = 99) was higher than that of the rural (2.8%, n = 288) and estate sectors (0.2%, n = 2) (p < 0.001); it also declined with the wealth index up to the 4th quintile with a slight rise in the 5th quintile (p < 0.001). The likelihood of travel overseas was 1.75 times (95% CI: 1.38–2.22) higher for urban residents as compared rural estate residents; it was 1.46 times (95% CI: 1.16–1.92) higher for persons from the upper wealth index quintile as compared to persons from the 1st and 2nd quintiles after controlling for sex, age and area of residence. 177 persons had fever within the past 2 weeks of the survey. There was no association between presence of fever within the last 2 weeks and sector or travel abroad.

Conclusions

Urban residents, upper socioeconomic class persons and males are more likely to travel overseas and bring the parasite into the country. Social vulnerability and risk of re-establishment of malaria can be assessed by combining susceptibility with resilience and receptivity.
Supervised consumption site enables cost savings by avoiding emergency services: a cost analysis study
Authors: Khair Shahreen , Eastwood Cathy A. , Lu Mingshan , Jackson Jennifer
Published: March 2022

Background and aims

We report on a cost analysis study, using population level data to determine the emergency service costs avoided from emergency overdose management at supervised consumption services (SCS).

Design

We completed a cost analysis from a payer’s perspective. In this setting, there is a single-payer model of service delivery.

Setting

In Calgary, Canada, ‘Safeworks Harm Reduction Program’ was established in late 2017 and offers 24/7 access to SCS. The facility is a nurse-led service, available for client drop-in. We conducted a cost analysis for the entire duration of the program from November 2017 to January 2020, a period of 2 years and 3 months.

Methods

We assessed costs using the following factors from government health databases: monthly operational costs of providing services for drug consumption, cost of providing ambulance pre-hospital care for clients with overdoses who could not be revived at the facility, cost of initial treatment in an emergency department, and benefit of costs averted from overdoses that were successfully managed at the SCS.

Results

The proportion of clients who have overdosed at the SCS has decreased steadily for the duration of the program. The number of overdoses that can be managed on site at the SCS has trended upward, currently 98%. Each overdose that is managed at the SCS produces approximately $1600 CAD in cost savings, with a savings of over $2.3 million for the lifetime of the program.

Conclusion

Overdose management at an SCS creates cost savings by offsetting costs required for managing overdoses using emergency department and pre-hospital ambulance services.
Validation of a novel quality of life questionnaire: the Digestion-associated Quality of Life Questionnaire (DQLQ)
Authors: Beke Matthew , Burns Alyssa M. , Weir Sydney , Solch Rebecca J. , Judkins Taylor C. , Nieves Carmelo , Langkamp-Henken Bobbi
Published: March 2022

Background

Few health-related quality of life (QOL) questionnaires are designed specifically for healthy populations and are specific to gastrointestinal (GI) symptoms even though healthy individuals may frequently experience gas, bloating, constipation, diarrhea, and abdominal pain. The purpose of this study was to develop and validate a tool that could assess the impact of GI symptoms on digestion-associated QOL in otherwise healthy individuals.

Methods

After a review of current literature and with input from experienced GI researchers, a 24-item questionnaire was created. The questionnaire was reduced to 9 items with input from focus groups comprised of healthy adults experiencing GI-related symptoms and through variability analysis. The Digestion-associated QOL Questionnaire (DQLQ) was designed to be sensitive to the physical and mental well-being changes that may occur due to GI symptoms. The DQLQ was assessed for internal consistency reliability (Cronbach’s alpha; McDonald’s omega), test–retest reliability (intraclass correlation coefficient, ICC), and construct validity (Pearson correlations) in a study with healthy, academically stressed, undergraduate students. Convergent validity was evaluated by correlating the DQLQ with gastrointestinal symptom rating scale (GSRS) scores. Divergent validity was assessed by correlating DQLQ scores with stress scores, and bowel satisfaction scores.

Results

A total of 594 students (age 18–30 years) completed the DQLQ. Internal consistency reliability was favorable (n = 594; α = 0.84, ω = 0.84). A high level of agreement and correlation between DQLQ scores was found with the test–retest reliability analysis (n = 273; ICC = 0.89). The questionnaire was shown to have good convergent validity through correlation with the GSRS (n = 594; r = 0.54). Divergent validity was also shown to be appropriate by correlating DQLQ scores with stress (n = 592; r = 0.13, p < 0.005), and bowel satisfaction (n = 592; r = 0.18, p < 0.001) scores.

Conclusion

The DQLQ is a reliable and valid questionnaire for assessing digestion-associated QOL in healthy individuals.
Development and validation of the health-related quality of life instrument for Chinese infertile couples: a mixed-methods study protocol
Authors: Shi Zhao , Mao Zhuxin , Nie Hongwei , Geng Ling , Chen Gang , Li Shunping
Published: March 2022

Background

Infertility and its treatment have negative impacts on a couple’s marital relationship, sexual life, psychological state and interpersonal relationships, causing personal distress. Health-related quality of life (HRQoL) has become an important component of health outcomes. HRQoL instruments developed in western culture are not always appropriate for use in China due to cultural differences. Probably due to the unique concept of fertility in China, infertility patients can be looked down upon and the family may  feel shameful. This study aims to develop a HRQoL instrument for infertile couples based on the Chinese social and cultural setting.

Methods

Complementary mixed methods will be used to develop a new HRQoL instrument for Chinese infertile couples. The study consists of four stages: the first stage will involve a systematic review and qualitative interviews to construct draft candidate items. In the second stage, quantitative research [e.g., exploratory factor analysis (EFA), item response theory (IRT)] and cognitive interviews will be used for item selection. The third stage will be instrument validation, in which classical test theory (CTT) and IRT will be applied. In the final stage, the minimal clinically important difference (MCID) will be calculated by using distribution-based methods and anchor-based methods (e.g., logistic regression, receiver operating characteristic curve).

Discussion

The new HRQoL instrument for Chinese infertile couples will be developed, which will provide a standard and effective HRQoL instrument in clinical outcome assessment and health outcome measurement.
LncRNA MSTO2P promotes colorectal cancer progression through epigenetically silencing CDKN1A mediated by EZH2
Authors: Guo Mengjun , Zhang Xiling
Published: March 2022

Background

Pseudogene-derived long non-coding RNAs (lncRNAs) have been reported to act as key regulatory factors of cancers. However, the study focused on pseudogene misato family member 2 (MSTO2P) in the occurrence and development of colorectal cancer (CRC) remains unclear.

Methods

CCK-8, colony formation, and transwell assays clarified HT-29 and SW480 cell proliferation and invasion. Furthermore, flow cytometry was carried out to detect cell cycle and cell apoptosis. Subcellular localization assay indicated the location of MSTO2P in HT-29 cells. RIP and CHIP assays clarified the relationship of MSTO2P with target protein and gene in HT-29 cells.

Results

MSTO2P expression was upregulated in CRC tissues and cells. Functional experiments revealed that inhibition of MSTO2P suppressed HT-29 and SW480 cell proliferation and invasion, and promoted cell cycle arrest and cell apoptosis. Besides, MSTO2P epigenetically down-regulated cyclin-dependent kinase inhibitor 1A (CDKN1A) via binding to the enhancer of zeste homolog 2 (EZH2) in the nucleus. At last, rescue experiments proved the anti-tumor effect of inhibition of MSTO2P was partially recovered due to the knockdown of CDKN1A in HT-29 cells.

Conclusion

LncRNA MSTO2P promoted colorectal cancer progression through epigenetically silencing CDKN1A mediated by EZH2.
Cytokine-induced killer cells mediated pathways in the treatment of colorectal cancer
Authors: Fayyaz Farimah , Yazdanpanah Niloufar , Rezaei Nima
Published: March 2022

Cytokine-induced killer (CIK) cell therapy is a type of adoptive immunotherapy that due to its high proliferation rate and anti-tumor characteristics, is being investigated to treat various solid tumors. Since advanced colorectal cancer (CRC) has high mortality and poor survival rates, and the efficacy of chemotherapy and radiotherapy is limited in treatment, the application of CIK cell therapy in CRC has been evaluated in numerous studies. This review aims to summarize the clinical studies that investigated the safety and clinical efficacy of CIK cell therapy in CRC. Therefore, 1,969 enrolled CRC patients in the clinical trials, of which 842 patients received CIK cells in combination with chemotherapy with or without dendritic cell (DC) infusions, were included in the present review. Furthermore, the signaling pathways involved in CIK cell therapy and novel methods for improving migration abilities are discussed.
Multi-use physical activity trails in an urban setting and cardiovascular disease: a difference-in-differences analysis of a natural experiment in Winnipeg, Manitoba, Canada
Authors: McGavock Jonathan , Hobin Erin , Prior Heather J. , Swanson Anders , Smith Brendan T. , Booth Gillian L. , Russell Kelly , Rosella Laura , Isaranuwatchai Wanrudee , Whitehouse Stephanie , Brunton Nicole , Burchill Charles
Published: March 2022

Objective

To determine if expansion of multi-use physical activity trails in an urban centre is associated with reduced rates of cardiovascular disease (CVD).

Methods

This was a natural experiment with a difference in differences analysis using administrative health records and trail-based cycling data in Winnipeg, Canada. Prior to the intervention, each year, 314,595 (IQR: 309,044 to 319,860) persons over 30 years without CVD were in the comparison group and 37,901 residents (IQR: 37,213 to 38,488) were in the intervention group. Following the intervention, each year, 303,853 (IQR: 302,843 to 304,465) persons were in the comparison group and 35,778 (IQR: 35,551 to 36,053) in the intervention group. The natural experiment was the construction of four multi-use trails, 4-7 km in length, between 2010 and 2012. Intervention and comparison areas were based on buffers of 400 m, 800 m and 1200 m from a new multi-use trail. Bicycle counts were obtained from electromagnetic counters embedded in the trail. The primary outcome was a composite of incident CVD events: CVD-related mortality, ischemic heart disease, cerebrovascular events and congestive heart failure. The secondary outcome was a composite of incident CVD risk factors: hypertension, diabetes and dyslipidemia.

Results

Between 2014 and 2018, 1,681,125 cyclists were recorded on the trails, which varied ~ 2.0-fold across the four trails (2358 vs 4264 counts/week in summer months). Between 2000 and 2018, there were 82,632 CVD events and 201,058 CVD risk events. In propensity score matched Poisson regression models, the incident rate ratio (IRR) was 1.06 (95% CI: 0.90 to 1.24) for CVD events and 0.95 (95%CI: 0.88 to 1.02) for CVD risk factors for areas within 400 m of a trail, relative to comparison areas. Sensitivity analyses indicated this effect was greatest among households adjacent to the trail with highest cycling counts (IRR = 0.85; 95% CI: 0.75 to 0.96).

Conclusions

The addition of multi-use trails was not associated with differences in CVD events or CVD risk factors, however the differences in CVD risk may depend on the level of trail use.

Trial registration

Trial registration number: NCT04057417.
Trend change in delayed first antenatal care visit among reproductive-aged women in Ethiopia: multivariate decomposition analysis
Authors: Alamneh Asaye , Asmamaw Achenef , Woldemariam Mehari , Yenew Chalachew , Atikilt Getaneh , Andualem Minwuyelet , Mebrat Amare
Published: March 2022

Background

Early first antenatal care visit is a critical health care service for the well-being of women and newborn babies. However, many women in Ethiopia still start their first antenatal care visit late. We aimed to examine the trend in delayed first antenatal care visit and identify the contributing factors for the trend change in delayed first antenatal care visits in Ethiopia over the study period 2000–2016.

Method

We analyzed the data on reproductive-aged women from the four consecutive Ethiopian Demographic and Health Surveys to determine the magnitude and trend of delayed first antenatal care visit. A weighted sample of 2146 in 2000, 2051 in 2005, 3368 in 2011, and 4740 women in 2016 EDHS were involved in this study. All statistical analysis was undertaken using STATA 14. Multivariate logistic decomposition analysis was used to analyze the trends of delayed first antenatal care visit over time and the contributing factors to the change in delayed first antenatal care visit.

Results

The prevalence of delayed first antenatal care visit in Ethiopia decreased significantly from 76.8% (95% CI 75.1−78.6) in 2000 to 67.3% (95% CI 65.9−68.6) in 2016. Decomposition analysis revealed that 39% of the overall change in delayed first antenatal care visit overtime was due to differences in women’s composition, whereas 61% was due to women’s behavioral changes. In this study, residence, husband's education, maternal occupation, ever told about pregnancy complications, cesarean delivery and family sizes were significantly contributing factors for the decline in delayed first antenatal care visit over the study periods.

Conclusion

The prevalence of delayed first antenatal care visit in Ethiopia among women decreased significantly over time. More than halves (61%) decline in delayed first antenatal care visits was due to women’s behavioral changes. Public health interventions targeting rural residents, poor household economic status and improving awareness about pregnancy-related complications would help to reduce the prevalence of delayed first antenatal care visit.
A descriptive, cross-sectional study of postpartum education: midwives’ self-reported knowledge and teaching of postpartum complications in Ghana
Authors: Adams Yenupini Joyce , Sladek Lynn
Published: March 2022

Background

Obstetric complications remain the leading causes of maternal deaths. Since it is not always possible to ascertain which women will develop complications and which women will not, all women who have a baby should be educated about warning signs of complications. In this study, we assessed postpartum education provided by midwives, midwives’ knowledge to teach patients about complications and their skills to manage postpartum complications.

Methods

Descriptive, cross-sectional study of 245 midwives in four hospitals in Tamale, Ghana, using an electronic questionnaire. Data analyzed in Stata 16 software using descriptive, bivariate, and multivariate statistics.

Results

Majority of midwives were female (98%). Mean age of midwives was 32 years. Most midwives spent 6 to 15 min teaching patients on warning signs of complications (61.89%). Mode of discharge education was mostly individual (83.13%). Most midwives reported no reference materials given to patients (66.39%). About 93.45% of midwives strongly agreed or agreed it is their responsibility to teach all patients, regardless of risk factors, about warning signs of complications. However, midwives did not always teach patients about complications. The majority of midwives felt they were knowledgeable or very knowledgeable to teach patients about hemorrhage (95.08%), infection (94.67%), preeclampsia/ eclampsia (90.95%), and hypertension (89.35%). Similarly, most midwives felt they had the skills to manage these same four obstetric complications. Unsurprisingly, most midwives were more likely to always educate their patients about hemorrhage, infection, preeclampsia/ eclampsia, and hypertension—the complications they were more knowledgeable about. Many midwives felt not knowledgeable about and not competent to manage postpartum depression, cardiac events, pulmonary embolism, and venous thrombosis. In the same regard, many midwives did not teach patients about the life-threatening complications they were least knowledgeable about.

Conclusions

Midwives did not always teach patients about complications. Most midwives felt knowledgeable to teach and manage hemorrhage, infection, and preeclampsia/hypertension but not cardiac events, pulmonary embolism, and venous thrombosis. Additional training of midwives on life-threatening complications such as pulmonary embolism and cardiac events is recommended.
Reproductive outcome of hysteroscopic metroplasty for women with T-shaped uterus: a retrospective study
Authors: Zhang Yuxin , Zhu Yiping , Ge Beilei , Sui Mengsong , Zheng Zhenzhen , Sun Jing
Published: March 2022

Background

T-shaped uterus is a Müllerian malformation with unapparent clinical manifestations. Intrauterine adhesion and tuberculosis may lead to T-shaped uterus, too. Hysteroscopic metroplasty is a treatment option for T-shaped uterus, while the postoperative reproductive outcomes have not been thoroughly investigated. The aim of this study was to determine the reproductive outcome in Chinese women with T-shaped uterus who had hysteroscopic metroplasty with cold scissors.

Methods

This retrospective cohort study was conducted in the reproductive surgery unit of a university-affiliated hospital. One hundred and eleven patients with T-shaped uterus who underwent hysteroscopic metroplasty from Jan. 2017 to Sept. 2019 were followed-up by telephone in Apr. 2021. All patients received hysteroscopic metroplasty using microcissors, followed by estrogen-progesterone sequential treatment, with or without intrauterine device (IUD) implantation. According to whether they had had history of intrauterine operation, patients were divided into congenital group and acquired group. The main outcome measure was postoperative live birth rate. χ2 test and t test were used for comparison between groups. Cochran-Mantel–Haenszel test were used for stratified analysis. P < 0.05 was considered statistically significant.

Results

One hundred and eleven patients were included in total, with 46 in congenital group and 65 in acquired group. After hysteroscopic metroplasty, in the congenital group, the pregnancy rate increased from 28.3% to 87.0% (P < 0.001) and the live birth rate increased from 23.1% to 79.5% (P = 0.001); in the acquired group, the pregnancy rate slightly dropped from 98.5% to 72.3% (P < 0.001) while the live birth rate increased from 20.8% to 74.5% (P < 0.001). No statistically significant difference was observed in postoperative reproductive outcome indicators between the two subgroups except mode of conception.

Conclusions

For both groups, hysteroscopic metroplasty may improve reproductive outcomes for patients with T-shaped uterus.
Designing a respectful maternity care guideline: a multiphase study
Authors: Hajizadeh Khadije , Vaezi Maryam , Meedya Shahla , Charandabi Sakineh Mohammad Alizadeh , Mirghafourvand Mojgan
Published: March 2022

Background

There is no comprehensive guideline for respectful maternity care (RMC) promotion in Iran. This study aimed to design a RMC guideline based on a multiphase study.

Methods

In this multiphase mixed-methods study, recommendations were made for RMC promotion through the data obtained from Phase I (i.e., the quantitative section with a cross-sectional design), Phase II (i.e., the qualitative section with a content analysis method), and Phase III (i.e., focus group discussions with birth attendants as well as opinions of the specialized panel through the Delphi technique). The composed recommendations were then analyzed and finalized by relevant specialists in terms of execution capacity, approvability, and cost-effectiveness within the current context of Iran. Eventually, the resultant guideline were evaluated and approved by two members of the research team specializing in the research area in accordance with the Appraisal of Guideline for Research and Evaluation (AGREE).

Results

The results of this multiphase study led to 80 recommendations for RMC promotion. The recommendations were classified as eight areas called recommendations for the pregnancy period, recommendations for the labor period and delivery, recommendations for the neonatal period, occupational recommendations, supervision recommendations, national policy recommendations, recommendations for training students and staff, and general public recommendations.

Discussion

Based on the outcomes of disrespect and abuse, it is recommended to provide comprehensive guideline for policymakers and planners to formulate plans through the RMC promotion approach. Healthcare service policymakers can use this guideline to design some interventions to meet women’s financial, psychological, and legal needs.
Non-coding RNAs in the regulation of blood–brain barrier functions in central nervous system disorders
Authors: Sun Ping , Hamblin Milton H. , Yin Ke-Jie
Published: March 2022

The blood–brain barrier (BBB) is an essential component of the neurovascular unit that controls the exchanges of various biological substances between the blood and the brain. BBB damage is a common feature of different central nervous systems (CNS) disorders and plays a vital role in the pathogenesis of the diseases. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circRNAs), are important regulatory RNA molecules that are involved in almost all cellular processes in normal development and various diseases, including CNS diseases. Cumulative evidences have demonstrated ncRNA regulation of BBB functions in different CNS diseases. In this review, we have summarized the miRNAs, lncRNAs, and circRNAs that can be served as diagnostic and prognostic biomarkers for BBB injuries, and demonstrated the involvement and underlying mechanisms of ncRNAs in modulating BBB structure and function in various CNS diseases, including ischemic stroke, hemorrhagic stroke, traumatic brain injury (TBI), spinal cord injury (SCI), multiple sclerosis (MS), Alzheimer's disease (AD), vascular cognitive impairment and dementia (VCID), brain tumors, brain infections, diabetes, sepsis-associated encephalopathy (SAE), and others. We have also discussed the pharmaceutical drugs that can regulate BBB functions via ncRNAs-related signaling cascades in CNS disorders, along with the challenges, perspective, and therapeutic potential of ncRNA regulation of BBB functions in CNS diseases.
Primary lung hyalinizing clear cell carcinoma: a diagnostic challenge in biopsy
Authors: Zhang Yanling , Han Wen , Zhou Jun , Yong Xiang
Published: March 2022

Introduction

Hyalinizing clear cell carcinomas (HCCCs) are rare, low-grade, malignant tumors. They most commonly involve the minor salivary glands of the head and neck. HCCC that occurs in uncommon locations and examining samples from small biopsy pose a diagnostic challenge for most pathologists.

Case presentation

We herein report a primary pulmonary HCCC diagnosed by small biopsy and summarize its histologic, immunophenotypic, and molecular features along with a review of 11 previously reported cases to emphasize the potential diagnostic pitfalls.

Conclusions

Small biopsy diagnosis of primary pulmonary HCCC is challenging. A collection of mimics needed to be ruled out. Awareness of the key morphologic features of pulmonary HCCC combined with essential immunohistochemistry and molecular tests contributes to the correct diagnosis.
Locus specific reduction of L1 expression in the cortices of individuals with amyotrophic lateral sclerosis
Authors: Pfaff Abigail L. , Bubb Vivien J. , Quinn John P. , Koks Sulev
Published: March 2022

The activation and dysregulation of retrotransposons has been identified in the CNS of individuals with the fatal neurodegenerative disorder Amyotrophic lateral sclerosis (ALS). This includes elements from multiple different families and subfamilies of retrotransposons, however there is limited knowledge of the specific loci from which this expression occurs in ALS. The long interspersed element-1 (L1) is the only autonomous retrotransposon in the human genome and members of this family of elements maintain the ability to mobilise. Despite L1s contributing to 17% of the human genome only 80–100 L1s encode the required proteins for mobilisation and are retrotransposition competent. Identifying the specific loci from which L1 expression occurs will inform on the potential functional consequences of their expression, such as the potential for somatic retrotransposition or DNA damage caused by the endonuclease activity of the ORF2 protein of the L1. Here we characterised L1 loci expression using the L1EM tool (https://github.com/FenyoLab/L1EM) in RNA sequencing data from 518 samples across four tissues (motor cortex, frontal cortex, cerebellum and cervical spinal cord) in the Target ALS cohort obtained from the New York Genome Center. There was a significant reduction in total intact L1 expression (those that encode functional proteins) in two brain regions of individuals with ALS compared to controls and clustering of the ALS brain regions occurred based on their intact L1 expression profile. Although overall the levels of L1 expression were reduced in ALS/ALS with other neurological disorder (ND) there were individuals in which L1s were expressed at much higher levels than the rest of the ALS/ALSND cohort. Expressed L1 loci were more frequently located in introns compared to those not expressed and the level of L1 expression positively correlated with the expression of the gene in which it was located. Significant differences were observed in the expression profiles of L1s in ALS and specific features of these elements, such as location in the genome and whether or not they are intact, were significantly associated with those that were expressed in the cohort.
Oxytocin ameliorates impaired social behavior in a mouse model of 3q29 deletion syndrome
Authors: Takemoto Tomoya , Baba Masayuki , Yokoyama Kazumasa , Kitagawa Kohei , Nagayasu Kazuki , Ago Yukio , Seiriki Kaoru , Hayata-Takano Atsuko , Kasai Atsushi , Mori Daisuke , Ozaki Norio , Takuma Kazuhiro , Hashimoto Ryota , Hashimoto Hitoshi , Nakazawa Takanobu
Published: March 2022

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by specific social symptoms, restricted interests, stereotyped repetitive behaviors, and delayed language development. The 3q29 microdeletion (3q29del), a recurrent copy number variant, confers a high risk for ASD and schizophrenia, and serves as an important pathological model for investigating the molecular pathogenesis of a large number of neurodevelopmental and psychiatric conditions. Recently, mouse models carrying a deletion of the chromosomal region corresponding to the human 3q29 region (Df/+ mice) were generated and demonstrated neurodevelopmental and psychiatric conditions associated behavioral abnormalities, pointing to the relevance of Df/+ mice as a model for these conditions with high construct and face validity. Currently, the molecular pathogenesis of these behavioral phenotypes in Df/+ mice remains unclear. The oxytocin (OXT) system plays a central role in social behavior across species and has a potential role in ASD. In this study, to elucidate the molecular mechanisms behind impaired social behavior in Df/+ mice, we investigated the possible involvement of OXT signaling in impaired social behavior in Df/+ mice. We demonstrated that OXT administration restored the impaired social behavior in Df/+ mice. We also demonstrated that the number of OXT-positive cells in the paraventricular nucleus (PVN) was significantly lower in Df/+ mice than in wild-type (WT) littermates. Consistent with this, the level of OXT peptide in the cerebral cortex of Df/+ mice was lower than in WT littermates. Our study may provide important insights into the molecular pathophysiological basis of neurodevelopmental and psychiatric conditions, including ASD.
L-alanine supplementation in Pompe disease (IOPD): a potential therapeutic implementation for patients on ERT? A case report
Authors: Rovelli Valentina , Zuvadelli Juri , Piotto Marta , Scopari Andrea , Dionigi Alice Re , Ercoli Vittoria , Paci Sabrina , Cefalo Graziella , Salvatici Elisabetta , Banderali Giuseppe
Published: March 2022

Background

Pompe disease (PD) is a disorder of glycogen metabolism conditioning a progressive and life conditioning myopathy. Enzyme replacement therapy (ERT) is currently the best treatment option for PD, but is not resolutive. While other potential therapeutic approaches have been reported before, these have never been tried as co- treatments. L-alanine oral supplementation (LAOS) has been proven to reduce muscle breakdown: we hereby report the first case of supplementation on a PD patient on ERT.

Case presentation

F. is a 9 y.o. infantile onset Pompe Disease (IOPD) girl ERT-treated since age 1 developing a progressive myopathy. We started her on LAOS and performed assessments at baseline, 6 and 9 months. At baseline, F.’s weight, height and BMI were within normal ranges, while body composition showed low fat mass -FM and high resting energy expenditure—REE levels. After LAOS, a progressive FM increase and REE reduction could be observed both at 6 and 9 months.

Conclusions

ERT is not curative for PD patients thus additional treatments could be considered to improve outcomes. Our patient showed physical signs of inability to accumulate energy when exclusively on ERT, while FM increase and REE reduction occurred when supplemented with LAOS, likely reflecting anabolic pathways’ implementation. This is the first case reporting potential LAOS benefits in PD-on ERT patients. Longitudinal case control studies are yet needed to evaluate possible efficacy of combined LAOS And ERT treatment in PD patients.
Whole-genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program
Authors: Venner Eric , Muzny Donna , Smith Joshua D. , Walker Kimberly , Neben Cynthia L. , Lockwood Christina M. , Empey Phillip E. , Metcalf Ginger A. , Kachulis Chris ,   The All of Us Research Program Regulatory Working Group, Mian Sana , Musick Anjene , Rehm Heidi L. , Harrison Steven , Gabriel Stacey , Gibbs Richard A. , Nickerson Deborah , Zhou Alicia Y. , Doheny Kimberly , Ozenberger Bradley , Topper Scott E. , Lennon Niall J.
Published: March 2022

Background

The All of Us Research Program (AoURP, “the program”) is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the USA. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants.

Methods

Whole-genome sequencing (WGS), variant calling processes, data interpretation, and return-of-results procedures had to be created and receive an Investigational Device Exemption (IDE) from the United States Food and Drug Administration (FDA). The performance of the entire workflow was assessed through the largest known cross-center, WGS-based, validation activity that was refined iteratively through interactions with the FDA over many months.

Results

The accuracy and precision of the WGS process as a device for the return of certain health-related genomic results was determined to be sufficient, and an IDE was granted.

Conclusions

We present here both the process of navigating the IDE application process with the FDA and the results of the validation study as a guide to future projects which may need to follow a similar path. Changes to the program in the future will be covered in supplementary submissions to the IDE and will support additional variant classes, sample types, and any expansion to the reportable regions.
Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort
Authors: Newsome Rachel C. , Gharaibeh Raad Z. , Pierce Christine M. , da Silva Wildson Vieira , Paul Shirlene , Hogue Stephanie R. , Yu Qin , Antonia Scott , Conejo-Garcia Jose R. , Robinson Lary A. , Jobin Christian
Published: March 2022

Background

Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored.

Methods

RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria. Pooled and individual responder and non-responder microbiota were transplanted into a gnotobiotic mouse model of lung cancer and treated with ICIs. 16S rDNA and RNA sequencing was performed on patient fecal samples, 16S rDNA sequencing on mouse fecal samples, and flow cytometric analysis on mouse tumor tissue.

Results

Responder patients have both a different microbial community structure than non-responders (P= 0.004) and a different bacterial transcriptome (PC2 = 0.03) at baseline. Taxa significantly enriched in responders include amplicon sequence variants (ASVs) belonging to the generaRuminococcus,Akkermansia, andFaecalibacterium. Pooled and individual responder microbiota transplantation into gnotobiotic mice decreased tumor growth compared to non-responder colonized mice following ICI (P= 0.023,P= 0.019,P= 0.008, respectively). Responder tumors showed an increased anti-tumor cellular phenotype following ICI treatment. Responder mice are enriched with ASVs belonging to the generaBacteroides,Blautia,Akkermansia, andFaecalibacterium. Overlapping taxa mapping between human and mouse cohorts correlated with tumor size and weight revealed a network highlighting responder-associated ASVs belonging to the generaColidextribacter,Frisingicoccus,Marvinbryantia, andBlautiawhich have not yet been reported.

Conclusions

The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.
Urinary galectin-3 binding protein (G3BP) as a biomarker for disease activity and renal pathology characteristics in lupus nephritis
Authors: Ding Huihua , Shen Yiwei , Lin Cheng , Qin Ling , He Shijun , Dai Min , Okitsu Shinji L. , DeMartino Julie A. , Guo Qiang , Shen Nan
Published: March 2022

Objective

There is an urgent need to identify novel biomarkers of LN to reflect renal histological changes. This study aims to investigate urinary G3BP levels in LN patients and their association with renal disease activity both clinically and pathologically.

Methods

This is a cross-sectional study. A total of 119 lupus nephritis patients were recruited. Thirty patients with chronic kidney diseases (CKD) and 27 healthy volunteers were also recruited as controls. Urinary G3BP was tested by ELISA. Renal histopathology was reviewed by an experienced renal pathologist. Other clinical variables were collected through chart review.

Results

The levels of uG3BP were significantly increased in active LN patients compared to those in inactive LN (p<0.001), CKD patients (p=0.01), and healthy controls (p<0.001). ROC analysis indicated a good discrimination ability of uG3BP to differentiate active LN from CKD patients (AUC=0.7), inactive LN (AUC=0.76), or healthy controls (AUC=0.87). uG3BP was positively correlated with SLEDAI (ρ=0.352, p<0.001), rSLEDAI (ρ=0.302, p<0.001), and SLICC RAS (ρ=0.465, p<0.001), indicating a role as a biomarker of disease activity. It also correlated with clinical parameters, including 24-h urine protein, ESR, and serum C3 levels. In patients with 24-h urine protein > 3.0 g/24h, uG3BP levels were higher in proliferative LN than in membranous LN (p=0.04). They could discriminate the two pathogenic types of LN (AUC=0.72), and they also positively correlated with AI (ρ=0.389, p=0.008) and scores of hyaline deposits (ρ=0.418, p=0.006). While in patients with 24-h urine protein ≤ 3.0 g/24h, uG3BP levels were not significantly different between proliferative and membranous LN, and there was no apparent relationship between uG3BP levels with AI or with scores of hyaline deposits, but they correlated positively with scores of cellular/fibrocellular crescents (ρ=0.328, p=0.04).

Conclusion

uG3BP is a non-invasive biomarker for clinically and histologically reflecting disease activity. It is associated with active histological changes and can be used as a surrogate biomarker when the renal biopsy is impractical.
Musculoskeletal pain as the effect of internal compensatory mechanisms on structural and functional changes in body build and posture in elite Polish sitting volleyball players
Authors: Zwierzchowska Anna , Gawel Eliza , Celebanska Diana , Rosolek Barbara
Published: March 2022

Background

With the dynamic development of professional Paralympic sport, the prevalence of musculoskeletal pain and structural and/or functional disturbances in Para athletes constantly increases. The aim of the study was to evaluate the impact of internal compensatory mechanisms on selected aspects of body structure and function in elite sitting volleyball players.

Methods

The study included eighteen elite sitting volleyball players (male; n = 12, female; n = 6, age; 36.0 ± 6.1, body mass; 76.6 ± 16.1, body height; 179.3 ± 0.1) from the Polish national team. Retrospective and direct participatory observation methods were used in the study. NMQ-7 was used to assess the current prevalence and location of musculoskeletal pain. The evaluation of spinal curvature and pelvic inclination was performed using a non-invasive Medi Mouse method (Idiag M360) in three different trunk positions. All statistical analyses were performed using Statistica 13.3 software package.

Results

Lumbar hypolordosis was a predominant sagittal deviation of spinal curvature (n = 15;83%). Low back pain (LBP) and neck pain were the most frequent complaints (50%). Statistically significant differences in the values of thoracic kyphosis angle, pelvic inclination, and spine length (SL) in sagittal standing flexion and extension were found. However, there was no statistically significant difference in sagittal standing flexion for the lumbar lordosis angle with a simultaneous significant change in pelvic inclination (66.9°). Moreover, a tendency to interpenetration of relationships between variables that characterize (a) body structure and (b) function of the spine and musculoskeletal pain were observed. Shoulder pain correlated with SL (R = 0.6; p < 0.05) and body height (R = 0.5; p < 0.05). Pelvic inclination correlated with shoulder pain, LBP (R = 0.5; p < 0.05/R = 0.6; p < 0.01), and body trunk fat mass (R = − 0.6; p < 0.05).

Conclusions

Trunk fat mass induces internal compensatory mechanisms to maintain optimal pelvic inclination and sagittal spinal balance. Furthermore, the level of pelvic mobility may determine musculoskeletal pain in Para athletes with lower limb impairment.
Text messaging interventions to support smoking cessation among hospitalized patients in Brazil: a randomized comparative effectiveness clinical trial
Authors: do Amaral Lígia Menezes , Ronzani Telmo Mota , Cruvinel Erica , Richter Kimber , Oliveira Andrade Rafaela de , Lanzieri Isabella Oliveira , de Macêdo Ângela Caroline Dias Albino Destro , Leite Isabel Cristina Gonçalves
Published: March 2022

Objective

A clinical trial carried out in patients hospitalized for clinical and surgical conditions. This study evaluated the effectiveness of text messaging interventions (TM) versus telephone counseling (TC) to promote smoking cessation among hospitalized smokers in a middle-income country. Seven-day abstinence was measured during follow-up phone calls one month after discharge. The comparative cost of the two interventions considered the cost of calls, time spent on phone calls and sending SMS and cost of the professional involved in the approaches.

Results

Past 7-day tobacco abstinence was not statistically different between groups (30.5% in TM group and 26% in TC, p = 0.318). Costs were significantly lower in the TM group (U$9.28 × U$19.45- p < 0,001). Continuous abstinence was reported by 26% of TM participants and 24.5% of TC participants (p = 0.730). In the 3-month follow-up, 7-day abstinence was 23% in the TMI and 27% in the TC (p = 0.356) group. Continuous abstinence was reported by 20% of TM participants and 24% of TC participants (p = 0.334).

Trial registration: ClinicalTrials.gov ID: NCT03237949 Registred on: 30th May 2017.