bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a novel signature based on unfolded protein response-related gene for predicting prognosis in bladder cancer
Authors: Zhu Ke , Xiaoqiang Liu , Deng Wen , Wang Gongxian , Fu Bin
Published: December 2021

Background

The unfolded protein response (UPR) served as a vital role in the progression of tumors, but the molecule mechanisms of UPR in bladder cancer (BLCA) have been not fully investigated.

Methods

We identified differentially expressed unfolded protein response-related genes (UPRRGs) between BLCA samples and normal bladder samples in the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and the least absolute shrinkage and selection operator penalized Cox regression analysis were used to construct a prognostic signature in the TCGA set. We implemented the validation of the prognostic signature in GSE13507 from the Gene Expression Omnibus database. The ESTIMATE, CIBERSORT, and ssGSEA algorithms were used to explore the correlation between the prognostic signature and immune cells infiltration as well as key immune checkpoints (PD-1, PD-L1, CTLA-4, and HAVCR2). GDSC database analyses were conducted to investigate the chemotherapy sensitivity among different groups. GSEA analysis was used to explore the potential mechanisms of UPR-based signature.

Results

A prognostic signature comprising of seven genes (CALR, CRYAB, DNAJB4, KDELR3, CREB3L3, HSPB6, and FBXO6) was constructed to predict the outcome of BLCA. Based on the UPRRGs signature, the patients with BLCA could be classified into low-risk groups and high-risk groups. Patients with BLCA in the low-risk groups showed the more favorable outcomes than those in the high-risk groups, which was verified in GSE13507 set. This signature could serve as an autocephalous prognostic factor in BLCA. A nomogram based on risk score and clinical characteristics was established to predict the over survival of BLCA patients. Furthermore, the signature was closely related to immune checkpoints (PD-L1, CTLA-4, and HAVCR2) and immune cells infiltration including CD8+ T cells, follicular helper T cells, activated dendritic cells, and M2 macrophages. GSEA analysis indicated that immune and carcinogenic pathways were enriched in high-risk group.

Conclusions

We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of patients with bladder cancer.
Bioefficacy and durability of Olyset® Plus, a permethrin and piperonyl butoxide-treated insecticidal net in a 3-year long trial in Kenya
Authors: Gichuki Paul M. , Kamau Luna , Njagi Kiambo , Karoki Solomon , Muigai Njoroge , Matoke-Muhia Damaris , Bayoh Nabie , Mathenge Evan , Yadav Rajpal S.
Published: December 2021

Background

Long-lasting insecticide nets (LLINs) are a core malaria intervention. LLINs should retain efficacy against mosquito vectors for a minimum of three years. Efficacy and durability of Olyset® Plus, a permethrin and piperonyl butoxide (PBO) treated LLIN, was evaluated versus permethrin treated Olyset® Net. In the absence of WHO guidelines of how to evaluate PBO nets, and considering the manufacturer’s product claim, Olyset® Plus was evaluated as a pyrethroid LLIN.

Methods

This was a household randomized controlled trial in a malaria endemic rice cultivation zone of Kirinyaga County, Kenya between 2014 and 2017. Cone bioassays and tunnel tests were done against Anopheles gambiae Kisumu. The chemical content, fabric integrity and LLIN survivorship were monitored. Comparisons between nets were tested for significance using the Chi-square test. Exact binomial distribution with 95% confidence intervals (95% CI) was used for percentages. The WHO efficacy criteria used were ≥ 95% knockdown and/or ≥ 80% mortality rate in cone bioassays and ≥ 80% mortality and/or ≥ 90% blood-feeding inhibition in tunnel tests.

Results

At 36 months, Olyset® Plus lost 52% permethrin and 87% PBO content; Olyset® Net lost 24% permethrin. Over 80% of Olyset® Plus and Olyset® Net passed the WHO efficacy criteria for LLINs up to 18 and 12 months, respectively. At month 36, 91.2% Olyset® Plus and 86.4% Olyset® Net survived, while 72% and 63% developed at least one hole. The proportionate Hole Index (pHI) values representing nets in good, serviceable and torn condition were 49.6%, 27.1% and 23.2%, respectively for Olyset® Plus, and 44.9%, 32.8% and 22.2%, respectively for Olyset® Net but were not significantly different.

Conclusions

Olyset® Plus retained efficacy above or close to the WHO efficacy criteria for about 2 years than Olyset® Net (1–1.5 years). Both nets did not meet the 3-year WHO efficacy criteria, and showed little attrition, comparable physical durability and survivorship, with 50% of Olyset® Plus having good and serviceable condition after 3 years. Better community education on appropriate use and upkeep of LLINs is essential to ensure effectiveness of LLIN based malaria interventions.

Graphical Abstract
Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
Authors: Wasserman Emily , Worgall Stefan
Published: December 2021

Childhood asthma derives from complex host-environment interactions occurring in the perinatal and infant period, a critical time for lung development. Sphingolipids are bioactive molecules consistently implicated in the pathogenesis of childhood asthma. Genome wide association studies (GWAS) initially identified a link between alleles within the 17q21 asthma-susceptibility locus, childhood asthma, and overexpression of the ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), an inhibitor of de novo sphingolipid synthesis. Subsequent studies of pediatric asthma offer strong evidence that these asthma-risk alleles correlate with early-life aberrancies of sphingolipid homeostasis and asthma. Relationships between sphingolipid metabolism and asthma-related risk factors, including maternal obesity and respiratory viral infections, are currently under investigation. This review will summarize how these perinatal and early life exposures can synergize with 17q21 asthma risk alleles to exacerbate disruptions of sphingolipid homeostasis and drive asthma pathogenesis.
Liquid biopsy to identify biomarkers for immunotherapy in hepatocellular carcinoma
Authors: Ao Huang , Xin Zhang , Jian Zhou
Published: December 2021

The past years have witnessed the vigorous development of immunotherapy, mainly immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Indeed, ICIs have largely revolutionized the management and improved the prognosis of patients with intermediate and advanced hepatocellular carcinoma (HCC). However, biomarker-based stratification of HCC patients for optimal response to ICI treatment is still of unmet need and again, there exists the necessity to dynamically monitor treatment effect in real-time manner. The role of conventional biomarkers in immunotherapy surveillance is largely limited by spatial and temporal tumor heterogeneity whereas liquid biopsy seems to be promising to circumvent tumor heterogeneity to identify candidate patients who may response to immunotherapy, to dynamically monitor treatment effect and to unveil resistance mechanism. Herein, we provide a thorough review about the potential utility of liquid biopsy in immunotherapy for HCC and discuss its future perspectives.
Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer
Authors: Viet Chi T. , Zhang Xinyu , Xu Ke , Yu Gary , Asam Kesava , Thomas Carissa M. , Callahan Nicholas F. , Doan Coleen , Walker Paul C. , Nguyen Khanh , Kidd Stephanie C. , Lee Steve C. , Grandhi Anupama , Allen Clint T. , Young Simon , Melville James C. , Shum Jonathan W. , Viet Dan T. , Herford Alan S. , Roden Dylan F. , Gonzalez Manuel L. , Zhong Jiang F. , Aouizerat Bradley E.
Published: December 2021

Background

Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients.

Methods

Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies.

Results

There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11).

Conclusions

Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.
A partial migrant relies upon a range-wide cue set but uses population-specific weighting for migratory timing
Authors: Linek Nils , Brzęk Paweł , Gienapp Phillip , O’Mara M. Teague , Pokrovsky Ivan , Schmidt Andreas , Shipley J. Ryan , Taylor Jan R. E. , Tiainen Juha , Volkmer Tamara , Wikelski Martin , Partecke Jesko
Published: December 2021

Background

Many birds species range over vast geographic regions and migrate seasonally between their breeding and overwintering sites. Deciding when to depart for migration is one of the most consequential life-history decisions an individual may make. However, it is still not fully understood which environmental cues are used to time the onset of migration and to what extent their relative importance differs across a range of migratory strategies. We focus on departure decisions of a songbird, the Eurasian blackbirdTurdus merula, in which selected Russian and Polish populations are full migrants which travel relatively long-distances, whereas Finnish and German populations exhibit partial migration with shorter migration distances.

Methods

We used telemetry data from the four populations (610 individuals) to determine which environmental cues individuals from each population use to initiate their autumn migration.

Results

When departing, individuals in all populations selected nights with high atmospheric pressure and minimal cloud cover. Fully migratory populations departed earlier in autumn, at longer day length, at higher ambient temperatures, and during nights with higher relative atmospheric pressure and more supportive winds than partial migrants; however, they did not depart in higher synchrony. Thus, while all studied populations used the same environmental cues, they used population-specific and locally tuned thresholds to determine the day of departure.

Conclusions

Our data support the idea that migratory timing is controlled by general, species-wide mechanisms, but fine-tuned thresholds in response to local conditions.
Gradually progressive cholangiolocellular carcinoma: a case report
Authors: Akiyama Kosuke , Abe Tomoyuki , Oshita Akihiko , Shimizu Akinori , Hanada Keiji , Yonehara Shuji , Kobayashi Tsuyoshi , Ohdan Hideki , Noriyuki Toshio , Nakahara Masahiro
Published: December 2021

Background

Cholangiolocellular carcinoma (CoCC) is a relatively rare primary liver tumor. We present a literature review and case report of a patient who presented with a slow-growing CoCC that was completely resected after a 5-year follow-up period.

Case presentation

The patient was a 66-year-old man with a history of inflammatory thoracic and intra-abdominal pseudo-tumors. He was regularly followed up at our hospital for partial dilation of the pancreatic duct branch located in the body of the pancreas. Five years earlier, computed tomography (CT) demonstrated a small tumor in liver segment 4. Radiological findings were suggestive of hemangioma. Tumor size gradually increased during the 5-year follow-up period. CT scans showed that the tumor had progressed in size from 10 to 20 mm. Positron emission tomography CT revealed an accumulation of fluorodeoxyglucose (standardized uptake value max 5.3) at the tumor site. The tumor exhibited high intensity on T2-weighted and diffusion-weighted images of ethoxybenzyl magnetic resonance imaging. The tumor showed high intensity during the early phase but low intensity during the hepatobiliary phase. Tumor markers were within their respective normal ranges. Suspecting intrahepatic cholangiocarcinoma, left hepatectomy was performed. The tumor was diagnosed as CoCC based on pathological findings. The patient’s post-operative course was uneventful. The patient survived for a year, without any recurrence.

Conclusions

In cases dealing with small tumor sizes, it is difficult to distinguish between CoCC and hemangioma due to their similar radiological findings. Thus, it is important to consider the diagnosis of CoCC in small benign hepatic tumors. As such, follow-up radiological examination is recommended.
Immune cell targeting nanoparticles: a review
Authors: Lee Na Kyeong , Kim Se-Na , Park Chun Gwon
Published: December 2021

Immune cells are attractive targets for therapy as they are direct participants in a variety of diseases. Delivering a therapeutic agent only to cells that act on a disease by distinguishing them from other cells has the advantage of concentrating the therapeutic effect and lowering systemic side effects. Distinguishing each immune cell from other immune cells to deliver substances, including drugs and genes, can be achieved using nanotechnology. And also nanoparticles can ensure in vivo stability and sustained drug release. In addition, there is an ease of surface modification, which is an important characteristic that can be utilized in targeted drug delivery systems. This characteristic allows us to utilize various properties that are specifically expressed in each immune cell. A number of studies have delivered various substances specifically to immune cells through surface engineering with active target ligands that can target each immune cell and enzyme-responsive coating, and demonstrated high therapeutic effects compared to conventional treatments. Progress in research on target delivery has been suggested to be a breakthrough for the treatments of various diseases, including cancer treatment.
Efficacy and safety of rhBMP/β-TCP in alveolar ridge preservation: a multicenter, randomized, open-label, comparative, investigator-blinded clinical trial
Authors: Han Jeong Joon , Chang Ah. Ryum , Ahn Jaemyung , Jung Seunggon , Hong Jongrak , Oh Hee-Kyun , Hwang Soon Jung
Published: December 2021

Background

The aim of this multicenter, randomized, open-label, comparative, investigator-blinded study was to investigate the efficacy and safety of recombinant human bone morphogenetic protein 2 (rhBMP-2) combined with β-TCP (rhBMP-2/β-TCP) in alveolar ridge preservation.

Materials and methods

Eighty-four subjects from three centers were enrolled in this clinical trial. After tooth extraction, rhBMP-2/β-TCP (n = 41, test group) or β-TCP (n = 43, control group) were grafted to the extraction socket with an absorbable barrier membrane for alveolar ridge preservation. Using computed tomography images obtained immediately after and 12 weeks after surgery, changes in the alveolar bone height and width were analyzed for each group and compared between the two groups.

Results

Both the test and control groups showed a significant decrease in alveolar bone height in the 12 weeks after surgery (both groups, p < 0.0001). However, the test group exhibited a significantly lower decrease in alveolar bone height than the control group (p = 0.0004). Alveolar bone width also showed significantly less resorption in the test group than in the control group for all extraction socket levels (ESL) (p = 0.0152 for 75% ESL; p < 0.0001 for 50% ESL; p < 0.0001 for 25% ESL). There were no statistically significant differences in the incidence of adverse events between the two groups. No severe adverse events occurred in either group.

Conclusions

The results of this study suggest that rhBMP-2/β-TCP is a safe graft material that provides a high alveolar bone preservation effect in patients receiving dental extraction.

Trial registration

Clinicaltrials.gov, NCT02714829, Registered 22 March 2016
The academic performance of students with a migrant background: evidence from a cohort enrolled at Sapienza University of Rome
Authors: Giudici Cristina , Trappolini Eleonora , Vicari Donatella
Published: December 2021

This study investigates the demographic characteristics and academic performances of foreign students with an Italian educational background in a cohort of 1st-year Bachelor students enrolled at Sapienza University of Rome, in the a.y. 2012/2013, comparing them to Italian and to International students. First, we employed a discrete-time competing risk hazard model to analyse differences in academic performances between Italian, foreign students with an Italian educational background and foreign students with a foreign educational background. Second, we applied regression trees to investigate final grades and the time-to-degree completion of Bachelor’s degree holders. Results show differences in the academic performances of foreign students with an Italian educational background compared to Italian students. Policies are needed, these results suggest, that strengthen opportunities for students from a migrant background since high school.
Distribution of G6PD deficiency genotypes among Southeast Asian populations
Authors: Tantular Indah S. , Kawamoto Fumihiko
Published: December 2021

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a group of X-linked, hereditary genetic disorders caused by mutations in the G6PD gene and results in functional variants of about 400 biochemical and clinical phenotypes. Among them, more than 215 genotypes have been identified so far. In this review, specific features of the genotype distribution in different communities and countries are discussed based on multiple reports and our molecular epidemiological studies of Southeast Asian countries. Particularly, in Indonesia, the frequency distribution of G6PD deficiency variants was distinct between western and eastern Indonesian populations, suggesting two different gene flows during Indonesian expansions.
Examining minimal important change of the Canadian Occupational Performance Measure for subacute rehabilitation hospital inpatients
Authors: Ohno Kanta , Tomori Kounosuke , Sawada Tatsunori , Kobayashi Ryuji
Published: December 2021

Background

The Canadian Occupational Performance Measure (COPM) is an individualized patient-reported outcome designed to evaluate the self-perceptions of a patient’s occupational performance. Our study aimed to examine the minimal important change (MIC) in inpatients undergoing subacute rehabilitation. The MIC values were calculated using the three different anchor-based analyses with the transition index as an external criterion; the mean change method (MICMeanChange), the receiver operating characteristic (MICROC) analysis, and the predictive modeling method adjusted for the proportion of improved patients (MICadjust). In this study, the MICadjust value was considered as the most valid statistical method. We recruited 100 inpatients with various health conditions from subacute rehabilitation hospitals. Data were collected twice: an initial assessment and a reassessment one month later. The systematic interview format (Five Ws and How) was used for both the initial and second assessments to prevent information bias (response shift).

Results

Three patients who indicated deterioration on the transition index were excluded from all analyses, and 97 patients were analyzed in this study. The MICadjust values were 2.20 points (95% confidence interval 1.80–2.59) for the COPM performance score and 2.06 points (95% confidence interval 1.73–2.39) for the COPM satisfaction score. The MICMeanChange and MICROC values were considered less reasonable to interpret because the proportions of the improved patients subgroup were more than 50% (82.5%).

Conclusions

The MICadjust value estimates from this study can help detect whether the patients’ perceived occupational performance improved or did not change. The results support the multidisciplinary use of COPM in clinical practice and research on subacute rehabilitation inpatients.
Role of imaging in early diagnosis of acute ischemic stroke: a literature review
Authors: Akbarzadeh Mohammad Amin , Sanaie Sarvin , Kuchaki Rafsanjani Mahshid , Hosseini Mohammad-Salar
Published: December 2021

Stroke is a serious health condition that is responsible for more than 5% of total deaths. Near 20% of patients experiencing stroke die every year, resulting in the stroke being at the top of the list of preventable causes of death. Once an acute stroke is suspected, a golden hour of less than an hour is available to prevent the undesirable consequences. Since neuroimaging is mandatory in the diagnosis of stroke, the proper use of neuroimaging could help saving time and planning the right treatment for the patient. Some of the available imaging methods help us with rapid results, while others benefit us from a more accurate diagnosis. Hereby, we aim to provide a clinical review of the advantages and disadvantages of different available neuroimaging methods in approaching acute stroke to help clinicians choose the best method according to the settings.
Gamma knife radiosurgery in patients with Cushing's Disease: Is it a curative option?
Authors: Esene Ignatius N. , Elserry Tarek , Radwan Hesham , Mohammed Elsabaa Ahmad
Published: December 2021

Background

The first line of treatment of Cushing’s disease (CD) is surgery. However, surgical resection is not amenable in all cases and the role of radiosurgical management of residual tumors or upfront treatment has been reported. Our study highlights the effectiveness and safety of Gamma Knife Radiosurgery for the treatment of Cushing’s disease.

Methods

This was an ambidirectional descriptive cohort study on 16 consecutive patients with a confirmed Cushing’s disease that underwent Gamma Knife Radiosurgery (GKR) before July 2014 and assessed for outcome during the study period between January 2014 and June 2016 (30 Months). We included patients with a minimum of two years follow up. The main outcomes were biochemical remission and tumor volume control. Secondary outcomes were visual field changes and morbidity.

Results

Sixteen cases with CD were included into the study. The Mean age ± SD was 34.81 ± 10.10 years. The male to female sex ratio was 1:3.

Six cases (37.5%) were de novo. Normalization of hypersecretion at 2 years was achieved in 13 cases (81.3%).The median hormone normalization time was 23 months. Tumor volume control was achieved in all the cases, whereas tumor shrinkage was achieved in (10 cases) 62.5%. The median shrinkage time was 13 months. Of the 12 eyes with pre-Gamma Knife visual affection, 8 (75%) normalized, 4 (25%) improved, and none deteriorated. No patient developed new hypopituitarism after GK radiosurgery. One case developed diplopia at 24 months follow up from abducens palsy. No mortality occurred in our series.

Conclusion

Gamma Knife Stereotactic Radiosurgery is an effective and safe treatment option for Cushing’s disease. It can be used as a complementary therapeutic procedure to classic surgery or as a first line treatment in selected number of patients.
Clinical health issues, reproductive hormones, and metabolic hormones associated with gut microbiome structure in African and Asian elephants
Authors: Keady Mia M. , Prado Natalia , Lim Haw Chuan , Brown Janine , Paris Steve , Muletz-Wolz Carly R.
Published: December 2021

Background

The gut microbiome is important to immune health, metabolism, and hormone regulation. Understanding host–microbiome relationships in captive animals may lead to mediating long term health issues common in captive animals. For instance, zoo managed African elephants (Loxodonta africana) and Asian elephants (Elephas maximus) experience low reproductive rates, high body condition, and gastrointestinal (GI) issues. We leveraged an extensive collection of fecal samples and health records from the Elephant Welfare Study conducted across North American zoos in 2012 to examine the link between gut microbiota and clinical health issues, reproductive hormones, and metabolic hormones in captive elephants. We quantified gut microbiomes of 69 African and 48 Asian elephants from across 50 zoos using Illumina sequencing of the 16S rRNA bacterial gene.

Results

Elephant species differed in microbiome structure, with African elephants having lower bacterial richness and dissimilar bacterial composition from Asian elephants. In both species, bacterial composition was strongly influenced by zoo facility. Bacterial richness was lower in African elephants with recent GI issues, and richness was positively correlated with metabolic hormone total triiodothyronine (total T3) in Asian elephants. We found species-specific associations between gut microbiome composition and hormones: Asian elephant gut microbiome composition was linked to total T3 and free thyroxine (free T4), while fecal glucocorticoid metabolites (FGM) were linked to African elephant gut microbiome composition. We identified many relationships between bacterial relative abundances and hormone concentrations, including Prevotella spp., Treponema spp., and Akkermansia spp.

Conclusions

We present a comprehensive assessment of relationships between the gut microbiome, host species, environment, clinical health issues, and the endocrine system in captive elephants. Our results highlight the combined significance of host species-specific regulation and environmental effects on the gut microbiome between two elephant species and across 50 zoo facilities. We provide evidence of clinical health issues, reproductive hormones, and metabolic hormones associated with the gut microbiome structure of captive elephants. Our findings establish the groundwork for future studies to investigate bacterial function or develop tools (e.g., prebiotics, probiotics, dietary manipulations) suitable for conservation and zoo management.
Early life skin microbial trajectory as a function of vertical and environmental transmission in Bornean foam-nesting frogs
Authors: McGrath-Blaser Sarah , Steffen Morgan , Grafe T. Ulmar , Torres-Sánchez María , McLeod David S. , Muletz-Wolz Carly R.
Published: December 2021

Background

The amphibian skin microbiome is an important mediator of host health and serves as a potential source of undiscovered scientifically significant compounds. However, the underlying modalities of how amphibian hosts obtain their initial skin-associated microbiome remains unclear. Here, we explore microbial transmission patterns in foam-nest breeding tree frogs from Southeast Asia (Genus:Polypedates) whose specialized breeding strategy allows for better delineation between vertically and environmentally derived microbes. To facilitate this, we analyzed samples associated with adult frog pairs taken after mating—including adults of each sex, their foam nests, environments, and tadpoles before and after environmental interaction—for the bacterial communities using DNA metabarcoding data (16S rRNA). Samples were collected from frogs in-situ in Brunei, Borneo, a previously unsampled region for amphibian-related microbial diversity.

Results

Adult frogs differed in skin bacterial communities among species, but tadpoles did not differ among species. Foam nests had varying bacterial community composition, most notably in the nests’ moist interior. Nest interior bacterial communities were discrete for each nest and overall displayed a narrower diversity compared to the nest exteriors. Tadpoles sampled directly from the foam nest displayed a bacterial composition less like the nest interior and more similar to that of the adults and nest exterior. After one week of pond water interaction the tadpole skin microbiome shifted towards the tadpole skin and pond water microbial communities being more tightly coupled than between tadpoles and the internal nest environment, but not to the extent that the skin microbiome mirrored the pond bacterial community.

Conclusions

Both vertical influence and environmental interaction play a role in shaping the tadpole cutaneous microbiome. Interestingly, the interior of the foam nest had a distinct bacterial community from the tadpoles suggesting a limited environmental effect on tadpole cutaneous bacterial selection at initial stages of life. The shift in the tadpole microbiome after environmental interaction indicates an interplay between underlying host and ecological mechanisms that drive community formation. This survey serves as a baseline for further research into the ecology of microbial transmission in aquatic animals.
Egyptian practical guidance in hypertriglyceridemia management 2021
Authors: Taha Hesham Salah El Din , Kandil Hossam , Farag Nabil , Oraby Abbas , Sharkawy Magdy El , Fawzy Fouad , Mahrous Hossam , Bahgat Juliette , Samy Mina , Aboul Mohamed , Abdrabou Mostafa , Shaker Mirna Mamdouh
Published: December 2021

Hypertriglyceridemia (HTG) is a very common, yet underappreciated problem in clinical practice. Elevated triglyceride (TG) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD) risk. Furthermore, severe HTG may lead to acute pancreatitis. Although LDL-guided statin therapy has improved ASCVD outcomes, residual risk remains. Recent trials have demonstrated that management of high TG levels, in patients already on statin therapy, reduces the rate of major vascular events. Few guidelines were issued, providing important recommendations for HTG management strategies. The goal of treatment is to reduce the risk of ASCVD and acute pancreatitis. The management stands on lifestyle modification, detection of secondary causes of HTG and pharmacological therapy, when indicated. In this guidance we review the causes and classification of HTG and summarize the current methods for risk estimation, diagnosis and treatment. The present guidance provides a focused update on the management of HTG, outlined in a simple user-friendly format, with an emphasis on the latest available data.
Using a participatory method to test a strategy supporting the implementation of a state policy on screening children for adverse childhood experiences (ACEs) in a Federally Qualified Health Center system: a stepped-wedge cluster randomized trial
Authors: Perez Jolles Monica , Mack Wendy J. , Reaves Christina , Saldana Lisa , Stadnick Nicole A. , Fernandez Maria E. , Aarons Gregory A.
Published: December 2021

Background

Adverse childhood experiences (ACEs) are potentially traumatic events occurring before age 18, such as maltreatment or exposure to violence. ACE screening is increasingly recommended to prevent and address physical and mental health conditions associated with ACEs. To promote ACE screening uptake, the state of California issued the “ACEs Aware” policy that provides Medicaid reimbursement for ACE screening annually for child primary care visits. However, policy directives alone often do not translate into effective screening efforts and greater access to care. Few rigorous studies have developed and tested implementation strategies for ACE pediatric screening policies. This study will fill this gap by testing a multifaceted implementation strategy in partnership with a Federally Qualified Health Center (FQHC) system serving low-income families in Southern California to support the ACE Aware policy.

Methods

We will use Implementation Mapping, with study process and consideration of determinants and mechanisms guided by the EPIS framework, to co-create and refine an implementation strategy. The proposed strategy is comprised of online training videos, a customized algorithm and use of technology to improve workflow efficiency, implementation training to internal FQHC personnel, clinic support and coaching, and written implementation protocols. A hybrid type 2, stepped-wedge cluster randomized trial design with five primary care clinics will test whether a multifaceted implementation strategy improves (a) fidelity to the ACE screening protocol, (b) reach defined as the proportion of eligible children screened for ACEs, and (c) the impact of the ACE policy on child-level mental health referrals and symptom outcomes. The study will use mixed methods with data to include electronic health records, surveys, and interviews with clinic personnel and caregivers.

Discussion

This study is designed to increase the capacity of FQHCs’ inner context to successfully implement an outer context-initiated ACE policy designed to benefit pediatric patients. It capitalizes on a rare opportunity to use a co-creation approach to develop, adapt, refine, and pilot test an implementation strategy to maximize the impact of a new state-wide policy intended to improve ACE assessment and subsequent care to improve child health, particularly those from underserved communities.

Trial registration

Trial # NCT04916587 registered at ClinicalTrials.gov on June 4, 2021.
Assessing Causal Pathways and Targets of Implementation Variability for EBP use (Project ACTIVE): a study protocol
Authors: Becker-Haimes Emily M. , Mandell David S. , Fishman Jessica , Williams Nathaniel J. , Wolk Courtney Benjamin , Wislocki Katherine , Reich Danielle , Schaechter Temma , Brady Megan , Maples Natalie J. , Creed Torrey A.
Published: December 2021

Background

Advancing causal implementation theory is critical for designing tailored implementation strategies that target specific mechanisms associated with evidence-based practice (EBP) use. This study will test the generalizability of a conceptual model that integrates organizational constructs and behavioral theory to predict clinician use of cognitive-behavioral therapy (CBT) techniques in community mental health centers. CBT is a leading psychosocial EBP for psychiatric disorders that remains underused despite substantial efforts to increase its implementation.

Methods

We will leverage ongoing CBT implementation efforts in two large public health systems (Philadelphia and Texas) to recruit 300 mental health clinicians and 600 of their clients across 40 organizations. Our primary implementation outcomes of interest are clinician intentions to use CBT and direct observation of clinician use of CBT. As CBT comprises discrete components that vary in complexity and acceptability, we will measure clinician use of six discrete components of CBT. After finishing their CBT training, participating clinicians will complete measures of organizational and behavior change constructs delineated in the model. Clinicians also will be observed twice via audio recording delivering CBT with a client. Within 48 h of each observation, theorized moderators of the intention-behavior gap will be collected via survey. A subset of clinicians who report high intentions to use CBT but demonstrate low use will be purposively recruited to complete semi-structured interviews assessing reasons for the intention-behavior gap. Multilevel path analysis will test the extent to which intentions and determinants of intention predict the use of each discrete CBT component. We also will test the extent to which theorized determinants of intention that include psychological, organizational, and contextual factors explain variation in intention and moderate the association between intentions and CBT use.

Discussion

Project ACTIVE will advance implementation theory, currently in its infancy, by testing the generalizability of a promising causal model of implementation. These results will inform the development of implementation strategies targeting modifiable factors that explain substantial variance in intention and implementation that can be applied broadly across EBPs.
A peek behind the curtain: exploring coaching styles within the implementation and sustainment facilitation (ISF) strategy in the substance abuse treatment to HIV care study
Authors: Ford James H. , Gilson Aaron M. , Maurer Martha A. , Hoffman Kimberly A. , Garner Bryan R.
Published: December 2021

Background

The Grasha-Riechmann teaching styles, which includes three didactic and two prescriptive styles, have been shown to help enhance learning within educational settings. Although an adaption of the Grasha-Riechmann style classification has enabled coaching styles to be identified for use as part of quality improvement (QI) initiatives, research has not examined the styles actually utilized by coaches within a QI initiative or how the styles change overtime when the coach is guiding an organization through change implementation. Interactions between coaches and HIV service organization (HSO) staff participating in a large implementation research experiment called the Substance Abuse Treatment to HIV care (SAT2HIV) Project were evaluated to begin building an evidence base to address this gap in implementation research.

Methods

Implementation & Sustainment Facilitation (ISF) Strategy meetings (n = 137) between coaches and HSO staff were recorded and professionally transcribed. Thematic coding classifications were developed from the Grasha-Riechmann framework and applied to a purposively selected sample of transcripts (n = 66). Four coders independently coded transcripts using NVivo to facilitate text identification, organization, and retrieval for analysis. Coaching style use and changes across the three ISF phases were explored.

Results

Facilitator and formal authority were the two coaching styles predominately used. Facilitator sub-themes shifted from asking questions and providing support to supporting independent action over time. Coaches’ use of formal authority sub-styles shifted notably across time from setting expectations or ensuring preparation to offering affirmation or feedback about changes that the HSO’s were implementing. The use of the delegator or personal model coaching styles occurred infrequently.

Conclusions

The current research extends implementation research’s understanding of coaching. More specifically, findings indicate it is feasible to use the Grasha-Riechmann framework to qualitatively identify coaching styles utilized in a facilitation-based implementation strategy. More importantly, results provide insights into how different coaching styles were utilized to implement an evidence-based practice. Further research is needed to examine how coaching styles differ by organization, impact implementation fidelity, and influence both implementation outcomes and client outcomes.

Trial registration

ClinicalTrials.gov NCT02495402. Registered on July 6, 2015.
A mixed-method evaluation of the adoption and implementation of the College Alcohol Intervention Matrix among prevention experts: a study protocol
Authors: Helle Ashley C. , Sher Kenneth J. , Masters Joan , Washington Karla , Hawley Kristin M.
Published: December 2021

Background

Risky drinking among college campuses has been a long-standing concern and there have been dedicated efforts to develop evidence-based prevention and treatment strategies (EBSs) to decrease alcohol use and increase healthy behaviors among college students. Further, the College Alcohol Intervention Matrix (CollegeAIM) was developed as a tool with accompanying resources, to assist institutions of higher education in selecting EBSs that are appropriate and a good fit for their campuses. However, the CollegeAIM tool and selection of prevention strategies from stakeholders’ perspectives has yet to be evaluated. This study protocol describes the methodology for a research project evaluating CollegeAIM from an implementation science perspective using the Exploration, Preparation, Implementation, and Sustainment framework.

Methods

The aims of this study will be accomplished with a mixed-method design comprised of reviews of strategic planning documents, quantitative surveys and interviews with prevention experts, and focus groups to identify key components of a decision-support program for prevention experts to support the use of CollegeAIM. Participants are members of the multi-site Missouri Partners in Prevention coalition to reduce risky substance use on college campuses across the state.

Discussion

The results of this study will provide key information to support the development of additional supportive tools for campuses that can improve their selection and implementation of EBSs that fit the needs of their respective campuses. This work is important to further advance the implementation and sustainment of extant EBSs for risky college alcohol use.
Health care resources utilization and costs associated with different clinical stages of chronic hepatitis B in Egypt
Authors: Abd El-Halim Jackleen Azer , Gewaifel Gihan Ismael , Darwish Eman Ahmed Fawzy , Ramadan Ahmed Maher , ElSisi Gihan Hamdy
Published: December 2021

Introduction

Chronic hepatitis B (CHB) is associated with many serious clinical and social consequences. Despite Egypt being classified as a country of low endemicity, the infection is associated with a 15–25% risk of premature death from liver cancer or end-stage liver disease. The national committee of treatment and control of viral hepatitis has already offered a high-quality service for the diagnosis and treatment of CHB on a free basis. The current study aims to estimate the health care resources utilization and the annual direct medical cost associated with different clinical stages of CHB-related disease in Egypt.

Methodology

The data was retrieved through record review for three months in the General Administration of Hepatitis Viruses Control, Egypt. Then, the data was extrapolated to the population level by multiplying the prevalence in Egypt with a focus on the productive age groups (25–59 years).

Results

The cost and utilization of different health care resources increase with disease progression. The total annual direct medical costs due to CHB in Egypt is 21.3 L.E. Billion (4.7 Int$ billion/year) for the management of estimated 1,420,700 CHB patients. The direct medical costs among the productive age group (25–59 years) constitute more than half of the total cost (57%). The highest disease burden is encountered among (25–29 years) age group; 2.695 L.E. billion (0.59 Int$ billion/year). Despite liver transplantation phase being associated with the highest annual cost/patient, the number of patients in this stage is the lowest. Then, it only constitutes 0.04% of the disease direct medical cost in the country. The chronic hepatitis clinical stage constitutes 57.26% of the disease direct medical cost in Egypt’s working age group.

Conclusion

Strengthening the preventive and control measures is mandatory to alleviate the disease’s direct medical costs. Close monitoring of the chronic hepatitis stage is mandatory to prevent disease progression. Enhancement of vaccination efforts will lower the disease prevalence and its cost. The universal health insurance system which is gradually implemented in Egypt nowadays will be a cornerstone in relieving the economic stresses by allowing more access to high-quality health care services.
Effect of training on health outcome including fatigue, depression and quality of life in patients with systemic lupus erythromatosus
Authors: Youssef Manal K.
Published: December 2021

Background

Systemic lupus erythematosus is an inflammatory condition that causes significant tissue damage and inflammation, and is more common in women. Despite the fact that medical treatment seeks to prevent flare-ups and organ damage, up to 50% of patients believe their wellbeing is suboptimal due to unmet needs like exhaustion and pain. The aim of the new systemic lupus erythematosus treatment guidelines is to improve people's quality of life. In people with systemic lupus erythematosus, fatigue is associated with reduced health, exercise capacity, muscle strength, and impairment. The aim of the study is to compare the effects of strengthening exercise on fatigue, depression, and quality of life in patients with systemic lupus erythematosus compared to the control sedentary group. This study included 20 patients with systemic lupus erythematosus from the department of internal medicine, compared to 25 control patients. Both groups had been treated with strengthening exercises for three months. Self-rating depression scale, quality of life questioner, fatigue severity scale, 6 min’ walk test, 2 min step test and body mass index (BMI). All parameters were measured before and after 3 months of treatment.

Results

Analysis of data showed that systemic lupus erythematosus has more depression and fatigue than sedentary control. After exercises, both groups have a significant difference between pre and post treatment, but still have a difference between both groups. Both groups have a significant difference between pre and post treatment in 6-min walk test, 2-min step test, and quality of life measured by SF-36. No significant difference was found between both groups pre and post treatment in BMI, although each group has a significant difference between pre and post treatment BMI.

Conclusions

Exercises are very important in the management of systemic lupus erythematosus. They help to decrease fatigue, depression, and improve quality of life.