bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with development of symptomatic disease in Ethiopian COVID-19 patients: a case-control study
Authors: Leulseged Tigist W. , Alemahu Degu G. , Hassen Ishmael S. , Maru Endalkachew H. , Zewde Wuletaw C. , Chamiso Negat W. , Yegele Kalkidan T. , Abebe Daniel S. , Abdi Firaol M. , Minyelshewa Etsegenet Y. , Gerbi Tegenu G. , Hagos Helen T.
Published: August 2021

Background

Studies show that having some symptoms seems to be associated with more severe disease and poor prognosis. Therefore, knowing who is more susceptible to symptomatic COVID-19 disease is important to provide targeted preventive and management practice. The aim of the study was to assess factors associated with the development of symptomatic disease among COVID-19 patients admitted to Millennium COVID-19 Care Center in Ethiopia.

Methods

A case-control study was conducted from August to September 2020 among a randomly selected 730 COVID-19 patients (337 Asymptomatic and 393 Symptomatic patients). Chi-square test and independent t-test were used to detect the presence of a statistically significant difference in the characteristics of the cases (symptomatic) and controls (asymptomatic), where p-value of < 0.05 considered as having a statistically significant difference. Multivariable binary logistic regression was used to assess a statistically significant association between the independent variables and developing symptomatic COVID-19 where Adjusted Odds ratio (AOR), 95% CIs for AOR, and P-values were used for testing significance and interpretation of results.

Results

The result of the multivariable binary logistic regression shows that age group (AOR = 1.89, 95% CI = 1.25, 2.87, p-value = 0.002 for 30–39 years; AOR = 1.69, 95% CI = 1.06, 2.73, p-value = 0.028 for 40–49 years and AOR = 4.42, 95% CI = 2.75, 7.12, p-value = 0.0001 for ≥50 years), sex (AOR = 1.76, 95% CI = 1.26, 2.45, p-value = 0.001) and history of diabetes mellitus (AOR = 3.90, 95% CI = 1.92, 7.94, p-value = 0.0001) were found to be significant factors that determine the development of symptomatic disease in COVID-19 patients.

Conclusions

Developing a symptomatic COVID-19 disease was found to be associated with exposures of old age, male sex, and being diabetic. Therefore, patients with the above factors should be given enough attention in the prevention and management process, including inpatient management, to pick symptoms earlier and to manage accordingly so that these patients can have a favorable treatment outcome.
Clinical features and death risk factors in COVID-19 patients with cancer: a retrospective study
Authors: Zhou Yi , Yang Qiao , Ye Jun , Wu Xiaocheng , Hou Xianhua , Feng Yimei , Luo Bangyu , Li Jixi , Yang Guangrong , Li Lingchen , Yang Xiu , Wang Bin , Zhao Songtao , Li Li , Li Qi , Xu Zhi , Wu Hao , Sun Jianguo
Published: August 2021

Background

Coronavirus disease 2019 (COVID-19) has spread around the world. This retrospective study aims to analyze the clinical features of COVID-19 patients with cancer and identify death outcome related risk factors.

Methods

From February 10th to April 15th, 2020, 103 COVID-19 patients with cancer were enrolled. Difference analyses were performed between severe and non-severe patients. A propensity score matching (PSM) analysis was performed, including 103 COVID-19 patients with cancer and 206 matched non-cancer COVID-19 patients. Next, we identified death related risk factors and developed a nomogram for predicting the probability.

Results

In 103 COVID-19 patients with cancer, the main cancer categories were breast cancer, lung cancer and bladder cancer. Compared to non-severe patients, severe patients had a higher median age, and a higher proportion of smokers, diabetes, heart disease and dyspnea. In addition, most of the laboratory results between two groups were significantly different. PSM analysis found that the proportion of dyspnea was much higher in COVID-19 patients with cancer. The severity incidence in two groups were similar, while a much higher mortality was found in COVID-19 patients with cancer compared to that in COVID-19 patients without cancer (11.7% vs. 4.4%, P = 0.028). Furthermore, we found that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were related to death outcome. And a nomogram based on the factors was developed.

Conclusion

In COVID-19 patients with cancer, the clinical features and laboratory results between severe group and non-severe group were significantly different. NLR and CRP were the risk factors that could predict death outcome.
Longitudinal Changes of Tongue Thickness and Tongue Pressure in Neuromuscular Disorders
Authors: Umemoto George , Fujioka Shinsuke , Arahata Hajime , Sakae Nobutaka , Sasagasako Naokazu , Toda Mine , Furuya Hirokazu , Tsuboi Yoshio
Published: August 2021

Background

Swallowing dysfunction is related to major cause of adverse events and an indicator of shorter survival among patients with neuromuscular disorders (NMD). It is critical to assess the swallowing function during disease progression, however, there are limited tools that can easily evaluate swallowing function without using videofluoroscopic or videoendoscopic examination. Here, we evaluated the longitudinal changes in tongue thickness (TT) and maximum tongue pressure (MTP) among patients with amyotrophic lateral sclerosis (ALS), myotonic dystrophy type 1 (DM1), and Duchenne muscular dystrophy (DMD).

Methods

Between 2010 and 2020, TT and MTP were measured from 21 ALS, 30 DM1, and 14 DMD patients (mean ages of 66.9, 44.5, and 21.4 years, respectively) at intervals of more than half a year. TT was measured, by ultrasonography, as the distance from the mylohyoid muscle raphe to the tongue dorsum, and MTP was determined by measuring the maximum compression on a small balloon when pressing the tongue against the palate. Then we examined the relationship between these evaluations and patient background and swallowing function.

Results

Mean follow-up periods were 24.0 months in the ALS group, 47.2 months in the DM1group, and 61.1 months in the DMD group. The DMD group demonstrated larger first TT than the other groups, while the DM1 group had lower first MTP than the ALS group. The ALS group showed a greater average monthly reduction in mean TT than the DM1 group and greater monthly reductions in mean body weight (BW) and MTP than the other groups. Significant differences between the first and last BW, TT, and MTP measures were found only in the ALS group.

Conclusions

This study suggests that ALS is associated with more rapid degeneration of tongue function over several years compared to DMD and DM1.
Clinical characteristics of post-traumatic epilepsy and the factors affecting the latency of PTE
Authors: Yu Tingting , Liu Xiao , Sun Lei , Wu Jianping , Wang Qun
Published: August 2021

Objectives

To summarize the clinical characteristics of post-traumatic epilepsy (PTE), and to identify the factors affecting the latency of PTE after traumatic brain injury (TBI).

Methods

We conducted a retrospective clinical analysis in patients with PTE who visited the outpatient Department of Epilepsy, Beijing Tiantan Hospital from January 2013 to December 2018. The clinical characteristics, including gender, age distribution, seizure type, and latency were summarized. Factors affecting the latency of PTE were evaluated using Kaplan-Meier curves and Cox proportional hazard regression analysis.

Results

Complete clinical information was available for 2862 subjects, of which 78.48% were males. The mean age at TBI was 21.4 ± 15.1 years and peaked in the 0 to 12-year-old and 15 to 27-year-old groups. Generalized onset seizure was the most frequent seizure type (72.82% of patients). Approximately 19.95% PTE patients developed drug-resistant epilepsy. The latency of PTE ranged from 8 days to 20 years, with a median of 24.0 (IQR, 5.0–84.0) months. The Kaplan-Meier curves demonstrated that gender, age at TBI, severity of TBI, multiple craniocerebral injuries, post-TBI treatments, acute seizures, and residual disability were associated with PTE latency. The Cox regression model indicated that age ≥ 18 years old, severe TBI with multiple surgical operations, acute seizures, and residual disability were risk factors for shorter PTE latency.

Conclusions

PTE is more common in males than females, and peaked in the 0 to 12-year-old and 15 to 27-year-old groups. Generalized onset seizure was the most common seizure type and 19.95% of participants developed drug-resistant epilepsy. Patients aged ≥18 years old, who suffered severe TBI followed by multiple surgical operations, experienced acute seizures, or with residual disabilities had shorter PTE latency.
The radiological outcome in lumbar interbody fusion among rheumatoid arthritis patients: a 20-year retrospective study
Authors: Tung Kuan-Kai , Wu Yun-Che , Chen Kun-Hui , Pan Chien-Chou , Lu Wen-Xian , Chin Ning-Chien , Shih Cheng-Min , Hsu Fang-Wei , Lee Cheng-Hung
Published: August 2021

Background

Clinical outcomes amongst Rheumatoid Arthritis (RA) patients have shown satisfactory results being reported after lumbar surgery. The increased adoption of the interbody fusion technique has been due to a high fusion rate and less invasive procedures. However, the radiographic outcome for RA patients after receiving interbody fusion has scarcely been addressed in the available literature.

Methods

Patients receiving interbody fusion including ALIF, OLIF, and TLIF were examined for implant cage motion and fusion status at two-year follow-up. Parameters for the index correction level including ADH, PDH, WI, SL, FW, and FH were measured and compared at pre-OP, post-OP, and two-year follow-up.

Results

We enrolled 64 RA patients at 104 levels (mean 64.0 years old, 85.9% female) received lumbar interbody fusion. There were substantial improvement in ADH, PDH, WI, SL, FW, and FH after surgery, with both ADH and PDH having significantly dropped at two-year follow up. The OLIF group suffered from a higher subsidence rate with no significant difference in fusion rate when compared to TLIF. The fusion rate and subsidence rate for all RA patients was 90.4 and 28.8%, respectively.

Conclusions

We revealed the radiographic outcomes of lumbar interbody fusions towards symptomatic lumbar disease in RA patients with good fusion outcome despite the relative high subsidence rate amongst the OLIF group. Those responsible for intra-operative endplate management should be more cautious to avoid post-OP cage subsidence.
Implementing the Smile4life intervention for people experiencing homelessness: a path analytical evaluation
Authors: Beaton Laura , Humphris Gerry , Rodriguez Andrea , Freeman Ruth
Published: August 2021

Background

People experiencing homelessness have high levels of dental decay, oral cancer and poor oral health-related quality of life. The Scottish Government sought to address these issues by developing a national oral health improvement programme for people experiencing homelessness, named Smile4life. The aim was to investigate implementation behaviours and the role of work-related beliefs upon the delivery of the Smile4life programme across NHS Board areas in Scotland.

Methods

Non-probability convenience sampling, supplemented by snowball sampling, was used to recruit practitioners working across the homelessness sector. The overall evaluation of the implementation of the Smile4life programme was theoretically informed by the Behaviour Change Wheel. The questionnaire was informed by the Theoretical Domains Framework and was divided into three sections, demography and Smile4life Awareness; Smile4life Activities; and Smile4life work-related beliefs. A psychometric assessment was used to develop Smile4life Awareness, Smile4life Activities, Ability to Deliver and Positive Beliefs and Outcomes subscales. The data were subjected to K-R20, exploratory factor analysis, Cronbach’s alpha, t-tests, ANOVA, Pearson’s correlation analysis and a multivariate path analysis.

Results

One hundred participants completed the questionnaire. The majority were female (79%) and worked in NHS Boards across Scotland (55%). Implementation behaviour, constructed from the Delivering Smile4life scale and the summated Smile4life activities variable, was predicted using a linear model a latent variable. The independent variables were two raw variables Positive Beliefs and Outcomes, and Ability to deliver Smile4life. Results showed relatively good model fit (chi-square (1.96; p > 0.15), SRMR (< 0.08) and R2 (0.62) values). Positive and highly significant loadings were found describing the Implementation Behaviour latent variable (0.87 and 0.56). The two independent variables were associated (p < 0.05) with Implementation Behaviour.

Conclusions

Work-related factors, such as positive beliefs and outcomes and ability to deliver are required for implementation behaviours associated with the delivery of the Smile4life programme. Future work should include training centred on the specific needs of those involved in the homelessness sector and the development of accessible training resources, thereby promoting implementation behaviours to assist the progression and sustainability of the Smile4life programme.
Does teaching medical ethics ensure good knowledge, attitude, and reported practice? An ethical vignette-based cross-sectional survey among doctors in a tertiary teaching hospital in Nepal
Authors: Shrestha Carmina , Shrestha Ashma , Joshi Jasmin , Karki Shuvechchha , Acharya Sajan , Joshi Suchita
Published: August 2021

Background

Importance of awareness of medical ethics and its integration into medical curriculum has been frequently highlighted. Study 1 aimed to assess the knowledge, attitude, and reported practices of medical ethics among clinicians at Patan Academy of Health Sciences, a tertiary care teaching hospital in Nepal. Study 2 was conducted to assess whether there was a difference in knowledge, attitude, and reported practices of medical ethics among doctors who received formal medical ethics education during undergraduate studies and those who did not.

Methods

Two cross-sectional surveys using self-administered questionnaires were conducted. Study 1 included 72 participants; interns, medical officers, and consultants working at Patan Academy of Health Sciences. Study 2 was a comparative study conducted among 54 medical officers who had received formal medical ethics education (Group 1) and 60 medical officers who did not (Group 2).

Results

Participants who had completed post-graduate education had higher knowledge (p = 0.050), practice (p < 0.001), and overall combined scores (p = 0.011). Participants with ethics education had higher knowledge (p < 0.001), attitude (p = 0.001), practice (p < 0.001), and overall score (p < 0.001). Most participants preferred consulting colleagues if an ethical dilemma arose. Fewer participants had heard of the Declaration of Helsinki. Most participants thought doctors to be most capable of judging what is best for the patient (Study 1: 70.42%, Study 2 Group 1: 42.59%, Group 2: 80%). Case scenarios in which participants demonstrated poor practice were ethical issues concerning truth-telling, end-of-life decisions, treating HIV/AIDS patients, treating a minor, and reporting colleague’s errors.

Conclusions

This study found that participants who have received medical ethics education have higher knowledge, attitude, and practice scores. The results further justify the need for medical ethics education to be a part of the core medical curriculum. A blame-free environment where seniors can be approached for advice should be created. Research ethics should also be given attention. During medical ethics training, ethical issues where doctors perform poorly should be given more priority and should be discussed in a country-specific context.
ACCV: automatic classification algorithm of cataract video based on deep learning
Authors: Hu Shenming , Luan Xinze , Wu Hong , Wang Xiaoting , Yan Chunhong , Wang Jingying , Liu Guantong , He Wei
Published: August 2021

Purpose

A real-time automatic cataract-grading algorithm based on cataract video is proposed.

Materials and methods

In this retrospective study, we set the video of the eye lens section as the research target. A method is proposed to use YOLOv3 to assist in positioning, to automatically identify the position of the lens and classify the cataract after color space conversion. The data set is a cataract video file of 38 people's 76 eyes collected by a slit lamp. Data were collected using five random manner, the method aims to reduce the influence on the collection algorithm accuracy. The video length is within 10 s, and the classified picture data are extracted from the video file. A total of 1520 images are extracted from the image data set, and the data set is divided into training set, validation set and test set according to the ratio of 7:2:1.

Results

We verified it on the 76-segment clinical data test set and achieved the accuracy of 0.9400, with the AUC of 0.9880, and the F1 of 0.9388. In addition, because of the color space recognition method, the detection per frame can be completed within 29 microseconds and thus the detection efficiency has been improved significantly.

Conclusion

With the efficiency and effectiveness of this algorithm, the lens scan video is used as the research object, which improves the accuracy of the screening. It is closer to the actual cataract diagnosis and treatment process, and can effectively improve the cataract inspection ability of non-ophthalmologists. For cataract screening in poor areas, the accessibility of ophthalmology medical care is also increased.
Secondary bacterial infections and antimicrobial resistance in COVID-19: comparative evaluation of pre-pandemic and pandemic-era, a retrospective single center study
Authors: Karataş Mustafa , Yaşar-Duman Melike , Tünger Alper , Çilli Feriha , Aydemir Şöhret , Özenci Volkan
Published: August 2021

Purpose

In this study, we aimed to evaluate the epidemiology and antimicrobial resistance (AMR) patterns of bacterial pathogens in COVID-19 patients and to compare the results with control groups from the pre-pandemic and pandemic era.

Methods

Microbiological database records of all the COVID-19 diagnosed patients in the Ege University Hospital between March 15, 2020, and June 15, 2020, evaluated retrospectively. Patients who acquired secondary bacterial infections (SBIs) and bacterial co-infections were analyzed. Etiology and AMR data of the bacterial infections were collected. Results were also compared to control groups from pre-pandemic and pandemic era data.

Results

In total, 4859 positive culture results from 3532 patients were analyzed. Fifty-two (3.59%) patients had 78 SBIs and 38 (2.62%) patients had 45 bacterial co-infections among 1447 COVID-19 patients. 22/85 (25.88%) patients died who had bacterial infections. The respiratory culture-positive sample rate was 39.02% among all culture-positive samples in the COVID-19 group. There was a significant decrease in extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (8.94%) compared to samples from the pre-pandemic (20.76%) and pandemic era (20.74%) (p = 0.001 for both comparisons). Interestingly, Acinetobacter baumannii was the main pathogen in the respiratory infections of COVID-19 patients (9.76%) and the rate was significantly higher than pre-pandemic (3.49%, p < 0.002) and pandemic era control groups (3.11%, p < 0.001).

Conclusion

Due to the low frequency of SBIs reported during the ongoing pandemic, a more careful and targeted antimicrobial prescription should be taken. While patients with COVID-19 had lower levels of ESBL-producing Enterobacterales, the frequency of multidrug-resistant (MDR) A. baumannii is higher.
SPOP-mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions
Authors: Jiang Qiwei , Zheng Nana , Bu Lang , Zhang Xiaomei , Zhang Xiaoling , Wu Yuanzhong , Su Yaqing , Wang Lei , Zhang Xiaomin , Ren Shancheng , Dai Xiangpeng , Wu Depei , Xie Wei , Wei Wenyi , Zhu Yasheng , Guo Jianping
Published: August 2021

Background

3-phosphoinositide-dependent protein kinase-1 (PDK1) acts as a master kinase of protein kinase A, G, and C family (AGC) kinase to predominantly govern cell survival, proliferation, and metabolic homeostasis. Although the regulations to PDK1 downstream substrates such as protein kinase B (AKT) and ribosomal protein S6 kinase beta (S6K) have been well established, the upstream regulators of PDK1, especially its degrader, has not been defined yet.

Method

A clustered regularly interspaced short palindromic repeats (CRISPR)-based E3 ligase screening approach was employed to identify the E3 ubiquitin ligase for degrading PDK1. Western blotting, immunoprecipitation assays and immunofluorescence (IF) staining were performed to detect the interaction or location of PDK1 with speckle-type POZ protein (SPOP). Immunohistochemistry (IHC) staining was used to study the expression of PDK1 and SPOP in prostate cancer tissues. In vivo and in vitro ubiquitination assays were performed to measure the ubiquitination conjugation of PDK1 by SPOP. In vitro kinase assays and mass spectrometry approach were carried out to identify casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3)-mediated PDK1 phosphorylation. The biological effects of PDK1 mutations and correlation with SPOP mutations were performed with colony formation, soft agar assays and in vivo xenograft mouse models.

Results

We identified that PDK1 underwent SPOP-mediated ubiquitination and subsequent proteasome-dependent degradation. Specifically, SPOP directly bound PDK1 by the consensus degron in a CK1/GSK3β-mediated phosphorylation dependent manner. Pathologically, prostate cancer patients associated mutations of SPOP impaired PDK1 degradation and thus activated the AKT kinase, resulting in tumor malignancies. Meanwhile, mutations that occurred around or within the PDK1 degron, by either blocking SPOP to bind the degron or inhibiting CK1 or GSK3β-mediated PDK1 phosphorylation, could markedly evade SPOP-mediated PDK1 degradation, and played potently oncogenic roles via activating the AKT kinase.

Conclusions

Our results not only reveal a physiological regulation of PDK1 by E3 ligase SPOP, but also highlight the oncogenic roles of loss-of-function mutations of SPOP or gain-of-function mutations of PDK1 in tumorigenesis through activating the AKT kinase.
Factors affecting addiction severity index (ASI) among clients enrolled in methadone maintenance treatment (MMT) program in Myanmar
Authors: Tun Sun , Vicknasingam B. , Singh Darshan
Published: August 2021

Background

Opioid substitution with methadone maintenance treatment (MMT) is shown to reduce illicit opioid use and renew social functioning. Understanding factors that undermine clients’ social functioning during MMT treatment is vital for improving treatment compliance and quality of life.

Method

A total of 210 respondents who were already enrolled in a formal MMT program in Myanmar were recruited from five cities through stratified random sampling for this cross-sectional study. The addiction severity index (ASI) was used to objectively assess respondents social functioning in the last 30 days. Higher ASI scores denote poorer social functioning.

Result

Respondents total ASI scores in the respective domains were: employment (47.4%), alcohol (44.4%), drug use (7.2%), legal (49.2%) and social–family relationship (10.7%). Those reported to have never injected drugs in the last 30 days had lower ASI total scores than those who reported injection drug use (p = 0.01). After identifying the differences in ASI total scores, we found there were significant associations in the clients’ hepatitis C status, age category, frequency of heroin injection, quality of life score, marital status, current leisure status with family/friend, current history of injection in the last 30 days, income status, satisfaction with current marital status, as well as reported drug and alcohol use (p < 0.05). Stepwise binary logistic regression showed that alcohol and higher frequency of heroin injection were associated with higher ASI scores. Meanwhile, older age, respondents those who had leisure time with family, and satisfied with current marital status had lower ASI scores (p < 0.05).

Conclusion

Our results indicate that those enrolled in the MMT program in Myanmar faced many challenges in their daily social functioning. Treatment providers must take heed of these apparent impediment to ensure clients chequered social functioning does not undermine their treatment compliance.

Trial registration: NA
A practical measure of health facility efficiency: an innovation in the application of routine health information to determine health worker productivity in Ethiopia
Authors: Hasan Md Zabir , Dinsa Girmaye D. , Berman Peter
Published: August 2021

Background

A simple indicator of technical efficiency, such as productivity of health workers, measured using routine health facility data, can be a practical approach that can inform initiatives to improve efficiency in low- and middle-income countries. This paper presents a proof of concept of using routine information from primary healthcare (PHC) facilities to measure health workers’ productivity and its application in three regions of Ethiopia.

Methods

In four steps, we constructed a productivity measure of the health workforce of Health Centers (HCs) and demonstrated its practical application: (1) developing an analytical dataset using secondary data from health management information systems (HMIS) and human resource information system (HRIS); (2) principal component analysis and factor analysis to estimate a summary measure of output from five indicators (annual service volume of outpatient visits, family planning, first antenatal care visits, facility-based deliveries by skilled birth attendants, and children [< 1 year] with three pentavalent vaccines); (3) calculating a productivity score by combining the summary measure of outputs and the total number of health workers (input), and (4) implementing regression models to identify the determinant of productivity and ranking HCs based on their adjusted productivity score.

Results

We developed an analytical dataset of 1128 HCs; however, significant missing values and outliers were reported in the data. The principal component and factor scores developed from the five output measures were highly consistent (correlation coefficient = 0.98). We considered the factor score as the summary measure of outputs for estimating productivity. A very weak association was observed between the summary measure of output and the total number of staff. The result also highlighted a large variability in productivity across similar health facilities in Ethiopia, represented by the significant dispersion in summary measure of output occurring at similar levels of the health workers.

Conclusions

We successfully demonstrated the analytical steps to estimate health worker productivity and its practical application using HMIS and HRIS. The methodology presented in this study can be readily applied in low- and middle-income countries using widely available data—such as DHIS2—that will allow further explorations to understand the causes of technical inefficiencies in the health system.
E3 ubiquitin ligase TRIM29 promotes pancreatic cancer growth and progression via stabilizing Yes-associated protein 1
Authors: Deng Xueqiang , Fu Xiaowei , Teng Hong , Fang Lu , Liang Bo , Zeng Rengui , Chen Lian , Zou Yeqing
Published: August 2021

Background

Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear.

Methods

Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay.

Results

TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation.

Conclusion

Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.
Establishing a genomic database for the medicinal plants in the Brazilian Pharmacopoeia
Authors: Zhou Guan-Ru , Liao Bao-Sheng , Li Qiu-Shi , Xu Jiang , Chen Shi-Lin
Published: August 2021

Background

Brazil is exceptionally abundant in medicinal plant resources and has a rich ethnopharmacological history. Brazilian Pharmacopoeia (BP) acts as a national standard that regulates drug quality and has six published editions. Recent genomic approaches have led to a resurgence of interest in herbal drugs. The genomic data of plants has been used for pharmaceutical applications, protecting natural resources, and efficiently regulating the market. However, there are few genomic databases specifically for medicinal plants, and the establishment of a database that focuses on the herbs contained in the BP is urgently required.

Methods

The medicinal plant species included in each edition of the BP were analyzed to understand the evolution of the Brazilian herbal drugs. The data of 82 plants in the BP were collected and categorized into four sections: DNA barcodes, super-barcodes, genomes, and sequencing data. A typical web server architecture pattern was used to build the database and website. Furthermore, the cp-Gs of the Aloe genus in the database were analyzed as an illustration.

Results

A new database, the Brazilian Pharmacopoeia Genomic Database (BPGD) was constructed and is now publicly accessible. A BLAST server for species identification and sequence searching with the internal transcribed spacer 2 (ITS2), the intergenic region (psbA-trnH), and the chloroplast genome (cp-G) of Brazilian medicinal plants was also embedded in the BPGD. The database has 753 ITS2 of 76 species, 553 psbA-trnH and 190 genomes (whole genome and chloroplast genome) of 57 species. In addition, it contains 37 genome sequence data sets of 24 species and 616 transcriptome sequence data sets of 34 species and also includes 187 cp-Gs representing 57 medicinal species in the BP. Analyses of the six cp-Gs of three Aloe species identified the variable regions in the cp-Gs. These can be used to identify species and understand the intraspecific relationships.

Conclusions

This study presents the first genomic database of medicinal plants listed in the latest BP. It serves as an efficient platform to obtain and analyze genomic data, accelerate studies regarding Brazilian medicinal plants and facilitate the rational development on their market regulation.
Prevalence of fibrodysplasia ossificans progressiva (FOP) in the United States: estimate from three treatment centers and a patient organization
Authors: Pignolo Robert J. , Hsiao Edward C. , Baujat Genevieve , Lapidus David , Sherman Adam , Kaplan Frederick S.
Published: August 2021

Background

Fibrodysplasia ossificans progressiva (FOP), an ultra-rare, progressive, and permanently disabling disorder of extraskeletal ossification, is characterized by episodic and painful flare-ups and irreversible heterotopic ossification in muscles, tendons, and ligaments. Prevalence estimates have been hindered by the rarity of FOP and the heterogeneity of disease presentation. This study aimed to provide a baseline prevalence of FOP in the United States, based on contact with one of 3 leading treatment centers for FOP (University of Pennsylvania, Mayo Clinic, or University of California San Francisco), the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) membership list, or the IFOPA FOP Registry through July 22, 2020.

Results

Patient records were reviewed, collected, and deduplicated using first and last name initials, sex, state, and year of birth. A Kaplan–Meier survival curve was applied to each individual patient to estimate the probability that he or she was still alive, and a probability-weighted net prevalence estimate was calculated. After deduplication, 373 unique patients were identified in the United States, 294 of whom who were not listed as deceased in any list. The average time since last contact for 284 patients was 1.5 years. Based on the application of the survival probability, it is estimated that 279 of these patients were alive on the prevalence date (22 July 2020). An adjusted prevalence of 0.88 per million US residents was calculated using either an average survival rate estimate of 98.4% or a conservative survival rate estimate of 92.3% (based on the Kaplan–Meier survival curve from a previous study) and the US Census 2020 estimate of 329,992,681 on prevalence day.

Conclusions

This study suggests that the prevalence of FOP is higher than the often-cited value of 0.5 per million. Even so, because inclusion in this study was contingent upon treatment by the authors, IFOPA membership with confirmed clinical diagnosis, and the FOP Registry, the prevalence of FOP in the US may be higher than that identified here. Thus, it is imperative that efforts be made to identify and provide expert care for patients with this ultra-rare, significantly debilitating disease.
Feasibility of a home-based interdisciplinary rehabilitation program for patients with Post-Intensive Care Syndrome: the REACH study
Authors: Major Mel E. , Dettling-Ihnenfeldt Daniela , Ramaekers Stephan P. J. , Engelbert Raoul H. H. , van der Schaaf Marike
Published: August 2021

Background

Survivors of critical illness experience long-term functional challenges, which are complex, heterogeneous, and multifactorial in nature. Although the importance of rehabilitation interventions after intensive care unit (ICU) discharge is universally recognized, evidence on feasibility and effectiveness of home-based rehabilitation programs is scarce and ambiguous. This study investigates the feasibility of an interdisciplinary rehabilitation program designed for patients with Post-Intensive Care Syndrome (PICS) who are discharged home.

Methods

A mixed method, non-randomized, prospective pilot feasibility study was performed with a 6-month follow-up, comparing the intervention (REACH) with usual care. REACH was provided by trained professionals and included a patient-centered, interdisciplinary approach starting directly after hospital discharge. Primary outcomes were patient safety, satisfaction, adherence, referral need and health care usage. Secondary outcomes, measured at 3 timepoints, were functional exercise capacity, self-perceived health status, health-related quality of life (HRQoL), return to work and psychotrauma. Risk of undernutrition was assessed at baseline.

Results

43 patients with a median mechanical ventilation duration of 8 (IQR:10) days, were included in the study and 79.1% completed 6-month follow-up. 19 patients received the intervention, 23 received usual care. Groups were similar for gender distribution and ICU length of stay. No adverse events occurred. REACH participants showed higher satisfaction with treatment and reported more allied health professional visits, while the usual care group reported more visits to medical specialists. Qualitative analysis identified positive experiences among REACH-professionals related to providing state-of-the-art interventions and sharing knowledge and expertise within an interprofessional network. Similar recovery was seen between groups on all secondary outcomes, but neither group reached reference values for HRQoL at 6 months. Larger return to work rates were seen in the REACH group. Prevalence of undernutrition at hospital discharge was high in both groups (> 80%), warranting the need for careful tuning of physical therapy and nutritional interventions.

Conclusions

This study shows that providing early, home-based rehabilitation interventions for patients with PICS-related symptoms is feasible and perceived positively by patients and professionals. When provided in an interdisciplinary collaborative network state of the art, person-centered interventions can be tailored to individual needs potentially increasing patient satisfaction, adherence, and efficacy.

Registered in the Dutch Trial register: NL7792:https://www.trialregister.nl/trial/7792, registered 7-06-2019.
Course and predictors of posttraumatic stress-related symptoms among family members of deceased ICU patients during the first year of bereavement
Authors: Tang Siew Tzuh , Huang Chung-Chi , Hu Tsung-Hui , Chou Wen-Chi , Chuang Li-Pang , Chiang Ming Chu
Published: August 2021

Background/Objective

Death in intensive care units (ICUs) may increase bereaved family members’ risk for posttraumatic stress disorder (PTSD). However, posttraumatic stress-related symptoms (hereafter as PTSD symptoms) and their precipitating factors were seldom examined among bereaved family members and primarily focused on associations between PTSD symptoms and patient/family characteristics. We aimed to investigate the course and predictors of clinically significant PTSD symptoms among family members of deceased ICU patients by focusing on modifiable quality indicators for end-of-life ICU care.

Method

In this longitudinal observational study, 319 family members of deceased ICU patients were consecutively recruited from medical ICUs from two Taiwanese medical centers. PTSD symptoms were assessed at 1, 3, 6, and 13 months post-loss using the Impact of Event Scale-Revised (IES-R). Family satisfaction with end-of-life care in ICUs was assessed at 1 month post-loss. End-of-life care received in ICUs was documented over the patient’s ICU stay. Predictors for developing clinically significant PTSD symptoms (IES-R score ≥ 33) were identified by multivariate logistic regression with generalized estimating equation modeling.

Results

The prevalence of clinically significant PTSD symptoms decreased significantly over time (from 11.0% at 1 month to 1.6% at 13 months post-loss). Longer ICU stays (adjusted odds ratio [95% confidence interval] = 1.036 [1.006, 1.066]), financial insufficiency (3.166 [1.159, 8.647]), and reported use of pain medications (3.408 [1.230, 9.441]) by family members were associated with a higher likelihood of clinically significant PTSD symptoms among family members during bereavement. Stronger perceived social support (0.937 [0.911, 0.965]) and having a Do-Not-Resuscitate (DNR) order issued before the patient’s death (0.073 [0.011, 0.490]) were associated with a lower likelihood of clinically significant PTSD symptoms. No significant association was observed for family members’ satisfaction with end-of-life care (0.988 [0.944, 1.034]) or decision-making in ICUs (0.980 [0.944, 1.018]).

Conclusions

The likelihood of clinically significant PTSD symptoms among family members decreased significantly over the first bereavement year and was lower when a DNR order was issued before death. Enhancing social support and facilitating a DNR order may reduce the trauma of ICU death of a beloved for family members at risk for developing clinically significant PTSD symptoms.
Specific splice junction detection in single cells with SICILIAN
Authors: Dehghannasiri Roozbeh , Olivieri Julia Eve , Damljanovic Ana , Salzman Julia
Published: August 2021

Precise splice junction calls are currently unavailable in scRNA-seq pipelines such as the 10x Chromium platform but are critical for understanding single-cell biology. Here, we introduce SICILIAN, a new method that assigns statistical confidence to splice junctions from a spliced aligner to improve precision. SICILIAN is a general method that can be applied to bulk or single-cell data, but has particular utility for single-cell analysis due to that data’s unique challenges and opportunities for discovery. SICILIAN’s precise splice detection achieves high accuracy on simulated data, improves concordance between matched single-cell and bulk datasets, and increases agreement between biological replicates. SICILIAN detects unannotated splicing in single cells, enabling the discovery of novel splicing regulation through single-cell analysis workflows.
Expression of Sonic Hedgehog and pathway components in the embryonic mouse head: anatomical relationships between regulators of positive and negative feedback
Authors: Sigulinsky Crystal L. , Li Xiaodong , Levine Edward M.
Published: August 2021

Objective

The Hedgehog pathway is a fundamental signaling pathway in organogenesis. The expression patterns of the ligand Sonic Hedgehog (Shh) and key pathway components have been studied in many tissues but direct spatial comparisons across tissues with different cell compositions and structural organization are not common and could reveal tissue-specific differences in pathway dynamics.

Results

We directly compared the expression characteristics of Shh, and four genes with functional roles in signaling and whose expression levels serve as readouts of pathway activity in multiple tissues of the embryonic mouse head at embryonic day 15.5 by serial in situ hybridization. The four readout genes were the positive feedback regulator Gli1, and three negative feedback regulators, Patched1, Patched2, and Hedgehog Interacting Protein. While the relative abundance of Gli1 was similar across tissues, the relative expression levels and spatial distribution of Shh and the negative feedback regulators differed, suggesting that feedback regulation of hedgehog signaling is context dependent. This comparative analysis offers insight into how consistent pathway activity could be achieved in tissues with different morphologies and characteristics of ligand expression.
Examination of social determinants of health among patients with limited English proficiency
Authors: Fischer Austin , Conigliaro Joseph , Allicock Shaun , Kim Eun Ji
Published: August 2021

Objectives

The purpose of this study is to examine the prevalence of social needs by English proficiency using data from Northwell Health’s social determinants of health screening program. The screening program evaluates 12 domains of social needs: material need, employment, medical-legal assistance, health insurance, public benefits, health literacy, transportation, medical care, utilities, housing quality, food security, and housing insecurity. We have identified patients to have limited English proficiency if they have selected a language other than English as their primary language.

Results

The study population includes 92,958 individuals; of these, 83,445 (89.8%) patients are English proficient, and 9513 (10.2%) patients have limited English proficiency. A higher percentage of patients with limited English proficiency has social needs, including material need, employment, medical-legal assistance, health insurance, public benefit, health literacy, medical care, utility bill, poor housing quality, and food insecurity (all p-values < 0.05). In multivariable logistic regression models adjusting for sociodemographic information, LEP status (odds ratio = 1.36 [1.25–1.49]) has been associated with having social needs. These findings suggest that system-wide SDH screening and referral programs should identify ways to ensure capturing social needs among patients with limited English proficiency.
Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer’s continuum
Authors: Vilor-Tejedor Natalia , Ciampa Iacopo , Operto Grégory , Falcón Carles , Suárez-Calvet Marc , Crous-Bou Marta , Shekari Mahnaz , Arenaza-Urquijo Eider M. , Milà-Alomà Marta , Grau-Rivera Oriol , Minguillon Carolina , Kollmorgen Gwendlyn , Zetterberg Henrik , Blennow Kaj , Guigo Roderic , Molinuevo José Luis , Gispert Juan Domingo ,   for the ALFA study, Beteta Annabella , Brugulat Anna , Cacciaglia Raffaele , Cañas Alba , Deulofeu Carme , Cumplido Irene , Dominguez Ruth , Emilio Maria , Fauria Karine , Fuentes Sherezade , Hernandez Laura , Huesa Gema , Huguet Jordi , Marne Paula , Menchón Tania , Polo Albina , Pradas Sandra , Rodriguez-Fernandez Blanca , Sala-Vila Aleix , Sánchez-Benavides Gonzalo , Salvadó Gemma , Soteras Anna , Vilanova Marc
Published: August 2021

Background

Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer’s disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and these pathophysiological mechanisms remains unknown.

Objective

We aimed to investigate the association between ePVS and CSF biomarkers of several pathophysiological mechanisms for AD. We hypothesized that ePVS will be associated to CSF biomarkers early in the AD continuum (i.e., amyloid positive cognitively unimpaired individuals). Besides, we explored associations between ePVS and demographic and cardiovascular risk factors.

Methods

The study included 322 middle-aged cognitively unimpaired participants from the ALFA + study, many within the Alzheimer’s continuum. NeuroToolKit and Elecsys® immunoassays were used to measure CSF Aβ42, Aβ40, p-tau and t-tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α-synuclein. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4-point visual rating scale. Odds ratios were calculated for associations of cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aβ status (positivity defined as Aβ42/40 < 0.071).

Results

The degree of PVS significantly increased with age in both, BG and CS regions independently of cardiovascular risk factors. Higher levels of p-tau, t-tau, and neurogranin were significantly associated with ePVS in the CS of Aβ positive individuals, after accounting for relevant confounders. No associations were detected in the BG neither in Aβ negative participants.

Conclusions

Our results support that ePVS in the CS are specifically associated with tau pathophysiology, neurodegeneration, and synaptic dysfunction in asymptomatic stages of the Alzheimer’s continuum.
Canadian food ladders for dietary advancement in children with IgE-mediated allergy to milk and/or egg
Authors: Chomyn Alanna , Chan Edmond S. , Yeung Joanne , Vander Leek Timothy K. , Williams Brock A. , Soller Lianne , Abrams Elissa M. , Mak Raymond , Wong Tiffany
Published: August 2021

Food ladders are clinical tools already widely used in Europe for food reintroduction in milk- and egg-allergic children. Previously developed milk and egg ladders have limited applicability to Canadian children due to dietary differences and product availability. Herein we propose a Canadian version of cow’s milk and egg food ladders and discuss the potential role that food ladders may have in the care of children with IgE-mediated allergies to cow’s milk and/or egg, as either a method of accelerating the acquisition of tolerance in those who would outgrow on their own, or as a form of modified oral immunotherapy in those with otherwise persistent allergy.