bluuebunny/crossref_metadata_2025 huggingface dataset:
A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis
Authors: Roussel Murielle , Merlini Giampaolo , Chevret Sylvie , Arnulf Bertrand , Stoppa Anne Marie , Perrot Aurore , Palladini Giovanni , Karlin Lionel , Royer Bruno , Huart Antoine , Macro Margaret , Morel Pierre , Frenzel Laurent , Touzeau Cyrille , Boyle Eileen , Dorvaux Véronique , Le Bras Fabien , Lavergne David , Bridoux Frank , Jaccard Arnaud
Published: February 2020

Daratumumab is a human monoclonal antibody targeting CD38, an antigen uniformly expressed by plasma cells in multiple myeloma and light-chain amyloidosis (AL). We report the results of a prospective multicenter phase 2 study of daratumumab monotherapy in AL (NCT02816476). Forty previously treated AL patients with a difference between involved and uninvolved free light chains (dFLC) >50 mg/L were included in 15 centers between September of 2016 and April of 2018. Patients received 6 28-day cycles of IV daratumumab, every week for cycles 1 and 2 and every 2 weeks for cycles 3 through 6. Median age was 69 years (range, 45-83). Twenty-six patients had ≥2 organs involved, with heart in 24 and kidney in 26. Median time from diagnosis to enrollment was 23 months (interquartile range, 4-122), with a median of 3 prior therapies (range, 1-5). At data cutoff (September of 2019), all patients discontinued therapy; 33 received the planned 6 cycles. Overall, 22 patients had hematological response, and 19 patients (47.5%) achieved very good partial response (dFLC <40 mg/L) or better. Median time to hematological response was 1 week. Patients with no response after 4 doses were unlikely to respond further. Renal and cardiac responses occurred in 8 and 7 patients, respectively. Daratumumab was well tolerated, with no unexpected adverse events. With a median follow-up of 26 months, the 2-year overall survival rate was 74% (95% confidence interval, 62-81). Daratumumab monotherapy is associated with deep and rapid hematological responses in previously treated AL patients, with a good safety profile. Further studies of daratumumab in combination regimens are warranted.
Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis
Authors: Liu Pengfei , Feng Yetong , Li Hanwei , Chen Xin , Wang Guangsuo , Xu Shiyuan , Li Yalan , Zhao Lei
Published: February 2020

Background

Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI.

Methods

In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated.

Results

The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues.

Conclusions

Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.
Unusual sequence characteristics of human chromosome 19 are conserved across 11 nonhuman primates
Authors: Harris R. Alan , Raveendran Muthuswamy , Worley Kim C. , Rogers Jeffrey
Published: February 2020

Background

Human chromosome 19 has many unique characteristics including gene density more than double the genome-wide average and 20 large tandemly clustered gene families. It also has the highest GC content of any chromosome, especially outside gene clusters. The high GC content and concomitant high content of hypermutable CpG sites raises the possibility chromosome 19 exhibits higher levels of nucleotide diversity both within and between species, and may possess greater variation in DNA methylation that regulates gene expression.

Results

We examined GC and CpG content of chromosome 19 orthologs across representatives of the primate order. In all 12 primate species with suitable genome assemblies, chromosome 19 orthologs have the highest GC content of any chromosome. CpG dinucleotides and CpG islands are also more prevalent in chromosome 19 orthologs than other chromosomes. GC and CpG content are generally higher outside the gene clusters. Intra-species variation based on SNPs in human common dbSNP, rhesus, crab eating macaque, baboon and marmoset datasets is most prevalent on chromosome 19 and its orthologs. Inter-species comparisons based on phyloP conservation show accelerated nucleotide evolution for chromosome 19 promoter flanking and enhancer regions. These same regulatory regions show the highest CpG density of any chromosome suggesting they possess considerable methylome regulatory potential.

Conclusions

The pattern of high GC and CpG content in chromosome 19 orthologs, particularly outside gene clusters, is present from human to mouse lemur representing 74 million years of primate evolution. Much CpG variation exists both within and between primate species with a portion of this variation occurring in regulatory regions.
The use of taxon-specific reference databases compromises metagenomic classification
Authors: R. Marcelino Vanessa , Holmes Edward C. , Sorrell Tania C.
Published: February 2020

A recent article in BMC Genomics describes a new bioinformatics tool, HumanMycobiomeScan, to classify fungal taxa in metagenomic samples. This tool was used to characterize the gut mycobiome of hunter-gatherers and Western populations, resulting in the identification of a range of fungal species in the vast majority of samples. In the HumanMycobiomeScan pipeline, sequence reads are mapped against a reference database containing fungal genome sequences only. We argue that using reference databases comprised of a single taxonomic group leads to an unacceptably high number of false-positives due to: (i) mapping to conserved genetic regions in reference genomes, and (ii) sequence contamination in the assembled reference genomes. To demonstrate this, we replaced the HumanMycobiomeScan’s fungal reference database with one containing genome sequences of amphibians and reptiles and re-analysed their case study. The classification pipeline recovered all species present in the reference database, revealing turtles (Geoemydidae), bull frogs (Pyxicephalidae) and snakes (Colubridae) as the most abundant herpetological taxa in the human gut. We also re-analysed their case study using a kingdom-agnostic pipeline. This revealed that while the gut of hunter-gatherers and Western subjects may be colonized by a range of microbial eukaryotes, only three fungal families were retrieved. These results highlight the pitfalls of using taxon-specific reference databases for metagenome classification, even when they are comprised of curated whole genome data. We propose that databases containing all domains of life provide the most suitable option for metagenomic species profiling, especially when targeting microbial eukaryotes.
Transcriptome analysis reveals the defense mechanism of cotton against Verticillium dahliae in the presence of the biocontrol fungus Chaetomium globosum CEF-082
Authors: Zhang Yun , Yang Na , Zhao Lihong , Zhu Heqin , Tang Canming
Published: February 2020

Background

Verticillium wilt of cotton is a serious soil-borne disease that causes a substantial reduction in cotton yields. A previous study showed that the endophytic fungus Chaetomium globosum CEF-082 could control Verticillium wilt of cotton, and induce a defense response in cotton plants. However, the comprehensive molecular mechanism governing this response is not yet clear.

Results

To study the signalling mechanism induced by CEF-082, the transcriptome of cotton seedlings pretreated with CEF-082 was sequenced. The results revealed 5638 DEGs at 24 h post inoculation with CEF-082, and 2921 and 2153 DEGs at 12 and 48 h post inoculation with Verticillium dahliae, respectively. At 24 h post inoculation with CEF-082, KEGG enrichment analysis indicated that the DEGs were enriched mainly in the plant-pathogen interaction, MAPK signalling pathway-plant, flavonoid biosynthesis, and phenylpropanoid biosynthesis pathways. There were 1209 DEGs specifically induced only in cotton plants inoculated with V. dahliae in the presence of the biocontrol fungus CEF-082, and not when cotton plants were only inoculated with V. dahliae. GO analysis revealed that these DEGs were enriched mainly in the following terms: ROS metabolic process, H2O2 metabolic process, defense response, superoxide dismutase activity, and antioxidant activity. Moreover, many genes, such as ERF, CNGC, FLS2, MYB, GST and CML, that regulate crucial points in defense-related pathways were identified and may contribute to V. dahliae resistance in cotton. These results provide a basis for understanding the molecular mechanism by which the biocontrol fungus CEF-082 increases the resistance of cotton to Verticillium wilt.

Conclusions

The results of this study showed that CEF-082 could regulate multiple metabolic pathways in cotton. After treatment with V. dahliae, the defense response of cotton plants preinoculated with CEF-082 was strengthened.
Cotton roots are the major source of gossypol biosynthesis and accumulation
Authors: Zhao Tianlun , Xie Qianwen , Li Cong , Li Cheng , Mei Lei , Yu John Z. , Chen Jinhong , Zhu Shuijin
Published: February 2020

Background

Gossypol is a specific secondary metabolite in Gossypium species. It not only plays a critical role in development and self-protection of cotton plants, but also can be used as important anti-cancer and male contraceptive compound. However, due to the toxicity of gossypol for human beings and monogastric animals, the consumption of cottonseeds was limited. To date, little is known about the gossypol metabolism in cotton plants.

Results

In this study, we found that cotyledon was the primary source of gossypol at the seed germination stage. But thereafter, it was mainly originated from developing roots. Grafting between glanded and glandless cotton as well as sunflower rootstocks and cotton scion revealed that gossypol was mainly synthesized in the root systems of cotton plants. And both glanded and glandless cotton roots had the ability of gossypol biosynthesis. But the pigment glands, the main storage of gossypol, had indirect effects on gossypol biosynthesis. In vitro culture of root and rootless seedling confirmed the strong gossypol biosynthesis ability in root system and the relatively weak gossypol biosynthesis ability in other organs of the seedling. Expression profiling of the key genes involved in the gossypol biosynthetic pathway also supported the root as the major organ of gossypol biosynthesis.

Conclusions

Our study provide evidence that the cotton root system is the major source of gossypol in both glanded and glandless cottons, while other organs have a relatively weak ability to synthesize gossypol. Gossypol biosynthesis is not directed related to the expression of pigment glands, but the presence of pigment glands is essential for gossypol accumulation. These findings can not only clarify the complex regulation network of gossypol metabolism, but it could also accelerate the crop breeding process with enhanced commercial values.
Contamination in complex healthcare trials: the falls in care homes (FinCH) study experience
Authors: Robinson K. , Allen F. , Darby J. , Fox C. , Gordon A. L. , Horne J. C. , Leighton P. , Sims E. , Logan P. A.
Published: February 2020

Background

Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents.

Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes.

During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants.

Conclusion

Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise.
Prevalence, associated factors and medication for symptoms related to gastroesophageal reflux disease among 1114 private-tuition students of Anuradhapura, Sri Lanka
Authors: Gunasinghe Darsha , Gunawardhana Chathurika , Halahakoon Shakthi , Haneeka Ali , Hanim Najiyya , Hapuarachchi Chamara , Rathish Devarajan
Published: February 2020

Background

Gastroesophageal reflux disease (GORD) is a chronic and a common condition worldwide which causes mild to severe symptoms. Private tuition attendees are a group which could have potential risk factors for GORD. Therefore, we aimed to determine the prevalence, associated factors and medication for symptoms related to GORD among advanced level private-tuition attendees of Anuradhapura, Sri Lanka.

Methods

A descriptive cross-sectional study was conducted among students aged ≥18 years. A self-administered questionnaire was used to collect data. Students scoring ≥ eight on the Frequency Scale for Symptoms of GORD were categorised to have symptoms related to GORD. Logistic regression was performed to determine the significant association between the variables of interest and the presence of symptoms related to GORD (P < 0.05).

Results

Data of 1114 students were included for the analysis. A high prevalence of symptoms related to GORD (52% - 580/1114) was noted. Heartburn received the highest score among GORD symptoms. Biology students had the highest prevalence of GORD symptoms (63% - 127/201). Also, Biology students had the highest percentage for the utilisation of overall (17% - 35/201) and prescribed (13% - 27/201) medication for GORD symptoms. Presence of symptoms related to GORD was significantly associated with female sex [OR - 0.436 (95% CI 0.342–0.555)], being boarded [OR - 2.021 (95% CI 1.325–3.083)], chronic illness [OR - 2.632 (95% CI 1.439–4.813)], midnight snack [OR - 1.776 (95% CI 1.379–2.287)], frequent lack of breakfast [OR - 2.145 (95% CI 1.688, 2.725)], quick eating [OR - 1.394 (95% CI 1.091–1.780)] and inadequate sleep [OR - 2.077 (95% CI 1.624–2.655)].

Conclusion

A high prevalence of symptoms related to GORD in comparison to previous literature was found among private tuition attendees. Possible reasons for the above findings were discussed.
Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis
Authors: Takai Atsuko , Kikuchi Kentaro , Ichimura Mayuko , Tsuneyama Koichi , Moritoki Yuki , Matsumoto Kotaro , Tsunashima Hiromichi , Onda Takeshi , Kuniyoshi Noriyuki , Nariyama Tomoyuki , Ohyatsu Sho , Kubota Juri , Nagumo Kozue , Sato Shinpei , Hara Masumi , Miyakawa Hiroshi
Published: February 2020

Background

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH.

Methods

Twelve newborn C57BL/6 J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured.

Results

Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 μmol/L, P = 0.001).

Conclusions

FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production.
Predictors of healthcare utilisation among poor older people under the livelihood empowerment against poverty programme in the Atwima Nwabiagya District of Ghana
Authors: Agyemang-Duah Williams , Peprah Charles , Arthur-Holmes Francis
Published: February 2020

Background

Like many other low- and middle-income countries (LMICs), the Ghanaian healthcare system remains poor which is likely to affect the utilisation of healthcare services, especially among poor older people who are faced with multiple health problems. Yet, factors that explain healthcare use among poor older people in LMICs, particularly Ghana remain largely unexplored. Understanding the predictors of healthcare use among poor older people could have a huge impact on health policies in LMICs including Ghana. This study, therefore, examined factors associated with healthcare use among poor older people under the Livelihood Empowerment Against Poverty (LEAP) programme in the Atwima Nwabiagya District of Ghana.

Methods

Cross-sectional data were obtained from an Ageing, Health, Lifestyle and Health Services (AHLHS) study conducted between 1 and 20 June 2018 (N = 200) in Atwima Nwabiagya District, Ghana. Sequential logistic regression models were performed to estimate the variables that predict healthcare use among poor older people. All test results were considered significant at 0.05 or less.

Results

The fully adjusted model showed that respondents aged 85–89 years (AOR = 0.094, CI: 0.007–1.170), acquired basic education (AOR =0.251, CI: 0.085–0.987), received no family support (AOR = 0.771, CI: 0.120–0.620), with no past illness records (AOR = 0.236, CI: 0.057–0.197) and who were not diagnosed of chronic non-communicable diseases (AOR = 0.418, CI: 0.101–0.723) were significantly less likely to utilise health facility compared with their respective counterparts. Moreover, those with no disability (AOR = 19.245, CI: 2.415–29.921) and who consumed low fruits (AOR = 1.435 = CI: 0.552–8.740) and vegetables (AOR = 1.202 = CI: 0.362–10.20) had a higher likelihood to use healthcare.

Conclusion

The study has outlined multiple factors influencing utilisation of healthcare among poor older people under the LEAP programme in Ghana. The results, therefore, validate the importance of social and behavioural determinants of healthcare use in the Ghanaian poor older population. We highlight the need for health planners and stakeholders to consider demographic, socio-economic, health-related and lifestyle factors when formulating health policy for poor older people in Ghana.
Do healthcare needs-based population segments predict outcomes among the elderly? Findings from a prospective cohort study in an urbanized low-income community
Authors: Chong Jia Loon , Low Lian Leng , Matchar David Bruce , Malhotra Rahul , Lee Kheng Hock , Thumboo Julian , Chan Angelique Wei-Ming
Published: February 2020

Background

A rapidly ageing population with increasing prevalence of chronic disease presents policymakers the urgent task of tailoring healthcare services to optimally meet changing needs. While healthcare needs-based segmentation is a promising approach to efficiently assessing and responding to healthcare needs at the population level, it is not clear how available schemes perform in the context of community-based surveys administered by non-medically trained personnel. The aim of this prospective cohort, community setting study is to evaluate 4 segmentation schemes in terms of practicality and predictive validity for future health outcomes and service utilization.

Methods

A cohort was identified from a cross-sectional health and social characteristics survey of Singapore public rental housing residents aged 60 years and above. Baseline survey data was used to assign individuals into segments as defined by 4 predefined population segmentation schemes developed in Singapore, Delaware, Lombardy and North-West London. From electronic data records, mortality, hospital admissions, emergency department visits, and specialist outpatient clinic visits were assessed for 180 days after baseline segment assignment and compared to segment membership for each segmentation scheme.

Results

Of 1324 residents contacted, 928 agreed to participate in the survey (70% response). All subjects could be assigned an exclusive segment for each segmentation scheme. Individuals in more severe segments tended to have lower quality of life as assessed by the EQ-5D Index for health utility. All population segmentation schemes were observed to exhibit an ability to differentiate different levels of mortality and healthcare utilization.

Conclusions

It is practical to assign individuals to healthcare needs-based population segments through community surveys by non-medically trained personnel. The resulting segments for all 4 schemes evaluated in this way have an ability to predict health outcomes and utilization over the medium term (180 days), with significant overlap for some segments. Healthcare needs-based segmentation schemes which are designed to guide action hold particular promise for promoting efficient allocation of services to meet the needs of salient population groups. Further evaluation is needed to determine if these schemes also predict responsiveness to interventions to meet needs implied by segment membership.
Associations with rates of falls among home care clients in Ontario, Canada: a population-based, cross-sectional study
Authors: Manis Derek R. , McArthur Caitlin , Costa Andrew P.
Published: February 2020

Background

Accidental falls among older adults are a leading cause of injury-related hospitalizations. Reducing falls is an ongoing quality improvement priority for home care, given that many home care clients experience falls. In this study, we identify factors associated with the rate of falls among home care clients.

Methods

We conducted a population-based, cross-sectional study using secondary data from the Hamilton, Niagara, Haldimand, and Brant health region of Ontario, Canada from January 1 – March 31, 2018. We captured person-level characteristics with falls from the Resident Assessment Instrument – Home Care (RAI-HC). Negative binomial regression was used to model the rate of falls.

Results

Functional characteristics of home care clients had strong, statistically significant associations with the rate of falls. Declines in activities of daily living, assistive device use for locomotion indoors, polypharmacy, and health conditions, such as dizziness or lightheadedness, and parkinsonism, were associated with a higher rate of falls. Males who used assistive devices had a higher rate of falls compared to females; however, males with neurological and cardiovascular health conditions had a decrease in the rate of falls compared to females. Home care clients with parkinsonism who used a cane and took eight or more drugs had stronger associations with an increased rate of falls compared to those who do not have parkinsonism.

Conclusions

Functional characteristics, polypharmacy, and health conditions are associated with increased rates of falls among home care clients. Home care clients who are at a greater risk of falls may require environmental adjustments in their home to reduce or eliminate the possibility of falling.
Correction to: Prepared for PrEP: preferences for HIV pre-exposure prophylaxis among Chinese men who have sex with men in an online national survey
Authors: Huang Wenting , Wu Dan , Ong Jason J. , Smith M. Kumi , Pan Stephen , Yang Fan , Fu Hongyun , Tang Weiming , Tucker Joseph D.
Published: February 2020

After publication of the original article [1], the authors would like to add a co-author, Dr. Stephen Pan, who contributed sufficiently to this manuscript.
Undiagnosed HIV, hepatitis B, and hepatitis C infections in people with severe psychiatric disorders in Ethiopia
Authors: Ayano Getinet , Haile Kibrom , Tesfaye Abel , Haile Kelemua , Demelash Sileshi , Tulu Mikias , Tsegaye Belachew , Solomon Melat , Kebede Alem , Biru Aynalem , Birhanu Habte , Zenawi Gebresilassie , Habtamu Yodit , Kibron Esias , Eshetu Seneshet , Sefiw Meseret , Assefa Dawit , Yohannes Zegeye
Published: February 2020

Background

Worldwide, there is limited epidemiologic evidence on the seroprevalence of undiagnosed chronic viral infections including HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients with severe psychiatric disorders. To our knowledge, this is the first study to explore and compare undiagnosed seroprevalence rates of HIV, HBV, and HCV infections among patients with severe psychiatric disorders.

Method

In this study, we included a random sample of 309 patients with severe psychiatric disorders selected by systematic sampling technique. We used a structured clinical interview for DSM-IV (SCID) to confirm the diagnosis of severe psychiatric disorders among the participants. Binary and multivariable logistic regression models, adjusting for the potential confounding factors was used to explore the potential determinants of chronic viral infections.

Result

The prevalence estimates of HIV infection among patients with severe psychiatric disorders in this study (3.24%) was roughly 3 times the estimated population prevalence of HIV infection in Ethiopia (1.1%). This study showed that the prevalence rates of HBV and HCV infections among patients with severe psychiatric disorders were 4.85 and 1.29%, respectively. Our results also showed that among patients with chronic viral infections, HIV, HBV and HCV, 76.92, 60, 80, and 75% respectively were undiagnosed. Regarding associated factors, the presence of chronic viral infection was found to be significantly associated with the age of the participants (ranging between 30 and 40 years) after adjusting for the possible confounding factors [AOR = 3.95 (95%CI.18–13.17)].

Conclusion

Even though the prevalence estimates of HIV (3.24%), HBV (4.85%), and HCV (1.29%) infections were high among patients with severe psychiatric disorders, the majority of them remained undiagnosed. HBV was found to be the commonly undiagnosed infection (4 out of 5) followed by HCV (3 out of 4) and HIV (6 out of 10). The present study provided evidence of a significant association between the age of the participant (between 30 and 40 years) and chronic viral infections in patients with severe psychiatric disorders. Increasing the awareness of psychiatry professionals and early screening, as well as interventions of chronic viral infections among patients with severe psychiatric disorders are imperative.
Cramping, crashing, cannulating, and clotting: a qualitative study of patients’ definitions of a “bad run” on hemodialysis
Authors: Kuo Pei-Yi , Saran Rajiv , Argentina Marissa , Heung Michael , Bragg-Gresham Jennifer , Krein Sarah , Gillespie Brenda W. , Zheng Kai , Veinot Tiffany C.
Published: February 2020

Background

Hemodialysis sessions frequently become unstable from complications such as intradialytic hypotension and untoward symptoms. Previous patient safety initiatives promote prevention of treatment complications; yet, they have placed little specific focus on avoidable session instability. A patient-centered definition of session instability grounded in patient experiences, and an understanding of patient perceptions of causes and solutions to instability, may enable such efforts.

Methods

Twenty-five participants participated in three focus groups and/or a survey. They were purposively sampled for variation in region of residence, and sensitivity to patient well-being. Focus group recordings were analyzed using descriptive coding, in vivo coding, and thematic analysis.

Results

Patients define unstable sessions (“bad runs”) as those in which they experience severe discomfort or unanticipated events that interfere with their ability to receive therapy. Bad runs were characterized primarily by cramping, low blood pressure (“crashing”), cannulation-related difficulties (“bad sticks”), and clotting of the dialysis circuit or vascular access. Patients believed that cramping and crashing could be explained by both patient and clinician behavior: patient fluid consumption and providers’ fluid removal goals. Patients felt that the responsibility for cannulation-related problems lay with dialysis staff, and they asked for different staff or self-cannulated as solutions. Clotting was viewed as an idiosyncratic issue with one’s body, and perceived solutions were clinician-driven. Patients expressed concern about “bad runs” on their ability to achieve fluid balance.

Conclusions

Findings point to novel priorities for efforts to enhance hemodialysis session stability, and areas in which patients can be supported to become involved in such efforts.
Elevated C-reactive protein and complement C3 levels are associated with preterm birth: a nested case–control study in Chinese women
Authors: Huang Shengzhu , Tian Jiarong , Liu Chaoqun , Long Yu , Cao Dehao , Wei Luyun , Zhu Xiujuan , Tang Ruiqiang , Liu Weiwu , Zeng Dingyuan , Li Mujun , Yang Xiaobo , Mo Zengnan
Published: February 2020

Background

Currently, there are many studies researched the associations between maternal serum inflammatory indicators (i.e. ferritin, C-reactive protein [CRP], C3 and C4) and preterm birth (PTB). The results, however, are inconsistent. Therefore, the aim of this study was to estimate the relationship between maternal serum inflammatory indicators and PTB in a nested case-control (NCC)study.

Methods

A NCC study was conducted by Guangxi Birth Cohort Study which enrolled a total of 6203 pregnant women between 50/7 and 346/7 weeks of gestational age (wGA) from six cities in China between 2015 and 2016. There were 206women who delivered preterm (< 370/7 wGA), and 412 women who delivered term birth, those women were matched by maternal age, birth place, gender of infants, and wGA at blood collection.

The inflammatory indicators were quantified by immunoturbidimetric methods.

Results

Highest quartile concentrations of all inflammatory indicators were determined versus median. After adjusting for maternal age, high levels of CRP (CRP > 16.60 mg/L) are related to the risk of PTB (OR = 2.16, 95% CI: 1.02–4.56, p = 0.044) in the first trimester. The association of C3 was extremely related to those who delivered PTB (OR = 2.53, 95% CI: 1.14–5.64, p = 0.023) in the first trimester. Moreover, no significant associations were found in C4 (p = 0.079) and ferritin (p = 0.067) between PTB.

Conclusions

Elevated concentrations of CRP and C3 in the first trimester were associated with increased risk of PTB. Inflammatory indicators may act a pivotal part in early diagnosis and prognosis of PTB.
Modifiable risk factors of congenital malformations in bale zone hospitals, Southeast Ethiopia: an unmatched case-control study
Authors: Mekonnen Alemayehu Gonie , Hordofa Alemu Girma , Kitila Tamiru Tesfaye , Sav Adem
Published: February 2020

Background

Congenital malformations are structural, functional, and metabolic defects that develop during the organogenesis period and present at birth or later in life. There has been little research on congenital malformations in Ethiopia, knowledge on the incidence of birth defects at birth is unknown and the etiologies of the anomalies are limited. This study, therefore, aimed to assess the modifiable risks of congenital anomalies among women in Bale zone hospitals, Ethiopia.

Methods

An unmatched case-control study was conducted from February 2018 to January 2019 in the Bale zone; namely Goba referral hospital, Robe, Ginnir and Dolomena hospitals. A total of 409 women were selected. Mothers who gave birth with any type of congenital malformation were assigned as cases and those who gave live births without any congenital abnormalities were assigned as controls. Controls were selected by the lottery method from the labor ward. For each case, two consecutive controls were included. Data were entered into Epi-data 3.1 and exported into Statistical Package for the Social Sciences (SPSS) version 21 for analysis. Logistic regression was conducted to analyze the data.

Results

Alarmingly, women who had been exposed to pesticides during the current pregnancy were two times more prone to give congenital malformed infants than their counterparts (AOR = 3.19; 95% CI = 1.31, 10.96). Additionally, those women who chewedkhatduring the periconceptional period were two times more likely to have congenital malformed infants as compared to women who did not engage in this activity (AOR = 2.40; 95% CI = 1.11, 5.19).

Conclusions

Urgent attention needs to be given by public health professionals and services tokhatchewing and maternal exposure to pesticides during pregnancy to reduce the risk of congenital malformations.
Efficacy and safety of bupropion in cancer-related fatigue, a randomized double blind placebo controlled clinical trial
Authors: Salehifar Ebrahim , Azimi Saeid , Janbabai Ghasem , Zaboli Ehsan , Hendouei Narjes , Saghafi Fatemeh , Borhani Samaneh
Published: February 2020

Background and objectives

Cancer-related fatigue (CRF) is one of the most prevalent complications experienced by cancer patients during and after the process of treatment. Despite conducting a lot of studies, there is no approved therapy to help manage CRF. This study aims to investigate the efficacy of bupropion on CRF.

Materials and methods

In this double-blind randomized placebo-controlled clinical trial, a total of 30 eligible cancer patients suffering from fatigue were randomly divided into two groups (15 patients in each group). Bupropion was administered 75 mg/day for the first three days and 150 mg/day (divided in two doses) till the end of the study at week 6. Fatigue as the primary outcome was measured by BFI (Brief Fatigue Inventory) and FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy) scales. Secondary outcomes included HADS (Hospital Anxiety and Depression Scale) and performance status (PS) measured by Karnofsky and ECOG (Eastern Cooperative Oncology Group) scales. Assessments were done at baseline, end of the second and sixth week.

Results

There was no significant difference between placebo and bupropion at baseline and the end of second week. Significant difference was seen between two groups at the end of week six (P = 0.006 based on BFI) in favor of bupropion. In-group assessment showed improvement in fatigue levels in both groups during study time (P = 0.000 based on BFI for both bupropion and placebo). Secondary outcomes (e.g., HADS and PS) were not different at baseline and the end of second week. However, at the end of week six, the difference was significant in favor of bupropion.

Conclusion

A six-week trial of bupropion reduces the CRF and improves the PS of cancer patients. Trial registration: Current Controlled Trials IRCT20090613002027N12, registration date: 2018-06-01.
Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer
Authors: Oba Takaaki , Maeno Kazuma , Takekoshi Daiya , Ono Mayu , Ito Tokiko , Kanai Toshiharu , Ito Ken-ichi
Published: February 2020

Background

The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).

Methods

We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed.

Results

In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042).

Conclusions

High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.
GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy
Authors: Ueki Shunsuke , Fujishima Fumiyoshi , Kumagai Takuro , Ishida Hirotaka , Okamoto Hiroshi , Takaya Kai , Sato Chiaki , Taniyma Yusuke , Kamei Takashi , Sasano Hironobu
Published: February 2020

Background

Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm.

The glucocorticoid (GC)-glucocorticoid receptor (GR) pathway plays pivotal roles in cellular response to various stresses of tumor cells, including chemotherapy. However, the status of the GC-GR pathway in ESCC, including its correlation with chemotherapeutic responses, is largely unknown.

Methods

GR, serum-and glucocorticoid-regulated kinase 1 (Sgk1), and N-myc down regulation gene 1 (NDRG1) were immunolocalized in 98 patients with ESCC who had undergone esophagectomy following neoadjuvant chemotherapy (NAC) with 2 courses of 5-fluorouracil + cisplatin. We also examined biopsy specimens before NAC in 42 cases and compared the results between those before and after NAC.

Results

Overall survival (OS) of the patients treated with surgery following NAC was significantly shorter in the group with high GR than that with low GR status (P = 0.0473). Both OS and disease-free survival (DFS) were significantly shorter in both Sgk1- and NDRG1-high groups than in the low groups (OS: Sgk1, P = 0.0055; NDRG1, P = 0.0021; DFS: Sgk1, P = 0.0240; NDRG1, P = 0.0086). Biopsy specimens before NAC showed significantly shorter DFS in the high Sgk1 group (P = 0.0095), while both OS and DFS were shorter in the high NDRG1 group (OS, P = 0.0233; DFS, P = 0.0006) than in the respective low groups. In the high NDRG1 group of biopsy specimens before NAC, the tumor reduction rate by NAC was significantly attenuated (P = 0.021).

Conclusions

High GR, Sgk1, and NDRG1 statuses in ESCC after NAC was significantly associated with an overall worse prognosis, with no significant changes in their expression levels before and after NAC. Therefore, increased activity of the GC-GR pathway with enhanced induction of Sgk1 and NDRG1 in carcinoma cells play pivotal roles in tumor progression and development of chemo-resistance in patients with ESCC undergoing NAC.
Self-reported symptoms of depression, anxiety and stress in Portuguese primary school-aged children
Authors: Costa Diogo , Cunha Marina , Ferreira Cláudia , Gama Augusta , Machado-Rodrigues Aristides M. , Rosado-Marques Vítor , Nogueira Helena , Silva Maria-Raquel G. , Padez Cristina
Published: February 2020

Background

Symptoms of depression, anxiety and stress experienced during childhood might have a negative impact on development. This study explores factors associated with such symptoms among Portuguese primary school-aged children.

Methods

A sample of children (n = 1022, mean age = 8.77 years old) was recruited in public and private schools from the cities of Coimbra, Lisbon and Porto, Portugal. The children’s version of the Depression, Anxiety and Stress Scale (DASS-C) was self-administered. Multivariate logistic regression models were fitted to measure associations (expressed as Odds Ratio, OR and 95% Confidence Intervals, CI) between each DASS-C subscale, dichotomized by its 4th vs. 3rd or less quartiles (symptoms increase with scores), and covariates: child sex, age, socioeconomic status (SES), sports activity beyond school, children self-assessed health status, child and mother’s body mass index and mother’s DASS scores.

Results

Age was negatively associated with anxiety symptoms (adjusted OR, 95% CI: 0.70, 0.57–0.87) and girls, compared to boys, presented lower odds of depressive and stress symptoms (adjusted OR, 95% CI: 0.65, 0.47–0.92 and 0.57, 0.41–0.80, respectively). A low socioeconomic status was associated with more frequent symptoms of stress (adjusted OR, 95%CI for low compared to high SES: 1.61, 1.01–2.56). Children with poorer self-assessed health status and whose mothers scored higher in the DASS also presented significantly higher odds of scoring in the 4th quartile (vs. 3rd or less) of the three DASS-C subscales.

Conclusions

These results suggest the need to tailor preventive efforts targeting childhood mental health symptoms.
Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial
Authors: Karimi-Zarchi Mojgan , Allahqoli Leila , Nehmati Ameneh , Kashi Abolfazl Mehdizadeh , Taghipour-Zahir Shokouh , Alkatout Ibrahim
Published: February 2020

Background

Human papillomavirus (HPV) is one of the most significant risk factors for cervical cancer. The HPV vaccine has a very significant impact on the incidence of cervical cancer. The present study aimed to investigate the impact of prophylactic quadrivalent HPV vaccine in the treatment of women with cervical intraepithelial neoplasia (CIN 1–3).

Methods

This randomized controlled trial was conducted in the Shahid Sadoughi University of Medical Sciences (SSUMS), Yazd, Iran, from October 2011 to November 2015 in women with histologically confirmed residual/recurrent CIN 1 or high-grade CIN (CIN 2–3). Eligible women were assigned randomly to an intervention and a control group. Women in the intervention group were given HPV vaccinations while those in the control group were not. Participants were followed up for 24 months. Primary and secondary outcomes, and adverse effects of the treatment in the two groups were compared using Student’s t test, the chi-square test, or Fisher’s exact test. P values < 0.05 or less were considered statistically significant.

Results

Three-hundred and twelve women were randomized to the two groups; the data of 138 in the intervention group and 104 in the control group were analyzed. The mean age of the women was 32.59 ± 4.85 years. Differences in age, marital status, and grades of CIN weren’t significant between the two groups. At the end of the two-year follow-up period, the number of women with CIN 2–3 in the intervention and control groups was reduced by 75% (from 93 to 23) versus 40% (from 69 to 41). The efficacy of the HPV vaccine in women with CIN 1–3 was 58.7% (p = 0.018). No serious adverse effects related to the vaccines were reported.

Conclusions

The prophylactic quadrivalent HPV vaccine after treatment may have a therapeutic effect in women with residual/recurrent CIN 1 or high-grade CIN (CIN 2–3).

Trial registration

Iranian Registry of Clinical Trials, IRCT20190603043801N1. Registered 24 July 2019 – Retrospectively registered, http://www.irct.ir/user/trial/40017/view
Prognostic factors for survival after bronchoscopic intervention in patients with airway obstruction due to primary pulmonary malignancy
Authors: Kim Bo-Guen , Shin Beomsu , Chang Boksoon , Kim Hojoong , Jeong Byeong-Ho
Published: February 2020

Background

Malignant central airway obstruction (MCAO) occurs in 20–30% of patients with primary pulmonary malignancy. Although bronchoscopic intervention is widely performed to treat MCAO, little data exist on the prognosis of interventional bronchoscopy. Therefore, we evaluated the clinical outcomes and prognostic factors of bronchoscopic interventions in patients with MCAO due to primary pulmonary malignancy.

Methods

This retrospective study was conducted at a university hospital and included 224 patients who received interventional bronchoscopy from 2004 to 2017, excluding patients with salivary gland-type tumor. A multivariable Cox proportional hazard regression analysis was used to identify independent prognostic factors associated with survival after the first bronchoscopic intervention.

Results

Among 224 patients, 191 (85.3%) were males, and the median age was 63 years. The most common histological type of malignancy was squamous cell carcinoma (71.0%). Technical success was achieved in 93.7% of patients. Acute complications and procedure-related death occurred in 15.6 and 1.3% of patients, respectively. The median survival time was 7.0 months, and survival rates at one year and two years were 39.7 and 28.3%, respectively. Poor survival was associated with underlying chronic pulmonary disease, poor performance status, extended lesion, extrinsic or mixed lesion, and MCAO due to disease progression and not receiving adjuvant treatment after bronchoscopic intervention.

Conclusions

Interventional bronchoscopy could be a safe and effective procedure for patients who have MCAO due to primary pulmonary malignancy. In addition, we found several prognostic factors for poor survival after intervention, which will help clinicians determine the best candidates for bronchoscopic intervention.