bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of serum hemoglobin level with the risk of carotid plaque beyond metabolic abnormalities among asymptomatic adults without major adverse clinical events: a cross-sectional cohort study
Authors: Choi Yunsuk , Won Ki-Bum , Kang Hyeon Hui , Change Hyuk-Jae
Published: March 2021

Background

The serum hemoglobin (Hb) level is closely related to adverse clinical outcomes. However, data on the association of Hb levels with subclinical atherosclerosis beyond metabolic abnormalities are limited.

Methods

This study evaluated the association among serum Hb level, metabolic syndrome (MetS), and the risk of carotid plaque formation in asymptomatic adults without a history of major adverse clinical events.

Results

A total of 2560 participants (mean age: 60 ± 8 years, 32.9% men) were stratified into four groups based on Hb quartiles, as follows: ≤ 12.8 g/dL (group I), 12.9–13.6 g/dL (group II), 13.7–14.5 g/dL (group III), and ≥ 14.6 g/dL (group IV). The overall prevalence of MetS and carotid plaque was 37.2% and 33.4%, respectively. The prevalence of MetS increased with increasing Hb level (group I: 27.4% vs. group II: 35.9% vs. group III: 42.6% vs. group IV: 44.1%,p < 0.001). The prevalence of carotid plaque was 34.3%, 28.1%, 32.8%, and 39.5% in groups I, II, III, and IV, respectively. Univariate logistic regression analysis showed that MetS was associated with an increased risk of carotid plaque (odds ratio [OR] 1.568, 95% confidence interval [CI] 1.326–1.856,p < 0.001). Only group II showed a lower risk of carotid plaque than group I (OR 0.750, 95% CI 0.596–0.943,p = 0.014). Multiple logistic regression models showed consistent results after adjusting for clinical factors, including MetS and its individual components.

Conclusion

Serum Hb level is associated with the risk of carotid plaque beyond MetS and its components in a relatively healthy adult population.
Psychosocial risk factors for postpartum depression in Chinese women: a meta-analysis
Authors: Qi Weijing , Zhao Fuqing , Liu Yutong , Li Qing , Hu Jie
Published: March 2021

Background

Postpartum depression (PPD) has been identified as a recognized public health problem that may adversely affect mothers, infants, and family units. Recent studies have identified risk factors for PPD in Westerners; however, societal and cultural differences between China and the West could, potentially, lead to differences in risk factors for PPD. No comprehensive study has been conducted to collect all the evidence to provide estimates of psychological and social risk factors in China. Therefore, this study aimed to quantitatively assess all studies meeting the review’s eligibility criteria and identify the psychological and social risk factors for PPD in Chinese women.

Methods

The following databases were used in the literature search from their inception until December 2020: PubMed, Embase, Foreign Medical Literature Retrieval Service (FMRS), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), and China Biology Medicine disc (CBM). The quality was assessed through Newcastle-Ottawa quality assessment scale. The I2statistic was used to quantify heterogeneity. We extracted data for meta-analysis and generated pooled-effect estimates from a fixed-effects model. Pooled estimates from a random-effects model were also generated if significant heterogeneity was present. Funnel plot asymmetry tests were used to check for publication bias. Statistical analysis was conducted using Review Manager version 5.3 software.

Results

From a total of 1175 identified studies, 51 were included in the analysis. Prenatal depression (OR 7.70; 95% CI 6.02–9.83) and prenatal anxiety (OR 7.07; 95% CI 4.12–12.13) were major risk factors for PPD. A poor economic foundation (OR 3.67; 95% CI 3.07–4.37) and a poor relationship between husband and wife (OR 3.56; 95% CI 2.95–4.28) were moderate risk factors. Minor risk factors included a poor relationship between mother-in-law and daughter-in-law (OR 2.89; 95% CI 2.12–3.95), a lack of social support (OR 2.57; 95% CI 2.32–2.85), unplanned pregnancy (OR 2.55; 95% CI 2.08–3.14), and poor living conditions (OR 2.44; 95% CI 1.92–3.10), mother-in-law as the caregiver (1.95; 95% CI 1.54–2.48) .

Conclusions

This study demonstrated a number of psychological and social risk factors for PPD in Chinese women. The major and moderate risk factors are prenatal depression, prenatal anxiety, a poor economic foundation, and a poor relationship between husband and wife. These findings have potential implications for informing preventive efforts and modifying screening to target at-risk populations.
Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery
Authors: Fan Biao , Bu Zhaode , Zhang Ji , Zong Xianglong , Ji Xin , Fu Tao , Jia Ziyu , Zhang Yinan , Wu Xiaojiang
Published: March 2021

Background

HIPEC is an emerging procedure to treat peritoneal metastasis of gastric cancer. Data about HIPEC in locally advanced gastric cancer is scarce. The purpose of this trial is to evaluate the safety and toxicity of prophylactic HIPEC with cisplatin for patients with locally advanced gastric cancer.

Methods

From March 2015 to November 2016, a prospective, randomized phase II trial was conducted. After radical gastrectomy, patients in the experimental group underwent HIPEC with cisplatin followed by adjuvant chemotherapy with SOX regime. Patients in the other group were treated with SOX regime alone. Postoperative complications and patient survival were compared.

Results

In total, 50 patients were eligible for analyses. No significant difference was found in the incidence of postoperative complications including anastomotic/intestinal leakage, liver dysfunction, bone marrow suppression, wound infection and ileus (P > 0.05). Mean duration of hospitalization after radical gastrectomy was 11.7 days. 12.2 days in experimental group and 10.8 days in control group respectively (P = 0.255). The percentage of patients with elevated tumor markers was 12.1% in experimental group, which was significantly lower than 41.2% in control group (P = 0.02). 3-year RFS of patients who treated with or without prophylactic HIPEC were 84.8 and 88.2% respectively (P = 0.986). In the multivariate analysis, pathological T stage was the only independent risk factor for the RFS of patients (P = 0.012, HR =15.071).

Conclusion

Additional intraoperative HIPEC with cisplatin did not increase postoperative complications for locally advanced gastric cancer after curative surgery. Prophylactic HIPEC with cisplatin was safe and tolerable, while it did not reduce the risk of peritoneal recurrence in this trial, supporting further studies to validate the efficacy of it.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2000038331. Registered 18 September 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=59692.
Sequential and co-occurring DNA damage response genetic mutations impact survival in stage III colorectal cancer patients receiving adjuvant oxaliplatin-based chemotherapy
Authors: Lin Peng-Chan , Yeh Yu-Min , Chan Ren-Hao , Lin Bo-Wen , Chen Po-Chuan , Pan Chien-Chang , Shen Meng-Ru
Published: March 2021

Background

Certain sequences of genomic mutations can lead to cancer formation and affect treatment outcomes and drug resistance. We constructed a cancer evolutionary tree using bulk-targeted deep sequencing to explore the impact of sequential and co-occurring somatic mutations on patients with stage III colorectal cancer (CRC).

Methods

A total of 108 stage III CRC patients from National Cheng Kung University Hospital (NCKUH) were recruited for this study between Jan. 2014 and Jan. 2019. Clinical information and tumor-targeted deep sequencing data were collected. Phylogenetic trees were reconstructed for evolutionary trajectories. We used a machine learning model for survival analysis.

Results

Six sequential somatic mutations stratified patients into seven subgroups based on survival. Patients carrying sequential germline followed by DNA damage response-related ATM or BRCA2 somatic mutations or non-TP53, APC somatic mutations had a better outcome than those without such mutations. The 4-year recurrence-free survival (RFS) probability was 88% in the low-risk group (G1) and 46% in the high-risk group (G2) (log-rank p-value 2e-05). The predictive efficacy by the area under the curve (AUC) was 0.73, 0.7, 0.797, and 0.88 at 2, 4, 6, and 8 years, respectively. The mutation status of mismatch repair (MMR) genes was not associated with RFS. Different genomic features were found between the groups. The orders of APC, KRAS and APC, BRCA2 sequential somatic mutations were associated with clinical outcomes. The occurrence of somatic mutations in BRCA2, such as TP53 somatic mutations, affected recurrence-free survival.

Conclusions

According to the evolution model, DNA damage response (DDR)-related ATM or BRCA2 somatic mutations are promising biomarkers for assessing the response of stage III CRC patients to oxaliplatin-based chemotherapy. The sequential order and co-occurring DDR somatic mutations are associated with recurrence-free survival.
PM2.5 exposure and anxiety in China: evidence from the prefectures
Authors: Chen Buwei , Ma Wen , Pan Yu , Guo Wei , Chen Yunsong
Published: March 2021

Background

Anxiety disorders are among the most common mental health concerns today. While numerous factors are known to affect anxiety disorders, the ways in which environmental factors aggravate or mitigate anxiety are not fully understood.

Methods

Baidu is the most widely used search engine in China, and a large amount of data on internet behavior indicates that anxiety is a growing concern. We reviewed the annual Baidu Indices of anxiety-related keywords for cities in China from 2013 to 2018 and constructed anxiety indices. We then employed a two-way fixed effect (FE) model to analyze the relationship between PM2.5 exposure and anxiety at the prefectural level.

Results

The results indicated that there was a significant positive association between PM2.5 and anxiety index. The anxiety index increased by 0.1565258 for every unit increase in the PM2.5 level (P < 0.05), which suggested that current PM2.5 levels in China pose a considerable risk to mental health.

Conclusion

The enormous impact of PM2.5 exposure indicates that the macroscopic environment can shape individual mentality and social behavior, and that it can be extremely destructive in terms of societal mindset.
Night-shift work duration and breast cancer risk: an updated systematic review and meta-analysis
Authors: Manouchehri E. , Taghipour A. , Ghavami V. , Ebadi A. , Homaei F. , Latifnejad Roudsari R.
Published: March 2021

Background

The International Agency for Research on Cancer (IARC) has classified shift work as a possible human carcinogen. The results of systematic on this topic is contradictory. This systematic review and meta-analysis, therefore, aimed to update the current evidence regarding the relationship between night-shift work duration and breast cancer risk.

Methods

PubMed, Web of Science, and Scopus as well as reference list of included studies were searched until December 19, 2020. Observational case–control or cohort studies investigating the relationship between the duration of night-shift work and breast cancer in women were included, which all quantified night-shift work exposure. All statistical analyses were done by Stata version 11.2.

Results

Our literature search was resulted in retrieval of 4854 publications from which 26 eligible studies with 1,313,348 participants were included in the meta-analyses. The pooled relative risk (RR) and 95% confidence intervals (CIs) of breast cancer for short-term night-shift workers (< 10 years) was 1.13 (95% CI 1.03–1.24, p = 0.008, I2 = 71.3%), and for long-term night-shift workers (≥ 10 years) was 1.08 (95% CI 0.99–1.17, p = 0.09, I2 = 42.2%), with moderate to substantial statistical heterogeneity observed in both analyses. The results of subgroup analysis showed that flight attendants with long overnight flights were at an elevated risk of breast cancer, but unmeasured confounders limited these results. The risk of breast cancer in case control studies, adjusted for reproductive factors and family history of breast cancer as well as studies with high quality was increased in both short term and long term night-shift workers.

Conclusions

This systematic review found a positive statistical relationship between night work and breast cancer risk in short-term night-shift workers but no increase was observed in the long-term night-shift workers.
Facing new challenges to informed consent processes in the context of translational research: the case in CARPEM consortium
Authors: Jacquier Elise , Laurent-Puig Pierre , Badoual Cécile , Burgun Anita , Mamzer Marie-France
Published: March 2021

Background

In the context of translational research, researchers have increasingly been using biological samples and data in fundamental research phases. To explore informed consent practices, we conducted a retrospective study on informed consent documents that were used for CARPEM’s translational research programs. This review focused on detailing their form, their informational content, and the adequacy of these documents with the international ethical principles and participants’ rights.

Methods

Informed consent forms (ICFs) were collected from CARPEM investigators. A content analysis focused on information related to biological samples and data treatment (context of sampling and collect, aims, reuse, consent renewal), including the type of consent. An automatic assessment of the readability of the ICFs were performed with the IT program “Flesch Score”.

Results

29 ICFs from 25 of 49 studies were analyzed after selection criteria were applied. Three types of consent were identified: 11 broad consents, six specific consents, and two opt-out consents. The Flesch Scores showed that most of the documents were too complex to be fully understood by most of the potential research participants. Most of the biological samples were collected during the healthcare routine, but the information content about secondary use of biological samples varied between ICFs. All documents mentioned personal data treatment but information about their reuse was not standardized in the ICFs.

Conclusions

Our review of current IC procedures of CARPEM showed that practices could be improved considering new translational research methods. “Old fashion written ICFs” should be adapted to the translational research approach, to better respect individual rights and international research ethics principles. In this context, theoretically, a digital tool allowing dynamic information and consent of participants, through an electronic interactive platform may be a good way to promote more active participation in research. Nevertheless, its feasibility in the complex environment of biological samples and data research remains to prove. The way of a combination of a broad consent followed by dynamic information may be alternatively tested.
An improved BM25 algorithm for clinical decision support in Precision Medicine based on co-word analysis and Cuckoo Search
Authors: Zhang Zicheng
Published: March 2021

Background

Retrieving gene and disease information from a vast collection of biomedical abstracts to provide doctors with clinical decision support is one of the important research directions of Precision Medicine.

Method

We propose a novel article retrieval method based on expanded word and co-word analyses, also conducting Cuckoo Search to optimize parameters of the retrieval function. The main goal is to retrieve the abstracts of biomedical articles that refer to treatments. The methods mentioned in this manuscript adopt the BM25 algorithm to calculate the score of abstracts. We, however, propose an improved version of BM25 that computes the scores of expanded words and co-word leading to a composite retrieval function, which is then optimized using the Cuckoo Search. The proposed method aims to find both disease and gene information in the abstract of the same biomedical article. This is to achieve higher relevance and hence score of articles. Besides, we investigate the influence of different parameters on the retrieval algorithm and summarize how they meet various retrieval needs.

Results

The data used in this manuscript is sourced from medical articles presented in Text Retrieval Conference (TREC): Clinical Decision Support (CDS) Tracks of 2017, 2018, and 2019 in Precision Medicine. A total of 120 topics are tested. Three indicators are employed for the comparison of utilized methods, which are selected among the ones based only on the BM25 algorithm and its improved version to conduct comparable experiments. The results showed that the proposed algorithm achieves better results.

Conclusion

The proposed method, an improved version of the BM25 algorithm, utilizes both co-word implementation and Cuckoo Search, which has been verified achieving better results on a large number of experimental sets. Besides, a relatively simple query expansion method is implemented in this manuscript. Future research will focus on ontology and semantic networks to expand the query vocabulary.
Differences in nursing home admission between functionally defined populations in Germany and the association with quality of health care
Authors: Domhoff Dominik , Seibert Kathrin , Stiefler Susanne , Wolf-Ostermann Karin , Peschke Dirk
Published: March 2021

Background

People prefer to age in place and not move into a nursing home as long as possible. The prevention of cognitive and functional impairments is feasible to support this goal. Health services play a key role in providing support for underlying medical conditions. We examined differentials in nursing home admissions between patient sharing networks in Germany and whether potential variations can be attributed to indicators of health care provision.

Methods

We conducted an ecological study using data of patients of 65 years and above from all 11 AOK statutory health insurance companies in Germany. Nursing home admissions were observed in a cohort of persons becoming initially care-dependent in 2006 (n = 118,213) with a follow-up of up to 10 years. A patient sharing network was constructed and indicators for quality of health care were calculated based on data of up to 6.6 million patients per year. Community detection was applied to gain distinct patient populations. Analyses were conducted descriptively and through regression analyses to identify the variation explained by included quality indicators.

Results

The difference in the proportion of nursing home admissions between identified clusters shows an interquartile range (IQR) of 12.6% and the average time between onset of care-dependency and admission to a nursing home an IQR of 10,4 quarters. Included quality indicators attributed for 40% of these variations for the proportion of nursing home admissions and 49% for the time until nursing home admission, respectively. Indicators of process quality showed the single highest contribution. Effects of single indicators were inconclusive.

Conclusions

Health services can support persons in their preference to age in place. Research and discussion on adequate health care for care-dependent persons and on conditions, where nursing home admission may be beneficial, is necessary.
Cancer related knowledge, attitude, and practice among community health care providers and health assistants in rural Bangladesh
Authors: Mubin Nazirum , Bin Abdul Baten Redwan , Jahan Sayeeda , Zohora Fatema Tuz , Chowdhury Naim Mahmud , Faruque Golam Mohiuddin
Published: March 2021

Background

Cancer remains one of the primary causes of death in Bangladesh. The success of cancer control in rural areas depends on the ability of the health care system and workforce to identify and manage cases properly at early stages. Community Health Workers (CHW) can play a vital role in this process. The present study aims to assess cancer related Knowledge, Attitude, and Practice (KAP) among 2 categories of CHWs - Community Health Care Providers (CHCP) and Health Assistants (HA) in rural Bangladesh.

Methods

A descriptive cross-sectional study was conducted using a self-administered questionnaire from July 2019 to June 2020. Multi-stage sampling technique was used to determine the sample. One Upazilla Health Complex (UHC) from each of the eight administrative divisions of Bangladesh were randomly chosen as study sites, from which 325 CHCPs and HAs were in the final sample. Multivariate logistic regression models were developed to determine the association between KAP scores and demographic variables.

Results

Our study shows that a modest number of respondents scored above average in the knowledge (54.15%), attitude (58.15%), and practice (65.54%) sections. Majority CHCPs (90.91%) and HAs (96.06%) did not receive govt. training on cancer. Only 20.71% HAs and 25.2% CHCPs knew about the availability of cancer treatment options in Bangladesh. Uncertainty about the availability of relevant treatments or vaccinations at public facilities was also high. Having cancer in the family, income, duration of employment and workplace locations were important predictors of cancer related KAP scores.

Conclusion

Healthcare workforce’s knowledge gap and unfavorable attitude towards cancer may result in poor delivery of care at the rural level. For many people in rural areas, CHCPs and HAs are the first point of contact with the healthcare system and thus effective cancer control strategies must consider them as key stakeholders. Targeted training programs must be adopted to address the cancer related KAP gaps among CHCPs and HAs.
Meat consumption and risk of 25 common conditions: outcome-wide analyses in 475,000 men and women in the UK Biobank study
Authors: Papier Keren , Fensom Georgina K. , Knuppel Anika , Appleby Paul N. , Tong Tammy Y. N. , Schmidt Julie A. , Travis Ruth C. , Key Timothy J. , Perez-Cornago Aurora
Published: March 2021

Background

There is limited prospective evidence on the association between meat consumption and many common, non-cancerous health outcomes. We examined associations of meat intake with risk of 25 common conditions (other than cancer).

Methods

We used data from 474,985 middle-aged adults recruited into the UK Biobank study between 2006 and 2010 and followed up until 2017 (mean follow-up 8.0 years) with available information on meat intake at baseline (collected via touchscreen questionnaire), and linked hospital admissions and mortality data. For a large sub-sample (~ 69,000), dietary intakes were re-measured three or more times using an online, 24-h recall questionnaire.

Results

On average, participants who reported consuming meat regularly (three or more times per week) had more adverse health behaviours and characteristics than participants who consumed meat less regularly, and most of the positive associations observed for meat consumption and health risks were substantially attenuated after adjustment for body mass index (BMI). In multi-variable adjusted (including BMI) Cox regression models corrected for multiple testing, higher consumption of unprocessed red and processed meat combined was associated with higher risks of ischaemic heart disease (hazard ratio (HRs) per 70 g/day higher intake 1.15, 95% confidence intervals (CIs) 1.07–1.23), pneumonia (1.31, 1.18–1.44), diverticular disease (1.19, 1.11–1.28), colon polyps (1.10, 1.06–1.15), and diabetes (1.30, 1.20–1.42); results were similar for unprocessed red meat and processed meat intakes separately. Higher consumption of unprocessed red meat alone was associated with a lower risk of iron deficiency anaemia (IDA: HR per 50 g/day higher intake 0.80, 95% CIs 0.72–0.90). Higher poultry meat intake was associated with higher risks of gastro-oesophageal reflux disease (HR per 30 g/day higher intake 1.17, 95% CIs 1.09–1.26), gastritis and duodenitis (1.12, 1.05–1.18), diverticular disease (1.10, 1.04–1.17), gallbladder disease (1.11, 1.04–1.19), and diabetes (1.14, 1.07–1.21), and a lower IDA risk (0.83, 0.76–0.90).

Conclusions

Higher unprocessed red meat, processed meat, and poultry meat consumption was associated with higher risks of several common conditions; higher BMI accounted for a substantial proportion of these increased risks suggesting that residual confounding or mediation by adiposity might account for some of these remaining associations. Higher unprocessed red meat and poultry meat consumption was associated with lower IDA risk.
Strategy for mass production of lytic Staphylococcus aureus bacteriophage pSa-3: contribution of multiplicity of infection and response surface methodology
Authors: Kim Sang Guen , Kwon Jun , Giri Sib Sankar , Yun Saekil , Kim Hyoun Joong , Kim Sang Wha , Kang Jung Woo , Lee Sung Bin , Jung Won Joon , Park Se Chang
Published: March 2021

Background

Antibiotic-resistant bacteria have emerged as a serious problem; bacteriophages have, therefore, been proposed as a therapeutic alternative to antibiotics. Several authorities, such as pharmacopeia, FDA, have confirmed their safety, and some bacteriophages are commercially available worldwide. The demand for bacteriophages is expected to increase exponentially in the future; hence, there is an urgent need to mass-produce bacteriophages economically. Unlike the replication of non-lytic bacteriophages, lytic bacteriophages are replicated by lysing host bacteria, which leads to the termination of phage production; hence, strategies that can prolong the lysis of host bacteria in bacteria–bacteriophage co-cultures, are required.

Results

In the current study, we manipulated the inoculum concentrations of Staphylococcus aureus and phage pSa-3 (multiplicity of infection, MOI), and their energy sources to delay the bactericidal effect while optimizing phage production. We examined an increasing range of bacterial inoculum concentration (2 × 108 to 2 × 109 CFU/mL) to decrease the lag phase, in combination with a decreasing range of phage inoculum (from MOI 0.01 to 0.00000001) to delay the lysis of the host. Bacterial concentration of 2 × 108 CFU/mL and phage MOI of 0.0001 showed the maximum final phage production rate (1.68 × 1010 plaque forming unit (PFU)/mL). With this combination of phage–bacteria inoculum, we selected glycerol, glycine, and calcium as carbon, nitrogen, and divalent ion sources, respectively, for phage production. After optimization using response surface methodology, the final concentration of the lytic Staphylococcus phage was 8.63 × 1010 ± 9.71 × 109 PFU/mL (5.13-fold increase).

Conclusions

Therefore, Staphylococcus phage pSa-3 production can be maximized by increasing the bacterial inoculum and reducing the seeding phage MOI, and this combinatorial strategy could decrease the phage production time. Further, we suggest that response surface methodology has the potential for optimizing the mass production of lytic bacteriophages.
Diagnostic performance of an ultrasensitive HRP2-based malaria rapid diagnostic test kit used in surveys of afebrile people living in Southern Ghana
Authors: Acquah Festus K. , Donu Dickson , Obboh Evans K. , Bredu Dorcas , Mawuli Bernice , Amponsah Jones A. , Quartey Joseph , Amoah Linda E.
Published: March 2021

Background

The Alere™ Malaria Ag P.f Ultra-sensitive RDT (UsmRDT) kit is an HRP2-based malaria rapid diagnostic test (RDT) with enhanced sensitivity relative to the SD Bioline Malaria Ag P.f RDT (mRDT) kit. However, the diagnostic performance of the UsmRDT kit has not been evaluated in Ghana.

Methods

A total of 740 afebrile participants aged between 3 and 88 years old were recruited from the Central and Greater Accra Regions of Ghana during the off-peak malaria season. Axillary body temperature was measured, and a volume of 1 ml venous blood was drawn from each participant. Prior to separating the blood into plasma and packed cell pellets via centrifugation, the blood was spotted onto one UsmRDT and one mRDT kit and also used to prepare thick and thin blood smears as well as filter paper blood spots. Plasmodium falciparum specific polymerase chain reaction (PCR) was performed on gDNA extracted from 100 µl of the whole blood.

Results

The overall positivity rate for microscopy, PCR, UsmRDT and mRDT kit were 20.4%, 40.8%, 31.3% and 30.8%, respectively. Overall, the UsmRDT identified 9.3% (28/302) more PCR positive samples than the mRDT kits. All samples that were negative by the UsmRDT kit were also negative by the mRDT kit. Overall, the sensitivity and specificity of the UsmRDT was 73% (221/302) and 89% (388/436), respectively, while that for the mRDT kit was 58% and 90%, respectively.

Conclusion

Although the UsmRDT kit was not as sensitive as PCR at detecting asymptomatic P. falciparum carriage, it correctly identified P. falciparum in 9.3% of the study participants that were not captured by the mRDT kit. In malaria endemic settings, the UsmRDT would provide an added advantage by identifying more asymptomatic P. falciparum carriers than the mRDT kit for targeted treatment interventions.
Task-shifting to improve asthma education for Malawian children: a qualitative analysis
Authors: Nkhalamba Lovemore , Rylance Sarah , Muula Adamson S. , Mortimer Kevin , Limbani Felix
Published: March 2021

Background

Asthma education, a key component of long-term asthma management, is challenging in resource-limited settings with shortages of clinical staff. Task-shifting educational roles to lay (non-clinical) staff is a potential solution. We conducted a randomised controlled trial of an enhanced asthma care intervention for children in Malawi, which included reallocation of asthma education tasks to lay-educators. In this qualitative sub-study, we explored the experiences of asthmatic children, their families and lay-educators, to assess the acceptability, facilitators and barriers, and perceived value of the task-shifting asthma education intervention.

Methods

We conducted six focus group discussions, including 15 children and 28 carers, and individual interviews with four lay-educators and a senior nurse. Translated transcripts were coded independently by three researchers and key themes identified.

Results

Prior to the intervention, participants reported challenges in asthma care including the busy and sometimes hostile clinical environment, lack of access to information and the erratic supply of medication. The education sessions were well received: participants reported greater understanding of asthma and their treatment and confidence to manage symptoms. The lay-educators appreciated pre-intervention training, written guidelines, and access to clinical support. Low education levels among carers presented challenges, requiring an open, non-critical and individualised approach.

Discussion

Asthma education can be successfully delivered by lay-educators with adequate training, supervision and support, with benefits to the patients, their families and the community. Wider implementation could help address human resource shortages and support progress towards Universal Health Coverage.

Trial registration The RCT was registered in the Pan African Clinical Trials Registry: PACTR201807211617031
B cell‐activating factors in autoimmune pulmonary alveolar proteinosis
Authors: Hirose Masaki , Arai Toru , Sugimoto Chikatoshi , Takimoto Takayuki , Sugawara Reiko , Minomo Shojiro , Shintani Sayoko , Takeuchi Naoko , Katayama Kanako , Inoue Yasushi , Kagawa Tomoko , Kasai Takahiko , Akira Masanori , Inoue Yoshikazu
Published: March 2021

Background

Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP.

Subjects and methods

BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles.

Results

In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p < 0.0001 and p < 0.05, respectively), and BALF BAFF and APRIL levels were significantly increased versus disease controls (p < 0.0001 and p < 0.01, respectively). Serum BAFF levels (but not APRIL levels) were significantly correlated with Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, SP-A, and lactate dehydrogenase (p < 0.0001). There was no significant correlation between serum BAFF or APRIL levels and anti-GM-CSF autoantibody. BAFF and APRIL were negatively correlated with single-breath diffusion capacity for carbon monoxide (DLco) (p = 0.004) and forced vital capacity (p = 0.04), respectively. BAFF (but not APRIL) in BALF was negatively correlated with vital capacity (p = 0.04) and DLco (p = 0.006). There were significant correlations between disease severity and BAFF levels in serum (p = 0.04) and BALF (p = 0.007). Serum levels of anti-GM-CSF autoantibody, BAFF, and APRIL were not significantly affected by WLL or inhalation of recombinant human GM-CSF.

Conclusions

BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP.
Ethosuximide inhibits acute histamine- and chloroquine-induced scratching behavior in mice
Authors: Gadotti Vinicius M. , Zamponi Gerald W.
Published: March 2021

We have recently reported that the Cav3.2 T-type calcium channel which is well known for its key role in pain signalling, also mediates a critical function in the transmission of itch/pruritus. Here, we evaluated the effect of the clinically used anti-seizure medication ethosuximide, a well known inhibitor of T-type calcium channels, on male and female mice subjected to histaminergic- and non-histaminergic itch. When delivered intraperitoneally ethosuximide significantly reduced scratching behavior of mice of both sexes in response to subcutaneous injection of either histamine or chloroquine. When co-delivered subcutaneously together with either pruritogenic agent ethosuximide was also effective in inhibiting scratching responses in both male and female animals. Overall, our results are consistent with an important role of Cav3.2 T-type calcium channels in modulating histamine-dependent and histamine-independent itch transmission in the primary sensory pathway. Our findings also suggest that ethosuximide could be explored further as a possible therapeutic for the treatment of itch.
Genomic alterations in KMT2 family predict outcome of immune checkpoint therapy in multiple cancers
Authors: Zhang Peng , Huang Yixuan
Published: March 2021

Immune checkpoint therapy (ICT) can produce durable antitumor responses in various cancer types; however, the responses are not universal, and the predictive biomarkers are urgently needed. Growing evidence points to a link between epigenetic regulation and anti-tumor immunity, while clinical data on the association of genomic alterations in transcriptional dysregulation-related genes and ICT clinical benefit are lacking. Histone–lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on the histone H3 tail at important regulatory regions in the genome and thereby impart crucial functions through modulating chromatin structures and DNA accessibility, which is associated with tumorigenesis, mutagenesis, and immune tolerance in various cancers, indicating its possible correlation with the output of immune checkpoint therapy. We hypothesized that genomic mutations in the KMT2 family have the potential to be a novel predictor of immunotherapeutic efficacy. Through integrative cancer genomic analyses of baseline tumor tissues from multiple cohorts involving immunotherapeutic patients, we uncovered a remarkable correlation between KMT2 family mutation and better immune checkpoint therapy responses in multiple patient cohorts. Then, we gathered all the independent ICT-treated datasets as a combination cohort consisted of 418 patients. Significant enrichment of KMT2 family genomic alterations in responding tumors was observed (odds ratio = 2.60, P value = 1.67e−04). This work distinguished the mutations in the KMT2 family as a potential predictor of favorable ICT response in multiple cancers, highlighting the importance of genomic profiling in immunotherapy.
Incident gout and weight change patterns: a retrospective cohort study of US adults
Authors: Bai Lu , Zhou Jian-Bo , Zhou Tao , Newson Roger B. , Cardoso Marly Augusto
Published: March 2021

Background

Although the relationship between obesity and incident gout has been clarified, the influence of weight changes during the transition from early adulthood to midlife and the different weight change patterns in specific age ranges on the incidence of gout in later life remain unknown. Therefore, we aimed to investigate the association between weight change patterns across adulthood and incident gout.

Methods

Using data from the National Health and Nutrition Examination Survey (NHANES), we categorized individuals into four weight change patterns: those who remained obese (stable obese), those who moved from a non-obese body mass index (BMI) to an obese BMI (gaining), those who moved from an obese BMI to a non-obese BMI (losing), and those who remained non-obese (stable non-obese). Incident gout reflected its occurrence over the 10-year follow-up from the recalled midlife weight measure to the time of this survey. Hazard ratios (HRs) and 95% confidence intervals relating weight change patterns to incident gout over the 10-year follow-up period were calculated using Cox models adjusted for covariates. The hypothetical population attributable fraction (PAF) for the weight change patterns was calculated.

Results

Among our sample of adults aged 40–74 years at their midlife weight measure (n = 11,079), 320 developed gout. The highest risk of incident gout was found for participants with the stable obese pattern (HR 1.84; 1.08–3.14) and not for participants who remained stable non-obese during adulthood. Moreover, gaining weight was a significant risk factor for incident gout (HR 1.65; 1.19–2.29). No significant associations were found between losing weight change patterns and the risk of gout during the study period. If participants who gained weight had become non-obese during the 10-year follow-up, an estimated 3.2% (95% CI 0–6.3) of observed gout cases could have been averted. In addition, if the population had maintained a normal BMI, 32.9% (95% CI 18.2–44.9) cases could have been prevented during the 10 years.

Conclusions

Gaining weight over adulthood was associated with an increased risk of gout. These findings have highlighted that maintaining non-obese weight and weight loss across adulthood is essential for the prevention and treatment of gout in adult life.
Predictors of the length of stay of psychiatric inpatients: protocol for a systematic review and meta-analysis
Authors: Carranza Navarro Farid , Álvarez Villalobos Neri Alejandro , Contreras Muñoz Andrea Muriel , Guerrero Medrano Andrea Fernanda , Tamayo Rodríguez Natalia Sofía , Saucedo Uribe Erasmo
Published: March 2021

Background

Length of stay (LOS) for inpatient psychiatric services is an important factor with serious drawbacks when it is extended more than needed. Impacts on economy, social functioning, and stigma can hamper improvement and affect the patients’ experiences on future mental healthcare. Predictions of which patients have a higher chance for prolonged LOS have been extensively researched. Previous systematic reviews found consistent predictors of both longer and shorter LOS. However, they do not provide an estimate from the pooled effect sizes. Furthermore, to our knowledge, there is no meta-analysis on the influence of these factors. The primary objective of this study will be to provide point estimates on the effect sizes of all studied predictors of the LOS of psychiatric inpatients.

Methods

We will conduct a systematic search in PubMed, MEDLINE, EMBASE, and PsycINFO for observational studies evaluating the effect size of independent factors on the length of stay of psychiatric inpatients. Prospective and retrospective cohorts that assess the influence of predictors through the reporting of standardized regression coefficients will be included. We will provide a qualitative synthesis of the findings from each study and perform a meta-analysis from pooled regression coefficients that were adjusted for other variables or confounders in order to obtain a point estimate and confidence interval for all factors extracted from the included studies.

Discussion

The results from this study may provide more accurate predictions for mental health institutions, psychiatrists, mental health service providers, patients, and families on the prognosis regarding the length of stay for needed inpatient care. This information may be used to anticipate individuals with a higher chance for prolonged hospitalization to plan the necessary interventions for these specific situations. Considering both the benefits and disadvantages of longer and shorter stays, the pooled estimates for independent factors may be used by mental healthcare providers and patients for informed decision-making. The results from this study will also update results presented in previous studies and identify the strengths and limitations from the current available evidence.

Systematic review registration

PROSPERO ID CRD42020172840
Predictive biomarkers of anti-PD-1/PD-L1 therapy in NSCLC
Authors: Niu Mengke , Yi Ming , Li Ning , Luo Suxia , Wu Kongming
Published: March 2021

Immunotherapy, especially anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) treatment has significantly improved the survival of non-small cell lung cancer (NSCLC) patients. However, the overall response rate remains unsatisfactory. Many factors affect the outcome of anti-PD-1/PD-L1 treatment, such as PD-L1 expression level, tumor-infiltrating lymphocytes (TILs), tumor mutation burden (TMB), neoantigens, and driver gene mutations. Further exploration of biomarkers would be favorable for the best selection of patients and precisely predict the efficacy of anti-PD-1/PD-L1 treatment. In this review, we summarized the latest advances in this field, and discussed the potential applications of these laboratory findings in the clinic.
Fine-scale behaviour of the Lusitanian toadfish assessed in situ with the AccelTag
Authors: Pereira Tadeu J. , Almeida Pedro R. , Quintella Bernardo R. , Gronningsaeter Aage , Costa Maria J. , Marques João P. , Costa José L.
Published: March 2021

Background

Three-axis acceleration sensor acoustic transmitters (AccelTag) programmed to identify specific acceleration patterns associated with particular behaviours (e.g., burrowing, attack) were used to study some aspects of the ecology of the Lusitanian toadfish Halobatrachus didactylus (Bloch & Schneider 1801). The AccelTag combines the features of archival tags (records acceleration in all three directions measuring also roll-independent pitch/tilt angle and roll around the fish’s axis) and acoustic transmitters. Therefore, this tag can autonomously identify and record specific signatures (i.e., behaviour patterns) of different movements transmitting autonomously and periodically the data to an acoustic biotelemetry receiver. Lusitanian toadfish is a subtropical marine teleost confined to estuaries in its northern limit of distribution due to thermal constraints. During 2010 (August and October), 24 toadfish were captured, tagged with the AccelTag and released in the Mira estuary, SW coast of Portugal, where an array of underwater automatic acoustic biotelemetry receivers was deployed.

Results

Around 40% of AccelTag transmissions from tagged fish that stayed in the study area were logged by the acoustic receiver array. The Lusitanian toadfish exhibited low activity during late summer and early autumn (< 3% of time active). The tidal stage and time of day were important factors that influenced the species behaviour and activity. Increased burrowing and re-burrowing movements were registered during spring tides, while attacks prevailed on neap tides and during the night. The tidal cycle only influenced toadfish behaviour and activity in interaction with time of day, with more attacks and higher levels of activity during nocturnal high tides.

Conclusions

Higher activity levels and attacks displayed by the Lusitanian toadfish during the night, at high tide periods and during Spring tides are considered to be associated with increased activity and vulnerability of its prey during these periods. The AccelTag proved to be a powerful tool to assess and monitor the activity and fine-scale behaviour of fish in situ. This technology is particularly suited for fish species with biological and ecological features similar to Lusitanian toadfish, i.e., resident species with low activity levels and behaviours with a distinct 3D acceleration signature.
Palaeobotanical and biomarker evidence for Early Permian (Artinskian) wildfire in the Rajmahal Basin, India
Authors: Murthy Srikanta , Mendhe Vinod Atmaram , Uhl Dieter , Mathews Runcie Paul , Mishra Vivek Kumar , Gautam Saurabh
Published: March 2021

This study provides a combined analysis on the palynology, fossil charcoal and biomarkers of the subsurface coal deposits from a borehole RMB #2 drilled at the Dhulia Coal Block, Rajmahal Basin, India, in attempts to establish the chronology of sedimentation and to propose palaeobotanical as well as geochemical evidence for the occurrence of wildfires in these sediments. The palynological investigation suggests aScheuringipollenites barakarensispalynoassemblage from the lower Barakar Formation, dated as Artinskian (Early Permian) in age. This assemblage reveals the dominance of Glossopteridales and sub-dominance of taxa belonging to Cordaitales and Coniferales. Fossil charcoal in sediments is usually recognized as a direct indicator for the occurrence of palaeo-wildfires. More data involving the anatomical features of fossil charcoal analyzed by Field Emission Scanning Electronic Microscope broaden our knowledge on Early Permian wildfires from the peninsula of India. The studied macroscopic charcoal fragments exhibit anatomical details such as homogenized cell walls, uniseriate simple and biseriate alternate pitting on tracheid walls and rays of varying heights pointing to a gymnospermous wood affinitity. The excellent preservation of charcoal fragments, shown by their large sizes and almost unabraded edges, suggests a parautochthonous origin. The embedded biomarker study performed for charcoal sediments and its characterization demonstrate the presence ofn-alkanes, isoprenoids, terpenoids and aromatic compounds. A bimodal distribution pattern ofn-alkanes with a Cmaxatn-C25is identified. Diterpenoids and pentacyclic terpenoids are identified, indicating the input of an early conifer vegetation and bacterial activity, respectively. The identified polyaromatic hydrocarbon (PAH) compounds, together with the charcoal fragments, clearly suggest that repeated wildfire events occurred during the deposition of these Artinskian sediments in the Rajmahal Basin.