bluuebunny/crossref_metadata_2025 huggingface dataset:
Underuse of cardiorenal protective agents in high-risk diabetes patients in primary care: a cross-sectional study
Authors: Hao Robin , Myroniuk Tyler , McGuckin Taylor , Manca Donna , Campbell-Scherer Denise , Lau Darren , Yeung Roseanne O.
Published: May 2022

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown benefits in patients with diabetes and cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD).

Objective

We assessed benchmark outcomes (Hemoglobin A1c, LDL-C, and blood pressure), identified the prevalence of cardiorenal indications for SGLT2i and GLP-1RA, and compared prescribing rates of GLP1-RA and SGLT2i in those with and without cardiorenal indications.

Methods

We analyzed data from January 2018–June 2019 for 7168 patients with diabetes using electronic medical records from the Northern Alberta Primary Care Research Network, a regional network of the Canadian Primary Sentinel Surveillance Network (CPCSSN). Patients with and without cardiorenal comorbidities were compared using descriptive statistics and two proportion Z tests.

Results

Hemoglobin A1c ≤ 7.0% was met by 56.8%, blood pressure < 130/80 mmHg by 62.1%, LDL-C ≤ 2.0 mmol/L by 45.3% of patients. There were 4377 patients on glucose lowering medications; metformin was most common (77.7%), followed by insulin (24.6%), insulin secretagogues (23.6%), SGLT2i (19.7%), dipeptidyl peptidase-4 inhibitor (19.3%), and GLP-1RA (9.4%). A quarter of patients had cardiorenal indications for SGLT2i or GLP-1RA. Use of SGLT2i in these patients was lower than in patients without cardiorenal comorbidities (14.9% vs 21.2%, p < 0.05). GLP-1RA use in these patients was 4.6% compared with 11% in those without cardiorenal comorbidities (p < 0.05).

Discussion

Contrary to current evidence and recommendations, SGLT2i and GLP1-RA were less likely to be prescribed to patients with pre-existing CVD, HF, and/or CKD, revealing opportunities to improve prescribing for patients with diabetes at high-risk for worsening cardiorenal complications.
Assessment of dementia knowledge and its associated factors among final year medical undergraduates in selected universities across Malaysia
Authors: Chan Chee Mun , Ong Marjorie Jia Yi , Zakaria Adam Aiman , Visusasam Monikha Maria , Ali Mohd Fairuz , Jamil Teh Rohaila , Aizuddin Azimatun Noor , Abdul Aziz Aznida Firzah
Published: May 2022

Background

The elderly population in Malaysia are projected to reach almost one third of the total population by 2040. The absence of a National Dementia Strategy (NDS) in preparing the healthcare services for the ageing population is compounded by the lack of assessment of preparedness of future healthcare workers to manage complications related to ageing i.e., dementia. Studies in countries with NDS demonstrated lack of dementia knowledge among medical undergraduates. Hence, this study aimed to assess the knowledge on dementia among final year medical undergraduates in Malaysia and its associated factors, using the Dementia Knowledge Assessment Scale (DKAS).

Methods

This cross-sectional study, employed multistage sampling method to recruit final year medical undergraduates from eleven selected public and private medical institutions across Malaysia. Online self-administered measures were delivered to final year medical undergraduates through representatives of medical students’ society after approval from Deanery and institutional ethics board of participating universities. The measure collected demographic information, previous dementia exposure (i.e., formal or informal) and the 25-item Likert scale DKAS. Bivariate analysis and linear regression were conducted to confirm factors influencing dementia knowledge components.

Results

A total of 464 respondents from 7 universities participated in this study. Overall dementia knowledge among respondents with and without exposure, was low, with average score of 29.60 ± 6.97 and 28.22 ± 6.98, respectively. DKAS subscales analysis revealed respondents scored highest in care consideration subscale (9.49 ± 2.37) and lowest in communication and behaviour subscale (4.38 ± 2.39). However, only causes and characteristic subscale recorded significantly higher knowledge score among respondents with previous exposure (7.88 ± 2.58) (p =0.015). Higher knowledge of dementia was associated with previous formal dementia education (p=0.037) and informal occupational/working experience in caring for dementia patients (p = 0.001). Informal occupational/working experience (B = 4.141, 95% CI 1.748–6.535, p = 0.001) had greater effect than formal education (i.e. lectures/workshops) (B = 1.393, 95% CI 0.086–2.700, p = 0.037) to influence respondents’ knowledge on dementia.

Conclusion

Dementia knowledge among final year medical undergraduates is low. To improve dementia knowledge, Malaysian medical curriculum should be reviewed to incorporate formal education and informal occupational/working experience, as early as in undergraduate training to help prepare future healthcare providers to recognise dementia among ageing Malaysians.
Utilisation of supplementary prenatal screening and diagnostics in Germany: cross-sectional study using data from the KUNO Kids Health Study
Authors: Mayer Johanna , Brandstetter Susanne , Tischer Christina , Seelbach-Göbel Birgit , Malfertheiner Sara Fill , Melter Michael , Kabesch Michael , Apfelbacher Christian ,   KUNO Kids Study group, Arndt Petra , Baessler Andrea , Berneburg Mark , Böse- O’Reilly Stephan , Brunner Romuald , Buchalla Wolfgang , Malfertheiner Sara Fill , Franke Andre , Häusler Sebastian , Heid Iris , Herr Caroline , Högler Wolfgang , Kerzel Sebastian , Koller Michael , Leitzmann Michael , Rothfuß David , Rösch Wolfgang , Schaub Bianca , Weber Bernhard H. F. , Weidinger Stephan , Wellmann Sven
Published: May 2022

Background

Appropriate health system utilisation during pregnancy is fundamental for maintaining maternal and child’s health. To study the use and determinants of supplementary prenatal screening and diagnostics in Germany this study provides comprehensive data.

Methods

We obtained data from a recently established prospective German birth cohort study, the KUNO Kids Health Study. Analyses are based on Andersen’s Behavioural Model of health system use, which distinguishes between predisposing (e.g. country of birth), enabling (e.g. health insurance) and need factors (e.g. at-risk pregnancy). We examined bi- and multivariate association with the use of supplementary prenatal screening and diagnostics using logistic regression.

Results

The study has a sample size of 1886 participating mothers. One fifth of the mothers investigated did not use any supplementary prenatal screening or diagnostics. Notably, the chance of using supplementary prenatal screening and diagnostics more than doubled if the pregnant woman had a private health insurance (OR 2.336; 95% CI 1.527–3.573). Higher maternal age (OR 1.038; 95% CI 1.006–1.071) and environmental tobacco smoke exposure (OR 1.465 95% CI 1.071–2.004) increased the use of supplementary prenatal screening and diagnostics. However, regarding need factors only having an at-risk-pregnancy (OR 1.688; 95% CI 1.271–2.241) showed an independent association.

Conclusion

The important role of the type of health insurance and the relatively small influence of need factors was surprising. Especially with respect to equity in accessing health care, this needs further attention.
Coronary artery spasm due to acute myocarditis in an adolescent: a case report
Authors: Ko Hoon , Kim Taehong , Lee Hyoung Doo , Byun Joung-Hee , Choo Ki Seok
Published: May 2022

Background

Myocarditis refers to the inflammation of the myocardium caused by infection or autoimmune disease that may or may not present with clinical manifestations, such as gastrointestinal symptoms, dyspnea, chest pain, or sudden death. Although myocarditis and coronary artery vasospasm may mimic ST-segment elevation myocardial infarction (STEMI) with normal coronary arteries on angiography, acute myocarditis rarely causes coronary artery spasm. Here, we report a case of coronary artery spasm with reversible electrocardiographic changes mimicking STEMI in an adolescent with acute myocarditis.

Case presentation

A 15-year-old boy present with sudden-onset repeated chest pain following a 3-day history of flu-like illness. Cardiac biomarkers were significantly elevated. Electrocardiography showed ST-segment elevation in the absence of detectable vasospasm on coronary angiography. These findings were consistent with the diagnosis of coronary artery spasm secondary to acute myocarditis. Treatment with immunoglobulin for 2 days improved his condition. The patient was discharged on the 12th day with complete resolution of symptoms and normalization of electrocardiogram findings.

Conclusions

We reported a case of coronary artery spasm due to acute myocarditis. This study highlights the importance of considering coronary artery spasm due to acute myocarditis as a differential diagnosis in patients presenting with signs of STEMI as these diseases have different medical management strategies.
The progress in quantitative evaluation of callus during distraction osteogenesis
Authors: Liu Qi , Liu Ze , Guo Hongbin , Liang Jieyu , Zhang Yi
Published: May 2022

The manual monitoring of callus with digital radiography (X-ray) is the primary bone healing evaluation, assessing the number of bridged callus formations. However, this method is subjective and nonquantitative. Recently, several quantitative monitoring methods, which could assess the recovery of the structure and biomechanical properties of the callus at different stages and the process of bone healing, have been extensively investigated. These methods could reflect the bone mineral content (BMC), bone mineral density (BMD), stiffness, callus and bone metabolism at the site of bone lengthening. In this review, we comprehensively summarized the latest techniques for evaluating bone healing during distraction osteogenesis (DO): 1) digital radiography; 2) dual-energy X-ray scanning; 3) ultrasound; 4) quantitative computed tomography; 5) biomechanical evaluation; and 6) biochemical markers. This evidence will provide novel and significant information for evaluating bone healing during DO in the future.
“Discussion or silent accompaniment: a grounded theory study about voluntary stopping of eating and drinking in Switzerland”
Authors: Stängle Sabrina , Fringer André
Published: May 2022

Background

Voluntary stopping of eating and drinking as an option to end life prematurely is gaining international attention, and health care professionals are increasingly confronted with the wish to die through voluntary stopping of eating and drinking by individuals. While to date, there are no guidelines in Switzerland to orient professional support, it is of interest how professionals and other people involved react to the situation. The aim of this qualitative study was to explore how health care professionals in Switzerland accompany individuals during voluntary stopping of eating and drinking and to analyze this decision-making process.

Methods

Charmaz's grounded theory constructivist methodology uses guidelines for systematic, theory-driven data analysis underpinned by a pragmatic philosophical perspective. Data were collected in autumn 2016 as part of a regional palliative care conference on voluntary stopping of eating and drinking. All participants of the expert meeting (N = 50, including nurses, counsellors, ethicists, medical doctors, politicians, volunteers, and relatives) were invited to the focus group interviews, of whichN = 47 participated. We conducted five focus group interviews, each lasting one hour.

Results

The results showed that the accompaniment of those willing to die during voluntary stopping of eating and drinking was either discussed and cleared with one another or was unspoken and silently accompanied.

Conclusions

The demands of participants for more knowledge must be heeded, and there is also a need for systematic instructions on how to proceed in the case of voluntary stopping of eating and drinking support and what needs to be considered.
Health workers' use of routine health information and related factors at public health institutions in Illubabor Zone, Western Ethiopia
Authors: Abdisa Amanuel Benti , Hajito Kifle Woldemichael , Daka Dawit Wolde , Ergiba Meskerem Seboka , Senay Asaye Birhanu , Abdi Ketema Lemma , Wordofa Muluemebet Abera
Published: May 2022

Background

Proper utilization of health data has paramount importance for health service management. However, it is less practiced in developing countries, including Ethiopia. Therefore, this study aimed to assess routine health information utilization and identify factors associated with it among health workers in the Illubabor zone, Western Ethiopia.

Methods

A facility based cross-sectional study was conducted from March to June 2021 with a total of 423 randomly selected health workers. Data were collected using an interviewer-administered questionnaire that was developed based on the performance of routine information system management (PRISM) framework. We created composite variables for health workers' knowledge, attitude, abilities, and information utilization based on existing data. Multivariate logistic regression analysis was performed and the statistical association between the outcome and independent variables was declared using 95% CI and a P < 0.05.

Results

About two-thirds or 279 health workers (66.0%, 95% CI 61.3, 70.4) had good health information utilization. Two-thirds of health workers think organizational decision-making culture (67.1%, 95% CI 62.6, 71.5) and facility managers' or supervisors' promotion of information use (65.5%, 95% CI 60.9, 69.9) are positive. Over half of health workers (57.0%, 95% CI 52.2, 61.6) have a positive attitude toward data management, and the majority (85.8%, 95% CI 82.2, 88.9) believe they are competent of performing routine data analysis and interpretation activities. Only about two-thirds of health workers (65.5%, 95% CI 60.9, 69.9) were proficient in data analysis and interpretation.

Conclusions

The use of routine health information was lower than the national target and data from other literatures. Unacceptably large number of health personnel did not use information. As a result, efforts should be made to increase health workers' data management knowledge and skills, as well as the organizational culture of data utilization.
Genome of the parasitoid wasp Cotesia chilonis sheds light on amino acid resource exploitation
Authors: Ye Xinhai , Xiong Shijiao , Teng Ziwen , Yang Yi , Wang Jiale , Yu Kaili , Wu Huizi , Mei Yang , Xue Cheng , Yan Zhichao , Yin Chuanlin , Wang Fang , Yao Hongwei , Fang Qi , Song Qisheng , Ye Gongyin , Li Fei
Published: May 2022

Background

A fundamental feature of parasitism is the nutritional exploitation of host organisms by their parasites. Parasitoid wasps lay eggs on arthropod hosts, exploiting them for nutrition to support larval development by using diverse effectors aimed at regulating host metabolism. However, the genetic components and molecular mechanisms at the basis of such exploitation, especially the utilization of host amino acid resources, remain largely unknown. To address this question, here, we present a chromosome-level genome assembly of the parasitoid wasp Cotesia chilonis and reconstruct its amino acid biosynthetic pathway.

Results

Analyses of the amino acid synthetic pathway indicate that C. chilonis lost the ability to synthesize ten amino acids, which was confirmed by feeding experiments with amino acid-depleted media. Of the ten pathways, nine are known to have been lost in the common ancestor of animals. We find that the ability to synthesize arginine was also lost in C. chilonis because of the absence of two key genes in the arginine synthesis pathway. Further analyses of the genomes of 72 arthropods species show that the loss of arginine synthesis is common in arthropods. Metabolomic analyses by UPLC-MS/MS reveal that the temporal concentrations of arginine, serine, tyrosine, and alanine are significantly higher in host (Chilo suppressalis) hemolymph at 3 days after parasitism, whereas the temporal levels of 5-hydroxylysine, glutamic acid, methionine, and lysine are significantly lower. We sequence the transcriptomes of a parasitized host and non-parasitized control. Differential gene expression analyses using these transcriptomes indicate that parasitoid wasps inhibit amino acid utilization and activate protein degradation in the host, likely resulting in the increase of amino acid content in host hemolymph.

Conclusions

We sequenced the genome of a parasitoid wasp, C. chilonis, and revealed the features of trait loss in amino acid biosynthesis. Our work provides new insights into amino acid exploitation by parasitoid wasps, and this knowledge can specifically be used to design parasitoid artificial diets that potentially benefit mass rearing of parasitoids for pest control.
Rhythm disturbance in osteoarthritis
Authors: Du Ze , You Xuanhe , Wu Diwei , Huang Shishu , Zhou Zongke
Published: May 2022

Osteoarthritis (OA) is one of the main causes of disabilities among older people. To date, multiple disease-related molecular networks in OA have been identified, including abnormal mechanical loadings and local inflammation. These pathways have not, however, properly elucidated the mechanism of OA progression. Recently, sufficient evidence has suggested that rhythmic disturbances in the central nervous system (CNS) and local joint tissues affect the homeostasis of joint and can escalate pathological changes of OA. This is accompanied with an exacerbation of joint symptoms that interfere with the rhythm of CNS in reverse. Eventually, these processes aggravate OA progression. At present, the crosstalk between joint tissues and biological rhythm remains poorly understood. As such, the mechanisms of rhythm changes in joint tissues are worth study; in particular, research on the effect of rhythmic genes on metabolism and inflammation would facilitate the understanding of the natural rhythms of joint tissues and the OA pathology resulting from rhythm disturbance.
Impact of estrogen receptor expression on prognosis of ovarian cancer according to antibody clone used for immunohistochemistry: a meta-analysis
Authors: Ng Chun Wai , Wong Kwong-Kwok
Published: May 2022

Background

The prognostic value of the expression of estrogen receptor (ER) subtypes ER⍺ and ERβ in ovarian cancer has previously been evaluated by meta-analyses. However, the results are contradictory and controversial.

Methods

We conducted an updated meta-analysis with stringent inclusion criteria to ensure homogeneous studies to determine the effect of ER subtypes on ovarian cancer prognosis. Articles were retrieved by systematic search of PubMed and Web of Science for articles dated up to June 2021. Only studies with known hazard ratio (HR) and antibody clone for immunochemistry (IHC) were included. Pooled HRs with the corresponding 95% confidence intervals (CIs) were calculated for the effect of ER⍺ and ERβ expression on ovarian cancer patient progression-free survival (PFS) and overall survival (OS).

Results

A total of 17 studies were included, of which 11 and 13 studies examined the relationships between ER⍺ expression and PFS and OS, respectively, and 5 and 7 studies examined the relationships between ERβ expression and PFS and OS, respectively. Neither ER⍺ expression (random-effects model; HR = 0.99, 95% CI = 0.83–1.18) nor ERβ expression (fixed-effects model; HR = 0.94, 95% CI = 0.69–1.27) was associated with PFS. Random-effects models showed that ER⍺ expression (HR = 0.81, 95% CI = 0.64–1.02) and ERβ expression (HR = 0.75, 95% CI = 0.50–1.13) were only marginally and not significantly associated with better OS. Subgroup analysis revealed that ER⍺ expression determined using antibody clone 1D5 (HR = 0.75, 95% CI = 0.64–0.88) and ERβ expression determined using ERβ1-specific-antibody clone PPG5/10 or EMR02 (HR = 0.65, 95% CI = 0.50–0.86) were associated with significantly better OS, but ER expression determined using other antibodies was not.

Conclusions

In conclusion, a higher ER⍺ expression and ERβ expression are significantly associated with a better survival of ovarian cancer patients, but the results from previous prognostic studies are significantly dependent on the choice of specific ER antibody clones used in immunohistochemistry analysis.
Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation
Authors: Reijnders Tom D. Y. , Peters-Sengers Hessel , van Vught Lonneke A. , Uhel Fabrice , Bonten Marc J. M. , Cremer Olaf L. , Schultz Marcus J. , Stuiver Martijn M. , van der Poll Tom ,   the MARS consortium, de Beer Friso M. , Bos Lieuwe D. J. , Glas Gerie J. , van Hooijdonk Roosmarijn T. M. , Horn Janneke , Schouten Laura R. A. , Straat Marleen , Wieske Luuk , Witteveen Esther , Reijnders Tom D. Y. , Schuurman Alex R. , van Engelen Tjitske S. R. , Pereverzeva Liza , Hoogendijk Arie J. , Huson Mischa A. , Wiewel Maryse A. , Klouwenberg Peter M. C. Klein , Ong David S. Y. , Frencken Jos F. , Koster-Brouwer Maria E. , van de Groep Kirsten , Verboom Diana M.
Published: May 2022

Background

Immunomodulatory therapies that improve the outcome of sepsis are not available. We sought to determine whether treatment of critically ill patients with sepsis with low-dose erythromycin—a macrolide antibiotic with broad immunomodulatory effects—decreased mortality and ameliorated underlying disease pathophysiology.

Methods

We conducted a target trial emulation, comparing patients with sepsis admitted to two intensive care units (ICU) in the Netherlands for at least 72 h, who were either exposed or not exposed during this period to treatment with low-dose erythromycin (up to 600 mg per day, administered as a prokinetic agent) but no other macrolides. We used two common propensity score methods (matching and inverse probability of treatment weighting) to deal with confounding by indication and subsequently used Cox regression models to estimate the treatment effect on the primary outcome of mortality rate up to day 90. Secondary clinical outcomes included change in SOFA, duration of mechanical ventilation and the incidence of ICU-acquired infections. We used linear mixed models to assess differences in 15 host response biomarkers reflective of key pathophysiological processes from admission to day 4.

Results

In total, 235 patients started low-dose erythromycin treatment, 470 patients served as controls. Treatment started at a median of 38 [IQR 25–52] hours after ICU admission for a median of 5 [IQR 3–8] total doses in the first course. Matching and weighting resulted in populations well balanced for proposed confounders. We found no differences between patients treated with low-dose erythromycin and control subjects in mortality rate up to day 90: matching HR 0.89 (95% CI 0.64–1.24), weighting HR 0.95 (95% CI 0.66–1.36). There were no differences in secondary clinical outcomes. The change in host response biomarker levels from admission to day 4 was similar between erythromycin-treated and control subjects.

Conclusion

In this target trial emulation in critically ill patients with sepsis, we could not demonstrate an effect of treatment with low-dose erythromycin on mortality, secondary clinical outcomes or host response biomarkers.
A new ferritin SjFer0 affecting the growth and development of Schistosoma japonicum
Authors: Zeng Fanyuan , Yi Cun , Zhang Wei , Cheng Shaoyun , Sun Chengsong , Luo Fang , Feng Zheng , Hu Wei
Published: May 2022

Background

Schistosomiasis, an acute and chronic parasitic disease, causes substantial morbidity and mortality in tropical and subtropical regions of the world. Iron is an essential constituent of numerous macromolecules involving in important cellular reactions in virtually all organisms. Trematodes of the genus Schistosoma live in iron-rich blood, feed on red blood cells and store abundant iron in vitelline cells. Ferritins are multi-meric proteins that store iron inside cells. Three ferritin isoforms in Schistosoma japonicum are known, namely SjFer0, SjFer1 and SjFer2; however, their impact on the growth and development of the parasites  is still unknown. In this study we report on and characterize the ferritins in S. japonicum.

Methods

A phylogenetic tree of the SjFer0, SjFer1 and SjFer2 genes was constructed to show the evolutionary relationship among species of genus Schistosoma. RNA interference in vivo was used to investigate the impact of SjFer0 on schistosome growth and development.  Immunofluorescence assay was applied  to localize the expression of the ferritins. RNA-sequencing was performed  to characterize the iron transport profile after RNA interference.

Results

SjFer0 was found to have low similarity with SjFer1 and SjFer2 and contain an additional signal peptide sequence. Phylogenetic analysis revealed that SjFer0 can only cluster with some ferritins of other trematodes and tapeworms, suggesting that this ferritin branch might be unique to these parasites. RNA interference in vivo showed that SjFer0 significantly affected the growth and development of schistosomula but did not affect egg production of adult female worms. SjFer1 and SjFer2 had no significant impact on growth and development. The immunofluorescence study showed that SjFer0 was widely expressed in the somatic cells and vitelline glands but not in the testicle or ovary. RNA-sequencing indicated  that, in female, the ion transport process and calcium ion binding function were downregulated after SjFer0 RNA interference. Among the differentially downregulated genes, Sj-cpi-2, annexin and insulin-like growth factor-binding protein may be accounted for the suppression of schistosome growth and development.

Conclusions

The results indicate that SjFer0 affects the growth and development of schistosomula but does not affect egg production of adult female worms. SjFer0 can rescue the growth of the fet3fet4 double mutant Saccharomyces cerevisiae (strain DEY1453), suggesting being able to promote iron absorption. The RNA interference of SjFer0 inferred that  the suppression of worm growth and development may via  down-regulating Sj-cpi-2, annexin, and IGFBP.

Graphic Abstract
Protein profiling of hemolymph in Haemaphysalis flava ticks
Authors: Liu Lei , Yan Fen , Zhang Lu , Wu Zhi-feng , Duan De-yong , Cheng Tian-yin
Published: May 2022

Background

Tick hemolymph bathes internal organs, acts as an exchange medium for nutrients and cellular metabolites, and offers protection against pathogens. Hemolymph is abundant in proteins. However, there has been limited integrated protein analysis in tick hemolymph thus far. Moreover, there are difficulties in differentiating tick-derived proteins from the host source. The aim of this study was to profile the tick/host protein components in the hemolymph of Haemaphysalis flava.

Methods

Hemolymph from adult engorged H. flava females was collected by leg amputation from the Erinaceus europaeus host. Hemolymph proteins were extracted by a filter-aided sample preparation protocol, digested by trypsin, and assayed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). MS raw data were searched against the UniProt Erinaceidae database and H. flava protein database for host- and tick-derived protein identification. Protein abundance was further quantified by intensity-based absolute quantification (iBAQ).

Results

Proteins extracted from hemolymph unevenly varied in size with intense bands between 100 and 130 kDa. In total, 312 proteins were identified in the present study. Therein 40 proteins were identified to be host-derived proteins, of which 18 were high-confidence proteins. Top 10 abundant host-derived proteins included hemoglobin subunit-α and subunit-β, albumin, serotransferrin-like, ubiquitin-like, haptoglobin, α-1-antitrypsin-like protein, histone H2B, apolipoprotein A-I, and C3-β. In contrast, 169 were high-confidence tick-derived proteins. These proteins were classified into six categories based on reported functions in ticks, i.e., enzymes, enzyme inhibitors, transporters, immune-related proteins, muscle proteins, and heat shock proteins. The abundance of Vg, microplusin and α-2-macroglobulin was the highest among tick-derived proteins as indicated by iBAQ.

Conclusions

Numerous tick- and host-derived proteins were identified in hemolymph. The protein profile of H. flava hemolymph revealed a sophisticated protein system in the physiological processes of anticoagulation, digestion of blood meal, and innate immunity. More investigations are needed to characterize tick-derived proteins in hemolymph.

Graphical Abstract
Wolbachia 16S rRNA haplotypes detected in wild Anopheles stephensi in eastern Ethiopia
Authors: Waymire Elizabeth , Duddu Sowmya , Yared Solomon , Getachew Dejene , Dengela Dereje , Bordenstein Sarah R. , Balkew Meshesha , Zohdy Sarah , Irish Seth R. , Carter Tamar E.
Published: May 2022

Background

About two out of three Ethiopians are at risk of malaria, a disease caused by the parasites Plasmodium falciparum and Plasmodium vivax. Anopheles stephensi, an invasive vector typically found in South Asia and the Middle East, was recently found to be distributed across eastern and central Ethiopia and is capable of transmitting both P. falciparum and P. vivax. The detection of this vector in the Horn of Africa (HOA) coupled with widespread insecticide resistance requires that new methods of vector control be investigated in order to control the spread of malaria. Wolbachia, a naturally occurring endosymbiotic bacterium of mosquitoes, has been identified as a potential vector control tool that can be explored for the control of malaria transmission. Wolbachia could be used to control the mosquito population through suppression or potentially decrease malaria transmission through population replacement. However, the presence of Wolbachia in wild An. stephensi in eastern Ethiopia is unknown. This study aimed to identify the presence and diversity of Wolbachia in An. stephensi across eastern Ethiopia.

Methods

DNA was extracted from An. stephensi collected from eastern Ethiopia in 2018 and screened for Wolbachia using a 16S targeted PCR assay, as well as multilocus strain typing (MLST) PCR assays. Haplotype and phylogenetic analysis of the sequenced 16S amplicons were conducted to compare with Wolbachia from countries across Africa and Asia.

Results

Twenty out of the 184 mosquitoes screened were positive for Wolbachia, with multiple haplotypes detected. In addition, phylogenetic analysis revealed two superclades, representing Wolbachia supergroups A and B (bootstrap values of 81 and 72, respectively) with no significant grouping of geographic location or species. A subclade with a bootstrap value of 89 separates the Ethiopian haplotype 2 from other sequences in that superclade.

Conclusions

These findings provide the first evidence of natural Wolbachia populations in wild An. stephensi in the HOA. They also identify the need for further research to confirm the endosymbiotic relationship between Wolbachia and An. stephensi and to investigate its utility for malaria control in the HOA.

Graphical Abstract
Systematic identification of the lysine lactylation in the protozoan parasite Toxoplasma gondii
Authors: Zhao Wei , Yu Helin , Liu Xiaona , Wang Tingting , Yao Yinning , Zhou Qixin , Zheng Xiaozi , Tan Feng
Published: May 2022

Background

Lysine lactylation (Kla) is a novelposttranslational modification (PTM) identified in histone and nonhistone proteins of several eukaryotic cells that directly activates gene expression and DNA replication. However, very little is known about the scope and cellular distribution of Kla in apicomplexan parasites despite its significance in public and animal health care.

Methods

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular apicomplexan parasite that can infect different nucleated cell types of animals and humans. We used this parasite as a model organism and extracted the total protein of tachyzoites to produce the first global lysine lactylome profile of T. gondii through liquid chromatography–tandem mass spectrometry. We also investigated the level and localization of the Kla protein in T. gondii using western blotting and the indirect fluorescent antibody test (IFA), respectively.

Results

A total of 983 Kla sites occurring on 523 lactylated proteins were identified in the total protein extracted from Toxoplasma tachyzoites, the acute toxoplasmosis-causing stage. Bioinformatics analysis revealed that the lactylated proteins were evolutionarily conserved and involved in a wide variety of cellular functions, such as energy metabolism, gene regulation and protein biosynthesis. Subcellular localization analysis and IFA results further revealed that most of the lactylated T. gondii proteins were localized in the nucleus, indicating the potential impact of Kla on gene regulation in the T. gondii model. Notably, an extensive batch of parasite-specific proteins unique to phylum Apicomplexa is lactylated in T. gondii.

Conclusions

This study revealed that Kla is widespread in early dividing eukaryotic cells. Lactylated proteins, including a batch of unique parasite proteins, are involved in a remarkably diverse array of cellular functions. These valuable data will improve our understanding of the evolution of Kla and potentially provide the basis for developing novel therapeutic avenues.

Graphical Abstract
Comment on “The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis” by Yu et al.
Authors: Yueh Hann-Ziong , Wei James Cheng-Chung , Zhang Liyun
Published: May 2022

With great interest, we have read the recent article “The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis” by Yu et al. While we have a great appreciation for the work conducted by the authors there are some methodological issues need to be considered. First, the period of articles included in the study, almost before 2013, implied that most follow-up days in these articles were earlier than the established date of a unified definition of IgG4-RD, 2011. Thus, it may lead to misclassification bias in the study. Second, IgG4-RD is a fibrous-inflammatory process that often involves multiple organs; however, malignant tumors related to IgG4-RD proposed in the study were only confined to four diseases. Therefore, we suggest adding subgroup analysis for more malignancies depending on the prevalence of IgG4-RD involved organs to ensure better clinical practice. Third, the causation between IgG4-RD and malignancy remains obscure currently. The time course for development in different malignancies varies significantly so that we cannot infer that malignancies discovered after IgG4-RD are directly relevant. With problems mentioned above, we recommend solutions to make this article more convincing.
Medical student lifestyle counselling for non-communicable disease: impact on students’ competence and patients’ health behaviors
Authors: Malatskey Lilach , Essa-Hadad Jumanah , Eldar Reut , Filipov Inna , Eilat-Tsanani Sophia , Rudolf Mary C. J.
Published: May 2022

Background

Promoting healthy lifestyle is key to tackling lifestyle-induced diseases, yet many doctors feel unskilled and medical schools lack its inclusion in their curricula. The impact of a novel elective lifestyle course is described, where students provided 3 months’ coaching to at-risk patients.

Methods

Students’ attitudes, competence and lifestyle were assessed pre- and post the 18-month course. Patients’ health measures and behaviors were measured. Student and patient views were ascertained.

Results

Nineteen students, 13 controls, and 29 patients participated. Perception of physicians’ importance as lifestyle consultants increased in coaching students (mean ± SD 3.7 ± 0.4 vs. 3.2 ± 0.5; p = 0.05). Self-perceived competence remained high in coaching students (6.7 ± 1.8 vs. 6.7 ± 1.2; p = 0.66). Controls’ competence increased but did not attain coaching students’ levels (3.6 ± 2.1 vs. 5.5 ± 1.9; p = 0.009). Focus groups of students confirmed self-perceived acquisition of skills. More patients exercised (38% vs. 82.7%; p = 0.001); spent more time in physical activity (median mins/week + IQR) 25 + [0.180] vs. 120 + [45,300]; p = 0.039), and avoided less desirable foods, such as unhealthy snacks, sweets and drinks. LDL cholesterol showed declining trend. Patients highlighted students’ empathy and attentiveness; satisfaction was extremely high.

Conclusions

The course successfully enhanced students’ counselling skills, with beneficial effects for patients. This model for teaching experience-based lifestyle medicine has potential policy implications in terms of promoting effective lifestyle counselling by future physicians.
Health-related quality of life and psychological distress among adults in Tanzania: a cross-sectional study
Authors: Ivanova Olena , Sineke Tembeka , Wenzel Rebekka , Siyame Elimina , Lalashowi Julieth , Bakuli Abhishek , Zekoll Fidelina Cumbe , Hoelscher Michael , Rachow Andrea , Evans Denise , Sabi Issa , Ntinginya Nyanda Elias
Published: May 2022

Background

Little data is available on health-related quality of life (HRQoL) and mental health of the general population in Tanzania. We aimed to describe HRQoL and level of psychological distress among adults in Mbeya and Songwe Regions of Tanzania.

Methods

We conducted a cross-sectional study between April and October 2019 in Mbeya and Songwe Regions. Data were collected using the Medical Outcomes Short Form-36 (SF-36) questionnaire and the Page Kessler Psychological Distress Scale (K10). We described demographic characteristics of participants and used log-binomial regression to identify participant characteristics associated with psychological distress (K10 score ≥ 20).

Results

A total of 393 adults were enrolled. The participants had a median age of 29 years (IQR 23–40) and 54.2% were male. Participants reported a physical component summary score (PCS) with a mean of 54.7 (SD7.1) and a mental component summary score (MCS) with a mean of 55.5 (SD5.1). Older participants (≥ 40 year) and those that were divorced/widowed reported lower physical functioning, energy/vitality and emotional well-being compared to their counterparts (p < 0.05). In terms of psychological distress, majority of participants (78.4%; 305/389) reported that they were likely to be well (K10 score < 20), while 13.4% (52/389) reported to have mild (K10 score 20–24), 5.7% (22/389) moderate (K10 score 25–29), and 2.6% (10/389) severe (K10 score ≥ 30) psychological distress.

Conclusions

Physical function and mental well-being in this adult population from Tanzania were lower than that reported in other similar research in Tanzania and other African countries. This study provides valuable references for other research initiatives and clinical services in this region.
How much is that doodle in the window? Exploring motivations and behaviours of UK owners acquiring designer crossbreed dogs (2019-2020)
Authors: Burnett E. , Brand C. L. , O’Neill D. G. , Pegram C. L. , Belshaw Z. , Stevens K. B. , Packer R. M. A.
Published: May 2022

Background

Demand for intentional crosses of purebred dog breeds, often labelled ‘designer crossbreeds’ (e.g., Labrador Retriever X Poodle, the ‘Labradoodle’), has recently increased in the UK. This study aimed to explore this phenomenon by comparing pre-purchase motivations, pre-purchase and purchase behaviours of UK owners of designer crossbred puppies purchased during 2019-2020 with those of owners of purebred puppies purchased during the same period.

Results

Data were collected in an online cross-sectional survey between November-December 2020. Responses from n = 6293 puppies (designer crossbred puppies: n = 1575; purebred puppies: n = 4718) were analysed. Perceived hypoallergenicity was cited as a motivator for breed/crossbreed choice by almost half of designer crossbreed owners (47.1%), six times more than purebred dog owners (7.86%; odds ratio [OR]: 9.12, 95% CI: 7.70-10.8). Designer crossbred puppies were more likely to have been acquired via a general selling website (e.g., Gumtree; 13.8%) compared to purebred puppies (7.67%; OR: 2.19, 95% CI: 1.77-2.71), or an animal-specific selling websites (e.g., Pets4Homes; 55.7%) compared to purebred puppies (37.4%; OR: 1.89, 95% CI: 1.65-2.17). Designer crossbreed owners were less likely to see their puppy in person prior to purchase than purebred owners (60.4% vs. 67.0%, respectively; OR: 0.74, 95% CI: 0.64-0.85), and at purchase, designer crossbred puppies were less likely to be seen with their mother (73.1% vs. 79.8%, respectively; OR: 0.82, 95% CI: 0.70-0.95), and littermates (67.7% vs. 78.1%, respectively; OR: 0.63, 95% CI: 0.55-0.73). Designer crossbreeds had a significantly higher purchase price, with 25.7% of designer crossbreed puppies costing £2000-£2999 compared to 15.1% of purebred puppies (X2 = 207.31, p <  0.001).

Conclusions

The recent boom in designer crossbreeds in the UK has been fuelled by a desire for perceived hypoallergenic and generally healthy dogs that fit the lifestyles of households with children and limited experience with dogs. Some sought-after traits in designer crossbreeds are misconceptions that risk canine welfare, including relinquishment risk, if owner expectations are not met. Purchasing practices fuelling this boom support irresponsible breeding and selling practices, which combined with reduced pressure for health testing from buyers, may result in a higher disease burden and poorer future welfare for this growing designer dog population.
Breed distributions for diabetes mellitus and hypothyroidism in Norwegian dogs
Authors: Ringstad N. K. , Lingaas F. , Thoresen S. I.
Published: May 2022

Background

Diabetes mellitus (DM) and hypothyroidism are common canine endocrinopathies. Both canine DM and primary hypothyroidism are assumed to originate from autoimmune destruction of the respective endocrine glands and have been associated with the major histocompatibility complex (MHC) gene region. This study aims to investigate breed distributions for DM and hypothyroidism in the Norwegian canine population by calculating odds ratios (OR) from two different comparator groups.

Methods

Results from canine serum samples submitted from 2001 to 2018 to the Veterinary Clinical Pathology Laboratory (VCPL) at the Faculty of Veterinary Medicine, Norwegian University of Life Sciences for analysis of fructosamine and thyroid hormones in serum were used as cases in a retrospective bivariate analysis of canine breeds. The ORs were calculated as a measure of risk for the included breeds, where all the submitted blood samples to the VCPL and dogs registered in the Norwegian Kennel Club (NKK), the national organization for dog owners, were used as two comparator groups.

Results

Significant differences in disease prevalence between breeds were discovered using both comparator groups. Australian terrier, Swedish lapphund, Samoyed, and Schipperke were at highest risk for DM. German Shepherd, Golden retriever, German pointing dog, and Collie presented as the breeds with lowest risk for DM. For hypothyroidism, Schnauzer, Eurasier, Dunker, and English setter were at highest risk for developing the disease. The breeds at lowest risk of developing hypothyroidism were Rottweiler, Dachshund, German shepherd, and Border collie. The results from the different comparator groups gave different ORs and ranks, but the breeds with highest and lowest odds showed the same susceptibility using both comparators.

Conclusions

These findings support that there are breeds more and less prone to develop DM and hypothyroidism. A strong genetic predisposition involved in the aetiology of these two diseases is therefore likely. Interestingly, there also appeared to be an inverse relationship of odds for the two diseases for some of the breeds since some breeds that had a high OR for DM or hypothyroidism had a lower OR for the other disease. This indicates that there may be different risk alleles/haplotypes for the two diseases. The possible aetiological relationship between canine DM and hypothyroidism should be further investigated.
Applicability of a national strategy for patient-oriented research to people who use(d) substances: a Canadian experience
Authors: Pauly Bernadette , Sullivan Ginger , Inglis Dakota , Cameron Fred , Phillips Jack , Rosen Conor , Bullock Bill , Cartwright Jennifer , Hainstock Taylor , Trytten Cindy , Urbanoski Karen
Published: May 2022

Background

Europe and North America are in the grips of a devastating overdose crisis. People who use substances often feel unsafe to access healthcare due to fears of stigma, blame, judgement, poor treatment, or other repercussions. As a result, they often avoid, delay, or leave care, resulting in premature death and missed opportunities for care. Internationally, there have been concerted efforts to move towards patient-engaged research to enhance the quality of health care systems and services. In Canada, the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR) initiative promotes engagement of patients as active partners in health care research. As part of a community based patient oriented research project, we critically analyze the SPOR framework to provide insights into what constitutes safer research with people who use(d) substances.

Methods

We undertook a two-stage process that began with a review of community based research principles and the SPOR framework. At the second stage, we undertook a qualitative descriptive study employing focus groups to generate description of the adequacy and appropriateness of the SPOR framework for guiding research with people who use(d) substances on four key dimensions (patient engagement, guiding principles, core areas of engagement and benefits). The data were analyzed using qualitative content analysis to identify key issues and insights.

Results

While the SPOR framework includes a range of patient roles, principles and areas for engagement, there are issues and gaps related to essential elements of safe patient-oriented research for people who use substances. These include an individualized focus on patients as partners, lack of recognition of community benefits, power imbalances and distrust due to systemic stigma, engagement as one way capacity building and learning, and lack of accountability for taking action on research findings.

Conclusions

Given the extent of stigma in health care and the ongoing illicit drug policy crisis, strategies for enhancing equitable Patient-Oriented Research (POR) include shifting language from patient partners to community researchers, recognizing power inequities and adding trust and equity as core POR principles including pay equity. Employing community based participatory research as a POR methodology allows the lead researchers to fully engage community throughout the research process, enhances community benefits and accountability for action.
DecNet: Decomposition network for 3D gravity inversion
Authors: Zhang Shuang , Yin Changchun , Cao Xiaoyue , Sun Siyuan , Liu Yunhe , Ren Xiuyan
Published: May 2022

Three dimensional gravity inversion is an effective way to extract subsurface density distribution from gravity data. Different from the conventional geophysics-based inversions, machine-learning-based inversion is a data-driven method mapping the observed data to a 3D model. We have developed a new machine-learning-based inversion method by establishing a decomposition network (DecNet). Unlike existing machine-learning-based inversion methods, the proposed DecNet method is a mapping from 2D to 2D, which requires less training time and memory space. Instead of learning the density information of each grid point, this network learns the boundary position, vertical center, thickness, and density distribution by 2D-to-2D mapping and reconstructs the 3D model by using these predicted parameters. Furthermore, by using the highly accurate boundary information learned from this network as supplement information, the DecNet method is optimized into a DecNetB method. By comparing the least-squares inversion and U-Net inversion on synthetic and real survey data, the DecNet and DecNetB methods have shown the advantage in dealing with inverse problems for targets with boundaries.