bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of lumateperone in the treatment of schizophrenia
Authors: Syed Alveena Batool , Brašić James Robert
Published: July 2021

Schizophrenia is a devastating mental disorder resulting in marked morbidity and mortality despite the optimal use of all currently available interventions. For this reason, the release of lumateperone (CaptylaR), also known as ITI-007, an orally administered, atypical antipsychotic provided a welcome novel tool for clinicians to utilize precision medicine to tailor an optimal treatment plan to the specific needs of each person with schizophrenia. To generate a foundation for clinicians to assess the risks and benefits of lumateperone in relation to other interventions for schizophrenia, we conducted a search of items for ‘ITI-007’ and ‘lumateperone’ on PubMed, ScienceDirect, Web of Science, Google Scholar, and www.clinicaltrials.gov . We present a critical evaluation of the limited information about lumateperone for schizophrenia, its use approved by the US Food and Drug Administration. Lumateperone merits consideration for patients with treatment-resistant schizophrenia and for patients with schizophrenia who are vulnerable to developing metabolic dysfunction and movement disorders. On the other hand, lumateperone should not be used for (a) women who are pregnant or breastfeeding, children, adolescents, and elderly patients with dementia-related psychosis, (b) patients who are at risk for cerebrovascular diseases, (c) patients who use inducers and moderate or strong inhibitors of the cytochrome P450-3A4 (CYP3A4) isozyme, and (d) patients who use alcohol and other sedating agents. Clinical trials from multiple centers without financial conflicts of interest to market lumateperone are needed to directly compare and contrast lumateperone and other antipsychotic agents to generate trustworthy evidence to be assessed objectively by clinicians treating patients with schizophrenia. Future investigations will provide the foundations to identify the evidence for comprehensive evaluations of the role of lumateperone in the treatment of people with schizophrenia and other conditions.
High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19
Authors: Karawajczyk Malgorzata , Douhan Håkansson Lena , Lipcsey Miklos , Hultström Michael , Pauksens Karlis , Frithiof Robert , Larsson Anders
Published: July 2021

Background and Aims:

The pronounced neutrophilia observed in patients with coronavirus disease 2019 (COVID-19) infections suggests a role for these leukocytes in the pathology of the disease. Monocyte and neutrophil expression of CD64 and CD11b have been reported as early biomarkers to detect infections. The aim of this study was to study the expression of receptors for IgG (CD64) and adhesion molecules (CD11b, CD15s, CD65, CD162, CD66b) on neutrophils and monocytes in patients with severe COVID-19 after admission to an intensive care unit (ICU).

Methods:

The expression of receptors was analyzed using flow cytometry. EDTA blood from 23 patients with confirmed COVID-19 infection was sampled within 48 h of admission to the ICU. Leukocytes were labeled with antibodies to CD11b, CD15s, CD65s, CD162, CD64, and CD66b. Expression of receptors was reported as mean fluorescence intensity (MFI) or the percentage of cells expressing receptors.

Results:

Results are presented as comparison of COVID-19 patients with the healthy group and the receptor expression as MFI. Neutrophil receptors CD64 (2.5 versus 0.5) and CD66b (44.5 versus 34) were increased and CD15 decreased (21.6 versus 28.3) when CD65 (6.6 versus 4.4), CD162 (21.3 versus 21.1) and CD11b (10.5 versus 12) were in the same range. Monocytes receptors CD64 (30.5 versus 16.6), CD11b (18.7 versus 9.8), and CD162 (38.6 versus 36.5) were increased and CD15 decreased (10.3 versus 17.9); CD65 were in the same range (2.3 versus 1.96).

Conclusion:

Monocytes and neutrophils are activated during severe COVID-19 infection as shown by strong upregulation of CD64. High monocyte and neutrophil CD64 can be an indicator of a severe form of COVID19. The adhesion molecules (CD11b, CD162, CD65, and CD15) are not upregulated on otherwise activated neutrophils, which might lead to relative impairment of tissue migration. Low adhesion profile of neutrophils suggests immune dysfunction of neutrophils. Monocytes maintain upregulation of some adhesion molecules (CD11b, CD162) suggesting the persistence of an increased ability to migrate into tissues, even during a severe stage of COVID-19. Future research should focus on CD64 and CD11b kinetics in the context of prognosis.
Quality of antiretroviral therapy services in Ghana: Implications for the HIV response in resource-constrained settings
Authors: Alhassan Robert Kaba , Ketor Courage Edem , Ashinyo Anthony , Ashinyo Mary Eyram , Nutor Jerry John , Adjadeh Conrad , Sarkodie Emmanuel
Published: July 2021

Objective:

Number of People Living with Human Immune-deficiency Virus in Ghana is over 300,000 and unmet need for antiretroviral therapy is approximately 60%. This study sought to determine the quality of antiretroviral therapy services in selected ART sites in Ghana using the input-process-outcome approach.

Methods:

This is a descriptive cross-sectional case study that employed modified normative evaluation to assess quality of antiretroviral therapy services in the Oti and Volta regions of Ghana among People Living with HIV (n = 384) and healthcare providers (n = 16). The study was conducted from 11 March to 9 May 2019.

Results:

Resources for managing HIV clients were largely available with the exception of viral load machines, reagents for CD4 counts, and antifungals such as Fluconazole and Cotrimoxazole. Patients enrolled on antiretroviral therapy within 2 weeks was 71% and clients retained in care within 2 weeks of enrolment was 90%. Approximately 26% of enrolled clients recorded viral load suppression; 33% of People Living with HIV who were not insured with the National Health Insurance Scheme paid for some antiretrovirals and cotrimoxazole. Adherence to ART and Cotrimoxazole were 95% and 88%, respectively, using pill count on their last three visits. Time spent with clinical team was among the worst rated (mean = 2.98, standard deviation = 0.54) quality indicators by patients contrary to interpersonal relationship with health provider which was among the best rated (mean = 3.25, standard deviation = 0.41) indicators.

Conclusion:

Observed quality care gaps could potentially reverse gains made in HIV prevention and control in Ghana if not addressed timely; an important value addition of this study is the novel application of input-process-outcome approach in the context of antiretroviral therapy services in Ghana. There is also the need for policy dialogue on inclusion of medications for prophylaxis in antiretroviral therapy on the National Health Insurance Scheme to promote adherence and retention.
Clinical and laboratory profiles of visceral leishmaniasis among adult patients admitted to Felege Hiwot Hospital, Bahir Dar, Ethiopia
Authors: Tarekegn Berhanu , Tamene Ayanaw
Published: July 2021

Background:

Visceral leishmaniasis is a vector-borne disease caused by Leishmania donovani transmitted by sand fly species. It is the third most common vector-borne disease globally. Visceral leishmaniasis is endemic in Ethiopia with an estimated annual incidence ranging from 3700 to 7400 cases. This research aimed to assess the clinical presentations and laboratory profiles of visceral leishmaniasis for early diagnosis and timely initiation of management.

Objective:

To describe the clinical and laboratory manifestation and diagnostic modalities of visceral leishmaniasis among adult patients admitted to Felege Hiwot Hospital, from 1 September 2016 to 30 August 2019.

Method:

Institution-based retrospective cross-sectional study was conducted among 141 patients admitted to Felege Hiwot Hospital from 1 September 2016 to 30 August 2019. Descriptive statistics were used to describe the clinical presentation and laboratory profiles of patients with visceral leishmaniasis.

Results:

Among a total of 141 enrolled patients in the study, males were affected 13-fold. Most of them were travelers to endemic areas during the winter season for labor work. The mean duration of illness was 48 days. Common symptoms were fever (96.5%), weightless (82.5%), jaundice (18.4%), vomiting/diarrhea (13.5%), and bleeding episodes (11.3%). Splenomegaly was seen in 98.6%, ascites in 35.5%, and lymphadenopathy in 9.9%. Lymphadenopathy was seen significantly in HIV patients (40%). Anemia was seen in 95%, thrombocytopenia in 90.2%, leukopenia in 86.4%, and pancytopenia in 79.4%. Half of the patients had coinfection. Neutropenic sepsis was seen in 21.3%. The diagnosis was made by tissue aspiration in 65% of patients.

Conclusion:

The majority of patients who were diagnosed to have visceral leishmaniasis were young male adults who traveled to the endemic areas seasonally. Fever and splenomegaly were seen as the commonest clinical presentation. Lymphadenopathy occurred in high frequency among HIV co-infected patients. Anemia was the commonest hematologic finding.
Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: The WAVES randomized parallel-arm clinical trial
Authors: Wahls Terry L , Titcomb Tyler J , Bisht Babita , Eyck Patrick Ten , Rubenstein Linda M , Carr Lucas J , Darling Warren G , Hoth Karin F , Kamholz John , Snetselaar Linda G
Published: July 2021

Objective

To compare the effect of the modified Paleolithic elimination (Wahls) and low-saturated fat (Swank) diets in relapsing-remitting MS (RRMS).

Methods

Individuals (n = 87) with RRMS were randomized to the Swank or Wahls diets in a parallel group clinical trial consisting of four timepoints: 1) run-in, 2) baseline, 3) 12-weeks, and 4) 24-weeks.

Results

77 participants completed 12 weeks and 72 completed 24 weeks. The 12-week change from baseline in fatigue was -0.94 ± 0.18 (FSS) and -9.87 ± 1.93 (MFIS; both p < 0.0001) for Swank, and -0.71 ± 0.24 (FSS; p = 0.004) and -14.41 ± 2.22 (MFIS; p ≤ 0.0001) for Wahls. Physical MSQoL scores improved by 6.04 ± 2.18 (p = 0.006) for Swank and by 14.5 ± 2.63 (p < 0.0001) for Wahls. Mental MSQoL scores improved by 11.3 ± at 2.79 (p < 0.0001) for Wahls while the Swank did not change (3.85 ± 2.63; p = 0.14). Neither group showed significant changes in 6-minute walking distance at 12 weeks. All outcomes were maintained or further improved at 24 weeks.

Conclusions

Both diets were associated with clinically meaningful within-group reductions in fatigue and improvements in QoL. Trial Registration: Clinicaltrials.gov Identifier: NCT02914964
Comparative Analysis of Rural Health Demographics in 2 East African Communities During Medical Camps: Volunteers’ Perspectives’
Authors: Olowu Adekunle , Kachala Rabson , Bamigbade Oluwadamilola , Olowu Omotinuolawa , Chibeza Faith
Published: July 2021

Malawian and Zambian governments have made efforts to improve healthcare for rural dwellers but possible differences or similarities in health demographics may inform targeted interventions and volunteers may have a greater role to play in improving health outcomes.

Aims and Objectives

To compare of basic health and social demographics observed during 4-day medical camps in 2 rural communities in Zambia and Malawi to determine any significant differences or similarities.

Method

About 12 and 10 local and international volunteers at medical camps (at a temporary rural health post or community hall) in rural Zambia and Malawi respectively treated 488 patients in total, with basic health and social demographic data collected and results analyzed.

Results

The mean age of patients seen in Malawi and Zambia were 34.5 and 38.9 years respectively, with 39% and 40% of patients in Malawi and Zambia respectively being within the 18 to 44 years age group, and mostly females (59.7% in Malawi and 65.7% in Zambia). Most were non-infectious diseases (97.3% in Zambia, 95% in Malawi), mostly musculoskeletal (17.0% in Malawi and 30.5% in Zambia), while medications prescribed were mostly analgesics (35.7% in Malawi and 29.9% in Zambia). Only a small proportion of patients were referred to local secondary facilities or district hospitals, 51 (28.7%) in Malawi and 59 (19.9%) in Zambia respectively. Chi square test shows a significant difference ( P < .001) in diseases in both countries, but there was no statistically significant difference between the mean age of patients seen in both countries, using the independent t-test ( P = .365).

Conclusion

This study highlights statistically significant demographic differences between the 2 communities and possible reasons for these, and how volunteers’ roles in rural healthcare in the East African communities could be further evaluated.
Hyperinflammation in COVID-19 Obese Patients Treated With Tocilizumab: A Successful Case Series
Authors: Beltrão Beatriz Amorim , Teixeira Rafael Cabral , Porto Diego Bastos
Published: July 2021

The cytokine storm syndrome has been suggested as a mechanism in the pathophysiology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; COVID-19 [coronavirus disease 2019]) infection. Drugs such as tocilizumab, an interleukin-6 antagonist, have shown good results in other scenarios of hyperinflammatory state and might also be effective in COVID-19 disease. However, the best dosing regimen and the timing of infusion is currently unknown, specifically in obese patients. We report the first cases of tocilizumab administration in obese patients during the first days of COVID-19 worsening hypoxemia. This infusion was not adjusted by weight, following the manufacturer maximal dose limit. We kept a strict monitoring for possible infections, prior and during the treatment. All patients showed good improvements on chest-computed tomography images and oxygenation and were discharged from hospital shortly after, without complications or intubation. This case series highlights that tocilizumab seems to be effective to treat hyperinflammation of critical COVID-19 obese patients, even when the infusion of the ideal dose is not feasible to be administered. It also shows the importance of early timing in the decision to treat and the relevance of infections exclusion prior to the induction of immunosuppression by tocilizumab.
Prevalence of Intestinal Parasitosis and Its Associated Factors Among Children Aged 6 to 59 months Attending Mekane Eyesus Primary Hospital, Northcentral Ethiopia
Authors: Eyayu Tahir , Wubie Amilaku , Kiros Teklehaimanot , Tiruneh Tegenaw , Damtie Shewaneh , Sema Meslo , Abebaw Aynework , Chanie Ermias Sisay , Workineh Lemma
Published: July 2021

Background. Intestinal parasites are still a serious public health problem and important cause of morbidity and mortality all over the world, particularly in developing countries. Unfortunately, pre-school children are more susceptible to infection. However, information is scarce in the study area. Thus, this study aimed to assess the prevalence of intestinal parasitosis and associated factors among children aged 6 to 59 months in Northcentral Ethiopia. Methods. An institutional-based cross-sectional study was carried out at Mekane Eyesus primary hospital from June 10 to November 30, 2020. Stool samples were collected from 322 children and examined by using direct wet mount and formal ether concentration techniques. The data were entered and analyzed using EPI Info v7 and SPSS v23 statistical software, respectively. Both bivariable and multivariable logistic analysis was carried out and potential associated factors were identified based on adjusted odds ratio with 95% confidence interval and P-value <.05. Results. The prevalence of intestinal parasitosis was 18.0% (95% CI: 14.0%-22.0%). A total of 4 parasites were examined and the dominant parasite was E. histolytica /dispar (8.1%) followed by A. limbricoide (4.7%). Children with irregular trimming of fingernails (AOR = 3.14, 95% CI: 1.59-6.21), and child who have habit of eating unwashed fruits/vegetables (AOR = 3.80, 95% CI: 1.14-12.82) were strongly associated with IPIs. Conclusions. Protozoa parasites are most common cause of diseases in children. The study identified some preventable and modifiable factors to address the prevalence of IPIs. Additionally, improving mothers/guardians awareness about source of infection and mode of transmission is necessary.
Adolescent Experiences with Self-Asphyxial Behaviors and Problematic Drinking in Emerging Adulthood
Authors: Austin Jillian E. , Lang Amy C. , Nacker Anna M. , Wallace Alexander L. , Schwebel David C. , Brown B. Bradford , Davies W. Hobart
Published: July 2021

Self-asphyxial behavior to achieve a euphoric high (The Choking Game; TCG), occurs most often during early adolescence. Participants in TCG often engage in other risky behaviors. This study investigated the relationship between prior experience with TCG and problematic drinking behaviors in emerging adulthood. Emerging adults, 18 to 25 years old (N = 1248), 56% female, and 78% Caucasian completed an online survey regarding knowledge of and prior engagement in TCG and current drinking behaviors. Participants who personally engaged in TCG during childhood/adolescence or were familiar with TCG reported significantly more problematic drinking behaviors during emerging adulthood. Those present when others engaged in TCG but resisted participation themselves reported significantly less current problematic drinking behaviors than those who participated, but significantly more current problematic drinking behaviors than those never present. Emerging adults with increased social familiarity with TCG during adolescence endorsed greater problematic drinking behaviors. Results suggest resistance skills may generalize across time/activities.
Patient Expectations From Consultation and Treatment of Spine Pain in a Private Spine Rehabilitation Clinic in Urban India
Authors: Jain Shikha , Jha Shivani , Shetty Gautam , Ram CS
Published: July 2021

Despite high prevalence of spine pain among the Indian population, patient expectations regarding consultation and its treatment are unknown. We aimed to determine consultation and treatment expectations among patients visiting a spine rehabilitation clinic in urban India. We included 194 consecutive patients who completed a consultation expectation (CE) and treatment outcome expectation (OE) questionnaires and the Patient-Centered Outcome Questionnaire (PCOQ). To learn about the most suitable treatment for their problem (98%), and to know what kind of activities they could do and should avoid (96%) were the most important CEs, and to achieve complete relief of symptoms (96%), and prevent recurrence of pain (95%) were the most important OEs. For successful treatment, patients expected PCOQ pain levels of 2.0 (96.5% reduction) and interference levels of 1.5 (96% reduction). Patients expected to know the most suitable treatment, activities they could do and avoid after consultation, and to achieve complete relief of symptoms and prevent recurrence after treatment. Incorporating and addressing these expectations may help improve outcomes and satisfaction with the consultation and treatment of spine pain.
“It’s a walk of shame”: Experiences of unintended pregnancy and abortion among sexual- and gender-minoritized females in urban India
Authors: Bowling Jessamyn , Simmons Megan , Blekfeld-Sztraky Donna , Bartelt Elizabeth , Dodge Brian , Sundarraman Vikram , Lakshmi Brindaa , Herbenick Debby
Published: July 2021

Background:

Unintended pregnancy and safe abortion access in India remain critical public health concerns. The health of sexual- and gender-minoritized females (SGMF; those assigned female at birth and identify as other than heterosexual and/or as other than cisgender women) in India is understudied.

Aim:

We examined experiences of unintended pregnancy and abortion among SGMF individuals in urban India.

Methods:

We used focus group discussions ( n = 8 individuals in two groups) and interviews ( n = 20) with SGMF individuals. Data were collected in December 2017. Transcripts were analyzed using a priori thematic analysis and then open thematic analysis in Dedoose online software.

Results:

Nine participants experienced or suspected they had unintended pregnancies. Pregnancy circumstances were mostly due to sex without using a barrier method. Participants discussed using traditional methods to induce abortion or changing their approach to contraception. Social support was often lacking, though partners were supportive of abortion choices. Participants reported stigma and surveillance from family, friends, providers, and community members.

Conclusion:

These findings highlight the effects of stigma in relation to abortion and unintended pregnancy on health and relationships.
Subarachnoid haemorrhage in pregnancy after in vitro fertilisation with egg donation: a case report and review of the literature
Authors: Hughes Noemi J. , Choudhury Saeed M.S.R. , Liyanage Sidath H. , Hussain Munawar
Published: July 2021

We report a rare case of in vitro fertilisation (IVF) with egg donation complicated by a subarachnoid haemorrhage (SAH). Haemostatic changes related to IVF are known to increase risk of venous thrombosis; however, less is known regarding the risk of arterial events such as cerebrovascular accidents (CVA). Matrix metalloprotease-9 (MMP-9) upregulated in IVF patients may have a role in arterial aneurysm formation, which is the most common cause of SAH. Further research is required to assess the benefit of screening for risk of CVA and the best way to manage this in the IVF population. This may have implications for the ethics of offering certain procedures such as egg donation to women with pre-existing risk factors.
Impact of Electronic Medication Reminder Caps on Patient Adherence and Blood Pressure
Authors: Mehas Nicolette , Hudmon Karen Suchanek , Jaynes Heather , Klink Steve , Downey Laura , Zillich Alan J.
Published: July 2021

Background: Medication adherence is widely recognized as an essential component of chronic disease management, yet only 50% of patients take their medication as prescribed. Newer technologies have the potential to improve medication adherence. Objective: To conduct a pilot study estimating the impact of a pharmacy-dispensed electronic reminder cap (SMARxT cap), which also records cap openings, on medication adherence and blood pressure (BP). Methods: After a 30-day run-in period, 28 individuals were randomized to receive a SMARxT or placebo cap on each BP medication. The primary outcome was adherence measured via (1) the medication possession ratio, (2) number of cap openings, and (3) self-report. The secondary outcome was the average of 2 BP readings at 6 months. Mean changes from baseline to 6 months were compared between the 2 groups. Results: The medication possession ratio increased 2.7% in the SMARxT cap group and decreased 1.1% in the control group ( P = .13), and cap openings increased 11.9% in the SMARxT cap group and 9.9% in the control group ( P = .83). Self-reported adherence increased 1.1 points in the SMARxT cap group and 0.8 points in the control group ( P = .64). Systolic BP decreased 8.2 mm Hg in the SMARxT cap group and 2.8 mm Hg in the placebo cap group ( P = .35), and diastolic BP decreased to 6.2 mm Hg in the SMARxT cap group and was unchanged in the placebo cap group ( P = .06). Conclusions: Use of SMARxT cap showed nonsignificant improvement in medication adherence and BP lowering. This technology has potential to characterize and improve medication-taking behavior.
β-acetoxyisovaleryl alkannin (AAN-II) from Alkanna tinctoria promotes the healing of pressure-induced venous ulcers in a rabbit model through the activation of TGF-β/Smad3 signaling
Authors: Yang Xiao , Fan Weijing , Huang Renyan , Liu Guobin
Published: July 2021

Alkannin-based pharmaceutical formulations for improving wound healing have been on the market for several years. However, detailed molecular mechanisms of their action have yet to be elucidated. Here, we investigated the potential roles of AAN-II in improving the healing of pressure-induced venous ulcers using a rabbit model generated by combining deep vein thrombosis with a local skin defect/local skin defect. The extent of healing was evaluated using hematoxylin and eosin (HE) or vimentin staining. Rabbit skin fibroblasts were cultured for AAN-II treatment or TGFB1-sgRNA lentivirus transfection. ELISA was used to evaluate the levels of various cytokines, including IL-1β, IL-4, IL-6, TNF-α, VEGF, bFGF, TGF-β and PDGF. The protein levels of TGF-β sensors, including TGF-β, Smad7 and phosphor-Smad3, and total Smad3, were assayed via western blotting after TGF-β knockout or AAN-II treatment. The results show that, for this model, AAN-II facilitates ulcer healing by suppressing the development of inflammation and promoting fibroblast proliferation and secretion of proangiogenic factors. AAN-II enhances the activation of the TGF-β1-Smad3 signaling pathway during skin ulcer healing. In addition, the results demonstrate that AAN-II and TGF-β have synergistic effects on ulcer healing. Our findings indicate that AAN-II can promote healing of pressure-induced venous skin ulcers via activation of TGF-β-Smad3 signaling in fibroblast cells and provide evidence that could be used in the development of more effective treatments.
CKAP4 Antibody-Conjugated Si Quantum Dot Micelles for Targeted Imaging of Lung Cancer
Authors: Huang Xin , Chen Qian , Li Xin , Lin Chenyu , Wang Kun , Luo Cici , Le Wenjun , Pi Xiaodong , Liu Zhongmin , Chen Bingdi
Published: July 2021

At present, various fluorescent nanomaterials have been designed and synthesized as optical contrast agents for surgical navigation. However, there have been no reports on the preparation of fluorescent contrast agents for lung cancer surgery navigation using silicon quantum dots (Si QDs). This study improved and modified the water-dispersible Si QD micelles reported by Pi et al. to prepare Si QD micelles-CKAP4. The data showed that the Si QD micelles-CKAP4 were spherical particles with a mean hydrodiameter of approximately 78.8 nm. UV–visible absorption of the Si QD micelles-CKAP4 ranged from 200 to 500 nm. With an excitation wavelength of 330 nm, strong fluorescence at 640 nm was observed in the fluorescence emission spectra. Laser confocal microscopy and fluorescence microscopy assay showed that the Si QD micelles-CKAP4 exhibited good targeting ability to lung cancer cells and lung cancer tissues in vitro. The in vivo fluorescence-imaging assay showed that the Si QD micelles-CKAP4 was metabolized by the liver and excreted by the kidney. In addition, Si QD micelles-CKAP4 specifically targeted lung cancer tissue in vivo compared with healthy lung tissue. Cytotoxicity and hematoxylin and eosin staining assays showed that the Si QD micelles-CKAP4 exhibited high biosafety in vitro and in vivo. Si QD micelles-CKAP4 is a specifically targeted imaging agent for lung cancer and is expected to be a fluorescent contrast agent for lung cancer surgical navigation in the future.
A chromosome-level genome assembly of Cairina moschata and comparative genomic analyses
Authors: Jiang Fan , Jiang Yaoxin , Wang Wenxuan , Xiao Changyi , Lin Ruiyi , Xie Tanghui , Sung Wing-Kin , Li Shijun , Jakovlić Ivan , Chen Jianhai , Du Xiaoyong
Published: July 2021

Background

The Muscovy duck (Cairina moschata) is an economically important duck species, with favourable growth and carcass composition parameters in comparison to other ducks. However, limited genomic resources for Muscovy duck hinder our understanding of its evolution and genetic diversity.

Results

We combined linked-reads sequencing technology and reference-guided methods for de novo genome assembly. The final draft assembly was 1.12 Gbp with 29 autosomes, one sex chromosome and 4,583 unlocalized scaffolds with an N50 size of 77.35 Mb. Based on universal single-copy orthologues (BUSCO), the draft genome assembly completeness was estimated to be 93.30 %. Genome annotation identified 15,580 genes, with 15,537 (99.72 %) genes annotated in public databases. We conducted comparative genomic analyses and found that species-specific and rapidly expanding gene families (compared to other birds) in Muscovy duck are mainly involved in Calcium signaling, Adrenergic signaling in cardiomyocytes, and GnRH signaling pathways. In comparison to the common domestic duck (Anas platyrhynchos), we identified 104 genes exhibiting strong signals of adaptive evolution (Ka/Ks > 1). Most of these genes were associated with immune defence pathways (e.g. IFNAR1 and TLR5). This is indicative of the existence of differences in the immune responses between the two species. Additionally, we combined divergence and polymorphism data to demonstrate the “faster-Z effect” of chromosome evolution.

Conclusions

The chromosome-level genome assembly of Muscovy duck and comparative genomic analyses provide valuable resources for future molecular ecology studies, as well as the evolutionary arms race between the host and influenza viruses.
Prevalence and mechanisms of antibiotic resistance in Escherichia coli isolated from mastitic dairy cattle in Canada
Authors: Majumder Satwik , Jung Dongyun , Ronholm Jennifer , George Saji
Published: July 2021

Background

Bovine mastitis is the most common infectious disease in dairy cattle with major economic implications for the dairy industry worldwide. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from dairy farms is vital not only for animal husbandry but also for public health.

Methods

In this study, the prevalence of AMR in 113 Escherichia coli isolates from cases of bovine clinical mastitis in Canada was investigated. Kirby-Bauer disk diffusion test with 18 antibiotics and microdilution method with 3 heavy metals (copper, zinc, and silver) was performed to determine the antibiotic and heavy-metal susceptibility. Resistant strains were assessed for efflux and ß-lactamase activities besides assessing biofilm formation and hemolysis. Whole-genome sequences for each of the isolates were examined to detect the presence of genes corresponding to the observed AMR and virulence factors.

Results

Phenotypic analysis revealed that 32 isolates were resistant to one or more antibiotics and 107 showed resistance against at least one heavy metal. Quinolones and silver were the most efficient against the tested isolates. Among the AMR isolates, AcrAB-TolC efflux activity and ß-lactamase enzyme activities were detected in 13 and 14 isolates, respectively. All isolates produced biofilm but with different capacities, and 33 isolates showed α-hemolysin activity. A positive correlation (Pearson r = + 0.89) between efflux pump activity and quantity of biofilm was observed. Genes associated with aggregation, adhesion, cyclic di-GMP, quorum sensing were detected in the AMR isolates corroborating phenotype observations.

Conclusions

This investigation showed the prevalence of AMR in E. coli isolates from bovine clinical mastitis. The results also suggest the inadequacy of antimicrobials with a single mode of action to curtail AMR bacteria with multiple mechanisms of resistance and virulence factors. Therefore, it calls for combinatorial therapy for the effective management of AMR infections in dairy farms and combats its potential transmission to the food supply chain through the milk and dairy products.
Extracellular volume quantification using synthetic haematocrit assessed from native and post-contrast longitudinal relaxation T1 times of a blood pool
Authors: Opatril Lukas , Panovsky Roman , Machal Jan , Holecek Tomas , Masarova Lucia , Feitova Vera , Kincl Vladimir , Hodejovsky Marek , Spinarova Lenka
Published: July 2021

Background

In terms of cardiovascular magnetic resonance are haematocrit values required for calculation of extracellular volume fraction (ECV). Previously published studies have hypothesized that haematocrit could be calculated from T1 blood pool relaxation time, however only native T1 relaxation time values have been used and the resulting formulae had been both in reciprocal and linear proportion. The aim of the study was to generate a synthetic haematocrit formula from only native relaxation time values first, calculate whether linear or reciprocal model is more precise in haematocrit estimation and then determine whether adding post-contrast values further improve its precision.

Methods

One hundred thirty-nine subjects underwent CMR examination. Haematocrit was measured using standard laboratory methods. Afterwards T1 relaxation times before and after the application of a contrast agent were measured and a statistical relationship between these values was calculated.

Results

Different linear and reciprocal models were created to estimate the value of synthetic haematocrit and ECV. The highest coefficient of determination was observed in the combined reciprocal model “− 0.047 + (779/ blood native) − (11.36/ blood post-contrast)”.

Conclusions

This study provides more evidence that assessing synthetic haematocrit and synthetic ECV is feasible and statistically most accurate model to use is reciprocal. Adding post-contrast values to the calculation was proved to improve the precision of the formula statistically significantly.
Use of machine learning techniques to identify HIV predictors for screening in sub-Saharan Africa
Authors: Mutai Charles K. , McSharry Patrick E. , Ngaruye Innocent , Musabanganji Edouard
Published: July 2021

Aim

HIV prevention measures in sub-Saharan Africa are still short of attaining the UNAIDS 90–90-90 fast track targets set in 2014. Identifying predictors for HIV status may facilitate targeted screening interventions that improve health care. We aimed at identifying HIV predictors as well as predicting persons at high risk of the infection.

Method

We applied machine learning approaches for building models using population-based HIV Impact Assessment (PHIA) data for 41,939 male and 45,105 female respondents with 30 and 40 variables respectively from four countries in sub-Saharan countries. We trained and validated the algorithms on 80% of the data and tested on the remaining 20% where we rotated around the left-out country. An algorithm with the best mean f1 score was retained and trained on the most predictive variables. We used the model to identify people living with HIV and individuals with a higher likelihood of contracting the disease.

Results

Application of XGBoost algorithm appeared to significantly improve identification of HIV positivity over the other five algorithms by f1 scoring mean of 90% and 92% for males and females respectively. Amongst the eight most predictor features in both sexes were: age, relationship with family head, the highest level of education, highest grade at that school level, work for payment, avoiding pregnancy, age at the first experience of sex, and wealth quintile. Model performance using these variables increased significantly compared to having all the variables included. We identified five males and 19 females individuals that would require testing to find one HIV positive individual. We also predicted that 4·14% of males and 10.81% of females are at high risk of infection.

Conclusion

Our findings provide a potential use of the XGBoost algorithm with socio-behavioural-driven data at substantially identifying HIV predictors and predicting individuals at high risk of infection for targeted screening.
Machine learning in medicine: a practical introduction to natural language processing
Authors: Harrison Conrad J. , Sidey-Gibbons Chris J.
Published: July 2021

Background

Unstructured text, including medical records, patient feedback, and social media comments, can be a rich source of data for clinical research. Natural language processing (NLP) describes a set of techniques used to convert passages of written text into interpretable datasets that can be analysed by statistical and machine learning (ML) models. The purpose of this paper is to provide a practical introduction to contemporary techniques for the analysis of text-data, using freely-available software.

Methods

We performed three NLP experiments using publicly-available data obtained from medicine review websites. First, we conducted lexicon-based sentiment analysis on open-text patient reviews of four drugs: Levothyroxine, Viagra, Oseltamivir and Apixaban. Next, we used unsupervised ML (latent Dirichlet allocation, LDA) to identify similar drugs in the dataset, based solely on their reviews. Finally, we developed three supervised ML algorithms to predict whether a drug review was associated with a positive or negative rating. These algorithms were: a regularised logistic regression, a support vector machine (SVM), and an artificial neural network (ANN). We compared the performance of these algorithms in terms of classification accuracy, area under the receiver operating characteristic curve (AUC), sensitivity and specificity.

Results

Levothyroxine and Viagra were reviewed with a higher proportion of positive sentiments than Oseltamivir and Apixaban. One of the three LDA clusters clearly represented drugs used to treat mental health problems. A common theme suggested by this cluster was drugs taking weeks or months to work. Another cluster clearly represented drugs used as contraceptives. Supervised machine learning algorithms predicted positive or negative drug ratings with classification accuracies ranging from 0.664, 95% CI [0.608, 0.716] for the regularised regression to 0.720, 95% CI [0.664,0.776] for the SVM.

Conclusions

In this paper, we present a conceptual overview of common techniques used to analyse large volumes of text, and provide reproducible code that can be readily applied to other research studies using open-source software.
The survey visit as a key evaluative event in accreditation–a qualitative study of survey visit experiences among surveyors and general practice professionals
Authors: Due Tina Drud , Thorsen Thorkil , Kousgaard Marius Brostrøm
Published: July 2021

Background

Accreditation is a widely employed quality assurance concept in health care and the survey visit is the central method for assessing participating organisations’ compliance with accreditation standards. Despite this, research on the survey visit as a method for assessing compliance is scarce. In Denmark a mandatory accreditation programme was introduced for general practice clinics in 2016. We performed a qualitative, explorative study of the reflections and actions of surveyors and general practice professionals (GPs and staff) concerning the production of information about compliance with the accreditation standards in relation to the survey visit.

Methods

We conducted qualitative interviews with GPs and staff from general practices in two Danish regions before and after their survey visit. We also interviewed the surveyors. We observed survey visits to qualify the interviews and analysis. All interviews were audio recorded, transcribed, and analysed using an integrative approach.

Results

The surveyors combined documents, questioning of the professionals, and visual impressions of the clinic to assess compliance. They sought to de-dramatise the survey visit and to generate a natural conversation with attention to workflows. Trust in the professionals’ statements was fundamental to the surveyors’ approach, and they were confident in their ability to assess compliance. Their level of scrutiny was influenced by their observations and the quality of documents. The general practice professionals had generally sought to comply with the standards and to give an authentic portrait of the clinic. The few cases of misrepresention concerned standards that the professionals found too excessive.

Conclusion

The validity of the survey visit as a method to assess compliance was highly dependent on the professionals’ willingness to convey a realistic picture of their practice. Since they were generally willing to do so, the trust-based approach seemed suitable for identifying cases of non-compliance caused by insufficient understanding of the standards. However, it can be difficult for the surveyors to detect when the professionals engage in misrepresentation due to disagreements with the standards. Thus, when adopting a trust-based approach to the survey visit, it seems particularly important to ensure that the professionals view the standards as meaningful and manageable.
Gap between desired and self-determined roles of general practitioners: a multicentre questionnaire study in Japan
Authors: Chinen Takashi , Sasabuchi Yusuke , Kotani Kazuhiko , Yamaguchi Hironori
Published: July 2021

Background

Primary care physicians have diverse responsibilities. To collaborate with cancer specialists efficiently, they should prioritise roles desired by other collaborators rather than roles based on their own beliefs. No previous studies have reported the priority of roles such clinic-based general practitioners are expected to fulfil across the cancer care continuum. This study clarified the desired roles of clinic-based general practitioners to maximise person-centred cancer care.

Methods

A web-based multicentre questionnaire in Japan was distributed to physicians in 2019. Physician roles within the cancer care continuum were divided into 12 categories, including prevention, diagnosis, surgery, follow-up with cancer survivors, chemotherapy, and palliative care. Responses were evaluated by the proportion of three high-priority items to determine the expected roles of clinic-based general practitioners according to responding physicians in similarly designated roles.

Results

Seventy-eight departments (25% of those recruited) from 49 institutions returned questionnaires. Results revealed that some physicians had lower expectations for clinic-based general practitioners to diagnose cancer, and instead expected them to provide palliative care. However, some physicians expected clinic-based general practitioners to be involved in some treatment and survivorship care, though the clinic-based general practitioners did not report the same priority.

Conclusion

Clinic-based general practitioners prioritised involvement in prevention, diagnoses, and palliative care across the cancer continuum, although lower expectations were placed on them than they thought. Some additional expectations of their involvement in cancer treatment and survivorship care were unanticipated by them. These gaps represent issues that should be addressed.
Comorbid early esophageal cancer and Gongylonema pulchrum infection: a case report
Authors: Zhou Qiaozhi , Wei Yongqiu , Zhai Huihong , Li Shaogang , Xu Rui , Li Peng
Published: July 2021

Background

Gongylonema pulchrum is a zoonotic parasite rarely found in humans. To date, there have been no reports on the carcinogenic properties of G. pulchrum, and there are few reports overall on the relationship between esophageal cancer and parasites.

Case presentation

This report describes the first case of esophageal gongylonemiasis coexisting with early esophageal cancer. The patient had no high-risk factors for esophageal cancer, such as smoking, flushing after drinking, or tumor history. We speculate the existence of unknown links between esophageal cancer and parasitic infection in this patient.

Discussion and conclusions

We report the first case of a human presenting both esophageal G. pulchrum infection and esophageal squamous cell carcinoma with the hope that it may provide evidence for a new hypothesis of tumorigenesis.
Cecal retroflexion is infrequently performed in routine practice and the retroflexed view is of poor quality
Authors: Keswani Rajesh N. , Kahi Charles J. , Benson Mark , Gawron Andrew J. , Kaltenbach Tonya R. , Yadlapati Rena H. , Gregory Dyanna L. , Duloy Anna
Published: July 2021

Background

As right colon polyps are challenging to detect, a retroflexed view of right colon (RV) may be useful. However, cecal retroflexion (CR) without a RV to the hepatic flexure (HF) is inadequate. We aimed to determine the frequency of CR and quality of the RV in routine practice.

Methods

This prospective observational study performed at an academic medical center assessed colonoscopy inspection technique of endoscopists who had performed ≥ 100 annual screening colonoscopies. We video recorded ≥ 28 screening/surveillance colonoscopies per endoscopist and randomly evaluated 7 videos per endoscopist. Six gastroenterologists blindly reviewed the videos to determine if CR was performed and HF withdrawal time (cecum to HF time, excluding ileal/polypectomy time).

Results

Reviewers assessed 119 colonoscopies performed by 17 endoscopists. The median HF withdrawal time was 3 min and 46 s. CR was performed in 31% of colonoscopies. CR frequency varied between endoscopists with 9 never performing CR and 2 performing CR in all colonoscopies. When performed, nearly half (43%) of RVs did not extend to the HF with median RV duration of 16 s (IQR 9–30 s). Three polyps were identified in the RV (polyp detection rate of 8.1%), all identified prior to a forward view.

Conclusions

CR is performed infrequently in routine practice. When CR is performed, the RV is of low quality with a very short inspection duration and insufficient ascending colon examination. Further education is required to educate endoscopists in optimal technique to improve overall colonoscopy quality.
Study protocol P-MAPS: microbiome as predictor of severity in acute pancreatitis—a prospective multicentre translational study
Authors: Ammer-Herrmenau C. , Asendorf T. , Beyer G. , Buchholz S. M. , Cameron S. , Damm M. , Frost F. , Henker R. , Jaster R. , Phillip V. , Placzek M. , Ratei C. , Sirtl S. , van den Berg T. , Weingarten M. J. , Woitalla J. , Mayerle J. , Ellenrieder V. , Neesse A.
Published: July 2021

Background

Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients.

Methods

We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality.

Discussion

If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future.

Trial registration: ClinicalTrials.gov Identifier: NCT04777812