bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular phenotypes and clinical characterization of familial hereditary breast cancer among half and full sisters
Authors: Xu Yingjie , He Jun , Qian Chen , Yang Chengguang
Published: May 2022

Background

Preliminary clinical observations show that contemporaneous hereditary breast cancer (CHBC) patients suffered breast cancer at an early age, which requires further analysis.

Methods

38 familial hereditary breast cancer patients (18 CHBC patients and 20 non-CHBC patients) were screened out and 152 non-hereditary breast cancer patients were used as control subjects. Clinical pathologic subtypes, age, tumor location, histological grade, lymph node metastasis, and molecular phenotype expression (ER, PR, HER-2, Ki-67, CK5/6, E-cad, P63, and P120) were compared across all subgroups.

Results

The incidence of CHBC was 9.47% (18/190) in breast cancer patients. The average ages of onset of CHBC patients, non-CHBC patients, and non-hereditary breast cancer patients were 49.06 ± 6.42, 60.75 ± 9.95 and 61.69 ± 14.34 respectively; whereas there were no significant differences with respect to pathological type or tumor location. There were significant differences in some histological grading (grade II/III), lymph node metastasis and PR expression between hereditary and non-hereditary breast cancers (P < 0.05; P < 0.05 and P < 0.005, respectively). Significantly different HER-2 expression was observed when comparing all hereditary or CHBC patients with non-hereditary breast cancers (P < 0.05 and P < 0.005, respectively). There were significant differences in E-cad and P63 between contemporaneous hereditary and non-hereditary breast cancers (P < 0.005 and P < 0.05, respectively).

Conclusions

CHBC patients accounted for 9.47% (18/190) of breast cancer patients, had earlier disease onset, and showed differences compared to non-hereditary breast cancer patients with respect to molecular phenotype and clinical characteristics.
Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Authors: Xue Chunling , Li Xuechun , Ba Li , Shen Yamei , Sun Zhao , Gu Junjie , Yang Ying , Han Qin , Zhao Robert Chunhua
Published: May 2022

Background

Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potential targets for therapeutic approaches in metabolic disorders, including obesity. All adipocytes, including beige adipocytes, differentiate from mesenchymal stem cells (MSCs), which may provide an important path for clinical intervention; however, the mechanism of beiging of human adipose cell-derived MSCs is not fully understood. Here, we provide insights on the role of IRISIN, which is known to be secreted by skeletal muscle and promote beiging of white fat.

Results

We established an IRISIN-induced mesenchymal stem cell beiging model and found that IRISIN protein interacts with the MSC membrane protein TRPC3. This interaction results in calcium influx and consequential activation of Erk and Akt signaling pathways, which causes phosphorylation of PPARγ. The phosphorylated PPARγ enters the nucleus and binds the UCP1 promoter region. Furthermore, the role of TRPC3 in the beiging of MSCs was largely abolished in Trpc3−/− mice. We additionally demonstrate that the calcium concentration in the brain of mice increases upon IRISIN stimulation, followed by an increase in the content of excitatory amino acids and norepinephrine, while Trpc3−/− mice exhibit the reverse effect.

Conclusions

We found that TRPC3 is a key factor in irisin-induced beiging of MSCs, which may provide a new target pathway in addressing metabolic disorders. Our results additionally suggest that the interaction of irisin with TRPC3 may affect multiple tissues, including the brain.

Graphical abstract
Transcriptomic underpinnings of high and low mirror aggression zebrafish behaviours
Authors: Reichmann Florian , Pilic Johannes , Trajanoski Slave , Norton William H. J.
Published: May 2022

Background

Aggression is an adaptive behaviour that animals use to protect offspring, defend themselves and obtain resources. Zebrafish, like many other animals, are not able to recognize themselves in the mirror and typically respond to their own reflection with aggression. However, mirror aggression is not an all-or-nothing phenomenon, with some individuals displaying high levels of aggression against their mirror image, while others show none at all. In the current work, we have investigated the genetic basis of mirror aggression by using a classic forward genetics approach - selective breeding for high and low mirror aggression zebrafish (HAZ and LAZ).

Results

We characterized AB wild-type zebrafish for their response to the mirror image. Both aggressive and non-aggressive fish were inbred over several generations. We found that HAZ were on average more aggressive than the corresponding LAZ across generations and that the most aggressive adult HAZ were less anxious than the least aggressive adult LAZ after prolonged selective breeding. RNAseq analysis of these fish revealed that hundreds of protein-encoding genes with important diverse biological functions such as arsenic metabolism (as3mt), cell migration (arl4ab), immune system activity (ptgr1), actin cytoskeletal remodelling (wdr1), corticogenesis (dgcr2), protein dephosphorylation (ublcp1), sialic acid metabolism (st6galnac3) and ketone body metabolism (aacs) were differentially expressed between HAZ and LAZ, suggesting a strong genetic contribution to this phenotype. DAVID pathway analysis showed that a number of diverse pathways are enriched in HAZ over LAZ including pathways related to immune function, oxidation-reduction processes and cell signalling. In addition, weighted gene co-expression network analysis (WGCNA) identified 12 modules of highly correlated genes that were significantly associated with aggression duration and/or experimental group.

Conclusions

The current study shows that selective breeding based of the mirror aggression phenotype induces strong, heritable changes in behaviour and gene expression within the brain of zebrafish suggesting a strong genetic basis for this behaviour. Our transcriptomic analysis of fish selectively bred for high and low levels of mirror aggression revealed specific transcriptomic signatures induced by selective breeding and mirror aggression and thus provides a large and novel resource of candidate genes for future study.
The COVID-19 pandemic in the African continent
Authors: Bwire Godfrey , Ario Alex Riolexus , Eyu Patricia , Ocom Felix , Wamala Joseph F. , Kusi Kwadwo A. , Ndeketa Latif , Jambo Kondwani C. , Wanyenze Rhoda K. , Talisuna Ambrose O.
Published: May 2022

In December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus spread quickly and in March, 2020, it was declared a pandemic. Scientists predicted the worst scenario to occur in Africa since it was the least developed of the continents in terms of human development index, lagged behind others in achievement of the United Nations sustainable development goals (SDGs), has inadequate resources for provision of social services, and has many fragile states. In addition, there were relatively few research reporting findings on COVID-19 in Africa. On the contrary, the more developed countries reported higher disease incidences and mortality rates. However, for Africa, the earlier predictions and modelling into COVID-19 incidence and mortality did not fit into the reality. Therefore, the main objective of this forum is to bring together infectious diseases and public health experts to give an overview of COVID-19 in Africa and share their thoughts and opinions on why Africa behaved the way it did. Furthermore, the experts highlight what needs to be done to support Africa to consolidate the status quo and overcome the negative effects of COVID-19 so as to accelerate attainment of the SDGs.
Impact of switching from triple therapy to dual bronchodilation in COPD: the DACCORD ‘real world’ study
Authors: Vogelmeier Claus F. , Worth Heinrich , Buhl Roland , Criée Carl-Peter , Gückel Eva , Kardos Peter
Published: May 2022

Introduction

Chronic obstructive pulmonary disease (COPD) guidelines recommend reserving triple therapy of inhaled corticosteroid (ICS), long-acting β2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) for patients with exacerbations despite dual therapy. However, many patients receive triple therapy without a clear indication. For these patients, it would be useful to know whether ICS can be withdrawn.

Methods

DACCORD was a longitudinal, non-interventional ‘real-world’ study in three cohorts. This manuscript describes the results of Cohort 3, which recruited patients with COPD who had received triple therapy for ≥ 6 months. Prior to entry, each patient’s physician decided to continue triple therapy, or switch to a LABA/LAMA; patients were then followed for 12 months, with exacerbations and COPD Assessment Test (CAT) data recorded every 3 months. The primary endpoint was the time until COPD worsening, defined as the occurrence of a moderate/severe exacerbation or clinically relevant CAT worsening.

Results

Of the 1192 patients recruited into the study, 967 completed the end-of-study visit and ≥ 2 of the three interim visits, 292 and 675 receiving LABA/LAMA and triple therapy, respectively. Most baseline demographics were similar between the two groups. A lower proportion of patients in the LABA/LAMA group had COPD worsening than with triple therapy (32.5% vs 55.7% at 12 months), with the time to worsening extended in the LABA/LAMA group (hazard ratio 2.004, p < 0.001). In addition, a significantly lower proportion of patients in the LABA/LAMA group exacerbated (18.5% vs 28.7%; p < 0.001), accompanied by a greater improvement from baseline in CAT total score. Overall, fewer patients in the LABA/LAMA group reported adverse events than in the triple therapy group (12.9% vs 15.1%).

Conclusions

These results suggest that in a real world setting physicians are able to identify patients who can be ‘stepped down’ from triple therapy to LABA/LAMA. Following step down, there was no overall decline in COPD—indeed, some patients had better outcomes.
Establishment and characterization of a novel ovarian high-grade serous carcinoma cell line—IPO43
Authors: Silva Fernanda , Coelho Filipa , Peixoto Ana , Pinto Pedro , Martins Carmo , Frombach Ann-Sophie , Santo Vítor E. , Brito Catarina , Guimarães António , Félix Ana
Published: May 2022

Background

Epithelial ovarian cancer (EOC) is an aggressive and lethal malignancy and novel EOC cell lines with detailed characterization are needed, to provide researchers with diverse helpful resources to study EOC biological processes and cancer experimental therapies.

Methods

The IPO43 cell line was established from the ascitic fluid of a patient with a diagnosis of high-grade serous carcinoma (HGSC) of the ovary, previously treated with chemotherapy.

Cell immortalization was achieved in 2D cell culture and growth obtained in 2D and 3D cell cultures. The characterization of immortalized cells was done by immunocytochemistry, flow cytometry, cell proliferation, chromosomal Comparative Genomic Hybridization (cCGH), STR profile and Next Generation Sequencing (NGS).

Results

Characterization studies confirmed that IPO43 cell line is of EOC origin and maintains morphological and molecular features of the primary tumor. cCGH analysis showed a complex profile with gains and losses of specific DNA regions in both primary ascitic fluid and cell line IPO43. The cell line was successfully grown in a 3D system which allows its future application in more complex assays than those performed in 2D models. IPO43 cell line is resistant to standard drug treatment in vitro.

Conclusions

IPO43 is available for public research and we hope it can contribute to enrich the in vitro models addressing EOC heterogeneity, being useful to investigate EOC and to develop new therapeutic modalities.
Prevalence of malaria among febrile patients and assessment of efficacy of artemether-lumefantrine and artesunate-amodiaquine for uncomplicated malaria in Dolisie, Republic of the Congo
Authors: Pembet Singana Brice , Casimiro Prisca Nadine , Matondo Diassivi Brunelle , Kobawila Simon Charles , Youndouka Jean-Mermoz , Basco Leonardo K. , Ringwald Pascal , Briolant Sébastien , Ndounga Mathieu
Published: May 2022

Background

In the Republic of the Congo, malaria represents a major public health problem affecting all age groups. A regular surveillance of the current efficacy of first-line anti-malarial drugs is required in the face of possible emergence and spread of artemisinin-resistant Plasmodium falciparum strains in Africa. The purpose of this study was to determine the prevalence of malaria among febrile patients of all ages and assess the efficacy of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) in Congolese children.

Methods

Febrile patients of all ages were initially screened for malaria by both rapid diagnostic test (RDT) and microscopy. Patients less than 12 years of age, with parasitaemia ≥ 1000 asexual parasites of P. falciparum/µL of blood, without any signs of severity, were enrolled in a therapeutic efficacy study and treated after obtaining their parents' (or legal guardian’s) informed consent in two health centres in Dolisie. The patients were followed for 28 days in accordance with the 2009 World Health Organization standard protocol. If parasitaemia reappeared on or after day 7, the genetic profiles (genes expressing merozoite surface protein-1 [msp1], merozoite surface protein-2 [msp2], and glutamine-rich protein [glurp]) of pre-treatment and post-treatment isolates were compared by nested polymerase chain reaction (PCR) followed by capillary electrophoresis to make a distinction between recrudescence and re-infection. The clinical and parasitological outcome was analysed by the per-protocol method and Kaplan–Meier survival curves.

Results

A total of 994 febrile patients of all ages were screened by RDT and microscopy. Of 994 patients, 323 (32.5%) presented a positive RDT, and 266 (26.8%) were microscopy-positive. Based on microscopy as the reference diagnostic method, the sensitivity and the specificity of the RDT were 98.9 and 91.8%, respectively. The Cohen’s kappa coefficient was 0.86. A total of 121 children aged less than 12 years (61 in AL treatment group and 60 in ASAQ treatment group) were included in therapeutic efficacy study. Before PCR correction, the proportions of adequate clinical and parasitological response were 96.6% for AL and 86.0% for ASAQ in the per-protocol population (P < 0.05). The PCR-corrected efficacy rates were 98.2% and 94.2% for AL and ASAQ, respectively (P > 0.05). Both treatments were well tolerated.

Conclusions

AL and ASAQ remain highly effective for the first-line treatment of uncomplicated P. falciparum malaria in Dolisie. Despite high efficacy of first- and second-line treatment, there is a continuing need to scale up effective malaria preventive interventions and vector control strategies in the country.

Trial Registration Number: ACTRN12616001422415.
A community-led mobile health clinic to improve structural and social determinants of health among (im)migrant workers
Authors: Guillot-Wright Shannon , Farr N. Miles , Cherryhomes Ellie
Published: May 2022

Background

Community-led interventions that address structural and social determinants of health are lacking among (im)migrant workers, especially seafood workers. This lack of medical attention is especially alarming given their high rate of injury and death.

Methods

Community-based participatory research (CBPR), a relational model that values the participants as equal partners in research, dissemination, and implementation, guided the interviews and mobile clinic. Seafood workers were engaged throughout data collection, analysis, and interpretation and played a significant role in moving the findings from research into actionable change.

Results

To address the lack of healthcare options for (im)migrants, and at the request of the seafood workers participating in the ongoing CBPR study, we successfully implemented and treated workers in our mobile clinic.

Discussion

Many of these individuals had not been seen by a healthcare provider in years, highlighting the importance of community trust and rapport building when addressing interconnected health and safety issues.

Conclusions

Although CBPR and free (mobile) health clinics are in and of themselves not novel concepts, when applied to high-risk occupational settings with under-reached populations (e.g., (im)migrant workers), they have the ability to improve health and prevent injury. This intervention adds to the growing literature detailing the potential benefits of using CBPR, and meeting people where they are, especially with historically marginalized populations.
Extracellular vesicle-mediated crosstalk between pancreatic cancer and stromal cells in the tumor microenvironment
Authors: Li Ying , Zhao Wenjing , Wang Yanli , Wang Haiyan , Liu Shanglong
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) interacts closely with the tumor microenvironment (TME). The TME is remodeled by crosstalk between pancreatic cancer cells and stromal cells, and is critical for cancer progression. Extracellular vesicles (EVs), including exosomes and microvesicles, help facilitate an exchange of information both within the TME and to distant organs. EVs have also been identified as potential diagnostic biomarkers, therapeutic targets, and drug carriers for pancreatic cancer treatment. Thus, understanding the selective packaging of EVs cargo and its mechanistic impact will increase our understanding of cancer biology. In this review, we collect and analyze recent findings of the pancreatic cancer-stromal cell interactions mediated by EVs and the mechanisms involved in cancer-related immunity and chemoresistance. These studies demonstrate the vital role of EVs in pancreatic cancer reprogramming and TME remodeling. We also summarize the EVs identified as potential PDAC diagnostic biomarkers and possible therapeutic targets. This greater understanding is a promising avenue for transitioning EVs from bench to bedside.

Graphical Abstract
Severe bacterial infections in people who inject drugs: the role of injection-related tissue damage
Authors: Hrycko Alexander , Mateu-Gelabert Pedro , Ciervo Courtney , Linn-Walton Rebecca , Eckhardt Benjamin
Published: May 2022

Background

In the context of the current U.S. injection drug use epidemic, targeted public health harm reduction strategies have traditionally focused on overdose prevention and reducing transmission of blood-borne viral infections. Severe bacterial infections (SBI) associated with intravenous drug use have been increasing in frequency in the U.S. over the last decade. This qualitative study aims to identify the risk factors associated with SBI in hospitalized individuals with recent injection drug use.

Methods

Qualitative analysis (n = 15) was performed using an in-depth, semi-structured interview of participants admitted to Bellevue Hospital, NYC, with SBI and recent history of injection drug use. Participants were identified through a referral from either the Infectious Diseases or Addition Medicine consultative services. Interviews were transcribed, descriptively coded, and analyzed for key themes.

Results

Participants reported a basic understanding of prevention of blood-borne viral transmission but limited understanding of SBI risk. Participants described engagement in high risk injection behaviors prior to hospitalization with SBI. These practices included polysubstance use, repetitive tissue damage, nonsterile drug diluting water and multipurpose use of water container, lack of hand and skin hygiene, re-use of injection equipment, network sharing, and structural factors leading to an unstable drug injection environment. Qualitative analysis led to the proposal of an Ecosocial understanding of SBI risk, detailing the multi-level interplay between individuals and their social and physical environments in producing risk for negative health outcomes.

Conclusions

Structural factors and injection drug use networks directly impact drug use, injection drug use practices, and harm reduction knowledge, ultimately resulting in tissue damage and inoculation of bacteria into the host and subsequent development of SBI. Effective healthcare and community prevention efforts targeted toward reducing risk of bacterial infections could prevent long-term hospitalizations, decrease health care expenditures, and reduce morbidity and mortality.
Successes and challenges of health systems governance towards universal health coverage and global health security: a narrative review and synthesis of the literature
Authors: Debie Ayal , Khatri Resham B. , Assefa Yibeltal
Published: May 2022

Background

The shift in the global burden of disease from communicable to noncommunicable was a factor in mobilizing support for a broader post-Millennium Development Goals (MDGs) health agenda. To curb these and other global health problems, 193 Member States of the United Nations (UN) became signatories of the Sustainable Development Goals (SDGs) and committed to achieving universal health coverage (UHC) by 2030. In the context of the coronavirus disease 2019 (COVID-19) pandemic, the importance of health systems governance (HSG) is felt now more than ever for addressing the pandemic and continuing to provide essential health services. However, little is known about the successes and challenges of HSG with respect to UHC and health security. This study, therefore, aims to synthesize the evidence and identify successes and challenges of HSG towards UHC and health security.

Methods

We conducted a structured narrative review of studies published through 28 July 2021. We searched the existing literature using three databases: PubMed, Scopus and Web of Science. Search terms included three themes: HSG, UHC and health security. We synthesized the findings using the five core functions of HSG: policy formulation and strategic plans; intelligence; regulation; collaboration and coalition; and accountability.

Results

A total of 58 articles were included in the final review. We identified that context-specific health policy and health financing modalities helped to speed up the progress towards UHC and health security. Robust health intelligence, intersectoral collaboration and coalition were also essential to combat the pandemic and ensure the delivery of essential health services. On the contrary, execution of a one-size-fits-all HSG approach, lack of healthcare funding, corruption, inadequate health workforce, and weak regulatory and health government policies were major challenges to achieving UHC and health security.

Conclusions

Countries, individually and collectively, need strong HSG to speed up the progress towards UHC and health security. Decentralization of health services to grass root levels, support of stakeholders, fair contribution and distribution of resources are essential to support the implementation of programmes towards UHC and health security. It is also vital to ensure independent regulatory accreditation of organizations in the health system and to integrate quality- and equity-related health service indicators into the national social protection monitoring and evaluation system; these will speed up the progress towards UHC and health security.
Family planning knowledge, attitude and practice among Rohingya women living in refugee camps in Bangladesh: a cross-sectional study
Authors: Abul Kalam Azad Md. , Zakaria Muhammad , Nachrin Tania , Chandra Das Madhab , Cheng Feng , Xu Junfang
Published: May 2022

Background

Considering the high risk of maternal morbidity and mortality, increased risks of unintended pregnancy, and the unmet need for contraceptives prevalent among the Rohingya refugees, this study aims to explore the knowledge, attitude, and practice (KAP) of family planning (FP) and associated factors among Rohingya women living in refugee camps in Bangladesh.

Methods

Four hundred Rohingya women were interviewed. Data were collected using a structured and pretested questionnaire, which included study participants’ socio-demographic characteristics, access to FP services, knowledge, attitude, and practice of FP. Linear regression analysis was performed to identify the influencing factors of FP-KAP.

Results

Of the 400 Rohingya refugee women, 60% were unaware that there was no physical harm brought by using a permanent method of birth control. Half of the women lack proper knowledge regarding whether a girl was eligible for marriage before the age of 18. More than two-thirds of the women thought family planning methods should not be used without the husband’s permission. Moreover, 40% were ashamed and afraid to discuss family planning matters with their husbands. Of the study participants, 58% had the opinion that a couple should continue bearing children until a son is born. Linear regression analyses found that study participants’ who have a profession, have less children, whose primary source of FP knowledge was through a physician/nurse, have had FP interventions in the camp, and talk with a health care provider on FP were found to have better FP-KAP.

Conclusion

The study showed that Rohingya refugee women are a marginalized population in terms of family planning and their comprehensive FP-KAP capability was low. Contraceptives among the Rohingyas were unpopular, mainly due to a lack of educational qualifications and family planning awareness. In addition, family planning initiatives among Rohingya refugees were limited by a conservative culture and religious beliefs. Therefore, strengthening FP interventions and increasing the accessibility to essential health services and education are indispensable to improving improve maternal health among Rohingya refugees.
Effects of the pandemic on women’s reproductive health protective attitudes: a Turkish sample
Authors: Kaya Senol Derya , Polat Filiz
Published: May 2022

Objectives

This descriptive, cross-sectional study was performed to examine the effects of the COVID-19 pandemic on women’s reproductive health protective attitudes.

Methods

The study sample included 306 women and data were collected through a web-based, online questionnaire. The data were collected using the Personal Information Form, Determination of Married Women’s Reproductive Health Protective Attitudes Scale. Descriptive statistics, independent samples t-test, ANOVA test were used to assess the data.

Results

The mean scores for Determination of Married Women's Reproductive Health Protective Attitudes Scale significantly differed in terms of education, employment status, income, health insurance and perceived health status (p < 0.05). A total of 69.3% of women had their first pregnancy at the agerange of 21–34 years, 17.6% of the women had four or more pregnancies, 55.6% of the women gave birth 1–3 times, 13.4% of the women gave birth at home and 57.8% of the women did not use modern family planning methods. A total of 23.2% of women experienced a problem with their reproductive organs during the pandemic, 70.6% of them did not present to a health center for their problems and 74.5% of these women did not present to a health center to avoid the risk of COVID-19 transmission. A total of 40.2% of women used the methods they already know at home to relieve their problems and 16.0% of the women used them edications previously prescribed by their doctors.

Conclusion

The pandemic negatively affects there productive health of women. In the COVID-19 pandemic, health policies should be planned in accordance with the continuation of reproductive health and sexual health services.
Transcriptomic profiling of Trypanosoma congolense mouthpart parasites from naturally infected flies
Authors: Silva Pereira Sara , Mathenge Kawira , Masiga Daniel , Jackson Andrew
Published: May 2022

Background

Animal African trypanosomiasis, or nagana, is a veterinary disease caused by African trypanosomes transmitted by tsetse flies. In Africa, Trypanosoma congolense is one of the most pathogenic and prevalent causes of nagana in livestock, resulting in high animal morbidity and mortality and extensive production losses. In the tsetse fly, parasites colonise the midgut and eventually reach the mouthparts, from where they can be transmitted as the fly feeds on vertebrate hosts such as cattle. Despite the extreme importance of mouthpart-form parasites for disease transmission, very few global expression profile studies have been conducted in these parasite forms.

Methods

Here, we collected tsetse flies from the Shimba Hills National Reserve, a wildlife area in southeast Kenya, diagnosed T. congolense infections, and sequenced the transcriptomes of the T. congolense parasites colonising the mouthparts of the flies.

Results

We found little correlation between mouthpart parasites from natural and experimental fly infections. Furthermore, we performed differential gene expression analysis between mouthpart and bloodstream parasite forms and identified several surface-expressed genes and 152 novel hypothetical proteins differentially expressed in mouthpart parasites. Finally, we profiled variant antigen expression and observed that a variant surface glycoprotein (VSG) transcript belonging to T. congolense phylotype 8 (i.e. TcIL3000.A.H_000381200), previously observed to be enriched in metacyclic transcriptomes, was present in all wild-caught mouthpart samples as well as bloodstream-form parasites, suggestive of constitutive expression.

Conclusion

Our study provides transcriptomes of trypanosome parasites from naturally infected tsetse flies and suggests that a phylotype 8 VSG gene is constitutively expressed in metacyclic- and bloodstream-form parasites at the population level.

Graphical Abstract
Acquired hemophilia A in the setting of dual anticoagulation therapy and lupus anticoagulant: a case report
Authors: Chen Victor , Roby Lauren C. , Wentzel Stephanie , Li Mingjia , Jones Nicholas
Published: May 2022

Background

Acquired hemophilia A is a disorder caused by autoantibodies against coagulation factor VIII that may present with severe bleeding. We report a rare case of acquired hemophilia A presenting with coexisting lupus anticoagulant.

Case presentation

An 81-year-old Caucasian female presented with large ecchymoses over the torso and extremities in the setting of an enoxaparin bridge to warfarin. Anticoagulation was held, but she continued to develop bruises with significant anemia and prolonged coagulation studies that failed to correct with mixing. Workup revealed factor VIII activity < 1% and a positive lupus anticoagulant. Initial testing for a factor VIII inhibitor was confounded by the presence of lupus anticoagulant, requiring a chromogenic Bethesda assay to confirm the presence of the inhibitor, establishing the diagnosis of acquired hemophilia A. The patient was initially treated with oral prednisone 80 mg daily and factor VIII inhibitor bypassing activity 25 units/kg twice daily before transitioning to susoctocog alfa 50 units/kg twice daily after placement of a tunneled line for outpatient rituximab infusions. On discharge, the patient’s ecchymoses were resolving and factor VIII levels improved. Following completion of rituximab therapy, the patient’s factor VIII activity normalized and factor VIII inhibitor was suppressed.

Conclusions

Diagnosis of acquired hemophilia A can be confounded by other causes of abnormal coagulation studies and may require specialized testing, such as a chromogenic Bethesda assay, to confirm the presence of a factor VIII inhibitor.
Rethinking mental wellness among adolescents: an integrative review protocol of mental health components
Authors: Orth Zaida , van Wyk Brian
Published: May 2022

Background

Adolescents have been overlooked in global public health initiatives as this period is generally considered to be the healthiest in an individual’s life course. However, the growth of the global adolescent population and their changing health profiles have called attention to the diverse health needs of adolescents. The increased attention toward adolescent health has accentuated existing gaps as global health reports have emphasised that there is a continued need for valid and reliable health data. In this context, evidence has shown that mental health issues constitute one of the greatest burdens of disease for adolescents. This integrative review aims to unpack the meaning of mental wellness among adolescents and its associated constructs by analysing and synthesising empirical and theoretical research on adolescent mental wellness. In doing this, we will develop a working definition of adolescent mental wellness that can be used to develop an instrument aimed at measuring adolescent mental wellness.

Methods

The integrative review is guided by the five steps described by Whittemore and Knafl. A comprehensive search strategy which will include carefully selected terms that correspond to the domains of interest (positive mental health/mental wellness) will be used to search for relevant literature on electronic databases, grey literature and government or non-governmental organisations (NGO) websites. Studies will be included if they describe and/or define general mental wellness in adolescent populations aged 10–19. The screening and reporting of the review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from the integrative review will be analysed using narrative framework synthesis for qualitative and quantitative studies.

Discussion

This integrative review aims to search for and synthesise current research regarding adolescent mental wellness to identify how wellness is being described and conceptualised. We aim to identify gaps and to contribute to a more comprehensive definition of mental wellness which can aid in the development of an age- and culturally appropriate measure of adolescent mental wellness.
Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations
Authors: Rodriguez-Porcel Federico , Wyman-Chick Kathryn A. , Abdelnour Ruiz Carla , Toledo Jon B. , Ferreira Daniel , Urwyler Prabitha , Weil Rimona S. , Kane Joseph , Pilotto Andrea , Rongve Arvid , Boeve Bradley , Taylor John-Paul , McKeith Ian , Aarsland Dag , Lewis Simon J. G. ,   the Lewy Body Dementias Clinical Trials Workgroup from the Lewy Body Dementias Professional Interest Area - Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART)+
Published: May 2022

The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.
Coronavirus stress and overeating: the role of anxiety and COVID-19 burnout
Authors: Wang Ruining , Ye Baojuan , Wang Peiyi , Tang Chunyan , Yang Qiang
Published: May 2022

Background

This study examined the role of anxiety and coronavirus disease 2019 (COVID-19) burnout in the relationship between coronavirus stress and overeating among Chinese college students during the COVID-19 pandemic.

Methods

Chinese college students (N = 2926;Mage = 19.90,SD = 1.47, range = 18–25 years old; 54.34% female) completed self-reported online questionnaires regarding coronavirus stress, anxiety, COVID-19 burnout, and overeating.

Results

Anxiety showed partially indirect effect on the association between coronavirus stress and overeating. COVID-19 burnout exacerbated the indirect pathway between coronavirus stress and overeating via anxiety.

Discussion and conclusion

This is the first study, to our knowledge, that examines the underlying mechanisms of the coronavirus stress and overeating behavior association among Chinese college students. The results support several existing theories on stress and problematic eating behaviors and provide practical implications for prevention and intervention programs of overeating during the COVID-19 pandemic.
KetoCycle mobile app for ketogenic diet: a retrospective study of weight loss and engagement
Authors: Valinskas Sarunas , Aleknavicius Kasparas , Jonusas Justinas
Published: May 2022

Background

The ketogenic diet is one of the oldest diets that has been used for more than a centennial in the clinical setting, and it is gaining popularity as a measure to fight obesity, which is a major predisposing factor for many diseases to manifest, including diabetes mellitus, chronic heart disease, cancer, and others. Thus, we designed this retrospective investigation to determine if users of the mobile application KetoCycle achieved statistically significant weight loss outcomes.

Methods

The initial study cohort comprised 12,965 consecutive users who started using KetoCycle between January 2020 and December 2020. The final cohort comprised 10,269 users. The main parameters obtained from the database containing all self-reported data were gender, number of active days (AD), total time of use (TT), height, initial weight, and last recorded weight. The primary outcome of the study was weight loss. Statistical analyses were performed using IBM SPSS Statistics, version 26 (IBM Corp., Armonk, NY, USA). In addition, a standard multiple regression model was created to predict weight loss from significant actions.

Results

A retrospective analysis of KetoCycle user data showed that 87.3% of KetoCycle users lost some of their initial weight. Of those, 1645 users (18.3%) lost more than 10% of their initial body weight, 3528 (39.3%) users lost between 5 and 10% of their initial body weight, and 3796 (42.3%) users lost less than 5% of their body weight. When user activity was taken into account, it was found that active users lost statistically significantly more weight than non-active users (p < 0.05). App engagement was also associated with losing > 5% of initial weight. Using water tracking, weight tracking, and creation of a meals list within KetoCycle statistically significantly predicted weight loss in a multiple regression model.

Conclusions

We concluded that KetoCycle appeared as a promising mobile application suited for weight loss and weight control.

Trial registration

This retrospective chart review study was approved by BRANY IRB in January 2022 (registration ID.: 21-08-564-939).
Unfolding the learning behaviour patterns of MOOC learners with different levels of achievement
Authors: Li Shuang , Du Junlei , Sun Jingqi
Published: May 2022

In an open and flexible context of Massive Open Online Courses (MOOCs), learners who take final assessments exhibit the motivation for performance goals. The learning trajectories of this group usually provide more clues for course design and teaching improvement in that this group tend to interact more fully with course learning activities and resources for better learning outcomes. This study focused on such learners to investigate their learning engagement, time organization, content visit sequences, and activity participation patterns by applying statistical analysis, lag sequence analysis, and other data mining methods. This study examined the data of 535 learners taking the assessment in a MOOC to detect the differences in learning engagement and the above learning patterns amongst three groups of learners with different achievement levels, labeled failed, satisfactory and excellent. We found differences in both learning engagement and learning patterns among the three groups. The results indicated that for the learners to be successful, they require a certain degree of task completion as a basic guarantee for passing the course, effective session workload organization, reasonable learning content arrangement, and more cognitive engagement (rather than investing more time and energy). Based on the outcomes, implications for personalized instructional design and intervention to promote academic achievement in MOOCs are discussed.
Isolated CNS relapse of medullary aggressive high-grade B-cell lymphoma on 18F-FDG-PET/CT
Authors: Lambe Gerard , Doran Simon , Clifford Ruth , Nasoodi Afshin
Published: May 2022

This is a case of high-risk, aggressive, high-grade medullary B-cell lymphoma presenting with new onset of neurological dysfunction following initial complete response to the standard chemoimmunotherapy. A whole-body re-staging PET using fluorodeoxyglucose (18F-FDG) integrated with computed tomography (18FDG-PET/CT) performed with clinical suspicion of arachnoiditis, eloquently demonstrated unequivocal multifocal FDG uptake by the spinal cord without evidence of systemic recurrence, leading to a clinical diagnosis of secondary CNS lymphoma, which is a rare complication of DLBCL with ominous prognosis. Four cycles of Modified-MATRIX protocol resulted in a halt in fulminant course of the disease and the patient experienced slight reversal of the neurological deficits, although not deemed clinically fit for a repeat 18FDG-PET/CT due to his poor general well-being. Repeat MRI was suggestive of partial recovery, however. The clinical stability was proven short-lived, and the patient experienced progressive lower limb weakness only 3 weeks after discharge following his last cycle of treatment. Isolated CNS relapse of lymphoma is a rare occurrence in the literature. The CNS recurrence is more often leptomeningeal or confined to the brain parenchyma rather than the spinal cord. The role of 18FDG-PET/CT in the diagnostic algorithm of secondary CNS lymphoma is unclear and its significance in risk stratification and assessing the response to treatment has not been evaluated. This case report illustrates the imaging findings of a more unusual form of the disease with multifocal intramedullary involvement of the spinal cord, and highlights imaging features of this rare condition with 18FDG-PET/CT and MRI to support decision making in good clinical practice.
Validity and reliability of the Persian version of illness invalidation inventory (3*I) among patients with non-inflammatory rheumatic painful disorders
Authors: Ghavidel-Parsa Banafsheh , Khosousi Mohammad-Javad , Tohidi Sepehr , Bidari Ali , Soltani Saman , Zayeni Habib , Montazeri Ali
Published: May 2022

Background

The Invalidation Illness Inventory (3*I) is an instrument that assesses invalidation (including discounting and lack of understanding dimensions) experienced by patients with rheumatic disorders. This study aimed to translate and validate the 3*I in Iran.

Methods

Following translation of the 3*I into the Iranian language (Persian), a cross-sectional study was conducted. A consecutive sample of females with chronic non-inflammatory rheumatic painful diseases completed the questionnaire. Patients also completed the Revised Symptom Impact Questionnaire (SIQR) and the Short Form Health Survey-12 (SF-12). To examine convergent validity, the correlation between the 3*I, the SIQR, and the SF-12 was assessed. The reliability of the 3*I was examined by internal consistency (the Cronbach's alpha coefficient) and intraclass correlation coefficient (ICC).

Results

In all 196 patients participated in the study. The mean (SD) age of patients was 45.62 ± 10.70 years. Several significant correlations between the Invalidation Illness Inventory (discounting/lack of understanding) with the symptom impact (SIQR) and the short form health survey (SF-12) were observed lending support to the convergent validity of the 3*I. The Cronbach’s alpha coefficients were acceptable for most dimensions and sources, ranging from 0.52 to 0.88. Most ICC values for the dimensions of 3*I were above 0.75.

Conclusions

The findings indicated that the Persian version of Illness Invalidation Inventory (3*I) is a valid instrument for invalidation assessment in patients with chronic pain. Given the high frequency of perceived invalidation among patients with rheumatic painful disorders, serious attention is needed to the issue in clinical and research settings.
Impact of the fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), invasion on maize and the native Spodoptera litura (Fabricius) in East Java, Indonesia, and evaluation of the virulence of some indigenous entomopathogenic fungus isolates for controlling the pest
Authors: Afandhi Aminudin , Fernando Ito , Widjayanti Tita , Maulidi Agrintya Kurnia , Radifan Hirzi Ilman , Setiawan Yogo
Published: May 2022

Background

The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is an invasive alien species in Indonesia. This study aimed to assess the impact of its invasion in Indonesia by measuring the damaged area caused by the pest in maize fields located across East Java and simultaneously determine whether S. frugiperda outcompetes the native Asian armyworm Spodoptera litura (Fabricius). Secondly, the virulence of 14 entomopathogenic fungus (EPF) isolates against S. frugiperda larvae was evaluated in an effort to find effective biocontrol agent candidates.

Results

The damaged area caused by S. frugiperda was generally higher than that caused by S. litura during the survey period from August 2019 to December 2021. It indicated that S. frugiperda may have dominated the native armyworm and become the primary key pest of maize in Indonesia. Based on a single-concentration assay (106 conidia ml−1), the tested EPF isolates displayed varying degrees of virulence against S. frugiperda larvae, causing larval mortality of 3.5 to 71% at 10-day post-treatment, with the highest mortality rates provided by Beauveria bassiana sensu lato and Trichoderma asperellum sensu lato. At a concentration of 108 conidia ml−1, B. bassiana s.l. and T. asperellum s.l. elicited high larval mortality of 76 and 81%, respectively, at 10-day post-treatment. Nevertheless, the probit analysis based on a concentration–response assay revealed that T. asperellum s.l. had lower LC50 and LC90 values than B. bassiana s.l.

Conclusions

The attack and invasion of S. frugiperda seem to be a continual threat to the maize agro-ecosystem in Indonesia. As a consequence, Indonesia should mitigate and be well-prepared for future outbreaks of S. frugiperda. Indigenous EPF isolates used in this study may act as promising biocontrol agents of S. frugiperda, especially T. asperellum s.l. This study also serves as the first report documenting the direct lethality of Trichoderma fungus on S. frugiperda larvae.