bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sero-prevalence of malaria and the knowledge, attitudes and practices relating to the prevention of malaria among indigenous people living in the central forest spine in Peninsular Malaysia: a mixed-methods study
Authors: Kader Maideen Siti Fatimah , Rashid Abdul , Ahmad Nur Indah , Zahari Siti Nur Afiqah , Hamat Rukman Awang 
Published: October 2022

Abstract
Background
Malaria is still a major public health threat in some parts of the world. Many countries are targeting to achieve malaria free status country. This study aimed to determine the sero-prevalence of malaria and the knowledge, attitudes and practices relating to the prevention of malaria among the indigenous adults living in the central forest spine in Peninsular Malaysia.

Methods
A mixed method study was conducted in indigenous settlements in 2020. Blood film for malaria parasite (BFMP) was used to diagnose malaria in this study. A structured questionnaire was used to collect data from the participants. For the qualitative data, in-depth interviews were conducted and data was collected until data saturation was reached. Multiple linear regression was used to determine the predictors after adjusting for confounders. A p-value of < 0.05 is considered as statistically significant. Meaningful statements from the in-depth interviews were assigned to the relevant codes using NVivo version 12 software.

Results
A total of 284 indigenous people participated in the study. The prevalence of malaria in this study was 0%. Those in the middle age group between 25 and 41 years and tested positive for malaria previously were significantly more likely to have better knowledge and attitude scores. Significant correlations were also observed between knowledge-attitude and knowledge-practice. For the qualitative results, most of the respondents were unsure of monkey malaria, but all were aware of human malaria.

Conclusion
The present study highlighted the absence of malaria in the study population and relatively good knowledge, attitudes and practices relating to the prevention of malaria.
Cooking or heating with solid fuels increased the all-cause mortality risk among mid-aged and elderly People in China
Authors: Yang Yuxiang , Liu Yang , Peng Luolan , Zhang Shuai , Yuan Changzheng , Li Wenyuan , Liu Zuyun , Ma Yanan 
Published: October 2022

Abstract
Background
Our study aimed to explore the associations between solid fuels burning for either heating or cooking and all-cause mortality based on 2859 participants from the China Health and Retirement Longitudinal Study during 2011–2018.

Methods
Logistic regression models were performed to estimate the risk for all-cause mortality between different types of fuels in the current longitudinal study. Furthermore, the combined impacts of applying solid fuels for both cooking and heating and the effect among those who switched types of fuels in cooking or heating during follow-up were also analyzed. Interaction and stratification analysis by covariables was applied further to explore the relationship between fuel burning and all-cause mortality.

Results
After full-adjustment, usage of solid fuels was associated with higher all-cause mortality (for heating: OR = 1.93, 95% CI = 1.25, 3.00; for cooking: OR = 1.76, 95% CI = 1.10, 2.82). Using solid fuels for both cooking and heating (OR = 2.36; 95% CI, 1.38, 4.03) was associated with a higher risk of all-cause mortality, while using solid fuels with a single purpose was not (OR = 1.52; 95% CI, 0.90, 2.55). Protective tendencies were detected in switching solid to clean fuel for cooking (OR = 0.62; 95% CI, 0.32, 1.17) and heating (OR = 0.62; 95% CI, 0.35, 1.10).

Conclusion
Either cooking or heating with solid fuels increases the risk of all-cause mortality among Chinese mid-aged and aging people in the urban area of China.
Evidence of transgenerational effects on autism spectrum disorder using multigenerational space-time cluster detection
Authors: Richards Steed Rebecca , Bakian Amanda V. , Smith Ken Robert , Wan Neng , Brewer Simon , Medina Richard , VanDerslice James 
Published: October 2022

AbstractBackgroundTransgenerational epigenetic risks associated with complex health outcomes, such as autism spectrum disorder (ASD), have attracted increasing attention. Transgenerational environmental risk exposures with potential for epigenetic effects can be effectively identified using space-time clustering. Specifically applied to ancestors of individuals with disease outcomes, space-time clustering characterized for vulnerable developmental stages of growth can provide a measure of relative risk for disease outcomes in descendants.Objectives(1) Identify space-time clusters of ancestors with a descendent with a clinical ASD diagnosis and matched controls. (2) Identify developmental windows of ancestors with the highest relative risk for ASD in descendants. (3) Identify how the relative risk may vary through the maternal or paternal line.MethodsFamily pedigrees linked to residential locations of ASD cases in Utah have been used to identify space-time clusters of ancestors. Control family pedigrees of none-cases based on age and sex have been matched to cases 2:1. The data have been categorized by maternal or paternal lineage at birth, childhood, and adolescence. A total of 3957 children, both parents, and maternal and paternal grandparents were identified. Bernoulli space-time binomial relative risk (RR) scan statistic was used to identify clusters. Monte Carlo simulation was used for statistical significance testing.ResultsTwenty statistically significant clusters were identified. Thirteen increased RR (> 1.0) space-time clusters were identified from the maternal and paternal lines at a p-value < 0.05. The paternal grandparents carry the greatest RR (2.86–2.96) during birth and childhood in the 1950’s–1960, which represent the smallest size clusters, and occur in urban areas. Additionally, seven statistically significant clusters with RR < 1 were relatively large in area, covering more rural areas of the state.ConclusionThis study has identified statistically significant space-time clusters during critical developmental windows that are associated with ASD risk in descendants. The geographic space and time clusters family pedigrees with over 3 + generations, which we refer to as a person’sgeographic legacy, is a powerful tool for studying transgenerational effects that may be epigenetic in nature. Our novel use of space-time clustering can be applied to any disease where family pedigree data is available.
CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment
Authors: Pan Zongfu , Xu Tong , Bao Lisha , Hu Xiaoping , Jin Tiefeng , Chen Jinming , Chen Jianqiang , Qian Yangyang , Lu Xixuan , li Lu , Zheng Guowan , Zhang Yiwen , Zou Xiaozhou , Song Feifeng , Zheng Chuanming , Jiang Liehao , Wang Jiafeng , Tan Zhuo , Huang Ping , Ge Minghua 
Published: October 2022

AbstractAnaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC.Graphical Abstract
Spontaneous rectus sheath hematoma associated with apixaban in an elderly gentleman with chronic obstructive airway disease – a case report
Authors: Wong Cheuk-Lik , So Clarence Hao-Yu 
Published: October 2022

Abstract
Background
Rectus sheath hematoma (RSH) is a relatively uncommon cause of acute abdominal pain and can be mistaken as other surgical causes of acute abdomen. A diagnosis requires high index of suspicion especially in susceptible patients, for example, in patients on anticoagulation. While anticoagulation is the commonest risk factor for RSH, direct-acting oral anticoagulants have only been very recently implicated as a potential cause with fewer than ten cases reported in the literature.
Case presentation.
An 82-year-old Chinese man with chronic obstructive airway disease, ischemic heart disease, heart failure and atrial fibrillation on apixaban presenting with acute onset of lower abdominal pain. Physical examination showed peritoneal signs with tenderness and guarding over the lower quadrants with hypotension. Computed tomography (CT) of the abdomen confirmed a large rectus sheath hematoma (RSH) without active extravasation. He was given fluid resuscitation and was managed successfully with supportive treatment and cessation of apixaban. A follow-up CT two months later showed resolving hematoma and aspirin was resumed primarily for ischemic heart disease. The patient tolerated anti-platelet therapy without recurrence of RSH. The risk factors, treatment options, prognosis and issue related to anticoagulation resumption after an episode of RSH are discussed. Reported cases of RSH associated with direct-acting oral anticoagulants are reviewed.

Conclusions
Direct-acting oral anticoagulant-associated rectus sheath hematoma is rare. With increasing use of direct-acting oral anticoagulants in multiple clinical settings, clinicians should remain vigilant of this potentially life-threatening bleeding complication when a patient presents with acute abdominal pain. Conservative treatment with cessation of anti-coagulant and supportive transfusion remains the mainstay of treatment.
Incidence and severity prediction score of COVID-19 in people living with HIV (SCOVHIV): experience from the first and second waves of the pandemic in Indonesia
Authors: Yunihastuti Evy , Karjadi Teguh Harjono , Widhani Alvina , Mahdi Haridana Indah Setiawati , Sundari Salma , Hapsari Aljira Fitya , Koesnoe Sukamto , Djauzi Samsuridjal 
Published: October 2022

Abstract
Background
People living with HIV (PLHIV) have higher risk of COVID-19 infection and mortality due to COVID-19. Health professionals should be able to assess PLHIV who are more likely to develop severe COVID-19 and provide appropriate medical treatment. This study aimed to assess clinical factors associated with COVID-19 severity and developed a scoring system to predict severe COVID-19 infection among PLHIV.

Methods
This retrospective cohort study evaluated PLHIV at four hospitals diagnosed with COVID-19 during the first and second wave COVID-19 pandemic in Indonesia. The independent risk factors related to the severity of COVID-19 were identified with multivariate logistic regression.

Results
342 PLHIV were diagnosed with COVID-19, including 23 with severe-critical diseases. The cumulative incidence up to December 2021 was 0.083 (95% CI 0.074–0.092). Twenty-three patients developed severe-critical COVID-19, and the mortality rate was 3.2% (95% CI 1.61%–5.76%). Having any comorbidity, CD4 count of < 200 cells/mm3, not being on ART, and active opportunistic infection were independent risk factors for developing severe COVID-19. SCOVHIV score was formulated to predict severity, with 1 point for each item. A minimum score of 3 indicated a 58.4% probability of progressing to severe COVID-19. This scoring system had a good discrimination ability with the area under the curve (AUC) of 0.856 (95% CI 0.775–0.936).

Conclusion
SCOVHIV score, a four-point scoring system, had good accuracy in predicting COVID-19 severity in PLHIV.
VHHs as tools for therapeutic protein delivery to the central nervous system
Authors: Wouters Yessica , Jaspers Tom , Rué Laura , Serneels Lutgarde , De Strooper Bart , Dewilde Maarten 
Published: October 2022

Abstract
Background
The blood brain barrier (BBB) limits the therapeutic perspective for central nervous system (CNS) disorders. Previously we found an anti-mouse transferrin receptor (TfR) VHH (Nb62) that was able to deliver a biologically active neuropeptide into the CNS in mice. Here, we aimed to test its potential to shuttle a therapeutic relevant cargo. Since this VHH could not recognize the human TfR and hence its translational potential is limited, we also aimed to find and validate an anti-human transferrin VHH to deliver a therapeutic cargo into the CNS.

Methods
Alpaca immunizations with human TfR, and subsequent phage selection and screening for human TfR binding VHHs was performed to find a human TfR specific VHH (Nb188). Its ability to cross the BBB was determined by fusing it to neurotensin, a neuropeptide that reduces body temperature when present in the CNS but is not able to cross the BBB on its own. Next, the anti–β-secretase 1 (BACE1) 1A11 Fab and Nb62 or Nb188 were fused to an Fc domain to generate heterodimeric antibodies (1A11AM-Nb62 and 1A11AM-Nb188). These were then administered intravenously in wild-type mice and in mice in which the murine apical domain of the TfR was replaced by the human apical domain (hAPI KI). Pharmacokinetic and pharmacodynamic (PK/PD) studies were performed to assess the concentration of the heterodimeric antibodies in the brain over time and the ability to inhibit brain-specific BACE1 by analysing the brain levels of Aβ1–40.

Results
Selections and screening of a phage library resulted in the discovery of an anti-human TfR VHH (Nb188). Fusion of Nb188 to neurotensin induced hypothermia after intravenous injections in hAPI KI mice. In addition, systemic administration 1A11AM-Nb62 and 1A11AM-Nb188 fusions were able to reduce Aβ1-40 levels in the brain whereas 1A11AM fused to an irrelevant VHH did not. A PK/PD experiment showed that this effect could last for 3 days.

Conclusion
We have discovered an anti-human TfR specific VHH that is able to reach the CNS when administered systemically. In addition, both the currently discovered anti-human TfR VHH and the previously identified mouse-specific anti-TfR VHH, are both able to shuttle a therapeutically relevant cargo into the CNS. We suggest the mouse-specific VHH as a valuable research tool in mice and the human-specific VHH as a moiety to enhance the delivery efficiency of therapeutics into the CNS in human patients.
One size does not fit all: Participants’ experiences of the selfBACK app to support self-management of low back pain—a qualitative interview study
Authors: Svendsen Malene J. , Nicholl Barbara I. , Mair Frances S. , Wood Karen , Rasmussen Charlotte D. N. , Stochkendahl Mette J. 
Published: October 2022

Abstract
Background
Low back pain (LBP) is one of the most common reasons for disability globally. Digital interventions are a promising means of supporting people to self-manage LBP, but implementation of digital interventions has been suboptimal. An artificial intelligence-driven app, selfBACK, was developed to support self-management of LBP as an adjunct to usual care. To better understand the process of implementation from a participant perspective, we qualitatively explored factors influencing embedding, integrating, and sustaining engagement with the selfBACK app, and the self-perceived effects, acceptability, and satisfaction with the selfBACK app.

Methods
Using a qualitative interview study and an analytic framework approach underpinned by Normalization Process Theory (NPT), we investigated the experiences of patients who participated in the selfBACK randomized controlled trial (RCT). Interviews focused on the motivation to participate in the RCT, experiences of using the selfBACK app, and views about future intended use and potential of using digital health interventions for self-management of LBP. Participants were purposively sampled to represent diversity in age, sex, and implementation reflected by a proxy measure of number of app-generated self-management plans during the first three months of RCT participation.

Results
Twenty-six participants aged 21–78, eleven females and fifteen men, with two to fourteen self-management plans, were interviewed between August 2019 and April 2020. A broad range of factors influencing implementation of selfBACK within all constructs of NPT were identified. Key facilitating factors were preferences and beliefs favoring self-management, a friendly, motivational, and reassuring supporter, tailoring and personalization, convenience and ease of use, trustworthiness, perceiving benefits, and tracking achievements. Key impeding factors were preferences and beliefs not favoring self-management, functionality issues, suboptimal tailoring and personalization, insufficient time or conflicting life circumstances, not perceiving benefits, and insufficient involvement of health care practitioners. Self-perceived effects on pain and health, behavior/attitude, and gaining useful knowledge varied by participant.

Conclusions
The high prevalence of LBP globally coupled with the advantages of providing help through an app offers opportunities to help countless people. A range of factors should be considered to facilitate implementation of self-management of LBP or similar pain conditions using digital health tools.
Non-infectious sternal dehiscence after coronary artery bypass surgery
Authors: Silverborn Martin , Heitmann Leon Arnar , Sveinsdottir Nanna , Rögnvaldsson Sigurjon , Kristjansson Tomas Thor , Gudbjartsson Tomas 
Published: October 2022

Abstract
Introduction
Non-infectious sternal dehiscence (NISD) is a known complication following coronary artery bypass grafting (CABG), with previous studies estimating an incidence of 0.4–1% of surgeries. We aimed to study the incidence of NISD together with short- and long-term outcomes in a whole-nation cohort of patients.

Materials and methods
A retrospective study on consecutive CABG patients diagnosed with NISD at Landspitali from 2001 to 2020. Patients diagnosed with infectious mediastinitis (n = 20) were excluded. NISD patients were compared to patients with an intact sternum regarding patient demographics, cardiovascular risk factors, intra- and postoperative data, and estimated overall survival. The median follow-up was 9.5 years.

Results
Twenty out of 2280 eligible patients (0.88%) developed NISD, and the incidence did not change over the study period (p = 0.98). The median time of diagnosis was 12 days postoperatively (range, 4–240). All patients were re-operated using a Robicsek-rewiring technique, with two cases requiring a titanium plate for fixation. Patients with NISD were older, had a higher BMI and EuroSCORE II, lower LVEF, and more often had a history of COPD, MI, and diabetes compared to those without NISD. Length of stay was extended by 15 days for NISD patients, but short and long-term survival was not statistically different between the groups.

Conclusions
The incidence of NISD was low and in line with previous studies. Although the length of hospital stay was extended, both short- and long-term survival of NISD patients was not significantly different from patients with an intact sternum.
Right ventricular outflow tract Doppler flow analysis and pulmonary arterial coupling by transthoracic echocardiography in sepsis: a retrospective exploratory study
Authors: Bowcock Emma Maria , Gerhardy Benjamin , Huang Stephen , Orde Sam 
Published: October 2022

Abstract
Introduction
Right ventricular (RV) and pulmonary vascular dysfunction appear to be common in sepsis. RV performance is frequently assessed in isolation, yet its close relationship to afterload means combined analysis with right ventricular outflow tract (RVOT) Doppler and RV–pulmonary arterial (RV–PA) coupling may be more informative than standard assessment techniques. Data on feasibility and utility of these parameters in sepsis are lacking and were explored in this study.

Methods
This is a retrospective study over a 3-year period of one-hundred and thirty-one patients admitted to ICU with sepsis who underwent transthoracic echocardiography (TTE) with RVOT pulsed wave Doppler. RVOT Doppler flow and RV–PA coupling was evaluated alongside standard measurements of RV systolic function and pulmonary pressures. RVOT Doppler analysis included assessment of pulmonary artery acceleration time (PAAT), velocity time integral and presence of notching. RV–PA coupling was assessed using tricuspid annular planar systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio.

Results
PAAT was measurable in 106 (81%) patients, and TAPSE/PASP was measurable in 77 (73%). Seventy-three (69%) patients had a PAAT of ≤ 100 ms suggesting raised pulmonary vascular resistance (PVR) is common. RVOT flow notching occurred in 15 (14%) of patients. TRV was unable to be assessed in 24 (23%) patients where measurement of PAAT was possible. RV dysfunction (RVD) was present in 28 (26%), 26 (25%) and 36 (34%) patients if subjective assessment, TAPSE < 17 mm and RV dilatation definitions were used, respectively. There was a trend towards shorter PAAT with increasing severity of RVD. RV–PA uncoupling defined as a TAPSE/PASP < 0.31 mm/mmHg was present in 15 (19%) patients. As RV dilatation increased the RV–PA coupling ratio decreased independent of LV systolic function, whereas TAPSE appeared to be more susceptible to changes in LV systolic function.

Conclusion
Raised PVR and RV–PA uncoupling is seen in a significant proportion of patients with sepsis. Non-invasive assessment with TTE is feasible. The role of these parameters in assisting improved definitions of RVD, as well as their therapeutic and prognostic utility against standard parameters, deserves further investigation.