bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review of Australian initiatives to reduce stigma towards people with complex mental illness: what exists and what works?
Authors: Morgan Amy J. , Wright Judith , Reavley Nicola J. 
Published: January 2021

Abstract
Background
Australian national mental health policy outlines the need for a nationally coordinated strategy to address stigma and discrimination, particularly towards people with complex mental illness that is poorly understood in the community. To inform implementation of this policy, this review aimed to identify and examine the effectiveness of existing Australian programs or initiatives that aim to reduce stigma and discrimination.

Method
Programs were identified via a search of academic databases and grey literature, and an online survey of key stakeholder organisations. Eligible programs aimed to reduce stigma towards people with complex mental illness, defined as schizophrenia, psychosis, personality disorder, or bipolar disorder; or they focused on nonspecific ‘mental illness’ but were conducted in settings relevant to individuals with the above diagnoses, or they included the above diagnoses in program content. Key relevant data from programs identified from the literature search and survey were extracted and synthesized descriptively.

Results
We identified 61 programs or initiatives currently available in Australia. These included face-to-face programs (n = 29), online resources (n = 19), awareness campaigns (n = 8), and advocacy work (n = 5). The primary target audiences for these initiatives were professionals (health or emergency), people with mental illness, family or carers of people with mental illness, and members of the general population. Most commonly, programs tended to focus on stigma towards people with non-specific mental illness rather than on particular diagnostic labels. Evidence for effectiveness was generally lacking. Face-to-face programs were the most well-evaluated, but only two used a randomised controlled trial design.

Conclusions
This study identified areas of strength and weakness in current Australian practice for the reduction of stigma towards people with complex mental illness. Most programs have significant input from people with lived experience, and programs involving education and contact with a person with mental illness are a particular strength. Nevertheless, best-practice programs are not widely implemented, and we identified few programs targeting stigma for people with mental illness and their families, or for culturally and linguistically diverse communities, Aboriginal and Torres Strait Islander communities and LGBTIQ people. These can inform stakeholder consultations on effective options for a national stigma and discrimination reduction strategy.
Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150glued
Authors: Suh Bo Kyoung , Lee Seol-Ae , Park Cana , Suh Yeongjun , Kim Soo Jeong , Woo Youngsik , Nhung Truong Thi My , Lee Su Been , Mun Dong Jin , Goo Bon Seong , Choi Hyun Sun , Kim So Jung , Park Sang Ki 
Published: January 2021

AbstractMitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information. In this study, we present evidence that dystrobrevin-binding protein 1 (dysbindin), a schizophrenia-associated factor, plays a critical role in axonal mitochondrial movement. We observed that mitochondrial movement was impaired in dysbindin knockout mouse neurons. Reduced mitochondrial motility caused by dysbindin deficiency decreased the density of mitochondria in the distal part of axons. Moreover, the transport and distribution of mitochondria were regulated by the association between dysbindin and p150glued. Furthermore, altered mitochondrial distribution in axons led to disrupted calcium dynamics, showing abnormal calcium influx in presynaptic terminals. These data collectively suggest that dysbindin forms a functional complex with p150gluedthat regulates axonal mitochondrial transport, thereby affecting presynaptic calcium homeostasis.
Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort
Authors: Liu Yun , Wang Honglian , Wang Xin , Liu Jiaqi , Li Junjian , Wang Xiang , Zhang Yun , Bai Zhigang , Zhou Qinghua , Wu Ying , Shen Yi , Weng Xiaoling , Liu Fatao , Guo Jiancheng , Di Lijun , Gires Olivier , Zhang Zhongtao , Chen Yiding , Wang Hongxia 
Published: January 2021

AbstractAccurate interpretation of BRCA1/2 variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based BRCA1/2 variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect BRCA1/2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls.
Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174/21,216) in BC patients and 1.1% (71/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of > 0.45‰ in BC patients (≥ 10 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic BRCA1/2 variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers.
Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071/21,216) in BC patients and 6.9% (446/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2–5 and 15–23) of the BRCA1 genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic BRCA1/2 variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of BRCA1/2 variants tailored to the Chinese population into clinical risk assessment.
Utility of a pediatric observation unit for the management of children admitted to the emergency department
Authors: Gatto Antonio , Rivetti Serena , Capossela Lavinia , Pata Davide , Covino Marcello , Chiaretti Antonio 
Published: January 2021

Abstract
Background
Observation Units (OU), as part of emergency department (ED), are areas reserved for short-term treatment or observation of patients with selected diagnoses to determine the need for hospitalization or home referral.

Methods
In this retrospective cohort study, we analyzed similarities and differences of children admitted to the pediatric ED of the Fondazione Policlinico Universitario A. Gemelli IRCCS hospital in the first 2 years of OU activity, analyzing general patient characteristics, access modalities, diagnosis, triage, laboratory and instrumental examinations, specialist visits, outcome of OU admission and average time spent in OU. Furthermore, we compared total numbers and type of hospitalization of the first 2 years of OU activity with those of previous 2 years.

Results
The most frequent diagnoses were abdominal pain, minor head injury without loss of consciousness, vomiting, epilepsy and acute bronchiolitis. The most performed laboratory examinations were blood count. The most commonly performed instrumental examination was abdominal ultrasound. Neurological counseling was the most commonly requested.
Average time spent in OU was 13 h in 2016 and 14.1 h in 2017. Most OU admissions did not last longer than 24 h (90.5% in 2016 and 89.5% in 2017).
In the years 2014–2015, 13.4% of pediatric patients accessing the ED were hospitalized, versus 9.9% the years 2016–2017 reducing pediatric hospital admissions by 3.6% (p <  0.001).

Conclusions
This study demonstrate that OU is a valid alternative to ordinary wards for specific pathologies. In accordance with the literature, our study showed that, in the first 2 years of the OU activity, admissions to hospital ward decreased compared with the previous 2 years with an increase of complex patients.
Prediction and mechanistic analysis of drug-induced liver injury (DILI) based on chemical structure
Authors: Liu Anika , Walter Moritz , Wright Peter , Bartosik Aleksandra , Dolciami Daniela , Elbasir Abdurrahman , Yang Hongbin , Bender Andreas 
Published: January 2021

Abstract
Background
Drug-induced liver injury (DILI) is a major safety concern characterized by a complex and diverse pathogenesis. In order to identify DILI early in drug development, a better understanding of the injury and models with better predictivity are urgently needed. One approach in this regard are in silico models which aim at predicting the risk of DILI based on the compound structure. However, these models do not yet show sufficient predictive performance or interpretability to be useful for decision making by themselves, the former partially stemming from the underlying problem of labeling the in vivo DILI risk of compounds in a meaningful way for generating machine learning models.

Results
As part of the Critical Assessment of Massive Data Analysis (CAMDA) “CMap Drug Safety Challenge” 2019 (http://camda2019.bioinf.jku.at), chemical structure-based models were generated using the binarized DILIrank annotations. Support Vector Machine (SVM) and Random Forest (RF) classifiers showed comparable performance to previously published models with a mean balanced accuracy over models generated using 5-fold LOCO-CV inside a 10-fold training scheme of 0.759 ± 0.027 when predicting an external test set. In the models which used predicted protein targets as compound descriptors, we identified the most information-rich proteins which agreed with the mechanisms of action and toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs), one of the most important drug classes causing DILI, stress response via TP53 and biotransformation. In addition, we identified multiple proteins involved in xenobiotic metabolism which could be novel DILI-related off-targets, such as CLK1 and DYRK2. Moreover, we derived potential structural alerts for DILI with high precision, including furan and hydrazine derivatives; however, all derived alerts were present in approved drugs and were over specific indicating the need to consider quantitative variables such as dose.

Conclusion
Using chemical structure-based descriptors such as structural fingerprints and predicted protein targets, DILI prediction models were built with a predictive performance comparable to previous literature. In addition, we derived insights on proteins and pathways statistically (and potentially causally) linked to DILI from these models and inferred new structural alerts related to this adverse endpoint.
Diabetes management intervention studies: lessons learned from two studies
Authors: Petersen Bettina , Vesper Iris , Pachwald Bernhild , Dagenbach Nicole , Buck Sina , Waldenmaier Delia , Heinemann Lutz 
Published: January 2021

Abstract
Introduction
Several clinical studies investigated improvements of patient outcomes due to diabetes management interventions. However, chronic disease management is intricate with complex multifactorial behavior patterns. Such studies thus have to be well designed in order to allocate all observed effects to the defined intervention and to exclude effects of other confounders as well as possible.
This article aims to provide challenges in interpreting diabetes management intervention studies and suggests approaches for optimizing study implementation and for avoiding pitfalls based on current experiences.

Main body
Lessons from the STeP and ProValue studies demonstrated the difficulty in medical device studies that rely on behavioral changes in intervention group patients. To successfully engage patients, priority should be given to health care professionals being engaged, operational support in technical issues being available, and adherence being assessed in detail.
Another difficulty is to avoid contamination of the control group with the intervention; therefore, strict allocation concealment should be maintained. However, randomization and blinding are not always possible. A limited effect size due to improvements regarding clinical endpoints in the control group is often caused by the Hawthorne effect. Improvements in the control group can also be caused with increased attention paid to the subjects. In order to reduce improvements in the control group, it is essential to identify the specific reasons and adjust study procedures accordingly. A pilot phase is indispensable for this. Another option is to include a third study arm to control for enhanced standard of care and study effects. Furthermore, retrospective data collection could be a feasible option. Adaptive study designs might reduce the necessity of a separate pilot study and combine the exploratory and confirmatory stages of an investigation in one single study.

Conclusion
There are several aspects to consider in medical device studies when using interventions that rely on changes in behavior to achieve an effective implementation and significant study results. Improvements in the control group may reduce effect sizes and limit statistical significance; therefore, alternatives to the traditional randomized controlled trials may be considered.
Molecular detection of Leishmania donovani, Leishmania major, and Trypanosoma species in Sergentomyia squamipleuris sand flies from a visceral leishmaniasis focus in Merti sub-County, eastern Kenya
Authors: Owino Barrack O. , Mwangi Jackline Milkah , Kiplagat Steve , Mwangi Hannah Njiriku , Ingonga Johnstone M. , Chebet Alphine , Ngumbi Philip M. , Villinger Jandouwe , Masiga Daniel K. , Matoke-Muhia Damaris 
Published: January 2021

Abstract
Background
Visceral leishmaniasis (VL) and zoonotic cutaneous leishmaniasis (ZCL) are of public health concern in Merti sub-County, Kenya, but epidemiological data on transmission, vector abundance, distribution, and reservoir hosts remain limited. To better understand the disease and inform control measures to reduce transmission, we investigated the abundance and distribution of sand fly species responsible for Leishmania transmission in the sub-County and their blood-meal hosts.

Methods
We conducted an entomological survey in five villages with reported cases of VL in Merti sub-County, Kenya, using CDC miniature light traps and castor oil sticky papers. Sand flies were dissected and identified to the species level using standard taxonomic keys and PCR analysis of the cytochrome c oxidase subunit 1 (cox1) gene. Leishmania parasites were detected and identified by PCR and sequencing of internal transcribed spacer 1 (ITS1) genes. Blood-meal sources of engorged females were identified by high-resolution melting analysis of vertebrate cytochrome b (cyt-b) gene PCR products.

Results
We sampled 526 sand flies consisting of 8 species, Phlebotomus orientalis (1.52%; n = 8), and 7 Sergentomyia spp. Sergentomyia squamipleuris was the most abundant sand fly species (78.71%; n = 414) followed by Sergentomyia clydei (10.46%; n = 55). Leishmania major, Leishmania donovani, and Trypanosoma DNA were detected in S. squamipleuris specimens. Humans were the main sources of sand fly blood meals. However, we also detected mixed blood meals; one S. squamipleuris specimen had fed on both human and mouse (Mus musculus) blood, while two Ph. orientalis specimens fed on human, hyrax (Procavia capensis), and mouse (Mus musculus) blood.

Conclusions
Our findings implicate the potential involvement of S. squamipleuris in the transmission of Leishmania and question the dogma that human leishmaniases in the Old World are exclusively transmitted by sand flies of the Phlebotomus genus. The presence of Trypanosoma spp. may indicate mechanical transmission, whose efficiency should be investigated. Host preference analysis revealed the possibility of zoonotic transmission of leishmaniasis and other pathogens in the sub-County. Leishmania major and L. donovani are known to cause ZCL and VL, respectively. However, the reservoir status of the parasites is not uniform. Further studies are needed to determine the reservoir hosts of Leishmania spp. in the area.

Graphical Abstract
RNAi gene knockdown in the poultry red mite, Dermanyssus gallinae (De Geer 1778), a tool for functional genomics
Authors: Chen Wan , Bartley Kathryn , Nunn Francesca , Bowman Alan S. , Sternberg Jeremy M. , Burgess Stewart T. G. , Nisbet Alasdair J. , Price Daniel R. G. 
Published: January 2021

Abstract
Background
The avian haematophagous ectoparasite Dermanyssus gallinae, commonly known as the poultry red mite, causes significant economic losses to the egg-laying industry worldwide and also represents a significant welfare threat. Current acaricide-based controls are unsustainable due to the mite’s ability to rapidly develop resistance, thus developing a novel sustainable means of control for D. gallinae is a priority. RNA interference (RNAi)-mediated gene silencing is a valuable tool for studying gene function in non-model organisms, but is also emerging as a novel tool for parasite control.

Methods
Here we use an in silico approach to identify core RNAi pathway genes in the recently sequenced D. gallinae genome. In addition we utilise an in vitro feeding device to deliver double-stranded (ds) RNA to D. gallinae targeting the D. gallinae vATPase subunit A (Dg vATPase A) gene and monitor gene knockdown using quantitative PCR (qPCR).

Results
Core components of the small interfering RNA (siRNA) and microRNA (miRNA) pathways were identified in D. gallinae, which indicates that these gene silencing pathways are likely functional. Strikingly, the P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway was absent in D. gallinae. In addition, feeding Dg vATPase A dsRNA to adult female D. gallinae resulted in silencing of the targeted gene compared to control mites fed non-specific lacZ dsRNA. In D. gallinae, dsRNA-mediated gene knockdown was rapid, being detectable 24 h after oral delivery of the dsRNA, and persisted for at least 120 h.

Conclusions
This study shows the presence of core RNAi machinery components in the D. gallinae genome. In addition, we have developed a robust RNAi methodology for targeting genes in D. gallinae that will be of value for studying genes of unknown function and validating potential control targets in D. gallinae.

Graphical Abstract
Insecticide resistance status of malaria vectors Anopheles gambiae (s.l.) of southwest Burkina Faso and residual efficacy of indoor residual spraying with microencapsulated pirimiphos-methyl insecticide
Authors: Soma Dieudonné Diloma , Zogo Barnabas , Hien Domonbabele François de Sales , Hien Aristide Sawdetuo , Kaboré Didier Alexandre , Kientega Mahamadi , Ouédraogo Anicet Georges , Pennetier Cédric , Koffi Alphonsine Amanan , Moiroux Nicolas , Dabiré Roch Kounbobr 
Published: January 2021

Abstract
Background
The rapid spread of insecticide resistance in malaria vectors and the rebound in malaria cases observed recently in some endemic areas underscore the urgent need to evaluate and deploy new effective control interventions. A randomized control trial (RCT) was conducted with the aim to investigate the benefit of deploying complementary strategies, including indoor residual spraying (IRS) with pirimiphos-methyl in addition to long-lasting insecticidal nets (LLINs) in Diébougou, southwest Burkina Faso.

Methods
We measured the susceptibility of the Anopheles gambiae (s.l.) population from Diébougou to conventional insecticides. We further monitored the efficacy and residual activity of pirimiphos-methyl on both cement and mud walls using a laboratory susceptible strain (Kisumu) and the local An. gambiae (s.l.) population.

Results
An. gambiae (s.l.) from Diébougou was resistant to DDT, pyrethroids (deltamethrin, permethrin and alphacypermethrin) and bendiocarb but showed susceptibility to organophosphates (pirimiphos-methyl and chlorpyrimiphos-methyl). A mixed-effect generalized linear model predicted that pirimiphos-methyl applied on cement or mud walls was effective for 210 days against the laboratory susceptible strain and 247 days against the local population. The residual efficacy of pirimiphos-methyl against the local population on walls made of mud was similar to that of cement (OR = 0.792, [0.55–1.12], Tukey’s test p-value = 0.19).

Conclusions
If data on malaria transmission and malaria cases (as measured trough the RCT) are consistent with data on residual activity of pirimiphos-methyl regardless of the type of wall, one round of IRS with pirimiphos-methyl would have the potential to control malaria in a context of multi-resistant An. gambiae (s.l.) for at least 7 months.

Graphical Abstract
Serum biomarker panel for the diagnosis of rheumatoid arthritis
Authors: Mun Sora , Lee Jiyeong , Park Mira , Shin Jieun , Lim Mi-Kyoung , Kang Hee-Gyoo 
Published: January 2021

Abstract
Background
Rheumatoid arthritis (RA) is an autoimmune disease of inflammatory joint damage, wherein C-reactive protein and autoantibodies including rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) are rapidly elevated. These serological factors are diagnostic markers of RA; however, their sensitivity and specificity for prediction warrant improvement for an early and accurate diagnosis.

Methods
We aimed to identify alternative biomarkers by serum protein profiling using LC-MS/MS. We performed statistical and functional analysis of differentially expressed proteins to identify biomarker candidates complementing conventional serological tests.

Results
Seven biomarker candidates were verified through multiple reaction monitoring-based quantitative analysis, of which angiotensinogen (AGT), serum amyloid A-4 protein (SAA4), vitamin D-binding protein (VDBP), and retinol-binding protein-4 (RBP4) had an area under the curve over 0.8, thus distinguishing RA patients, including seronegative (RF- and anti-CCP-negative) RA patients, from healthy controls.

Conclusions
Therefore, among seronegative RA patients, a four-biomarker panel (AGT, SAA4, VDBP, and RBP4) can prevent false negatives and help diagnose RA accurately.