bluuebunny/crossref_metadata_2025_split huggingface dataset:
ECNano: A cost-effective workflow for target enrichment sequencing and accurate variant calling on 4800 clinically significant genes using a single MinION flowcell
Authors: Leung Amy Wing-Sze , Leung Henry Chi-Ming , Wong Chak-Lim , Zheng Zhen-Xian , Lui Wui-Wang , Luk Ho-Ming , Lo Ivan Fai-Man , Luo Ruibang , Lam Tak-Wah 
Published: March 2022

Abstract
Background
The application of long-read sequencing using the Oxford Nanopore Technologies (ONT) MinION sequencer is getting more diverse in the medical field. Having a high sequencing error of ONT and limited throughput from a single MinION flowcell, however, limits its applicability for accurate variant detection. Medical exome sequencing (MES) targets clinically significant exon regions, allowing rapid and comprehensive screening of pathogenic variants. By applying MES with MinION sequencing, the technology can achieve a more uniform capture of the target regions, shorter turnaround time, and lower sequencing cost per sample.

Method
We introduced a cost-effective optimized workflow, ECNano, comprising a wet-lab protocol and bioinformatics analysis, for accurate variant detection at 4800 clinically important genes and regions using a single MinION flowcell. The ECNano wet-lab protocol was optimized to perform long-read target enrichment and ONT library preparation to stably generate high-quality MES data with adequate coverage. The subsequent variant-calling workflow, Clair-ensemble, adopted a fast RNN-based variant caller, Clair, and was optimized for target enrichment data. To evaluate its performance and practicality, ECNano was tested on both reference DNA samples and patient samples.

Results
ECNano achieved deep on-target depth of coverage (DoC) at average > 100× and > 98% uniformity using one MinION flowcell. For accurate ONT variant calling, the generated reads sufficiently covered 98.9% of pathogenic positions listed in ClinVar, with 98.96% having at least 30× DoC. ECNano obtained an average read length of 1000 bp. The long reads of ECNano also covered the adjacent splice sites well, with 98.5% of positions having ≥ 30× DoC. Clair-ensemble achieved > 99% recall and accuracy for SNV calling. The whole workflow from wet-lab protocol to variant detection was completed within three days.

Conclusion
We presented ECNano, an out-of-the-box workflow comprising (1) a wet-lab protocol for ONT target enrichment sequencing and (2) a downstream variant detection workflow, Clair-ensemble. The workflow is cost-effective, with a short turnaround time for high accuracy variant calling in 4800 clinically significant genes and regions using a single MinION flowcell. The long-read exon captured data has potential for further development, promoting the application of long-read sequencing in personalized disease treatment and risk prediction.
Oral susceptibility to ivermectin is over fifty times greater in a wild population of Anopheles albimanus mosquitoes from Belize than the STECLA laboratory reference strain of this mosquito
Authors: Dreyer Staci M. , Morin Kelsey J. , Magaña Marla , Pott Marie , Leiva Donovan , Achee Nicole L. , Grieco John P. , Vaughan Jefferson A. 
Published: March 2022

Abstract
Background
The STECLA strain of Anopheles albimanus has been in continuous colony for many years and is the reference strain on which genomic studies for the species are based. Recently, the STECLA strain was demonstrated to be much less susceptible to ivermectin ingested in a blood meal (4-day LC50 of 1468 ng/ml) than all other Anopheles species tested to-date (LC50 values range from 7 to 56 ng/ml). The ability of An. albimanus to survive ingestion of ivermectin at concentrations far beyond that typically found in the blood of ivermectin-treated people or livestock (i.e., 30–70 ng/ml) could invalidate the use of ivermectin as a malaria vector control strategy in areas where An. albimanus is a primary vector.

Methods
To investigate this, host-seeking An. albimanus were captured in northern Belize and used in membrane feeding bioassays of ivermectin, employing the same methods as described earlier with the STECLA strain.

Results
Field-collected An. albimanus in Belize were 55 times more susceptible to ingested ivermectin than were the STECLA reference strain. Oral susceptibility to ivermectin in wild An. albimanus from Belize (4-day LC50 of 26 ng/ml) was equivalent to that of other Anopheles species tested.

Conclusions
Contrary to initial assessments using a highly inbred strain of mosquito, laboratory studies using a field population indicate that ivermectin treatment of livestock could reduce An. albimanus populations in areas of Central America and the Caribbean where malaria transmission may occur. Toxicity screening of ivermectin and other systemic parasiticides for malaria control should examine wild populations of the vector species being targeted.
Therapeutic nucleus-access BNCT drug combined CD47-targeting gene editing in glioblastoma
Authors: Chen Jiejian , Dai Qi , Yang QiYao , Bao Xiaoyan , Zhou Yi , Zhong Haiqing , Wu Linjie , Wang Tiantian , Zhang Zhicheng , Lu Yiying , Zhang Zhentao , Lin Mengting , Han Min , Wei Qichun 
Published: March 2022

AbstractGlioblastoma is the most common brain primary malignant tumor with the highest mortality. Boron neutron capture therapy (BNCT) can efficiently kill cancer cells on the cellular scale, with high accuracy, short course and low side-effects, which is regarded as the most promising therapy for malignant brain tumors like glioma. As the keypoint of BNCT, all boron delivery agents currently in clinical use are beset by insufficient tumor uptake, especially in the tumor nucleus, which limits the clinical application of BNCT. In this study, nuclear targeting of boron is achieved by DOX-CB, consisting of doxorubicin (DOX) and carborane (CB) utilizing the nuclear translocation property of DOX. The nucleus of GL261 cells takes up almost three times the concentration of boron required for BNCT. To further kill glioma and inhibit recurrence, a new multifunctional nanoliposome delivery system DOX-CB@lipo-pDNA-iRGD is constructed. It combines DOX-CB with immunotherapy strategy of blocking macrophage immune checkpoint pathway CD47-SIRPα by CRISPR-Cas9 system, coupling BNCT with immunotherapy simultaneously. Compared with clinical drug Borocaptate Sodium (BSH), DOX-CB@lipo-pDNA-iRGD significantly enhances the survival rate of tumor-bearing mice, reduces tumor stemness, and improves the prognosis. The excellent curative effect of this nanoliposome delivery system provides an insight into the combined treatment of BNCT.
Graphical Abstract
Dealing with low access to harm reduction: a qualitative study of the strategies and risk environments of people who use drugs in a small Swedish city
Authors: Holeksa Julie 
Published: March 2022

Abstract
Background
The development of harm reduction has been limited in many areas of Sweden. This study aims to understand the implications that this has for the life circumstances and risk management of people who use drugs in areas of low access.

Methods
Eleven qualitative, semi-structured interviews were undertaken with people who use drugs in a small urban centre with no needle and syringe exchange program (NSP) or Housing First policy.

Results
Participants reported many solutions to lack of NSP, including travel to an external NSP, creating bridging distribution networks, stealing, borrowing, reusing, ordering online, and smuggling injection equipment. They were at risk of having their equipment confiscated by police. Participants were mostly homeless, and to address exclusion from housing services, were forced to frequently find new temporary solutions, sheltering themselves in public places, with friends, in cars, among others. Participants felt the lack of services reflected stigmatized notions of drug use and heightened their exclusion from general society. For example, they avoided accessing other health care services for fear of discrimination. These issues caused high levels of stress and anxiety, in addition to serious risk for many somatic and psychological health conditions, including HIV and HCV transmission.

Conclusion
Lack of harm reduction services placed a great burden on study participants to develop strategies due to gaps in official programming. It also contributes to a vicious cycle of exclusion from services. The implementation of such evidence-based programs will reduce this burden, as well as provide the indirect, symbolic effect of inclusion.
One-month alcohol abstinence national campaigns: a scoping review of the harm reduction benefits
Authors: de Ternay Julia , Leblanc Pierre , Michel Philippe , Benyamina Amine , Naassila Mickael , Rolland Benjamin 
Published: March 2022

AbstractOver the last decade, one-month alcohol abstinence campaigns (OMACs) have been implemented within the general population in an increasing number of countries. We identified the published studies reporting data on OMACs to explore the following aspects: profile of participants, rates and factors associated with the completion of the abstinence challenge, and outcomes and harm reduction benefits in participating in the challenges. We screened 322 records, including those found in the grey literature, and reviewed 6 studies and 7 Dry July Annual Reports. Compared to non-participating alcohol users, participants were more likely to be female, have a higher income, and a higher level of education. They were heavier drinkers and were more concerned by the consequences of alcohol on health and by their health in general. Participants who achieved the one-month abstinence challenge were lower drinkers and more likely to have registered on the campaign-related Internet communities. Both successful and unsuccessful participants frequently reported health benefits, including sleep improvement and weight loss. Successful participants were more likely to durably change their alcohol drinking habits. Overall, OMACs provide short- or mid-term harm reduction benefits for both successful and unsuccessful participants. Findings were limited by the paucity of studies, their observational nature, and heterogeneity in the features of the different national campaigns, which would probably gain in enhanced internationalization.
Cross-cultural adaptation of the Spanish MINICHAL instrument into English for use in the United Kingdom
Authors: Jordan Andrew N. , Anning Christine , Wilkes Lindsay , Ball Claire , Pamphilon Nicola , Clark Christopher E. , Bellenger Nicholas G. , Shore Angela C. , Sharp Andrew S. P. , Valderas Jose M. 
Published: March 2022

Abstract
Background
Hypertension is a highly prevalent condition, with optimal treatment to BP targets conferring significant gains in terms of cardiovascular outcomes. Understanding why some patients do not achieve BP targets would be enhanced through greater understanding of their health-related quality of life (HRQoL). However, the only English language disease-specific instruments for measurement of HRQoL in hypertension have not been validated in accordance with accepted standards. It is proposed that the Spanish MINICHAL instrument for the assessment of HRQoL in hypertension could be translated, adapted and validated for use in the United Kingdom. The aim of the study was therefore to complete this process.

Methods
The MINICHAL authors were contacted and the original instrument obtained. This was then translated into English by two independent English-speakers, with these versions then reconciled, before back-translation and subsequent production of a 2nd reconciled version. Thereafter, a final version was produced after cognitive debriefing, for administration and psychometric analysis in the target population of patients living in the Exeter area (Southwest UK) aged 18–80 years with treatment-naïve grade II-III hypertension, before, during and after 18 weeks’ intensive treatment.

Results
The English-language instrument was administered to 30 individuals (median age: 58.5 years, 53% male). Psychometric analysis demonstrated a floor effect, though no ceiling effect. Internal consistency for both state of mind (StM) and somatic manifestations (SM) dimensions of the instrument were acceptable (Cronbach’s alpha = 0.81 and 0.75), as was test–retest reliability (ICC = 0.717 and 0.961) and construct validity, which was measured through co-administration with the EQ-5D-5L and Bulpitt-Fletcher instruments. No significant associations were found between scores and patient characteristics known to affect HRQoL. The EQ-5D-5L instrument found an improvement in HRQoL following treatment, with the StM and SM dimensions of the English language MINICHAL trending to support this (d = 0.32 and 0.02 respectively).

Conclusions
The present study details the successful English translation and validation of the MINICHAL instrument for use in individuals with hypertension. The data reported also supports an improvement in HRQoL with rapid treatment of grade II-III hypertension, a strategy which has been recommended by contemporaneous European guidelines.
Trial registration ISRCTN registry number: 57475376 (assigned 25/06/2015).
Comparison of prolonged postoperative ileus between laparoscopic right and left colectomy under enhanced recovery after surgery: a propensity score matching analysis
Authors: Lin Zhenmeng , Yang Chunkang , Wang Yi , Yan Mingfang , Zheng Huizhe 
Published: March 2022

Abstract
Background
There were differences in the recovery of bowel function and prolonged postoperative ileus (PPOI) between laparoscopic right colectomy (RC) and left colectomy (LC) under the guidance of enhanced recovery after surgery.

Methods
We selected 870 patients who underwent elective laparoscopic colectomy from June 2016 to December 2021, including 272 patients who had RC and 598 who had LC. According to 1:1 proportion for propensity score matching and correlation analysis, 247 patients who had RC and 247 who had LC were finally enrolled.

Results
The incidence of PPOI in all patients was 13.1%. Age, sex, smoking habit, preoperative serum albumin level, operation type, and operation time were the important independent risk factors based on multivariate logistic regression and correlation analysis for PPOI (p<0.05). Age, sex, body mass index, preoperative serum albumin level, operation time, and degree of differentiation between the two groups were significantly different before case matching (p<0.05). There were no statistically significant differences in baseline characteristics and preoperative biochemical parameters between the two groups after case matching (p>0.05). The incidence of PPOI in patients who had RC was 21.9%, while that in patients who had LC was 13.0%. The first flatus, first semi-liquid, and length of stay in LC patients were lower than those in RC patients (p<0.05).

Conclusion
The return of bowel function in LC was faster than that in RC, and the incidence of PPOI was relatively lower. Therefore, caution should be taken during the early feeding of patients who had laparoscopic RC.
Effect of deploying biomedical equipment technician on the functionality of medical equipment in the government hospitals of rural Nepal
Authors: Thapa Rita , Yih Alison , Chauhan Ashish , Poudel Salomi , Singh Sagar , Shrestha Suresh , Tamang Suresh , Shrestha Rishav , Rajbhandari Ruma 
Published: March 2022

Abstract
Background
Medical equipment plays a crucial role in the provision of quality healthcare services, despite this more than 50% of equipment in developing countries are non-functioning due to a lack of appropriate human resources to maintain. To address this problem some government hospitals of Nepal have deployed a mid-level technical cadre called 'Biomedical Equipment Technician' (BMET). This study aims to evaluate the effectiveness of deploying a BMET on the functionality of medical equipment in government hospitals of rural Nepal.

Methods
We used a mixed-methods approach with a comparative research design. A comprehensive range of 2189 pieces of medical equipment at 22 hospitals with and without BMET were observed to assess their functional status. Medical equipment were stratified into 6 categories based on department and T tests were conducted. We collected qualitative data from 9 BMETs, 22 medical superintendents, and 22 health staff using semi-structured interviews and focus-group discussions. Thematic content analysis was conducted to explore how the BMET's work was perceived.

Findings
The quantity of non-functional devices in hospitals without BMETs was double that of hospitals with BMETs (14% and 7% respectively, p < 0.005). Results were similar across all departments including General (16% versus 3%, p = 0.056), Lab (15% versus 7%, p < 0.005) and Operation Theater (14% versus 5%, p < 0.005). Hospitals with BMETs had fewer overall non-functional devices requiring simple or advanced repair compared to hospitals without BMETs [3% versus 7% (p < 0.005) simple; 4% versus 6% (p < 0.005) advanced]. In our qualitative analysis, we found that BMETs were highly appreciated by hospital staff. Hospital workers perceived that having a BMET on staff, rather than twice-yearly visits from central-level maintenance technicians, is an effective way to keep medical equipment functional. However, without a favorable working environment, the BMET alone cannot perform optimally.

Conclusions
Having a BMET at a rural government hospital has a substantial positive effect on the functional status of medical devices at the hospital. BMETs should be deployed at all rural hospitals to increase the functionality of medical devices, thereby improving the working environment and quality of health services provided.
Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy
Authors: Mashiko Takanobu , Tsukada Kunihisa , Takada Hitomi , Wu Szu-Hsien , Kanayama Koji , Asahi Rintaro , Mori Masanori , Kurisaki Akira , Oka Shinichi , Yoshimura Kotaro 
Published: March 2022

Abstract
Background
The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients.

Methods
All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV− healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry.

Results
The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV.

Conclusions
Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes’ sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.
The patterns of co-occurrence variation are explained by the low dependence of bark beetles (Coleoptera: Scolytinae and Platypodinae) on hosts along altitude gradients
Authors: Luo Fang , Meng Ling-Zeng , Wang Jian , Liu Yan-Hong 
Published: March 2022

Abstract
Background
Separation of biotic and abiotic impacts on species diversity distribution patterns across a significant climatic gradient is a challenge in the study of diversity maintenance mechanisms. The basic task is to reconcile scale-dependent effects of abiotic and biotic processes on species distribution models. Here, we used a hierarchical modeling method to detect the host specificities of bark beetles (Scolytinae and Platypodinae) with their dependent tree communities across a steep climatic gradient, which was embedded within a relatively homogenous spatial niche.

Results
Species turnover of both trees and bark beetles have an opposite pattern along the climatic proxy (represented by the elevation gradients) at the regional scale, but not at local spatial scales. This pattern confirmed the hypothesis wherein emphasis was on influences of macro-climate on local biotic interactions between trees and hosted bark beetle communities, whereas local biotic relations, represented by host specificity dependence, were regionally conserved.

Conclusions
At a confined spatial scale, cross-taxa comparisons of β-diversity highlighted the importance of simultaneous impacts from both extrinsic factors related to geography and environment, and intrinsic factors related to organism characteristics. The effects of tree abundance and phylogeny diversity on bark beetle diversity were, to a large extent, indirect, operating via changes in bark beetle abundance through spatial and temporal dynamics of resources distribution. Tree host dependence, which was considered and represented by host specificities, plays a minor role on the hosted beetle community in this concealed wood decomposing interacting system.
Application of a VP4/VP2-inferred transmission clusters in estimating the impact of interventions on rhinovirus transmission
Authors: Ng Kim Tien , Ng Liang Jie , Oong Xiang Yong , Chook Jack Bee , Chan Kok Gan , Takebe Yutaka , Kamarulzaman Adeeba , Tee Kok Keng 
Published: March 2022

Abstract
Background
Despite the clinical burden attributable to rhinovirus (RV) infections, the RV transmission dynamics and the impact of interventions on viral transmission remain elusive.

Methods
A total of 3,935 nasopharyngeal specimens were examined, from which the VP4/VP2 gene was sequenced and genotyped. RV transmission clusters were reconstructed using the genetic threshold of 0.005 substitutions/site, estimated from the global VP4/VP2 sequences. A transmission cluster is characterized by the presence of at least two individuals (represent by nodes), whose viral sequences are genetically linked (represent by undirected edges) at the estimated genetic distance threshold supported by bootstrap value of ≥ 90%. To assess the impact of facemask, pleconaril and social distancing on RV transmission clusters, trials were simulated for interventions with varying efficacy and were evaluated based on the reduction in the number of infected patients (nodes) and the reduction in the number of nodes-connecting edges. The putative impact of intervention strategies on RV transmission clusters was evaluated through 10,000 simulations.

Results
A substantial clustering of 168 RV transmission clusters of varying sizes were observed. This suggests that RV disease burden observed in the population was largely due to multiple sub-epidemics, predominantly driven by RV-A, followed by RV-C and -B. No misclassification of RV species and types were observed, suggesting the specificity and sensitivity of the analysis. Through 10,000 simulations, it was shown that social distancing may be effective in decelerating RV transmission, by removing more than 95% of nodes and edges within the RV transmission clusters. However, facemask removed less than 8% and 66% of nodes and edges, respectively, conferring moderate advantage in limiting RV transmission.

Conclusion
Here, we presented a network-based approach of which the degree of RV spread that fuel disease transmission in the region was mapped for the first time. The utilization of RV transmission clusters in assessing the putative impact of interventions on disease transmission at the population level was demonstrated.