bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allele frequency deviation (AFD) as a new prognostic model to predict overall survival in lung adenocarcinoma (LUAD)
Authors: Al-Dherasi Aisha , Liao Yuwei , Al-Mosaib Sultan , Hua Rulin , Wang Yichen , Yu Ying , Zhang Yu , Zhang Xuehong , Jalayta Raeda , Mousa Haithm , Al-Danakh Abdullah , Alnadari Fawze , Almoiliqy Marwan , Baldi Salem , Shi Leming , Lv Dekang , Li Zhiguang , Liu Quentin 
Published: August 2021

Abstract
Background
Lung adenocarcinoma (LUAD) remains one of the world’s most known aggressive malignancies with a high mortality rate. Molecular biological analysis and bioinformatics are of great importance as they have recently occupied a large area in the studies related to the identification of various biomarkers to predict survival for LUAD patients. In our study, we attempted to identify a new prognostic model by developing a new algorithm to calculate the allele frequency deviation (AFD), which in turn may assist in the early diagnosis and prediction of clinical outcomes in LUAD.

Method
First, a new algorithm was developed to calculate AFD using the whole-exome sequencing (WES) dataset. Then, AFD was measured for 102 patients, and the predictive power of AFD was assessed using Kaplan–Meier analysis, receiver operating characteristic (ROC) curves, and area under the curve (AUC). Finally, multivariable cox regression analyses were conducted to evaluate the independence of AFD as an independent prognostic tool.

Result
The Kaplan–Meier analysis showed that AFD effectively segregated patients with LUAD into high-AFD-value and low-AFD-value risk groups (hazard ratio HR = 1.125, 95% confidence interval CI 1.001–1.26, p = 0.04) in the training group. Moreover, the overall survival (OS) of patients who belong to the high-AFD-value group was significantly shorter than that of patients who belong to the low-AFD-value group with 42.8% higher risk and 10% lower risk of death for both groups respectively (HR for death = 1.10; 95% CI 1.01–1.2, p = 0.03) in the training group. Similar results were obtained in the validation group (HR = 4.62, 95% CI 1.22–17.4, p = 0.02) with 41.6%, and 5.5% risk of death for patients who belong to the high and low-AFD-value groups respectively. Univariate and multivariable cox regression analyses demonstrated that AFD is an independent prognostic model for patients with LUAD. The AUC for 5-year survival were 0.712 and 0.86 in the training and validation groups, respectively.

Conclusion
AFD was identified as a new independent prognostic model that could provide a prognostic tool for physicians and contribute to treatment decisions.
Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection
Authors: Mukaka Mavuto , Peerawaranun Pimnara , Parker Daniel M. , Kajeechiwa Ladda , Nosten Francois H. , Nguyen Thuy-Nhien , Hien Tran Tinh , Tripura Rupam , Peto Thomas J. , Phommasone Koukeo , Mayxay Mayfong , Newton Paul N. , Imwong Mallika , Day Nicholas P. J. , Dondorp Arjen M. , White Nicholas J. , von Seidlein Lorenz 
Published: August 2021

Abstract
Background
Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources.

Methods
Data from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL).

Results
At baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected.

Conclusion
Reactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.
Impact of cattle on the abundance of indoor and outdoor resting malaria vectors in southern Malawi
Authors: Mburu Monicah M. , Zembere Kennedy , Mzilahowa Themba , Terlouw Anja D. , Malenga Tumaini , van den Berg Henk , Takken Willem , McCann Robert S. 
Published: August 2021

Abstract
Background
Understanding the blood feeding preferences and resting habits of malaria vectors is important for assessing and designing effective malaria vector control tools. The presence of livestock, such as cattle, which are used as blood meal hosts by some malaria vectors, may impact malaria parasite transmission dynamics. The presence of livestock may provide sufficient blood meals for the vectors, thereby reducing the frequency of vectors biting humans. Alternatively, the presence of cattle may enhance the availability of blood meals such that infectious mosquitoes may survive longer, thereby increasing the risk of malaria transmission. This study assessed the effect of household-level cattle presence and distribution on the abundance of indoor and outdoor resting malaria vectors.

Methods
Houses with and without cattle were selected in Chikwawa district, southern Malawi for sampling resting malaria vectors. Prokopack aspirators and clay pots were used for indoor and outdoor sampling, respectively. Each house was sampled over two consecutive days. For houses with cattle nearby, the number of cattle and the distances from the house to where the cattle were corralled the previous night were recorded. All data were analysed using generalized linear models fitted with Poisson distribution.

Results
The malaria vectors caught resting indoors were Anopheles gambiae sensustricto (s.s.), Anopheles arabiensis and Anopheles funestuss.s. Outdoor collections consisted primarily of An. arabiensis. The catch sizes of indoor resting An. gambiae sensulato (s.l.) were not different in houses with and without cattle (P = 0.34). The presence of cattle near a house was associated with a reduction in the abundance of indoor resting An. funestuss.l. (P = 0.04). This effect was strongest when cattle were kept overnight ≤ 15 m away from the houses (P = 0.03). The blood meal hosts varied across the species.

Conclusion
These results highlight differences between malaria vector species and their interactions with potential blood meal hosts, which may have implications for malaria risk. Whereas An. arabiensis remained unaffected, the reduction of An. funestuss.s. in houses near cattle suggests a potential protective effect of cattle. However, the low abundance of mosquitoes reduced the power of some analyses and limited the generalizability of the results to other settings. Therefore, further studies incorporating the vectors’ host-seeking behaviour/human biting rates are recommended to fully support the primary finding.
Direct detection of resistance to fluoroquinolones/SLIDs in sputum specimen by GenoType MTBDRsl v.2.0 assay A study from Eastern Uttar Pradesh, India
Authors: Singh Kamal , Kumari Richa , Gupta Smita , Tripathi Rajneesh , Srivastava Anjali , Shakya Vidisha , Gupta Ankush , Anupurba Shampa 
Published: August 2021

Abstract
Background
According to World Health Organization (WHO), drug-resistant tuberculosis (DR-TB) is a major contributor to antimicrobial resistance globally and continues to be a public health threat. Annually, about half a million people fall ill with DR-TB globally. The gradual increase in resistance to fluoroquinolones (FQs) and second-line injectable drugs (SLIDs), poses a serious threat to effective TB control and adequate patient management. Therefore, WHO suggests the use of GenoType MTBDRsl v.2.0 assay for detection of multiple mutations associated with FQs and SLIDs. Hence, the study was conducted to determine the prevalence of resistance to FQs and SLIDs by comparing direct GenoType MTBDRsl v.2.0 assay with phenotypic drug susceptibility testing (DST).

Methods
The study was conducted on 1320 smear positive sputum samples from a total of 2536 RR-TB, confirmed by GeneXpert MTB/RIF. The smear positive specimens were decontaminated, and DNA extraction was performed. Furthermore, the extracted DNA was used for GenoType MTBDRsl v.2.0 assay. While 20% of the decontaminated specimens were inoculated in Mycobacterium growth indicator tube (MGIT) for drug susceptibility testing (DST).

Results
Out of 1320 smear positive sputum samples, 1178 were identified as Mycobacterium tuberculosis complex (MTBC) and remaining were negative by GenoType MTBDRsl v.2.0 assay. Of the 1178 MTBC positive, 26.6% were sensitive to both FQs and SLIDs, whereas 57.3% were only FQs resistant and 15.9% were resistant to both FQs and SLIDs. Further DST of 225 isolates by liquid culture showed that 17% were sensitive to both FQs and SLIDs, 61.3% were only FQs resistant and 21.3% were resistant to both. The specificity for FQs and SLIDs was 92.31% and 100% whereas sensitivity was 100% respectively by GenoType MTBDRsl v.2.0 assay in direct sputum samples.

Conclusions
Our study clearly suggests that GenoType MTBDRsl v.2.0 assay is a reliable test for the rapid detection of resistance to second-line drugs after confirmation by GeneXpert MTB/RIF assay for RR-TB. Though, high rate FQ (ofloxacin) resistance was seen in our setting, moxifloxacin could be used as treatment option owing to very low resistance.
Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders
Authors: Chen Jianling , Chen Jing , Xu Yun , Cheng Peipei , Yu Shunying , Fu Yingmei , Du Yasong 
Published: August 2021

Abstract
Background
About 20–40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon.

Methods
A total of 60 autistic individuals (18 with regression phenomenon, 42 without regression phenomenon) (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low–density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents.

Results
Compared with control subjects, autistic individuals had lower levels of TC (P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG (r = 0.355, P = 0.005), HDLC (r = 0.257, P = 0.047), TG/TC (r = 0.376, P = 0.003) and TG/LDLC (r = 0.363, P = 0.004), and were negatively correlated with CARS (r=-0.296, P = 0.003). Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors.

Conclusions
Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon.
A drug-related Good Samaritan Law and calling emergency medical services for drug overdoses in a Canadian setting
Authors: Moallef Soroush , Choi JinCheol , Milloy M.-J. , DeBeck Kora , Kerr Thomas , Hayashi Kanna 
Published: August 2021

Abstract
Background
People who use drugs (PWUD) are known to fear calling emergency medical services (EMS) for drug overdoses. In response, drug-related Good Samaritan Laws (GSLs) have been widely adopted in the USA and Canada to encourage bystanders to call emergency medical services (EMS) in the event of a drug overdose. However, the effect of GSLs on EMS-calling behaviours has been understudied. We sought to identify factors associated with EMS-calling, including the enactment of the Canadian GSL in May 2017, among PWUD in Vancouver, Canada, a setting with an ongoing overdose crisis.

Methods
Data were derived from three prospective cohort studies of PWUD in Vancouver in 2014–2018. Multivariable logistic regression was used to determine factors associated with EMS-calling among PWUD who witnessed an overdose event. An interrupted time series (ITS) analysis was employed to assess the impact of GSL on monthly prevalence of EMS-calling.

Results
Among 540 eligible participants, 321 (59%) were males and 284 (53%) reported calling EMS. In multivariable analysis, ever having administered naloxone three or more times (adjusted odds ratio [AOR] 2.00; 95% confidence interval [CI] 1.08–3.74) and residence in the Downtown Eastside (DTES) neighbourhood of Vancouver (AOR 1.96; 95% CI 1.23–3.13) were positively associated with EMS-calling, while living in a single occupancy hotel (SRO) was negatively associated with EMS-calling (AOR 0.51; 95% CI 0.30–0.86). The post-GSL enactment period was not associated with EMS-calling (AOR 0.81; 95% CI 0.52–1.25). The ITS found no significant difference in the monthly prevalence of EMS-calling between pre- and post-GSL enactment periods.

Conclusion
We observed EMS being called about half the time and the GSL did not appear to encourage EMS-calling. We also found that individuals living in SROs were less likely to call EMS, which raises concern given that fatal overdose cases are concentrated in SROs in our setting. The link between many naloxone administrations and EMS-calling could indicate that those with prior experience in responding to overdose events were more willing to call EMS. Increased efforts are warranted to ensure effective emergency responses for drug overdoses among PWUD.
Drug use, homelessness and health: responding to the opioid overdose crisis with housing and harm reduction services
Authors: Milaney Katrina , Passi Jenna , Zaretsky Lisa , Liu Tong , O’Gorman Claire M. , Hill Leslie , Dutton Daniel 
Published: August 2021

Abstract
Background
Canada is in the midst of an opioid overdose crisis and Alberta has one of the highest opioid use rates across the country. Populations made vulnerable through structural inequities who also use opioids, such as those who are unstably housed, are at an increased risk of experiencing harms associated with opioid use. The main purpose of this study was to explore if there was an association between unstable housing and hospital use for people who use opioids.

Methods
Analysis utilized self-reported data from the Alberta Health and Drug Use Survey which surveyed 813 Albertans in three cities. Hospital use was modeled using a logistic regression with our primary variable of interest being housing unstable status. Chi square tests were conducted between hospital use and variables associated with demographics, characteristics of drug use, health characteristics, and experiences of receiving services to establish model inclusion.

Results
Results revealed a significant association between housing instability and hospital use with unstably housed individuals twice as likely torequire hospital care.

Conclusions
Results highlight the importance of concurrently addressing housing instability alongside the provision of harm reduction services such as safe supply and supervised consumption sites. These findings have significant implications for policy and policymakers during the opioid overdose epidemic, and provide a foundation for future areas of research.
Method for reconstructing mortality by educational groups
Authors: Németh László , Jasilionis Domantas , Brønnum-Hansen Henrik , Jdanov Dmitri A. 
Published: August 2021

Abstract
Background
The lack of classification by educational attainment in death and population exposure data at older ages is an important constraint for studying changes and patterns of mortality disparities by education in Denmark and Sweden. The missing educational distribution of population also restricts analyses aiming at estimating contributions of compositional change to the improvements in national longevity. This study proposes a transparent approach to solve the two methodological issues allowing to obtain robust education-specific mortality estimates and population weights.

Methods
Using nonparametric approach, we redistribute the unknown cases and extrapolate the mortality curves of these sub-populations with the help of population-level data on an aggregate level from the Human Mortality Database.

Results
We present reconstructed and harmonized education-specific abridged and complete life tables for Sweden and Denmark covering 5-year-long periods from 1991–1995 to 2011–2015. The newly estimated life tables are in good agreement with the national life tables and show plausible age- and education-specific patterns. The observed changes in life expectancy by education suggest about the widening longevity gap between the highest and lowest educated for males and females in both countries.

Conclusions
The proposed simple and transparent method can be applied in similar country-specific cases showing large proportions of missing education or other socio-economic characteristics at older ages.
Applying low coverage whole genome sequencing to detect malignant ovarian mass
Authors: Chen Ming , Zhong Pengqiang , Hong Mengzhi , Tan Jinfeng , Yu Xuegao , Huang Hao , Ouyang Juan , Lin Xiaoping , Chen Peisong 
Published: August 2021

AbstractTo evaluate whether low coverage whole genome sequencing is suitable for the detection of malignant pelvic mass and compare its diagnostic value with traditional tumor markers. We enrolled 63 patients with a pelvic mass suspicious for ovarian malignancy. Each patient underwent low coverage whole genome sequencing (LCWGS) and traditional tumor markers test. The pelvic masses were finally confirmed via pathological examination. The copy number variants (CNVs) of whole genome were detected and the Stouffers Z-scores for each CNV was extracted. The risk of malignancy (RM) of each suspicious sample was calculated based on the CNV counts and Z-scores, which was subsequently compared with ovarian cancer markers CA125 and HE4, and the risk of ovarian malignancy algorithm (ROMA). Receiver Operating Characteristic Curve (ROC) were used to access the diagnostic value of variables. As confirmed by pathological diagnosis, 44 (70%) patients with malignancy and 19 patients with benign mass were identified. Our results showed that CA125 and HE4, the CNV, the mean of Z-scores (Zmean), the max of Z-scores (Zmax), the RM and the ROMA were significantly different between patients with malignant and benign masses. The area under curve (AUC) of CA125, HE4, CNV, Zmax, and Zmean was 0.775, 0.866, 0.786, 0.685 and 0.725 respectively. ROMA and RM showed similar AUC (0.876 and 0.837), but differed in sensitivity and specificity. In the validation cohort, the AUC of RM was higher than traditional serum markers. In conclusion, we develop a LCWGS based method for the identification of pelvic mass of suspicious ovarian cancer. LCWGS shows accurate result and could be complementary with the existing diagnostic methods.
CRISPR/Cas9 revitalizes adoptive T-cell therapy for cancer immunotherapy
Authors: Ghaffari Sasan , Khalili Nastaran , Rezaei Nima 
Published: August 2021

AbstractCancer immunotherapy has gained attention as the supreme therapeutic modality for the treatment of various malignancies. Adoptive T-cell therapy (ACT) is one of the most distinctive modalities of this therapeutic approach, which seeks to harness the potential of combating cancer cells by using autologous or allogenic tumor-specific T-cells. However, a plethora of circumstances must be optimized to produce functional, durable, and efficient T-cells. Recently, the potential of ACT has been further realized by the introduction of novel gene-editing platforms such as the CRISPR/Cas9 system; this technique has been utilized to create T-cells furnished with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR) that have precise tumor antigen recognition, minimal side effects and treatment-related toxicities, robust proliferation and cytotoxicity, and nominal exhaustion. Here, we aim to review and categorize the recent breakthroughs of genetically modified TCR/CAR T-cells through CRISPR/Cas9 technology and address the pearls and pitfalls of each method. In addition, we investigate the latest ongoing clinical trials that are applying CRISPR-associated TCR/CAR T-cells for the treatment of cancers.