bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidrug resistance genes screening of pancreatic ductal adenocarcinoma based on sensitivity profile to chemotherapeutic drugs
Authors: Zhao Bangbo , Qin Cheng , Li Zeru , Wang Yuanyang , Li Tianhao , Cao Hongtao , Yang Xiaoying , Li Tianyu , Wang Weibin 
Published: December 2022

Abstract
Backgrounds
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types and chemotherapeutic drug resistance is a stumbling block in improving the overall survival of PDAC patients. The nature of specific drug resistant subpopulation within pancreatic ductal adenocarcinoma is believed to be partly attributed to epithelial-mesenchymal transition (EMT) and cell stemness. Various PDAC cell lines show various degrees of resistance to chemotherapeutic agents including gemcitabine (GEM) and 5-fluorouracil (5-FU). In-depth understanding of drug resistance mechanisms and profile heterogeneities could lead to the development of novel and precise therapeutic strategies for addressing the chemo-resistant dilemma in PDAC patients.

Methods
Cytotoxicity assays were performed by CCK8 in ten common PDAC cell lines including AsPC-1, BxPC-3, CAPAN-1, CFPAC, HPAFII, MIA PaCa-2, PANC-1, Patu-8988, SW1990 and T3M4. RNA-seq data of the ten cell lines were downloaded from Cancer Cell Line Encyclopedia (CCLE) database and subsequently analyzed for differentially expressed genes (DEGs). Based on first-line chemotherapy regimens of PDAC, DEGs between resistant and sensitive cell lines were validated by qRT-PCR. Enriched pathways of differentially expressed genes between the resistant and sensitive cell lines were acquired by Metascape database.

Results
We found that the top two toxic drugs for PDAC cell lines were paclitaxel (PTX) and GEM. Among the ten PDAC cell lines, SW1990 was the most resistant PDAC cell line with the highest IC50 levels for three drugs, while MIA PaCa-2 and BxPC-3 were the most sensitive PDAC cell lines. Differential expression analysis revealed the highest number of DEGs associated with cisplatin (CIS) sensitivity up to 642 genes, of which 181 genes were upregulated and 461 genes were downregulated in CIS-resistant cell lines. The least number of DEGs are associated with GEM sensitivity, of which 37 genes were highly expressed in GEM-resistant PDAC cell lines and 25 genes were lowly expressed. Enrichment analysis of the DEGs revealed that pathways associated with drug resistance were mainly extracellular matrix and cell–cell junction related pathways.

Conclusions
PDAC cell lines showed diverse sensitivities to commonly used chemotherapeutic agents, which was caused by differential gene expression between the resistant and sensitive cell lines. The heterogeneity and its associated genes were enriched in extracellular matrix and cell–cell junction related pathways. Our study first portrayed the sensitivity profile to chemotherapeutic drugs of PDAC, which would benefit the chemoresistance mechanism study by reemphasizing the vital role of extracellular matrix and cell–cell junction related pathways and helping the selection of suitable PDAC cell lines.
Therapeutic efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and chloroquine and dihydroartemisinin-piperaquine for uncomplicated Plasmodium vivax infection in Ethiopia
Authors: Assefa Ashenafi , Mohammed Hussein , Anand Anjoli , Abera Adugna , Sime Heven , Minta Anna A. , Tadesse Mekonnen , Tadesse Yehualashet , Girma Samuel , Bekele Worku , Etana Kebede , Alemayehu Bereket Hailegiorgis , Teka Hiwot , Dilu Dereje , Haile Mebrahtom , Solomon Hiwot , Moriarty Leah F. , Zhou Zhiyong , Svigel Samaly Souza , Ezema Bryan , Tasew Geremew , Woyessa Adugna , Hwang Jimee , Murphy Matthew 
Published: December 2022

Abstract
Background
Routine monitoring of anti-malarial drugs is recommended for early detection of drug resistance and to inform national malaria treatment guidelines. In Ethiopia, the national treatment guidelines employ a species-specific approach. Artemether-lumefantrine (AL) and chloroquine (CQ) are the first-line schizonticidal treatments for Plasmodium falciparum and Plasmodium vivax, respectively. The National Malaria Control and Elimination Programme in Ethiopia is considering dihydroartemisinin-piperaquine (DHA/PPQ) as an alternative regimen for P. falciparum and P. vivax.

Methods
The study assessed the clinical and parasitological efficacy of AL, CQ, and DHA/PPQ in four arms. Patients over 6 months and less than 18 years of age with uncomplicated malaria mono-infection were recruited and allocated to AL against P. falciparum and CQ against P. vivax. Patients 18 years or older with uncomplicated malaria mono-infection were recruited and randomized to AL or dihydroartemisinin-piperaquine (DHA/PPQ) against P. falciparum and CQ or DHA/PPQ for P. vivax. Patients were followed up for 28 (for CQ and AL) or 42 days (for DHA/PPQ) according to the WHO recommendations. Polymerase chain reaction (PCR)-corrected and uncorrected estimates were analysed by Kaplan Meier survival analysis and per protocol methods.

Results
A total of 379 patients were enroled in four arms (n = 106, AL-P. falciparum; n = 75, DHA/PPQ- P. falciparum; n = 142, CQ-P. vivax; n = 56, DHA/PPQ-P. vivax). High PCR-corrected adequate clinical and parasitological response (ACPR) rates were observed at the primary end points of 28 days for AL and CQ and 42 days for DHA/PPQ. ACPR rates were 100% in AL-Pf (95% CI: 96–100), 98% in CQ-P. vivax (95% CI: 95–100) at 28 days, and 100% in the DHA/PPQ arms for both P. falciparum and P. vivax at 42 days. For secondary endpoints, by day three 99% of AL-P. falciparum patients (n = 101) cleared parasites and 100% were afebrile. For all other arms, 100% of patients cleared parasites and were afebrile by day three. No serious adverse events were reported.

Conclusion
This study demonstrated high therapeutic efficacy for the anti-malarial drugs currently used by the malaria control programme in Ethiopia and provides information on the efficacy of DHA/PPQ for the treatment of P. falciparum and P. vivax as an alternative option.
Low dimensional nanomaterials for treating acute kidney injury
Authors: Nie Yuanpeng , Wang Liying , You Xinru , Wang Xiaohua , Wu Jun , Zheng Zhihua 
Published: December 2022

AbstractAcute kidney injury (AKI) is one of the most common severe complications among hospitalized patients. In the absence of specific drugs to treat AKI, hemodialysis remains the primary clinical treatment for AKI patients. AKI treatment has received significant attention recently due to the excellent drug delivery capabilities of low-dimensional nanomaterials (LDNs) and their unique therapeutic effects. Diverse LDNs have been proposed to treat AKI, with promising results and the potential for future clinical application. This article aims to provide an overview of the pathogenesis of AKI and the recent advances in the treatment of AKI using different types of LDNs. In addition, it is intended to provide theoretical support for the design of LDNs and implications for AKI treatment.
Graphical Abstract
Cost-effectiveness analysis of dapagliflozin in the management of heart failure with reduced ejection fraction (HFrEF): a systematic review
Authors: Mohammadnezhad Ghader , Azadmehr Behniya , Mirheidari Mehdi , Yousefi Nazila 
Published: December 2022

Abstract
Objectives
This study was aimed to systematically review published economic studies to determine whether dapagliflozin, a sodium-glucose co-transporter inhibitor, plus standard care therapy (SCT) is cost-effective in heart failure with reduced ejection fraction (HFrEF).

Method
We searched relevant keywords in PubMed, Scopus, Web of science, and Google Scholar to find related articles. Costs, QALYs, ICERs were extracted from eligible studies.

Results
Ten studies finally included in the systematic review. The results of quality assessment of the study showed that a reasonable quality of all studies. Incremental QALYs were in favor of dapagliflozin plus SCT treatment regimen. In all the studies, the incremental costs per QALY was below the willingness-to-pay (WTP) threshold with the exception of one study in United Kingdom which the ICER and WTP were $83,650 and $50,000. All the studies determined the National Health Care perspective. The highest and lowest ICERs were $83,650 and $1991 per QALY in United Kingdom and Thailand, respectively.

Conclusion
Results of cost-effectiveness analyses showed that adjunct dapagliflozin plus SCT is cost-effective compared to SCT alone despite the additional costs of the drug. Finally it can be concluded that dapagliflozin is a worldwide cost-effective as an adjunct medicine in HFrEF management.
“I am not shy anymore”: A qualitative study of the role of an interactive mHealth intervention on sexual health knowledge, attitudes, and behaviors of South African adolescents with perinatal HIV
Authors: Bergam Scarlett , Sibaya Thobekile , Ndlela Nompumelelo , Kuzwayo Mpume , Fomo Messaline , Goldstein Madeleine H. , Marconi Vincent C. , Haberer Jessica E. , Archary Moherndran , Zanoni Brian C. 
Published: December 2022

Abstract
Background
South Africa has one of the highest burdens of adolescents with perinatally-acquired HIV (APHIV) in the world. APHIV in South Africa have limited access to sexual and reproductive health (SRH) education and services specific to their HIV status. When lacking comprehensive SRH education, APHIV are prone to sexual risk behaviors that can lead to unintended pregnancy, sexually transmitted infections, and HIV transmission. The use of mHealth interventions has been shown to deliver information, foster social support, and improve decision-making skills. In this study, we evaluate how an mHealth intervention influences sexual health knowledge and behaviors in APHIV.

Methods
We purposively enrolled adolescents from the intervention arm of a randomized clinical trial assessing a multi-module, moderated WhatsApp-based intervention—Interactive Transition Support for Adolescents Living with HIV (InTSHA)—within a government supported clinic in KwaMashu, an urban township of KwaZulu-Natal, South Africa. We conducted in-depth interviews based on World Health Organization guidelines for asking adolescents about SRH. We thematically analyzed data through an iterative, team-based coding approach combining deductive and inductive elements to contextualize SRH attitudes, knowledge, and behaviors before and after receiving the InTSHA intervention.

Results
Of the 21 participants, 13 (61.9%) were female and the mean age was 16.6 years. Most participants reported first learning about SRH as young teenagers in school through non-targeted and negative ways, seeking clarification through peers and the internet rather than clinicians or caregivers. Participants reported that InTSHA provided a holistic perspective on relationships, gender, and sexuality specific to growing up with HIV in South Africa. They praised the ability to give and receive information from peers in a moderated setting through the mHealth intervention, building their confidence, decision-making skills, and communication with partners and caregivers throughout their everyday lives. Despite reporting some technological challenges, adolescents agreed that InTSHA was convenient, confidential, and user-friendly.

Conclusions
South African APHIV receive incomplete and conflicting sexual education from peers, caregivers, teachers, and technology that can be supplemented by mHealth curricula targeted for the unique needs of APHIV. Future, scaled-up mHealth interventions can lower SRH stigma by expanding access to sexual education and peer support, supplementing adolescents’ existing SRH education.
Hepatitis B and C viral coinfections and their association with HIV viral load suppression among HIV-1 infected patients on ART at Mekelle hospital, northern Ethiopia
Authors: Teame Gebrecherkos , Gebreyesus Araya , Tsegay Ephrem , Gebretsadik Mulu , Adane Kelemework 
Published: December 2022

AbstractBackgroundAlthough Ethiopia is endemic to viral hepatitis and HIV, data that could guide population-specific interventions are limited. In this study, we determined the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) and assessed their associations with HIV-1 viral load suppression among HIV-1 infected patients on antiretroviral therapy (ART) at Mekelle hospital in northern Ethiopia.MethodsBetween February and April 2020, blood samples were collected from 439 participants. Samples were screened for HBsAg and anti-HCV on the immunochromatographic test and confirmed using the Enzyme-Linked Immuno-sorbent assay (Beijing Wantai Co. China). HIV-1 viral load was quantified using reverse transcription-polymerase chain reaction (RT-PCR) on the Abbott platform. Binary and multivariable logistic regression was performed to identify potential predictors.ResultsOverall, 10% (44/439) and 3.6% (16/439) of the participants were coinfected with HBV and HCV, respectively. In a multivariate analysis, being illiterate (AOR = 6.57; 95% CI 1.04–41.6), and having a history of sexually transmitted infections (AOR = 4.44; 95% CI 1.31–15.0) and multiple sexual partners (AOR = 29.9; 95% CI 7.82–114.8) were associated with HBV infection. On the other hand, participants with a history of chronic non-communicable diseases (AOR = 10.6, 95% CI 1.61–70.1), and those reporting a history of sexually transmitted infections (AOR = 5.21, 95% CI 1.39–19.5) were more likely to be infected with HCV. In further analysis, HCV infection status was significantly associated with decreased viral load suppression rate (AOR = 7.14; 95% CI 2.18–23.3) whereas no significant association was observed with the HBV infection.ConclusionsThe HBV coinfection rate in our study is high and, as per WHO's standard, corresponds to a hyperendemic level. The HCV coinfection rate is also substantially high and urges attention given its influence on the viral load suppression of HIV patients on ART at our study site. Our findings suggest the need to adopt universal screening and vaccination of people with HIV against HBV and screening for HCV at our study site and in Ethiopia at large, which contributes to Ethiopia's progress towards the 2030 global target of reducing the HBV infection.
Abdominal obesity in COPD is associated with specific metabolic and functional phenotypes
Authors: Cruthirds Clayton L. , Deutz Nicolaas E. P. , Mizubuti Yani G. G. , Harrykissoon Rajesh I. , Zachria Anthony J. , Engelen Mariëlle P. K. J. 
Published: December 2022

Abstract
Background
Abdominal obesity (AO) is linked to reduced health status and mortality. While it is known that AO is prevalent in chronic obstructive pulmonary disease (AO-COPD), the specific metabolic and functional consequences associated with AO-COPD remain understudied.

Methods
We studied 199 older adults with COPD and 168 control subjects with and without AO and assessed visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry. VAT > 70th percentile of the control group qualified a subject as AO in a sex specific manner. We measured plasma concentrations and whole body production (WBP) rates of multiple amino acids to assess the metabolic profile. We assessed medical history, body composition by Dual-Energy X-ray Absorptiometry, muscle strength, and cognitive function. We performed statistics by analysis of covariance (p) and FDR (q) for multiple comparisons.

Results
AO-COPD subjects had 27% more VAT (q < 0.01) than AO-Control subjects despite correction for BMI. Branched-chain amino acid concentrations and WBP rates were generally elevated in AO-COPD but whole body clearance rate was only elevated in COPD. Metabolic syndrome comorbidities (p < 0.01) and systemic inflammation (P < 0.05) were most prevalent in the AO-COPD group. Muscle strength was reduced in COPD subjects (p < 0.001), but partially preserved when combined with AO. Cognitive dysfunction and mood disturbances were present in COPD subjects (p < 0.001) with worst performers in AO-COPD (q < 0.05).

Conclusion
The presence of AO is associated with specific metabolic and functional phenotypes in COPD.
Clinical trial registry Trial registration ClinicalTrials.gov. In the present paper, we report an analysis of the baseline measurements of COPD subjects and healthy controls from the study numbers: NCT01787682, NCT01787682, NCT02157844, NCT02082418, NCT02065141, NCT02770092, NCT02908425, NCT03159390, NCT02780219, NCT03327181, NCT03796455, NCT04928872, NCT04461236, NCT01173354, NCT01154400.
The association between breastfeeding and childhood obesity/underweight: a population-based birth cohort study with repeated measured data
Authors: Li Weiqin , Yuan Jiarong , Wang Leishen , Qiao Yijuan , Liu Enqing , Wang Shuo , Leng Junhong 
Published: December 2022

Abstract
Background
The impact of breastfeeding on childhood obesity has long been under debate, with most research showing significant association, and others showing weak or no association between breastfeeding and childhood obesity. What’s more, almost all of the previous studies focused on the association between breastfeeding and childhood obesity, and no studies have assessed the association between breastfeeding and childhood underweight.
This study aimed to examine the association between breastfeeding and childhood obesity as well as childhood underweight from 1 to 6 years old.

Methods
A retrospective population-based cohort study of 59,564 children born between May 2009 and April 2013 in China was conducted using the healthcare records data from the Tianjin Maternal and Child Healthcare System. Information on infant breastfeeding (exclusive breastfeeding, mixed feeding, and exclusive formula feeding) within 6 months old and childhood growth (6 times of repeated measured weight and height from 1 to 6 years old) was collected. Multinomial logistic regression was used to test the potential associations between infant feeding modalities and childhood growth (underweight, normal weight and obesity).

Results
Compared with exclusive formula feeding, breastfeeding was inversely associatied with childhood obesity from 2 to 6 years old, and there was a trend from mixed feeding to exclusive breastfeeding (Ptrend < 0.05). The largest association with obesity was displayed at 3 years old, with the multivariable adjusted odds ratios (ORs) for exclusive formula feeding, mixed feeding and exclusive breastfeeding of 1.00, 0.62 (95% CI 0.49, 0.80) and 0.57 (95% CI 0.44, 0.74) (Ptrend = 0.001), respectively. Compared with exclusive breastfeeding, exclusive formula feeding may increase the risk of childhood underweight at 3 and 5 years old.

Conclusions
Breastfeeding was inversely associated with the risk of childhood obesity from 2 to 6 years old, and there was a trend from mixed feeding to exclusive breastfeeding. Infant exclusive formula feeding might be a risk factor for childhood underweight at preschool time.
High-throughput and automatic structural and developmental root phenotyping on Arabidopsis seedlings
Authors: Fernandez Romain , Crabos Amandine , Maillard Morgan , Nacry Philippe , Pradal Christophe 
Published: December 2022

Abstract
Background
High-throughput phenotyping is crucial for the genetic and molecular understanding of adaptive root system development. In recent years, imaging automata have been developed to acquire the root system architecture of many genotypes grown in Petri dishes to explore the Genetic x Environment (GxE) interaction. There is now an increasing interest in understanding the dynamics of the adaptive responses, such as the organ apparition or the growth rate. However, due to the increasing complexity of root architectures in development, the accurate description of the topology, geometry, and dynamics of a growing root system remains a challenge.

Results
We designed a high-throughput phenotyping method, combining an imaging device and an automatic analysis pipeline based on registration and topological tracking, capable of accurately describing the topology and geometry of observed root systems in 2D + t. The method was tested on a challenging Arabidopsis seedling dataset, including numerous root occlusions and crossovers. Static phenes are estimated with high accuracy ($$R^2=0.996$$

R
2

=
0.996

and $$0.923$$

0.923

for primary and second-order roots length, respectively). These performances are similar to state-of-the-art results obtained on root systems of equal or lower complexity. In addition, our pipeline estimates dynamic phenes accurately between two successive observations ($$R^2=0.938$$

R
2

=
0.938

for lateral root growth).

Conclusions
We designed a novel method of root tracking that accurately and automatically measures both static and dynamic parameters of the root system architecture from a novel high-throughput root phenotyping platform. It has been used to characterise developing patterns of root systems grown under various environmental conditions. It provides a solid basis to explore the GxE interaction controlling the dynamics of root system architecture adaptive responses. In future work, our approach will be adapted to a wider range of imaging configurations and species.
Radiotherapy modulates tumor cell fate decisions: a review
Authors: Chen Haoran , Han Zhongyu , Luo Qian , Wang Yi , Li Qiju , Zhou Lisui , Zuo Houdong 
Published: December 2022

AbstractCancer has always been a worldwide problem, and the application of radiotherapy has greatly improved the survival rate of cancer patients. Radiotherapy can modulate multiple cell fate decisions to kill tumor cells and achieve its therapeutic effect. With the development of radiotherapy technology, how to increase the killing effect of tumor cells and reduce the side effects on normal cells has become a new problem. In this review, we summarize the mechanisms by which radiotherapy induces tumor cell apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis, autophagy, senescence, mitotic catastrophe, and cuproptosis. An in-depth understanding of these radiotherapy-related cell fate decisions can greatly improve the efficiency of radiotherapy for cancer.