bluuebunny/crossref_metadata_2025_split huggingface dataset:
The germline/somatic DNA damage repair gene mutations modulate the therapeutic response in Chinese patients with advanced pancreatic ductal adenocarcinoma
Authors: Shui Lin , Li Xiaofen , Peng Yang , Tian Jiangfang , Li Shuangshuang , He Du , Li Ang , Tian Bole , Li Mao , Gao Heli , An Ning , Yi Cheng , Cao Dan 
Published: July 2021

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with molecular heterogeneity, inducing differences in biological behavior, and therapeutic strategy. NGS profiles of pathogenic alterations in the Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precision medicine.

Methods
The NGS profiles were performed on resected tissues from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics and survival status were collected. The Kaplan–Meier survival analyses were performed by the R version 3.6.1.

Results
The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed a worse OS than KRAS wild-type (p = 0.048). DDR pathogenic deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n = 9, 4.62%), ATM (n = 8, 4.10%) and RAD50 genes (n = 3, 1.54%). No significance of OS between patients with or without DDR mutations (p = 0.88). But DDR mutation was an independent prognostic factor for survival analysis of advanced PDAC patients (p = 0.032). For DDR mutant patients, treatment with platinum-based chemotherapy (p = 0.0096) or olaparib (p = 0.018) respectively improved the overall survival. No statistical difference between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significantly improved OS to DDR-mutated patients than the naive DDR group (p = 0.14).

Conclusions
In this retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy in Chinese patients. However, the value of DDR mutation in the prediction of hypermutation status and the sensitivity to the PD-1 blockade needed further investigation.
Bone quality and quantity of the mandibular symphyseal region in autogenous bone grafting using cone-beam computed tomography: a cross-sectional study
Authors: Safi Yaser , Amid Reza , Kadkhodazadeh Mahdi , Mortazavi Hamed , Sharifi Mohamad Payam , Gandomi Shiva 
Published: July 2021

Abstract
Background
Bone volume plays a pivotal role in the success of dental implant treatment. Autogenous bone grafts should be harvested from reliable sites in the maxillofacial region. This study sought to assess the quantity and quality of bone in the mandibular symphysis for autogenous bone graft harvesting using cone-beam computed tomography (CBCT).

Methods
This cross-sectional study evaluated the CBCT scans of 78 adults presenting to three oral and maxillofacial radiology centers. The vertical (VD) and horizontal (HD) alveolar bone dimensions, cortical thickness (CT), and cancellous to cortical bone ratio (C/C) were measured in the interforaminal region of the mandible at the sites of central incisor to first premolar teeth. The interforaminal distance (ID) and the anterior loop length were also measured. Nonparametric statistical tests were used to analyze the data with respect to sex, age, and tooth position.

Results
The median VD, HD, and CT of the symphysis were 20.21 (3.26), 4.13 (0.37), and 2.25 (0.23) mm, respectively. The median C/C was 1.51 (0.11). The median ID was 52.24 (8.24) mm, and the median anterior loop length was 1.82 (1.06) mm. Significant differences were observed in all parameters among different teeth. Most of the measured parameters were greater in males compared with females. There were significant differences in ID, VD, and CT between different age groups.

Conclusions
The quantity and quality of the available bone in the mandibular symphysis for bone graft harvesting vary by gender, age, and harvesting site, necessitating careful preoperative evaluation.
Effectiveness of peer counseling and membership in breastfeeding support groups in promoting optimal breastfeeding behaviors in the Philippines
Authors: Saniel Ofelia P. , Pepito Veincent Christian F. , Amit Arianna Maever L. 
Published: July 2021

Abstract
Background
The prevalence of early initiation of breastfeeding and exclusive breastfeeding (EBF) at 6 months remain low in the Philippines. To help meet the 90% early initiation of breastfeeding target and to improve infant and young child feeding practices in the Philippines, the Millennium Development Goals - Fund 2030 Joint Programme (JP) on Ensuring Food Security and Nutrition for Children 0–24 months old was implemented. We aimed to determine the effectiveness of visits by peer counselors during pregnancy and after delivery, and membership in breastfeeding support groups in promoting these optimal breastfeeding practices.

Methods
We used data from the Endline Survey of the JP to study the effects of prenatal and postnatal peer counselor visits, and membership in breastfeeding support groups, and their possible interactions with initiation of breastfeeding within 1 hour of birth among children aged 0 to 24 months and EBF at 6 months among children aged 6 to 24 months, while adjusting for confounding. We used logistic regression methods for survey data to assess these associations.

Results
Of the 2343 mother-infant pairs, only 1500 (63.1%) practiced early initiation of breastfeeding. Of the 1865 children aged 6 months or older, only 621 (34.7%) were exclusively breastfed at 6 months. After adjusting for confounding variables, there was no strong evidence that peer counselor visits were associated with early initiation or EBF at 6 months. However, members of breastfeeding support groups had 1.49 times higher odds of early initiation of breastfeeding (95% CI [Confidence Interval] 1.12, 1.98) and 1.65 times higher odds of EBF (95% CI 1.20, 2.24) compared to those who were not members of breastfeeding support groups. There was no interaction between the different exposure variables and early initiation and EBF at 6 months.

Conclusions
Our findings suggest breastfeeding support groups may be institutionalized to promote both early initiation of breastfeeding and EBF in the Philippines, while the role of peer counselors in promoting optimal breastfeeding behaviors should be further reviewed. Our suggestion to integrate non-healthcare professionals to promote early initiation of breastfeeding and EBF could be tested in future intervention studies.
A cassava common mosaic virus vector for virus-induced gene silencing in cassava
Authors: Tuo Decai , Zhou Peng , Yan Pu , Cui Hongguang , Liu Yang , Wang He , Yang Xiukun , Liao Wenbin , Sun Di , Li Xiaoying , Shen Wentao 
Published: July 2021

AbstractBackgroundCassava is an important crop for food security and industry in the least-developed and developing countries. The completion of the cassava genome sequence and identification of large numbers of candidate genes by next-generation sequencing provide extensive resources for cassava molecular breeding and increase the need for rapid and efficient gene function analysis systems in cassava. Several plant virus-induced gene silencing (VIGS) systems have been developed as reverse genetic tools for rapid gene function analysis in cassava. However, these VIGS vectors could cause severe viral symptoms or inefficient gene silencing.ResultsIn this study, we constructed agroinfection-compatible infectious cDNA clones of cassava common mosaic virus isolate CM (CsCMV-CM, genusPotexvirus, family Alphaflexiviridae) that causes systemic infection with mild symptoms in cassava. CsCMV-CM was then modified to a viral vector carrying the Nimble cloning frame, which facilitates the rapid and high-throughput cloning of silencing fragments into the viral genome. The CsCMV-based vector successfully silencedphytoene desaturase(PDS) andmagnesium chelatase subunit I(ChlI) in different cassava varieties andNicotiana benthamiana. The silencing of theChlIgene could persist for more than two months.ConclusionsThis CsCMV-based VIGS system provides a new tool for rapid and efficient gene function studies in cassava.
Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth
Authors: Buccarelli Mariachiara , D’Alessandris Quintino Giorgio , Matarrese Paola , Mollinari Cristiana , Signore Michele , Cappannini Andrea , Martini Maurizio , D’Aliberti Pierluigi , De Luca Gabriele , Pedini Francesca , Boe Alessandra , Biffoni Mauro , Pallini Roberto , Ricci-Vitiani Lucia 
Published: July 2021

Abstract
Background
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, characterized by a poor prognosis mainly due to recurrence and therapeutic resistance. It has been widely demonstrated that glioblastoma stem-like cells (GSCs), a subpopulation of tumor cells endowed with stem-like properties is responsible for tumor maintenance and progression. Moreover, it has been demonstrated that GSCs contribute to GBM-associated neovascularization processes, through different mechanisms including the transdifferentiation into GSC-derived endothelial cells (GdECs).

Methods
In order to identify druggable cancer-related pathways in GBM, we assessed the effect of a selection of 349 compounds on both GSCs and GdECs and we selected elesclomol (STA-4783) as the most effective agent in inducing cell death on both GSC and GdEC lines tested.

Results
Elesclomol has been already described to be a potent oxidative stress inducer. In depth investigation of the molecular mechanisms underlying GSC and GdEC response to elesclomol, confirmed that this compound induces a strong increase in mitochondrial reactive oxygen species (ROS) in both GSCs and GdECs ultimately leading to a non-apoptotic copper-dependent cell death. Moreover, combined in vitro treatment with elesclomol and the alkylating agent temozolomide (TMZ) enhanced the cytotoxicity compared to TMZ alone. Finally, we used our experimental model of mouse brain xenografts to test the combination of elesclomol and TMZ and confirmed their efficacy in vivo.

Conclusions
Our results support further evaluation of therapeutics targeting oxidative stress such as elesclomol with the aim of satisfying the high unmet medical need in the management of GBM.
Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen
Authors: Ma Penglin , Liu Jingtao , Shen Feng , Liao Xuelian , Xiu Ming , Zhao Heling , Zhao Mingyan , Xie Jing , Wang Peng , Huang Man , Li Tong , Duan Meili , Qian Kejian , Peng Yue , Zhou Feihu , Xin Xin , Wan Xianyao , Wang ZongYu , Li Shusheng , Han Jianwei , Li Zhenliang , Ding Guolei , Deng Qun , Zhang Jicheng , Zhu Yue , Ma Wenjing , Wang Jingwen , Kang Yan , Zhang Zhongheng 
Published: July 2021

Abstract
Background
Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class.

Methods
Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset.

Results
A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion.

Conclusions
Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.
A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)
Authors: Kristensen Tilde , Birn Henrik , Ivarsen Per 
Published: July 2021

Abstract
Background
Minimal change nephropathy (MCN) is a common cause of nephrotic syndrome in both adults and children. International guidelines recommend treatment with prednisolone 1 mg/kg/day to adults. This dose is derived from an empirically established dose in children, although children generally attain remission faster and relapse more rapidly than adults. Prednisolone is associated with multiple and serious adverse events. Activated vitamin D has been shown to reduce albuminuria in other glomerular renal diseases with a minimum of adverse events. This study tests the hypothesis that a new treatment regimen in MCN combining reduced dose prednisolone and active vitamin D is as efficient in inducing remission and has fewer and less severe adverse events than standard prednisolone. Furthermore, we aim to establish models allowing for more personalized medicine based on assessment of the individual’s prednisolone metabolism.

Methods
A randomised controlled multicentre non-inferior unblinded trial including 96 adult, incident patients with biopsy-proven MCN, albuminuria > 3 g/day, and an estimated glomerular filtration rate (eGFR) > 30 ml/min from renal departments in Denmark. Patients are randomised to standard prednisolone (1 mg/kg/day) or reduced prednisolone (0.5 mg/kg/day) and alfacalcidol (0.5 μg/day). The primary outcome is the rate of remissions after 16 weeks and the time from diagnosis to remission. The study will include a saliva test to characterise prednisolone pharmacokinetics and compare them to genetic variations in specific liver enzymes responsible for prednisolone metabolism.

Discussion
Reducing the prednisolone dose is expected to reduce the number of severe adverse events. This study will examine if reduced prednisolone dose with active vitamin D but without additional immunosuppression is feasible in the treatment of MCN and will reduce the number of adverse events. The findings can potentially change current guidelines for treatment of MCN in adults. Additional outcomes on inter-individual pharmacokinetic and metabolic variations may allow for a more personalised treatment strategy.

Trial registration
EudraCT 2017-001206-16, ClinicalTrials.gov NCT03210688. Registered on June 3, 2017.
Voltage-sensitive sodium channel (Vssc) mutations associated with pyrethroid insecticide resistance in Aedes aegypti (L.) from two districts of Jeddah, Kingdom of Saudi Arabia: baseline information for a Wolbachia release program
Authors: Endersby-Harshman Nancy M. , Ali AboElgasim , Alhumrani Basim , Alkuriji Mohammed Abdullah , Al-Fageeh Mohammed B. , Al-Malik Abdulaziz , Alsuabeyl Mohammed S. , Elfekih Samia , Hoffmann Ary A. 
Published: July 2021

AbstractBackgroundDengue suppression often relies on control of the mosquito vector,Aedes aegypti, through applications of insecticides of which the pyrethroid group has played a dominant role. Insecticide resistance is prevalent inAe.aegyptiaround the world, and the resulting reduction of insecticide efficacy is likely to exacerbate the impact of dengue. Dengue has been a public health problem in Saudi Arabia, particularly in Jeddah, since its discovery there in the 1990s, and insecticide use for vector control is widespread throughout the city. An alternative approach to insecticide use, based on blocking dengue transmission in mosquitoes by the endosymbiontWolbachia, is being trialed in Jeddah following the success of this approach in Australia and Malaysia. Knowledge of insecticide resistance status of mosquito populations in Jeddah is a prerequisite for establishing aWolbachia-based dengue control program as releases ofWolbachiamosquitoes succeed when resistance status of the release population is similar to that of the wild population.MethodsWHO resistance bioassays of mosquitoes with deltamethrin, permethrin and DDT were used in conjunction with TaqMan®SNP Genotyping Assays to characterize mutation profiles ofAe.aegypti.ResultsScreening of the voltage-sensitive sodium channel (Vssc), the pyrethroid target site, revealed mutations at codons 989, 1016 and 1534 inAe.aegyptifrom two districts of Jeddah. The triple mutant homozygote (1016G/1534C/989P) was confirmed from Al Safa and Al Rawabi. Bioassays with pyrethroids (Type I and II) and DDT showed that mosquitoes were resistant to each of these compounds based on WHO definitions. An association betweenVssc mutations and resistance was established for the Type II pyrethroid, deltamethrin, with one genotype (989P/1016G/1534F) conferring a survival advantage over two others (989S/1016V/1534C and the triple heterozygote). An indication of synergism of Type I pyrethroid activity with piperonyl butoxide suggests that detoxification by cytochrome P450s accounts for some of the pyrethroid resistance response inAe.aegyptipopulations from Jeddah.ConclusionsThe results provide a baseline for monitoring and management of resistance as well as knowledge ofVssc genotype frequencies required inWolbachiarelease populations to ensure homogeneity with the target field population.Vssc mutation haplotypes observed show some similarity with those fromAe.aegyptiin southeast Asia and the Indo-Pacific, but the presence of the triple mutant haplotype in three genotypes indicates that the species in this region may have a unique population history.Graphical Abstract
Facility assessment and qualitative analysis of health worker perspectives on neonatal health in Malawi
Authors: Kinshella Mai-Lei Woo , Nyondo-Mipando Alinane Linda , Dube Queen , Goldfarb David M. , Kawaza Kondwani 
Published: July 2021

Abstract
Objectives
The “Integrating a neonatal healthcare package for Malawi” (IMCHA#108030) project conducted mixed-methods to understand facility-based implementation factors for newborn health innovations in low-resourced health settings. The objective of the two datasets was to evaluate: (a) capacity of quality newborn care in three districts in southern Malawi, and (b) barriers and facilitators the scale up of bubble continuous positive airway pressure (CPAP), a newborn health innovation to support babies with respiratory distress.

Data description
The Integrated Maternal, Neonatal and Child Quality of Care Assessment and Improvement Tool (version April-2014) is a standardized facility assessment tool developed by the World Health Organization (WHO) that examines quality as well as quantity and availability. The facility survey is complemented by a qualitative dataset of illustrative quotes from health service providers and supervisors on bubble CPAP implementation factors. Research was conducted in one primary health centre (facility assessment only), three district-level hospitals (both) and a tertiary hospital (qualitative only) in southern Malawi. These datasets may be used by other researchers for insights into health systems of low-income countries and implementation factors for the roll-out of neonatal health innovations as well as to frame future research questions or preliminary exploratory research on similar topics.
Recurrent COVID-19 infection in a health care worker: a case report
Authors: Garg Jaya , Agarwal Jyotsna , Das Anupam , Sen Manodeep 
Published: July 2021

Abstract
Background
Recurrent coronavirus disease 2019 (COVID-19) infection is an emerging problem and may prove to be one of the greatest problems in controlling the pandemic in the future. Recurrent infections can be due to reactivation of dormant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or reinfection with similar or different strains of SARS-CoV-2.

Case presentation
Here we present an interesting case of a health care worker working as a laboratory assistant at a COVID-19 laboratory who developed recurrent COVID-19 infection. He did not develop an immune response after the first episode of COVID-19; however, immunoglobulin G (IgG) antibodies were detected after the second episode.

Conclusions
Through this case, we discuss the concept of reactivation and reinfection in the post-COVID period. We suggest that standard guidelines should be established to check for viral shedding and immune response among cured cases of COVID-19 after discharge via serial real-time polymerase chain reaction (RT-PCR) testing and IgG antibody detection. Further, strict hygiene practices should be stressed to these patients with possibility of COVID-19 recurrence.
Cerebral venous thrombosis in a patient with Down syndrome and coronavirus disease 2019: a case report
Authors: Robayo-Amortegui Henry , Valenzuela-Faccini Natalia , Quecano-Rosas Cesar , Zabala-Muñoz Darlyng , Perez-Garzon Michel 
Published: July 2021

Abstract
Background
The new coronavirus disease 2019 pandemic has spread throughout most of the world. Cerebral venous thrombosis is a rare thromboembolic disease that can present as an extrapulmonary complication in coronavirus disease 2019 infection.

Case presentation
We report the case of a Hispanic woman with Down syndrome who has coronavirus disease 2019 and presents as a complication extensive cerebral venous thrombosis.

Conclusions
Cerebral venous thrombosis is a rare thromboembolic disease that can present as an extrapulmonary complication in coronavirus disease 2019 infection. In the absence of clinical and epidemiological data, it is important to carry out further investigation of the risk factors and pathophysiological causes related to the development of cerebrovascular thrombotic events in patients with Down syndrome with coronavirus disease 2019 infection.