bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective review of serious infections in febrile infants 0–90 days old
Authors: Khoo Zi Xean , Chua Cherie , Yap Zhi Min , Koh Janine Cynthia , Chong Sarah Xin , Wijedasa Nishanti Han Ying , Peng Kaitian , Chong Chia Yin 
Published: June 2021

Background: Fever without source in infants is a common clinical problem that accounts for many ambulatory care visits and hospitalisations. Currently, there is no reliable method of identifying those at risk of serious infection (SI). Objective: The goal of this study was to determine the incidence and identify the predictors of SI in febrile infants who presented to the emergency department (ED). Methods: This was a single-centre retrospective cohort study of children presenting to a Singapore tertiary hospital paediatric unit between 1 July 2018 and 31 December 2018. Children were included if they were aged 0–90 days and presented to the ED with a fever. SI was defined as urinary tract infection (UTI), sepsis, bacteraemia, meningitis (viral and bacterial), enterocolitis, osteomyelitis, abscess or pneumonia. Results: Of the 659 infants, 161 (24.4%) were diagnosed with SI. Meningitis (49.7%) was the most common SI, followed by UTI (45.3%), enterocolitis (5.6%), sepsis (3.1%) and bacteraemia (2.5%). Factors significantly associated with SI were aged 29–60 days, male sex, Severity Index Score (SIS) <10, absolute neutrophil counts >10×109/L, C-reactive protein (CRP) >20 mg/L and procalcitonin >0.5 ng/mL. Multivariate analysis entering all these items retained only male sex, SIS <10 and CRP >20. Conclusion: Among hospitalised infants aged 0–90 days, the incidence of SI was 24.4%, and invasive bacterial infection was 0.6%. Meningitis was the most common SI followed by UTI. SIS and CRP can be used to predict SI in infants <90 days old.
Direct P70S6K1 inhibition to replace dexamethasone in synergistic combination with MCL-1 inhibition in multiple myeloma
Authors: Spaan Ingrid , Timmerman Laura M. , Kimman Thomas , Slomp Anne , Cuenca Marta , van Nieuwenhuijzen Niels , Moesbergen Laura M. , Minnema Monique C. , Raymakers Reinier A. , Peperzak Victor 
Published: June 2021

AbstractNovel combination therapies have markedly improved the lifespan of patients with multiple myeloma (MM), but drug resistance and disease relapse remain major clinical problems. Dexamethasone and other glucocorticoids are a cornerstone of conventional and new combination therapies for MM, although their use is accompanied by serious side effects. We aimed to uncover drug combinations that act in synergy and, as such, allow reduced dosing while remaining effective. Dexamethasone and the myeloid cell leukemia 1 (MCL-1) inhibitor S63845 (MCL-1i) proved the most potent combination in our lethality screen and induced apoptosis of human myeloma cell lines (HMCLs) that was 50% higher compared with an additive drug effect. Kinome analysis of dexamethasone-treated HMCLs revealed a reduction in serine/threonine peptide phosphorylation, which was predicted to result from reduced Akt activity. Biochemical techniques showed no dexamethasone-induced effects on FOXO protein or GSK3 but did show a 50% reduction in P70S6K phosphorylation, downstream of the Akt-mTORC1 axis. Replacing dexamethasone by the P70S6K1 isoform-specific inhibitor PF-4708671 (S6K1i) revealed similar and statistically significant synergistic apoptosis of HMCLs in combination with MCL-1i. Interestingly, apoptosis induced by the P70S6K1i and MCL-1i combination was more-than-additive in all 9 primary MM samples tested; this effect was observed for 6 of 9 samples with the dexamethasone and MCL-1i combination. Toxicity on stem and progenitor cell subsets remained minimal. Combined, our results show a strong rationale for combination treatments using the P70S6K inhibitor in MM. Direct and specific inhibition of P70S6K may also provide a solution for patients ineligible or insensitive to dexamethasone or other glucocorticoids.
A novel approach to minimally invasive hysterectomy without the use of a uterine manipulator: Kamran’s TLH
Authors: Gendia Ahmed M. , Donlon Noel E. , Kamran Waseem M. 
Published: June 2021

Abstract
Background
Hysterectomy remains one of the most common major gynaecological procedures, with total laparoscopic hysterectomy (TLH) now established as the technique of choice over conventional open approaches. This approach depends on the use of a uterine manipulator to facilitate uterine retraction and colpotomy. This study describes a novel approach in performing total laparoscopic hysterectomy without the use of uterine manipulator or vaginal tubes and reports the intra- and postoperative outcome of this technique.

Methods
A single-centre retrospective analysis of patients who underwent TLH without uterine manipulator or vaginal tube “Kamran’s TLH” for benign conditions was performed from January 2017 to October 2019. Data collected included patients’ demographics, intraoperative finding and postoperative course.

Results
A total of eighty-six hysterectomies were performed utilizing the Kamran’s TLH (KTLH) approach. Mean age was 52.2 (± 11) years old and BMI was 28.2 (± 7). TLH with bilateral salpingo-oophorectomy was performed in 63 (73.3%) patients and TLH with preservation of ovaries in 23 (26.7%) patients. Mean operative time was 64.7 (± 27.9) min and estimated bloods loss was 46.2 (± 54.6) ml. No intraoperative complications were recorded and there was no conversion to open surgery. Only one patient required readmission and surgery for vaginal vault dehiscence during their postoperative course.

Conclusion
Uterine manipulator is a key component in performing laparoscopic hysterectomy. However, our approach demonstrated that TLH can be safely performed without the use of any uterine or vaginal manipulation.
Characterization of contrasting rice (Oryza sativa L.) genotypes reveals the Pi-efficient schema for phosphate starvation tolerance
Authors: Kumar Suresh , Pallavi  , Chugh Chetna , Seem Karishma , Kumar Santosh , Vinod K. K. , Mohapatra Trilochan 
Published: June 2021

AbstractBackgroundPhosphorus (P), being one of the essential components of nucleic acids, cell membranes and enzymes, indispensable for diverse cellular processes like photosynthesis/carbohydrate metabolism, energy production, redox homeostasis and signaling. Crop yield is severely affected due to Phosphate (Pi) deficiency; and to cope with Pi-deficiency, plants have evolved several strategies. Some rice genotypes are compatible with low Pi availability, whereas others are sensitive to Pi deficiency. However, the underlying molecular mechanism for low Pi tolerance remains largely unexplored.ResultSeveral studies were carried out to understand Pi-deficiency responses in rice at seedling stage, but few of them targeted molecular aspects/responses of Pi-starvation at the advanced stage of growth. To delineate the molecular mechanisms for low Pi tolerance, a pair of contrasting rice (Oryza sativaL.) genotypes [viz.Pusa-44 (Pi-deficiency sensitive) and its near isogenic line (NIL-23, Pi-deficiency tolerant) harboringPhosphorus uptake 1(Pup1) QTL from anauslandrace Kasalath] were used. Comparative morphological, physiological, and biochemical analyses confirmed some of the well-known findings. Transcriptome analysis of shoot and root tissues from 45-day-old rice plants grown hydroponically under P-sufficient (16 ppm Pi) or P-starved (0 ppm Pi) medium revealed that Pi-starvation stress causes global transcriptional reprogramming affecting several transcription factors, signaling pathways and other regulatory genes. We could identify several significantly up-regulated genes in roots of NIL-23 under Pi-starvation which might be responsible for the Pi starvation tolerance. Pathway enrichment analysis indicated significant role of certain phosphatases, transporters, transcription factors, carbohydrate metabolism, hormone-signaling, and epigenetic processes in improving P-starvation stress tolerance in NIL-23.ConclusionWe report the important candidate mechanisms for Pi acquisition/solubilization, recycling, remobilization/transport, sensing/signalling, genetic/epigenetic regulation, and cell wall structural changes to be responsible for P-starvation tolerance in NIL-23. The study provides some of the novel information useful for improving phosphorus-use efficiency in rice cultivars.
Development and validation of a risk index to predict kidney graft survival: the kidney transplant risk index
Authors: Senanayake Sameera , Kularatna Sanjeewa , Healy Helen , Graves Nicholas , Baboolal Keshwar , Sypek Matthew P. , Barnett Adrian 
Published: June 2021

AbstractBackgroundKidney graft failure risk prediction models assist evidence-based medical decision-making in clinical practice. Our objective was to develop and validate statistical and machine learning predictive models to predict death-censored graft failure following deceased donor kidney transplant, using time-to-event (survival) data in a large national dataset from Australia.MethodsData included donor and recipient characteristics (n = 98) of 7,365 deceased donor transplants from January 1st, 2007 to December 31st, 2017 conducted in Australia. Seven variable selection methods were used to identify the most important independent variables included in the model. Predictive models were developed using: survival tree, random survival forest, survival support vector machine and Cox proportional regression. The models were trained using 70% of the data and validated using the rest of the data (30%). The model with best discriminatory power, assessed using concordance index (C-index) was chosen as the best model.ResultsTwo models, developed using cox regression and random survival forest, had the highest C-index (0.67) in discriminating death-censored graft failure. The best fitting Cox model used seven independent variables and showed moderate level of prediction accuracy (calibration).ConclusionThis index displays sufficient robustness to be used in pre-transplant decision making and may perform better than currently available tools.
Sepsis-related hospital admissions and ambient air pollution: a time series analysis in 6 Chinese cities
Authors: Wang Yu , Liu Zhen , Yang Lian , Zhou Jiushun , Li Jia , Liao Hai Lun , Tian Xing Jun 
Published: June 2021

Abstract
Background
Some prevalent but rarely studied causes of hospital admissions, such as sepsis is still unknown whether affected by air pollution.

Methods
We used time-series regression within generalized additive models to estimate the effect of air pollutant level on the sepsis-related hospital admissions, for the years 2017–18, using data from six cities in Sichuan, China. Potential effect modifications by age and sex were also explored. The effects of air pollutant on hospital stays for sepsis were also quantified.

Results
Positive associations between short-term exposure to NO2 and O3 and risk of sepsis-related hospital admissions and stays were found. Each 10 μg/m3 increase in short-term NO2 at lag 03 and O3 at lag 4 was associated with an increase of 2.76% (95% CI: 0.67, 4.84%) and 0.64% (95% CI: 0.14, 1.14%) hospital admissions, respectively. An increase of 0.72% (95% CI: 0.05, 1.40%) hospital stay was associated with 10 μg/m3 increase in O3 concentration at lag 4. Besides, the adverse effect of exposure to NO2 was more significant in males and population aged less than 14 years; while more significant in females and population aged 14 ~ 65 and over 65 years for exposure to O3. These associations remained stable after the adjustment of other air pollutants.8.

Conclusion
Exposure to ambient NO2 and O3 may cause substantial sepsis hospitalizations, and hospital stays in Sichuan, China. These associations were different in subgroup by age and sex.
The role of FOLFIRINOX in metastatic pancreatic cancer: a meta-analysis
Authors: Zhang Beilei , Zhou Fengyan , Hong Jiaze , Ng Derry Minyao , Yang Tong , Zhou Xinyu , Jin Jieyin , Zhou Feifei , Chen Ping , Xu Yunbao 
Published: June 2021

Abstract
Background
The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC.

Methods
We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS).

Results
We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, p<0.001) but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than monochemotherapy (HR 0.59, 95% Cl 0.52–0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR 0.76, 95% Cl 0.61–0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR 0.91, 95% Cl 0.82–1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea.

Conclusion
These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors.

Graphical abstract
The household financial burden of non-communicable diseases in low- and middle-income countries: a systematic review
Authors: Kazibwe Joseph , Tran Phuong Bich , Annerstedt Kristi Sidney 
Published: June 2021

Abstract
Background
The chronic nature of noncommunicable diseases (NCD) and costs associated with long-term care can result in catastrophic health expenditure for the patient and their household pushing them deeper into poverty and entrenching inequality in society. As the full financial burden of NCDs is not known, the objective of this study was to explore existing evidence on the financial burden of NCDs in low- and middle-income countries (LMICs), specifically estimating the cost incurred by patients with NCDs and their households to inform the development of strategies to protect such households from catastrophic expenditure.

Methods
This systematic review followed the PRISMA guidelines, PROSPERO: CRD42019141088. Eligible studies published between 1st January 2000 to 7th May 2020 were systematically searched for in three databases: Medline, Embase and Web of Science. A two-step process, comprising of qualitative synthesis proceeded by quantitative (cost) synthesis, was followed. The mean costs are presented in 2018 USD.

Findings
51 articles were included, out of which 41 were selected for the quantitative cost synthesis. Most of the studies were cross-sectional cost-of-illness studies, of which almost half focused on diabetes and/or conducted in South-East Asia. The average total costs per year to a patient/household in LMICs of COPD, CVD, cancers and diabetes were $7386.71, $6055.99, $3303.81, $1017.05, respectively.

Conclusion
This review highlighted major data and methodological gaps when collecting data on costs of NCDs to households along the cascade of care in LMICs. More empirical data on cost of specific NCDs are needed to identify the diseases and contexts where social protection interventions are needed most. More rigorous and standardised methods of data collection and costing for NCDs should be developed to enable comprehensive and comparable evidence of the economic and financial burden of NCDs to patients and households in LMICs. The available evidence on costs reveals a large financial burden imposed on patients and households in seeking and receiving NCD care and emphasizes the need for adequate and reliable social protection interventions to be implemented alongside Universal Health Coverage.
The missing link between legal age of sexual consent and age of marriage in sub-Saharan Africa: implications for sexual and reproductive health and rights
Authors: Ahinkorah Bright Opoku , Okyere Joshua , Hagan John Elvis , Seidu Abdul-Aziz , Aboagye Richard Gyan , Yaya Sanni 
Published: June 2021

AbstractChild marriage is a fundamental violation of human rights and a threat to access to education, sexual and reproductive health care, and employment. It also threatens freedom from violence, reproductive rights, movement, and the right to consensual marriage. In most countries in sub-Saharan Africa, the legal age of marriage is 18 years. Hence, girls who marry before 18 years are considered as victims of child marriage. Closely knitted to legal age for marriage is the issue of age for sexual consent, which refers to the minimum age at which a person is considered to have the legal capacity to consent to sexual intercourse. While there seem to be a standard legal age for marriage, the legal age for sexual consent varies in most countries in sub-Saharan Africa and is often lower than the legal age of marriage. In this commentary, we argue that the gap between the legal age of sexual consent and marriage partly accounts for some of the sexual and reproductive health challenges such as intimate partner violence, sexually transmitted infections, adolescent pregnancy, early childbirth, including unsafe abortions among adolescent girls in sub-Saharan Africa and infringements on their sexual and reproductive health rights. This commentary highlights strategic potential interventions that could help address the identified gaps. We argue that aligning the age for sexual consent and marriage is not the solution to the problem. However, what is critical is the education of young people about sexual and reproductive health issues and comprehensive sexuality education through advocacy networks at the national and local levels. Thus, the key is to provide accurate, timely, and non-judgmental sexual and reproductive health and rights information to young people irrespective of the prevailing age of consent. This provision will empower them to make informed decisions about their sexual and reproductive health.
Designing the next generation of implementation research training for learners in low- and middle-income countries
Authors: Penkunas Michael J. , Chong Shiau Yun , Rhule Emma L. M. , Berdou Evangelia , Allotey Pascale 
Published: June 2021

AbstractEfficacious health interventions tested through controlled trials often fail to show desired impacts when implemented at scale. These challenges can be particularly pervasive in low- and middle-income settings where health systems often lack the capacity and mechanisms required for high-quality research and evidence translation. Implementation research is a powerful tool for identifying and addressing the bottlenecks impeding the success of proven health interventions. Implementation research training initiatives, although growing in number, remain out of reach for many investigators in low- and middle-income settings, who possess the knowledge required to contextualize challenges and potential solutions in light of interacting community- and system-level features. We propose a realigned implementation research training model that centers on team-based learning, tailored didactic opportunities, learning-by-doing, and mentorship.
Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors
Authors: Li Jian , Deng Yanhong , Zhang Weijie , Zhou Ai-Ping , Guo Weijian , Yang Jianwei , Yuan Ying , Zhu Liangjun , Qin Shukui , Xiang Silong , Lu Haolan , Gong John , Xu Ting , Liu David , Shen Lin 
Published: June 2021

AbstractBackgroundMonoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion. Envafolimab, a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment, represents a potential advance because it can be conveniently administered subcutaneously.MethodsThis open-label, single-arm, phase 2 study evaluated the efficacy and safety of envafolimab in patients with previously treated advanced dMMR/MSI-H tumors from 25 clinical sites across China. Adults with histologically confirmed locally advanced or metastatic malignant dMMR/MSI-H solid tumors received weekly 150 mg subcutaneous envafolimab injections in a 28-day treatment cycle. The primary efficacy endpoint was the objective response rate (assessed by a blinded independent review committee). Secondary efficacy outcomes were disease control rate, duration of response, progression-free survival, and overall survival.ResultsOne hundred and three patients (65 with colorectal cancer, 18 with gastric cancer, and 20 with other solid tumors) were enrolled. Median follow-up was 11.5 months. The objective response rate was 42.7% (95% confidence interval [CI] 33.0–52.8), and the disease control rate was 66.0% (95% CI 56.0–75.1). Median duration of response was not reached; the duration of response rate at 12 months was 92.2% (95% CI 77.5–97.4). Median progression-free survival was 11.1 months (95% CI 5.5 to not evaluable). Overall survival at 12 months was 74.6% (95% CI 64.7–82.1). Sixteen patients (16%) had at least one grade 3 or 4 related treatment-emergent adverse event. No grade 5 treatment-emergent adverse events related to envafolimab were reported. Injection site reactions, all grade 1–2, were reported in nine patients (9%), but there were no infusion reactions. Eight patients (8%) had grade 3 or 4 immune-related adverse events.ConclusionsThis is the first pivotal phase 2 study to examine the efficacy and safety of a single-domain immune checkpoint antibody in the treatment of cancer. Envafolimab was effective and had acceptable safety in the treatment of previously treated advanced dMMR/MSI-H solid tumors. As the first single-domain PD-L1-targeting antibody administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treatment of cancer.Trial registrationClinicalTrials.gov, NCT03667170. Registered 10 September 2018—Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT03667170.