bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning in predicting extracapsular extension (ECE) of prostate cancer with MRI: a protocol for a systematic literature review
Authors: Guerra Adalgisa , Negrão Eduardo , Papanikolaou Nickolaos , Donato Helena 
Published: May 2022

IntroductionIn patients with prostate cancer (PCa), the detection of extracapsular extension (ECE) and seminal vesicle invasion is not only important for selecting the appropriate therapy but also for preoperative planning and patient prognosis. It is of paramount importance to stage PCa correctly before surgery, in order to achieve better surgical and outcome results. Over the last years, MRI has been incorporated in the classical prostate staging nomograms with clinical improvement accuracy in detecting ECE, but with variability between studies and radiologist’s experience.Methods and analysisThe research question, based on patient, index test, comparator, outcome and study design criteria, was the following: what is the diagnostic performance of artificial intelligence algorithms for predicting ECE in PCa patients, when compared with that of histopathological results after radical prostatectomy. To answer this question, we will use databases (EMBASE, PUBMED, Web of Science and CENTRAL) to search for the different studies published in the literature and we use the QUADA tool to evaluate the quality of the research selection.Ethics and disseminationThis systematic review does not require ethical approval. The results will be disseminated through publication in a peer-review journal, as a chapter of a doctoral thesis and through presentations at national and international conferences.PROSPERO registration numberCRD42020215671.
End-of-life care in cancer patients: how much drug therapy and how much palliative care? Record linkage study in Northern Italy
Authors: Formoso Giulio , Marino Massimiliano , Guberti Monica , Grilli Roberto Giuseppe 
Published: May 2022

ObjectivesInvestigating end-of-life use of anticancer drugs and of palliative care services.DesignPopulation based cohort linked to mortality registry and administrative databases.SettingEmilia-Romagna Region (Northern Italy).Participants55 625 residents who died of cancer between 2017 and 2020.Primary and secondary outcome measuresMultivariate analyses were carried out to assess the relationship between cancer drug therapy and palliative care services, and their association with factors related to tumour severity.ResultsIn the last month of life, 15.3% of study population received anticancer drugs (from 12.5% to 16.9% across the eight Local Health Authorities—LHA) and 40.2% received palliative care services (from 36.2% to 43.7%). Drug therapy was inversely associated with receiving palliative care services within the last 30 days (OR 0.92, 95% CI 0.87 to 0.97), surgery within the last 6 months (OR 0.59, 95% CI 0.52 to 0.67), aggressive tumours (OR 0.88, 95% CI 0.84 to 0.93) and increasing age (OR 0.95, 95% CI 0.95 to 0.95). Drug therapy was more likely among those with haematologic tumours (OR 2.15, 95% CI 2.00 to 2.30) and in case of hospital admissions within the last 6 months (OR 1.63, 95% CI 1.55 to 1.72). Palliative care was less likely among those with haematologic compared with other tumours (OR 0.52, 95% CI 0.49 to 0.56), in case of surgery (OR 0.44, 95% CI 0.39 to 0.49) or hospital admissions (OR 0.70, 95% CI 0.67 to 0.72) within the last 6 months, if receiving anticancer drugs during the last 30 days (OR 0.90, 95% CI 0.85 to 0.94) and for each year of increasing age (OR 0.99, 95% CI 0.99 to 0.99). Palliative care was more likely in the presence of aggressive tumours (OR 1.12, 95% CI 1.08 to 1.16).ConclusionUse of anticancer drugs and palliative care in the last month of life were inversely associated, showing variability across different LHAs. While administrative data have limits, our findings are in line with conclusions of other studies.
Social and psychological impact of the COVID-19 pandemic on UK medical and nursing students: protocol for a national medical and nursing student survey
Authors: Richardson George E , Gillespie Conor S , Mantle Orla , Clynch Abigail , Ooi Setthasorn Zhi Yang , Park Jay J , Bligh Emily R , Kundu Shantanu , Georgiou Ioannis , Bandyopadhyay Soham , Saunders Kate E ,   Neurology and Neurosurgery Interest Group (NANSIG)
Published: May 2022

IntroductionHealthcare students have played a significant role in the National Health Service during the COVID-19 pandemic. We captured data on the well-being of medical students during the acute phase of the pandemic with the Social and Psychological Impact of COVID-19 on medical students: a national survey Evaluation (SPICE-19) study. We will evaluate changes in mental health and well-being of medical and nursing students 1 year after SPICE-19, in a cross-sectional study, to understand the impact of the pandemic, and inform well-being policies.Methods and analysisThis study will be a national, multi-institution, cross-discipline study. An online 53-item survey of demographics, mental health and well-being will be used to record responses. Students studying for a medical or nursing degree at any UK universities will be eligible to participate. The survey will be advertised through the Neurology and Neurosurgery Interest Group national network. Participation is anonymous and voluntary, with relevant mental health resources made available to participants.Ethics and disseminationEthical approval was granted by the University of Oxford Central University Research Ethics Committee (R75719/RE001) on 21 May 2021. Study findings will be presented at national and international meetings, and submitted for publication in a peer-reviewed journal.
Demand and supply-side barriers and opportunities to enhance access to healthcare for urban poor populations in Kenya: a qualitative study
Authors: Bakibinga Pauline , Kisia Lyagamula , Atela Martin , Kibe Peter M. , Kabaria Caroline , Kisiangani Isaac , Kyobutungi Catherine 
Published: May 2022

ObjectiveTo explore the barriers to and options for improving access to quality healthcare for the urban poor in Nairobi, Kenya.Design and participantsThis was a qualitative approach. In-depth interviews (n=12), focus group discussions with community members (n=12) and key informant interviews with health providers and policymakers (n=25) were conducted between August 2019 and September 2020. Four feedback and validation workshops were held in December 2019 and April–June 2021.SettingKorogocho and Viwandani urban slums in Nairobi, Kenya.ResultsThe socioe-conomic status of individuals and their families, such as poverty and lack of health insurance, interact with community-level factors like poor infrastructure, limited availability of health facilities and insecurity; and health system factors such as limited facility opening hours, health providers’ attitudes and skills and limited public health resources to limit healthcare access and perpetuate health inequities. Limited involvement in decision-making processes by service providers and other key stakeholders was identified as a major challenge with significant implications on how limited health system resources are managed.ConclusionDespite many targeted interventions to improve the health and well-being of the urban poor, slum residents are still unable to obtain quality healthcare because of persistent and new barriers due to the COVID-19 pandemic. In a devolved health system, paying attention to health services managers’ abilities to assess and respond to population health needs is vital. The limited use of existing accountability mechanisms requires attention to ensure that the mechanisms enhance, rather than limit, access to health services for the urban slum residents. The uniqueness of poor urban settings also requires in-depth and focused attention to social determinants of health within these contexts. To address individual, community and system-level barriers to quality healthcare in this and related settings and expand access to health services for all, multisectoral strategies tailored to each population group are needed.
Overview on L-asparagine monohydrate single crystal: A non-essential amino acid
Authors: Khan Naghma , Vijayan N. , Kumar Ravinder , Gupta Neha 
Published: May 2022

This paper reviews the growth and properties of L-asparagine monohydrate (L-ASPM) single crystal. The growth technique by which a well-defined bulk-sized single crystal can be grown is also reported. The various reported studies done over titled crystal signify its suitability for various optoelectronic applications. This paper also includes few derivative compounds of L-asparagine (L-ASP), their structural review has also been incorporated to evaluate its structural bonding and atomic arrangement. Various advanced characterization and their outcomes were also discussed in detail from all the available reported literature which mainly emphasizes on the vast applicability of the crystal. The L-ASPM single crystal is a potential candidate to be used in various optical applications.
Myeloma Genome Project Panel is a Comprehensive Targeted Genomics Panel for Molecular Profiling of Patients with Multiple Myeloma
Authors: Sudha Parvathi , Ahsan Aarif , Ashby Cody , Kausar Tasneem , Khera Akhil , Kazeroun Mohammad H. , Hsu Chih-Chao , Wang Lin , Fitzsimons Evelyn , Salminen Outi , Blaney Patrick , Czader Magdalena , Williams Jonathan , Abu Zaid Mohammad I. , Ansari-Pour Naser , Yong Kwee L. , van Rhee Frits , Pierceall William E. , Morgan Gareth J. , Flynt Erin , Gooding Sarah , Abonour Rafat , Ramasamy Karthik , Thakurta Anjan , Walker Brian A. 
Published: May 2022

Abstract

Purpose:
We designed a comprehensive multiple myeloma targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards.

Experimental Design:
The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNA). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical FISH (translocations), multiplex ligation probe analysis (MLPA; CNAs), whole-genome sequencing (WGS; CNAs, mutations, translocations), or droplet digital PCR (ddPCR) of known standards (mutations).

Results:
Canonical immunoglobulin heavy chain translocations were detected in 43.2% of patients by sequencing, and aligned with FISH except for 1 patient. CNAs determined by sequencing and MLPA for 22 regions were comparable in 103 samples and concordance between platforms was R2 = 0.969. Variant allele frequency (VAF) for 74 mutations were compared between sequencing and ddPCR with concordance of R2 = 0.9849.

Conclusions:
In summary, we have developed a targeted sequencing panel that is as robust or superior to FISH and WGS. This molecular panel is cost-effective, comprehensive, clinically actionable, and can be routinely deployed to assist risk stratification at diagnosis or posttreatment to guide sequencing of therapies.
Relationship of iothalamate clearance and NRM in patients receiving fludarabine and melphalan reduced-intensity conditioning
Authors: Kutzke Jade L. , Merten Julianna A. , Pawlenty Amanda G. , Barreto Erin F. , Bartoo Gabe T. , Mara Kristin C. , Litzow Mark R. , Hogan William J. , Shah Mithun V. , Mangaonkar Abhishek A. , Leung Nelson , Alkhateeb Hassan B. 
Published: May 2022

Abstract
The reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the active metabolite of fludarabine, F-ara-A, are excreted via the kidneys. Existing methods to assess clearance in this setting are based on serum creatinine, which has known limitations for glomerular filtration rate (GFR) estimation in patients with malignancy. Measured GFR (mGFR) may better predict drug dosing to mitigate toxicity and increase the chances of successful engraftment. The primary objective of this study was to assess the association between mGFR and risk for nonrelapse mortality (NRM) in patients who have undergone allogeneic HSCT receiving conditioning with fludarabine and melphalan. In the 109 included patients, mGFR &lt;65 mL/min/1.73 m2 predicted a significantly higher rate of overall NRM (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.35; P = 04) and 1-year incidence of infection (HR, 2.63; 95% CI, 1.54-4.55; P &lt; .001) in addition to a significantly lower 2-year survival (P = .019). Kidney function estimated via estimated GFR (eGFR) and estimated creatinine clearance did not correlate with posttransplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in patients who have undergone allogeneic HSCT and may be preferred to standard creatinine-based eGFR strategies.
Comparative analysis of novel and common reference genes in adult tissues of the mussel Mytilus galloprovincialis
Authors: Salatiello Federica , Gerdol Marco , Pallavicini Alberto , Locascio Annamaria , Sirakov Maria 
Published: May 2022

Abstract
Background
Real-time quantitative PCR is a widely used method for gene expression analyses in various organisms. Its accuracy mainly relies on the correct selection of reference genes. Any experimental plan involving real-time PCR needs to evaluate the characteristics of the samples to be examined and the relative stability of reference genes. Most studies in mollusks rely on reference genes commonly used in vertebrates.

Results
In this study, we focused on the transcriptome of the bivalve mollusk Mytilus galloprovincialis in physiological state to identify suitable reference genes in several adult tissues. Candidate genes with highly stable expression across 51 RNA-seq datasets from multiple tissues were selected through genome-wide bioinformatics analysis. This approach led to the identification of three genes (Rpl14, Rpl32 and Rpl34), whose suitability was evaluated together with 7 other reference genes commonly reported in literature (Act, Cyp-A, Ef1α, Gapdh, 18S, 28S and Rps4). The stability analyses performed with geNorm, NormFinder and Bestkeeper identified specific either single or pairs of genes suitable as references for gene expression analyses in specific tissues and revealed the Act/Cyp-A pair as the most appropriate to analyze gene expression across different tissues.

Conclusion
Mytilus galloprovincialis is a model system increasingly used in ecotoxicology and molecular studies. Our transcriptome-wide approach represents the first comprehensive investigation aimed at the identification of suitable reference genes for expression studies in this species.
Optimized Cas9:sgRNA delivery efficiently generates biallelic MSTN knockout sheep without affecting meat quality
Authors: Zhou Shiwei , Kalds Peter , Luo Qi , Sun Kexin , Zhao Xiaoe , Gao Yawei , Cai Bei , Huang Shuhong , Kou Qifang , Petersen Bjoern , Chen Yulin , Ma Baohua , Wang Xiaolong 
Published: May 2022

Abstract
Background
CRISPR/Cas9-based genome-editing systems have been used to efficiently engineer livestock species with precise genetic alterations intended for biomedical and agricultural applications. Previously, we have successfully generated gene-edited sheep and goats via one-cell-stage embryonic microinjection of a Cas9 mRNA and single-guide RNAs (sgRNAs) mixture. However, most gene-edited animals produced using this approach were heterozygotes. Additionally, non-homozygous gene-editing outcomes may not fully generate the desired phenotype in an efficient manner.

Results
We report the optimization of a Cas9 mRNA-sgRNA delivery system to efficiently generate homozygous myostatin (MSTN) knockout sheep for improved growth and meat production. Firstly, an sgRNA selection software (sgRNAcas9) was used to preliminarily screen for highly efficient sgRNAs. Ten sgRNAs targeting the MSTN gene were selected and validated in vitro using sheep fibroblast cells. Four out of ten sgRNAs (two in exon 1 and two in exon 2) showed a targeting efficiency > 50%. To determine the optimal CRISPR/Cas9 microinjection concentration, four levels of Cas9 mRNA and three levels of sgRNAs in mixtures were injected into sheep embryos. Microinjection of 100 ng/μL Cas9 mRNA and 200 ng/μL sgRNAs resulted in the most improved targeting efficiency. Additionally, using both the highly efficient sgRNAs and the optimal microinjection concentration, MSTN-knockout sheep were generated with approximately 50% targeting efficiency, reaching a homozygous knockout efficiency of 25%. Growth rate and meat quality of MSTN-edited lambs were also investigated. MSTN-knockout lambs exhibited increased body weight and average daily gain. Moreover, pH, drip loss, intramuscular fat, crude protein, and shear force of gluteal muscles of MSTN-knockout lambs did not show changes compared to the wild-type lambs.

Conclusions
This study highlights the importance of in vitro evaluation for the optimization of sgRNAs and microinjection dosage of gene editing reagents. This approach enabled efficient engineering of homozygous knockout sheep. Additionally, this study confirms that MSTN-knockout lambs does not negatively impact meat quality, thus supporting the adoption of gene editing as tool to improve productivity of farm animals.
A patient with severe metformin-associated lactic acidosis complicated by acute coronary syndrome: a case report
Authors: Mammadova N. , Soukup J. , Shkodivskyi P. , Gudowski C. , Ahmed A. , Pliquett R. U. 
Published: May 2022

Abstract
Introduction
Metformin-associated lactic acidosis (MALA) is a rare but life-threatening condition. Here, we report the outcome of a patient with MALA complicated by acute coronary syndrome.

Case presentation
A 47-year-old obese woman of Caucasian ethnicity was admitted for syncope and tachypnea with Kussmaul breathing. She had a type-2 diabetes and was on oral antidiabetic therapy. Hemoglobin A1c was 6.6%. On admission, a severe acute kidney injury (serum creatinine: 1251 µmol/L) with hyperkalemia (7.5 mmol/L) and severe lactic acidosis (ph:7.042, bicarbonate: 9.9 mmol/L, partial pressure of carbon dioxide: 21.8 mmHg, lactate: 20.0 mmol/L) was found. Despite bicarbonate therapy, ph further decreased. Within 2.5 h of admission, a temporary hemodialysis catheter was placed, and one session of a high-efficiency hemodialysis was performed. 8 h after admission, a continuous venovenous hemodiafiltration was initiated and maintained for 2 days. The metformin therapy was stopped. Supplemental oxygen, intravenous catecholamines (4 days) and antibiotic therapy (7 days) were applied. During this therapy of lactic acidosis, an acute coronary syndrome evolved by day 2 after admission and resolved by day 5 in hospital. After recovery, the patient was transferred to a general ward on day 7 and left the hospital on day 11. By discharge, both the acute kidney injury and the acute coronary syndrome were reversible.

Conclusion
In the patient with MALA complicated by acute coronary syndrome, the combination of a high-efficiency hemodialysis and, consecutively, continuous venovenous hemodiafiltration led to a favorable outcome.
A propensity score-matched analysis of the impact of statin therapy on the outcomes of patients with non-small-cell lung cancer receiving anti-PD-1 monotherapy: a multicenter retrospective study
Authors: Takada Kazuki , Shimokawa Mototsugu , Takamori Shinkichi , Shimamatsu Shinichiro , Hirai Fumihiko , Tagawa Tetsuzo , Okamoto Tatsuro , Hamatake Motoharu , Tsuchiya-Kawano Yuko , Otsubo Kohei , Inoue Koji , Yoneshima Yasuto , Tanaka Kentaro , Okamoto Isamu , Nakanishi Yoichi , Mori Masaki 
Published: May 2022

Abstract
Background
Many studies have recently reported the association of concomitant medications with the response and survival in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy. However, the clinical impact of statin therapy on the outcome of cancer immunotherapy in patients with NSCLC is poorly understood.

Methods
In our database, we retrospectively identified and enrolled 390 patients with advanced or recurrent NSCLC who were treated with anti-programmed cell death-1 (PD-1) monotherapy in clinical practice between January 2016 and December 2019 at 3 medical centers in Japan to examine the clinical impact of statin therapy on the survival of patients with NSCLC receiving anti-PD-1 monotherapy. A propensity score-matched analysis was conducted to minimize the bias arising from the patients’ backgrounds.

Results
The Kaplan–Meier curves of the propensity score-matched cohort showed that the overall survival (OS), but not the progression-free survival (PFS), was significantly longer in patients receiving statin therapy. However, a Cox regression analysis in the propensity score-matched cohort revealed that statin therapy was not an independent favorable prognostic factor, although it tended to be correlated with a favorable outcome.

Conclusions
Statin therapy may be a combination tool for cancer immunotherapy in patients with NSCLC. These findings should be validated in further prospective studies with larger sample sizes.
Combined therapy guided by multimodal imaging of fifteen retinal capillary hemangioblastomas in a monocular Von Hippel- Lindau syndrome case report
Authors: Guo Ju , Du Liping , Zhou Pengyi , Guo Xiaohong , Dai Fangfang , Jin Xuemin 
Published: May 2022

Abstract
Background
To report the multimodal imaging and treatment of fifteen retinal capillary hemangioblastomas (RCHs) associated with Von Hippel-Lindau syndrome in a monocular patient during a long-term following-up, which supply high-resolution exquisite SS-OCTA images (VG200; SVision Imaging, Ltd., Luoyang, China) and management experience about multiple RCHs.

Case presentation
A 34-year-old monocular male patient complained decreased visual acuity (20/100) without pain and redness in the left eye five years ago. Von Hippel-Lindau syndrome were diagnosed with genetic testing. He, his son and daughter all carried a heterozygosity missense variant c.499C > T (p. Arg167Trp) in the Hg19 gene, a VHL gene located in Chr3:10,191,506. Fifteen RCHs were identified by the application of multimodal imaging, which including fundus photo, fundus autofluorescence (FAF), B-scan ultrasonography (US), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) and swept-source optical coherence tomography angiography (SS-OCTA). Transscleral cryotherapy and laser photocoagulation were performed to destroy the largest RCH with the size of 4 PD in diameter. Laser photocoagulation was conducted to seal the middle or tiny RCHs (< 1.5 PD) and their nourishing vessels. The retinal edema and exudative macular detachment were successfully relieved by intraocular injection of bevacizumab for 5 times. The RCHs in the left eye responded well to these treatments and best corrected visual acuity was 20/25 for three years. Three-month recall visits were recommended for him.

Conclusion
For multiple retinal capillary hemangioblastomas in monocular patients, precise combined therapy guided by multimodal imaging has a profound impact on the management of new and recurrent RCHs.