bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies
Authors: Davies Rebecca , Liu Ling , Taotao Sheng , Tuano Natasha , Chaturvedi Richa , Huang Kie Kyon , Itman Catherine , Mandoli Amit , Qamra Aditi , Hu Changyuan , Powell David , Daly Roger J. , Tan Patrick , Rosenbluh Joseph 
Published: January 2021

Abstract
Introduction
Genes contain multiple promoters that can drive the expression of various transcript isoforms. Although transcript isoforms from the same gene could have diverse and non-overlapping functions, current loss-of-function methodologies are not able to differentiate between isoform-specific phenotypes.

Results
Here, we show that CRISPR interference (CRISPRi) can be adopted for targeting specific promoters within a gene, enabling isoform-specific loss-of-function genetic screens. We use this strategy to test functional dependencies of 820 transcript isoforms that are gained in gastric cancer (GC). We identify a subset of GC-gained transcript isoform dependencies, and of these, we validate CIT kinase as a novel GC dependency. We further show that some genes express isoforms with opposite functions. Specifically, we find that the tumour suppressor ZFHX3 expresses an isoform that has a paradoxical oncogenic role that correlates with poor patient outcome.

Conclusions
Our work finds isoform-specific phenotypes that would not be identified using current loss-of-function approaches that are not designed to target specific transcript isoforms.
The circulating levels of CTRP1 and CTRP5 are associated with obesity indices and carotid intima-media thickness (cIMT) value in patients with type 2 diabetes: a preliminary study
Authors: Majidi Ziba , Emamgholipour Solaleh , Omidifar Abolfazl , Rahmani Fard Soheil , Poustchi Hossein , Shanaki Mehrnoosh 
Published: January 2021

Abstract
Background
There is growing evidence that the C1qTNF-related protein (CTRP) family has a crucial role in the pathophysiology of metabolic disorders such as type 2 diabetes (T2D) and obesity. We sought to identify the association of CTRP1 and CTRP5 circulating levels with various obesity parameters such as visceral adipose tissue (VAT) thickness, visceral adiposity index (VAI), and with carotid intima-media thickness (cIMT) in patients with T2D and controls.

Methods
This preliminary study consisted of men with T2D (n = 42) and men without T2D (n = 42). The measurement of cIMT and VAT thickness was performed using an Accuvix XQ ultrasound. Circulating levels of CTRP1, CTRP5, and adiponectin were measured by enzyme-linked immunosorbent assay (ELISA).

Results
CTRP-1 and CTRP1/CTRP5 ratio were markedly higher in patients with T2D compared to controls (p < 0001 and p = 0004 respectively). Interestingly, binominal logistic regression revealed that a higher circulating level of CTRP1 was associated with the presence of T2D (odds ratio [OR]: 1.009 [95% CI: 1.004–1.015]; P = .001). CTRP1 circulating levels were correlated with WHR, VAT, and HOMA-IR in the whole population study. Also, we observed that the ratio of CTRP1 to CTRP5 in plasma (β = 0.648, P = 0.005) and CTRP5 circulating levels (β = 0.444, P = 0.049) are independently associated with cIMT value.

Conclusions
Our results indicated that CTRP1 and CTRP5 concentrations were correlated with atherosclerosis in men with T2D and these adipokines might have a causal role for cardiometabolic risk in T2D.However, more studies in large sample sizes are required to clarify the role of CTRPs in T2D pathogenesis.
Performance of diabetes screening tests: an evaluation study of Iranian diabetes screening program
Authors: Kianpour Fateme , Fararouei Mohammad , Hassanzadeh Jafar , Mohammadi Mohammadnabi , Dianatinasab Mostafa 
Published: January 2021

Abstract
Background
Type 2 diabetes is a common non-communicable disease that is responsible for about 9% of all deaths and a 25% reduction in life expectancy. However, nearly half of the diabetic patients are not aware of their disease. In this regard, to identify un-known diabetic patients, diabetes screening is of great importance. This study was conducted to evaluate the performance of two commonly used diabetes screening tests that are currently recommended by the Iranian diabetes screening program for (DSP).

Methods
The validity of the two diabetes screening tests were measured among 1057 participants who were older than 30 years of age. The studied screening tests included capillary fasting blood glucose (CBG) and glycated hemoglobin (HbA1c). The golden standard for measuring the validity of the tests was venous fasting plasma glucose (VPG).

Results
According to the results, the sensitivity of CBG and HbA1c tests was 69.01% and 84.5%, and the specificity of the tests were 95.7% and 79.3%, respectively. Positive and negative predictive values were 53.84% and 97.72% for CBG and 22.72% and 98.61% for HbA1c, respectively. The recommended cut points for CBG and HbA1c were 116.5 mg/dl and 7.15%, respectively. Using these values as the new cut points, sensitivity and specificity of CBG and HbA1c changed to 80.30% and 89.10%, and 77.50% and 94.20%, respectively.

Conclusions
Compared to several other countries, the performance of Iranian DSP is relatively better. The Receiver Operating Characteristic Curve suggested new cut points for significantly better performance of DSP.
Israel’s rapid rollout of vaccinations for COVID-19
Authors: Rosen Bruce , Waitzberg Ruth , Israeli Avi 
Published: January 2021

AbstractAs of the end of 2020, the State of Israel, with a population of 9.3 million, had administered more COVID-19 vaccine doses than all countries aside from China, the US, and the UK. Moreover, Israel had administered almost 11.0 doses per 100 population, while the next highest rates were 3.5 (in Bahrain) and 1.4 (in the United Kingdom). All other countries had administered less than 1 dose per 100 population.While Israel’s rollout of COVID-19 vaccinations was not problem-free, its initial phase had clearly been rapid and effective. A large number of factors contributed to this early success, and they can be divided into three major groups.The first group of factors consists of long-standing characteristics of Israel which are extrinsic to health care. They include: Israel’s small size (in terms of both area and population), a relatively young population, relatively warm weather in December 2020, a centralized national system of government, and well-developed infrastructure for implementing prompt responses to large-scale national emergencies.The second group of factors are also long-standing, but they are health-system specific. They include: the organizational, IT and logistical capacities of Israel’s community-based health care providers, the availability of a cadre of well-trained, salaried, community-based nurses who are directly employed by those providers, a tradition of effective cooperation between government, health plans, hospitals, and emergency care providers – particularly during national emergencies; and support tools and decisionmaking frameworks to support vaccination campaigns.The third group consists of factors that are more recent and are specific to the COVID-19 vaccination effort. They include: the mobilization of special government funding for vaccine purchase and distribution, timely contracting for a large amount of vaccines relative to Israel’s population, the use of simple, clear and easily implementable criteria for determining who had priority for receiving vaccines in the early phases of the distribution process, a creative technical response that addressed the demanding cold storage requirements of the Pfizer-BioNTech COVID-19 vaccine, and well-tailored outreach efforts to encourage Israelis to sign up for vaccinations and then show up to get vaccinated.While many of these facilitating factors are not unique to Israel, part of what made the Israeli rollout successful was its combination of facilitating factors (as opposed to each factor being unique separately) and the synergies it created among them. Moreover, some high-income countries (including the US, the UK, and Canada) are lacking several of these facilitating factors, apparently contributing to the slower pace of the rollout in those countries.
Trendelenburg maneuver predicts fluid responsiveness in patients on veno-arterial extracorporeal membrane oxygenation
Authors: Luo Jing-chao , Su Ying , Dong Li-li , Hou Jun-yi , Li Xin , Zhang Ying , Ma Guo-guang , Zheng Ji-li , Hao Guang-wei , Wang Huan , Zhang Yi-jie , Luo Zhe , Tu Guo-wei 
Published: January 2021

Abstract
Background
Evaluation of fluid responsiveness during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support is crucial. The aim of this study was to investigate whether changes in left ventricular outflow tract velocity–time integral (ΔVTI), induced by a Trendelenburg maneuver, could predict fluid responsiveness during VA-ECMO.

Methods
This prospective study was conducted in patients with VA-ECMO support. The protocol included four sequential steps: (1) baseline-1, a supine position with a 15° upward bed angulation; (2) Trendelenburg maneuver, 15° downward bed angulation; (3) baseline-2, the same position as baseline-1, and (4) fluid challenge, administration of 500 mL gelatin over 15 min without postural change. Hemodynamic parameters were recorded at each step. Fluid responsiveness was defined as ΔVTI of 15% or more, after volume expansion.

Results
From June 2018 to December 2019, 22 patients with VA-ECMO were included, and a total of 39 measurements were performed. Of these, 22 measurements (56%) met fluid responsiveness. The R2 of the linear regression was 0.76, between ΔVTIs induced by Trendelenburg maneuver and the fluid challenge. The area under the receiver operating characteristic curve of ΔVTI induced by Trendelenburg maneuver to predict fluid responsiveness was 0.93 [95% confidence interval (CI) 0.81–0.98], with a sensitivity of 82% (95% CI 60–95%), and specificity of 88% (95% CI 64–99%), at a best threshold of 10% (95% CI 6–12%).

Conclusions
Changes in VTI induced by the Trendelenburg maneuver could effectively predict fluid responsiveness in VA-ECMO patients.
Trial registration ClinicalTrials.gov, NCT 03553459 (the TEMPLE study). Registered on May 30, 2018
PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews
Authors: Rethlefsen Melissa L. , Kirtley Shona , Waffenschmidt Siw , Ayala Ana Patricia , Moher David , Page Matthew J. , Koffel Jonathan B. ,   PRISMA-S Group, Blunt Heather , Brigham Tara , Chang Steven , Clark Justin , Conway Aislinn , Couban Rachel , de Kock Shelley , Farrah Kelly , Fehrmann Paul , Foster Margaret , Fowler Susan A. , Glanville Julie , Harris Elizabeth , Hoffecker Lilian , Isojarvi Jaana , Kaunelis David , Ket Hans , Levay Paul , Lyon Jennifer , McGowan Jessie , Murad M. Hassan , Nicholson Joey , Pannabecker Virginia , Paynter Robin , Pinotti Rachel , Ross-White Amanda , Sampson Margaret , Shields Tracy , Stevens Adrienne , Sutton Anthea , Weinfurter Elizabeth , Wright Kath , Young Sarah 
Published: January 2021

Abstract
Background
Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse, and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration.

Methods
The checklist was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process.

Results
The final checklist includes 16 reporting items, each of which is detailed with exemplar reporting and rationale.

Conclusions
The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and therefore reproducible.
Texture analysis of iodine maps and conventional images for k-nearest neighbor classification of benign and metastatic lung nodules
Authors: Lennartz Simon , Mager Alina , Große Hokamp Nils , Schäfer Sebastian , Zopfs David , Maintz David , Reinhardt Hans Christian , Thomas Roman K. , Caldeira Liliana , Persigehl Thorsten 
Published: January 2021

Abstract
Background
The purpose of this study was to analyze if the use of texture analysis on spectral detector CT (SDCT)-derived iodine maps (IM) in addition to conventional images (CI) improves lung nodule differentiation, when being applied to a k-nearest neighbor (KNN) classifier.

Methods
183 cancer patients who underwent contrast-enhanced, venous phase SDCT of the chest were included: 85 patients with 146 benign lung nodules (BLN) confirmed by either prior/follow-up CT or histopathology and 98 patients with 425 lung metastases (LM) verified by histopathology, 18F-FDG-PET-CT or unequivocal change during treatment. Semi-automatic 3D segmentation of BLN/LM was performed, and volumetric HU attenuation and iodine concentration were acquired. For conventional images and iodine maps, average, standard deviation, entropy, kurtosis, mean of the positive pixels (MPP), skewness, uniformity and uniformity of the positive pixels (UPP) within the volumes of interests were calculated. All acquired parameters were transferred to a KNN classifier.

Results
Differentiation between BLN and LM was most accurate, when using all CI-derived features combined with the most significant IM-derived feature, entropy (Accuracy:0.87; F1/Dice:0.92). However, differentiation accuracy based on the 4 most powerful CI-derived features performed only slightly inferior (Accuracy:0.84; F1/Dice:0.89, p=0.125). Mono-parametric lung nodule differentiation based on either feature alone (i.e. attenuation or iodine concentration) was poor (AUC=0.65, 0.58, respectively).

Conclusions
First-order texture feature analysis of contrast-enhanced staging SDCT scans of the chest yield accurate differentiation between benign and metastatic lung nodules. In our study cohort, the most powerful iodine map-derived feature slightly, yet insignificantly increased classification accuracy compared to classification based on conventional image features only.
Widespread distribution of radiocesium-bearing microparticles over the greater Kanto Region resulting from the Fukushima nuclear accident
Authors: Abe Yoshinari , Onozaki Seika , Nakai Izumi , Adachi Kouji , Igarashi Yasuhito , Oura Yasuji , Ebihara Mitsuru , Miyasaka Takafumi , Nakamura Hisashi , Sueki Keisuke , Tsuruta Haruo , Moriguchi Yuichi 
Published: January 2021

AbstractThe Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in March 2011 emitted a considerable amount of radioactive materials. This study isolated radiocesium-bearing microparticles (CsMPs), a form of radioactive materials emitted from the FDNPP at the early stage of the accident, from aerosols collected hourly on filter tapes at seven monitoring stations at the greater Kanto Region, including the Tokyo metropolitan area, on 15 March 2011. The aerosols had a spherical shape ~ 1 μm in diameter with activity of less than 1 Bq of 137Cs per particle. Their physical and chemical characteristics, including radioactivity ratio 134Cs/137Cs as well as chemical composition and state, are essentially the same as previously reported CsMPs. This study demonstrated that air parcels containing CsMPs emitted from the FDNPP were widespread over the greater Kanto Region, more than 250 km away from the FDNPP, during the daytime of 15 March. Trajectory analysis indicated that these particles were emitted from the reactor No. 2 of FDNPP between 14 March evening and 15 March early morning. The information obtained on the widespread distribution of CsMPs can be useful for assessing the actual impacts of radioactive contamination from the FDNPP accident on the environment and human health.
A focal extramedullary hematopoiesis of the spleen in a patient with essential thrombocythemia presenting with a complicated postoperative course: a case report
Authors: Hosoda Kiyotaka , Shimizu Akira , Kubota Koji , Notake Tsuyoshi , Sugenoya Shinsuke , Yasukawa Koya , Hayashi Hikaru , Kobayashi Ryoichiro , Soejima Yuji 
Published: January 2021

Abstract
Background
Extramedullary hematopoiesis is a compensatory response occurring secondary to inadequate bone marrow function and is occasionally observed in essential thrombocythemia (ET). This disease usually presents as multifocal masses in the paravertebral or intra-abdominal region; however, formation of a focal mass in the liver or spleen is rare. In addition, ET is characterized by increased platelet count and shows a tendency toward thrombosis and, occasionally, bleeding. Serious bleeding is common in ET patients, caused by the decrease in or abnormalities of von Willebrand factor (vWF) as a consequence of the precipitous rise in platelets. Therefore, strict management of platelet count using medication is crucial in patients with ET who require invasive procedures, especially splenectomy.

Case presentation
A 68-year-old man with ET was found to have an enlargement of a focal splenic tumor. Imaging findings revealed that the tumor was likely a hemangioma or hamartoma; however, the possibility of malignant disease could not be completely ruled out because of short-term tumor enlargement, and we conducted a splenectomy. The surgery was uneventful, but the patient presented with severe polycythemia and vWF abnormalities postoperatively, which resulted in bleeding from the drain insertion site and wound, epistaxis, and hemorrhoidal bleeding. Three months after discharge, polycythemia still persisted and the level of vWF gradually decreased. With a decrease in vWF, the patient suffered from an increased bleeding tendency. Therefore, the patient has been referred for bone marrow transplantation and is currently awaiting a suitable donor.

Conclusions
Extramedullary hematopoiesis should be listed as a differential diagnosis of focal enlarged splenic tumors, especially in patients with myeloproliferative disorders. Additionally, in splenectomy for ET patients, careful perioperative management taking into consideration the conflicting features of a tendency toward thrombus formation and bleeding is necessary.
Potassium Concentration in Initial Fluid Therapy and In-Hospital Mortality of Patients with Diabetic Ketoacidosis
Authors: Okada Akira , Yamana Hayato , Morita Kojiro , Sato Yukihito , Yamaguchi Satoko , Kurakawa Kayo Ikeda , Michihata Nobuaki , Matsui Hiroki , Fushimi Kiyohide , Nangaku Masaomi , Yamauchi Toshimasa , Yasunaga Hideo , Kadowaki Takashi 
Published: January 2021

Abstract

Context
Guidelines worldwide recommend potassium replacement of 10 to 40 mmol/L in the initial fluid therapy for patients with diabetic ketoacidosis. However, evidence is lacking as to the association between infused potassium concentration and mortality.

Objective
We aimed to determine the association between infused potassium concentration and in-hospital mortality.

Methods
Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients admitted for treatment of diabetic ketoacidosis from July 2010 to March 2018. Patients with kidney dysfunction or serum potassium abnormalities were excluded. We evaluated the association of the potassium concentration in the total infused solutions in the first 2 days of hospitalization with 28-day in-hospital mortality using multivariable regression analysis with a cubic spline model. We also assessed the association between potassium concentration and occurrence of hyperkalemia.

Results
We identified 14 216 patients with diabetic ketoacidosis and observed 261 deaths. The quartile cut-points for potassium concentration were 7.7, 11.4, and 16.1 mmol/L. Within the range of approximately 10 to 40 mmol/L, potassium concentration was not associated with occurrence of hyperkalemia or death. Lower potassium concentrations were associated with higher 28-day in-hospital mortality; the odds ratio for patients receiving 8 mmol/L was 1.69 (95% CI, 1.03 to 2.78; reference: 20 mmol/L), and the odds ratio increased monotonically as potassium concentration decreased further.

Conclusion
Patients receiving potassium replacement at concentrations of 10 to 40 mmol/L had similar in-hospital mortality rates, whereas lower concentrations were associated with higher mortality.
Relationship of Preoperative Thyroid Dysfunction to Clinical Outcomes in Pediatric Cardiac Surgery
Authors: Brown Morgan L , Quinonez Luis G , Staffa Steven J , DiNardo James A , Wassner Ari J 
Published: January 2021

Abstract

Context
Thyroid function may be assessed in children before cardiac surgery because of concerns that hypothyroidism or thyrotoxicosis might adversely affect cardiac function perioperatively. However, the relationship between preoperative thyroid dysfunction and surgical outcomes is unknown.

Objective
Determine the relationship between preoperative thyroid dysfunction and outcomes of pediatric cardiac surgery.

Methods
Retrospective cohort study (January 2005 to July 2019).

Setting
Academic pediatric hospital.

Patients
All patients &lt;19 years old who underwent cardiac surgery with cardiopulmonary bypass and had thyrotropin (TSH) measured within 14 days preoperatively. Exclusion criteria included neonates (≤30 days), preoperative extracorporeal life support, salvage operations, or transplantation procedures.

Main Outcome Measures
Subjects were stratified by preoperative TSH concentration (mIU/L): low (&lt;0.5), normal (0.5-5), mildly high (5.01-10), or moderately high (&gt;10). Outcomes were compared among subjects with normal TSH (control) and each group with abnormal TSH concentrations. The primary outcome was 30-day mortality. Secondary outcomes included time to extubation, intensive care unit and hospital length of stay, and operative complications.

Results
Among 592 patients analyzed, preoperative TSH was low in 15 (2.5%), normal in 347 (58.6%), mildly high in 177 (29.9%), and moderately high in 53 (9.0%). Free thyroxine was measured in 77.4% of patients and was low in 0 to 4.4% of subjects, with no differences among TSH groups. Thirty-day mortality was similar among TSH groups. There were no differences in any secondary outcome between patients with abnormal TSH and patients with normal TSH.

Conclusion
Preoperative mild to moderate subclinical hypothyroidism was not associated with adverse postoperative outcomes in children undergoing cardiopulmonary bypass procedures.