bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of patient engagement in a French telemonitoring programme for heart failure on hospitalization and mortality
Authors: Sabatier Rémi , Legallois Damien , Jodar Mouna , Courouve Laurène , Donio Valérie , Boudevin Florence , De Chalus Thibault , Hauchard Karine , Belin Annette , Milliez Paul
Published: June 2022

Aims

Management of patients with recently decompensated heart failure by hospital services is expensive, complicated to plan, and not always effective. Telemedicine programmes in heart failure may improve the quality of care, but their effectiveness is poorly documented in real‐world settings. The study aims to evaluate the impact of patient engagement in home‐based telemonitoring for heart failure (SCAD programme) on rehospitalization and mortality rates.

Methods and results

A retrospective observational study was performed in 659 SCAD participants. SCAD is a patient‐oriented service of home‐based interactive telemonitoring offered to heart failure patients during hospitalization who agree to participate in a therapeutic education programme. Patients were telemonitored for at least 3 months, and rehospitalization and mortality were documented at 12 months and 5 years. During the telemonitoring period, patients provided daily information on health and lifestyle through an internet‐based interface. Data were linked on a patient‐by‐patient basis between the SCAD database and the French national health insurance database (Système National des Données de Santé). Outcomes were compared as a function of use of the programme. Low, intermediate, and high users were classified by tercile of data return during telemonitoring. Patients were followed for a median of 32.9 months. Rehospitalization rates for cardiovascular disease decreased from 79.4% in the year preceding enrolment to 41.1% in the following year and from 52.8% to 18.8% for hospitalizations for heart failure. The 12 month mortality rate was 11.2%. Significant associations were observed between level of use of the SCAD programme and all‐cause rehospitalization (P = 0.0085), rehospitalization for cardiovascular disease (P = 0.0010), rehospitalization for heart failure (27.8% in low users, 12.9% in intermediate users, and 13.5% in high users; P < 0.0001), and mortality (26.8%, 15.2%, and 15.9% respectively; P = 0.0157) in the 12 months following enrolment. The mean number of days alive outside hospital were 279 ± 111 in low users, 312 ± 90 in intermediate users, and 304 ± 100 in high users (P = 0.0022).

Conclusions

Educational home telemonitoring of patients with heart failure following hospitalization provides long‐term clinical benefits in terms of rehospitalization and death in real‐world settings, according to the level of use of the programme by the patient. These benefits would be expected to have a major impact on the burden of this disease. Low engagement in telemonitoring could be used as a signal of poor prognosis and taken into account in the management strategy.
Combined mechanical circulatory support for ventricular fibrillation in left ventricular assist device patient
Authors: Abu Akel Mahmood , Shaul Aviv A. , Goldenberg Gustavo R. , Barac Yaron D. , Ben‐Avraham Binyamin , Gorfil Dan , Aravot Dan , Ben‐Gal Tuvia
Published: June 2022

Ventricular fibrillation, a life‐threatening ventricular arrhythmia, may result in pulselessness, loss of consciousness and sudden cardiac death. In this case report, we describe our experience in managing a 54‐year‐old man with HeartMate3 left ventricular assist device (LVAD) as a bridge to transplantation due to dilated non‐ischemic cardiomyopathy, presenting with incessant ventricular arrhythmia for 35 days despite multiple attempts to restore normal rhythm with external direct current cardioversion and anti‐arrhythmic medications. The patient remained stable in ventricular arrhythmia with no progression to asystole, but hemodynamic collapse due to right heart failure occurred in the third week. Combined use of two mechanical circulatory support devices (LVAD with VA ECMO) was needed to achieve haemodynamic and metabolic stability, eventually leading to successful heart transplantation in the index admission. The patient was discharged home 2 weeks after transplantation in good clinical condition.
An Adenine‐Based Biological Metal‐Organic Framework as an Efficient Luminescent Sensor for Tetracycline Detection
Authors: Wu Xia , Xiong Xiao , Li Jia‐Li , Luo Dong , Wu Kun , Wei Yu‐Bai , Liu Xin‐Yi , Lu Weigang , Li Dan , He Jian
Published: June 2022

Because of their misuse and poor management, antibiotics pose a significant threat to the ecological environment and human health. The development of highly sensitive and effective sensors to detect such environmental contaminants is a crucial and challenging task. As a new class of desirable biocompatible materials, biological metal‐organic frameworks are considered as a viable platform for sensing applications. Herein, we report the synthesis of biological luminescent metal‐organic framework [Zn6Ad4(BPDC‐(OH)2)4]n (JNU‐104) using adenine (Ad) and 2,2′‐dihydroxy‐1,1′‐biphenyl‐4,4′‐dicarboxylic acid [BPDC‐(OH)2] as organic linkers. JNU‐104 serves as a robust and sensitive luminescent sensor for detecting tetracycline antibiotics in aqueous media with low limits of detection (LODs) of 0.023, 0.029 and 0.024 μM for tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC), respectively. Furthermore, the MOF‐based test strips show a rapid and visualizable luminescence response to tetracycline antibiotics, making JNU‐104 a promising candidate for practical applications in sensing.
What Happens to MnO2 When It Comes in Contact with Zn2+? An Electrochemical Study in Aid of Zn/MnO2‐Based Rechargeable Batteries
Authors: Rossi Francesca , Marini Emanuele , Boniardi Marco , Casaroli Andrea , Bassi Andrea Li , Macrelli Andrea , Mele Claudio , Bozzini Benedetto
Published: June 2022

In the science and technology of electrochemical energy storage, different allotropes of MnO2, fabricated with a variety of methods, are assembled into electrodes, playing the role of cathode or oxygen reduction reaction (ORR) electrocatalyst. Often, MnO2‐based cathodes are combined with Zn anodes into different types of batteries, resulting in contact between MnO2 and its electrochemical reaction products, and Zn2+. Awareness is growing that this interaction adversely affects the functional performance of MnO2, but no definitive understanding has been reached for this issue. This study contributes, through electrochemical measurements accompanied by microscopy and Raman spectroscopy, to a better understanding of the way the electrochemical behavior of two technologically representative types of manganese dioxide ‐ hydrothermally grown α‐MnO2 and electrodeposited γ‐MnO2 (EDM) ‐ is degraded when these materials are exposed to neutral and alkaline aqueous solutions, containing Zn2+. Specifically, we highlighted different types of irreversible changes in electrochemical response, which can be interpreted with phase‐formation processes. Such changes result in the deactivation of α‐MnO2 as ORR electrocatalyst, and of both α‐MnO2 and EDM as zinc‐ion battery (ZIB) cathodes. The electroactivity of EDM for ZIB operation can be restored if Mn2+ is added to the neutral electrolyte, because a phase, active in discharge, is electrodeposited during charging.
Projecting Recent Advancements in Battery Technology to Next‐Generation Electric Vehicles
Authors: Kim Sangwook , Tanim Tanvir R. , Dufek Eric J. , Scoffield Don , Pennington Timothy D. , Gering Kevin L. , Colclasure Andrew M. , Mai Weijie , Meintz Andrew , Bennett Jesse
Published: June 2022

Electric vehicles (EVs) have seen rapid growth in adoption over the last several years. Advancements to increase battery life and performance, policy shifts, and high charging rate are expected to further accelerate the development of next generation of EVs. Battery improvements continue to emerge, enabling increased driving range, total distance driven over the life of vehicles, and ability to charge at high rates. Herein, an analysis framework to provide insights into inclusive design metrics, such as specific energy of batteries, energy consumption of vehicles, and charging power infrastructure development, is developed. Various cell‐level fast charge protocols to realistic battery designs to understand the infrastructure needs associated with achieving range replacement of 32.25 km min−1 (20 mi min−1) are also scaled. By calculating scaled power and peak to average power ratio, it is found that there needs to be more distinct alignment between the research efforts focused at the cell level and what is being developed for EV charging infrastructure needs. Finally, impact of high direct current voltage architecture in next‐generation EVs is discussed. The findings in this work provide an insight into recent advancements in battery technology to next‐generation EVs.
A multi‐perspective framework for seismic retrofit optimization of urban infrastructure systems
Authors: Liu Chuang , Ouyang Min , Mao Zijun , Xu Xiaolin
Published: June 2022

Urban infrastructure systems play essential roles in the smooth functioning of modern society but are also threatened by seismic hazards in the earthquake‐prone areas. Retrofitting critical components of those systems has been considered as the most frequently used mitigation strategy in both the literature and practice. The seismic retrofit budget is usually limited, then it needs to identify a set of critical components to be retrofitted, which is generally formulated as a seismic retrofit optimization problem. This article proposes a multi‐perspective modeling and solution framework for the seismic retrofit optimization of urban infrastructure systems, which allows choosing different performance measures including vulnerability, resilience loss and economic loss as the objective function. The proposed framework can be used to explore how different performance measures and the infrastructure interdependencies affect the seismic retrofit decision. Taking the interdependent Shelby power and gas systems as an example, results show that if considering single systems, the optimal economic loss‐based performance improvement ratio (PIR) is larger than the best resilience loss‐based PIR, which is larger than the vulnerability‐based PIR; if considering interdependent systems, the interdependency intensity is indeed a key factor affecting the retrofit decision.
H2RUN: An efficient vendor lock‐in solution for multi‐cloud environment using horse herd Runge Kutta based data placement optimization
Authors: Hari Kumar P , Mala G. S. Anandha
Published: June 2022

Vendor lock‐in is a scenario where the cost of switching to another vendor is mainly high and for this reason, the consumer is mainly struck with a single cloud vendor. The vendor lock‐in mainly implies the situation of an organization where it is locked into a service or product of a single Cloud Service Providers (CSP) to prevent the disruption of the business operation or due to an insufficient workforce. Due to its high availability, portability, and other benefits, various researchers frequently adopt the multi‐cloud strategy to prevent vendor lock‐in. However, the multi‐cloud architecture also comes with major drawbacks such as cost, multiple CSP management, and the tradeoff between cost and availability. The organizations are mainly considerate about achieving the tradeoff between the cost and availability. To overcome this problem, we have proposed an H2RUN (Horse Herd Runge Kutta) optimization algorithm to achieve a tradeoff between the cost and availability using erasure coding. The proposed H2RUN optimization algorithm selects the optimal CSP and erasure coding parameters that enhance the availability of the CSP with minimal cost. The efficiency of the proposed methodology can be evaluated using the experiments conducted on different real‐time CSPs using various metrics. Based on the results achieved, the H2RUN optimizer minimizes the cost up to 48% and availability up to 58%.
A systematic survey of data mining and big data in human behavior analysis: Current datasets and models
Authors: Ding Xuefeng , Gan Qihong , Bahrami Sara
Published: June 2022

In recent years, understanding human behavior has become one of the most important topics in the field of computer vision research. The reason for this growing attention is the wide range of applications that can benefit from the results of this field of research. The human behavior analysis (HBA) includes a wide range of research areas from the detection of human motion and action. Datasets created through actions and detection of human activities make it possible to compare different detection methods with the same input data. Data mining and big data approaches are very popular for analyzing data related to human behavior and can be used to address the challenges of fast processing. This article provides a systematic survey of data mining and big data in the HBA. We focus on current datasets and models related to the detection of human behavior patterns in the literature. The purpose of this survey is to assist researchers in select appropriate datasets and models to evaluate algorithms, as well as to identify research gaps for future work. To achieve this goal, articles published between 2010 and 2021 have been reviewed. These articles fall into five general categories in terms of dataset focus: object detection, motion, action, activity, and behavior. This article provides a summary of data mining and big data models in the HBA, as well as related datasets based on these categories, to highlight promising research avenues for future work.
A modified global neighborhood algorithm for designing labeling diversity mappers
Authors: Solwa Shaheen , Olayinka Ayanda Dauda
Published: June 2022

Genetic algorithms (GAs) have been recently applied to uncoded space‐time labeling diversity systems (USTLD) to improve upon diversity in wireless links. GAs were used to optimize the secondary mappers that are used to encode the information to be transmitted. Existing literature only achieved a local optimal design, at the fraction of the computational costs. Hence, this article focuses on improving upon the GAs for USTLD systems by merging it with a global‐local search technique, called the global neighborhood algorithm (GNA). The GNA algorithm was tested on M‐QAM, M‐PSK, M‐APSK, and asymmetric M‐APSK constellations of modulation order M , and . In the case of M‐QAM constellations, the GNA was able to match, but not improve upon existing mapper designs. In the case of the 64PSK constellation, the GNA was able to produce mapper designs that improved upon the error performance of existing mapper designs by approximately 1 dB. In the case of the 32APSK constellation, the GNA was able to improve upon the error performance of existing mapper designs by approximately 0.5 dB. Moreover, the GNA produced mapper designs for the 11+5APSK and asymmetric 16APSK constellations that improved upon the error performance of existing mapper designs by approximately 0.5 and 4 dB respectively. Finally, the computational complexity of the proposed GNA algorithm was analyzed and the algorithm was shown to be which is slightly more complex than the initial GA approach with complexity , but significantly less complex than the enhanced GA with complexity . The increased complexity also came with significant gains such as improved LD mapper designs.
Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of CIC‐rearranged sarcoma
Authors: Satomi Kaishi , Ohno Makoto , Kubo Takashi , Honda‐Kitahara Mai , Matsushita Yuko , Ichimura Koichi , Narita Yoshitaka , Ichikawa Hitoshi , Yoshida Akihiko
Published: June 2022

CIC‐rearranged sarcoma is a high‐grade sarcoma, most often harboring CIC::DUX4 fusion, and is characterized by a distinct round cell histology, co‐expression of ETV4 and WT1, and a specific DNA methylation class. Herein, we report a brain tumor with ATXN1::DUX4 that had an indistinguishable phenotype and DNA methylation profile from CIC‐rearranged sarcoma. A 40‐year‐old man presented with a 5 cm hemorrhagic mass in the right frontal lobe of the cerebrum. The tumor was resected and histologically showed a dense proliferation of relatively monomorphic round cells with multifocal myxoid changes. Immunohistochemically, the tumor was diffusely positive for ETV4, WT1, and DUX4. Through classic histomorphology and immunoprofile, the tumor was provisionally diagnosed as CIC‐rearranged sarcoma. However, no CIC fusions or mutations were identified using CIC break‐apart fluorescence in situ hybridization (FISH) or FoundationOne CDx. Despite multiple surgeries and adjuvant chemoradiation therapy, the patient succumbed 16 months after presentation. RNA exome sequencing detected an in‐frame intraexonic ATXN1 (exon 9)::DUX4 (exon 1) fusion, which was validated by reverse transcription‐polymerase chain reaction and ATXN1 FISH assay. Upon DNA methylation analysis, the tumor matched with CIC‐rearranged sarcoma both by the Deutsche Krebsforschungszentrum classifier and t‐distributed stochastic neighbor embedding. Along with a recent report of a similar pediatric brain tumor, the present case suggests that ATXN1::DUX4 is a recurrent alternative molecular event in the sarcoma type that is presently defined by CIC rearrangement, which prompts an expansion of the tumor concept.
Infantile metastatic ependymoma with a novel molecular profile and favorable outcome to intensive chemotherapy without irradiation: Case‐based review
Authors: De Faria Flavia Watusi , Schieffer Kathleen M. , Pierson Christopher R. , Boue Daniel R. , LaHaye Stephanie , Miller Katherine E. , Amayiri Nisreen , Koboldt Daniel C. , Lichtenberg Tara , Leraas Kristen , Brennan Patrick , Kelly Ben , White Peter , Magrini Vincent , Wilson Richard K. , Mardis Elaine R. , Cottrell Catherine E. , Rusin Jerome , Finlay Jonathan L. , Osorio Diana S.
Published: June 2022

Ependymal tumors are the third most common brain tumor under 14 years old. Even though metastatic disease is a rare event, it affects mostly young children and carries an adverse prognosis. The factors associated with dissemination and the best treatment approach have not yet been established and there is limited published data on how to manage metastatic disease, especially in patients under 3 years of age. We provide a review of the literature on clinical characteristics and radiation‐sparing treatments for metastatic ependymoma in children under 3 years of age treated. The majority (73%) of the identified cases were above 12 months old and had the PF as the primary site at diagnosis. Chemotherapy‐based approaches, in different regimens, were used with radiation reserved for progression or relapse. The prognosis varied among the studies, with an average of 50%–58% overall survival. This study also describes the case of a 7‐month‐old boy with metastatic posterior fossa (PF) ependymoma, for whom we identified a novel SPECC1L‐RAF1 gene fusion using a patient‐centric comprehensive molecular profiling protocol. The patient was successfully treated with intensive induction chemotherapy followed by high‐dose chemotherapy and autologous hematopoietic progenitor cell rescue (AuHSCR). Currently, the patient is in continuous remission 5 years after his diagnosis, without radiation therapy. The understanding of the available therapeutic approaches may assist physicians in their management of such patients. This report also opens the perspective of newly identified molecular alterations in metastatic ependymomas that might drive more chemo‐sensitive tumors.
Proteogenomic characterization of cholangiocarcinoma
Authors: Deng Mengjie , Ran Peng , Chen Lingli , Wang Yunzhi , Yu Zixiang , Cai Ke , Feng Jinwen , Qin Zhaoyu , Yin Yanan , Tan Subei , Liu Yang , Xu Chen , Shi Guoming , Ji Yuan , Zhao Jian‐Yuan , Zhou Jian , Fan Jia , Hou Yingyong , Ding Chen
Published: June 2022

Background and Aims:

Cholangiocarcinoma (CCA) is a highly heterogeneous cancer with limited understanding and few effective therapeutic approaches. We aimed at providing a proteogenomic CCA characterization to inform biological processes and treatment vulnerabilities.

Approach and Results:

Integrative genomic analysis with functional validation uncovered biological perturbations downstream of driver events including DPCR1, RBM47 mutations, SH3BGRL2 copy number alterations, and FGFR2 fusions in CCA. Proteomic clustering identified three subtypes with distinct clinical outcomes, molecular features, and potential therapeutics. Phosphoproteomics characterized targetable kinases in CCA, suggesting strategies for effective treatment with CDK and MAPK inhibitors. Patients with CCA with HBV infection showed increased antigen processing and presentation (APC) and T cell infiltration, conferring a favorable prognosis compared with those without HBV infection. The characterization of extrahepatic CCA recommended the feasible application of vascular endothelial‐derived growth factor inhibitors. Multiomics profiling presented distinctive molecular characteristics of the large bile duct and the small bile duct of intrahepatic CCA. The immune landscape further revealed diverse tumor immune microenvironments, suggesting immune subtypes C1 and C5 might benefit from immune checkpoint therapy. TCN1 was identified as a potential CCA prognostic biomarker, promoting cell growth by enhancing vitamin B12 metabolism.

Conclusions:

We characterized the proteogenomic landscape of 217 CCAs with 197 paired normal adjacent tissues and identified their subtypes and potential therapeutic targets. The multiomics analyses with other databases and some functional validations have indicated strategies regarding the clinical, biological, and therapeutic approaches to the management of CCA.
Neuroplastic changes inc‐Fos,ΔFosB,BDNF,trkB, and Arc expression in the hippocampus of male Roman rats: differential effects of sexual activity
Authors: Sanna Fabrizio , Serra Maria Pina , Boi Marianna , Bratzu Jessica , Poddighe Laura , Sanna Francesco , Carta Antonella , Corda Maria Giuseppa , Giorgi Osvaldo , Melis Maria Rosaria , Argiolas Antonio , Quartu Marina
Published: June 2022

Sexual activity causes differential changes in the expression of markers of neural activation (c‐Fos and ΔFosB) and neural plasticity (Arc and BDNF/trkB), as determined either by Western Blot (BDNF, trkB, Arc, and ΔFosB) or immunohistochemistry (BDNF, trkB, Arc, and c‐Fos), in the hippocampus of male Roman high (RHA) and low avoidance (RLA) rats, two psychogenetically selected rat lines that display marked differences in sexual behavior (RHA rats exhibit higher sexual motivation and better copulatory performance than RLA rats). Both methods showed (with some differences) that sexual activity modifies the expression levels of these markers in the hippocampus of Roman rats depending on: (i) the level of sexual experience, that is, changes were usually more evident in sexually naïve than in experienced rats; (ii) the hippocampal partition, that is, BDNF and Arc increased in the dorsal but tended to decrease in the ventral hippocampus; (iii) the marker considered, that is, in sexually experienced animals BDNF, c‐Fos, and Arc levels were similar to those of controls, while ΔFosB levels increased; and (iv) the rat line, that is, changes were usually larger in RHA than RLA rats. These findings resemble those of early studies in RHA and RLA rats showing that sexual activity influences the expression of these markers in the nucleus accumbens, medial prefrontal cortex, and ventral tegmental area, and show for the first time that also in the hippocampus sexual activity induces neural activation and plasticity, events that occur mainly during the first phase of the acquisition of sexual experience and depend on the genotypic/phenotypic characteristics of the animals.
Long‐term survival of nonlocalized epithelial ovarian cancer among women using menopausal hormone therapy prior to diagnosis: The extreme study
Authors: Baandrup Louise , Galanakis Michael , Hannibal Charlotte G. , Dehlendorff Christian , Hertzum‐Larsen Rasmus , Mørch Lina S. , Kjaer Susanne K.
Published: June 2022

Prediagnostic use of menopausal hormone therapy (MHT) has been suggested to be associated with improved survival of epithelial ovarian cancer (EOC). We investigated the potential long‐term survival benefit of prediagnostic MHT use in women ≥50 years with nonlocalized EOC using the Extreme study including all women in Denmark registered with nonlocalized EOC during 2000 to 2014 (N = 3776). We obtained individual‐level information on prediagnostic use of systemic estrogen therapy (ET) and estrogen plus progestin therapy (EPT) from the National Prescription Registry and estimated absolute and relative 5‐ and 10‐year survival probabilities with 95% confidence intervals (CIs) using pseudo‐values, taking into account histology, comorbidity, income and residual disease. Among women not having used prediagnostic MHT, 5‐ and 10‐year absolute survival probabilities were 19% and 11%, respectively. Compared to MHT nonusers, prediagnostic systemic ET use for 3 to 4 years and ≥ 5 years was associated with 1.43 (95% CI: 1.01‐2.02) and 1.22 (95% CI: 0.96‐1.55) times higher 5‐year survival probabilities, respectively. Ten‐year survival probabilities were also increased but not statistically significantly. Among prediagnostic EPT users, increased 5‐year (1.14, 95% CI: 0.85‐1.53) and 10‐year (1.38, 95% CI: 0.91‐2.08) survival probabilities were observed after use for 3 to 4 years compared to MHT nonuse, whereas EPT use for ≥5 years was not associated with long‐term survival of nonlocalized EOC. Our findings may suggest a better long‐term survival of nonlocalized EOC in women having used long‐term prediagnostic ET. However, the statistical precision of our results did not allow firm conclusions and more studies are needed.
Adherence to a healthy lifestyle in relation to colorectal cancer incidence and all‐cause mortality after endoscopic polypectomy: A prospective study in three U.S. cohorts
Authors: Wang Liang , Knudsen Markus D. , Lo Chun‐Han , Wang Kai , He Mingming , Polychronidis Georgios , Hang Dong , He Xiaosheng , Zhong Rong , Wu Kana , Chan Andrew T. , Ogino Shuji , Giovannucci Edward L. , Song Mingyang
Published: June 2022

It remains unknown whether maintenance of a healthy lifestyle after endoscopic polypectomy could still confer benefit for colorectal cancer (CRC) incidence and mortality. In this study, we defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption and diet (range, 0‐5). We used Cox proportional hazards regression to estimate the hazard ratios (HRs) for the associations of healthy lifestyle score and individual lifestyle factors with CRC incidence and all‐cause mortality. During a median of 10 years of follow‐up of 24 668 participants who underwent endoscopic polypectomy, we documented 161 CRC cases and 4857 all‐cause deaths. A higher healthy lifestyle score after endoscopic polypectomy was associated with lower risk of CRC and all‐cause mortality. Compared with individuals with 0 to 1 healthy lifestyle factors, those with 2, 3 and 4 to 5 healthy lifestyle factors had a HR for CRC risk of 0.86 (95% confidence interval [CI], 0.60‐1.24), 0.73 (95% CI, 0.47‐1.14) and 0.52 (95% CI, 0.27‐1.01), respectively (Ptrend = .03). The corresponding HR (95% CI) for all‐cause mortality was 0.83 (95% CI, 0.76‐0.90), 0.63 (95% CI, 0.56‐0.70) and 0.56 (95% CI, 0.48‐0.65), respectively (Ptrend < .0001). In the joint analysis of pre‐ and postpolypectomy periods, patients with a healthy postpolypectomy lifestyle had a lower incidence of CRC regardless of their prepolypectomy exposure, whereas those with a healthy lifestyle in both periods had a lower mortality than those with an unhealthy lifestyle in either period. In conclusion, adherence to a healthy lifestyle after polypectomy may confer significant benefit for CRC prevention and reduction in all‐cause mortality.
Improving identification of symptomatic cancer at primary care clinics: A predictive modeling analysis in Botswana
Authors: Molebatsi Kesaobaka , Iyer Hari S. , Kohler Racquel E. , Gabegwe Kemiso , Nkele Isaac , Rabasha Bokang , Botebele Kerapetse , Barak Tomer , Balosang Siamisang , Tapela Neo M. , Dryden‐Peterson Scott L.
Published: June 2022

In resource‐limited settings, augmenting primary care provider (PCP)‐based referrals with data‐derived algorithms could direct scarce resources towards those patients most likely to have a cancer diagnosis and benefit from early treatment. Using data from Botswana, we compared accuracy of predictions of probable cancer using different approaches for identifying symptomatic cancer at primary clinics. We followed cancer suspects until they entered specialized care for cancer treatment (following pathologically confirmed diagnosis), exited from the study following noncancer diagnosis, or died. Routine symptom and demographic data included baseline cancer probability assessed by the primary care provider (low, intermediate, high), age, sex, performance status, baseline cancer probability by study physician, predominant symptom (lump, bleeding, pain or other) and HIV status. Logistic regression with 10‐fold cross‐validation was used to evaluate classification by different sets of predictors: (1) PCPs, (2) Algorithm‐only, (3) External specialist physician review and (4) Primary clinician augmented by algorithm. Classification accuracy was assessed using c‐statistics, sensitivity and specificity. Six hundred and twenty‐three adult cancer suspects with complete data were retained, of whom 166 (27%) were diagnosed with cancer. Models using PCP augmented by algorithm (c‐statistic: 77.2%, 95% CI: 73.4%, 81.0%) and external study physician assessment (77.6%, 95% CI: 73.6%, 81.7%) performed better than algorithm‐only (74.9%, 95% CI: 71.0%, 78.9%) and PCP initial assessment (62.8%, 95% CI: 57.9%, 67.7%) in correctly classifying suspected cancer patients. Sensitivity and specificity statistics from models combining PCP classifications and routine data were comparable to physicians, suggesting that incorporating data‐driven algorithms into referral systems could improve efficiency.
Eventual success rate and predictors of success for oncology drugs tested in phase I trials
Authors: Haslam Alyson , Olivier Timothée , Powell Kerrington , Tuia Jordan , Prasad Vinay
Published: June 2022

Previous estimates of the likelihood of a drug tested in phase I trials obtaining FDA clearance are out of date. In the intervening years, newer pharmaceuticals have been developed, resulting in new delivery systems and lines of therapies. We sought to explore and update these estimates by comprehensively searching drugs tested in phase I trials and to determine the factors associated with later receiving FDA approval. In a cross‐sectional analysis, we searched for anti‐tumor drugs tested in phase I trials and published in scientific journals or presented at hematology/oncology conferences. For each drug, we searched PubMed for phase II and phase III studies testing the drug for the same indication tested in phase I studies. We found 51 drug approvals; four were withdrawn. The probability of a drug tested in 2015 being approved by 2021 was 6.2%. Drugs tested as monotherapy were more likely to receive approval than drugs tested in combination, and monoclonal antibodies were more likely to receive approval than drugs of other mechanisms. In adjusted models, response rates higher than 40% in phase I studies, demonstrating an improvement in overall survival (OS) in phase III studies, and drugs tested as monotherapy were associated with receiving FDA approval. When looking at all drugs tested during a single year, most drugs were not approved, and among those that are approved, almost 8% are withdrawn. Response rates higher than 40%, testing a drug as monotherapy, and demonstrating an improvement in OS were associated with receiving FDA approval.
A modified contrast source inversion method for microwave tomographic imaging of Debye dispersive media
Authors: Liu Guangdong , Zhang Kaiyin
Published: June 2022

The Debye empirical formulas are often used for the description of the dispersion characteristics of common media, such as biological tissues, water, and soil. In order to reconstruct their frequency‐related electrical properties, a multi‐frequency contrast source inversion (CSI) method is modified from the direct estimation of the contrast between Debye scatterers and background medium, into the reconstruction of three kinds of Debye model parameters, namely, the optical relative permittivity, relative permittivity difference, and static conductivity. Through three two‐dimensional (2D) benchmark numerical experiments, detailed comparisons between the results by the improved CSI method, and those by the frequency hopping (FH) technique, single frequency subspace‐based optimization method (SOM) with deep learning (DL), multi frequency (MF) dispersive SOM, and time‐domain inverse scattering (TDIS) approach, show preliminarily that the modified CSI (M‐CSI) method is feasible and robust, and that it exhibits acceptable compromise performance by the comprehensive consideration of convergence characteristics, positioning accuracy, reconstruction errors, and computational efficiency. Also, the M‐CSI method has been successfully applied to quantitatively reconstruct the internal breast composition in a 2D cancerous phantom extracted from a realistic numerical breast, dielectrically and anatomically.
Engineering extracellular vesicles by three‐dimensional dynamic culture of human mesenchymal stem cells
Authors: Yuan Xuegang , Sun Li , Jeske Richard , Nkosi Dingani , York Sara B. , Liu Yuan , Grant Samuel C. , Meckes David G. , Li Yan
Published: June 2022

Human mesenchymal stem cell (hMSC) derived extracellular vesicles (EVs) have shown therapeutic potential in recent studies. However, the corresponding therapeutic components are largely unknown, and scale‐up production of hMSC EVs is a major challenge for translational applications. In the current study, hMSCs were grown as 3D aggregates under wave motion to promote EV secretion. Results demonstrate that 3D hMSC aggregates promote activation of the endosomal sorting complexes required for transport (ESCRT)‐dependent and ‐independent pathways. mRNA sequencing revealed global transcriptome alterations for 3D hMSC aggregates. Compared to 2D‐hMSC‐EVs, the quantity of 3D‐hMSC‐EVs was enhanced significantly (by 2‐fold), with smaller sizes, higher miR‐21 and miR‐22 expression, and an altered protein cargo (e.g., upregulation of cytokines and anti‐inflammatory factors) uncovered by proteomics analysis, possibly due to altered EV biogenesis. Functionally, 3D‐hMSC‐EVs rejuvenated senescent stem cells and exhibited enhanced immunomodulatory potentials. In summary, this study provides a promising strategy for scalable production of high‐quality EVs from hMSCs with enhanced therapeutic potential.
International multidisciplinary survey on the initial management of acute pancreatitis: Perspective of point‐of‐care specialists focused on daily practice
Authors: Lluís Nuria , Asbun Horacio , Besselink Marc G. , Capurso Gabriele , Garg Pramod Kumar , Gelrud Andres , Khannoussi Wafaa , Lee Hong Sik , Leppäniemi Ari , Löhr Johannes‐Matthias , Mahapatra Soumya Jagannath , Mancilla Carla , van Santvoort Hjalmar C , Zapater Pedro , Lluís Felix , de Madaria Enrique , Ramia José Manuel
Published: June 2022

Background

The initial management of patients with acute pancreatitis impacts both morbidity and mortality. Point‐of‐care decisions have been reported to differ from clinical guideline recommendations.

Methods

An online anonymous questionnaire was distributed through scientific associations and social media using REDCap. Multivariable logistic regression was used to identify the characteristics of participants associated with compliance with the recommendations.

Results

A total of 1054 participants from 94 countries completed the questionnaire; median age (IQR) was 39 (32–47) years; 30.7% were women. Among the participants, 37% opted for nonmoderate flow of i.v. fluid, 31% for fluid type other than Ringer’s lactate; 73.4% were in favor of nil per os to patients who could eat, 75.5% for other than enteral feeding to patients with oral intolerance; 15.5% used prophylactic antibiotic in patients with severe acute pancreatitis, 34.1% in necrotizing acute pancreatitis, and 27.4% in patients with systemic inflammatory response syndrome; 27.8% delayed cholecystectomy after biliary acute pancreatitis. Participants with publications in PubMed on acute pancreatitis showed better compliance (OR, 1.62; 95% CI: 1.15–2.32; P = .007) with recommendations of the clinical guidelines.

Conclusions

Feeding and nutrition require the greatest improvement efforts, but also the use of prophylactic antibiotics and timing of cholecystectomy should be improved.
ALG8‐CDG: Molecular and phenotypic expansion suggests clinical management guidelines
Authors: Albokhari Daniah , Ng Bobby G. , Guberinic Alis , Daniel Earnest James Paul , Engelhardt Nicole M. , Barone Rita , Fiumara Agata , Garavelli Livia , Trimarchi Gabriele , Wolfe Lynne , Raymond Kimiyo M. , Morava Eva , He Miao , Freeze Hudson H. , Lam Christina , Edmondson Andrew C.
Published: June 2022

Congenital disorders of glycosylation are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid glycan biosynthesis. These disorders mostly manifest with multisystem involvement. Individuals with ALG8‐CDG commonly present with hypotonia, protein‐losing enteropathy, and hepatic involvement. Here, we describe seven unreported individuals diagnosed with ALG8‐CDG based on biochemical and molecular testing and we identify nine novel variants in ALG8, bringing the total to 26 individuals with ALG8‐CDG in the medical literature. In addition to the typical multisystem involvement documented in ALG8‐CDG, our cohort includes the two oldest patients reported and further expands the phenotype of ALG8‐CDG to include stable intellectual disability, autism spectrum disorder and other neuropsychiatric symptoms. We further expand the clinical features in a variety of organ systems including ocular, musculoskeletal, dermatologic, endocrine, and cardiac abnormalities and suggest a comprehensive evaluation and monitoring strategy to improve clinical management.
Effect of Obesity on Left Ventricular Remodeling and Clinical Outcome in Chinese Patients With Hypertrophic Cardiomyopathy: Assessed by Cardiac MRI
Authors: Shi Ke , Huang Shan , Li Xiang , Xu Hua‐Yan , Yang Meng‐Xi , Li Yuan , Guo Ying‐Kun , Yang Zhi‐Gang
Published: June 2022

Background

Obesity is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and believed to influence its phenotype.

Purpose

To explore the effects of obesity on left ventricular (LV) remodeling and long‐term clinical course in Chinese patients with HCM.

Study Type

Longitudinal.

Population

A total of 247 patients with HCM classified according to body mass index (BMI) (normal weight: BMI = 18.0–22.9 kg/m2 [N = 90]; overweight: BMI = 23.0–24.9 kg/m2 [N = 58]; and obese: BMI ≥ 25 kg/m2 [N = 99]).

Field Strength/Sequence

3.0 T/Balanced steady‐state free precession sequence and phase‐sensitive inversion recovery late gadolinium enhancement (LGE) sequence.

Assessment

LV function and geometry were measured. LV peak strain analysis was performed. The presence and percentage of LGE in the LV were recorded. The endpoints including heart failure, sudden cardiac death, and overall composite outcome were assessed during a median follow‐up of 4.1 years (interquartile range, 3.0–6.2 years).

Statistical Tests

One‐way analysis of variance, Kruskal–Wallis test, or chi‐square test; Pearson correlation coefficient (r); multivariable linear regression analysis; Kaplan–Meier survival analysis; and Cox proportional hazards model analysis were conducted. A two‐tailed P‐value < 0.05 was considered statistically significant.

Results

Obese patients exhibited a significant progressive increase in LV mass compared with normal‐weight patients. The magnitude of all LV strain indices gradually and significantly decreased as BMI increased, whereas LV ejection fraction was not significantly different among BMI groups (P = 0.364). Multivariable linear regression analysis showed that obesity had a significant association with impaired strain indices as well as with indexed LV mass. Multivariable Cox model analysis retained obesity as an independent marker for future endpoints, and conveyed a > 3‐fold increase in risk compared with patients with normal weight (hazard ratio, 3.04; 95% confidence interval, 1.07–6.57).

Data Conclusion

Obesity is an important environmental modifier that is associated with adverse LV remodeling and is independently associated with future clinical outcomes in Chinese patients with HCM.

Level of Evidence

3

Technical Efficacy

Stage 2
Correcting rotational error in rectal cancer radiation therapy: Can planning target volume margins be safely reduced?
Authors: Seah Vivian , Dundas Kylie , Hudson Felicity , Surjan Yolanda , Bartlett Rebecca , Ko Rebecca , Smith Sandie , Arumugam Sankar , Johnston Meredith , Wong Karen , Lee Mark
Published: June 2022

Introduction

The magnitude and impact of rotational error is unclear in rectal cancer radiation therapy. This study evaluates rotational errors in rectal cancer patients, and investigates the feasibility of planning target volume (PTV) margin reduction to decrease organs at risk (OAR) irradiation.

Methods

In this study, 10 patients with rectal cancer were retrospectively selected. Rotational errors were assessed through image registration of daily cone beam computed tomography (CBCT) and planning CT scans. Two reference treatment plans (TPR) with PTV margins of 5 mm and 10 mm were generated for each patient. Pre‐determined rotational errors (±1°, ±3°, ±5°) were simulated to produce six manipulated treatment plans (TPM) from each TPR. Differences in evaluated dose‐volume metrics between TPR and TPM of each rotation were compared using Wilcoxon Signed‐Rank Test. Clinical compliance was investigated for statistically significant dose‐volume metrics.

Results

Mean rotational errors in pitch, roll and yaw were −0.72 ± 1.81°, −0.04 ± 1.36° and 0.38 ± 0.96° respectively. Pitch resulted in the largest potential circumferential displacement of clinical target volume (CTV) at 1.42 ± 1.06 mm. Pre‐determined rotational errors resulted in statistically significant differences in CTV, small bowel, femoral heads and iliac crests (P < 0.05). Only small bowel and iliac crests failed clinical compliance, with majority in the PTV 10 mm margin group.

Conclusion

Rotational errors affected clinical compliance for OAR dose but exerted minimal impact on CTV coverage even with reduced PTV margins. Both PTV margin reduction and rotational correction decreased irradiated volume of OAR. PTV margin reduction to 5 mm is feasible, and rotational corrections are recommended in rectal patients to further minimise OAR irradiation.
Peri‐anesthetic hypothermia in rodents: A factor to consider for accurate and reproducible outcomes in orthopedic device‐related infection studies
Authors: Constant Caroline , Moriarty Thomas F. , Arens Daniel , Pugliese Brenna , Zeiter Stephan
Published: June 2022

Orthopedic device‐related infection (ODRI) preclinical models are widely used in translational research. Most ODRI models require induction of general anesthesia, which frequently results in hypothermia in rodents. This study aimed to evaluate the impact of peri‐anesthetic hypothermia in rodents on outcomes in preclinical ODRI studies. A retrospective analysis of all rodents that underwent surgery under general anesthesia to induce an ODRI model with inoculation of Staphylococcus epidermidis between 2016 and 2020 was conducted. A one‐way multivariate analysis of covariance (one‐way MANCOVA) was used to determine the fixed effect of peri‐anesthetic hypothermia (hypothermic defined as rectal temperature <35°C) on the combined harvested tissue and implant colony‐forming unit (CFU) counts, and having controlled for the study groups including treatments received, duration of surgery and anesthesia, and study period. The results showed a significant effect of peri‐anesthetic hypothermia on the post‐mortem combined CFU counts from the harvested tissue and implant(s) (p = 0.01) when comparing normo‐ versus hypothermic rodents. Using Wilks’ Λ as a criterion to determine the contribution of independent variables to the model, peri‐anesthetic hypothermia was the most significant, though still a weak predictor, of increased harvested CFU counts. Altogether, the data corroborate the concept that bacterial colonization is affected by abnormal body temperature during general anesthesia at the time of bacterial inoculation in rodents, which needs to be taken into consideration to decrease infection data variability and improve experimental reproducibility.
Eccentric contraction‐dominant exercise leads to molecular biological changes in enthesis and enthesopathy‐like morphological changes
Authors: Ozone Kaichi , Minegishi Yuki , Takahata Kei , Takahashi Haruna , Yoneno Moe , Hattori Shinya , Xianglan Li , Oka Yuichiro , Murata Kenji , Kanemura Naohiko
Published: June 2022

Entheses, which are tendon‐to‐bone attachment sites in the musculoskeletal system, play important roles in optimizing the mechanical stress and force transmitted from the muscle to the bone. Sports‐related enthesopathy shows pathological features, including hyperplasia of the fibrocartilage (FC) region in the enthesis. The amount of exercise and type of muscle contraction during movement is involved in the pathogenesis of sports‐related enthesopathy; however, the details of this condition are unclear. Here we examined the molecular pathways involved in the morphological changes of the muscle–tendon–enthesis complex and enthesis FC region in the supraspinatus muscle enthesis of mice under different exercise conditions. Following intervention, morphological changes in the muscle–tendon–enthesis complex were initiated in the eccentric contraction‐dominant exercise group at 2 weeks, with activation of the transforming growth factor‐β (TGFβ) superfamily pathway predicted by proteome and ingenuity pathway analyses. Histological and molecular biological analyses confirmed the activation of the TGFβ/bone morphogenetic protein (BMP)‐Smad pathway. The concentric contraction‐dominant exercise group showed no change in the morphology of the muscle–tendon–enthesis complex or activation of the TGFβ/BMP‐Smad pathway, despite overuse exercise. Statement of Clinical Significance: These results suggest that eccentric contraction‐dominant exercise induces sports‐related enthesopathy‐like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor‐β superfamily pathway in enthesis.

Statement of Clinical Significance: These results suggest that eccentric contraction‐dominant exercise induces sports‐related enthesopathy‐like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor‐β superfamily pathway in enthesis.