bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer cells in clinical development as non-engineered, engineered, and combination therapies
Authors: Lamers-Kok Nina , Panella Denise , Georgoudaki Anna-Maria , Liu Haiping , Özkazanc Didem , Kučerová Lucia , Duru Adil Doganay , Spanholtz Jan , Raimo Monica 
Published: November 2022

AbstractNatural killer (NK) cells are unique immune effectors able to kill cancer cells by direct recognition of surface ligands, without prior sensitization. Allogeneic NK transfer is a highly valuable treatment option for cancer and has recently emerged with hundreds of clinical trials paving the way to finally achieve market authorization. Advantages of NK cell therapies include the use of allogenic cell sources, off-the-shelf availability, and no risk of graft-versus-host disease (GvHD). Allogeneic NK cell therapies have reached the clinical stage as ex vivo expanded and differentiated non-engineered cells, as chimeric antigen receptor (CAR)-engineered or CD16-engineered products, or as combination therapies with antibodies, priming agents, and other drugs. This review summarizes the recent clinical status of allogeneic NK cell-based therapies for the treatment of hematological and solid tumors, discussing the main characteristics of the different cell sources used for NK product development, their use in cell manufacturing processes, the engineering methods and strategies adopted for genetically modified products, and the chosen approaches for combination therapies. A comparative analysis between NK-based non-engineered, engineered, and combination therapies is presented, examining the choices made by product developers regarding the NK cell source and the targeted tumor indications, for both solid and hematological cancers. Clinical trial outcomes are discussed and, when available, assessed in comparison with preclinical data. Regulatory challenges for product approval are reviewed, highlighting the lack of specificity of requirements and standardization between products. Additionally, the competitive landscape and business field is presented. This review offers a comprehensive overview of the effort driven by biotech and pharmaceutical companies and by academic centers to bring NK cell therapies to pivotal clinical trial stages and to market authorization.
The ICU Bridge Program: volunteers bridging medicine and people together
Authors: Petrecca Sarah , Goin Adrian , Hornstein David , Stevanovic Milanka , Donovan Adamo Anthony 
Published: November 2022

Abstract
Background
The intensive care unit (ICU) is an emotionally taxing environment. Patients and family members are at an increased risk of long-term physical and psychological consequences of critical illness, known collectively as post-intensive care syndrome (PICS). These environmental strains can lead to a high incidence of staff turnover and burnout.

Aim
The ICU Bridge Program (ICUBP) is a student-led organization that attempts to mitigate these stressors on patients, family, and staff, by assigning university volunteers to ICUs across Montreal.

Setting
ICU.

Participants
ICU volunteers, staff, patients, and families.

Program description
The ICUBP volunteers support staff by orienting patients and families, while using effective communication strategies to provide comfort and promote a calm environment. The presence of volunteer visitors is helpful to patients who do not have the support of family members and/or friends. The program provides students with profound learning experiences by allowing them to shadow multidisciplinary teams, gaining a privileged and varied exposure to an acute medical environment, while developing their communications skills.

Program evaluation
The program reassesses its methods and impact via internal student-designed surveys distributed on a yearly basis to staff and volunteers.

Discussion
Research is warranted to assess the impact of the program on ICU patients, visitors, staff, and volunteers.
Functional imaging-guided carbon ion irradiation with simultaneous integrated boost for localized prostate cancer: study protocol for a phase II randomized controlled clinical trial
Authors: Hu Wei , Li Ping , Hong Zhengshan , Guo Xiaomao , Pei Yulei , Zhang Zhenshan , Zhang Qing 
Published: November 2022

Abstract
Background
Due to the physical dose distribution characteristic of “Bragg peak” and the biological effect as a kind of high linear energy transfer ray, heavy ion therapy has advantages over conventional photon therapy in both efficacy and safety. Based on the evidence that prostate cancer lesions before treatment are the most common sites of tumor residual or recurrence after treatment, simultaneous integrated boost radiation therapy for prostate cancer has been proven to have the advantage of improving efficacy without increasing toxicities.

Methods
This study is a prospective phase II randomized controlled clinical trial evaluating the efficacy and safety of functional imaging-guided carbon ion irradiation with simultaneous integrated boost for localized prostate cancer. One hundred and forty patients with localized prostate cancer will be randomized into carbon ion radiotherapy group and simultaneous integrated boost carbon ion radiotherapy group at a 1:1 ratio. The primary endpoint is to compare the incidence of treatment-related grade 2 and higher acute toxicities between the two groups according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Secondary endpoints are late toxicities, biochemical relapse-free survival, overall survival, progression-free survival, and quality of life.

Discussion
This study adopts functional imaging-guided simultaneous integrated boost of carbon ion radiotherapy for localized prostate cancer, aiming to evaluate the differences in the severity and incidence of acute toxicities in patients with localized prostate cancer treated with carbon ion radiotherapy and simultaneous integrated boost carbon ion radiotherapy, in order to optimize the carbon ion treatment strategy for localized prostate cancer.

Trial registration
ClinicalTrials.gov NCT05010343. Retrospectively registered on 18 August 2021
The effect of mHealth-based exercise on Insulin Sensitivity for patients with Hepatocellular carcinoma and insulin resistance (mISH): protocol of a randomized controlled trial
Authors: Yeo Seung Mi , Oh Joo Hyun , Yu Hee Ju , Sinn Dong Hyun , Hwang Ji Hye 
Published: November 2022

Abstract
Background
The importance of insulin resistance is gaining increasing attention as it plays an important role in carcinogenesis in hepatocellular carcinoma (HCC). Although exercise is the most important intervention for lowering insulin resistance, it is not easy for HCC patients to maintain high compliance and do appropriate exercise. Mobile health (mHealth) with wearable devices can be the solution to carry out an adjusted and supervised exercise that can normalize insulin resistance in patients with HCC. We developed an HCC-specific application equipped with patient-centered exercise. In this paper, we present a randomized controlled trial protocol comparing an intervention group with a control group to determine whether mHealth-based exercise is effective in normalizing insulin sensitivity in HCC patients with insulin resistance after anticancer treatment.

Methods
An assessor unblinded open label randomized controlled trial (RCT) will be conducted for 80 participants with treatment-naïve or recurrent HCC who have received treatment and achieved complete response at the time of screening. They will be randomly assigned (1:1) to one of two groups: an intervention group (n = 40) and a control group (n = 40). The intervention group will carry out mHealth-based exercise for 6 months from baseline, whereas the control group will receive the usual follow-up care for the first 3 months and mHealth-based exercise for the next 3 months. Both groups will be assessed at baseline, 3 months, and 6 months from baseline. The primary outcome is the normalized rate of insulin resistance in each group at 3 months. Insulin resistance is estimated by calculating homeostatic model assessment for insulin resistance (HOMA-IR). The secondary outcomes are body composition, physical fitness level, physical activity, and quality of life at 3 months.

Discussion
This study is the first RCT to investigate the effect of mHealth-based home exercise with a wrist-wearable device on insulin sensitivity, physical fitness, and quality of life for HCC patients with insulin resistance. The result of this RCT will confirm not only safety and functional improvement but also biological effect when exercising using mHealth in HCC patients.

Trial registration
ClinicalTrials.gov NCT04649671. Registered on 2 December 2020. The World Health Organization Trial Registration Data Set is not registered.
Adherence to exercise and fitness following exercise-based outpatient cardiac rehabilitation: a cross-sectional survey for Germany
Authors: Tilgner Nina , Nehls Dominik , Lichtmess Celine , Kober Alexandra , Küsel Cinja , Radloff Lisa , Gabrys Lars 
Published: November 2022

Abstract
Background
Exercise-based cardiac rehabilitation is safe and effective, evidence-based and implemented in national and international cardiac rehabilitation guidelines. Recent data show a decrease in cardiovascular mortality, reduced hospital admissions and an overall improvement in quality of life. To maintain positive effects and to prevent further cardiovascular events a major goal of cardiac rehabilitation is to induce a long-term health behaviour change and the integration of regular physical activity and exercise training in everyday life. The aim of this study is to evaluate the adherence of cardiac patients to exercise-based programs following rehabilitation phase III.

Methods
A nationwide online cross-sectional survey was conducted. All outpatient aftercare providers who offer sports rehabilitation programs (heart groups) for cardiac patients in Germany were contacted. The questionnaire comprised 15 questions in five subcategories (general information regarding the outpatient aftercare provider, structure of rehabilitation sport programs, membership structure, content of heart groups, adherence to exercise-based programs).

Results
560 of 2447 outpatient aftercare providers participated in the survey (response rate: 23%). On average, rehabilitation sport facilities hosted 2 (IQR 2) heart groups per week, and 23 patients (IQR 30) (61% males; 31% females) per facility completed rehabilitation sport prescription in 2018. Almost all providers offer follow-up programs on a self-payer basis after rehabilitation sport prescription ends. Adherence to follow-up programs was at 54% (IQR 65; 55% males and 50% females). With 60% (IQR 71), patients with a statutory health insurance (mainly pensioners) adhere slightly more often to a follow-up program compared to privately insured persons (mainly population with a high income or civil servants) with 50% and significantly more often compared to persons who were insured by the German pension fund (covering working population) with only 9% (IQR 89) adherence.

Conclusion
Almost all outpatient aftercare providers offer follow-up programs for cardiac rehabilitation patients but only half of them actually participate. Younger people (working population) do not adhere sufficiently to sport and exercise programs following rehabilitation phase III. This seems critical to address in terms of achieving long-term rehabilitation goals.
Decellularized bovine ovarian niche restored the function of cumulus and endothelial cells
Authors: Amjadi Farhad , Beheshti Rahim , Nasimi Fatemeh Sokouti , Hassani Ayla , Shirazi Reza , Tamadon Amin , Rahbarghazi Reza , Mahdipour Mahdi 
Published: November 2022

Abstract
Objective:
Recently, the decellularization technique is introduced as one of the tissue engineering procedures for the treatment of various deficiencies. Here, we aimed to assess the dynamic activity of CCs and HUVECs within decellularized bovine ovarian tissue transplanted subcutaneously in rats. Ovarian tissue was decellularized using a cocktail consisting of different chemicals, and the efficiency of decellularization was assessed using hematoxylin-eosin and DAPI staining. The cell survival was evaluated using an LDH leakage assay. Thereafter, decellularized samples were recellularized using HUVECs and CCs, encapsulated inside alginate (1.2%)-gelatin, (1%) hydrogel, and transplanted subcutaneously to rats. The existence of CD31- and estrogen-positive cells was assessed using immunohistochemistry staining.

Results:
Bright-field imaging and DAPI staining revealed the lack of nuclei with naive matrix structure in ovarian tissue subjected to decellularization protocol. SEM imaging revealed a normal matrix in decellularized ovaries. LDH assay showed a lack of cytotoxicity for CCs after 7-days compared to the control group. Immunohistochemistry staining showed both CD31- and estrogen-positive cells in CCs + HUVECs compared to the CCs group. CD31 cells appeared with flattened morphology aligned with matrix fibers. The existence of estrogen and CD31 positive cells showed the efficiency of decellularized ovarian tissue to restore cellular function and activity.
Field testing a new ICD coding system: methods and early experiences with ICD-11 Beta Version 2018
Authors: Eastwood Cathy A. , Southern Danielle A. , Khair Shahreen , Doktorchik Chelsea , Cullen Denise , Ghali William A. , Quan Hude 
Published: November 2022

Abstract
Objective
A beta version (2018) of International Classification of Diseases, 11th Revision for MMS (ICD-11), needed testing. Field-testing involves real-world application of the new codes to examine usability. We describe creating a dataset and characterizing the usability of ICD-11 code set by coders. We compare ICD-11 against ICD-10-CA (Canadian modification) and a reference standard dataset of diagnoses. Real-world usability encompasses code selection and time to code a complete inpatient chart using ICD-11 compared with ICD-10-CA.

Methods and results
A random sample of inpatient records previously coded using ICD-10-CA was selected from hospitals in Calgary, Alberta (N = 2896). Nurses examined these charts for conditions and healthcare-related harms. Clinical coders re-coded the same charts using ICD-11 codes. Inter-rater reliability (IRR) and coding time improved with ICD-11 coding experience (23.6 to 9.9 min average per chart). Code structure comparisons and challenges encountered are described. Overall, 86.3% of main condition codes matched. Coder comments regarding duplicate codes, missing codes, code finding issues enabled improvements to the ICD-11 Browser, Coding Tool, and Reference Guide. Training is essential for solid IRR with 17,000 diagnostic categories in the new ICD-11. As countries transition to ICD-11, our coding experiences and methods can inform users for implementation or field testing.
High prevalence of resistance to third-generation cephalosporins detected among clinical isolates from sentinel healthcare facilities in Lagos, Nigeria
Authors: Chukwu Emelda E. , Awoderu Oluwatoyin B. , Enwuru Christian A. , Afocha Ebelechukwu E. , Lawal Rahman G. , Ahmed Rahaman A. , Olanrewaju Ishola , Onwuamah Chika K. , Audu Rosemary A. , Ogunsola Folasade T. 
Published: November 2022

Abstract
Background
Antimicrobial resistance (AMR) in bacterial pathogens is a worldwide concern that demands immediate attention. Most information on AMR originates from high-income countries and little is known about the burden in Africa, particularly Nigeria. Using four sentinel sites (General hospitals) in Lagos State, this study sought to estimate the burden of AMR.

Methods
This is a hospital-based surveillance using secondary health care centres. Four sites were randomly selected and included in the study. Clinical isolates were collected over a period of 6 months for each site from August 2020 to March 2021. All isolates were characterised and analysed for resistance to 15 antibiotics using the Kirby-Baur method. Multiplex PCR assay was used for the detection of Extended spectrum beta lactamase genes. Data analysis was done using SPSS version 27.0.

Results
Four hundred and ninety-nine (499) patients consented and participated in this study, consisting of 412 (82.6%) females and 87 (17.4%) males. The mean age ± SD of the participants was 33.9 ± 13.8 with a range of 1–89 years. The majority (90.8%) of the participants were outpatients. Two hundred and thirty-two (232) isolates were obtained from 219 samples, comprising of 120 (51.7%) Gram positive and 112 (48.3%) Gram negative organisms. Key bacterial pathogens isolated from this study included Staphylococcus aureus (22.8%), Escherichia coli (16.4%), Staphylococcus spp. (15.9%), Enterococcus spp. (7.3%) and Klebsiella pneumoniae (6.5%). There was high prevalence of multi-drug resistance (79.3%) among the isolates with 73.6% of Staphylococcus aureus phenotypically resistant to methicillin and 70% possessed the MecA gene. 76.5% of Enterococcus spp. isolated were Vancomycin resistant. Overall, resistance to Cephalosporins was most frequently/commonly observed (Cefotaxime 87.5%).

Conclusion
A high incidence of AMR was identified in clinical bacteria isolates from selected general hospitals in Lagos State, highlighting the necessity for the implementation of national action plans to limit the prevalence of AMR. Surveillance via collection of isolates has a lot of promise, especially in resource-limited environments.
Prognostic potential of liver injury in patients with dilated cardiomyopathy: a retrospective study
Authors: Wang Hai-Yan , Huang Yuan , Chen Xiao-Zhen , Zhang Zi-Lan , Gui Chun 
Published: November 2022

Abstract
Background
Liver injury (LI) has been frequently observed in patients with dilated cardiomyopathy (DCM), whereas its prognostic value remains blurry. We attempted to appraise the prognostic effect of LI in patients with DCM.

Methods
This retrospective study included 523 patients with DCM. LI was defined as a threefold increase in aspartate transaminase (≥ 135 U/L) or alanine transaminase (≥ 180 U/L) or a twofold increase in total bilirubin (≥ 41 umol/L) during hospitalization. The population was segmented into non-liver injury (NLI) group and LI group based on liver function test data. To balance differences in covariates at baseline, 1:1 propensity score matching (PSM) was performed.

Results
Patients with LI had lower survival rate, compared with those with NLI (44.6% vs. 73.8%, P < 0.001). Similar results were also found in age (age > 50, 39.6% vs. 70.9%, P < 0.001; age ≤ 50, 51.3% vs. 79.5%, P < 0.001) and gender stratified analysis (male, 46.2% vs. 74.4%, P < 0.001; female 35.7% vs. 72.0%, P = 0.001). After PSM, the survival rate of patients with LI remained lower than those with NLI (44.6% vs. 64.1%, P = 0.019). Multivariable Cox regression analysis manifested that LI (hazard ratio [HR]: 1.692, 95% confidence interval [CI] 1.194–2.398, P = 0.003; HR: 1.675, 95% CI 1.078–2.604, P = 0.022, respectively) showed potent predictive effect on all-cause mortality in patients with DCM, both before and after PSM.

Conclusions
The occurrence of LI herald adverse outcomes in patients with DCM and attention to LI may be conducive to risk stratification and management.
CMT inversion for small-to-moderate earthquakes applying to dense short-period OBS array at off Ibaraki region
Authors: Yamaya Lina , Mochizuki Kimihiro , Akuhara Takeshi , Takemura Shunsuke , Shinohara Masanao , Yamada Tomoaki 
Published: November 2022

AbstractWe conducted centroid moment tensor (CMT) inversion for small-to-moderate aftershocks in the off Ibaraki region of the 2011 off the Pacific coast of Tohoku earthquake. In this study, we used high-frequency (0.4–1.0 Hz) seismograms from a dense array of short-period ocean bottom seismometers (OBSs) and a reliable three-dimensional (3-D) seismic velocity model. Higher frequency analysis and dense OBS arrays offer CMT solutions with high spatial resolutions. Since our OBS array observed aftershocks occurring immediately following the 2011 off the Pacific coast of Tohoku earthquake, we determined 536 CMT solutions for small-to-moderate aftershocks in the off Ibaraki region (JMA-scale magnitudes of 2.5–4.0). According to our CMT solutions, characteristics of the aftershock activities in the off Ibaraki region are classified into 5 groups: (1) thrust earthquakes, which are considered as interplate earthquakes, separated by the large slip area of the 2011 Ibaraki-oki earthquake (the largest $${\mathrm{M}}_{\mathrm{w}}$$

M
w

7.6 aftershock of the 2011 off the Pacific coast of Tohoku earthquake) and the tectonic tremors; (2) intraslab strike-slip earthquakes located at the north of the fault area of the 2011 Ibaraki-oki earthquake; (3) intraslab normal-fault earthquakes, which suggest a tensional stress field within the subducting Pacific Plate due to the plate bending by the overriding Philippine Sea Plate; (4) various earthquake focal mechanisms above a subducting seamount, which suggest the 3-D complex fractures; and (5) normal-fault earthquakes shallower than the interplate earthquakes, which were possibly caused by the heterogeneity of the subducting seamount.
Graphical Abstract
Household Credit and Regulatory Arbitrage: Evidence from Online Marketplace Lending
Authors: Braggion Fabio , Manconi Alberto , Zhu Haikun 
Published: November 2022

We study the relationship between new intermediaries and regulatory arbitrage, analyzing marketplace credit around a tightening of mortgage loan-to-value (LTV) caps in several cities in China in 2013. Using novel data covering over 20% of Chinese marketplace credit as well as the universe of loans and loan applications at a leading online lending platform, we provide evidence consistent with home buyers borrowing online to bypass the tighter LTV cap. Our findings point to new, lightly regulated financial intermediaries as a driver of household leverage, suggesting that they can open nonnegligible regulatory arbitrage channels. This paper was accepted by Victoria Ivashina, finance. Supplemental Material: Data and the online appendix are available at https://doi.org/10.1287/mnsc.2022.4592 .