bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Priming Intermittent Theta Burst Stimulation With High-Definition tDCS on Upper Limb Function in Hemiparetic Patients With Stroke: A Randomized Controlled Study
Authors: Bian Li , Zhang Li , Huang Guilan , Song Da , Zheng Kai , Xu Xinlei , Dai Wenjun , Ren Caili , Shen Ying
Published: February 2024

Background

Preconditioning with cathodal high-definition transcranial direct current stimulation (HD-tDCS) can potentiate cortical plasticity induced by intermittent theta burst stimulation (iTBS) and enhance the after-effects of iTBS in healthy people. However, it is unclear whether this multi-modal protocol can enhance upper limb function in patients with stroke.

Objective

The aim of this study was to investigate whether priming iTBS with cathodal HD-tDCS over the ipsilesional M1 can augment upper limb motor recovery in poststroke patients.

Methods

A total of 66 patients with subacute stroke were randomly allocated into 3 groups. Group 1 received priming iTBS with HD-tDCS (referred to as the tDCS + iTBS group), Group 2 received non-priming iTBS (the iTBS group), and Group 3 received sham stimulation applied to the ipsilesional M1. One session was performed per day, 5 days per week, for 3 consecutive weeks. In Group 1, iTBS was preceded by a 20-minute session of cathodal HD-tDCS at a 10-minute interval. The primary outcome measure was the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score. Moreover, the secondary outcome measures for muscle strength and spasticity were the Motricity Index-Upper Extremity (MI-UE) and the Modified Ashworth Scale Upper-Extremity (MAS-UE), respectively, and the Hong Kong Version of the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) and the Modified Barthel Index (MBI) for activity and participation.

Results

Significant differences were detected in the changes in FMA-UE, MI-UE, and MBI scores between the 3 groups from baseline to post-intervention (χ2FMA-UE = 10.856, P = .004; χ2MI-UE = 6.783, P = .034; χ2MBI = 9.608, P = .008). Post hoc comparisons revealed that the priming iTBS group demonstrated substantial improvements in FMA-UE ( P = .004), MI-UE ( P = .028), and MBI ( P = 0.006) compared with those in the sham group. However, no significant difference was observed between the iTBS group and the sham group. Moreover, no significant differences were found in the changes in MAS-UE or FTHUE-HK between the groups.

Conclusions

Priming iTBS with HD-tDCS over the ipsilesional M1 cortex had beneficial effects on augmenting upper limb motor recovery and enhancing daily participation among subacute stroke patients.
CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
Authors: Choi Seung Jun , Kim Hyun Kyung , Suh Eun Jung , Kwon Soon Sung , Shin Saeam , Lee Seung-Tae , Kim Sinyoung
Published: February 2024

ABO antigen weakness is rarely observed in ABO typing for transfusion. Hematologic diseases and associated gene mutations have been suggested as potential causes of this phenomenon, yet the precise etiology has not been elucidated. Through ABO typing and genetic analysis data conducted over 7 years, we have reconfirmed the association between ABO antigen weakness and hematologic diseases, especially acute myeloid leukemia (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.12-5.83) and myelodysplastic syndrome (OR, 6.94; 95% CI, 2.86-16.83), and discovered previously unidentified candidate genes, CEBPA (OR, 43.70; 95% CI, 18.12-105.40), NRAS (OR, 3.37; 95% CI, 1.46-7.79), U2AF1 (OR, 8.12; 95% CI, 2.86-23.03), and PTPN11 (OR, 4.52; 95% CI, 1.51-13.50), seemingly associated with this phenomenon. Among these, CEBPA double mutations displayed a significant association, with ABO antigen weakness being observed in 20 of the 25 individuals (80.0%) possessing these mutations. From this study, new factors associated with ABO antigen weakness have been identified.
Extracorporeal photopheresis as a promising strategy for the treatment of graft-versus-host disease after CAR T-cell therapy
Authors: Han Huixiu , Wang Lei , Ding Yuntian , Neuber Brigitte , Hückelhoven-Krauss Angela , Lin Min , Yao Hao , Chen Qian , Sauer Tim , Schubert Maria-Luisa , Guo Zhiqiang , Müller-Tidow Carsten , Schmitt Michael , Schmitt Anita
Published: February 2024

Graft-versus-host disease (GVHD) occurs in about 10% to 33% of patients receiving “allogeneic” or “autologous” chimeric antigen receptor T (CAR-T) cells after preceding allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the substantial presence of alloreactive T cells. Extracorporeal photopheresis (ECP) shows promising clinical outcomes in the treatment of GVHD after allo-HSCT without hampering antitumor and antiviral effects. This raises an interesting question: whether ECP might constitute a new way to treat patients with GVHD after CAR T-cell therapy without compromising CAR-T cells significantly. Third-generation CD19-specific CAR-T cells were generated and an in vitro ECP protocol was established. The impact of ECP on CAR-T cells was comprehensively investigated in 2 models: the nondilution model reflects days after CAR T-cell infusion and the dilution model weeks after infusion. The therapeutic effect of ECP on GVHD was examined in an in vitro mixed lymphocyte reaction (MLR) assay. We found, ECP-treated CAR-T cells demonstrated reduced potency in inducing alloreaction compared with that of the group without ECP treatment in MLR assay. ECP could selectively induce apoptosis, thereby enriching the naive and central memory CAR-T cells with a reduced alloreactivity. The cytokine milieu of CAR-T cells could be switched from immune stimulation to immune tolerance in both models. Moreover, ECP could modulate the proliferative capacity of CAR-T cells without hampering their long-term functionality in the dilution model. In conclusion, ECP constitutes a promising treatment strategy for GVHD after allo-HSCT and CAR T-cell transfusion, as ECP reduces the alloreactivity without hampering CAR T-cell functionality.
Calibration and XGBoost reweighting to reduce coverage and non-response biases in overlapping panel surveys: application to the Healthcare and Social Survey
Authors: Castro Luis , Rueda María del Mar , Sánchez-Cantalejo Carmen , Ferri Ramón , Cabrera-León Andrés
Published: February 2024

Background

Surveys have been used worldwide to provide information on the COVID-19 pandemic impact so as to prepare and deliver an effective Public Health response. Overlapping panel surveys allow longitudinal estimates and more accurate cross-sectional estimates to be obtained thanks to the larger sample size. However, the problem of non-response is particularly aggravated in the case of panel surveys due to population fatigue with repeated surveys.

Objective

To develop a new reweighting method for overlapping panel surveys affected by non-response.

Methods

We chose the Healthcare and Social Survey which has an overlapping panel survey design with measurements throughout 2020 and 2021, and random samplings stratified by province and degree of urbanization. Each measurement comprises two samples: a longitudinal sample taken from previous measurements and a new sample taken at each measurement.

Results

Our reweighting methodological approach is the result of a two-step process: the original sampling design weights are corrected by modelling non-response with respect to the longitudinal sample obtained in a previous measurement using machine learning techniques, followed by calibration using the auxiliary information available at the population level. It is applied to the estimation of totals, proportions, ratios, and differences between measurements, and to gender gaps in the variable of self-perceived general health.

Conclusion

The proposed method produces suitable estimators for both cross-sectional and longitudinal samples. For addressing future health crises such as COVID-19, it is therefore necessary to reduce potential coverage and non-response biases in surveys by means of utilizing reweighting techniques as proposed in this study.
Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study
Authors: Nakamura Kazuyo , Kaya Michihiro , Yanagisawa Yuki , Yamamoto Keisuke , Takayashiki Nana , Ukita Hirotoshi , Nagura Mariko , Sugiue Kaori , Kitajima Mariko , Hirano Kumi , Ishida Hiroki , Onoda Chiharu , Kobayashi Yutaka , Nakatani Eiji , Odagiri Keiichi , Suzuki Takaya
Published: February 2024

Background

Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment.

Methods

We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis.

Results

Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia.

Conclusions

Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.
Maternal macronutrient and energy intake during pregnancy: a systematic review and meta-analysis
Authors: Khammarnia Mohammad , Ansari-Moghaddam Alireza , kakhki Fatemeh Govahi , Clark Cain Craig Truman , Barahouei Fatemeh Bagher
Published: February 2024

Background

Nutritional status during pregnancy can have a significant impact on infant and maternal health outcomes. To maintain maternal homeostasis and support fetal growth, adequate macronutrient and energy intake during pregnancy is essential. Therefore, this study sought to systematically review and meta-analyze macronutrient and energy intakes during pregnancy.

Methods

A systematic review and meta-analysis was carried out based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The required data were collected from four databases including: Web of Sciences, ProQuest, Scopus, and PubMed, from 1 January 1980 to 30 May 2023, by using a combination of search terms (dietary pattern" OR "diet quality" OR "food habits" OR "nutrition surveys" OR "diet surveys" OR "food-frequency questionnaire" OR "diet record" OR "dietary recall") AND ( "pregnancy" OR "reproduction" OR "maternal health" OR "neonatal outcomes") among interventional and observational studies. Excel and STATA version 11 were used for data analysis.

Results

Among 7081 published articles, 54 studies were included in the review. Most of the 33 (61%) studies were cohort studies and a total of 135,566 pregnant women were included. The overall average of energy, carbohydrate, fat, and protein intake was 2036.10 kcal/day, 262.17 gr/day, 74.17 gr/day, and 78.21 gr/day, respectively. Also, energy intake during pregnancy was higher in American (2228.31 kcal/day, CI95%: 2135.06–2325.63) and Eastern Mediterranean regions (2226.70 kcal/day, CI95%: 2077.23–2386.92) than other regions (P < 0.001). Energy intake was higher in the third trimester than others (2115.64 kcal/day, CI95%: 1974.15–2267.27). Furthermore, based on the findings, there was a significant difference between energy intake in different World Health Organization (WHO) regions (P < 0.05).

Conclusions

According to the results of meta-analysis, the average total energy was below than average total energy required during pregnancy. More efforts are needed to encourage women to adopt healthy eating habits during pregnancy to support healthy fetal and infant development.
Virtual reality cricothyrotomy - a case-control study on gamification in emergency education
Authors: Speck I , Merk A , Burkhardt V , O Flayyih , Huber C , Widder A , Everad F , Offergeld C
Published: February 2024

Background

Cricothyrotomy is an invasive and rare emergency intervention to secure the airway in a “cannot intubate, cannot ventilate” situation. This leads to lack of routine. Cricothyrotomy is performed only hesitantly. Therefore, we aim to improve teaching by including a virtual reality (VR) cricothyrotomy as a learning tool.

Methods

We programmed the VR cricothyrotomy in the C# programming language on the open-source Unity platform. We could include 149 students that we randomly assigned to either a study group (VR cricothyrotomy) or control group (educational video). We asked the study group to subjectively rate the VR cricothyrotomy. To evaluate our intervention (VR cricothyrotomy) we took the time participants needed to perform a cricothyrotomy on a plastic model of a trachea and evaluated the correct procedural steps.

Results

The majority of students that performed the VR simulation agreed that they improved in speed (81%) and procedural steps (92%). All participants completed the cricothyrotomy in 47s ± 16s and reached a total score of 8.7 ± 0.7 of 9 possible points. We saw no significant difference in time needed to perform a cricothyrotomy between study and control group (p > 0.05). However, the total score of correct procedural steps was significantly higher in the study group than in the control group (p < 0.05).

Conclusions

Virtual reality is an innovative learning tool to improve teaching of emergency procedures. The VR cricothyrotomy subjectively and objectively improved correct procedural steps. Digitized education fills an educational gap between pure haptic experience and theoretical knowledge. This is of great value when focusing on extension of factual knowledge.

Trial registration

DRKS00031736, registered on the 20th April 2023.
Nurses’ job preferences on the internet plus nursing service program: a discrete choice experiment
Authors: He Yan , Feng Guanrui , Wang Chenchen , Yang Dan , Hu Lei , Ming Wai-kit , Chen Weiju
Published: February 2024

Background

The Internet Plus Nursing Service (IPNS) is being instigated in all provincial-level regions throughout China, in which registered nurses (with more than five years of experience from qualified medical institutions) will provide services to those in their communities or homes after receiving online applications. The growing shortage of human resources in nursing is a critical issue for this project, so effective policies for recruiting and retaining nurses are critical.

Objective

This study aims to pinpoint the significant job characteristics that play a crucial role in shaping the job decisions of sharing nurses in the IPNS program, and to estimate the strength of job attributes.

Methods

A discrete choice experiment (DCE) was used to assess job attributes influencing sharing nurses’ preferences. A qualitative design, including in-depth interview and focus interview methods, was conducted to determine the inclusion of attributes. The final included six attributes were: work modes, duration per visit, income per visit, personal safety, medical risk prevention, and refresher training. This study was conducted at 13 hospitals in Guangdong Province, China, from April to June 2022, and a total of 220 registered sharing nurses participated in the survey. The multinomial logit model explored attributes and relative valued utility. Preference heterogeneity is explored via latent class analysis (LCA) models.

Results

A total of 220 participants answered the questionnaire. Income was the most influential characteristic of a sharing nursing position, followed by personal safety management, duration per visit, medical risk prevention, and refresher training, and nurses’ preferences differed among different types of classes.

Conclusions

Sharing nurses place most value on income and personal safety with career-related decisions, which indicates an urgent need to develop complete security for personal safety. This study can be helpful to decision-makers in the Chinese government.
Clinical application and nursing experience of the plan-do-check-act cycle in daytime varicocelectomy
Authors: He Kang , Li Jianxiong , Yang Cheng , Wu Junping , Wu Biling , Xia Hui
Published: February 2024

Background

Varicocele is the most prevalent correctable cause of male infertility. Currently, surgical treatment is the primary method to enhance fertility.For many young varicocele patients who have postponed surgery due to time constraints, daytime surgery is especially crucial. Thus, this study aims to investigate the clinical and nursing application value of the Plan-Do-Check-Act (PDCA) cycle in daytime varicocelectomy.

Methods

Retrospective collection of clinical data was conducted on 130 patients undergoing laparoscopic varicocelectomy in the Third Affiliated Hospital of Southern Medical University, Guangzhou,China.Among them, 65 patients who underwent daytime surgery were assigned to the observation group, while 65 patients who underwent routine hospital surgeries were assigned to the control group.The former also implemented PDCA cycle management.A comparison was made between the two groups regarding hospitalization time, hospitalization costs, and patient satisfaction.

Results

The observation group exhibited a shorter hospitalization time and lower hospitalization costs compared to the control group, with higher patient satisfaction and pre-discharge visual analog scale (VAS) scores noted (P < 0.05).No significant difference was observed in the incidence of postoperative complications between the two groups during hospitalization (P > 0.05). The implementation of the PDCA cycle in the observation group has demonstrated its effectiveness, ensuring the smooth conduct of the daytime varicocelectomy.

Conclusion

In conclusion,daytime varicocelectomy can reduce hospitalization time,lower hospitalization costs, improve patient satisfaction. The PDCA Cycle enhances the rationality and efficacy of the daytime varicocelectomy procedure and is highly recommended. Furthermore, it offers valuable reference for the application of the PDCA Cycle in various other diseases and nursing management approaches.

Trial Registration

The Trial Registration Number: ChiCTR2300077465;Date of registration: November 9, 2023.
Impact of point-of-care ultrasound use on patient referral decisions in rural Kenya: a mixed methods study
Authors: Wanjiku Grace W. , Bell Gregory , Kapadia Sonja , Wachira Benjamin W.
Published: February 2024

Background

Point-of-care ultrasound (POCUS) is recognized as a key imaging modality to bridge the diagnostic imaging gap in Low- and Middle-Income Countries (LMICs). POCUS use has been shown to impact patient management decisions including referral for specialist care. This study explored the impact of POCUS use on referral decisions among trained healthcare providers working in primary rural and peri-urban health facilities in Kenya.

Methods

A concurrent mixed methods approach was used, including a locally developed survey (N = 38) and semi-structured interviews of POCUS trained healthcare providers (N = 12). Data from the survey was descriptively analyzed and interviews were evaluated through the framework matrix method.

Results

Survey results of in-facility access to Xray, Ultrasonography, CT scan and MRI were 49%, 33%, 3% and 0% respectively. Only 54% of the facilities where trainees worked had the capacity to perform cesarean sections, and 38% could perform general surgery. Through a combined inductive and deductive evaluation of interview data, we found that the emerging themes could be organized through the framework of the six domains of healthcare quality as described by the Institute of Medicine: Providers reported that POCUS use allowed them to make referral decisions which were timely, safe, effective, efficient, equitable and patient-centered. Challenges included machine breakdown, poor image quality, practice isolation, lack of institutional support and insufficient feedback on the condition of patients after referral.

Conclusion

This study highlighted that in the setting of limited imaging and surgical capacity, POCUS use by trained providers in Kenyan primary health facilities has the potential to improve the patient referral process and to promote key dimensions of healthcare quality. Therefore, there is a need to expand POCUS training programs and to develop context specific POCUS referral algorithms.
The effectiveness of sodium-glucose co-transporter 2 inhibitors on cardiorenal outcomes: an updated systematic review and meta-analysis
Authors: Ali Muhammad Usman , Mancini G. B. John , Fitzpatrick-Lewis Donna , Connelly Kim A. , O’Meara Eileen , Zieroth Shelley , Sherifali Diana
Published: February 2024

Background

The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) use. Since then, additional trials of relevance for SGLT2i have been published. This update re-evaluates the clinical recommendations for using SGLTi and their indirect comparison with existing evidence on GLP-1RA as compared to the standard of care to reduce cardiorenal morbidity and mortality.

Methods

We updated our existing search and screening of the literature from September 2021 to April 2023 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. We conducted risk of bias assessment, data extraction and updated our meta-analysis of studies with similar interventions and components. The certainty of the evidence was determined using GRADE.

Results

Evidence from three new trials and additional results from an updated existing trial on SGLT2i met our inclusion criteria after an updated search. Across all the included studies, the total sample size was 151,023 adults, with 90,943 in SGLT2i trials and 60,080 in GLP-1 RA trials. The mean age ranged from 59.9 to 68.4 years. Compared with standard care, the use of SGLT2i and GLP-1 RA showed significant reductions in the outcomes of cardiovascular (CV) mortality (14% & 13%), any-cause mortality (12% & 12%), major adverse CV events (MACE) (11% & 14%), heart failure (HF) hospitalization (30% & 9%), CV death or HF hospitalization (23% & 11%), and kidney composite outcome (32% & 22%). In participants with T2D, both classes demonstrated significant cardiorenal protection. But, only GLP-1RA showed a reduction in non-fatal stroke (16%) and only SGLT2i showed a reduction in HF hospitalization (30%) in this population of people living with T2D.

Conclusions

This updated and comprehensive meta-analysis substantiates and strengthens the clinical recommendations of the CCS cardiorenal guidelines.
The association between lifelines diet score (LLDS) with depression and quality of life in Iranian adolescent girls
Authors: Darabi Zahra , Sangouni Abbas Ali , Ghayour-Mobarhan Majid , Ferns Gordon A. , Khayyatzadeh Sayyed Saeid
Published: February 2024

Background

It has been proposed that a greater degree of adherence to a healthy dietary pattern is associated with a lower risk of depression and a poor quality of life (QoL). The Lifelines diet score (LLDS) is a new, evidence-base scoring system to define the quality of diet. We designed a cross-sectional study to investigate the association between LLDS with depression and QoL in Iranian adolescent girls.

Methods

A total of 733 female adolescents were recruited from Mashhad and Sabzevar cities, Iran. Depression and QoL were assessed utilizing the Beck Depression Inventory (BDI) and SF-12v2 questionnaires, respectively. The LLDS was defined by dividing intakes of 12 food groups with negative or positive health effects into quintiles ranging 12 to 60 points. To explore the association between LLDS with QoL and depression, logistic regression was used in crude and adjusted models.

Results

The prevalence of depression and poor QoL was 24% and 49%, respectively. After adjusting for confounding factors, adolescent girls in the highest quartile of LLDS compared with the participants in the lowest quartile had a 42% lower probability of reporting depressive symptoms (OR: 0.58; 95% CI: 0.35–0.97, P = 0.03). In addition, the participants in the highest quartile of LLDS had lower odds of poor QoL compared with the subjects in the lowest quartile (OR: 0.65; 95% CI: 0.42–0.92, P = 0.04).

Conclusions

There is an inverse relationship between LLDS with risk of depression and poor QoL. Prospective and interventional investigations are needed to reach a clear vision.
Patterns of cannabis use, perception of harm, and perceived impact of legislative change in an online sample of young adults from Lebanon: insight on recreational users versus dual motive users
Authors: Ghandour Lilian , Slim Andre , Abbas Nada , El-Khoury Joseph
Published: February 2024

Background

Lebanon remains as one of the major sources of cannabis worldwide. In 2020, its government passed a legislation enabling the cultivation of local medicinal cannabis. This first study following the legislative change examines the overlapping use of cannabis for recreational/medicinal purposes and characteristics of the distinct cannabis user types.

Methods

A total of 1230 young adults (18–24 years) filled an anonymous online survey in early 2020.

Results

Young adults in the sample were distributed as follows: 33% 18–20 years; 60% males; 94% Lebanese; 75% students; and 89% living with family. The older young adults (21–24), males, those employed, living with non-family members, and who perceived themselves as being a little/lot richer than most were statistically significantly more present in the cannabis user subtypes (recreational only or recreational/medicinal) than non-cannabis users. When dual recreational/medicinal users are compared to recreational users only, the latter seemed to have a more conservative profile of behaviours, attitudes, and perceptions and acts of harm. The prevalence ratio comparing the prevalence of users supporting consuming cannabis “once or twice” in dual motive users vs. recreational users only was 1.13 for “once or twice”, 1.25 for “occasionally”, 1.64 for “regularly”, and 2.4 for “daily”. Any other illicit drug use was reported by 1% of the non-cannabis users, 36% of the recreational users only, and 58% of the recreational/medicinal users (p-value < 0.01). Similarly, any prescription drug use was reported by 3% of the non-cannabis users, 16% of the recreational users only, and 28% of both recreational/medicinal users (p-value < 0.01).

Conclusion

The interface between recreational and medicinal cannabis use is complex. Dual motive users may warrant special attention as a subpopulation of cannabis users. This is relevant to contexts experiencing medicinal cannabis legislation changes, such as Lebanon, as policymakers and implementers should be sensitized to the emerging evidence for more data-informed policy changes.
Glycosaminoglycan modifications of betaglycan regulate ectodomain shedding to fine-tune TGF-β signaling responses in ovarian cancer
Authors: Choi Alex S. , Jenkins-Lane Laura M. , Barton Wade , Kumari Asha , Lancaster Carly , Raulerson Calen , Ji Hao , Altomare Diego , Starr Mark D. , Whitaker Regina , Phaeton Rebecca , Arend Rebecca , Shtutman Michael , Nixon Andrew B. , Hempel Nadine , Lee Nam Y. , Mythreye Karthikeyan
Published: February 2024

In pathologies including cancer, aberrant Transforming Growth Factor-β (TGF-β) signaling exerts profound tumor intrinsic and extrinsic consequences. Intense clinical endeavors are underway to target this pathway. Central to the success of these interventions is pinpointing factors that decisively modulate the TGF-β responses. Betaglycan/type III TGF-β receptor (TβRIII), is an established co-receptor for the TGF-β superfamily known to bind directly to TGF-βs 1–3 and inhibin A/B. Betaglycan can be membrane-bound and also undergo ectodomain cleavage to produce soluble-betaglycan that can sequester its ligands. Its extracellular domain undergoes heparan sulfate and chondroitin sulfate glycosaminoglycan modifications, transforming betaglycan into a proteoglycan. We report the unexpected discovery that the heparan sulfate glycosaminoglycan chains on betaglycan are critical for the ectodomain shedding. In the absence of such glycosaminoglycan chains betaglycan is not shed, a feature indispensable for the ability of betaglycan to suppress TGF-β signaling and the cells' responses to exogenous TGF-β ligands. Using unbiased transcriptomics, we identified TIMP3 as a key inhibitor of betaglycan shedding thereby influencing TGF-β signaling. Our results bear significant clinical relevance as modified betaglycan is present in the ascites of patients with ovarian cancer and can serve as a marker for predicting patient outcomes and TGF-β signaling responses. These studies are the first to demonstrate a unique reliance on the glycosaminoglycan chains of betaglycan for shedding and influence on TGF-β signaling responses. Dysregulated shedding of TGF-β receptors plays a vital role in determining the response and availability of TGF-βs’, which is crucial for prognostic predictions and understanding of TGF-β signaling dynamics.
Targeting cancer-derived extracellular vesicles by combining CD147 inhibition with tissue factor pathway inhibitor for the management of urothelial cancer cells
Authors: Boddu Vijay Kumar , Zamzow Piet , Kramer Mario Wolfgang , Merseburger Axel S. , Gorantla Sivahari Prasad , Klinger Matthias , Cramer Lena , Sauer Thorben , Gemoll Timo , von Bubnoff Nikolas , Gieseler Frank , Darabi Masoud
Published: February 2024

Background

Extracellular vesicles (EVs), including microvesicles, hold promise for the management of bladder urothelial carcinoma (BLCA), particularly because of their utility in identifying therapeutic targets and their diagnostic potential using easily accessible urine samples. Among the transmembrane glycoproteins highly enriched in cancer-derived EVs, tissue factor (TF) and CD147 have been implicated in promoting tumor progression. In this in vitro study, we explored a novel approach to impede cancer cell migration and metastasis by simultaneously targeting these molecules on urothelial cancer-derived EVs.

Methods

Cell culture supernatants from invasive and non-invasive bladder cancer cell lines and urine samples from patients with BLCA were collected. Large, microvesicle-like EVs were isolated using sequential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and flow cytometry. The impact of urinary or cell supernatant-derived EVs on cellular phenotypes was evaluated using cell-based assays following combined treatment with a specific CD147 inhibitor alone or in combination with a tissue factor pathway inhibitor (TFPI), an endogenous anticoagulant protein that can be released by low-molecular-weight heparins.

Results

We observed that EVs obtained from the urine samples of patients with muscle-invasive BLCA and from the aggressive bladder cancer cell line J82 exhibited higher TF activity and CD147 expression levels than did their non-invasive counterparts. The shedding of GFP-tagged CD147 into isolated vesicles demonstrated that the vesicles originated from plasma cell membranes. EVs originating from invasive cancer cells were found to trigger migration, secretion of matrix metalloproteinases (MMPs), and invasion. The same induction of MMP activity was replicated using EVs obtained from urine samples of patients with invasive BLCA. EVs derived from cancer cell clones overexpressing TF and CD147 were produced in higher quantities and exhibited a higher invasive potential than those from control cancer cells. TFPI interfered with the effect when used in conjunction with the CD147 inhibitor, further suppressing homotypic EV-induced migration, MMP production, and invasion.

Conclusions

Our findings suggest that combining a CD147 inhibitor with low molecular weight heparins to induce TFPI release may be a promising therapeutic approach for urothelial cancer management. This combination can potentially suppress the tumor-promoting actions of cancer-derived microvesicle-like EVs, including collective matrix invasion.

Graphical Abstract
Autophagy inhibition improves the targeted radionuclide therapy efficacy of 131I-FAP-2286 in pancreatic cancer xenografts
Authors: Liu Xingyu , Li Danni , Ma Tianbao , Luo Xiu , Peng Ye , Wang Tao , Zuo Changjing , Cai Jianming
Published: February 2024

Purposes

Radiotherapy can induce tumor cell autophagy, which might impair the antitumoral effect. This study aims to investigate the effect of autophagy inhibition on the targeted radionuclide therapy (TRT) efficacy of 131I-FAP-2286 in pancreatic cancer.

Methods

Human pancreatic cancer PANC-1 cells were exposed to 131I-FAP-2286 radiotherapy alone or with the autophagy inhibitor 3-MA. The autophagy level and proliferative activity of PANC-1 cells were analyzed. The pancreatic cancer xenograft-bearing nude mice were established by the co-injection of PANC-1 cells and pancreatic cancer-associated fibroblasts (CAFs), and then were randomly divided into four groups and treated with saline (control group), 3-MA, 131I-FAP-2286 and 131I-FAP-2286 + 3-MA, respectively. SPECT/CT imaging was performed to evaluate the bio-distribution of 131I-FAP-2286 in pancreatic cancer-bearing mice. The therapeutic effect of tumor was evaluated by 18F-FDG PET/CT imaging, tumor volume measurements, and the hematoxylin and eosin (H&E) staining, and immunohistochemical staining assay of tumor tissues.

Results

131I-FAP-2286 inhibited proliferation and increased the autophagy level of PANC-1 cells in a dose-dependent manner. 3-MA promoted 131I-FAP-2286-induced apoptosis of PANC-1 cells via suppressing autophagy. SPECT/CT imaging of pancreatic cancer xenograft-bearing nude mice showed that 131I-FAP-2286 can target the tumor effectively. According to 18F-FDG PET/CT imaging, the tumor growth curves and immunohistochemical analysis, 131I-FAP-2286 TRT was capable of suppressing the growth of pancreatic tumor accompanying with autophagy induction, but the addition of 3-MA enabled 131I-FAP-2286 to achieve a better therapeutic effect along with the autophagy inhibition. In addition, 3-MA alone did not inhibit tumor growth.

Conclusions

131I-FAP-2286 exposure induces the protective autophagy of pancreatic cancer cells, and the application of autophagy inhibitor is capable of enhancing the TRT therapeutic effect.
Low rate of severe-end-stage kidney disease after SABR for localised primary kidney cancer
Authors: Ali Muhammad , Koo Kendrick , Chang David , Chan Phil , Oon Sheng F. , Moon Daniel , Murphy Declan G. , Eapen Renu , Goad Jeremy , Lawrentschuk Nathan , Azad Arun A. , Chander Sarat , Shaw Mark , Hardcastle Nicholas , Siva Shankar
Published: February 2024

Background

Stereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC). However, its impact on renal function is unclear. This study aimed to evaluate incidence and clinical factors predictive of severe to end-stage chronic kidney disease (CKD) after SABR for RCC.

Methods and materials

This was a Single institutional retrospective analysis of patients with diagnosed primary RCC receiving SABR between 2012–2020. Adult patients with no metastatic disease, baseline estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2, and at least one post-SABR eGFR at six months or later were included in this analysis. Patients with upper tract urothelial carcinoma were excluded. Primary outcome was freedom from severe to end-stage CKD, determined using the Kaplan–Meier estimator. The impact of baseline CKD, age, hypertension, diabetes, tumor size and fractionation schedule were assessed by Cox proportional hazard models.

Results

Seventy-eight consecutive patients were included, with median age of 77.8 years (IQR 70–83), tumor size of 4.5 cm (IQR 3.9–5.8) and follow-up of 42.2 months (IQR 23–60). Baseline median eGFR was 58 mls/min; 55% (n = 43) of patients had baseline CKD stage 3 and the remainder stage 1–2. By last follow-up, 1/35 (2.8%) of baseline CKD 1–2, 7/27 (25.9%) CKD 3a and 11/16 (68.8%) CKD 3b had developed CKD stage 4–5. The estimated probability of freedom from CKD stage 4–5 at 1 and 5 years was 89.6% (CI 83.0–97.6) and 65% (CI 51.4–81.7) respectively. On univariable analysis, worse baseline CKD (p < 0.0001) and multi-fraction SABR (p = 0.005) were predictive for development of stage 4–5 CKD though only the former remained significant in multivariable model.

Conclusion

In this elderly cohort with pre-existing renal dysfunction, SABR achieved satisfactory nephron sparing with acceptable rates of severe to end-stage CKD. It can be an attractive option in patients who are medically inoperable.
Characterizing the detection of inactivated Mycoplasma hyopneumoniae DNA in the respiratory tract of pigs
Authors: Canturri Albert , Pieters Maria
Published: February 2024

A positive Mycoplasma hyopneumoniae PCR result in a clinical specimen may eventually represent the mere detection of non-viable bacteria, complicating the diagnostic interpretation. Thus, the objective of this study was to evaluate the PCR detection of non-viable M. hyopneumoniae and its residual cell-free DNA in live pigs. Pigs were inoculated with either active or inactivated M. hyopneumoniae and were sampled for up to 14 days. Mycoplasma hyopneumoniae was not detected by PCR at any timepoint in pigs inoculated with the inactivated bacterium, suggesting that in healthy pigs, the non-viable M. hyopneumoniae DNA was rapidly sensed and cleared.
Anti-inflammatory effects of TP1 in LPS-induced Raw264.7 macrophages
Authors: Kim Minji , An Jangeun , Shin Seong-Ah , Moon Sun Young , Kim Moonsu , Choi Seyeon , Kim Huiji , Phi Kim-Hoa , Lee Jun Hyuck , Youn Ui Joung , Park Hyun Ho , Lee Chang Sup
Published: February 2024

Inflammation is an essential defense mechanism in health; however, excessive inflammation contributes to the pathophysiology of several chronic diseases. Although anti-inflammatory drugs are essential for controlling inflammation, they have several side effects. Recent findings suggest that naturally derived compounds possess physiological activities, including anti-inflammatory, antifungal, antiviral, anticancer, and immunomodulatory activities. Therefore, this study aimed to investigate the anti-inflammatory effects and molecular mechanisms of 2,5,6-trimethoxy-p-terphenyl (TP1), extracted from the Antarctic lichen Stereocaulon alpinum, using in vitro models. TP1 treatment decreased the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-stimulated Raw264.7 macrophages. Additionally, TP1 treatment significantly decreased the mRNA levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and the mRNA and protein levels of the pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2). Moreover, TP1 suppressed lipopolysaccharide-induced phosphorylation of the NF-κB and MAPK signaling pathways in Raw264.7 macrophages. Conclusively, these results suggest that TP1 ameliorates inflammation by suppressing the expression of pro-inflammatory cytokines, making it a potential anti-inflammatory drug for the treatment of severe inflammatory diseases.
Utilization of early postnatal care services and associated factors among mothers who gave birth in the last 12 months in South Gondar Zone District, Amhara Regional State, Ethiopia
Authors: Yimer Tigist Seid , Ferede Wassie Yazie , Sisay Fillorence Ayalew
Published: February 2024

Introduction

Postnatal care is care that is provided to mothers and newborn baby after delivery. The care given after childbirth is the most critical time because most maternal and neonatal mortality occurs during this period. Utilization of this service is low in Ethiopia, and no evidence exists to describe the status of early postnatal care service utilization among women in the study area.

Objective

This study aimed to assess the utilization of early postnatal care services and associated factors among mothers who gave birth in the last 12 months in the South Gondar Zone District, Amhara Region, Ethiopia, in 2021.

Method

This study was conducted in South Gondar Zone Districts from October 1 to 30, 2021. A total of 761 participants were included in this study using a simple random sampling method. The study participants were mothers who gave birth in the last 12 months. The data were collected via interview-guided semistructured questionnaires. The collected data were coded and entered into EPI Info version 7.2 and exported into SPSS version 23 for analysis. Both binary and multivariate logistic regression analyses were applied to identify factors affecting the outcome variables. The results of the final model are presented as the adjusted odds ratio (AOR) and 95% confidence interval (CI). A P value less than 0.05 was considered to indicate statistical significance.

Results

In this study, 761 mothers participated, for a response rate of 100%. The overall prevalence of early utilization of postnatal care services was 20.6%. Mothers who live in urban areas were five times more likely to have early visits than those living in rural areas with adjusted odds ratio [AOR (95% CI) = 5.2 (3.19, 8.54)], a mothers who had a history of more than four parity had more likely to visit than the others at [AOR (95% CI) = 2.25 (1.18, 4.29)], mothers who had a history of pregnancy had two times more likely to visit than the other [AOR (95% CI) = 2.06 (1.05, 4.05)], and mothers who had delivered by instrumental vaginal delivery or cesarean section delivery and those mothers who had mass media exposure were two and five times more likely to visit, respectively [AOR (95% CI) = 2.62 (1.40, 4.91)] and [AOR (95% CI) = 5.18 (2.55, 10.52)].

Conclusion and recommendation

Compared with those of other studies, the overall prevalence of early utilization of postnatal care services was low. Improving mothers’ knowledge of early postnatal care visits is very important for enhancing quality of life and minimizing neonatal and maternal morbidity and mortality.
3D Monte Carlo geometry inversion using gravity data
Authors: Wei Xiaolong , Sun Jiajia , Sen Mrinal
Published: February 2024

Diverse Monte Carlo methods have gained widespread use across a broad range of applications. However, the challenge of 3D Monte Carlo sampling remains due to the curse of dimensionality. To date, only a few works have been published regarding 3D Monte Carlo sampling. This study aims to develop an efficient 3D transdimensional Monte Carlo framework for reconstructing the spatial geometry of an anomalous body using gravity data. Our framework also can quantify the uncertainty of the shape of an anomalous body recovered from geophysical measurements. To improve the computational efficiency of 3D Monte Carlo sampling, we develop a sparse geometry parameterization strategy. This approach adequately approximates the shape of a complex 3D anomalous body using a set of simple geometries, such as ellipsoids. Each ellipsoid can be characterized by a few parameters, such as the centroid, axes, and orientations, significantly reducing the number of parameters to be sampled. During the sampling, we randomly perturb the number, locations, sizes, and orientations of the ellipsoids. To impose prior structural constraints from other geophysical methods, such as seismic imaging, we design a new method by placing a fixed layer oriented along the top boundary of the anomalous body. The fixed layer is then connected to the randomly sampled ellipsoids using an alpha shape, allowing us to estimate the geometry of the anomalous source body. The current work focuses on the reconstruction of salt bodies. We start with a synthetic spherical salt model and then conduct a more realistic study using a simplified 3D SEG/EAGE salt model, which has a much more complex geometry than the synthetic spherical model. Finally, we apply our method to the Galveston Island salt dome, offshore Texas. The numerical results demonstrate that our framework can effectively recover the shape of an anomalous body and quantify the uncertainty of the reconstructed geometry.
Development and Internal Validation of a Prediction Model for Nasopharyngeal Carcinoma: Using BMI and Inflammatory Response for Deciding Sequence of Chemotherapy
Authors: Setakornnukul Jiraporn , Petsuksiri Janjira , Chaysiri Panid , Danchaivijitr Pongwut , Ngamphaiboon Nuttapong , Thephamongkhol Kullathorn
Published: February 2024

PURPOSE

Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and induction chemotherapy followed by concurrent chemoradiotherapy (IC-CRT) are among the best treatments in nasopharyngeal carcinoma (NPC). This study aimed to develop a model for deciding the sequence of chemotherapy in NPC.

METHODS

Data were separated into two cohorts. The CRT-AC cohort had 295 patients, while the IC-CRT cohort had 112. The predictors were standard factors with BMI and neutrophil-lymphocyte ratio (NLR) to predict overall survival (OS). A flexible parametric survival model was used.

RESULTS

A total of 132 (44.7%) and 72 patients (64.3%) died in the CRT-AC and IC-CRT cohorts, respectively. The predictors in the final models were age, sex, T, N, NLR, and BMI. The models of OS for CRT-AC and IC-CRT had concordance indices of 0.689 and 0.712, respectively, with good calibration curves. When changing the burden of disease along with NLR and BMI, we found that CRT-AC was not significantly different OS from IC-CRT when low NLR (<3) and high burden of disease (T3N3). By contrast, CRT-AC was remarkably more effective when there were high levels of NLR (≥3) and BMI (≥25) with any burden of disease (anyT anyN).

CONCLUSION

With additional BMI and NLR in model, it could be easier to decide between CRT-AC and IC-CRT in countries with limited health care resources.