bluuebunny/crossref_metadata_2025 huggingface dataset:
Sports activity participation and subjective health status of patients after total hip arthroplasty via the anterolateral-supine approach: a case series study
Authors: Takahashi Yoshiki , Takahira Naonobu , Uchiyama Katsufumi , Fukushima Kensuke , Moriya Mitsutoshi , Shibuya Manaka
Published: October 2022

Background

No reports have been published about participation in sports activity and subjective health status after total hip arthroplasty via the anterolateral approach in the supine position (ALS-THA) in Japanese patients. This study assessed sports activity participation and subjective health status, as well as factors potential associated with these variables, in patients who underwent ALS-THA.

Methods

Of 698 patients who underwent total hip arthroplasty at our institution between 2013 and 2018, questionnaires were sent to 355 patients under 80 years old who had undergone ALS-THA and 242 responded. Patients were asked about their subjective health status, participation in sports activity, the EuroQol 5-dimensions 5-level (EQ-5D-5L), the University of California Los Angeles (UCLA) activity scale score and the Forgotten Joint Score (FJS). Patient characteristics and hospitalization information were also collected. Patients’ subjective health status was categorized as “healthy” or “unhealthy”. Univariate and multivariate logistic regression analyses were performed to determine factors associated with participation in sports activity after ALS-THA and a “healthy” status.

Results

The pre- and postoperative sports activity participation rates were 54.0% and 57.8%, respectively. Most patients (76.8%, n = 182) were considered “healthy”. Age (P = .019) and UCLA activity score (P < .001) were significantly associated with sports activity after ALS-THA. FJS (P = .002) and EQ-5D-5L (P = .004) were significantly associated with a “healthy” status.

Conclusion

Patients participating in sports activity after ALS-THA are older and have higher UCLA activity scores and patients considered “healthy” have higher FJS and EQ-5D-5L scores.
Clinical and radiologic outcomes of the modified phemister procedure with coracoclavicular ligament augmentation using mersilene tape versus hook plate fixation for acute acromioclavicular joint dislocation
Authors: Chang Yu-Jui , Chou Wen-Yi , Ko Jih-Yang , Liu Hao-Chen , Yang Ya-Ju , Siu Ka-Kit
Published: October 2022

Background

The clinical superiority of surgical treatment for acromioclavicular (AC) joint dislocation remains controversial. The aim of this study was to compare the clinical and radiological outcomes of the modified Phemister procedure with CC ligament augmentation using Mersilene tape to those of hook plate fixation for acute AC joint dislocation.

Methods

In this study, patients who received modified Phemister surgery with CC ligament augmentation using Mersilene tape (PM group) or hook plate fixation (HK group) for acute unstable AC joint dislocation with a minimum 5-year follow-up period were retrospectively reviewed. The clinical outcomes were evaluated according to blood loss during surgery, surgical duration, visual analogue scale (VAS), Constant-Murley score (CMS), University of California at Los Angeles (UCLA) shoulder rating scale, and the occurrence of complications. Radiological outcomes were assessed from radiographs according to multiple parameters, including CC distance maintenance, acromion osteolysis, and the presence of distal clavicle osteolysis.

Results

A total of 35 patients completed follow-up for more than 5 years and were analyzed in this study (mean = 74.08 months). There were 18 patients in the PM group and 17 in the HK group. The PM group exhibited similar improvement in functional outcome to the HK group. Regarding radiological outcomes, the HK group had a superior performance in terms of CC distance maintenance, of statistical significance (CCDR: 94.29 ± 7.01% versus 111.00 ± 7.69%, p < 0.001) after a one-year follow-up period. However, there were 4 cases of acromion osteolysis and 2 cases of distal clavicle osteolysis in the HK group.

Conclusion

Hook plate fixation was found to be superior to the modified Phemister technique with CC ligament augmentation using Mersilene tape in terms of CC distance maintenance, but there was no significant difference in the functional outcome after 5 years of follow-up. Both surgical methods are reliable options for the treatment of acute AC joint dislocation. Modified Phemister surgery with CC ligament augmentation using Mersilene tape is a relatively lower-cost option for acute AC joint dislocation without the need of a second surgery for implant removal.
Preparation of a novel monoclonal antibody against active components of PHA-L from Phaseolus vulgaris and its functional characteristics
Authors: Wang Peipei , Hu Junmei , Duan Jiaqi , Min Shitong , Chen Congliang , Zhu Yue , Pan Yan , Wang Yitian , Wei Dapeng , Wang Xia
Published: October 2022

Background

Leukocyte phytohemagglutinin (PHA-L), derived from the L4 tetramer of PHA, has been frequently employed as a mitogen to induce T lymphocyte proliferation in vitro. The biological application of PHA-L in cancer diagnosis and treatment has gained traction in recent years. However, it has been noted that PHA-L obtained using traditional procedures has a massive amount of impurities or toxic components, which interfere with the activity of PHA-L. Preparation of a monoclonal antibody against active PHA-L is a significant tool for studying PHA-L's function and therapeutic potential.

Results

We successfully prepared monoclonal antibodies against the active components of PHA-L based on the whole PHA-L protein as an antigen, and found that monoclonal antibody 3C1C6G11 can be employed in western blot, immunofluorescence, and immunohistochemistry detection. Importantly, preliminary result shows that the mAb 3C1C6G11 may prevent PHA-L-induced cell aggregation and AICD (activation-induced cell death).

Conclusions

The monoclonal antibody mAb 3C1C6G11 prepared in this study can be used as an effective tool for detecting PHA-L active components, investigating PHA-L's function and antineoplastic application.
Evaluation of factors that influenced the length of hospital stay using data mining techniques
Authors: Eskandari Mehrnoosh , Alizadeh Bahmani Amir Hossein , Mardani-Fard Heydar Ali , Karimzadeh Iman , Omidifar Navid , Peymani Payam
Published: October 2022

Background

length of stay (LOS) is the time between hospital admission and discharge. LOS has an impact on hospital management and hospital care functions.

Methods

A descriptive, retrospective study was designed on about 27,500 inpatients between March 2019 and 2020. Required data were collected from six wards (CCU, ICU, NICU, General, Maternity, and Women) in a teaching hospital. Clinical data such as demographic characteristics (age, sex), type of ward, and duration of hospital stay were analyzed by the R-studio program. Violin plots, bar charts, mosaic plots, and tree-based models were used to demonstrate the results.

Results

The mean age of the population was 40.8 ± 19.2 years. The LOS of the study population was 2.43 ± 4.13 days. About 60% of patients were discharged after staying one day in the hospital. After staying one day in the hospital, 67% of women were discharged. However, 23% of men were discharged within this time frame. The majority of LOS in the CCU, ICU, and NICU ranged from 5 to 9 days.; In contrast, LOS was one day in General, Maternity, and Woman wards. Due to the tree plot, there was a different LOS pattern between Maternity-Women and the CCU-General-ICU-NICU wards group.

Conclusion

We observed that patients with more severe diseases hospitalized in critical care wards had a longer LOS than those not admitted to critical care wards. The older patient had longer hospital LOS than the younger. By excluding Maternity and Woman wards, LOS in the hospital was comparable between males and females and demonstrated a similar pattern.
Creating conditions for effective knowledge brokering: a qualitative case study
Authors: Burns Prue , Currie Graeme , McLoughlin Ian , Robinson Tracy , Sohal Amrik , Teede Helena
Published: October 2022

Background

Process improvement in healthcare is informed by knowledge from the private sector. Skilled individuals may aid the adoption of this knowledge by frontline care delivery workers through knowledge brokering. However, the effectiveness of those who broker knowledge is limited when the context they work within proves unreceptive to their efforts. We therefore need greater insight into the contextual conditions that support individuals to broker process improvement knowledge to the frontline of care delivery, and how policy makers and organizations might generate such conditions.

Methods

Our research took place in a healthcare system within an Australian State. We undertook a qualitative, embedded single case study over the four year period of a process improvement intervention encompassing 57 semi-structured interviews (with knowledge brokers, policy makers, and executive sponsors), 12 focus groups, and 137 h of observation, which included the frontline implementation of actual process improvement initiatives, where knowledge brokering took place.

Results

We identified four phases of the process improvement intervention that moved towards a more mature collaboration within which knowledge brokering by improvement advisors began to emerge as effective. In the first phase knowledge brokering was not established. In the second phase, whilst knowledge brokering had been initiated, the knowledge being brokered lacked legitimacy amongst frontline practitioners, resulting in resistance. Only in the fourth and final phase of the intervention did the collective experience of policy makers result in reflections on how they might engender a more receptive context for knowledge brokering.

Conclusion

We highlight a number of suggested actions that policy makers might consider, if they wish to engender contextual conditions that support knowledge brokering. Policy makers might consider: ensuring they respect local context and experience, by pulling good ideas upward, rather than imposing foreign knowledge from on high; facilitating the lateral diffusion of knowledge by building cultural linkages between people and organizations; strengthening collaboration, not competition, so that trans-organisational flow of ideas might be encouraged; being friend, not foe, to healthcare organizations on their knowledge integration journey. In sum, we suggest that top-down approaches to facilitating the diffusion and adoption of new ideas ought to be reconsidered.
Hospital managers’ views on the state of patient safety culture across three regions in Ghana
Authors: Tenza Immaculate Sabelile , Attafuah Priscilla Y. A. , Abor Patience , Nketiah-Amponsah Edward , Abuosi Aaron Asibi
Published: October 2022

Background

Improving patient safety culture in healthcare organisations contributes positively to the quality of care and patients’ attitudes toward care. While hospital managers undoubtedly play critical roles in creating a patient safety culture, in Ghana, qualitative studies focussing on hospital managers’ views on the state of patient safety culture in their hospitals remain scanty.

Objective

This study aimed to explore the views of hospital managers regarding compliance to patient safety culture dimensions in the selected hospitals in the Bono, Greater Accra, and Upper East regions of Ghana.

Methodology

This was a qualitative exploratory study. A purposive sampling of all hospital managers involved in patient safety practices was conducted. The sampled managers were then invited to a focus group discussion. Twelve focus group discussions with each consisting of a maximum of twelve participants were conducted. The ten patient safety culture dimensions adapted from the Agency for Healthcare Research and Quality’s patient safety culture composite measures framed the interview guide. Deductive thematic content analysis was done. Lincoln and Guba’s methods of trustworthiness were applied to ensure that the findings are valid and reliable.

Findings

Positive patient safety culture behaviours such as open communication, organisational learning, and strong teamwork within units, were an established practice in the selected facilities across Ghana. Lack of teamwork across units, fear of reporting adverse events, the existence of a blame culture, inconsistent response to errors, extreme shortage of staff, sub-standard handover, lack of management support with resources constrained the patient safety culture. The lack of standardised policies on reporting adverse events and response to errors encouraged managers to use various approaches, some resulting in a blame culture. Staff shortage contributed to poor quality of safety practices including poor handover which was also influenced by lateness to duty.

Conclusion

Prompt and appropriate responses by managers to medical errors require improvements in staffing and material resources as well as the enactment of standard policies across health facilities in the country. By so doing, hospital managers would contribute significantly to patient safety, and help build a patient safety culture in the selected hospitals.
Satisfactory breeding potential is transiently eliminated in beef bulls with clinical anaplasmosis
Authors: Lovett Anne C. , Reppert Emily J. , Jaeger John R. , Kang Qing , Flowers Macy R. , Bickmeier Naemi P. , Anantatat Tippawan , O’Day Shannon C. , Armstrong Chance L. , Reif Kathryn E.
Published: October 2022

Background

Natural service breeding is common in U.S. cow-calf operations. Diseases impacting bull reproductive performance have significant economic consequences for producers. Anaplasmosis may be an underappreciated cause of poor reproductive performance in bulls. The primary systemic effects of bovine anaplasmosis including anemia, fever, and weight loss, can all result in unsatisfactory reproductive performance. The objective of this pilot study was to evaluate breeding soundness examination (BSE) outcomes and clinical changes in bulls during and upon resolution of clinical anaplasmosis.Anaplasma marginale-challenged bulls were observed for clinical disease and infection progression and changes in breeding soundness compared to uninfected control bulls for 16 weeks.

Results

AllAnaplasma marginale-challenged bulls were PCR-positive, seropositive, and showed clinical signs by 3-, 17-, and 24-days post-challenge, respectively. Clinical signs of anaplasmosis included pallor, icterus, fever (≥ 40.2 °C), and weight loss. Acute anemia was observed in all challenged bulls with PCV nadirs ≤ 18% and peak percent parasitized erythrocyte ≥ 50%. Decreased scrotal circumference and poor semen quality (e.g., increased percentage of abnormal spermatozoa, decreased progressively motile sperm), were initially observed within days after onset of clinical anaplasmosis signs and continued weeks beyond disease resolution. Control bulls remained negative forA. marginale.

Conclusion

This pilot study demonstrates that clinical anaplasmosis reduces breeding soundness in beef bulls. Anaplasmosis should be considered as a differential for bulls with decreased semen quality, especially within endemic areas. A 90 day or greater retest window is recommended for bulls of unsatisfactory breeding potential recently recovered from clinical anaplasmosis.
Increasing the data on elasmobranch plasma protein electrophoresis: electrophoretogram reference values determination in the undulate skate (Raja Undulata) and the nursehound shark (Scyliorhinus stellaris) maintained under human care
Authors: Morón-Elorza Pablo , Rojo-Solís Carlos , Steyrer Christine , Álvaro-Álvarez Teresa , Valls-Torres Mónica , Ortega Javier , Encinas Teresa , García-Párraga Daniel
Published: October 2022

Background

This study determined plasma protein electrophoresis (PPE) reference intervals in two elasmobranch species: the undulate skate (Raja undulata) and the nursehound shark (Scyliorhinus stellaris), using a reference population of 48 undulate skates (27 males, 21 females) and 62 nursehounds (32 males, 30 females), considered to be clinically healthy. Plasma samples were analyzed using capillary zone electrophoresis (CZE).

Results

The undulate skate electrophoretogram resembled those previously reported in other batoids and could be divided into seven consistent fractions. No statistically significant differences were detected between sexes and developmental stages. The nursehound electrophoretogram was similar to that previously described in other shark species and could be divided into eight consistent fractions. Fraction 5% was significantly higher in juvenile nursehounds when compared to adults, while fraction 6 concentration and percentage were significantly higher in adults. Fraction 4% was higher in males than in females. Albumin band was not detected, and pre-albumin was negligible in both studied species. Alpha-globulins were predominant in the undulate skate, while beta-globulins were predominant in nursehounds. Statistically significant differences were found in all electrophoretogram fraction percentages and concentrations between the two species.

Conclusion

To the authors knowledge, this is the first study reporting PPE values in undulate skates and nursehounds, and the first study using CZE in elasmobranch plasma. These findings can serve as a primary reference for health monitoring in both species and will add to the limited data available on PPE in elasmobranchs.
Chinese never smokers with adenocarcinoma of the lung are younger and have fewer lymph node metastases than smokers
Authors: Shan Longyu , Zhang Liang , Zhu Xiaolei , Wang Zhilin , Fang Shaohan , Lin Junfeng , Wang Jianweng , Li Ning , Liu Hongming , Zhang Xiaowen , Feng Yihui , Liu Jingwei , Pan Jianyun , Ye Guanzhi , Yu Xiuyi , Tufman Amanda , Katalinic Alexander , Goldmann Torsten , Petersen Frank , Jiang Jie , Geng Guojun , Yu Xinhua
Published: October 2022

Background

Lung cancers arising in never smokers have been suggested to be substantially different from lung cancers in smokers at an epidemiological, genetic and molecular level. Focusing on non-small cell lung cancer (NSCLC), we characterized lung cancer patients in China looking for demographic and clinical differences between the smoking and never-smoking subgroups.

Methods

In total, 891 patients with NSCLC, including 841 with adenocarcinoma and 50 with squamous cell carcinoma, were recruited in this study. Association of smoking status with demographic and clinical features of NSCLC was determined, and risk factors for lymph node metastasis and TNM stage were evaluated using Multivariate logistic regression analysis.

Results

In patients with adenocarcinoma, never smokers showed a younger age at diagnosis (54.2 ± 12.7vs. 59.3 ± 9.4, padjusted<0.001), a lower risk for lymph node metastasis than smokers (7,6% vs. 19.5%, padjusted<0.001) and less severe disease as indicated by lower percentages of patients with TNM stage of III or IV (5.5% vs. 14.7%, padjusted<0.001 ). By contrast, these associations were not observed in 50 patients with squamous cell carcinoma. Multivariate logistic regression analysis showed that smoking status was a risk factor for lymph node metastasis (OR = 2.70, 95% CI: 1.39–5.31, p = 0.004) but not for TNM stage (OR = 1.18, 95% CI: 0.09–14.43, p = 0.896) in adenocarcinoma.

Conclusion

This study demonstrates that lung adenocarcinoma in never smokers significantly differ from those in smokers regarding both age at diagnosis and risk of lymph node metastasis, supporting the notion that they are distinct entries with different etiology and pathogenesis.
End-of-life care for idiopathic pulmonary fibrosis patients with acute exacerbation
Authors: Akiyama Norimichi , Fujisawa Tomoyuki , Morita Tatsuya , Koyauchi Takafumi , Matsuda Yoshinobu , Mori Masanori , Miyashita Mitsunori , Tachikawa Ryo , Tomii Keisuke , Tomioka Hiromi , Hagimoto Satoshi , Kondoh Yasuhiro , Inoue Yoshikazu , Suda Takafumi
Published: October 2022

Background

Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). AE-IPF patients require optimal palliative care; however, the real-world clinical situations are poorly understood. We aimed to survey the palliative care received by AE-IPF patients, especially with respect to opioid use for dyspnea and the end-of-life discussions (EOLd).

Methods

Self-administered questionnaires were dispatched to 3423 of the certified pulmonary physicians in Japan. They were asked to report a care report form of one patient each with AE-IPF who died very recently about opioid use for dyspnea and EOLd. We further explored the factors associated with the early use of opioids for dyspnea.

Results

Among the 3423 physicians, 1226 (35.8%) returned the questionnaire with the report forms of 539 AE-IPF patients. Of 539 AE-IPF patients, 361 (67.0%) received opioids for dyspnea. Of the 361 patients, 72 (20.0%) received opioids during the initial treatment with an intention of recovery (early use), while 289 (80.0%) did when the recovery was deemed impossible. EOLd was held before the onset of AE in 124 patients (23.0%); however, the majority of patients had EOLd after the admission for AE-IPF. EOLd before the onset of AE was significantly associated with the early use of opioids.

Conclusion

In terminally ill AE-IPF patients, opioids are usually administered when the recovery is deemed impossible, and EOLd are rarely held before the onset of AE. Further studies are warranted on the efficacy of opioids for dyspnea and the appropriate timing of EOLd.
Prognostic value of coronary microvascular dysfunction assessed by coronary angiography-derived index of microcirculatory resistance in diabetic patients with chronic coronary syndrome
Authors: Zhang Wen , Singh Shekhar , Liu Lu , Mohammed Abdul-Quddus , Yin Guoqing , Xu Siling , Lv Xian , Shi Tingting , Feng Cailin , Jiang Rong , Mohammed Ayman A. , Mareai Redhwan M. , Xu Yawei , Yu Xuejing , Abdu Fuad A. , Che Wenliang
Published: October 2022

Background

Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS).

Methods

CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE.

Results

Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR < 25 (20.6% vs. 8.2%, p = 0.002). Of these, the MACE rate was higher among DM patients with caIMR ≥ 25 than those with caIMR < 25 (33.9% vs. 14.0%; p = 0.022). In multivariable Cox analysis, caIMR ≥ 25 was independently associated with MACE in the DM patients but not in non-DM patients (HR, 2.760; 95% CI, 1.066–7.146; P = 0.036).

Conclusion

CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy.
Long-term cardiovascular outcomes of gestational diabetes mellitus: a prospective UK Biobank study
Authors: Lee Seung Mi , Shivakumar Manu , Park Ji Won , Jung Young Mi , Choe Eun Kyung , Kwak Soo Heon , Oh Sohee , Park Joong Shin , Jun Jong Kwan , Kim Dokyoon , Yun Jae-Seung
Published: October 2022

Background

Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes.

Methods

Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk.

Results

After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18–1.55)], including coronary artery disease [aHR 1.31 (1.08–1.59)], myocardial infarction [aHR 1.65 (1.27–2.15)], ischemic stroke [aHR 1.68 (1.18–2.39)], peripheral artery disease [aHR 1.69 (1.14–2.51)], heart failure [aHR 1.41 (1.06–1.87)], mitral regurgitation [aHR 2.25 (1.51–3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18–1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome.

Conclusions

GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.
LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal
Authors: Zhu Guanghui , Xia Yu , Zhao Ziyue , Li Aoyu , Li Hui , Xiao Tao
Published: October 2022

Background

Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whether BMSCs derived exosomes transmit XIST to regulate the growth and metastasis of osteosarcoma and the related mechanism are still unclear.

Method

In this study, BMSCs derived exosomes were used to treat human osteosarcoma cells MG63 and 143B, and the level of XIST in BMSCs was intervened by siRNA. CCK-8, EdU, transwell assays were used to analyze the changes of cell proliferation, migration and invasion. Bioinformatics analysis, RNA pulldown and dual-luciferase reporter gene assays validated the targeted relationship of XIST with miR-655 and the interaction between miR-655 and ACLY 3’-UTR. 143B/LUC cell line was used to establish an animal model of in situ osteosarcoma to verify the found effects of XIST on osteosarcoma. Oil Red O staining, Western blot and so on were used to detect the changes of lipid deposition and protein expression.

Results

It was found that BMSCs derived exosomes promoted the proliferation, migration and invasion of osteosarcoma cells, and the down-regulation of XIST inhibited this effect. miR-655 mediated the role of BMSCs derived exosomal XIST in promoting the progression of osteosarcoma and down-regulation of miR-655 could reverse the effects of inhibiting XIST on the proliferation, migration and invasion of osteosarcoma cells. Meanwhile, animal level results confirmed that BMSCs derived exosomal XIST could promote osteosarcoma growth and lung metastasis by combining with miR-655. In-depth mechanism study showed that BMSCs derived exosomal XIST combined with miR-655 to increase the protein level of ACLY, which led to lipid deposition and activate β-catenin signal to promote the proliferation, migration and invasion of osteosarcoma cells.

Conclusion

This study showed that BMSCs derived exosomal XIST could enter osteosarcoma cells, bind and down-regulates the level of miR-655, resulting in an increase in the level of ACLY, thus increasing the lipid deposition and the activity of β-catenin signal to promote the growth and metastasis of osteosarcoma.
Human amniotic epithelial cells exert anti-cancer effects through secretion of immunomodulatory small extracellular vesicles (sEV)
Authors: Bolouri Mohammad-Reza , Ghods Roya , Zarnani Kayhan , Vafaei Sedigheh , Falak Reza , Zarnani Amir-Hassan
Published: October 2022

We identified here mechanism by which hAECs exert their anti-cancer effects. We showed that vaccination with live hAEC conferred effective protection against murine colon cancer and melanoma but not against breast cancer in an orthotopic cancer cell inoculation model. hAEC induced strong cross-reactive antibody response to CT26 cells, but not against B16F10 and 4T1 cells. Neither heterotopic injection of tumor cells in AEC-vaccinated mice nor vaccination with hAEC lysate conferred protection against melanoma or colon cancer. Nano-sized AEC-derived small-extracellular vesicles (sEV) (AD-sEV) induced apoptosis in CT26 cells and inhibited their proliferation. Co-administration of AD-sEV with tumor cells substantially inhibited tumor development and increased CTL responses in vaccinated mice. AD-sEV triggered the Warburg’s effect leading to Arginine consumption and cancer cell apoptosis. Our results clearly showed that it is AD-sEV but not the cross-reactive immune responses against tumor cells that mediate inhibitory effects of hAEC on cancer development. Our results highlight the potential anti-cancer effects of extracellular vesicles derived from hAEC.
Mechanistic insights into the health benefits of fish-oil supplementation against fine particulate matter air pollution: a randomized controlled trial
Authors: Zhou Lu , Jiang Yixuan , Lin Zhijing , Chen Renjie , Niu Yue , Kan Haidong
Published: October 2022

Background:

Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM2.5) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM2.5-induced health effects.

Methods:

We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM2.5 on the metabolic profile between the sunflower-seed oil and fish oil groups.

Results:

A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM2.5 concentration on the day of health measurements was 34.9 µg/m3 in the sunflower-seed oil group and 34.5 µg/m3 in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM2.5 in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses.

Conclusion:

This trial suggests fish-oil supplementation could mitigate the PM2.5-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM2.5 exposure.

Trial registration:

This study is registered at ClinicalTrails.gov (NCT03255187).
Pitfalls in methods to study colocalization of nanoparticles in mouse macrophage lysosomes
Authors: Moreno-Echeverri Aura Maria , Susnik Eva , Vanhecke Dimitri , Taladriz-Blanco Patricia , Balog Sandor , Petri-Fink Alke , Rothen-Rutishauser Barbara
Published: October 2022

Background

In the field of nanoscience there is an increasing interest to follow dynamics of nanoparticles (NP) in cells with an emphasis on endo-lysosomal pathways and long-term NP fate. During our research on this topic, we encountered several pitfalls, which can bias the experimental outcome. We address some of these pitfalls and suggest possible solutions. The accuracy of fluorescence microscopy methods has an important role in obtaining insights into NP interactions with lysosomes at the single cell level including quantification of NP uptake in a specific cell type.

Methods

Here we use J774A.1 cells as a model for professional phagocytes. We expose them to fluorescently-labelled amorphous silica NP with different sizes and quantify the colocalization of fluorescently-labelled NP with lysosomes over time. We focus on confocal laser scanning microscopy (CLSM) to obtain 3D spatial information and follow live cell imaging to study NP colocalization with lysosomes.

Results

We evaluate different experimental parameters that can bias the colocalization coefficients (i.e., Pearson’s and Manders’), such as the interference of phenol red in the cell culture medium with the fluorescence intensity and image post-processing (effect of spatial resolution, optical slice thickness, pixel saturation and bit depth). Additionally, we determine the correlation coefficients for NP entering the lysosomes under four different experimental set-ups. First, we found out that not only Pearson’s, but also Manders’ correlation coefficient should be considered in lysosome-NP colocalization studies; second, there is a difference in NP colocalization when using NP of different sizes and fluorescence dyes and last, the correlation coefficients might change depending on live-cell and fixed-cell imaging set-up.

Conclusions

The results summarize detailed steps and recommendations for the experimental design, staining, sample preparation and imaging to improve the reproducibility of colocalization studies between the NP and lysosomes.

Graphical Abstract
Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice
Authors: García-García Patricia , Reyes Ricardo , García-Sánchez Daniel , Pérez-Campo Flor María , Rodríguez-Rey José Carlos , Évora Carmen , Díaz-Rodríguez Patricia , Delgado Araceli
Published: October 2022

Osteoporosis (OP) is characterized by a loss in bone mass and mineral density. The stimulation of the canonical Wnt/β-catenin pathway has been reported to promote bone formation, this pathway is controlled by several regulators as secreted frizzled-related protein-1 (Sfrp-1), antagonist of the pathway. Thus, Sfrp-1 silencing therapies could be suitable for enhancing bone growth. However, the systemic stimulation of Wnt/β-catenin has been correlated with side effects. This work hypothesizes the administration of lipid-polymer NPs (LPNPs) functionalized with a MSC specific aptamer (Apt) and carrying a SFRP1 silencing GapmeR, could favor bone formation in OP with minimal undesired effects. Suitable SFRP1 GapmeR-loaded Apt-LPNPs (Apt-LPNPs-SFRP1) were administered in osteoporotic mice and their biodistribution, toxicity and bone induction capacity were evaluated. The aptamer functionalization of the NPs modified their biodistribution profile showing a four-fold increase in the bone accumulation and a ten-fold decrease in the hepatic accumulation compared to naked LPNPs. Moreover, the histological evaluation revealed evident changes in bone structure observing a more compact trabecular bone and a cortical bone thickness increase in the Apt-LPNPs-SFRP1 treated mice with no toxic effects. Therefore, these LPNPs showed suitable properties and biodistribution profiles leading to an enhancement on the bone density of osteoporotic mice.
Circulating Anti-Müllerian hormone in a cohort-study of women with severe obesity with and without polycystic ovary syndrome and the effect of a one-year weight loss intervention
Authors: Kataoka Josefin , Larsson Ingrid , Lindgren Eva , Kindstrand Li Oskarson , Schmidt Johanna , Stener-Victorin Elisabet
Published: October 2022

Background

Women with polycystic ovary syndrome (PCOS) have high circulating anti-Müllerian hormone (AMH) levels which is correlated with antral follicle count and polycystic ovarian morphology and negatively correlated with body mass index (BMI). Moreover, diet-induced weight loss in women with PCOS and overweight or obesity, reduce or normalize AMH-levels. There is, however, no previous study investigating the circulating AMH levels in women with severe obesity and how a structured diet-induced weight loss program affects circulating AMH levels in these women. Therefore, this study aims to investigate circulating AMH levels in a population of women with severe obesity (BMI ≥ 35 kg/m2) with and without PCOS, as diagnosed by the NIH-criteria, and to investigate the effect of a one-year weight loss program with a very low-energy diet (VLED) on circulating levels of AMH.

Methods

In a prospective cohort-study, were 246 women with severe obesity were screened for PCOS diagnosis with the NIH-criteria, circulating AMH and anthropometry were measured at baseline and after a 12-month weight loss intervention with very low-energy diet (VLED).

Results

Mean BMI was 39.9 ± 4.7 (PCOS), 39.6 ± 4.3 (non-PCOS) P = 0.960. Circulating AMH was higher in women with PCOS (5.47 ± 4.89 µg/L) compared with non-PCOS (2.66 ± 3.71 µg/L) P < 0.001 and was positively correlated with circulating total testosterone in both groups. Next, we performed ROC-analyses, and show that circulating AMH could not discriminate women with PCOS and severe obesity from non-PCOS women with severe obesity. Finally, a one-year weight reduction program does not affect circulating AMH levels despite significant weight loss neither in women with PCOS, nor without PCOS and severe obesity.

Conclusion

Women with severe obesity and PCOS have elevated levels of circulating AMH compared to women without the syndrome. AMH-levels could not discriminate women with PCOS from non-PCOS because of low sensitivity and specificity. Significant weight loss was not associated with changes in circulating AMH levels, neither in women with, nor without PCOS and severe obesity. These results imply that in women with severe obesity, a greater weight loss may be needed to improve reproductive features, independent of PCOS diagnosis.

Trial registration number:

Clinical trial.gov: NCT01319162.
Silencing eL31 suppresses the progression of colorectal cancer via targeting DEPDC1
Authors: Sharen Gaowa , Li Xiongfeng , Sun Jiaxin , Zhang Lei , Xi Wen , Zhao Xiaodong , Han Fei , Jia Longlong , A Rong , Cheng Haidong , Hou Mingxing
Published: October 2022

Background

Colorectal cancer (CRC) is one of the most commonly diagnosed human malignancies. Ribosomal protein L31 (RPL31, aka eL31) is a component of the 60S large ribosomal subunit, and its expression pattern and functional role in CRC have not been reported.

Methods

Herein, we identified that eL31 protein level was dramatically increased in CRC tissues through using IHC analysis. More notably, elevated eL31 was associated with larger tumor size and shorter overall survival. Besides, we evaluated the effects of eL31 depletion on CRC cell phenotypes in vitro.

Results

The data indicated that eL31 knockdown restricted CRC cell proliferation, migration and colony formation whilst enhancing cell apoptosis. Importantly, eL31 was also essential for CRC tumor growth in vivo, as demonstrated by impaired tumor growth markers and reduced Ki67 levels in xenografts from eL31-depleted cells. In addition, our evidence indicated that DEP domain containing 1 (DEPDC1) was a potential downstream target of eL31 in regulating CRC. Consistently, DEPDC1 depletion restrained CRC cell proliferation and migration, as well as facilitated cell apoptosis. More interestingly, DEPDC1 depletion could reverse the promotion effects of eL31 elevation on CRC cells.

Conclusions

Identification of eL31’s function in CRC may pave the way for future development of more specific and more effective targeted therapy strategies against CRC.
Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study
Authors: Wang Yong-Bo , Yang Lan , Deng Yu-Qing , Yan Si-Yu , Luo Li-Sha , Chen Ping , Zeng Xian-Tao
Published: October 2022

Background

Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear.

Methods

We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10–8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis.

Results

The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07–1.43, P = 0.0045), 1.08 (95% CI 1.01–1.17, P = 0.0175), 0.94 (95% CI 0.67–1.30, P = 0.6891), 1.29 (95% CI 0.88–1.89, P = 0.1922), 1.23 (95% CI 0.85–1.78, P = 0.2623), and 1.04 (95% CI 0.76–1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92–1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96–1.26, P = 0.1725) and 0.84 (95% CI 0.69–1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08–1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11–1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05–1.23, P = 0.0021) were associated with BPH after the adjustment of BMI.

Conclusion

This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.
HUSH-mediated HIV silencing is independent of TASOR phosphorylation on threonine 819
Authors: Vauthier Virginie , Lasserre Angélique , Morel Marina , Versapuech Margaux , Berlioz-Torrent Clarisse , Zamborlini Alessia , Margottin-Goguet Florence , Matkovic Roy
Published: October 2022

Background

TASOR, a component of the HUSH repressor epigenetic complex, and SAMHD1, a cellular triphosphohydrolase (dNTPase), are both anti-HIV proteins antagonized by HIV-2/SIVsmm Viral protein X. As a result, the same viral protein is able to relieve two different blocks along the viral life cell cycle, one at the level of reverse transcription, by degrading SAMHD1, the other one at the level of proviral expression, by degrading TASOR. Phosphorylation of SAMHD1 at T592 has been shown to downregulate its antiviral activity. The discovery that T819 in TASOR was lying within a SAMHD1 T592-like motif led us to ask whether TASOR is phosphorylated on this residue and whether this post-translational modification could regulate its repressive activity.

Results

Using a specific anti-phospho-antibody, we found that TASOR is phosphorylated at T819, especially in cells arrested in early mitosis by nocodazole. We provide evidence that the phosphorylation is conducted by a Cyclin/CDK1 complex, like that of SAMHD1 at T592. While we could not detect TASOR in quiescent CD4 + T cells, TASOR and its phosphorylated form are present in activated primary CD4 + T lymphocytes. In addition, TASOR phosphorylation appears to be independent from TASOR repressive activity. Indeed, on the one hand, nocodazole barely reactivates HIV-1 in the J-Lat A1 HIV-1 latency model despite TASOR T819 phosphorylation. On the other hand, etoposide, a second cell cycle arresting drug, reactivates latent HIV-1, without concomitant TASOR phosphorylation. Furthermore, overexpression of wt TASOR or T819A or T819E similarly represses gene expression driven by an HIV-1-derived LTR promoter. Finally, while TASOR is degraded by HIV-2 Vpx, TASOR phosphorylation is prevented by HIV-1 Vpr, likely as a consequence of HIV-1 Vpr-mediated-G2 arrest.

Conclusions

Altogether, we show that TASOR phosphorylation occurs in vivo on T819. This event does not appear to correlate with TASOR-mediated HIV-1 silencing. We speculate that TASOR phosphorylation is related to a role of TASOR during cell cycle progression.
A framework for clinical utilization of robotic exoskeletons in rehabilitation
Authors: Hohl Kristen , Giffhorn Matt , Jackson Steven , Jayaraman Arun
Published: October 2022

Exoskeletons are externally worn motorized devices that assist with sit-to-stand and walking in individuals with motor and functional impairments. The Food & Drug Administration (FDA) has approved several of these technologies for clinical use however, there is limited evidence to guide optimal utilization in every day clinical practice. With the diversity of technologies & equipment available, it presents a challenge for clinicians to decide which device to use, when to initiate, how to implement these technologies with different patient presentations, and when to wean off the devices. Thus, we present a clinical utilization framework specific to exoskeletons with four aims.

These aims are to assist with clinical decision making of when exoskeleton use is clinically indicated, identification of which device is most appropriate based on patient deficits and device characteristics, providing guidance on dosage parameters within a plan of care and guidance for reflection following utilization. This framework streamlines how clinicians can approach implementation through the synthesis of published evidence with appropriate clinical assessment & device selection to reflection for success and understanding of these innovative & complex technologies.
A high-throughput screening assay to identify inhibitory antibodies targeting alphavirus release
Authors: Ramjag Anushka , Cutrone Sergej , Lu Kai , Crasto Christine , Jin Jing , Bakkour Sonia , Carrington Christine V. F. , Simmons Graham
Published: October 2022

Background

Several studies have demonstrated neutralizing antibodies to be highly effective against alphavirus infection in animal models, both prophylactically and remedially. In most studies, neutralizing antibodies have been evaluated for their ability to block viral entry in vitro but recent evidence suggests that antibody inhibition through other mechanisms, including viral budding/release, significantly contributes to viral control in vivo for a number of alphaviruses.

Results

We describe a BSL-2, cell-based, high-throughput screening system that specifically screens for inhibitors of alphavirus egress using chikungunya virus (CHIKV) and Mayaro virus (MAYV) novel replication competent nano-luciferase (nLuc) reporter viruses. Screening of both polyclonal sera and memory B-cell clones from CHIKV immune individuals using the optimized assay detected several antibodies that display potent anti-budding activity.

Conclusions

We describe an “anti-budding assay” to specifically screen for inhibitors of viral egress using novel CHIKV and MAYV nLuc reporter viruses. This BSL-2 safe, high-throughput system can be utilized to explore neutralizing “anti-budding” antibodies to yield potent candidates for CHIKV and MAYV therapeutics and prophylaxis.