bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate: a single-center, randomized, controlled, open label, phase III study
Authors: Bertolo Riccardo , Cipriani Chiara , Vittori Matteo , Carilli Marco , Maiorino Francesco , Iacovelli Valerio , Ganini Carlo , Antonucci Michele , Signoretti Marta , Petta Filomena , Panei Massimo , Bove Pierluigi
Published: February 2022

Background

Several studies described post-operative irritative symptoms after laser enucleation of prostate, sometimes associated with urge incontinence, probably linked to laser-induced prostatic capsule irritation, and potential for lower urinary tract infections We aimed to evaluate the efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate (ThuLEP).

Methods

In this single-center, prospective, randomized, open label, phase-III study, patients with indication to ThuLEP were enrolled (Dec2019–Feb2021—Institutional ethics committee STS CE Lazio approval no.1/N-726—ClinicalTrials.gov NCT05130918). The report conformed to CONSORT 2010 guidelines. Eligible patients were 1:1 randomized. Randomization defined Group A: patients who were administered Mictalase® suppositories twice a day for 5 days, then once a day for other 10 days; Group B: patients who did not receive Mictalase® (“controls”). Study endpoints were evaluated at 15 and 30 days postoperation. Primary endpoint included evaluation of effects of the suppository on irritative symptoms by administering IPSS + QoL questionnaire. Secondary endpoint included evaluation of effects on urinary tract infections by performance of urinalysis with urine culture.

Results

111 patients were randomized: 56 in Group A received Mictalase®. Baseline and perioperative data were comparable. At 15-days, no significant differences were found in terms of IPSS + QoL scores and urinalysis parameters. A significant difference in the rate of positive urine cultures favored Group A (p = 0.04). At 30-days follow-up, significant differences were found in median IPSS score (6 [IQR 3–11] versus 10 [5–13], Group A vs B, respectively, p = 0.02). Urinalysis parameters and rate of positive urine cultures were not significantly different.

Conclusions

The present randomized trial investigated the efficacy of Mictalase® in control of irritative symptoms and prevention of lower urinary tract infections in patients undergoing ThuLEP. IPSS improvement 30-days postoperation was more pronounced in patients who received Mictalase®. Lower rate of positive urine culture favored Mictalase® group 15-days postoperatively.

Trial registration

The clinical trial has been registered on ClinicalTrials.gov on November 23rd, 2021—Registration number NCT05130918.
A comparison of three organisational levels in one health care region in Sweden implementing person-centred care: coupled, decoupled or recoupled in a complex organisation
Authors: Tistad Malin , Wallin Lars , Carlström Eric
Published: February 2022

Background

Establishing more substantial patient involvement in the health care has become fundamental to Western health care services. Person-centred care (PCC) has been developed as a way of working that involve the patients and family members. However, the implementation of PCC in clinical practice has proven to be challenging. The aim of this study was to explore the congruence of managers’ perceptions and understanding of various aspects of PCC across three organisational levels in one health care region in Sweden in terms of coupling, decoupling and recoupling.

Methods

A policy on increased patient participation in health care was adopted in one health care region in Sweden. This policy was embodied in the form of PCC and a support strategy for the implementation was put in place. Participants representing three organisational levels (senders: politicians, n = 3; messengers: senior management, n = 7; and receivers: middle- and frontline managers, n = 13) were interviewed and documents collected. A deductive qualitative content analysis was performed and findings from the three organisational levels compared.

Results

Descriptions of PCC at all the three organisational levels included health care provided in partnership between provider and patient. However, messengers and receivers also included aspects of how work was organised as part of the concept. Representatives at all levels expected high-quality care while reducing health care costs as an outcome, however, messengers and receivers also anticipated improvements in the work environment and reduced staff turnover. Strategies to support implementation included continuation and enhancement of existing routines that were considered person-centred and development of new ones. A need to make PCC less ‘fuzzy’ and ambiguous and instead communicate a more tangible care process was described. Representatives among messengers and receivers also suggested that no actions were needed because the practice was already considered person-centred.

Conclusion

The findings indicated that congruence between organisational levels existed in some aspects, suggesting coupling between policy and practice. However, also incongruences were identified that might be due to the fuzziness of definitions and the application of PCC in practice, and the difficulty in assessing the level of patient-centredness in clinical practice.
Outpatient visit trends for internal medicine ambulatory care sensitive conditions after the COVID-19 pandemic: a time-series analysis
Authors: Pendrith Ciara , Nayyar Dhruv , Chu Cherry , O’Brien Tara , Lyons Owen D. , Agarwal Payal , Martin Danielle , Bhatia R. Sacha , Mukerji Geetha
Published: February 2022

Background

The COVID-19 pandemic led to a dramatic shift in the delivery of outpatient medicine with reduced in-person visits and a transition to predominantly virtual visits. We sought to understand trends in visit patterns for ambulatory care sensitive conditions (ACSCs) commonly seen in internal medicine clinics.

Methods

We included adult outpatients seen for an ACSC between March 15th, 2017 and March 14th, 2021 at a single-centre in Ontario, Canada. Monthly visits were assessed by visit type (new consultation, follow-up), diagnosis, and clinic. Time series analyses compared visit volumes pre- and post-pandemic. Proportion of virtual visits were compared before and during the pandemic. Patient and visit factors were compared between in-person and virtual visits.

Results

8274 patients with 34,021 visits were included. Monthly visits increased by 15% during the pandemic (p <  0.0001). New consultations decreased by 10% (p = 0.0053) but follow-up visits increased by 21% (p <  0.0001). Monthly heart failure visits increased by 43% (p <  0.0001) whereas atrial fibrillation visits decreased. Pre- pandemic, < 1% of visits were virtual compared to 82% during the pandemic (p <  0.0001). Less than half of heart failure visits were virtual whereas > 95% of diabetes visits were virtual.

Conclusions

We found a significant increase in overall visits to internal medicine clinics driven by increased volumes of follow-up visits, which more than offset decreased new consultations. There was variability in visit trends and uptake of virtual care by visit diagnosis, which may indicate challenges with delivery of virtual care for certain conditions.
Cost-effectiveness analysis of combined cognitive and vocational rehabilitation in patients with mild-to-moderate TBI: results from a randomized controlled trial
Authors: Howe Emilie Isager , Andelic Nada , Fure Silje C R , Røe Cecilie , Søberg Helene L , Hellstrøm Torgeir , Spjelkavik Øystein , Enehaug Heidi , Lu Juan , Ugelstad Helene , Løvstad Marianne , Aas Eline
Published: February 2022

Background

Traumatic brain injury (TBI) represents a financial burden to the healthcare system, patients, their families and society. Rehabilitation interventions with the potential for reducing costs associated with TBI are demanded. This study evaluated the cost-effectiveness of a randomized, controlled, parallel group trial that compared the effectiveness of a combined cognitive and vocational intervention to treatment as usual (TAU) on vocational outcomes.

Methods

One-hundred sixteen participants with mild-to-moderate TBI were recruited from an outpatient clinic at Oslo University Hospital, Norway. They were randomized to a cognitive rehabilitation intervention (Compensatory Cognitive Training, CCT) and Supported Employment (SE) or TAU in a 1:1 ratio. Costs of CCT-SE and TAU, healthcare services, informal care and productivity loss were assessed 3, 6 and 12 months after study inclusion. Cost-effectiveness was evaluated from the difference in number of days until return to pre-injury work levels between CCT-SE and TAU and quality-adjusted life years (QALYs) derived from the EQ-5D-5L across 12 months follow-up. Cost-utility was expressed in incremental cost-effectiveness ratio (ICER).

Results

The mean total costs of healthcare services was € 3,281 in the CCT-SE group and € 2,300 in TAU, informal care was € 2,761 in CCT-SE and € 3,591 in TAU, and productivity loss was € 30,738 in CCT-SE and € 33,401 in TAU. Costs related to productivity loss accounted for 84% of the total costs. From a healthcare perspective, the ICER was € 56 per day earlier back to work in the CCT-SE group. Given a threshold of € 27,500 per QALY gained, adjusting for baseline difference in EQ-5D-5L index values revealed a net monetary benefit (NMB) of € -561 (0.009*27,500–979) from the healthcare perspective, indicating higher incremental costs for the CCT-SE group. From the societal perspective, the NMB was € 1,566 (0.009*27,500-(-1,319)), indicating that the CCT-SE intervention was a cost-effective alternative to TAU.

Conclusions

Costs associated with productivity loss accounted for the majority of costs in both groups and were lower in the CCT-SE group. The CCT-SE intervention was a cost-effective alternative to TAU when considering the societal perspective, but not from a healthcare perspective.

Trial registration

ClinicalTrails.gov NCT03092713.
The complexities, coordination, culture and capacities that characterise the delivery of oncology services in the common areas of ambulatory settings
Authors: Nic Giolla Easpaig Bróna , Tran Yvonne , Winata Teresa , Lamprell Klay , Fajardo Pulido Diana , Arnolda Gaston , Delaney Geoff P. , Liauw Winston , Smith Kylie , Avery Sandra , Rigg Kim , Westbrook Johanna , Olver Ian , Currow David , Karnon Jonathan , Ward Robyn L. , Braithwaite Jeffrey
Published: February 2022

Background

Relatively little is understood about real-world provision of oncology care in ambulatory outpatient clinics (OPCs). This study aimed to: 1) develop an understanding of behaviours and practices inherent in the delivery of cancer services in OPC common areas by characterising the organisation and implementation of this care; and 2) identify barriers to, and facilitators of, the delivery of this care in OPC common areas.

Methods

A purpose-designed ethnographic study was employed in four public hospital OPCs. Informal field scoping activities were followed by in-situ observations, key informant interviews and document review. A view of OPCs as complex adaptive systems was used as a scaffold for the data collection and interpretation, with the intent of understanding ‘work as done’. Data were analysed using an adapted “Qualitative Rapid Appraisal, Rigorous Analysis” approach.

Results

Field observations were conducted over 135 h, interviews over 6.5 h and documents were reviewed. Analysis found six themes. Staff working in OPCs see themselves as part of small local teams and as part of a broader multidisciplinary care team. Professional role boundaries could be unclear in practice, as duties expanded to meet demand or to stop patients “falling through the cracks.” Formal care processes in OPCs were supported by relationships, social capital and informal, but invaluable, institutional expertise. Features of the clinic layout, such as the proximity of departments, affected professional interactions. Staff were aware of inter- and intra-service communication difficulties and employed strategies to minimise negative impacts on patients. We found that complexity, coordination, culture and capacity underpin the themes that characterise this care provision.

Conclusions

The study advances understanding of how multidisciplinary care is delivered in ambulatory settings and the factors which promote or inhibit effective care practice. Time pressures, communication challenges and competing priorities can pose barriers to care delivery. OPC care is facilitated by: self-organisation of participants; professional acumen; institutional knowledge; social ties and relationships between and within professional groups; and commitment to patient-centred care. An understanding of the realities of ‘work-as-done’ may help OPCs to sustain high-quality care in the face of escalating service demand.
Health care providers’ understanding of self-management support for people with chronic low back pain in Ethiopia: an interpretive description
Authors: Chala Mulugeta Bayisa , Miller Jordan , Ghahari Setareh , Wondie Yemataw , Abebe Abey , Donnelly Catherine
Published: February 2022

Background

Healthcare providers play a key role in supporting people with chronic low back pain to self-manage their condition. The study aimed at exploring how health care providers understand and conceptualize self-management and how they provide self-management support for people with chronic low back pain in Ethiopia.

Methods

Health care providers who have supported people with low back pain, including medical doctors and physiotherapists, were approached and recruited from three hospitals in Ethiopia. This study employed an interpretive descriptive approach using semi-structured interviews.

Findings

Twenty-four participants (7 women; 17 men) with a median age of 28 (range 24 to 42) years and a median of 9.5 years (range 1 to 11 years) of helping people with chronic low back pain were interviewed. Seven major themes related to health care providers’ understanding of self-management support for people with chronic low back pain in Ethiopia emerged. The findings show that self-management was a new concept to many and health care providers’ had a fragmented understanding of self-management. They used or suggested several self-management support strategies to help people with CLBP self-manage their condition without necessarily focusing on enhancing their self-efficacy skills. The participants also discussed several challenges to facilitate self-management support for people with chronic low back pain. Despite the lack of training on the concept, the providers discussed the potential of providing self-management support for people with the condition.

Conclusions

Self-management was a new concept to health care providers. The providers lack the competencies to provide self-management support for people with chronic low back pain. There is a need to enhance the health care providers’ self-management support competencies through training.
Lovastatin production by an oleaginous fungus, Aspergillus terreus KPR12 using sago processing wastewater (SWW)
Authors: Srinivasan Naganandhini , Thangavelu Kiruthika , Uthandi Sivakumar
Published: February 2022

Background

Lovastatin is one of the first statins to be extensively used for its cholesterol-lowering ability. It is commercially produced by fermentation. Species belonging to the genusAspergillusare well-studied fungi that have been widely used for lovastatin production. In the present study, we produced lovastatin from sago processing wastewater (SWW) under submerged fermentation using oleaginous fungal strains,A. terreusKPR12 andA. caespitosusASEF14.

Results

The intra- and extracellular concentrations of lovastatin produced byA. terreusKPR12 andA. caespitosusASEF14 were lactonized. BecauseA. caespitosusASEF14 produced a negligible amount of lovastatin, further kinetics of lovastatin production in SWW was studied using the KPR12 strain for 9 days. Lovastatin concentrations in the intra- and extracellular fractions of theA. terreusKPR12 cultured in a synthetic medium (SM) were 117.93 and 883.28 mg L–1, respectively. However, these concentrations in SWW were 142.23 and 429.98 mg L–1, respectively. The yeast growth inhibition bioassay confirmed the antifungal property of fungal extracts.A. terreusKPR12 showed a higher inhibition zone of 14 mm than the ASEF14 strain. The two-way analysis of variance (ANOVA;p < 0.01) showed significant differences in the localization pattern, fungal strains, growth medium, and their respective interactions. The lovastatin yield coefficient values were 0.153 g g–1on biomass (YLOV/X) and 0.043 g g–1on the substrate, starch (YLOV/S). The pollutant level of treated SWW exhibited a reduction in total solids (TS, 59%), total dissolved solids (TDS, 68%), biological oxygen demand (BOD, 79.5%), chemical oxygen demand (COD, 57.1%), phosphate (88%), cyanide (65.4%), and void of nutrients such as nitrate (100%), and ammonia (100%).

Conclusion

The starch-rich wastewater serves as a suitable medium forA. terreusKPR12 for the production of lovastatin. It simultaneously decontaminates the sago processing wastewater, enabling its reuse for irrigation/recreation.

Graphical Abstract
NORAD-sponged miR-378c alleviates malignant behaviors of stomach adenocarcinoma via targeting NRP1
Authors: Hu Yongjun , Luo Ming
Published: February 2022

Background

Stomach adenocarcinoma (STAD) is the most common type of gastric cancer (GC), with a high recurrence rate and poor prognosis, but the potential indicators for STAD are insufficient.

Methods

Herein, we found that MicroRNA-378c (miR-378c) was lowly expressed in STAD, and the low expression of miR-378c was highly correlated with poor overall survival (OS), T stage, Reflux history, DSS events and PFI events of STAD patients.

Results

In addition, univariate analysis displayed that miR-378c was significantly associated with OS (Hazard ratio 0.735; 95% CI, 0.542–0.995; P = 0.046). Furthermore, it was validated that miR-378c inhibition accelerated STAD cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), while they were suppressed by miR-378c overexpression. Mechanistically, Neuropilin 1 (NRP1) was confirmed as the target of miR-378c, and Lnc-NORAD was identified as its sponger. More importantly, NORAD-mediated miR-378c inhibited malignant behaviors of STAD both in vitro and in vivo.

Conclusions

Collectively, these results suggest miR-378c as a promising indicator for the treatment of STAD.
A pan-cancer analysis of molecular characteristics and oncogenic role of gasdermins
Authors: Mu Mingchao , Yu Qiaoling , Zhang Qin , Guo Jing , Wang Xingjie , Sun Xuejun , Yu Junhui
Published: February 2022

Background

The gasdermins (GSDMs) family is proposed to be pore-forming effector proteins that cause cell membrane permeabilization and pyroptosis. Despite our increasing knowledge of GSDMD, GSDME and GSDMB, the biological functions and the regulation of GSDM expression and activation remain elusive for most GSDMs. In this study, we analyzed the molecular characteristics and oncogenic role of GSDM family genes systematically.

Methods

TCGA, CCLE, cBioPortal, GEPIA, CellMiner and BioGRID databases were utilized in this study. Immunohistochemical analysis and a series of in vitro experiments were conducted.

Results

We found that, in cancer, GSDM genes and their expressions extensively changed, which were associated with patient survival. The expression of GSDMs was widely associated with cancer-related pathways, drug resistance, immune subtypes, tumor microenvironment and cancer cell stemness. However, an intra- and inter-cancer heterogeneity was discovered regarding the corresponding GSDM gene. We found that GSDMA and GSDMB regulated drug resistance to the opposite direction of GSDME. In colorectal cancer, GSDME might be a positive regulator in cell invasion and metastasis through cell migration and angiogenesis, while GSDMA, GSDMB and GSDMD might be a negatively regulator of cell migration.

Conclusions

GSDM family genes might play important roles in cancer other than pyroptosis. We suggest more efforts be made to investigate the GSDM family and each GSDM gene be studied as an entity in each type of cancer.
Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Thailand
Authors: Jongdeepaisal Monnaphat , Khonputsa Panarasri , Prasert Orathai , Maneenet Suphitsara , Pongsoipetch Kulchada , Jatapai Anchalee , Rotejanaprasert Chawarat , Sudathip Prayuth , Maude Richard J. , Pell Christopher
Published: February 2022

Background

Across the Greater Mekong Subregion, malaria remains a dangerous infectious disease, particularly for people who visit forested areas where residual transmission continues. Because vector control measures offer incomplete protection to forest goers, chemoprophylaxis has been suggested as a potential supplementary measure for malaria prevention and control. To implement prophylaxis effectively, additional information is needed to understand forest goers’ activities and their willingness to use malaria prevention measures, including prophylaxis, and how it could be delivered in communities. Drawing on in-depth interviews with forest goers and stakeholders, this article examines the potential acceptability and implementation challenges of malaria prophylaxis for forest goers in northeast Thailand.

Methods

In-depth interviews were conducted with forest goers (n = 11) and stakeholders (n = 16) including healthcare workers, community leaders, and policymakers. Interviews were audio-recorded, transcribed and coded using NVivo, employing an inductive and deductive approach, for thematic analysis.

Results

Forest goers were well aware of their (elevated) malaria risk and reported seeking care for malaria from local health care providers. Forest goers and community members have a close relationship with the forest but are not a homogenous group: their place and time-at-risk varied according to their activities and length of stay in the forest. Among stakeholders, the choice and cost of anti-malarial prophylactic regimen—its efficacy, length and complexity, number of tablets, potential side effects, and long-term impact on users—were key considerations for its feasibility. They also expressed concern about adherence to the preventive therapy and potential difficulty treating malaria patients with the same regimen. Prophylaxis was considered a low priority in areas with perceived accessible health system and approaching malaria elimination.

Conclusions

In the context of multi-drug resistance, there are several considerations for implementing malaria prophylaxis: the need to target forest goers who are at-risk with a clear period of exposure, to ensure continued use of vector control measures and adherence to prophylactic anti-malarials, and to adopt an evidence-based approach to determine an appropriate regimen. Beyond addressing current intervention challenges and managing malaria incidence in low-transmission setting, it is crucial to keep malaria services available and accessible at the village level especially in areas home to highly mobile populations.
Estimating the costs for implementing a maternity leave cash transfer program for women employed in the informal sector in Brazil and Ghana
Authors: Carroll Grace , Vilar-Compte Mireya , Teruel Graciela , Moncada Meztli , Aban-Tamayo David , Werneck Heitor , de Moraes Ricardo Montes , Pérez-Escamilla Rafael
Published: February 2022

Background

Maternity leave policies are designed to protect gender equality and the health of mothers in the workforce and their children. However, maternity leave schemes are often linked to jobs in the formal sector economy. In low- and middle-income countries a large share of women work in the informal sector, and are not eligible to such benefit. This is worrisome from a social justice and a policy perspective and suggests the need for intervening. Costing the implementation of potential interventions is needed for facilitating informed decisions by policy makers.

Methods

We developed and applied a costing methodology to assess the cost of a maternity leave cash transfer to be operated in the informal sector of the economy in Brazil and Ghana, two countries with very different employment structures and socioeconomic contexts. We conducted sensitivity analysis by modeling different numbers of weeks covered.

Results

In Brazil, the cost of the maternity cash transfer would be between 0.004% and 0.02% of the GDP, while in Ghana it would range between 0.076% and 0.28% of the GDP. The relative cost of rolling out a maternity intervention in Brazil is between 2.2 to 3.2 times the cost in Ghana depending on the benchmark used to assess the welfare measure. The differences in costs between countries was related to differences in labor market structure as well as demographic characteristics.

Conclusions

Findings show how a standard methodology that relies on routinely available information is feasible and could assist policymakers in estimating the costs of supporting a maternity cash transfer for women employed in the informal sector, such intervention is expected to contribute to social justice, gender equity, and health trajectories.
Facklamia hominis pyelonephritis in a pediatric patient: first case report and review of the literature
Authors: Pérez-Cavazos Samantha , Cisneros-Saldaña Daniela , Espinosa-Villaseñor Fernando , Castillo-Bejarano José Iván , Vaquera-Aparicio Denisse Natalie , Sánchez-Alanís Hugo , Mascareñas-De los Santos Abiel
Published: February 2022

Background

Pyelonephritis is one of the most serious bacterial illnesses during childhood. Gram-negative organisms account for up to 90% of the cases. Gram-positive bacteria are uncommon causes of urinary tract infections, and only a few cases caused by Facklamia hominis have been reported in the literature.

Case presentation

A five-year-old girl with tracheostomy and gastrostomy and past medical history of congenital lymphangioma presented with a two-week history of with intermittent fever, frequent urination, and vesical tenesmus. Diagnosis of pyelonephritis was made. Urine culture reported colonies with alpha-hemolysis in blood agar at 48-h of incubation and Facklamia hominis was identified by MALDI-TOF. The patient was successfully treated with gentamicin.

Conclusions

This is the first reported case of pyelonephritis by Facklamia hominis in a child, and the second involving infection in a pediatric patient. Although this pathogen is uncommon, current treatment of F. hominis is a challenge for physicians. This case illustrates the requirement to standardize identification and treatment of care to avoid treatment failure and antimicrobial resistance.
Extracellular microparticles derived from hepatic progenitor cells deliver a death signal to hepatoma-initiating cells
Authors: Hou Xiaojuan , Liu Wenting , Yang Xue , Shao Changchun , Gao Lu , Zhang Li , Wei Lixin
Published: February 2022

The malignant transformation of normal resident hepatic stem/progenitor cells has a critical role in hepatocarcinogenesis and the recurrence of hepatocellular carcinoma (HCC). We defined such hepatic progenitor cells as hepatoma-initiating cells. An efficient strategy is required to target and kill the hepatoma-initiating cells. We isolated extracellular microparticles (MPs) derived from apoptotic hepatic progenitor cells (HPCs) and tested their ability to inhibit hepatocarcinogenesis. Extracellular MPs were isolated from HPCs, hepatocytes and liver tumor cells. Their effects on tumor growth were investigated in rat primary HCC models, in which hepatocarcinogenesis is induced by diethylnitrosamine (DEN). The extracellular MPs derived from apoptotic HPCs, apoptotic hepatocytes and apoptotic liver tumor cells were similar in morphology, diameter and zeta potential. However, they had different antitumor effects. In DEN-exposed rats, only the MPs derived from apoptotic HPCs effectively inhibit hepatocarcinogenesis. In vitro and in vivo analyses confirmed that HPCs preferentially take up MPs derived from apoptotic HPCs compared to MPs from other liver cell types. Proteomic analysis of MPs from apoptotic HPCs showed enrichment of proteins involved in cell death pathways. Thus, HPC-derived MPs contain a death signal to induce the killing of hepatoma-initiating cells. Our findings provide evidence that a death signal encapsulated in HPC-derived extracellular microparticles can efficiently clear hepatoma-initiating cells and prevent hepatocarcinogenesis.

Graphical Abstract
Infrapatellar fat pad adipose-derived stem cells co-cultured with articular chondrocytes from osteoarthritis patients exhibit increased chondrogenic gene expression
Authors: Mak Christopher C. H. , To Kendrick , Fekir Karim , Brooks Roger A. , Khan Wasim S.
Published: February 2022

Aim

The variable results in clinical trials of adipose tissue-derived stem cells (ASCs) for chondral defects may be due to the different ex vivo culture conditions of the ASCs which are implanted to treat the lesions. We sought to determine the optimal in vitro chondrocyte co-culture condition that promotes infrapatellar fat pad-derived (IFPD) ASC chondrogenic gene expression in a novel co-culture combination.

Methods

In our study, we utilized an in vitro autologous co-culture of IFPD ASCs and articular chondrocytes derived from Kellgren–Lawrence Grade III/IV osteoarthritic human knee joints at ASC-to-chondrocyte seeding log ratios of 1:1, 10:1, and 100:1. Gene expression following in vitro co-culture was quantified by RT-qPCR with a panel comprising COL1A1, COL2A1, COL10A1, L-SOX5, SOX6, SOX9, ACAN, HSPG2, and COMP for chondrogenic gene expression.

Results

The chondrogenic gene expression profiles from co-cultures were greater than would be expected from an expression profile modeled from chondrocyte and ASC-only monocultures. Additionally, chondrogenic gene expression decreased with increasing ASC-to-chondrocyte seeding ratios.

Conclusions

These findings provide insight into the mechanisms underlying clinical ASC therapies and signifies that IFPD ASCs pre-conditioned by chondrocyte co-culture may have improved chondrogenic potential for cartilage repair. This model can help further understand IFPD ASCs in chondral and osteochondral repair and the chondrogenic pathways involved.
The POR rs10954732 polymorphism decreases susceptibility to hepatocellular carcinoma and hepsin as a prognostic biomarker correlated with immune infiltration based on proteomics
Authors: Fang Yan , Yang Hongming , Hu Guiming , Lu Jiakun , Zhou Jun , Gao Na , Gu Yuhan , Zhang Cunzhen , Qiu Jinhuan , Guo Yuanyuan , Zhang Yunfei , Wen Qiang , Qiao Hailing
Published: February 2022

The effect of the cytochrome P450 oxidoreductase (POR) rs10954732 (G > A) polymorphism on hepatocellular carcinoma (HCC) susceptibility is unknown. Here we found that A allele carriers showed a 69% decrease in susceptibility to HCC with overall survival (OS) prolonged to 199%, accompanied by lower activity for cytochrome P450 2E1. A total of 222 differentially expressed proteins were mainly enriched in neutrophil and T cell activation and involved in the immune and inflammatory responses, constituting the altered immune tumor microenvironment related with A allele by proteomics analysis. Hepsin (HPN) showed significant down-regulation in HCC and up-regulation in A allele carriers. A lower HPN level was associated with increased susceptibility to HCC and a worse prognosis. Moreover, HPN is a potential independent prognostic biomarker for HCC and is strongly associated with clinicopathological features, tumor-infiltrating status of immune cells both in our discovery cohort and database surveys. Our findings provide a new potential mechanism by which HPN may play an important role in the susceptibility of rs10954732 A allele carriers to HCC and their prognosis through tumor immune infiltration, thus offering potential insights for future studies on tumor immunotherapy.
Adiponectin suppresses tumor growth of nasopharyngeal carcinoma through activating AMPK signaling pathway
Authors: Zhang Zongmeng , Du Jinlin , Shi Hui , Wang Shuai , Yan Yunjing , Xu Qihua , Zhou Sujin , Zhao Zhenggang , Mu Yunping , Qian Chaonan , Zhao Allan Zijian , Cao Sumei , Li Fanghong
Published: February 2022

Background

Adiponectin is an adipocyte-secreted cytokine that enhances insulin sensitivity and attenuates inflammation. Although circulating adiponectin level is often inversely associated with several malignancies, its role in the development of nasopharyngeal carcinoma (NPC) remains unclear. Here, we investigated the clinical association between circulating adiponectin level and NPC, and examined the impact of adiponectin, as well as the underlying mechanisms, on NPC growth both in vitro and in vivo.

Methods

The association between circulating adiponectin level and the risk of developing NPC was assessed in two different cohorts, including a hospital-based case–control study with 152 cases and 132 controls, and a nested case–control study with 71 cases and 142 controls within a community-based NPC screening cohort. Tumor xenograft model, cell proliferation and cycle assays were applied to confirm the effects of adiponectin on NPC growth in cultured cells and in xenograft models. We also investigated the underlying signaling mechanisms with various specific pharmacological inhibitors and biochemistry analysis.

Results

High adiponectin levels were associated with a monotonic decreased trend of NPC risk among males in both the hospital-based case–control study and a nested case–control study. In vitro, recombinant human full-length adiponectin significantly inhibited NPC cell growth and arrested cell cycle, which were dependent on AMPK signaling pathway. The growth of xenograft of NPC tumor was sharply accelerated in the nude mice carrying genetic adiponectin deficiency. An adiponectin receptor agonist, AdipoRon, displayed strong anti-tumor activity in human xenograft models.

Conclusions

These findings demonstrated for the first time that circulating adiponectin is not only inversely associated with NPC, but also controls the development of NPC via AMPK signaling pathway. Stimulation of adiponectin function may become a novel therapeutic modality for NPC.
Ligand-activated PPARδ expression promotes hepatocellular carcinoma progression by regulating the PI3K-AKT signaling pathway
Authors: Han Wei , Wang Nan , Kong Rui , Bao Wen , Lu Jie
Published: February 2022

Background

Peroxisome proliferator-activated receptor-beta/delta (PPARδ) was considered as the key regulator involved in the evolution of various tumors. Given that PPARδ potential role in hepatocellular carcinoma (HCC) is still obscure, we comprehensively assessed its expression pattern, prognosis, functions and correlation with tumor microenvironment in HCC using public database data and in vitro studies.

Methods

Transcriptional data and clinical data in the TCGA and GEO database were analyzed in R software. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry were used to detect the expression level of related RNA and proteins. The malignant biological characteristics were explored by cell counting Kit-8 (CCK8), 5-Ethynyl-2ʹ-deoxyuridine (EdU) assay and wound healing assay.

Results

Our results illustrated that PPARδ expression was significantly higher in HCC tissues and HCC cell lines. Elevated expression of PPARδ suggested poor clinical staging and prognosis in HCC. Ligand-activated PPARδ expression promoted the proliferation and invasion of HCC cells via PDK1/AKT/GSK3β signaling pathway. The expression of PPARδ was closely related to the HCC tumor microenvironment.

Conclusions

PPARδ plays an important part in HCC progression, penetrating investigation of the related regulatory mechanism may shed light upon further biological and pharmacological value.
Juglans regia L. extract promotes osteogenesis of human bone marrow mesenchymal stem cells through BMP2/Smad/Runx2 and Wnt/β-catenin pathways
Authors: Pang Xianlun , Zhong Zhendong , Jiang Feng , Yang Jian , Nie Hai
Published: February 2022

Background

The present study investigates the effects of Juglans regia L. (walnut, JRL) leaves extract on osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs).

Methods

hBMSCs were incubated with different concentrations of JRL extract (10, 20, 40, or 80 μM). Cell proliferation was evaluated by Cell Counting Kit-8 assay (CCK-8) assay. ALP activity and Alizarin Red staining were used to assess the osteogenesis of BMSCs. Western blot was performed to measure the levels of proteins.

Results

Our results showed all concentrations of JRL extract had no significant effect on cell proliferation. JRL extract concentration-dependently promoted osteoblastic differentiation and cell autophagy of hBMSCs, characterized by the increased expression of pro-osteogenic markers alkaline phosphatase (ALP), osteocalcin (BGLAP), osterin, and osteoprotegerin (OPG) and autophagy marker proteins (LC3II, Beclin-1, and p62). Furthermore, JRL extract stimulated the activation BMP2/Smad/Runx2 and Wnt/β-catenin signaling pathways in hBMSCs, which play key roles in osteogenesis differentiation. Meanwhile, BMP inhibitor (Noggin) and Wnt antagonist Dickkopf-1 (DKK1) both reversed the increases of BGLAP, osterin, and OPG expression induced by JRL extract.

Conclusions

Our findings indicate that JRL extract regulated osteogenic differentiation and cell autophagy of hBMSCs through the BMP2/Smad/Runx2 and Wnt/β-catenin pathways.
Verification of a cryptic t(Y;15) translocation in a male with an apparent 45,X karyotype
Authors: Qin Shengfang , Wang Xueyan , Wang Jin , Zhang Zhuo , Chen Ximin , Yin Yan , Ye Mengling , Li-Ling Jesse
Published: February 2022

Background

A rare disease is that an individual with a non-chimeric karyotype of 45,X develops into a male. We explored the genetic aetiology of an infertile male with an apparent 45,X karyotype, which was subsequently verified as cryptic translocation between chromosomes Y and 15.

Methods

DNA was extracted from the patient's peripheral blood. A range of genetic testing was performed, including conventional chromosomal karyotyping, short tandem repeat (STR) analysis for azoospermia factor (AZF) region, fluorescence in situ hybridization (FISH) with specific probes groups of DXZ1/DYZ3, DYZ3/D15Z1/PML and SRY/D15Z1/PML, and chromosomal microarray analysis (CMA) for genomic copy number variations (CNVs).

Results

The patient was found to have an apparent 45,X karyotype. STR analysis showed that he possessed a short arm of the Y chromosome, including the SRY gene; however, he was missing the long arm of the Y chromosome, including AZFa + b + c and Yqter. A FISH assay of DXZ1 and DYZ3 probes showed a green signal of the X centromere and a red of the Y centromeric signal on a D-group-sized chromosome. By FISH assaying with D15Z1 and DYZ3 probes, chromosomes 15 and Y centromeric signals appeared closely on a single chromosome, as the PML control probe ascertained. A further FISH assay with D15Z1 and SRY probes revealed a signal of the SRY gene at the end of one arm of chromosome 15. The result of the CMA indicated a deletion with an approximate size of 45.31 Mb spanning from Yq11 to Yter.

Conclusion

Our study enriched the karyotype-phenotype correlation of Y and 15 chromosomes translocation. It strengthened the critical roles of molecular genetic techniques in identifying the chromosomal breakpoints and regions involved. Genetic aetiology can guide early intervention in childhood and assisted reproduction in adulthood.
PredictPTB: an interpretable preterm birth prediction model using attention-based recurrent neural networks
Authors: AlSaad Rawan , Malluhi Qutaibah , Boughorbel Sabri
Published: February 2022

Background

Early identification of pregnant women at risk for preterm birth (PTB), a major cause of infant mortality and morbidity, has a significant potential to improve prenatal care. However, we lack effective predictive models which can accurately forecast PTB and complement these predictions with appropriate interpretations for clinicians. In this work, we introduce a clinical prediction model (PredictPTB) which combines variables (medical codes) readily accessible through electronic health record (EHR) to accurately predict the risk of preterm birth at 1, 3, 6, and 9 months prior to delivery.

Methods

The architecture of PredictPTB employs recurrent neural networks (RNNs) to model the longitudinal patient’s EHR visits and exploits a single code-level attention mechanism to improve the predictive performance, while providing temporal code-level and visit-level explanations for the prediction results. We compare the performance of different combinations of prediction time-points, data modalities, and data windows. We also present a case-study of our model’s interpretability illustrating how clinicians can gain some transparency into the predictions.

Results

Leveraging a large cohort of 222,436 deliveries, comprising a total of 27,100 unique clinical concepts, our model was able to predict preterm birth with an ROC-AUC of 0.82, 0.79, 0.78, and PR-AUC of 0.40, 0.31, 0.24, at 1, 3, and 6 months prior to delivery, respectively. Results also confirm that observational data modalities (such as diagnoses) are more predictive for preterm birth than interventional data modalities (e.g., medications and procedures).

Conclusions

Our results demonstrate that PredictPTB can be utilized to achieve accurate and scalable predictions for preterm birth, complemented by explanations that directly highlight evidence in the patient’s EHR timeline.
Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity
Authors: Archilla-Ortega Adrià , Domuro Carla , Martin-Liberal Juan , Muñoz Purificación
Published: February 2022

Immunotherapy has emerged as a promising strategy for boosting antitumoral immunity. Blockade of immune checkpoints (ICs), which regulate the activity of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells has proven clinical benefits. Antibodies targeting CTLA-4, PD-1, and PD-L1 are IC-blockade drugs approved for the treatment of various solid and hematological malignancies. However, a large subset of patients does not respond to current anti-IC immunotherapy. An integrative understanding of tumor-immune infiltrate, and IC expression and function in immune cell populations is fundamental to the design of effective therapies. The simultaneous blockade of newly identified ICs, as well as of previously described ICs, could improve antitumor response. We review the potential for novel combinatory blockade strategies as antitumoral therapy, and their effects on immune cells expressing the targeted ICs. Preclinical evidence and clinical trials involving the blockade of the various ICs are reported. We finally discuss the rationale of IC co-blockade strategy with respect to its downstream signaling in order to improve effective antitumoral immunity and prevent an increased risk of immune-related adverse events (irAEs).
Core self-evaluation, mental health and mobile phone dependence in Chinese high school students: why should we care
Authors: Li Yun , Wang Zhibin , You Weiquan , Liu Xiuqin
Published: February 2022

Background

Mobile phone dependence is a common problem in the population of high school students. We aimed to evaluate the core self-evaluation, mental health and mobile phone dependence in Chinese high school students, to provide reliable evidence to the support of high school students.

Methods

We conducted a survey of high school students in Xiamen, China. The self-assessment questionnaire on mobile phone use dependence among teenagers (SQAPMPU), Mental Health Scale for Middle School Students (MSSMHS) and Core self-evaluation scale were used to evaluate the mobile phone dependence, mental health and core self-evaluation. t-tests, Pearson correlation and multiple linear stepwise regression analyses were conducted to analyze the potential relationships.

Results

A total of 1692 students were enrolled. The total score of mobile phone dependence of students in grades 10–12 was higher than that of students in grades 7–9. A total of 329 students in grades 7–9 and 371 students in grades 10–12 had abnormal mental status. The detection rate of psychological abnormalities among students in grades 10–12 was higher than that of students in grades 10–12. Core self-evaluation had significantly negative correlation with various factors of mental health (P < 0.01). The worse the mental health, the higher the degree of mobile phone dependence, core self-evaluation played a mediating role between mental health and mobile phone dependence (8.03%).

Conclusions

Core self-evaluation is an important factor affecting the mental health of high school students and mobile phone dependence. Educators should strengthen core self-evaluation of high school students to improve the mental health and reduce the mobile phone dependence.
Improvement of participation rate in colorectal cancer (CRC) screening by training general practitioners in motivational interviewing (AmDepCCR)
Authors: Aujoulat Paul , Le Goff Delphine , Dany Antoine , Robaskiewick Michel , Nousbaum Jean Baptiste , Derrienic Jeremy , Cariou Mélanie , Guillou Morgane , Le Reste Jean Yves
Published: February 2022

Background

Colorectal cancer (CRC) is the second leading cause of cancer death in France (17,712 annual deaths). However, this cancer is preventable in the majority of cases by the early detection of adenomas. In France, the organized screening for CRC relies on general practitioners (GPs). The tests delivered by the GPs are carried out in 89% of cases. However, GPs do not systematically offer the test, because of time management and communication.

Methods

AmDepCCR is a cluster randomized trial. Patients are prospectively included by their GPs. The study is designed in 2 phases for the GPs: first, GPs who have never participated in motivational interviewing (MI) training will be recruited then randomly split in 2 groups. Secondly, a 6-day motivational interviewing training will be carried out for the intervention group. Then, patients will be included in both groups during a period of 1 year. The primary outcome will be the number of CRC screenings achieved in each group and its difference. The secondary outcome will be the reluctance to screening and the patient’s self-estimated life expectancy at 0, 6, 12, and 24 months using the Health Belief Model (HBM).

Discussion

This study will help to know if GPs motivational interviewing is useful to improve organized CRC screening. In addition, it may help to improve communication between patients and GPs. GPs will be able to improve their practice in other fields of application through motivational interviewing (other screenings, addictions…).

Trial registration

2019-A01776-51 NCT04492215.