bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between serum Sestrin2 and the risk of coronary heart disease in patients with type 2 diabetes mellitus
Authors: Tian Xue , Gao Yu , Zhong Min , Kong Mowei , Zhao Lihua , Feng Zengbin , Sun Qitian , He Jianqiu , Liu Xiaoyan
Published: June 2022

Background

Coronary heart disease (CHD) is one of the most common causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Oxidative stress is one of the important contributors to the pathogenesis of CHD. Sestrin2 is a stress-induced antioxidant protein that plays a important role in T2DM and CHD. However, the relationship between serum Sestrin2 levels and T2DM with CHD remains unclear.

Aim

This study aimed to investigate the relationship between serum Sestrin2 levels and CHD in patients with type 2 diabetes.

Methods

A total of 70 T2DM patients with CHD and 69 T2DM patients were enrolled in this study. Clinical features and metabolic indices were identified. Serum Sestrin2 was measured by ELISA.

Results

Serum Sestrin2 levels in T2DM-CHD groups were significantly lower compared with the T2DM group (11.17 (9.79, 13.14) ng/mL vs 9.46 (8.34, 10.91) ng/mL). Bivariate correlation analysis revealed that serum Sestrin2 levels were negatively correlated with age (r = − 0.256,P = 0.002), BMI (r = − 0.206,P = 0.015), FBG (r = − 0.261,P = 0.002) and Tyg index (r = − 0.207,P < 0.014). Binary logistic regression suggested that low serum Sestrin2 levels were related to the increased risk of T2DM-CHD (P < 0.05). In addition, the receiver operating characteristic analysis revealed that the area under the curve of Sestrin2 was 0.724 (95% CI 0.641–0.808,P < 0.001) to predict T2DM-CHD patients (P < 0.001).

Conclusion

The Sestrin2 levels were highly associated with CHD in diabetes patients. Serum Sestrin2 may be involved in the occurrence and development of diabetic with CHD.
Healthcare professionals’ experiences and attitudes to care coordination across health sectors: an interview study
Authors: Persson Maiken Hjuler , Søndergaard Jens , Mogensen Christian Backer , Skjøt-Arkil Helene , Andersen Pernille Tanggaard
Published: June 2022

Background

The number of older people is increasing, resulting in more people endure chronic diseases, multimorbidities and complex care needs. Insufficient care coordination across healthcare sectors has negative consequences for health outcomes, costs and patient evaluation. Despite introducing initiatives to solve coordination challenges within healthcare, the need remains for more consistent solutions. In particular, improved care coordination would benefit older adults characterised by complex care needs, high use of healthcare resources and multiple care providers.

Aims and objectives

To identify and analyse healthcare professionals’ perspectives and approaches to care coordination across sectors when older people are acutely hospitalised.

Design

Qualitative interview study.

Methods

Semi-structured, individual interviews with 13 healthcare professionals across health sectors and professions were conducted. The strategy for the qualitative analysis was inspired by Kirsti Malterud and labelled ‘systematic text condensation’. This strategy is a descriptive and explorative method for thematic cross-case analysis of qualitative data.

Results

Four themes/categories emerged from the analysis; “Organisational factors”, “Approaches to care”, “Communication and knowledge”, and “Relations”.

Conclusion

Different organisational cultures can discourage intersectoral care coordination. Approaches to care vary at all levels across health sectors and professions. Organisational, leadership and professional identity affect the working cultures and must be considered in the future recruitment and socialisation of healthcare staff. Our research suggests that combinations of healthcare standardisations and flexible, adaptive solutions are required to improve intersectoral care coordination.
Predicting the survival of kidney transplantation: design and evaluation of a smartphone-based application
Authors: Shahmoradi Leila , Borhani Alireza , Langarizadeh Mostafa , Pourmand Gholamreza , fard Ziba Aghsaei , Rezayi Sorayya
Published: June 2022

Background

Prediction of graft survival for Kidney Transplantation (KT) is considered a risky task due to the scarcity of donating organs and the use of health care resources. The present study aimed to design and evaluate a smartphone-based application to predict the survival of KT in patients with End-Stage Renal Disease (ESRD).

Method

Based on the initial review, a researcher-made questionnaire was developed to assess the information needs of the application through urologists and nephrologists. By using information obtained from the questionnaire, a checklist was prepared, and the information of 513 patients with kidney failure was collected from their records at Sina Urological Research Center. Then, three data mining algorithms were applied to them. The smartphone-based application for the prediction of kidney transplant survival was designed, and a standard usability assessment questionnaire was used to evaluate the designed application.

Results

Three information elements related to the required data in different sections of demographic information, sixteen information elements related to patient clinical information, and four critical capabilities were determined for the design of the smartphone-based application. C5.0 algorithm with the highest accuracy (87.21%) was modeled as the application inference engine. The application was developed based on the PhoneGap framework. According to the participants’ scores (urologists and nephrologists) regarding the usability evaluation of the application, it can be concluded that both groups participating in the study could use the program, and they rated the application at a "good" level.

Conclusion

Since the overall performance or usability of the smartphone-based app was evaluated at a reasonable level, it can be used with certainty to predict kidney transplant survival.
Comparing the effect of peritoneal dialysis cycler type on patient-reported satisfaction, support needs and treatments
Authors: El Shamy Osama , Atallah Sara , Sharma Shuchita , Uribarri Jaime
Published: June 2022

Background

Most patients on peritoneal dialysis (PD) in the United States choose automated PD via cyclers. Cyclers have evolved considerably over time with older versions (e.g. HomeChoice Pro) replaced by more sophisticated and technologically advanced versions (e.g. Amia). Understanding the effect that different cyclers and their features have on patient treatments and support needs is important. 

Methods

Single center study with retrospective and prospective arms. Retrospective arm: Patients > 18 years old, on Amia or HomeChoice Pro (HC) for ≥ 3 months between 8/1/17 and 1/31/18. Number of office/telephone encounters, PD-related emergency room visits/hospitalizations, PD training days, and dialysis adequacy (Kt/V) were recorded.

Prospective arm: Patients > 18 years old, on Amia or HC for ≥ 3 months between 9/1/19 and 2/29/20 were surveyed on their comfort, troubleshooting, satisfaction and reported assistance needed with their cyclers.

Results

Retrospective arm: 43 patients on AMIA and 27 patients on HC. Number of PD training days, Kt/Vs achieved, PD-related telephone/office encounters, and PD-related emergency room visits/hospitalizations were all similar.

Prospective Arm: 32 patients on AMIA and 6 patients on HC. Higher rate of patient comfort with AMIA, but similar overall patient satisfaction with both cyclers. No difference in terms of patient-reported troubleshooting issues requiring assistance.

Conclusions

Despite the difference in features provided between the 2 cyclers, patient overall satisfaction rates were high irrespective of the PD cycler. The HomeChoice Pro and AMIA cycler patients had a similar number of PD training days, PD-related telephone/office encounters, and PD-related emergency room visits/hospitalizations.

Trial registration

This study was approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board (IRB-17–02704).
Preoperative PDW levels predict pulmonary metastasis in patients with hepatocellular carcinoma
Authors: Huang Wen-juan , Wang Guang-yu , Liu Zeng-yao , Zhang Meng-lin , Wang Wen , Zhang Xin , Wang Rui-tao
Published: June 2022

Background

In hepatocellular carcinoma (HCC), pulmonary metastasis (PM) after hepatectomy is associated with poor clinical outcomes. The crucial phases of tumour cell proliferation, angiogenesis, and metastasis all entail platelet activation. In HCC, platelet distribution width (PDW) suggests platelet size changes and predicts a worse prognosis. The aim of this study was to assess the association between PDW and PMs in HCC patients receiving hepatectomy.

Material/methods

From January 2013 to December 2015, a cohort of patients who underwent hepatectomy for HCC at the Harbin Medical University Cancer Hospital in China were retrospectively evaluated. The relationship between PDW levels and clinical and demographic parameters was examined. To investigate the relationships between predicted factors and PM, a competing risk model was used. From January 2016 to December 2018, a validation cohort of 109 patients from the First Affiliated Hospital of Harbin Medical University was studied independently.

Results

In the primary cohort, 19 out of 214 patients had postoperative PMs. In HCC patients with PM, PDW levels were lower than in those without PM. There was a significant difference in the cumulative incidence of 2-year PM between the high-PDW and low-PDW groups after controlling for competing risk events (death prior to the development of PM) (p < 0.001). In addition, PDW was also found to be an independent predictor for PM in a multivariable competing risk analysis. The results were externally validated in another cohort.

Conclusions

In HCC, preoperative PDW is significantly associated with PM. PDW could be a biomarker for post-operative PM in HCC patients.
Case series: pachychoroid pigment epitheliopathy transformed to polypoidal choroidal vasculopathy after long-term follow-up
Authors: Tang Jiyang , Han Xinyao , Tang Ran , Li Mengyang , Wang Zongyi , Zhao Mingwei , Qu Jinfeng
Published: June 2022

Background

Pachychoroid pigment epitheliopathy (PPE), a retinal disorder that falls into the pachychoroid spectrum, is characterized by retinal pigment epithelium changes in pachychoroid eyes without existing or previous subretinal fluid or soft drusen. Previous reports have indicated that PPE may share some pathophysiologic component with other pachychoroid spectrum diseases and could transform into central serous chorioretinopathy (CSC) during follow-up. CSC transformation to PNV and PCV has also been reported, but PPE transformation to PCV has not been reported. 

Case presentation

Seven eyes of seven patients (four male three female, aged 62.7 ± 8.4 years) who presented with PPE at baseline transformed to PCV during follow-up. All study eyes had baseline contralateral eye diagnoses of PCV. All PPE eyes reported no symptoms at baseline and were followed up regularly for the treatment of their contralateral eyes. All PPE presented as pigment epithelium detachment (PED) at baseline. The mean central macular thickness (CMT) was 217.6 ± 14.6 µm, the mean subfoveal choroidal thickness (SFCT) was 354.9 ± 94.9 µm, and the mean sub-PPE choroidal thickness was 332.3 ± 84.6 µm. The mean PPE width and height were 1326.4 ± 791.4 µm and 58.7 ± 23.6 µm, respectively, at baseline. Disruption of the ellipsoid zone (EZ) was noted in 3 eyes, while choroidal vascular hyperpermeability (CVH) was noted in 5 eyes at baseline. The follow-up period was 75.0 ± 41.1 months, and the mean transformation time was 49.6 ± 24.8 months. All study eyes received no intervention before transformation.

Conclusions

PPE could transform to PCV after a long follow-up period. Regular follow-ups for a long time should be recommended for patients with PPE.
Posterior scleral reinforcement for the treatment of myopic traction maculopathy
Authors: He Qing , Wang Xiu , Shi Qianhui , Xie Caiyuan , Xue Anquan , Wei Ruihua
Published: June 2022

Background

This study aimed to investigate the clinical effectiveness of posterior scleral reinforcement(PSR) for the treatment of myopic traction maculopathy (MTM).

Methods

This was a prospective study of 32 eyes from 20 patients with MTM treated with PSR using genipin-cross-linked donor sclera. The length of the scleral strip used for the surgery was designed to be 1.5-times the axial length of the eye, whereas its width was 0.4-times the axial length of the eye. The optical coherence tomography images, spherical equivalent of refractive error, axial length, best corrected visual acuity, electroretinogram findings, and intraocular pressure of the patients were assessed postoperatively.

Results

The mean duration of follow-up was 17.80 ± 8.74 months. The differences between the spherical equivalent of refractive error, best corrected visual acuity, axial length, and electroretinogram findings recorded preoperatively and those measured postoperatively were statistically significant (p < 0.05). The final reduction in axial length was 1.64 ± 0.85 mm. At the end of the follow-up, optical coherence tomography showed essential foveal reattachment in 30 eyes (93.75%), partial reattachment in two eyes (6.25%), and closure of macular holes in seven eyes (77.78%). No retinal detachment, vitreous haemorrhage, or other serious complications occurred following the surgery.

Conclusions

Posterior scleral reinforcement with genipin-cross-linked sclera showed safe and effective outcomes for the treatment of MTM during a follow-up period of at least one year.

Trial registration

11\12\2018, ChiCTR1800020012.
Do interventions principally targeting excessive alcohol use in young people improve depression symptoms?: a systematic review and meta-analysis
Authors: Fredman Stein Kim , Allen Jennifer L. , Robinson Ross , Smith Cassandra , Sawyer Katherine , Taylor Gemma
Published: June 2022

Background

Excessive alcohol use is common in young people and is associated with a range of adverse consequences including an increased risk of depression. Alcohol interventions are known to be effective in young people, however it is not known if these interventions can also improve depression.

Objective

To investigate whether psychosocial interventions principally targeting excessive alcohol use in young people reduce depression symptoms compared to controls.

Design

We conducted a systematic review and meta-analysis of controlled intervention trials, that measured depression symptoms at follow-up. We used a generic inverse variance random effect meta-analysis to pool the standardised mean difference in change in depression symptoms from baseline to follow-up between intervention and control arms. We used I2 to measure heterogeneity, the Cochrane tool for randomised trials to assess risk of bias, and Egger’s tests to assess small study bias.

Data sources

APA PsycNET, PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Embase (including MEDLINE), and clinicaltrials.gov were searched for relevant studies published from inception to December 2020. Reference lists of studies were also searched, and authors contacted where articles presented insufficient data.

Study eligibility criteria

Intervention studies that primarily targeted existing excessive alcohol use in young people (aged 10 to 24) and assessed depression outcomes at baseline with a minimum of four-week follow-up.

Results

Five studies were included in the meta-analysis. Interventions targeting excessive alcohol use were associated with a reduction in depression symptoms from baseline to follow-up when compared to control, standardised mean difference = − 0.26, and 95% confidence interval [− 0.41, − 0.12], p < .001.

Conclusions

This study found evidence that interventions primarily targeting excessive alcohol use can reduce depression symptoms in young people. However, this finding should be taken with caution given concerns about risk of bias in all studies. More research is needed to examine whether these findings generalise beyond populations of undergraduate students primarily living in high income countries.

Trial registration

PROSPERO registration number: CRD42020177260.
Policy responses to the COVID-19 pandemic in the Manitoba grocery sector: a qualitative analysis of media, organizational communications, and key informant interviews
Authors: Riediger Natalie D. , Slater Joyce J. , Mann Kelsey , Pilli Bhanu , Derksen Hannah , Perchotte Chantal , Penner Avery L.
Published: June 2022

Objectives

The COVID-19 pandemic has impacted all aspects of the food system, including the retail grocery sector. We sought to (objective 1) document and (objective 2) analyze the policies implemented in the grocery sector during the first wave of the pandemic in Manitoba, Canada.

Methods

Our qualitative policy analysis draws from organizational communications (websites and social media) (n = 79), news media articles (n = 95), and key informant interviews with individuals (n = 8) working within the grocery sector in urban and rural, Manitoba. Media and communications were extracted between March 9-May 8, 2020 and interviews were conducted in July–August, 2020.

Results

Newly implemented policies due to the pandemic fell under four inter-related themes:Employee health and wellbeing,Safety measures,Operational measures, andCommunity support. Employee health and wellbeing included sub-themes of financial and social support, health recommendations and protocols, and new employee guidelines. Safety measures encompassed numerous policies pertaining to sanitation, personal protection, transmission prevention, physical distancing, and limiting access. Overall, new policies were discussed as effective in making grocery shopping as safe as possible given the situation.Compliance and enforcement,employee teamwork, andsupport for employeeswere key themes related to perceptions of policy success in a challenging and inequitable context. Nevertheless,government support and communicationwas needed as well to ensure safety within the grocery sector.

Conclusions

The grocery sector reacted to the pandemic with the swift implementation of policies to address food supply issues, prevent transmission of the virus, support their employees as essential workers, and better serve high-risk populations.
Risk factors for acute respiratory distress syndrome in sepsis patients: a retrospective study from a tertiary hospital in China
Authors: Shi Yuequan , Wang Liang , Yu Sihan , Ma Xiaochun , Li Xu
Published: June 2022

Background

Less is known about the risk factors for acute respiratory distress syndrome (ARDS) in sepsis patients diagnosed according to sepsis 3.0 criteria. Moreover, the risk factors for ARDS severity remain unclear.

Methods

We retrospectively collected the characteristics of sepsis patients from the intensive care unit of the First Affiliated Hospital of China Medical University from January 2017 to September 2018. Logistic regression was used in determining the risk factors.

Results

529 patients with sepsis were enrolled and 179 developed ARDS. The most common infection sites were acute abdominal infection (n = 304) and pneumonia (n = 117). Multivariate analysis showed that patients with pancreatitis with local infection (odds ratio [OR], 3.601; 95% confidence interval [CI], 1.429–9.073, P = 0.007), pneumonia (OR 3.486; 95% CI 1.890–6.430, P < 0.001), septic shock (OR 2.163; 95% CI 1.429–3.275, P < 0.001), a higher sequential organ failure assessment (SOFA) score (OR 1.241; 95% CI 1.155–1.333, P < 0.001) and non-pulmonary SOFA score (OR 2.849; 95% CI 2.113–3.841, P < 0.001) were independent risk factors for ARDS. Moreover, pneumonia is associated with increased severity of ARDS (OR 2.512; 95% CI 1.039–6.067, P = 0.041).

Conclusions

We determined five risk factors for ARDS in sepsis patients. Moreover, pneumonia is significantly associated with an increased severity of ARDS.
Implementing evidence into practice to improve chronic lung disease management in Indigenous Australians: the breathe easy, walk easy, lungs for life (BE WELL) project (protocol)
Authors: Meharg David P. , Jenkins Christine R. , Maguire Graeme P. , Jan Stephan , Shaw Tim , Dennis Sarah M. , McKeough Zoe , Lee Vanessa , Gwynne Kylie G. , McCowen Debbie , Rambaldini Boe , Alison Jennifer A.
Published: June 2022

Background

Strong evidence exists for the benefits of pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD), however the availability of culturally safe PR for Aboriginal and Torres Strait Islander (Indigenous) Peoples is limited. The study aims to determine whether PR can be implemented within Aboriginal Community Controlled Health Services (ACCHS) to improve outcomes for Indigenous people with COPD.

Methods

Multi-centre cohort study using participatory action research guided by the Knowledge-to-Action Framework. ACCHS supportive of enhancing services for chronic lung disease will be recruited. Aboriginal Health Workers (AHW) and the exercise physiologist (EP) or physiotherapist (PT) within these ACCHS will attend a workshop aimed at increasing knowledge and skills related to management of COPD and the provision of PR. Indigenous people with COPD will be invited to attend an 8-week, twice weekly, supervised PR program. Outcomes: AHW, EP/PT knowledge, skills and confidence in the assessment and management of COPD will be measured before and immediately after the BE WELL workshop and at 3, 6 and 12 months using a survey. PR participant measures will be exercise capacity (6-minute walk test (6MWT), health-related quality of life and health status at commencement and completion of an 8-week PR program. Secondary outcomes will include: number, length and cost of hospitalisations for a COPD exacerbation in 12-months prior and 12-months post PR; local contextual factors influencing implementation of PR; specific respiratory services provided by ACCHS to manage COPD prior to project commencement and at project completion. Repeated measures ANOVA will be used to evaluate changes in knowledge and confidence over time of AHWs and EP/PTs. Paired t-tests will be used to evaluate change in patient outcomes from pre- to post-PR. Number of hospital admissions in the 12 months before and after the PR will be compared using unpaired t-tests.

Discussion

Pulmonary rehabilitation is an essential component of best-practice management of COPD and is recommended in COPD guidelines. Indigenous peoples have limited access to culturally safe PR programs. This study will evaluate whether PR can be implemented within ACCHS and improve outcomes for Indigenous people with COPD.

Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001337369, Registered 2nd September 2017 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373585&isClinicalTrial=False
Impact of an electronic medical record-based automated screening program for critical congenital heart disease: Emirates Health Services, United Arab Emirates
Authors: Zarouni Sumaya Al , Mheiri Noor Majed Al , Blooshi Kalthoom Al , Serkal Yousif Al , Preman Neema , Naqvi Sadaf Ahsan , Khan Yasir
Published: June 2022

Background

Almost eight children per 1000 live births are expected to have a congenital heart defect globally. The seven most critical congenital heart conditions that cause severe compromise on the patient’s quality and duration of life are collectively referred to as the Critical Congenital Heart Diseases (CCHD). CCHD is a critical condition that requires prompt detection and intervention as a life-saving measure. Pulse oximetry is a non-invasive, highly specific, and moderately sensitive method that can be used for screening new-borns for CCHD. The Emirates Health Services (EHS), UAE, adopted a strategy of developing a stringent program for newborn screening of Critical Congenital Heart disease, which would help in the early diagnosis and treatment of CCHD patients. An automated EMR (Wareed) driven solution was introduced to enhance this program as part of the routine workflow for the nurse care providers.

Methods

Our study is a retrospective observational study that aims to understand: the prevalence of CCHD in our target population and to study the impact of an automated program on screening compliance and its implications for early diagnosis of CCHD.

Results

We found that an EMR-driven automated screening program was highly effective in achieving high compliance (98.9%). It created a (statistically significant) improvement in the disease identification for CCHD in live births at EHS facilities.

Conclusion

We conclude that implementing an automated protocol through the EMR can effectively improve new-born screening coverage. It reduces the days to CCHD diagnosis, which would improve health outcomes in neonates.
Impacts of racism on First Nations patients' emergency care: results of a thematic analysis of healthcare provider interviews in Alberta, Canada
Authors: McLane Patrick , Mackey Leslee , Holroyd Brian R. , Fitzpatrick Kayla , Healy Chyloe , Rittenbach Katherine , Plume Tessy Big , Bill Lea , Bird Anne , Healy Bonnie , Janvier Kristopher , Louis Eunice , Barnabe Cheryl
Published: June 2022

Background

First Nations people experience racism in society and in the healthcare system. This study aimed to document emergency care providers’ perspectives on care of First Nations patients. First Nations research partner organizations co-led all aspects of the research.

Methods

Sixteen semi-structured interviews were conducted with Alberta emergency department (ED) physicians and nurses between November 2019 and March 2020.

Results

ED providers reported that First Nations patients are exposed to disrespect through tone and body language, experience overt racism, and may be neglected or not taken seriously. They described impacts of racist stereotypes on patient care, and strategies they took as individuals to address patient barriers to care. Recognized barriers to care included communication, resources, access to primary care and the ED environment itself.

Conclusions

Results may inform the content of anti-racist and anti-colonial pedagogy that is contextually tailored to ED providers, and inform wider systems efforts to counter racism against First Nations members and settler colonialism within healthcare.
OnkoRiskNET: a multicenter, interdisciplinary, telemedicine-based model to improve care for patients with a genetic tumor risk syndrome
Authors: Tecklenburg Johanna , Vajen Beate , Morlot Susanne , Anders Petra , Memenga Paula , Link Elena , Baumann Eva , Wölffling Sarah , Schröck Evelin , Bergmann Anke Katharina , Schlegelberger Brigitte
Published: June 2022

Background

Genetic tumor risk syndromes are responsible for at least five to ten percent of the 4 million cases of cancer diagnosed in Europe every year. Currently, the care of oncological patients suffers from a lack of specialists in medical genetics and also a lack of access to genetic care in rural areas and structured care pathways between oncologists and medical geneticists. As a result, genetic tumor risk syndromes are underdiagnosed with potentially fatal consequences for patients and their families.

Methods

The OnkoRiskNET study is supported by a grant from the Federal Joint Committee of the Federal Republic of Germany. The study will include 2,000 oncological index patients from oncology practices in Lower Saxony and Saxony after the start of the study in July 2021. Randomization is carried out by means of a stepped wedge design at the level of the practices. Patients either go through routine care or the new form of care with structured cooperation between medical geneticists and oncologists, case management and the use of telemedical genetic counseling. Using a mixed-methods approach, the following parameters will be evaluated in the control and intervention group: (1) Conducted genetic counseling sessions by patients with suspected tumor risk syndrome and their first degree relatives; (2) Patient satisfaction and psychological distress after genetic counseling and testing; (3) Factors influencing the acceptance and experience of telemedical genetic counseling; (4) Satisfaction of oncologists and medical genetics with the structured pathway; (5) Cost efficiency of the new form of care.

Discussion

OnkoRiskNET aims to close the gap in care through the formation of a cooperation network between practicing oncologists and specialists in medical genetics and the use of telemedical genetic counseling, thereby, increasing the diagnostic rate in genetic tumor risk syndromes and serving as a model for future genetic care in Germany.

Trial registration

Trial was registered on 01.12.2021 in the German
Clinical Trial Register (https://trialsearch.who.int/) with the DRKS-ID: DRKS00026679. Title: Cooperation network for the provision of local
care for patients and families with a genetic tumour risk syndrome. Trial
acronym: OnkoRiskNET. Protocol version 1.1.
Effect size of rituximab on pulmonary function in the treatment of connective-tissue disease-related interstitial lung disease: a systematic review and meta-analysis
Authors: Zhao Yuanchen , Gao Yang , Petnak Tananchai , Cheungpasitporn Wisit , Thongprayoon Charat , Zhang Xing , Moua Teng
Published: June 2022

Background

Rituximab (RTX) has been previously reported as directed treatment in patients with connective-tissue disease-related interstitial lung diseases (CTD-ILD). A systematic assessment of treatment effect size on pulmonary function outcomes and related adverse effects in patients with CTD-ILD has not been previously reported.

Methods

We performed a systematic review and meta-analysis of published reports from PubMed, Embase, and Cochrane Libraries. Randomized and non-randomized controlled trials, case–control, cohort, and case series (with five or more cases) containing individual pulmonary function data and adverse effects were included. Study endpoints were pre- and post-treatment change in percent predicted forced vital capacity (FVC %) and diffusion capacity for carbon monoxide (DLCO%), along with reported drug-related adverse events.

Results

Twenty studies totaling 411 patients were identified with 14 included in the meta-analysis of pulmonary function and six in the descriptive review. Random effects meta-analysis of pre- and post-treatment pulmonary function findings demonstrated increases in FVC% (n = 296) (mean difference (MD) 4.57%, [95% CI 2.63–6.51]) and DLCO% (n = 246) (MD 5.0% [95% CI 2.71–7.29]) after RTX treatment. RTX treatment-related adverse effects were reported in 13.6% of the pooled cohort.

Conclusions

A systematic assessment of post-treatment effect size suggests a potential role for RTX in stabilizing or improving lung function in patients with CTD-ILD, with a modest but not insignificant adverse effect profile.
Soluble RAGE in COPD, with or without coexisting obstructive sleep apnoea
Authors: Marin-Oto Marta , Sanz-Rubio David , Santamaría-Martos Fernando , Benitez Ivan , Simon Ana L. , Forner Marta , Cubero Pablo , Gil Ana , Sanchez-de-laTorre Manuel , Barbe Ferran , Marin José M.
Published: June 2022

Background

Hypoxia can reduce the levels of soluble receptor for advanced glycation end-products (sRAGE), a new anti-inflammatory biomarker of COPD. We assessed sRAGE in patients with hypoxia-related diseases such as COPD, OSA and OSA-COPD overlap.

Methods

Plasma levels of sRAGE were measured in 317 subjects at baseline (57 heathy nonsmokers [HNS], 84 healthy smokers [HS], 79 OSA, 62 COPD and 35 OSA-COPD overlap patients) and in 294 subjects after one year of follow-up (50 HNS, 74 HS, 77 OSA, 60 COPD and 33 overlap).

Results

After adjusting for age, sex, smoking status and body mass index, sRAGE levels showed a reduction in OSA (− 12.5%, p = 0.005), COPD (− 14.8%, p < 0.001) and OSA-COPD overlap (− 12.3%, p = 0.02) compared with HNS. There were no differences when comparing sRAGE plasma levels between overlap patients and those with OSA or COPD alone. At follow-up, sRAGE levels did not change significantly in healthy subjects, COPD and OSA or OSA-COPD overlap nontreated with continuous positive airway pressure (CPAP). Moreover, in patients with OSA and OSA-COPD overlap who were treated with CPAP, sRAGE increased significantly.

Conclusions

The levels of sRAGE are reduced in COPD and OSA. Treatment with CPAP appears to improve sRAGE levels in patients with OSA who also had COPD.
PHB production from cellobiose with Saccharomyces cerevisiae
Authors: Ylinen Anna , de Ruijter Jorg C. , Jouhten Paula , Penttilä Merja
Published: June 2022

Replacement of petrochemical-based materials with microbially produced biodegradable alternatives calls for industrially attractive fermentation processes. Lignocellulosic materials offer non-edible alternatives for cultivated sugars, but require often use of expensive sugar releasing enzymes, such as β-glucosidases. These cellulose treatment costs could be reduced if microbial production hosts could use short cellodextrins such as cellobiose directly as their substrates. In this study, we demonstrate production of poly(hydroxybutyrate) (PHB) in yeast Saccharomyces cerevisiae using cellobiose as a sole carbon source. Yeast strains expressing PHB pathway genes from Cupriavidus necator and cellodextrin transporter gene CDT-1 from Neurospora crassa were complemented either with β-glucosidase gene GH1-1 from N. crassa or with cellobiose phosphorylase gene cbp from Ruminococcus flavefaciens. These cellobiose utilization routes either with Gh1-1 or Cbp enzymes differ in energetics and dynamics. However, both routes enabled higher PHB production per consumed sugar and higher PHB accumulation % of cell dry weight (CDW) than use of glucose as a carbon source. As expected, the strains with Gh1-1 consumed cellobiose faster than the strains with Cbp, both in flask and bioreactor batch cultures. In shake flasks, higher final PHB accumulation % of CDW was reached with Cbp route (10.0 ± 0.3%) than with Gh1-1 route (8.1 ± 0.2%). However, a higher PHB accumulation was achieved in better aerated and pH-controlled bioreactors, in comparison to shake flasks, and the relative performance of strains switched. In bioreactors, notable PHB accumulation levels per CDW of 13.4 ± 0.9% and 18.5 ± 3.9% were achieved with Cbp and Gh1-1 routes, respectively. The average molecular weights of accumulated PHB were similar using both routes; approximately 500 kDa and 450 kDa for strains expressing either cbp or GH1-1 genes, respectively. The formation of PHB with high molecular weights, combined with efficient cellobiose conversion, demonstrates a highly potential solution for improving attractiveness of sustainable polymer production using microbial cells.
The TetR-type regulator AtsR is involved in multidrug response in Corynebacterium glutamicum
Authors: Su Tao , Che Chengchuan , Han Jiyu , Zhao Yuying , Zhang Zihan , An Guangdi , Si Meiru , Chen Can
Published: June 2022

Background

The TetR (tetracycline repressor) family is one of the major transcription factor families that regulate expression of genes involved in bacterial antimicrobial resistance systems. NCgl0886 protein, designated as AtsR, is a member of the TetR family identified in Corynebacterium glutamicum, which is conserved in several species of the genera Corynebacterium, also including the well-known pathogen C. diphtheriae. AtsR is located at no far upstream of the identically oriented ncgl0884 gene, encoding a putative multidrug efflux pump protein, and in the same operon with ncgl0887, encoding a resistance, nodulation and cell division (RND) superfamily drug exporter. However, the role of AtsR is not clearly understood.

Results

Here we showed that dimeric AtsR directly repressed the expression of the ncgl0887-atsR operon, as well as indirectly controlled the ncgl0884 transcription. Antibiotics and toxic compounds induced the expression of ncgl0887-atsR operon. A perfect palindromic motif (5΄-TGCAA-N2-TTGCA-3΄; 12 bp) was identified in the upstream region of ncgl0887-atsR operon. Electrophoretic mobility shift assays (EMSAs) demonstrated specific binding of AtsR to this motif, and hydrogen peroxide (H2O2) blocked binding. H2O2 oxidized cysteine residues to form Cys123-Cys187 intermolecular disulfide bonds between two subunits in AtsR dimer, which altered its DNA-binding characteristics and caused its dissociation, thereby leading to derepression of the drug efflux protein. Deletion of ncgl0884 and ncgl0887 increased the susceptibilities of C. glutamicum for several toxic compounds, but overexpression of atsR decreased the drug tolerance of C. glutamicum.

Conclusions

Our study revealed that AtsR was a redox regulator that sensed oxidative stress via thiol modification. The results obtained here will contribute to our understanding of the drug response mechanism not only in C. glutamicum but also in the related bacteria C. diphtheriae.
Escherichia coli cell factories with altered chromosomal replication scenarios exhibit accelerated growth and rapid biomass production
Authors: Yang Hee Jin , Kim Kitae , Kwon Soon-Kyeong , Kim Jihyun F.
Published: June 2022

Background

Generally, bacteria have a circular genome with a single replication origin for each replicon, whereas archaea and eukaryotes can have multiple replication origins in a single chromosome. In Escherichia coli, bidirectional DNA replication is initiated at the origin of replication (oriC) and arrested by the 10 termination sites (terA–J).

Results

We constructed E. coli derivatives with additional or ectopic replication origins, which demonstrate the relationship between DNA replication and cell physiology. The cultures of E. coli derivatives with multiple replication origins contained an increased fraction of replicating chromosomes and the cells varied in size. Without the original oriC, E. coli derivatives with double ectopic replication origins manifested impaired growth irrespective of growth conditions and enhanced cell size, and exhibited excessive and asynchronous replication initiation. The generation time of an E. coli strain with three replication origins decreased in a minimal medium supplemented with glucose as the sole carbon source. As well as cell growth, the introduction of additional replication origins promoted increased biomass production.

Conclusions

Balanced cell growth and physiological stability of E. coli under rapid growth condition are affected by changes in the position and number of replication origins. Additionally, we show that, for the first time to our knowledge, the introduction of replication initiation sites to the chromosome promotes cell growth and increases protein production.
Polymalic acid for translational nanomedicine
Authors: Huang Xing , Xu Liusheng , Qian Hui , Wang Xinghuan , Tao Zhimin
Published: June 2022

With rich carboxyl groups in the side chain, biodegradable polymalic acid (PMLA) is an ideal delivery platform for multifunctional purposes, including imaging diagnosis and targeting therapy. This polymeric material can be obtained via chemical synthesis, or biological production where L-malic acids are polymerized in the presence of PMLA synthetase inside a variety of microorganisms. Fermentative methods have been employed to produce PMLAs from biological sources, and analytical assessments have been established to characterize this natural biopolymer. Further functionalized, PMLA serves as a versatile carrier of pharmaceutically active molecules at nano scale. In this review, we first delineate biosynthesis of PMLA in different microorganisms and compare with its chemical synthesis. We then introduce the biodegradation mechanism PMLA, its upscaled bioproduction together with characterization. After discussing advantages and disadvantages of PMLA as a suitable delivery carrier, and strategies used to functionalize PMLA for disease diagnosis and therapy, we finally summarize the current challenges in the biomedical applications of PMLA and envisage the future role of PMLA in clinical nanomedicine.

Graphical Abstract
Fast, streamlined fluorescence nanoscopy resolves rearrangements of SNARE and cargo proteins in platelets co-incubated with cancer cells
Authors: Bergstrand Jan , Miao Xinyan , Srambickal Chinmaya Venugopal , Auer Gert , Widengren Jerker
Published: June 2022

Background

Increasing evidence suggests that platelets play a central role in cancer progression, with altered storage and selective release from platelets of specific tumor-promoting proteins as a major mechanism. Fluorescence-based super-resolution microscopy (SRM) can resolve nanoscale spatial distribution patterns of such proteins, and how they are altered in platelets upon different activations. Analysing such alterations by SRM thus represents a promising, minimally invasive strategy for platelet-based diagnosis and monitoring of cancer progression. However, broader applicability beyond specialized research labs will require objective, more automated imaging procedures. Moreover, for statistically significant analyses many SRM platelet images are needed, of several different platelet proteins. Such proteins, showing alterations in their distributions upon cancer progression additionally need to be identified.

Results

A fast, streamlined and objective procedure for SRM platelet image acquisition, analysis and classification was developed to overcome these limitations. By stimulated emission depletion SRM we imaged nanoscale patterns of six different platelet proteins; four different SNAREs (soluble N-ethylmaleimide factor attachment protein receptors) mediating protein secretion by membrane fusion of storage granules, and two angiogenesis regulating proteins, representing cargo proteins within these granules coupled to tumor progression. By a streamlined procedure, we recorded about 100 SRM images of platelets, for each of these six proteins, and for five different categories of platelets; incubated with cancer cells (MCF-7, MDA-MB-231, EFO-21), non-cancer cells (MCF-10A), or no cells at all. From these images, structural similarity and protein cluster parameters were determined, and probability functions of these parameters were generated for the different platelet categories. By comparing these probability functions between the categories, we could identify nanoscale alterations in the protein distributions, allowing us to classify the platelets into their correct categories, if they were co-incubated with cancer cells, non-cancer cells, or no cells at all.

Conclusions

The fast, streamlined and objective acquisition and analysis procedure established in this work confirms the role of SNAREs and angiogenesis-regulating proteins in platelet-mediated cancer progression, provides additional fundamental knowledge on the interplay between tumor cells and platelets, and represent an important step towards using tumor-platelet interactions and redistribution of nanoscale protein patterns in platelets as a basis for cancer diagnostics.
Individual and joint influence of cytokeratin 19 and microvascular invasion on the prognosis of patients with hepatocellular carcinoma after hepatectomy
Authors: Qin Shang-Dong , Zhang Jie , Qi Ya-Peng , Zhong Jian-Hong , Xiang Bang-De
Published: June 2022

Background and objectives

To evaluate the individual and combined associations of cytokeratin 19 (CK19) and microvascular invasion (MVI) with prognosis of patients with hepatocellular carcinoma (HCC).

Methods

Clinicopathological data on 352 patients with HCC who underwent radical resection at our hospital between January 2013 and December 2015 were retrospectively analyzed. Patients were divided into four groups: CK19(−)/MVI(−), CK19(−)/MVI(+), CK19(+)/MVI(−), and CK19(+)/MVI(+).

Results

Of the 352 HCC patients, 154 (43.8%) were CK19(−)/MVI(−); 116 (33.0%), CK19(−)/MVI(+); 31 (8.8%), CK19(+)/MVI(−); and 51 (14.5%), CK19(+)/MVI(+). The disease-free survival of CK19(−)/MVI(−) patients was significantly higher than that of CK19(−)/MVI(+) patients and CK19(+)/MVI(+) patients. Similar results were observed for overall survival. CK19(+)/MVI(+) patients showed significantly lower overall survival than the other three groups.

Conclusions

CK19 expression and MVI predict poor prognosis after radical resection of HCC, and the two markers jointly contribute to poor OS. Combining CK19 and MVI may predict post-resection prognosis better than using either factor on its own.
Safety and efficacy of endovascular thrombectomy in acute ischemic stroke treated with anticoagulants: a systematic review and meta-analysis
Authors: Chen Jia-Hung , Hong Chien-Tai , Chung Chen-Chih , Kuan Yi-Chun , Chan Lung
Published: June 2022

Background

Endovascular thrombectomy (EVT) is an effective therapy in acute ischemic stroke (AIS) with large vessel occlusion, especially for those who are unsuitable for intravenous thrombolysis. However, the safety and efficacy of EVT in AIS patients who receiving oral anticoagulants (OACs) is unclear, especially for the risk of symptomatic intracranial hemorrhage (sICH). 

Methods

Database of PubMed, Embase, and Cochrane Library were searched from Jan 1, 2000, through the final search date of Jun 2, 2021. Eligible studies for enrollment required outcomes reported for events of sICH, mortality, functional status, and successful reperfusion. Meta-analysis was conducted to compare the outcomes difference after EVT between AIS patients with or without OACs use. The primary safety outcome was sICH after EVT, and the primary efficacy outcome was functional status at 3 months. 

Results

One thousand nine hundred forty studies were screened for eligibility and 15 of them were included in the meta-analysis. Compared the OACs group to control arm, vitamin K antagonists (VKAs) was associated with higher risk of sICH (OR 1.49, 95% CI 1.10–2.02) and mortality (OR 1.67, 95% CI 1.35–2.06). Poor functional outcomes were noted both in the VKAs and direct oral anticoagulants (DOACs) groups (OR 0.62, 95% CI 0.54–0.71 and OR 0.61, 95% CI 0.53–0.71, respectively). No differences in successful reperfusion were observed.

Conclusions

Comparing with DOACs, VKAs use was associated with a higher risk of sICH and mortality after EVT. Patients who did not receive OACs exhibited more favorable outcomes. The successful reperfusion did not differ between groups. However, results for mortality and functional outcomes have to be interpreted with caution since they are based on non-randomized data and unadjusted proportions.